Heart rate variability in evaluation of the autonomic nervous system. A review

Analysis of heart rate variability is increasingly used for testing the function of the autonomic nervous system in cardiovascular disease and for the diagnosis of autonomic neuropathy. In cardiovascular disease, long-term data collection (several hours) is primarily used to describe the static activity in the different branches of the autonomic nervous system. In the diagnosis of autonomic neuropathy, short-term forced variations in heart rate are employed in order to describe the dynamic capacity of the parasympathetic nervous system. In the subsequent data-analysis several different principles may be used, and the purpose of this review is to describe these principles and their use in clinical and experimental settings.     

Concurrent primary carcinoma of the gallbladder and acute cholecystitis

BACKGROUND/AIMS: Primary carcinoma of the gallbladder is rare and associated with a late diagnosis and poor prognosis. Concurrent acute cholecystitis frequently obscures the presence of carcinoma. The information regarding gallbladder carcinoma with acute cholecystitis is limited. In order to better understand the presentation of gallbladder carcinoma with acute cholecystitis, we retrospectively reviewed the data of patients with primary carcinoma of the gallbladder. METHODOLOGY: The data of 86 patients with primary carcinoma of the gallbladder treated between 1979 and 1994 were compiled and reviewed. The patients were divided into 2 groups: Group 1 (with acute cholecystitis, 21 patients) and Group 2 (without cholecystitis, 65 patients). Clinicopathological comparisons were made and evaluated between these two groups RESULTS: The average age of Group 1 patients was older than that of Group 2 patients (75+/-2 years vs. 63+/-2 years; p<0.05). Three Group 1 patients presented with sepsis. The interval between the onset of symptoms and hospital admission in Group 2 patients was significantly (p<0.05) longer than that in Group 1 patients (243+/-95 days vs. 20+/-11 days). Leukocytosis (>11,000/mm3) was more common in Group 1 patients than in Group 2 patients (47.6% vs. 15.4%). Jaundice was more common in Group 2, and fever was common in Group 1. The majority of Group 2 gallbladder cancers were stage V (75.4%). In contrast, 52.4% of Group 1 gallbladder cancers were stage III and 38.1% were stage V. The 30-day postoperative mortality rate in Group 1 and Group 2 patients was 9.5% and 7.7%, respectively. The cumulative survival of Group 1 patients was not different from that of Group 2 patients (log-rank test, p>0.05). CONCLUSIONS: Age, the interval of symptoms prior to admission, the location of abdominal pain, fever, leukocytosis, and the absence of jaundice suggested the presence of acute cholecystitis in gallbladder carcinoma. A high index of suspicion of the disease, intraoperative examination of gallbladder specimens, and more aggressive surgical treatment may improve patient survival.     

Adolescents and sexually transmitted diseases. Epidemiologic, preventive and social aspects]

Investigation in neurophysiology usually involves measurements of large population-average signals or small sample recordings. There is an underlying assumption that the observations express activity of large groups of similarly acting neurons that is the result of a bottom-up scenario in which individual cells, via their synaptic interactions, lead to the large scale phenomena. The connection between the levels must be provided by theory, which must also provide the relevant variables for observation. It is suggested that between the experiment and the full theory there is a creative, mixed role for simulation: both experimental and theoretical. A simulation presents complex dynamics and hence is an empirical board for testing theoretical tools, yet its controlled behaviour can make predictions about the biological system.     

Case study: needs-based technology assessment and essential national health research. Experience in the Philippines

We investigated the effects of RGH-2202 (posatirelin, (-)-(2S)-N-[(1S)-1-[[(2S)-2-carbamoyl-1-pyrrolidinyl[carbonyl]-3- methylbutyl]-6-oxopipecolamide), a thyrotropin-releasing hormone (TRH) analog, on behavioral changes during a chronic phase of focal ischemia in rats in comparison with the parent peptide. The left middle cerebral artery (MCA) was occluded under halothane anesthesia, and the subsequent behavioral changes were observed for 35 days. RGH-2202 (1, 3, and 10 mg/kg) and TRH (10 mg/kg) were given IP just after the operation and afterward once a day for 14 days. MCA-occluded rats exhibited neurologic symptoms including hemiplegia and abnormal posture and disturbance of passive avoidance learning during the entire 35-day observation period. The repeated treatment with either peptides improved the neurologic and cognitive deficits. In addition, a recovery from deficits was still advanced after discontinuation of the drug treatment. In these effects, RGH-2202 was about three times more potent than TRH. Neural tissue damage in drug-treated groups, measured by omega 3 binding site densities 35 days after MCA occlusion, was included to be less than that in the vehicle-treated group. These results suggest that appropriate treatment with RGH-2202 may be useful in the treatment of functional disturbances after focal cerebral ischemia.     

Flow cytometric assay of modulation of P-glycoprotein function in whole blood by the multidrug resistance inhibitor GG918

Galactose-1-phosphate uridyl transferase (GALT) deficiency causes classical galactosemia in humans. Mice deficient in this enzyme were created by gene targeting. GALT-deficient mice develop biochemical features similar to those seen in humans with GALT deficiency, but fail to develop the pattern of acute toxicity seen in newborns with classical galactosemia. This study suggests that alternative routes of galactose metabolism are important in the pathogenesis of galactosemia.     

Beta 1 integrin ligation stimulates tyrosine phosphorylation of phospholipase C gamma 1 and elevates intracellular Ca2+ in pancreatic acinar cells

We have recently reported increased tyrosine (TYR) phosphorylation of a number of pancreatic acinar cell proteins following antibody ligation of beta 1 integrins (Wrenn and Herman, Biochem, Biophys. Res. Commun. 208, 1995, 978-984). Concurrent with this TYR phosphorylation was a marked activation of protein kinase C (PKC). This led us to investigate phospholipase C gamma 1 (PLC gamma 1), a key enzyme responsible for diacylglycerol generation, as a target for integrin-mediated TYR phosphorylation. Staining with antiphosphotyrosine antibodies revealed increased TYR phosphorylation of immunoprecipitated PLC gamma 1 prepared from beta 1 integrin-ligated acinar cells. Subsequent stripping and reprobing of Western blots with polyclonal anti-PLC gamma 1 was confirmatory. Over this same time period, intracellular [Ca2+] increased from < 100 nM to 600 nM, further suggesting a functional relevance of integrin-linked phosphorylation as a regulatory mechanism in exocrine pancreas.     

A light and electron microscopic study of cytoplasmic phospholipase A2 and cyclooxygenase-2 in the hippocampus after kainate lesions

Tamoxifen, the major adjuvant drug treatment for estrogen-dependent breast cancer, has been shown previously to affect both estrogen-dependent and calcium/calmodulin-dependent pathways. In the current study, we developed an in vitro slice system to study the effects of tamoxifen on ATP levels in hypothalamic (HTH) and preoptic areas (POA) of the rat brain. Baseline data showed that, following a 2-h incubation, HTH and POA slices had comparable ATP levels to hippocampal slices, a system used extensively by researchers examining the metabolic responsiveness of the hippocampal region (HPC) of the brain. HTH-POA slice ATP levels remained steady for 2, 4 and 6 h, but fell to 11% of initial levels by 12 h. Neurons from HTH-POA slices incubated for 4 h appeared healthy and demonstrated robust protein synthesis as measured autoradiographically by incorporation of [3H]leucine. We explored the effects of tamoxifen (TAM), fluphenazine (FLU) and estradiol (E2) on ATP levels in HTH and POA slices. The effects of TAM were complex: a 4-h incubation with 10-6 M TAM led to decreased ATP levels in HTH (but not POA), and a 4-h incubation with 10-8 M led to increased ATP levels in POA (but not HTH); a 15-min exposure to 10-6 M TAM decreased ATP levels in POA (but not HTH) slices, while the exposure of slices to the lower concentration of TAM was without effect in either area. As with higher concentrations of TAM, 4-h incubation with 10-6 M FLU decreased ATP levels in HTH (but not POA), while incubation with E2 did not affect slice ATP levels. These data are consistent with the hypothesis that both TAM and FLU alter ATP levels in HTH slices via calmodulin- or calcium-mediated processes.