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Biomedical subjects

D A Kerr

Publications and source records attributed to D A Kerr.

At least 19 recordsLinked to original sources

Herpes simplex encephalitis and bilateral acute retinal necrosis syndrome after craniotomy.

PURPOSE: Acute retinal necrosis (ARN) syndrome is associated with members of the herpes virus family, but the mechanisms of infection remain unclear. The purpose of this study is to report a unique case of acute retinal necrosis syndrome associated with herpetic encephalitis in order to elucidate possible factors involved in herpetic central nervous system disease. METHOD: Case report. RESULTS: A 64-year-old woman who developed acute herpes simplex virus encephalitis associated with bilateral acute retinal necrosis syndrome after craniotomy for resection of a suprasellar craniopharyngioma is presented. The results of lumbar puncture, magnetic resonance imaging, and ophthalmologic examination are consistent with herpetic infection. The origin of acute retinal necrosis syndrome and the association of acute retinal necrosis syndrome with encephalitis are reviewed. CONCLUSIONS: After craniotomy, we hypothesize reactivation of previously latent herpes simplex virus in the area of the inferior frontal lobe and optic chiasm. Reactivated virus may have migrated to the retina by axonal transport, through the optic nerves, to produce the acute retinal necrosis syndrome.

Acyclovir

Absolute size and proportionality characteristics of World Championship female basketball players.

In total, 168 players from 14 national teams were measured using 38 anthropometric dimensions before the Women's World Basketball Championships held in Australia in 1994. Measures of segment length, breadth and girth were recorded by a team of trained anthropometrists using standard protocols. The subjects were divided according to playing position and team performance so that univariate analyses of variance could be administered using absolute size and proportionality data as dependent variables. Clear differences in absolute size were found between guards, forwards and centres, but in terms of proportionality the latter two groups exhibited some similarities, particularly for measures of relative size in upper body dimensions. With guards displaying a different proportionality profile from either forwards or centres, the various roles of each position within the team were considered to rationalize the findings.

Adult

Evidence that the soluble factors secreted by activated immune cells suppress replication of human neurotropic JC virus DNA in glial cells.

Coordination of the immune response to viral infection and disease in the brain is believed to involve bidirectional interaction between the immune system and the central nervous system (CNS). Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the CNS that generally affects patients exhibiting an immunocompromised condition due to various illnesses. The human polyomavirus, JCV, which infects greater than 70% of the adult population is the etiological agent of this disease. Infection with JCV occurs during childhood and the virus remains in the latent state with no apparent clinical signals. However, under immunocompromised conditions, the virus enters the lytic cycle, and upon cytolytic destruction of glial cells, causes PML. To understand the molecular mechanism underlying immune regulation of JCV replication, we have developed a cell culture system and have investigated the effect of soluble factors from T-cell cultures on replication of JCV DNA in glial cells. Our data demonstrate that replication of JCV DNA in the presence of PMA-stimulated T-cell supernatant is substantially decreased in transfected glial cells. Heat-inactivation and size-fractionation studies revealed participation of a heat labile factor(s) which loses its maximum activity at 60 degrees and ranges between 30 and 100 kDa in size. The unfractionated T-cell supernatant and the fraction enriched in 30- to 100-kDa proteins reduced the level of viral DNA replication during the early phase of the lytic cycle. These observations suggest that regulatory factors which are secreted by immune cells may modulate the level of JCV DNA replication in glial cells. The importance of these observations in reactivation of JCV in immunocompromised individuals and development of PML is discussed.

Antigens, Polyomavirus Transforming

Cooperative action of cellular proteins YB-1 and Pur alpha with the tumor antigen of the human JC polyomavirus determines their interaction with the viral lytic control element.

Human JC polyomavirus (JCV) is the etiologic agent of the neurodegenerative disease progressive mulifocal leukoencephalopathy. By using JCV as a model, we investigated the role of the viral early protein tumor antigen (TAg) in the binding of two cellular proteins, Pura alpha and YB-1, to JCV regulatory sequences. Results from band-shift assays with purified YB-1, Pur alpha, and TAg indicated that efficient binding of Pur alpha, a strong activator of early gene transcription, to a single-stranded target sequence corresponding to the viral lytic control element, is diminished in the presence of the late gene activator YB-1, which recognizes the opposite strand of the Pur alpha binding site. Of particular interest was the ability of Pur alpha and TAg to enhance binding of YB-1 to DNA molecules without being associated with this complex. Binding studies using a mutant peptide encompassing the N terminus of YB-1 indicated that the C terminus of YB-1 is important for its DNA binding activity. The ability of Pur alpha and TAg to increase binding of YB-1 to DNA is independent of the YB-1 C terminus. Similarly, results from band-shift assays using Pur alpha variants indicated that two distinct regions of this protein contribute either to its ability to bind DNA or to its ability to enhance YB-1 DNA binding activity. Based on the interaction of Pur alpha, YB-1, and TAg, and their binding to DNA, a model is proposed for the role of these proteins in transcription of viral early and late genes during the lytic cycle.

Animals

A longitudinal study of the effect of sodium and calcium intakes on regional bone density in postmenopausal women.

The influence of urinary sodium excretion and dietary calcium intake was examined in a 2-y longitudinal study of bone density in 124 women postmenopausal for > 10 y. Analysis of bone density changes showed that urinary sodium excretion was negatively correlated with changes in bone density at the intertrochanteric and total hip sites. Multiple-regression analysis of dietary calcium intake and urine sodium excretion on the change in bone density showed that both dietary calcium and urinary sodium excretion were significant determinants of the change in bone mass over 2 y at the hip and ankle sites. These data suggest that an effect of reducing bone loss equivalent to that achieved by a daily dietary increase of 891 mg (22 mmol) Ca can also be achieved by halving daily sodium excretion. No bone loss occurred at the total hip site at a calcium intake of 1768 mg/d (44 mmol/d) or a urine sodium excretion of 2110 mg/d (92 mmol/d). We report a significant effect of sodium excretion on bone loss in this population.

Bone Density

Inhibition of human neurotropic virus (JCV) DNA replication in glial cells by camptothecin.

Progressive multifocal leukoencephalopathy is a subacute demyelinating disease of the central nervous system (CNS) resulting from opportunistic infections in immunocompromised patients infected with a common polyomavirus, JC virus (JCV). Unlike other polyomaviruses, JCV exhibits an unusually narrow tissue tropism by primarily infecting glial cells of the CNS. JCV DNA replication is similar to that of the well-characterized papovavirus, SV40, which requires the viral early protein T-antigen and host-replication factors including DNA polymerases and DNA topoisomerase I. In this study we have been able to effectively block replication of viral DNA in glial cells using camptothecin, a drug which inhibits DNA topoisomerase activity. Pulse-treatment of cells with non-toxic levels of camptothecin specifically blocks viral DNA replication with no inhibitory effect on host transcription and translation processes as examined by viral gene expression in the transfected cells. Furthermore, drug treatment of the cells exhibits no significant effect on DNA topoisomerase I gene transcription. We further demonstrate that repeated pulse-treatment of cells with the drug is required for complete blockage of viral DNA replication. The importance of these findings in the treatment of AIDS encephalopathy is discussed.

Antineoplastic Agents

Correlates of intestinal calcium absorption in women 10 years past the menopause.

Because intestinal calcium absorption may be an important independent determinant of calcium balance and therefore bone mass, we have studied this factor and other potential predictors in 196 healthy postmenopausal women. Gut calcium absorption was measured in each subject by a stable strontium method and expressed as a fractional absorption. The fractional absorption was significantly negatively correlated with years since menopause (YSM) (r = -0.15 P < 0.05) and dietary calcium intake (r = -0.15 P < 0.05), and significantly positively correlated with 24-hour urine calcium excretion (r = 0.31 P < 0.001) and body mass index (r = 0.20 P < 0.01). Apart from YSM, these factors remained as correlates in multiple regression analysis; the standardized regression coefficient was largest for 24-hour urine calcium excretion (0.32). Fractional absorption of calcium was not correlated with vertebral bone density. Thus, intestinal calcium absorption, although falling with increasing menopausal age and increasing calcium intake, is best correlated with the urine calcium excretion. This indicates either that gut calcium absorption is regulated in response to the magnitude of the urine calcium excretion or that the kidney maintains calcium balance by excreting what is absorbed by the intestine. The mechanisms whereby gut and renal calcium handling are correlated are uncertain.

Absorptiometry, Photon

Iron status and diet in athletes.

Plasma ferritin (F) concentrations were measured (range 12-245 ng.ml-1) as an indicator of iron status in 24 male and 45 female healthy, nonanemic athletes. Usual food intake was assessed using a self-completed but supervised food frequency questionnaire. Linear regression was applied to determine the relationship between log F (as data was skewed) and average daily intake of iron (Fe), meat (M), protein (Pr), carbohydrate (CHO), fat (Fa), fiber (Fi), and kilojoules (Kj). There were negative correlations between F and each of Kj (P < 0.01) and CHO (P < 0.001), and a positive correlation between F and Pr/Kj (P < 0.01). No significant relationship existed between F and any of Fe, M, Fa, or Fi. These data suggest that iron or meat intake may not be important determinants of iron status in these athletes. Instead, the percentage of protein in the diet may be more influential on F, as may the (negative) effect of Kj and CHO intake, or at least their reflection of energy expenditure.

Adolescent

Plasma ferritin concentration and physical work capacity in athletes.

This investigation aimed to determine whether the physical work capacity of nonanemic athletes could be improved when plasma ferritin concentrations of below 30 ng/ml were raised at least 15 ng/ml. The experimental group consisted of 15 training athletes, each of whose plasma ferritin concentration was less than 30 ng/ml (mean and SD of 19.8 +/- 8.4 ng/ml). In a control group of 16, each was measured with a plasma ferritin concentration of more than 40 ng/ml (mean and SD of 83.3 +/- 37.6 ng/ml). All participated in submaximal and maximal tests for aerobic and anaerobic power. Following iron supplementation, plasma ferritin concentration in each experimental subject increased by at least 15 ng/ml to more than 30 ng/ml, to a new mean of 46.3 +/- 15.5 ng/ml. The performance measures were also repeated, but no significant overall effects were associated with the increased plasma ferritin concentrations. These data provide no sound evidence that physical work capacity of athletes is enhanced when plasma ferritin concentrations of around 20 ng/ml are increased by at least 15 ng/ml.

Female

Physique characteristics of Pan American Games lightweight rowers.

The emergence of lightweight rowing as an international sport has made the optimization of physique within the weight restrictions a matter of primary importance in selection and training of the participants. The occasion of the Xth Pan American Games provided opportunity to obtain comprehensive anthropometric data on 20 male and 13 female lightweight rower finalists including most of the medal winners. Anthropometric characteristics, somatotype, and proportionality profiles showed the male rowers to be similar in most aspects to a student control sample, with the exception of short sitting height and large transverse chest breadth. The females, on the other hand, appeared to be very different from the control sample, having a number of characteristics similar to those of Olympic rowers. The female lightweight rowers also uniquely demonstrated two distinct physique prototypes.

Anthropometry

Relationship of the body mass index with skinfolds, girths, and bone breadths in Canadian men and women aged 20-70 years.

The relationship of Quetelet index (w/h2), or body mass index (BMI), with the sum of skinfolds at five sites, two skinfold-corrected limb girths, and two bone breadths were studied in a cross-sectional sample of 12,282 men and 6,593 women aged 20-70 years. The correlations of the BMI with skinfolds (0.50), bone breadths (0.51), and girths (0.58) were too low for individual prediction. Contingency tables of the BMI and sum of skinfold categories further indict its use for the purpose of assessing adiposity status or monitoring change in individuals.

Adult

Bioavailability of three oral dosage forms of cisapride, a gastrointestinal stimulant agent.

Relative bioavailability of the investigational gastrointestinal stimulant agent cisapride after oral administration was determined in healthy men. Treatments administered were (A) two 5-mg tablets; (B) one 10-mg tablet; (C) 10 mL of a 1-mg/mL suspension; and (D) 10 mL of a 1-mg/mL aqueous reference solution. The study had a randomized four-way, crossover design; drug administration was followed by a standard breakfast. Plasma cisapride concentrations in blood samples drawn over 48 hours were measured by high-performance liquid chromatography. Individual and mean values for bioavailability parameters were subjected to analysis of variance followed by multiple comparison testing. Time to maximum concentration was shortest after administration of the solution. There was a significant difference in mean peak plasma concentrations between treatment A (48.8 +/- 12.8 ng/mL) and treatment D (41.6 +/- 10.6 ng/mL), with treatment A producing a 17.3% higher peak concentration. No significant differences between treatments were found for area under the plasma concentration-time curve. The overall mean elimination half-life was 7.01 hours. The results of the study indicate that the tablet and suspension dosage forms of cisapride are bioequivalent to the reference solution.

Administration, Oral

A family planning risk scoring system for health care providers.

The potential usefulness of a Family Planning Risk Scoring Sheet was studied in 1720 consecutive women who completed a family planning visit and were prescribed a specific contraceptive method. The results demonstrated that many women had relative or absolute contraindications to their prescribed method that were detected later by the Family Planning Risk Scoring Sheet. There were 29 women in the oral contraceptive and intrauterine device groups who had absolute contraindications detected (2.8 and 2.4%, respectively). The nurse practitioners tended to have fewer unrecognized problems in their groups than did the physicians. The usefulness of the Family Planning Risk Scoring Sheet was demonstrated and its routine use in a busy family planning unit is recommended.

Adult

Odontogenic tumors: analysis of 706 cases.

From a total of 54,534 oral biopsy specimens, 706 (1.3%) odontogenic tumors were retrieved and reviewed. Odontomas comprised more than 65% of the odontogenic tumors, ameloblastomas about 10%, and the remaining six categories of odontogenic tumors accounted for approximately 25% of the lesions. The distribution by age, sex, and location of these tumors generally supported the data from other previously reported cases. A possible variant of the calcifying epithelial odontogenic tumor was described, and instances of two granular cell ameloblastic fibromas were reported. The myxomas as a group were characterized histologically more by residual bony trabeculae than by the presence of odontogenic rests. Because the clinical, histological, and behavioral features of the ameloblastic fibroma and ameloblastic fibro-odontoma were similar, these lesions were considered to be essentially the same. From limited follow-up information, the ameloblastoma was the only lesion that recurred. With the exception of one ameloblastoma found in the lung, no malignant odontogenic tumors were encountered.

Adolescent

Neurofibrosarcoma of the mandible.

A case has been reported to illustrate the apparent transition of a neurofibroma into a neurofibrosarcoma. Biopsy of the inferior alveolar nerve, proximal to the lesion, was used to determine the extent of tumor extension. En block excision of the tumor was performed. The patient has been without evidence of recurrence for approximatley 3 1/2 years. Bone graft reconstruction has been completed and full function has been restored to the mandible.

Adult

Dental management of patients irradiated for oral cancer.

Management of patients irradiated for oral cancer should include consideration of their oral health prior to, and after, radiation therapy. Data from 130 patients, followed for a period of 1 to 10 years, are presented and evaluated. The philosophy of retention and maintenance of as many teeth as possible is supported by this data. Extraction of teeth with severe periodontal disease after irradiation also proves to be a relatively safe operation. Osteoradionecrosis tends to be limited in extent and is generally well tolerated by the patient when treated conservatively. A treatment regimen is presented that significantly reduces the morbidity from therapeutic irradiation of the jaws. A comprehensive dental evaluation and follow-up plan coupled with patient cooperation are instrumental to the success of this program.

Adolescent