Use of cardiac procedures in the United States and Canada.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to J Green.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
A wedding reception at a North Yorkshire hotel was followed by an explosive outbreak of gastroenteritis. The attack rate among the 111 guests was 50% and vomiting was a predominant feature. The results of laboratory and epidemiological investigations were consistent with a common source outbreak of small round structured virus (SRSV) infection genotype II. The source of the outbreak was traced to a kitchen assistant who suddenly became ill on the eve of the reception and vomited into a sink used for preparing vegetables. The sink was cleaned with a chlorine based disinfectant and used the next morning to prepare a potato salad, subsequently identified as the vehicle of infection in a cohort study of guests (odds ratio 3.21; CI 1.78-5.78, p = 0.0001). No other food was associated with illness. The outbreak provides further supporting evidence of the importance of vomiting in the transmission of SRSV infection, highlights the virulence of this group of viruses, and indicates their relative resistance to environmental disinfection and decontamination. It also highlights the need for the adequate training of catering staff and the implementation and enforcement of food hygiene regulations.
Osteoblasts are established targets of estrogen action in bone. We screened 66 conditionally immortalized clonal human osteoblast cell lines for estrogen receptors (ERs) using reverse transcriptase-polymerase chain reaction (RT-PCR) analysis for ER alpha mRNA and transactivation of adenovirus-estrogen response element (ERE)-tk-luciferase by 17 beta-estradiol (17 beta-E2) for functional ER protein. One of these cell lines, termed HOB-03-CE6, was chosen for further characterization. The cells, which were conditionally immortalized with a temperature-sensitive SV40 large T antigen, proliferated at the permissive temperature (34 degrees C) but stopped dividing at the nonpermissive temperature (> or = 39 degrees C). Alkaline phosphatase activity and osteocalcin secretion were upregulated by 1 alpha, 25-dihydroxyvitamin D3 in a dose-dependent manner. The cells also expressed type I collagen and other bone matrix proteins, secreted a variety of growth factors and cytokines, formed mineralized nodules based on alizarin red-S and von Kossa histochemical staining, and responded to dexamethasone, all-trans retinoic acid, and transforming growth factor-beta 1. This cell line expressed 42-fold less ER message than MCF-7 human breast cancer cells, as determined by quantitative RT-PCR. However, adenovirus-ERE-tk-luciferase activity was upregulated three- to fivefold in these cells by 17 beta-E2 with an EC50 of 64 pM. Furthermore, this upregulation was suppressed by co-treatment with the anti-estrogen ICI-182, 780. Cytosolic extracts of these cells specifically bound [125I]-17 beta-E2 in a concentration-dependent manner with a Bmax of 2.7 fmoles/mg protein (approximately 1,200 ERs/cell) and a Kd of 0.2 nM. DNA gel-shift analysis using a [32P]-ERE demonstrated the presence of ERs in nuclear extracts of these cells. Moreover, binding of the extracts to this ERE was blocked by a monoclonal antibody to the human ER DNA-binding domain. We evaluated these cells for 14 of 20 reported endogenous responses to 17 beta-E2 in osteoblasts. Although most of these responses appeared to be unaffected by the steroid, 17 beta-E2 suppressed parathyroid hormone-induced cAMP production, as well as basal interleukin-6 mRNA expression; conversely, the steroid upregulated the steady-state expression of alkaline phosphatase message in these cells. In summary, we have identified a clonal, conditionally phenotypic, human osteoblast cell line that expresses functional ERs and exhibits endogenous responses to 17 beta-E2. This cell line will be a valuable in vitro model for exploring some of the molecular mechanisms of estrogen action in bone.
"America's Best Hospitals," by US News & World Report, is a sophisticated and influential appraisal of hospital care. Using measures of health care structure, process, and outcome, the report identifies outstanding hospitals in 16 medical specialties through an overall "index of hospital quality." This strong conceptual design, however, has not been adequately implemented because national data sources for all 3 components are severely limited. Most importantly, since there are no national data on process of care, a reputation survey has been used to measure this component of quality. One consequence of reliance on reputation is that a small group of prominent hospitals in each specialty receives such high scores that they automatically rise to the top of the rankings, regardless of structure or outcome score. "America's Best Hospitals" identifies America's best regarded hospitals, but provides limited additional insight into quality. Adequate surveillance and protection of quality in an era of managed care requires measurement systems beyond the scope of existing data and methods.
Explore the source record for details and available documents.
UNLABELLED: The occurrence of rhabdomyosarcoma (RMS) primary in or metastatic to breast has been regarded as an uncommon event, associated with an unfavorable outcome. Records of 26 patients with diagnoses of breast RMS, either primary or secondary, entered in the Intergroup Rhabdomyosarcoma Study (IRS) (1972-1992) were reviewed and compared with data regarding 47 similar patients in published reports. Of the 26 IRS cases, the histologic subtype was alveolar in 24, embryonal in 1, and not determined in 1. All were female with ages ranging from 11.5 to 20.2 years (median, 15.2 years; mode, 14-16 years). This compact age distribution of both primary (n = 7) and metastatic (n = 19) breast RMS was seen in previously reported series. Among the 19 cases of RMS with initial dissemination to breast, primary tumor sites, were extremity (n = 8), nasopharynx/paranasal sinuses (n = 7), and trunk (n = 4). IRS treatment was risk-based according to site and extent of disease. Four of 7 patients with primary RMS remain disease free 2.9 to 7 years post diagnosis. Among 19 patients with RMS initially metastatic to breast, including 7 in IRS clinical group IV at original diagnosis, three are disease free at 7.6, 15.7 and 17.0 years. CONCLUSIONS: primary or metastatic RMS in breast is almost confined to adolescent females having tumors with alveolar histology. Approximately one-half of the patients with primary breast disease and 15% of those with metastatic breast disease as an initial recurrence are long-term survivors.
1. In previous studies we have shown that, after the administration of adriamycin, hypertension developed in rats who became pregnant (adriamycin-pregnant rats), whereas virgin animals remained normotensive. Subsequently, we showed that this hypertension was prevented by administration of L-arginine, suggesting that deficient synthesis of nitric oxide may be pathogenetic in this model. 2. To further assess the role of nitric oxide in this model, we measured mean arterial blood pressure after administration of L-arginine to adriamycin-pregnant rats or of NG-nitro-L-arginine-methyl ester (L-NAME) to normal pregnant rats. In other experiments, we assessed the response of isolated perfused arterial mesenteric vessels, precontracted with noradrenaline, to acetylcholine, L-arginine or L-NAME. 3. Blood pressure was decreased in normal pregnant rats, whereas it was elevated in adriamycin-pregnant rats. L-NAME treatment increased blood pressure in normal pregnant rats and L-arginine decreased it in adriamycin-pregnant rats. 4. Mesenteric vessels of adriamycin-pregnant rats exhibited an exaggerated vasoconstrictory response to noradrenaline, when compared with the blunted response observed in normal pregnancy. The addition of L-NAME in vitro induced a further contraction, significantly greater in normal pregnant rats. The vasodilatory response to acetylcholine and L-arginine was greater in vessels from adriamycin-pregnant rats. In contrast, responses to either nitroprusside or diazoxide were similar in all groups. 5. The results suggest a state of reduced nitric oxide synthesis in rats with adriamycin nephropathy, leading to vascular maladaption and hypertension in pregnancy.
BACKGROUND: Ulcerative colitis is predominantly a disease of non-smokers, and transdermal nicotine is therapeutic but often results in side-effects. Administration of nicotine as a liquid rectal enema results in less systemic nicotine absorption. AIM: To determine the safety and clinical response of nicotine tartrate liquid enemas for active left-side ulcerative colitis in a pilot study. METHODS: Ten non-smoking patients with mildly to moderately active left-sided ulcerative colitis unresponsive to first-line therapy were treated in an open protocol with nightly nicotine tartrate liquid enemas at a dose of 3 mg nicotine base for 1 week then 6 mg for 3 weeks. Clinical assessments were determined at baseline and 4 weeks by endoscopy, physician assessment and a patient diary of daily symptoms. Peak and trough serum nicotine and trough plasma cotinine were determined by gas chromatography/mass spectrometry and high performance liquid chromatography, respectively. RESULTS: After 4 weeks of treatment, 5/7 patients (71%) showed clinical and sigmoidoscopic improvement (per protocol analysis). The other three patients discontinued therapy within 7 days because of inability to retain the liquid enemas. No patients showed histologic improvement. Six of the patients who completed the 4-week study had peak and trough serum nicotine concentration determined, only 1 of 6 patients had a detectable peak nicotine concentration (value 2.3 ng/mL), and all six patients had undetectable trough nicotine concentrations. The mean trough plasma cotinine concentration was 13 +/- 10 ng/mL. Transient and mild adverse events occurred in 4/10 patients (nausea, lightheadedness, tremor, sleep disturbance). Given the low or undetectable serum nicotine concentrations, these adverse events are not likely to be related to the nicotine enemas. CONCLUSIONS: Nicotine tartrate liquid enemas administrated at a dose of 3 mg nicotine base/day for 1 week and then 6 mg/day for 3 weeks are safe and appear to result in clinical improvement in some patients with mildly to moderately active, left-sided ulcerative colitis unresponsive to first-line therapy. Placebo-controlled trials are warranted to confirm these preliminary findings.
BACKGROUND: Ulcerative colitis is predominantly a disease of non-smokers, and transdermal nicotine is therapeutic but often results in side-effects. Administration of nicotine tartrate as a liquid enema decreases systemic nicotine absorption and may be effective for treatment of active distal ulcerative colitis. Ileocolonic delivery of nicotine tartrate via a delayed release oral capsule would be the preferred route to deliver nicotine to the colon. AIM: To determine the bioavailability and pharmacokinetic parameters of delayed-release oral nicotine tartrate capsules (Eudragit S100 coated) at doses of 3 mg and 6 mg nicotine. METHODS: Twenty healthy human subjects received delayed-release oral nicotine tartrate at one of two doses (each group n = 10): 3 mg and 6 mg nicotine. All subjects also received intravenous nicotine tartrate (at a dose of 15 micrograms nicotine base/kg) during a separate study period. Serum nicotine concentrations were determined by gas chromatography-mass spectrometry. In addition, concentrations of serum cotinine (major nicotine metabolite) were determined by high-performance liquid chromatography in all samples for two subjects (both given 6 mg nicotine). Adverse reactions were determined by questionnaire. RESULTS: The mean bioavailabilities of nicotine after ileocolonic nicotine tartrate administration via delayed-release oral capsules at doses 3 mg and 6 mg nicotine were 41% and 42%, respectively. The ratios (after adjusting for nicotine dose) of cotinine area under the curve (AUC) for delayed-release oral nicotine to cotinine AUC for intravenous nicotine were 1.5 and 1.6 for the two subjects undergoing cotinine pharmacokinetics, demonstrating significant first-pass metabolism. Serum nicotine concentrations did not predict adverse reactions. CONCLUSIONS: Nicotine tartrate delivered to the ileocolon as a delayed-release oral capsule at doses of 3 mg and 6 mg nicotine considerably reduced systemic nicotine bioavailability. This reduction in bioavailability appears to be a result of first-pass hepatic metabolism rather than poor mucosal absorption of nicotine. The therapeutic potential of an ileocolonic delivery formulation of nicotine tartrate, which can potentially limit toxicity by local delivery of high doses of nicotine, should be investigated in patients with ulcerative colitis.
The hlyX gene of the pig pathogen Actinobacillus pleuropneumoniae encodes HlyX, a homologue of FNR, the anaerobic transcription regulator of Escherichia coli. The hlyX gone complements the anaerobic respiratory deficiencies of E. coli fnr mutants but also induces the expression of an otherwise latent haemolysin. Therefore, FNR and HlyX have distinct but overlapping regulons. The hlyX gene has been overexpressed as a gst::hlyX fusion and the HlyX protein purified. Similar to FNR, HlyX can acquire a [4Fe-4S] cluster, which promotes binding to the FNR box (Kd of 20-30 nM) under anaerobic conditions. Expression of hlyX in E. coli induced the anaerobic production of at least five polypeptides, including the yfiD gene product, which were not induced by fnr. Analysis of the yfiD promoter region revealed the presence of two FNR boxes situated at -61.5 and -114.5. Consistent with this observation, expression from the semi-synthetic Class I promoter FF + 20pmelR was efficiently activated by HlyX but not by FNR. The weaker level of FNR-mediated activation of Class I promoters suggests that there is a poorer activating contact (activating region 1 (AR1) equivalent) between FNR and RNA polymerase at these promoters and that HlyX possesses an additional or improved AR1. The AR1 of HlyX is partially characterized by a surface-exposed region around amino acid A187, which confers the altered specificity and provides an explanation for the existence of distinct but overlapping HlyX and FNR regulons.
BACKGROUND: The research described in this paper arose out of the need to address the growing waiting list for orthodontic treatment in Northamptonshire. Although the prevalence of dento-facial anomalies is the same across time, sex, race and socio-economic class, studies in the United States and this country suggest that certain groups are over-represented among patients who receive orthodontic treatment. The introduction of valid and reliable indices of therapeutic need such as the index of Orthodontic Treatment Need (IOTN) will allow improved focusing of services. The aim of the study was to determine the variables affecting access to orthodontic care, and the extent to which services were delivered according to objective measures of need. METHODS: Analyses were undertaken for speed, appropriateness, timing of referral, duration and complexity of the pathway for new referrals to specialist orthodontic care. possible explanations for the length of pathway were examined, including socio-demographic factors, location of residence and the IOTN. RESULTS: A total of 405 patients were approached, of whom 400 (99 per cent) agreed to participate. There was an over-representation among socio-economic groups I and V among patients referred to orthodontic treatment. By contrast, those of male sex and from socio-economic class IV were under-represented. This appeared to be the case irrespective of treatment setting. There was also a wide range of waiting times to treatment and complexity of pathway. Over a quarter of the sample had been inappropriately referred, and objective need as measured by the IOTN was not a determinant in the speed of access to specialist treatment. Adult patients waited longer for treatment. CONCLUSIONS: These results suggest that the delivery of care is neither based on objective need nor equitably distributed. More appropriate directing of resources is required, using the IOTN and agreed protocols, so that referrals are made to the most suitable provider.
Explore the source record for details and available documents.
Pregnancy-associated glycoprotein (PAG)-1 (PAG1) and pregnancy-specific protein B are either identical or closely related antigens released by trophoblast binucleate cells of placentas of cattle. Sheep and other ruminants produce similar products. There is evidence, however, that these antigens, which are related structurally to the pepsinogens and other aspartic proteinases, are not single gene products but members of an extensive family. Here, the sequential use of ammonium sulfate precipitation and Sepharose blue, anion-exchange, and cation-exchange chromatographies, as well as isoelectric elution from a Mono P column, has allowed several PAG1-related molecules to be purified from the medium after culture of explants from Day 100 sheep placentas. Each of these PAGs cross-reacted to a varying extent with a panel of three different anti-PAG1 antisera. Four of them, all of which were major secretory products of the placenta, were subjected to amino-terminal microsequencing. Although each was related to ovine (ov) PAG1, none was identical. Reverse transcription-polymerase chain reaction was then used to amplify PAG1-related cDNA from Day 100 placental RNA. Seven novel full-length cDNA, all distinct from ovPAG1, were identified from 25 cDNA selected for sequencing. Only two of these (ovPAG3 and ovPAG7) encoded polypeptides identical in sequence at their inferred amino termini to one of the PAGs (ovPAG65) purified from explant cultures. Even so, they were only 84% identical in overall sequence. The remaining five cDNA were unique. In situ hybridization analysis revealed that expression of ovPAG3 and ovPAG7, like that of ovPAG1, is confined to trophoblast binucleate cells. The data confirm that at Day 100 of pregnancy the ovine placenta produces many different PAGs, which differ considerably in sequence and immunological cross-reactivity.
Twelve of 14 proximal third tibial shaft fractures were successfully treated with a new technique for intramedullary nailing of these fractures. The average anterior displacement was 3.0 mm (range 0-17). The average coronal plane alignment was 2.0 degrees valgus (range 2 degrees varus to 12 degrees valgus). There was one nonunion. The technique's success is dependent on neutralizing the primary factors causing malreduction: wide effective diameters of tibial nails, narrow diameter of the medial tibial metaphysis, and a posteriorly directed sagittal plane entrance angle.
Regular proficiency testing of pathologists and cytotechnologists who undertake the analysis of cervical smears has been carried out in cytology laboratories in the North Thames (West) region since 1989. The protocol followed is one that has been adopted nationally. Since the scheme started, laboratory personnel from 17 cytology laboratories in the Region have participated and seven rounds of testing have been completed. Nine hundred and seventy-one tests were carried out and a pass rate of 96.4% was recorded. Two hundred and forty-seven cytologists took the test on at least one occasion and 63 cytologists took part in all seven rounds. Our results indicate that proficiency testing is capable of detecting cytologists who consistently perform below an acceptable standard and require retraining. They also show that even the most competent screeners can miss an abnormal smear. Seven cytologists who had proved their competence to screen on six occasions, missed an abnormal smear on the seventh, despite the fact that they were screening under test conditions when their vigilance should have been at its peak. Our findings indicate that false-negative reporting will inevitable occur during manual screening, and emphasize the need for further research into the causes and prevention of screening error.
Explore the source record for details and available documents.
HIV presents a number of challenges to the dentist. There is a need to control infection risks and, in spite of all the information available, a minority of dentists still have incomplete infection control procedures. The reasons for this and the implications for dental education are explored. There is also a need to ensure that the patient is optimally managed by the dentist and the importance of linkages to other services and the likely demands of patients on the dentist are reviewed. Finally the impact of treating the patient with HIV disease on the dentist and ways of minimising stress associated with the work are considered.