Dietary calcium modulates Mycobacterium paratuberculosis infection in beige mice.
A 6-month study was conducted to evaluate the effects of feeding different levels of dietary calcium (Ca) on the persistence of Mycobacterium paratuberculosis infection using a mouse model. Beige mice, averaging 8 weeks of age, were randomly assigned to one of the following dietary treatments: 1) 0.02% Ca, 2) 0.15% Ca, 3) 0.45% Ca, and 4) 1.0% Ca. Mice were infected intraperitoneally with 10(8) CFU viable M. paratuberculosis for 1, 3, and 6 month periods. Plasma Ca levels was unaffected by dietary Ca (x = 7.3 mg/dl). Plasma levels of 1,25(OH)2D3 was elevated significantly in 0.02% and 0.15% Ca groups compared to other treatments at the end of each period, with the highest levels observed for 0.02% Ca mice and intermediate values for 0.15% Ca mice. One month after infection, numbers of viable M. paratuberculosis cultured from the spleen were significantly reduced for 0.15% Ca mice, whereas the number of bacteria isolated from the liver and mesenteric lymph node (MLN) were higher for the 0.02% Ca group. There were no differences in bacterial numbers in the ileum although they tended to be higher for the 0.02% Ca group. Three months after infection, bacterial numbers in the spleen, ileum, and MLN did not differ across treatments, however, significantly lower numbers were found in the liver of 1.0% Ca mice. Reduced bacterial counts were also observed in the liver of 0.15%. 0.45%, and 1.0% Ca mice after a 6-month infection period compared to the 0.02% Ca group, with the lowest numbers isolated from the 1.0% Ca mice. Numbers of viable bacteria cultured from the ileum and MLN after 6 months of infection were also significantly reduced in 1.0% Ca mice. These results suggest that Ca metabolism is an important modulator of M. paratuberculosis infection.


PIM1 encodes a mitochondrial ATP-dependent protease that is required for mitochondrial function in the yeast Saccharomyces cerevisiae.
The PIM1 nuclear gene in the yeast Saccharomyces cerevisiae encodes a mitochondrial ATP-dependent protease that exhibits over 30% identity with ATP-dependent protease La from Escherichia coli, Lon from Bacillus brevis, and one from Myxococcus xanthus. In addition, Pim1 is 1133 amino acids long and has a putative mitochondrial import signal in the N-terminal region. Enzymatic comparisons of normal PIM1+ and deficient pim1-delta strains revealed that the ATP-dependent protease is located within the mitochondrial matrix. The pim1-delta strains are unable to utilize nonfermentable substrates as the sole carbon source and are unable to maintain functional mitochondrial DNA, indicating that the Pim1 protease is required for mitochondrial function. PIM1 mRNA is constitutively expressed but is increased after thermal stress, suggesting that Pim1 may play a role in the heat shock response.


[Quality assurance programs through the accreditation of hospitals in Latin America and the Caribbean].
The majority of the approximately 14,000 hospitals in Latin America and the Caribbean face enormous challenges to live up to the basic prepositions of quality assurance in health care. If methods of quality control in medical education and hospitals are not implemented soon in Latin America, we will face, in the very near future, the same situation that has marred the quality of medical care in the U.S. This could turn our health care environment in Latin America into a controversial reality, just as vulnerable to malpractice lawsuits. This situation should be avoided at all costs, before the current absence of quality control favors financial external forces over the implementation of self-assessment methods or external control by accreditation commissions. The following conditions are needed for the effective development of quality assurance programs; a) professional technical skills; b) efficient use of resources; c) reduction to a minimum of lesions derived from services; d) patient satisfaction in his requirements, expectations and accessibility to health services, and e) local health systems, where comprehensive outpatient and inpatient services are provided.


Manipulating immune cells for adoptive immunotherapy of cancer.
The immune system can be induced to respond against cancer with some success reported in clinical trials using a range of approaches including vaccines and antibodies. In addition to these approaches, cell based therapies are demonstrating much promise as potential therapies for cancer. In cell therapies autologous patient leukocytes are isolated and manipulated in vitro before transfer back to the patient in adoptive transfer regimens. The majority of approaches utilize conventional T cells or dendritic cells, but a wide variety of other types of leukocytes exist which can possess anti-cancer activity. In this review, we present a brief overview of T cell adoptive cell transfer followed by a review of approaches using alternate lymphocyte subsets and other leukocytes including neutrophils, macrophages and eosinophils.


Changes in the plasma membrane surface of lymphocytes stimulated in vivo with DNCB.
Stereological principles have been used to evaluate ultrastructural changes which accompany the transformation of lymphocytes stimulated in vivo with dinitrochlorobenzene (DNCB). Whereas unstimulated lymphocytes and blast cells have slightly more than the minimal containing plasmalemmal surface for their volume, stimulated (blast-derived) lymphocytes have an excess surface area in the order of 30%. This observation is discussed in the context of altered cell function and the biosynthesis of additional membrane components.


Potential radiological impact of the phosphate industry on wildlife.
The activities of the phosphate industry may lead to enhanced levels of naturally occurring radioactivity in terrestrial and aquatic ecosystems. We performed a preliminary environmental risk assessment (ERA) of environmental contamination resulting from the activities of 5 phosphate fertiliser plants (located in Belgium, Spain, Syria, Egypt, Brazil), a phosphate-mine and a phosphate-export platform in a harbour (both located in Syria). These sites were selected because of the availability of information on concentrations of naturally occurring radionuclides in the surrounding environments. Assessments were generally performed considering highest environmental concentrations reported in the studies. The ERICA Tool, operating in a Tier 2 assessment mode, was used to predict radiation dose rates and associated risk to the selected reference organisms using the ERICA default parameter setting. Reference organisms were those assigned as default by the ERICA Tool. Potential impact is expressed as a best estimate risk quotient (RQ) based on a radiation screening value of 10 μGy h(-1). If RQ ≤ 1, the environment is considered unlikely to be at risk and further radiological assessment is not deemed necessary. Except for one of the cases assessed, the best estimate RQ exceeded 1 for at least one of the reference organisms. Internal exposure covered for 90-100 % of the total dose. (226)Ra or (210)Po were generally the highest contributors to the dose. The aquatic ecosystems in the vicinity of the phosphate fertiliser plants in Tessenderlo (Belgium), Huelva (Spain), Goiás (Brazil) and the terrestrial environment around the phosphate mine in Palmyra (Syria) are the ecosystems predicted to be potentially most at risk.


HIV-1 co-receptor CCR5 and CCR2 mutations among Greeks.
The frequency of CCR5 and CCR2 alleles in human immunodeficiency virus (HIV)-positive and HIV-negative populations of Northern Greece was investigated. The frequency of the CCR5Delta32 allele among the HIV-negative subjects was 0.052, while it was approximately two-fold lower among the seropositives, suggesting that the heterozygous genotype confers a partial resistance to the HIV infection. No significant difference in CCR2 allele frequency between the two groups was observed.


Changes in mammary uptake of free fatty acids, triglyceride, cholesterol and phospholipid in relation to milk synthesis during lactation in goats.
Uptake of free fatty acids (FFA), triglycerides (TG), cholesterol (CHOL) and phospholipids (PL) was measured in both mammary glands of dairy goats during lactation. Arterial concentrations of TG, CHOL and PL as well as arterio-venous difference (AV) and extraction rate (E) for TG were highest in goats with the highest dietary feed intake. AV were linearly related to arterial concentrations for the four lipid classes, and arterial concentrations of CHOL were linearly related to output of lactose, protein and fat in milk. Arterial supply, and not mammary synthetic activity, is the main determinant of mammary FFA, TG and CHOL uptake.


[Arthroscopic treatment of tibial plateau fractures].
The aim of arthroscopically assisted treatment of tibial plateau fractures is to achieve minimally invasive reduction and internal fixation of the joint fracture of the tibial plateau. Using the arthroscopic procedure, both the approach morbidity and the control of the articular reduction can be optimized. Displaced tibia plateau fractures of AO type A1 and B1/2/3 or Tscherne P2. Strongly displaced tibial plateau fractures, which require an open surgical approach and stabilization with plate fixation (e.g., AO type C fractures or Moore type 5 fractures); 2nd and 3rd degree open fractures. Danger of compartment syndrome. Planning of the surgical approach and confirmation of the indication by CT imaging. Diagnostic arthroscopy of the knee joint with treatment of associated injuries and confirming the indications for arthroscopically assisted reduction. Under arthroscopic control, insertion of an ACL tibial aiming device. In the central portion of the dislocated fracture fragment, a 2.4 mm K-wire is placed with the help of the aiming device. Opening of the outer cortex using a cannulated drill (9-11 mm diameter), introduction of a cannulated plunger below the fracture resulting in reduction of the fracture and compression of the cancellous bone below the fracture. Simultaneously the reduction is controlled by arthroscopy. Finally, the fracture is fixed using minimally invasive screw fixation (3.5-7.3 mm cancellous screws with washers) or by plate osteosynthesis (e.g., support plate). The metaphyseal defect can optionally be filled with bone substitute material. Rehabilitation is dependent on the extent of the fracture. In arthroscopically treated fractures, partial weight bearing of 20 kg over a period of 6-12 weeks is usually necessary.


Circular RNA In Invasive and Recurrent Clinical Nonfunctioning Pituitary Adenomas: Expression Profiles and Bioinformatic Analysis.
The invasion and recurrence of clinical nonfunctioning pituitary adenomas (NFA) often lead to surgical treatment failure. Circular RNAs (circRNAs) are a novel class of RNAs whose 3' and 5' ends are joined together and have been shown to play important roles in cancer development. Until now, the roles of circRNAs have remained unclear in invasive and recurrent NFA. We detected and summarized the circRNA expression pattern in 75 NFA tissues from 10 noninvasive cases and 65 invasive cases and 9 pairs of NFA tumor tissues from 9 recurrent cases by circRNA microarrays. Accordingly, functional enrichment analysis and pathway analysis were performed and the circRNA-microRNA (miRNA) network was generated by bioinformatic analysis tools. Five new invasive NFA samples and 5 noninvasive NFA samples were collected to measure the microarray results. A total of 570 dysregulated circRNAs (invasive tumor vs. noninvasive tumor) and 10 upregulated circRNAs (recurrent tumor tissue vs. first surgery tumor tissue) were identified based on the situation (fold change >2; P < 0.05). The parental genes of the dysregulated circRNAs in the comparison between invasion tumor and noninvasion tumor were found to be enriched in some cell adhesion signaling pathways such as Focal adhesion, Hippo signaling pathway, PI3K-Akt signaling pathway, and Adherens junction. The circRNA-miRNA network showed that the dysregulated circRNA may function as miRNA sponges. This is the first study to conduct and comprehensively analyze the circRNA expression profile in invasive and recurrent NFA. Our finding will provide evidence for the significance of circRNAs in NFA diagnosis, prognosis, and clinical treatment.


Quantifying the cepstral peak prominence, a measure of dysphonia.
The purpose of this study is to establish normative values for the smoothed cepstral peak prominence (CPPS) and its sensitivity and specificity as a measure of dysphonia. Prospective cohort study. Voice samples of running speech were obtained from 835 patients and 50 volunteers. Eight laryngologists and four speech-language pathologists performed perceptual ratings of the voice samples on the degree of dysphonia/normality using an analog scale. The mean of their perceptual ratings was used as the gold standard for the detection of the presence or absence of dysphonia. CPPS was measured using the CPPS algorithm of Hillenbrand, and the cut-off value for positivity that has the highest sensitivity and specificity for discriminating between normal and severely dysphonia voices was determined based on ROC-curve analysis. The cut-off value for normal for CPPS was set at 4.0 or higher, which gave a sensitivity of 92.4%, a specificity of 79%, a positive predictive value of 82.5%, and a negative predictive value of 90.8%. The area under the receiver operating characteristic (ROC) curve was 0.937 (P < 0.05). CPPS is a good measure of dysphonia, with the normal value of CPPS (Hillenbrand algorithm) of a running speech sample being defined as a value of 4.0 or higher.


Replacement by homologous recombination of the minK gene with lacZ reveals restriction of minK expression to the mouse cardiac conduction system.
The minK gene encodes a 129-amino acid peptide the expression of which modulates function of cardiac delayed rectifier currents (IKr and IKs), and mutations in minK are now recognized as one cause of the congenital long-QT syndrome. We have generated minK-deficient mice in which the bacterial lacZ gene has been substituted for the minK coding region such that beta-galactosidase expression is controlled by endogenous minK regulatory elements. In cardiac myocytes isolated from wild-type neonatal mice, IKs is rarely recorded, while IKr is common. In minK (-/-) myocytes, IKs is absent and IKr is significantly reduced and its deactivation slowed; these results further support a role for minK in modulating both IKs and IKr. Despite these changes, ECGs in (+/+) and (-/-) animals are no different at adult and at neonatal stages. ECG responses to isoproterenol are also similar in the 2 groups. beta-Galactosidase staining in postnatal minK (-/-) hearts is highly restricted, to the sinus-node region, caudal atrial septum, and proximal conducting system. Moreover, as early as embryonal day 11, segmentally restricted beta-galactosidase expression is observed in the portions of the sinoatrial and atrioventricular junctions that are thought to give rise to the conducting system, thereby implicating minK expression as an early event in conduction system development. More generally, the restricted nature of minK expression in the mouse heart suggests species-specific roles of this gene product in mediating the electrophysiological properties of the heart.


Pharmacokinetics of ethyl biscoumacetate and its metabolite 7-hydroxy ethyl biscoumacetate in healthy volunteers.
Disposition kinetics of ethyl biscoumacetate and its metabolite 7-hydroxy ethyl biscoumacetate were evaluated in ten healthy volunteers, after a single 300 mg oral dose of ethyl biscoumacetate. Serum concentrations of parent compound and its metabolite were measured by HPLC. The maximum serum ethyl biscoumacetate concentrations were reached 1.0-4.0 hours after drug dosing. From 3 hours after drug administration the concentration of the metabolite was always higher than the concentration of the parent compound. Geometric mean of elimination half-life was 0.66 hours for ethyl biscoumacetate and 2.03 hours for the 7-hydroxy ethyl metabolite.


In situ carcinoma in branchial cysts.
Two cases of in situ squamous cell carcinoma in the epithelium of a branchial cyst are described. These are the only cases reported that fulfill the established criteria for in situ branchial carcinomas.


The organization of the lateral posterior nucleus in neonatal golden hamsters.
The present series of experiments was designeneonatal golden hamsters.


Recurrent hepatitis C virus infection after liver transplantation: immunohistochemical assessment of the viral antigen.
The value of immunohistochemical methods to identify hepatitis C virus antigen (HCVAg) in liver tissue has not been established. We have evaluated the significance of HCVAg expression in livers of patients with transplants and recurrent hepatitis C virus (HCV) infection. Forty-two liver biopsy specimens from 32 liver-transplant recipients with recurrent HCV infection were tested for HCVAg using fluorescein isothiocyanate-labeled polyclonal, polyreactive human immunoglobulin. Histologic assessment of liver and quantitation of HCV RNA in sera were carried out in specimens obtained simultaneously with biopsies. HCVAg was found in 33% of the liver specimens obtained during the first month after transplantation and in all liver specimens obtained between 1 and 18 months after transplantation. Amounts of the antigen were significantly greater in specimens obtained more than 1 month after transplantation. A statistically significant increase of the average HCV RNA level in serum was observed in samples tested after the first month after the transplantation, and some decrease in the HCV RNA level was found in those obtained between 6 and 18 months after transplantation. Larger amounts of HCVAg were observed in specimens corresponding to episodes of acute or chronic hepatitis than in those associated with minimal parenchymal evidence of rejection. OBSERVATIONS of HCVAg expression in liver biopsy specimens indicated that the presence of viral antigens in hepatocytes is a constant finding in specimens obtained 1 month or longer after transplantation. Although large amounts of HCVAg correlated with acute or chronic hepatitis, the nature of this association with the development of pathologic changes remains to be established.


Stability of concentrated trimethoprim-sulfamethoxazole admixtures.
The stability of trimethoprim-sulfamethoxazole (TMP-SMX) at various concentrations in 5% dextrose injection or 0.9% sodium chloride injection was studied. Appropriate volumes of TMP-SMX formulation (80 mg TMP and 400 mg SMX/5 mL) were mixed with 5% dextrose injection or 0.9% sodium chloride injection to provide dilutions of 1:25 v/v, 1:20 v/v, 1:15 v/v, and 1:10 v/v. Aliquots were removed at 0, 0.5, 1, 2, 4, 8, 14, 24, and 48 hours and filtered. The pH of the samples was determined, and the samples were assayed for trimethoprim and sulfamethoxazole content by high-performance liquid chromatography. Admixtures were visually inspected for precipitate before each sample was removed. The concentration of SMX in all admixtures did not change during the study period. The stability of TMP was dependent on concentration and vehicle. At a 1:25 v/v dilution, TMP was stable for 48 hours in 5% dextrose injection and 0.9% sodium chloride injection. At a 1:20 v/v dilution, TMP was stable for 24 hours in 5% dextrose injection and 14 hours in 0.9% sodium chloride injection. At a 1:15 v/v dilution, TMP was stable for four hours in 5% dextrose injection and two hours in 0.9% sodium chloride injection. At a 1:10 v/v dilution, TMP was stable for one hour in 5% dextrose injection and 0.9% sodium chloride injection. Concentrated solutions of TMP-SMX should be prepared in 5% dextrose injection, infused within one hour of preparation, and visually inspected for precipitation before and during infusion.


[THE STATE AND PERSPECTIVES OF DEVELOPMENT OF TRAUMATOLOGICAL ORTHOPEDIC OUT-PATIENT CARE TO POPULATION OF THE PRIVOLJSKII FEDERAL OKRUG].
The article presents the results of analysis ofmanpower support of specialized out-patient traumatological orthopedic care in the Privoljskii federal okrug. The manpower deficiency of traumatologist-orthopedist at the out-patient stage was established especially especially in rural area. This is cause of low indicators ofdispensary monitoring of patients with consequences of traumas and diseases of musculo-skeletal system and factual unavailability of rehabilitation care to patients of given profile. The experience oftraining and re-training of traumatologist-orthopedist is presented. The organization of hospital-substituting forms of medical service of profile patients in the Saratovskaia oblast. The directions of development of organization of specialized out-patient care to population of the region.


Ultrastructural mechanisms of macrophage-induced demyelination in CIDP.
Chronic inflammatory demyelinating polyneuropathy (CIDP) is a form of chronic neuropathy that is presumably caused by heterogeneous immune-mediated processes. Recent advances in the search for autoantibodies against components expressed at nodal regions, such as the nodes of Ranvier and paranodes, have substantially contributed to clarifying the pathogenesis of CIDP in a subpopulation of patients. In particular, immunoglobulin G4 (IgG4) antibodies to paranodal junction proteins, including neurofascin-155 and contactin-1, have attracted the attention of researchers. Paranodal dissection resulting from the attachment of IgG4 at paranodal junctions and the absence of macrophage-induced demyelination are characteristic pathologic features in patients who have these antibodies. By contrast, the mechanisms of neuropathy in cases with classical macrophage-induced demyelination remain unclear despite the long-standing recognition of this process in CIDP. In addition to complement-dependent damage provoked by autoantibodies, recent studies have shed light on antibody-dependent phagocytosis by macrophages without participation of complements. However, a direct association between specific autoantibodies and macrophage-induced demyelination has not been reported. Electron microscopic examination of longitudinal sections of sural nerve biopsy specimens suggested that macrophages recognize specific sites of myelinated fibers as the initial target of demyelination. The site that macrophages select to initiate myelin breakdown is located around the nodal regions in some patients and internode in others. Hence, it seems that the components that distinguish between the nodal regions and internode play a pivotal role in the behavior of macrophages that initiate phagocytosis of myelin. Further studies are needed to elucidate the mechanisms underlying macrophage-induced demyelination from this perspective.


Derivation and analytic evaluation of an equivalence relation clustering algorithm.
Clustering algorithms have been recently used in multitarget multisensor tracking (MMT) problems in order to reduce the size of the data association problem. This paper derives an equivalence relation (ER) clustering algorithm used in a MMT problem and briefly compares it to other clustering schemes such as the nearest neighbor method. The main contribution of this work is the analytical evaluation of ER clustering performance, in the context of multitarget multisensor tracking, as a function of the distance between targets, measurement probability density function, and cluster parameter.


Quantitative prediction of protein folding behaviors from a simple statistical model.
The statistical nature of the protein folding process requires the use of equally detailed yet simple models that lend themselves to characterize experiments. One such model is the Wako-Saitô-Muñoz-Eaton model, that we extend here to include solvation effects (WSME-S), introduced via empirical terms. We employ the novel version to analyze the folding of two proteins, gpW and SH3, that have similar size and thermodynamic stability but with the former folding 3 orders of magnitude faster than SH3. A quantitative analysis reveals that gpW presents at most marginal barriers, in contrast to SH3 that folds following a simple two-state approximation. We reproduce the observed experimental differences in melting temperature in gpW as seen by different experimental spectroscopic probes and the shape of the rate-temperature plot. In parallel, we predict the folding complexity expected in gpW from the analysis of both the residue-level thermodynamics and kinetics. SH3 serves as a stringent control with neither folding complexity nor dispersion in melting temperatures being observed. The extended model presented here serves as an ideal tool not only to characterize folding data but also to make experimentally testable predictions.


Arithmetic word problem solving: evidence for the construction of a mental model.
In the first experiment reported here, adults were given an unexpected task of problem recognition after a resolution task. During the recognition task, participants were presented with the original problems, inconsistent problems that had never been solved, and paraphrases, which respected the relational structure of the original problems but not their exact wording. More precisely, paraphrases were constructed by inversing the terms and the linguistic expressions in the original problems. Whereas the literal form of paraphrastic problems bore the least resemblance to original problems, paraphrastic problems were associated to higher recognition rates than inconsistent problems. A second experiment ruled out the interpretation that this result was due to a mere remembering of the exact values used in the problem text. Taken together, these results provide evidence that a non-propositional representation is built by individuals to solve arithmetic word problems and suggest that a mental model is constructed (Johnson-Laird, 1983).


Effects of mechanical and osmotic pressure on the rate of glycosaminoglycan synthesis in the human adult femoral head cartilage: an in vitro study.
We studied the effects of mechanical and osmotic compression on sulphate incorporation into glycosaminoglycans of human femoral head cartilage. We found that both mechanical and osmotic compression produce the same lowering of sulphate uptake relative to uncompressed controls. It appears that this effect is not associated with changes in solute transport or changes in solute concentration in the matrix, but is due, in part at least, to an increased osmotic pressure acting on the chondrocytes. A second mechanism of action might be involved directly through the increased proteoglycan concentration in the pericellular environment, resulting from a reduction in the water content. We also found that glycosaminoglycan synthesis returned to its control level when the conditions prevailing in the matrix, in the absence of pressure or added solute, were restored.


Modulation of the motion aftereffect by selective attention.
The motion aftereffect is a much studied and well documented phenomenon. After viewing a moving visual pattern for a period of time, the same pattern appears to drift in the opposite direction when it is stopped. Psychophysical experiments involving interocular transfer, dichoptic stimulation, and motion aftereffects contingent upon other visual parameters such as colour, orientation and texture, imply that the motion aftereffect is generated at the level of the visual cortex. It has been hypothesized that cortical neurons specialized for the detection of motion along a particular direction become 'fatigued' during the adaptation period so that the resting equilibrium subsequently shifts in the opposite direction to that of the adapting stimulus, giving rise to the sensation of the aftereffect. I have found that if observers are engaged in a separate discrimination task superimposed on a moving textured background, the subsequent motion aftereffect to the background is considerably reduced. It seems that motion aftereffects are susceptible to attentional mechanisms.


Toxicity equivalents and EPA's risk assessment of 2,3,7,8-TCDD.
Toxicity equivalent factors (TEFs) have proved useful in estimating the toxicity of complex mixtures of chlorinated dibenzo-p-dioxins and dibenzofurans (CDDs/CDFs). An international consensus has formed around a specific set of TEF values as interim solution for addressing environmental contamination by CDDs/CDFs. This procedure capitalizes on the congener-specific analytical results that are more routinely available in recent years. The TEF approach should be updated as necessary and replaced by more definitive bioassay approaches as soon as practicable. In an independent activity, the USEPA considered a proposal to change (reduce) the cancer potency ascribed to 2,3,7,8-TCDD by a factor of 16. The recommendation was based upon an analysis of the literature and the Agency's earlier risk assessment. The proposal was reviewed by the Science Advisory Board, a group of outside scientific advisors. Subsequently, the Agency decided against making any changes in its assessment at this time. However, it is likely that a reassessment will be conducted shortly that will incorporate new data and a new approach to estimating of cancer risks posed by 2,3,7,8-TCDD.


[The clinical picture and diagnosis of pancreatic carcinoma].
A total of 97 patients with pancreatic carcinoma were examined with sonography, computed tomography of the pancreas and endoscopy of the stomach and duodenum. The tumor involved mainly the head of the pancreas in 69 (71.1%), the body in 21 (21.7%) and the tail in 7 (7.2%) patients. Two basic types of the disease were identified: disseminated in 83 patients and rare in 14 patients. The disseminated type included a central (45 patients) and a peripheral (38 patients) variant. The latter is classed as peripheral (n = 30) and paraduodenal (n = 8). The rare types included masked variants (n = 6), miniblastomas (n = 3), megablastomas (n = 2) of the pancreas, as well as thrombotic variants of the disease (n = 3). The highest diagnostic value of sonography and computed tomography was observed in intrinsic peripheral variants of carcinoma. Gastroduodenal endoscopy along with biopsy of suspected segments is highly diagnostic in paraduodenal variants of the disease.


[Atypical presentation of a carcinoid syndrome].
A 76-year-old woman presenting with right heart failure is reported. The investigation showed an ileal carcinoid tumour with multiple metastases and tricuspid regurgitation caused by a cardiac carcinoid lesion. Echocardiographic study and histopathological examination revealed typical characteristics of carcinoid heart disease. Nevertheless, except for the cardiac symptomatology, the patient did not show any other clinical manifestation of the carcinoid syndrome. Isolated right heart failure as the first sign of a carcinoid syndrome is rare; only two other cases have been described in the literature.


Nd:YAG laser ablation of the prostate as a treatment for benign prostatic hypertrophy.
Many techniques have been used to relieve obstructive symptoms associated with benign prostatic hypertrophy. Transurethral resection of the prostate (TURP) with an electrocautery loop is the most commonly performed operation to relieve bladder neck and urethral obstruction caused by prostatic adenoma. There is increased interest in alternative therapies to reduce prostatic size for symptom relief in this condition. We describe a technique using the neodymium:YAG (Nd:YAG) laser and a 600-microns laser quartz fibre with an attached terminal gold-plated metal alloy reflector to provide reliable deep penetration into prostatic tissue for prostatic adenoma ablation. We report the first use of this technique in three patients with benign prostatic obstruction and one with localised adenocarcinoma of the prostate.


Production of podophyllotoxin using cross-species coculture of Linum flavum hairy roots and Podophyllum hexandrum cell suspensions.
Novel cross-species coculture systems using Linum flavum hairy roots and Podophyllum hexandrum cell suspensions were applied for in vitro production of podophyllotoxin. The hairy roots and suspensions were cocultured in Linsmaier and Skoog medium in dual shake flasks and dual bioreactors. In separate experiments, coniferin feeding was shown to be an effective strategy for increasing the accumulation of podophyllotoxin in P. hexandrum suspensions. Because roots of L. flavum are a natural source of coniferin, hairy roots of this species were used in coculture with P. hexandrum to provide an in situ supply of coniferin. Compared with P. hexandrum suspensions cultured alone in shake flasks or bioreactors, podophyllotoxin concentrations in cocultured P. hexandrum cells were increased by 240% and 72% in dual shake flask and dual bioreactor systems, respectively. The availability and stability of coniferin in the medium are the most likely factors limiting podophyllotoxin synthesis in coculture. Intensification of the coculture process is required to further improve total podophyllotoxin accumulation on a volumetric basis.


The course of post-traumatic amnesia: three little words.
To provide a simple means of "real time" recognition of emergence from post-traumatic amnesia (PTA). Ninety-one patients with traumatic brain injury (PBI); 53 minor (GCS 13-15), 19 moderate (GCS 9-12), 18 severe (GCS 3-8). Twenty-seven control subjects treated at two regional trauma units for their acute phase and followed in a hospital-based research institute were studied prospectively. Subjects were examined repeatedly following injury with the Galveston Orientation and Amnesia Test (GOAT) and tests of their ability to learn and retain new information. Word triplets balanced for concreteness and frequency were presented. Immediate and 24-hour recall were tested. If 24-hour recall was imperfect, recognition was tested by presenting the 3 target words and 6 distracters. The target words were then re-presented and recall was tested the next day. The time intervals to first perfect recognition and first free perfect recall were compared with the patients' first GOAT score of 75 or greater on 2 successive days. Simple line drawings of common objects were also presented to the subjects using an identical paradigm. The outcome measures were GOAT, 3-word recognition and recall, 3 picture recognition and recall. For all categories of head injury severity, the median interval to perfect free recall of words followed the achievement GOAT criterion by a significant interval. The mean GOAT scores for perfect 3-word recall and recognition corresponding to minor, moderate and severe injuries were 97, 90 and 88, and 97, 76 and 68 respectively. The recognition and recall of pictures preceded the recognition and recall of words by approximately 1 day. The orientation measures of the GOAT that contain material that the patient knew prior to injury obscure the determination of recovery of continuous memory and should be tested separately. Three-word recall which is simpler to administer than the GOAT is a more reliable measure of emergence from PTA. For patients who are dysphasic or who do not share a common language with the examiner, 3-picture recognition and recall may substitute for word recognition and recall.


Presence and differential distribution of distinct forms of immunoreactive gonadotropin-releasing hormone in the musk shrew brain.
Gonadotropin-releasing hormone (GnRH) immunoreactive cells and fibers were revealed in olfactory regions, the ventral forebrain, and in the midbrain of the musk shrew (Suncus murinus). Immunoreactive neurons in olfactory and telencephalic areas were specific for the mammalian form of GnRH. Cell bodies in the midbrain, however, cross-reacted with an antibody specific for chicken-II GnRH. High-performance liquid chromatography and radioimmunoassay analyses confirmed these results; high levels of chicken II GnRH were present in the midbrain, and mammalian GnRH was detected in both forebrain and midbrain. In addition, a third, late-eluting form of GnRH was revealed using high-performance liquid chromatography in both forebrain and midbrain of the musk shrew. Midbrain neurons containing GnRH have not been reported previously in a mammal, although mesencephalic GnRH immunoreactivity within cell bodies is common among nonmammalian vertebrates. Likewise, while multiple forms of GnRH have been reported in nonmammalian vertebrates and several metatherian species of mammals, this is the first report on multiple forms of GnRH in the brain of a placental mammal. Taken together, the findings suggest that this primitive eutherian mammal has retained the ability to produce GnRH protein in the midbrain. This feature of the GnRH system has been conserved among nonmammalian vertebrates, but appears to have been lost in modern placental mammal species. The functional significance of this group of neurons has yet to be determined.


Microscopic model of superconductivity in carbon nanotubes.
We propose the model of a manifold of one-dimensional interacting electron systems to account for the superconductivity observed in ropes of nanotubes. We rely on the strong suppression of single-particle hopping between neighboring nanotubes in a disordered rope and conclude that the tunneling takes place in pairs of electrons, which are formed within each nanotube due to the existence of large superconducting correlations. Our estimate of the transition temperature is consistent with the values that have been measured experimentally in ropes with about 100 metallic nanotubes.


Estrogen potentiates vasopressin-induced contraction of female rat aorta by enhancing cyclooxygenase-2 and thromboxane function.
To determine the roles of estrogen and constrictor prostanoids in vasopressin (VP)-induced contraction of female rat aorta, vascular reactivity to VP was determined in thoracic aortas of intact, ovariectomized, and ovariectomized + estrogen-replaced female rats in the presence of indomethacin (Indo), NS-398, SQ-29,548, or vehicle control. The effects of estrogen on vascular reactivity to the thromboxane A(2) analog U-46619 were also examined. Maximal contractile response to VP in intact female rats (5,567 +/- 276 mg/mg of aortic ring wt) was markedly attenuated by ovariectomy (2,485 +/- 394 mg; P < 0.001) and restored by estrogen replacement with 17beta-estradiol (5,059 +/- 194 mg; P > 0.1). Indo and NS-398 significantly attenuated maximal responses to VP in intact female rats to a similar extent [3,176 +/- 179 (P < 0.0001) and 3,258 +/- 152 mg (P < 0.0001), respectively]. Ovariectomy abolished and estrogen replacement restored the inhibitory effects of Indo, NS-398, and SQ-29,548. Contractile responses of rat aorta to U-46619 were significantly greater (P < 0.0001) in females (5,040 +/- 238 mg) than in males (3,679 +/- 96 mg). Ovariectomy markedly attenuated (3,923 +/- 84 mg; P < 0.01) and estrogen replacement restored (5,024 +/- 155 mg; P > 0.1) responses to U-46619 in female aortas. These data reveal that estrogen is an important regulator of the contractile responses of female rat aorta to VP, which appears to potentiate both cyclooxygenase-2 and constrictor prostanoid function in the vascular wall.


Computerized resources in language therapy with children of the autistic spectrum.
The use of computerized technology in language therapy with children of the autistic spectrum. To assess the interference of using computers and specific programs during language therapy in the functional communicative profile and socio-cognitive performance of children of the autistic spectrum. 23 children with ages ranging between 3 and 12 years were individually video recorded prior to and after a set of 10 regular language therapy sessions (i.e. a total of two video samples per subject) using computerized games according to the child's choice. The following expressions were used by the therapists to describe the children's performance during the use of computers: more attentive, more communicative initiatives, more eye contact, more interactive, more verbalizations, more attention and more action requests. Qualitative and quantitative progresses were identified, although without statistical significance. Those progresses were observed after a time period that is smaller than the usually applied to this kind of comparison and it seems to be a promising result. More controlled associations and comparisons were not possible due to the groups' heterogeneity and therefore more consistent conclusions are not possible. It was clear that the subjects presented different reactions to the use of computerized resources during language therapy.


Tackling the diversity of breast cancer related lymphedema: Perspectives on diagnosis, risk assessment, and clinical management.
Breast cancer related lymphedema (BCRL) develops as a consequence of surgical treatment and/or radiation therapy in a significant number of breast cancer patients. The etiology of this condition is multifactorial and has not yet been completely elucidated. Risk factors include high body mass index, radical surgical procedures (i.e. mastectomy and axillary lymph node dissection), number of lymph nodes removed and number of metastatic lymph nodes, as well as nodal radiation, and chemotherapy. However, these predisposing factors explain only partially the BCRL occurrence, suggesting the possible involvement of individual determinants. Despite the implementation of conservative approaches, BCRL still remains in a proportion of cases an incurable and progressive condition with major physical and psychological implications. To date, diagnostic methods and staging systems lack uniformity, leading to a possible underestimation of the real incidence of this condition, decreasing early detection and thus the possibility of an effective treatment. Several preventive and therapeutic options are available, both conservative and surgical, but are not included in a standardized intervention protocol, tailored on patient's specific characteristics. In this review, we provide a comprehensive overview of the current state-of-knowledge of BCRL management, novel advantages in the assessment of pre-operative evaluation and risk prediction and discuss strengths and weaknesses of diagnostic and treatment strategies currently accessible in clinical practice.


[A 20-year-old man with a dislocation of the great toe].
A 20-year-old student came to our Emergency Department with a dislocated great toe with interposition of the sesamoid bone on the plantair side of the proximal phalanx (Miki Type 2 dislocation). Attempts of closed reduction at the Emergency Room were unsuccessful and open reduction and K-wire fixation was performed.


[Establishment and application of TaqMan Real-Time PCR in detection and serogrouping of Neisseria meningitidis].
To establish TaqMan Real-Time PCR method for detection and identification of Neisseria meningitidis. Seven sets of primers and FAM-labeled probes targeting different genes of Neisseria meningitidis were designed and synthesized. ctrA gene was used for identification of N. meningitidis species. Six serogruops (A, B, C, X, Y, W135) of N. meningitidis were detected with following genes: sacB (A), siaD (B), siaD (C), xcbB (X), synF (Y) and synG (W135) respectively. Sensitivity and specificity of Real-Time PCR were assessed for different primers and probes. 121 cerebrospinal fluid (CSF) specimens from suspected N. meningitidis invasive meningitis cases were detected by latex agglutination test and Real-Time PCR assay simultaneously. 79 N. meningitidis isolates of different serogroups could be detected and identified by seven sets of primers and probes in this study. Real-Time PCR seemed more sensitive than standard PCR by 10(1)-10(3) times. The respective sensitivities for ctrA, sacB, siaD (B), siaD (C), xcbB, synF and synG were 8, 8, 80, 8, 8, 80, 8 genome DNA copies in each reaction. Of the 121 CSF specimens, 11 were positive for Real-Time PCR and 6 for latex agglutination test. Real-Time PCR could rapidly detect and identify N. meningitidis of different serogroups and seemed more sensitive. It could be widely used for diagnose of invasive meningitis caused by N. meningitidis.


Mineral distribution in the enamel of teeth with amelogenesis imperfecta as determined by quantitative microradiography.
The aim of the present investigation was to determine the mineral distribution in the enamel of teeth with amelogenesis imperfecta (AI) by quantitative microradiography. A further aim was to correlate the findings to clinical manifestations and inheritance patterns for AI. Included in the study were a total of 29 teeth with AI, 28 primary and one permanent, and seven unaffected teeth, five primary and two permanent. Quantitative microradiography was applied to sagittally ground sections, 70-90 microns, of the teeth. The mineral content of the enamel, expressed as percentage by volume, was lower in most of the teeth with AI than in the unaffected teeth. The largest range for the mineral distribution was found in the enamel of the variants clinically characterized by hypomineralization. These teeth showed a mineral distribution pattern that reflected an extremely low mineral content in the bulk of the enamel. In the AI teeth clinically characterized by hypoplasia, the mineral distribution pattern was similar to that of the unaffected teeth, although with larger local variations in mineral content. Apart from the teeth connected with X-linked inheritance, no differences were found among teeth with similar clinical variants connected with different inheritance patterns.


Genetic determinants of rheumatoid arthritis: the inducible nitric oxide synthase (NOS2) gene promoter polymorphism.
An association study and a linkage analysis were carried out in parallel in order to investigate the association of the inducible nitric oxide synthase (NOS2) gene promoter polymorphism with rheumatoid arthritis (RA) predisposition and/or outcome including a -954G-C mutation, a di-allelic (TAAA)(n) marker and the highly polymorphic (CCTTT). The -954G-C point mutation occurred non-polymorphic and the di-allelic (TAAA)(n) marker was not associated with RA predisposition. The (CCTTT)(n)locus showed a trend for RA association in the case-control study, however, stratification data by Class II status did not yield significant effect and overall, the family study showed no significant association nor linkage for any of the markers under study using TDT and non-parametric linkage respectively. Finally, no influence was detected regarding any of the clinical parameters tested. After evaluating for the first time the influence of NOS2 promoter polymorphism in RA, it seems to have no major effect on disease susceptibility and/or outcome.


Increased expired NO and roles of CO2 and endogenous NO after venous gas embolism in rabbits.
Venous gas embolism (VGE) is a feared complication in diving, aviation, surgery and trauma. We hypothesized that air emboli in the lung circulation might change expired nitric oxide (FeNO). A single intravenous infusion of air was given (100 mul kg(-1)) to three groups of anaesthetized mechanically ventilated rabbits: (A) one with intact NO production, (B) one with intact NO production and where end-tidal CO(2) was controlled, and (C) one with endogenous NO synthesis blockade (L: -NAME, 30 mg kg(-1)). Air infusions resulted in increased FeNO of the control group from 20 (4) [mean (SD)] ppb to a peak value of 39 (4) ppb within 5 min (P < 0.05), and FeNO was still significantly elevated [27 (2) ppb] after 20 min (P < 0.05). Parallel to the NO increase there were significant decreases in end-tidal CO(2 )(ETCO(2)) and mean arterial pressure and an increase in insufflation pressure. In group B, when CO(2) was supplemented after air infusion, NO was suppressed (P = 0.033), but was still significantly elevated compared with pre-infusion control (P < 0.05). In group C, all animals died within 40 min of air infusion whereas all animals in the other groups were still alive at this time point. We conclude that venous air embolization increases FeNO, and that a part of this effect is due to the concomitant decrease in ETCO(2). Furthermore, an intact NO production may be critical for the tolerance to VGE. Finally, FeNO might have a potential in the diagnosis and monitoring of pulmonary gas embolism.


"Walking and watching" in queer London: Sarah Waters' Tipping The Velvet and The Night Watch.
This article argues that Sarah Waters' representation of London in her historical fictions Tipping the Velvet and The Night Watch is used to delineate the gendered bodies and sexual identities of her characters. A historical summary demonstrates that female masculinity was slowly mapped onto sexual identity between the 1880s and 1940s in Britain. The article argues that Waters' "inventive" use of this history allows her to question the construction of both historical and contemporary identifications. The way that Waters' characters are constricted and liberated by London's urban landscape demonstrates the spatial and temporal contingency of both gender and sexuality.


Radiographs associated with one episode of orthodontic therapy.
Obtaining lifetime diagnostic radiation histories in head and neck cancer studies is often challenging due to the almost universal lack of centralized registries on X-ray utilization in medicine and dentistry. Both the common nature of orthodontics and the young age at which orthodontics typically occurs make it important to quantify what diagnostic radiographs are typically taken during orthodontic therapy. The aim of this study was to assess the number and type of radiographic films associated with one episode of orthodontic therapy in an educational setting. Charts stored in an orthodontic clinic at one academic setting were randomly sampled, and the type and number of radiographic examinations were tallied for the 325 individuals who were in orthodontic therapy for at least one year. Being under orthodontic therapy for one or more years was associated with a median number of seven extra-oral radiographs and twenty-four intra-oral radiographic films. The extra-oral radiographs included three panoramic radiographs and three cephalometric radiographs. Less than 10 percent of the variability was explained by factors such as age, gender, calendar year, surgical orthodontic therapy, and duration of therapy. Head and neck cancer etiology studies should take into account the ionizing radiation during episodes of orthodontic care. The substantial variability in radiographic practices in orthodontics could be reduced by research into clinical utility and by establishing guidelines.


Likelihood-Based Parameter Estimation for High-Dimensional Phylogenetic Comparative Models: Overcoming the Limitations of "Distance-Based" Methods.
Recently, a suite of distance-based multivariate phylogenetic comparative methods has been proposed for studying the evolution of high-dimensional traits, such as morphometric coordinates, gene expression data, and function-valued traits. These methods allow for the statistical comparison of evolutionary rates, assessment of phylogenetic signal, and tests of correlated high-dimensional trait evolution. Simulations reveal that distance-based comparative methods exhibit low statistical power and high Type I error under various evolutionary scenarios. Distance-based methods are also limited to relatively simple model specification (e.g., Brownian motion evolution) due to the lack of a likelihood function for parameter estimation. Here I propose an alternative method for studying high-dimensional trait evolution which overcomes some of the statistical limitations associated with distance-based methods. This framework, based on parametric bootstrapping and maximum pseudolikelihood parameter estimation, opens up the ability to estimate alternative evolutionary models, combine multiple evolutionary hypotheses, and potentially allow missing data and within-species variation. Simulations reveal that pairwise composite likelihood methods demonstrate appropriate Type I error and high statistical power, thus providing a robust framework for studying high-dimensional trait evolution. These methods are implemented in the R package phylocurve [Covariance; distance; evolutionary rate; function-valued trait; high-dimensional; morphometric; multivariate; pairwise composite likelihood; phylogenetic comparative method; phylogenetic generalized least squares; phylogenetic signal.].


Long-term atmospheric mercury wet deposition at Underhill, Vermont.
Section 112(m) of the 1990 Clean Air Act Amendments, referred to as the Great Waters Program, mandated an assessment of atmospheric deposition of hazardous air pollutants (HAPs) to Lake Champlain. Mercury (Hg) was listed as a priority HAP and has continued to be a high priority for a number of national and international programs. An assessment of the magnitude and seasonal variation of atmospheric Hg levels and deposition in the Lake Champlain basin was initiated in December 1992 which included event precipitation collection, as well as collection of vapor and particle phase Hg in ambient air. Sampling was performed at the Proctor Maple Research Center in Underhill Center, VT. The range in the annual volume-weighted mean concentration for Hg in precipitation was 7.8-10.5 ng/l for the 11-year sampling period and the average amount of Hg deposited with each precipitation event was 0.10 microg/m2. The average amount of Hg deposited through precipitation each year from 1993 to 2003 was 9.7 microg/m2/yr. A seasonal pattern for Hg in precipitation is clearly evident, with increased Hg concentrations and deposition observed during spring and summer months. While a clear trend in the 11-year event deposition record at Underhill was not observed, a significant decrease in the event max-to-monthly ratio was observed suggesting that a major source influence was controlled over time. Discrete precipitation events were responsible for significant fractions of the monthly and annual loading of Hg to the forested ecosystem in Vermont. Monthly-averaged temperatures were found to be moderately correlated with monthly volume-weighted mean Hg concentrations (r2 = 0.61) and Hg deposition (r2 = 0.67) recorded at the Vermont site. Meteorological analysis indicated the highest levels of Hg in precipitation were associated with regional transport from the west, southwest, and south during the warmer months.


A generalized analytical compliance model for transversely symmetric three-segment flexure hinges.
This paper presents a generalized compliance model for a three-segment notch flexure hinge with transverse symmetry. This flexure hinge configuration is most frequently employed in planar-motion, small-displacement compliant mechanisms. The axial and bending compliances are derived for this flexure hinge based on the compliances of two flexure components. The derivation is generalized such that it can be applied to various segment geometries. Using this open-ended model, a three-segment right elliptical corner-filleted flexure hinge design was analyzed. This geometric configuration introduces additional geometric parameters, which can be used to optimize the compliance of the flexure hinge without modifying its gross dimensions. The results of the analysis were validated in part by modifying the geometric parameters of the center segment and elliptical corner fillets to form limiting cases corresponding to several previously investigated configurations, namely right elliptical, three-segment right circular corner-filleted, and right circular geometries. Finite element analysis simulation and experimental testing were used to further validate the three-segment right elliptical corner-filleted analytical model. Additional simulations based on the analytical model were performed to highlight the influence of geometric parameters on compliances and to investigate shear effects for short flexure hinges.


Hydrogen bonding and structure of uracil-water and thymine-water complexes.
The complexes uracil-water and thymine-water have been investigated using laser ablation molecular-beam Fourier transform microwave (LA-MBFTMW) spectroscopy. Only one conformer of each complex has been observed. The spectra of the parent and several isotopically enriched species with (15)N at uracil moiety and D or (18)O at water have been measured. For uracil-water the spectra are characterized by the hyperfine structure of two (14)N nuclei. For thymine-water only the parent and (18)O-water enriched species have been observed. Their spectra are characterized by the hyperfine structure of two (14)N nuclei with an additional doubling due to the A and E states of the torsion of the methyl group. The barrier to internal rotation of the methyl group has been determined from the analysis of the spectrum. Investigation of the structure of the adducts from the rotational constants of the different isotopologues shows that the observed conformers correspond to the most stable forms in which water closes a cycle with the nucleic acid bases forming N-H(NB)...O(w) and H(W)...O=C(2) hydrogen bonds.


[Microbiological aspects and antibiotic therapy of diabetic foot infections].
IMMUNOLOGICAL AND MICROBIOLOGICAL ASPECTS OF DIABETIC FOOT INFECTIONS: Diabetic patients are at increased risk of severe skin and bone infections. Immunological disturbances are reasonable and due to altered specific and unspecific cellular immune responses. Analysis of epidemiology and microbial pathogenicity shows that staphylococci seem to be predestined to induce such infections. Staphylococcus aureus and coagulase-negative staphylococci are able to adhere to the wound ground by a sequela of mechanisms. Initial bacterial adherence is due to hydrophobicity, ion exchanges, and specific binding of bacterial adhesion molecules to cellular receptors. Moreover, staphylococci secrete polysaccharides which form a biofilm together with multilayer cell clusters. The highly structured communities within a biofilm are resistant to distinct immunoeffectors and have a decreased susceptibility to antibiotics in vivo. Assessing the severity of an infection is essential to selecting an antibiotic regimen, the mode of drug administration, and the duration of therapy. Regimens for severe and chronic infections are broader spectrum and often intravenously to obtain high drug concentrations immediately. Infections of the bone often require an antibiotic therapy for > 4 weeks, while a 1- to 2-week therapy for mild to moderate infections has been found to be effective. Because of the tremendous progress in diagnostics and therapy of diabetic foot infections, infectious complications can be successfully treated by appropriate wound care, metabolic control, and early surgical and antibiotic intervention. Bacterial biofilms involved into chronic infections are new aspects currently not visualized by clinical therapy. Besides the classic antimicrobial therapy, new concepts of an enzymatic therapy or the inhibition of bacterial "communication" (quorum sensing) are in progress and the hope for the future.


Congenital vascular tumours in the skin of horses.
Congenital vascular tumours in the skin of the legs of two horses showed histological features at biopsy which were consistent with capillary haemangioma but, at necropsy, one tumour had invaded the superficial digital flexor tendon and was therefore classified as a haemangiosarcoma.


Central melatonin receptors in red deer (Cervus elaphus).
Red deer display characteristic seasonal changes in appetite, growth, and reproduction which are mediated by the pineal hormone, melatonin, which provides a direct neuroendocrine transduction of the ambient photoperiod. To identify potential central sites of action for this hormone, [2(-125)I]iodomelatonin binding sites were localized and characterized within the cervine brain and pituitary by in vitro autoradiography. Specific binding was distributed over a number of discrete regions of the brain, including the cortex, septum, putamen, hippocampus, cerebellum, and superior colliculus. The choroid plexus, the pars tuberalis, and the pars distalis of the pituitary were also specifically labeled. Specific binding was completely abolished in the presence of 10(-7) M melatonin and inhibited in the presence of 10(-4) M GTP gamma S (guanosine-5-O-(3-thiotriphosphate)), a nonhydrolysable analogue of GTP, in the pars tuberalis, pars distalis, choroid plexus, and all neuronal regions examined apart from the hippocampus and layer III of the cerebral cortex. Inhibition of [2(-125)I]iodomelatonin binding by GTP gamma S is indicative that binding is representative of a G-protein-coupled receptor. Characterization studies showed that [2(-125)I]iodomelatonin binding was time-dependent and saturable with a dissociation constant (Kd) in the low picomolar range (approximately 10 pM). Competition studies with iodomelationin, melatonin, and N-acetylserotonin gave IC50 values similar to those previously characterized for the melatonin receptor in the ovine pars tuberalis.


Altered expression of the growth and transformation suppressor PML gene in human hepatocellular carcinomas and in hepatitis tissues.
The promyelocytic leukaemia (PML) gene, which encodes a transformation and growth suppressor, was first identified at a chromosomal translocation break point in acute promyelocytic leukaemia. To elucidate if PML may be involved in hepatocellular carcinoma (HCC), the expression of PML was analysed using immunohistochemistry in human HCC and hepatitis tissues. Our studies demonstrated overexpression of PML protein in the PML-oncogenic domain (POD) structure in 50% of HCC (11/22). Enhanced expression and cytoplasmic localisation of PML was associated with cirrhosis. Increased expression of PML was also found in liver abscesses. However, in colon metastasis to the liver, the expression of PML was moderate to low, although strong expression was seen in the surrounding interstitial cells, macrophages and lymphocytes, an indication of the inflammation process associated with tumour growth. Most interestingly, strong expression of PML was found in neoplastic cells at the periphery of the tumours, but progressively decreased in cells at the centre of the tumours, which may be associated with an altered transform phenotype or apoptosis. The altered expression of PML indicates that this nuclear protein may play an important role in cellular response to stress and inflammation, as well as in compensatory cell growth.


Sentinel lymph node biopsy in patients with malignant melanoma: analysis of post-operative complications.
This study investigates the incidence of post-operative complications and risk factors of sentinel lymph node biopsy (SLNB) in melanoma patients. A retrospective cohort study was conducted at a single cancer institution on 408 consecutive SLNBs. Fifty-five post-operative complications occurred in 39 (9.5%) patients and included: wound infection in 24 (5.9%), seroma and lymphorrhea in 15 (3.7%), wound dehiscence in seven (1.7%), lymphocele in six (1.5%) and others in three (0.7%). Univariate analysis failed to identify possible risk factors (i.e. gender, age, lymph node region, number of excised lymph nodes, Breslow index, pT levels, comorbidities, length of surgery and hospital stay). Metastatic sentinel nodes occurred in four of 135 (3%) patients with thin melanoma (Breslow <1 mm) and in 68 of 262 (25.9%) patients with Breslow >1 mm. For patients with thin melanoma in whom the incidence of lymph node metastasis is low, the reported post-operative morbidity of almost 10% of SLNB highlights the need for careful patient selection.


Medullary breast carcinoma vs. poorly differentiated ductal carcinoma: an immunohistochemical study with keratin 19 and oestrogen receptor staining.
Sixty breast carcinomas previously indexed as medullary carcinomas over a 24-year-period were reviewed and reclassified according to definitions suggested by Ridolfi et al. as typical medullary carcinoma, atypical medullary carcinoma, and non-medullary carcinoma. Paraffin sections of tumour tissue were examined by an avidin-biotin complex method using two keratin 19-specific monoclonal antibodies (BA17, DAKO and clone 170-2-14, Boehringer) and a monoclonal oestrogen receptor antibody (DAKO). For comparison 52 ductal carcinomas of grade II and grade III were immunostained as well. The results showed that all 60 tumours with medullary features and all 52 ductal carcinomas reacted moderately to strongly positive with anti-keratin 19 (Boehringer). The staining was diffuse in all cases, except one case of ductal carcinoma (grade III), which stained focally. Immunostaining with the second keratin 19 antibody (BA17) revealed similar results with positive staining in 59 (95%) cases of carcinomas with medullary features and 51 (98%) cases of ductal carcinomas. Only one case in each group did not express keratin 19 (BA17), one re-classified case of non-medullary carcinoma with neuroendocrine features and one case of ductal carcinoma of grade III. None of the 13 cases of typical medullary carcinoma were oestrogen receptor positive and only seven (12%) of the carcinomas with medullary features (2 atypical, 5 non-medullary) were oestrogen receptor positive with quantitative values from 20 to 100%. The 52 ductal carcinomas of grade II and III were oestrogen receptor positive in 56% and 47% of cases. It is concluded that keratin 19 staining is of no particular value in differentiating medullary from poorly differentiated ductal carcinoma. A carcinoma with positive oestrogen receptor staining is not likely to be a typical medullary carcinoma.


Impact of a practice guideline for patients with atrial fibrillation on medical resource utilization and costs.
Health care resource utilization is high for patients presenting with acute atrial fibrillation (AF). The potential for treatment algorithms to safely reduce resource consumption in this setting has not been prospectively evaluated. We designed and implemented a practice guideline for the management of patients presenting to the emergency department (ED) with the primary diagnosis of AF, with emphasis on appropriate cardioversion, use of oral rate-controlling medications, and expedited referral to an outpatient AF clinic. We prospectively collected clinical and resource utilization data on all such patients for 14 months before and after institution of the guideline. Institution of the guideline was associated with a decreased rate of hospital admission (from 74% to 38%), with no differences in ED return visits or hospital readmission within 30 days. No strokes or deaths were observed. This large decrease in resource utilization during the intervention phase of the study translated to an average decrease in 30-day total direct health care costs of approximately $1,400 US dollars per patient. Our clinical and cost outcomes were minimally affected after statistical adjustment for baseline differences between study groups. We conclude that the implementation of our practice guideline was feasible, safe, and effective. Widespread adoption of such practices may have large financial implications for the health care system.


Orchiectomy alone for Stage I testicular non-seminoma. A progress report on the Royal Marsden Hospital study.
Eighty-four patients with clinical Stage I non-seminomatous germ-cell testicular tumours were entered into a prospective study after orchiectomy to evaluate a policy of close surveillance without lymph node irradiation or node dissection; 16 (19%) have manifested evidence of metastatic disease and received chemotherapy. All patients in the study are alive, 3 of the 16 relapsing patients are receiving chemotherapy and the 13 who have completed it are in complete remission at 4 to 43 months (mean 21). Relapses were diagnosed at 2 to 8 months (mean 5.3 months) after orchiectomy and were not invariably associated with elevated serum markers. The relapse rate was significantly higher for malignant teratoma undifferentiated (MTU) primary tumours than malignant teratoma intermediate (MTI) (40.7 and 6.8% respectively) and preliminary data suggest that the association of MTU with vascular invasion places the patient at high risk of relapse. Pre-orchiectomy serum marker status was not a significant prognostic factor. Despite sub-optimal surgical management in 11/84 patients no example of scrotal recurrence has been encountered. It is concluded that a rigorously monitored policy of close surveillance after orchiectomy is a feasible and successful method of management in Stage I testicular non-seminoma. Further experience should allow patients requiring immediate post-orchiectomy chemotherapy to be identified.


[Emergency medicine: general principles governing the hospital management of victims of multiple trauma].
The management of the trauma victim admitted to the emergency department must be rapid and efficient. Within the first hour, vital functions must be stabilised while a systematic survey of all injuries is carried out. This survey must be as complete as possible, and depends on the patient's status and response to initial resuscitative measures. The need for urgent surgical intervention, therapeutic radiology, or other treatment modalities must be quickly established. This systematic approach, which follows a seven step sequence, can only be carried out by a well-trained team. Because at this time emergency and SMUR are often staffed with general practitioners, and because the trauma centers do not yet exist in Belgium, the application of the treatment protocol presented in this paper is a pre-requisite to quality of care for these patients. It is the only means to end, once and for all, the improvised or intuitive, and often erroneous, approach to these patients.


[Interest of ambulatory simplified acute physiology score (ASAPS) applied to patients admitted in an intensive care unit of an infectious diseases unit in Dakar].
The evaluation of patients by a scale of gravity allows a better categorization of patients admitted in intensive care unit (ICU). Our study had for objective to estimate interest of Ambulatory Simplified Acute Physiologic Score (ASAPS) applied to patients admitted in ICU of infectious diseases department of FANN hospital. It was about a descriptive and analytical retrospective study, made from the data found in patients' files admitted into the USI infectious diseases department of FANN hospital in Dakar, from January 1(st), 2009 till December 31st, 2009.The data of 354 patients' files were analyzed. The sex-ratio was 1.77 with an average age of 37.6 years ± 19.4 years old [5-94 years]. The majority of the patients were unemployed paid (39.6%). The most frequent failures were the following ones: neurological (80.5%), cardio-respiratory (16.7%). The average duration of stay was 6.2 days ± 8.2 days going of less than 24 hours to more than 10 weeks. The deaths arose much more at night (53.1%) than in the daytime (46.9%) and the strongest rate of death was recorded in January (61.5%), most low in October (26.7%). The global mortality was 48.3%. The rate of lethality according to the highest main diagnosis was allocated to the AIDS (80.5%). The average ambulatory simplified acute physiology score was 5.3 ± 3.6 with extremes of 0 and 18. The deaths in our series increased with this index (p = 0.000005). The female patients had a rate of lethality higher than that of the men people, 55.5% against 44.2% (p = 0.03). In spite of a predictive score of a high survival (ASAPS < 8), certain number of patients died (n = 105) that is 61.4% of the deaths. The metabolic disturbances, hyperleukocytosis or leukopenia when realised, the presence of a chronic disease, seemed also to influence this lethality. ASAPS only, although interesting, would not good estimate the gravity of patients, where from the necessity thus of a minimum biological balance sheet. It seems better adapted for patients with a high value (ASAPS≥8). This score when it is low, is not correlated, in our study, at a high survival rate as waited in this population.


Phase III comparison of preoperative chemotherapy compared with chemoradiotherapy in patients with locally advanced adenocarcinoma of the esophagogastric junction.
Preoperative chemotherapy is an accepted standard in the treatment of localized esophagogastric adenocarcinoma. Adding radiation therapy to preoperative chemotherapy appears promising, but its definitive value remains unknown. Patients with locally advanced (uT3-4NXM0) adenocarcinoma of the lower esophagus or gastric cardia were randomly allocated to one of two treatment groups: induction chemotherapy (15 weeks) followed by surgery (arm A); or chemotherapy (12 weeks) followed by chemoradiotherapy (3 weeks) followed by surgery (arm B). Primary outcome was overall survival time. A total of 354 patients were needed to detect a 10% increase in 3-year survival from 25% to 35% by addition of radiation therapy. The study was prematurely closed due to low accrual. The median observation time was 46 months. A total of 126 patients were randomly assigned and 119 eligible patients were evaluated. The number of patients undergoing complete tumor resection was not different between treatment groups (69.5% v 71.5%). Patients in arm B had a significant higher probability of showing pathologic complete response (15.6% v 2.0%) or tumor-free lymph nodes (64.4% v 37.7%) at resection. Preoperative radiation therapy improved 3-year survival rate from 27.7% to 47.4% (log-rank P = .07, hazard ratio adjusted for randomization strata variables 0.67, 95% CI, 0.41 to 1.07). Postoperative mortality was nonsignificantly increased in the chemoradiotherapy group (10.2% v 3.8%; P = .26). Although the study was closed early and statistical significance was not achieved, results point to a survival advantage for preoperative chemoradiotherapy compared with preoperative chemotherapy in adenocarcinomas of the esophagogastric junction.


Adsorption of hyaluronic acid on solid supports: role of pH and surface chemistry in thin film self-assembly.
Owing to its biocompatibility, resistance to biofouling, and desirable physicochemical and biological properties, hyaluronic acid (HA) has been widely used to modify the surface of various materials. The role of various physicochemical factors in HA adsorption remains, however, to be clarified. Herein, we employed quartz crystal microbalance with dissipation (QCM-D) in order to investigate HA adsorption at different pH conditions onto three substrates-silicon oxide, amine-terminated self-assembled monolayer (SAM) on gold, and carboxylic acid-terminated SAM on gold. The QCM-D experiments indicated specific pH conditions where either strong or weak HA adsorption occurs. The morphology of the adsorbed HA layers was investigated by atomic force microscopy (AFM), and we identified that strong HA adsorption produced a complete, homogenous and smooth HA layer, while weak HA adsorption resulted in rough and inhomogeneous HA layers. The observed specifics of the kinetics of HA adsorption, including a short initial linear phase and subsequent long non-linear phase, were described by using a mean-field kinetic model taking HA diffusion limitations and reconfiguration in the adsorbed state into account. The findings extend the physicochemical background of design strategies for improving the use of passive HA adsorption for surface modification applications.


Infant oral mutilation: a New Zealand case series.
Infant oral mutilation is a practice performed by traditional healers in many Eastern African countries. The sequelae of this practice have been recognised and reported on in many developed countries due to the migration of populations, customs and beliefs. This article describes three cases of infant oral mutilation that have been diagnosed in the Dental Department at Hutt Hospital, Lower Hutt.


Prevalence and Angiographic Characteristics of Coronary Vasospasm Detected at Surveillance Coronary Angiograms Among Patients With Heart Transplants.
Coronary vasospasm in heart transplant recipients occurs through various mechanisms. It has been linked to allograft rejection and coronary vasculopathy, which can result in mortality during follow-up. Here, we investigated the prevalence of coronary vasospasm among heart transplant recipients undergoing surveillance coronary angiography procedures. This study was prospectively performed at Başkent University Faculty of Medicine by retrospectively analyzing medical information of patients who underwent bicaval heart transplant between 2003 and 2016 and subsequently had coronary angiography to rule out allograft vasculopathy. We analyzed prevalence of coronary vasospasm, affected vessels, underlying vessel properties, and treatment modalities. Coronary vasospasm was defined as transient diffuse or localized luminal narrowing, either spontaneously or catheter-induced, relieved spontaneously or with nitroglycerine. Forty-one coronary angiography procedures were performed using the standard Judkins technique. Among these, 5 patients showed coronary vasospasm a mean of 2 years after cardiac transplant. All vasospasm episodes involved the left anterior descending artery, with 2 also involving the circumflex artery and 1 involving the right coronary artery. The degree of luminal narrowing ranged from mild to severe. Episodes that involved the left anterior descending artery more often diffusely involved most of the vessel. In 3 patients, vasospasms were recurrent. Three patients had underlying coronary artery disease, which was relieved in 2 patients who progressed by stent implant. Neither ischemic events nor reduction of ejection fraction was observed during follow-up. There were also no occurrences of cellular or humoral rejection or death in any of the patients with vasospasm. Coronary vasospasm is common in heart transplant recipients. It may be diffuse or localized and occur spontaneously or because of underlying coronary artery disease. Factors, including allograft vasculopathy, associated with coronary vasospasm remain to be determined, and further related research is needed.


Utility of procalcitonin, C-reactive protein and white blood cells alone and in combination for the prediction of clinical outcomes in community-acquired pneumonia.
The added value of biomarkers, such as procalcitonin (PCT), C-reactive protein (CRP), and white blood cells (WBC), as adjuncts to clinical risk scores for predicting the outcome of patients with community-acquired pneumonia (CAP) is in question. We investigated the prognostic accuracy of initial and follow-up levels of inflammatory biomarkers in predicting death and adverse clinical outcomes in a large and well-defined cohort of CAP patients. We measured PCT, CRP and WBC on days 1, 3, 5, and 7 and followed the patients over 30 days. We applied multivariate regression models and area under the curve (AUC) to investigate associations between these biomarkers, the clinical risk score CURB-65, and clinical outcomes [i.e., death and intensive care unit (ICU) admission]. Of 925 patients with CAP, 50 patients died and 118 patients had an adverse clinical outcome. None of the initial biomarker levels significantly improved the CURB-65 score for mortality prediction. Follow-up biomarker levels showed significant independent association with mortality at days 3, 5, and 7 and with improvements in AUC. Initial PCT and CRP levels were independent prognostic predictors of adverse clinical outcome, and levels of all biomarkers during the course of disease provided additional prognostic information. This study provides robust insights into the added prognostic value of inflammatory markers in CAP. Procalcitonin, CRP, and to a lesser degree WBC provided some prognostic information on CAP outcomes, particularly when considering their kinetics at days 5 and 7 and when looking at adverse clinical outcomes instead of mortality alone.


[German gynecologist and obstetrician Christian Gerhard Leopold (1846-1911)].
Christian Gerhard Leopold was one of the most important gynecologists and obstetricians at the end of the 19th century. He is mainly remembered for the eponymous "Leopold's grips" (Leopold-Handgriffe) which are used to determine the position of the fetus within the uterus. He was a student of Carl Siegmund Franz Credé, taught midwifery at the Frauenklinik in Leipzig, and was appointed as an associate professor at Leipzig University in 1883. Afterwards, he succeeded Franz von Winckel as the director of the Royal Gynecological Infirmary in Dresden. In the journal "Archiv für Gynäkologie" he published the four classic "Leopold's grips". A third grip or maneuver known as "Pawlik's grip" is still used by obstetricians today, though some, especially abroad, favored and recommended the two-handed approach. Leopold himself oriented strictly on the external investigation of the pregnant to reduce the danger of infection. His main domain was the prevention of the puerperal fever.


Factors associated with referrals to high security forensic services among people with severe mental illness and receiving inpatient care in prison.
Prison mental health care is a significant topic which has been already studied and described in literature, particularly because of important implications both in the prison and in the health care system. It's not uncommon that inmates suffering from mental disorders are referred to high security forensic services (HSFS) but, to date, studies assessing factors associated with relevant referrals to these services are missing. So, the aim of our study is to investigate socio-demographic, criminological, psychopathological and toxicological variables among those who were referred to HSFS as compared to their non-referred counterpart. We conducted a cross-sectional study recruiting 159 subjects receiving prison inpatient care in an Italian jail, between January 2010 and August 2015. No subjects were excluded from the study. The mean age was 39. About half of included prisoners suffered from personality disorder while one-third from psychotic disorders. >60% of the subjects had comorbid substance use disorders. The odds of being referred to HSFS were related to previous admission (odds ratio [OR] = 5.34, 95% confidence interval [CI] 1.66-17.16), diagnosis of psychosis (OR = 2.79, 95% CI 1.11-7.04) and cannabis use disorder (OR = 2.68, 95% CI 1.14-6.28). Personality disorder was inversely associated to the referral to forensic facilities (OR = 0.37, 95% CI 0.14-0.97). Mental health services should improve preventive measures for vulnerable prisoners in order to reduce criminal recidivism and forensic readmission.


Santorinicele as a cause of chronic pancreatic pain.
The role pancreas divisum plays in recurrent pancreatitis and chronic pancreatic pain remains controversial. When pancreatic disease does occur secondary to pancreas divisum, the pathogenesis is thought to be stenosis of the accessory duct with a resulting increase in ductal pressure. A case is reported in which stenosis of the accessory papilla orifice is thought to be responsible for cystic dilatation of the terminal portion of the duct of Santorini in a patient with pancreas divisum. This resulted in chronic pancreatic pain that resolved after sphincterotomy of the accessory papilla.


Multiple level noncontiguous fractures of the spine.
From 1970 to 2000, 81 patients with noncontiguous fractures of the spine were evaluated. Of these 81 patients, 36 had a neurologic deficit. Sixty-six patients with stable injuries were treated conservatively, whereas 15 patients with unstable injuries required surgical stabilization. There was no neurologic deterioration either in the patients who had surgical stabilization or in the patients who were treated conservatively. Thirteen patients with an A score on the American Spinal Injury Association neurologic impairment scale did not improve and had a high mortality rate (61.5%). Although multiple level noncontiguous fractures of the spine are uncommon, they constitute a threat to neurologic function, and therefore warrant radiographic evaluation of the entire spine with multiple injuries.


Genomic analysis of in vivo acquired resistance to colistin and rifampicin in Acinetobacter baumannii.
Acinetobacter baumannii is an opportunistic pathogen in healthcare facilities responsible for nosocomial infections mostly in immunocompromised patients. Colistin resistance is increasingly reported worldwide in A. baumannii. Here we describe the in vivo selection of colistin and rifampicin resistance in carbapenem-resistant A. baumannii. Antimicrobial susceptibility testing, plasmid analysis and whole-genome sequencing (WGS) were performed to fully characterise the resistome of two clinical isolates (AbS1 and AbS2) selected during treatment. Clinical isolate AbS1 remained susceptible to colistin, rifampicin and tigecycline, whilst AbS2 was susceptible only to tigecycline. PCR analysis revealed the presence of a blaOXA-23-like carbapenemase gene. Kieser extraction revealed an ca. 74 kb plasmid harbouring blaOXA-23. WGS revealed genomes of 3.8 Mbp in size with a G + C content of 38.9%, and both belonged to ST281 according to the Oxford MLST scheme and ST641 according to the Institut Pasteur scheme. The resistome was also composed of naturally occurring β-lactamases, i.e. ADC-25 cephalosporinase and OXA-82 oxacillinase, aminoglycoside resistance genes [aac(3)-Ia, aadA1 and aph(3')-VIa (aphA6)], and mutations in DNA gyrases explaining fluoroquinolone resistance. Single nucleotide polymorphism analysis revealed that both isolates were identical except for a 30-nucleotide duplication within the pmrB gene and a point mutation in the rpoB gene resulting in colistin and rifampicin resistance, respectively. This study highlights the genomic plasticity of A. baumannii under antibiotic pressure. The 10-amino acid duplication in PmrB affects colistin susceptibility by regulating lipopolysaccharide modification through the PmrAB two-component system. These findings provide further information on the molecular mechanisms leading to colistin resistance in A. baumannii.


Brain and plasma pharmacokinetics and anticancer activities of cyclophosphamide and phosphoramide mustard in the rat.
By a sensitive and quantitative fluorometric assay, brain and plasma time-dependent concentration profiles were generated for phosphoramide mustard (PM) and active alkylating metabolites derived from cyclophosphamide (CPA) administration to rats. Whereas PM rapidly disappeared from plasma, with a monophasic half-life of 15.1 min, equimolar administration of CPA generated active metabolites in plasma that disappeared monoexponentially, with a composite half-life of 63 min. As a consequence, the time-dependent concentration integral of active alkylating metabolites derived from CPA administration, calculated between 5 min and infinity, was 3-fold that of PM. Pharmacokinetic parameters were calculated for each compound. The brain/plasma concentration-integral ratios of PM and active alkylating metabolites derived from CPA were 0.18 and 0.20, respectively. The cerebrovascular permeability-surface area product of PM was 7.5 x 10(-5) s-1, which is similar to that of other water-soluble anticancer agents that are restricted from entering the brain. The activities of a range of daily doses of PM and CPA were assessed against subcutaneous and intracerebral implants of Walker 256 carcinosarcoma tumor in rats. Inhibition of subcutaneous tumor growth by 50% was caused by CPA and PM doses of 6.6 and 12.0 mg/kg (daily for 5 consecutive days, starting 36 h after tumor implantation), respectively. However, administration of daily doses of up to 40 mg/kg did not significantly increase the survival of animals with intracerebral tumor implants. These studies indicate that active metabolites of CPA are restricted from entering the brain and that only subtherapeutic concentrations are achieved in brain tissue after systemic administration of CPA or PM.


Expression of oestrogen receptors in foetal lung tissue of mice.
Oestrogens are responsible for the sexual dimorphism in adult mice lung tissue, and this difference is most notable at sexual maturity. Oestrogen receptor-alpha (ERα) and the oestrogen receptor-beta (ERβ) are the two receptors that mediate oestrogen action, but adult mice lung tissue only expresses ERβ, and it is probably through this receptor that oestrogens exert their action. The goal of our study was to detect the expression of ERα and ERβ in mouse foetal lung tissues and identify possible gender differences. The foetal lung tissue was collected between developmental days E15-E19, processed for histology and the expression of oestrogen receptors was detected by immunohistochemistry. Over the 5 days of lung development that were evaluated ERα was not expressed in the foetal lung tissues of neither male nor female mice. In contrast, ERβ was detected in both sexes, although the immunoreactivity differed for each developmental day whilst the staining intensity observed for ERβ also indicated differences between male and female lung tissues. The results demonstrate the existence of a gender difference in the foetal expression of ERβ in lungs of mice.


How accurately can the acetabular rim be trimmed in hip arthroscopy for pincer-type femoral acetabular impingement: a cadaveric investigation.
The purpose of this study was to evaluate the precision of central hip arthroscopy in the assessment and treatment of pincer-type femoroacetabular impingement (FAI) avoiding the posterolateral portal, with its close proximity to the main arterial blood supply of the femoral head, the medial circumflex femoral artery. Seven human cadaveric hips underwent arthroscopic trimming of the acetabular labrum and rim along a preoperatively defined 105 degrees arc of resection for treatment of a presumed pincer-type lesion. After the arthroscopic procedure, all specimens were dissected and measured for evaluation of the location, quantity, and quality of the area undergoing resection. The difference between the actual and planned arc of resection was 18.7 degrees +/- 4.7 degrees (range, 2 degrees to 34 degrees). This was mainly because of a lack of accuracy in the presumed posterior starting point (PSP), with a mean deviation of 19 degrees +/- 3.4 degrees (range, 10 degrees to 36 degrees). Correlation analysis showed that variance in the arc of resection was mainly dependent on the PSP (r = 0.739, P = .058). Central hip arthroscopy is a feasible option in treating anterosuperior pincer-type FAI by use of the anterior and anterolateral portals only. This cadaveric study showed that there is a significant risk of underestimating the actual arc of resection compared with the planned arc of resection for posterosuperior pincer-type lesions because of the modest accuracy in determining the PSP of the resection. Accurate preoperative planning and arthroscopic identification of anatomic landmarks at the acetabular side are crucial for the definition of the appropriate starting and ending points in the treatment of pincer-type FAI. Whereas anterosuperior pincer-type lesions can be addressed very precisely with our technique, the actual resection of posterosuperior lesions averaged 19 degrees less than the planned resection, which may have clinical implications.


Implantation and early embryonic development: implications for pregnancy.
Implantation represents the limiting step in governing reproductive outcomes. The process is driven by both embryo and endometrium alike. Minute perturbations in this orchestration lay foundation for pregnancy-associated complications that may manifest throughout the gestational course. Furthermore, placental function dictates many aspects of fetal development inclusive of preeclampsia and intrauterine growth restriction (IUGR). Novel techniques such as Multigate Spectral Doppler Analysis (MSDA) may allow for early detection and diagnosis of potentially deleterious fetal outcomes.


Identification and classification of epithelial cells in nephron segments by actin cytoskeleton patterns.
The basic functional unit in a kidney is the nephron, which is a long and morphologically segmented tubule. The nephron begins with a cluster of capillaries called glomerulus through which the blood is filtered into the Bowman's space. The filtrate flows through the nephron segments. During this flow, electrolytes and solutes are reabsorbed by channels and transport systems into the capillaries wrapped around the nephron. Many questions related to renal function focus on identifying the sites of expression of these systems. In this study, we mapped whole kidney sections by confocal microscopic imaging of fluorescent phalloidin, which binds to actin filaments. In tile scans (composed of hundreds of images) of these sections, the cortex and the medullary regions (outer and inner stripes of the outer medulla, and inner medulla) could be easily identified by their cytoskeletal patterns. At a higher resolution, we identified distinct features of the actin cytoskeleton in the apical, basal, and lateral borders of the cells. These features could be used to identify segments of a nephron (the proximal tubule, thin and thick segments of Henle's loop, and distal tubule), the collecting duct system, the papillary ducts in the papilla, and the urothelium that covers the pelvis. To verify our findings, we used additional markers, including aquaporin isoforms, cytokeratin 8-18, and WGA lectin. This study highlights the power of high-resolution confocal microscopy for identifying specific cell types using the simple probe of F-actin-binding phalloidin.


Apoptosis and gene expression in Jurkat human T cells and lymphoid tissues of fusarenon-X-treated mice.
Fusarenon X, a member of the type B trichothecene mycotoxin group, has been frequently observed, along with deoxynivalenol (DON) and nivalenol (NIV) as a contaminant in cereals. Our previous study demonstrated that a 14-day FX exposure caused apoptosis in the lymphoid tissues of mice, especially at 0.5 mg/kg bodyweight. However, the relationship between low concentrations of FX and apoptotic molecular machinery remains unclear. In the present study, we investigated the genetic regulatory mechanisms in the thymus and Peyer's patches of mice after 14 days oral administration of FX at 0.5 mg/kg bodyweight. FX caused the up-regulation of Bax, Bid, Trp53, and Caspase-9 mRNA but the relative expression of Fas, TNF, and Caspase-8 remained unchanged. Furthermore, we also determined the toxicity of FX in Jurkat T-cells. FX exhibited a concentration- and time-dependent inhibition of cell viability. Thus, incubation time and FX concentration influence the percentage of apoptotic cells. These data suggested that treatment with low dosage of FX can induce apoptosis in lymphocytes through an effect on Bax, Bid, Trp53, and Caspase-9 and therefore the mitochondrial apoptotic pathway.


Toward optimizing dental implant performance: Surface characterization of Ti and TiZr implant materials.
Targeting understanding enhanced osseointegration kinetics, the goal of this study was to characterize the surface morphology and composition of Ti and TiZr dental implant substrates subjected to one of two surface treatments developed by Straumann. These two treatments are typically known as SLA and SLActive, with the latter resulting in more rapid osseointegration. A range of techniques was applied to characterize four different substrate/surface treatment combinations (TiSLA, TiSLActive, TiZrSLA, and TiZrSLActive). Contact angle measurements established their hydrophilic/hydrophobic nature. Surface morphology was probed with scanning electron microscopy. X-ray diffraction, Raman μ-spectroscopy, and X-ray photoelectron spectroscopy were used to elucidate the composition of the near-surface region. Consistent with previous work, surface morphology was found to differ only at the nanoscale, with both SLActive substrates displaying nano-protrusions. Spectroscopic data indicate that all substrates exhibit surface films of titanium oxide displaying near TiO2 stoichiometry. Raman μ-spectroscopy reveals that amorphous TiO2 is most likely the only phase present on TiSLA, whilst rutile-TiO2 is also evidenced on TiSLActive, TiZrSLA, and TiZrSLActive. For TiZr alloy substrates, there is no evidence of discrete phases of oxidized Zr. X-ray photoelectron spectra demonstrate that all samples are terminated by adventitious carbon, with it being somewhat thicker (∼1nm) on TiSLA and TiZrSLA. Given previous in vivo studies, acquired data suggest that both nanoscale protrusions, and a thinner layer of adventitious carbon contribute to the more rapid osseointegration of SLActive dental implants. Composition of the surface oxide layer is apparently less important in determining osseointegration kinetics.


[Neuro-neutrophilic Disease and Dementia].
Neuro-neutrophilic diseases are multisystem inflammatory disorders that include neuro-Behçet and neuro-Sweet disease. These disorders ectopically damage the nervous system due to the abnormal chemotaxis of neutrophils. The neutrophils' chemotaxis is induced by oral muco-cutaneous bacterial infections and the dysregulation of cytokines, including interleukins. The frequencies of human leukocyte antigen (HLA)-B51 in neuro-Behçet disease and HLA-B54 as well as Cw1 in neuro-Sweet disease significantly higher than the levels present in Japanese normal controls. Notably, their frequencies are also higher in patients exhibiting neurological complications than in patients without neurological complications. These HLA types are considered risk factors that are directly related to the etiology of these diseases. Prednisolone and colchicine, which suppress neutrophil activation, are used to treat the acute phase of both diseases. Alternatively, dapsone is prescribed to prednisolone-dependent recurrent cases of neuro-Sweet disease. Dementia is a neurological symptom of these disorders, especially in the chronic progressive subtype of neuro-Behçet disease. Other immunosuppressant drugs, including methotrexate and infliximab, are administered to patients with the chronic progressive type of neuro-Behçet disease. Neuro-neutrophilic diseases are a form of dementia considered treatable.