Local hyperthermia and SR 4233 enhance the antitumor effects of radioimmunotherapy in nude mice with human colonic adenocarcinoma xenografts

Local hyperthermia and the hypoxic cytotoxin SR 4233 were administered to nude mice with 693 +/- 47 mm3 (mean +/- SE) s.c. HCT-8 human colonic adenocarcinoma xenografts in an attempt to enhance the antitumor effects of radioimmunotherapy. Biodistribution studies revealed preferential binding of NR-Lu-10, a murine monoclonal antibody, to the tumors compared with an isotype-matched control antibody, CCOO16-3.A single injection of 25 microCi 90Y-NR-Lu-10 significantly inhibited tumor growth (control versus 90Y-NR-Lu-10: P = 0.048). The administration of hyperthermia at 41.5 degrees C for 1 h immediately following the injection of 111In-labeled NR-Lu-10 up-regulated tumor-associated antigen expression and increased antibody uptake in the tumors by 73% (P = 0.001) without significantly affecting antibody uptake in normal tissues. However, the heat treatment did not produce a more homogeneous distribution of the antibodies in the tumors and did not significantly enhance the tumor growth delay produced by 90Y-NR-Lu-10 (P = 0.07). The administration of local hyperthermia at 43.0 degrees C for 1 h, on the other hand, had direct cytotoxic effects (P = 0.03) and enhanced the tumor growth delay produced by 90Y-NR-Lu-10 (P = 0.01). SR 4233 also enhanced the tumor growth delay produced by 90Y-NR-Lu-10 (P = 0.03). The greatest antitumor effects were observed when both hyperthermia at 43.0 degrees C and SR 4233 were administered in combination with 90Y-NR-Lu-10 (P = 0.002). No toxicity was produced by the local hyperthermia, and the only toxicities produced by 90Y-NR-Lu-10 and SR 4233 were neutropenia and weight loss.     

Non-medical drug use amongst non-student youth in India

In a survey of non-medical drug use by 266 non-students in the age range 10-24 years, tobacco, alcohol and cannabis were found to be the drugs more commonly used. Use was greater in males, older age groups, those with lower educational levels and those from urban areas. In comparison to students, among non-students use was practically limited to tobacco, alcohol and cannabis, the use was more regular and the age at onset lower. In a pilot trial of two additional strategies to identify drug users among non-student youth, namely cross-validation by fellow employees and verbal group administration of the questionnaire, the number of current users identified was very similar to that found by individual verbal administration, suggesting that these cheaper methods may be useful in some circumstances.     

The use of trypsin and lysozyme immobilized on a cellulose carrier in treating otitis externa

In December 1991, an outbreak of Streptococcus bovis septicaemia occurred in a Belgian pigeon loft where 25 male and 25 female racing pigeons were housed. The main clinical signs included inability to fly and poor breeding results. None of the female pigeons and only one male pigeon was able to fly. Nine affected pigeons were necropsied. Histologically a tenosynovitis of the tendon of the deep pectoral muscle was observed in most of them and S bovis was isolated from the canalis triosseus or the shoulder joints of five of the nine pigeons. The pigeons were successfully treated with ampicillin administered in the drinking water for seven days.     

Optical amplification of ligand-receptor binding using liquid crystals

Liquid crystals (LCs) were used to amplify and transduce receptor-mediated binding of proteins at surfaces into optical outputs. Spontaneously organized surfaces were designed so that protein molecules, upon binding to ligands hosted on these surfaces, triggered changes in the orientations of 1- to 20-micrometer-thick films of supported LCs, thus corresponding to a reorientation of approximately 10(5) to 10(6) mesogens per protein. Binding-induced changes in the intensity of light transmitted through the LC were easily seen with the naked eye and could be further amplified by using surfaces designed so that protein-ligand recognition causes twisted nematic LCs to untwist. This approach to the detection of ligand-receptor binding does not require labeling of the analyte, does not require the use of electroanalytical apparatus, provides a spatial resolution of micrometers, and is sufficiently simple that it may find use in biochemical assays and imaging of spatially resolved chemical libraries.     

Surgical treatment of lymphadenopathy in children

Clinical observations of 1365 children with the lymph nodes affection were summarized. The diagnosis verification was conducted using the broad arsenal of general clinical and special methods of investigation. In complicated situations the histochemical and immunogenetic methods were applied for the diagnosis. The structure and dynamics of children's morbidity with lymphadenopathies (LAP) was studied up, the age, sexual and seasonal peculiarities were systematized, the analysis of primary localizations and clinico-morphological comparisons was conducted. The basic thesises of the standardized approach were elaborated on the ground of the diagnostical and tactical mistakes results analysis.     

Prevention of subclinical vitamin K deficiency based on PIVKA-II levels: oral versus intramuscular route

A 20-year-old man was admitted to our hospital with the complaint of hemoptysis. A bruit was best heard at the lower portion of the left posterior chest. CT scan and MRI revealed clearly the existence of a large aberrant vessel from the descending thoracic aorta. Aorto- and pulmonary arteriography demonstrated that a large systemic artery from the descending thoracic aorta supplied the basilar segments of the left lower lobe, and to which there was no pulmonary artery supply. The pulmonary veins from these segments drained into the left atrium. The properative diagnosis was Pryce's type I pulmonary sequestration. A left lower lobectomy was performed. The aberrant vessel was 15 mm in diameter and was elastic walled. The systemic artery of the basilar segments revealed proliferation of media and obstructive changes. Some discussions were made about hemoptysis and bruit in 23 cases of Pryce's type I pulmonary sequestration in Japan.     

Response of Brazilian crossbred cows to varying doses of bovine somatotropin

The effect of n-methionyl bovine somatotropin (bST) on milk yield was evaluated in crossbred cows (40 1/2 Bos indicus x 1/2 Bos taurus and 18 1/4 B. indicus x 3/4 B. taurus) in Brazil. Cows were randomly assigned to treatments within stage of lactation [stage 1 = 56 to 100 d in milk (DIM); stage 2 = 101 to 199 DIM] and breed groups (1/2 vs. 1/4 B. indicus blood). Treatments were 250 or 500 mg of bST administered every 14 d. Cows in the control group did not receive bST or a placebo. Treated cows received bST injected subcutaneously in the postscapular region, alternating between the left and right sides. The 26-wk experiment consisted of 2 wk of pretreatment and 24 wk of treatment. Cows were housed in an open lot with regulated access to pasture. Cows were milked twice daily and scored for body condition at 2-wk intervals. Compared with controls, milk yield increased equally (22%) for cows receiving 250 or 500 mg of bST. Milk yield response to bST was higher and persisted longer during stage 1 of lactation than during stage 2 of lactation. No difference in response to bST was noted between cows with 1/2 or 1/4 B. indicus blood. Cows treated with 500 mg of bST tended to have more mastitis, but no other adverse health effects were observed. The potential use of 250-mg doses of bST at 14-d intervals in crossbred cattle in Brazil and other subtropical regions throughout the world is suggested, particularly before about 220 DIM.     

Phase I study of a five-day dose schedule of 4-Ipomeanol in patients with non-small cell lung cancer

The mammalian pulmonary toxin 4-ipomeanol (IPO) is activated by the cytochrome P450 system in bronchial Clara cells in animals. The resulting metabolites bind rapidly to macromolecules, producing localized cytotoxicity. IPO has in vitro and in vivo antitumor activity in non-small cell lung cancer (NSCLC) and thus was proposed as a lung cancer-specific antitumor agent. We have completed a directed Phase I trial in patients with NSCLC. Forty-four patients (34 men and 10 women) with NSCLC were treated with IPO. All but two patients had an Eastern Cooperative Oncology Group performance status of 0 or 1. They received 91 courses of therapy with i.v. IPO; 82 courses were administered daily for five days, and 9 were single bolus doses. The dose-limiting toxicity of elevated serum transaminases was observed in three of seven patients at 922 mg/m2/day. The maximum tolerated dose was 693 mg/m2/day on 5 consecutive days every 3 weeks. One patient developed grade 4 pulmonary toxicity at 167 mg/m2/day. There was no significant hematological or renal toxicity. No objective antitumor responses were observed. Pharmacokinetic analysis of 39 patients from day 1 of IPO administration showed biexponential elimination with mean half-lives of 8.6 (alpha half-life) and 76 min (beta half-life). There was a linear relationship between the area under the plasma drug concentration-time curve and the dose of IPO. There was no significant difference between the pharmacokinetic parameters measured on day 1 and day 5. Using a 4-day in vitro cytotoxicity assay, two tumor cell lines established from patients treated at 693 mg/m2/day had IC50s of approximately 6 mM, a concentration more than 75-fold higher than the plasma levels measured in these patients. Thus, although the total amount of drug administered per cycle on a daily times five dose schedule is more than 2.5-fold higher than the recommended single daily dose, IPO is unlikely to be a useful drug for patients with lung cancer.