Unusual clinical manifestation of a disfiguring necrobiotic granulomatous disease.

A 39-year-old woman had a disfiguring granulomatous disease of 36 years' duration. Nodules appeared on her lower extremities and later extended to her face; this led to ulceration and destruction of the nasal cartilage. This disease of unknown origin does not conform to any previously described entity. Some patients with a similar case presentation have been observed in France.

Inhibition of the metabolism of endogenous retinoic acid as treatment for severe psoriasis: an open study with oral liarozole.

Retinoids derived from retinol or beta-carotene are inactivated, among other ways, by enzymes belonging to the P450 cytochrome group. Liarozole, an imidazole-containing compound, is known to be a potent inhibitor of the cytochrome P450-mediated metabolism of all-trans retinoic acid. As a result, increased levels of this retinoid are found in skin and plasma. Therefore, in the treatment of psoriasis, therapeutic effects may be expected with liarozole which are similar to those observed with synthetic retinoids. In an open study, oral liarozole was given at a daily dose of 75 mg b.i.d., for 12 weeks to 31 patients with severe psoriasis. After 1 month, this dosage could be increased to 150 mg b.i.d. if there was no improvement or only moderate improvement. Initially, the effect of liarozole was mainly on scaling. A decrease in the Psoriasis Area and Severity Index (PASI) score of 45% at week 4, of 69% at week 8 and of 77% at week 12 was obtained, compared with baseline. A further decrease in the PASI score of up to 87% was observed in the 16 patients who were allowed to continue treatment for a maximum period of 12 months. An excellent or good improvement was noted in 77% of the patients within 12 weeks of starting treatment. This response rate had increased to 88% by the last follow-up visit. Nearly all patients (29 of 31) experienced adverse reactions, such as dry oral mucosa, headache and itching. These were mostly mild and transient, but four patients dropped out of the study because of an adverse event. Haematological, biochemical and cardiovascular parameters were not significantly influenced by liarozole. Six patients showed an increase in triglycerides, which normalized in three of four patients during further treatment. The results of this pilot study suggest that, at doses of 75-150 mg b.i.d., liarozole is an active antipsoriatic drug, and may be a useful addition to the existing therapeutic armamentarium. Controlled studies should be performed to compare liarozole with standard oral treatments.

The antihypertensive and cardiac hemodynamic effects of nebivolol.

Acute, subacute, and chronic treatment with nebivolol, a novel beta 1-selective adrenergic antagonist, significantly lowered systolic and diastolic blood pressure and heart rate in patients with essential hypertension. No orthostatism and bradycardia were reported. A comparison between a normal control group and 23 hypertensive patients revealed that the ratio between the preejection period (PEP) and the left ventricular ejection time (LVET) of the systolic time intervals (STI) was significantly increased in the hypertensive patients, owing to a prolongation of the PEPc (PEP corrected for heart rate). Treatment with nebivolol 5 mg once a day significantly improved the PEP/LVET, in acute conditions from 0.42 +/- 0.023 to 0.39 +/- 0.018, after one month of treatment from 0.40 +/- 0.013 to 0.36 +/- 0.013 and after one year of treatment from 0.41 +/- 0.012 to 0.36 +/- 0.010, owing to a significant shortening of the PEPc. There was no correlation between changes of blood pressure and changes of STI. Diastolic dysfunction is an early finding in hypertension and may well be reflected in the prolongation of the PEPc. The improvement of left ventricular performance, as measured with STI, suggests that treatment with nebivolol may favorably influence the underlying diastolic dysfunction and be of therapeutic value for hypertensive patients with left ventricular damage.

The effects of short-term treatment with levamisole on cytokines in volunteers and cancer-patients.

In search for clues to the potential immunomodulating mechanism of action of levamisole which might be used as monitoring parameters, we have determined a variety of cytokines in the peripheral blood of volunteers and carcinoma patients before and after a single or a 3-day-treatment with 150 mg/day. In cancer patients no changes could be detected 4 days after a 3-day-treatment course in the levels of TNF-alpha, IL-1beta, IL-2 or IL-6. In a placebo-controlled volunteer study the same treatment did not affect the levels of beta2-microglobulin, IL-1beta, IL-1alpha, IL-2 or IL-6. However, 24hr after the last treatment the concentration of neopterin was slightly but significantly increased and the concentration of soluble IL-2 receptors decreased. A single treatment failed to produce such an effect. It is suggested that the measurement of neopterin and soluble IL-2 receptors may provide useful information in future trials.

Modulation of immunity in multiple sclerosis: a double-blind levamisole-placebo controlled study in 85 patients.

Levamisole seems to regulate cell-mediated immunity by restoring T-cell function. Since a deficiency of T lymphocytes has been described by various authors in multiple sclerosis patients. Of the 85 patients involved in the trial, evaluation of functional and neurological scores was possible in 54 (32 with placebo and 22 with levamisole). The mean follow-up period was 2 years. This double-blind controlled study indicates that both neurological function and disability significantly deteriorated in the placebo-treated patients, but remained fairly stable in the levamisole-treated group. Since the difference between both groups was not significant, no levamisole effect was demonstrated on progression in multiple sclerosis. With the exception of one case of granulocytopenia (which had no clinical effect), no drug-related changes could be demonstrated. This contrasts with the general impression that this immunomodulator agent might be harmful to patients with multiple sclerosis. The fact that during this blind study both annual relapse rate and disability score remained more stable in treated patients with severe disability suggests that, while waiting for a more effective treatment, long-term levamisole therapy could be useful in patients with multiple sclerosis.