Biomedical subjects
Publications and source records attributed to K Thomsen.
Pseudoporphyria with formation of bullae and vulnerability of skin exposed to light, particularly the backs of the hands, may be provoked medicinally by nalidixinic acid, tetracyclin, nabumeton, pyridoxine, dapsone and high-dosage furosemide and by excessive use of solaria. The present article demonstrates that the condition may also be precipitated by quinidine and ibuprophen.
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BACKGROUND: High-dose hydroxychloroquine is rarely used in the treatment of porphyria cutanea tarda (PCT). OBJECTIVE: The purpose of this study was to evaluate the efficacy and safety of a novel high-dose hydroxychloroquine regimen in patients with PCT. METHODS: Sixty-five first episodes and 28 recurrent episodes of PCT were treated with hydroxychloroquine, 250 mg three times daily, for 3 days. In patients with a high urine porphyrin concentration a single phlebotomy of 500 ml was performed before therapy of the first episode. Modified high-dose hydroxychloroquine regimens were used in patients with markedly elevated liver transaminases with or without associated chronic liver disease. RESULTS: Long-term follow-up data showed an overall relapse rate of 33%, significantly higher among male patients (45%) than among female patients (17%) (p less than 0.05). A transient hepatotoxic reaction occurred in the majority of patients. The reaction seemed to be especially severe among phlebotomized female patients. CONCLUSION: Hydroxychloroquine, 250 mg three times daily, is a rapid, efficacious, and safe treatment in patients with PCT.
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Examination of biopsy samples from 62 patients with--or with suspected--cutaneous T-cell lymphoma (CTCL) revealed 2 cases in which the neoplastic cells were positive for the T-cell receptor (TCR) gamma delta complex. One patient had mycosis fungoides and 1 patient had a pleomorphic lymphoma of medium and large-cell type. Both cases showed aggressive courses with dissemination to internal organs and short survival times. The phenotypic examination showed that the neoplastic cells were positive with TCR delta 1, CD3, CD25, CD29, CD45R0 and CD54. No staining was seen with antibodies against framework determinants or variable regions on the TCR alpha beta heterodimer. Negative reactions were also seen with CD4, CD8, CD5, CD7, CD16, CD30 and CD57. It is concluded that rare CTCL express TCR gamma delta chains. These malignancies may originate from the TCR gamma delta-positive T cells seen in normal skin, and it is possible that their recognition may be important for clinical reasons.
The objective of this double-blind study was to compare the therapeutic effects of acitretin with those of etretinate in patients with Darier's disease. Twenty-six patients (10 males and 16 females) were included in the study. Patients were treated with 30 mg daily for the first 4 weeks and with an individually adjusted dose (10-50 mg/day) for the subsequent 12 weeks. Remission or marked improvement was obtained in 10 of the 13 acitretin-treated patients and in 8 of the 11 etretinate-treated patients who completed the 16-week treatment. The usual mucocutaneous adverse reactions of retinoids were observed in all but one patient. There were no significant differences between treatment groups with regard to the incidence of these reactions.
The effect of a single oral dose of 10 mg of the calcium antagonist felodipine or placebo was investigated in 10 cyclosporin-treated renal transplant recipients before, during, and after an acute intravenous infusion of cyclosporin in a randomised, single-blind cross-over study. Renal plasma flow (RPF), glomerular filtration rate (GFR), renal tubular sodium and water handling as judged by the lithium clearance technique, and plasma concentrations of angiotensin II (AngII), aldosterone (Aldo), atrial natriuretic factor (ANF), and arginine vasopressin (AVP) were measured. Both RPF and GFR increased after felodipine (mean increase: RPF, 38.7%; GFR, 16.2%; P less than 0.01 for both) in spite of a significant decrease in both systolic and diastolic blood pressure (mean decrease 10.6% and 16.0% respectively, P less than 0.02 for both). Estimated by the lithium clearance technique felodipine induced a decrease in fractional reabsorption in the proximal tubules (mean 72.0% vs 63.0%, P less than 0.01), an increase in proximal output of fluid (mean 11.0 ml/min vs 16.0 ml/min, P less than 0.01), and a decrease in distal fractional reabsorption of sodium (mean 90.5% vs 83.9%, P less than 0.05) resulting in a significant natriuresis and diuresis. Ang II, Aldo, ANF, or AVP did not change. Intravenous infusion of cyclosporin per se did not influence any of the parameters. It is concluded that a single dose of felodipine in cyclosporin treated renal transplant recipients has beneficial effects on blood pressure, renal haemodynamics, and renal tubular sodium and water handling, which seems to compensate for some of the adverse effects of cyclosporin. It is suggested that these effects result from a direct vasodilatation and an effect on proximal tubular function.
To examine the fractional excretion of amino acids after an increase in the filtered load, and to study a possible coupling between proximal tubular reabsorption of individual amino acids and sodium/water, eleven healthy subjects were examined before and during intravenous infusion of a mixture of essential and non-essential amino acids. Thirteen healthy subjects, who received isotonic glucose instead, participated in an identical time-control study. Glomerular filtration rate (GFR), renal plasma flow (RPF), and proximal and distal absolute and fractional tubular reabsorption of sodium and water (PARNa, PFRNa/water, DARNa, and DFRNa) evaluated by the lithium clearance method were determined during four clearance periods of 30 min each. After amino acid infusion, GFR and RPF increased, whereas filtration fraction (FF) was unchanged. PARNa was unchanged, but lithium clearance increased significantly (P less than 0.05) and PFRNa/water fell, indicating an increased delivery of sodium and water out of the proximal tubules. DARNa increased, but DFRNa was unchanged, thus no net increase was recorded in urinary sodium and water output. In the time-control study, no changes in kidney function were seen. Absolute excretion of amino acids increased for glutamic acid, serine, glutamine, glycine, threonine, histidine, alanine, arginine, tyrosine, valine, methionine, isoleucine, phenylalanine, leucine, and lysine (P less than 0.01), and fractional excretion increased for all but glutamic acid, tyrosine, arginine, isoleucine, and leucine. Reabsorption of amino acids was enhanced uniformly and almost paralleled the filtered load without any sign of saturation of the reabsorption mechanisms.(ABSTRACT TRUNCATED AT 250 WORDS)
The object of this study was to test the hypothesis that the natriuretic and uricosuric effect of calcium-entry blockers could be mediated through antagonism of angiotensin II dependent intrarenal mechanisms. The antihypertensive efficacy, haemodynamic and excretional effects of superimposed calcium blockade with isradipine were investigated in seven hypertensives with unsatisfactorally controlled blood pressure with captopril 50 mg twice daily. Glomerular filtration rate (GFR) and renal plasma flow (RPF), clearances (C) of sodium (Na), potassium (K), uric acid (UA) and lithium (Li), were measured before and after a low-dose bolus of isradipine, i.v. Subsequently, measurements were repeated during constant i.v. infusion of a higher dose with definite systemic haemodynamic effects. After 4 months of combined treatment with isradipine and captopril renal investigations were carried out again. The low isradipine dose induced a slight but statistically significant increment in CNa (22% +/- 28) and heart rate (4% +/- 4), whereas no other variables changed significantly. Infusion of the high isradipine dose caused a pronounced fall in renal vascular resistance (27% +/- 14), systolic (8% +/- 2) and diastolic blood pressure (17% +/- 5). RPF increased significantly (15% +/- 18) whereas no changes were noted in GFR, filtration fraction and urinary albumin excretion rate. In spite of the pronounced fall in BP during the high dose infusion, significant increments in natriuresis (91% +/- 63) and diuresis (41% +/- 27) were induced. The natriuresis was caused by a proximal tubular action as indicated by increased CLi and CLi/GFR.(ABSTRACT TRUNCATED AT 250 WORDS)
The nephrotoxic adverse effect of cyclosporine in renal transplantation may be counteracted by calcium antagonists. The effect of a single oral dose of 10 mg of the calcium antagonist felodipine or placebo was studied in ten cyclosporine-treated renal transplant recipients before, during, and after an acute intravenous infusion of cyclosporine in a randomized, single-blind crossover study. Glomerular filtration rate, and renal plasma flow, and tubular function evaluated by the lithium clearance technique were determined. Both glomerular filtration rate, renal plasma flow, urinary sodium excretion, fractional excretion of sodium, and lithium clearance increased after felodipine, whereas proximal and distal fractional reabsorption and blood pressure were reduced. Intravenous infusion of cyclosporine per se did not influence any of the parameters. It is concluded that a single dose of felodipine in cyclosporine-treated renal transplant recipients has beneficial effects on renal hemodynamics, tubular function and blood pressure. It is suggested that these effects result from a direct vasodilatation and an effect on tubular function, and that felodipine given intravenously seems to antagonize at least some of the nephrotoxic effects of cyclosporine.
A case of elephantiasis nostras in a lower limb is presented. A thorough programme of investigation could only reveal a single episode of erysipelas as the possible etiological origin. The therapeutic possibilities are briefly reviewed. The most important are early institution of adequate antibiotic treatment and antibiotic treatment of every recurrence of disease.
The effect of an analogue of atrial natriuretic peptide (P-ANP) on glomerular filtration rate (GFR), renal plasma flow (RPF), urinary flow rate, urinary sodium excretion, tubular function estimated by the lithium clearance technique, and plasma levels of sodium and water homeostatic hormones, has been studied in 40 healthy males. Placebo or P-ANP 0.3, 1.5, or 3.0 micrograms.kg-1 bwt were given as an intravenous bolus injection to different groups. P-ANP did not cause any immediate change in GFR or RPF, but significant dose-dependent increases in filtration fraction, urinary flow rate and urinary excretion rate of sodium were detected during the first 30 min after administration. Proximal absolute and fractional tubular reabsorption and distal absolute tubular reabsorption of sodium did not change after injection of P-ANP, while the distal fractional reabsorption of sodium was reduced in a dose dependent manner during the first 30 min. Plasma angiotensin II and aldosterone were significantly increased 30 and 150 min after dosage, whereas plasma atrial natriuretic peptide, plasma arginine vasopressin, and urinary excretion of prostaglandin E2 were unchanged. Cyclic guanosine monophosphate both in plasma and urine were increased in a dose-dependent manner. P-ANP cause a significant reduction in diastolic blood pressure and an increase in pulse rate. Two subjects had vasovagal syncope 30-60 min after injection of P-ANP. It is concluded that P-ANP has natriuretic, diuretic and hypotensive properties in healthy man.
The renal and hormonal effects of atrial natriuretic peptide given as a bolus injection (2.0 micrograms/kg) were studied in 12 patients with congestive heart failure before and after treatment with captopril for 4 weeks and in 13 healthy control subjects. Atrial natriuretic peptide caused a rise in urinary excretion of sodium and urinary flow in the controls, whereas no increases were observed in the patients. Both proximal and distal fractional reabsorption of sodium, as evaluated by the lithium clearance technique, decreased less in the patients than in the controls. Basal plasma concentrations of atrial natriuretic peptide and cyclic guanosine monophosphate (cGMP), and the basal urinary excretion of cGMP, were elevated in the patients. The increases in both plasma and urinary cGMP after administration of atrial natriuretic peptide were blunted in heart failure. Basal glomerular filtration rate and renal plasma flow were reduced, and filtration fraction increased, in the patients. A positive correlation (r = 0.958, P less than 0.01) was found between renal plasma flow and the relative increase in urinary excretion of sodium in the patients with heart failure. Treatment with captopril did not improve the natriuretic and diuretic effect of exogenous atrial natriuretic peptide, but resulted in an increase in filtration fraction after administration of atrial natriuretic peptide not present before captopril.(ABSTRACT TRUNCATED AT 250 WORDS)
The effect of two different regimens of intravenous infusion of amino acids on glomerular filtration rate (GFR), renal plasma flow (RPF), tubular sodium and water handling judged from the clearance of lithium (CLi), and plasma concentrations of angiotensin II (Ang II), aldosterone (Aldo), arginine vasopressin (AVP), atrial natriuretic peptide (ANP), growth hormone (GH), and glucagon was investigated in healthy humans. In the first protocol (n = 11) the infusion lasted 90 min; both GFR and RPF increased significantly (median increase 7.1% and 9.1% respectively, P less than 0.05 both). In the second protocol (n = 13) the infusion lasted 30 min; both GFR and RPF tended to increase (median increase 3.5% and 7.4%) but the change did not reach significance. The changes in tubular sodium and water handling were similar in the two protocols. Absolute reabsorption rates in the proximal tubules were unaltered, resulting in an increased output into the distal tubules that was totally compensated for by an increased distal reabsorption. Thus no changes in urinary excretion of sodium and water were observed. Ang II, Aldo, AVP, ANP and GH were unchanged by amino acid infusion, but glucagon increased. It is suggested that the alterations in renal haemodynamics and distal tubular reabsorption may be mediated by glucagon.
Fourteen normotensive patients with chronic glomerulonephritis and well-preserved renal function and thirteen healthy control subjects were studied. Glomerular filtration rate (GFR), proximal and distal absolute and fractional tubular reabsorption (PAR, PFR, DARNa, DFRNa), evaluated by the lithium clearance technique, were determined before and in four 30-60-min periods after intravenous injection of frusemide 0.5 mg/kg body weight (Study 1) and 1.0 mg/kg body weight (Study 2). Plasma concentrations of angiotensin II (Ang II), aldosterone (Aldo), atrial natriuretic peptide (ANP) and arginine vasopressine (AVP) were measured before, and 60 and 180 min after frusemide. GFR decreased and UNa and FENa increased significantly in patients and controls after frusemide in both studies, but in study 2 GFR decreased significantly more in patients than in controls, and UNa and FENa increased significantly less above baseline in patients compared to controls. PAR, PFR, DARNa, and DFRNa were reduced in patients and controls in both studies. In study 2 the reduction in PAR was significantly (P less than 0.05) less pronounced in patients (23%) than in controls (43%), whereas DARNa was reduced significantly more (P less than 0.05) in patients (36%) than in controls (21%). The efficiency of frusemide with regard to renal sodium excretion was significantly reduced in patients compared to controls in both studies. Angiotensin II and aldosterone increased, ANP decreased, and AVP was unchanged in patients and controls in both studies. It is concluded that in comparison to control subjects, patients with chronic glomerulonephritis and well-preserved GFR respond to frusemide with an exaggerated reduction in GFR, a lesser decrease in absolute proximal tubular reabsorption, and a larger reduction in absolute distal tubular reabsorption. Thus, primary glomerular disease with well-preserved glomerular function may be accompanied by a distinctly disturbed tubular function.
Biopsies from normal skin (n = 17) and various cutaneous disorders (n = 83) were examined immunohistologically for reactivity with an antibody (CD29) against the common beta chain of the VLA integrin family. In normal skin, CD29 recognized a number of cell types, i.e. endothelial cells, fibroblasts, T lymphocytes and basal keratinocytes. Similar cells were positive in diseased skin, but the expression of VLA beta was upregulated on keratinocytes. The phenotype of the VLA beta-positive T cells was examined in more detail by staining with anti-T-cell antibodies, i.e. CD3, CD4, CD8, CD45RO (UCHL1) and CD45R (2H4). These studies showed that most of the T cells in normal skin, benign cutaneous conditions and early cutaneous T-cell lymphomas (CTCL) expressed a similar phenotype and resembled antigen committed 'memory' (helper/inducer) cells (CD4+, CD29+, CD45RO+, CD45R-). In advanced CTCL, expression of these antigens was more variable, and many of these infiltrates showed aberrant (or unusual) expression of CD29, CD45RO, CD45R and other T-cell antigens. It is concluded that several cells involved in cutaneous immune reactions express a molecule (VLA beta) which acts as a receptor for extracellular matrix components. This molecule is important for the attachment of cells to connective tissue constituents and may act to facilitate the migration of lymphocytes (and other cells) during immune reactions in normal and diseased cutaneous conditions. Advanced CTCL differ from the early lesions and it is possible that there is a progressive accumulation of increasingly malignant (or transformed) cells in these conditions.
Renal plasma flow (RPF), glomerular filtration rate (GFR), renal proximal tubular delivery of sodium and water evaluated by lithium clearance, and hormonal parameters were measured in 12 patients with congestive heart failure NYHA class II-IV before and after captopril treatment for 4 wk and in 13 healthy control subjects. RPF and GFR were significantly decreased in heart failure, whereas the filtration fraction (FF) was increased. Treatment with captopril increased RPF and decreased FF, whereas GFR was unchanged. Total and fractional urinary excretion of sodium were reduced in the patients compared with the controls, but increased after captopril. Fractional excretion of lithium was normal in heart failure and was increased by captopril. Atrial natriuretic peptide, guanosine 3',5'-cyclic monophosphate, and aldosterone in plasma were significantly elevated in heart failure and were reduced by treatment with captopril. Plasma renin activity was increased in patients, correlated inversely with RPF, and increased further after captopril treatment. It is concluded that the reduced sodium excretion in heart failure was caused by a combination of diminished glomerular filtration and enhanced tubular reabsorption beyond the proximal tubule and that treatment with captopril increased urinary sodium excretion partly due to an attenuated sodium reabsorption in the proximal tubule. The present data in patients with congestive heart failure are consistent with an increased intrarenal angiotensin II generation and an elevated plasma level of aldosterone being involved in the pathogenesis of the glomerular hemodynamic changes and the enhanced distal tubular reabsorption, respectively.
Intercellular adhesion molecule-1 (ICAM-1) is a membrane-bound glycoprotein that is a ligand for lymphocyte function-associated antigen-1 (LFA-1) and is important for a number of cell adhesions in immune reactions. The molecule is expressed by several cell types (e.g. macrophages, endothelial cells, keratinocytes, melanoma cells and cell lines) and there are some indications that expression of this molecule in melanocytic lesions is confined to malignant tumours and is more pronounced in metastatic and advanced tumours than in earlier lesions. In an attempt to elucidate this issue, we have studied biopsy samples from benign naevi (n = 7) and malignant melanomas (n = 33) regarding reactivity with monoclonal anti-ICAM-1 (CD54). The results indicate that the great majority of malignant melanomas are ICAM-1-positive. The most abundant staining is seen in metastatic melanomas. In primary melanomas, staining is more variable and generally weaker. However, no correlation was found between the degree of ICAM-1 labelling and the degree of tumour invasion. Furthermore, ICAM-1 expression was not confined to malignant lesions, but was also seen in benign naevi. These data contrast with earlier reports and indicate that ICAM-1 expression is unlikely to be of major prognostic or diagnostic value in melanocytic tumours.