Hypocomplementemic panniculitis with paraprotein.

Two episodes of severe panniculitis accompanied by fever and an acute phase response were the main clinical features in a patient who had an unusual IgG kappa paraprotein. Both episodes responded promptly to steroids. Complement proteins of the early classical pathway were depleted in the patient's serum, and in vitro experiments indicated that the IgG kappa paraprotein activated complement directly. The association of recurrent panniculitis and paraproteinemia-hypocomplementemia has been described in 2 other patients. It should be recognized since its response to steroids is immediate.

Drug-drug interactions of new active substances: mibefradil example.

INTRODUCTION: Mibefradil was approved as a novel calcium antagonist in Switzerland in 1996. Following its launch as an antihypertensive and anti-anginal agent, there were reports about serious pharmacokinetic and pharmacodynamic interactions occurring with other drugs frequently administered to patients with cardiovascular diseases. Despite appropriate modifications of the prescribing information, such interactions continued to occur. The drug was finally withdrawn after a study in patients with congestive heart failure showed a trend to higher mortality with mibefradil. This increase in mortality could again be due to multiple interactions between mibefradil and other drugs. In retrospect, it can be concluded that several of the interactions, including the theoretical risk of severe toxicity in some patients, could have been and in fact were predicted on the basis of the data available before introduction to the market. Depending on the benefits, these problems would however not necessarily represent an unacceptable risk for a new active compound. RESULTS AND CONCLUSION: The most important points revealed by this analysis were: (1) when interpreting the results of interaction studies, it is important to consider not only the mean of the interaction effect but also the observed and the theoretically conceivable extreme effects in individual subjects and (2) a drug with a high interaction potential may represent a high risk even if an adequate warning is included in the product information. The need for specific pharmacokinetic and pharmacodynamic interaction studies with new drugs and the limitations of the pivotal clinical efficacy and safety studies during phase III in order to reveal such interactions are discussed.

Monomeric complement-activating IgG paraproteins.

Three patients presented a unique syndrome of recurrent panniculitis with an IgGkappa paraprotein and depletion of the early components of the classical pathway of complement. The IgGkappa paraproteins were monomers with a normal structure, and with no evidence for aggregation, as assessed by electron microscopy and ultracentrifugation. Both heavy and light chains were of normal molecular size (SDS-PAGE), and the paraproteins were not heavily glycosylated. However, the paraproteins from all three patients had unusual features that included abnormal behavior on gel filtration chromatography and a heavy chain of high pI. When analyzed by fast protein liquid chromatography (Superdex 200), elution of the paraproteins was retarded, particularly when the ionic strength was increased. This retardation was partially reversed in 20% alcohol, and fully reversed in 6 M guanidine-HCl. Neither anti-C1 inhibitor nor anti-C1q autoantibodies were found in any of the patients' sera. However, the paraproteins bound to the globular heads of C1q at normal ionic strength. They activated C4 in normal human serum, but not in C1q-deficient serum. Activation led to the formation of C1s-C1 inhibitor complexes. Taken together, the data suggest that the unusual paraproteins have the capacity to bind C1q, which then leads to activation of C1. The ability of these paraproteins to activate C1, in spite of their being soluble monomers, is likely to be related to their unique physicochemical features.

Pseudoporphyria induced by nabumetone.

Nabumetone is a nonsteroidal anti-inflammatory drug, which has only rarely been associated with photosensitivity. We report a case of bullous lesions arising over photoexposed areas in a patient treated with nabumetone.

[Co-trimoxazole administration: a rare cause of hypoglycemia in elderly persons]. / Prise de co-trimoxazole: une cause rare d'hypoglycémie chez la personne âgée.

We report a case of severe hypoglycaemia following co-trimoxazole therapy. An 88-year-old woman was admitted with urinary tract infection and treated with co-trimoxazole (960 mg bid). Seven days after initiation of the treatment she became comatose. Blood sugar was 1.3 mmol/l and C-peptide at the upper limit of normal range. Glucose infusion restored normal consciousness and no hypoglycaemia recurred after interruption of co-trimoxazole therapy. Advanced aged was the only risk factor identified. Other risk factors described in previous case reports are renal failure, poor nutritional state and high doses of co-trimoxazole.

[Factors associated with refractory cancer pain]. / Facteurs associés aux douleurs cancéreuses réfractaires.

Cancer pain can be effectively controlled in most patients by classical pharmacological treatment. We retrospectively studied the characteristics and factors associated with non responsive pain. Between 1989 and 1996, 1767 patients were referred to our pain center; 831 (47%) had cancer pain and from 787 evaluable cases 118 (15%) experienced non-controlled pain whereas good pain control was achieved within a few days in 669 (85%) patients. Gender, age, cancer type, metastasis, initial pain intensity, nociceptive or neuropathic components and administration of adjuvant therapies were similar in both groups. On the other hand, diffuse pain, abdominal pain, terminal care, near death and doses of strong opioids were significantly different. Factors associated with therapeutic failure were conflicts, life and complications and breakthrough pain. In the presence of refractory cancer pain the factors predictive of therapeutic failure should be identified in order to optimize individual pain treatment.

[Influence of sex on reporting pain]. / Influence du sexe sur la plainte douloureuse.

In many epidemiological pain studies, women more frequently report more intense, frequent and long-lasting or chronic transient pain than men. In our retrospective study including hospitalised patients referred to a pain centre, prevalence of headaches, musculoskeletal pain and somatoform pain was observed in women, as described in the literature. Generally pain intensity was higher in women and pain was more frequently controlled in men, but when intensity and pain control were compared according to the pain aetiologies, no gender difference was found. Drug treatments were adapted to pain aetiologies, which accounted for the observed differences. In hospitalised patients the significant differences observed in intensity, pain control and treatment reflect the heterogeneity of pain aetiologies rather than gender differences.