All Vibrio cholerae infections are not created equal.
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Cholera↗
Biomedical subjects
R Harris
Publications and source records attributed to R Harris.
Clinical strategies for breast cancer screening: weighing and using the evidence.
When balancing the benefits of screening women for breast cancer against the harms and costs of such screening, one needs to consider the risk for dying of breast cancer, the relative reduction in that risk that will result from screening women in different age groups, and the harms and costs associated with screening. Seven randomized controlled trials provide evidence of the relative risk reduction that results from screening women in different age groups; other studies estimate the harms and costs of screening. These studies indicate that the benefit of screening, expressed as the absolute number of lives extended per 1000 women screened, increases with age and that the harm of screening, expressed as the number of follow-up procedures per cancer detected, decreases with age. Thus, the tradeoff between the benefits and the harms and costs of screening is better for older than for younger women. Because there is no clear cut-point for determining when benefits outweigh harms and costs, it is important to involve women in discussions of breast cancer screening. The women who most need to be involved are those for whom the benefits of screening clearly outweigh the harms and costs and those for whom the benefits and the harms and costs constitute a "close call." For women in both groups, the physician should routinely raise the issue of screening, first eliciting the patient's perceptions and then providing information and discussion about the risk for breast cancer and about the benefits and the harms and costs of screening. Furthermore, the physician should encourage the patient to use her own values to weigh the benefits against the harms and costs, pointing out biases in reasoning and minimizing socioeconomic barriers. Finally, when the benefits obviously outweigh the harms and costs, the physician should make a clear recommendation for screening.
Age Factors↗
Conductance of idealized rough channels.
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Journal Article↗
Site-specific N-terminal auto-degradation of human serum albumin.
Human serum albumin prepared by blood fractionation for clinical purposes was found to degrade when stored at or above 30 degree C. Mass spectrometry and N-terminal sequencing of the protein identified degradation corresponding to the loss of the first two residues, aspartic acid and alanine. The reaction was shown to be dependent upon temperature and the N-terminal alpha-amino group. In addition, comparison with serum albumins derived from other species showed that the instability of the N-terminus was specific to the human albumin sequence. An intact aspartyl-alanyl dipeptide, purified from degraded albumin solutions, differed substantially from a synthetic dipeptide on amino acid analysis, N-terminal sequencing and NMR. It is suggested that the released dipeptide may be cyclic, implying a novel cleavage mechanism.
Amino Acid Sequence↗
Bone marrow transplantation in a young child with sickle cell anemia.
Bone marrow transplantation (BMT) is the only curative therapy available for hemoglobinopathies. BMT was performed on a young child with sickle cell anemia (SCA) after approximately 9 months of transfusion therapy following her initial stroke. The patient received a matched sibling donor (sickle trait) BMT. The conditioning regimen consisted of busulfan 4 mg/kg/day x 4, cyclophosphamide 50 mg/kg/day x 4. Graft vs. host disease prophylaxis was daily cyclosporine for 6 months. There were no significant complications during BMT. Engraftment occurred on day +17 and the patient was transfusion independent since day +45. Pre-BMT cerebral arteriography showed multiple stenotic cerebral vessels and a moya-moya pattern. Perfusion MRI demonstrated reduced capillary perfusion. Approximately 170 days after BMT the patient experienced episodes of transient left-sided weakness and speech problems. Neuroimaging revealed progression of large vessel pathology by angiography despite significant improvement in cortical perfusion (MR perfusion scan). Molecular analysis by PCR and DNA fingerprinting confirmed absence of mixed mosaicism. Rheologic evaluation showed normal corrected bulk viscosity. It is possible that progression of large vessel pathology and return of clinical symptoms in the face of normal rheologic parameters may be due to worsening of the already damaged cerebral vessels by the BMT conditioning regimen. Further evaluations of patients with SCA undergoing BMT after a stroke are needed to answer this question.
Anemia, Sickle Cell↗
Progress with gene-product mapping of the Mollicutes: Mycoplasma genitalium.
A protein map of the smallest known self-replicating organism, Mycoplasma genitalium (Class: Mollicutes), revealed a high proportion of acidic proteins. Amino acid composition was used to putatively identify, or provide unique parameters, for 50 gene products separated by two-dimensional gel electrophoresis. A further 19 proteins were subjected to peptide-mass fingerprinting using matrix-assisted laser desorption ionisation-time of flight (MALDI-TOF) mass spectrometry and 4 were subjected to N-terminal Edman degradation. The majority of M. genitalium proteins remain uncharacterised. However, the combined approach of amino acid analysis and peptide-mass fingerprinting allowed gene products to be linked to homologous genes in a variety of organisms. This has allowed proteins to be identified prior to detection of their respective genes via the M. genitalium sequencing initiative. The principle of 'hierarchical' analysis for the mass screening of proteins and the analysis of microbial genomes via their protein complement or 'proteome' is detailed. Here, characterisation of gene products depends upon the quickest and most economical technologies being employed initially, so as to determine if a large number of proteins are already present in both homologous and heterologous species databases. Initial screening, which lends itself to automation and robotics, can then be followed by more time and cost intensive procedures, when necessary.
Amino Acids↗
Enhancement of peritoneal macrophages reduces postoperative peritoneal adhesion formation.
Postoperative adhesion formation results from a fibroproliferative inflammatory reaction. Macrophages are critical in the final resolution of the inflammatory process and tissue repair, including modulation of proliferation and differentiation of fibroblasts and secretion of neutral proteases like plasminogen activator. We, therefore, studied the influence of peritoneal macrophage enhancement on postoperative adhesion formation in five groups of rabbits. Group 1 was a control with normal peritoneum. Animals in group 2 had increased macrophage population in their peritoneum by intraperitoneal injection of protease peptone 3 days before adhesion induction. In group 3, animals were treated by protease peptone as in group 2 and then depleted of the increased macrophage population by peritoneal lavage before adhesion induction. In group 4 macrophages were transplanted from animals enriched as in group 2 into a nonenriched peritoneum at the time of adhesion induction. Group 5 had a normal peritoneum with peritoneal lavage before adhesion induction. Peritoneal adhesions were induced at laparotomy by repairing a peritoneal defect in two different models. It was found that enhancement of peritoneal macrophages by protease peptone reduced markedly the degree of postoperative adhesion formation. After depletion of the enhanced peritoneal macrophages by peritoneal lavage the degree of adhesion formation was equivalent to that of controls. Finally, macrophage transplantation into a nonenhanced macrophage peritoneum also reduced the degree of postoperative adhesion formation. It is concluded that enhancement of peritoneal macrophages reduces postoperative peritoneal adhesion formation.
Animals↗
Are patients of women physicians screened more aggressively? A prospective study of physician gender and screening.
OBJECTIVE: To determine the effects of physician gender on rates of Pap testing, mammography, and cholesterol testing when identifying and adjusting for demographic, psychosocial, and other patient variables known to influence screening rates. DESIGN: A prospective design with baseline and six-month follow-up assessments of patients' screening status. SETTING: Twelve community-based group family practice medicine offices in North Carolina. PARTICIPANTS: 1,850 adult patients, aged 18-75 years (six-month response rate, 83%), each of whom identified one of 37 physicians as being his or her regular care provider. MAIN RESULTS: Where screening was indicated at baseline, the patients of the women physicians were 47% more likely to get a Pap test [odds ratio (OR) = 1.47, 95% confidence interval (CI) = 1.05, 2.04] and 56% more likely to get a cholesterol test (OR = 1.56, 95% CI = 1.08, 2.24) during the study period than were the patients of the men physicians. For mammography, the younger patients (aged 35-39 years) of the women physicians were screened at a much higher rate than were the younger patients of the men physicians (OR = 2.69, 95% CI = 0.98, 7.34); however, at older ages, the patients of the women and the men physicians had similar rates of screening. CONCLUSIONS: In general, the patients of the women physicians were screened at a higher rate than were the patients of the men physicians, even after adjusting for important patient variables. These findings were not limited to gender-specific screening activities (e.g., Pap testing), as in some previous studies. However, the patients of the women physicians were aggressively screened for breast cancer at the youngest ages, where there is little evidence of benefit from mammography. Larger studies are needed to determine whether this pattern of effects reflects a broader phenomenon in primary care.
Adolescent↗
Limited toxicity of prolonged therapy with high doses of amphotericin B lipid complex.
We describe six patients with invasive fungal infections who received large cumulative doses (22.3-73.6 g) of amphotericin B lipid complex (ABLC) over 21-121 weeks. The drug was well tolerated at these very large doses, and there was limited toxicity. Collectively, these patients received ABLC therapy for a mean of 53.8 weeks (range, 21-121 weeks). The mean serum creatinine level at the start of ABLC therapy was 1 mg/dL (range, 0.4-1.9 mg/dL), and at the end of therapy this level was 1.5 mg/dL (range, 1.0-2.0 mg/dL). Over the course of therapy, only two patients had serum creatinine levels of > or = 2 mg/dL, with transient peak serum creatinine levels of 3.5 and 2.8 mg/dL, respectively. Several patients required replacement therapy with oral or intravenous potassium. None of the patients had ABLC-associated toxic effects necessitating discontinuation of the treatment. ABLC may be given in substantially larger doses than conventional amphotericin B, and very high doses of ABLC that are administered over several months appear to be relatively less toxic than those of conventional amphotericin B.
Adolescent↗
Source of dietary carbohydrate affects life span of Fischer 344 rats independent of caloric restriction.
Previous investigations suggest that increased life span of calorie-restricted rodents is a function of caloric intake rather than the macro- or micronutrient composition of the diet. However, the dietary source of carbohydrate has not been widely investigated. We hypothesized that the dietary carbohydrate source may affect the life span of rats independent of caloric restriction. This hypothesis was tested in male Fischer 344 rats fed ad libitum or restricted to 60% of ad libitum, an isocaloric diet containing 14% protein, 10% fat, and 66% sucrose or cornstarch. Body weights of the ad libitum- and restricted-fed sucrose rats were consistently greater throughout the experimental period compared to diet-matched animals. Food intake did not differ significantly. The survival curves of ad libitum starch- vs sucrose-fed rats were significantly different. That is, the mean, median and upper 10th percentile survival were significantly greater in the ad libitum starch- vs sucrose-fed rats (mean life span: cornstarch-fed, 720 +/- 23 days; sucrose-fed, 659 +/- 19 days). Calorie-restricted starch-fed rats had poorer early life survival, and no significant increase in mean life span compared to ad libitum cornstarch-fed animals (726 vs 720 days). These animals did, however, have the greatest upper 10th percentile survival of all four experimental groups. Mean life span of calorie-restricted sucrose-fed rats was significantly greater than that of all other groups (890 +/- 18 days). The differences in survival rates between sucrose- and cornstarch-fed animals could not be attributed to the effects of carbohydrate source on body weight, energy absorption, or on the timing and severity of the pathological lesions normally associated with aging and/or caloric restriction in this species. These data support the hypothesis that the dietary source of carbohydrate, i.e., sucrose vs cornstarch, can significantly affect life span independently of caloric intake.
Animals↗
Presentation of peptides by cultured monocytes or activated T cells allows specific priming of human cytotoxic T lymphocytes in vitro.
The conditions favouring effective specific cytotoxic T lymphocyte (CTL) priming have been exploited to set up a simple and reproducible method to induce a primary CTL response in vitro. We report that cultured monocytes, as well as activated T cells, pulsed with exogenous HLA-A2 binding immunogenic peptides, can induce primary peptide-specific CTL responses in vitro in a Th-independent manner. Primary viral peptide-induced CTL were HLA-A2 restricted, and recognized both peptide-pulsed target cells and targets infected with recombinant vaccinia virus expressing viral endogenous antigens. In addition, both cultured monocytes and activated T cells primed peptide-specific CD8+ T cells depleted from the CD45RO+ memory cell fraction. The efficiency of CTL priming by monocytes was dependent upon the strong up-regulation of class I, adhesion and co-stimulatory molecules occurring spontaneously upon in vitro culture. The inability of unseparated peripheral blood mononuclear cells to mount a peptide-specific CTL response could be reverted by direct co-stimulation of responding CD8+ T cells by soluble B7.1 or a stimulatory anti-CD28 antibody, that allowed a specific response to take place. Although co-stimulation via the B7-CD28 interaction appeared sufficient to trigger CTL responses, it was not essential for CTL priming, since neither anti-B7.1 mAb nor soluble CTLA-4 inhibited induction of primary CTL response. This new method for induction of specific CD8+ T cell response in vitro may be exploited in adoptive immunotherapy in cancer or in HIV-infected patients.
Amino Acid Sequence↗
A logit analysis of the likelihood of leaving rural settings for registered nurses.
This study examined the net effects of individual and community factors on the likelihood of registered nurses leaving current jobs using a logit analysis. Based on data from a survey of 2,509 rural nurses, four separate models were estimated and compared: one for nurses in rural settings as a whole and the other three for nurses in hospitals, skilled nursing facilities, and community/public health agencies. Results of the general model indicated that nurses' marital status, age, position, income, job satisfaction, and satisfaction with the community were significant determinants of the likelihood of leaving current jobs. Job satisfaction was the most significant factor, followed by satisfaction with the community. Findings from the models for three different employment settings were similar to those of the general model. However, the significance of factors and their strength of effect on nurses' decisions to leave or stay in their current jobs differed across the three types of facilities. Based on these findings rural nursing administrators and policy-makers should give priority to retention strategies that focus on improving the job environment. The development of different strategies for different groups of nurses (i.e., by age or marital status) and different types of facilities should increase the benefit/cost ratio. In addition, programs that involve rural health care agencies in community and economic development should be further explored as an avenue to increased nurse retention in rural areas.
Adult↗
The dental phenotype in familial adenomatous polyposis: diagnostic application of a weighted scoring system for changes on dental panoramic radiographs.
A weighted scoring system (Dental Panoramic Radiograph Score) taking into consideration the nature, extent, and site of osseous and dental changes on dental panoramic radiographs in familial adenomatous polyposis is described. The weighting takes into consideration the incidence of the anomaly in the general population. The reliability of the system was tested by application to 85 people known to be affected by clinical or mutation analysis, 30 people lacking mutation in the adenomatous polyposis gene, and 19 people shown to be at low risk (< 1%) by linkage analysis. Using the highest thresholds, a specificity of 100% and sensitivity of approximately 68% was obtained. If all positive findings were considered as significant, sensitivity was increased to approximately 82% but the specificity was reduced to approximately 88%. Significant DPRS findings were observed at a significantly higher frequency in patients aged over 20 compared to the patients aged 20 and under. Overall, approximately 68% of the affected subjects had significant changes, and approximately 18% had normal appearance on DPR, with the remainder having changes classified as minimal or equivocal.
Adenomatous Polyposis Coli↗
Impact on empiric treatment of group A streptococcal pharyngitis using an optical immunoassay.
The potential impact of using a rapid diagnostic test (Strep A OIA) on detection and treatment of group A beta-hemolytic streptococcal (GABHS) pharyngitis in a large-volume pediatric and adolescent clinic was examined. Of 519 swabs processed for both culture and the OIA test, 114 were culture-positive for GABHS compared with 133 positive by the OIA test, for an agreement of 94%. OIA test sensitivity compared with culture was 96%, and specificity was 94%. Forty-seven percent of all study patients were empirically placed on antibiotics. In-clinic OIA testing could have reduced inappropriate therapy and been a cost-effective alternative to culture.
Adolescent↗
Messenger more important than message in HIV prevention.
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Black or African American↗
The nitric oxide synthase inhibitor, L-NG-monomethylarginine, reduces carrageenan-induced pleurisy in the rat.
Nitric oxide (NO) is a biological mediator that, when produced by the type II (inducible) nitric oxide synthase (NOS), has been implicated in the pathophysiology of inflammatory diseases. To examine this putative role of NO, pleural inflammation was elicited in rats by the intrapleural injection of carrageenan (1 mg). A pleural exudate and cellular influx developed, which peaked at 24 h and generally resolved by 72 h. The cellular influx was primarily composed of polymorphonuclear cells during the first 24 h, followed by macrophages during the subsequent 24 h. Inflammatory cell-associated NOS activity and pleural exudate nitrite (NO2-) + nitrate (NO3-) (NOx) also increased, peaking at 6 h and 24 h, respectively. Cell-associated NOS activity was calcium-independent, indicating the presence of the type II NOS isoform; NOS activity in the pleural cavity and polymorphonuclear cells influx were temporally correlated. Administration of L-NG-monomethylarginine (L-NMA) (200 mg/kg/day) attenuated the pleural exudation, cellular influx, pleural exudate NOx, and cell-associated NOS activity. The relative composition of the pleural cavity cellular infiltrate was not changed by L-NMA, indicating the influx of individual cell types were affected equally. L-Arginine (500 mg/kg/day) completely prevented the effects of L-NMA on pleural exudation and cellular influx and partially prevented the inhibition of pleural exudate NOx accumulation by L-NMA. These data implicate NO as a modulator of the pleural inflammatory response and support a future clinical role for NOS inhibitors in the treatment of inflammatory disease.
Amino Acid Oxidoreductases↗
Developing a team approach to weaning.
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Humans↗
Deletion mapping on the short arm of chromosome 3 in squamous cell carcinoma of the oral cavity.
Loss of heterozygosity indicative of the presence of tumor suppressor genes on chromosome 3p is commonly observed in carcinomas of various tissues. We have examined loss of heterozygosity on chromosome 3p in 27 oral squamous cell carcinomas using 15 highly informative microsatellite polymorphisms and constructed a deletion map of chromosome 3p. Overall, loss of heterozygosity at one or more loci was observed in 14 tumors (approximately 52%). A majority of these tumors (86%) show loss in more than one area. Three distinct regions were identified: 3p13-3p21.1, 3p21.3-3p23, and 3p25. These data suggest a role for at least three tumor suppressor genes on chromosome 3p in oral squamous carcinomas. The regions of deletions overlap with those described for carcinomas of other tissues and parallel those observed in lung carcinomas. This may reflect the common etiology of the two cancers.
Carcinoma, Squamous Cell↗