Central pontine myelinolysis at autopsy; a twelve year retrospective analysis

Central pontine myelinolysis (CPM) was first described in 1959 and only later was associated with a rapid, sustained rise in serum sodium from a hyponatremic baseline. This discovery in 1981 led to modifications in recommendations for clinical treatment of hyponatremia. Our interest has been in tracking the incidence of CPM found at autopsy by year to see whether changes in medical treatment in hyponatremia have resulted in a decrease in CPM over time. Clinically asymptomatic CPM found at autopsy has always been at least as frequent as cases diagnosed premortem and serves as a reasonable indicator for the incidence of the disease. In over 3,000 autopsies, on most of which the brain was examined macroscopically and microscopically by the same neuropathologist, we have discovered 15 cases of asymptomatic, small pontine CPM. Of these 15, 6 were active lesions and 9 were remote; in the active group, 5 of the 6 cases were associated with a rapid, sustained rise in serum sodium during the appropriate time period. The incidence of asymptomatic CPM has remained steady over the 13-year time period. In contrast, we have encountered no cases of CPM diagnosed premortem that have come to autopsy in the same time period. These cases emphasize that CPM still occurs, but most often as an asymptomatic disorder with small, midline pontine lesions. When small active CPM is found, it still is associated with a rapid sustained rise in serum sodium.     

Human intramuscular and cutaneous pain: psychophysical comparisons

We used psychophysical methods to compare the central processing of nociceptive inputs from skin and muscle in ten normal humans. Both intramuscular electrical and infrared CO2 laser cutaneous stimulation showed increasing but decelerating (downward concave) stimulus-response curves and similar temporal summation characteristics. Intramuscular stimulation was rated significantly more unpleasant than cutaneous stimulation. The results are consistent with a common mode of central nociceptive processing for skin and muscle pain intensity but suggest a relatively larger activation of affective mechanisms by muscle afferents.     

On the Influence of Microstructure on the Fracture Behavior of Gamma-Based Titanium Aluminides. III. Effects of Interstitials and Microalloying with W

The results of a recent study of the effects of interstitial elements and microalloying with 0.2 at.% W on the tensile and fracture properties of Ti-48Al (compositions quoted in atomic % unless stated otherwise) base gamma alloys are presented in this paper. Lower interstitial oxygen levels are shown to promote higher levels of tensile ductility at the expense of yield/ultimate tensile strength and fracture toughness. Microalloying with W is also shown to result in microstructural instability and a concomitant degradation in tensile and fracture properties. Ductility and yield/ultimate tensile strengths in binary gamma alloys at room - and elevated-temperature are shown to exhibit a simple Hall-Petch dependence on the average grain/lamellar packet size. The observed Hall-Petch behavior is found to be independent of lamellar volume fraction and fracture mechanism at room- and elevated-temperature. The implications of the results are discussed for future alloy/process development.     

Molecular analysis of Salmonella enteritidis by pulsed-field gel electrophoresis and ribotyping

A total of 61 isolates of Salmonella enteritidis were analyzed by the techniques of pulsed-field gel electrophoresis (PFGE) and ribotyping. Twenty-three of the isolates were from Zurich, Switzerland, and 38 isolates were from the University Hospital, Kuala Lumpur, Malaysia. Five of the Malaysian isolates were hospital-related outbreak strains and were shown to be indistinguishable by PFGE analysis following digestion with three different restriction endonucleases, XbaI (5'-TCTAGA-3'), SpeI (5'-ACTAGT-3'), and AvrII (5'-CCTAGG-3'). The PFGE pattern of an isolate from a suspected carrier staff nurse was found to be identical to those of the hospital outbreak isolates. These isolates were also indistinguishable by ribotyping with SmaI and SphI. The same single PFGE pattern was also detected in 29 of 32 sporadic isolates of S. enteritidis. Four closely related ribotypes were detected among these 29 isolates. Similarly, outbreak-related strains from Switzerland showed close genetic identity by PFGE and ribotyping. Strains obtained from poultry showed more variations in their PFGE patterns and ribotypes, although the patterns were still closely related. In addition, SphI ribotypes A and D among the Swiss strains correlated with phage types 4 and 8, respectively. No correlation of phage types with PFGE pattern was noted. Both PFGE and ribotyping indicate that the S. enteritidis strains circulating in Malaysia and Switzerland are very similar and may be clonally related. Comparison of the PFGE patterns with the ribotypes for 23 Swiss and 16 Malaysian isolates showed that there was a 69% concordance in the grouping of isolates. We conclude that the close genetic similarity observed between epidemiologically unrelated and outbreak-related isolates of S. enteritidis suggests that both PFGE and ribotyping are of limited value in the epidemiological analysis of these particular isolates, possibly because of the highly clonal nature of pathogenic strains of S. enteritidis.     

A new role for IP3 receptors: Ca2+ release during nuclear vesicle fusion

During nuclear assembly, vesicles derived from the mitotic disassembly of the nuclear membranes reform the nuclear envelope. The vesicles first bind to chromosomes, specifically recognize other nuclear vesicles and then fuse to enclose the chromosomes. The proteins that mediate these events are largely unknown. Using reconstituted extracts of Xenopus eggs, we found that nuclear vesicle fusion required elevated (microM) concentrations of free Ca2+ [Sullivan KMC. Busa WB. Wilson KL. (1993) Cell, 73, 1411-1422]. Our data suggest that Ca2+ is released from the vesicle lumen by the activation of IP3 receptors (ligand-gated Ca2+ channels). We propose that the role of IP3 receptors during nuclear assembly may be analogous to that of voltage-gated Ca2+ channels during regulated secretion: to provide a microdomain of high cytosolic Ca2+ that triggers fusion. In this article, we will briefly describe current ideas about nuclear assembly and disassembly, and summarize the evidence that IP3 receptors are required for nuclear vesicle fusion. We will discuss parallels between our results and the role of voltage-gated Ca2+ channels, and Ca2+, in regulated exocytosis. Finally, we will address the question of how IP3 receptors are activated during nuclear vesicle fusion: is there a signal that stimulates IP3 production, or is the channel activated directly?     

Evidence for a single gene effect causing polycystic ovaries and male pattern baldness

OBJECTIVE: Polycystic ovary syndrome is one of the most common endocrine disorders but its aetiology remains unknown. It is highly prevalent within families, suggesting a genetic basic for the syndrome, but the mode of inheritance is unclear. The purpose of this study was to determine the mode of inheritance of polycystic ovary syndrome, within the families of affected individuals, by classic segregation analysis. DESIGN: All first degree relatives of affected individuals were screened for the presence or absence of polycystic ovaries in post-menarchal-premenopausal women and early onset male pattern baldness (MPB) in the males. In extended pedigrees, assignment of affected status in post-menopausal women was made by consideration of the clinical history alone. PATIENTS: Fourteen women (probands), presenting with a variety of clinical symptoms, were identified sequentially as having polycystic ovaries (PCO) by ultrasound scan. They were examined in detail to determine their family structure, clinical and endocrine status. Ten families were found to have sufficient members for further study. MEASUREMENTS: All family members had their body mass index calculated, their degree of hirsutism assessed using the Ferriman and Gallwey score and serum levels of gonadotrophins (FSH and LH), testosterone, prolactin and 17 alpha-hydroxyprogesterone measured by radioimmunoassay. A careful reproductive history was taken for each woman and any menstrual disturbance was noted. Obese probands had their glucose and insulin response to a standard 75-g oral glucose tolerance test determined. Each male family member was also assessed for the degree and time of onset of balding. RESULTS: First degree female relatives of affected individuals had a 51% chance of being affected. Early onset male pattern baldness (MPB) was found to be an accurate phenotype for obligate male carriers. Each family showed autosomal dominant inheritance for PCO with greater than 90% penetrance. CONCLUSIONS: We postulate that PCO and male pattern baldness are caused by alleles of the same gene which affect androgen production or action. The different frequencies of PCO and male pattern baldness arise from differing thresholds for phenotypic expression in females and males respectively. The modifying effects of other genes is the most likely explanation of the somewhat variable phenotype.     

Subclavian hemodialysis catheter infections: a prospective, randomized trial of an attachable silver-impregnated cuff for prevention of catheter-related infections

OBJECTIVE: To determine if an attachable silver-impregnated cuff is effective in reducing subclavian hemodialysis catheter-related infections. DESIGN: Prospective, randomized, nonblinded study. SETTING: Community teaching hospital. PATIENTS: One hundred one acute and chronic renal failure patients requiring subclavian venipuncture and catheterization. After randomization, 47 patients underwent subclavian catheterization with a silver-impregnated cuff (Ag-CC), and 54 patients had routine catheter (RC) placements. MEASUREMENTS: Multiple presumed predictor variables for catheter-related infections, exit site infection rate, bacteremia rates, and semiquantitative cultures of all catheters.