Autonomic nervous system activity and the spontaneous initiation of ventricular tachycardia. ESVEM Investigators. Electrophysiologic Study Versus Electrocardiographic Monitoring Trial

OBJECTIVES: We hypothesized that neurohormonal activity contributes to the initiation of sustained ventricular tachycardia (VT) as reflected in indices of heart rate variability (HRV). BACKGROUND: Autonomic nervous system activity participates in experimental arrhythmias but clinical studies have been inconsistent. METHODS: Holter electrocardiograms from 53 patients with VT were analyzed. Heart rate variability indices were determined over 5 and 15 min and 24 h and examined for changes before the onset of VT. Heart rate variability indices in the frequency domain included ultra low frequency power (FP) (ULFP): 0-0.0033 Hz; very low FP (VLFP): 0.0033-0.04 Hz; low FP (LFP): 0.04-0.15 Hz; high FP (HFP): 0.15-0.4 Hz; total power (TP); normalized LFP (LFPn); normalized HFP (HFPn), and the ratio: LFP/HFP. RESULTS: Heart rate variability indices were severely diminished: TP: 12,009+/-11,076 ms2; ULFP: 10,087+/-9,565 ms2; VLFP: 1,416+/-1,571 ms2; LFP: 544+/-620 ms2; HFP: 161+/-176 ms2, and LFP/HFP: 3.68+/-2.83. Heart rate increased before VT (80.4+/-17.3 to 85.3+/-17.4 bpm, p < 0.001). Several HRV variables declined 30 min before VT compared to 24-h values (VLFP: -5.89+/-17.81%, p = 0.031; LFP: -5.23+/-14.3%, p = 0.003; HFP: -4.35+/-13.7%, p = 0.04). LFPn and the LFP/HFP ratio decreased significantly before the onset of VT (-17.7+/-46.9%, p = 0.035 and -8.24+/-38.8%, p = 0.037, respectively), whereas HFPn increased slightly (4.29+/-29.9%, p = 0.097). CONCLUSIONS: Heart rate rose, whereas LFP, LFPn and LFP/HFP fell before the onset of VT. This pattern of changes could be explained by a rise in sympathetic activity and saturation of the HRV signal resulting in dissociation of the average and rhythmical effects of sympathetic activity. These findings suggest that alterations in autonomic activity contributed to arrhythmogenesis in this group of patients.     

Sexual abuse and bulimia: response to inpatient treatment and preliminary outcome

The purpose of this study was to explore the clinical impact of child sex abuse on bulimic patients. Specifically, differences in treatment response and preliminary treatment outcome between hospitalized bulimic patients with and without a reported history of sexual abuse were examined. The patients were evaluated for past history of alleged sexual abuse by investigator-based interview and ratings of severity of sexual abuse were made. Assessments of mood, eating disordered-related attitudes, and eating behaviors were conducted at the start of treatment, weekly during treatment, and three months post discharge. Sixty-one per cent (45) of the 74 patients enrolled in the study reported a history of child sexual abuse. The majority of such events constituted serious and very serious abuse by this study's criteria. The abused subjects exhibited higher levels of depression, anxiety, and eating disordered attitudes at each assessment point relative to nonabused subjects. In addition, abused subjects were more likely to be re-hospitalized in the 3 month post-discharge period. Significant differences in the extent of actual bulimic behaviors were not detected. Both the abused and nonabused bulimic patients demonstrated significant reductions in psychiatric symptomatology from pretreatment to posttreatment, and from posttreatment to follow-up. Contrary to prediction, differences in symptomatology between the very serious, serious, and least serious abused groups were not detected. Results suggest that bulimic patients with reported histories of sexual abuse can be effectively engaged in a conventional eating disorder treatment program, but that such abuse may place patients at a disadvantage owing to higher levels of pretreatment symptom severity. Findings suggest that extended and/or more specific intervention may be warranted for the abused bulimic patient.     

Genotypic and phenotypic analysis of Salmonella strains associated with an outbreak of equine neonatal salmonellosis

Isolates of Salmonella choleraesuis serotype ohio (S. ohio) recovered during an outbreak of equine neonatal salmonellosis on a Thoroughbred farm were compared with isolates of the same serotype from various animal, feed and environmental sources. Biochemical profiles, antimicrobial susceptibility patterns, phage susceptibility, plasmid profiles, restriction endonuclease analysis and ribotyping were used to compare relatedness of the strains. A total of 46 outbreak and non-outbreak associated isolates of S. ohio were studied. Differences in antimicrobial susceptibility patterns, phage susceptibility and plasmid profiles were useful for differentiating outbreak isolates from other equine isolates as well as bovine, porcine and some poultry isolates. Feed and other poultry isolates, most in geographic proximity to the outbreak, were indistinguishable from outbreak isolates by any of the methods employed. Investigative studies on the farm along with results of genotypic and phenotypic analysis of isolates suggested that contaminated feed was the most likely source of Salmonella in this outbreak.     

Targeting of gliadin peptides, CD8, alpha/beta-TCR, and gamma/delta-TCR to Golgi complexes and vacuoles within celiac disease enterocytes

Celiac disease (CD) is characterized by autodestruction of enterocytes after exposure of genetically susceptible individuals to dietary gluten. To define the transport pathways of proteins involved in the celiac immune response, we wished to determine the subcellular compartments of the intestinal mucosa where wheat gliadin peptides colocalize with receptors of T lymphocytes, including alpha/beta-TCR, gamma/delta-TCR, and CD8. Semithin and ultrathin frozen section of jejunal biopsies from CD patients and controls were used to perform immunofluorescence and immunogold labeling as well as in situ hybridization experiments. In patients with active CD, we detected gliadin peptides in vacuoles and Golgi complexes of enterocytes. CD8, alpha/beta-TCR, and gamma/delta-TCR were found in vacuoles and Golgi complexes within these gliadin-containing enterocytes in addition to the surface of intraepithelial and mucosal T lymphocytes. In contrast, we observed that the localization of CD4, CD3, T cell-restricted intracellular antigen (TIA), and leukocyte common antigen (LCA) was restricted to lymphocytes in CD patients. We further detected labeling signals for gliadin peptides, CD8, alpha/beta-TCR, and gamma/delta-TCR at the basal membrane of enterocytes that were interdigitated by extensions of lymphocytes. In situ hybridization experiments revealed that CD8 and gamma/delta-TCR were not expressed by CD enterocytes. We conclude that CD8, alpha/beta-TCR, and gamma/delta-TCR are targeted to Golgi complexes and vacuoles of small intestinal enterocytes in active CD. The observed process may be involved in the pathogenesis of CD enterocytes. We propose a mechanism for the uptake of CD8, alpha/beta-TCR, and gamma/delta-TCR by the basolateral membrane of small intestinal enterocytes.     

Pivotal issues in forensic psychiatry

OBJECTIVE AND METHOD: This review examines the scope of forensic psychiatry with particular emphasis on its ethical and social implications. Some comparisons are made between the development of the subspecialty in Australasia and similar developments in the United Kingdom and North America, and the reasons for differences. RESULTS: There has been inadequate debate in Australasia about some of the ethical issues relating to the practice of forensic psychiatry. Furthermore, Australian forensic psychiatry in particular has been slow to develop comprehensive and integrated services compared to other jurisdictions, and remains predominantly an assessment-based activity with primacy of the expert witness. CONCLUSIONS: Australasian psychiatry faces significant problems with respect to maldistribution of services. Governments are becoming more radical in their attempts to address this maldistribution and this has ethical implications for the profession itself and the practice of forensic psychiatry. Greater emphasis on the development of integrated and community-based forensic services, with leadership being provided by the profession itself, may deflect some of the present criticism, thereby allowing the subspecialty to more fully mature and develop with the approach of the new millennium.     

Effect of acetylation of ovalbumin on its adsorption behavior at solid/liquid interface

PURPOSE: Of the HMG-CoA reductase inhibitors, the hydrophilic pravastatin has been shown to exhibit relatively specific inhibition of cholesterol synthesis in the liver. As one of the reasons for this relatively specific pharmacological activity, we demonstrated that the tissue distribution of pravastatin is limited because of its high hydrophilicity, while hepatic uptake by active transport takes place at the liver surface via a multispecific anion transporter (M. Yamazaki et al., Am. J. Physiol., 264, G36-44, 1993). In this study, we examined the hepatic elimination of pravastatin at steady-state. METHODS: After i.v. infusion, the plasma concentrations of pravastatin in both arterial and hepatic venous blood were measured. RESULTS: The hepatic availability at steady-state exhibited a clear increase on increasing the infusion rate of pravastatin. The total hepatic elimination rate at steady-state exhibited Michaelis-Menten type saturation with the drug concentration in the capillary defined by typical mathematical models (i.e., well-stirred, parallel-tube and dispersion models), K(m) and Vmax values being comparable with those obtained from analysis of the initial uptake velocity using in vitro isolated hepatocytes. CONCLUSIONS: These results indicate that overall hepatic intrinsic clearance of pravastatin at steady-state is regulated by the uptake process, followed by rapid metabolism and/or biliary excretion with minimal efflux to the circulating blood.     

The Mini-Mental State Examination in general medical practice: clinical utility and acceptance

OBJECTIVE: To examine the psychometric properties, acceptance, and screening efficacy of the Mini-Mental State Examination (MMSE) in an internal medicine practice. MATERIAL AND METHODS: The MMSE was administered more than 4,000 times by 27 internists to 3,513 elderly patients (2,299 women and 1,214 men, 60 to 102 years old) who underwent general medical examinations. The efficacy of the MMSE for screening was measured in a subsample of age- and sex-matched patients with dementia (N = 185) and control subjects (N = 227). MMSE scores were correlated with age and education in the community sample. The attitudes of physicians about the MMSE were assessed with a 12-question survey. Sensitivity, specificity, and predictive values were calculated. RESULTS: Performance on the MMSE among persons older than 59 years was influenced by age and education but not by sex. During an interval of 1 to 4 years, a change of 4 or more points in the total MMSE score is needed to indicate substantial cognitive deterioration. Participating physicians considered the MMSE of little value for routine screening in unselected populations but wanted it available for use as a clinical test. The traditional MMSE cutoff score of 23 or less had a sensitivity of 69% and a specificity of 99%. Use of age- and education-specific cutoff scores improved the sensitivity to 82% with no loss of specificity. With use of typical base rates for dementia in a general medical practice, the positive predictive value was less than 35%. CONCLUSION: The clinical utility of the MMSE and acceptance by physicians may be improved through awareness of the influences of age and education on the MMSE and by its application in settings with a high base rate of dementia. The MMSE is ineffective when used to screen unselected populations; it should be used for persons at risk of cognitive compromise.     

Development of hydroxyapatite derived from Indian coral

A simple method of converting the calcium carbonate skeleton of the corals available in the Indian coast into hydroxyapatite granules has been developed. By heating the coral to 900 degrees C, the organic materials were eliminated. Powder X-ray diffraction analysis (XRD), Fourier transform infrared spectroscopy (FTIR) and thermogravimetric analysis (TGA) were employed to characterize the coral and to optimize the processing parameters as well as to confirm the hydroxyapatite formation. The coral used exhibits the presence of both aragonite and calcite phases (dimorphism). At a temperature of 900 degrees C the coral was found to decompose all the carbonate phases. The pre-heated coral is converted into hydroxyapatite by a chemical exchange reaction with di-ammonium phosphate under hydrothermal conditions. The hydroxyapatite obtained was in powder form and does not contain any impurities. The in vitro solubility test of the apatite granules performed in Gomoris, Michalelis, Sorensens, Ringer's and phosphate buffer of pH 7.2 and de-ionized water indicated the stability of the coralline hydroxyapatite.     

FGF2 promotes neuronal differentiation in explant cultures of adult and embryonic mouse olfactory epithelium

Neurogenesis in the adult olfactory epithelium is highly regulated in vivo. Little is known of the molecular signals which control this process, although contact with the olfactory bulb or with astrocytes has been implicated. Explants of mouse olfactory epithelium were grown in the presence or absence of several peptide growth factors. Basic fibroblast growth factor (FGF2) stimulated differentiation of sensory neurons in adult and embryonic olfactory epithelium. Other growth factors tested were ineffective. FGF2-stimulated neurons were born in vitro and expressed neurofilament, neural cell adhesion molecule, and beta-tubulin. The cells also expressed olfactory marker protein, a marker for mature olfactory sensory neurons in vivo. These bipolar neurons did not express glial fibrillary acidic protein or low-affinity nerve growth factor receptor. These results indicate that neither astrocytes nor olfactory bulb are necessary for differentiation of olfactory sensory neurons in vitro.