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Biomedical subjects

J Harrison

Publications and source records attributed to J Harrison.

At least 91 records · Page 5Linked to original sources
PubMed1997

Extensive DNA methylation spanning the Rb promoter in retinoblastoma tumors.

The retinoblastoma gene (Rb) is one of the best characterized tumor suppressor genes, and its inactivation is associated with a number of cancers. Previous studies have shown, by restriction enzyme analysis, that the promoter region of the Rb gene is methylated in a significant proportion of primary retinoblastoma tumors. We now report the first detailed methylation sequence analysis of the CpG island spanning the retinoblastoma promoter from hypermethylated retinoblastoma tumors. Our results show methylation is not confined to a specific CpG site, as detected by restriction enzyme studies, but extends to essentially all 27 CpG dinucleotides spanning the retinoblastoma CpG island, including the core promoter. The methylation pattern from each tumor DNA sample is different, ranging from densely to sparsely methylated profiles. Single CpG sites, in particular the E2F transcription factor binding site, as well as blocks of CpGs, were undermethylated in some tumor samples. Possible interference of methylation could be due to the binding of sequence-specific protein factors at these sites in the tumor cells. This study highlights that the dynamics of DNA methylation in cancer cells are clearly different from normal cells and gives an insight into the mechanism of abnormal methylation of CpG islands in cancer cells.

Base Sequence↗
PubMed1997

Inflammatory polyarthropathy and bone remodeling in HTLV-I Tax-transgenic mice.

Transgenic mice carrying the tax gene of human T-cell lymphotropic virus type I displayed a high prevalence of arthropathy. The percentage of affected animals increased with age, reaching a peak of 43% at 20 months. Southern analysis of deoxyribonucleic acid (DNA) from tissue samples indicated that disease development was related to tax copy number. Histopathologic evaluation of the ankle joints disclosed deep erosion of the synovial lining, fibrous tissue proliferation together with angiogenesis, mononuclear cell infiltration, and activation of osteoclasts. Radiologic examination confirmed joint involvement and revealed bone architecture modifications. The phenotype exhibited by the affected animals closely resembles that of seronegative arthritis in humans, and may indicate tax protein as a causal agent of arthropathy observed in HTLV-I infected individuals.

Age Factors↗
PubMed1997

A prospective study on the effect of recipient nutritional status on outcome in liver transplantation.

In a prospective study, we have examined the effect of nutritional status, using anthropometric measurements, on outcome in 102 consecutive adult patients undergoing elective orthotopic liver transplantation. Mid-arm muscle circumference was calculated from these two measurements. Patient outcome variables were time spent in the intensive therapy unit, total time in hospital, infective complications and mortality within 6 months. Graft outcome variables were early graft function, peak aspartate transaminase, alkaline phosphatase, bilirubin and prothrombin time. Group A patients were below and group B patients above the 25th percentile for mid-arm circumference and triceps skin fold thickness. Eighty-four patients (79%) were at or below the 25th percentile of anthropometric measurements and 30 patients (28%) were below the 5th percentile. The median mid-arm muscle circumference in group A was 22.3 (range 16.4-28.9) cm and 25.7 (range 21.7-31.8) cm in group B. The medial albumin level was similar in the two groups. There were significantly more bacterial infections in group A (27/84, 32%) than in group B (2/22, 8%; chi(2) = 5.4, P = 0.02). There was a difference in mortality up to 6 months post-operatively that failed to reach statistical significance (Wilcoxon-Gehan statistic -199, P = 0.09). There were 11/84 (13%) deaths in group A and no deaths in group B (chi(2) = 2.8, P = 0.09). Post transplantation, there were significant differences (Kruskal-Wallis Anova) between groups A and B for peak alkaline phosphatase (683 vs 334 IU/I, P = 0.05) and peak prothrombin time [16 (range 13-25) vs 19.5 (range 12-65), P = 0.03]. These data suggest that a significant proportion of patients undergoing liver transplantation are nutritionally compromised and that this has effects on patient infection, susceptibility, graft function and mortality, which may possibly be improved by nutritional intervention.

Adult↗
PubMed1997

Dorzolamide hydrochloride and visual function in normal eyes.

PURPOSE: To determine by a pilot study whether standard treatment with the topical carbonic anhydrase inhibitor dorzolamide hydrochloride influences visual function under normal breathing conditions, during carbon dioxide inhalation, or during hyperventilation, and to establish criteria for future larger-scale studies. METHODS: We enrolled 12 normal subjects into this randomized double-masked placebo-controlled crossover study. Each subject was treated with either dorzolamide 2% or placebo, three times daily, for 4 days. After a 2-week washout period, the alternative topical agent was used under identical testing conditions. On day 2 of each treatment phase, contrast sensitivities to sinusoidal gratings of 1 and 4 cycles per degree (cpd) were assessed. On day 4, mean deviation values from full-threshold 10-2 visual fields were obtained. Three sets of each visual function test were obtained before each treatment phase, and in sequence on each testing day, during normal breathing (baseline), inhalation of carbon dioxide-enriched air, and hyperventilation while intraocular pressure was monitored. RESULTS: Contrast sensitivity at 4 cpd decreased significantly (P < .01) during carbon dioxide supplementation with placebo but showed no significant change with dorzolamide. The decrease in contrast sensitivity accompanying hyperventilation was attenuated (by nearly 50% at 1 cpd) during dorzolamide treatment. Dorzolamide treatment was associated with higher perimetry mean deviation values under each treatment condition and was statistically significant (P < .05) at baseline. CONCLUSIONS: Dorzolamide appears to enhance contrast sensitivity in normal subjects during physiologic hypercapnia and hypocapnia at 4 and 1 cpd, respectively. Also, under normal breathing conditions, dorzolamide therapy increases perimetric light sensitivity.

Adult↗
PubMed1997

Influence of behavioral and social science on public health policymaking.

Public health policies are important guiding principles that serve to shape the well-being of individuals, groups, and society. Behavioral and social scientists can play key influential roles in public health policymaking. The actors and processes involved in setting public health policy are described, and several substantive examples of public health decision making are discussed, emphasizing HIV prevention policy experiences at the Centers for Disease Control and Prevention. The significant influence of behavioral and social science in each of these examples is identified and critiqued. Challenges to further integration of behavioral science and public health policy are identified, and potential solutions are proposed.

Behavioral Sciences↗
PubMed1997

Implementation of Department of Health guidelines for hepatitis B vaccination: a regional audit of NHS occupational health policies and procedures.

The objective of this study was to assess the implementation of the UK Health Departments' guidelines on protecting healthcare workers and patients from hepatitis B infection. The survey took place in February 1994 in the form of a postal questionnaire survey of occupational health departments. The study frame was the 18 district-based occupational health departments in the northern region of the NHS. The main outcome measures were compliance with the national guidelines on vaccination and the assessment of the hepatitis B status of employees performing exposure prone procedures. Compliance with the guidelines was variable. There were marked variations in the interpretation of serological data and there was a failure to establish the hepatitis B status of surgeons, in some cases. There is a need to provide training for occupational health practitioners about hepatitis B and to ensure that there is a uniform standard of practice within the NHS.

Health Personnel↗
PubMed1997

Access to psychiatric care; the results of the Pathways to Care study in Preston.

BACKGROUND: The aim of the present research was to study factors that might determine speed of access to psychiatric care, including the effect of the introduction of a community psychiatric service. METHODS: A Pathways to Care analysis was used to detail new referrals to mental health professionals (MHPs) during two one-month intervals one year apart, before and after the introduction of a community service (n = 279). Univariate analysis of possible factors that might affect access was undertaken, including socio-demographic factors, clinical factors and style of service. Significant associations were then investigated using stepwise logistic regression. RESULTS: The inception rate for treatment was similar to that reported for other services (0.10 per cent). After the establishment of community teams, there was an overall 22 per cent increase in the number of patients seen, with the greatest increase being for neurotic disorders and patients seen by non-medical staff. Of patient-based factors, younger age and suicidal ideation were associated with shorter pathways. Older age, married status, somatic symptoms, anxiety and depression were associated with slower pathways. Patients with suicidal ideation were seen within three days. The introduction of a community pathways team was associated with a lengthening of time to specialist care. CONCLUSIONS: Following a non-experimental change in service delivery, an increase in referrals for less severe mental illness was demonstrated. Continued comprehensive data collection of this type can be used by purchasers to monitor referral patterns and can provide a basis for determining priorities in service delivery.

Adolescent↗
PubMed1997

Salmonella typhimurium aroA, htrA, and aroD htrA mutants cause progressive infections in athymic (nu/nu) BALB/c mice.

Athymic (nu/nu) BALB/c mice and their euthymic (nu/+) littermates were inoculated intravenously with live attenuated vaccine strains of Salmonella typhimurium. All strains caused progressive infections in the athymic mice but not in their euthymic littermates. Athymic mice given strain SL3261, an aroA derivative of SL1344, in doses between log 4.7 and 5.7 CFU were all severely ill and were killed by weeks 4 to 5. Athymic mice given log 4.7 CFU of a derivative of S. typhimurium C5 carrying a mutation in htrA, encoding a stress protein, were ill and were killed by week 7 in one experiment but survived to week 13 in another. Athymic mice given log 4.6 CFU of a C5 aroD htrA double mutant were ill and were killed at week 7. Athymic mice given SL3261 had high bacterial counts in the reticuloendothelial system at 4 weeks. Athymic mice given SL3261 or C5 htrA made immunoglobulin G3 (IgG3) (and to a lesser extent IgM) antibody to lipopolysaccharide (LPS), whereas euthymic mice made IgM, IgG1, IgG2a, IgG2b, and IgG3 anti-LPS antibodies. The results indicate that both aroA and htrA strains will produce slow, progressively lethal infections in athymic mice, that the htrA strain is more attenuated than the aroA strain as measured by time to death in this model, and that IgG3 anti-LPS antibody alone cannot suppress the progress of infections by very attenuated strains in athymic mice.

3-Phosphoshikimate 1-Carboxyvinyltransferase↗
PubMed1997

Cerebral areas associated with motor control of speech in humans.

We have defined areas in the brain activated during speaking, utilizing positron emission tomography. Six normal subjects continuously repeated the phrase "Buy Bobby a poppy" (requiring minimal language processing) in four ways: A) spoken aloud, B) mouthed silently, C) without articulation, and D) thought silently. Statistical comparison of images from conditions A with C and B with D highlighted areas associated with articulation alone, because control of breathing for speech was controlled for; we found bilateral activations in sensorimotor cortex and cerebellum with right-sided activation in the thalamus/caudate nucleus. Contrasting images from conditions A with B and C with D highlighted areas associated with the control of breathing for speech, vocalization, and hearing, because articulation was controlled for; we found bilateral activations in sensorimotor and motor cortex, close to but distinct from the activations in the preceding contrast, together with activations in thalamus, cerebellum, and supplementary motor area. In neither subtraction was there activation in Broca's area. These results emphasize the bilaterality of the cerebral control of "speaking" without language processing.

Adult↗
PubMed1997

Economics of thromboprophylaxis in total hip replacement surgery.

In 1997, 50,000 hip replacements will be performed in the UK, and over 1 million worldwide. Venous thromboembolism is the most frequent serious complication following joint replacement; its effective and economic management is essential. Antithrombotic prophylaxis can be used to reduce the incidence of venous thromboembolic disease, which presents as either deep vein thrombosis or pulmonary embolism. A number of published studies have shown that prophylaxis against venous thromboembolism is financially beneficial in terms of reduced diagnostic and treatment costs. Cost-effectiveness studies have provided a comparison of the costs and consequences resulting from alternative prophylactic programmes. This article reviews the epidemiology of venous thromboembolism after total hip replacement, prophylaxis against it and a model for cost-effectiveness analysis. Its aim is to highlight inadequacies in the available data and areas of uncertainty within the model that require further research. Pharmacoeconomic studies published to date have all used a similar framework to allow prophylactic options to be compared. However, assumptions made about the frequency of clinical disease have varied widely between studies. This degree of uncertainty calls into question the validity of reported incremental cost savings between treatments. Some studies have also failed to address the cost of complications resulting from the prophylactic method under consideration. Future studies must carefully consider the validity of their models, understand the limitations on current knowledge of outcome rates, and carefully consider all outcomes (both beneficial and detrimental) that result from the intervention.

Cost-Benefit Analysis↗
PubMed1997

Designing a search strategy to identify and retrieve articles on evidence-based health care using MEDLINE.

The practice of evidence-based health care requires that information on methodology be identified from databases such as MEDLINE. Up until this year there have been no designated medical subject headings (MeSH) for evidence-based health care. 'EVIDENCE-BASED MEDICINE' appears as a MeSH term from 1997. The absence of designated MeSH for this concept prior to 1997 provides a challenge to the searcher. This paper describes the creation of a MEDLINE search strategy to retrieve articles on the methods of evidence-based health care published prior to the introduction of the new term, where an optimal combination of free-text and MeSH terms is required to identify relevant material. The study examines both free-text and subject heading searching and attempts an optimal balance of sensitivity and specificity. It begins by examining separate free-text and subject heading searches. Sensitivity of the subject heading search was 33% and specificity 80%, while the free-text search produced a sensitivity of 50% and a specificity of 67%. The final strategy, combining both approaches, was more successful with sensitivity reaching between 82 and 90% and specificity 83%. It is therefore possible to devise a search strategy to retrieve articles on the methods of evidence-based health care with relatively successful rates of sensitivity and specificity. The limitations of MEDLINE, however, necessitate the use of additional approaches in identifying articles on the methods of evidence-based health care.

Evidence-Based Medicine↗
PubMed1997

High-dose infusional doxorubicin and cyclophosphamide: a feasibility study of tandem high-dose chemotherapy cycles without stem cell support.

The purpose of this study was to determine the maximally tolerated dose of doxorubicin administered during two cycles of intensive chemotherapy with cyclophosphamide and doxorubicin without stem cell support in patients with advanced cancer and to assess the cumulative cardiac toxicity of the regimen by noninvasive radionuclide imaging and by pre-and postchemotherapy endomyocardial biopsies. Thirty-eight patients (thirty-six with high risk or metastatic breast cancer) were treated in a dose-escalation trial using a fixed dose of i.v. cyclophosphamide (4.2 g/m2) administered over 2 h on day 5 and escalating doses of doxorubicin (50-175 mg/m2) given as a 96-h continuous i.v. infusion on days 1-4, using Filgrastim (granulocyte colony-stimulating factor) for hematological support beginning on day 6. All patients underwent pretreatment, and 28 patients underwent postchemotherapy endomyocardial biopsies. Twenty-nine of 38 patients received two cycles of treatment (median number of days between cycles, 44; range, 34-62). Twenty-one patients had received doxorubicin previously at cumulative dose levels </=150 mg/m2; all patients had pretreatment endomyocardial biopsy scores less than 1. One patient treated at the highest dose level of doxorubicin (175 mg/m2) developed symptoms of mild congestive heart failure following two cycles of chemotherapy. Pre- and posttreatment radionuclide ejection fractions were 65 and 45%, respectively; this patient had a posttreatment endomyocardial biopsy score of 1 (damage to <5% of myocytes). One additional patient at this dose level had an asymptomatic biopsy score of 1, with a decrease in ejection fraction from 62 to 43%; this recovered to 58% 5 months after completion of chemotherapy. Six additional patients treated at lower dose levels had abnormal posttreatment endomyocardial biopsies without abnormal posttreatment ejection fractions. Nine patients received only one cycle of chemotherapy: five patients due to decreased cardiac ejection fraction following cycle 1 (two of these patients had normal endomyocardial biopsies, and two patients had biopsy scores of 1); one patient secondary to tumor progression following cycle one; one patient due to persistently detectable Clostridium difficile toxin in the stool; one patient refused cycle two; and one patient died following cycle one of complications related to sepsis. A single patient experienced a grand mal seizure associated with orthostatic hypotension, which was considered the dose-limiting toxicity. The median duration (over two cycles) of granulocytopenia (absolute granulocyte count <500/microliter) at the maximally tolerated dose level of 150 mg/m2 was 8.5 days (range, 5-13 days), and the median duration of thrombocytopenia (platelets <20,000/microliter) was 2.5 days (range, 0-9 days). The median duration of hospitalization including chemotherapy administration was 23 days (range, 19-36 days). Other toxicities included stomatitis, fever, diarrhea, and emesis. One patient developed acute leukemia 54 months posttreatment. We conclude that two courses of high-dose cyclophosphamide and doxorubicin using granulocyte colony-stimulating factor are feasible and safe with tolerable myocardial toxicity as evidenced by serial endomyocardial biopsies. The dose-limiting toxicity encountered was a grand mal seizure. The recommended Phase II dose is doxorubicin 150 mg/m2 administered as a 96-h infusion on days 1-4, with cyclophosphamide 4. 2 g/m2 on day 5 and G-CSF 5 microgram/kg/day started on day 6 and administered until the total WBC is above 10,000/microliter for three consecutive days.

Adult↗
PubMed1996

A comparison of four patient immobilization devices in the treatment of prostate cancer patients with three dimensional conformal radiotherapy.

PURPOSE: To determine the variability of patient positioning during three-dimensional conformal radiotherapy (3D-CRT) for prostate cancer treated with no immobilization or one of four immunobilization devices, and to determine the effects of patient body habitus and pelvic circumference on patient movement with each individual inmobilization technique. METHODS AND MATERIALS: To see whether our immobilization techniques have improved day-to-day patient movement, a retrospective analysis was carried out. A total of 62 patients treated at one facility on a single machine with 3D-CRT via a four-field box technique (anterior-posterior and opposed laterals) in the supine position with either no immobilization or one of four immobilization devices. Five groups of patients were compared: (a) group 1-no immobilization; (b) group 2-alpha cradle from the waist to upper thigh; (c) group 3-alpha cradle from waist to below the knees; (d) group 4-styrofoam leg immobilizer (below knees); and (e) group 5-aquaplast cast encompassing the entire abdomen and pelvis to midthigh with alpha cradle immobilization to their lower legs and feet. Prior to starting radiotherapy, portal films of all four treatment fields were obtained 1 day before treatment. Subsequently, portal films were then obtained at least once a week. Portal films were compared with the simulation films and appropriate changes were made and verified on the next day prior to treatment. A deviation of greater than 0.5 cm or greater was considered to be clincally significant in our analysis. We studied the difference among the types of immobilization and no immobilization by looking at the frequency of movements (overall, and on each of the three axes) that a patient had during the course of his treatment. Using a logistic regression model, the probability of overall and individual directional movement for each group was obtained. In addition, the effects of patient body habitus and pelvic circumference on movement were analyzed. RESULTS: The maximum deviation was 2 cm and the median deviation was 1.2 cm. For each patient, the probability of movement ranged from 0 to 76%, with a mean of 39%. There was no significant difference seen in overall movement with any of the immobilzation devices compared to no immobilization, but there was less vertical (9 vs. 18%; p = 0.03) and AP (6 vs. 15%; p = 0.14) movement with the aquaplast than any other group. However, when examining the lateral direction, the aquaplast had significantly more movement (32 vs. 9%; p < 0.001). When accounting for body habitus and pelvic circumference, no immobilization device was effective in reducing movement in obese patients or in patients with pelvic circumference greater than 105 cm. The aquaplast group had a significantly increased amount of lateral movement with obesity (42 vs. 23%; p < 0.05), and with pelvic circumference >105 cm (33 vs. 29%; p < 0.05). CONCLUSIONS: There was no significant reduction in overall patient movement noted with any of the immobilization devices compared to no immobilization. The aquaplast group had reduced vertical and AP movement of greater than 0.5 cm. There was significantly more lateral movement with aquaplast appreciated in obese patients or patients with pelvic circumferences greater than 105 cm. The aquaplast immobilization appears to be useful in reducing movement in two very clinicaly important dimensions (AP and vertical). Despite our findings, other immobilization may still be useful especially in the treatment of nonobese patients. It is clear that the optimal immobilization technique and patient positioning are yet to be determined.

Body Constitution↗