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Biomedical subjects

S White

Publications and source records attributed to S White.

At least 163 records · Page 9Linked to original sources

Felbamate monotherapy: implications for antiepileptic drug development.

We studied the effect of felbamate (FBM) monotherapy on seizure rate in patients with partial and secondarily generalized seizures undergoing presurgical monitoring at a single site. The study design was a double-blind placebo-controlled parallel monotherapy trial. Forty patients whose seizures had not been controlled by standard antiepileptic drugs (AEDs) were randomized. Seizure type was confirmed by video-EEG monitoring. All baseline AEDs were discontinued, and patients were drug-free for 5.3 +/- 2.4 days before randomization to FBM or placebo. After a 4-day titration, seizures were counted for 14 days. Patients receiving FBM had significantly lower seizure rates, whether all randomized patients, patients who survived titration, or study completers were compared. Eight of 19 placebo patients randomized to placebo, as compared with 13 of 21 receiving FBM, completed the 18-day study. Two FBM patients dropped out due to seizures, and 6 dropped out due to side effects, including anxiety, difficulty sleeping, abdominal discomfort, acute psychosis, and orobuccal dyskinesias. Ten placebo patients met the criteria for premature discontinuation owing to seizures, and 1 hd an episode of panic. There was no evidence of hepatic or hematologic toxicity. FBM reduces seizure frequency in patients with localization-related epilepsy.

Adolescent↗

Genes required for cellulose synthesis in Agrobacterium tumefaciens.

A region of the chromosome of Agrobacterium tumefaciens 11 kb long containing two operons required for cellulose synthesis and a part of a gene homologous to the fixR gene of Bradyrhizobium japonicum has been sequenced. One of the cellulose synthesis operons contained a gene (celA) homologous to the cellulose synthase (bscA) gene of Acetobacter xylinum. The same operon also contained a gene (celC) homologous to endoglucanase genes from A. xylinum, Cellulomonas uda, and Erwinia chrysanthemi. The middle gene of this operon (celB) and both the genes of the other operon required for cellulose synthesis (celDE) showed no significant homology to genes contained in the databases. Transposon insertions showed that at least the last gene of each of these operons (celC and celE) was required for cellulose synthesis in A. tumefaciens.

Agrobacterium tumefaciens↗

Prostate cancer: effect of postbiopsy hemorrhage on interpretation of MR images.

PURPOSE: To assess the frequency of changes in signal intensity after prostatic biopsy and the effect of these changes on the magnetic resonance (MR) imaging staging of prostate cancer. MATERIALS AND METHODS: Seventy-three patients with biopsy-proved prostate cancer were divided into two groups according to time between biopsy and imaging (less than and more than 21 days). The findings at MR imaging were compared with those at pathologic examination. RESULTS: Postbiopsy hemorrhage was detected in 21 of 26 (81%) patients who underwent imaging less than 21 days after biopsy and in 23 of 47 (49%) patients who underwent imaging more than 21 days after biopsy (P < .01). Postbiopsy changes persisted for as long as 4 1/2 months. Less than 21 days after biopsy, there was a tendency to overestimate tumor presence and extracapsular extension. After 21 days, tumor presence was underestimated but the positive predictive value for extracapsular extension was improved. Staging accuracy less than 21 days after biopsy was 46%; this improved to 83% after 21 days (P < .01). CONCLUSION: Staging accuracy is significantly improved when imaging is deferred for 21 days after biopsy.

Biopsy, Needle↗

Interictal metabolism and blood flow are uncoupled in temporal lobe cortex of patients with complex partial epilepsy.

We used positron emission tomography (PET) with 18F-2-deoxyglucose (FDG) and 15O water in 20 patients with complex partial seizures to compare glucose metabolism and blood flow in temporal lobe epileptic foci identified by ictal scalp-sphenoidal video-EEG telemetry. Glucose metabolism was measured 20 minutes after blood flow without moving the patient from the scanner. We also studied 11 patients with 99mTc-HMPAO single-photon emission computed tomography (SPECT). Both local cerebral metabolic rate of glucose (LCMRGlc) and regional cerebral blood flow (rCBF) were significantly decreased in temporal cortex ipsilateral to the EEG focus. However, LCMRGlc was reduced by 11.2% in inferior lateral and 11.1% in inferior mesial temporal cortex and rCBF by only 3.2% and 6.1%. The ratio of LCMRGlc to rCBF was significantly reduced in inferior lateral temporal cortex ipsilateral to the ictal focus (p < 0.009). Moreover, using standardized criteria, blinded raters found that 16 of 20 patients had focal FDG-PET hypometabolism, all in the epileptogenic region; 10 of 20 had focal 15O water PET hypoperfusion, but it was falsely lateralized in two of these 10; and five of 11 had focal 99mTc-HMPAO SPECT hypoperfusion, but it was falsely lateralized in two of these five. Our data suggest that interictal glucose metabolism and blood flow may be uncoupled in epileptogenic cortex.

Adult↗

Changes in alpha (1-2)-fucosyltransferase activity in the murine endometrial epithelium during the estrous cycle, early pregnancy, and after ovariectomy and hormone replacement.

alpha (1-2)-Fucosyltransferase (alpha (1-2)-FT) activity in the uterine luminal epithelium was investigated during the estrous cycle, during early pregnancy, and in ovariectomized mice treated with ovarian steroids. Phenyl-beta-D-galactoside was used as a specific acceptor for alpha (1-2)-FT activity. Enzyme activity fell dramatically throughout the pre- and peri-implantation period (Days 1-6 of pregnancy). Activity on Day 4 of pregnancy represented less than a tenth of the Day 1 level and by Day 6 became undetectable. During the estrous cycle alpha (1-2)-FT showed a peak of activity at estrus, the level being similar to that observed on Day 1 of pregnancy. In proestrus, postestrus, and diestrus, activity was similar and was approximately one fifth of that during estrus. Ovariectomized mice were primed with estrogen and treated with progesterone only, estradiol benzoate only, or progesterone followed by a single injection of progesterone and estradiol. Estrogen alone stimulated alpha (1-2)-FT activity, while progesterone treatment was strongly inhibitory. These results correlate well with the pattern of expression of the fucosylated H-type-1 carbohydrate epitope found on the endometrial epithelium and believed to have a role in implantation. alpha (1-2)-FT is capable of catalyzing the final step in formation of the H-type-1 oligosaccharide, and on the basis of our results it is likely that control of this enzyme is the major factor responsible for modulating H-type-1 expression.

Adenosine Triphosphate↗

The 1-month outcome of patients with a low probability Technegas ventilation/perfusion lung scan.

The objective was to study the 1-month outcome of patients who had a low probability ventilation/perfusion lung scan using Technegas radioaerosol as the inhalational agent and who did not receive anticoagulation. One hundred consecutive patients with suspected pulmonary embolism were studied retrospectively. Their Technegas lung scans were classified by two blinded and independent nuclear medicine physicians and the medical records of all patients with a low probability scan were reviewed. One hundred inpatients (42 males and 58 females) with a mean age of 63 years were studied. The three most common clinical presentations leading to lung scintigraphy were unexplained dyspnoea (30 cases), unexplained dyspnoea with pleuritic chest pain (26 cases) and pleuritic chest pain only (15 cases). Nine patients had been judged by their managing medical team to have a high clinical probability of true pulmonary embolism, 32 had an intermediate probability clinical presentation and 59 a low clinical probability of pulmonary embolism. None of the 100 patients experienced further episodes of suspected or proven pulmonary embolism during the follow-up period. Six patients died. In none of them was pulmonary embolism either the cause of or a major contributing factor to death. The finding of a low probability scan using Technegas as the ventilation scintigram agent of choice describes a group of patients who, even in the absence of therapeutic anticoagulation, have a favourable 1-month outcome free of either true or suspected clinical pulmonary embolism. Invasive, pulmonary angiography-based diagnostic strategies may not be needed in this group of patients.

Female↗

Carcinoma of the prostate gland: MR imaging with pelvic phased-array coils versus integrated endorectal--pelvic phased-array coils.

PURPOSE: To compare the performance of pelvic phased-array (PPA) coils and integrated endorectal PPA coils in evaluation of local extent of prostate cancer. MATERIALS AND METHODS: Seventy-one men underwent magnetic resonance (MR) imaging within 3 weeks of radical prostatectomy. MR findings of tumor, extracapsular extension, seminal vesicle invasion, nodal involvement, and stage were compared with step-sectioned (3-4-mm intervals) whole-mounted pathologic specimens. Prospective consensus versus single-reader interpretation (kappa statistics) and PPA versus integrated endorectal PPA coils (McNemar test) were compared, and a rating scale of 1-6 was developed for analysis of receiver operating characteristics. Statistical significance was calculated at delta = .05. RESULTS: Comparison between consensus and single-reader image interpretation showed positive but poor agreement (kappa = .38) and no statistical significance. Staging accuracy was better (difference approached significance) for integrated endorectal PPA coils (77%) than for PPA coils (68%). CONCLUSION: The integrated endorectal PPA coil is better for evaluation of local prostatic cancer than is the PPA coil.

Humans↗

Total quality management in the public sector--issues for implementation.

The Quality Matters Article is reprinted from the Australian Association for Quality in Health Care (AAGQHC) Newsletter (Vol 4, No 2). Researched and written by Sharyn White (Senior Planner, Southern Health Advancement Planning Unit, with the South Australian Health Commission) it is an excerpt from a qualifying dissertation for for a Masters in Policy and Administration at Flinders University. Written when the author was the Quality Co-ordinator, Noarlunga Health Services, SA, the article examines the literature related to some of the differences between the public and private health sectors, and explores the use of Total Quality Management systems in public health care facilities in light of the literature. Many of the issues around the use of Total Quality Management in health care remain unresolved. Will it achieve better results than other quality approaches? Can an industrial model achieve improvements in patient care? Is it more appropriate in teh public or private sectors? Is TQM appropriate in health care? Is it just a jargonistic name change? What's the difference, when all is said and done, between TQM and other ways of addressing quality? Does the cost of implementing TQM justify the results? Sharyn White's research addresses some of these issues from a refreshing perspective. My thanks to the author, and to the editors of the AAQHC Newsletter for their permission to reprint the article in Health Information Management Journal.

Industry↗

A study of stabilisation of p53 protein versus point mutation in colorectal carcinoma.

Abnormalities of the p53 tumour suppressor gene occur in many types of cancer including approximately 60% of colorectal carcinomas. This study investigates in 47 colorectal carcinomas the relationship between stabilised p53 protein detected by immunocytochemistry (ICC), and p53 mutation. 27 cases stained positively with the antibody PAb1801. Sequencing of exons 5-8 revealed 19 mutations in 18 of these cases (one tumour contained two different mutations). A rapid, non-radioactive method was developed to screen for mutations in this region of the gene involving Single Strand Conformational Polymorphism analysis (SSCP) and a MspI restriction digestion. This screen detected 17/19 (89%) of the sequenced mutations, and a further four mutations in 20 PAb1801 negative cases that were confirmed by sequencing. Reproducibility of ICC in detecting stabilised protein was assessed by restaining the 47 cases with the antibody DO7 after pre-treatment to optimise detection. Fewer cases were negative with DO7 although overall concordance with PAb1801 was good. A substantial proportion of carcinomas with stabilised p53 as detected by ICC do not contain mutations in exons 5-8, whilst some mutations (the majority in exon 6) are not associated with stabilisation.

Base Sequence↗

Characterization of cloned aortic smooth muscle cells from young rats.

Clones were derived by dilute plating from cultured aortic smooth muscle cells of 12-day-old rats. Clones Pup I to III resemble uncloned smooth muscle cultures from aortas of rat pups and from adult rat neointimas. They have a cobblestone morphology and proliferate in plasma-derived serum. By Northern analysis they contain platelet-derived growth factor B chain (PDGF-B) mRNA and high levels of CYPIA1, elastin, and osteopontin mRNAs, and they lack platelet-derived growth factor alpha-receptor (PDGF-alpha R) mRNA. In contrast, Pup V resembles smooth muscle cultures derived from uninjured adult rat arteries. It has an elongated morphology and proliferates poorly in plasma-derived serum. This clone expresses PDGF-alpha R mRNA, low levels of elastin and osteopontin mRNAs, and lacks CYPIA1 and PDGF-B mRNAs. Pup IV and VI have most of the properties of Pup I to III. We conclude that uncloned pup cultures are heterogeneous, but that the growth properties and gene expression pattern described for the uncloned culture is characteristic of individual clones within the population.

Actins↗

Tumour incidence, spectrum and ploidy in mice with a large deletion in the p53 gene.

In human tumourigenesis the tumour suppressor gene most commonly affected by mutation, inactivation or allele loss is p53. Loss of p53 function is associated both with failure to maintain a normal diploid status and inability to delete cells by apoptosis following DNA damage. To investigate further the role of p53 we have generated mice carrying a large deletion within the gene. All animals homozygous for this deletion develop spontaneous tumours, predominantly lymphomas, by the age of 6 months. 10% of heterozygotes develop a range of neoplasms, with a lower predisposition towards lymphoma, by 9 months. Both tumour incidence and spectrum in heterozygotes differ from those previously reported in another p53 mutant stock, suggesting either difference in exposure to carcinogens between the two stocks, or a role for modulating genes within different genetic backgrounds. Tumours showed frequent loss of diploid status, and the majority of those arising in heterozygotes showed loss of the wild type allele. These findings are consistent with the concept that p53 acts as a tumour suppressor by preventing the propagation of DNA damage to daughter cells.

Alleles↗

The active site structure of the calcium-containing quinoprotein methanol dehydrogenase.

Pyrroloquinoline quinone (PQQ), widely found in nature, serves as the redox cofactor in bacterial methanol dehydrogenase (MEDH), a heterotetrameric enzyme that oxidizes methanol to formaldehyde. The refined structure of MEDH at 2.4-A resolution, based on recently obtained amino acid sequence data, reveals that the PQQ, located in a central channel of the disk-shaped protein, is sandwiched between a Trp side chain and a very unusual vicinal disulfide. A Ca2+ ion forms a bridge between PQQ and the protein molecule, very close to a putative substrate binding pocket. The vicinal disulfide may form during PQQ incorporation and possibly act to hold the latter in place.

Alcohol Oxidoreductases↗

Postpartum haemorrhoids--evaluation of a cooling device (Anurex) for relief of symptoms.

Postpartum haemorrhoids are a common problem, for which the recently marketed cooling device, Anurex (Roussel Uclaf Australia, Pennant Hills, NSW), was evaluated in 129 women randomly allocated to treatment and control groups. There was no difference in the rate of resolution of pain between the groups. The test group estimated a greater duration of pain relief, but this was not statistically significant. Anal bleeding and itching were not significantly reduced in the test group. There was no difference between discomfort scores related to application of the device in the groups, but a significant number in the test group encountered difficulty in insertion of the device. It is concluded that the introduction of the Anurex device as a standard method of treatment of postpartum haemorrhoids is not justified.

Cryotherapy↗