Autoimmune enteropathy, anti-tubular basement membrane antibodies, and glomerulonephritis.
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Biomedical subjects
Publications and source records attributed to M Levy.
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Single-dose (200 mg) carbamazepine pharmacokinetics was evaluated in six obese, otherwise healthy subjects, before and after a mean +/- SEM weight reduction of 30.0 +/- 5.0 kg over 11.3 +/- 1.2 months. After weight loss the mean +/- SEM plasma elimination half-life (t1/2) of carbamazepine was significantly shortened (60.3 +/- 3.1 versus 30.8 +/- 3.3 hours, p less than 0.01) and the total plasma clearance (CL) increased (20.4 +/- 1.8 versus 31.6 +/- 5.0 ml/min, p less than 0.05). The apparent volume of distribution (Varea) decreased (106.2 +/- 9.9 versus 77.7 +/- 4.5 L, p less than 0.01); however, no difference was evident when carbamazepine Varea was corrected for body weight. In addition, weight loss coincided in all participants with a complete sonographic disappearance of the initial fatty liver infiltration noted on enrollment. In conclusion, obesity associated with fatty liver presents an enlarged carbamazepine Varea, prolonged carbamazepine t1/2, and reduced carbamazepine CL. Whenever carbamazepine is initiated in obese subjects, steady-state concentrations should be expected only after twice the time required to achieve steady state in lean subjects. Thus carbamazepine maintenance dose should be reduced, dose interval prolonged, and monitoring of carbamazepine plasma levels provided.
The relationship between hostility and coronary artery disease may be partially mediated by unhealthy lifestyle behaviors. This study examined the relationship between hostility, lifestyle behaviors, and physical risk factors in 138 adult men and women. Subjects completed the Cook and Medley Hostility Scale (Ho scale) and self-reports of their dietary habits, consumption of alcohol and cigarettes, and physical activity. Recent findings indicated that a composite hostility score from three rationally derived subscales of the Ho scale tapping the dimensions of cynicism, hostile affect, and aggressiveness was a better predictor of mortality than the total Ho score. Thus, this composite measure of hostility and the total Ho score were used in data analyses. Measures of resting blood pressure, height, weight, and adiposity were also obtained. In men and women, both measures of hostility were positively associated with cholesterol intake and vigorous physical activity. Among women, both hostility measures were positively related to animal fat intake and negatively related to fiber intake. The composite measure was positively related to their resting systolic pressures. Among men, both hostility measures were positively related to cigarette smoking and sugar intake and negatively associated with systolic blood pressure and calcium intake. Findings are discussed in terms of previous research linking hostility to lifestyle behaviors and CAD.
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Infection of the mouse with Theiler's virus is one of the best animal models for the study of multiple sclerosis, a chronic demyelinating disease of the human central nervous system. The identification of the virus target cell(s) is fundamental to an understanding of the viral persistence as well as the inflammation and demyelination observed in the chronic phase of the disease. This paper reports that a small fraction of brain macrophages grown in vitro can be efficiently infected with Theiler's virus without significant cytolytic effect. Viral replication as well as continuous production of infectivity were observed in these cultures.
Chronic caval dogs with ascites were identified as being natriuretic "responders" or "nonresponders" (delta UNaV less than 20 microequiv./min) following an infusion of atrial natriuretic peptide (ANP) (100 ng.kg-1.min-1). To learn more about the factors modulating tubular resistance to ANP, we attempted to convert responders into nonresponders and vice versa by manipulating the physiological environment. To responding dogs, we readministered ANP in the presence of noradrenaline (n = 5), angiotensin (n = 5), indomethacin (n = 4), and adenosine receptor blockage with theophylline (n = 4), and with purposeful reduction of blood pressure (n = 5). To nonresponding dogs, we readministered the ANP in the face of alpha-adrenergic blockade (n = 4), saralasin (n = 4), dipyridamole to block adenosine cellular uptake (n = 5), and elevation of blood pressure (n = 4). In no case were we able to alter the initial natriuretic response to ANP. Binding parameters of ANP receptors in suspensions of renal papillary cells were equivalent in responding caval dogs (n = 6), nonresponding dogs (n = 7), and normal controls (n = 7), as was cGMP generation. We conclude that the tubular resistance to ANP in caval dogs unresponsive to this natriuretic peptide is not due to antagonism from catecholamines or angiotensin but may be due to a post-cGMP problem in signal transduction, or a reduction in the delivery of ANP to the distal nephron.
The diverse biological actions of endothelins (ET) appear to be mediated by specific cell-surface receptors. Autoradiography and membrane binding studies have shown abundant ET binding sites in the kidney. However, their expression in specific types of renal cells is unclear. We studied the binding of 125I-labelled endothelin-1 in freshly isolated cell suspensions from canine inner medullary collecting duct. Competition binding experiments revealed the presence of specific high-affinity binding sites: unlabelled ET-1 and ET-2 compared with the radioligand with an IC50 of 135 and 83 pM, respectively, while the IC50 of ET-3 and big ET-1 were 2 and 4 orders of magnitude higher, indicating the presence of ETA-type receptor. Angiotensin II, vasopressin, and atrial natriuretic peptide (ANP) did not compete for ET binding even at a concentration of 10(-6) M. Saturation binding experiments showed a single class of binding sites of high density (Bmax = 56.7 +/- 10.3 fmol/10(6) cells) and high affinity (Kd = 69.8 +/- 10 pM). In contrast, ANP receptors in the same cell preparations appeared as two classes of binding sites with widely different affinity and density. The high-affinity ANP site (Kd = 311 +/- 48 pM) was compatible with ANP-B (guanylate cyclase-coupled) receptor. ET-1 did not compete for this receptor. ET-1 (10(-7) M) did not alter ANP-induced cGMP generation in these cells (3.8-fold increase at 10(-7) M ANP), nor basal levels of cGMP.(ABSTRACT TRUNCATED AT 250 WORDS)
It has been reported that the intraportal infusion of glutamine in Munich-Wistar rats will cause depression of renal perfusion and the urinary excretion of salt and water. We have attempted to reproduce these findings in anaesthetized dogs. L-Glutamine was infused at doses between 120 and 150 mumol/min into the portal vein and femoral vein of anaesthetized dogs. No effect was observed on portal venous pressure, blood pressure, or kidney function. Similar data were obtained with D-glutamine. Liver biopsy revealed no abnormalities. When 1.5-3 micrograms histamine (free base) was infused into the portal system, portal venous pressure rose from 15.2 +/- 0.33 to 24.8 +/- 0.40 cmH2O (p < 0.05) (1 cmH2O = 98.1 Pa). Glutamine infusions do not appear to initiate hepatorenal reflexes in dogs as they have been reported to do in rats.
Inhibition of intrarenal neutral endopeptidase 24:11 (NEP) increases the natriuretic response to infused atrial natriuretic peptide (ANP). In various models of canine heart failure, angiotensin and kinins have been shown to modulate ANP and (or) NEP activity. In the present study, we examined possible modulators of NEP activity in normal dogs by infusing various agents into the left renal artery (or by denervating the left kidney) and comparing the response of this kidney with that of the contralateral one following the combined intravenous infusion of Squibb 28603 (a potent NEP inhibitor) and ANP (75 ng.kg-1.min-1). Four dogs received angiotensin (1.5 ng.kg-1.min-1) into the left renal artery, 8 dogs received saralasin (5 micrograms/min), 5 dogs received noradrenaline (2 micrograms/min), and 6 dogs received bradykinin (3 micrograms/min). Five dogs underwent left renal denervation. Angiotensin inhibited sodium excretion following the NEP inhibitor alone and after the NEP inhibitor plus ANP. Saralasin augmented the natriuretic response. None of the other protocols influenced sodium excretion. We conclude that angiotensin may modulate either the enzymatic degradation of ANP or influence its renal tubular effects.
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60% of chronic caval dogs with ascites did not respond to atrial natriuretic peptide (ANP) (75 ng.kg-1.min-1) with a natriuresis (TIVC-NR; delta UNaV = 2 +/- 0.8 mu eq/min) whereas the remaining 40% responded normally (TIVC-R; delta UNaV = 216 +/- 50 mu eq/min). Since proximal tubule neutral endopeptidase 24:11 (NEP) destroys most of intrarenal luminal ANP and kinins, we attempted to convert TIVC-NR into TIVC-R by providing NEP inhibition with SQ 28603 at 30 mg/kg. This potent and specific NEP inhibitor produced a natriuresis when administered alone to nine TIVC-NR dogs (delta UNaV = 67 +/- 2 mu eq/min) and permitted a natriuresis in the presence of ANP (delta UNaV = 97 +/- 18 mu eq/min). A natriuretic response to ANP could also be induced in TIVC-NR dogs by providing renal arterial bradykinin or intravenous captopril, a kininase inhibitor. Urodilatin, a natriuretic peptide not destroyed by intrarenal NEP was without effect in TIVC-NR dogs but increased UNaV when given to TIVC-R and normal dogs. Providing bradykinin to TIVC-NR now permitted an increment in delta UNaV (62 mu eq/min) when urodilatin was reinfused. TIVC-R dogs could be converted into TIVC-NR by pretreating with a specific bradykinin antagonist before infusing ANP. We conclude that TIVC-NR dogs are deficient in intrarenal kinins but are converted to responding dogs after NEP inhibition because of increased kinin delivery to the inner medullary collecting duct.
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PURPOSE: To describe the initial experience of a heart transplant program in Recife, Pernambuco. METHODS: Six patients in the final stage of heart failure were submitted to heart transplant. There were 4 male and 2 female patients, ranging in age from 15 to 61 years (mean, 43.8). Four had coronary heart disease and two dilated cardiomyopathy. The conventional operative technique of orthotopic heart transplant was used. All patients received a triple drug immunosuppressive therapy. RESULTS: There was one death due to acute rejection on the 28th postoperative day. The 5 survivors are in functional class I in a mean follow-up period of 113 days. CONCLUSION: The initial experience of a heart transplant program in Recife, Pernambuco, suggests that good long term results could be expected.
From a clinical standpoint, laser light differs from ordinary light in two important ways: (1) laser light, unlike ordinary light, is monochromatic; (2) laser light is highly directional, making it possible to efficiently collect and focus the light. Laser light is produced through a process known as stimulated emission. Tissue effects produced by laser light are governed by the light's wavelength. Recently, hollow, flexible fibers have been introduced for CO2 laser beam delivery; compared with existing beam delivery systems, the flexible fiber provides the clinician with increased tactile sensitivity and effective access into restricted spaces.
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Statistical correlations and predictive values were calculated for 330 gastrointestinal biopsies and tissues, of which 248 were from the stomach from 115 patients in this retrospective study, which graded 10 inflammatory and 14 morphological mucosal and submucosal abnormalities and compared them with the presence of Helicobacter pylori. Analysis revealed that 78 (31.5%) of the 248 stomach biopsies and tissues showed H. pylori, and 21 (8.5%) had non-Helicobacter-like bacteria, such as rods and cocci. Inflammatory components had high correlations, with specimens containing polymorphonuclear leukocytes (PMNs) showing high specificities and predictive values for a positive test, whereas the chronic inflammatory components had high sensitivities and predictive values for a negative test. Positive morphological correlations existed for mucus depletion, degeneration, regeneration, and ulceration, but intestinal metaplasia and adenocarcinoma had negative correlations. The antrum was most commonly infected, suggesting that intact healthy antral morphology and the neutral mucin in the surface epithelial cells represents the optimal environment for infection. Also, 8.5% of the gastric biopsies and tissues showed non-Helicobacter bacteria associated with inflammation, thus raising the question of colonization versus pathogenesis.
ANP administered to cirrhotic dogs or chronic caval dogs with ascites and urinary sodium retention (USR) usually causes heterogeneity of natriuretic response. To assess whether this same phenomenon would occur in the absence of edema, ANP at 100 ng/kg/min was given to dogs before and after the induction of USR by a variety of techniques. Eight dogs were over-diuresed with furosemide over a 2-day period, and 9 dogs were subjected to subacute hemorrhage over a similar period. These dogs were retested with ANP one day later. All 8 dogs given furosemide showed no response to ANP (delta UNa V = 7.4 +/- 4.8 microEq/min), compared to a normal response prior to the diuretic (delta UNa V = 128 +/- 34 microEq/min). The 9 hemorrhaged dogs also responded normally to ANP prior to this manipulation (delta UNa V = 74 +/- 14 microEq/min), but a blunted response post-hemorrhage (delta UNa V = 35 +/- 13 microEq/min). This profile was made up of 5 dogs who responded to ANP (delta UNaV = 62 microEq/min) and 4 who had no response whatsoever (delta UNa V = 3 microEq/min). When 8 dogs were given USR because of continuous mineralocorticoid administration, none responded, but all had a magnified natriuretic response to ANP during the 'escape' phase. Eight dogs were administered minoxidil (10 mg) by mouth daily to induce USR. All 8 dogs responded to ANP (delta UNa V = 93 +/- 6 microEq/min) which was no different from the pretreatment response (delta UNa V = 65 +/- 3 microEq/min).(ABSTRACT TRUNCATED AT 250 WORDS)