Biomedical subjects
Publications and source records attributed to C Schmid.
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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.
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.
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.
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.
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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.
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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.
BACKGROUND: The survival benefit of screening mammography may be influenced by the age of the screened population. The current series examines the influence of age on the clinical, histopathologic, and prognostic features of nonpalpable breast carcinoma. METHODS: Needle localization and biopsy of suspicious mammographic lesions identified 173 breast carcinomas that were occult by physical examination. The mammographic appearance, the tumor histology and size, as well as axillary lymph node and estrogen receptor status of these carcinomas were reviewed. RESULTS: Mammographic findings of a mass or density (without calcifications) were most common (46%) and the majority of tumors were invasive ductal carcinoma (70%). The median age of the patients was 59 years. Tumor histology and mammographic findings varied by age: women with ductal carcinoma in situ (DCIS) had a median age of 50 years, whereas patients with invasive ductal carcinoma without associated intraductal tumor had a median age of 65 years. Both younger age (P = 0.001) and microcalcifications (P = 0.0001) were strongly correlated with DCIS. The mean greatest tumor dimension was 1.34 cm. Axillary metastases were found in 21%, 15%, and 50% of invasive tumors with sizes of < 1 cm, < 2 cm, and > 2 cm, respectively, and were uninfluenced by age. Estrogen receptor analysis of invasive tumors was > 10 fmol/mg in 47% and 84% of women aged < 50 years and > 50 years, respectively. CONCLUSIONS: Mammographically detected lesions in younger women are typified by a higher incidence of DCIS or tumors with an intraductal component. Nonpalpable invasive carcinomas in women < or = 50 years and > 50 years appear to be biologically similar by virtue of axillary lymph node status, although estrogen receptor positive tumors are more common in older patients. These age-related differences may partially account for age-related variations in the survival impact of mammographic screening programs.
PURPOSE: The purpose of this study was to assess bone mineral density (BMD) and parameters for bone metabolism in patients with end-stage heart disease awaiting heart transplantation to determine whether these patients are at increased risk of bone disease. PATIENTS AND METHODS: 39 adult men (mean age 52.3, range 21-65 years) with ischemic (41%), idiopathic (43.5%), valvular (2.5%) and diverse (13%) end-stage heart disease were studied prior to heart transplantation. BMD was measured using dual-energy x-ray absorptiometry at the lumbar spine (L2-L4) and at the upper femur (Ward's triangle and femoral neck). Renal and bone biochemical profiles, parathyroid hormone (PTH), 25-OH-vitamin D3, testosterone, alkaline bone phosphatase, osteocalcin, and deoxypyridinoline and calcium excretion were measured. RESULTS: No fractures were found. Mean z-scores were -1.06 +/- 2.02 (mean +/- SD) at the lumbar spine, -1.12 +/- 2.03 at the femoral neck and -0.25 +/- 1.06 at Ward's triangle. Significantly decreased values were seen at the lumbar spine and at the femoral neck compared to age matched healthy controls. Mean values of serum creatinine and parathyroid hormone were elevated (114.4 +/- 29.5 mumol/l and 84.3 +/- 67.8 ng/l, respectively). 7 (18%), 10 (26%) and 22 (56%) of the 39 patients had values beneath the normal range of 25-OH-vitamin D3, testosterone and osteocalcin respectively. Mean urinary deoxypyridinoline/creatinine ratios were elevated (9.46 +/- 8.52 nmol/mmol, normal range 2.5-5). No correlation existed between osteocalcin and urinary deoxypyridinoline/creatinine ratio. Using a multiple linear regression model, serum PTH and cardiac ejection fraction (EF) weakly predicted BMD at the femoral neck (r2 = 0.26). CONCLUSIONS: (1.) Lumbar spine and femoral neck BMD are low in patients awaiting heart transplantation. (2.) A low EF and a high PTH weakly correlate with a decrease in BMD at the femoral neck. (3.) In patients with end-stage heart failure the coupling of bone formation to bone resorption is frequently disturbed. (4.) Testosterone and 25-OH-vitamin D3 levels are low in a number of patients and in such cases replacement therapy may be appropriate.
Rat osteoblasts produce insulin-like growth factors (IGFs) and IGF binding proteins (IGFBPs). Expression of IGFBP-5, an IGFBP which stimulates DNA synthesis of osteoblasts, was studied in vitro under the influence of 1 alpha,25-dihydroxyvitamin D3 (1,25(OH)2D3) and parathyroid hormone (PTH). These two calcium-regulating hormones stimulated the expression of IGFBP-5 mRNA in cultured rat osteoblasts at low concentrations (10 pM) and in a dose- and time-dependent manner. Intact IGFBP-5 was not detected in the culture medium, but was found attached to the cell layer. IGFBP-5 may thus direct IGFs to the sites of bone remodeling.
Episodes of acute rejection seem to play an important role in the development of chronic allograft failure. Whereas acute rejection appears to be fully reversible, at least at early stages, reversibility of chronic graft alterations is still unclear. Male Fisher F344 rat hearts were heterotopically transplanted into Lewis recipients (n=8/group). Minimal immunosuppression (rapamycin 0.5 mg/kg for 14 days) guaranteed allograft survival during the observation period (group 1). Allografted hearts were retransplanted into syngeneic recipients after 14 days (group 2) and 50 days (group 3) and compared with F344 isografts undergoing retransplantation after 4 days (group 4) and with F344 isografts without a second procedure (group 5). All organs were removed after 100 days and morphologically and immunohistologically assessed. Allografts of group 1 developed concentric myointimal proliferation with dense intramural and perivascular mononuclear infiltration and intravascular thrombosis in 59 +/- 7% of coronary arteries. Retransplantation into syngeneic recipients almost completely abolished mononuclear infiltration, but did not affect the development of myointimal proliferation (groups 2/3: 46 +/- 7%/31 +/- 24%, NS). Isograft retransplantation resulted in a similar incidence of coronary lotions (group 4: 37 +/- 9%, NS), whereas coronary arteries of isografts without a second transplant procedure (group 5) remained normal (0%, P<0.001). In conclusion, syngeneic retransplantation of allografts reverses mononuclear infiltration but not myointimal proliferation. The development of coronary lesions in retransplanted isografts underlines the participation of antigen-independent stimuli in the development of myointimal proliferation. These experiments further support the hypothesis of an interaction of antigen-dependent and antigen-independent factors for the development of coronary myointimal proliferation.
Effects of T3 treatment (day 2-day 12) on the expression of the insulin-regulated GLUT4, on 2-deoxyglucose uptake, and on glycogen synthesis were studied in ARC after 12 days of culture in T3-depleted 20% fetal calf serum. GLUT4 mRNA expression was low in controls, but increased in a dose-dependent manner by T3 treatment up to 2.8-fold at 100 nM. In parallel, 100 nM T3 increased basal 2-deoxyglucose uptake 1.95-fold and insulin-stimulated uptake 1.75-fold. In addition, T3 enhanced basal and insulin-stimulated [14C] glucose incorporation into glycogen 1.86- and 1.5-fold, respectively. Hence, ARC may meet part of their increased energy requirements in response to T3 by enhancing GLUT4 expression.
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OBJECTIVE: To study the effect of fluoxetine (FL) and amitriptyline (AM), alone and in combination, in patients with fibromyalgia (FM). METHODS: Nineteen patients with FM completed a randomized, double-blind crossover study, which consisted of 4 6-week trials of FL (20 mg), AM (25 mg), a combination of FL and AM, or placebo. Patients were evaluated on the first and last day of each trial period. Outcome measures included a tender point score, the Fibromyalgia Impact Questionnaire (FIQ), the Beck Depression Inventory (BDI) scale, and visual analog scales (VAS) for global well-being (1 completed by the physician and 1 by the patient), pain, sleep trouble, fatigue, and feeling refreshed upon awakening. RESULTS: Both FL and AM were associated with significantly improved scores on the FIQ and on the VAS for pain, global well-being, and sleep disturbances. When combined, the 2 treatments worked better than either medication alone. Similar, but nonsignificant, improvement occurred in the BDI scale, the physician global VAS, and the VAS for fatigue and feeling refreshed upon awakening. Trends were less clear for the tender point score. CONCLUSION: Both FL and AM are effective treatments for FM, and they work better in combination than either medication alone.
The etiology of chronic rejection is unknown, although acute rejection, viral infection, and initial graft ischemia have been implicated. To test the effects of infections on the process of chronic rejection, we simulated bacterial infection by the administration of the endotoxin lipopolysaccharide (LPS), a potent activator of various cell types in an established rat model of chronic rejection. Lewis recipients of Fisher 344 kidneys were treated with a single dose of LPS or vehicle 8 weeks following transplantation and grafts were examined at various time points. In the chronically rejecting controls, leukocytic infiltration and the expression of cytokines peaked at 16 weeks. In LPS-treated hosts, leukocyte infiltration and cytokine expression peaked at 12 weeks. By 16 weeks, glomeruli in LPS-treated recipients had become far more sclerotic than those in controls, mimicking the changes observed in controls at 24 weeks. We conclude that infections may play an important role in the development of chronic rejection.
BACKGROUND: In patients with heparin-induced thrombocytopenia undergoing cardiac operations, anticoagulation with heparin should be avoided. The low-molecular-weight glycosaminoglycan Orgaran has been used as an alternative, but the overall experience is limited. METHODS: Two patients with heparin-induced thrombocytopenia underwent cardiopulmonary bypass using Orgaran for anticoagulation. A 30-year-old woman suffered from emboli to her brain through a secondary atrial septal defect, a 14-year-old boy from ischemia of his left leg due to recurrent embolism originating from the mitral valve. In both cases, cardiopulmonary bypass was performed in a routine manner, except for using low-dose Orgaran instead of heparin. Anticoagulation was monitored during cardiopulmonary bypass by measuring Orgaran plasma levels and activated clotting time. RESULTS: No thromboembolic or bleeding complications occurred during and after atrial septal defect repair and mitral valve replacement, respectively. In the former case, thrombotic material from the inferior vena cava was removed during hypothermic circulatory arrest within the same procedure. Activated clotting time did not correlate with plasma levels of Orgaran. CONCLUSIONS: Orgaran might be a useful alternative for anticoagulation during extracorporeal circulation. Adequate dosages and measurement of plasma levels are recommended for its use in cardiopulmonary bypass.