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Biomedical subjects

H Zachariae

Publications and source records attributed to H Zachariae.

At least 37 records · Page 2Linked to original sources

[Occupational systemic sclerosis in men].

An analysis of the history of 28 men suffering from systemic sclerosis, diagnosed at our department during the last 25 years, showed that 21 (75%) had been subject to exposures previously suggested to be of importance in occupational scleroderma. The exposures were revealed by patient files, reports to health authorities, interviews and/or answers to questionnaires. Organic solvents being the most frequent exposure. This was found in thirteen of the patients (46%). A significant difference was found between scleroderma patients and control patients not suffering from connective tissue diseases in relation to total number of subjects exposed to one or several of the agents in question.

Adult↗

Effects of the calcium antagonist felodipine on renal haemodynamics, tubular sodium handling, and blood pressure in cyclosporin-treated dermatological patients.

BACKGROUND: Deterioration of renal function and rise in blood pressure are clinically important side-effects of cyclosporin (CsA) treatment. Calcium antagonists may have a renoprotective effect against CsA nephrotoxicity. PURPOSE: To investigate the effect of the dihydropyridine calcium-channel blocker felodipine on renal haemodynamics, tubular sodium handling, and blood pressure in CsA-treated patients with no primary renal disease, 18 patients with various CsA-treated dermatological diseases were allocated to receive either felodipine 5 mg (extended release tablets) once daily for 4 weeks followed by placebo for 4 weeks, or vice versa, in a prospective, randomized, double-blind study. The patients were investigated before treatment and at the end of each treatment period. RESULTS: After felodipine, both glomerular filtration rate (GFR) and renal plasma flow (RPF) were significantly higher compared to placebo (89.4 +/- 17.5 (mean +/- SD) vs 79.0 +/- 15.9 ml/min and 412.0 +/- 107.6 vs 326.1 +/- 78.0 ml/min respectively, P < 0.001 for both), and filtration fraction (FF) was lower (0.22 +/- 0.03 vs 0.25 +/- 0.03, P < 0.001). Both systolic and diastolic blood pressure were lower after felodipine compared to placebo (116 +/- 11/71 +/- 7 vs 133 +/- 18/83 +/- 10 mmHg, P < 0.001 for both). Furthermore, proximal output of sodium, i.e. fractional excretion of lithium, was higher after felodipine (26.9 +/- 7.3% vs 20.4 +/- 5.5%, P < 0.001) as well as total sodium excretion (0.33 +/- 0.19 vs 0.19 +/- 0.08 mmol/min, P < 0.001). CONCLUSIONS: It is concluded, that felodipine 5 mg once daily for 4 weeks increased GFR, RPF, and sodium excretion in cyclosporin-treated dermatological patients with no primary renal disease. Furthermore, felodipine lowers blood pressure in these patients. The effects of felodipine may be due to an antagonizing effect against CsA-induced nephrotoxicity.

Adolescent↗

The steroid-sparing effect of long-term plasmapheresis in pemphigus: an update.

Glucocorticoids and immunosuppressive agents can induce remission in most pemphigus patients, but mortality remains at 5 to 15% as a result of side effects. We reviewed the adjunctive effect of long-term plasmapheresis in 8 pemphigus patients. Four cases had been resistant to conventional therapy. One or 2 large-volume plasmapheresis treatments were given monthly over 5 to 141 months. All patients, were in clinical remission within 2 months. Relapses seldom occurred: the patients stayed in remission 90% (40-94) (median, ranges) of the period. In all cases the daily dose of glucocorticoid was reduced. The prednisone level could be decreased from 38 (15-80) mg/day to 7.5 (2.5-35) mg/day (p = 0.002). The overall level of other immunosuppressive agents remained unchanged, except in 1 patient for whom cyclosporine was introduced. This indicates that long-term plasmapheresis could have a steroid-sparing effect and clinical efficacy in pemphigus.

Adult↗

The flashlamp-pumped dye laser and dermabrasion in psoriasis--further studies on the reversed Köbner phenomenon.

Eleven patients with chronic plaque psoriasis were treated with the flashlamp-pumped pulsed dye laser and 6 of the same patients were at the same time treated by dermabrasion. Complete remissions were observed in 3 patients following laser-treatment and in 5 of 6 after dermabrasion. The observation periods were from 4 to 9 months. Our data suggest that the mechanism of the reversed Köbner phenomenon, which is thought to be responsible for the results of dermabrasion, is partly due to destruction of the dermal papillary vasculature. Partial responses were seen in 6 laser-treated and in one patient treated by dermabrasion. Two patients showed no response to laser treatment. These clinically unsatisfactory results can be explained by the great variety in thickness of plaques and in variability of penetration of the laser light. Measurements of absorption and scattering properties of plaques scheduled for laser treatment could probably allow improvements in the technique by optimizing laser beam diameter and pulse duration as well as wavelength and energy levels. The use of the dye laser is far less traumatic to the patient than dermabrasion.

Adult↗

Increased levels of type I and III collagen and hyaluronan in scleroderma skin.

The aminoterminal propeptide of type III procollagen (PIIINP) and the carboxyterminal propeptide of type I procollagen (PICP) and hyaluronan (HA) were measured in plasma and suction blister fluid from 13 systemic sclerosis patients and 11 healthy volunteers. Suction blisters and skin biopsies were from the transition zone between normal skin and scleroderma, and uninvolved abdominal skin of patients. The median value of suction blister PIIINP from the transition zone was 38% higher than suction blister PIIINP from uninvolved skin. PIIINP was localized to the dermis by immunohistochemical techniques. PICP and HA levels in blisters from the transition zone were 87% and 53%, respectively, above the levels measured in uninvolved skin. Furthermore, PICP and HA blister levels from the transition zone were 67% and 63%, respectively, higher than the levels measured in healthy volunteers. In plasma from scleroderma patients levels of PIIINP and HA were 38% and 127% higher, respectively, than in plasma of healthy volunteers. The plasma PICP level was not significantly higher in scleroderma patients. Finally, PICP, PIIINP and HA levels were several times higher in suction blister fluid than in plasma. The data indicate that a fibrogenetic process takes place in the transition zone of scleroderma. The method may be used to monitor the progression of scleroderma skin lesions in vivo.

Adult↗

Renal biopsy findings in long-term cyclosporin treatment of psoriasis.

Renal biopsies were performed in 30 psoriatics during long-term low-dose cyclosporin (CsA) therapy (range 2.5-6 mg/kg per day) of from 6 months to 8 years. The study included pretreatment biopsies in 25 of the patients. After 2 years all biopsies shared features consistent with CsA nephropathy despite completely normal pretreatment morphology in 17 of the 25 patients. The severity of the findings which consisted of arteriolar hyalinosis, focal interstitial fibrosis and sclerotic glomeruli increased with length of therapy. Mild renal lesions were seen during the first 2 years. After 4 years all but one had arteriolar hyalinosis, with interstitial fibrosis pronounced in five and moderate in six of 11 patients. At the same time glomerular sclerosis had become significant. A decrease in glomerular filtration rate (GFR) correlated with severity of structural lesions. The data from our study together with experiences from cardiac-transplanted patients treated with CsA indicate that patients with psoriasis after 2 years therapy with CsA should be rotated to other treatments or be followed carefully by GFR and sequential renal biopsies.

Adult↗

Methotrexate-induced liver cirrhosis. Clinical, histological and serological studies--a further 10-year follow-up.

BACKGROUND: Methotrexate (MTX) may induce liver damage, which in some psoriatics will lead to fibrosis or cirrhosis. Studies performed 10 years ago on 25 patients with MTX-induced liver cirrhosis indicated that this type of cirrhosis was not of an aggressive nature. OBJECTIVE: The aim of this study was to evaluate the present status of surviving patients 10 years later, together with the latest clinical and histological data on patients who had died. METHODS: The investigations were carried out on 186 liver biopsies and 5 autopsies. All biopsies were studied by the same pathologist. Eleven surviving patients were also studied by analysis of serum aminoterminal propeptide of type III procollagen (PIIINP), which is an indicator of fibrogenesis, which is especially suitable for follow-up of fibrotic liver disease. RESULTS: Thirteen patients had died; 1 of these died of liver failure. Another patient died form an overdose due to misunderstanding of the prescribed dosage given elsewhere. The remaining deaths were non-MTX related, but all 5 autopsies showed some degree of cirrhosis. On the other hand, 13 patients had no histologically verified liver cirrhosis in their latest biopsy, and PIIINP was within the normal range in all 11 patients investigated, this in spite of total cumulative MTX doses from 1,120 to 18,645 mg (mean 7,171 mg). CONCLUSIONS: This study confirmed that in most patients MTX-induced liver cirrhosis is not aggressive. However, continued low-dose MTX led, in spite of normal liver tests, 8 years after the last biopsy to liver failure and death in 1 of our patients. Our data support the continued use of liver biopsies in the surveillance of MTX-treated psoriatics.

Adult↗

Treatment of ischaemic digital ulcers and prevention of gangrene with intravenous iloprost in systemic sclerosis.

Twelve patients with systemic sclerosis were treated with intravenous infusions of the prostacyclin-stable analogue iloprost 0.5-2.0 ng/kg/min for 6 h from 8 to 13 days. Imminent gangrene was stopped in 2 patients and followed by healing. In 4 of 6 patients iloprost led to complete healing of ischaemic ulcers and in the remaining 2 patients to partial healing. One patient with severe Raynaud's phenomenon discontinued the study after 3 days due to severe headache. The 2 remaining patients with Raynaud's phenomenon as an indication improved, while no improvement was recorded in a patient with vasculitis of the lower leg. Side-effects such as headache, nausea and flushing were the reason that only 5 patients reached the maximum infusion rate. No statistical differences were recorded in digital bloodflow before and after the study or in plasma endothelin in the 9 patients investigated. Three of the 6 patients with healing ulcers, however, showed a pronounced decrease in plasma endothelin. Iloprost appears useful as a treatment of imminent gangrene and ischaemic ulcers in systemic sclerosis. This reparatory capacity could also be of a more general importance in therapy of this disease.

Adult↗

Plasma endothelin in psoriasis: possible relations to therapy and toxicity.

Plasma endothelin levels were studied in 71 patients suffering from severe psoriasis. The psoriatics were treated either with topical therapy alone (n = 18) or with cyclosporin A (n = 26), methotrexate (n = 21), or with hydroxyurea, acitretin or ranitidin (n = 6) with or without topical therapy. The psoriatics had a significantly higher average plasma endothelin than 40 healthy controls. The patients treated with cyclosporin A had the highest values and these were in contrast to patients on methotrexate and other systemic therapy higher than patients treated with topical therapy alone. There was not significant difference between endothelin levels in patients treated with methotrexate compared to those in patients only receiving topical treatment. Whether the increased endothelin levels in plasma are derived from keratinocytes or enlarged vessels need to be investigated. An increased plasma endothelin level could be related to therapy and for patients on cyclosporin A be of importance for toxicity.

Acitretin↗

Improvement in renal function by felodipine during cyclosporine treatment in acute and short-term studies.

The purpose was to study whether the calcium entry blocker, felodipine, could reduce the nephrotoxic and hypertensive effect of cyclosporine. The effect of felodipine on glomerular filtration rate (GFR), renal plasma flow (RPF), fractional excretion of sodium, lithium clearance and blood pressure was measured in three randomized, placebo-controlled studies of cyclosporine treated patients. In study one, 10 renal transplant recipients were examined within the first six months after transplantation in a cross-over design. Renal hemodynamics were determined after the acute ingestion of felodipine or placebo, with an interval of less than one week between the two examinations. In study two, 79 renal transplant recipients were randomized to a treatment with felodipine or placebo just before transplantation, and renal hemodynamics were determined after twelve weeks. In study three, 18 patients, who were treated with cyclosporine due to dermatological diseases, were examined in a cross-over design to determine their renal hemodynamics after four weeks of treatment with felodipine or placebo. Felodipine increased renal hemodynamics in study one (GFR 16%, RPF 33%, P < 0.01 for both), in study two (GFR 23%, RPF 28%, P < 0.05 for both), and in study three (GFR 13%, RPF 26%, P < 0.01 for both). FE(Na) was significantly increased by felodipine in studies one and three, but not in study two. Lithium clearance was significantly increased and blood pressure significantly reduced by felodipine in all three studies. It can be concluded that felodipine counteracts both the cyclosporine induced impairment in renal hemodynamics and the increase in blood pressure in acute and short-term studies.

Adult↗

The use of serologic markers for collagen synthesis and degradation in systemic sclerosis.

BACKGROUND: Systemic sclerosis is characterized by excessive accumulation of collagen in all involved organs. Serum markers of collagen synthesis and degradation, the aminoterminal propeptide of type III procollagen (PIIINP), the carboxyterminal propeptide of type I procollagen (PICP), and the crosslinked telopeptide of type I collagen (ICTP), can be measured. OBJECTIVE: Our purpose was to investigate these markers in different subgroups of untreated patients with systemic sclerosis and in patients before and after various types of therapy. PIIINP and PICP were also investigated in blister fluid from involved and uninvolved skin. METHODS: Sera from 97 patients and suction blister fluid from 13 patients were radioimmunoassayed. RESULTS: The highest levels of PIIINP and PICP were found in blister fluid from involved skin. Patients with systemic sclerosis had higher serum levels of PIIINP than control subjects. The highest levels were found in patients with diffuse cutaneous systemic (type III) sclerosis; increased serum PIIINP was also characteristic of type II limited cutaneous systemic sclerosis. Most patients with limited cutaneous type I systemic sclerosis had normal levels. Serum PICP was within normal limits in all three types of systemic sclerosis. Variations in ICTP type I collagen degradation in general followed PICP. Immunosuppressive drugs significantly reduced PIIINP, whereas no significant decrease was found after photopheresis. PICP and ICTP also diminished after treatment with D-penicillamine and cyclophosphamide given together with prednisone. CONCLUSION: PIIINP can be recommended for monitoring collagen synthesis in systemic sclerosis. Our data support the use of immunosuppressive therapy for this disease.

Biomarkers↗

Photopheresis in the red man or pre-Sézary syndrome.

BACKGROUND: The beneficial effect of extracorporeal photochemotherapy has clearly been established for patients with cutaneous T-cell lymphoma with Sézary's syndrome. But this treatment has not been used in the red man syndrome or pre-Sézary syndrome. Some of these patients do not respond sufficiently or do not tolerate other therapies. OBJECTIVE: The purpose of this open study was to evaluate the clinical efficacy of photopheresis in this group of patients. METHODS: Seven patients with the red man syndrome were treated on 2 consecutive days every 4 weeks for 6-22 months. Six had been on systemic steroids and 3 had also received retinoids without sufficient effects. All were initially treated with topical nitrogen mustard but no longer tolerated this treatment. RESULTS: All signs of erythroderma disappeared in 6 of the 7 patients. All systemic therapy could be discontinued in all but 2 patients. No side effects were observed. CONCLUSION: Photopheresis may be an effective alternative treatment for this group of patients, when other types of therapy have failed.

Acitretin↗

The steroid-sparing effect of long-term plasmapheresis in pemphigus.

Glucocorticoids and immunosuppressive agents can induce remission in most patients with pemphigus, but mortality remains at 5 to 15% due to complications from these drugs. We reviewed the adjunctive effect of long-term plasmapheresis in 8 patients with pemphigus. Four cases had been resistant to conventional therapy. One or two large-volume plasmapheresis treatments were given monthly for 5 to 73 months. All patients were in clinical remission within 2 months after the addition of plasmapheresis. Relapses of pemphigus seldom occurred, and the patients stayed in remission 90% (40-100%) (median and ranges) of the plasmapheresis period. In all cases the daily dose of glucocorticoid was reduced. The prednisone level could be decreased significantly from 38 (15-80) mg/day to 10 (5-35) mg/day (p = 0.008). The overall level of other immunosuppressive agents remained unchanged, except in one patient where cyclosporine was introduced. This first report of long-term plasmapheresis demonstrates clinical efficacy in pemphigus and a considerable steroid-sparing effect.

Adult↗

Efficacy of cyclosporin A (CyA) in psoriasis: an overview of dose/response, indications, contraindications and side-effects.

Since 1985, the efficacy of cyclosporin A (CyA) in severe psoriasis has been evaluated in a number of open and controlled studies, all of which have clearly established CyA as an effective antipsoriatic agent. The efficacy of CyA has also provided new insights into the pathophysiology of psoriasis. The effects of CyA treatment can be seen within weeks; they are dose-dependent and quickly reversible on stopping treatment. Hypertension and nephrotoxicity remain the greatest concerns associated with long-term use. In general, the incidence of hypertension is approximately 10%. A dosage of approximately 2.5-5 mg/kg/day of CyA induces a slight, but significant, dose-dependent increase in serum creatinine. Studies of pre- and post-treatment renal biopsies have also disclosed slight, but significant, increases in interstitial fibrous tissue which are negatively correlated to creatinine clearance. This review assesses the current knowledge of the prospects of CyA in the treatment of psoriasis with respect to dose/response, indications, contraindications and side-effects.

Biopsy↗