Genetic studies on chromosome 12 in late-onset Alzheimer disease

BACKGROUND: Gastroesophageal reflux (GER) appears to be related to laryngeal carcinoma. Little is known about GER and gastropharyngeal reflux (GPR) in the laryngectomized patient. Therefore, GER and GPR were studied in laryngectomized patients. METHODS: In 11 patients, 24-hour double-probe pH monitoring was performed in an ambulant setting. An optic fiberscope was used for the accurate positioning of the proximal probe in the upper esophageal sphincter. RESULTS: In 9 of 11 patients pathologic GPR was found. Four of these 9 patients had reflux in upright and supine position, 5 patients had reflux only in upright position. CONCLUSIONS: A high incidence of GPR in laryngectomized patients was found. These results raise the question whether all laryngectomized patients should be investigated for reflux and in the presence of pathologic reflux findings should be treated with reflux prophylaxis.     

Morbidity and mortality of incontinence surgery in elderly women: an analysis of Medicare data

Homicides in which the victims are first subdued with a chemical asphyxiant rare unusual and quite rare. We report three cases in which victims were first overcome by ether containing compounds and then killed by other means of asphyxiation. The ether containing compounds used in these three cases were readily available commercial products. In two cases, the distinctive spectra of the volatile compounds in the decedents' blood, from the gas chromatograph and from the gas chromatograph/mass spectrometer, were compared with suspect ether containing products recovered during the scene investigations. In one case, an identical match was obtained. In the other case, the chromatographic spectra differed slightly from the compounds found at the scene, but the difference was explainable by metabolic breakdown of the compounds in vivo.     

Effect of benazepril on complex ventricular arrhythmias in older patients with congestive heart failure, prior myocardial infarction, and normal left ventricular ejection fraction

Sixty patients, mean age 82 +/- 8 years, with congestive heart failure, prior myocardial infarction, normal left ventricular ejection fraction, and > or = 30 ventricular premature complexes per hour detected by 24-hour ambulatory electrocardiograms, and who were treated with diuretics, were randomized to treatment with benazepril 20 to 40 mg/day (30 patients) or to no benazepril (30 patients). At a median of 6 months after treatment, follow-up 24-hour ambulatory electrocardiograms showed that compared with no benazepril, benazepril caused no significant reduction in the number of ventricular premature complexes per hour or in the number of runs of ventricular tachycardia per 24 hours.     

Molecular cloning of capillary permeability-increasing enzyme-2 from Agkistrodon caliginosus (Korean viper)

The gene of capillary permeability-increasing enzyme-2 (CPI enzyme-2) was cloned from the cDNA library of Agkistrodon caliginosus and its nucleotide sequence was determined. Its sequence indicates that CPI enzyme-2 is synthesized as a pre-zymogen of 258 amino acid residues, including a putative secretory signal peptide of 18 amino acids and a proposed zymogen peptide of 6 amino acids. The amino terminal sequence deduced from the cDNA sequence was exactly consistent with that of CPI enzyme-2 except for the substitution of an amino acid (Gly27-->Ser). The open reading frame is very similar to those of plasminogen activator and thrombin-like proteases cloned from other snakes. The clone encoding CPI enzyme-2 belongs to the serine protease family. The active site of the enzyme is highly conserved at His41, Asp86 and Ser180. Its possible glycosylation sites, Asn-X-Thr/Ser, are located at amino acid residues 20-22, 55-57, 79-81 and 97-99.     

Functional consequences of a Na+ channel mutation causing hyperkalemic periodic paralysis

Hyperkalemic periodic paralysis (HYPP), one of several inheritable myotonic diseases, results from genetic defects in the human skeletal muscle Na+ channel. In some pedigrees, HYPP is correlated with a single base pair substitution resulting in a Met replacing Thr704 in the fifth transmembrane segment of the second domain. This region is totally conserved between the human and rat channels. We have introduced the human mutation into the corresponding region of the rat muscle Na+ channel cDNA and expressed it in human embryonic kidney 293 cells. Patch-clamp recordings show that this mutation shifts the voltage dependence of activation by 10-15 mV in the negative direction. The shift results in a persistent Na+ current that activates near -70 mV; this phenomenon could underlie the abnormal muscle activity observed in patients with HYPP.     

Prospective evaluation of the gastrointestinal tract in patients with iron deficiency and no systemic or gastrointestinal symptoms or signs

BACKGROUND: Although endoscopic evaluation of the gastrointestinal tract is commonly performed to evaluate iron deficiency, little data is available regarding the underlying causes, yield of evaluation, and long-term outcome for those in whom gastrointestinal and systemic symptoms and signs are absent. METHODS: In- or out-patients seen by the gastroenterology consultative service at a large inner-city hospital over a 56-month period were considered eligible for the study when iron deficiency (serum ferritin <50 ng/mL) was documented. Exclusion criteria included: any gastrointestinal or systemic symptoms/signs, radiographic or endoscopic examinations of the gastrointestinal tract within 3 and 5 years, respectively, or obvious source of blood loss. Patients underwent colonoscopy and if no lesions other than carcinoma were found, upper endoscopy was then performed with a pediatric colonoscope. RESULTS: Fifty-two patients were evaluated (mean age, 66 +/- 13 years; range, 20 to 89 years; 32 men/20 women). At the time of evaluation, the mean (+/-SD) hematocrit was 25% +/- 7% (range, 14% to 42%). Overall, 23 patients (44%; 95% CI 30% to 59%) had an identifiable gastrointestinal lesion considered the cause of iron deficiency, including: colonic carcinoma, 11 (21%); colonic and/or esophagogastric/duodenal vascular ectasias, 9 (17%); and gastric carcinoma, colonic polyposis, and colonic ulcers in 1 patient each. Long-term follow-up (median 24 months, range 2 to 63 months) identified only 1 patient with a cause found (colonic carcinoma), and in this patient, complete colonoscopy was not technically possible at the time of initial evaluation. There were no clinical or laboratory features that distinguished patients with an etiology for iron deficiency to the idiopathic group. CONCLUSIONS: Approximately half of patients with iron deficiency in whom gastrointestinal or systemic signs or symptoms are absent have an underlying gastrointestinal lesion. Nevertheless, despite a thorough endoscopic evaluation, some patients will have no etiology found; the prognosis for these patients is excellent.     

Micronuclei in nasal mucosa, oral mucosa and lymphocytes in students exposed to formaldehyde vapor in anatomy class

The developing heart primordium strongly expresses N-cadherin. In order to investigate the role of this adhesion molecule in heart morphogenesis, chicken embryos were cultured at stages 5-12, and injected with anti-N-cadherin antibodies that can specifically block the activity of this cadherin. In the injected embryos, the epimyocardial layers, which develop bilaterally from the splanchnic mesoderm, did not fuse to form a single cardiac tube. Moreover, each of the unfused layers became fragmented into epithelioid clusters. At the cellular level, large intercellular gaps were observed in the antibody-treated myocardial layers. These disorganized myocardial layers beat to some extent, suggesting that their differentiation was not blocked; however, their contraction was not coordinated. Morphogenesis of other tissues, not only N-cadherin-negative but also N-cadherin-positive tissues, such as the neural tube and notochord, proceeded normally even in the presence of anti-N-cadherin antibodies. These results suggest that N-cadherin is indispensable for heart formation, but not for morphogenesis of the other tissues, at the developmental stages examined. For the latter processes, expression of other cadherin subtypes presumably compensated for the loss of N-cadherin activity.     

Rupture of the perivisceral aorta: atherosclerotic versus mycotic aneurysm

This study examines the contribution of GABAergic inhibition to the discharge pattern and recovery properties of 110 bat inferior collicular neurons by means of bicuculline application to their recording sites. When stimulated with single pulses, 74 (67%) neurons discharged one or two impulses (phasic responders), 19 (17%) discharged three to ten impulses (phasic bursters) and 17 (16%) discharged impulses throughout the entire stimulus duration (tonic responders). Bicuculline application changed phasic responders into phasic bursters or tonic responders, increased the number of impulses by 10-2000% and shortened the response latency of most neurons. When stimulated with pairs of sound pulses, the recovery cycles of these neurons can be described as: (1) long inhibition (n = 49, 45%); (2) short inhibition (n = 41, 37%); and (3) fast recovery (n = 20, 18%) based upon the 50% recovery time that was either longer than 20 ms, between 10 and 20 ms or shorter than 10 ms. Bicuculline application shortened the 50% recovery time of most neurons by 11-2350% allowing them to respond to pairs of sound pulses at very short interpulse intervals. These data demonstrate that GABAergic inhibition contributes significantly to auditory temporal processing.     

Relative contributions of cardiopulmonary and sinoaortic baroreflexes in causing sympathetic activation in the human skeletal muscle circulation during orthostatic stress

The aim of this study was to reexamine the hypothesis that cardiopulmonary baroreflexes are more important than sinoaortic baroreflexes in causing vasoconstriction in the skeletal muscle circulation during orthostatic stress. We recorded muscle sympathetic nerve activity (MSNA) with microelectrodes in the peroneal nerve (and forearm blood flow with venous occlusion plethysmography) in normal subjects (innervated ventricles) and in heart transplant recipients (denervated ventricles) during graded lower body negative pressure (LBNP) performed alone and in combination with intravenous infusion of phenylephrine, which was titrated to eliminate the orthostatically induced fall in blood pressure and thus the unloading of both carotid and aortic baroreceptors. The principal new findings are as follows: (1) The increases in both MSNA and forearm vascular resistance during multiple levels of LBNP were not attenuated by heart transplantation, which causes ventricular but not sinoaortic deafferentation. (2) In heart transplant recipients, a small increase in MSNA during mild LBNP was dependent on a decrease in arterial pressure, but in normal subjects, a similar increase in MSNA occurred in the absence of any detectable decrease in the aortic pressure stimulus to the sinoaortic baroreceptors. (3) In normal subjects, the large increase in MSNA during a high level of LBNP was dependent on a decrease in arterial pressure and could be dissociated from the decrease in central venous pressure. Taken together, the findings strongly suggest that sinoaortic baroreflexes are much more important and ventricular baroreflexes are much less important than previously thought in causing reflex sympathetic activation and vasoconstriction in the human skeletal muscle circulation during orthostatic stress.