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Biomedical subjects

R Williams

Publications and source records attributed to R Williams.

At least 289 records · Page 16Linked to original sources
PubMed1998

Autoimmune hepatitis overlapping with primary sclerosing cholangitis in five cases.

OBJECTIVE: We report five cases (four male; median age 20 yr, range 14-38 yr) of an autoimmune hepatitis/primary sclerosing cholangitis overlap syndrome. The patients presented with jaundice, elevated serum aminotransferase and alkaline phosphatase activities, hyperglobulinemia with high immunoglobulin G (IgG) levels, circulating antinuclear and/or smooth muscle autoantibodies (> or = 1:40), and moderate to severe interface hepatitis on liver biopsy (with biliary features in four). METHODS: All five fulfilled criteria for diagnosis of "definite" autoimmune hepatitis and showed marked responses to prednisolone and azathioprine therapy, with relapses occurring during reduction or withdrawal of treatment. Cholangiographic features of primary sclerosing cholangitis were found in three patients at presentation and after intervals of 7 and 14 yr in the other two. Only two had evidence of inflammatory bowel disease. Diagnostic criteria for identifying those patients who may benefit from immunosuppressive therapy were reviewed. RESULTS: Review of the literature revealed only 11 similar cases that were sufficiently well described for comparison. However, in contrast to these and the present cases, preliminary data from other studies have suggested a marked association with ulcerative colitis and a poor response to immunosuppressive therapy. CONCLUSIONS: It is recommended that the possibility of an autoimmune hepatitis/primary sclerosing cholangitis overlap syndrome responsive to immunosuppressive therapy should be considered in any patient presenting with a hepatitic illness with hyperglobulinemia, antinuclear or smooth muscle autoantibodies, and biliary changes on liver biopsy. Cholangiography should be considered in such patients.

Adolescent↗
PubMed1998

Neisseria gonorrhoeae induces focal polymerization of actin in primary human urethral epithelium.

The pathogenic Neisseria species induce cytoskeletal reorganization in immortalized cell lines. In Chang conjunctival epithelium and T84 intestinal epithelium, focal cytoskeletal rearrangements in which bacteria contacted the epithelial surface were observed. We show that actin footprints are induced in gonococcus-challenged primary urethral epithelium. Moreover, the microbes induced microvillus extension from the epithelial cell surface. Our results indicate that formation of actin footprints is not an artifact of commonly used immortalized cell lines.

Actins↗
PubMed1998

Acute liver failure secondary to hepatic infiltration: a single centre experience of 18 cases.

BACKGROUND: Acute liver failure (ALF) secondary to malignant infiltration of the liver is rare and is diagnosed often only after death. AIMS: To determine diagnostic factors and particular clinical patterns of illness. METHODS: Review of case notes from all patients with ALF secondary to hepatic infiltration admitted to this unit over an 18 year period (1978-1995). RESULTS: From a total of 4020 admissions, 18 patients were identified with ALF attributable to hepatic infiltration. Mean age was 40.7 years. Aetiology was non-Hodgkin's lymphoma in nine patients, Hodgkin's disease in three, infiltrative metastatic carcinoma in four, and haemophagocytosis with no precipitant cause in two cases. Prodromal symptoms were non-specific, but occurred at least two to four weeks before onset of ALF, making the presence of such symptoms of value in differential diagnosis of the cause of ALF. Clinical examination and investigations were unhelpful in distinguishing these cases from more usual causes of ALF. Usually, the clinical course was of rapid deterioration and death from multiorgan failure, and only one patient survived. Diagnosis was made during life in 15 patients. Histology showed evidence of widespread hepatocellular necrosis, with diffuse infiltration by tumour cells rather than focal cellular aggregation. CONCLUSIONS: Only with accurate histological diagnosis from liver biopsy and institution of specific therapy early in the management of such patients will the best chance of recovery be achieved. In every case of ALF with prodromal symptoms or abnormal imaging, hepatic histology should be obtained by liver biopsy as soon as possible to diagnose infiltrative hepatic disease.

Adolescent↗
PubMed1998

Generational continuity and change in British Asian health and health behaviour.

OBJECTIVES: To trace patterns of health and health behaviour in those with ancestry in the Indian subcontinent (British Asians) compared with the general population of their age (1) in the younger generation age 14-15 mainly born in the UK and (2) in the older mainly migrant generation. DESIGN: Cross sectional random sample surveys of two age groups in Glasgow. SAMPLES: 334 British Asians (86% born in the UK) and 490 non-Asians, all aged 14-15; 173 British Asians aged 30-40 (mean age 35, 93% born abroad), and 344 general population aged 35. MEASURES: Health: self assessed health/fitness, longstanding/limiting illness, chronic phlegm, accidents, symptoms, tooth loss. Health behaviour: smoking, alcohol, drugs, exercise. RESULTS: At age 14-15, compared with non-Asian counterparts: fewer British Asian girls reported limiting illness (p < 0.05) or chronic phlegm (p < 0.01), fewer boys reported accidents (p < 0.01), and fewer of both sexes had lost second teeth (p < 0.05); more of both sexes reported not smoking, drinking alcohol, or using drugs (p < 0.01 or below), fewer reported frequent exercise (p < 0.05 or below). Smoking patterns were consistently related to ethnic differences in chronic phlegm, and patterns of alcohol consumption to those in accidents. In health, British Asian girls aged 14-15 generally compared more favourably with non-Asian counterparts than did those aged 30-40. The reverse was true for British Asian male subjects. In health behaviour, British Asians of both sexes aged 14-15 showed strong continuities with those aged 30-40. CONCLUSIONS: Favourable health behaviour has brought a health advantage to young British born Asians, even though this was not the case in the migrant generation. Female health disadvantage is also much less marked than in migrants aged 30-40, but may re-emerge between ages 15-30. Migrant Asian male subjects may have had misleadingly high respiratory health levels because of positive selection.

Adolescent↗
PubMed1998

Assessing local health needs in primary care: understanding and experience in three English districts.

BACKGROUND: Assessing the health needs of a local population has been promoted as a key component in effective targeting of healthcare services and quality improvement. The understanding and experience of assessing health needs in general practice were investigated in three English districts. AIM: To identify the issues surrounding the potential for assessing health needs in primary care. METHOD: Postal survey of 347 general practices in three health authorities. Telephone interviews with a random stratified sample of 35 general practitioners. RESULTS: Although most practices identified assessing health needs as important, it is clear that this identification was typically based on an understanding of assessing needs as primarily focused on individual patient care, based on clinical priorities and involving practice held data. Most practices had not undertaken local consultation, whatever their understanding of assessing health needs. The few practices which had completed population oriented, proactive assessment of needs considered it to have led to tangible improvements in clinical or practice management. Overall, there was apparent confusion over the nature and purpose of assessing needs, although the principled aims and objectives of a population oriented, proactive component to primary care were generally upheld. The need for additional resources and support was identified. In four out of the five cases where specifically population based assessment of health needs had been undertaken, the local public health department had been involved. CONCLUSION: The value of the concept of assessing health needs in primary care holds considerable uncertainty and ambivalence. The findings from this study show that any attempts to promote assessing needs into primary care which focus either primarily or exclusively on the provision of "education" are unduly simplistic. More fundamental questions about the perceived relevance and opportunities for assessing health needs should be considered if primary care groups are to meet future commissioning challenges.

Community Health Planning↗
PubMed1998

Hospital days in clozapine-treated patients.

OBJECTIVE: To examine inpatient hospital days used by a group of patients with treatment-resistant schizophrenia for 3 years before and 3 years after clozapine initiation. METHOD: A retrospective chart review of 26 consecutive admissions to an outpatient clozapine clinic was conducted for a 6-year period. The total number of hospital days was recorded. RESULTS: Patients separated into 3 groups: those who used clozapine for 3 uninterrupted years (N = 11, 42.3%), those who interrupted but resumed clozapine and continued on to 3 years (N = 4, 15.4%), and those who abandoned clozapine treatment (N = 11, 42.3%). Only the group that was continuously on clozapine showed a decline in percentage of inpatient days during the 3-year follow-up period. Three of the 11 patients who discontinued clozapine died during the posttreatment period: 2 suicides and 1 "death by misadventure." CONCLUSIONS: Continuous clozapine treatment significantly reduces days in hospital; this reduction was sustained throughout 3 years' follow-up. While the sample size is small, all patients were tracked over a 6-year period, and both drug continuers and dropouts were followed. The reduction in inpatient days may be lost if patients stop and then restart clozapine. For patients who do not respond to or abandon trials of clozapine, there is an urgent need to develop more effective treatment strategies.

Adult↗
PubMed1998

Assessment and management of antipsychotic-induced adverse events.

OBJECTIVE: To review and discuss the spectrum of adverse events caused by antipsychotic agents that can directly influence the outcome of treatment by interfering with patient acceptance of and adherence to therapy. METHOD: The adverse effects of traditional and second-generation antipsychotic medications were discussed during a series of clinical workshops attended by psychiatrists from across Canada. The various adverse effects of antipsychotic drugs as well as their assessment and management are reviewed. RESULTS: Simple techniques for assessing adverse effects such as extrapyrimidal symptoms (EPS) are described. In some cases, adverse effects can be managed by dosage reduction and/or the use of adjunctive therapies such as antiparkinsonian agents and benzodiazepines. However, in some patients dose reduction carries the risk of symptom reemergence, while the commonly used adjunctive medications are associated with adverse effects of their own. CONCLUSIONS: Treatment-related side effects often require a reduction in dosage or a change in medication. Proper management can help encourage patient compliance and improve the outcome of antipsychotic treatment. The availability of the newer atypical antipsychotics offers another alternative, because they are associated with a much lower incidence of antipsychotic-induced side effects.

Akathisia, Drug-Induced↗
PubMed1998

Room service improves patient food intake and satisfaction with hospital food.

Cancer therapy causes side effects that interfere with oral intake. Frequently, patients undergoing such therapy suffer from anorexia, nausea, vomiting, food aversions, dysgeusia, and xerostomia, all which adversely affect oral intake. Adequate nutrition intake is an important part of therapy for the cancer patient, especially when that patient is a child. Children who are well nourished are better able to withstand infection and tolerate therapy. Parents and staff at our hospital have worked diligently to improve patient's oral intake with limited success. Hence, a multidisciplinary team was organized to develop a new approach to food services that would improve patients' oral intake. The team initiated patient "room service," and patients were allowed to call the kitchen when they were ready to eat. The system works much like room service in a hotel. After the introduction of room service, patients' caloric intake improved significantly (P = .008), and protein intake increased by 18%. Patient satisfaction with hospital food service also improved; excellent ratings increased by as much as 35%. We conclude that room service is a viable alternative to traditional food services in the pediatric oncology setting and may be useful in other patient populations, such as maternity and general pediatrics.

Boston↗
PubMed1998

Quality of life and cancer pain: satisfaction and side effects with transdermal fentanyl versus oral morphine.

PURPOSE: To compare pain-related treatment satisfaction, patient-perceived side effects, functioning, and well-being in patients with advanced cancer who were receiving either transdermal fentanyl (Duragesic, Janssen Pharmaceuticals, Titusville, NJ) or sustained-release oral forms of morphine (MS Contin, Perdue Frederick Co, Norwalk, CT, or Oramorph SR, Roxanne Laboratories, Columbus, OH). PATIENTS AND METHODS: A total of 504 assessable cancer patients participated in this cross-sectional, quality-of-life study. Relevant elements of four validated scales were used--the Functional Assessment of Cancer Therapy-General (FACT-G) scale, the Brief Pain Inventory (BPI), the Medical Outcomes Study (MOS) questionnaire, and the Memorial Symptom Assessment Scale (MSAS)--as well as original scales that were developed and validated for this study. RESULTS: The majority of patients in both treatment groups had late-stage (IV/D) cancer. Patients who received transdermal fentanyl were more satisfied overall with their pain medication than those who received sustained-release oral forms of morphine (P = .035). Fentanyl patients also experienced a significantly lower frequency (P < .002) and impact (P < .001) of pain medication side effects. These results occurred despite the fact that cancer patients who received fentanyl were significantly older (P < .001) and had significantly lower functioning and well-being scores (P = .001). Measures of pain intensity, sleep adequacy, and symptoms demonstrated no significant differences between treatment groups. CONCLUSION: These data suggest that patients are more satisfied with transdermal fentanyl compared with sustained-release oral forms of morphine. A lower frequency and reduced impact of side effects with transdermal fentanyl may be one reason cancer patients who receive fentanyl are more satisfied with their pain management.

Administration, Cutaneous↗
PubMed1998

Circumflex coronary artery dissection following waterskiing.

A previously healthy 35-year-old woman experienced chest discomfort following mild blunt chest trauma while waterskiing. During the following 48 h, she underwent evaluation in two separate emergency departments (EDs) where she was found to have normal ECGs and cardiac enzyme values. She was subsequently discharged from both EDs. Twelve hours after the second ED visit, she was discovered unconscious at home and was resuscitated from ventricular fibrillation. Emergency cardiac catheterization demonstrated moderate circumflex disease without angiographic evidence of a false lumen or intimal flap. Left ventriculography demonstrated posterolateral wall hypokinesis. Eight days after remaining ventilator-dependent and unconscious, the patient was declared brain-dead. At autopsy, the patient was found to have a dissection of the circumflex artery. Waterskiing is an unusual source of cardiac trauma; however, we believe this to be the first reported case of dissection in the circumflex artery following blunt chest trauma.

Adult↗
PubMed1998

Pediatric cardiac surgery: the effect of hospital and surgeon volume on in-hospital mortality.

OBJECTIVE: To examine the relationship between annual provider (hospital and surgeon) volume of pediatric cardiac surgery and in-hospital mortality. DESIGN: Population-based retrospective cohort study using a clinical database. SETTING: The 16 acute care hospitals in New York with certificate of need approval to perform pediatric cardiac surgery. PATIENTS: All children undergoing congenital heart surgery in New York from 1992 to 1995. MAIN OUTCOME MEASURES: Risk-adjusted mortality rates for various hospital and surgeon volume ranges. Adjustments were made for severity of illness using logistic regression. RESULTS: A total of 7169 cases were analyzed. After controlling for severity of preprocedural illness using clinical risk factors, hospitals with annual pediatric cardiac surgery volumes of fewer than 100 had significantly higher mortality rates (8.26%) than hospitals with volumes of 100 or more (5.95%), and surgeons with annual volumes of fewer than 75 had significantly higher mortality rates (8.77%) than surgeons with annual volumes of 75 or more (5.90%). CONCLUSIONS: Both hospital volume and surgeon volume are significantly associated with in-hospital mortality, and these differences persist for both high-complexity and low-complexity pediatric cardiac procedures.

Cardiac Surgical Procedures↗
PubMed1998

Periodontitis: a risk factor for coronary heart disease?

This paper evaluates the current information on the relationship between oral disease (specifically periodontitis) and atherosclerosis/coronary heart disease (CHD) to determine whether the information is sufficient to conclude that periodontitis is a risk factor for atherosclerosis/CHD. As background for this evaluation, the term "risk factor" is defined, and the 3 criteria used to establish exposures as risk factors are reviewed. In addition, epidemiologic criteria for defining an exposure as causal are presented. The available evidence then is evaluated according to the criteria for causality, which are extensions of the criteria for establishing a risk factor. This review is done in the context of the relationship between atherosclerosis/CHD and inflammation. A number of findings are briefly reviewed that link inflammation and atherosclerosis/CHD, such as: 1) prior flu-like symptoms were more common in cases of myocardial infarction than in concurrently sampled controls; 2) high levels of cytomegalovirus antibody titers were associated with elevated carotid intimal-medial wall thickness 18 years later; 3) prior infection with cytomegalovirus was a strong independent risk factor for restenosis after coronary atherectomy; 4) dental infections were more common in cases of cerebral infarction compared to community controls matched on age and sex; and 5) the gingival index was significantly correlated with fibrinogen and white cell counts in periodontal patients and controls, adjusted for age, smoking, and socioeconomic status. Three case-control studies and 5 longitudinal studies investigating the relationship between dental conditions and atherosclerosis/CHD are reviewed in terms of strength of associations, consistency of associations, specificity. of associations, time sequence between exposure and outcome, and degree of exposure and outcome. Related to the last criterion, new findings are presented which indicate that the extent of the periodontal infection, a measure reflecting microbial burden, also is related to onset of new CHD events. Our previously published model describing the potential biological mechanisms underlying the associations found is reviewed. This model places the associations into a context of an intrinsic or acquired hyperinflammatory monocyte trait that results in a more intense inflammatory response to lipopolysaccharide (LPS) challenges, such as periodontal infections. This hyperinflammatory response may promote atheroma formation and thromboembolic events. finally, new findings from ongoing animal studies are presented, indicating that high fat diets in atherosclerotic-susceptible mice induce greater inflammatory responses to Porphyromonas gingivalis challenges. We conclude that the available evidence does allow an interpretation of periodontitis being a risk factor for atherosclerosis/CHD. This conclusion, however. is made with some qualifications. While the associations found across a wide variety of subjects are remarkably consistent, for the most part they are represented by incidence odds ratios around 2.0. While this level of association would result in oral conditions contributing to a large number of CHD cases, it is possible that associations of this magnitude are due to bias in the study designs. In addition, some studies report that periodontitis is associated with all-cause mortality and low birth weight infants. These multiple associations detract from the credibility of periodontitis as a risk factor, as specificity of association is more often related to causality. However, all-cause mortality may largely be driven by mortality from cardiovascular events: and some exposures, such as smoking. are indeed risk factors for multiple conditions. On the other hand, current findings regarding the associations between oral conditions and atherosclerosis/CHD imply that the criteria for causality may be met in the not-too-distant future.

Animals↗
PubMed1998

Validity of insurance information on California birth certificates.

OBJECTIVES: This study assessed the validity of health insurance information on California birth certificates. METHODS: Insurance information from birth certificates and linked face-to-face interviews was compared for 7428 postpartum women in California. RESULTS: There was excellent agreement between insurance information in birth certificate and interview data, especially when capitated plans were grouped with all other private coverage. Analyses using both data sources produced similar estimates of the likelihood of untimely prenatal care according to type of insurance coverage. CONCLUSIONS: Birth certificate data including insurance information appear to be an appropriate resource for examining both the extent of coverage for maternity care and associations between prenatal care use and insurance status.

Birth Certificates↗
PubMed1998

Analysis of N-ras gene mutation and p53 gene expression in human hepatocellular carcinomas.

AIM:To study the relationship between N-ras gene mutation and p53 gene expression in the carcinogenesis and the development of human hepatocellular carcinomas (HCC).METHODS:The N-ras gene mutation and the p53 gene expression were analyzed in 29 cases of HCC by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) and immunohistochemistry.RESULTS:Thirteen cases of HCCs were p53 positive (44.8%), which showed a rather high Cpercen-tage of p53 gene mutation in Guangxi. The aberrations at N-ras codon 2-37 were found in 79.31% of HCCs and 80.77% of adjacent non-tumorous liver tissues. More than 2 point mutations of N-ras gene were observed in 22 cases (75.86%). Twelve cases (41.37%) of HCCs showed both N-ras gene mutation and p53 gene expression.CONCLUSION:N-ras gene and p53 gene may be involved in the carcinogenesis and the development of HCC.That 38% of HCCs with N-ras gene mutation did not express p53 protein indicates that some other genes or factors may participate in the carcinogenesis and the development of HCC.

Journal Article↗
PubMed1998

Discovery of MC-02,331, a new cephalosporin exhibiting potent activity against methicillin-resistant Staphylococcus aureus.

A systematic approach toward building activity against methicillin-resistant staphylococci into the cephalosporin class of beta-lactam antibiotics is described. Initial work focused on finding the optimal linkage between the cephem nucleus and a biphenyl pharmacophore, which established that a thio linkage afforded potent activity in vitro. Efforts to optimize this activity by altering substitution on the pharmacophore afforded iodophenylthio analog MC-02,002, which although highly potent against MRSA, was also highly bound to serum proteins. Further work to decrease serum protein binding showed that replacement of the iodo substituent by the positively-charged isothiouronium group afforded potent activity and reduced serum binding, but insufficient aqueous solubility. Solubility was enhanced by incorporation of a second positively-charged group into the 7-acyl substituent. Such derivatives (MC-02,171 and MC-02,306) lacked sufficient stability to staphylococcal beta-lactamase enzymes. The second positive charge was incorporated into the cephem 3-substituent in order to utilize the beta-lactamase-stable aminothiazolyl(oximino)acetyl class of 7-substituents. These efforts culminated with the discovery of bis(isothiouroniummethyl)phenylthio analog MC-02,331, whose profile is acceptable with respect to potency against MRSA, serum binding, aqueous solubility, and beta-lactamase stability.

Animals↗