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Biomedical subjects

B Clark

Publications and source records attributed to B Clark.

At least 19 recordsLinked to original sources

Prevalence of hepatitis C virus antibodies in Sydney blood donors.

OBJECTIVE: To determine the prevalence of hepatitis C virus (HCV) antibodies in the Sydney blood donor population. DESIGN: All blood donations collected from Red Cross blood donors in Sydney from February 1990 until April 1991 were tested for HCV antibodies. For those samples found reactive in an anti-HCV screening test, a confirmatory test was carried out for the presence of HCV antibodies and the alanine aminotransferase level was measured. RESULTS: The prevalence of repeated reactivity to the screening test was 0.45% among blood donations overall, and 1.02% in donors giving blood for the first time in the study period. The confirmatory test result was positive for 30.8% of donations found to be repeatedly reactive in the screening test. There was little change over the study period in the HCV antibody prevalence of donors giving blood for the first time, but there was a clear decrease in the prevalence among all donations. Prevalence in males was nearly twice the prevalence in females--a difference which was consistent across age groups. The highest prevalence in both sexes was in the age group 30-34 years. Among samples for which the screening test results was positive, there was a strong correlation between the reactivity recorded for the screening test and both the proportion found positive by the confirmatory test and the proportion with an elevated alanine aminotransferase level. CONCLUSION: The small proportion of blood donations found to be repeatedly reactive by anti-HCV screening and the relatively good correlation with the confirmatory test and liver function assay indicate that a policy of discarding these donations will decrease the risk of transfusion-transmitted HCV infection without materially affecting the supply of blood.

Adult

Gangliogliomas in childhood.

Ganglioglioma is a tumour of the central nervous system composed of an admixture of dysplastic nerve cells resembling pleomorphic ganglion cells, and glial elements, which may be astrocytic and/or oligodendroglial in appearance. A series of 12 patients aged between 9 months and 15 years 9 months, all of whom had suffered epilepsy refractory to medical treatment for up to 8 years, is presented. Computed tomographic and magnetic resonance scans were of prime use in localisation of the tumours. Calcification was noted preoperatively in 4 of 12 cases. The majority of patients obtained at least partial relief from symptoms after complete or partial resection. Histologically, 11 of the tumours included grade 1 astrocytic elements and the remaining one exhibited grade 2 areas. The diagnosis of ganglioglioma should be suspected in a child with refractory, long-standing epilepsy. Prognosis of these tumours is determined by the astrocytic component; if this is of low grade, surgical excision may result in marked symptomatic improvement or cure.

Adolescent

Restoration of learning ability in fornix-transected monkeys after fetal basal forebrain but not fetal hippocampal tissue transplantation.

Monkeys with bilateral transection of the fornix were severely but selectively impaired on learning and retention of visuospatial conditional discriminations, visual conditional discriminations and non-conditional spatial-response tasks. Bilateral transplantation of cholinergic-rich fetal basal forebrain tissue into the hippocampus abolished significant learning impairments on all those tasks impaired by fornix lesions when tested three to nine months after transplantation whereas bilateral transplants of non-cholinergic fetal hippocampal tissue into hippocampus showed no such beneficial effect. Acetylcholinesterase staining was severely depleted throughout the dentate gyrus and hippocampus in fornix-transected monkeys compared with animals with control corpus callosum ablations. Staining was largely restored to normal in the host hippocampus and dentate gyrus in monkeys with cholinergic transplants, whereas acetylcholinesterase staining was abnormal in those with non-cholinergic grafts. These experiments suggest that where a "higher order" cognitive function, in this case the acquisition of specific types of information into long-term memory, is disturbed by a neuropharmacologically simple lesion, cognitive function can be restored by transplantation of neurons containing appropriate neurotransmitters.

Analysis of Variance

Striatal monoamine neurotransmitters and metabolites in dominantly inherited olivopontocerebellar atrophy.

We measured the levels of the monoamine neurotransmitters and metabolites in striatum of 14 patients with end-stage dominantly inherited olivopontocerebellar atrophy (OPCA). On average, dopamine levels were reduced in putamen (-53%), caudate (-35%), and nucleus accumbens (-31%). However, individual patient values showed a wide variation, indicating that mild to moderate striatal dopamine loss is a common but not constant feature of OPCA. Seven patients had marked putamen dopamine loss (-62% to -81%) but without evidence of correspondingly severe substantia nigra cell damage; this suggests the possibility of a "dying-back" phenomenon in which nerve terminal loss precedes cell body degeneration. Severe substantia nigra cell loss with almost total (-95% to -99%) putamen and caudate dopamine depletion was present in two patients; however, none of the 14 patients had had a clinical diagnosis of parkinsonism or was receiving antiparkinsonian medication. Mean striatal serotonin levels were normal, whereas concentrations of the serotonin metabolite 5-hydroxyindoleacetic acid were elevated by 47% to 63%; this suggests increased activity of raphe dorsalis serotonin neurons innervating the striatum, which might aggravate the functional consequences of the dopamine deficit.

Biogenic Amines

Transmitter-operated channels in rabbit retinal astrocytes studied in situ by whole-cell patch clamping.

Glutamate and GABA open ion channels in the membranes of astrocytes found on the vitreal surface of the rabbit retinal visual streak. The glutamate-operated channels are opened by kainate, quisqualate, and AMPA, but not by NMDA, aspartate, or the metabotropic agonist 1-aminocyclopentane-1 S,3R-dicarboxylic acid. The effects of glutamate and its analogs can be blocked by 20 microM 6-cyano-7-nitroquinoxaline-2,3-dione. The conductance increase evoked by 10 microM glutamate, a concentration of this transmitter near to that found in the vitreous humor that bathes these cells, was equivalent to 22% of the cell's resting conductance. The conductance increase evoked by 1 microM GABA, a concentration near that found in the vitreous, was equivalent to 131% of the cell's resting conductance. The effects of GABA can be blocked by bicuculline. These data show that GABA, and non-NMDA-type glutamate receptors play an important part in determining the resting potential of visual streak astrocytes in situ and that these channels may be of general importance for the functions of astrocytes in vivo.

Animals

Congenital ossifying fibroma (osteofibrous dysplasia) of the tibia--a case report.

Ossifying fibromas of the long bones of the leg are benign lesions occurring in the pediatric age group identical in histological appearance to the similarly named tumor of the jaw in adults. Most frequently presentation occurs after minor trauma with symptoms of a swelling of the tibia or fibula which may be painful. Pathological fracture or limp are also occasional presentations. Congenital cases are extremely rare. We describe an otherwise normal male neonate who presented at birth with a bowed right lower leg. The limb was 1 cm shorter than the other side, with tibia vara and a firm mass situated anteriorly. X-ray showed a mixed lytic and sclerotic lesion in the proximal metaphysis of the tibia. Biopsy showed collagenous stroma containing spindle cells and irregular trabeculae of woven bone rimmed by plump osteoblasts. As the appearances were typical of an ossifying fibroma (osteofibrous dysplasia) no surgical treatment was given. The patient was well with no growth of the tumor and with radiological evidence of healing at 1 year follow up. This case is presented to draw attention to the clinicopathological features of this unusual lesion which must be considered in the differential diagnosis of congenital lesions of the tibia.

Bone Neoplasms

Comparison of clinical, radionuclide, and radiographic features of osteoarthritis of the hands.

Simultaneous clinical, scintigraphic, and macroradiographic assessments were carried out on 32 patients with hand osteoarthritis and the results at entry and one year reported. The presence and growth of osteophyte correlated with symptoms and a positive scan. The scan did not detect the radiographic features of juxta-articular radiolucencies, subchondral sclerosis, or cartilage thinning. Osteophytes, particularly when fast growing, produce pain, a 'hot' scan, and may predict disintegration of joint architecture.

Arthrography

Sequences of taxol and cisplatin: a phase I and pharmacologic study.

Untreated and minimally pretreated solid tumor patients received alternating sequences of taxol and cisplatin. Sequential dose escalation of each agent using taxol doses of 110 or 135 mg/m2 and cisplatin doses of 50 or 75 mg/m2 resulted in four dosage permutations that induced grades 3 and 4 neutropenia in 72% to 84% and 50% to 53% of courses, respectively. Neutropenia was brief, and hospitalization for neutropenia and fever was required in 13% to 24% of courses. However, further escalation of taxol to 170 or 200 mg/m2 induced grade 4 neutropenia in 79% to 82% of courses. At the highest taxol-cisplatin dose level (200 mg/m2 to 75 mg/m2), the mean neutrophil count nadir was 98/microL, and hospitalization for neutropenia and fever was required in 64% of courses. The sequence of cisplatin before taxol, which has less antitumor activity in vitro, induced more profound neutropenia than the alternate sequence. Pharmacologic studies indicated that this difference was probably due to 25% lower taxol clearance rates when cisplatin preceded taxol. Although neurotoxicity was initially thought to be a potentially serious effect of the combination, mild to modest neurotoxicity occurred in only 27% of patients. Adverse effects also included myalgias, alopecia, vomiting, diarrhea, bradycardia, and asymptomatic ventricular tachycardia. Objective responses were noted in melanoma, as well as non-small-cell lung, ovarian, breast, head and neck, colon, and pancreatic carcinomas. Based on these results, the sequence of taxol before cisplatin at doses of 135 and 75 mg/m2, respectively, is recommended for phase II/III trials, with escalation of taxol to 170 mg/m2 if treatment is well tolerated.

Adult

Mentors and role models for women in academic medicine.

Senior mentors and role models have a positive influence on the career advancement of junior professionals in law, business, and medicine. In medicine an increasing number of women are pursuing academic careers, but available senior mentors to provide career guidance are often lacking. We report on the results of a national survey of 558 full-time faculty women, aged 50 years and younger, in departments of medicine in the United States, regarding their experience with role models and mentors. Women with mentors report more publications and more time spent on research activity than those without mentors. Women with a role model reported higher overall career satisfaction. This report, with illustrative examples, may be helpful to other women pursuing academic careers and to physicians who serve as mentors or role models to others.

Data Collection

Toward a rational therapeutic strategy for arachnoiditis. A possible role for d-penicillamine.

Twenty-six patients (13 men and 13 women), ranging in age from 38 to 75 years, with surgical and/or radiculographic evidence of chronic adhesive spinal arachnoiditis (CASA) were admitted to a randomly allocated, double-blind, 6-month crossover trial of d-penicillamine (500 mg/day) versus matching placebo. Assessments using subjective and objective criteria at 3-month intervals demonstrated no statistically significant effect with either d-penicillamine or placebo or between them. Thirteen of the 17 patients completing the trial expressed no clear preference. One patient preferred placebo. The remaining three patients who expressed strong preference for d-penicillamine (supported by objective data) subsequently maintained improvement on long-term therapy for up to 5 years. It is concluded that there may be a small subgroup of patients with CASA who might benefit from d-penicillamine therapy.

Adult

Quantitative microfocal radiographic assessment of progression in osteoarthritis of the hand.

We studied 32 patients with osteoarthritis who had 5x macroradiographs taken of their wrists and hands at 6-month intervals over an 18-month period. The higher magnification and resolution of microfocal radiography permitted the quantitative detection of progressive changes in 4 different features: subchondral sclerosis, the number and size of osteophytes, juxtaarticular radiolucencies, and joint space narrowing. Compared with normal control subjects, subchondral cortical thickness was greater in all patients at entry and showed a variable degree of change over the study period. Osteophytes and juxtaarticular radiolucencies were present in all patients at study entry; by the end of the study, osteophytes had increased in number and area, and juxtaarticular radiolucencies had increased in area, but not in number. At entry, 44% of the patients had joint space narrowing significantly greater than that in the control subjects; by 18 months, this proportion increased to 65%. No correlation was found between subchondral sclerosis, osteophytes, juxtaarticular radiolucencies, and joint space narrowing. We conclude that in osteoarthritis of the hand, the bony changes have progressed significantly before the occurrence of radiographically evident joint space narrowing indicative of cartilage thinning.

Aged

Differential binding of P. aeruginosa and S. aureus to corneal epithelium in culture.

Adherence of bacteria to corneal epithelium is a prerequisite for corneal infection. We used two methods to study the binding of Pseudomonas aeruginosa and Staphylococcus aureus to rabbit corneal epithelial cells in culture. In the first method, rabbit corneal epithelial cells grown on glass slides were incubated with P. aeruginosa or S. aureus (10(7) CFU/ml) at room temperature for 90 min, and the bacterial binding to the epithelial cells was examined by light microscopy. Both P. aeruginosa and S. aureus bound to epithelial cells. P. aeruginosa was bound to the cell periphery whereas S. aureus was bound randomly to the cell surface. In the second method, suspension cultures of corneal epithelial cells were used. In contrast to the findings in cultures on slides, binding pattern with cells in suspension was similar for both species and resembled that for S. aureus in cultures on slides. A much greater number of P. aeruginosa (186 +/- 11 bacteria/epithelial cell) than S. aureus (30 +/- 1.5 bacteria/epithelial cell) bound to epithelial cells grown on glass slides. In contrast, a similar number of P. aeruginosa (25 +/- 5.1) and S. aureus (20 +/- 4.7) bound to epithelial cells grown in suspension cultures. Using either method, Escherichia coli and Streptococcus pyogenes did not bind significantly (less than 5/cell) to corneal epithelial cells. The above methods should prove useful for characterization of bacterial binding to corneal epithelial cells in culture.

Animals

Biological function of the rotavirus protein VP4: observations on porcine isolates from China.

Rotaviruses isolated from pigs in China were grown in MA104 cells. One tissue-culture-adapted isolate consisted of two subpopulations (variants), the RNA profiles of which differed in the relative migration of RNA segment 4 only. The variants were separated by plaque purification and by recovery from limiting dilutions and remained genetically stable. The variant possessing the slower migrating RNA segment 4, called 4S, grew faster and formed large plaques after 4-6 days incubation, whereas the variant possessing the faster migrating RNA segment 4, called 4F, grew more slowly and formed only microscopic plaques after 10-14 days incubation. The protein product of the 4F RNA occurred in much lower concentration in infected cells than the product of the 4S RNA. The RNA segments 4 of the two variants were found to be closely related when tested by dot hybridization under stringent conditions. The 4S RNA is more resistant to denaturation with methyl mercuric hydroxide than is the 4F RNA. The relevance of these findings to the biological functions of rotaviruses is discussed.

Animals