Ethnic differences in serum testosterone concentration among Malay, Chinese and Indian men: A cross-sectional study.

OBJECTIVE: To investigate non-urological patients with multiple comorbidities for factors contributing towards differences in testosterone concentration in multiethnic Malaysian men. DESIGN: An observational study. PATIENTS: Sexually active men, ≥40 years, with no known urological problems, were recruited at the phlebotomy clinic at our centre. MEASUREMENTS: A brief history along with latest fasting lipid profile and plasma glucose levels were obtained. An Aging Male Symptoms questionnaire was administered; waist circumference (WC) and serum testosterone concentration were measured. STATSTICAL ANALYSIS: Analysis of testosterone concentration between Malay, Indian and Chinese men was performed. Statistical tests such as analysis of variance, χ2 test, univariate and multivariable regression were performed. Any p < .05 was noted as statistically significant. RESULTS: Among the 604 participants analysed, mean testosterone concentration was significantly lower in Malays (15.1 ± 5.9 nmol/L) compared to the Chinese (17.0 ± 5.9 nmol/L) and Indian (16.1 ± 6.5 nmol/L) participants. The mean WC was also found to be higher among the Malays (96.1 ± 10.9 cm) compared to Chinese (92.6 ± 9.6 cm) and Indians (95.6 ± 9.9 cm). Testosterone concentration tended to be lower with higher age, but this was not statistically significant (p > .05). In the multivariable analysis only Malay ethnicity, WC ≥ 90 cm and low high-density lipoprotein (HDL) were associated with lower testosterone concentration. CONCLUSION: In this study, Malaysian men of Malay origin had lower testosterone concentration compared with Indian and Chinese men. WC and low HDL were also associated with lower testosterone concentrations.

Actual and estimated adenoma detection rates: a 2-year monocentric colonoscopic screening outcome in Shenzhen, China.

BACKGROUND AND AIM: While adenoma detection rate (ADR) is an important quality metric for screening colonoscopy, it remains difficult to be accessed due to the lack of integrated endoscopy and pathology databases. Hence, the use of an adenoma-to-polyp detection rate quotient and polyp detection rate (PDR) has been proposed to predict ADR. This study aimed to examine the usefulness of estimated ADR across different colonic segments in two age groups for Shenzhen people in China. METHODS: We retrospectively analyzed 7329 colonoscopy procedures performed by 12 endoscopists between January 2012 and February 2014. The PDR, actual ADR, and estimated ADR of the entire, proximal, and distal colon, and within each colonic segment, in two patient age groups: <50 and ≥50 years, were calculated for each endoscopist. RESULTS: The overall polyp and adenoma prevalence rates were 19.1 and 9.3%, respectively. The average age of adenoma-positive patients was significantly higher than that of adenoma-negative patients (54 ± 12.6 years vs 42.9 ± 13.2 years, respectively). A total of 1739 polyps were removed, among which 826 were adenomas. More adenomatous polyps were found in the proximal colon (60.4%, 341/565) than in the distal colon (40.9%, 472/1154). Overall, both actual and estimated ADR correlated strongly at the entire colon level and within most colonic segments, except for the cecum and rectum. In both age groups, these parameters correlated strongly within the traverse colon and descending colon. CONCLUSION: Caution should be exercised when predicting ADR within the sigmoid colon and rectum.

Refining the latent structure of neuropsychological performance in schizophrenia.

BACKGROUND: Elucidating the cognitive architecture of schizophrenia promises to advance understanding of the clinical and biological substrates of the illness. Traditional cross-sectional neuropsychological approaches differentiate impaired from normal cognitive abilities but are limited in their ability to determine latent substructure. The current study examined the latent architecture of abnormal cognition in schizophrenia via a systematic approach. METHOD: Exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) were carried out on a large neuropsychological dataset including the Brief Assessment of Cognition in Schizophrenia, Continuous Performance Test, Wisconsin Card Sorting Test, Benton Judgment of Line Orientation Test, and Wechsler Abbreviated Scale of Intelligence matrix reasoning derived from 1012 English-speaking ethnic Chinese healthy controls and 707 schizophrenia cases recruited from in- and out-patient clinics. RESULTS: An initial six-factor model fit cognitive data in healthy and schizophrenia subjects. Further modeling, which accounted for methodological variance between tests, resulted in a three-factor model of executive functioning, vigilance/speed of processing and memory that appeared to best discriminate schizophrenia cases from controls. Factor analytic-derived g estimands and conventionally calculated g showed similar case-control discrimination. However, agreement analysis suggested systematic differences between both g indices. CONCLUSIONS: Factor structures derived in the current study were broadly similar to those reported previously. However, factor structures between schizophrenia subjects and healthy controls were different. Roles of factor analytic-derived g estimands and conventional composite score g were further discussed. Cognitive structures underlying cognitive deficits in schizophrenia may prove useful for interrogating biological substrates and enriching effect sizes for subsequent work.

Genome technologies and personalized dental medicine.

The addition of genomic information to our understanding of oral disease is driving important changes in oral health care. It is anticipated that genome-derived information will promote a deeper understanding of disease etiology and permit earlier diagnosis, allowing for preventative measures prior to disease onset rather than treatment that attempts to repair the diseased state. Advances in genome technologies have fueled expectations for this proactive healthcare approach. Application of genomic testing is expanding and has already begun to find its way into the practice of clinical dentistry. To take full advantage of the information and technologies currently available, it is vital that dental care providers, consumers, and policymakers be aware of genomic approaches to understanding of oral diseases and the application of genomic testing to disease diagnosis and treatment. Ethical, legal, clinical, and educational initiatives are also required to responsibly incorporate genomic information into the practice of dentistry. This article provides an overview of the application of genomic technologies to oral health care and introduces issues that require consideration if we are to realize the full potential of genomics to enable the practice of personalized dental medicine.

Synthesis, characterization and biological activity of dimethyltin dicarboxylates containing germanium.

A series of diorganotin dicarboxylates of the general formula (CH(3))(2)Sn(OCOCHR(3)CHR(2)GeR(1))(2) where R(1)=(C(6)H(5))(3), (P-CH(3)C(6)H(4))3, N(CH(2)CH(2)O)(3), R(2)=C(6)H(5), H, CH(3), P-CH(3)OC(6)H(4), P-ClC(6)H(4), P-CH(3)C(6)H(4), R(3)=CH(3) and H, have been synthesized by the reaction of dimethyltin oxide with germanium substituted propionic acid in 1:2 molar ratio in toluene. The H(2)O formed was removed azeotropically using a Dean and Stark apparatus. All the compounds have been characterized by IR, multinuclear ((1)H, (13)C, (119)Sn) NMR, mass and Mössbauer spectroscopies. All compounds were found to have potential activity against bacteria.

Synthesis and biophysical analysis of transmembrane domains of a Saccharomyces cerevisiae G protein-coupled receptor.

The Ste2p receptor for alpha-factor, a tridecapeptide mating pheromone of the yeast Saccharomyces cerevisiae, belongs to the G protein-coupled family of receptors. In this paper we report on the synthesis of peptides corresponding to five of the seven transmembrane domains (M1-M5) and two homologues of the sixth transmembrane domain corresponding to the wild-type sequence and a mutant sequence found in a constitutively active receptor. The secondary structures of all new transmembrane peptides and previously synthesized peptides corresponding to domains 6 and 7 were assessed using a detailed CD analysis in trifluoroethanol, trifluoroethanol-water mixtures, sodium dodecyl sulfate micelles, and dimyristoyl phosphatidyl choline bilayers. Tryptophan fluorescence quenching experiments were used to assess the penetration of the membrane peptides into lipid bilayers. All peptides were predominantly (40-80%) helical in trifluoroethanol and most trifluoroethanol-water mixtures. In contrast, two of the peptides M3-35 (KKKNIIQVLLVASIETSLVFQIKVIFTGDNFKKKG) and M6-31 (KQFDSFHILLINleSAQSLLVPSIIFILAYSLK) formed stable beta-sheet structures in both sodium dodecyl sulfate micelles and DMPC bilayers. Polyacrylamide gel electrophoresis showed that these two peptides formed high molecular aggregates in the presence of SDS whereas all other peptides moved as monomeric species. The peptide (KKKFDSFHILLIMSAQSLLVLSIIFILAYSLKKKS) corresponding to the sequence in the constitutive mutant was predominantly helical under a variety of conditions, whereas the homologous wild-type sequence (KKKFDSFHILLIMSAQSLLVPSIIFILAYSLKKKS) retained a tendency to form beta-structures. These results demonstrate a connection between a conformational shift in secondary structure, as detected by biophysical techniques, and receptor function. The aggregation of particular transmembrane domains may also reflect a tendency for intermolecular interactions that occur in the membrane environment facilitating formation of receptor dimers or multimers.

Chemical specificity of the PDR5 multidrug resistance gene product of Saccharomyces cerevisiae based on studies with tri-n-alkyltin chlorides.

To understand the chemical basis of action for the PDR5-encoded multidrug resistance transporter of Saccharomyces cerevisiae, we compared the relative hypersensitivities of the wild-type (RW2802) and null mutant strains toward a series of tri-n-alkyltin compounds. These compounds differ from each other in a systematic fashion-either by hydrocarbon chain length or by anion composition. Using zone-of-inhibition and fixed-concentration assays, we found that the ethyl, propyl, and butyl compounds are strong PDR5 substrates, whereas the methyl and pentyl compounds are weak. We conclude that hydrophobicity and anion makeup are relatively unimportant factors in determining whether a tri-n-alkyltin compound is a good PDR5 substrate but that the dissociation of the compound and the molecular size are significant.

Effect of immobilization on the penicillin binding and reactivity properties of DD-peptidase from Streptomyces R61.

An affinity gel matrix containing an enzyme (DD-peptidase) with specific beta-lactam binding properties was characterized with respect to its binding and reactivity behavior with penicillin. The data show that immobilization of DDP by reaction with the enzymes susceptible amino groups resulted in changes in catalytic activity on a tripeptide substrate, penicillin binding efficiency and pH stability of drug binding. Properties unaffected by immobilization were the drug-enzyme complex stability, binding reaction mechanism, drug selectivity and method of complex desorption. The affinity of DDP for penicillin-G was investigated by surface plasmon resonance. These characteristics were compared with those of the soluble enzyme. Conditions for elution of the bound drug were determined and a method for immobilizing Streptomyces DDP by which its binding site structure is sustained was also evaluated.

Obstetrical brachial plexus palsy (OBPP) outcome with conservative management.

Resurgence of neurosurgical intervention of obstetrical brachial plexus palsy prompted our review of 186 patients evaluated between 1981 and 1993, correlating clinical examination, electrodiagnosis, and functional outcome with conservative management. Eighty-eight percent had upper brachial plexus palsies, and 63% were mild. Forty-two infants required no long-term follow-up because they rated 1 or 2 on initial physical examination. Comparing first and last follow-up clinical findings of the remaining 149 patients, there was high agreement (correlation r= 0.81; P < 0.001). Pearson correlation of initial physical exam with electrodiagnosis at three intervals was relatively stable (r= 0.87, 0.88, 0.69). One hundred eight (72%) of the patients remained in their original severity groups. Thirty-three of 41 patients with discrepant follow-up scores improved by at least one category. Eight patients deteriorated. The natural pathophysiology and recovery of OBPP is presented.

Structural changes associated with the spontaneous inactivation of the serine proteinase human tryptase.

Human skin tryptase, a serine proteinase stored within mast cell secretory granules, rapidly loses enzymatic activity in solutions of physiological salt concentration, pH, and temperature. The inactivation of tryptase can be slowed and even reversed by addition of heparin, a highly sulfated glycosaminoglycan also found in the secretory granules. These properties may be relevant to tryptase regulation after secretion from mast cells. To further characterize the molecular changes underlying the functional instability of tryptase, circular dichroism (CD) and analytical ultracentrifugation were used to investigate structural changes during spontaneous inactivation. The CD spectra of active and spontaneously inactivated tryptase are different, particularly in the region around 230 nm where active tryptase displays a distinct negative peak. This peak is also observed in the CD spectrum of bovine chymotrypsin but not in trypsin, elastase, or chymotrypsinogen. Loss of activity resulting from spontaneous inactivation was accompanied by a diminution of the 230-nm signal. The kinetics for the signal loss appeared to be first-order and closely paralleled the rate of enzymatic activity loss. Dextran sulfate, a highly sulfated polysaccharide, was capable of reactivating tryptase and restoring the CD signal. After 2 h of decay (> 90% loss of activity), addition of dextran sulfate resulted in an almost immediate return of the CD signal to that of active tryptase. The return of the CD signal appeared to be more rapid than the return of enzymatic activity, thereby suggesting the presence of an unidentified step which is rate-limiting for activity return (and loss) and subsequent (prior) to the CD change accompanying activity loss. Ultracentrifugation analysis of tryptase showed a marked change in its association state upon inactivation. Sedimentation equilibrium under stabilizing conditions demonstrated the presence of a single species with the molecular weight of a tetramer. After spontaneous inactivation, a mixture of species was evident, which was characterized as monomers and tetramers in equilibrium. These results demonstrate that spontaneous inactivation of tryptase is associated with reversible conformational changes and that a consequence of inactivation is the formation of a destabilized tetrameric form. Although the molecular mechanism initiating these changes remains unclear, possible insights into the process are discussed on the basis of the similarity between the CD spectra of tryptase and chymotrypsin.

Persistent pulmonary hypertension in newborn infants with cogenital myotonic dystrophy.

We describe two infants with congenital myotonic dystrophy that was complicated by persistent pulmonary hypertension. Both infants died of respiratory insufficiency that was unresponsive to ventilatory and pharmacologic support. One of the two infants was supported with extracorporeal membrane oxygenation before the diagnosis of congenital myotonic dystrophy was made.

Human skin tryptase: kinetic characterization of its spontaneous inactivation.

The spontaneous loss of human tryptase hydrolytic activity was investigated. Time course studies monitoring the loss in catalytic activity were biphasic and correlated with a reduction in the concentration of catalytic sites. There was an initial rapid phase leading to greater than 85% loss in activity. The remaining activity gradually decayed toward completion over a 40-h period. The initial phase could be described as a first-order process with a t1/2 of approximately 6.0 min in 0.2 M NaCl (pH 6.8, 30 degrees C). The rate constant for this phase showed little, if any, sensitivity to changes in enzyme concentration, consistent with a first-order process, and analysis of the reaction as a function of temperature was consistent with a single rate-determining step. The rate of this process, however, showed marked sensitivity to changes in NaCl concentration and pH. Increasing the NaCl concentration as well as decreasing the pH below the pI (pH 6.3) reduced the rate of activity loss, whereas increasing the pH above pH 8.0 markedly increased the rate of activity loss. The effect of NaCl concentration and pH on the rate of activity loss suggests that the rate-limiting step governing the fast phase of the reaction involves electrostatic interactions. The presence of a fast and a slow phase in the decay process may suggest heterogeneity in the sample or the rapid formation of an inactive, but reversible, intermediate. A reversible intermediate was demonstrated when "inactivated tryptase" was incubated in the presence of heparin, and an increase in tryptase catalytic activity was observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Heterotopic ossification in children with burns: two case reports.

Heterotopic ossification is the formation of ectopic bone in soft tissue, and has been reported as a rare complication in pediatric burn patients. At our hospital, two 86% body surface area burn patients developed heterotopic ossification in the shoulder, elbows, distal femur, proximal tibia, fibula, and ribs approximately four months after the burn injury. These two rare and unusual cases are presented documenting the clinical involvement, radiological studies, laboratory data, as well as treatment of their heterotopic ossification. Discussion will focus on the incidence, diagnosis, pathophysiology, and treatment of heterotopic ossification in burn patients and how this information relates to the specific diagnosis and management of the complication of heterotopic ossification in the burn child.

Normal values for the soleus H-reflex in newborn infants 31-45 weeks post conceptional age.

Normal values for the soleus H-reflex were established in 83 preterm and term infants 31 to 45 weeks postconceptional age. Infants at conceptional ages 31 to 34 weeks (n = 30) had a mean H-latency (msec) of 19.2 +/- 2.16; infants 35 to 39 weeks (n = 26), 16.67 +/- 1.48; and infants 40 to 45 weeks (n = 27), 15.94 +/- 1.45. Simple linear regression shows a significant relationship between conceptional age and H-latency (Pearson correlation = .68, R2 = 0.47, f = 71.31, p = .0001). Adjusting H-latency values for leg length, the regression of H-soleus latency/leg length (msec/cm) against conceptional age provides an even stronger relationship (r = 0.81, R2 = 0.66, f = 154.5, p = .0001). These results reflect the degree of myelination in infants of increasing conceptional ages. They can indicate the gestational age of the infants and afford comparative data in the event of peripheral nerve pathology.

Lyme disease presenting with bilateral facial nerve palsy.

Facial palsy bilateral, or recurrent, suggests a myriad of diagnostic possibilities. An 11-year-old boy is described whose diagnosis remained elusive for several months. Clinical evolution and subsequent laboratory studies confirmed that he had Lyme disease. Literature review suggests that this disorder is ubiquitous in its manifestations. The diagnosis should be remembered in unexplained neurologic disorders, particularly in cranial and peripheral neuropathies.