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Biomedical subjects

J Williams

Publications and source records attributed to J Williams.

At least 253 records · Page 14Linked to original sources
PubMed2000

Altered sleeping arrangements in pediatric patients with epilepsy.

Parental fears concerning seizure occurrence may be associated with behavioral changes within the home environment. One possible change involves sleeping arrangements. Questionnaires concerning demographics, medical history, and sleeping arrangements were completed by parents of 179 children with epilepsy and by parents of 155 children with diabetes for comparison purposes. Based on parental response, 40 (22%) children with epilepsy changed to less independent sleeping arrangements. Logistic regression suggested that parental concern over seizure occurrence was highly associated with this change (p=<0.001). In contrast, 13 (8%) of the children with diabetes changed to a less independent sleep pattern. Results suggest changes in sleeping arrangements may alert the pediatrician to possible parental anxiety that may need to be addressed.

Adolescent↗
PubMed2000

Familial influence on variation in age of onset and behavioural phenotype in Alzheimer's disease.

BACKGROUND: Alzheimer's disease manifests considerable heterogeneity, the cause of which is unknown. AIMS: To determine the familial (genotypic) influence on phenomenology (phenotype) in Alzheimer's disease. METHOD: Affected sibling pairs with Alzheimer's disease were assessed for a range of cognitive and non-cognitive symptoms. Resemblance for phenotypic characteristics was estimated using intraclass correlations for continuous traits and by pairwise concordance for dichotomous traits. The relationship between age of onset and APOE genotype was examined using linear regression analysis. RESULTS: Significant familial effects on age of onset (intraclass correlation 0.41) and mood state (intraclass correlation 0.26), and a relatively high pairwise concordance for agitation (excess concordance 0.1) were found. The APOE locus was found to account for 4% of the variance in age of onset. CONCLUSIONS: Substantial familial influence on age of onset, depression and agitation suggests that genotype does influence phenotype in Alzheimer's disease. Establishing the molecular basis for this phenotypic variation may prove relevant to other neuropsychiatric disorders.

Affect↗
PubMed2000

APOE epsilon 4 influences the manifestation of Alzheimer's disease in adults with Down's syndrome.

BACKGROUND: Recent studies of the relationship between the apolipoprotein E (APOE) gene and Alzheimer's disease in adults with Down's syndrome have revealed inconsistent results. AIMS: To assess the role of the APOE gene in the manifestation of Alzheimer's disease in adults with Down's syndrome. METHOD: We studied the APOE genotypes of 24 adults with dementia and 33 non-demented adults with Down's syndrome over 35 years of age, and an additional group of 164 non-learning disabled adults. We also carried out a meta-analysis of all previously published studies of association between APOE and Down's syndrome, incorporating the current data. RESULTS: We observed a non-significant excess of APOE epsilon 4 and a reduction of epsilon 2 in adults with dementia compared with non-demented adults with Down's syndrome in our sample. However, meta-analysis showed a significantly higher frequency of epsilon 4 in adults with dementia compared with non-demented adults with Down's syndrome (odds ratio = 2.02, 95% CI 1.33-3.07, P = 0.001), but no significant reduction in the frequency of epsilon 2. CONCLUSIONS: The APOE epsilon 4 allele acts as a risk factor for the age-specific manifestation of Alzheimer's disease in people with Down's syndrome.

Adult↗
PubMed2000

Assessment of the stanford V regimen and consolidative radiotherapy for bulky and advanced Hodgkin's disease: Eastern Cooperative Oncology Group pilot study E1492.

PURPOSE: This study was performed, in a multi-institutional setting, to evaluate the efficacy and feasibility of the Stanford V chemotherapy regimen plus radiotherapy to bulky Hodgkin's disease sites. PATIENTS AND METHODS: A two-stage design was implemented in a phase II study involving 47 patients with bulky mediastinal stage I/II or stage III/IV Hodgkin's disease. Twelve weeks of the Stanford V chemotherapy regimen were given with consolidative radiotherapy (36 Gy) to lymph nodes >/= 5 cm and/or macroscopic splenic disease. Treatment was administered in one of five institutions participating in the Eastern Cooperative Oncology Group. RESULTS: With a median follow-up of 4.8 years, 45 patients are alive and 40 have been continuously disease-free. The estimated freedom from progression was 87% at 2 years and 85% at 5 years. Overall survival was 96% at 2 and 5 years. There was one death from Hodgkin's disease and one death from an M5 acute leukemia. Six of seven relapsed patients received high-dose therapy and autologous stem-cell transplantation. The freedom from second progression for the seven relapsed patients was estimated at 98% at 3 years. CONCLUSION: Stanford V chemotherapy and consolidative radiotherapy to bulky disease is effective in bulky and advanced Hodgkin's disease in a multi-institutional setting. On this basis, an Intergroup study comparing doxorubicin, bleomycin, vinblastine, and dacarbazine with the Stanford V regimen has been initiated.

Adolescent↗
PubMed2000

Gene therapy strategies for intracranial tumours: glioma and pituitary adenomas.

Intracranial tumours such as brain gliomas and pituitary adenomas pose a challenging area of research for the development of gene therapy strategies, both from the point of view of the severity of the diseases, to the physiological implication of gene delivery into the central nervous system and pituitary gland. On the one hand, brain gliomas are very malignant tumours, with a life expectancy of six months to a year at the most after the time of diagnosis, in spite of advances in treatment modalities which involve chemotherapy, surgery and radiotherapy. Gene therapy for these tumours is therefore a very attractive therapeutic modality which due to the severity of the disease is already in clinical trials. On the other hand, pituitary tumours are usually benign, and in most cases, treatment is successful. Nevertheless, there are some instances, especially with the macroadenomas and some invasive tumours in which treatment fails. Gene therapy strategies for these adenomas therefore needs to progress substantially in terms of safety, adverse side effects and physiological impact on the normal pituitary gland before clinical implementation. In this paper, we will review gene delivery systems both viral and non-viral and several therapeutic strategies which could be implemented for the treatment of these diseases. These include cytotoxic approaches both conditional and direct, immune-stimulatory strategies, anti-angiogenic strategies and approaches which harness pro-apoptotic and tumour suppressor gene targets. We will also review the models which are currently available in which these gene therapy strategies can be tested experimentally. This new therapeutic modality holds enormous promise, but we still need substantial improvements both from the delivery, efficacy and safety stand points before it can become a clinical reality.

Adenoma↗
PubMed2000

Sensitive method to identify and characterize proteinases in situ after SDS-PAGE.

Cells and body fluids contain numerous, different proteinases; to identify and characterize them are both important and difficult tasks. Especially difficult to identify and characterize are highly specific proteinases. Here, we present an extremely sensitive and quantitative method to characterize proteinases fractionated by SDS-PAGE that cleave specific rhodamine-based fluorogenic substrates. To test the sensitivity of the technique, we used trypsin as our model system. Filter paper impregnated with rhodamine-based fluorogenic substrates was placed on a gel, and bands of fluorescence originating from specific proteinases were visualized in real time. The method is very sensitive; picogram amounts of trypsin can be detected. The method should be very general, in that even proteinases whose substrates require amino acids C-terminal to the cleavage site may be identified and characterized. The results allow one to obtain not only information on the substrate specificity of a specific enzyme but also information about its molecular weight.

Animals↗
PubMed2000

Effect of transforming growth factor beta1 on chondrogenic differentiation of cultured equine mesenchymal stem cells.

OBJECTIVE: To determine the morphologic and phenotypic effects of transforming growth factor beta1 (TGFbeta1) on cultured equine mesenchymal stem cells (MSC) and articular chondrocytes. SAMPLE POPULATION: Bone marrow aspirates and articular cartilage samples from a 2-year-old and two 8-month-old horses. PROCEDURE: After initial isolation and culture, MSC and chondrocytes were cultured in Ham's F-12 medium supplemented with TGF-beta1 at a concentration of 0, 1, 5, or 10 ng/ml. Medium was exchanged on day 2, and cells were harvested on day 4. Medium was assayed for proteoglycan (PG) content. Total RNA was isolated from cell cultures, and expression of aggrecan, decrin, collagen type-I, and collagen type-II mRNA was assessed by means of Northern blot analyses. Cell cultures were stained with H&E or toluidine blue and examined histologically. Additional cultures were examined after immunohistochemical staining for type-I and -II collagen. RESULTS: MSC cultures exposed to TGF-beta1 had an increased cellular density with cell layering and nodule formation that was most pronounced in cultures treated with 5 ng of TGF-beta1/ml. Expression of collagen type-II mRNA in MSC cultures exposed to 5 ng of TGF-beta1/ml was 1.7 times expression in control cultures, and expression of collagen type-I mRNA was 2.8 times expression in control cultures. Treatment of MSC with TGF-beta1 led to dose-related increases in area and intensity of type-II collagen immunoreaction. CONCLUSION: Results suggest that TGF-beta1 enhances chondrogenic differentiation of bone marrow-derived MSC in a dose-dependent manner.

Animals↗
PubMed2000

The effectiveness of osteopathic manipulative treatment as complementary therapy following surgery: a prospective, match-controlled outcome study.

CONTEXT: Osteopathic manipulative treatment has been reported to relieve a variety of conditions, but no studies have examined the outcome effects of osteopathic manipulative treatment as a complementary modality for treating musculoskeletal problems during postoperative recovery. OBJECTIVE: To assess osteopathic manipulative treatment as a complementary therapy for patients undergoing elective knee or hip arthroplasty. DESIGN: Prospective, single-blinded, 2-group, match-controlled outcome study. SETTING: Osteopathic teaching hospital. PATIENTS: Of 166 eligible patients, 38 were assigned to a treatment group and matched with 38 control subjects. INTERVENTION: The treatment group received osteopathic manipulative treatment on postoperative days 2 through 5. MAIN OUTCOME MEASURES: Days to independent negotiation of stairs, distance ambulated, supplemental intramuscular analgesic use, length of hospital stay, and patients' perceptions of treatment. RESULTS: Compared to control subjects, the intervention group negotiated stairs 20% earlier (mean = 4.3 postoperative days, SD = 1.2; control subjects 5.4, SD = 1.6, P = .006) and ambulated 43% farther on the third postoperative day (mean = 24.3 m, SD = 18.3; controls = 13.9, SD = 14.4, P = .008). The intervention group also required less analgesia, had shorter hospital stays, and ambulated farther on postoperative days 1, 2, and 4. CONCLUSIONS: Patients receiving osteopathic manipulative treatment in the early postoperative period negotiated stairs earlier and ambulated greater distances than did control group patients.

Aged↗
PubMed2000

Histopathologic findings in the alopecia associated with Vogt-Koyanagi-Harada disease.

BACKGROUND: Vogt-Koyanagi-Harada (VKH) disease is a rare autoimmune disease primarily involving pigmented structures. The commonly associated alopecia usually precedes leukodermic changes seen in the hair and skin. OBJECTIVE: We present a 46-year-old oriental woman with VKH disease who developed diffuse alopecia followed by the regrowth of nonpigmented hairs. The biopsy specimens showed a peribulbar mononuclear infiltrate with increased telogen/catagen:anagen follicles. The most prominent additional histologic finding was melanin pigment release from the matrix into the dermal papillae, fibrous tracks, and surrounding perifollicular sheaths. The peribulbar mononuclear cells showed diffuse immunohistochemical staining of approximately 80 to 90% of the cells for CD3, CD45RO. More than 50% of the mononuclear cells showed positive staining for CD4, whereas approximately 10 to 20% showed staining for TIA with TIA+ cells within the follicular epithelium. CONCLUSION: Although the histologic features seen in the alopecia associated with VKH are consistent with alopecia areata, the prominent pigment release does suggest that the prime target are the melanocytes and that keratinocytes may be secondarily involved.

Alopecia↗
PubMed2000

The work commitments of British general practitioners: a national survey.

Many qualified general practitioners (GPs) are choosing not to become principals. With the current problems in recruitment and retention of GPs, workforce planning for the future of general practice is contingent upon the work commitments of both GP principals and non-principals. A questionnaire survey of 5966 vocationally trained doctors in the UK suggests that shortfalls in the GP workforce will not be alleviated by relying on the non-principal pool increasing their time commitment to general practice work.

Career Choice↗
PubMed2000

Injuries and risk factors in an 18-day Marine winter mountain training exercise.

OBJECTIVES: This study determined the incidence of and risk factors for injuries among 356 Marines during a winter mountain training exercise. METHODS: Marines received a podiatry screening and completed a questionnaire on race, education, tobacco use, height, weight, and fitness (4.8-km run, sit-ups, pull-ups). RESULTS: Forty-five Marines (12.6%) reported at least one injury each, 68.9% of which were traumatic injuries. Total injuries resulted in 114 days of limited duty time. A final foot examination (N = 141) revealed 118 injuries (82.2% blisters and abrasions, 11.9% frostnip). White ethnicity was a risk factor for overall injuries, and forefoot varus alignment was a risk factor for traumatic injuries. Lower education and rank and smokeless tobacco use were associated with foot injuries. The Marine ski-march leather boot and smoking were related to foot cold injuries. CONCLUSIONS: Military winter training is associated with injuries and lost training time. Risk factors were identified, suggesting that these injuries may be preventable.

Adult↗
PubMed2000

Analytic solutions to compartmental models of the HIV/AIDS epidemic.

For many years compartmental models have provided useful insights into the spread of epidemics. Such models are usually fairly easy to set up, but even the simpler models have the disadvantage that they are intractable to analytic solution. In this paper we examine models of the HIV/AIDS epidemic, and show that the equations may be linearized in a piecewise manner over time, thus allowing analytic solutions to be obtained. Indications of the usefulness of this approach are provided. In particular, an analytic solution gives insight into the mechanism of the epidemic, together with a clearer picture of the sensitivity of results to changes in parameter values. Further, the processes of parameter estimation and the methodology of back-calculation also benefit from the provision of functional forms for the state variables.

Acquired Immunodeficiency Syndrome↗
PubMed1999

Antitransferrin receptor antibody-RNase fusion protein expressed in the mammary gland of transgenic mice.

Antibodies fused to human enzymes offer an alternative to specifically targeting tumors with antibodies linked to plant or bacterial toxins. Since large amounts of these reagents can be administered without eliciting non-specific toxicities, efficient methods of production are needed. The goal of this work was to express a complex immunoenzyme fusion protein (immunotoxin) in the mammary gland of transgenic mice. A chimeric mouse/human antibody directed against the human transferrin receptor (E6) was fused at its CH2 domain to the gene for a human angiogenic ribonuclease, angiogenin (Ang). It was expressed in the mammary gland of mice and secreted into mouse milk. Expression levels in milk were approximately 0.8 g/l. The chimeric protein retained antibody binding activity and protein synthesis inhibitory activity equivalent to that of free Ang. It was specifically cytotoxic to human tumor cells in vitro.

Animals↗
PubMed1999

Mitochondrial DNA determines the cellular response to cancer therapeutic agents.

Mutations in the mitochondrial genome leading to mitochondrial dysfunction have been reported in a variety of cancers. However, the potential implication of these findings in the cellular response to cancer therapeutic agents is unclear. To examine the importance of mitochondrial DNA (mitDNA) encoded functions in cancer therapeutic response, we determined the clonogenic survival of HSL2 (Rho+, HeLa subline), and its derivative cell line lacking mitDNA (Rho0) after exposure to different anticancer agents. We found that isogenic Rho0 cells lacking mitDNA were extremely resistant to adriamycin and photodynamic therapy (PDT) induced cell death, whereas the Rho+ cell line was sensitive. However, there was no measurable difference in the responses of these cell lines to either alkylating agent or gamma-radiation. We show that the development of resistance to adriamycin was not due to changes in apoptotic cell death, cell cycle response or to the uptake of adriamycin in isogenic Rho0 cells. We also demonstrate that exposure of HeLa cells to adriamycin leads to mutations in mitDNA. These studies provide direct evidence that mitDNA plays an important role in cellular sensitivity to cancer therapeutic agents.

Antineoplastic Agents↗
PubMed1999

Clinical features of patients with stage IIIB and IV bronchioloalveolar carcinoma of the lung.

BACKGROUND: The incidence of bronchioloalveolar carcinoma of the lung (BAC), a pathologically distinct type of nonsmall cell lung carcinoma (NSCLC), appears to be rising. In this study, the authors compared data on the clinical presentation and clinical courses of patients with Stage IIIB and IV BAC with data on other types of NSCLC. METHODS: The authors collected clinical, radiographic, and pathology information about 28 patients with Stage IIIB and IV BAC and 124 patients with other histologic types of NSCLC. RESULTS: Twelve of 28 BAC patients (43%) were women, compared with 40 of 124 control patients (32%). Nine (32%) of the patients with BAC had never smoked cigarettes, versus 20 controls (16%) (P = 0.02). Eighteen patients (64%) with BAC had bilateral multilobar or multicentric pulmonary involvement, compared with 13 controls (15%) (P < 0.001). Patients with advanced stage (IIIB and IV) BAC had a median survival of 15 months from the time of diagnosis; for patients with other types of Stage IIIB and IV NSCLC, had a median survival of 10 months (P = 0.01). CONCLUSIONS: Patients with BAC of the lung have clinical, radiographic, and pathologic characteristics that distinguish them from patients with other types of NSCLC. A greater proportion of women and nonsmokers present with BAC than with other types of NSCLC. Patients with advanced stage BAC are more likely to have bilateral diffuse pulmonary involvement, are less likely to develop brain metastases, and have longer survival than patients with other types of Stage IIIB and IV NSCLC. Further research is warranted to define etiology, molecular abnormalities, and more effective therapeutic interventions.

Adenocarcinoma, Bronchiolo-Alveolar↗