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Biomedical subjects

K Brown

Publications and source records attributed to K Brown.

At least 109 records · Page 6Linked to original sources
PubMed2000

Effect of the angiotensin-converting enzyme gene deletion polymorphism on the risk of venous thromboembolism.

Allele frequencies for the insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene were determined in a large case-control study of 517 unselected patients with venous thromboembolism and 478 blood donors. The D allele frequency was 0. 53 [95% confidence interval (CI) 0.50-0.56] in patients and 0.54 (95% CI 0.50-0.57) in controls, giving an odds ratio for the D allele of 0.97 (95% CI 0.81-1.16). In the same population, the odds ratio for the factor V Leiden mutation (F5G1691A) was 6.9 (95% CI 4. 0-11.9). Therefore, the ACE I/D polymorphism is not a risk factor in a representative group of unselected patients with venous thromboembolism. The possibility that the I/D polymorphism is a risk factor for venous thromboembolism specifically after hip replacement cannot be excluded.

Arthroplasty, Replacement, Hip↗
PubMed2000

Transient exotropia after posterior spinal fusion in a child: a new case.

Ocular complications after spinal surgery are rare, although ischemic optic neuropathy, occipital lobe infarcts, and central retinal vein thrombosis have been reported. Our purpose is to report a case of an acute, comitant, postoperative exotropia that rapidly and spontaneously resolved. This case is particularly interesting in that it may indirectly shed some light on mechanisms of vergence control.

Child↗
PubMed2000

Chemoprevention of breast cancer by tamoxifen: risks and opportunities.

The antiestrogen tamoxifen is widely used in the adjuvant therapy of breast cancers in women and helps to prevent the occurrence of breast tumors in healthy women. However, epidemiological studies have shown tamoxifen treatment to be associated with a 2- to 5-fold increased risk of endometrial cancer. In rats but not in mice, long-term administration of tamoxifen results in an increase in hepatocellular carcinomas. Mechanistically, this occurs through metabolic activation of the drug, mainly by the CYP3A family, to an electrophilic species, that causes DNA damage in target tissues, and subsequently leads to gene mutations. It is controversial whether low levels of DNA damage occur in human uterine tissues, and there is no evidence that this can be causally related to the mechanisms of carcinogenesis. In healthy women, the risk:benefits for the use of tamoxifen is in part related to the risk of developing breast cancer. The results from the carcinogenicity studies in rats do not predict the likelihood that women will develop liver cancer or indeed cancers in other organs. The mechanism of endometrial cancer in women remains unresolved, but the experience with tamoxifen has highlighted the potential problems that need to be addressed in the assessment of future generations of selective estrogen receptor modulators.

Animals↗
PubMed2000

Major inter-species differences in the rates of O-sulphonation and O-glucuronylation of alpha-hydroxytamoxifen in vitro: a metabolic disparity protecting human liver from the formation of tamoxifen-DNA adducts.

Tamoxifen is a hepatic genotoxin in rats and mice but a hepatocarcinogen only in rats. It is not associated with DNA adducts and liver tumours in patients. The proposed major pathway for its bioactivation in rats involves alpha-hydroxylation, O-sulphonation and generation of a carbocation that reacts with DNA. Rat liver microsomes catalyse alpha-hydroxylation at approximately 2- and 4-fold the rate achieved by human and murine liver microsomes, respectively. O-glucuronylation will deactivate alpha-hydroxytamoxifen and compete with sulphonation. Rates of O-sulphonation of alpha-hydroxytamoxifen in hepatic cytosol have been determined by a HPLC assay of substrate-dependent 3'-phosphoadenosine 5'-phosphate production. The rank order of O-glucuronylation in hepatic microsomes was estimated by HPLC-mass spectrometry. The rate of sulphonation of trans-alpha-hydroxytamoxifen (25 microM) in cytosol from adult female Sprague-Dawley rats and CD1 mice was 5.3 +/- 0.8 and 3.9 +/- 0.5 pmol/min/mg protein (mean +/- SD, n = 3), respectively. In cytosol fractions from women aged 40-65 years, the rate was 1.1 +/- 0.4 pmol/min/mg protein (mean +/- SD, n = 6). The K(m) for trans-alpha-hydroxytamoxifen in rat, mouse and human cytosol was 84. 6 +/- 3.8, 81.4 +/- 4.6 and 104.3 +/- 5.6 microM (mean +/- SD, n = 3), respectively; the corresponding V:(max) values were 22.4 +/- 3.4, 17.1 +/- 3.1 and 6.3 +/- 1.9 pmol/min/mg protein. These K:(m) were similar to a value obtained by others using purified rat liver hydroxysteroid sulphotransferase a. Turnover of the cis epimer was too slow for accurate determination of rates. Sulphonation of trans-alpha-hydroxytamoxifen in human uterine cytosol was undetectable. The rank order of O-glucuronylation of trans-alpha-hydroxy- tamoxifen in liver microsomes was human > > mouse > rat. In combination, lower rates of alpha-hydroxylation and O-sulphonation and a higher rate of O-glucuronylation in human liver would protect patients from the formation of tamoxifen-DNA adducts.

Adult↗
PubMed2000

Pathologic features of fatal shark attacks.

To examine the pattern of injuries in cases of fatal shark attack in South Australian waters, the authors examined the files of their institution for all cases of shark attack in which full autopsies had been performed over the past 25 years, from 1974 to 1998. Of the seven deaths attributed to shark attack during this period, full autopsies were performed in only two cases. In the remaining five cases, bodies either had not been found or were incomplete. Case 1 was a 27-year-old male surfer who had been attacked by a shark. At autopsy, the main areas of injury involved the right thigh, which displayed characteristic teeth marks, extensive soft tissue damage, and incision of the femoral artery. There were also incised wounds of the right wrist. Bony injury was minimal, and no shark teeth were recovered. Case 2 was a 26-year-old male diver who had been attacked by a shark. At autopsy, the main areas of injury involved the left thigh and lower leg, which displayed characteristic teeth marks, extensive soft tissue damage, and incised wounds of the femoral artery and vein. There was also soft tissue trauma to the left wrist, with transection of the radial artery and vein. Bony injury was minimal, and no shark teeth were recovered. In both cases, death resulted from exsanguination following a similar pattern of soft tissue and vascular damage to a leg and arm. This type of injury is in keeping with predator attack from underneath or behind, with the most severe injuries involving one leg. Less severe injuries to the arms may have occurred during the ensuing struggle. Reconstruction of the damaged limb in case 2 by sewing together skin, soft tissue, and muscle bundles not only revealed that no soft tissue was missing but also gave a clearer picture of the pattern of teeth marks, direction of the attack, and species of predator.

Adult↗
PubMed2000

Searching for one versus two identical targets: when visual search has a memory.

A recent study has suggested that observers' visual explorations of the external world can proceed unimpaired when the visual environment precludes the operation of memory processes (as, for instance, when the display elements change locations every 100 ms). One theoretical limitation of this study was that distractors were the only elements that had the potential to be tagged during visual search. The present study sought to clarify the amnesic-search hypothesis by investigating whether memory processes can guide search in other contexts in which targets also have the potential to be tagged. Accordingly, the experimental conditions of the previous study were repeated using a different search task in which observers had to decide whether one target or two were present among a variable number of similar distractors. Under these search conditions, the present findings provided strong evidence that memory processes can guide visual search.

Adult↗
PubMed2000

The effects of presession exposure to attention on the results of assessments of attention as a reinforcer.

The effects of presession exposure to attention on responding during subsequent assessments of attention as a reinforcer were evaluated across three behavioral assessments. In Experiment 1, a contingent attention assessment condition was preceded by either a noncontingent attention condition (free play) or a contingent escape condition. In Experiment 2, a diverted attention with extinction condition was preceded by either an alone or a free-play condition. In Experiment 3, a two-choice preference assessment was preceded by either 10 min of free play or 10 min of playing alone. In each experiment, the participant responded differentially within the test condition according to the presence or absence of dense schedules of attention immediately prior to that condition. The results of this study show that events occurring immediately prior to an assessment condition can influence behavior within the assessment.

Attention↗
PubMed2000

The factor V R2 allele: risk of venous thromboembolism, factor V levels and resistance to activated protein C.

Case-control studies have yielded conflicting results regarding the relative risk of venous thromboembolism associated with the factor V R2 allele. We calculated odds ratios in 581 patients and 469 age-matched controls. The odds ratio for the R2 allele in patients relative to controls was 1.21 (95% CI 0.84 to 1.74). These results do not support the hypothesis that the R2 allele is a risk factor for venous thromboembolism. There was no relationship between factor V levels and R2 carrier status. Normalised APC sensitivity ratios were not lower in carriers of the R2 allele. In an in vitro model progressive APC resistance was observed with factor V levels of 60% and less but ratios less than 2.4 (equivalent to a normalised ratio of 0.73) did not occur until factor V levels were less than 20%. The relationship between APC resistance and factor V level was not observed in a factor VIII-independent model.

Activated Protein C Resistance↗
PubMed2000

Confidentiality dilemmas in clinical education.

Through an analysis of three cases, this article illustrates many of the subtleties of ethical discernment involved during clinical fieldwork rotations when allied health students decide to withhold information about their disabilities. By law in the United States, educators are bound to uphold students' confidentiality in this regard. However, this analysis examines many of the complexities that clinical coordinators, preceptors, and students must grasp when faced with conflicting ethical duties.

Allied Health Personnel↗
PubMed2000

The impact of nursing home patients on general practitioners' workload.

BACKGROUND: Although the number of people in nursing homes has risen substantially in recent years, the shift of responsibility into general practice has rarely been accompanied by extra resources. These patients may be associated with a higher general practitioner (GP) workload than others of similar age and sex. AIM: To assess the GP workload associated with nursing home residents and its associated costs. METHOD: All nursing home residents aged over 65 years and registered with nine Nottinghamshire practices during one year were matched with patients living in the community for general practice, age, and sex. Data were collected retrospectively for both groups on key workload measures. Costs for the workload measures were calculated using published estimates. RESULTS: Data were collected for 270 pairs of patients. Nursing home patients had more face-to-face contacts in normal surgery hours, telephone calls, and out-of-hours visits. The mean workload cost per month of a nursing home patient (assuming that one patient was seen per visit) was estimated to be 18.21 Pounds (10.49 Pounds higher than the cost of controls). A sensitivity analysis demonstrated that potential savings in visiting costs associated with increasing the numbers of patients seen per visit were 27% for one extra patient seen per visit and 44% for four extra patients. CONCLUSION: Nursing home residents were associated with higher workload for GPs than other patients of the same age and sex living in the community. Our costings provide a basis for negotiating suitable reimbursement of GPs for their additional work.

Aged↗
PubMed2000

Congenital nasal pyriform aperture stenosis.

Congenital nasal pyriform aperture stenosis is a rare cause of pediatric nasal airway obstruction. As infants are obligate nasal breathers, nasal obstruction and even severe nasal congestion can lead to apnea and respiratory distress. Congenital nasal pyriform aperture stenosis was first described by Brown et al in 1989. The narrowing of the nasal pyriform aperture is thought to be due to bony overgrowth of the nasal process of the maxilla during fetal development. Because of the association this anomaly has with other midline defects, such as holoprosencephaly, it is important to recognize it and pursue a thorough workup. We present a case of a patient with pyriform aperture stenosis and solitary central megaincisor. This patient initially presented to our clinic with a history of nasal airway obstruction, poor feeding, and failure to thrive.

Diagnosis, Differential↗
PubMed1999

Induction of autophagy and inhibition of tumorigenesis by beclin 1.

The process of autophagy, or bulk degradation of cellular proteins through an autophagosomic-lysosomal pathway, is important in normal growth control and may be defective in tumour cells. However, little is known about the genetic mediators of autophagy in mammalian cells or their role in tumour development. The mammalian gene encoding Beclin 1, a novel Bcl-2-interacting, coiled-coil protein, has structural similarity to the yeast autophagy gene, apg6/vps30, and is mono-allelically deleted in 40-75% of sporadic human breast cancers and ovarian cancers. Here we show, using gene-transfer techniques, that beclin 1 promotes autophagy in autophagy-defective yeast with a targeted disruption of agp6/vps30, and in human MCF7 breast carcinoma cells. The autophagy-promoting activity of beclin 1 in MCF7 cells is associated with inhibition of MCF7 cellular proliferation, in vitro clonigenicity and tumorigenesis in nude mice. Furthermore, endogenous Beclin 1 protein expression is frequently low in human breast epithelial carcinoma cell lines and tissue, but is expressed ubiquitously at high levels in normal breast epithelia. Thus, beclin 1 is a mammalian autophagy gene that can inhibit tumorigenesis and is expressed at decreased levels in human breast carcinoma. These findings suggest that decreased expression of autophagy proteins may contribute to the development or progression of breast and other human malignancies.

Animals↗
PubMed1999

Structure of the Escherichia coli TolB protein determined by MAD methods at 1.95 A resolution.

BACKGROUND: The periplasmic protein TolB from Escherichia coli is part of the Tol-PAL (peptidoglycan-associated lipoprotein) multiprotein complex used by group A colicins to penetrate and kill cells. TolB homologues are found in many gram-negative bacteria and the Tol-PAL system is thought to play a role in bacterial envelope integrity. TolB is required for lethal infection by Salmonella typhimurium in mice. RESULTS: The crystal structure of the selenomethionine-substituted TolB protein from E. coli was solved using multiwavelength anomalous dispersion methods and refined to 1. 95 A. TolB has a two-domain structure. The N-terminal domain consists of two alpha helices, a five-stranded beta-sheet floor and a long loop at the back of this floor. The C-terminal domain is a six-bladed beta propeller. The small, possibly mobile, contact area (430 A(2)) between the two domains involves residues from the two helices and the first and sixth blades of the beta propeller. All available genomic sequences were used to identify new TolB homologues in gram-negative bacteria. The TolB structure was then interpreted using the observed conservation pattern. CONCLUSIONS: The TolB beta-propeller C-terminal domain exhibits sequence similarities to numerous members of the prolyl oligopeptidase family and, to a lesser extent, to class B metallo-beta-lactamases. The alpha/beta N-terminal domain shares a structural similarity with the C-terminal domain of transfer RNA ligases. We suggest that the TolB protein might be part of a multiprotein complex involved in the recycling of peptidoglycan or in its covalent linking with lipoproteins.

Amino Acid Sequence↗