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.     

Natural history of the benign breast lump

A prospective study of 112 patients with clinically discrete benign breast lumps has shown that 68 per cent of patients experienced resolution of their lumps over a period of up to 2 years. Resolution of both fibro-adenomas and discrete areas of fibro-adenosis was observed. Diagnosis was achieved by clinical examination and fine needle aspiration cytology. Four patients thought clinically to have benign disease were proven by cytology to have a carcinoma, but no patient with a cytopathological diagnosis of benign disease has developed cancer during or subsequent to this study. We recommend that patients under 35 years of age with clinically and cytologically benign breast lumps can be offered the option of non-excision in the reasonable expectation of resolution of their lesion.     

Ärztliche Fehleroffenbarung – Strafrechtliche Strategien für postinvasive Arzt-Patientengespräche

Ohne Zusammenfassung     

Chlorinated hydrocarbon levels in human serum: Effects of fasting and feeding

Twenty healthy adult humans had serum samples drawn on four occasions within a 24-hr period: after a 12 hr overnight fast, 4–5 hr after a high fat breakfast, at midafternoon, and the next morning after another 12 hr fast. Nonfasting samples had 22% to 29% higher mean concentrations (p < 0.05) than did fasting samples for polychlorinated biphenyls (PCBs, 4.81 vs 3.74 ng/g serum wt), hexachlorobenzene (HCB, 0.163 vs 0.134 ng/g serum wt), andp,p-dichlorodiphenyldichloroethylene (p,p-DDE, 6.74 vs 5.37 ng/g serum wt) measured by electron capture gas liquid chromatography. Total serum lipids were estimated from measurements of total cholesterol, free cholesterol, triglycerides, and phospholipids and were 20% higher in nonfasting samples than in fasting samples (7.05 g/L vs 5.86 g/L). When PCBs, HCB, andp,p-DDE concentrations were corrected by total serum lipids, results from fasting and nonfasting samples were not statistically different. Because of the differences in these chlorinated hydrocarbon concentrations observed with different sample collection regimens, meaningful comparison of analytical results requires standardizing collection procedures or correcting by total serum lipid levels.     

Antibody levels in mothers colonised with group B streptococci during pregnancy and in their newborn infants,as measured by an enzyme linked immunosorbent assay

An enzyme-linked immunosorbent assay (ELISA) was developed to measure serum antibodies to group B streptococci in 20 healthy pregnant women before delivery and in their newborn infants. The sera from 10 of these women who were colonised with group B streptococci and umbilical cord sera from their infants, had higher levels of type-specific lgG antibody than the 10 non-colonised controls and their neonates. All the babies remained well. The results demonstrate that infants from colonised mothers receive type-specific antibody. The possibility that this antibody may provide some degree of protection at birth against this potentially lethal organism warrants investigation.