[Erythema and fever after diclofenac i.m]. / Erythem und Fieber nach Diclofenac i.m.

We describe a patient with a streptococcal myositis/fasciitis and toxic shock syndrome following an intramuscular injection with diclofenac. A patient complaining of sore throat and headaches for two days and fever up to 38.5 degrees C for one day consulted her family physician. 75 mg of diclofenac were injected intramuscularly for symptomatic treatment. On the next day massive pain at the injection site and a generalized erythema occurs and fever up to 38.5 degrees C persists. She is admitted to the local hospital for suspected abscess formation. Despite rapid antibiotic treatment a septic shock develops. The patient is transferred to a tertiary care hospital. An extensive debridement is performed and the antibiotic regimen changed to high dose penicillin and clindamycin. The association of life threatening diseases due to Group A streptococci and non-steroidal anti-inflammatory drugs (NSAID) is well documented by several case reports. We believe there is no longer any need for intramuscular injections of NSAID. The rare but severe complications preclude further use of the intramuscular dosage in view of the availability of oral alternatives.

Hyperuricaemia in cyclosporin-treated patients: GFR-related effect.

BACKGROUND: Hyperuricaemia is a well known side-effect of cyclosporin A (CsA) treatment. The pathogenic mechanisms, however, remain controversial. There is no convincing evidence that hyperuricaemia is due to CsA-induced, impaired tubular handling of uric acid. The impact of diminished GFR in this particular context has never been investigated. METHODS: We prospectively studied plasma uric acid, inulin clearances, and fractional clearances of uric acid in two groups of CsA-treated patients (bone-marrow transplant patients, n = 50; renal transplant patients, n = 32), and one healthy control group without CsA (living related kidney donors, n = 28). Bone-marrow transplant patients were examined before transplantation and 6, 12, 18, 24 months after transplantation, renal transplant patients 1 year after transplantation, and living related kidney donors before and 1 year after unilateral nephrectomy. RESULTS: After 1 year of CsA treatment, hyperuricaemia was found in 36% of bone-marrow transplant patients and in 53% of renal transplant patients. Thirty per cent of living related kidney donors were borderline hyperuricaemic 1 year after unilateral nephrectomy. The fractional clearance of uric acid, measured serially in bone-marrow transplant patients did not change significantly over time; it was, however, slightly higher during CsA treatment than after CsA withdrawal. Moreover, the bone-marrow transplant patients' fractional clearance of uric acid was not statistically different from the renal transplant patients' and the living related kidney donors' (values 1 year after transplantation/unilateral nephrectomy: bone-marrow transplant patients, 15.3 +/- 2.3%; renal transplant patients, 11.9 +/- 0.9%; living related kidney donors, 11.1 +/- 0.8%). The GFR at 1 year measured by inulin clearance, was identical in the CsA-treated groups and slightly higher in the living related kidney donors (bone-marrow transplant patients, 51 +/- 6 ml/min per 1.73 m2; renal transplant patients, 49 +/- 3 ml/min per 1.73 m2; living related kidney donors, 61 +/- 2 ml/min per 1.73 m2). CONCLUSION: There is no evidence for impaired tubular handling of uric acid, induced by a CsA-specific tubulotoxic effect. Hyperuricaemia in CsA-treated transplant patients can therefore be attributed to the cyclosporin-associated decrease of GFR.

A randomized prospective trial of prophylactic immunosuppression with ATG-fresenius versus OKT3 after renal transplantation.

We carried out a randomized prospective trial to compare OKT3 (5 mg/d, 51 patients) with ATG-Fresenius (ATG-F, 4 mg/kg/d, 53 patients) for induction therapy after renal transplantation, concerning side effects, rejection, and infection incidence within a one year follow-up period. Concomitant immunosuppression included azathioprine/steroids from day 0 and cyclosporine A from day 4. OKT3 patients experienced significantly more and more-severe side effects, particularly pyrexia, headache, and pulmonary fluid overload. One-year graft survival was excellent in the ATG-F group (91%), but only 78% in the OKT3 group (P < 0.05) due to a series of rejections that occurred beyond day 100; patient survival (96% and 92%) was similar in both groups. OKT3-treated patients experienced more biopsy-proven rejections (0.6 +/- 0.1/pt.) than ATG-F patients (0.3 +/- 0.1, P < 0.05), and there was a similar, albeit not significant trend in clinical rejections (OKT3: 1.1 +/- 0.2/pt.; ATG-F: 0.8 +/- 0.1/pt.). Infections were more common in the OKT3 group (OKT3: 3.2 +/- 0.3, ATG-F: 2.0 +/- 0.2, P < 0.05), although this was entirely attributable to "minor" infections. On days 1 through 6, CD3 counts were more profoundly depressed with OKT3 therapy. Beyond day 10, however, CD3 counts were lower in the ATG-F group, as were CD2 counts, CD4 counts, and the CD4/CD8 ratio, suggesting a more prolonged immunosuppressive effect of ATG-F. Sensitization occurred more frequently with OKT3 (31%) than with ATG-F (10%), but was usually irrelevant, except in two patients (one in each group), whose grafts were lost because of immunization against OKT3 and ATG-F, respectively. In conclusion, a 7-day induction therapy with OKT3 does not improve outcome or diminish immunological graft loss when compared with ATG-F, but is associated with more rejections, infections, and side effects. ATG-F appears to be preferable for induction immunosuppression after renal transplantation.

Excellent uricosuric efficacy of benzbromarone in cyclosporin-A-treated renal transplant patients: a prospective study.

Patients on cyclosporin A (CsA) often develop hyperuricaemia and gout. In transplant patients the use of uricosuric drugs for treating hyperuricaemia may be preferable to allopurinol because of the known interaction of the latter with azathioprine. We therefore prospectively studied the uricosuric efficacy of 100 mg benzbromarone (Bbr;Desuric) daily in 25 CsA-treated renal transplant patients with stable graft function and hyperuricaemia (> 359 mumol/l for females, > 491 mumol/l for males). Benzbromarone decreased plasma uric acid from 579 + 18 mumol/l to 313 +/- 24 mumol/l (mean +/- SEM; P < 0.0001) and thereby normalized plasma uric acid in 21 of 25 patients. The remaining four patients had creatinine clearances between 21 and 25 ml/min, the lowest of the entire study group. Mean fractional clearance of uric acid increased from 5.4 +/- 0.4% to 17.2 +/- 1.0% (P < 0.001). The relative decrease of plasma uric acid closely correlated with baseline creatinine clearance (r = 0.67; P < 0.001). CsA trough values were not influenced. None of the patients experienced any significant side-effects. As an unexpected find-ing, urinary uric acid excretion increased from 2082 +/- 175 mumol/24 h to 3233 +/- 232 mumol/24 h after 4 weeks' treatment with benzbromarone. In conclusion, benzbromarone normalized plasma uric acid in all CsA-treated renal transplant recipients with a creatinine clearance > 25 ml/min. Due to its excellent efficacy and lack of significant side-effects, benzbromarone appears to be preferable to allopurinol in CsA-treated renal transplant recipients with a creatinine clearance over 25 ml/min.

Effect of thyroid dysfunction on thigh muscle efficiency.

To establish whether muscle weakness in thyroid dysfunction can be attributed solely to muscle atrophy (i.e. reduction in the total muscle cross-section) or whether the intrinsic contractile strength of the muscle is reduced per unit cross-sectional area, the ratio between thigh muscle strength and thigh muscle area was determined before and after treatment of hyper- and hypothyroidism. Midthigh muscle areas, assessed by computer tomography, increased in all seven hyperthyroid and decreased in three of four hypothyroid patients investigated after treatment of the thyroid disease. Peak torque and total work output, assessed by an isokinetic dynamometer (Cybex II), increased in both groups of patients. The muscle efficiency (total work output per cm2 muscle) increased in all patients after therapy [mean +/- SD values before vs. after therapy in hyperthyroid patients, 17.6 +/- 5.3 vs. 30.5 +/- 3.7 joules (J)/cm2 (P less than 0.001); in hypothyroid patients, 12.8 +/- 6.1 J/cm2 vs. 25.8 +/- 8.6 J/cm2 (P less than 0.05)]. Thus, the present study demonstrates that patients with thyroid dysfunction have altered muscle mass and diminished muscle efficiency.

Impact of ketoconazole on the metabolism of prednisolone.

The impact of ketoconazole (200 mg for 7 days) on the kinetics of oral prednisone and intravenous prednisolone and on the apparent activity of the 6 beta-hydroxylase was investigated in 10 healthy volunteers. The ratio of urinary 6 beta-OH-cortisol/17-OH-corticosteroids declined by greater than 50% and the urinary excretion of 6 beta-OH-prednisolone decreased more than twofold in all subjects. The decline of the activity of the 6 beta-hydroxylase was associated with impaired metabolic and renal clearances of total and unbound prednisolone. The ratios of the AUCs of prednisolone/prednisone after oral prednisone and intravenous prednisolone were independent of the administration of ketoconazole, suggesting that the enzymes responsible for the interconversion of prednisolone in equilibrium prednisone were not affected by ketoconazole. Thus ketoconazole inhibits 6 beta-hydroxylase and increases the exposure of the body to the biologically active unbound prednisolone after oral prednisone or intravenous prednisolone.

Altered body fat distribution in patients with glucocorticoid treatment and in patients on long-term dialysis.

Fat distribution was assessed by computed tomography in normal volunteers (n = 42), patients on long-term dialysis (n = 18), and patients on glucocorticoids [renal transplant patients (n = 49), other diseases (n = 17)]. Patients on glucocorticoids had higher mediastinal (deep) and identical or increased posterior cervical, buccal, and midthigh (superficial) fat areas when compared with normal subjects. The pattern of fat distribution in dialysis patients mimicked the distribution observed in patients taking glucocorticoids. Healthy females had higher ratios of superficial to deep fat than healthy male subjects. Patients on prednisone or on dialysis lost this sex-associated difference in fat distribution. Since patients on prednisone exhibit increased or normal thigh fat depots in the presence of increased mediastinal fat, the current concept that glucocorticoids induce redistribution of body fat from peripheral to central fat compartments has to be revised. Furthermore, disease states and/or glucocorticoids abrogate sex-associated differences in body fat distribution.