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Biomedical subjects

J A Roberts

Publications and source records attributed to J A Roberts.

At least 127 records · Page 7Linked to original sources
PubMed1994

Is travel prophylaxis worth while? Economic appraisal of prophylactic measures against malaria, hepatitis A, and typhoid in travellers.

OBJECTIVES: To estimate the costs and benefits of prophylaxis against travel acquired malaria, typhoid fever, and hepatitis A in United Kingdom residents during 1991. DESIGN: Retrospective analysis of national epidemiological and economic data. MAIN OUTCOME MEASURES: Incidence of travel associated infections in susceptible United Kingdom residents per visit; costs of prophylaxis provision from historical data; benefits to the health sector, community, and individuals in terms of avoided morbidity and mortality based on hospital and community costs of disease. RESULTS: The high incidence of imported malaria (0.70%) and the low costs of providing chemoprophylaxis resulted in a cost-benefit ratio of 0.19 for chloroquine and proguanil and 0.57 for a regimen containing mefloquine. Hepatitis A infection occurred in 0.05% of visits and the cost of prophylaxis invariably exceeded the benefits for immunoglobulin (cost-benefit ratio 5.8) and inactivated hepatitis A vaccine (cost-benefit ratio 15.8). Similarly, low incidence of typhoid (0.02%) and its high cost gave whole cell killed, polysaccharide Vi, and oral Ty 21a typhoid vaccines cost-benefit ratios of 18.1, 18.0, and 22.0 respectively. CONCLUSIONS: Fewer than one third of travellers receive vaccines but the total cost of providing typhoid and hepatitis A prophylaxis of 25.8m pounds is significantly higher than the treatment costs to the NHS (1.03m pounds) of cases avoided by prophylaxis. Neither hepatitis A prophylaxis nor typhoid prophylaxis is cost effective, but costs of treating malaria greatly exceed costs of chemoprophylaxis, which is therefore highly cost effective.

Antimalarials↗
PubMed1994

Three-dimensional treatment planning of intracavitary gynecologic implants: analysis of ten cases and implications for dose specification.

PURPOSE: Results of 3-dimensional treatment planning for ten intracavitary gynecologic implants and implications for dose specification are presented. METHODS AND MATERIALS: Using a computed tomographic (CT) compatible intracavitary applicator we have performed CT scans during gynecologic brachytherapy in 10 cases. A CT-based treatment planning system with 3-dimensional capabilities was used to calculate and display dose in three dimensions. Conventional point doses including the estimated bladder and rectal maximum doses and dose to Point A were acquired from orthogonal simulation films. CT maximum bladder and rectal doses and minimum cervix doses were ascertained from isodose lines displayed on individual CT images. Dose volume histograms for the bladder, rectum and cervix were generated and used to obtain volume of the cervix target volume receiving less than the prescribed dose and the volume of bladder and rectum receiving more than the orthogonal maximum doses. The 5 cc volume of bladder and rectum receiving the highest dose were also calculated. RESULTS: Average values of CT point doses and volumes are compared with the traditionally obtained doses. As demonstrated by others, much higher bladder and rectal doses are found using the CT information. The minimum dose to the cervix target volume is lower than the dose to Point A in each case. CT maximum bladder and rectum and minimum cervix target doses may not be the best index doses to correlate with outcome because of the small volumes receiving the dose. CONCLUSION: We hypothesize that clinically useful bladder, rectal and cervix target volume doses will include volume information which is obtainable with dose volume histogram analysis.

Brachytherapy↗
PubMed1994

Protein kinase C-dependent and -independent pathways mediate epidermal growth factor (EGF) effects in human endometrial adenocarcinoma cell line KLE.

The role of EGF in the proliferation of the poorly differentiated endometrial adenocarcinoma cell line (KLE) was examined. EGF (10 ng/ml) and the tumor promoter, protein kinase C agonist, phorbol 12-myristate 13-acetate (PMA) were potent stimulators (P < 0.01) of DNA synthesis in this cell line as determined by [3H]thymidine incorporation into DNA. Staurosporine, a protein kinase C inhibitor, partially blocked the EGF effects on [3H]thymidine incorporation. Similarly, downregulation of protein kinase C also failed to completely abolish EGF effect on DNA synthesis and cell division. These results suggest that in the KLE cell line EGF stimulation of cell growth is exerted through both protein kinase C-dependent and -independent pathways.

Adenocarcinoma↗
PubMed1994

Exponential regression of CA 125 during salvage treatment of ovarian cancer with taxol.

The role of serum CA 125 in monitoring the response of epithelial ovarian cancer to treatment has been extensively investigated. The exponential regression curve [1n(CA 125) = i+s (days after initiation of treatment)] has been reported to describe the rate of change of serum CA 125 during treatment. In this model, the y-axis intercept (i) represents the initial CA 125-secreting tumor burden, while the slope (s) is determined by the response to treatment. The exponential regression curve was calculated for 66 patients undergoing salvage chemotherapy with taxol. At a mean follow-up of 121 days, 50 (75%) patients had progressed and 35 (53%) had died. Stratification of the patients by stage, grade, or histology did not reveal any significant differences in the regression rate. When the patients were stratified by response, the mean regression rate was 0.0157 +/- 0.011 for patients with progressive disease (N = 19) vs -0.0250 +/- 0.031 for those with stable disease (N = 25) and -0.0250 +/- 0.015 for those with a partial response (N = 22) (P < 0.0001). The regression rate did not correlate with progression-free interval or survival (P > 0.05). We conclude that changes in serum CA 125 levels follow an exponential regression curve in patients undergoing salvage chemotherapy with taxol for progressive or recurrent ovarian cancer. A positive regression rate may predict which patients will progress prior to the time progression becomes clinically evident. However, a negative rate fails to provide discriminatory utility in predicting progression-free interval or survival.

Adult↗
PubMed1994

Hard choices: the gynecologic cancer patient's end-of-life preferences.

Few reports in gynecologic literature have addressed patient preferences about terminal care. In light of the current discussions about end-of-life decision-making, a study was designed to assess the desires of patients with gynecologic cancer. A questionnaire was completed by 108 patients under treatment for gynecologic cancer at the University of Michigan Medical Center and by 39 patients from the routine gynecology clinic at the same institution. Participants were asked about their reactions to a poor prognosis, their desires for the location of terminal care, and their preferences for withdrawing or withholding life-sustaining technologies. Five percent of these cancer patients anticipated giving up the fight against their disease. Seventy-eight percent specifically expressed resolve to continue the fight against their disease. Feedback from these patients about their end-of-life preferences served to define the concept "fight." A majority preferred to receive care at home. Ninety percent of these cancer patients could envision their conditions deteriorating to the point that they would not want ventilator support. Thirty-four percent could envision refusing surgery for another life-threatening condition; 37%, a time when artificial nutrition would be refused; 22%, a time when antibiotics would be rejected. This study suggests that limiting the use of artificial respiratory support while continuing the use of artificial nutrition and hydration support would be consistent with the preferences of gynecologic cancer with end-stage disease.

Adult↗
PubMed1994

Characterization and accumulation pattern of an mRNA encoding an abscission-related beta-1,4-glucanase from leaflets of Sambucus nigra.

A cDNA library was produced using mRNA extracted from ethylene-treated leaflet abscission zones of common elder (Sambucus nigra). Screening of the library with the insert from pBAC10, which encodes an abscission beta-1,4-glucanase (cellulase) from bean (Phaseolus vulgaris), resulted in the isolation of a near-full-length cDNA which was designated JET 1. Northern analysis, using JET 1 as a probe, detected a transcript of 1.9 kb that accumulated prior to the first visible signs of cell separation. Accumulation of the JET 1 transcript is promoted by ethylene and primarily restricted to the tissue comprising the abscission zone. Sequence analysis of JET 1 indicates it is 1768 bp in length and shares significant homology at the amino acid level with beta-1,4-glucanases from the leaf abscission zone of P. vulgaris (67%) and ripening avocado fruit (48%). The predicted peptide sequence of the S. nigra enzyme contains two potential glycosylation sites. Genomic Southern analysis of S. nigra DNA reveals that JET 1 may belong to a multi-gene family.

Amino Acid Sequence↗
PubMed1994

Isolation of a mRNA encoding a nucleoside diphosphate kinase from tomato that is up-regulated by wounding.

A cDNA clone (TAB2) encoding a nucleoside diphosphate (NDP) kinase has been isolated from a tomato (Lycopersicon esculentum Mill. cv. Ailsa Craig) cDNA library. The clone is 590 bp long and exhibits a high degree of sequence identity with spinach NDP kinases I and II, Pisum sativum NDP kinase I, Arabidopsis thaliana NDP kinase, Drosophila melanogaster NDP kinase, Dictyostelium discoideum NDP kinase and human Nm 23-H1 and Nm23-H2. Northern analysis has revealed that the mRNA encoded by TAB2 is up-regulated in both leaf and stem tissue in response to wounding. The increase is apparent within 1 h of wounding and is not further elevated by application of ethylene. Southern blot analysis indicates that TAB2 is a member of a small gene family.

Amino Acid Sequence↗
PubMed1994

Characterization of a mRNA that accumulates during development of oilseed rape pods.

Dehiscence of oilseed rape pods, commonly known as pod shatter, is a process of agronomic importance that results in seed loss causing yield reductions and carry-over of the crop into the following growing season. In an effort to understand the mechanisms underlying this developmental event, the changes in gene expression that accompany pod shatter have been examined with a view to understanding how the process is regulated. In order to achieve this, cDNA library was constructed using mRNA extracted from the dehiscence zone of developing pods. Differential screening with non-dehiscence zone cDNA led to the isolation of a pod-specific clone, SAC25, with a transcript size of 1100 nucleotide encoding a predicted polypeptide of 34 kDa. The level of SAC25 mRNA accumulation increased during pod development. The sequence shows no significant homology to others within the databases but has two identifiable amino acid motifs, one is an adenine nucleotide binding site for NAD/FAD dehydrogenases and the other is a conserved feature of the ribitol dehydrogenase family. The amino acid sequence has four putative glycosylation sites and contains four cysteine residues. Genomic Southern analysis indicates that SAC25 may be encoded by a single gene or a small gene family. The function of this mRNA is unknown but possible roles in dehiscence and pod development are discussed.

Amino Acid Sequence↗
PubMed1994

The socio-economic impact of human Salmonella enteritidis infection.

Recent government and public concern about the recorded increase in human salmonellosis in the UK and abroad has stimulated investigations of both the causes and consequences of these infections. This paper discusses the framework for economic analysis of food-borne disease and problems associated with the estimation of costs. A brief review of the literature in this area is given and the results of a national study of the costs of human salmonellosis in England and Wales are presented and used to estimate the likely costs of S. enteritidis infection.

Adolescent↗
PubMed1994

Penile erection in the primate: induction with nitric-oxide donors.

The primate model has been used for investigations on the physiology and pharmacology of erection. Recent in vitro investigations indicate that nitric oxide acts as the mediator of penile erection, but in vivo primate studies are needed to corroborate these findings. Penile erections were induced in a primate model using intracavernosal injections of nitric oxide donors s-nitrocysteine (NO-CYS) and sodium nitroprusside (SNP), and acetylcholine (ACh) which stimulates the formation of nitric oxide. Penile length and intracavernosal pressures following agonist injection were compared with baseline (flaccid) and control erections (elicited by injection of a papaverine/phentolamine/PGE1 standard mixture). Dose-response curves for each drug were determined with respect to maximal intracavernosal pressure, duration of effect and penile length, and systemic arterial pressure was monitored. All three agents induced erections, with dose-dependent increases in cavernosal pressure and penile length. The maximal cavernosal pressure attained was similar for all three agents, but the duration of action was significantly shorter with ACh (p < .05). Injection of L-nitro-arginine-methyl-ester (L-NAME), a nitric oxide synthase inhibitor, before injection of the nitric oxide donor shortened the duration of effect but did not alter maximal cavernosal pressure or penile length attained. Although systemic hypotension was induced by each agent, digital compression at the base of the penis at the time of injection prevented such changes. These results suggest that the primate is a useful model to evaluate the action of substances that induce or inhibit penile erection. The findings provide support for the hypothesis that nitric oxide is a mediator of penile erection and that nitric oxide donors may be useful in the treatment of erectile dysfunction.

Acetylcholine↗
PubMed1994

Interleukin-4, -5, and -6 and tumor necrosis factor-alpha in normal and asthmatic airways: evidence for the human mast cell as a source of these cytokines.

Asthma is characterized by the presence of an inflammatory cell infiltrate in the bronchial mucosa consisting of activated mast cells, eosinophils, and T cells. Several cytokines are considered to play a pivotal role in this response, particularly interleukin (IL)-4, IL-5, IL-6, and tumor necrosis factor-alpha (TNF-alpha). In this study, we have used immunohistochemistry applied to thin glycol methacrylate sections of bronchial mucosal biopsies to define the cellular provenance of these cytokines in normal and asthmatic airways. Both the asthmatic and normal mucosa contained numerous cells staining positively for all four cytokines, with the majority identified as mast cells by their tryptase content. Eosinophils also accounted for some IL-5 immunostaining in the asthmatic biopsies. By using two monoclonal antibodies directed to different epitopes of IL-4, we provide tentative evidence for enhanced IL-4 secretion in asthma. Similarly, a sevenfold increase in the number of mast cells staining for TNF-alpha in the asthmatic biopsies suggests that this cytokine is also up-regulated in this disease. These findings clearly identify human mast cells as a source of IL-4, IL-5, IL-6, and TNF-alpha and add to the view that, along with T cells, mast cells may play an important role in initiating and maintaining the inflammatory response in asthma.

Adult↗
PubMed1994

Loss of heterozygosity and overexpression of the p53 gene in ovarian carcinoma.

Mutation and allelic loss of the p53 gene have been demonstrated in a variety of human cancers. In this study, DNA was extracted from formalin-fixed paraffin sections of ovarian carcinoma from 33 patients informative for a restriction fragment length polymorphism (RFLP) for BstU 1 within the 4th exon of the p53 gene. Allelic loss of p53 as indicated by loss of heterozygosity for this RFLP was demonstrated in 16/33 cases (48%). Because immunoreactivity for p53 correlates closely with the presence of mutation in the p53 gene, we performed immunohistochemical staining with the monoclonal antibody PAb1801. Diffuse nuclear p53 immunoreactivity was observed in 16 of the 33 (48%) informative cases used for loss of heterozygosity analysis (37/80 (46%) cases of ovarian carcinoma overall). A significant correlation (Fisher's exact test, P = 0.04) was observed between p53 overexpression and allelic loss. We found no evidence of association of p53 allelic loss or overexpression with advanced stage or other clinical or pathologic prognostic parameters. We conclude that mutation and allelic loss of p53 are common and probably related events in the development of ovarian carcinoma. This study demonstrates the use of paraffin sections in the analysis of p53 alterations in neoplasia.

Base Sequence↗
PubMed1994

Surgery for ovarian remnant syndrome. Lessons learned from difficult cases.

Ten cases of ovarian remnant syndrome jointly managed by gynecology and urology departments are presented. Complications of the surgery included a high incidence of ureteral and bowel injury. Preoperative, intraoperative and postoperative considerations may reduce the complications or minimize their significance. One case of ovarian cancer developed among the instances of ovarian remnant syndrome in this series. Preoperative, intraoperative and postoperative considerations can reduce the complications of surgery for ovarian remnant syndrome.

Adult↗
PubMed1993

Cost analysis of early discharge after hip fracture.

OBJECTIVE: To ascertain the economic impact of an early discharge scheme for hip fracture patients. DESIGN: Population based study comparing costs of care for patients who had "hospital at home" as an option for rehabilitation and those who had no early discharge service available in their area of residence. SETTING: District hospital orthopaedic and rehabilitation wards and community hospital at home scheme. PATIENTS: 1104 consecutively admitted patients with fractured neck of femur. 24 patients from outside the district were excluded. MAIN OUTCOME MEASURES: Cost per patient episode and number of bed days spent in hospital. RESULTS: Patients with the hospital at home option spent significantly less time as inpatients (mean of 32.5 v 41.7 days; p < 0.001). Those patients who were discharged early spent a mean of 11.5 days under hospital at home care. The total direct cost to the health service was significantly less for those patients with access to early discharge than those with no early discharge option (4884 pounds v 5606 pounds; p = 0.048). CONCLUSIONS: About 40% of patients with fractured neck of femur are suitable for early discharge to a scheme such as hospital at home. The availability of such a scheme leads to lower direct costs of rehabilitative care despite higher readmission costs. These savings accrue largely from shorter stays in orthopaedic and geriatric wards.

Aged↗
PubMed1993

In vivo imaging of the 5-hydroxytryptamine reuptake site in primate brain using single photon emission computed tomography and [123I]5-iodo-6-nitroquipazine.

Previous experiments have demonstrated that 5-iodo-6-nitro-2-piperazinylquinoline (5-I-6-NQP) is a potent and selective ligand for studying brain 5-hydroxytryptamine (5-HT) reuptake sites. We performed in vivo imaging in non-human primates using single photon emission computed tomography (SPECT) and the 123I-labeled compound [123I]5-I-6-NQP. These studies showed rapid brain uptake, with slow egress of the tracer from the brainstem, a region rich in 5-HT reuptake sites. Loss of the tracer from regions with a lower density of these sites, such as cerebellum, was relatively more rapid. Pretreatment of animals with paroxetine increased the washout of tracer from the brainstem to rates similar to that seen in cerebellum. Brainstem to cerebellar ratios of tracer accumulation were > 2 by 8 h after injection, and in paroxetine pretreated animals remained close to 1. These results indicate that the radiotracer has characteristics suitable for use as a SPECT imaging agent of serotonin reuptake sites.

Animals↗