A cohort study of stomach cancer in a high-risk American population

Demographic, smoking and dietary information was obtained from a cohort of 17,633 white American men, largely of Scandinavian and German descent, who responded to a mailed questionnaire in 1966. After 20 years of follow-up, 50% to 90% increases in mortality from stomach cancer (75 deaths) were found among foreign-born, their children, and among residents of the North Central states. An association was seen with low educational attainment and laboring or semiskilled occupations, primarily among immigrants and their children. Risk was evaluated in subjects who regularly smoked cigarettes (RR = 2.6, 95% CI = 1.1 to 5.8). A significant dose-response trend was observed, with subjects who smoked 30 or more cigarettes per day having more than a five-fold increased risk compared with those who never smoked. Elevated risks were also found for pipe smoking and smokeless tobacco use, but not for alcohol consumption. Analysis of dietary consumption of nine food groups revealed no significant associations with stomach cancer. However, total carbohydrate intake and a few individual food items (salted fish, bacon, cooked cereal, milk, and apples) were associated with increased risk. The findings of this prospective study of a high-risk population add to the limited evidence relating tobacco consumption to stomach cancer risk and suggest clues to ethnic, geographic, and dietary risk factors.     

Detection of Norwalk-like virus and specific antibody by immune-electron microscopy with colloidal gold immune complexes.

Direct electron-microscopy (DEM), immune electron microscopy (IEM) and four different procedures of immune electron microscopy with colloidal gold immune complexes were evaluated for the detection of Norwalk-like virus and specific antibody. A solid-phase immune electron microscopy with colloidal gold immune complexes-triple layer method (SPIEMGIC-TLM) is developed for screening patients' specimens for the detection of Norwalk-like virus and its specific antibody. The method demonstrates low non-specific background labelling and is simple, sensitive and easy to perform. A quadruple layer method (SPIEMGIC-QLM), which is a modification of the triple layer method, has been established by adding a cross-linking anti-IgG layer to amplify the reaction and to provide a more sensitive test which is suitable for screening monoclonal antibodies prepared against 32-34-nm Norwalk-like virus isolated in our laboratory.     

Experience with zona drilling and zona cutting to improve fertilization rates of human oocytes in vitro

Zona drilling (ZD) and zona cutting (ZC) were used in an IVF programme to assist fertilization in semen defect patients. Twenty-seven patients consented to ZD where acidified Tyrode's was used to create a hole in the zona pellucida. In 19 patients, ZD increased the fertilization rate to 29% compared with 8% (P less than 0.001) in their routine IVF cycles, and in eight patients precluded from routine IVF, a fertilization rate of 14% was achieved. Twenty-two patients consented to ZC where a slit in the zona is made mechanically. In 12 patients ZC increased the fertilization rate to 31% compared with 14% (P less than 0.01) from previous routine IVF cycles, and in 10 patients precluded from routine IVF, a fertilization rate of 34% was achieved. In 13 cycles, 68 uncut control oocytes were inseminated. In five cycles both control and ZC oocytes were fertilized (n.s.d.). In eight cycles no control oocytes were fertilized compared with 27% of ZC oocytes. The polyspermy rate was 4.6%. Twenty-four per cent of ZD and 12% of ZC (P less than 0.01) oocytes and embryos were degenerate after 42 h. Both ZD and ZC can increase the fertilization rate of sub-optimal semen, however, in our hands neither technique produced a pregnancy.     

Comparison of cold air, ultrasonic mist, and methacholine inhalations as tests of bronchial reactivity in normal and asthmatic children

The sensitivity and specificity of cold air, ultrasonically nebulized distilled water mist (USM), and standard methacholine (MCH) challenges were studied in 21 children with asthma (mean age 11.5 years) and 12 normal children (mean age 14.2 years). The cold air challenge consisted of successive 3-minute periods of hyperventilation during which incremental volumes of subfreezing air (mean temperature -16 degrees C) were inhaled. To perform the USM challenge, subjects inhaled increasingly larger volumes of nebulized distilled water while breathing tidally. The specificity of both nonpharmacologic challenges was found to be 100%, whereas that of MCH was only 83%. The sensitivity of the cold air and USM tests was 57% and 71%, respectively, compared with 95% obtained with MCH challenge. We conclude that cold air and USM challenges are promising alternatives to the MCH challenge, and may be superior to it if optimal standard testing protocols are defined.     

Ferromagnetic contrast agents: a new approach

Most contrast agents used in NMR imaging studies to date have been paramagnetic. However, it is also possible to obtain selective contrast with a ferromagnetic agent, and these agents are potentially more sensitive than paramagnetic compounds because of their large magnetic moments. The water relaxation ability of ferromagnetic, albumin-coated magnetite (Fe3O4) particles has been investigated. These particles are quite effective at reducing both T1 and T2 at relatively low particle concentrations. The potential applications of these particles include improved visualization of the liver, gastrointestinal tract, and genitourinary tract, as well as specific targeting and detection of small tumors or other cells with unique surface receptors.     

A cost-utility analysis of the home parenteral nutrition program at Toronto General Hospital: 1970-1982

We performed an economic evaluation of a home parenteral nutrition (HPN) program by measuring the incremental costs and health outcomes for a cohort of 73 patients treated at our institution from November 1970 to July 1982. Over a 12-year time frame, we estimate that HPN resulted in a net savings in health care cost of $19,232 per patient and an increase in survival, adjusted for quality of life, of 3.3 years, compared with the alternative of treating these patients in hospital with intermittent nutritional support when needed. This result was sensitive to assumptions made about the cost of the alternative treatment strategy. When these assumptions were most unfavorable to the HPN program, we estimated that HPN resulted in incremental costs of $48,180 over 12 years, $14,600 per quality-adjusted life-year gained. We conclude that the cost-utility of HPN compares favorably with other health care programs, when HPN is used to treat patients with gut failure secondary to conditions such as Crohn's disease or acute volvulus. Since only one patient with active malignancy was enrolled in our HPN program, these results should not be extrapolated to patients with active malignancy.     

Clinical, biologic, and histologic features of late relapses in diffuse large cell lymphoma.

After completing chemotherapy and achieving a complete remission (CR), patients with diffuse intermediate-grade lymphoma and immunoblastic lymphoma are usually considered cured if they are able to maintain that remission continuously for 24 months. Recently, we observed a number of patients with these disorders who relapsed after a continuous CR of greater than or equal to 30 months from the beginning of therapy or 24 months from completing chemotherapy. This finding led us to examine 503 consecutive cases to determine the risk of late relapse and their clinical and biologic features. We found that the overall risk of late relapse of those who attained CR was 6.8%, but several features at presentation were associated with a high risk: (1) the presence of a divergent histology; (2) a sclerosing large cell lymphoma; (3) a diagnosis based on an extranodal site with no nodal tissue available for examination. When none of these features were present, the risk of late relapse was minimal (only 3%). When any of these features was present, the risk was 14%. Most striking was the 43% late relapse rate of patients with divergent histology. All but one of the eight B-cell tumors studied at relapse showed kappa light chain restriction. Five of these eight has a low S phase at the time of relapse, suggesting chemotherapeutic selection of a clone of cells with a low proliferative potential that could have given rise to the late relapse. Nucleic acid flow cytometry and immunophenotypic studies on three tumors at initial diagnosis and after relapse failed to support the hypothesis of a second de novo lymphoma and were consistent with a true recurrence of the original tumor. The results of salvage chemotherapy in this group of late relapses showed a high CR rate (57%) but no evidence of a trend for cure in the time to treatment failure curve. In contrast to the experience with Hodgkin's disease, retreatment with the same or a similar regimen used for the original induction was not associated with durable response. Clinicians should be aware of the potential for a late relapse in cases with divergent histology and the need for new treatment strategies for such cases.     

Bullatalicinone,a new potent bioactive acetogenin,and squamocin from annona bullata (Annonaceae)

Further fractionation of the EtOH extract of the bark of Annona bullata Rich. (Annonaceae) has led to the isolation of a new nonadjacent bis-tetrahydrofuran acetogenin, bullatalicinone, and the known adjacent bis-tetrahydrofuran acetogenin, squamocin. These two compounds showed potent and selective cytotoxicities for certain human tumor cell lines. Their structures have been elucidated by chemical and spectral methods. Bullatalicinone is the methylketo-lactone derivative of bullatalicin which we found previously in this plant.     

Biologically active gamma-lactones and methylketoalkenes from Lindera benzoin.

Brine shrimp lethality-directed fractionation of the 95% EtOH extract of ripe berries from Lindera benzoin led to the isolation of three new C21 alkane-alkene gamma-lactones designated isolinderanolide, isolinderenolide, and linderanolide as well as the known series of C17 and C19 obtusilactones (isoobtusilactone A, obtusilactone A, isoobtusilactone, and obtusilactone) previously isolated from Lindera obtusiloba. The novel (6Z,9Z,12Z)-pentadecatrien-2-one, the known (6Z,9Z)-pentadecadien-2-one, and the known (+)-(Z)-nerolidol were also isolated as bioactive compounds. The structural elucidation and biological activities of these compounds are reported.