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Biomedical subjects

R Smith

Publications and source records attributed to R Smith.

At least 505 records · Page 28Linked to original sources

Pediatric aerodigestive foreign body injuries are complications related to timeliness of diagnosis.

Foreign body (FB) injury from aspiration or ingestion is a common pediatric health problem. Diagnosis relies on clinical judgment plus medical history, physical examination, and radiographic evaluation. A multi-institutional review of 1269 FB events revealed that 85% were correctly diagnosed following a single physician encounter. However, 15% of the children had an elusive diagnosis (>1 week), despite previous evaluation. Delays in diagnosis were seven times more likely to occur in aspirations than in ingestions. Secondary injuries (e.g., pneumonia and atelectasis) occurred in 13% of airway FBs but in only 1.7% of esophageal FBs. Plain radiographs were used in 82% of children, and special studies (e.g., fluoroscopy) in only 7%. We conclude that diagnosis of FB injury in children is frequently achieved at the initial evaluation but that continued surveillance by follow-up visits to health care facilities from parents and other caretakers is important, to reduce pulmonary injuries.

Adolescent↗

Predicting poor outcome in perforated peptic ulcer disease.

BACKGROUND: Despite modern medications for peptic ulcers, patients frequently require emergency surgery for complications of ulcer disease. Many of these patients have coexisting medical problems which not only predispose to perforated ulcer disease, but also influence the clinical outcome. This study reviews the outcome of a group of patients with perforated ulcer disease and examines the influence of a range of comorbidity factors on the outcome. METHODS: A retrospective chart review of all cases of perforated peptic occurring over a period of 9 years. RESULTS: One hundred and forty-nine perforated peptic ulcers in 147 patients were diagnosed between 1987 and 1996. Coexisting malignancy, use of immunosuppressives or corticosteroids, pre-operative shock and admission to intensive care were all significantly associated with reperforation by univariate analysis. However, logistic regression analysis indicated that none of these factors independently predicted reperforation which, therefore, occurs as a multifactorial event with all the above factors contributing. Death from perforated ulcer disease was related to pre-operative shock, malignancy, admission to intensive care and reperforation when examined by univariate analysis. Furthermore, logistic regression analysis showed that coexisting malignancy and reperforation were significant predictors of mortality. CONCLUSIONS: Perforated peptic ulcer disease remains a frequent clinical problem in patients with short dyspeptic histories, who may or may not have been using ulcerogenic medications. It is a significant cause of morbidity and mortality among an often aged and otherwise unwell group of patients. Patients with underlying malignant disease, who may be immunosuppressed with corticosteroids or cytotoxics, are at increased risk of dying from perforated ulcer disease. Reperforation of an ulcer, following simple closure or conservative treatment, is also highly predictive of increased mortality.

Aged↗

Lower serum high-density lipoprotein cholesterol (HDL-C) in major depression and in depressed men with serious suicidal attempts: relationship with immune-inflammatory markers.

Recently, there have been some reports that changes in serum lipid composition may be related to suicide, major depression and immune-inflammatory responses. Findings from our laboratory suggest that major depression is accompanied by reduced formation of cholesteryl esters and perhaps by impairment of reverse cholesterol transport. The latter is reportedly accompanied by lower serum high-density lipoprotein cholesterol (HDL-C). The aim of this study was to examine whether (i) major depression is accompanied by lower serum HDL-C or by abnormal levels of serum total cholesterol, triglycerides, low-density lipoprotein-C (LDL-C) or vitamin E, (ii) suicidal attempts are related to lower serum HDL-C and (iii) there are significant associations between serum HDL-C and immune/inflammatory markers. A total of 36 subjects with major depression, of whom 28 patients showed treatment resistance, as well as 28 normal control subjects, had blood sampled for the assay of the above lipids, serum zinc (Zn), albumin (Alb) and flow cytometric determination of the T-helper/T-suppressor (CD4+/CD8+) T-cell ratio. In total, 28 depressed subjects had repeated measures of these variables both before and after treatment with antidepressants. Serum HDL-C and total cholesterol, as well as the HDL-C/cholesterol ratio, were significantly lower in subjects with major depression than in normal controls. Serum HDL-C levels were significantly lower in depressed men who had at some time made serious suicidal attempts than in those without such suicidal behaviour. Treatment with antidepressants for 5 weeks did not significantly alter either serum HDL-C or other lipid variables. Serum HDL-C levels were significantly and negatively correlated with the (CD4+/CD8+) T-cell ratio, and positively correlated with serum Alb and Zn. These results suggest that (i) lower serum HDL-C levels are a marker for major depression and suicidal behaviour in depressed men, (ii) lower serum HDL-C levels are probably induced by the immune/inflammatory response in depression and (iii) there is impairment of reverse cholesterol transport from the body tissues to the liver.

Adult↗

Antibacterial activity in bovine lactoferrin-derived peptides.

Several peptides sharing high sequence homology with lactoferricin B (Lf-cin B) were generated from bovine lactoferrin (Lf) with recombinant chymosin. Two peptides were copurified, one identical to Lf-cin B and another differing from Lf-cin B by the inclusion of a C-terminal alanine (lactoferricin). Two other peptides were copurified from chymosin-hydrolyzed Lf, one differing from Lf-cin B by the inclusion of C-terminal alanyl-leucine and the other being a heterodimer linked by a disulfide bond. These peptides were isolated in a single step from chymosin-hydrolyzed Lf by membrane ion-exchange chromatography and were purified by reverse-phase high-pressure liquid chromatography (HPLC). They were characterized by N-terminal Edman sequencing, mass spectrometry, and antibacterial activity determination. Pure lactoferricin, prepared from pepsin-hydrolyzed Lf, was purified by standard chromatography techniques. This peptide was analyzed against a number of gram-positive and gram-negative bacteria before and after reduction of its disulfide bond or cleavage after its single methionine residue and was found to inhibit the growth of all the test bacteria at a concentration of 8 microM or less. Subfragments of lactoferricin were isolated from reduced and cleaved peptide by reverse-phase HPLC. Subfragment 1 (residues 1 to 10) was active against most of the test microorganisms at concentrations of 10 to 50 microM. Subfragment 2 (residues 11 to 26) was active against only a few microorganisms at concentrations up to 100 microM. These antibacterial studies indicate that the activity of lactoferricin is mainly, but not wholly, due to its N-terminal region.

Amino Acid Sequence↗

The carboxyl-terminal 120-residue polypeptide of infectious bronchitis virus nucleocapsid induces cytotoxic T lymphocytes and protects chickens from acute infection.

Specific cytotoxic T-lymphocyte (CTL) responses to nucleocapsid of infectious bronchitis virus (IBV) were identified by using target cells infected with a Semliki Forest virus (SFV) vector. Effector cells for CTL assays were collected from chickens infected with the Gray strain of IBV or inoculated with a DNA plasmid encoding nucleocapsid proteins. IBV-specific CTL epitopes were mapped within the carboxyl-terminal 120 amino acids of the nucleocapsid protein. CTL lysis of target cells infected with SFV encoding nucleocapsid was major histocompatibility complex restricted and mediated by CD8+ T cells. In addition, splenic T cells collected from chickens inoculated in the breast muscle with a DNA plasmid encoding this CTL epitope(s) recognized target cells infected with wild-type virus or an SFV vector encoding nucleocapsid proteins. CTL activity of splenic T cells collected from chicks immunized with a DNA plasmid encoding CTL epitopes was cross-reactive, in that lysis of target cells infected with serologically distinct strains of IBV was dose responsive in a manner similar to that for lysis of target cells infected with the homologous strain of IBV. Furthermore, chickens immunized with a DNA plasmid encoding a CTL epitope(s) were protected from acute viral infection.

Animals↗

Exposure-response analysis of risk of respiratory disease associated with occupational exposure to chrysotile asbestos.

OBJECTIVES: To evaluate alternative models and estimate risk of mortality from lung cancer and asbestosis after occupational exposure to chrysotile asbestos. METHODS: Data were used from a recent update of a cohort mortality study of workers in a South Carolina textile factory. Alternative exposure-response models were evaluated with Poisson regression. A model designed to evaluate evidence of a threshold response was also fitted. Lifetime risks of lung cancer and asbestosis were estimated with an actuarial approach that accounts for competing causes of death. RESULTS: A highly significant exposure-response relation was found for both lung cancer and asbestosis. The exposure-response relation for lung cancer seemed to be linear on a multiplicative scale, which is consistent with previous analyses of lung cancer and exposure to asbestos. In contrast, the exposure-response relation for asbestosis seemed to be nonlinear on a multiplicative scale in this analysis. There was no significant evidence for a threshold in models of either the lung cancer or asbestosis. The excess lifetime risk for white men exposed for 45 years at the recently revised OSHA standard of 0.1 fibre/ml was predicted to be about 5/1000 for lung cancer, and 2/1000 for asbestosis. CONCLUSIONS: This study confirms the findings from previous investigations of a strong exposure-response relation between exposure to chrysotile asbestos and mortality from lung cancer, and asbestosis. The risk estimates for lung cancer derived from this analysis are higher than those derived from other populations exposed to chrysotile asbestos. Possible reasons for this discrepancy are discussed.

Adult↗

An experimental comparison of three types of case management for homeless mentally ill persons.

OBJECTIVE: Three types of case management were compared to determine their relative effectiveness in helping people with severe mental illness who were homeless or at risk of homelessness. METHODS: Subjects recruited from a psychiatric emergency room and inpatient units were randomly assigned to one of the three treatment conditions: broker case management, in which the client's needs were assessed, services were purchased from multiple providers, and the client was monitored; assertive community treatment only, in which comprehensive services were provided for an unlimited period; and assertive community treatment augmented by support from community workers, who assisted with activities of daily living and were available for leisure activities. Of 165 subjects recruited, 135 were followed for 18 months. RESULTS: Compared with clients assigned to broker case management, clients assigned to assertive community treatment only and assertive community treatment with community workers had superior outcomes on several variables. They were number of contacts with the assigned treatment program, resource utilization (for example, use of entitlements), severity of thought disorder, activity level, and client satisfaction. Clients in the assertive community treatment only condition achieved more days in stable housing than those in the other two treatment conditions. No significant treatment group effects were found on income, self-esteem, or substance abuse. CONCLUSIONS: Assertive community treatment is superior to broker case management in assisting individuals with serious mental illness who are at risk of homelessness.

Activities of Daily Living↗

Nitric oxide inhibits corticotropin-releasing hormone exocytosis but not synthesis by cultured human trophoblasts.

Nitric oxide (NO) plays an important role in many cell-cell signaling systems, but its mechanism of action is variable. We have previously reported that NO reduces secretion of the peptide hormone, CRH, from cultured placental cells and the perfused placenta. Because placental CRH production seems linked to human parturition, we wished to explore the mechanism of action of NO in this setting in more detail. We report here that in the placenta, NO specifically inhibited CRH exocytosis, not synthesis, and that endogenous NO affects this process. Cytotrophoblasts were prepared from term human placentas and cultured as monolayers. CRH immunoreactivity in the cell supernatants and cell extracts were measured by RIA. CRH messenger RNA was determined by Northern blot analysis. Sodium nitroprusside (SNP; 1-100 mumol/L) and S-nitroso-N-acetyl-penicillamine (SNAP; 1-100 mumol/L), NO donors, significantly reduced basal CRH concentration in the media, while increasing the concentration of CRH in the cells (P < 0.01), suggesting that exocytosis of CRH was inhibited. These effects could be attenuated by the NO scavenger hemoglobin (20 micrograms/mL). KCl (45 mmol/L), which causes exocytosis by depolarizing the cell membrane, increased CRH release by 2- to 3-fold, and this was inhibited by SNP. Basal release of CRH was augmented by the NO synthase competitive inhibitor N omega-L-arginine methyl ester (1 mmol/L; P < 0.01) and the guanylate cyclase inhibitor, LY83583 (1 mumol/L; P < 0.01). The inhibitory effect of SNP was also blocked by LY83583. CRH messenger RNA content did not change when the placental cells were incubated with SNP, N omega-L-arginine methyl ester, and LY83583 for 6 and 24 h, and this was consistent with studies showing that total CRH immunoreactivity (cells plus media) did not change in the presence of SNP. These studies indicate that exogenous NO inhibits CRH exocytosis, rather than biosynthesis, by human trophoblasts and that endogenous NO has tonic inhibitory effects on CRH release by these cells. The inhibitory effect of NO on basal and stimulated CRH release by placental trophoblasts seems to be a guanylate cyclase-mediated inhibition of exocytosis.

Adult↗

A prospective study of coronary heart disease in relation to fasting insulin, glucose, and diabetes. The Atherosclerosis Risk in Communities (ARIC) Study.

OBJECTIVE: To determine the association of coronary heart disease (CHD) incidence with diabetes, fasting serum glucose, and insulin in a biracial cohort of middle-aged men and women. RESEARCH DESIGN AND METHODS: We examined a population-based sample (n = 13,446 free of baseline CHD) from four U.S. communities in 1987-1989. We defined diabetes on the basis of baseline fasting glucose concentration (> or = 7.8 mmol/l), medical history, and current medications. A central laboratory measured fasting insulin with a nonspecific radioimmunoassay. After 4-7 years, 209 men and 96 women developed CHD. RESULTS: After adjustment for sociodemographic characteristics, smoking status, ethanol intake, sports participation, and hormone replacement therapy, the relative risk of CHD for people with diabetes versus those without diabetes was 3.45 (95% CI 2.16-5.50) among women and 2.52 (1.78-3.56) among men. Relative risks of CHD with diabetes were somewhat lower in blacks than non-blacks, but because diabetes was more than twice as prevalent in blacks, the percentage of CHD cases attributable to diabetes (population attributable risk) was 27% for black women, 15% for non-black women, 8% for black men, and 12% for non-black men. Among people without diabetes, fasting glucose was not independently associated with CHD incidence. Among women without diabetes, there was a positive association between fasting insulin and CHD; multivariable adjusted relative risks of CHD across quintiles of fasting insulin were 1.00, 0.76, 2.08, 2.08 and 2.82 (P for linear trend = 0.02). However, among men without diabetes, fasting insulin and CHD were not associated. CONCLUSIONS: Diabetes conveys a high risk of CHD in black and non-black middle-aged men and women. Fasting insulin, however, is a CHD risk factor only among women in this cohort.

Black or African American↗

The effect of aging on the utilization of chemotherapy for metastatic breast cancer: a population-based study.

Older women (i.e., > or = 65 years of age) receive less adjuvant chemotherapy than younger women, in part because chemotherapy has been less effective in postmenopausal than premenopausal women in clinical trials. Metastatic breast cancer, however, does not respond differently to chemotherapy by age. Therefore, to evaluate further the effect of age on chemotherapy utilization, we conducted a population-based study of the treatment of metastatic breast cancer. Patients (n = 132) were identified by cross-tabulating death certificates from 1984 to 1991 with breast cancer cases in the Washington County Cancer Registry. Treatment information was obtained from the Tumor Registry of the Washington Country Hospital and Hospital medical records. Forty patients (74%) < 65 years old received chemotherapy compared to 11 (42%) 65-74 and 6 (12%) > or = 75 (p < 0.0001). Adjusting for other medical conditions and whether or not the patient saw a medical oncologist, there was still a significant effect of age in patients > or = 75 (p < 0.001) and a trend (p = 0.17) for patients 65-74. The different patterns of chemotherapy utilization were not associated with survival differences. Radiation therapy was also utilized significantly less frequently in older than younger patients, but the age effect was not as pronounced as with chemotherapy. There was no age effect on the utilization of hormonal therapy. Less frequent utilization of chemotherapy in older patients is probably caused by a combination of patient and physician factors and may result in less effective palliation for older patients.

Age Factors↗

Maximizing physician performance: a systems approach.

Managed care organizations are aware of the importance of managing the quality of care and controlling costs associated with the delivery of care. By utilizing physician-level performance reporting, an organization can help its physicians manage the organization's resources across the continuum of care. Physician participation can be obtained by developing a multicomponent program that includes opportunities for physician input regarding resource allocation and benefit packages; by articulating and documenting the organization's goals and priorities; by providing physicians with systemwide data related to indicators of their performance levels; and by offering financial incentives.

Continuity of Patient Care↗

Effect of embryo density and growth factors on in vitro preimplantation development of mouse embryos.

Embryo development depends on maternal and embryonic factors that may regulate genetic programs in early development. Effects of growth factors on proliferation, differentiation and morphogenesis along embryogenesis have been documented. However, studies have not established the role of growth factors in the preimplantational period. The purpose of this study was to investigate the possible effects of growth factors and embryo density on mouse preimplantation development in vitro. Two- and eight-cell CF-1 embryos were cultured individually or in groups of ten in HTF medium, alone or with EGF, TGF-beta 1 and IGF-I. Cleavage rate varied greatly with growth factors and increased significantly when eight-cell embryos were cultured in groups. On the other hand, when two-cell embryos were cultured in groups, the cleavage rate was slower than that obtained when embryos were individually cultured. The differentiation rate increased significantly in two-cell embryos cultured in groups (p < 0.05). EGF, TGF-beta 1 and IGF-I increased differentiation rates significantly in two-cell embryos individually cultured for 68 hours. The combination of EGF and TGF-beta 1 increased the differentiation rates significantly. The other combinations were not effective in modifying this parameter. Hatching rates increased in embryos cultured in groups (p < 0.05). TGF-beta 1 decreased this parameter significantly in two- or eight-cell embryos cultured in groups (p < 0.05). The data described in this report suggest that preimplantational mouse embryos produce some factor or factors that enhance its development, specially the differentiation and hatching rates. However, a functional role for polypeptide growth factors during preimplantational development has to be determined.

Animals↗

Dermabrasion. Is it an option?

Skin resurfacing by dermabrasion was largely abandoned in the 1980s because of its long and painful recovery period. Moist environment hydrogel dressing systems suddenly allowed rapid and painless recovery. This article discusses the revitalized role of the procedure in modern surgical usage.

Acne Vulgaris↗