摘要:

The glomerular expression (mRNA levels) of transforming growth factor‐β1 (TGF‐β1) was assessed in two forms of rat anti‐glomerular basement membrane (GBM) disease, a macrophage‐independent and a macrophage‐de‐pendent variant. After a single intravenous injection of rabbit anti‐rat GBM immune serum, significant proteinuria and histopathologic changes developed in both variants. Increased TGF‐β1 mRNA levels were found in isolated glomeruli of the macrophage‐dependent variant only in which glomerular infiltration by macrophages also occurred. Macrophages isolated from glomeruli of animals with this variant demonstrated TGF‐β1 mRNA levels comparable to those found in glomeruli isolated at the same time point after injection of the anti‐GBM serum. The observations indicate that in anti‐GBM disease, enhanced glomerular TGF‐β1 expression occurs in the macrophage‐dependent variant and suggest that infiltrating macrophages account for this event.

ISSN:0002-9629    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

The present experiments tested the hypothesis that decreased production of an endothelium‐derived relaxing factor in arteries of hypertensive animals contributes to impaired endothelium‐dependent relaxation. Acetylcholine‐induced relaxation of freshly isolated spontaneously hypertensive rat (SHR) vessels precontracted with norepinephrine was impaired compared with Wistar‐Kyoto rats (WKY). 10 μM indomethacin partially normalized the SHR response. Inhibition of nitric oxide synthesis with 100 μM. nitro‐L‐arginine methyl ester or 100 μM. NG‐monomethyl arginine shifted the acetylcho‐line relaxation curve to the right, but had no effect on the maximal relaxation in WKY and completely inhibited relaxation of SHR. A similar pattern was observed with methylene blue (0.3 μM). Acetylcholine‐induced relaxation of WKY vessels pre‐contracted with 5 μM norepinephrine and 100 mM K+was attenuated 60% compared with vessels pre‐contracted with norepinephrine alone, and was completely inhibited by nitro‐L‐arginine methyl ester; relaxation of SHR vessels was decreased by 50%. Six‐hour storage at 37° C significantly attenuated acetylcholine‐induced relaxation in both strains; treatment with indomethacin improved the response. Moreover, relaxation of WKY vessels was completely inhibited by nitro‐L‐arginine methyl ester and NG‐monomethyl arginine after the storage period. The absence of L‐arginine‐induced relaxation and lack of effect of supplementation with L‐arginine indicated that the constitutively active NO synthetase was not induced and that L‐arginine substrate was limiting. The results indicate that mesenteric resistance arteries of the WKY express a relaxing factor generated by a non‐cyclo‐oxygenase, non‐nitric oxide synthetase pathway that is possibly a hyperpolarizing factor. This factor is either absent or expressed in very low amounts in vessels of the SHR. After a 6‐hour incubation period, expression of this factor is decreased and the nitric oxide pathway predominates. It is proposed that impaired relaxation of SHR resistance arteries may in part reflect the absence of this pathway.

ISSN:0002-9629    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

The prothrombotic state of patients with coronary artery disease (CAD) can be attributed partially to platelet activity. Management of such patients is hindered by a lack of techniques to assess hemostatic function. This study used a sensitive technique to monitor platelet function by measuring platelet force development during clot retraction. This technique allowed simultaneous measurement of clot elastic modulus on the same sample. Fibrin mass-length ratio (μ), fibrinopeptide A, D-Dimer, von Wille-brand's factor, thromboxane A2, platelet aggregation studies, and bleeding times also were performed. Fourteen patients with CAD were compared with 10 healthy volunteers. Despite more than 95% suppression of thromboxane B2and prolongation bleeding times in patients taking aspirin, force development remained significantly elevated over healthy control patients (8,279 ± 476 dynes versus 4,857 ± 380 dynes, p < 0.0006). Patients not taking aspirin had normal bleeding times and force development of 19,110 ± 3,700 dynes. Clot elastic moduli were enhanced in patients with CAD whether taking or not taking aspirin. Adenosine diphosphate and ristocetin-induced platelet aggregation were insensitive to the effect of aspirin in patients with CAD. Fibrinopeptide A, von Willebrand's factor, and D-Dimer levels were significantly elevated, and fibrin mass-length ratios were significantly larger in patients with CAD. Therefore, despite aspirin therapy, patients with severe CAD have evidence of persistent platelet activation and rigid clot structure. Monitoring of platelet force development may prove useful in delineating enhanced platelet function.

ISSN:0002-9629    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

The specific binding sites of125I-insulin in platelets from nondiabetic patients with acute myocardial infarction and unstable angina pectoris was significantly decreased (192 ± 84/cell) during the acute ischemic condition when compared with normal platelets (496 ± 76/ cell; p < 0.001, n = 9). A relatively low mean plasma insulin level (20 μU/mL) with an elevated mean glucose level (130 mg/dL) was noted. The decreased binding of insulin and the relatively low mean plasma insulin level during the acute ischemic condition improved into the normal range during 8 to 12 weeks of recuperation. The decrease of insulin binding sites in the acute phase and their subsequent increase during recovery were directly related to the hormone-induced increase in sensitivity to prostaglandin Ex through the stimulation of adenosine 3′,5′-cyclic monophosphate formation in platelets by the prostanoid.

ISSN:0002-9629    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

It has been demonstrated that expansion of extracellular fluid volume induces the release of a low-molecular-weight natriuretic and sodium-potassium-activated adenosine triphosphatase inhibiting hormone (NKAI). In this study, we used a highly purified hormone extracted from pooled hypertensive urines (u-NKAI). Like ouabain, this compound was found to be a potent inhibitor of the sodium-potassium-activated adenosine-triphosphatase and potassium-stimulated paranitrophenyl phosphatase enzyme systems as well as a vasoconstrictor in vitro. In contrast to ouabain, which is a competitive inhibitor of both enzyme systems with respect to potassium, u-NKAI is noncompetitive. Furthermore, u-NKAI differs from ouabain by its lack of cross-reactivity with digoxin antibodies. In addition, whereas ouabain binds to both high-affinity and low-affinity binding sites on the sodium-potassium-activated adenosine-triphosphatase enzyme in the absence of potassium, u-NKAI binds only to the low-affinity binding sites. This study demonstrates that the highly purified u-NKAI, although ouabain-like in certain respects, is not an “endogenous ouabain.”

ISSN:0002-9629    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Students were allocated randomly to participate in a simple ambulatory experience during their third-year medicine clerkship. A convenience sample was surveyed by questionnaire in the fall of their fourth year, after decisions were made regarding future career plans. The questionnaire assessed medical student attitudes toward general internal medicine and career choice.Valuation of the effectiveness of the clerkship was associated with choosing a career in internal medicine (p = 0.007); having an ambulatory experience was not associated with subsequent career choice. Sixty-two percent of all students felt the clerkship affected their career choice a great deal or moderately; these students were likely to find a career in general internal medicine less attractive as a result of their clerkship (p = 0.008). When stratified, this association disappeared in those students who participated in the ambulatory experience (p = 0.39) but persisted in those who did hot (p = 0.01). A simple experience in internal medicine clinics during a third-year clerkship was not associated with subsequent career choice, but had some positive effects on attitudes toward general internal medicine as a career.

ISSN:0002-9629    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Two common screening tools for detecting hearing loss, the Hearing Handicap Inventory for the Elderly-Screening Version (HHIE-S) and Audioscope, are compared. One hundred eighty-five consecutive patients over age 60 at a primary care clinic received both screening tests followed by pure tone audiometry. Three criteria for hearing loss were considered: Speech Frequency Pure Tone Average ≥ 25 dB; High Frequency Pure Tone Average ≥: 25 dB; and Ventry and Weinstein's criteria of a 40 dB loss at 1.0 or 2.0 kHz. Ranges of respective operating characteristics for the Audioscope versus the HHIE-S were: sensitivities 0.64 to 0.96 versus 0.29 to 0.63; specificities 0.80 to 0.91 versus 0.75 to 0.93; and positive likelihood ratios 4.86 to 7.52 versus 2.42 to 4.27. Most patients preferred screening with the Audioscope (60%) over the HHIE-S (13%). The Audioscope is preferred by patients, and outperforms the HHIE-S using a variety of reference standard definitions.

ISSN:0002-9629    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

The effects of hypercalcemia on the heart and the resulting alterations of the electrocardiogram are well established. However, there are only rare reports of arrhythmias caused by hypercalcemia in primary hyperparathyroidism. This article describes a case of severe hypercalcemia secondary to hyperparathyroid-ism causing tachy-brady syndrome.

ISSN:0002-9629    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Transverse myelitis is a rare complication of Epstein-Barr virus (EBV) infection. This article describes a case of a previously healthy patient with a subacute transverse my-elopathy. The cerebrospinal fluid showed lymphocytic pleocytosis and protein elevation. A magnetic resonance imaging scan demonstrated abnormal spinal cord signal intensity over several cervical and thoracic segments, suggesting the diagnosis of transverse myelitis. The patient was treated with high-dose corticosteroids and had a rapid improvement. Serologic studies for other viruses were negative; antibody tests indicated acute EBV infection. It is thought this represents a case of transverse myelitis associated with acute EBV infection. Although a few similar patients have been reported previously, this case is the first where EBV serology suggested the etiology at the time of diagnosis, when EBV antibody titers and polymerase-chain reaction for EBV DNA in the cerebrospinal fluid were performed, and when a magnetic resonance imaging scan was used for diagnosis and follow-up.

ISSN:0002-9629    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Sotalol was developed as a nonselective beta-blocker in the 1960s for the treatment of hypertension and later for cardiac risk management after myocardial infarction. Extensive research has since well described class III type electrophysiologic effects on the repolarization of myocardial fibers. Sotalol prolongs and homogenizes ventricular refractoriness, resulting in good antifibrillatory/antitachycardia protection. The unique combination of beta-blockade and antiarrhythmic effects probably will promote sotalol's use in postmyocardial infarction patients with ventricular tachycardia and sudden death. This article summarizes the pharmacologic and cardiovascular effects of this new drug, outlining its clinical use.

ISSN:0002-9629    

出版商:OVID    

年代:1994

数据来源: OVID