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Biomedical subjects

R Herbert

Publications and source records attributed to R Herbert.

At least 19 recordsLinked to original sources
PubMed1992

Novel 5-HT3 antagonists: indol-3-ylspiro(azabicycloalkane-3,5'(4'H)-oxazoles).

The synthesis and biochemical evaluation of a series of spirofused indole oxazoline 5-HT3 antagonists is described in which the oxazoline ring acts as a bioisosteric replacement for esters and amides. The effect of substitution about the indole ring has shown the steric limitations of the aromatic binding site. Incorporation of a variety of azabicyclic systems within the rigid spirofused framework has allowed the definition of a binding model which incorporates a number of known antagonists and agonists. In this model steric constraints limit substitution around the indole ring although there is some bulk tolerance at the 1- and 2-positions. The importance of constraining the basic nitrogen within an azabicyclic system is underlined by comparison with the monocyclic piperidine. The highest affinity was observed for those compounds in which the basic nitrogen occupies a bridgehead position, the most potent analogue in this group being the azabicyclic [3.3.1] system (pIC50 = 8.95), suggesting lipophilic interactions may play a role in increasing affinity. A suggested model for agonist binding is included in which the basic nitrogens are superimposed and the 5-hydroxyl group of 5-HT is superimposed on the H-bond-accepting atom of the heterocyclic linking group.

Animals↗
PubMed1992

Results of colectomy in elderly patients with colon cancer, based on Medicare claims data.

Currently available estimates of outcomes following colon resection in elderly patients with colon cancer are based on series collected at academic medical centers. We used Medicare Part A claims and enrollment records of a 5% nationally random sample of elderly Medicare beneficiaries from 1983 to 1985 to estimate how patient age and sex affected perioperative mortality and 1- and 2-year survival rates among elderly patients undergoing a colon resection procedure for colon cancer. Among the 5,586 individuals in our data set, the overall perioperative mortality rate was 5.0%, ranging from 3.3% in beneficiaries 66 to 69 years of age to 9.3% in those 85 years of age and older. Men had a 31% higher perioperative mortality rate than women (5.8% versus 4.4%, p less than 0.05). The overall postoperative survival rates at 1 and 2 years were 72% and 63%, respectively, decreasing with increasing age, but were similar in men and women. This analysis provides age- and sex-specific estimates of outcomes following surgery for elderly patients with colon cancer that are more precise and have more potential for generalization than those that were available previously.

Age Factors↗
PubMed1991

Accuracy of Medicare claims data for estimation of cancer incidence and resection rates among elderly Americans.

To explore the reliability of Medicare Part A claims data for clinical and health services research related to the care of patients with cancer, the authors compared estimates of the incidence of and resection rates for cancer of the breast, colon, and lung derived from analysis of Medicare Part A data versus data from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) Program. Incidence rates of breast, colon, and lung cancer estimated from Medicare Part A data were within 6% of estimates derived from SEER data. Resection rates estimated from Medicare Part A data, in contrast, were 12% to 27% lower than resection rates based on SEER data. This discrepancy is not explained by variations in practice between regions participating in versus those not participating in the SEER registries but may be due to undercoding of surgical procedures in Medicare Part A data. This analysis suggests that Medicare data can provide useful insights into the care of patients with cancer, but research regarding inpatient procedures employed in management of cancer should be based on analysis of Medicare Parts A and B data combined.

Abstracting and Indexing↗
PubMed1991

Use of Medicare claims data to evaluate outcomes in elderly patients undergoing lung resection for lung cancer.

OBJECTIVE: To estimate, using Medicare claims data, the outcomes in elderly Americans undergoing lung resection for lung cancer. DESIGN: We used discharge diagnosis and procedure codes in 1983 to 1985 Medicare hospital (part A) claims records to identify patients who underwent lung resection for lung cancer; we assessed perioperative, one-year, and two-year survival using Medicare enrollment file data. PATIENTS: From a nationally random sample of 1,138,000 Medicare beneficiaries over 65 years of age, we identified 1,290 individuals who fulfilled our definition for lung resection for lung cancer. MEASUREMENTS AND MAIN RESULTS: Overall perioperative (30-day) mortality was 7.4 percent. Postoperative survival at one and two years was 69 percent and 54 percent, respectively. Male sex, older age, and pneumonectomy, as opposed to a lesser procedure, were associated with reduced perioperative and one-year and two-year survival. The adverse effect of advanced age on one-year and two-year survival following lung resection was not explained by the lower life expectancy of older individuals. CONCLUSIONS: Medicare claims data can be used to estimate likely outcomes for elderly patients undergoing surgery for lung cancer. Expected outcomes vary with the patient's age, sex, and the type of surgical procedure performed.

Aged↗
PubMed1991

Immunologic measurement of polycyclic aromatic hydrocarbon-albumin adducts in foundry workers and roofers.

Roofers and iron foundry workers with high exposure to polycyclic aromatic hydrocarbons (PAH) were monitored for levels of covalent PAH serum albumin adducts, quantitated in enzymatically digested samples by a sensitive competitive enzyme-linked immunosorbent assay. Albumin adducts were higher in the foundry workers (5.22 fmol/micrograms, 0.314 mmol/mol) than in the reference group (4.07 fmol/micrograms, 0.245 mmol/mol), but only of borderline significance probably due to the small sample size. In a subset of foundry workers, a significant difference in adduct levels was observed for samples collected immediately after vacation and after six weeks of workplace exposure. The roofers also showed higher levels of adducts (5.19 fmol/micrograms, 0.312 mmol/mol) than their reference group (3.28 fmol/micrograms, 0.197 mmol/mol). These results demonstrate the feasibility of PAH protein adduct measurement as a marker of human exposure to this class of chemicals.

Antibodies, Monoclonal↗
PubMed1990

Development of clinical and economic prognoses from Medicare claims data.

Using a 5% nationally random sample of Medicare beneficiaries, we calculated the probability of dying, the probability of being readmitted, and the mean level of inpatient hospital expenditures within various time periods following discharge for those beneficiaries who were discharged alive from an acute-care hospital during 1983. We then examined the 674 most common principal discharge diagnoses and found significant variations by diagnosis code for all three outcomes. We believe that analyses of claims data by diagnosis code can provide useful information to clinicians and their patients regarding the clinical and economic prognosis of specific diseases, help managed-care programs identify patients likely to incur substantial costs over a several-year period, and inform insurers regarding the expected level of resources that will be used following discharge for patients with specific diseases.

Health Expenditures↗
PubMed1990

Detection of adducts of deoxyribonucleic acid in white blood cells of roofers by 32P-postlabeling. Relationship of adduct levels to measures of exposure to polycyclic aromatic hydrocarbons.

To assess the utility of adducts of deoxyribonucleic acid (DNA) as biomarkers of exposure to carcinogens in an industrial population, a pilot study of roofers occupationally exposed to polycyclic aromatic hydrocarbons was conducted. DNA isolated from white blood cells of roofers and nonoccupationally exposed comparison subjects matched for age, sex, and smoking status was analyzed for DNA adducts with the use of 32P-postlabeling methods. Occupational exposures to polycyclic aromatic hydrocarbons were assessed by personal air sampling and skin wipes. Ten of the 12 roofers, but only 2 of the 12 comparison subjects, had detectable levels of aromatic DNA adducts in the 32P-postlabeling assay. Among the roofers, the post-shift levels of polycyclic aromatic hydrocarbons in the skin wipes were correlated with the DNA adduct levels. These results suggest that 32P-postlabeling assay may be useful for monitoring internal exposures to complex mixtures of aromatic hydrocarbons in industrial populations.

Adult↗
PubMed1990

Setting payment rates for capitated systems: a comparison of various alternatives.

Numerous proposals have been suggested to revise the current adjusted annual per capita cost (AAPCC) method for paying HMOs in the Medicare program. Several evaluations of the various alternatives conclude that including a prior utilization variable is the most promising alternative. In this paper, using statistical and other criteria, we compare the current AAPCC method with three different prior utilization models. The results suggest that all three prior utilization models can predict expenditures for either individuals or a group--drawn from a cross section and a risk selected sample of aged Medicare beneficiaries--more accurately than the AAPCC method. Of the three prior utilization measures, Payment Amount for Capitated Systems (PACS) predicts actual expenditures most accurately.

Capitation Fee↗
PubMed1990

A pilot study of detection of DNA adducts in white blood cells of roofers by 32P-postlabelling.

To assess the utility of DNA adducts as biomarkers of exposure to carcinogens in an industrial population, a pilot study of roofers occupationally exposed to a mixture of polycyclic aromatic hydrocarbons was conducted. DNA was isolated from peripheral white blood cells of roofers and non-occupationally exposed subjects matched for age, sex and smoking status. Occupational exposures to anthracene, fluoranthene, pyrene, benzanthracene, benzo[a]pyrene, benzo[b]fluoranthene, benzo[g,h,i]perylene and benzo[k]fluoranthene were assessed by personal breathing zone air sampling and skin wipes. Exposures to benzo[a]pyrene in air of exposed subjects ranged from 0.60 microgram/m3 to 1.39 micrograms/m3, and exposures to total polycyclic aromatic hydrocarbon (the sum of eight hydrocarbons) ranged from 6.0 micrograms/m3 to 13.8 micrograms/m3 on the day before blood collection. In the biomarker studies 10 of 12 roofers, but only 2 of 12 comparison subjects, had detectable levels of aromatic DNA adducts by 32P-postlabelling assay (p less than 0.01). The two non-roofers with detectable adducts had levels at or near the detection limit of 2 adducts per 10(9) nucleotides. In two roofer samples which were studied in a mixing experiment, the major adduct spots did not co-migrate with the guanosine N2 adduct of benzo[a]pyrene diol epoxide. These results suggest that the 32P-postlabelling assay may be useful for monitoring exposures to complex mixtures of aromatic hydrocarbons in industrial populations.

Adult↗
PubMed1990

Ultrasound of the acute abdomen--Part V.

Patients with an acute abdomen have complaints of brief duration which must be properly diagnosed and treated to reduce mortality and morbidity. There are a few instances, mostly involving massive haemorrhage, where the patient's condition is so poor that minutes count and a delay in operation will result in fatality. Imaging techniques have no role in these circumstances. In the majority of cases, however, there is time to make use of the various diagnostic imaging methods available to help arrive at the correct diagnosis. The role of ultrasound in this setting has been reviewed. Our own experience supports the view that it is an important modality for the investigation of patients with acute abdomen. It should be available on a round-the-clock basis.

Abdomen, Acute↗
PubMed1989

Novel benzodiazepine receptor partial agonists: oxadiazolylimidazobenzodiazepines.

The synthesis and biochemical evaluation of a series of oxadiazole derivatives of imidazobenzodiazepines related to the benzodiazepine antagonist Ro 15-1788 (2a) are reported. Although the oxadiazole ring is seen as an isosteric replacement for the ester linkage, significant differences in structure-activity trends were observed. Specifically, oxadiazoles 9-12 invariably had increased receptor efficacy (as witnessed by measurements of the GABA shift) relative to the corresponding ester. Additionally, and in direct contrast to the classical agonists such as diazepam, affinity for the benzodiazepine receptor was enhanced by a 7- rather than 8-halo substituent. The results are discussed in terms of a six-point receptor-binding model originally based on the X-ray structure of 2a. For comparison, the crystal structures of two representative oxadiazole derivatives, 10h and 12o, having a 6-oxo and 6-phenyl group, respectively, were determined and the data incorporated into a modified binding model to account for the greater efficacy of these compounds. It is concluded that the antagonist behavior of 2a relies upon the hydrogen-bond-acceptor properties of the ester carbonyl oxygen whereas for the oxadiazole series this site is localized at the imidazole nitrogen.

Animals↗
PubMed1977

The release of plasticizer from polyvinyl chloride haemodialysis tubing.

The extent of migration of plasticizer from haemodialysis lines into saline and plasma has been examined and a number of different types of tubing have been compared. A model system designed to simulate in vivo haemodialysis was evolved. The method uses a continuous cyclohexane extraction in order to mimic uptake of plasticizer by body tissues. Although not an ideal system, the results obtained are indicative of the extent to which the plasticizers are leached.

Adipates↗
PubMed1975

Beta-thalassaemia of clinical significance in adult Jamaican Negroes.

Over a 9-year period, three adult Negro patients with beta-thalassaemia of clinical significance were recognized out of approximately 185 000 new adult patients attending the University Hospital. These patients, aged 15-58 years, have clinical and haematological characteristics within the spectrum of beta-thalassaemia intermedia; which in this paper refers to phenotypes resulting from defects in beta-chain synthesis clinically intermediate between classical Cooley's anaemia and beta-thalassaemia trait, genetic classification being dependent on family study. Family studies established the presence of two beta-thalassaemia genes conclusively in one case (proposita, family A); presumptively in another (propositus, family C); while in the remaining subject (proposita, family B), who has two similarly affected siblings, homozygosity is suspected, but not proven by family study. In simultaneous 59Fe and 51 Cr studies, estimates of effective erythropoiesis are in reasonable agreement with measurements of red cell destruction.

Adolescent↗