Phase I trial of doxorubicin-containing low temperature sensitive liposomes in spontaneous canine tumors.

PURPOSE: To determine the maximum tolerated dose, dose-limiting toxicities, and pharmacokinetic characteristics of doxorubicin encapsulated in a low temperature sensitive liposome (LTSL) when given concurrently with local hyperthermia to canine solid tumors. EXPERIMENTAL DESIGN: Privately owned dogs with solid tumors (carcinomas or sarcomas) were treated. The tumors did not involve bone and were located at sites amenable to local hyperthermia. LTSL-doxorubicin was given (0.7-1.0 mg/kg i.v.) over 30 minutes during local tumor hyperthermia in a standard phase I dose escalation study. Three treatments, given 3 weeks apart, were scheduled. Toxicity was monitored for an additional month. Pharmacokinetics were evaluated during the first treatment cycle. RESULTS: Twenty-one patients were enrolled: 18 with sarcomas and 3 with carcinomas. Grade 4 neutropenia and acute death secondary to liver failure, possibly drug related, were the dose-limiting toxicities. The maximum tolerated dose was 0.93 mg/kg. Other toxicities, with the possible exception of renal damage, were consistent with those observed following free doxorubicin administration. Of the 20 dogs that received > or = 2 doses of LTSL-doxorubicin, 12 had stable disease, and 6 had a partial response to treatment. Pharmacokinetic variables were more similar to those of free doxorubicin than the marketed liposomal product. Tumor drug concentrations at a dose of 1.0 mg/kg averaged 9.12 +/- 6.17 ng/mg tissue. CONCLUSION: LTSL-doxorubicin offers a novel approach to improving drug delivery to solid tumors. It was well tolerated and resulted in favorable response profiles in these patients. Additional evaluation in human patients is warranted.     

Inhaled iloprost controls pulmonary hypertension after cardiopulmonary bypass

PURPOSE: Severe pulmonary hypertension (PH) is a major cause of right ventricular (RV) dysfunction. Various iv vasodilator modalities have been used with limited results because of lack of pulmonary selectivity. The aim of the present controlled study was to evaluate the efficacy of inhaled iloprost, a synthetic prostacyclin analogue, in patients with elevated pulmonary vascular resistance (PVR) immediately after separation from cardiopulmonary bypass (CPB). METHODS: Twelve patients with persistent PH after discontinuation of CPB were included in the study. In all patients standard hemodynamic monitoring was used. Inhaled iloprost was administered via nebulized aerosol at a cumulative dose of 0.2 micro g*kg(-1) for a total duration of 20 min. Complete sets of hemodynamic measurements were performed before inhalation (baseline), during and after cessation of the inhalation period. Echocardiographic monitoring of RV function was also used. RESULTS: Inhaled iloprost induced a reduction in the transpulmonary gradient at the end of the inhalation period in comparison to baseline (9.33 +/- 3.83 mmHg vs 17.09 +/- 6.41 mmHg, P < 0.05). The mean pulmonary artery pressure to systemic artery pressure ratio decreased over this period (0.28 +/- 0.08 vs 0.45 +/- 0.17, P < 0.05). A statistically significant decrease of the PVR to systemic vascular resistance ratio was also observed (0.15 +/- 0.05 vs 0.21 +/- 0.05, P < 0.05). Improved indices of RV function were observed in echocardiographic monitoring. CONCLUSION: Inhaled iloprost appears to be a selective pulmonary vasodilator and may be effective in the initial treatment of PH and the improvement of RV performance in the perioperative setting.     

Comparative efficacy of Hanifin and Rajka''s criteria and the UK working party''s diagnostic criteria in diagnosis of atopic dermatitis in a hospital setting in North India

BACKGROUND: Diagnosis of atopic dermatitis (AD) depends on clinical features because no definitive diagnostic test exists. Criteria proposed by Hanifin and Rajka (Acta Derm Venereol (Stockh) 1980; Suppl 92: 44-47) were acceptable for hospital-based studies but were found not to be suitable for field studies. A UK working party formulated clinical diagnostic criteria that could be used in both hospital and epidemiological settings. Validation studies of the criteria showed widely variable results, probably due to different clinical settings and ethnicity. AIM AND OBJECTIVE: This study was undertaken to validate Hanifin and Rajka's criteria and to assess the comparative efficacy of their criteria and the UK working party's diagnostic criteria in the diagnosis of AD in a hospital setting in North India. SUBJECTS AND METHODS: This study serially included 101 patients with AD and 48 controls of paediatric age group. The study period was from July 2003 to December 2004. RESULTS: Hanifin and Rajka's criteria (sensitivity 96%, specificity 93.75%, positive predictive value 97% (PPV) and negative predictive value (NPV) 91.84%) had a statistical advantage over the UK working party's diagnostic criteria (sensitivity 86%, specificity 95.83%, PPV 97.75% and NPV 76.67%), with a P-value < 0.005.     

Multifocal ERG with the scanning laser ophthalmoscope: query on the ideal configuration for attaining high resolution and result stability

Graefe's Archive for Clinical and Experimental Ophthalmology -     

IMPOTENCE AND ITS NON-SURGICAL MANAGEMENT

SUMMARY Impotence is a common symptom which can cause considerable distress to both the sufferer and his partner. The use of pharmacotherapy to improve erectile function will continue to increase as safe and effective drugs are developed. However, restoring erectile function should not be the only treatment objective. It is also essential to address personal and emotional factors in the sufferer, conflicts in his relationship with his partner, and sexual problems in his partner, all of which may be instrumental in causing or maintaining the presenting impotence. We advocate a combined approach with appropriate medical treatment and sex and couple therapy     

Pharmacokinetics and pharmacodynamics of anticancer agents: contributions to the therapy of childhood cancer

Strategies for treating pediatric malignancies have not only been successful (i.e., curative) for several disseminated childhood cancers, they have also served as paradigms for the therapy of many adult cancers. Initial strategies included combined treatment modalities (chemotherapy, surgery, radiotherapy) and combinations of different pharmacologic classes of anticancer drugs given in the appropriate schedules. Despite the currently successful therapy for some malignancies (e.g., 70% 4-year disease-free survival in acute lymphocytic leukemia), many children die without known reason. Recent advances in the clinical pharmacology of anticancer drugs have identified relationships between dose intensity and response (efficacy, toxicity). Traditional methods of measuring dose intensity (prescribed dose) have evolved to more sophisticated approaches in maximizing the intensity of treatment, with good response rates. Other methods of optimizing chemotherapy for individual patients include bone marrow support procedures and therapy with biologic response modifiers. Relatively few clinically useful new anticancer drugs have been discovered in the past several years. Fortunately, the potential to improve therapy with currently available agents has come about through enhanced knowledge of the biochemical and clinical pharmacology of anticancer drugs and biologic response modifiers, as well as improved understanding drug resistance biology.