Biomedical subjects
Publications and source records attributed to M E Watson.
Acute scrotum is a common clinical problem and establishing its etiology can be difficult, often necessitating scrotal exploration. We report here a very rare case of acute scrotum: torsion of the epididymis. Only one such case has been reported previously in the literature.
FepA is the Escherichia coli outer membrane receptor for ferric enterobactin, colicin D and colicin B. The transport processes through FepA are energy-dependent, relying on the periplasmic protein TonB to interact with FepA. Through this interaction, TonB tranduces energy derived from the cytoplasmic membrane across the periplasmic space to FepA. In this study, random mutagenesis strategies were used to define residues of FepA important for its function. Both polymerase chain reaction (PCR)-generated random mutations in the N-terminal 180 amino acids of FepA and spontaneous chromosomal fepA mutations were selected by resistance to colicin B. The PCR mutagenesis strategy targeted the N-terminus because it forms a plug inside the FepA barrel that is expected to be involved in ligand binding, ligand transport, and interaction with TonB. We report the characterization of 15 fepA missense mutations that were localized to three regions of the FepA receptor. The first region was a stretch of eight amino acids referred to as the TonB box. The second region included extracellular loops of both the barrel and the plug. A third region formed a cluster near the barrel wall around positions 75 and 126 of the plug. These mutations provide initial insight into the mechanisms of ligand binding and transport through the FepA receptor.
OBJECTIVES: The aim of this study was to assess the impact of alosetron, a treatment recently approved in the United States for irritable bowel syndrome in diarrhea-predominant female patients, on health-related quality of life. METHODS: Quality of life was assessed as part of two 12-wk randomized, double-blind, placebo-controlled irritable bowel syndrome studies comparing alosetron 1 mg b.i.d. with placebo (S3BA3001 and S3BA3002). Patients completed a validated disease-specific quality of life questionnaire, the Irritable Bowel Syndrome Quality of Life Questionnaire (IBSQOL), at baseline and at the 12-wk or final visit. The clinical relevance of data were also evaluated by a minimal meaningful difference instrument. RESULTS: A total of 626 and 647 patients were enrolled in studies S3BA3001 and S3BA3002, respectively. Approximately 70% of patients in each study had diarrhea-predominant IBS. In diarrhea-predominant patients enrolled in S3BA3001, statistically significant (p < 0.05) improvements with alosetron versus placebo were observed on all nine IBSQOL scales (emotional health, mental health, sleep, energy, physical functioning, food/diet, social functioning, role-physical, and sexual relations) and for all but one scale (mental health) in S3BA3002. In both studies, a significantly greater percentage of patients treated with alosetron (p < 0.05) experienced clinically meaningful improvement on three of the nine IBSQOL scales (food/diet, social functioning, and role-physical) compared with patients treated with placebo. Patients treated with alosetron did not show worsening in any quality of life domain compared with patients treated with placebo. CONCLUSIONS: These results in women with diarrhea-predominant IBS demonstrate that alosetron significantly improves health-related quality of life.
This article summarizes the current state and future needs of research into saline-filled and silicone gel breast implants. The authors describe recent investigations into possible causes and potential risk factors for silicone gel and saline implant failure. Also discussed are local complications of breast implantation and the need for revisional operations in augmentation and reconstruction patients. In addition, the effects that surgical, implant, and patient variables have on the aesthetic outcome of surgery are addressed. The last portion of the article lays out future research needs, such as determining the incidence rate of implant failure, reducing the frequency of revisional surgery, and the difficulty of designing better breast implants in the current strict regulatory climate.
The naming impairments in Alzheimer's disease (AD) have been attributed to a variety of cognitive processing deficits, including impairments in semantic memory, visual perception, and lexical access. To further understand the underlying biological basis of the naming failures in AD, the present investigation examined the relationship of various classes of naming errors to regional brain measures of cerebral glucose metabolism as measured with 18 F-Fluoro-2-deoxyglucose (FDG) and positron emission tomography (PET). Errors committed on a visual naming test were categorized according to a cognitive processing schema and then examined in relationship to metabolism within specific brain regions. The results revealed an association of semantic errors with glucose metabolism in the frontal and temporal regions. Language access errors, such as circumlocutions, and word blocking nonresponses were associated with decreased metabolism in areas within the left hemisphere. Visuoperceptive errors were related to right inferior parietal metabolic function. The findings suggest that specific brain areas mediate the perceptual, semantic, and lexical processing demands of visual naming and that visual naming problems in dementia are related to dysfunction in specific neural circuits.
It is often recommended that consumption of dietary fibre should in increased to protect against colorectal cancer. However, although more than 95% of dietary fibre is contributed by whole plant cell walls, very little experimental work has been done using whole plant cell walls. These may protect by adsorbing carcinogens, thus lowering their effective concentration in the alimentary tract, and by carrying the carcinogens out of the body in the faeces. However, plant cell walls vary widely in their composition and physical properties, and not all cell walls will necessarily have protective properties. We therefore isolated 4 plant cell-wall preparations with contrasting compositions as models of the types of cell walls that occur in the diet. We investigated the abilities of these preparations to adsorb in vitro 6 heterocyclic aromatic amines (HAAs). HAAs occur in the human diet and several are colon carcinogens, at least in rats. We found that the ability of the HAAs to adsorb to the plant cell walls increased with increasing hydrophobicity of the HAA, measured as the calculated logarithm of the partition coefficient between 1-octanol and water (C logP). A cell-wall preparation containing mainly the walls of parenchyma cells (the most common cell type in food plants) had only poor adsorptive ability. A cell-wall preparation from commercial cork had the best adsorptive ability. This preparation was the most hydrophobic of those examined because the cell walls contained the polymer, suberin, together with associated waxes. The preparation modelled suberized cell walls which occur in the diet, for example in potato skins. The other two cell-wall preparations contained another hydrophobic polymer, lignin, and had intermediate adsorptive abilities which were not significantly different from one another. These preparations modelled lignified cell walls which occur in the diet, for example in wheat bran. Our results indicate that suberized and lignified cell walls may be important in protecting against colorectal cancer.
Line drawings were presented in either a spatial or a nonspatial format. Subjects recalled each of four sets of 24 items in serial order. Amount recalled in the correct serial order and sequencing errors were scored. In Experiment 1 items appeared either in consecutive locations of a matrix or in one central location. Subjects who saw the items in different locations made fewer sequencing errors than those who saw each item in a central location, but serial recall levels for these two conditions did not differ. When items appeared in nonconsecutive locations in Experiment 2, the advantage of the spatial presentation on sequencing errors disappeared. Experiment 3 included conditions in which both the consecutive and nonconsecutive spatial formats were paired with retrieval cues that either did or did not indicate the sequence of locations in which the items had appeared. Spatial imagery aided sequencing when, and only when, the order of locations in which the stimuli appeared could be reconstructed at retrieval.
Epidemiology and animal experiments indicate that dietary fibres protect against the development of colorectal cancer. However, insoluble dietary fibres appear to be more effective than soluble dietary fibres and one mechanism by which they may protect is by adsorbing dietary carcinogens. We found previously that the ability of a carcinogen to adsorb in vitro to alpha-cellulose (a model insoluble dietary fibre) was strongly related to the hydrophobicity of the carcinogen, measured as the calculated logarithm of the partition coefficient between 1-octanol and water (C log P). Furthermore, soluble dietary fibres (soluble-fibre polysaccharides), including gum arabic, reduced the adsorption of the hydrophobic carcinogen, DNP, to alpha-cellulose. In the present study we tested the ability of gum arabic to reduce the adsorption in vitro of the carcinogens BaP (C log P = 6.124), DNP (C log P = 4.384), and the heterocyclic amines, Trp-P-1 (C log P = 3.230) and MeIQx (C log P = 1.078). Gum arabic reduced the adsorption to alpha-cellulose of BaP and DNP, but not the adsorption of Trp-P-1 or MeIQx. Gum arabic also reduced the adsorption of BaP to an insoluble, dietary-fibre preparation from commercial cork which contains the hydrophobic component, suberin, but did not affect the adsorption of DNP, Trp-P-1 or MeIQx. It also did not affect the adsorption of DNP to an insoluble, dietary-fibre preparation from wheat straw, which contains the hydrophobic component, lignin. The results are discussed in terms of hydrophobic interactions between carcinogens and insoluble dietary fibres. In vivo, it is likely that soluble dietary fibres reduce the adsorption of only highly hydrophobic carcinogens to some insoluble dietary fibres.
Recent studies have suggested that nitric oxide (NO) may function as both an intracellular and intercellular signal that affects neural and immunological activity, vascular tone, platelet adhesion, and production of some hormones. Arginine analogs such as NG-monomethyl-L-arginine (L-NMMA) and N omega-nitro-L-arginine methyl ester (L-NAME) act to inhibit the intracellular formation of NO and have been used to study the effects of decreased NO formation on physiological systems. A single in vivo study has suggested that a similar analog, NG-nitro-L-arginine, increases serum testosterone (T), but the organ site and mechanism of action were not investigated. The present study was performed to investigate the effects of NO synthase inhibitors on Leydig cell function. L-NMMA and L-NAME, but not the inactive enantiomer (D-NMMA), increased both basal and human chorionic gonadotropin (hCG)-stimulated T production while decreasing guanosine 3':5'-cyclic monophosphate (cGMP). There was no effect on either adenosine 3':5'-cyclic monophosphate (cAMP) accumulation or specific hCG binding. These results suggest that NO formation, which is inhibited by L-NMMA and L-NAME, is important in the regulation of Leydig cell T production by interstitial cells of the testis, and that changes in cGMP levels might be involved in this process.
This report describes a case in which puncture of the brachial artery to obtain a sample for blood-gas analysis resulted in damage to the median nerve with a persisting neuropathy and apparent loss of function. Errors in judgment and contributions to possible negligence included (1) inappropriate choice of sampling site; (2) lack of knowledge of precautions and possible complications; (3) incomplete/inadequate description of optimal procedure in departmental procedure manual; (4) arbitrary selection of the dominant hand.
To determine the prevalence of firearm ownership and storage practices in New Mexico, we did a random-digit-dialing survey of New Mexico residents in October 1991. Of 200 households surveyed, 79 (40%) had 1 or more firearms in the home. Rural households were more likely than urban households to have firearms (44% versus 30%), and households with annual incomes of greater than $25,000 were more likely to have a firearm than households with incomes of $25,000 or less (41% versus 33%). Household firearm ownership did not vary with the presence of young (< 15 years old) children (38% with children versus 41% without). Handguns were generally owned for self-protection, and rifles were owned for hunting. Of households with firearms, 24% stored them unsafely (unlocked and loaded or unloaded but with ammunition nearby), including 21% of households with young children. Of the households with handguns only, 40% stored these firearms unsafely compared with 13% of those with rifles only. The prevalence of gun ownership in New Mexico is similar to that reported in national surveys; handguns are stored less safely than rifles; and the presence of young children in the home does not appear to improve firearm storage safety.
Nurses have a responsibility to maximize safety while minimizing the use of restraints. Assessment of fall risk factors for a specific population can aid in planning alternatives to the use of restraints while maximizing safety.
One of the ways dietary fibers may protect against colorectal cancer is by adsorbing carcinogens and carrying them out of the digestive tract, thus lessening interaction of the carcinogens with the colonic tissue. We investigated this mechanism of action by testing in vitro the abilities of a range of carcinogens, including known animal colon carcinogens, to adsorb to alpha-cellulose, which we have used as a model insoluble dietary fiber. The carcinogens were N-nitroso-N-methylurea (NMU), benzo[a]pyrene (B[a]P) and a number of heterocyclic aromatic amines which have been found in heated foods. It was found that the ability of a carcinogen to adsorb to alpha-cellulose is strongly related to the hydrophobicity of the carcinogen measured as the calculated logarithm of the partition coefficient between 1-octanol and water (C log P). The hydrophilic carcinogen, NMU, (C log P = -0.204), adsorbed only poorly, whereas the very hydrophobic carcinogen, B[a]P, (C log P = 6.124), adsorbed strongly. Carcinogens with intermediate hydrophobicities showed intermediate abilities to adsorb.
Dietary fiber is believed to decrease the incidence of colorectal cancer, but not all types of fiber are equally protective. Dietary fibers may be divided broadly into insoluble and soluble fibers, and there is evidence from animal experiments that the latter not only fails to protect against colorectal cancer but may enhance its development. Adsorption of carcinogens to insoluble dietary fiber in the intestinal tract is one of the mechanisms by which dietary fiber is believed to protect against colorectal cancer. In previous in vitro experiments, we showed that the hydrophobic carcinogen 1,8-dinitropyrene (DNP) adsorbs to insoluble plant cell wall components (insoluble dietary fibers). Soluble polysaccharides (pectic polysaccharides) extracted from the walls of parenchyma cells of dicotyledonous plants were found to maintain DNP in aqueous solutions and decrease its adsorption to insoluble wall components. In the present study, we examined a commercial preparation of pectin and seven other soluble-fiber polysaccharides with diverse structures for their effects on the distribution of DNP. Many of these are used as emulsifiers and stabilizers in the food industry. They all maintained DNP in aqueous solution and decreased its adsorption to alpha-cellulose, which we used as an example of an insoluble dietary fiber. Gum arabic was the most effective and kappa-carrageenan the least. The capacity of the polysaccharides to act as emulsifiers and stabilizers may explain their effects on DNP distribution. The monosaccharide glucose and the disaccharide cellobiose had no effect on the distribution of DNP. These results indicate three possible mechanisms by which soluble-fiber polysaccharides may enhance the development of colorectal cancer. First, because they reduce the ability of insoluble dietary fibers to adsorb hydrophobic carcinogens, more carcinogens may enter the colon maintained in solution than adsorbed onto insoluble fibers. Second, if soluble-fiber polysaccharides are maintaining hydrophobic carcinogens in solution and these polysaccharides are degraded by bacterial enzymes in the colon, then the carcinogens may come out of solution and be deposited onto the mucosal surface of the colon. Third, soluble-fiber polysaccharides may cross the intestinal epithelium and carry with them carcinogens maintained in solution. These studies have important consequences for nutrition, because soluble-fiber polysaccharides represent a common component of foods.
A cellular assay is described in which transient high-level expression of a heterologous reporter gene (chloramphenicol acetyltransferase, CAT) driven by the HIV LTR is used to determine trans-activation in a cell line constitutively expressing Tat. The use of a parallel ELISA system to determine effects on expression of CAT and of the neomycin phosphotransferase (NPT) marker gene effectively eliminated sample variability caused by cumulative processing errors or cell culture conditions. In addition the use of cationic liposome-mediated transfection minimized delay between DNA treatment that initiates trans-activation and addition of inhibitors, thereby eliminating background expression levels in treated samples. The assay has the potential to discriminate between inhibition of trans-activation and nonspecific effects such as inhibition of transfection and cytotoxicity. It has been adapted to a 96-well format suitable for high-throughput screening of natural products and synthetic chemicals.
The adsorption of mutagens by some dietary fibres has been suggested as one mechanism by which dietary fibres protect against colorectal cancer. It is thought that these dietary fibres carry the mutagen out of the digestive tract, decreasing the effective mutagen concentration to which epithelial cells are exposed. The ability of gastrointestinal mucin to alter the extent to which the hydrophobic mutagen 1,8-dinitropyrene (DNP) adsorbs in vitro onto the insoluble dietary fibre alpha-cellulose, was investigated. It was found that crude and purified human ileal mucins themselves adsorbed DNP and decreased the adsorption of DNP onto alpha-cellulose. Purified mucin which had been treated with trypsin also adsorbed DNP. These studies suggest that in the digestive tract there would be competition for the adsorption of DNP between mucin and insoluble dietary fibres, such as alpha-cellulose. This factor must be considered in predictions about the distribution of hydrophobic, mutagenic carcinogens in the digestive tract and their role in the etiology of colorectal cancer.