Evolution of Length of Stay After Surgical and Transcatheter Aortic Valve Implantation Over 8 Years in 1,849 Patients >75 Years of Age and Comparison Between Transfemoral and Transsubclavian Transcatheter Aortic Valve Implantation.
Minimized length of hospitalization (LoS) and lower risk of hospitalization-related complications are key requirements in the treatment of aortic valve disease, mainly in the elderly candidates. Our objective was to evaluate evolution of LoS after surgical (SAVR) or transcatheter aortic valve implantation (TAVI) and its predictors. We enrolled 1,849 elderly (aged >75) patients receiving SAVR or TAVI from 2009 to 2016. In the surgical cohort (n = 1,006) the mean LoS slightly decreased from 13.81 ± 9.27 days (2009) to 10.96 ± 3.77 (2016); in the TAVI cohort (n = 843), LoS passed from 13.33 ± 9.17 (2009) to 6.21 ± 4.30 days (2016). All-cause mortality at 1 month was 3.77 % (SAVR) versus 4.7% (TAVI) (p >0.05). Among Transfemoral TAVI (TF, n = 681), and Transsubclavian TAVI (TS, n = 62), average LoS was comparable (7.38 days ± 7.11 vs 7.31 ± 4.32; median 6.0 and 6.0 days, p = 0.07). Procedural success was reached in 93% (TF) and in 85.4% (TS) (p = 0.20). There were no meaningful differences among TF and TS in terms of VARC-2 postprocedural morbidity, except for the rate of vascular access-related complications; these occurred in 8.8% of cases in the TF group versus 1.6% in the TS group (p = 0.05). In conclusion the present analysis showed a faster improvement in terms of LoS for TAVI compared with SAVR over 8 years of activity. The 2 strategies presented comparable all-causes mortality at 30 days. LoS, rates of procedural success and complications were comparable among TF and TS TAVI; nonetheless, vascular access-related complications were more frequent in the TF cohort. This suggests the validity of the TS route as an alternative to the TF approach.


[Expression of RAD51 in carcinomas of cancer of larynx and its clinical significance].
To investigate the expression and clinical significance of RAD51 in laryngocarcinoma. The expression of RAD51 in laryngocarcinoma and polyp of vocal cord tissues were determined by immunohistochemical staining. The results were analyzed and compared with the clinical stage, lymph node metastasis and pathologic grade. (1) The expression of RAD51 in laryngocarcinoma group was extremely stronger than that in polyp of vocal cord group (P < 0.01). (2) There was significant difference for RAD51 expression in cancer cells between earlier clinical stage group and advanced clinical stage group (P < 0.01). (3) There was significant difference for RAD51 expression in different pathologic grades (P < 0.05). (4) There was also significant difference for RAD51 expression between groups with and without lymph node metastasis. RAD51 may play a critical role in tumorigenesis of laryngocarcinoma. RAD51 may be a potential marker for clinical diagnosis and treatment of Laryngocarcinoma. It may be significant in predicting clinical stage, pathologic grade and metastasis.


Effects of anti-reflux surgery on chronic cough and asthma in patients with gastro-oesophageal reflux disease.
This two-group prospective study evaluated the effect of anti-reflux surgery (fundoplication) on 24 patients with severe gastro-oesophageal reflux disease (GORD) and concomitant asthma (n=13) or chronic cough (n=11). Twenty-four hour oesophageal pH monitoring and lung function tests (FEV1, FVC) were done before and within 1 year after anti-reflux surgery. A diary was kept by the patient during the 4-week period prior to surgery and during 4-week periods 6 and 12 months postoperatively, with daily monitoring of peak expiratory flow rate, respiratory and reflux symptoms and medication. In non-asthmatic patients, coughing was reduced by 47% and 80% during the day and night, respectively, 12 months after surgery (P < 0.01). Concomitant hoarseness and expectoration were also significantly reduced (P<0.05). No effect on lung function was seen. In patients with asthma, small, non-significant reductions in asthma symptom scores and consumption of rescue medication were seen. Twenty-two patients were completely free from their GORD symptoms after surgery. In conclusion, anti-reflux surgery in patients with GORD had a more favourable effect on concomitant cough than concomitant asthma.


Management of forehead and brow deformities.
The subcutaneous trichophytic forehead browlift allows rejuvenation of the forehead with precise, stable brow positioning, excellent visualization, and direct treatment of the brow and forehead musculature. This method avoids lengthening the forehead and, with meticulous closure, can produce an imperceptible scar and natural-appearing hairline.


Mast cell accumulation at sites of murine tumor implantation: implications for angiogenesis and tumor metastasis.
To investigate the role of mast cells during the process of tumor angiogenesis, we compared the rates of tumor vascularization, growth and metastasis in control WBB6F1(-)+/+ mice and in their mast-cell-deficient WBB6F1-W/Wv littermates injected with MB49 murine bladder carcinoma cells. Our results demonstrate that in mast-cell-deficient mice injected with tumor cells, there is a decreased number of capillaries at the tumor periphery, reduced tumor size relative to control mice, and an absence of metastases. In contrast, when tumor cells were inoculated intravenously, both strains of mice showed high numbers of lung metastases. These results suggested that the reduction of blood vessels at the tumor periphery may lead to a reduction in the number of metastatic cells shed into the circulation in mast-cell-deficient mice.


Persistence of deafferentation-induced presynaptic dendrites in the cerebellar cortex of adult rats.
The paper provides morphological evidence for a long-lasting morphogenetic potential of the excitatory granule cells and the inhibitory small Golgi neurons to manufacture and to maintain presynaptic sites on their otherwise exclusively postsynaptic dendritic processes and somata. The development of new dendrodendritic and somato-dendritic synapses follows and is the direct consequence of the mossy fiber deafferentation of the cerebellar cortex. By GABA-immunocytochemistry it was demonstrated that not only Golgi axons but also the Golgi somata and presynaptic dendrites contain GABA, suggesting that this inhibitory transmitter is an operating factor in many of the newly formed synapses.


Tissue localization of threonine oxidation in pigs.
Two experiments were designed to determine the tissue distribution of threonine oxidation through the threonine dehydrogenase (EC 1.1.1.103) pathway in pigs. The first experiment was conducted on eleven Piétrain x Large White piglets. The piglets were slaughtered at 5, 12 or 20 kg after 1 h of infusion with L-[U-14C]threonine (55 kBq/kg) mixed with unlabelled threonine (100 mg/kg). In the second experiment, four Piétrain x Large White and four large White piglets (10 kg body weight) were infused with L-[1-13C]threonine (50 mg/kg) mixed with 50 mg/kg unlabelled threonine for 1 h, then killed for tissue sampling. In the two experiments, threonine dehydrogenase specific activity and threonine and glycine specific radioactivities and enrichments were measured in several tissues and in plasma. The higher level of labelling of threonine in the pancreas than in the liver suggested either a lower protein degradation rate or a faster rate of threonine transport in the liver than in the pancreas. Threonine dehydrogenase activity was found only in the liver and the pancreas. Whereas liver and pancreas threonine dehydrogenase specific activities were similar, glycine specific radioactivity and enrichment were 12- to 14-fold higher in the pancreas than in the liver. This is probably the consequence of a higher production rate of glycine from sources other than threonine (protein degradation, de novo synthesis from serine) in the liver than in the pancreas. Our results showed that Large White pigs could oxidize more threonine than Piétrain x Large White pigs. This could be related to the difference in growth performance and dietary N efficiency for protein deposition between these two genotypes.


Describing cognitive decline of patients at the mild or moderate stages of Alzheimer's disease using the Standardized MMSE.
To describe the progression of patients with mild or moderate Alzheimer's disease (AD) to a severe stage using the Standardized Mini-Mental State Examination (SMMSE). A cohort of 206 patients was stratified according to their baseline SMMSE scores: mild (19-24) and moderate (10-18). Proportional hazards analyses were used to determine the hazard of switching into a severe stage, defined as SMMSE score < 10. Among patients at the mild stage, 25% reached the severe stage within 2.6 years, and in the moderate group within 1.5 years. Patients with hallucinations at the mild stage experienced more rapid decline. The previous rate of decline was also found to be an important predictor. At the moderate stage, key predictors were lower SMMSE score and longer time since onset. Current SMMSE scores with other clinical details can be used to advise patients and caregivers about the expected progression of AD.


The relationship of the peroxisome proliferator-activated receptor-gamma 2 exon 2 and exon 6 gene polymorphism in Turkish type 2 diabetic patients with and without nephropathy.
Peroxisome proliferator-activated receptor gamma (PPAR gamma) has recently been shown to be associated with type 2 diabetes. We aim to investigate Turkish type 2 diabetic patients with/without diabetic nephropathy and healthy group and examined the contribution of the G/C exon 2 and T/C exon 6 of the PPAR gamma gene polymorphism to the development of diabetic nephropathy. The PPAR gamma genotypes were determined retrospectively in 43 patients with nephropathy and 48 without nephropathy and a control group of 50 healthy individuals. Genotyping of the G/C exon 2 and T/C exon 6 of the PPAR-gamma gene polymorphism for all individuals was performed by melting curve analysis of the generated amplicons after real-time online PCR. This genotype (exon 2 and exon 6) distribution did not differ between control subjects and type 2 diabetic patients. The genotype frequencies and allele exon 2 were CC, 100%; GC, 0%; GG, 0% and C, 100%; G, 0% in diabetic patients with nephropathy versus CC, 97.9%; GC, 2.1%; GG, 0% and C 98.9%, G 1.1% in those without nephropathy. Genotype exon 6 frequencies in diabetic patients with nephropathy were (T/T) 0%, (T/C) 14%; (C/C) 86% versus (G/G) 0%; (G/C) 2.1%; (C/C) 97.9% in those without nephropathy. The PPAR gamma exon 2 and exon 6 genotype and allele frequencies were not different between diabetic patients with and without nephropathy. PPAR gamma exon 2 and exon 6 gene polymorphism is not associated with the development of diabetic nephropathy in Turkish type 2 diabetic patients.


First clinical experience in urologic surgery with a novel robotic lightweight laparoscope holder.
To report the feasibility and the safety of a surgeon-controlled robotic endoscope holder in laparoscopic surgery. From March 2010 to September 2010, 20 patients were enrolled prospectively to undergo a laparoscopic procedure using an innovative robotic endoscope holder. Two surgeons performed six adrenalectomies, four sacrocolpopexies, five pyeloplasties, four radical prostatectomies, and one radical nephrectomy. Demographic data, overall setup time, operative time, number of assistants needed were reviewed. Surgeon satisfaction regarding the ergonomics was assessed using a 10-point scale. Postoperative clinical outcomes were reviewed at day 1 and 1 month postoperatively. The per-protocol analysis was performed on 17 patients for whom the robot was effectively used for surgery. Median age was 63 years; 10 (59%) patients were female. Median body mass index was 26.8. Surgical procedures were completed with the robot in 12 (71%) cases. Median number of surgical assistant was 0. Overall setup time with the robot was 19 minutes; operative time was 130 minutes during which the robot was used 71% of the time. Mean hospital stay was 6.94 ± 2.3 days. Median score regarding the easiness of use was 7. Median pain level was 1.5/10 at day 1 and 0 at 1 month postoperatively. Open conversion was needed in one (6%) case, and four minor complications occurred in two (12%) patients. This use of this novel robotic laparoscope holder is safe, feasible, and provides good comfort to the surgeon.


Pharmacological intervention of hippocampal CA3 NMDA receptors impairs acquisition and long-term memory retrieval of spatial pattern completion task.
Pattern completion is the ability to retrieve complete information on the basis of incomplete retrieval cues. Although it has been demonstrated that this cognitive capacity depends on the NMDA receptors (NMDA-Rs) of the hippocampal CA3 region, the role played by these glutamatergic receptors in the pattern completion process has not yet been specified. In the present study, we investigated the function of the CA3 NMDA-Rs during the different memory stages (acquisition, memory consolidation, and retrieval) in a spatial pattern completion task (when some visual cues were removed from the environment) in comparison to a standard spatial water maze task (when all visual cues were available in the environment). Thus, we coupled a massed training with the injection of NMDA-receptor antagonist (AP5) into the CA3 subfield of the dorsal hippocampus of C57BL/6 mice. Our results show that NMDA-Rs are not implicated in a standard situation but are crucial during both acquisition and long-term memory retrieval in pattern completion. This work provides the first evidence of a specific role of CA3 NMDA-Rs during memory process involved in the reactivation of incomplete memory trace, particularly when the amount of environmental information available is strongly limited.


HA-966 (1-hydroxy-3-aminopyrrolidone-2) selectively reduces N-methyl-D-aspartate (NMDA)-mediated brain damage.
The neuroprotective effects of the strychnine-insensitive glycine receptor antagonist, HA-966, against N-methyl-D-aspartate (NMDA)- and quisqualate (QA)-mediated brain injury were determined in perinatal rats. Postnatal day (PND) 7 rats received intrastriatal injections of NMDA (25 nmol) or QA (100 nmol) and then were administered intraperitoneal (i.p.) injections of varying doses of HA-966 or vehicle 15 min later. Animals were sacrificed 5 days later and the degree of brain injury was calculated by comparison of the weights of injected and contralateral cerebral hemispheres. HA-966 selectively reduced the degree of NMDA-mediated brain injury in a dose-dependent manner. However, HA-966 did not attenuate QA-mediated brain injury.


Axonal regeneration of identified septohippocampal projection neurons in vitro.
Previous studies have shown that the septohippocampal projection develops in vitro. It remained unclear, however, whether this in vitro projection resulted from axonal regeneration of septal neurons transected by the culture preparation, or from a priori outgrowth of undamaged cells that had not yet sent an axonal process to the hippocampus at the time of tissue preparation. Here we have prepared slice cultures of identified septohippocampal projection neurons that were retrogradely labeled by hippocampal tracer injection prior to slice preparation. We demonstrate that these identified projection neurons survive axotomy caused by culture preparation, are able to regrow an axonal process in vitro, and innervate a co-cultured hippocampal slice.


Optical elastography: tracking surface waves with digital image correlation.
Elastography consists in evaluating the propagation speed of waves into a tissue to estimate its stiffness. Usually this method is based on Ultrasounds, magnetic resonance imaging or optical coherent tomography. This paper proposes a simple optic method using ultrafast cameras. Based on digital image correlation (DIC), the tracking of elastic surface wave from white light intensity pattern, allows estimating the propagation speed as an indicator of the tissue local stiffness. Two configurations are presented: (1) 2D imaging of a flat phantom surface with a single camera and (2) 3D imaging of a curved phantom surface with two cameras. As a feasibility study of the first configuration, surface wave speed was measured on isotropic and anisotropic phantoms. Comparisons with ultrasound methods fully validate this approach. Although more sophisticated, the second configuration account for propagation distortions caused by locally curved topology. Triangulation techniques used to retrieve local topology are named stereo-correlation in the field of biomechanics. Stereo-elastography is thus proposed to determine tissue local elasticity from any soft tissue surface wave.


Microfluidic Approach to Cell Microencapsulation.
Bioartificial pancreas made of insulin-secreting islets cells holds great promise in the treatment of individuals with Type-1 diabetes. Successful islet cell microencapsulation in biopolymers is a key step for providing immunoisolation of transplanted islet cells. Because of the variability in the size and shape of pancreatic islets, one of the main obstacles in their microencapsulation is the inability to consistently control shape, size, and microstructure of the encapsulating biopolymer capsule. In this chapter, we provide a detailed description of a microfluidic approach to islet cell encapsulation in alginate that might address the microencapsulation challenges.


The coding region of TP53INP2, a gene expressed in the developing nervous system, is not altered in a family with autosomal recessive non-progressive infantile ataxia on chromosome 20q11-q13.
The locus for autosomal recessive infantile cerebellar ataxia (CLA3 or SCAR6) has been mapped to chromosome 20q11-q13 in a single Norwegian pedigree. We identified a relatively uncharacterised mouse gene Tp53inp2, and showed that its human orthologue mapped within this candidate interval. Tp53inp2 appears to encode a mammalian-specific protein with homology to the two Tp53inp1 isoforms that respond to cellular stress and interact with p53. We show that Tp53inp2 expression is highly restricted during mouse embryogenesis, with strong expression in the developing brain and spinal cord, as well as in the sensory and motor neuron tracts of the peripheral nervous system. Given this expression pattern, the neurological phenotype of CLA3 and the chromosomal localisation of TP53INP2, we searched the coding region for mutations in samples from individuals from the CLA3 pedigree. Our failure to detect causative mutations suggests that alterations in the coding region of TP53INP2 are not responsible for ataxia in this family, although we cannot rule out changes in non-coding elements of this gene.


Clinicopathological significance of SNPs in RAD51 and XRCC3 in oral and oropharyngeal carcinomas.
This study investigated the influence of single nucleotide polymorphisms (SNP) in RAD51 and XRCC3 on susceptibility to oral and oropharyngeal squamous cell carcinomas (SCC) and determined their clinicopathological significance. SNPs rs1801320 and rs1801321 in RAD51 and rs861539 in XRCC3 were genotyped in 81 patients presenting oral SCC, 45 presenting oropharyngeal SCC, and 130 healthy controls, using TaqMan allelic discrimination assays. Multiple logistic regression models were used to explore the association between SNPs and cancer development, as well as gene-gene (GxG) interaction and gene-environmental factor (GxE) interaction. Clinicopathological associations were verified through the chi-square test, and univariate and multivariate methods were applied for survival analyses. Although allelic and genotypic models and the GxG interaction analysis were nonsignificant, the GxE analysis revealed synergistic effects of the risk alleles of rs1801320, rs1801321, and rs861539 with smoking and alcohol consumption on susceptibility to oral and oropharyngeal SCC. Furthermore, oropharyngeal SCC patients carrying the XRCC3 rs861539 GT/TT genotype (T risk allele) presented a shorter overall survival than GG genotype carriers. Combined effects of RAD51 (rs1801320 and rs1801321) and XRCC3 (rs861539) SNPs with environmental carcinogens (tobacco and alcohol) are associated with oral and oropharyngeal SCC development.


Formation of salt crystal whiskers on porous nanoparticle coatings.
Salt crystal whiskers were grown from aqueous solution on porous nanoparticle silica coatings. Coated substrates were partially immersed in an aqueous potassium chloride solution and then kept in a controlled relative humidity chamber for whisker growth. The salt solution was pulled into the porous coating, reaching a steady level about 1 h after immersion. Crystals with whisker morphologies, typically 2-50 microm in lateral dimension and up to approximately 1 cm in length, emerged from the coating surface at a position above the original liquid level. Crystallites pushed upward by attached whiskers indicated a base growth mechanism in which ions are added to the surface of a growing whisker that is in contact with the coating. Sheetlike crystals formed from the base growth of whiskers that had fallen flat onto the porous coating surface. The effects of solution concentration and relative humidity on growth were characterized and used to elaborate the transport phenomena and growth mechanisms. Salt whiskers were also grown on bare substrates immersed in salt solutions containing nanoparticles. In this case, growth occurred below the original contact line on coatings created by convective assembly.


cis-Dichlorodiammineplatinum nephrotoxicity in rats of different ages.
In 5-, 15-, 30-, and 60-day-old rats there was a distinct decrease of body weight 24 hours after a single i.p. injection of cis-dichlorodiammineplatinum (CDDP) over a dose range from 0.25 to 2.0 mg/100 g b.w.t. Compared with a control group the kidney weights appeared nearly unchanged. The increase of blood urea nitrogen (BUN) concentrations following CDDP treatment was dose dependent and more profound in 5- and 15-day-old rats than in older animals. In higher doses, CDDP impaired the renal concentrating ability in rats of all age groups as reflected in a significant increase in urine volume with only a slightly increased renal sodium excretion. Following CDDP treatment there was a moderate proteinuria. In 30- and 60-day-old rats the renal excretion of p-aminohippurate (PAH) was more reduced by CDDP compared to younger rats.


[Effects of low-frequency pulsing magnetic field upon the respiratory metabolism and transmembrane ion fluxes of perfused rat livers].
Influence of magnetic fields on biological systems is not completely clear. Recently, experiments on the effects of weak not heat inducing electromagnetic fields concerning biological systems have been reported. We have investigated the effects of the weak low-frequency pulsing magnetic field (PMF) concerning the respiratory metabolism and transmembrane ion flux of perfused rat livers. Livers from male Wistar rats were perfused via the portal vein with 95% O2-5% CO2 saturated Krebs-Henseleit Bicarbonate Buffer maintained at 32 degrees C. In 48 hrs fasted rats, lactate was administered in the perfusate as a substrate of gluconeogenesis in case of necessity. PMF generated by the solenoid coil was applied to the perfused livers. For monitoring of respiratory metabolism of the perfused livers, scanning spectrophotometry and NADH fluorometry were applied to the surface of the liver. The effluent was monitored for PO2 and analyzed for glucose, lactate and pyruvate. Ca2+, Mg2+, Na+, K+, Cl- ion from effluent were also analyzed. By being exposed to a low-frequency PMF, the O2 consumption increased in the perfused livers of the fed rats, but the degree was variable according to the metabolic state of the liver of each rat. In order to bring about a maximum reductive state, ethanol was given to the perfusate. Ethanol caused an increase in NADH and Lactate/Pyruvate ratio and O2 consumption and an inhibition of glucose production. By exposure to PMF the metabolism of perfused liver was shifted to the re-oxidative state. In lactate administered perfused liver of the 48 hrs fasted rats, PMF caused an increase in the livers sensitivity to glucagon. As regards the transmembrane ion fluxes, PMF acted antagonistically to the ethanol effect, especially when we used perfusate with low Ca2+ concentrations. So that an intimate association between PMF and intracellular Ca2+ regulating system was suggested.


Protein tyrosine phosphorylation signaling in the differentiation of human endometrial stromal cells.
Reversible protein tyrosine phosphorylation, coordinately controlled by protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPs), is a critical element in signal transduction pathways regulating cell growth, differentiation, apoptosis, and tumorigenesis. The differentiation of human endometrial stromal cells (decidualization) is crucial for successful embryo implantation and maintenance of pregnancy; however, little is known about the molecular events involving tyrosine phosphorylation, PTKs, and PTPs in the process of decidualization. We have previously reported that the tyrosine kinase activity of c-Src belonging to the Src family kinase is increased together with altered tyrosine phosphorylation of several cellular proteins in the in vitro model of decidualization. Focal adhesion kinase (FAK) and paxillin are known to form a complex with c-Src at the focal contacts and to participate in the integrin-mediated signal transduction as c-Src substrates. Those focal adhesion proteins, however, are not hyperphosphorylated on tyrosine during decidualization. Moreover, the loss of focal adhesions and the disorganization of the actin-based cytoskeleton were observed in decidualized stromal cells, suggesting that the escape from regulation by c-Src may be in part due to the decidualization-induced disruption of the interaction between the focal adhesion proteins and c-Src. These findings collectively indicate that decidual c-Src may activate signaling pathway(s) different from the integrin-mediated signaling cascade involving FAK and paxillin. This review summarizes our recent studies on the tyrosine phosphorylation signaling pathway(s) in decidualization.


Can Selective Image-Guided Intraoperative Margin Resection Improve Re-Excision Rates after Lumpectomy in Ductal Carcinoma In Situ of the Breast?
The rate of positive margins after breast conserving surgery (BCS) can be as high as 50 per cent, and optimal techniques for reducing rates of positive margins are presently debated. Our institution has previously demonstrated low rates of margin re-excision using a standardized approach to intraoperative selective margin excision for patients undergoing BCS. We hypothesized that this approach can be used for patients with ductal carcinoma In Situ (DCIS) and can yield similar rates when compared with invasive cancer. We performed a retrospective analysis of women with breast cancer who underwent BCS from January 2012 through July 2016 using our institution's standardized approach to selective margin resection. Of the 152 patients who underwent BCS, there were 30 (20%) with DCIS and 122 (80%) with invasive cancer. There was no statistically significant difference in re-excision rates for DCIS (13.3%) and invasive cancer (13.1%). Notably, the DCIS group had a larger mean lesion size (P = 0.00009); however, the lesion was visible on ultrasound more often in the invasive cancer group (P = 0.007). This standardized approach to intraoperative selective margin excision can produce similar rates of margin re-excision for DCIS and invasive cancer and may be a viable option for lowering re-excision rates for patients with DCIS.


Correction of symptoms of platelet storage pool deficiency in animal models for Chediak-Higashi syndrome and Hermansky-Pudlak syndrome.
Two human diseases of platelet storage pool deficiency (SPD), Hermansky-Pudlak syndrome and Chediak-Higashi syndrome, are recessively inherited disorders characterized by hypopigmentation, prolonged bleeding, and normal platelet counts accompanied by a reduction in dense granule number. We have recently described seven independent recessive mutations in the mouse regulated by separate genes which are likely animal models for human SPD. Reciprocal bone marrow transplants were carried out between normal C57BL/6J mice and two of these mutants, beige and pallid, in order to test whether the platelet defects are due to a defect in platelet progenitor cells or to humoral factors. Normal and congenic mutant mice were transplanted with marrow after 950 rad whole body radiation. The long bleeding times and low serotonin concentrations of the two mutants were converted to normal values after transplantation with normal marrow. Likewise, normal mice displayed symptoms of SPD when transplanted with mutant marrow. These studies demonstrate that with each of the two mutations, platelet SPD results from a defect in bone marrow precursor cells. Also, the studies suggest that in severe cases, platelet SPD may be successfully treated by bone marrow transplantation.


Short peritoneal equilibration test: impact of preceding dwell time.
In the original peritoneal equilibration test (PET), which established standard values for membrane categorization in 1987, the dwell time of the preceding exchange was approximately 8 hours. Basing the test on an 8-hour prior exchange was convenient when almost all patients were on continuous ambulatory peritoneal dialysis (CAPD); however, many patients are now on some form of automated peritoneal dialysis (PD), and an 8-hour exchange before the PET requires a change in the dialysis schedule. Our goal in the present study was to determine whether the dialysate-to-plasma ratio (D/P) of solutes and the final dialysate to initial dialysate ratio (D/D0) of glucose in the short PET (2-hour equilibration time) are similar whether a 3-hour exchange or an 8-hour exchange precedes the test. The PETs were performed in 9 stable PD patients using 2 L of 2.5% dextrose dialysis solution (Baxter Healthcare, Deerfield, IL, U.S.A.). Before the equilibration exchange, the patients were on a randomly selected long (approximately 8-hour) or short (3-hour) dwell. During the equilibration exchange, dialysate samples were collected at 0.30, and 60 minutes of dwell time and from the drain bag (120-minute sample). Within a week, the PET was repeated in each patient after the alternate-length exchange. The values for D/P creatinine and urea and for D/D0 glucose were almost identical throughout the 2-hour PET after either the long or the short exchange. The D/P protein values tended to be higher in the PET after the long exchange. The short PET can be used for clinical purposes, and the creatinine and glucose results can be used for membrane categorization. Any dwell time between 3 and 12 hours is acceptable for the preceding exchange, and the equilibration test may be performed with either a 2-hour or a 4-hour dwell. The protein values obtained after a 3-hour prior dwell differ from those obtained after a long prior dwell. Protein values must therefore be standardized in a larger number of patients.


Observational study of the additive effects of pranlukast on inflammatory markers of clinically stable asthma with inhaled corticosteroids and long-acting beta 2 agonists.
Little is understood about the additive effects of leukotriene receptor antagonists (LTRA) on asthmatics currently medicated with inhaled corticosteroids (ICS) and long-acting beta(2)-agonists (LABA). The present study examines the anti-inflammatory effects of the LTRA pranlukast in addition to ICS and LABA, among asthmatic patients with normal pulmonary function and unremarkable clinical symptoms. Fifteen adult asthmatics participated in a 2-month, open-label, uncontrolled, prospective, multicenter, observational trial. Patients stabilized (predicted forced expiratory volume in 1 s >80%) by medication with ICS and LABA were also given pranlukast (450 mg daily). Asthma-related symptoms, pulmonary function, blood eosinophil counts and several inflammatory markers in sputum were monitored at week 0, as well as at 4 and 8 weeks after starting therapy with pranlukast. Adding pranlukast did not further improve blood eosinophil counts, pulmonary function and symptoms, but significantly attenuated sputum cysteinyl leukotrienes, tumor necrosis factor-alpha and interleukin-5 concentrations. Although the clinical relevance remains obscure, adding an LTRA attenuates allergic airway inflammation in some asthmatics undergoing treatment with ICS and LABA.


The protein tyrosine phosphatase non-receptor type 22 C1858T polymorphism is a joint susceptibility locus for immunthyroiditis and autoimmune diabetes.
The lymphoid tyrosine phosphatase (LYP) encoded by the protein tyrosine phosphatase non-receptor type 22 (PTPN22) gene is a strong inhibitor of T cells. The single nucleotide polymorphism (SNP) C1858T within the PTPN22 gene was recently associated with autoimmune thyroid disease (AITD) and type I diabetes (T1D). The purpose of this study was to examine the joint association of this polymorphism with the co-occurrence of AITD and T1D. In this association study, 310 white subjects were genotyped for the C1858T polymorphism. The study population included 70 patients with both AITD and T1D (AITD+T1D), 70 patients with AITD only, 70 patients with T1D only, and 100 healthy controls. Patients with both AITD and T1D, and controls were also typed for HLA-DRB1. PTPN22 C1858T genotyping was performed by minisequencing. For HLA-DRB1 typing, polymerase chain reaction (PCR) sequence-specific oligonucleotide probes were used. The PTPN22 1858 minor T-allele frequency was strongly increased in patients with AITD+T1D (23.6%) compared with controls (8.0%, pc<0.001), with patients with AITD only (8.6%, pc=0.006), or with T1D only (10.7%, pc=0.028). T-allele carriers were also more frequently present in the group with AITD+T1D versus controls (41.4% vs. 14.0%, OR=4.35, 95% CI=2.08-9.09), AITD (17.1%, OR=3.42, 95% CI=1.56-7.48), and T1D (21.4%, OR=2.59, 95% CI=1.23-5.45). Especially in subjects with Hashimoto's thyroiditis (HT)+T1D, T-allele carriers were mostly frequent (50% vs. 14%, OR=6.14, 95% CI=2.62-14.38, pc<0.001). Considering all included patients with AITD, T-allele carriers were 29.3% vs. 14.0% in controls (p=0.008, OR=2.54, 95% CI=1.30-4.98). Patients carrying the PTPN22 1858 T allele had a twofold increased frequency of the HLA-DRB1*03 allele (64.7% vs. 37.3%, pc=0.034). The PTPN22 gene is a joint susceptibility locus for AITD (especially HT) and T1D.


Familial corneal hypesthesia.
A 4-year-old boy with severe, diffuse, asymptomatic, punctate, epithelial corneal erosions had bilateral sharply decreased corneal sensation with normal skin sensation in the distribution of the trigeminal nerves. Subsequent family studies disclosed five family members with similar corneal changes and decreased corneal sensation and no punctate erosions. None had decreased skin sensation in the distribution of the fifth cranial nerve. No environmental factors or evidence of local or systemic disease accounted for these findings.


Differential association of somatic and cognitive symptoms of depression and anxiety with inflammation: findings from the Netherlands Study of Depression and Anxiety (NESDA).
Depression and anxiety have been suggested to be associated with systemic inflammation upregulation. However, results are not always consistent, which may be due to symptom heterogeneity of depression and anxiety. There are some indications that associations with inflammation are mainly driven by somatic symptoms of depression and anxiety. We therefore set out to evaluate the differential association of somatic and cognitive symptoms of depression and anxiety with inflammation, while adjusting for demographic, health related, and lifestyle related variables. We evaluated baseline data from 2861 participants from the Netherlands Study of Depression and Anxiety (NESDA). The Inventory of Depressive Symptomatology and the Beck Anxiety Inventory were used to assess depressive symptoms and anxiety symptoms. For both scales somatic and cognitive symptoms scales were calculated. Baseline blood samples were collected to determine high sensitivity C-Reactive Protein (CRP), interleukin (IL)-6, and Tumor Necrosis Factor (TNF)-α. We used linear regression to analyze the associations adjusting for demographics and health indicators and markers for an unhealthy lifestyle. After adjustment for sociodemographic and health indicators, depressive symptoms were associated with higher levels of CRP, IL-6 and TNF-α. This association was mainly driven by somatic symptoms. For anxiety, somatic symptoms were associated with higher levels of CRP, IL-6 and TNF-α, whereas cognitive anxiety symptoms were associated with CRP (men only). Markers of an unhealthy lifestyle explained the significant associations. Especially somatic symptoms of depression and anxiety are associated with inflammation. However, this association was mostly mediated through unhealthy lifestyles among depressed and anxious individuals.


Maturation of Oocytes in Vitro.
Only a fraction of oocytes present in the ovaries at birth are ever ovulated during the lifetime of a female mammal. In vitro maturation (IVM) offers the possibility to exploit what is a largely untapped biological resource. Although IVM is used routinely for the in vitro production of embryos in domestic species, especially cattle, its clinical use in human-assisted reproduction is still evolving. The successful recapitulation in vitro of the events associated with successful oocyte maturation is not always achieved, with the majority of immature oocytes typically failing to develop to the blastocyst stage. Evidence suggests that although culture conditions throughout in vitro embryo production may have a modest influence on the developmental potential of the early embryo, the quality of the oocyte at the start of the process is the key factor determining the proportion of oocytes developing to the blastocyst stage.


Is there a role for hemopoietic stem-cell transplantation in CTCL?
The role of autologous and allogeneic stem-cell transplantation (SCT) in the treatment of cutaneous T-cell lymphoma (CTCL) is reviewed. Patients most likely to benefit are those with advanced-stage disease, multiple relapses, and short remissions; chemosensitive disease is also a prerequisite for these treatments. Autologous SCT produces high response rates in patients with peripheral T-cell lymphoma, but these are generally of short duration. This therapy is relatively safe to administer, with little transplant-related mortality. In contrast, allogeneic SCT may be highly toxic and result in transplant-related mortality, but it has the potential to produce long-lasting responses. Prospective studies of these treatments in patients with CTCL are required. Nevertheless, selected patients could be considered for allogeneic SCT, preferably early in their disease when their performance status is still good.


The relationship between the mobility of human teeth and their supracrestal fiber support.
A method to study the relationship between the mobility of human teeth and their supracrestal fiber support was developed. The results of this study would indicate that: (1) The supracrestal fibers do not contribute significantly to the support of a normal premolar tooth. (2) As a human premolar tooth develops moderate to severe loss of osseous support, the relative contribution of the supracrestal fibers to the support of the tooth increases significantly.


Gene assignment in the spider monkey (Ateles paniscus chamek--APC): APE-MYH7 to 2q; AR-GLA-F8C to the X chromosome.
Comparative gene assignment between the spider monkey species Ateles paniscus chamek (APC) and man (HSA) showed conserved syntenic associations despite extensive karyotypic rearrangement between species. Two HSA 14q genes were allocated to APC 2q, being syntenic to other HSA 14q and HSA 15q markers previously assigned to APC 2q, and to HSA 12q genes previously assigned to APC 2p. These findings were consistent with A. geoffroyi chromosome painting with human whole-chromosome probes, indicating that the genus Ateles is karyotypically very rearranged. On the other hand, three human X-linked markers were assigned to the Ateles X chromosome, indicating that this chromosome is evolutionary stable.


Structural composition of blood erythrocytes in children with nephropathies.
Study of the structural characteristics of peripheral blood erythrocytes in the pathogenesis of nephropathies in children by means of automated recording of integral osmotic erythrograms and analysis of differential curves of hypoosmotic hemolysis showed decreased osmotic resistance of erythrocytes, which was most pronounced during renal dysfunction. A molecular model of possible modification of the erythrocyte membrane in the pathogenesis of nephropathies is proposed.


Transfection of human nm23-H1 into the human MDA-MB-435 breast carcinoma cell line: effects on tumor metastatic potential, colonization and enzymatic activity.
We report the phenotypic effects of transfection of human nm23-H1 cDNA into the human MDA-MB-435 breast carcinoma cell line. Upon mammary fat pad or subcutaneous injection into nude mice, both the nm23-H1 and control transfected lines produced primary tumors; however, the nm23-H1-transfected lines produced metastases in significantly fewer mice than did control transfected lines. Reductions in tumor metastatic potential in vivo were accompanied by decreased colonization in soft agar and an altered colonization response to transforming growth factor beta in vitro. Total nucleoside diphosphate kinase activity, an enzymatic activity possessed by the Nm23 family, was not directly correlated with Nm23-H1 expression levels or suppression of metastatic potential in all cases examined. The data establish that nm23-H1 has functional suppressive effects on the tumor metastatic potential of a human breast carcinoma cell line, and suggest that it may regulate signal responsiveness in the colonization response.


Smooth muscle autoantibodies in normal rabbit sera. Cross-reaction with human platelets as demonstrated by immunofluorescence.
27 normal rabbit sera were tested by indirect immunofluorescent technique. All sera stained smooth and skeletal muscle of human and mammalian tissues and human washed platelets. Two sera had ANA activity. These autoantibodies had low titres. Lysed but not intact platelets neutralized the rabbit SMA sera activity.


Genetic regulation of rejection and survival following human lung transplantation by the innate immune receptor CD14.
We have developed the hypothesis that genetic polymorphisms which alter the expression or function of innate immune receptors contribute to the marked interindividual differences in the onset and severity of lung transplant rejection. In this analysis, we considered the effects of a common promotor polymorphism of the lipopolysaccharide receptor CD14 associated with increased transcriptional activity upon the development of posttransplant rejection and graft survival. Genotyping was performed in 226 lung transplant recipients well characterized with regards to clinical outcomes. An earlier onset of acute rejection, bronchiolitis obliterans syndrome (BOS) and worse posttransplant graft survival due to greater BOS related deaths was evident in patients with the CD14 -159 TT genotype (TT). The adverse effect upon graft survival of the TT genotype remained significant in a multivariate Cox model (Hazard Ratio 1.65, 95% CI, 1.03-2.64, p-value = 0.04) after adjusting for other important covariates. Furthermore, TT patients have significantly greater sCD14, TNF-alpha and IFN-gamma in the peripheral blood implying a heightened state of innate immune activation drives the development of increased post-transplant rejection. Inhibition of innate immune activation through CD14 represents a novel and potentially important therapeutic target to prevent post-transplant rejection and improve outcomes after human lung transplantation.


Evaluation of the stability profile of anticancer drugs: A review of Ifosfamide and Mesna regimen for the treatment of metastatic soft tissue sarcoma.
This paper aims to summarise and critically review the existing published literature with regard to clinical considerations as well as stability testing studies of Ifosfamide and Mesna. It also aims to highlight the factors that should be considered when designing and conducting stability testing experiments. Ifosfamide and Mesna are currently given to patients for 14 days continuous home-based infusion for the treatment of soft tissue sarcoma. No previous work has evaluated their stability for more than 7 days under real-life conditions so the current regimen involves patients visiting hospital twice during the 14-day treatment. This may create extra disruption to patients' life style as well as increasing the workload for cancer services. There is a need to conduct stability testing experiments for Ifosfamide and Mesna taking into consideration all of the highlighted factors to mimic standard clinical practice.


[Changes of nitric oxide after trichloroethylene irritation in hairless mice skin and protection of ginkgo biloba extract and vitamin E].
To study the changes of nitric oxide (NO) in the BALB/c hairless mice skin after trichloroethylene (TCE) irritation and the protection of ginkgo biloba extract (GbE) and vitamin E (VE). 132 BALB/c hairless mice were randomly divided into blank control group, solvent group (olive oil), TCE groups (20%TCE, 40%TCE, 80%TCE and 100%TCE), GbE groups (0.1%GbE, 1%GbE and 10%GbE) and VE groups (5%VE, 10% VE and 20% VE), with 11 animals in each group, 5 for acute irritation test and 6 for the cumulative irritation test. The skin irritation was observed, and the levels of NO in the dorsal skin of BALB/C hairless mice were detected. The kit of NO was used to detect the levels of NO in the dorsal skin of BALB/c hairless mice. (1) The skin presented erythema and edema after TCE irritation both in acute irritation and cumulative irritation test and the skin inflammation showed time-dose effect relationship; the mice skin was protected in GbE or VE groups. (2) In the acute stimulation test, the levels of NO in 80%TCE group (69.895 +/- 9.605 micromol/mg pro) and 100%TCE group (77.273 +/- 9.290 micromol/mg pro) were significantly different compared with blank control group and solvent control group (P < 0.05 or P < 0.01). In the protection group, the NO level were reduced, with the statistically significant differences. (3) In acute irritation test, the levels of NO in 80%TCE group (60.362 +/- 9.817 micromol/mg pro) and 100%TCE group (68.027 +/- 9.354 micromol/mg pro) were significantly different compared with blank control group and solvent control group, (P < 0.05 or P < 0.01); In the protection group, 1% GbE, 10% GbE, 10% VE and 20%VE could reduce the levels of NO, with statistically significant differences. TCE can produce the irritation on the dorsal skin of BALB/c hairless mice and induce the significant increase of the NO levels. GbE and VE can protect the skin from TCE irritation damage.


A comprehensive approach to clinical evaluation.
Historically, the summative clinical evaluation of nursing students has been problematic. Tools of measurement for clinical performance have been subjective and, at times, biased at several levels. With these thoughts and past experiences in mind, the faculty in an associate degree nursing program developed a comprehensive approach to summative clinical evaluation. The process began with the development and implementation of a Clinical Performance Manual (CPM) describing five components of the summative evaluation process. These included the: ability to consistently exhibit professional behaviors; random skills performance examination; plan of care examination; critical situations examination; and required course assignments. These components were developed with the intent of objectifying the measurement of cognitive, affective, and psychomotor skills of students. After 1 year of implementing this process with 250 students, feedback received from faculty and students was reviewed and discussed. Reliability and validity studies have been conducted. A decision was made to continue with this new method of evaluation. Recommendations include piloting and implementing the process in others schools and programs.


Short-lived intermediates in photochemistry of an OsCl62- complex in aqueous solutions.
Two mechanisms of OsIVCl62- photolysis were studied by means of quantum chemical calculations in gas and aqueous phases. The difference between these mechanisms is in the nature of the possible Os(iv) key intermediates (KI). According to calculations, the intermediate is an OsIVCl5- complex of square pyramidal coordination geometry. The calculations do not give an opportunity to make an unambiguous choice between the triplet and quintet multiplicities of OsIVCl5-. The calculated CASSCF/IMCP-SR1 transition energies for 5OsIVCl5- are lower than for 3OsIVCl5-, while the calculated XMC-QDPT2/SBKJC spectra for the triplet state are in better agreement with the experimental absorption spectrum of the KI than for the quintet state.


Alveolar hypoxia is a powerful stimulus for ANF release in conscious lambs.
The effect of acute alveolar hypoxia [fractional concentration of O2 in inspired gas (FIo2) = 0.1] for 10 min [arterial PO2 = 37 +/- 4 (SE) mmHg] and of blood volume expansion (7 and 15% of calculated blood volume) on atrial natriuretic factor (ANF) release was examined in groups of awake, instrumented young lambs. Systemic venous plasma ANF concentrations increased 1.6-fold (P less than 0.01) during blood volume expansion of 7%, 1.9-fold (P less than 0.01) during acute hypoxia, and 2.2-fold (P less than 0.005) during blood volume expansion of 15%. In lambs with prior 15% blood volume expansion, alveolar hypoxia further increased ANF concentrations 3.1-fold (P less than 0.01), suggesting synergism between volume and hypoxia stimuli. Hypoxia-induced ANF release correlated best with increased pulmonary arterial pressure, a potential mediator of the ANF response (r = 0.67; P less than 0.016). Increased differences between pulmonary arterial and systemic venous plasma ANF concentrations (from 11 to 134 pg/ml) indicate that hypoxia causes increased release of ANF from the heart rather than decreased metabolism of circulating ANF. Pulmonary arterial plasma ANF during hypervolemic hypoxia had immunological and chromatographic (high-performance liquid chromatography) properties of Pro-ANF-(99-126) [alpha-ANF-(1-28)]. Thus alveolar hypoxia (FIo2 = 0.1) is as potent as 15% blood volume expansion in increasing the concentration of circulating ANF. This newly described endocrine response could be important during alveolar hypoxia to decrease pulmonary vasoconstriction and fluid accumulation in the lung.


Murine fetal liver augments proliferation in an allogenic mixed lymphocyte culture: benzo(a)pyrene reduces augmentation.
The effect of cells from the liver of C3H fetuses syngeneic to splenic responder cells on an allogeneic mixed lymphocyte response (MLR) was studied. After fractionation on ficoll-hypaque, interface cells from corn oil (vehicle for BP) or normal fetal liver (FL) controls (CO), obtained from 17-19 days gestation, enhanced proliferation in the mixed lymphocyte culture (> 2-fold), while cells from FLs transplacentally exposed to benzo(a)pyrene (BP) showed a decreased capacity for augmentation (> 2-fold less than CO). Unfractionated CO-FL cells at 0.5 x 10(6) did not augment proliferation, but at 0.25 x 10(6) enhancement with control FL cells was significantly higher than with BP-FL cells. Pelleted cells from BP- and CO-FLs were severely suppressive at the higher dose, while at 0.25 x 10(6) proliferation was augmented with CO-FL cells, but not affected with BP-FL cells. At doses of 0.1 x 10(6) or less, no effect was observed for either control or BP-FL cells. These data indicate that: a) FL cells syngeneic to responder cells of an allogenic mixed lymphocyte culture (MLC) have an augmenting but not suppressive capacity on cell proliferation; b) in utero insult with BP modifies the capacity of FL cells to augment proliferation in the MLC.


Rapid and selective inhibition of platelet aggregation and thromboxane formation by intravenous low dose aspirin in man.
1. One of the major problems in the clinical use of low dose aspirin for the prevention of vascular occlusion is that it takes about 3-5 days to become effective, a time too long for patients with unstable angina or coronary thrombolysis. Intravenous aspirin may be expected to exert a more rapid effect, but its influence on endothelial prostacyclin synthesis is uncertain. 2. In a single-blind, randomized, prospective study, we compared the effects of a single intravenous low dose (50 mg) or high dose (500 mg) of aspirin or placebo infused over a 60 min period on platelet aggregation, platelet thromboxane A2 production and whole-body prostanoid synthesis in 10 healthy male subjects by gas chromatography-tandem mass spectrometry. 3. Before the study, blood flow rates in the basilic and subclavian veins were determined by sonographic colour velocity imaging; the infusion rate for low dose aspirin was calculated to avoid biologically effective plasma levels of aspirin in the systemic circulation. 4. Platelet aggregation induced by 1 mmol/l arachidonic acid was similarly inhibited by > 85% within 30 min after the start of the infusion of high dose or low dose aspirin, respectively, and remained suppressed for 24 h. Platelet thromboxane A2 release declined gradually after low dose aspirin, reaching a minimum of 93% inhibition after 60 min. High dose aspirin suppressed platelet thromboxane A2 release to below the detection limit after 10 min. 5. Urinary excretion of the major urinary metabolite of thromboxane A2 (2,3-dinor-thromboxane B2) was equally suppressed by both dosages of aspirin [no significant difference between high dose (-83.2%) and low dose (-67.4%)].(ABSTRACT TRUNCATED AT 250 WORDS)


Entanglements of instruments and media in investigating organic life.
The question what constitutes organic life might be answered variously. This special issue explores how the rendering of life throughout the history of biology has been shaped by various instruments and media. While acknowledging the significance of the theoretical and social scenes of inquiry in which specific tools and techniques develop, and which delimit epistemic possibilities for making sense of life, the issue draws attention to material practices and instrumental mediations in experimental studies of life. Although it might seem self-evident that biology takes as its object of inquiry living organisms, it is productive to regard its subject matter as organic media rather than discrete organisms. The papers gathered in this issue show the rich potential for the critical study of how organic life has been constituted through the tools used to mediate its study.


Consequences for the bovine embryo of being derived from a spermatozoon subjected to post-ejaculatory aging and heat shock: development to the blastocyst stage and sex ratio.
The objective was to determine whether aging of sperm caused by incubation at normothermic (38.5 C) or heat shock (40 C) temperatures for 4 h prior to oocyte insemination affects sperm motility, fertilizing ability, competence of the resultant embryo to develop to the blastocyst stage and blastocyst sex ratio. In the first experiment, the percent of sperm that were motile was reduced by aging (P<0.001) and the reduction in motility was greater for sperm at 40 C compared to sperm at 38.5 C (P<0.01). In the second experiment, oocytes were inseminated with aged sperm. A smaller percent of oocytes fertilized with sperm aged at either temperature cleaved by Day 3 after insemination than oocytes fertilized with fresh sperm (P<0.05). There was no effect of sperm aging on the percent of oocytes or cleaved embryos that developed to the blastocyst stage. Aging of sperm before fertilization at 38.5 C reduced the percent of blastocysts that were male (P=0.08). In the third experiment, incubation of sperm at 38.5 C or 40 C for 4 h did not reduce fertilizing ability of sperm as determined by pronuclear formation at 18 h post insemination. In conclusion, aging of sperm reduced cleavage rate and the percent of blastocysts that were males but had no effect on the developmental capacity of the embryo. The effect of aging on cleavage rate may represent reduced motility and errors occurring after fertilization and pronuclear formation. Aging at a temperature characteristic of maternal hyperthermia had little additional effect except that polyspermy was reduced. Results indicate that embryo competence for development to the blastocyst stage is independent of sperm damage as a result of aging for 4 h at normothermic or hyperthermic temperatures.


An unusual presentation of disseminated histoplasmosis in a non-HIV patient from Vietnam.
Histoplasmosis is a systemic infection caused by the dimorphic fungus Histoplasma capsulatum, naturally found in nitrogen-rich soil, whose main transmission route is the inhalation of conidia. Up to 95% of histoplasmosis cases are asymptomatic or transient, and the remaining 5% of cases have pathological manifestations in the lungs, bone marrow, liver, spleen, intestine, mucous membranes, and rarely on the skin. This mycosis has been reported from many endemic areas, mainly in immunosuppressed patients, such as HIV-positive patients, and its disseminated form is rarely reported. Histoplama capsulatum was isolated and identified by means of microscopy, culture characteristics and nested PCR from the cutaneous lesions of a non-HIV patient from Vietnam. The patient improved significantly with systemic itraconazole treatment. Disseminated histoplasmosis with cutaneous involvement in non-HIV patients is an extremely unusual presentation.


Recommendations on health-related quality of life research to support labeling and promotional claims in the United States.
Health-related quality of life (HRQL) outcomes evaluation is becoming an important component of clinical trials of new pharmaceuticals and medical devices. HRQL research provides patients, providers, and decision makers with important information on the impact of disease and treatment on physical, psychological, and social functioning and well-being. These outcomes are also useful to the pharmaceutical and device industries as they attempt to understand and communicate product value to physicians, patients, health insurers and others. HRQL labeling and promotional claims in the US are likely to increase over the next few years. The evidentiary requirements to make such a claim should be based on accepted scientific standards of HRQL evaluation and consistent with the regulatory requirements for clinical efficacy. This report outlines the scientific practices that should be considered in the evaluation of evidence for an HRQL claim, including the selection of appropriate domains, evidence to support the reliability and validity of HRQL measurement, considerations in research design and statistical analyses, and the issue of clinical significance. Representatives from the pharmaceutical and device industries, regulatory agencies, and the HRQL scientific community should work together to make certain the use of HRQL in labeling and promotion are based on sound scientific evidence, and that these messages are clearly and accurately reported to the consumers.


External Mg2+-dependent early stimulation of nucleotide synthesis in Swiss 3T3 cells.
In quiescent Swiss 3T3 cells, metabolic flux through phosphoribosyl pyrophosphate into nucleotides increased within 1 h when various growth factors were added (S. Ishijima, K. Kita, N. Kinoshita, T. Ishizuka, N. Suzuki, and M. Tatibana. J. Biochem. 104: 570-575, 1988). The divalent cation ionophore A23187 mimicked the stimulatory effect of epidermal growth factor plus insulin, thereby suggesting involvement of divalent cation mobilization in signaling the stimulation by the growth factors. The stimulation induced by the growth factors was nil in medium devoid of added Mg2+ but was not affected by the omission of Ca2+. The dependency on external Mg2+ was also observed with the stimulations by bombesin plus insulin, fibroblast growth factor, and A23187. In contrast, the mitogenic stimulation of glycolysis was observed irrespective of the presence or absence of Mg2+, indicating that initial events in the signaling process, including mitogen binding to receptors, took place in the absence of exogenous Mg2+. These results suggest that a Mg2(+)-dependent process, subsequent to growth factor binding to receptors, plays an essential role in signaling the early mitogenic stimulation of nucleotide synthesis.


Measurement of systolic-diastolic ratio in the umbilical artery by continuous-wave and pulsed-wave Doppler ultrasound: comparison at different sites.
Analysis of umbilical artery flow velocity waveforms, especially systolic-diastolic (S-D) ratio, can predict some pregnancy abnormalities. Most of the earlier studies did not specify the exact segment of umbilical artery sampled. We studied 53 normal singleton pregnancies between 18-41 weeks' gestation to compare S-D ratio measurements of the umbilical artery at different sites: 1) abdominal insertion site, 2) placental insertion site, 3) mid-cord, and 4) an undetermined site. The mean S-D ratio was significantly different (P less than .01) at various segments of the umbilical artery--higher near the abdominal insertion site when compared with the mid-cord, near-placental, and undetermined sites. The S-D ratio at mid-cord was higher than at the undetermined site and the placental insertion site. The near-placental-site S-D ratio was not different from the undetermined site. A lower S-D ratio at the undetermined site may not adequately reflect the true physiologic status of the fetus. Specifying the site of measurement should be an integral part of any report, in order to describe accurately the pathophysiology of fetoplacental circulatory diseases.


Clinical features of the urge-to-cough in patients with chronic cough.
The urge-to-cough is a consciously perceived compulsion, previously investigated in healthy volunteers inhaling irritants. We aimed to characterise the urge-to-cough and associated sensations in a group of chronic cough patients attending a specialist clinic. 100 patients with chronic cough [mean age 60 yrs (±11.89), 71 female, median cough duration 7 yrs (IQR 11.13) completed an investigator-led survey describing aggravating and relieving factors for urge-to-cough, associated somatic sensations (quality, location, intensity) and emotions. Subjects rated each using a 5-point Likert scale (strongly disagree to strongly agree) or visual analogue scale (VAS). Cluster analysis identified groups of patients with similar patterns of responses. Subjects rated the severity of urge-to-cough highly (84.5 mm on VAS). The majority always cough in response to the urge-to-cough (91%), but fewer (69%) always experienced an urge-to-cough before coughing. The somatic sensations associated with the urge-to-cough were described as an irritation (86%) or tickle (73%), localised in the neck (75%). The urge-to-cough was triggered by various stimuli including smoky atmospheres (79%), talking (72%), cold temperatures (67%) and dry atmospheres (66%) and relieved by coughing (63%), and drinking (61%); in 42% nothing provided relief. Cluster analysis suggested two distinct patient groups, differing in the factors precipitating the urge-to-cough rather than quality or location of associated sensations. The unifying characteristics of patients with chronic cough are a severe urge-to-cough associated with throat irritation, consistent with sensory neuronal dysfunction of vagal afferents. Precipitants of the urge-to-cough vary though, and can be used to classify sub-groups of patients who may share similar underlying pathophysiology.


The hypothalamic pituitary axis in the fetus and newborn.
Glucocorticoid receptor activation in the fetal lung triggers maturation necessary for extra-uterine life. Antenatal treatment with betamethasone and dexamethasone has lowered severity of respiratory distress in very low birth weight infants, and dexamethasone given postnatally has resulted in short-term improvement in chronic lung disease. Recently, however, surfactant therapy has diminished the differential benefit of antenatal glucocorticoid treatment, and it has been difficult to show that postnatal dexamethasone therapy improves survival. Treated infants may have reduced weight gain, adrenal suppression, increased incidence of intestinal perforation and infection, and long-term developmental and metabolic problems. Recent data suggest that the fetal hypothalamic/pituitary/adrenal axis is active early and is precisely structured for an intricate sequence of specifically fetal developmental events, which may be deranged by dexamethasone therapy. We consider data suggesting that persistence of the fetal pattern in some premature infants constitutes adrenal insufficiency, and that therapy at stress replacement doses with less potent glucocorticoids might avoid side effects seen with traditional regimens.


[Management of mesh-related infections].
Infections of an implanted hernia mesh are a major challenge. The incidence of mesh infections after incisional hernia repair is about 1% for endoscopic techniques and can be more than 15% in open techniques. Intraoperative mesh contamination is considered to be the primary cause. All woven or knitted hernia meshes have recesses where bacteria may adhere and establish colonies. The bacterial spectrum for mesh infection includes skin pathogens, such as Staphylococcus aureus (including MRSA), Streptococcus spp., as well as E. coli, Enterococcus and Mycobacteria. The therapy approach needs to be tailored to the morphological findings and the treatment for uncomplicated phlegmon is broad spectrum antibiotic therapy. If there is encapsulated fluid accumulation, CT-controlled drainage and daily infusion of antiseptics via the drain is a good option. For dermal necrosis, mesh fistula, exposed mesh or enterocutaneous fistula, a precise CT evaluation is necessary to tailor the operation. Vacuum systems are gaining increased acceptance in conditioning the local findings. For most patients the therapeutic concept will be based on individual decisions. If parts of a formerly infected mesh remain in the patient, a lifelong follow-up is necessary.


Sequence and space: The critical role of a backward spatial span in the working memory deficit of visuospatial learning disabled children.
The clinical use of backward spatial short-term memory tasks, and in particular of the Corsi backward task, it has increased and it has generated a series of theoretical hypotheses. For example, it has been argued that (in its comparison with the forward version) it has the same implications as the backward digit span and/or it requires the use of amodal central executive components of working memory. This research tested the hypotheses that the backward spatial span does not involve the controlled use of the same type of sequential spatial processing involved in the forward version, that its impairment is modality specific, and that children with specific visuospatial learning disabilities (VSLD) have lower performance in backward than in forward Corsi Blocks test, compared to a control group. In Study 1, participants were administered a verbal span test (Digit Span test) and a visuospatial span test (Corsi Blocks task) both in the forward and backward versions, while in Study 2 only the Corsi test was administered. The comparison between the forward and backward span versions showed that both visuospatial learning disabled children (VSLD) and controls presented with the Digit Span had a lower performance with the backward version. However, for the Corsi task, this difference was present only for VSLD children. In fact, results revealed a significant impairment in the backward version of the Corsi test in the VSLD group, but not in the forward version, and in the Digit Span tasks. Results suggest that the Corsi backward task is not the spatial analogue of the Digit backward task and that it involves specific spatial processes.


Errata.
[This corrects the article on p. 28 in vol. 9.].


A monoclonal natural autoantibody that promotes remyelination suppresses central nervous system inflammation and increases virus expression after Theiler's virus-induced demyelination.
We have used an established experimental model of multiple sclerosis to investigate the potential beneficial relationship between natural autoimmunity and remyelination after central nervous system (CNS) demyelination. Intracerebral infection of SJL/J mice with Theiler's murine encephalomyelitis virus (TMEV) produces chronic, progressive, inflammatory CNS demyelination. Chronically infected SJL/J mice show minimal spontaneous remyelination, which is in part due to a T cell-mediated immune response inhibiting myelin repair. We previously identified a monoclonal natural autoantibody, designated SCH94.03, that promotes remyelination when passively transferred to chronically infected SJL/J mice. The mechanism whereby SCH94.03 promotes remyelination is unknown, although previous reports suggest that natural autoantibodies can modulate immune system function. In this report we demonstrate that treatment with SCH94.03 reduced by 2- to 3-fold the number of CD4(+) and CD8(+) cells infiltrating the CNS of SJL/J mice chronically infected with TMEV, in the absence of global lymphocyte depletion. Associated with the decreased inflammation was a 2- to 3-fold increase in virus antigen expression without a significant increase in viral RNA or virus titers. Treatment with SCH94.03 also suppressed the humoral immune response to a T cell-dependent antigen in chronically infected mice. Immunohistochemical staining showed that SCH94.03 labeled MHC class II-positive dendritic cells in peripheral lymphoid organs. These results are consistent with the proposed immunomodulatory function of natural autoantibodies and suggest that one mechanism whereby SCH94.03 promotes CNS remyelination in chronically infected SJL/J mice is through inhibition of a pathogenic immune response.


Vitamin B12 and folate status in early pregnancy and cardiometabolic risk factors in the offspring at age 5-6 years: findings from the ABCD multi-ethnic birth cohort.
To explore whether maternal vitamin B12 and folate status during early pregnancy are associated with cardiometabolic risk factors in the offspring at age 5-6. Prospective multi-ethnic birth cohort, the Amsterdam Born Children and their Development study (ABCD). 12,373 pregnant women living in Amsterdam were approached between 2003 and 2004 for participation in the study. Mother-child pairs for whom information on maternal vitamin B12 or folate status in early gestation and health at age 5-6 years was available (n = 1950). Vitamin B12 and folate concentrations were determined in maternal serum at intake in early pregnancy (median 13 weeks' gestation). Anthropometric measurements, blood pressure and fasting blood samples were collected during a health check of children aged 5-6 years. Multiple linear regression was performed to investigate the association between maternal serum concentrations and children's outcomes, corrected for confounders. Gestational age at birth, birthweight, body mass index (BMI), glucose levels, triglyceride levels, blood pressure and heart rate of the offspring at age 5-6. Low maternal folate levels during early pregnancy were associated with slightly higher BMI in the offspring [decrease per 10 units: β 0.07 kg/m(2), 95% confidence interval (CI) 0.01, 0.13]. Low maternal vitamin B12 concentrations were associated with higher heart rates (decrease per 100 units: β 0.49 beats/min, 95% CI 0.11, 0.87). This study provides further evidence that maternal nutrition in early pregnancy may possibly program cardiometabolic health of the offspring. Low folate and vitamin B12 levels during pregnancy are associated with higher BMI and heart rate in offspring.


[Cutaneous polyarteritis nodosa associated with streptococcal infection in a child and a review of the literature].
Polyarteritis nodosa (PAN) is a multisystem inflammatory disease associated with necrosis of small and medium arteries. It can occur in a systemic form with manifestations in skin, joints, heart, nervous system, gastrointestinal tracts, lungs and kidneys. It is relatively rare in adults and even more in children. It may be divided into a cutaneous form (C-PAN) and a more generalized form (G-PAN). Usually C-PAN is thought to run a benign course. But some cases were reported to run chronic courses and be diagnosed G-PAN. It has been reported that some adults with PAN are related to HBV infection. On the other hand most children with PAN had upper respiratory infections some with streptococcal infections. We described a 5-year-old boy who was suffering from high fever, joint pain, subcutaneous nodular and livedo reticularis. We diagnosed him C-PAN by examination and clinical course. Anti-streptolysin O (ASO) and anti-streptokinase (ASK) increased and we suspected that C-PAN followed after streptococcal infection. We reviewed the literatures of C-PAN and streptococcal infection in childhood. Streptococcal infection has been implicated by a positive throat swab or an increase in ASO. There were 25 cases (75.7%) which were thought to be related with prior streptococcal infection in 33 cases. We thought that C-PAN may be associated with streptcoccal infection in childhood.


Functional interaction of VEGF-C and VEGF-D with neuropilin receptors.
Lymphatic vascular development is regulated by vascular endothelial growth factor receptor-3 (VEGFR-3), which is activated by its ligands VEGF-C and VEGF-D. Neuropilin-2 (NP2), known to be involved in neuronal development, has also been implicated to play a role in lymphangiogenesis. We aimed to elucidate the mechanism by which NP2 is involved in lymphatic endothelial cell signaling. By in vitro binding studies we found that both VEGF-C and VEGF-D interact with NP2, VEGF-C in a heparin-independent and VEGF-D in a heparin-dependent manner. We also mapped the domains of VEGF-C and NP2 required for their binding. The functional importance of the interaction of NP2 with the lymphangiogenic growth factors was demonstrated by cointernalization of NP2 along with VEGFR-3 in endocytic vesicles of lymphatic endothelial cells upon stimulation with VEGF-C or VEGF-D. NP2 also interacted with VEGFR-3 in coprecipitation studies. Our results show that NP2 is directly involved in an active signaling complex with the key regulators of lymphangiogenesis and thus suggest a mechanism by which NP2 functions in the development of the lymphatic vasculature.


Maternal height and child mortality in 42 developing countries.
Previous research reports mixed results about the association between maternal height and child mortality. Some studies suggest that the negative association might be stronger in contexts with fewer resources. This hypothesis has yet not been tested in a cross-nationally comparative design. We use data on 307,223 children born to 194,835 women in 444 districts of 42 developing countries to estimate the association between maternal height and child mortality and test whether this association is modified by indicators at the level of the household (like sex, age and twin status of the child and socio-economic characteristics of the mother and her partner), district (regional level of development, public health facilities and female occupational attainment) and country (GDP per capita). We find a robust negative effect of logged maternal height on child mortality. The effect of maternal health is strongest for women with least education and is more important in the first year after birth and for twin births. The indicators of development at the district and country level do not modify the effect of maternal height.


CD4+ and CD8+ T cell interactions in IFN-gamma and IL-4 responses to viral infections: requirements for IL-2.
Cytokine responses to lymphocytic choriomeningitis virus infections were evaluated, and CD8+ T cell, CD4+ T cell, and IL-2 contributions delineated. In immunocompetent mice, lymphocytic choriomeningitis virus induced both IFN-gamma and IL-4 as well as IL-2. Experiments in mice either beta2-microglobulin-deficient, lacking MHC class I molecules and CD8+ T cells, or A beta(b)-deficient, lacking MHC class II molecules and CD4+ T cells, demonstrated that mixtures of T cell responses were required for optimal ex vivo cytokine productions. Intracellular cytokine expression analyses of cells from immunocompetent and immunodeficient mice showed that CD8+ T cells were predominant IFN-gamma producers, and that expansion of CD8+ T cells primed to make IFN-gamma was independent of CD4+ T cells in vivo. Studies in IL-2-deficient mice demonstrated that this cytokine promoted IFN-gamma and IL-4 responses, and ex vivo experiments showed that exogenous IL-2 was required to maintain high-level IFN-gamma production by in vivo-primed CD8+ T cells. Conditions associated with cytokine decreases were accompanied by reduced detectable plasma Ab responses. The results indicate that, although IL-2-dependent CD8+ T cell proliferation does not require endogenous CD4+ T cells, IL-2 production by the CD4+ T cells may promote continued cytokine release from activated CD8+ T cells. By defining these critical steps in cellular and cytokine interactions for shaping endogenous immune responses, the studies advance understanding of the unique conditions regulating CD8+ T cell responses to viral challenges.


Human papillomavirus deoxyribonucleic acid testing in developed countries.
Cervical cancer has been largely eliminated in developed countries with the implementation of cytology-based screening programmes that depend on a call-recall system, followed by colposcopy and biopsy, treatment of precancerous lesions and follow up. With the discovery that persistent infection with high-risk human papillomavirus types is necessary for the development of cervical cancer, several tests for human papillomavirus deoxyribonucleic acid have been developed that can identify women at risk. Human papillomavirus deoxyribonucleic acid testing is more sensitive and only slightly less specific than cytology for detecting cervical intraepithelial neoplasia. It is also more reproducible, with the potential for self-sampling. Human papillomavirus genotyping, messenger RNA analysis and other biomarkers can help to further stratify this group and diminish referrals to colposcopy. Initially, human papillomavirus testing was used as an adjunct to cytology for triage of borderline cases, but evidence has shown its superiority as a screening method and in the follow up of women treated for cervical intraepithelial neoplasia.


[Clinical study of healing abutment on sealing socket and preservation of the gingival natural profile in single-tooth immediate implantation].
To investigate the clinical results of use of healing abutment for sealing socket and preserving the gingival natural profile in single-tooth immediate implantation. The osteotomy site was prepared with pilot drill directed by the periodontal probe on palatal wall of the socket,and 31 single-implant were placed into fresh sockets with flapless surgery and filled with Bio-oss. Healing abutments were simultaneously fitted on implants and ceramic crowns fabricated three months post-operation. Scientific assessment of soft tissue contour was carried out by interdental papillae index immediately after restorations. One implant was lost at second week after operation. The remaining 30 implants gained perfect osseointegration and the gingival natural profile was preserved completely. Sealing socket and preserving the gingival natural profile by healing abutment is a predictable, safe and practical method with good aesthetic results in single-tooth immediate implantation.


Theoretical analysis of the distribution of isolated particles in totally asymmetric exclusion processes: Application to mRNA translation rate estimation.
The Totally Asymmetric Exclusion Process (TASEP) is a classical stochastic model for describing the transport of interacting particles, such as ribosomes moving along the messenger ribonucleic acid (mRNA) during translation. Although this model has been widely studied in the past, the extent of collision between particles and the average distance between a particle to its nearest neighbor have not been quantified explicitly. We provide here a theoretical analysis of such quantities via the distribution of isolated particles. In the classical form of the model in which each particle occupies only a single site, we obtain an exact analytic solution using the matrix ansatz. We then employ a refined mean-field approach to extend the analysis to a generalized TASEP with particles of an arbitrary size. Our theoretical study has direct applications in mRNA translation and the interpretation of experimental ribosome profiling data. In particular, our analysis of data from Saccharomyces cerevisiae suggests a potential bias against the detection of nearby ribosomes with a gap distance of less than approximately three codons, which leads to some ambiguity in estimating the initiation rate and protein production flux for a substantial fraction of genes. Despite such ambiguity, however, we demonstrate theoretically that the interference rate associated with collisions can be robustly estimated and show that approximately 1% of the translating ribosomes get obstructed.


Fabrication and reduction-sensitive behavior of polyion complex nano-micelles based on PEG-conjugated polymer containing disulfide bonds as a potential carrier of anti-tumor paclitaxel.
This work is aimed at the development of a reduction-sensitive drug carrier for the delivery of the anti-cancer drug paclitaxel (PTX). N,N'-bis(acryloyl)cystamine (CBA) was reacted with ethanolamine (AEOL) via Michael addition to synthesize cationic poly(CBA-AEOL) (PCA) containing disulfide bonds. Subsequently, polycaprolactone (PCL) was grafted from PCA to form a novel reduction-sensitive copolymer (PCA-g-PCL). The PCA-g-PCL copolymer self-assembled as spherical micelles with a mean size of ca. 108nm. The disulfide bonds in the PCA-g-PCL copolymer contributed to the reduction-sensitivity of the micelles, observed as stepwise aggregation under simulated reduction conditions. To improve the stability of PCA-g-PCL micelles in aqueous media, carboxyl-terminated poly(ethylene glycol) methyl ether (mPEG-COOH) was conjugated with the PCA-g-PCL copolymer via electrostatic interaction to produce polyion complex micelles with a hydrophilic PEG surface. The in vitro release of PTX from the mPEG@PCA-g-PCL micelle showed a reduction sensitive profile, namely the rate of drug release strongly depended upon the concentration of the reducing agent. Leakage of PTX was limited to below 30% under normal conditions while almost all the drug was released in 9h under reduction conditions with 40mM DTT. In conclusion, the assembled mPEG@PCA-g-PCL micelle with reduction-sensitive controlled release shows great potential for improving the therapeutic effect of paclitaxel.


Errata in Last Number.
[This corrects the article on p. 440 in vol. 46 PMCPMC5626061.].


Long-Term Consolidation of Ensemble Neural Plasticity Patterns in Hippocampal Area CA1.
Neural network remodeling underpins the ability to remember life experiences, but little is known about the long-term plasticity of neural populations. To study how the brain encodes episodic events, we used time-lapse two-photon microscopy and a fluorescent reporter of neural plasticity based on an enhanced form of the synaptic activity-responsive element (E-SARE) within the Arc promoter to track thousands of CA1 hippocampal pyramidal cells over weeks in mice that repeatedly encountered different environments. Each environment evokes characteristic patterns of ensemble neural plasticity, but with each encounter, the set of activated cells gradually evolves. After repeated exposures, the plasticity patterns evoked by an individual environment progressively stabilize. Compared with young adults, plasticity patterns in aged mice are less specific to individual environments and less stable across repeat experiences. Long-term consolidation of hippocampal plasticity patterns may support long-term memory formation, whereas weaker consolidation in aged subjects might reflect declining memory function.


Perseveration in behavioral neurology.
We tested a new taxonomy of perseverative behavior consisting of three categories: (1) repetition of a previous response to a subsequent stimulus (recurrent), (2) inappropriate maintenance of a category of activity (stuck-in-set), and (3) abnormal prolongation of a current activity (continuous). Three groups of neurologically impaired subjects (with aphasia, right hemisphere damage, and Parkinson's disease) were administered tests to elicit each category of perseveration. Patients with aphasia produced significantly more recurrent perseveration than did patients with right hemisphere damage or healthy controls. Stuck-in-set perseveration was associated with dopamine system dysfunction, and continuous perseveration with right hemisphere damage. We propose a theory of perseveration dependent on anatomic, neuropsychological, and pharmacologic factors related to cerebral dominance. According to this theory, disruption of specific anatomic and pharmacologic systems produces different forms of perseveration which, in turn, underlie particular neurobehavioral disorders.


Propagation and phenotypic preservation of rabbit limbal epithelial cells on amniotic membrane.
To describe the phenotypic characteristics of a limbal epithelial cell sheet outgrowth from a limbal explant cultured on amniotic membrane. Immunofluorescent staining and confocal microscopy were used to examine the expressions of p63, Ki-67, keratins 3 and 14, connexin 43, and the integrin alpha6/beta4 and alpha3/beta1 subunits in corneal and limbal tissues in a limbal explant and epithelial outgrowth cultured for 2 weeks on amniotic membrane. The expression patterns of p63, Ki-67, keratins, integrins, and connexin 43 in a limbal explant with an epithelial outgrowth cultured for 2 weeks on amniotic membrane resembled those in freshly prepared limbus. Moreover, the distribution of integrin subunits in positive cells of the limbal explant and its epithelial outgrowth was similar to that of the corneal epithelial cells during wound repair. The epithelial cell sheet grown from a limbal explant on amniotic membrane exhibited a phenotype similar to that of the limbus, suggesting that amniotic membrane is a substrate capable of supporting the propagation and preservation of p63-positive limbal epithelial cells.


Recurrence in Uterine Tumors with Ovarian Sex-Cord Tumor Resemblance: A Case Report and Systematic Review.
The aim of this study was to evaluate the prognostic factors of recurrence in uterine tumors resembling ovarian sex-cord tumors (UTROSCT) and to determine clinical-pathological characteristics, treatment options and outcome. An electronic literature search was conducted from 1976 to 2018. After the comprehensive evaluation and conjunction with our case, the study included 79 cases. The median age at initial diagnosis was 49 years (range; 16-86 years). The age was under 40 years in 21 (26.6%) patients. Whereas 68 patients underwent at least hysterectomy, 9 patients had organ sparing surgery. There was necrosis in 4 (5.1%) patients, atypia in 16 (20.3%) patients, and infiltrative tumor border in 34 (43%) patients. At least one mitosis per 10 high power fields was determined in 36 (45.5%) patients. The tumor involved at least part of the myometrium in 54 (68.3%) patients. Median follow-up time was 30 months (range; 3-296 months). Recurrence was determined in 5 (6.3%) patients. The disease free survival (DFS) was significantly related only to surgery type. None of the pathologic features were associated with DFS. The 5-year DFS was 86% and 96% in patients who underwent organ sparing surgery or not, respectively (p=0.038). The accurate pathologic diagnosis of UTROSCT has great value in shaping surgical management and management during the follow-up period. Organ sparing surgery was related to poor DFS. Although recurrence is rare, it should be kept in mind for patients with UTROSCT.


Pseudohyperkalemia occurring in a patient with chronic renal failure and polycythemia vera without severe leukocytosis or thrombocytosis.
Pseudohyperkalemia is defined as a serum potassium concentration 0.4 mEq/l greater than the plasma concentration. The basis of this phenomenon is the release of intracellular potassium from platelets, leukocytes, or erythrocytes, commonly in the setting of extreme leukocytosis (> 10 x 10(4)/microl) or thrombocytosis (> 60 x 10(4)/microl). We report a case of pseudohyperkalemia in a patient with chronic renal failure and polycythemia vera without the finding of severe leukocytosis or thrombocytosis (white blood cell count 1.88 x 10(4)/microl and platelet count 37.9 x 10(4)/microl, respectively). The serum potassium concentration was 8.2 mEq/l, while the plasma potassium level was 6.4 mEq/l in a sample obtained simultaneously. The concentrations of platelet factor IV and beta-thromboglobulin, known to be markers of platelet activation, were greater than 100 ng/ml and 200 ng/ml, respectively, indicating that platelet activation may have been related to the development of pseudohyperkalemia in this patient. These findings suggest that pseudohyperkalemia should be considered when hyperkalemia is seen in a patient with chronic renal failure and myeloproliferative disorders.


Hepatobiliary transport of IgA immune complexes: molecular and cellular aspects.
The molecular and cellular parameters of the transport of IgA immune complexes (IgA-IC) from the circulation to the bile in vivo were studied in mice. Polymeric MOPC 315 IgA was effective in the transport of 125I-DNP-HSA into the bile, whereas complexes containing monomeric IgA were not transported. The transport to IgA-IC could be blocked by excess from IgA of different antigen specificity, but not by IgG or IgM. Hepatobiliary transport did not appear to involve the galactose- or mannose-specific glycoprotein receptors of the liver. No differences in IgA-IC transport, relative to controls, could be seen in mice that had been treated with cobra venom factor or whose mononuclear phagocytic system had been blockaded with colloidal carbon. These data suggested that the hepatobiliary transport of IgA-IC proceeds by a mechanism similar to the selective transport of free polymeric IgA through the hepatocyte.


[Are SPA therapy and pulsed electromagnetic field therapy effective for chronic neck pain? Randomised clinical trial First part: clinical evaluation].
The purpose of this study was to compare SPA therapy (ST) with pulsed electromagnetic field (PEMF) therapy in chronic neck pain. Inclusion criteria were age between 18 and 80 years, neck pain of more than 3 months' duration and pain score>30 mm on a visual analog scale (VAS). Exclusion criteria were contraindication to ST or PEMF. The protocol was approved by the ethics committee of Grenoble Hospital. Randomisation to the ST (n=44) and PEMF groups (n=42) was blinded. The main outcome measure was number of improved patients at 6 months in each group. A patient was considered improved if pain score decreased by more than 20%. Secondary measures were score on the Copenhagen and MOS SF-36 scales. Evaluation and intent-to-treat analysis were also blinded. Patients' preferences were for PEMF. At 6 months, in the PEMF group, 33 patients were improved, 5 not improved and 4 lost to follow-up. In the ST group, 24 patients were improved, 14 not improved and 6 lost to follow-up, for significantly greater improvement in the PEMF than ST group (p=0.02). Significant improvement was seen in both groups in terms of pain score, Copenhagen scale score and score on some dimensions of the MOS SF-36 survey. PEMF seems to be superior to standard ST without massage in control of neck pain. The difference between groups, although perhaps biased, seem to suggest the importance of our conclusions.


Congenital localized stenosis of the pulmonary veins.
One case of localized stenosis of the extrapulmonary portion of pulmonary veins is reported in a 3 years old child. The chest X-Ray showed a rounded and pulsatile opacification over the right hilum and on angiocardiography the right superior pulmonary vein looked very dilated. 20 other cases of segmental stenoses of pulmonary veins were collected from the literature.


Chelation therapy of atherosclerosis.
Chelation therapy with intravenous injections of edetate disodium is being promoted to the public as a nonsurgical means to treat coronary or other arterial atherosclerosis. The rationale for use, clinical efficacy, and safety are reviewed. Acceptable evidence supporting chelation therapy for atherosclerotic vascular disease is lacking.


Prospective risk factors for new-onset post-traumatic stress disorder in National Guard soldiers deployed to Iraq.
National Guard troops are at increased risk for post-traumatic stress disorder (PTSD); however, little is known about risk and resilience in this population. The Readiness and Resilience in National Guard Soldiers Study is a prospective, longitudinal investigation of 522 Army National Guard troops deployed to Iraq from March 2006 to July 2007. Participants completed measures of PTSD symptoms and potential risk/protective factors 1 month before deployment. Of these, 81% (n=424) completed measures of PTSD, deployment stressor exposure and post-deployment outcomes 2-3 months after returning from Iraq. New onset of probable PTSD 'diagnosis' was measured by the PTSD Checklist - Military (PCL-M). Independent predictors of new-onset probable PTSD were identified using hierarchical logistic regression analyses. At baseline prior to deployment, 3.7% had probable PTSD. Among soldiers without PTSD symptoms at baseline, 13.8% reported post-deployment new-onset probable PTSD. Hierarchical logistic regression adjusted for gender, age, race/ethnicity and military rank showed that reporting more stressors prior to deployment predicted new-onset probable PTSD [odds ratio (OR) 2.20] as did feeling less prepared for deployment (OR 0.58). After accounting for pre-deployment factors, new-onset probable PTSD was predicted by exposure to combat (OR 2.19) and to combat's aftermath (OR 1.62). Reporting more stressful life events after deployment (OR 1.96) was associated with increased odds of new-onset probable PTSD, while post-deployment social support (OR 0.31) was a significant protective factor in the etiology of PTSD. Combat exposure may be unavoidable in military service members, but other vulnerability and protective factors also predict PTSD and could be targets for prevention strategies.


Laser pumping by intense discharges in z-pinch geometry.
Optical properties of high-current, low-pressure, noble-gas discharges in z-pinch geometry are studied and compared with theta-pinch discharges and standard commercial light sources. Results indicate possible usefulness in systems where high peak power, high repetition rates or high uv content are demanded.


Hydrogen sulfide and oxygen sensing in the cardiovascular system.
Vertebrate cardiorespiratory homeostasis is inextricably dependent upon specialized cells that provide feedback on oxygen status in the tissues, blood, and on occasion, environment. These "oxygen sensing" cells include chemoreceptors and oxygen-sensitive chromaffin cells that initiate cardiorespiratory reflexes, vascular smooth muscle cells that adjust perfusion to metabolism or ventilation, and other cells that condition themselves in response to episodic hypoxia. Identification of how these cells sense oxygen and transduce this into the appropriate physiological response has enormous clinical applicability, but despite intense research there is no consensus regarding the initial hypoxia-effector coupling mechanism. This review examines an alternative mechanism of oxygen sensing using oxidation of endogenously produced hydrogen sulfide (H(2)S) as the O(2)-sensitive couple. Support for this hypothesis includes the similarity of effects of hypoxia and H(2)S on a variety of tissues, augmentation of hypoxic responses by precursors of H(2)S production and their inhibition by inhibitors of H(2)S synthesis, and the rapid consumption of H(2)S by O(2) in the range of intracellular/mitochondrial Po(2). These studies also indicate that, under normoxic conditions, it is doubtful that free H(2)S has longer than a transient existence in tissue or extracellular fluid.


Effects of preshock experience on enhancement of rat brain noradrenaline turnover induced by psychological stress.
The present study examined alterations of brain noradrenaline (NA) turnover as a function of preshock and psychological stress treatments, by measuring contents of NA metabolite, 3-methoxy-4-hydroxyphenylethyleneglycol sulfate (MHPG-SO4), in discrete brain regions of male Wistar rats. Psychological stress induced by exposing to the sight, sound and odor of other rats being shocked produced higher levels of MHPG-SO4 in the hypothalamus, amygdala and locus coeruleus (LC) region, as well as higher levels of plasma corticosterone. Preshock experienced rats also showed marked increases of MHPG-SO4 levels in the same regions described above and elevated plasma corticosterone levels when placed but not shocked in the same environment in which the rats had previously received shocks. The effects of psychological stress on brain NA turnover were affected by the animal's shock history preferentially in the hypothalamus and amygdala. These results suggest that: a purely psychological stressor caused acutely enhanced NA turnover in specific brain regions; regional NA activity appeared to be reinstated simply by reexposure to the environment previously associated with shock; preshock experience further intensified the enhancement of amygdaloid NA turnover evoked by psychological stress. An additional experiment, studying the aftereffects of preshock experience, clearly showed that these findings result from sensitization or conditioning to the environment previously paired with shock, and not merely from the aftereffects of the shock per se.