Perceived race-based discrimination, employment status, and job stress in a national sample of black women: implications for health outcomes

This study examined concordance between self-reported drug use and urinalysis data among 341 applicants for methadone treatment in Sydney, Australia. Rates of under-reporting of use of specific drugs were low (0% to 10%). Irregular drug use, short half-life of some abused drugs, and relatively low sensitivity of the TLC assay procedure led to most detected drugs being found in only one of two urine samples collected. Subjects reported having recently used nearly twice as many drugs as were detected in their urine. Agreement (kappa) between self-report and urinalysis results was in the fair to good range for most drugs. None of the six predictors of misreporting examined were found to be of practical value.     

Decrease and inequalities of infant mortality in Salvador, 1980-1988

This study sought to describe the changes in mortality among infants under one year of age in different areas of the city of Salvador, Bahia, during the period 1980-1988. This was done using estimates of variation in two indicators: proportional infant mortality and the coefficient of infant mortality. Values for the first indicator were separated into low, intermediate, high, and very high quartiles for 1980 and then calculated again using 1988 data. The second indicator was derived from the estimated number of live births using the rate of 33.4/1,000 inhabitants for 1980 and 31.4/1,000 for the years thereafter. The results showed that infant mortality in that age group had declined over the period, but that at the end of the period inequalities persisted in the distribution of infant deaths, which confirmed that conditions remained adverse for certain segments of the population.     

Polyamine analogue regulation of NMDA MK-801 binding: a structure-activity study

A series of analogues and homologues of spermine were synthesized, and their impact on MK-801 binding to the N-methyl-D-aspartate (NMDA) receptor was evaluated. These tetraamines encompass both linear and cyclic compounds. The linear molecules include norspermine, N1, N11-diethylnorspermine, N1,N12-bis(2,2,2-trifluoroethyl)spermine, homospermine, and N1,N14-diethylhomospermine. The cyclic tetraamines consist of the piperidine analogues N1,N3-bis(4-piperidinyl)-1,3-diaminopropane, N1,N4-bis(4-piperidinyl)-1,4-diaminobutane, N1,N4-bis(4-piperidinylmethyl)-1,4-diaminobutane, and N1,N4-bis[2-(4-piperidinyl)ethyl]-1,4-diaminobutane and the pyridine analogues N1,N3-bis(4-pyridyl)-1,3-diaminopropane, N1,N4-bis(4-pyridyl)-1,4-diaminobutane, N1,N4-bis(4-pyridylmethyl)-1,4-diaminobutane, and N1,N4-bis[2-(4-pyridyl)-ethyl]-1,4-diaminobutane. This structure-activity set makes it possible to establish the importance of charge, intercharge distance, and terminal nitrogen substitution on polyamine-regulated MK-801 binding in the NMDA channel. Four families of tetraamines are included in this set: norspermines, spermines, homospermines, and tetraazaoctadecanes. Calculations employing a SYBYL modeling program revealed that the distance between terminal nitrogens ranges between 12.62 and 19.61 A. The tetraamines are constructed such that within families cyclics and acyclics have similar lengths but different nitrogen pKa's and thus different protonation, or charge, states at physiological pH. The pKa values for all nitrogens of each molecule and its protonation state at physiological pH are described. The modifications at the terminal nitrogens include introduction of ethyl and beta,beta,beta-trifluoroethyl groups and incorporation into piperidinyl or pyridyl systems. The studies clearly indicate that polyamine length, charge, and terminal nitrogen substitution have a significant effect on how the tetraamine regulates MK-801 binding to the NMDA receptor. Thus a structure-activity basis set on which future design of MK-801 agonists and antagonists can be based is now available.     

Neutral endopeptidase inhibition increases the potency of ANP in isolated rat pulmonary resistance vessels and isolated blood perfused lungs

We have investigated the effects of the neutral endopeptidase inhibitor, SCH 42354, on the vasoreactivity of atrial natriuretic peptide (ANP) in rat isolated pulmonary resistance vessels (PRV) and isolated perfused lungs (IPL). PRV (n = 37) were mounted onto the jaws of a myograph and precontracted with PGF2alpha (100 mu M). Concentration-responses to ANP (0.17 to 340 nM) were determined before and after the addition of SCH 42354 (10, 30 and 100 nM). Each concentration of SCH 42354 caused a significant increase in potency (- log EC50) of ANP in isolated PRV. Lungs from normoxic rats (n = 13) were isolated and perfused with whole blood. An increase in pulmonary artery pressure was achieved by ventilating with an hypoxic gas mixture and concentration-responses obtained by incremental additions of ANP (40 nM to 12 mu M), before and after the addition of SCH 42354 (100 nM). SCH 42354 significantly increased the potency (- log EC50) of ANP in the rat IPL. ANP is partly metabolized by NEP. That an inhibitor of NEP increased the potency of ANP in isolated pulmonary vessels, and in isolated perfused whole lungs, suggested that SCH 42354 may be having a local action within the pulmonary vasculature.     

Phase II trial of paclitaxel and granulocyte colony-stimulating factor in patients with pancreatic carcinoma: a Southwest Oncology Group study

PURPOSE: Pancreatic cancer is difficult to treat, with most patients surgically unresectable at the time of diagnosis. Radiotherapy and chemotherapy can offer palliation, but more effective therapy is needed. This trial evaluated the effects of an aggressive schedule of paclitaxel given with granulocyte colony-stimulating factor (G-CSF) to patients with advanced pancreatic cancer. PATIENTS AND METHODS: All patients were required to have a histologic diagnosis of pancreatic adenocarcinoma with measurable disease and no prior chemotherapy or radiation therapy. Patients had to have performance status of 0 to 2, pretreatment absolute granulocyte count > or = 1,500/microL, and platelet count greater than or equal to the institutional lower limit of normal. Following pretreatment with dexamethasone, diphenhydramine, and cimetidine, patients received paclitaxel at a dose of 250 mg/m2 by 24-hour infusion on day 1, repeated every 21 days. G-CSF was given at a dose of 5 microg/kg/d on days 3 to 18 or until two consecutive absolute neutrophil counts (ANCs) > or = 10,000/microL were obtained. Doses of paclitaxel were modified depending on nadir counts. RESULTS: Forty-five patients were entered onto this study, with six ineligible. For the 39 eligible patients, there was one complete response (CR) and two partial responses (PRs), five stable/no responses, 23 increasing disease, two early deaths, and six patients whose assessment was inadequate to determine response. The response rate was therefore three of 39 or 8% (95% confidence interval [CI], 2% to 21%). The median survival time for the 39 eligible patients was 5 months. The most common toxicities were anemia, leukopenia/granulocytopenia, malaise/fatigue, nausea/vomiting, alopecia, thrombocytopenia, paresthesias, and liver function abnormalities. There was one death due to sepsis. CONCLUSION: Single-agent paclitaxel in this dose and schedule has minimal activity in pancreatic adenocarcinoma patients.     

The putative tumor suppressor gene on chromosome 5q for hepatocellular carcinoma is distinct from the MCC and APC genes

We have previously shown that the tumor suppressor gene for hepatocellular carcinoma (HCC) without cirrhosis may be located on chromosome 5q35-qter. In this study, we analyzed nine cases of primary HCC without cirrhosis using probes from the MCC and APC genes, which are in the region 5q21-22. None of the informative cases had allele loss detected by these probes, whereas the probe lambda MS8 for the region 5q35-qter showed allele loss in six out of six informative cases. The results confirm that the putative tumor suppressor gene for HCC without cirrhosis on chromosome 5q is distinct from the MCC and APC genes.