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Biomedical subjects

C Schmid

Publications and source records attributed to C Schmid.

At least 163 records · Page 9Linked to original sources

Factors contributing to the development of chronic rejection in heterotopic rat heart transplantation.

BACKGROUND: The present study was devised to elucidate the influence of immunogenicity, immunosuppression, and ischemia on the development of transplant vasculopathy (TVP) as well as to investigate myointimal proliferation in syngeneic transplantation. METHODS: Fischer 344 and Brown Norway rat heart allografts and Lewis isografts were treated with rapamycin or cyclosporine, exposed to 4 hr of cold ischemia, and observed for 100 to 300 days before the incidence and degree of TVP and perivascular infiltration were assessed. RESULTS: The incidence of TVP in Fischer 344-->Lewis allografts (rapamycin, 0.5 mg/kg for 14 days) rose steadily, with dense mononuclear infiltration present in coronary lesions at all times (from 10+/-2% at 50 days to 85+/-15% at 150 days). Increased immunogenicity (Brown Norway-->Lewis) intensified TVP (62+/-13%) as compared with its control (25+/-15%, P<0.005). Enhanced immunosuppression (rapamycin, 0.5 mg/kg daily) decreased the incidence of TVP (22+/-11%, P<0.005), and additional low-dose cyclosporine was ineffective (1.5 mg/kg daily, 40+/-14%, NS). Four hours of cold ischemia before transplantation failed to have any effect on allografts, but promoted TVP in isografts (0 vs. 11+/-8%). CONCLUSIONS: The antigenic stimulus has probably the most important impact on the development of TVP, but is not necessarily essential. In most allografts, TVP probably reflects ongoing sublethal acute rejection, whereas myointimal proliferation in isografts presumably results from a perioperative antigen-independent response-to-injury mechanism.

Animals↗

Susceptibility of dyskinetoplastic Trypanosoma evansi and T. equiperdum to isometamidium chloride.

Isometamidium chloride (ISM) is an effective trypanocide with curative and prophylactive activity in husbandry animals. The mode of action of ISM against pathogenic trypanosomes is not fully understood, but there is evidence in the literature that kinetoplastic topoisomerase type II is selectively inhibited by the drug. This prompted the hypothesis that dyskinetoplastic trypanosomes would express a reduced level of susceptibility to ISM. From parental Trypanosoma evansi and T. equiperdum populations we generated clones containing only dyskinetoplastic organisms and clones containing organisms with kinetoplasts. The susceptibility of these clones to ISM was quantified by in vitro assays. The susceptibility of all clones was in the same range. Minor differences in drug susceptibility found between the clones showed that the dyskinetoplastic T. evansi and T. equiperdum clones were even more susceptible to ISM than their kinetoplastic counterparts. Thus, the hypothesis that the dyskinetoplastic trypanosomes would be less susceptible to or tolerant of ISM was clearly disproved. The previously demonstrated inhibition of kinetoplastic topoisomerase type II by ISM cannot be the primary toxic effect of the drug on trypanosomes, and the mode of action of ISM needs to be reassessed.

Animals↗

Cardiac pacemaker infection: surgical management with and without extracorporeal circulation.

BACKGROUND: Pacemaker infections are rare, but serious complications of pacemaker therapy. The generator pocket, the pacing leads, or both may be involved. METHODS: We report on 12 patients with infected pacemaker systems. Four patients suffered from localized generator pocket infections, 6 had infected leads, and 2 patients had both. Pacemaker systems were completely removed in all patients. When the infection was limited to the generator pocket, the pacemaker system was removed at the original implantation site. Extracorporeal circulation was employed for the explantation of infected pacing leads. RESULTS: No complications occurred in patients with localized generator pocket infections. One patient with infected leads who was preoperatively already in a serious clinical condition died of septic shock in the early postoperative period; another patient died of pulmonary complications after tricuspid valve replacement 14 months after pacemaker explantation. No recurrent infections were observed. CONCLUSIONS: Explantation of the complete pacemaker system has proved a reliable method to eradicate infection. Complications have been rare, except in patients in a critically ill state who undergo cardiopulmonary bypass.

Adult↗

Novacor LVAD bridge to transplantation in peripartum cardiomyopathy.

We report the case of a 22-year-old woman suffering from peripartum cardiomyopathy who was successfully bridged to cardiac transplantation with a Novacor left ventricular assist device (LVAD). Her course with the device is presented and emphasis is put on the size mismatch between the patient and the device, a fact with normally precludes the implantation of the Novacor LVAD.

Adult↗

1 alpha,25-dihydroxyvitamin D3 stimulates sodium-dependent phosphate transport in osteoblast-like cells.

1 alpha,25-Dihydroxyvitamin D3 [1,25(OH)2D3] stimulates calcium and phosphate absorption in the duodenum. Because osteoblastic cells appear to be responsible for Pi deposition in bone, we analyzed the effect of 1,25(OH)2D3 on sodium-dependent phosphate (NadPi) transport in newborn rat calvaria-derived osteoblasts and in a rat bone-derived cell line, PyMS. 1,25(OH)2D3 at 10(-9) mol/L stimulated NadPi uptake 1.6-fold in PyMS and 1.8-fold in calvaria cells after 24 h, but not after 2 h and 6 h. Insulin-like growth factor (IGF)-I stimulated NadPi transport 1.8-fold in both cell types within 2 h. There was no change in Na-dependent alanine transport or in Na-independent uptake of Pi and alanine, and the effects of 1,25(OH)2D3 on NadPi transport were not associated with corresponding changes in cell number, protein content, or alkaline phosphatase activity. Actinomycin D, an inhibitor of transcription, prevented the stimulatory effect of 1,25(OH)2D3 (but not that of IGF-I) on NadPi transport; stimulation of NadPi transport by 1,25(OH)2D3 may depend on an increased de novo synthesis of transporters. Our studies confirm that IGF-I stimulates NadPi uptake and show, for the first time, a specific stimulatory effect of 1,25(OH)2D3 on NadPi transport in osteoblasts in vitro.

Alanine↗

Effects of short-term insulin-like growth factor-I or growth hormone treatment on bone turnover, renal phosphate reabsorption and 1,25 dihydroxyvitamin D3 production in healthy man.

OBJECTIVES: To find out whether insulin-like growth factor-I (IGF-I) mimics the stimulatory effects of growth hormone (GH) on bone turnover and renal tubular phosphate reabsorption. DESIGN: Randomized, crossover study. SETTING: University Hospital, Zürich, Switzerland. SUBJECTS: Seven young healthy male subjects. INTERVENTIONS: Each subject was studied three times at 2-week intervals, treated with saline 0.9% (S), IGF-I [8 micrograms kg-1 h-1] by a continuous subcutaneous infusion and finally with GH (6 U. twice daily s.c.) for 5 days. MAIN OUTCOME MEASURES: 36 h after the start of treatment, IGF-I, biochemical markers of bone turnover, calcium, calcium regulating hormones, kidney function and phosphate reabsorption were measured in serum and in 2 h urine in fasting state. RESULTS: Serum levels of IGF-I were 26.8 +/- 7.3 (S), 119.4 +/- 11.4 (IGF-I) (P < 0.02) and 58.4 +/- 12.9 nmol L-1 (GH) (P < 0.02), respectively. Serum osteocalcin and carboxyterminal propeptide of type I collagen (PICP) as well as the urinary deoxypyridinoline/creatinine and the calcium/ creatinine ratios were all significantly higher after IGF-I (P < 0.02) or GH (P < 0.02) than after saline treatment. PTH levels did not change in response to treatment. Total albumin-corrected calcium increased only after GH treatment (P < 0.05). The free calcitriol index rose from 2.2 +/- 0.5 x 10(-5) (S) to 2.81 +/- 0.25 x 10(-5) (IGF-I) (P < 0.03) and 2.45 +/- 0.25 x 10(-5) (GH), respectively. Serum phosphate and maximal tubular reabsorption divided by glomerular filtration rate (TmP/GFR) were significantly raised by GH (P < 0.03) but not by IGF-I as compared to saline 0.9%. CONCLUSIONS: (i) Similar to GH, IGF-I rapidly activates bone turnover. (ii) IGF-I does not mimic the effect of GH on renal phosphate reabsorption in spite of comparable effects on renal blood flow and glomerular filtration rate. (iii) IGF-I increases free calcitriol index in face of unchanged serum levels of calcium, phosphate and PTH, consistent with a direct stimulatory effect on 25-OHD-1a-hydroxylase.

Amino Acids↗

Susceptibility of Ugandan Trypanosoma brucei rhodesiense isolated from man and animal reservoirs to diminazene, isometamidium and melarsoprol.

Thirty-six Trypanosoma brucei spp. stocks isolated from man and domestic animals in south-east Uganda were studied for susceptibility to diminazene, isometamidium and melarsoprol in vitro. All stocks were susceptible to melarsoprol. One T.b. rhodesiense stock isolated from a sleeping sickness patient showed reduced susceptibility to the veterinary drugs diminazene and isometamidium. More than 100 ng/ml diminazene or 0.78 ng/ml isometamidium were required to eliminate that stock during 10 days drug exposure. In contrast, the remaining stocks were eliminated by 0.8-6.3 ng/ml diminazene and 0.01-0.20 ng/ml isometamidium. Clones derived from the resistant T. b. rhodesiense stock showed reduced susceptibility to isometamidium and diminazene comparable to the parental population. Control of sleeping sickness by treatment of the animal reservoir could, therefore, face serious problems since drug-resistant stocks as reported here would most likely not be eliminated by recommended doses of diminazene and isometamidium.

Animals↗

Morphologic characterization and assessment of mitral regurgitation after repair of atrioventricular defects in children.

Severe postoperative mitral regurgitation renders information on the underlying mechanism before reoperation very important, as a potential for mitral valve reconstruction may facilitate the decision whether to reoperate, especially in the very young. This study compares the efficacy of transthoracic echo-cardiography (TTE) and left-ventricular angiography with that of transesophageal echocardiography (TEE) for detection of the mechanism underlying mitral regurgitation and its quantitative assessment in children after repair of common atrioventricular septal defect. Five children aged 1.5 to 16 years were evaluated by TTE, TEE, and angiography for postoperative mitral regurgitation 1 to 21 months after initial repair. TEE showed septal detachment of the mitral leaflet in four patients and reopening of the mitral cleft in one patient as the cause of mitral regurgitation whereas TTE failed in four and angiography in all patients. TEE allows definite identification of morphologic characteristics of mitral regurgitation and reliable assessment of its severity. Thus redo surgery may be safety performed on the bases of TEE findings alone without confirmation by cardiac catheterization.

Adolescent↗

Primary malignant mesothelioma of the tunica vaginalis of the testis. Immunohistochemistry and electron microscopy.

A case of primary malignant mesothelioma of the tunica vaginalis of the testis in a 75 year old man is here presented. Anamnesis for asbestos exposure was negative. Recurrent left hydrocele was the main symptom. Echography revealed a nodular mass in the caudal aspect of the epididymis and papillary projection on the surface of the tunica vaginalis of the testis. An inguinal left orchiectomy was performed. The tumor both in the solid area and in the papillary projections was identified as a malignant mesothelioma of epithelial type. The role of immunohistochemistry and ultrastructure for a correct definition of the tumor is underlined.

Aged↗

Dietary salt intake modulates angiotensin II type 1 receptor gene expression.

This study aimed to characterize the influence of dietary salt intake on the gene expression of angiotensin II type 1 (AT1) receptor subtypes in different organs. Male Sprague-Dawley rats were fed low salt (0.2 mg/g), normal salt (6 mg/g), or high salt (40 mg/g) diets for 5, 10, and 20 days. mRNA levels for the two AT1 receptor subtypes were determined in adrenal gland, kidney, liver, and lung. In all of the organs examined, with the exception of the adrenal glands, low salt diet led to a transient decrease in the abundance of AT1A receptor mRNA but not of AT1B mRNA, which reached their nadirs between days 5 and 10 of feeding. In the adrenal gland, in which the AT1B receptor is predominant, low salt diet led to a transient increase in the expression of this receptor gene, with a maximum around day 10 of feeding. High salt diet exerted no significant influence on AT1 receptor gene expression in these organs. These findings indicate that the rate of salt intake, in particular, a reduction of salt intake, significantly influences AT1 receptor gene expression in an organ-, time-, and subtype-dependent fashion. It appears that AT1 receptor subtypes are differentially influenced by low salt intake, in that AT1B receptor gene expression increases and AT1A receptor gene expression decreases in this situation. This differential response of AT1 receptor gene expression may be relevant for the organism to be able to adapt to a reduction in oral salt intake.

Adrenal Glands↗

"False negatives" and "false positives" in acute pulmonary embolism: a clinical-postmortem comparison.

Although recent advances have been made in understanding its epidemiology, diagnosis and treatment, pulmonary embolism (PE) is still largely undetected and untreated, and the mortality rate has not appreciably changed in the last decades. The aim of this study was to: compare the postmortem frequency of massive and sub-massive PE during two different time periods in the same general hospital; ascertain whether the percentage of correct clinical diagnosis of PE has changed; identify factors which might contribute to the inaccuracy of the clinical diagnosis of PE. Altogether, 288 patients with autopsy-proven PE and adequate clinical data were collected in the first period; 182 subjects with the same characteristics were found in the second period. Cases observed from 1989 through 1994 were evaluated in terms of frequency of false negatives and false positives, predictive value of the clinical diagnosis of PE, and correlations between clinical and post-mortem diagnosis of PE on one side and several independent variables such as age, gender, associated diseases, recent surgery on the other. In our hospital the frequency of massive and submassive PE at autopsy was 8.6% from 1966 through 1974, 12.6% from 1989 through 1994 (p < 0.01). The percentage of correct clinical diagnosis of PE was 19.6% in the former period, 21.6% in the latter (NS) with 78.57% of false negatives and only 1.73% of false positives. Altogether the true positives were 21.42%, most of them being patients with massive PE. Clinical findings showed the coexistence of heart disease in 51.6% of the cases, congestive heart failure in 20.15%, metabolic disease in 7%, stroke in 12.5%, recent surgery in 12.5%. Autopsy revealed the presence of pulmonary infarction in 22% of cases, malignancy in 24.0%, pneumonia in 17.05%, acute myocardial infarction in 14.8%. Seventy percent of the cases in whom the point of origin of thromboemboli could be demonstrated had one or more thrombus in the district of inferior vena cava, more frequently at the level of the femoral and iliac veins. The positive predictive value of the clinical diagnosis of PE was 0.60, the negative predictive value 0.84. Multivariate logistic regression analysis showed that the clinical diagnosis of PE was hindered by the presence of pneumonia, facilitated by admission to the Cardiological Department. Age, duration of hospitalization, presence of pulmonary infarction, cancer, obesity, stroke, heart failure and recent surgery did not influence the clinical diagnosis of PE in this series. A positive correlation (p < 0.05) was found between autopsy rate and the percentage of correct clinical diagnosis of PE in the various hospital departments. This relationship needs further investigation, all the more so as in most countries the autopsy rate has been dramatically declining in recent times, especially in late life. In conclusion, at least in some institutions, the autopsy frequency of PE has increased during the last decades, and this increase has not been paralleled by a significant improvement in clinical diagnosis.

Acute Disease↗

[Electromechanical dissociation in myocardial infarction. Anatomical-clincal study of 82 cases].

UNLABELLED: In our experience electromechanical dissociation (EMD) is the most common mechanism of fatal cardiac arrest in patients with acute myocardial infarction (AMI). METHODS: We reviewed retrospectively 82 autopsy cases of AMI in whom the medical record documented EMD as terminal cardiac arrest in order to outline the clinical and pathologic features of different subgroups: 26 cases with external cardiac rupture (CR) were compared with 56 cases without CR. In turn, inside the latter series, 16 cases of sudden EMD were compared with 40 cases of EMD occurring in the terminal phase of cardiac shock. RESULTS: In comparison with those without CR, patients with CR showed at multiple regression analysis less evidence of left ventricular failure (p < 0.05); less extended infarct areas (p < 0.01); more frequent sudden EMD (p < 0.05). Most patients with CR had massive pericardial effusion; cardiac rhythm at the onset of EMD was seldom slow in those cases. In the group without CR no discriminant characteristics were found in cases of sudden EMD vs cases preceded by cardiac shock. CONCLUSIONS: In case of CR EMD occurs in less extensively damaged hearts and is generally sudden; in AMI without CR EMD may affect patients with severe depression of pump performance, but not necessarily in shock. EMD after an AMI may result from several factors: cardiac tamponade is prevalent in the presence of CR; in cases without CR our data don't permit to conjecture a distinct pathogenesis for sudden EMD in comparison with cases preceded by shock.

Aged↗