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Biomedical subjects

J Harrison

Publications and source records attributed to J Harrison.

At least 73 records · Page 4Linked to original sources

Irritant contact dermatitis due to 1-bromo-3-chloro-5,5-dimethylhydantoin in a hydrotherapy pool. Risk assessments: the need for continuous evidence-based assessments.

A physiotherapist working in hydrotherapy presented to occupational health with irritant contact dermatitis. Subsequent investigation revealed that the likely causative agent was 1-bromo 3-chloro 5,5 dimethylhydantoin which was used to disinfect the hydrotherapy pool. A COSHH risk assessment had been performed which failed to take full account of current knowledge and this agent had been introduced into the workplace. The development of adverse health effects among staff and other pool users lead to a review of this risk assessment and eventually a return to less hazardous chlorine-based disinfection. Had an evidence-based approach been combined with an appropriate COSHH assessment prior to and following changes in the workplace then unnecessary risk to employees would not have occurred.

Dermatitis, Contact↗

At risk in two worlds: injury mortality among indigenous people in the US and Australia, 1990-92.

This paper outlines the commonalties and unique differences in injury experience among the indigenous people in the United States and Australia. Injury mortality rates among Indigenous people in the United States and Australia are approximately 2-3 times greater than rates for the non-Indigenous population in each country. Motor vehicle-related injuries accounted for one-third of the injury deaths for Native Americans and Australian Aboriginals. Suicide accounted for more deaths in Native Americans (15.5 per 100,000) than it did for Australian Aboriginals (11.1 per 100,000), whereas the injury death rate in Australian Aboriginals due to poisoning was almost twice that of Native Americans. Culturally appropriate interventions tailored to specific local settings and problems will be necessary to reduce injury mortality among Indigenous people.

Accidents, Traffic↗

Comparison of the use of a foot pump with the use of low-molecular-weight heparin for the prevention of deep-vein thrombosis after total hip replacement. A prospective, randomized trial.

We conducted a prospective, randomized trial to compare the safety and effectiveness of the A-V Impulse System foot pump with that of low-molecular-weight heparin for reducing the prevalence of deep-vein thrombosis after total hip replacement. Of 290 patients who were to have a primary total hip replacement, 143 were randomized to receive enoxaparin (forty milligrams daily) for seven days after the operation and 147, to use the foot pump for seven days. The primary outcome measure was the prevalence of deep-vein thrombosis, as determined by venography on the sixth, seventh, or eighth postoperative day. Secondary outcome measures included transfusion requirements, intraoperative blood loss, postoperative drainage, blood-loss index, appearance of the site of the wound according to a subjective visual-analog scale, and swelling of the thigh. The patients' compliance with the regimen for use of the foot pump was monitored with an internal timing device, and their acceptance of the device was assessed with a questionnaire. Symptoms consistent with pulmonary embolism were investigated with ventilation-perfusion scanning. The patients were contacted later for detection of symptoms of venous thromboembolism that may have occurred during the first three months after discharge from the hospital. Venography was performed on 274 patients: 136 who used the foot pump and 138 who received enoxaparin. Deep-vein thrombosis was detected in twenty-four (18 per cent) of the patients who used the foot pump compared with eighteen patients (13 per cent) who received enoxaparin (95 per cent confidence interval for the difference in proportions, -3.9 to +13.0 per cent). Thrombosis in the calf was found in seven patients (5 per cent) in the former group compared with six patients (4 per cent) in the latter (95 per cent confidence interval for the difference, -4.2 to +5.8 per cent), and proximal thrombosis was observed in seventeen patients (13 per cent) in the former group compared with twelve patients (9 per cent) in the latter (95 per cent confidence interval for the difference, -3.5 to +11.1 per cent). None of these differences was significant. No patient in either group had major proximal deep-vein thrombosis; all proximal thrombi were isolated entities involving the femoral valve cusp and were of unknown importance. One patient who used the foot pump had a non-fatal pulmonary embolism. One patient who received enoxaparin had a symptomatic deep-vein thrombosis during hospitalization. Two patients (one from each group [0.7 per cent]) were readmitted to the hospital because of a symptomatic deep-vein thrombosis despite normal venographic findings at the time of discharge. There was no difference in the transfusion requirements or the intraoperative blood loss between the two groups. There were more soft-tissue side effects in the patients who received enoxaparin than in those who used the foot pump: there was more bruising of the thigh and oozing of the wound (p < 0.001 for each), postoperative drainage (578 compared with 492 milliliters; p = 0.014), and swelling of the thigh (twenty compared with ten millimeters; p = 0.03). Of 124 patients who used the foot pump and were asked about the acceptability of the device, fourteen (11 per cent) said that it was uncomfortable, twenty-one (17 per cent) reported sleep disturbance, and four (3 per cent) stated that they had stopped using the device. Conversely, ten (8 per cent) found it relaxing. We concluded that the foot pump is a suitable alternative to low-molecular-weight heparin for prophylaxis against thromboembolism after total hip replacement and that it produces fewer soft-tissue side effects. Tolerance of the device is a problem for some patients.

Aged↗

9-Aminocamptothecin by 72-hour continuous intravenous infusion is inactive in the treatment of patients with 5-fluorouracil-refractory colorectal carcinoma.

BACKGROUND: 9-Aminocamptothecin (9AC) and its parent compound, camptothecin, have shown outstanding preclinical activity against colorectal carcinoma. Irinotecan (CPT-11), another camptothecin derivative, has demonstrated clinical activity in patients with 5-fluorouracil (5-FU)-refractory colorectal carcinoma. METHODS: The authors performed a Phase II trial of 9AC involving patients with measurable metastatic colorectal carcinoma who had progressed through only one prior regimen of 5-FU-based chemotherapy. 9AC was given initially at a dose of 59 microg/m2/hour by continuous intravenous infusion for 72 hours, with treatments repeated every 14 days. Granulocyte-colony stimulating factor was given on Days 5-12. RESULTS: Sixteen patients were treated on this trial. Fourteen were evaluable for response. Contrary to expectations, no major objective antitumor responses were observed. Eight patients experienced stable disease for a median of 4.1 months (range, 2.2-9.5 months). Toxicities, especially myelosuppression, were severe and necessitated a 15% reduction in the initial dose after the first 9 patients. Toxicities at this reduced dose remained unacceptable. CONCLUSIONS: 9AC did not demonstrate substantial activity against 5-FU-refractory colorectal carcinoma on the schedule studied. Toxicities at the doses and schedule studied were unacceptable in this patient population. Based on their results, the authors consider it unlikely that 9AC administered as a 72-hour continuous intravenous infusion will play a major role in the treatment of colorectal carcinoma.

Adult↗

Sp1 binding is inhibited by (m)Cp(m)CpG methylation.

Previously it has been found that binding of the Sp1 transcription factor is not significantly affected by methylation of the CpG dinucleotide within its binding site, 5'-GGGCGG (lower strand, 5'-CCGCCC). Since it has been established that mammalian cells also have the capacity to methylate cytosines (C) at CpNpG sites we examined the effect of methylation of the outer C of the CpCpG on Sp1 binding. We find that methylation of the outer C is inhibitory and in particular methylation of both cytosines (m)Cp(m)CpG inhibits binding by 95%. Furthermore, we have identified endogenous (m)Cp(m)CpG methylation of an Sp1 site in the CpG island promoter of the retinoblastoma (Rb) gene by genomic sequencing. This occurs in a proportion of retinoblastoma tumors which are extensively CpG methylated in the Rb promoter. The results raise the possibility that (m)Cp(m)CpG methylation could have a biological function in preventing Sp1 binding, thereby contributing to the subsequent abnormal methylation of CpG islands often observed in tumor cells.

Binding Sites↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗