Neuropeptides in idiopathic chronic constipation (slow transit constipation)

Tissue specimens from the large bowel of 18 patients with long-standing slow transit constipation were investigated to determine the distribution and density of several neuropeptides and amines in the enteric nerve system, and also of endocrine cells in comparison to normal individuals. CGRP (calcitonin gene-related peptide), galanin, glucagon, GRP (gastrin-releasing peptide), metenkephalin, motilin, neuropeptide Y (NPY), PACAP, peptide YY (PYY), serotonin, somatostatin, substance P and VIP were studied by immunohistochemistry. Tissue concentrations of VIP, substance P and galanin were also measured by radioimmunoassay. Significantly increased VIP, SP and galanin contents were found in specimens from the ascending colon. Levels of VIP and galanin were also increased in the transverse colon. Immunohistochemistry revealed only marginal changes with an increased density of PACAP nerve fibres in the smooth muscle and of VIP and PACAP nerves in the myenteric plexus of the transverse colon. In the descending colon substance P and NPY immunoreactivity were also increased in the myenteric plexus while the density of VIP nerve fibres was reduced in the mucosa/submucosa. The frequency of PYY-containing cells and the 5-HT-containing cells in the ascending colon was significantly increased in the constipated patients.     

Cortical and subcortical T2 shortening in multiple sclerosis.

Low signal intensity on long-repetition-time MR sequences has been observed in deep gray matter structures in patients with multiple sclerosis. This T2 shortening most likely represents a nonspecific degenerative process. We recently observed T2 shortening in the pericentral cortical gray matter and subcortical white matter in a patient with severe multiple sclerosis and we postulate that this represents an additional manifestation of neural degeneration.     

Estimates of disease incidence in women based on antenatal or neonatal seroprevalence data: HIV in new york city

Piecewise constant incidence models were developed to estimate the force of infection in women from age-and time-specific antenatal or neonatal seroprevalence data. Differential inclusion of infected women in sero-surveys compared to uninfected women was taken into account, with respect to both changes in inclusion rate following infection, and changes in relative inclusion rate over calendar time. These models were applied to anonymous HIV seroprevalence data collected from neonates born to black and Hispanic women in New York City 1988-1992, with incidence and fertility parameters estimated by maximum likelihood. Estimates of inclusion rate parameters accorded well with what is known about the natural history of HIV. The data could not distinguish between additive and multiplicative combination of the effects of age and time on incidence. Incidence was strongly dependent on age with the highest incidence in women aged 20-34 years. There was strong evidence that incidence had been falling in Hispanic women since 1982-1984. The results illustrate the extent to which trends in incidence over time may be confounded by changes in the relative inclusion rate of infected and uninfected women.     

Precise and limited decompression for lumbar spinal stenosis

Summary Fifty-eight consecutive patients with lumbosacral nerve root entrapment due to spinal stenosis were treated with modified microsurgical decompression. Only the clinically relevant sides and levels were decompressed while the spinous processes, the interspinous ligaments, the medial portion of ligamentum flavum and the functionally important parts of the facet joints were preserved. The reviewers rated recovery as good or excellent in 71% of patients while patient self-assessment indicated 76% good or excellent outcome. These data suggest that microsurgical decompression of spondyloarthritic changes can effectively relieve the signs and symptoms of nerve root compression and that with careful evaluation of all available data the number of nerve roots requiring decomperession is often fewer than what is suggested by diagnositic images alone.     

Adverse ocular effects associated with niacin therapy.

In a retrospective survey of patients taking medication for hyperlipidaemia, those taking niacin (nicotinic acid) were more likely (p < 0.05) to report sicca syndromes, blurred vision, eyelid oedema, and macular oedema compared with those who never took niacin. Additionally, 7% of those taking niacin discontinued the drug owing to adverse ocular side effects, while none of the other lipid lowering agents were found to cause these side effects (p = 0.016). Data from spontaneous reporting systems support a possible association of decreased vision, cystoid macular oedema, sicca-like symptoms, discoloration of the eyelids with or without periorbital or eyelid oedema, proptosis, loss of eyebrow or eyelashes, and superficial punctate keratitis with the use of niacin in high doses. Decreased vision may be marked, and if the drug is not discontinued, may progress to cystoid macular oedema. All ocular side effects listed above are reversible if the association with niacin is recognised and the drug is discontinued; both the incidence and severity of the ocular side effects seem to be dose dependent.     

Combined anti-bradycardia/anti-tachycardia pacemaker-cardioverter-defibrillator systems in patients with recurrent ventricular tachyarrhythmias]

In 41 patients with recurrent sustained ventricular tachycardia and/or ventricular fibrillation an integrated pacemaker-defibrillator-system (PCD, Medtronic, model 7216 A or 7217 B) was implanted. In 21 out of 24 (88%) patients a new transvenous implantation technique in combination with a subcutaneous patch electrode was used. The implanted devices comprise antibradycardiac pacemaker functions, two different forms of antitachycardiac pacemaker functions (ramp and burst pacing), and internal cardioversion or defibrillation capabilities. During a mean follow-up of 8 months 147 episodes of ventricular tachycardia were detected, 131 of them were terminated successfully by antitachycardiac pacing; in 13 episodes internal cardioversion was applied to revert ventricular tachycardia. Twenty-seven episodes of ventricular fibrillation or rapid ventricular tachycardia (greater than 200/min) were detected and successfully terminated by internal defibrillation. In six patients with intermittent rapid atrial fibrillation, change of antiarrhythmic therapy was required to avoid activation of the device. The new integrated pacemaker-defibrillator systems improve therapy in patients with life-threatening tachyarrhythmias by reducing the number of internal cardioversions/defibrillations; the non-thoracotomy approach reduces the post operative risk.     

Histology as a prognostic factor in early gastric cancer.

Of 431 patients with gastric cancer observed in our institution, 23 (5.3%) had early gastric cancer (EGC). Macroscopic presentation, histology, depth of invasion, and lymph node involvement were evaluated in all the cases. All patients underwent surgery and an intensive follow-up was performed. Five of the 23 patients progressed, and the risk factors were examined. Histology seemed to be the main prognostic factor in our study, since intestinal type of EGC was associated to a significantly better prognosis. Total gastrectomy is indicated in the proximal localization of EGC, and should perhaps be performed also in cases presenting undifferentiated histology.     

Formation of mitochondrial phospholipid adducts by nephrotoxic cysteine conjugate metabolites.

Nephrotoxic cysteine conjugates derived from a variety of halogenated alkenes are enzymatically activated via the beta-lyase pathway to yield reactive sulfur-containing metabolites which bind covalently to cellular macromolecules. Mitochondria contain beta-lyase enzymes and are primary targets for binding and toxicity. Previously, mitochondrial protein and/or DNA have been considered as molecular targets for cysteine conjugate metabolite binding. We now report that metabolites of nephrotoxic cysteine conjugates form covalent adducts with rat kidney mitochondrial phospholipids. Rat kidney mitochondria were incubated with the 35S-labeled conjugates S-(1,1,2,2-tetrafluoroethyl)-L-cysteine (TFEC), S-(2-chloro-1,1,2-trifluoroethyl)-L-cysteine (CTFC), S-(1,2-dichlorovinyl)-L-cysteine, and S-(1,2,3,4,4-pentachlorobutadienyl)-L-cysteine. Quantitation of metabolite binding to whole mitochondria and to mitochondrial protein and lipid fractions revealed that as much as 42% of the 35S-label associated with the mitochondria was found in the lipid fraction. Total lipids were also extracted from 35S-treated mitochondria and separated by thin-layer chromatography. 35S-Containing metabolites were found in the lipid fractions from mitochondria treated with each of the conjugates. Lipids from both [35S]CTFC- and [35S]-TFEC-treated mitochondria contained major 35S-labeled lipid adducts which had similar mobility by thin-layer chromatography. Fatty acid analysis, 19F and 31P NMR spectroscopy, and mass spectrometric analyses confirmed that the major TFEC and CTFC adducts are thioamides of phosphatidylethanolamine.