Naltrexone in the short-term decreases antiparkinsonian response to l-Dopa and in the long-term increases dyskinesias in drug-naïve parkinsonian monkeys

Nigrostriatal dopaminergic denervation and levodopa therapy in animal models and in parkinsonian patients are associated with an enhanced opioid transmission in the striatum. The functional role of this increase has always been a subject of debate. In this study two groups of drug-na?ve macaque monkeys with MPTP-induced parkinsonism were treated daily, during four weeks, with l-Dopa alone or l-Dopa plus naltrexone, a non-selective opioid receptor antagonist. The improvement of parkinsonism in all animals treated with l-Dopa alone was clearly displayed from the first day of treatment. By contrast, naltrexone co-treatment blocked the antiparkinsonian action of l-Dopa for 7-14 days. As soon as the therapeutical action of l-Dopa appeared in naltrexone-treated monkeys, the magnitude and duration of the antiparkinsonian response were similar in both groups. Furthermore, in animals treated with l-Dopa plus naltrexone the beginning of the therapeutical effect of l-Dopa was accompanied by the appearance of dyskinesias. In this group, the severity of dyskinesias during the third and fourth weeks of treatment was significantly higher than the group treated with l-Dopa alone. The results of the present study demonstrate that in de novo MPTP parkinsonian monkeys antagonizing the action of opioid receptors worsens the motor response to l-Dopa.     

Tuberculosis of the greater trochanter: a report of three cases

Trochanteric tuberculosis represents less than 2% of all musculo-skeletal tuberculosis. The diagnosis is difficult especially if abscess and fistula are missing. The authors report 3 cases of trochanteric tuberculosis. The diagnosis was established, respectively, 4, 9 months and 1 year after the beginning of the symptoms. The tuberculosis was plurifocal in all cases. Diagnosis was based on the presence of caseum granuloma in the first case, positive Lowenstein culture in the second case and on clinical and paraclinical arguments in the third one. Healing was obtained after medical treatment alone. The authors discuss the potential role of the newer imaging modalities in diagnosis of trochanteric tuberculosis and the indications of medical and surgical treatment.     

Emphysematous pyelonephritis. Two cases

The emphysematous pyelonephritis is a rare and severe renal infection characterized by the presence of gas in renal parenchyma and its perirenal spaces. We report two cases of emphysematous pyelonephritis in two diabetic women (53 and 50 years old respectively). In the first case, the treatment was based on nephrectomy because of the presence of a septic shock and three risk factors, which are acute renal failure, hematuria and thrombopenia. In the second case, the treatment was only medical. The evolution was favorable in the two cases. We insist in this article that this diagnosis should be considered in every female diabetic patient having severe acute pyelonephritis resistant to a well-conducted medical treatment.     

Cardiac manifestations of idiopathic hypereosinophilic syndrome

BACK GROUND: The aim of our study is to describe the more common cardiac manifestations of idiopathic hypereosinophilic syndrome representing the major cause of mortality. MAIN POINTS: Current therapy consists of corticosteroid, hydroxyurea and interferon alpha. Recent publications confirm the activity of imatinib mesylate, a selective tyrosine kinase inhibitor, in patients with idiopathic hypereosinophilic syndrome. In cases with marked valvular compromise or with endomyocardial thrombosis or fibrosis, cardiac surgery can provide substantial benefits. PERSPECTIVES: A better understanding of the pathophysiology of this syndrome could lead to the development of new therapeutic agents.     

Induction of somatic hypermutation by antigen-specific B cell receptors in the human BL2 cell line

The role of the B cell antigen receptor in the induction of somatic hypermutation is presently unclear. We established stable transfectants of the human BL2 cell line expressing hen-egg lysozyme-specific IgM or IgA and compared their ability to induce somatic hypermutation of the endogenous rearranged heavy-chain gene. We found that IgM and IgA were both able to induce somatic hypermutation in an antigen dose-independent manner. The mutations displayed most of the characteristics of somatic hypermutation in vivo. Notably, some replacements introduced stop codons in the coding region. Our data suggest that class-switched memory B cells may undergo somatic hypermutation. They also suggest that the transmembrane/cytoplasmic domains of the class-switched isotypes modulate the signaling and down-modulation activities of the BCR in an antigen dose-dependent manner.     

IgD kappa myeloma: a new case

IgD myeloma, which is particularly severe, accounts for only 1-3% of all myeloma cases, and the kappa subtype contributes only 10-30% of IgD myelomas. We report a new case. CASE-REPORT: A 59-year-old man was admitted for inflammatory low back pain with L5 sciatica and diffuse bone pain. The symptoms had been present for 3 months, during which he had experienced a severe decline in general health. Laboratory test abnormalities included an erythrocyte sedimentation rate of 70 mm/h, normochromic normocytic aplastic anemia, hypercalcemia (3.5 mmol/l), and serum creatinine elevation to 583 micromol/l. Tests were negative for cryoglobulinemia. Serum protein electrophoresis showed hypergammaglobulinemia but no monoclonal peak. Immunoelectrophoresis, however, detected a faint IgD kappa band in the blood and a homogeneous kappa band in the urine. Bone marrow aspirated from the sternum was found to contain 30% of malignant plasma cells. Biopsies for amyloidosis were negative. Radiographs disclosed multiple punched-out lesions with no evidence of spinal cord compression. Symptomatic treatment was given to correct the hypercalcemia, and combination chemotherapy was started. DISCUSSION: IgD kappa myeloma is a severe variant of myeloma often associated with extraosseous lesions, renal failure, and amyloidosis. The monoclonal component is absent or faint by serum protein electrophoresis, making the diagnosis difficult. The pathogenesis is unclear and the prognosis grim.     

CD81-induced behavioural changes during chronic cocaine administration: in vivo gene delivery with regulatable lentivirus

CD81, a tetraspanin transmembrane protein involved in cell adhesion, is up-regulated in the mesolimbic dopaminergic pathway 24 h following acute administration of high doses of cocaine [Brenz-Verca et al., (2001) Mol. Cell. Neurosci., 17, 303-316]. Further evidence consecutive with this observation and based on microarray analysis are presented here. In addition, a regulatable lentivirus was developed bearing the rat CD81 gene under the control of a tetracycline inducible system. This lentivirus vector was stereotaxically injected into the ventral tegmental area (VTA) of two groups of animals, one fed water (expressing CD81) and the other Doxycycline solution (which down-regulates CD81 expression) and locomotor activity after chronic cocaine administration (10 mg/kg daily) was monitored. After 2 weeks, the groups were inverted, animals receiving water were placed on Doxycycline and the second group was placed on water. In all cases highly a significant increase (3.2-fold) in locomotor activity was observed in animals expressing CD81 in the VTA vs. animals placed on Doxycycline. Similar studies where CD81 was delivered into the nucleus accumbens (NAcc) resulted in significantly higher effects (30%), in accordance with microarray data and our previous reports, yielding a 4.2-fold increase in locomotor activity. No change was observed under similar conditions in control animals, which were injected a regulatable lentivirus expressing GFP. These findings suggest that CD81 expression in the mesolimbic dopaminergic pathway contributes to behavioural changes associated with cocaine sensitization. This study provides a powerful approach for evaluating a gene function in vivo in a single animal under various paradigms, even on gene candidates, which display small changes of expression.     

Effect of triple antiretroviral therapy on Tunisian AIDS profile: study of 139 cases

We report a retrospective study to estimate highly active antiretroviral therapy (HAART) effect in 139 HIV infected patients. Four criteria are studied: prevalence of opportunistic infections, CD4 cell count evolution, viral load progression and mortality. Gastrointestinal side effects are the most common clinical adverse reaction (61.1 percent), and hematological side effects are the most common biological adverse reaction (61.2 percent). During the 22.8 months (3 months to 6 years) follow-up average period, CD4 cell counts remained above 500 per cubic millimeter in only 25.8 percent of cases, while 63.5 percent of patients had a viral load below 400 copies per milliliter. During the study on patients receiving HAART, opportunistic infections appeared in 17.3 percent of cases (24 cases) and mortality in 6.4 percent of cases.