Risperidone-associated new-onset diabetes.

BACKGROUND: Weight gain, and its associated complications such as the development of diabetes, is becoming increasingly recognized as an important potential side effect of the novel antipsychotic drugs. METHODS: Two retrospective cases are described in which patients with schizophrenia developed diabetes while taking the antipsychotic medication risperidone. RESULTS: Both patients had preexisting risk factors for diabetes and developed insulin resistance in the context of weight gain. Both cases necessitated medical intervention and one patient requires ongoing treatment with insulin. CONCLUSIONS: Although the exact mechanism of antipsychotic induced diabetes remains obscure, weight gain appears to be a significant risk factor. Careful monitoring of weight and fasting glucoses is recommended for any patient taking novel antipsychotic medications.

Prevention of bleomycin-induced pulmonary fibrosis after adenovirus-mediated transfer of the bacterial bleomycin resistance gene.

A serious limitation in the use of the DNA-cleaving, antitumoral-antibiotic, bleomycin during chemotherapy is pulmonary toxicity. Lung injury induced by bleomycin is characterized by an increased deposition of interstitial extracellular matrix proteins in the alveolar wall that compromises respiratory function. Several drugs have been tested in animal models to prevent the pulmonary toxicity of bleomycin, but have not led to a useful clinical treatment because of their adverse effects on other tissues. We have shown that transgenic mice expressing Streptoalloteichus hindustanus (Sh) ble bleomycin resistance protein in pulmonary epithelial cells in the lungs are protected against bleomycin-induced toxicity in lungs. In the present study, we used intranasal administration by adenovirus-mediated gene transfer of the bleomycin resistance Sh ble gene to mouse lung for prevention of bleomycin-induced pulmonary fibrosis. We constructed recombinant adenoviruses Ad.CMVble and Ad.RSVble harboring the bleomycin resistance Sh ble gene under the control of the cytomegalovirus early promoter and the Rous sarcoma virus early promoter, respectively. Transgene expression was detected in epithelia of conducting airways and alveolar septa by immunostaining with a rabbit polyclonal antibody directed against the bleomycin resistance protein and persisted for the duration of drug treatment; i.e., up to 17 d. No toxic effect was seen in adenovirus-treated mice. Pretreatment of mice with Ad.CMVble or Ad.RSVble completely prevented collagen deposition 42-133 d after bleomycin treatment, as measured by lung OH-proline content. Histologic studies indicated that there was little or no lung injury in the adenovirus/bleomycin-treated mice compared with the bleomycin-treated mice. These observations may lead to new approaches for the prevention of bleomycin-induced pulmonary fibrosis.

Transgenic mice expressing the Sh ble bleomycin resistance gene are protected against bleomycin-induced pulmonary fibrosis.

Despite the high efficiency of bleomycin (BLM) as a chemotherapeutic agent against various carcinomas, the potentially lethal and chronic fibrotic response of the lung is a major dose-limiting side effect. Here, we explore the possibility of a direct inhibition of lung tissue injury by in vivo expression of the actinomycetes BLM resistance protein Sh ble. Transgenic mice expressing the Sh ble gene under the control of a composite viral promoter were produced after introduction of the transgene into D3 ES cells. The protein was detected at high level in lungs, spleen, and kidney. We then assessed its ability to modulate the BLM-induced fibrotic response in the transgenic mice in comparison with C57BL/6 and 129/Sv parental mice. Cumulative doses of 300, 400, or 500 mg/kg BLM were administered either by i.p. or s.c. repeated injections in the different strains. Transgenic mice were shown to be clearly less sensitive to BLM toxicity, as assessed by lung histology. The pulmonary hydroxyproline content in the treated transgenic mice was close to its baseline level, whereas it was up to 50% higher than the control level in C57BL/6 and 129/Sv parental mice. These observations are consistent with the hypothesis that a resistance gene specifically expressed in lungs may prevent the BLM-induced inflammation.

Cephalometric changes during treatment with the open bite bionator.

Lateral cephalometric radiographs of 39 patients who were treated with an open bite bionator, also known as a "bionator to close the bite," were obtained from six private orthodontic practices. Comparisons of pretreatment cephalometric values with published standards indicate that clinicians do not generally use this appliance for patients who have marked excessive anterior vertical dimension. Rather, the cases appear to be Class II with mild anterior open bites or with some indication of open bite tendency, such as a steep mandibular plane angle. Changes in cephalometric values during treatment with the appliance were compared with normal growth standards. Patients exhibited a reduction in facial convexity and overjet, reduced eruption of maxillary molars, and less of an increase in facial height than expected. The appliance appears to be effective for Class II correction in patients who require control or improvement of moderately excessive vertical dimension.