Human lung cancer antigens recognized by autologous antibodies: definition of a novel cDNA derived from the tumor suppressor gene locus on chromosome 3p21.3

Supplementation with high doses of alpha-tocopherol has increased the oxidation resistance of LDL in many clinical trials. There have been only a few placebo-controlled trials in healthy persons of alpha-tocopherol doses usually contained in dietary supplements. We carried out a single-blind, placebo-controlled, randomized trial to examine the effect of 200 mg RRR-alpha-tocopheryl acetate/d on the oxidation resistance of atherogenic lipoproteins (VLDL+LDL including intermediate-density lipoproteins) in 40 smoking men. VLDL+LDL oxidation resistance was assessed as conjugated dienes after copper induction and hemin degradation after hydrogen peroxide induction. Also, the LDL total peroxyl-radical trapping antioxidant parameter (LDL TRAP) and plasma malondialdehyde were measured at baseline and after 2 mo of supplementation. Plasma RRR-alpha-tocopherol concentrations were measured at 2-h intervals for 12 h at baseline and after 2 mo of supplementation. Compared with placebo, 200-mg RRR-alpha-tocopheryl acetate supplementation elevated plasma and VLDL+LDL alpha-tocopherol concentrations, LDL TRAP, and oxidation resistance of VLDL+LDL. Plasma alpha-tocopherol increased by 88% (P < 0.0001), VLDL+LDL alpha-tocopherol increased by 90% (P < 0.0001), and LDL TRAP by 58% (P < 0.0001). The time to the start of oxidation (lag time) was prolonged by 34% when assessed with a copper-induced method and by 109% when assessed with a hemin + hydrogen peroxide-induced method; the time to maximal oxidation was prolonged by 21% (copper-induced method) in the vitamin E-supplemented group. Changes in plasma alpha-tocopherol, lipid-standardized alpha-tocopherol, and VLDL+LDL alpha-tocopherol correlated significantly with changes in LDL TRAP, lag time, and time to maximal oxidation. Differences in changes between groups in the area under the curve for plasma alpha-tocopherol were significant (P < 0.009). Our results suggest that 200 mg oral RRR-alpha-tocopheryl acetate/d had a clear effect on the in vitro oxidation of VLDL+LDL in smoking men.     

VRCTC-310--a novel compound of purified animal toxins separates antitumor efficacy from neurotoxicity

Two purified animal venom toxins, crotoxin and cardiotoxin, have been combined to produce a unique natural product (VRCTC-310) currently under investigation as an antitumor agent by the National Cancer Institute. In vitro, it has demonstrated cytotoxic disease specificity and a unique mechanism of action when submitted to COMPARE analysis. In vivo, tolerance was developed to the neurotoxic properties of crotoxin which allowed comparison of several schedules of fixed and escalating daily i.m. doses to mice bearing s.c. Lewis Lung carcinoma. An 83% inhibition of tumor growth was achieved using an escalating dose schedule starting at 1.8 mg/kg and reaching 6.3 mg/kg/day on day 20. Although some irritation around the sites of i.m. injection was noted, animal weight loss was negligible and there were no other signs of adverse toxicity. This natural product represents a new, membrane interactive anticancer agent which produces a unique spectrum of cytotoxicity in vitro and which has demonstrated interesting in vivo antitumor efficacy.     

Real-time X-ray diffraction study at different scan rates of phase transitions for dipalmitoylphosphatidylcholine in KSCN

A questionnaire survey was carried out to examine the attitudes and practices of Australian and New Zealand intensivists with regard to brain death and organ donation. A return rate of 82.5% was achieved. Fifty-eight per cent had written evidence of their own wishes to donate organs and 94% would agree to donation from a dependent. At least one intensivist is involved in certifying brain death on 95% of occasions. Intensivists are involved in the request for organ donation over 90% of the time although one-third do not believe that it is their role to request organ donation. Although two-thirds believe that the family should always be approached for organ donation, another 52 out of 254 indicated that it was their (the intensivist's) role to decide if families should be asked for organ donation. Possible reasons for not requesting are language or other communication problems, perceptions of cultural differences and degrees of family distress. Twenty per cent of respondents do not provide haemodynamic support before brain death confirmation. Australian and New Zealand intensivists overwhelmingly support the concept of brain death, current methods of confirmation of brain death, organ donation and transplantation. Possible reasons behind loss of potential donors include decisions not to resuscitate both before and after brain death is confirmed. Perceptions of family grief and cultural differences clearly inhibit requests for organ donation. A very few units have an effective policy on approaching families about organ donation. Intensivists have almost exclusive control over requests for organ donation and thus bear a full professional responsibility for this element of hospital practice.     

Respiratory infections in patients with HIV

Pneumocystis carinii pneumonia has long been considered the predominant pulmonary disease in patients with HIV, but several factors are changing this perception. The population infected with HIV is increasingly composed of injection drug users, and racial and ethnic minorities, which represent groups that have a high incidence of bacterial pneumonia and tuberculosis. The increased longevity attributed to antiretroviral therapy and P. carinii pneumonia prophylaxis is accompanied by more profound immunosuppression, rendering patients susceptible to Pseudomonas, Aspergillus, and other opportunistic pneumonias. Trimetrexate and atovaquone are now available for the treatment of P. carinii pneumonia. Both are less effective than standard regimens of trimethoprim-sulfamethoxazole, but have fewer adverse effects. The diagnosis of respiratory infections complicating HIV usually depends on isolation of the pathogen. The routine use of transbronchial biopsy during bronchoscopy is controversial because the prevalence of P. carinii pneumonia is high in most centers caring for patients with AIDS, and bronchoalveolar lavage is usually diagnostic in this disease. However, biopsy enhances the yield of bronchoscopy, especially in the diagnosis of noninfectious pulmonary disorders and infections other than P. carinii pneumonia.     

Prevalence of gastrointestinal symptoms in obese and normal weight binge eaters

OBJECTIVES: Disturbances in gastrointestinal function may result from disordered eating and may lead to increases in gastrointestinal (GI) symptoms. We compared GI symptoms in obese and non-obese binge eaters and non-binge eaters. METHODS: One hundred nineteen obese and 77 normal-weight females completed a questionnaire on bowel symptoms and binge eating behaviors for the previous 3 months. Based on binge behaviors and body mass index (> 30 kg/m2), individuals were grouped as obese binge eaters (n = 73), obese non-binge eaters (n = 43), non-obese binge eaters (n = 14), and normal-weight controls (n = 61). RESULTS: Obese binge eaters reported more upper GI symptoms than normal controls or obese non-binge eaters (p < 0.001). Compared with normal controls, nausea, vomiting, and bloating was 2-4 times more prevalent in both binge eating groups. Indigestion was more prevalent in both obese groups. Obese binge eaters reported more lower GI symptoms than normal-weight controls (p < 0.05). Binge eating in both weight groups was associated with more frequent abdominal pain and dyschezia. Obesity was associated with more frequent constipation, diarrhea, straining, and flatus, whether or not subjects reported binge eating. Chi-square showed a significant association between obesity, binge eating, and symptoms of irritable bowel syndrome, using the Manning criteria. CONCLUSIONS: Specific GI symptoms were associated with binge eating and obesity. Overall, symptoms were more prevalent and more severe in obese binge eaters. The high prevalence of GI symptoms in obese patients who indulge in binge eating should be considered in their evaluation and treatment.     

Nitrone spin-traps block calcium channels and induce pulmonary artery relaxation independent of free radicals

Free radicals react with nitrones to form stable nitroxides which can be identified by ESR spectroscopy. Unfortunately, little is known regarding the pharmacological properties of these compounds. In this study, three commonly used nitrones, 5,5-dimethylpyrroline-N-oxide (DMPO), alpha-phenyl-tert-butylnitrone (PBN), and alpha-(4-pyridyl 1-oxide)-N-tert-butylnitrone (POBN), were found to induce relaxation of preconstricted isolated rat pulmonary artery rings. Additional experiments with PBN indicated that vasorelaxation could not be attributed to production of endothelial derived factors, prostaglandins, or free radicals. Patch-clamp techniques revealed reversible calcium channel blockade with PBN at a concentration below that needed to detect free radicals. Calcium channel blockade probably accounts for the vasorelaxation observed in the isolated ring preparations described here, and should be considered when using nitrone spin-traps both in in vivo and clinical studies.     

Diagnostic neuroimaging: computed tomography and magnetic resonance imaging

BACKGROUND: Computed tomography (CT) and magnetic resonance imaging (MR) are commonly used neuroimaging modalities for patients with signs or symptoms of neuro-ophthalmic disorders. Understanding the technology and clinical uses of these modalities is vital in patient management. METHODS/RESULTS: Basic instrument design and technology are presented together with a discussion of indications and contraindications to the use of these imaging techniques. Case reports are presented to illustrate the usefulness in diagnosis of orbital and neuro-ophthalmic disease. CONCLUSIONS: A basic knowledge of CT and MR helps the optometrist correlate imaging with clinical signs and symptoms of disease. This understanding also results in more effective communication with other health care providers and patients.