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Biomedical subjects

E J Hall

Publications and source records attributed to E J Hall.

At least 37 records · Page 2Linked to original sources

The bystander response in C3H 10T1/2 cells: the influence of cell-to-cell contact.

Although radiation-induced heritable damage in mammalian cells was thought to result from the direct interaction of radiation with DNA, it is now accepted that biological effects may occur in cells that were not themselves traversed by ionizing radiation but are close to those that were. However, little is known about the mechanism underlying such a bystander effect, although cell-to-cell communication is thought to be of importance. Previous work using the Columbia microbeam demonstrated a significant bystander effect for clonogenic survival and oncogenic transformation in C3H 10T(1/2) cells. The present study was undertaken to assess the importance of the degree of cell-to-cell contact at the time of irradiation on the magnitude of this bystander effect by varying the cell density. When 10% of cells were exposed to a range of 2-12 alpha particles, a significantly greater number of cells (P < 0.0001) were inactivated when cells were irradiated at high density (>90% in contact with neighbors) than at low density (<10% in contact). In addition, the oncogenic transformation frequency was significantly higher in high-density cultures (P < 0.0004). These results suggest that when a cell is hit by radiation, the transmission of the bystander signal through cell-to-cell contact is an important mediator of the effect, implicating the involvement of intracellular communication through gap junctions.

Alpha Particles↗

Nursing attrition and the work environment in South African health facilities.

A number of media reports appeared on the shortages of professional health workers in the public health sector. Unsatisfactory working conditions in health facilities were mentioned as one of the key aspects responsible for the shortages. Literature indicates that stress caused by unsatisfactory work environments may play a major role in employees' decision to resign their jobs, in spite of enjoying the nature of their work. The aim of this article is to explore the current human resource situation in nursing i.e. to determine if a shortage of nursing skills exists, to establish the challenges that nurses have to face in performing their duties and to establish the potential effect of the work environment on attrition. Currently 155 484 nurses are practicing in South Africa at a rate of 343 nurses per 100 000 of the population, which compares favourably with the World Health Organisation minimum of 200:100 000. The lack of reliable data on the supply of and demand for nurses makes it difficult to determine whether real shortages exist. However the supply of nursing services is influenced by the uneven distribution of skills across regions and the outflow of professional skills. It seems that the existing situation will deteriorate because fewer people are interested in taking up or pursuing nursing as a career in South Africa. At the same time a need for more nurses was identified because of the growth in the population as well as a change in health care needs. Workplace conditions for health workers employed at hospitals and clinics in South Africa were explored as part of a recent national study on the impact of HIV/AIDS on the health sector. Health workers' opinions on aspects such as workload, staff morale and working hours were obtained during personal interviews, which were conducted at 222 health facilities. Nine hundred and twenty four professional nurses, enrolled nurses and nursing assistants, who were mostly employed in the public health sector, participated. A stressful work environment was identified in public hospitals and clinics. An increase in the number of patients visiting these facilities, accompanied by a lack of equipment, unsatisfactory work environment and a shortage of nurses were pointed out. Many patients cannot be accommodated elsewhere because of a lack of finance and alternative health care options. Nurses also indicated that they do not get much support from their employers. The effect of all these factors culminates in a stressed workforce who may be forced to consider alternative career options. This will be to the detriment of health care in the country.

Burnout, Professional↗

HIV/AIDS prevalence among South African health workers.

INTRODUCTION: Studies on HIV prevalence among health workers usually focus on occupational exposure to HIV. Little is known about HIV prevalence in this group. However, it is expected that HIV prevalence among health workers will reflect prevalence in their society. OBJECTIVE: To determine HIV prevalence among South African health workers. METHOD: A stratified cluster sample was drawn of 5% of health facilities in South Africa (N = 222) representative of the public and private health sectors in South Africa. The sample was designed to obtain a nationwide representative sample of medical professionals and non-professional health workers. A subsample comprising health workers in four provinces was tested for HIV status. The Orasure HIV-1 device in combination with the Vironostika HIV UNI-Form II plus O enzyme-linked immunosorbent assay (ELISA) kits were used to collect oral fluid specimens for HIV testing. RESULTS: Based on a sample of 721 health workers and a response rate of 82.5% (or 595 respondents), the study found that an estimated 15.7% (95% confidence interval (CI): 12.2-19.9%) of health workers employed in the public and private health facilities located in four South African provinces, were living with HIV/AIDS in 2002. Among younger health workers, the risk is much higher. This group (aged 18-35 years) had an estimated HIV prevalence of 20% (95% CI: 14.1-27.6%). Non-professionals had an HIV prevalence of 20.3%, while professionals had a prevalence of 13.7%. CONCLUSION: HIV prevalence among health workers in South Africa is high; this calls for the introduction of antiretroviral programmes targeting them. In addition, there is a need for the development of new policy regarding placement of infected health workers in tuberculosis (TB) wards, coupled with vigorous human resource planning to replace the health workers likely to die from AIDS. Infection control procedures also need to be reviewed.

Adult↗

Serum IgE and IgG responses to food antigens in normal and atopic dogs, and dogs with gastrointestinal disease.

In human food allergy, with or without concurrent atopy, there may be significant increases in serum allergen-specific IgE. Serological methods have been tried but are not currently recommended for diagnosis of suspected food allergy in dogs. The aim of this study was to investigate humoral immune responses to food antigens in dogs. Serum IgG and IgE antibodies specific for food antigens were measured by enzyme linked immunosorbent assay (ELISA) using polyclonal anti-dog IgG and IgE reagents. Antigens tested were beef, chicken, pork, lamb, chicken, turkey, white fish, whole egg, wheat, soybean, barley, rice, maize corn, potato, yeast and cow's milk. Three groups were examined: normal dogs, dogs with atopic dermatitis (AD); and dogs with one of four types of gastrointestinal (GI) disease: small intestinal bacterial overgrowth (SIBO), inflammatory bowel disease (IBD), food-responsive disease, and infectious diarrhoea. Statistically significant differences in food-specific antibodies were not detected between the GI subgroups. There were statistically significant differences in the IgE concentration between the normal dogs, and dogs with atopic or GI disease, for all of the antigens tested. There were statistically significant differences in the average IgG concentrations between the normal dogs, and dogs with atopic or GI disease, for all of the antigens tested, except egg and yeast. The relationship of antigen responses for pooled data was analysed using principle component analysis and cluster plots. Some clustering of variables was apparent for both IgE and IgG. For example, all dogs (normal and diseased) made a similar IgG antibody response to chicken and turkey. Compared with other groups, atopic dogs had more food allergen-specific IgE and this would be consistent with a Th(2) humoral response to food antigens. Dogs with GI disease had more food allergen-specific IgG compared with the other groups. This may reflect increased antigen exposure due to increased mucosal permeability which is a recognised feature of canine intestinal disease.

Animals↗

Sterile nodular panniculitis and pansteatitis in three weimaraners.

The clinical and pathological findings in three unrelated weimaraners with pyrexia and multiple subcutaneous nodules are reported. Abdominal pain was an additional feature in two of the dogs and clinical investigations revealed inflammation of subcutaneous, mesenteric and falciform fat. Histopathological findings were consistent with pansteatitis. In the third dog, lesions were apparently limited to the subcutis and, hence, a diagnosis of nodular panniculitis was made. Microbiological examination of tissues was negative in all dogs, and there was no evidence of pancreatic disease. This report thus describes a presumed sterile and idiopathic panniculitis/pansteatitis complex in weimaraner dogs. Although the aetiology is unknown, this may represent an immune-mediated disorder.

Animals↗

Fecal alpha1-proteinase inhibitor concentration in dogs with chronic gastrointestinal disease.

BACKGROUND: Fecal alpha(1)-proteinase inhibitor (alpha(1)-PI) clearance is a reliable, noninvasive marker for protein-losing enteropathy in human beings. An assay for use in dogs has been developed and validated. OBJECTIVE: The aim of this study was to evaluate fecal alpha(1)-PI concentration in dogs with chronic gastrointestinal disease, compared with healthy dogs, and to assess its correlation with serum albumin concentration. METHODS: Fecal samples were collected from 2 groups of dogs. Group 1 consisted of 21 clinically healthy client-owned dogs without signs of gastrointestinal disease. Group 2 consisted of 16 dogs referred for investigation of suspected gastrointestinal disease. On the basis of gastric and duodenal biopsies, group 2 was further subdivided into dogs with normal histology (n = 9) and those with histologic abnormalities (n = 7: inflammatory bowel disease, n = 3; lymphangiectasia, n = 4). An ELISA was used to measure alpha(1)-PI concentrations in fecal extracts. RESULTS: Fecal alpha(1)-PI concentrations, expressed as micro g/g of feces, were not significantly different between groups 1 and 2 as a whole. However, fecal alpha(1)-PI concentrations (median, minimum-maximum) were significantly higher in dogs with gastrointestinal diseases associated with histologic abnormalities (60.6 micro g/g, 7.4-201.7 micro g/g) compared with dogs with normal histology (3.8 micro g/g, 0.7-74.0 micro g/g) and control dogs (9.9 micro g/g, 0.0-32.1 micro g/g). There was no significant correlation between fecal alpha(1)-PI and serum albumin concentrations in dogs with gastrointestinal disease. CONCLUSIONS: Increased fecal alpha(1)-PI concentration may signal the need to obtain gastrointestinal biopsies for a final diagnosis. Fecal alpha(1)-PI concentration may be a useful test for early detection of protein-losing enteropathy before decreases in serum albumin concentration can be detected.

Animals↗

Fecal alpha1-proteinase inhibitor concentration in dogs receiving long-term nonsteroidal anti-inflammatory drug therapy.

BACKGROUND: Fecal alpha(1)-proteinase inhibitor (alpha(1)-PI) clearance is a reliable, noninvasive marker for protein-losing enteropathy (PLE) in human beings. An assay for measurement of this protein in the dog has been developed and validated and may be useful for the investigation of gastrointestinal disease in this species. Nonsteroidal anti-inflammatory drugs (NSAIDs) frequently are administered to dogs and may have adverse effects on the gastrointestinal tract, including gastroduodenal ulceration and altered mucosal permeability. The value of fecal alpha(1)-PI measurement in detecting unrelated gastrointestinal disease may be limited in dogs on NSAID therapy, but alpha(1)-PI may be a useful marker for NSAID-induced gastrointestinal damage. OBJECTIVE: The aim of this study was to evaluate the effects of long-term administration of NSAIDs on fecal alpha(1)-PI concentrations in dogs. METHODS: Fecal samples were collected from 2 groups of dogs: 1) 21 clinically-healthy client-owned dogs without signs of gastrointestinal disease and receiving no NSAIDs and 2) 7 dogs referred for investigation and treatment of orthopedic disorders; the dogs had received either meloxicam or carprofen daily for at least 30 days. Fecal alpha(1)-PI concentration was measured by ELISA. RESULTS: Fecal alpha(1)-PI concentrations, expressed as micro g/g of feces, were not significantly different between groups 1 and 2 (median [range], group 1: 9.9 micro g/g [0.0-32.1 micro g/g]; group 2: 5.6 micro g/g [1.1-32.3 micro g/g]; P =.81). CONCLUSIONS: These results suggest that use of cyclooxygenase-2-selective NSAIDs, such as carprofen and meloxicam, does not significantly affect fecal alpha(1)-PI measurements. However, study numbers were small, and larger prospective trials are required to assess more accurately the gastrointestinal effects of NSAIDs in dogs.

Animals↗

Microbeams: a potent mix of physics and biology. Summary of the 5th International Workshop on Microbeam Probes of Cellular Radiation Response.

Single-cell microbeam irradiators are of increasing interest to the biological community. The 5th International Workshop on Microbeam Probes of Cellular Radiation Response, which took place in Stresa, Italy, in May 2001, was attended by about 120 registrants, roughly evenly divided between physicists and biologists. Many new microbeam devices are now under development, and there has been a significant diversification of the biological questions addressed. Most current uses of microbeams have been to address radiobiological questions, but the advent of sub-micrometre targeting capabilities, and the development of new single-cell assays, point to the potential for microbeams to make an important contribution to biological, and not just radiobiological, studies.

Animals↗

Eosinophilic diseases in two Cavalier King Charles spaniels.

This report describes the clinical presentation of two Cavalier King Charles spaniels with different eosinophilic diseases. The first case presented with dyspnoea and a non-productive cough, and investigations demonstrated eosinophilic bronchopneumonopathy. The second dog was referred for the investigation of haemorrhagic vomiting and diarrhoea and was eventually diagnosed with eosinophilic enteritis. Both dogs had concurrent eosinophilic stomatitis, and both responded completely to immunosuppressive glucocorticoid therapy. This report is the first to describe the concurrence of eosinophilic stomatitis and systemic eosinophilic disease in Cavalier King Charles spaniels, and suggest that this breed may be predisposed to eosinophilic syndromes.

Animals↗

The radiation-induced bystander effect for clonogenic survival.

It has long been accepted that the radiation-induced heritable effects in mammalian cells are the result of direct DNA damage. Recent evidence, however, suggests that when a cell population is exposed to a low dose of alpha particles, biological effects occur in a larger proportion of cells than are estimated to have been traversed by alpha particles. Experiments involving the Columbia University microbeam, which allows a known fraction of cells to be traversed by a defined number of alpha particles, have demonstrated a bystander effect for clonogenic survival and oncogenic transformation in C3H 10T(1/2) cells. When 1 to 16 alpha particles were passed through the nuclei of 10% of a C3H 10T(1/2) cell population, more cells were unable to form colonies than were actually traversed by alpha particles. Both hit and non-hit cells contributed to the outcome of the experiments. The present work was undertaken to assess the bystander effect of radiation in only non-hit cells. For this purpose, Chinese hamster V79 cells transfected with hygromycin- or neomycin-resistance genes were used. V79 cells stably transfected with a hygromycin resistance gene and stained with a nuclear dye were irradiated with the charged-particle microbeam in the presence of neomycin-resistant cells. The biological effect was studied in the neomycin-resistant V79 cells after selective removal of the hit cells with geneticin treatment.

Alpha Particles↗

Modest increased sensitivity to radiation oncogenesis in ATM heterozygous versus wild-type mammalian cells.

Subpopulations that are genetically predisposed to radiation-induced cancer could have significant public health consequences. Individuals homozygous for null mutations at the ataxia telangiectasia gene are indeed highly radiosensitive, but their numbers are very small. Ataxia Telangiectasia heterozygotes (1-2% of the population) have been associated with somewhat increased radiosensitivity for some end points, but none directly related to carcinogenesis. Here, intralitter comparisons between wild-type mouse embryo fibroblasts and mouse embryo fibroblasts carrying ataxia telangiectasia mutated (ATM) null mutation indicate that the heterozygous cells are more sensitive to radiation oncogenesis than their normal, litter-matched, counterparts. From these data we suggest that Ataxia Telangiectasia heterozygotes could indeed represent a societally-significant radiosensitive human subpopulation.

Animals↗

Molecular alterations in tumorigenic human bronchial and breast epithelial cells induced by high LET radiation.

Carcinogenesis is a multi-stage process with sequence of genetic events governing the phenotypic expression of a series of transformation steps leading to the development of metastatic cancer. In the present study, immortalized human bronchial (BEP2D) and breast (MCF-10F) cells were irradiated with graded doses of either 150 keV/micrometer alpha particles or 1 GeV/nucleon 56Fe ions. Transformed cells developed through a series of successive steps before becoming tumorigenic in nude mice. Cell fusion studies indicated that radiation-induced tumorigenic phenotype in BEP2D cells could be completely suppressed by fusion with non-tumorigenic BEP2D cells. The differential expressions of known genes between tumorigenic bronchial and breast cells induced by alpha particles and their respective control cultures were compared using cDNA expression array. Among the 11 genes identified to be differentially expressed in BEP2D cells, three (DCC, DNA-PK and p21(CIP1)) were shown to be consistently down-regulated by 2 to 4 fold in all the 5 tumor cell lines examined. In contrast, their expressions in the fusion cell lines were comparable to control BEP2D cells. Similarly, expression levels of a series of genes were found to be altered in a step-wise manner among tumorigenic MCF-10F cells. The results are highly suggestive that functional alterations of these genes may be causally related to the carcinogenic process.

Alpha Particles↗

Do no harm--normal tissue effects.

Radiation therapy confers enormous benefits that must be balanced against the possibilities for harm including late toxicity in normal tissues and radiation-induced second malignancies. A small percentage of patients experience severe late complications. The question is, do these late sequelae occur randomly, or are they confined to individuals who are genetically predisposed to radiosensitivity. Experiments with knockout mice and with patients demonstrate that individuals heterozygous for a number of genes appear to be radiosensitive. If radiosensitive patients were identified prospectively by genetic analysis, they could be spared the trauma of late sequelae. Several large studies have shown a statistically significant excess of radiation-induced malignancies in radiotherapy patients. Most second cancers are carcinomas, developing in the lining cells of the body often remote from the treatment site. Radiation-induced sarcomas appear only in the heavily irradiated areas. These are small in number but appear with a very high relative risk.

Animals↗

Drugs and syringe drivers: a survey of adult specialist palliative care practice in the United Kingdom and Eire.

Subcutaneous delivery of drugs using a syringe driver is common practice within specialist palliative care units. There is, however, little documented information regarding clinical practice. A survey performed in 1992 reported that at least 28 drugs were used in combination with others in a single syringe driver. The aim of the present study was to reassess practice in this field and to enquire more specifically about newer drugs. Postal questionnaires were sent to all adult specialist palliative care in-patient units in the UK and Eire (n = 208). One hundred and sixty-five units (79%) responded. The most common syringe driver in use was the Graseby 26 (61% of responding units). Most units delivered the contents of the syringe over 24 h, and water was usually used as the diluent in 90% of cases. The maximum number of drugs that respondents were prepared to mix in a single syringe was usually three (51%) or four (35%). In the UK, all units used diamorphine in doses from 2.5 mg/24 h upwards. All respondents also used haloperidol, in doses from 0.5 to 60 mg/24 h. A total of 28 different drugs were used in syringe drivers. The most common combinations were diamorphine and midazolam (37%), diamorphine and levomepromazine (35%), diamorphine and haloperidol (33%), and diamorphine and cyclizine (31%). In conclusion, there is much in common with regard to the way in which drugs are delivered in syringe drivers. However, a wide variety of drugs and drug combinations are still in use.

Adult↗

Mechanisms of radiation-induced neoplastic transformation of human bronchial epithelial cells.

Carcinogenesis is a multistage process with sequences of genetic events that govern the phenotypic expression of a series of transformation steps that lead to the development of metastatic cancer. To better understand the mechanisms involved in human bronchial carcinogenesis induced by alpha particles from radon, we have developed a model of neoplastic transformation based on human papillomavirus-immortalized human bronchial epithelial (BEP2D) cells. Cells exposed to alpha particles become tumorigenic after progressing through a series of sequential stages including altered growth pattern, resistance to serum-induced terminal differentiation, agar-positive growth, tumorigenicity, and metastasis, with each step representing a necessary yet insufficient step toward the later, more malignant phase. Cell fusion studies indicated that the radiation-induced tumorigenic phenotype in BEP2D cells can be completely suppressed by fusion with nontumorigenic BEP2D cells. Several cellular differentiation and growth regulation genes such as DCC (deleted in colorectal cancer), CDKN1A (also known as p21(C1P1)) and the gene that encodes DNA-PK were frequently found to be modulated in tumorigenic BEP2D cells and may be related to the process of carcinogenesis.

Animals↗