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Biomedical subjects

S Whitaker

Publications and source records attributed to S Whitaker.

At least 19 recordsLinked to original sources

A polycistronic transcript in transformed cells encodes the dihydrofolate reductase of herpesvirus saimiri.

Herpesvirus saimiri, an oncogenic gamma herpesvirus of primates, is the only eukaryotic virus that carries the entire metabolic gene set for a complex biochemical synthesis. Every element of the thymidine synthesis gene cascade is present in the virus, and their function is probably related to the uniquely high A + T content of the genome. Although one member of the gene set, dihydrofolate reductase (DHFR), is mapped in a region required for oncogenesis, very little is known of the expression and function of this gene in transformed cells. We report the expression of the DHFR sequence on a novel, unique tricistronic transcript in virally transformed tumor cells. The DHFR sequence is the first open reading frame on a 5.3 kb minor transcript. Alpha-amanitine sensitivity indicates that it is an RNA polymerase II transcript, and since it is also polyadenylated it appears to be a functional, relatively unstable (half-life 3 hr) mRNA. Initiation of transcription uniquely overlaps with the HSUR3 small RNA gene. Expression of the small transcript appears to be alpha-amanitine resistant, implicating polymerase III transcription. Together with the remarkably low-level expression of HSUR3 in tumor cells, the data may indicate transcription interference between two different RNA polymerases, with unusual overlapping regulation and initiation.

Base Sequence

Audit of pre-employment assessments by occupational health departments in the National Health Service.

Pre-employment health assessment of applicants to the National Health Service (NHS) is one of the functions of occupational health departments in the NHS. This paper describes the results of a process and outcome audit of this activity, concentrating on the current practice of occupational health departments. The audit was carried out by 40 NHS occupational health units who provided information on a standard questionnaire on all pre-employment assessments undertaken over a three-month period. This produced 9139 questionnaire returns. The analysis showed that the most common method of assessment was the use of a self-administered questionnaire alone (49.4%). A self-administered questionnaire followed by a nurse interview as standard practice was the next most common method (34.1%), but referral to a physician was uncommon. The outcome of the assessments for 98% of all applicants was 'fit for work'. A total of 120 individuals (1.3%) were assessed as 'fit to work, but with some restriction' and 65 individuals (0.7%) were considered 'unfit'. The most common reasons for rejection were abnormal body mass index (40%), skin conditions (21.5%) and psychiatric conditions (10.8%). The most common reasons for restriction were musculoskeletal conditions (27.5%), skin conditions (15%) and abnormal body mass index and psychiatric conditions (both 10.8%). The audit identified wide variation between occupational health departments in the NHS in the practice of restriction and rejection. A decision on the value of pre-employment assessment in the NHS mus take into consideration the ability of the process to achieve its aim, the time and manpower involved in the process, and the probability of low restriction and rejection rates.(ABSTRACT TRUNCATED AT 250 WORDS)

Employment

The art and science of home infant apnea monitoring in the 1990s.

The use of home apnea monitoring (HAM) continues as an accepted or recommended intervention for infants with certain signs and symptoms or medical diagnoses. Results of HAM in terms of case outcomes versus cost-effectiveness and efficacy remain matters of controversy in relation to the limited number of studies that show conflicting results. There are no studies that document the effectiveness of apnea monitoring. When an apnea monitor is prescribed, nursing can provide quality care through education and emotional support of families using HAM.

Apnea

Ataxia telangiectasia: an investigation of the repair defect in the cell line AT5BIVA by plasmid reconstitution.

The ataxia telangiectasia cell line, AT5BIVA, exhibited low repair fidelity measured by the reconstitution of transfected linear plasmid. This assay involves transfecting a linear plasmid containing two selectable marker genes: one gene (neo) is undamaged and marks transfection and the other gene (gpt) is cleaved to test functional repair. The proportion of transfected cells which have a functionally intact gpt gene gives a measure of repair fidelity. Southern analysis of individual transfected clones showed that integrated plasmids in AT5BIVA had a high frequency of sequence rearrangement. Blunt or staggered-ended termini of a linear plasmid did not determine the type of misrepair. A variety of sizes of deletions and sequence insertions were found at and around the cleavage site. Loss of intact sequence occurred similarly following transfection by linear or circular plasmid (misrepair or rearrangement error). This suggests that the action of excess exonuclease activity upon, or lack of protection of, exposed DNA termini is not the sole mechanism of misrepair. Erroneous rearrangement of circular plasmid could involve any location along the plasmid. Rearrangement of transfected circular plasmid occurred in multiple copies of the same abnormal size, suggesting that error-prone recombination rather than degradation of presumed nicked circular plasmid was the underlying mechanism. It is hypothesized that misrepair in ataxia-telangiectasia arises by error-prone recombination.

Ataxia Telangiectasia

The reduction of aggression in people with learning difficulties: a review of psychological methods.

The literature on the reduction of aggression in people with learning difficulties is reviewed. The methods of reducing aggression identified were predominantly evaluated in staffed settings and with target behaviours more frequent than once a day. This contrasts with the findings of a recent survey that found the majority of aggressive individuals to live in the community and show aggression less than once a day. It is argued that the reasons for this disparity are as follows. That it is easier to do a controlled study in staffed settings with high-frequency aggression. That it is more difficult to do an analysis of the target behaviour if it is low frequency or if the subject is in the community; and that the methods that have been traditionally used to reduce aggression may not be effective with all subjects in all settings. It is suggested that it may be necessary to develop and evaluate a new technology for reducing aggression.

Adolescent

PEA: working towards standards of good practice in the NHS.

At the beginning of the year Stuart Whitaker described a pilot study for the national audit of pre-employment assessment in the NHS. Having completed the project he now presents its findings with a call for the introduction of standards of good practice.

Employment

Prognostic significance of tumor ploidy in patients with advanced ovarian carcinoma.

Fresh tumor specimens obtained from 53 consecutive patients with FIGO Stage III ovarian carcinoma were analyzed by flow cytometry. All patients were treated by a standard protocol: maximal tumor excision and cisplatin/cyclophosphamide/adriamycin chemotherapy, and followed-up for at least 24 months. Thirty-two percent of tumors were diploid (DNA index = 1.00) and 68% aneuploid (DNA index greater than 1.00), with more aneuploid tumors being associated with larger residual tumor and poor cellular differentiation. Patients with diploid tumors were found to survive significantly better than those with aneuploid tumors, in terms of survival rate (65% versus 31%), median survival time (33 months versus 13 months), and mean disease-free interval (17.8 months versus 8.2 months). The influence of the amount of residual tumor after primary surgery on survival was only significant in patients with diploid tumors. Our results support previous findings that tumor ploidy is an important prognostic indicator in ovarian cancer. We found aneuploidy to be associated with a poorer clinical outcome in Stage III disease, regardless of the amount of residual tumor after primary surgery and the degree of cellular differentiation.

Adenocarcinoma

Determination of cell membrane permeability in concentrated cell ensembles.

The method of volume averaging is used to analyze the process of diffusion in concentrated cell ensembles in which significant resistance to mass transfer is caused by the cellular membrane. A general closure scheme is given that allows for direct theoretical prediction of effective diffusivities for any cellular geometry. Numerical results are presented for the classical parallelepiped arrangement used to model cellular systems, and these results are used in conjunction with experimental studies of concentrated cell ensembles to determine membrane permeabilities for solute diffusion in several cellular systems. Membrane permeabilities are compared with predictions from other models of diffusion in cellular systems.

Animals

The transiency of oropharyngeal colonization with gram-negative bacilli in residents of a skilled nursing facility.

To determine the duration and persistence of gram-negative bacillary (GNB) oropharyngeal colonization over a specified period and the risk of subsequent GNB pneumonia developing in nursing home patients, we prospectively cultured for 31 weeks the oropharynges of patients in a skilled nursing facility. Over a 31-week period, an average of 13.8 percent of the patients showed colonization (weekly prevalence rates ranged from 0 to 29 percent). No patient had pneumonia during the study period. We concluded that the presence of GNB in the oropharynx of our patients is transient, continually changing over an extended period, and that GNB colonization as a transient occurrence is not directly associated with an increased risk of GNB pneumonia. Our data also emphasize the limitations of previously described single-culture survey studies in predicting the importance of GNB oropharyngeal colonization.

Adult

Idiopathic sudden hearing loss.

Idiopathic sudden hearing loss is an otologic emergency with an obscure cause. It is the acute onset of hearing loss of 30 cB in three contiguous frequencies, which may occur instantaneously or progressively over several days. Suspect etiologies include viral infections, cochlear artery occlusion, rupture of the intracochlear membranes, and biochemical alterations in the metabolism maintaining the endocochlear membrane potentials. Histopathology of the temporal bone most commonly reveals atrophy of the organ of Corti and striae vascularis. Treatments proposed include close observation for spontaneous recovery, steroid theray, and combination regimens of vasodilators, steroids, diuretics, and intravenous iodinated radiocontrast material. Prognosis and recovery are related to the audiometric pattern of the hearing loss and associated symptoms. The absence of vertigo at th clinical onset and low tone hearing loss are associated with better hearing recovery.

Adult

Predictive value of serial carcinoembryonic antigen levels in long-term follow-up of ovarian cancer.

The predictive value of serial levels of carcinoembryonic antigen (CEA) in tumor monitoring was examined in 213 patients with ovarian cancer; each patient had been followed-up at monthly intervals for at least 12 months. CEA was not detectable throughout the period of observation in 35% of the patients. In general. patterns showing a disappearance of CEA or persistently low levels were associated with a good prognosis, whereas those showing a reappearance or highly elevated and rising levels were associated with a poor prognosis. A transient reappearance of CEA was observed in 10 patients; this did not appear to be associated with tumor recurrence or progression. "False positive" results were obtained in 6 patients in whom no tumor has been clinically detectable to date. "False negative" results were obtained in 4 patients with obvious tumor progression. In terms of a good or poor prognosis, the use of CEA levels was highly accurate in patients with minimal or no residual disease (97% and 89%, respectively); the rate fell to 62% in patients with extensive disease. As the clinical significance and limitations become better known, serial CEA levels should contribute substantially to the monitoring of patients with ovarian cancer.

Carcinoembryonic Antigen

Effect of blood dilution on recovery of organisms from clinical blood cultures in medium containing sodium polyanethol sulfonate.

This clinical study was designed to evaluate the standard laboratory protocol that requires blood specimens be diluted with greater than or equal to 10 volumes of media. Blood was collected from hospitalized patients, and 1 ml was inoculated into each of three vials containing 2.3, 7.3, and 24 ml of BACTEC 6B aerobic medium resulting in dilutions of 1:4, 1:10, and 1:30, respectively. The three test vials were treated identically, and the study was carried out at four hospitals. Of the 2,550 sets of vials inoculated, 174 were positive with clinically significant isolates from 105 patients. There was no difference in the number of positive cultures recovered by 24 h (67%) or 48 h (90%) from any dilution. These percentages agreed with other reports from BACTEC users. The number of positive vials (139, 144, 147, respectively) at each dilution was not significantly different, indicating that all three dilutions showed equal recovery of pathogenic microorganisms. Despite this overall equality, two patients, one on antibiotic therapy, were found to have correlated cultures which failed to grow at the 1:4 dilution. This finding implies that a 1:4 dilution of blood cannot be recommended unequivocably despite the higher overall recovery rate of positive cultures.

Bacteria