Formulation optimization and in vitro skin penetration of spironolactone loaded solid lipid nanoparticles.
The aim of the current investigation was to prepare and evaluate the potential use of solid lipid nanoparticles for the dermal delivery of spironolactone (SP). The spironolactone loaded SLN (SP-SLN) was prepared by emulsion-solvent evaporation method followed by ultrasonication. The properties of obtained SLNs were characterized by photon correlation spectroscopy (PCS), scanning tunneling microscopy (STM) and differential scanning calorimetry. FT-IR was also used to investigate any interaction between SP and excipients in the molecular level during the preparation of SLNs. The performance of the formulations was investigated in terms of drug release, skin permeation and also the retention of drug by the skin. The SP-SLNs presented spherical shape with the mean diameter, zeta potential and entrapment efficiency of 88.9 nm, -23.9 mV and 59.86%, respectively. DSC study showed that SP alone encapsulated in SLNs was in the amorphous form. FT-IR analysis revealed that there were hydrogen bond interactions between the SP alone and SLN components. The dissolution results revealed that the drug release from SP-SLNs was at least 4.9 times faster than original SP within the first 30 min. The cumulative amount of SP penetrated through rat skin from SP-SLNs was almost twofold that of the SP alone in 24h after the administration. In vitro permeation studies indicated that SP-SLN may be a promising vector for use in the topical treatment. It can be concluded that SLNs provide good skin permeation for SP and may be a promising carrier for topical delivery of spironolactone offering the biphasic release pattern that might be interesting for topical application resulting in an effective treatment for skin disorders such as acne.


Effects of simulated pulmonary surfactant on the cytotoxicity and DNA-damaging activity of respirable quartz and kaolin.
Respirable-sized quartz and kaolin dusts were pretreated with simulated pulmonary surfactant dispersions of dipalmitoyl phosphatidylcholine (DPPC) in saline to model the conditioning of particles depositing in alveolar regions of the lung. DPPC-treated and untreated dusts were used to challenge lavaged rat pulmonary alveolar macrophages in vitro. Cytotoxicity was determined over a 5-d period using both total and viable cell counts from a fluorescence-based viability assay. DNA damage, as an indication of genotoxicity, was determined over a 7-d period by the single-cell gel electrophoresis assay. Untreated quartz and kaolin both expressed a significant and potent cytotoxicity, which increased with concentration and time. DPPC-surfactant pretreatment delayed significant expression of this cytotoxicity until 3 to 5 d after challenge. Untreated quartz also caused DNA damage, which increased with concentration and time. DPPC-surfactant treatment of quartz delayed most DNA damage expression to 5 and 7 d. Untreated kaolin expressed weaker activity for DNA damage, significant at the highest concentration through 5 d, and at the higher concentrations on d 7. Surfactant treatment delayed most kaolin activity for DNA damage to 7 d after challenge.


Organization of the human interleukin-1 receptor antagonist gene IL1HY1.
The interleukin (IL)-1 family of proteins plays an important role in inflammatory and defense mechanisms. The recently characterized IL1HY1 cDNA encodes a new member of the IL-1 receptor antagonist family (IL-1ra). In this report, we describe the complete nucleotide sequence of the human IL1HY1 gene. We sequenced approximately 7,600 nucleotides and found four coding exons ranging in size from 55 to 2,288 nucleotides. The 5' untranslated region is formed by one of two alternatively used exons and one invariably present exon which also contains the region encoding the first nine amino acids of the protein. IL1HY1 and IL-1ra intron positions are well conserved within the protein-coding region, providing evidence that these genes arose from a duplication of a primordial IL-1 receptor antagonist gene.


Effectiveness of whole brain radiotherapy in the treatment of brain metastases: a systematic review.
Brain metastases are the most common intracranial tumour in adults, estimated to occur in up to 40% of patients with cancer. Despite being used in clinical practice for 50 years, the effectiveness of whole brain radiotherapy for the treatment of brain metastases remains uncertain. To assess the effectiveness of whole brain radiotherapy (WBRT) on survival and quality of life. To identify whether patient performance status, number of brain metastases, extent of extracranial disease and primary site of cancer are important effect modifiers. Systematic literature review. Electronic searches of four databases, augmented by hand searches of the most frequently encountered journal and assessment of the reference lists of consensus statements and all retrieved papers. Included papers underwent structured data extraction, assessment and qualitative synthesis. Thirty-two primary studies were included, with a range of study designs, methodological quality, pre-treatment variables, interventions and outcome measures. From the limited evidence available, survival appeared to increase when patients were selected by performance status (survival increasing from approximately three to seven months in high performance status groups, as defined by Karnofsky performance status or Recursive Partitioning Analysis classification). The evidence suggests no survival benefit when patients with poor performance status were treated with whole brain radiotherapy. No studies undertook direct measurement of patients' quality of life. Surrogate measures of patients' quality of life, such as improvement in neurological function or improvement/maintenance of KPS > or =70, produced response rates ranging from 7 to 90%. The heterogeneity of study designs, quality and outcomes necessitates caution in interpreting the review findings. WBRT appears to be of benefit in higher performance status patients but not in low performance status patients. This suggests a basis for current practice, however further robust trial evidence is required.


Severe course of rat bite-associated Weil's disease in a patient diagnosed with a new Leptospira-specific real-time quantitative LUX-PCR.
Leptospirosis is a zoonotic disease with global distribution, caused by spirochaetes of the genus Leptospira. Transmission of Leptospira interrogans serovar Icterohaemorrhagiae, the causative agent of Weil's disease, to humans usually results from exposure to the urine of infected, but mostly asymptomatic, rodents, either by direct contact or indirectly through contaminated soil or water. Although regarded as a re-emerging infectious disease, human leptospirosis is probably underdiagnosed due to its often unspecific clinical appearance and difficulties in culturing leptospires. Therefore, more rapid and specific diagnostic procedures are needed. Here we describe a novel real-time quantitative PCR system developed for the accurate and fast diagnosis of pathogenic Leptospira spp. Its usefulness in the management of a patient with rat bite-associated multiorgan failure is demonstrated.


Conditional intercellular cohesion in a Dictyostelium discoideum mutant which is temperature sensitive for correct processing of asparagine-linked oligosaccharides.
Mutants of Dictyostelium discoideum have been isolated by a selection for cells with temperature-sensitive defects in the maturation of glycoprotein N-linked oligosaccharides. Here we describe a mutant, HT7, which is unable to aggregate at the restrictive temperature, but which aggregates and makes fruiting bodies at the permissive temperature. HT7 shows normal early developmental intercellular cohesion, but is temperature sensitive for expression of the ethylenediamine-tetraacetic acid (EDTA)-resistant cohesion characteristic of aggregation. The mutant initiates aggregation, but forms only loose cell mounds which later disperse. Metabolic labelling studies indicate that the thermolabile defect is not in protein synthesis, assembly of the lipid-linked precursor of N-linked oligosaccharides or transfer of the precursor to proteins. However, the defect does prevent assembly of fully processed N-linked oligosaccharides. Further, two glycopeptides, obtained from exhaustive Pronase digests of wild-type plasma membrane glycoproteins, inhibit intercellular cohesion of aggregation-stage wild-type cells. HT7 produces only approximately 50% of the wild-type level of these glycopeptides at the restrictive temperature and one of the glycopeptides has reduced cohesion inhibition ability. A revertant of HT7 was found to aggregate normally, to have restored EDTA-resistant cohesion, to have normal profiles of N-linked oligosaccharides and to express the two cohesion-inhibiting glycopeptides normally. These data strongly support a model in which cohesion during late aggregation is at least in part due to recognition between surface glycans and receptors on neighbouring cells.


Cloning of two cDNAs encoding a family of ATP sulfurylase from Camellia sinensis related to selenium or sulfur metabolism and functional expression in Escherichia coli.
ATP sulfurylase, the first enzyme in the sulfate assimilation pathway of plants, catalyzes the formation of adenosine phosphosulfate from ATP and sulfate. Here we report the cloning of two cDNAs encoding ATP sulfurylase (APS1 and APS2) from Camellia sinensis. They were isolated by RT-PCR and RACE-PCR reactions. The expression of APS1 and APS2 are correlated with the presence of ATP sulfurylase enzyme activity in cell extracts. APS1 is a 1415-bp cDNA with an open reading frame predicted to encode a 360-amino acid, 40.5kD protein; APS2 is a 1706-bp cDNA with an open reading frame to encode a 465-amino acid, 51.8kD protein. The predicted amino acid sequences of APS1 and APS2 have high similarity to ATP sulfurylases of Medicago truncatula and Solanum tuberosum, with 86% and 84% identity respectively. However, they share only 59.6% identity with each other. The enzyme extracts prepared from recombinant Escherichia coli containing Camellia sinensis APS genes had significant enzyme activity.


Novel molecular defect in the platelet ADP receptor P2Y12 of a patient with haemorrhagic diathesis.
The platelet adenosine 5'-diphosphate (ADP) receptor P2Y(12) plays a crucial role in haemostasis. Only a few patients with haemorrhagic diathesis due to molecular defects in the P2Y(12) receptor have been described so far. We report a novel molecular defect in the gene coding for P2Y(12) in a patient with a history of epistaxis, easy bruising and excessive posttraumatic blood loss. Platelet aggregation studies, perfusion studies, in which patient blood was perfused over collagen surfaces at arterial shear rates, and PCR and sequencing were used. Platelet aggregation studies showed impaired ADP and collagen-induced aggregation for patient G.S. Perfusion of patient blood over collagen surfaces showed small thrombi consisting of spread platelets overlayered with non-spread platelets. These thrombi were identical to control thrombi formed in the presence of a P2Y(12) antagonist. DNA analysis of the P2Y(12) gene revealed a novel heterozygous base pair C-->A substitution in exon 3, changing codon 258 from proline to threonine in the third extracellular loop of the P2Y(12) receptor. We conclude that perfusion studies with patient blood are of added value in the diagnostic process, which resulted in identification of a novel molecular defect in the P2Y(12) gene of a patient with haemorrhagic diathesis.


Panniculitis: a cutaneous manifestation of dermatomyositis.
Specific and nonspecific panniculitis sometimes occurs during the course of connective tissue diseases. However, the association of panniculitis and dermatomyositis (DM) has only rarely been described. Previous reports have suggested that panniculitis may be an inherent part of DM but, because the cases reported are few, it is difficult to know the significance of this unusual association. We describe 2 patients with DM in whom panniculitis developed during the course of the disease, and discuss its clinical and diagnostic significance.


TGF-β signalling and its role in cancer progression and metastasis.
The transforming growth factor-β (TGF-β) system signals via protein kinase receptors and SMAD mediators to regulate a large number of biological processes. Alterations of the TGF-β signalling pathway are implicated in human cancer. Prior to tumour initiation and early during progression, TGF-β acts as a tumour suppressor; however, at later stages, it is often a tumour promoter. Knowledge about the mechanisms involved in TGF-β signal transduction has allowed a better understanding of cancer progression, invasion, metastasis and epithelial-to-mesenchymal transition. Furthermore, several molecular targets with great potential in therapeutic interventions have been identified. This review discusses the TGF-β signalling pathway, its involvement in cancer and current therapeutic approaches.


Prevalence and characteristics of shiga toxin-producing Escherichia coli in beef cattle slaughtered on Prince Edward Island.
Fecal swabs obtained from a random sample of 1,000 beef slaughter steers and heifers from 123 Prince Edward Island (P.E.I.) farms were examined for the presence of Shiga toxin-producing Escherichia coli (STEC) using a Vero cell assay (VCA). Multiple isolates from each positive sample were tested similarly. VCA-positive isolates were confirmed as E. coli biochemically, tested for drug resistance, serotyped, and tested by polymerase chain reaction (PCR). Animals were classified as positive when an isolate was positive on VCA and the presence of the gene responsible for toxin production was confirmed by PCR. The prevalence of STEC in beef slaughter steers and heifers on P.E.I. was 4% (40 of 1,000). The total number of isolates was 43, and these comprised 26 serotypes, including 13 isolates belonging to 6 serotypes known to be associated with human illness. The most frequently isolated STEC serotype was E. coli O157 (5 isolates out of 43). Of the five E. coli O157 isolates, four were E. coli O157:H7, a serious human pathogen. The majority of STEC isolates, including all O157:H7, isolates, were susceptible to 16 commonly used antimicrobial drugs. According to PCR, 65% of the STEC isolates had the gene for Stx1. Four of these isolates, including two O157:H7, had genes for Shiga toxin (Stx)1 and Stx2.


Patient narratives of surgical site infection: implications for practice.
Exploring patients' experiences has been used widely within healthcare to improve clinical service delivery. To date there has been minimal patient input of this kind into aspects of surgical site infection (SSI), such as surveillance or prevention interventions. To obtain information from patients' experiences of SSIs to improve clinical practice. Narrative interviews with 17 patients with SSIs (four deep, 12 organ space and one superficial) from three hospitals in England were conducted followed by thematic content analysis. Patients lacked overall awareness, concern and understanding of SSIs. Seven patients did not know that they had SSIs and, judging from patients' accounts, staff may have contributed to the lack of awareness by not informing patients of SSIs or downplaying their existence. The use of primary care resources was considerable and six of the patients were absent from work for two to four months. SSIs have a low profile among patients which, if it were raised, could increase compliance with preventive interventions. This study confirms the appropriateness of using patient self-assessment post-discharge surveillance questionnaires to identify SSI symptoms, and highlights the need to identify total costings including to primary care, patients and the economy.


What women value in the midwifery continuity of care model: A systematic review with meta-synthesis.
There are a number of qualitative studies indicating women are more satisfied with a continuity model of midwifery care however, their experiences have not been understood to gain an overall picture of what it is they value, appreciate and want in such a model. A metasynthesis was undertaken in order to examine the current qualitative literature to gain a deeper understanding of the woman's perspective as a consumer of maternity care in a continuity model. To identify and synthesise research findings presenting childbearing women's perspectives on continuity of midwifery care. A search using key words was undertaken using the following databases: CINAHL, Cochrane Library, Ovid, Medline, Nursing Reference Centre and Joanna Briggs Institute. Papers were included if they were published since 2006, in English and included qualitative data from the woman's perspective. The selection process followed was the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Quality appraisal was conducted by all authors using the Critical Appraisal Skills Programme (CASP) tool as a screening tool. This allowed for each paper to be appraised to determine risk of bias. Thirteen quality appraised papers published between 2006 and 2016 were found which included qualitative data and were related to the woman's experience in a continuity model. Six papers were from Australia, three in the United Kingdom, two in New Zealand and one in the United States of America and Denmark. Themes identified included an overarching concept of the relationship which was underpinned by themes of personalised care, trust and empowerment. The midwife-woman relationship is the vehicle through which personalised care, trust and empowerment are achieved in the continuity of midwifery model of care.


Heterologous expression of thermostable acetylxylan esterase gene from Thermobifida fusca and its synergistic action with xylanase for the production of xylooligosaccharides.
The axe gene which encodes an acetylxylan esterase from Thermobifida fusca NTU22, was cloned, sequenced and expressed in Escherichia coli. The gene consists of 786 base pairs and encodes a protein of 262 amino acids. The deduced amino acid sequence of the acetylxylan esterase axe exhibited a high degree of similarity with BTA-hydrolase from T. fusca DSM43793, esterase from Thermobifida alba and lipase from Streptomyces albus. The optimal pH and temperature of the purified esterase were 7.5 and 60°C, respectively. Cooperative enzymatic treatment of oat-spelt xylan by transformant xylanase and acetylxylan esterase significantly increased the xylooligosaccharides production compared with the xylanase or acetylxylan esterase action alone. The synergy of transformant acetylxylan esterase and xylanase cannot increase the production of reducing sugars from lignocellulolytic substrate, bagasse.


Evaluation of the production of exopolysaccharides by two strains of the thermophilic bacterium Rhodothermus marinus.
The thermophile Rhodothermus marinus produces extracellular polysaccharides (EPSs) that forms a distinct cellular capsule. Here, the first data on EPS production in strains DSM4252T and MAT493 are reported and compared. Cultures of both strains, supplemented with either glucose, sucrose, lactose or maltose showed that the EPS were produced both in the exponential and stationary growth phase and that production in the exponential phase was boosted by maltose supplementation, while stationary phase production was boosted by lactose. The latter was higher, resulting in 8.8 (DSM4252T) and 13.7mg EPS/g cell dry weight (MAT493) in cultures in marine broth supplemented with 10g/L lactose. The EPSs were heteropolymeric with an average molecular weight of 8×104Da and different monosaccharides, including arabinose and xylose. FT-IR spectroscopy revealed presence of hydroxyl, carboxyl, N-acetyl, amine, and sulfate ester groups, showing that R. marinus produces unusual sulfated EPS with high arabinose and xylose content.


Continuously moving table time-of-flight angiography of the peripheral veins.
Time-of-flight (TOF) MR angiography allows for noninvasive vessel imaging. To overcome the limited volumetric coverage of standard TOF techniques, the aim of this study was to investigate the combination of TOF and continuously moving table (CMT) acquisitions for peripheral vein imaging based on image subtraction. Two acquisition strategies are presented: a simple two-step method based on 2-fold CMT acquisition and an advanced one-step method requiring only one continuous scan. Image quality of both CMT TOF techniques was evaluated by semiquantitative image grading and by signal-to-noise ratio and contrast-to-noise ratio analysis for veins of the upper and lower leg in 10 healthy volunteers. Results were compared to a standard stationary two-dimensional (2D) TOF multistation acquisition. Image grading revealed good image quality for both CMT TOF methods, thereby confirming the feasibility of axial 2D CMT TOF to assess the veins of the lower extremities during a single scan. Quantitative evaluation showed no significant difference in signal-to-noise ratio and contrast-to-noise ratio compared to the stationary experiment. Additional measurements in three patients with postthrombotic changes and varicosities demonstrated the clinical applicability of the presented methods. CMT TOF provides promising results and permits the detection of various pathologic changes of the venous system.


[Cerebrospinal fluid gamma globulins in neurological disorders affecting black Africans (author's transl)].
Four hundred C.S.F. electrophoreses were carried out in black West Africans (Ivory Coast) suffering from inflammatory disorders of the nervous system. In the normal state, the C.S.F. of the black African contains more gamma globulins than that of the white (15.8% as opposed to 10%). The study provides indirect evidence of the classical notion of the extreme rarity of DS (Disseminated sclerosis) in the tropics. Hypergammaglobulinorachia was demonstrated in 22% of cases, the two principal disorders responsible being trypanosomiasis (57.3%) and sub-acute sclerosing panencephalitis (16.8%). The oligoclonal distribution described in trypanosomiasis was not found. On the contrary, a homogeneous appearance of the gamma zone was constantly demonstrated (49/50). It is possible that these differences are related to the various phases in the course of the disease, and that oligoclonal disturbation is a marker of the auto-immune phase.


Monocyte adhesion to human saphenous vein in vitro.
Monocyte adhesion to endothelium is believed to be an initiating event in atherosclerosis both in arteries and in saphenous vein coronary artery bypass grafts. We have developed a method to quantify adhesion of 51Cr-labelled human blood monocytes to saphenous vein. Adhesion to the intimal surface was measured to uniform 6 mm diameter discs, the adventitia of which was embedded in a layer of inert silicone grease. The identity, number and location of bound cells was further defined by scanning electron microscopy. The proportion of monocytes adhering to discs of freshly-isolated vein was 7.1 +/- 1.2% (SE, n = 8), which was equivalent to 500 +/- 80 monocytes/mm2. The percentage of monocytes adhering was independent of the number of monocytes added in the range 5-50 x 10(4). Scanning micrographs showed 80% endothelial coverage with monocytes adhering preferentially but not exclusively to subendothelium. Endothelial removal increased monocyte adhesion by 1.60 +/- 0.15-fold (n = 8, P less than 0.01). Vein surgically prepared for use in coronary bypass surgery, had a 50% reduction in endothelial coverage and a small but non significant (1.14 +/- 0.13-fold, n = 8) increase in monocyte adhesion. Treatment of freshly-isolated vein for 4 h at 37 degrees C with 1 micrograms/ml of E. Coli endotoxin followed by extensive washing did not remove endothelium but increased monocyte adherence by 1.46 +/- 0.18-fold (n = 8, P less than 0.05). The proportion of monocytes adhering to veins which had been cultured for 14 days was similar to freshly isolated veins (6.4 +/- 0.8%, n = 7), but in cultured veins, monocytes adhered preferentially to cells with typical endothelial morphology. Endotoxin treatment of cultured freshly-isolated veins increased monocyte adhesion by 1.77 +/- 0.23-fold (n = 8, P less than 0.05). The data show that both endothelial activation, and exposure of subendothelium promote monocyte adhesion to human saphenous vein.


Accurate peptide sequencing by post-source decay matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.
Partial 18O-labeling of peptides has been applied to post-source decay experiments in a matrix-assisted laser desorption/ionization time-of-flight mass spectrometer. The ions which originate from the carboxyl terminus of a peptide partially retain 18O atoms which have readily been incorporated into the C-terminal carboxyl groups during enzymatic hydrolysis in a buffer containing 40 atom percent H218O. The isotopic resolution of singly charged precursor ions and their product ions obtained for peptides up to ca. 2800 Da has been achieved using the delayed extraction method, which permits the rapid identification and assignment of the 18O-labeled and non-labeled ion species in the PSD spectra. The results obtained from several 18O-labeled peptides, derived from an enzymatic digest, demonstrate the accuracy and reproducibility of the present method, which will be in widespread use for protein identification via database searching or for investigations of totally unknown proteins.


Hypothalamo-pituitary-adrenal axis, glucose metabolism and TNF-α in narcolepsy.
Narcolepsy with cataplexy is caused by a deficiency in the production of hypocretin/orexin, which regulates sleep and wakefulness, and also influences appetite, neuroendocrine functions and metabolism. In this case-control study, 11 patients with narcolepsy with cataplexy and 11 healthy adults underwent an oral glucose tolerance test, and dexamethasone suppression/corticotropin-releasing hormone stimulation test. The average age of patients and controls was 35.1 ± 13.2 and 41.0 ± 2.9 years, respectively, body mass index was 28.1 ± 6.6 and 25.5 ± 4.7 kg m(-2) . We did not find evidence of a significantly increased prevalence of disturbed glucose tolerance in patients with narcolepsy. After hypothalamo-pituitary-adrenal axis suppression, the number of non-suppressors did not differ between the groups, indicating normal negative feedback sensitivity. The level of cortisol after dexamethasone suppression was significantly lower in patients with narcolepsy, suggesting a slight basal downregulation and/or a slightly increased negative feedback sensitivity of the major endocrine stress system in narcolepsy. Following corticotropin-releasing hormone stimulation, there were no significant differences in levels of adrenocorticotropic hormone or cortisol, and in adrenocortical responsivity to adrenocorticotropic hormone. Finally, patients with narcolepsy displayed significantly higher plasma levels of tumour necrosis factor alpha, soluble tumour necrosis factor receptor p55, soluble tumour necrosis factor receptor p75 and interleukin 6 after adjustment for body mass index. The present study confirms that narcolepsy by itself is not associated with disturbances of glucose metabolism, but goes along with a subtle dysregulation of inflammatory cytokine production. We also found that dynamic hypothalamo-pituitary-adrenal system response is not altered, whereas negative feedback to dexamethasone might be slightly enhanced.


Aggressiveness and the intensity of psychopathic symptoms - gender differences.
The analysis of the recent international reports in the literature on psychopathy has proved irrefutablythat there is a necessity for the in-depth studies on psychopathy among the female sentenced offenders. Although there is no disagreement among the researchers on the 'male' form of this disorder, there are still very few gender comparative studies. The aim of this project was to investigate the relationship between the intensity of particular psychopathic features and aggressive tendencies in a group of female and male inmates. 100 incarcerated adult males and 100 incarcerated adult females were studied. To assess the intensity of the psychopathic features the Hare Psychopathy Checklist-Revised (PCL-R; Hare, 2003) was used. Aggressive tendencies were measured using the self-reported Buss-Perry Aggression Questionnaire (AQ; Buss and Perry, 1992). The analysis of variance showed that 12 out of the 20 PCL-R items differentiate indicators of aggressiveness at statistically significant level in the group of male and female prisoners. The obtained data suggest that there are gender differencesin the manifestation of psychopathy-characteristic features. In both gender groups psychopathic deficiencies can be linked with aggressive behaviors.


Normal palatal sutures in newborns and fetuses: a critical fact for successful palatal distraction.
Distraction osteogenesis (DO) has recently been applied to the palate. Successful posterior lengthening and medial advancement of the palates was continuously reported. Based on these studies, it is obvious that DO will play a major role in the management of problems related to palatal defects in the near future. Although the results are appealing, they may not be applicable for humans due to anatomic differences. All experimental studies used normal palatal sutures of young dogs for size expansion. Therefore, it is necessary to know normal palatal sutures in infants before one can clinically apply this new technique. With consent, palates of fetuses and neonates who died of various causes were examined. Eight fresh cadavers were available for the dissection, with two being skeletonized using the boiling process. There were three fetal deaths in utero (33-41 weeks of gestational age) and five postnatal deaths (aged between 5 hours and 6 months). All specimens were grossly normal in shape and size except for one with a unilateral complete cleft of lip and palate. A midline palatal suture was found in every noncleft specimen, while premaxillary and transverse palatomaxillary sutures were present in every specimen. Laterally, there was no true suture except for the most posterior portion, which was contiguous with the greater palatine foramen. The palatal sutures of third-trimester fetuses and neonates are not different from adult ones. There is no lateral suture that will allow distraction in the medial direction. It is only the posterior hard palate (palatine bones) that can potentially be moved medially and posteriorly by sutural expansion with DO.


The effect of i.v. enalaprilat in chronically treated hypertensive patients during cardiac surgery.
Angiotensin-converting enzyme (ACE) inhibitors are well established as long-term antihypertensives and have also been proved useful in hypertensive emergencies. Therefore, we investigated whether intraoperative i.v. enalaprilat may reduce the incidence of perioperative hypertensive reactions in coronary artery bypass grafting (CABG). Thirty-eight male patients chronically treated for arterial hypertension and scheduled for CABG randomly and double-blindly received either enalaprilat 30 micrograms.kg-1 or NaCl 0.9% at the time of skin incision. Intraoperatively, increases of mean arterial pressure (MAP) > 85 mmHg or > 80 mmHg during cardiopulmonary bypass (CPB) were treated by an urapidil bolus. The total intraoperative amount of urapidil was documented for both groups. Systemic and pulmonary hemodynamics as well as the plasma levels of epinephrine, norepinephrine, arginine vasopressin and renin were measured intraoperatively and up to 2 h after admission to the intensive care unit. Mean arterial pressure, cardiac index and systemic vascular resistance did not differ between the enalaprilat and the control group. Renin plasma levels significantly increased after infusion of enalaprilat and did not change in the placebo group. Catecholamine and arginine vasopressin plasma levels increased significantly during CPB and remained high in the postoperative period without any intergroup difference. The same amount of urapidil had to be given in the two groups to maintain MAP below the defined limit. We conclude that infusing 30 micrograms.kg-1 enalaprilat in patients chronically treated for arterial hypertension does not prevent hypertensive reactions during CABG.


Avoiding the pitfalls and perils of catheter care.
Twelve per cent of hospital inpatients and 4% of community patients have an indwelling urinary catheter. Urinary catheterization increases morbidity threefold. The main hazards of catheterization are tissue damage, bladder damage, infection, encrustation and blockage. Obtaining informed consent before catheterization is extremely important. Restricting catheterization to those who clinically require this invasive procedure can reduce the number of people who are exposed to the hazards of catheterization. The use of silver-coated catheters can reduce the risk of infection and encrustation. Ensuring that practice is evidence-based further reduces the risks of catheterization.


Women's postpartum stress, social support, and health status.
The purpose of this study was to examine women's postpartum stress, social support, and health status at different places of residence during their postpartum periods. Using proportional stratified quota sampling of hospitals by birth rate from clinics and hospitals in Kaohsiung City in southern Taiwan, postpartum married women were recruited for the study. The results show that the home of the women's parents (25.7%), her own home (with parents-in-law; 23.8%), and her own home (without parents or parents-in-law; 23.1%) were the main places of residence for women during the postpartum period. In addition, postpartum women's mean scores for postpartum stress were low. In contrast, the mean scores for social support were high, although they did not differ significantly for the respective places of postpartum residence. Furthermore, significant differences were not found in these women's postpartum health status at each of the places of postpartum residence.


Conservative and surgical treatment of chronic anal fissure: prospective longer term results.
The aim of this prospective study was to assess the efficacy of different medical treatments and surgery in the treatment of chronic anal fissure (CAF). From January 2004 to March 2009, 311 patients with typical CAF completed the study. All patients were initially treated with 0.2% nitroglycerin ointment (GTN) or anal dilators (DIL) for 8 weeks. If no improvement was observed after 8 weeks, the patients were assigned to the other treatment or a combination of the two. Persisting symptoms after 12 weeks or recurrence were indications for either botulinum toxin injection into the internal sphincter and fissurectomy or lateral internal sphincterotomy (LIS). During the follow-up (29 +/- 16 months), healing rates, symptoms, incontinence scores, and therapy adverse effects were prospectively recorded. Overall healing rates were 64.6% and 94% after GTN/DIL or BTX/LIS. Healing rate after GTN or DIL after 12 weeks course were 54.5% and 61.5%, respectively. Fifty-four patients (17.4%) responded to further medical therapy. One hundred two patients (32.8%) underwent BTX or LIS. Healing rate after BTX was 83.3% and overall healing after LIS group was 98.7% with no definitive incontinence. In conclusion, although LIS is far more effective than medical treatments, BTX injection/fissurectomy as first line treatment may significantly increase the healing rate while avoiding any risk of incontinence.


Trap efficiency for Glossina pallidipes (Diptera: Glossinidae) at Nguruman, south-west Kenya.
An incomplete ring of electric nets was evaluated as a means of estimating trap efficiency for Glossina spp. This methodology assumes flies approach the trap directly, and then enter, or leave directly in random directions. These results showed that the ratio of the number of flies intercepted on the outside of the electric nets to the number on the inside was lower than predicted by this single-approach behavioural model. Moreover, an incomplete ring of nets around a trap reduced trap catch more than the model predicted. These inconsistencies were greater early in the day, and greater for females than for males. It is suggested that flies may make several approaches to a trap before entering or departing. This mixes arriving and departing flies on each side of the electric nets. Use of a complete ring of nets around a trap to estimate trap efficiency entails fewer behavioural assumptions. Catches at a complete ring around a trap were compared to catches in a trap without nets, replicated in a cross-over design. The efficiency of an odour baited NG2G trap was estimated to be 58% for males and 37% for females. Biconical traps were much less efficient. Both trap types were less efficient in the early morning, suggesting entry response is temperature dependent. The NG2G trap was more efficient for non-teneral nulliparous females than for other ages. For both trap types there was little difference between mean fat content of approaching and trapped males, but the mean fat content of trapped females was lower than that of approaching females.


A panel study of peer norms and adolescent alcohol consumption: developing strategies for communication interventions.
Given that alcohol consumption and binge drinking among adolescents in the United States remain prevalent, this study assesses changes in the influence of peer norms-and their interactions with time, gender, and ethnicity-on alcohol consumption. Panel survey interviews of adolescents (N = 1,607) were completed in 9th grade and then again in 12th grade with students from Louisiana. Fixed effects multiple regression assessed the relations between the changes in 2 types of peer norms (i.e., descriptive norms and injunctive norms) and 2 alcohol consumption measures: 30-day alcohol prevalence and binge drinking. Increases in 30-day alcohol prevalence and binge drinking were associated with only descriptive norms. The effects of both types of peer norms intensified over time, and the effects of descriptive norms varied according to gender and ethnicity. Specifically, the influence of descriptive norms was greater on boys than on girls and on Caucasians than on African Americans. Communication interventions that target adolescents in the context of alcohol consumption should consider the temporal variability of peer normative influence and how it varies by gender and ethnicity.


Metabolic indicators of fibre recruitment in mammalian muscles during locomotion.
Fast-twitch-oxidative-glycolytic (FOG), fast-twitch-glycolytic (FG) and slow-twitch-oxidative (SO) fibres are distributed within and among physiological extensor muscles in mammals in predictable patterns. Deep muscles and the deep portions of extensor muscles are primarily composed of SO and FOG fibres, and the more peripheral portions of the muscles have higher concentrations of FG fibres. During terrestrial locomotion, the fibres are recruited in this same general order from postural standing through high speed running to jumping (i.e. during standing deep SO fibres are active and during locomotion there is a progressive peripheral recruitment of fibres from SO to FOG to FG). Several metabolic indicators may be used to map these fibre recruitment patterns, including glycogen loss in fibres, metabolic enzyme changes during training at different speeds, and distribution of blood flow within and among the muscles. Concerning the latter, during standing in rats blood flows in the hindlimb muscles are directly proportional to the SO fibre populations in the muscles. However, during locomotion the elevations in blood flow over pre-exercise are a function of the populations of FOG fibres in the muscles. Blood flows in the peripheral white portions (FG fibres) of extensor muscles are not significantly elevated until the rats run at high speeds, when the FG fibres presumably are recruited. During swimming, when flexor muscles are relatively more active than extensor muscles (as compared with terrestrial locomotion), blood flows in the flexors are correspondingly higher. Thus, there exists a clear 'biological economy' in the matching of blood flow to the specific fibres that are active within and among muscles during exercise.


Alkylation of the liver plasma membrane and inhibition of the Ca2+ ATPase by acetaminophen.
Acetaminophen is activated metabolically to yield reactive species that bind covalently to liver cell macromolecules. The extent of covalent binding correlates with the occurrence and severity of hepatic necrosis. We reported previously [J. O. Tsokos-Kuhn, E. L. Todd, J. B. McMillin-Wood and J. R. Mitchell, Molec. Pharmac. 28, 56 (1985)] that active Ca2+ accumulation of isolated liver plasma membranes is decreased 60-75% after a hepatotoxic dose of acetaminophen in vivo. We now report that the protein of isolated liver plasma membranes was substantially labeled with drug metabolites after administration of [3H]acetaminophen. There was no increase in passive membrane permeability that might cause diminished Ca2+ accumulation. Intravesicular volume and relative purity of the vesicle preparations after acetaminophen were not different from controls. However, (Ca2+,Mg2+)-ATPase, a possible biochemical expression of the Ca2+ pump, was decreased 31% (P less than 0.025) after acetaminophen treatment. ATPase activity in both control and treated groups was enhanced by isolating membranes in the presence of 5 mM reduced glutathione (GSH), but the effects of drug treatment were not reversed. A similar effect of GSH on Ca2+ accumulation was observed previously [J. O. Tsokos-Kuhn, E. L. Todd, J. B. McMillin-Wood and J. R. Mitchell, Molec. Pharmac. 28, 56 (1985)]. These data are consistent with a hypothesis wherein alkylation of membrane proteins by reactive acetaminophen metabolites is a factor in the onset of hepatic necrosis after acetaminophen. They are not consistent with an oxidative stress hypothesis where thiol S-thiolation of membrane components is postulated to produce altered membrane permeability or thiol-reversible alterations in membrane protein structure and enzymatic function.


RNA polymerase I termination: Where is the end?
The synthesis of ribosomal RNA (rRNA) precursor molecules by RNA polymerase I (Pol I) terminates with the dissociation of the protein-DNA-RNA ternary complex. Based on in vitro results the mechanism of Pol I termination appeared initially to be rather conserved and simple until this process was more thoroughly re-investigated in vivo. A picture emerged that Pol I termination seems to be connected to co-transcriptional processing, re-initiation of transcription and, possibly, other processes downstream of Pol I transcription units. In this article, our current understanding of the mechanism of Pol I termination and how this process might be implicated in other biological processes in yeast and mammals is summarized and discussed. This article is part of a Special Issue entitled: Transcription by Odd Pols.


Current ethical and legal issues in health-related direct-to-consumer genetic testing.
A variety of health-related genetic testing is currently advertized directly to consumers. This article provides a timely overview of direct-to-consumer genetic testing (DTC GT) and salient ethical issues, as well as an analysis of the impact of the recently adopted regulation on in vitro diagnostic medical devices on DTC GT. DTC GT companies currently employ new testing approaches, report on a wide spectrum of conditions and target new groups of consumers. Such activities raise ethical issues including the questionable analytic and clinical validity of tests, the adequacy of informed consent, potentially misleading advertizing, testing in children, research uses and commercialization of genomic data. The recently adopted regulation on in vitro diagnostic medical devices may limit the offers of predisposition DTC GT in the EU market.


Antibiotic therapy for patients with spinal cord injury undergoing urologic procedures.
This prospective study was performed to determine whether gentamicin can be prescribed routinely to patients with spinal cord injury undergoing urologic procedures, or whether antibiotic therapy must be selected on the basis of recent urine microbiologic test results. Between January 2004 and June 2005, procedures were performed on 38 patients, all of whom were prescribed antibiotics on the basis of a microbiology report. Sixteen patients who underwent urologic surgery during 2003 and received gentamicin empirically served as a control group. The patients' clinical course was monitored for postprocedure sepsis. Only 12 patients received gentamicin as the sole antibiotic; 10 patients required an additional antimicrobial for urine samples that grew more than 1 organism and contained bacteria resistant to gentamicin; 26 patients needed antibiotics other than gentamicin for gentamicin-resistant uropathogens. Three patients with organisms sensitive to gentamicin as well as another antibiotic received an agent considered less nephrotoxic than gentamicin. After the procedure, sepsis occurred in only 1 patient, a man with chronic lymphocytic leukemia and small cell carcinoma of the urinary bladder. Three control group patients developed a fever in excess of 39 degrees C. One of these patients did not require a change of antibiotic, another patient recovered after 3 changes of antibiotic, and the third patient recovered from septicemia after receiving ventilatory support. Antibiotics should be prescribed on the basis of recent urine microbiologic test results, and empiric therapy with gentamicin should be avoided in patients with spinal cord injury who are scheduled to undergo urologic procedures.


Histopathological Characterization of Cutaneous Delayed-type Hypersensitivity and Correlations with Intestinal Pathology and Systemic Immune Responses in Sheep with Paratuberculosis.
Cell-mediated immunity has been exploited historically in the diagnosis of mycobacterial diseases through elicitation of a delayed-type hypersensitivity (DTH) reaction following intradermal injection of an antigen. Here we describe the histopathological features of the cutaneous DTH reaction and its association with intestinal pathology and systemic immune responses in sheep with Mycobacterium avium subspecies paratuberculosis (MAP) infection. A mixed mononuclear cellular infiltrate dominated the DTH reaction and was present in perivascular and periadnexal patterns. Multiple multinucleate giant cells were present in the cellular infiltrate in one sheep while plasma cells were an obvious feature in six others. Sheep with paucibacillary intestinal lesions had the greatest degrees of cutaneous induration, more severe cellular infiltration in DTH lesions and high systemic interferon (IFN)-γ production. In contrast, sheep with multibacillary intestinal lesions, and particularly those with dissemination of MAP to extra-intestinal tissues, had minimal cutaneous induration, nil to mild cellular infiltration in DTH lesions and high serum anti-MAP antibody levels. Systemic IFN-γ production generally was augmented following skin sensitization. In general, the gross and histopathological features of the cutaneous DTH response matched the stage of paratuberculosis reflected by intestinal pathology and systemic measures of humoral and cellular immunity.


Analysis of peptide histidine-isoleucine/vasoactive intestinal polypeptide-immunoreactive neurons in the central nervous system with special reference to their relation to corticotropin releasing factor- and enkephalin-like immunoreactivities in the paraventricular hypothalamic nucleus.
The distribution of peptide histidine-isoleucine (PHI) and vasoactive intestinal polypeptide (VIP), two peptides derived from the same precursor molecule, was analysed with immunohistochemistry in the central nervous system of the rat, and to a limited extent in some other species including sheep, monkey and man. Special attention was focused on possible cross-reactivity between PHI antisera and corticotropin releasing factor in parvocellular neurons in the hypothalamic paraventricular nucleus projecting to the external layer of the median eminence. (1) Characterization of the PHI and VIP antisera revealed that they recognized different sequences of the peptide molecules. One of the PHI antisera (PHI-N), although mainly N-terminally directed, also probably contained an antibody population directed against the C-terminal amino acid in PHI which is an amidated isoleucine. Rat and human corticotropin releasing factor but not ovine also have an amidated isoleucine in C-terminal position. (2) PHI- and VIP-like immunoreactivity were found with parallel and overlapping distribution in all areas investigated in the rat central nervous system. In many cases coexistence of the two immunoreactivities could be directly demonstrated. PHI neurons were found in some areas so far not know to contain PHI/VIP neurons, including the dorsal septum, the septofimbrial nucleus, the stria terminalis and lamina V of the spinal cord. (3) Using an antiserum directed against the amino acid sequence 111-122 of the VIP/PHI precursor, immunoreactive cell bodies were seen in some areas containing VIP and PHI neurons. PHI- and VIP-like immunoreactivity were expressed in parallel in increasing amounts in the superficial laminae of the dorsal horn after transection of the sciatic nerve [G. P. McGregor et al. (1984) Neuroscience 13, 207-216; S. A. S. Shehab and M. E. Atkinson (1984) J. Anat. 139, 725; S. A. S. Shehab and M. E. Atkinson (1986) Expl Brain Res. 62, 422-430]. (5) The PHI-N antiserum stains large numbers of immunoreactive cells in the parvocellular part of the paraventricular nucleus and these cells are mostly identical with corticotropin releasing factor-positive neurons. Absorption experiments suggested that this PHI-N-like immunoreactivity to a large extent represented cross-reactivity with rat CRF and that earlier demonstration of many PHI-positive neurons in the paraventricular nucleus probably represents an artefact as proposed by F. Berkenbosch et al. (Neuroendocrinology 44, 338-346). However, some cells did, in fact, contain VIP- as well as PHI-like immunoreactivity as was shown with antisera not cross-reacting with corticotropin releasing factor.(ABSTRACT TRUNCATED AT 400 WORDS)


Thermal stability of L-ascorbic acid and ascorbic acid oxidase in broccoli (Brassica oleracea var. italica).
The thermal stability of vitamin C (including l-ascorbic acid [l-AA] and dehydroascorbic acid [DHAA]) in crushed broccoli was evaluated in the temperature range of 30 to 90 degrees C whereas that of ascorbic acid oxidase (AAO) was evaluated in the temperature range of 20 to 95 degrees C. Thermal treatments (for 15 min) of crushed broccoli at 30 to 60 degrees C resulted in conversion of l-AA to DHAA whereas treatments at 70 to 90 degrees C retained vitamin C as l-AA. These observations indicated that enzymes (for example, AAO) could play a major role in the initial phase (that is, oxidation of l-AA to DHAA) of vitamin C degradation in broccoli. Consequently, a study to evaluate the temperature-time conditions that could result in AAO inactivation in broccoli was carried out. In this study, higher AAO activity was observed in broccoli florets than stalks. During thermal treatments for 10 min, AAO in broccoli florets and stalks was stable until around 50 degrees C. A 10-min thermal treatment at 80 degrees C almost completely inactivated AAO in broccoli. AAO inactivation followed 1st order kinetics in the temperature range of 55 to 65 degrees C. Based on this study, a thermal treatment above 70 degrees C is recommended for crushed vegetable products to prevent oxidation of l-AA to DHAA, the onset of vitamin C degradation. The results reported in this study are applicable for both domestic and industrial processing of vegetables into products such as juices, soups, and purees. In this report, we have demonstrated that processing crushed broccoli in a temperature range of 30 to 60 degrees C could result in the conversion of l-ascorbic acid to dehydroascorbic (DHAA), a very important reaction in regard to vitamin C degradation because DHAA could be easily converted to other compounds that do not have the biological activity of vitamin C.


SSZ-52, a zeolite with an 18-layer aluminosilicate framework structure related to that of the DeNOx catalyst Cu-SSZ-13.
A new zeolite (SSZ-52, |(C14H28N)6Na6(H2O)18|[Al12Si96O216]), related to the DeNOx catalyst Cu-SSZ-13 (CHA framework type), has been synthesized using an unusual polycyclic quaternary ammonium cation as the structure-directing agent. By combining X-ray powder diffraction (XPD), high-resolution transmission electron microscopy (HRTEM) and molecular modeling techniques, its porous aluminosilicate framework structure (R3m, a = 13.6373(1) Å, c = 44.7311(4) Å), which can be viewed as an 18-layer stacking sequence of hexagonally arranged (Si,Al)6O6 rings (6-rings), has been elucidated. The structure has a three-dimensional 8-ring channel system and is a member of the ABC-6 family of zeolites (those that can be described in terms of 6-ring stacking sequences) like SSZ-13, but it has cavities that are twice as large. The code SFW has been assigned to this new framework type. The large cavities contain pairs of the bulky organic cations. HRTEM and XPD simulations show that stacking faults do occur, but only at the 5-10% level. SSZ-52 has considerable potential as a catalyst in the areas of gas conversion and sequestration.


[Three-dimensional volumetric display--a new application of frequency up-conversion].
This paper discusses the present research situation and the application prospect of 3-D volumetric display technology. The possible usability and science significance of frequency up-conversion in 3-D volumetric display field are also demonstrated systematically. In ZBLAN: Pr, Yb glasses, we primarily demonstrated and achieved a new application of frequency up-conversion three dimensional volumetric display, using the two-frequency up-conversion of the rare earth ions. The efficiency of luminescence of Pr was enhanced much by the energy transfer between Pr and Yb ions.


Improved cisplatin delivery in cervical cancer cells by utilizing folate-grafted non-aggregated gelatin nanoparticles.
Cisplatin is highly effective in the treatment of cervical cancer. However, in therapeutic doses, cisplatin induces several adverse effects due to undesirable tissue distribution. Therefore, it is worth targeting cisplatin in cervical cancer cells by implicating non-aggregated ligand-modified nanotherapeutics. Here, we report the preparation of non-aggregated folic acid-conjugated gelatin nanoparticles of cisplatin (Cis-GNs-FA) by two-step desolvation method with mean particle size of 210.6±9.6nm and 140.5±10.9nm for Cis-GNs to improve the drug delivery in cervical cancer, HeLa cells. FTIR and DSC spectra confirmed the presence and stability of cisplatin in gelatin matrix. Furthermore, amorphization of cisplatin in nanoparticles was ascertained by PXRD. Drug release followed a first-order release kinetic at both pH ∼ 5.6 (cervical cancer pH) and pH ∼ 7.4. In addition, a significant (P<0.05) decrease in IC50 value (8.3μM) and enhanced apoptosis were observed in HeLa cells treated with Cis-GNs-FA as compared to Cis-GNs (15.1μM) and cisplatin solution (40.2μM). In contrast, A549 lung cancer cells did not discriminate between Cis-GNs-FA and Cis-GNs due to the absence of folate receptors-α (FR-α). Consistently, higher cellular uptake, 80.54±7.60% was promoted by Cis-GNs-FA significantly (two-way ANOVA, P<0.05) greater than 51.68±9.78%, by Cis-GNs. This was also illustrated by CLSM images, which indicated that Cis-GNs-FA preferably accumulated in the cytoplasm of HeLa cells nearby nucleus by following receptor-mediated endocytosis pathway as compared to Cis-GNs. Therefore, Cis-GNs-FA warrants further in-depth in vitro and in vivo investigations to scale up the technology for clinical translation.


Virus diagnostics on microarrays.
Whereas the majority of microarray applications still deal with expression analysis for gathering information about levels of gene products at certain cell states, other approaches simply ask the question whether particular genes, which are usually indicative for particular microorganisms and pathogens, are present in a sample or not. Investigations that are more detailed try to evaluate the presence of particular subtypes of a given pathogen. The combination of microarray technology and virus diagnostics promises to generate an ideal platform for fast, sensitive, specific, and parallelized virus diagnostics. Performing virus diagnostics on microarrays, however, requires other basic techniques to be optimized. This is necessary in order to obtain unambiguous and reproducible results, which are compatible with the needs for clinical routine. Parameters that have to be considered include supports, coupling chemistry, chemical oligonucleotide synthesis, signal enhancement strategies, and optimal coordination of PCR reactions, hybridizations, and signal detection, as well as interpretation strategies. Finally, considerations should be given to economic aspects, one chip-one patient strategies and low integrated arrays as a custom-tailored way to fast and accurate diagnostic tools.


Analysis of the immunomodulatory properties of two heat-killed mycobacterial preparations in a human whole blood model.
The significant role played by mycobacteria in modulating immune responses through enhancing the crosstalk between innate and adaptive immunity has been highlighted in several studies. Owing to their unique antigenic profile, heat killed (HK) preparations of rapid-growing mycobacteria, currently undergoing clinical development, have been assessed as adjuvant therapy in various diseases. The purpose of this study is to investigate the regulation of leukocyte surface receptors, in whole blood from healthy donors, following in vitro stimulation with HK Mycobacterium vaccae (M. vaccae) or M. obuense. We have demonstrated the ability of both mycobacterial preparations to target monocytes and neutrophils and to regulate the surface expression of selected adhesion receptors, antigen-presenting and costimulatory receptors, pattern recognition receptors, complement and Fc receptors, as well as cytokine/chemokine receptors. Toll-like receptors (TLRs) 1 and 2 were also shown to be involved in mediating the M. obuense-induced upregulation of selected surface receptors on monocytes. Whole blood stimulation with M. vaccae or M. obuense resulted in a significant increase in the secretion of a specific set of cytokines and chemokines. Both mycobacterial preparations induced strong antigen-specific proliferative responses in peripheral blood mononuclear cells. Collectively, our data shows that M. vaccae and M. obuense have the potential to act as potent immunomodulators. Future research based on these findings may reveal novel immune pathways induced by these preparations with potential implication for their use in diverse immunotherapeutic approaches.


[Parameters of ocular hydrodynamics in case of major neck blood vessels compression by thyroid nodules].
to study aqueous humor secretion and outflow in patients, whose major blood vessels of the neck got compressed by thyroid nodules. Ocular hydrodynamics was assessed in 60 patients (119 eyes) with uni- or bilateral benign thyroid nodules compressing the major neck blood vessels. Most patients demonstrated a significant decrease in parameters of aqueous humor secretion and outflow. After decompression, ocular hydrodynamics usually improved reaching its normal level. Compression of the major neck blood vessels by thyroid nodules impedes drainage of the aqueous humor and serves as a risk factor of secondary phlebohypertensive glaucoma.


Veterans' psychiatric benefits: enter courts and attorneys.
In 1988, the Veterans Judicial Review Act (VJRA) was signed into law, ending more than a century of Congressional measures that kept veterans' benefits claims completely out of the appellate court system. Before this new law, any decision made by the Department of Veterans' Affairs (VA) about a veteran's claim was final, and there was no recourse for independent judgment of an appeal. The legislation modified the existing Board of Veterans Appeals (BVA) to enhance its independence from the Veterans' Administration and established a new Court of Veterans Appeals (CVA) with jurisdiction to review BVA decisions. Veterans' benefits proceedings have not only been insulated from the courts, they also have been undesirable to private attorneys, because since 1864 Congress has prohibited attorneys from charging more than $10 to advocate a VA disability claim. The new law allows attorneys to represent veterans before the CVA and receive appropriate remuneration. In 1991, the number of veterans was estimated at 26,897,000, and VA disability compensation programs spent $9.6 billion. Currently, there are about 2,179,000 veterans receiving service-connected monetary compensation; approximately 13.5 percent (293,200) have a primary psychiatric disability. The CVA is a specialized Article I court that has seven justices and sits in Washington, D.C. In its formative years, the Court has reached decisions that have had an impact on the veterans' psychiatric benefits examination process. Now more than ever, non-VA psychiatrists may be asked to offer probative opinions in veterans' benefits proceedings. The authors review VA psychiatric disability procedures and, using case examples, discuss both precedent decisions involving VA psychiatric claimants and the evolving standards of judicial review.


Quantitative significance of hypoxic vasoconstriction in the ferret lung.
Stimulus-response curves for the pulmonary vascular bed to alveolar hypoxia have been measured in ferrets under conditions of perfusion either at constant pressure or a constant flow in vivo or in isolated lungs. In all circumstances the relationship between alveolar oxygen tension and the fall in blood flow or rise in pulmonary artery pressure was sigmoid although there were important differences between the in vivo and in vitro preparations. The significance of these observations in constant pressure and constant flow preparations in relation to pulmonary hypertension and ventilation/perfusion regulation is discussed.


Transplacental passage and fetal kidney binding of 14C-dichlorovinyl cysteine (DCVC) in mice.
In order to assess the potential hazard of the nephrotoxic compound S-1,2-dichlorovinyl-L-cysteine (DCVC) during gestation, studies on its disposition and degenerative effects were performed in pregnant mice. In late gestation, binding of 14C-DCVC (spec. act. 1.01 microCi/mumol) equivalents was observed by autoradiography in the inner cortex of the kidney, in the liver and gastrointestinal tract of the fetuses. The uptake of radioactivity in the fetal kidney increased from day 13 to day 18 of gestation when measured by liquid scintillation. When fetuses were injected in utero, a distinct binding of 14C-DCVC was present in the kidney cortex. This fact suggests that bioactivation occurs in situ, as the reactive products are not likely to be transported far from their site of formation. The concentration of radioactivity in the fetal kidney at day 18 of gestation was about 10% of that found in the maternal kidney. Limiting factors for fetal kidney uptake may be both transplacental transfer, and renal bioactivation and transport activities. No distinct histopathological changes in the fetal kidney were observed when a nephrotoxic dose (25 mg/kg) of DCVC was given to the dam. These results suggest that the fetal kidney during late gestation is able to activate and bind DCVC. However, the degree of fetal binding seems too low to cause any visible histopathological effects.


Laparoscopic Davydov Procedure for the Creation of a Neovagina in Patients with Mayer-Rokitansky-Kuster-Hauser Syndrome: Analysis of 7 Cases.
Several surgical techniques have been described for creating a neovagina in patients with Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome, however as yet there is no standardized treatment. The aim of this report is to assess anatomic and functional outcomes after the laparoscopic Davydov procedure for the creation of a neovagina in patients with MRKH syndrome. Seven patients with MRKH syndrome underwent the laparoscopic Davydov technique from January 2005 to August 2010. The anatomic and functional results were evaluated after 3, 6, 12, 24, 36, 48, and 60 months. The surgical procedure was performed with no major complications except in one case in which an intraoperative bladder injury occurred and was successfully corrected. The mean duration of surgery was 162.9 minutes (range, 120-230 min). Mean lengths/widths (cm) of the neovagina were 6.4/2.6, 6.5/2.5, 6.5/2.8, 6.4/2.8, 7.1/2.8, and 7.2/2.8 at 3, 6,12, 24, 36, 48, and 60 postoperative months, respectively. The laparoscopic Davydov procedure seems to be a safe and effective surgical treatment for patients with MRKH syndrome if postoperative intermittent self dilation was done.


Rapid clot removal for acute stroke therapy: technical case report.
Endovascular therapy for acute ischemic stroke offers hope to those patients who do not meet the strict inclusion criteria for intravenous tissue plasminogen activator. Because no approach or device can be optimal for every patient, it is desirable to have options. This case is the first report on a novel retrieval device which proved to be very effective in our patient. A 69-year-old woman with an acute ischemic stroke was excluded from treatment with intravenous tissue plasminogen activator because of an elevated international normalized ratio. We successfully treated this patient endovascularly using a device newly approved by the Food and Drug Administration. We achieved rapid recanalization and an excellent clinical outcome. Using a new retrieval device, we were able to rapidly and successfully treat an acute ischemic stroke in a patient not eligible for intravenous thrombolysis. This may offer another alternative in endovascular acute stroke therapy.


The impact of domestic violence on the maternal-child relationship and preschool-age children's functioning.
Although preschool-age children are at risk for witnessing domestic violence, the majority of research has focused on children ages 6 to 12 years. This study examines the mediating role of the mother-child relationship on preschool-age children's functioning in families experiencing domestic violence. Maternal report and behavioral observations of mother-child interactions were used to assess relationship quality. Participants consisted of 103 children and their mothers. The data fit the model well but indicated that some of the correlations were not in the expected direction. Although depressed mothers were struggling with parenting, other mothers appeared to be compensating for the violence by becoming more effective parents. Domestic violence negatively impacted children's behavior with their mothers in interactions but did not influence maternal report of problem behaviors, suggesting that the impact of domestic violence begins very early and in the realm of relationships rather than in mental health.


BMI and hyperinsulinemia in children.
Overweight is associated with hyperinsulinemia in adults and children. The aim of our study was to test if body mass index (BMI) alone or in combination with waist circumference (WC) predicts hyperinsulinemia in individual children. In 466 healthy German schoolchildren aged 7 to 12 years enrolled in the population based PEP Family Heart Study, anthropometric data, standard laboratory data and fasting serum insulin concentrations were assessed. Among children with hyperinsulinemia (fasting serum insulin concentrations>85th age specific percentile), 56% were not overweight (BMI-for-age<85th percentile). Among overweight children, 54% were normoinsulinemic. Increased waist circumference (WC for age and gender>85th percentile) was not a better predictor of hyperinsulinemia, neither alone nor in combination with BMI. Overweight and abdominal obesity are poor indicators of hyperinsulinemia in individual German school children aged 7 to 12 years. Insulin measurement seems to be necessary to reliably detect hyperinsulinemia.


Results of treatment of ocular toxoplasmosis with injectable corticosteroids.
Sixty-seven patients with toxoplasmic retinochoroiditis who were treated with periocular injections of depot forms of corticosteroids were studied in an attempt to determine (1) whether patients who did poorly on this regimen could be differentiated predictively from those who responded in a more favorable fashion, and (2) whether a treatment regimen that would allow the safe use of periocular depot corticosteroids in patients with toxoplasmic retinochoroiditis could be delineated. The study did not reveal any reliable way of predicting which patients would be good risks for the use of periocular injections of depot corticosteroids. It does suggest that the concurrent use of antitoxoplasma agents might protect patients in such a way that periocular depot corticosteroids would not worsen their disease. For the reasons outlined, the use of periocular injections of depot corticosteroids in toxoplasmic uveitis must be approached with great caution in the future.


Tumor necrosis factor-alpha and interferon-gamma, but not HTLV-I tax, are likely factors in the epidermotropism of cutaneous T-cell lymphoma via induction of interferon-inducible protein-10.
We have previously shown that Interferon-Inducible Protein-10 (IP-10), a cytokine chemotactic for CD4-positive lymphocytes, is overexpressed by lesional epidermal keratinocytes and probably accounts for the epidermotropism of cutaneous T-cell lymphoma (CTCL). The tax gene of human T-lymphotropic virus-I (HTLV-I) immortalizes CD4-positive lymphocytes, induces IFN-gamma, and has been detected in patients with classical CTCL who are seronegative for HTLV-I. TNF-alpha is synergistic with IFN-gamma for the induction of IP-10. We therefore decided to define the presence of tax, IFN-gamma, TNF-alpha, and IP-10 in lesions of 19 adults with classical CTCL who were seronegative for HTLV-I. Lesional mRNAs for actin, TNF-alpha, IFN-gamma, and tax were detected by reverse-transcriptase polymerase chain reaction (RT-PCR) amplification. In addition IP-10, TNF-alpha, and IFN-gamma were detected and localized with immunocytochemistry of frozen sections. In agreement with previous observations IP-10 was overexpressed in lesional keratinocytes of all 19 patients. By RT-PCR, mRNA for IFN-gamma was detected in lesions of 8, and for TNF-alpha in lesions of 13 patients. By immunocytochemistry, TNF-alpha was expressed by lesional keratinocytes in 10 of 13 tested patients, whereas IFN-gamma was focally expressed by lesional lymphocytes and faintly by lesional keratinocytes in 9 of 13 tested patients. tax mRNA was not detected in lesions of any patient, but was easily detectable in cutaneous lesions or peripheral blood of control patients who were seropositive for HTLV-I. We conclude that TNF-alpha and IFN-gamma may cause epidermotropism by inducing IP-10. However, the tax gene of HTLV-I does not appear to be involved in the pathogenesis of classical CTCL.