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Biomedical subjects

J Hill

Publications and source records attributed to J Hill.

At least 145 records · Page 8Linked to original sources

Do junior doctors feel they are prepared for hospital practice? A study of graduates from traditional and non-traditional medical schools.

A valid and reliable questionnaire was developed which assesses eight subscales relating to key areas of medical hospital-based work. This was used to evaluate junior doctors' perceptions of the adequacy of their undergraduate medical training to prepare them for hospital practice. Data from 139 (60%) first-year doctors (interns) showed that graduates from the problem-based medical school rated their undergraduate preparation more highly than traditional medical school graduates in preparing them for practice in the areas of interpersonal skills, confidence, collaboration with other health care workers, preventive care, holistic care and self-directed learning. These findings persisted when ratings were adjusted for the effects of age and gender. There were no differences between the intern groups for patient management and understanding science. This research suggests that educational experiences in different undergraduate medical courses are important in preparing doctors for their early working life.

Attitude of Health Personnel↗

Increasing prevalence of wheeze and asthma in Nottingham primary schoolchildren 1988-1995.

The prevalence of asthma in children has increased substantially in many countries in recent decades, but it is not clear how much this trend has continued into the 1990s. This study aimed to estimate the current prevalence of asthma and wheeze in British primary schoolchildren and to determine whether there has been any increase in the prevalence of these conditions since 1988. The prevalence of self-reported wheeze and asthma was measured by parental questionnaire in 22,968 children aged 4-11 yrs attending primary schools in the Nottingham area of England in 1995, and these estimates were compared with data from a subsample of the same schools in 1988. In 1995, wheezing ever was reported in 24.0% of children, wheezing in the past year in 15.1% and diagnosed asthma symptomatic in the past year in 8.8%. All measures have increased in prevalence since 1988, in absolute terms by 7.7% for wheeze ever, by 2.6% for wheeze in the past year and by 2.7% for asthma. The increases were greater in females than males, but did not vary with age. In conclusion, the prevalence of asthma has continued to rise in British schoolchildren since the late 1980s, particularly in females, and across all ages.

Asthma↗

HER-2 expression and response to tamoxifen in estrogen receptor-positive breast cancer: a Southwest Oncology Group Study.

HER-2/neu is a growth factor receptor, the expression of which has been associated with a more aggressive breast tumor biology and resistance to some types of chemotherapy. Preliminary laboratory and clinical data have led to claims that HER-2/neu expression is also associated with resistance to tamoxifen. Therefore, to test the hypothesis that HER-2/neu expression is associated with a poorer response to tamoxifen, a shorter time to treatment failure (TTF), and worse survival in estrogen receptor (ER)-positive metastatic breast cancer, we examined 205 paraffin-embedded blocks of tumors from patients enrolled on Southwest Oncology Group 8228 for HER-2/neu expression. Tumors were ER positive (ER level > 3 fmol/mg cytosolic protein in either primary tumors or metastases), and patients had not received any prior therapy for metastatic disease. All patients were treated with daily tamoxifen. The study began in 1982, and median follow-up of patients who are still alive is now 9 years. Membrane staining for HER-2/neu was evaluated by immunohistochemistry using antibody TAB 250 and was scored according to the proportion of cells staining positive; tumors were deemed positive if > 1% of the cells stained for HER-2/neu. HER-2/neu positivity was associated with lower ER values (P = 0.04) and low bcl-2 (P = 0.01). HER-2/neu positivity was not significantly associated with response rate (negative versus positive, 57 versus 54%; P = 0.67), TTF (median, 8 versus 6 months; P = 0.15), or survival (median, 31 versus 29 months; P = 0.36). There was also no significant evidence of a progressive relationship between an increasing proportion of cells expressing HER-2/neu and a shorter TTF or survival. HER-2/neu expression in ER-positive metastatic breast cancer is not significantly associated with a poorer response to tamoxifen or a more aggressive clinical course. Earlier suggestions to the contrary may have been due to failure to rigorously exclude ER-negative tumors, which are much less likely to respond to tamoxifen and more likely to have high HER-2/neu levels.

Adult↗

How the principles of geriatric assessment are shaping managed care.

In traditional geriatric medicine, comprehensive assessment is considered crucial to the care of frail older patients. The principles of geriatric assessment--identifying high-risk patients and targeting them for preventive interventions--are also practiced by managed care organizations (MCOs). Self-reported health surveys and administrative data are two methods used by MCOs to identify members at high risk for adverse health outcomes and functional decline who may benefit from geriatric case management. For a successful partnership with primary care physicians, it is very important that geriatric care managers should be knowledgeable in the principles of geriatric medicine.

Activities of Daily Living↗

Meningeal carcinomatosis: an unusual cause of deafness.

Meningeal carcinomatosis is the diffuse infiltration of the meninges by metastatic carcinoma. Patients usually have a known underlying malignancy, but primary presentation can be with symptoms of meningeal involvement. The cases are reported of two patients who presented with sensorineural hearing loss. The roles of gadolinium-enhanced magnetic resonance imaging and cerebrospinal fluid cytology in reaching the diagnosis are discussed.

Adenocarcinoma↗

Aminoacyl tRNA synthetases as targets for new anti-infectives.

Because resistance has developed to mainline antibiotics, including vancomycin, new antibiotics are now being aggressively sought. For this purpose, aminoacyl tRNA synthetases are being pursued as targets for new drugs. These enzymes are universal and are essential for cell viability. The key to their usefulness lies in being able to find drugs that inhibit a pathogen synthetase but not its human cell counterpart. The possibility for species-specific inhibition was originally demonstrated with a natural product and has now been demonstrated with prototypical drugs that are based on the structure of an intermediate of the aminoacylation reaction. Efficacy of a rationally designed inhibitor has been shown in vivo with a pathogen infection established in an animal model. Although many challenges remain, these early results suggest that synthetases will continue to be of major interest for development of new anti-infectives.

Adenosine Monophosphate↗

Bacterial aspartic proteinases.

Regions of genomic DNA encoding putative aspartic proteinase domains were amplified by PCR from the bacterial species, Escherichia coli and Haemophilus influenzae. Expression of each of these DNA fragments resulted in the accumulation of the corresponding recombinant proteins in insoluble aggregates. Each recombinant protein was solubilised, refolded and shown to be able to cleave synthetic peptides that have been extensively used previously as substrates for aspartic proteinases of vertebrate, fungal and retroviral origin. Each activity was completely blocked by the diagnostic aspartic proteinase inhibitor, acetyl-pepstatin. This is thus the first report demonstrating unequivocally that aspartic proteinases may be present in bacteria.

Amino Acid Sequence↗

Stimulated human leukocytes cause activating mutations in the K-ras protooncogene.

Human tissues which are chronically infiltrated with inflammatory leukocytes are more likely to develop malignancies than non-inflamed tissues, however the mechanism(s) by which leukocytes contribute to carcinogenesis is unknown. Stimulated human leukocytes release superoxide anion and hydrogen peroxide which, in the presence of iron, can be converted into the potent oxidant, hydroxyl radical (.OH). Previous studies have shown that leukocyte-derived .OH (or a .OH-like species) can cause DNA damage, however a relationship between leukocyte-induced DNA damage and carcinogenesis has not been established. The present report demonstrates that leukocyte-derived .OH-induced DNA damage can cause K-ras oncogene activation, and suggests that there may be a characteristic pattern of .OH-induced K-ras oncogene activation. Since activation of the K-ras oncogene is believed to play a crucial role in the pathogenesis of many human malignancies, .OH-induced K-ras oncogene activation could be an important mechanism by which human leukocytes contribute to carcinogenesis.

3T3 Cells↗

Recombinant methionyl human stem cell factor and filgrastim for peripheral blood progenitor cell mobilization and transplantation in non-Hodgkin's lymphoma patients--results of a phase I/II trial.

To examine the safety and efficacy of recombinant-methionyl human stem cell factor (r-metHuSCF), 38 patients with intermediate-grade or immunoblastic high-grade non-Hodgkin's lymphoma who were eligible for autologous transplantation were randomized to receive r-metHuSCF (5, 10, 15, or 20 microg/kg/d) plus Filgrastim (10 microg/kg/d) or Filgrastim (10 microg/kg/d) alone to mobilize peripheral blood progenitor cells. Subcutaneous administration of r-metHuSCF was well tolerated in conjunction with a multi-agent pre-medication regimen; local injection site reactions were the most commonly seen adverse event. The total mononuclear cell count, CD34+ cell content, granulocyte-macrophage colony-forming cells (GM-CFC), and burst-forming units-erythroid (BFU-E) per kilogram in the apheresis product was similar when all patients were analyzed by treatment cohort and mobilization regimen (Filgrastim or r-metHuSCF in combination with Filgrastim); however, when prior chemotherapy was taken into account in a supplementary analysis, clinically important differences were observed. Extensive prior therapy was defined as the amount of exposure to specific stem cell toxic chemotherapeutic agents that patients received. These agents include procarbazine, nitrogen mustard, melphalan, nitrosoureas (> or = 2 cycles of any of these drugs) or greater than 7.5 g of cytosine arabinoside. In these patients, there was an increased number of CD34+ cells (1.76 v 0.28 x 10(6)/kg), GM-CFC (20.5 v 5.0 x 10(4)/kg), and BFU-E (36.9 v 8.9 x 10(4)/kg) in patients receiving r-metHuSCF and Filgrastim (N = 18) compared with Filgrastim alone (N = 5). These patients also had a decreased time to an untransfused platelet count of 20 x 10(9)/L that was 10.5 days shorter in the patients who received r-metHuSCF and Filgrastim (12.5 v 23 days). These differences were not found to be statistically significant, possibly because of small size, but are clinically important.

Adult↗

A study of forty-nine consecutive Whipple resections for periampullary adenocarcinoma.

BACKGROUND: We designed a program to evaluate the morbidity, mortality, survival rates, and patient's quality of life after Whipple resection for pancreatic and other periampullary adneocarcinoma. PATIENTS AND METHODS: After studying 11 fresh and unembalmed cadavers to learn the regional anatomy and to practice the surgical techniques for traditional Whipple procedure by the senior author (JS), 49 patients aged 56 to 84 years old were treated with Whipple's pancreatoduocenectomy. RESULTS: There was no postoperative mortality or morbidity from anastomotic leakage. All 49 patients were discharged in an improved condition following surgery, including 5 patients with emergency resection. Eight patients are alive at the time of this writing, including 2 patients who had their pancreatic cancer resected 168 and 139 months ago. CONCLUSIONS: In the opinion of these authors, treatment of all resectable cancers with Whipple's pancreatoduodenectomy offers not only a superior palliation but also the hope of cure.

Adenocarcinoma↗

Temperature and neural development of the Atlantic herring (Clupea harengus L.).

Embryos of Atlantic herring (Clupea harengus L.) from the Buchan (Northern North Sea) stock were incubated from fertilisation until hatching at temperatures of 5, 8, 12, and 15 degrees C. The relative timing of development of the Kolmer-Agduhr (KA) neurons, the posterior lateral line nerve, the motor neurons, and myotubes were determined with respect to somite stage of the embryo. Development of the KA neurons, the lateral line nerve, and the myotubes was similar at all temperatures. In contrast, timing of outgrowth of the motor neuron axons with respect to somite stage was earlier at higher (> or = 12 degrees C) than at lower temperatures (< or = 8 degrees C) although it reached a similar point at all temperatures by the 58-somite stage. Our hypothesis to explain these observations is that delayed motor axon outgrowth in the lower temperature groups is probably due to a delay in a signalling interaction between motor neurons and the somite.

Animals↗

Cognitive and behavioral effects of cholinergic, dopaminergic, and serotonergic blockade in humans.

The purpose of this study was to investigate the cognitive and behavioral effects of anticholinergic, antidopaminergic, and antiserotonergic agents given alone and in combination to normal volunteers. Twelve young male volunteers took part in this double-blind, randomized, placebo-controlled, crossover study of six drug conditions, each administered on separate days [haloperidol (2 mg p.o.) +/-scopolamine (0.5 mg i.v.), metergoline (4 mg p.o.) +/-scopolamine (0.5 mg i.v.), placebo, and scopolamine alone (0.5 mg i.v.)]. Scopolamine-induced sedation (p < .01), slowed information processing (p < .01) and impaired new learning and memory (p < .01), but did not affect attention or retrieval from semantic memory. Given alone, haloperidol selectively impaired the ability to rapidly switch cognitive sets (p < .05), and metergoline decreased pupil size (p < .01) but did not induce cognitive deficits. In combination with scopolamine, neither haloperidol nor metergoline produced a worsening of the subjects' cognitive performance above and beyond that seen with scopolamine alone. On the contrary, a trend (p < .10) for haloperidol to reverse some of the scopolamine-induced exacerbation of verbal short-term forgetting was observed. The data indicate that scopolamine and haloperidol can independently and selectively affect cognition and that at the doses tested in this study no synergistic exacerbation of cognitive functioning was found when cholinergic blockage was coupled with dopaminergic or serotonergic blockade.

Adult↗

A practical guide to patient education and information giving.

Patient education is accepted as an essential component in the management of rheumatoid arthritis (RA) and this chapter provides an overview of patient education for practising clinicians. It includes an explanation of the need for patient education including the results of studies into what patients already know. The effectiveness of patient education and its benefits to patients are discussed in the light of recent research, reviews and meta-analyses. Alternative methods of delivering patient education are compared including, one-to-one teaching, opportunity education, group teaching and self-management programmes. Topics for inclusion in education programmes are suggested and the merits of written literature, audio-visual and computer assisted learning are explained. Practical guidance is given on methods of ensuring that written information is readily understandable by patients, including the use of readability formulae.

Arthritis, Rheumatoid↗

Patient satisfaction in a nurse-led rheumatology clinic.

Patient satisfaction with a nurse-led rheumatology clinic was tested using the Leeds Satisfaction Questionnaire (LSQ), which was specially developed and shown to be both reliable (Cronbach's alpha, 0.96) and stable (test-re-test r = 0.83). A total of 70 patients with rheumatoid arthritis, aged 22-75 years were randomly allocated to either a nurse's or a rheumatologist's clinic and seen on six occasions over a year. They completed the LSQ on entry and on completion of the study. At week 0 both groups were satisfied with their care and there were no significant differences between them. By week 48 the medical cohort showed significantly increased satisfaction with access and continuity (P < 0.05) but no change in overall satisfaction. The patients in the nurse-led clinic recorded significant increases in overall satisfaction and in all subscales (P < 0.0001). Between-group comparison at week 48 showed the nurse's patients to be significantly more satisfied than those of the rheumatologist.

Adult↗

Gastritis in urease-immunized mice after Helicobacter felis challenge may be due to residual bacteria.

BACKGROUND & AIMS: Oral immunization with recombinant Helicobacter pylori urease (rUre) coadministered with a mucosal adjuvant protects mice against challenge with Helicobacter felis. In this study, the duration of protection and gastritis after challenge were characterized at sequential time intervals up to 1 year. METHODS: Outbred Swiss-Webster mice were orally immunized with rUre plus adjuvant and examined for the presence of H. felis infection and leukocyte infiltration into the gastric mucosa. RESULTS: When defined by gastric urease activity, 70%-95% of rUre-immunized mice were protected for between 2 and 57 weeks. Challenge with H. felis increased the inflammatory response in the gastric mucosa of rUre-immunized mice, which also had elevated CD4+ and CD8+ T cells. The CD8+ cells represented a population of gastric intraepithelial cells, which expressed the mucosal alpha E-integrin. Epithelial changes consisting of parietal cell loss and hyperplasia of the epithelium occurred in approximately 20% of the mice. Antimicrobial triple therapy significantly decreased the degree of gastritis and epithelial alteration in the stomach. CONCLUSIONS: These results indicate that oral immunization of mice with rUre produces a long-lasting inhibition of H. felis infection but that residual bacteria may produce a persistent lymphocytic infiltration under these experimental conditions.

Animals↗