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Biomedical subjects

S Larsen

Publications and source records attributed to S Larsen.

At least 235 records · Page 13Linked to original sources

Treatment with total lymphoid irradiation, cyclosporin A and a monoclonal anti-T-cell antibody in a hamster-to-rat heart transplantation model: graft survival and morphological analysis.

Treatment with preoperative total lymphoid irradiation and post-transplant cyclosporin A has been shown to have a synergistic effect on graft survival in allo- and xenotransplantation. Specific monoclonal antibodies against T cells and T cell subpopulations could offer new ways of preventing graft rejection in xenotransplantation. Graft survival and histology were examined after total lymphoid irradiation plus cyclosporin A treatment versus cyclosporin A plus a monoclonal antibody in a concordant, heterotopic, hamster-to-rat heart transplantation model. Preoperative total lymphoid irradiation was given at a dose of 1.25 Gy, 12 times over a period of 3 weeks. Cyclosporin A at a dose of 12.5 mg/kg per day was administered perorally and OX-19, a pan T cell monoclonal antibody, was given as intraperitoneal injections at doses of 100 micrograms or 500 micrograms/kg per day from day 0 until graft rejection. While total lymphoid irradiation alone prolonged graft survival to 9.4 days, total lymphoid irradiation plus cyclosporin A extended graft survival to a mean of 22 days. Cyclosporin alone or combined with the monoclonal antibody could not increase graft survival significantly when compared to untreated animals, which rejected their grafts within 3.7 days. Vascular rejection was the characteristic morphological finding, even after some weeks of excellent graft function. In conclusion, total lymphoid irradiation and cyclosporin A had a synergistic effect on graft survival in this concordant xenotransplantation model, although recent impressive results from other groups could not be reproduced. Total lymphoid irradiation combined with cyclosporin A appears to delay a primary humoral graft rejection, while the mechanism of rejection, judged by histology, stays the same.

Analysis of Variance↗

Glucose counterregulation in diabetes secondary to chronic pancreatitis.

Glucose counterregulation and hormonal responses after insulin-induced hypoglycemia were investigated in six patients with diabetes mellitus secondary to chronic pancreatitis, in seven with insulin-dependent (type I) diabetes mellitus, and in seven healthy subjects. Glucose counterregulation was identical in type I patients and in the patients with chronic pancreatitis, whereas both groups had impaired glucose recovery compared with the healthy subjects. The patients with chronic pancreatitis had no glucagon response to hypoglycemia, whereas epinephrine increased significantly. In an additional experiment, glucose recovery did not occur after hypoglycemia during concomitant beta-adrenoceptor blockade in these patients. In conclusion, glucose counterregulation is preserved but slightly impaired in patients with diabetes secondary to chronic pancreatitis, and the combination of total glucagon deficiency and pharmacological blockade of the metabolic actions of circulating epinephrine abolishes glucose counterregulation after hypoglycemia.

Adrenergic beta-Antagonists↗

Detection of CMV DNA and CMV antigen in renal allograft biopsies by in situ hybridisation and immunohistochemistry.

One hundred kidney allograft biopsies from 85 patients and tissue specimens from 31 failed allografts were analysed by immunohistochemistry (IMH) with a monoclonal antibody against a cytomegalovirus (CMV) antigen and by in situ hybridisation (ISH) with a biotinylated CMV DNA probe. Six clinically and serologically CMV-infected patients with AIDS served as positive controls. Biopsies from six seronegative donor kidneys and autopsy specimens from five clinically and serologically negative patients served as negative controls. Adequate serology in 56 patients showed 50% to be actively CMV infected. No statistically significant difference was found between the frequency of acute rejection in the seropositive and the seronegative patients. Four seropositive transplanted patients contained CMV DNA or CMV antigen in the biopsies and in the grafts. Both methods gave a negative result in 15 patients with glomerulopathy. Expression of MHC class I and II antigens in 17 of the biopsies demonstrated no relation to positive serology or local demonstration of CMV. In conclusion, (1) CMV was not renotropic, (2) there was no correlation between (a) CMV and acute rejection, (b) CMV and glomerulopathy, or (c) CMV and MHC class I and II antigen expression. The study suggests that CMV does not play a major role in rejection.

Antigens, Viral↗

Cultural background and drinking patterns in problem drinkers in northern Norway.

It was hypothesized that drinking patterns, treatment goals and psycho-social consequences of drinking (as measured by the MAST) would be different in Saami ('Lapp') and Norwegian in-patient problem drinkers, due to differences in cultural background. Drinking patterns and treatment goals differed significantly, implying that Saami clients demonstrated a more periodic drinking pattern and, to a smaller extent, tended to prefer total abstinence or a large reduction in alcohol consumption as their treatment goal compared to Norwegian clients. Furthermore, the Saami clients obtained significantly lower scores on the MAST than the Norwegian clients. No differences in degree of physical dependence and self-reported alcohol consumption were observed. These findings indicate that the drinking culture in the two groups is different. Furthermore, the results imply that the MAST yields different problem scores in Saami and Norwegian clients, probably due to differences in ways of living in the two ethnic groups.

Alcohol Drinking↗

NSAID-associated gastroduodenal damage: does famotidine protection extend into the mid- and distal duodenum?

Eighteen healthy volunteers were included in a cross-over, double-blind study where 500 mg naproxen b.d. was given for 1 week with 20 mg famotidine b.d., 40 mg nocte or placebo. Endoscopic evaluation of the gastroduodenal mucosa was performed before and after each treatment period, with separate evaluation of the mid- and distal duodenum. 51Cr-EDTA-permeability tests were done to study effects on the mid- and distal gut, and, in addition, symptom registration was performed. The mucosal damage was significant in all treatment periods, and a statistically significant reduction was seen with 20 mg famotidine b.d. for erosive lesions in the stomach/duodenal bulb region as well as for the sum of damage score in the mid- and distal duodenum. The reduction was considerable in a few subjects with extensive duodenal damage. The reduction was considerable in a few subjects with extensive duodenal damage. Intestinal permeation increased significantly in all periods, and was not reduced by famotidine. Symptoms were modest and equal in all periods.

Adult↗

A comparative study of microvascular complications in patients with secondary and type 1 diabetes.

The prevalence of retinopathy, albuminuria, and neuropathy were assessed in 25 patients with insulin-requiring diabetes secondary to chronic pancreatitis and in 25 patients with Type 1 (insulin-dependent) diabetes, matched for age at diabetes onset (secondary, 39 +/- 11 (+/- SD) years vs Type 1, 38 +/- 11 years) and duration of diabetes (10 +/- 6 vs 10 +/- 7 years). The prevalence of retinopathy was significantly higher in Type 1 diabetic patients (52%) than those with secondary diabetes (20%) (p less than 0.02). Median urinary excretion of albumin was 9 (range 1-206) mg 24-h-1 in patients with Type 1 diabetes and 7 (1-90) mg 24-h-1 in patients with secondary diabetes (NS). One secondary diabetic patient and five Type 1 diabetic patients had microalbuminuria (NS). Vibration perception threshold (measured at the big toe) was identical in the two groups of patients, and no patient had a threshold indicating somatic neuropathy (biothesiometry greater than 20 V). Retinopathy is more frequent in patients with Type 1 diabetes than in patients with insulin-requiring diabetes secondary to chronic pancreatitis. Retinopathy is so frequent in the latter group, however, that regular ophthalmoscopic examination is still required.

Albuminuria↗

Insulin-dependent diabetes mellitus secondary to chronic pancreatitis is not associated with HLA or the occurrence of islet-cell antibodies.

We assessed HLA-DR types and investigated serum samples for islet-cell cytoplasmic antibodies (ICA) in 31 Danish patients with chronic pancreatitis. The antigen frequencies were compared with those in 1177 unrelated healthy Danish controls. Twenty patients had insulin-dependent diabetes and 11 had normal intravenous glucose tolerance. No significant differences in the frequencies of DR3, DR4, or DR2 were found between patients with insulin-dependent diabetes and patients with normal glucose tolerance or between any of these groups and controls. ICA were negative in all patients with chronic pancreatitis. It is concluded that the beta-cell dysfunction in insulin-dependent diabetes in chronic pancreatitis differs from that of classical insulin-dependent diabetes.

Autoantibodies↗

Analysis of experimental mink enteritis virus infection in mink: in situ hybridization, serology, and histopathology.

Strand-specific hybridization probes were used in in situ hybridization studies to localize cells containing mink enteritis virus (MEV) virion DNA or MEV replicative-form DNA and mRNA. Following the experimental MEV infection of 3-month-old unvaccinated mink, a significant increase in serum antibodies to MEV was detected at postinfection day (PID) 6, 2 days after the onset of fecal shedding of virus. Prior to the appearance of virus in feces, viral DNA could be detected in the mesenteric lymph node and intestine. The largest percentage of cells positive for virion DNA was 10% and was detected in the intestine on PID 6. However, replication of the virus apparently peaked at PID 4. The number of MEV replicative-form DNA and mRNA molecules was found to be approximately 250,000 copies per infected lymph node cell or crypt epithelial cell. The localization, levels, and time course of viral replication have important implications for the pathogenesis of MEV-induced disease. The data presented on MEV are correlated with earlier results on the other mink parvovirus, Aleutian mink disease parvovirus, and a possible explanation for the remarkable differences in pathogenesis of disease caused by these two parvoviruses is discussed.

Animals↗

The relationship between some beta-adrenergic mediated responses and plasma concentrations of adrenaline and cyclic AMP in man.

To test the hypothesis that increments in plasma cyclic AMP during beta-adrenergic stimulation reflect integrated second messenger function of the tissues activated by the agonist, graded adrenaline infusion resulting in plasma adrenaline concentrations within the physiological range was performed in 8 healthy subjects with and without concomitant beta-adrenoceptor blockade by iv propranolol. A significant correlation was found between increments in plasma adrenaline and plasma cyclic AMP in the experiments without beta-blockade; during concomitant beta-blockade the increase in plasma cyclic AMP concentrations at low adrenaline infusion rates was prevented, whereas a small increase in cyclic AMP was found at high adrenaline infusion rates, probably owing to incomplete beta-receptor blockade. Likewise, the adrenaline-induced increments in blood substrates (glucose, lactate, glycerol and beta hydroxybutyric acid) were significantly reduced but not completely prevented by beta-blockade. We conclude that an altered relationship between beta-agonist concentrations and plasma cyclic AMP may provide evidence for the existence of differences in beta-adrenergic sensitivity in man.

Adrenergic beta-Antagonists↗

Visual analogue scales for endoscopic evaluation of nonsteroidal anti-inflammatory drug-induced mucosal damage in the stomach and duodenum.

The use of visual analogue scales in the evaluation of mucosal lesions may reduce sample size requirements in clinical trials, but they may be complex to use, and adding guide points may reduce their informative value. We found that two investigators with differing levels of endoscopic experience reached comparable conclusions in 4 clinical trials (738 scores), and their scores were highly correlated, with similar dispersion characteristics. With guide texts along the scales, thus avoiding points on the actual scales, no tendency towards accumulation was seen in 1449 scores. These results encourage the use of visual analogue scales in endoscopic studies.

Adolescent↗

Hope for successful xenografting by immunosuppression with monoclonal antibody against CD4, total lymphoid irradiation and cyclosporine. Six months' survival of hamster heart transplanted into rat.

Hamster hearts were transplanted to rats, and the effects of combinations of total lymphoid irradiation (TLI), cyclophosphamide, cyclosporine A (CyA) and monoclonal antibodies (MAB) were investigated. Controls not immunosuppressed rejected their xenograft in 3 to 5 days, while combination immunosuppression including MABs against CD4 or IL-2-receptors extended graft survival significantly. In one case, the graft was still functioning 180 days after transplantation, which is the longest survival seen in this model. The use of specific MABs may open a new era for both xeno- and allo-transplantation.

Animals↗

Gentamicin nephropathy and contrast media. A comparison between diatrizoate and iohexol in rats.

Urine profiles were followed for 3 or 9 days after intravenous injection of diatrizoate, iohexol or saline in 30 rats, where a tubulo-interstitial nephropathy was induced by gentamicin given over a 14-day period. Another 10 rats who had an injection of saline served as controls. Iohexol increased the excretion of lactate dehydrogenase significantly more than both saline and diatrizoate for the first 3 days, whereas diatrizoate had no effect. Both media caused significantly increased excretion of L-gamma-glutamyltransferase compared with saline, but iohexol significantly more than diatrizoate. Compared with saline S-creatinine was significantly increased following iohexol at 24 h, 3 and 9 days, and following diatrizoate only at 9 days. Among rats having gentamicin light microscopy revealed more severe changes in kidneys exposed to iohexol than to either diatrizoate or saline 3 days after their injection. Six days later no obvious differences were found between the 3 groups. In conclusion, iohexol induced more renal dysfunction than diatrizoate in this animal model of gentamicin induced nephropathy.

Acetylglucosaminidase↗

A three-year retrospective study of synovectomies in children.

The aim of this study was to evaluate the results of synovectomies in children with juvenile arthritis. Five hundred twenty-eight synovectomies and tenosynovectomies were performed over a period of 13 years. The patients were followed for one, two, three, five, and ten years postoperatively. The evaluation after three years was chosen as the basis for this article. One hundred twenty-five children with arthritis who were not evaluated three years postoperatively had less severe arthritis, both locally and generally, than the evaluated group of 389. The rate for good results and tolerability was high at one, two, and three years postoperatively but decreased with time; more patients went from good results to poor rather than vice versa. Global assessment, soft-tissue swelling, and limitation of movement seemed to be the best parameters for evaluating the results of synovectomies. It appears necessary to wait at least three years to evaluate the long-term effect of synovectomies.

Adolescent↗

Low sodium diet, indomethacin, and contrast media. A comparison between renal effects of diatrizoate and iohexol in rats.

Urine profiles were followed for 3 or 9 days after intravenous injection of diatrizoate, iohexol, or saline in 30 adult Wistar rats, which received a low sodium diet for 14 days, and indomethacin intravenously 2 hours and immediately before contrast medium or saline injection. A control group of 10 rats, which also received low sodium diet, got saline alone and no indomethacin or contrast medium. Diatrizoate increased albuminuria during the first 22 hours after its injection whereas iohexol did not have any significant effect on albuminuria. Both contrast media caused tubular dysfunction, but there was significant difference between them during the first 2 hours after injection. Compared to the effect of saline, iohexol but not diatrizoate caused increased excretion of lactate dehydrogenase and N-acetyl-beta-glucosaminidase for 2 days. Iodine measurements showed delayed excretion of both media. Light microscopy showed focal location of dilated tubular profiles with hydrophia, which were only present in kidneys exposed to contrast media. It is concluded that in rats fed on a low sodium diet administration of indomethacin in relation to iohexol has a greater tubular cell effect than diatrizoate, which in turn has a greater effect on the glomerular permeability. The excretion of both media is delayed.

Animals↗

Adriamycin nephrosis and contrast media. A comparison between diatrizoate and iohexol in rats.

Urine profiles (albumin, glucose, NAG, LDH, GGT and sodium) were followed for 9 days after intravenous injection of either diatrizoate, iohexol, or saline in 27 Wistar rats with nephrosis induced by Adriamycin 42 days before. Another 9 rats exposed to neither Adriamycin nor contrast media served as controls. None of the contrast media caused further increased albuminuria of significance, whereas both induced significantly increased excretion of all 5 tubular components. The excretion of NAG and sodium was significantly higher following diatrizoate than following iohexol. From 24 h post injection there was no significantly greater excretion of any of the components after either diatrizoate or iohexol than after saline among the rats given Adriamycin. At the end of day 9 after contrast medium injection neither serum sodium, potassium, glucose, urea, creatinine, nor albumin revealed any contrast media related changes. Kidney histology showed quantitatively larger lesions in kidneys exposed to Adriamycin and contrast media than in kidneys exposed to Adriamycin and saline. There were no differences between the two contrast media groups. It is thus concluded, that both high osmolar ionic and low osmolar non-ionic contrast media cause temporary tubular dysfunction but no further glomerular dysfunction in rats with nephrosis induced by Adriamycin. The histologic findings indicate that both media may worsen non-reversible renal lesions.

Animals↗