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Biomedical subjects

K Robinson

Publications and source records attributed to K Robinson.

At least 55 records · Page 3Linked to original sources

Impairments, disabilities, and handicaps after acoustic neuroma surgery.

The measurement of a patient's health-related quality of life following acoustic neuroma surgery is important because the surgery itself can impose significant symptoms postoperatively. This study describes the most common problems experienced by the patients, using an open-ended questionnaire mailed to a series of 70 patients who had undergone acoustic neuroma surgery. Patient responses were classified by impairment, disability and handicap, according to the World Health Organization (WHO) classification. Results showed that this group of patients had a wide variety of symptoms and concerns, and particularly highlighted the relative importance of visual (49% of the patients) and psychosocial problems (34% of the patients) associated with surgery in contrast to tinnitus that seemed to be of minor importance. Open-ended questionnaires are useful in assessing outcomes from a quality of life perspective.

Disability Evaluation↗

Helping women caregivers obtain support: barriers and recommendations.

Women frequently assume the role of caregiver, and the demands of the caregiving role may lead to stress. Social support may moderate the effects of this stress. This article describes characteristics of effective social support, barriers to obtaining adequate support, and recommendations for how a woman in a caregiving role can obtain the support she needs. Nurses caring for women and families throughout the life span can use this information to help caregivers to obtain the necessary social support.

Adaptation, Psychological↗

Homocysteine and renal disease.

Hyperhomocysteinemia refers to an elevated circulating level of the sulfur-containing amino acid homocysteine and has been shown to be a risk factor for vascular disease in the general population. In patients with renal failure, hyperhomocysteinemia is a common feature. The underlying pathophysiological mechanism for this phenomenon is unknown. Proposed mechanisms include reduced renal elimination of homocysteine and impaired nonrenal disposal, possibly because of inhibition of crucial enzymes in the methionine-homocysteine metabolism by the uremic milieu. Absolute or relative deficiencies of folate, vitamin B6, or vitamin B12 may also play a role. Several case-control and prospective studies have now indicated that hyperhomocystenemia is an independent risk factor for atherothrombotic disease in patients with predialysis and end-stage renal disease. In renal patients, plasma homocysteine concentration can be reduced by administration of folic acid in doses ranging from 1 to 15 mg per day. In more than 50% of the cases, however, the homocysteine concentration remains above 15 micromol/L. The effects of vitamin B12 or vitamin B6 are unclear. Large intervention trials are now needed to establish whether homocysteine-lowering therapy will reduce atherothrombotic events in patients with renal failure. These studies are now planned or are ongoing.

Adult↗

Preimplant measures of preverbal communicative behavior as predictors of cochlear implant outcomes in children.

OBJECTIVE: Comparison of preverbal communication behavior in young children before receiving cochlear implants with outcomes 3 yr after implantation on speech identification and speech production tasks, to assess whether outcomes can be predicted from characteristics inherent to the child before implantation. DESIGN: Video recordings of preverbal communicative behavior were examined before use of the implant to quantify turn-taking and demonstration of autonomy by the child. Speech identification ability was measured 3 yr after implantation based on the Iowa Closed-Set Speech Perception Sentence Test, continuous discourse tracking, and an observational measure of telephone use. Speech production ability was measured 3 yr after implantation by the Edinburgh Articulation Test. Associations between the preimplant measures and the 3-yr outcomes were assessed by correlation analysis of data from 33 children. RESULTS: The 3-yr performance measures of speech identification were correlated with the preimplant measure of autonomy. Telephone use and speech production ability were not significantly associated with the preimplant measures. CONCLUSIONS: Up to a fourth of the variance in speech identification performance 3 yr after cochlear implantation of young children may be predicted from characteristics that are inherent to the child before implantation. Those characteristics are represented by the demonstration of autonomy in preverbal communicative interactions, whether by means of vocalization or by gesture. If those characteristics are acquired during infancy, outcomes in children with auditory prostheses including cochlear implants may be enhanced by activities that encourage autonomy in early years.

Child Behavior↗

Heterologous expression of an immunogenic pneumococcal type 3 capsular polysaccharide in Lactococcus lactis.

In order to develop a new system for the analysis of capsular biosynthetic pathways we have explored the possibility of expressing type 3 capsular polysaccharide (CPS) from the pathogen Streptococcus pneumoniae in Lactococcus lactis, an unencapsulated lactic acid bacterium being developed as a vaccine delivery vehicle for mucosal immunization. Only three of the four type 3 CPS biosynthesis genes were found to be necessary for the abundant formation (120 mg liter(-1)) of an extracellular type 3 CPS in L. lactis, implying a role for the type 3-specific synthase in the extracellular transport of the CPS or implying the existence of an alternative export system in L. lactis. The authenticity of the expressed heterologous polysaccharide was established by chemical and immunological analyses. Proton and carbon nuclear magnetic resonance spectroscopy of CPSs purified from L. lactis and S. pneumoniae showed that the two CPS structures were identical. When mice were immunized intraperitoneally with 3.5 x 10(6) CFU of live recombinant lactococci expressing a total of approximately 0.5 microgram of type 3 CPS, the immune responses elicited appeared identical to those observed in mice inoculated with 0.5 microgram of type 3 CPS purified from S. pneumoniae. These findings show that L. lactis is a useful host in which to study the role and function of genes involved in the production of bacterial capsules. Additionally, L. lactis shows potential as a host for the safe production of capsule antigens and as a vaccine delivery vehicle for polysaccharide antigens.

Animals↗

Homocysteine and lipoprotein(a) interact to increase CAD risk in young men and women.

A biochemical link between homocysteine (tHcy) and lipoprotein(a) [Lp(a)] related to fibrin binding has been proposed. This hypothesis has not been specifically examined in human subjects. We sought to determine in a clinical setting whether these risk factors would interact to increase coronary artery disease (CAD) risk. We performed a cross-sectional analysis of 750 men and 403 women referred to a preventive cardiology clinic at the Cleveland Clinic Foundation, in whom baseline tHcy and Lp(a) data were available. Logistic regression after adjusting for standard cardiovascular risk factors was used to estimate the relative risk of CAD in patients with an Lp(a) >/=30 mg/dL and a tHcy >/=17 micromol/L. Neither isolated high tHcy (odds ratio [OR]=1.06, P=0.89) nor isolated high Lp(a) (OR=1.15, P=0.60) appeared to be associated with CAD in women. However, strong evidence of an association was seen when both risk factors were present (OR=4.83, P=0.003). Moreover, this increased risk showed evidence of an interactive effect beyond that attributable to either additive or multiplicative effects of tHcy and Lp(a) (P=0.03). In contrast, both elevated tHcy (OR=1.93, P=0. 05) and elevated Lp(a) (OR=1.87, P=0.01) showed evidence of being independent risk factors for CAD in men. The presence of both risk factors in men did not appear to confer additional risk (OR=2.00, P=0.09), even though ORs as high as 12.4 were observed within specific age intervals. Consistent with prior studies, tHcy and Lp(a) are risk factors, either independently or in concert, for CAD in this clinical population. More significantly, we found evidence that when both risk factors were present in women, the associated risk was greater than what would be expected if the 2 risks were simply acting independently. The absence of such an interactive effect in men may be due to the confounding effects of age manifested as "survivor bias." These clinical findings provide insights into the potential roles of both tHcy and Lp(a) in the pathogenesis of atherosclerosis.

Adult↗

Irradiation and postangioplasty restenosis: a recent overview.

One of the most intriguing developments in recent years towards prevention of restenosis after angioplasty is the use of ionizing radiation. The background for the use of radiation treatment for this application is sound, since radiation is used not only to treat malignant cancerous growths but also is used for treatment of benign hyperplastic disorders such as post-surgical keloid formation and recurrence of pterygium after surgical removal. Restenosis can be considered a form of overexuberant wound healing triggered by angioplasty. Ionizing radiation inhibits serum-stimulated proliferation of many cell types including fibroblasts and smooth muscle cells in vitro and also suppresses the synthesis of collagen by cultured fibroblasts. Liermann who showed inhibition of post-stent restenosis first used ionizing radiation for restenosis prevention clinically in iliac and iliofemoral arteries. Subsequently, extensive animal studies in various restenosis models have shown a profound inhibitory effect of catheter-based radiation (endovascular brachytherapy) on neointima formation and overall vessel shrinkage (negative remodeling). Based on these results clinical trials have been initiated with several types of devices and isotopes. Among these are 192Ir, 32P, 90Y, 90Sr/Y and 188Re. Additionally, radioactive stents have been developed; devices for clinical use are made radioactive at the microCi level by surface implantation of 32P ions. Results from early clinical trials are encouraging and brachytherapy appears safe for clinical use and at an appropriate dose, may be highly effective for restenosis prevention.

Angioplasty, Balloon↗

The evidence regarding the drugs used for ventricular rate control.

OBJECTIVE: Our goal was to determine what drugs are most efficacious for controlling the ventricular rate in patients with atrial fibrillation. SEARCH STRATEGY: We conducted a systematic review of the literature published before May 1998, beginning with searches of The Cochrane Collaboration's CENTRAL database and MEDLINE. SELECTION CRITERIA: We included English-language articles describing randomized controlled trials of drugs used for heart rate control in adults with atrial fibrillation. DATA COLLECTION/ANALYSIS: Abstracts of trials were reviewed independently by 2 members of the study team. We reviewed English-language abstracts of non-English-language publications to assess qualitative consistency with our results. MAIN RESULTS: Forty-five articles evaluating 17 drugs met our criteria for review. In the 5 trials of verapamil and 5 of diltiazem, heart rate was reduced significantly (P <.05), both at rest and with exercise, compared with placebo, with equivalent or improved exercise tolerance in 6 of 7 comparisons. In 7 of 12 comparisons of a beta-blocker with placebo, the beta-blocker was efficacious for control of resting heart rate, with evidence that the effect is drug specific, as nadolol and atenolol proved to be most efficacious. All 9 comparisons demonstrated good heart rate control with beta-blockers during exercise, although exercise tolerance was compromised in 3 of 9 comparisons. In 7 of 8 trials, digoxin administered alone slowed the resting heart rate more than placebo, but it did not significantly slow the rate during exercise in 4 studies. The trials evaluating other drugs yielded insufficient evidence to support their use, but those drugs may yet be promising. CONCLUSIONS: The calcium-channel blockers verapamil or diltiazem, or select beta-blockers are efficacious for heart rate control at rest and during exercise for patients with atrial fibrillation without a clinically important decrease in exercise tolerance. Digoxin is useful when rate control during exercise is less a concern.

Adrenergic beta-Antagonists↗

Serum glutathione in adolescent males predicts parental coronary heart disease.

BACKGROUND: Traditional risk factors account for only half of the morbidity and mortality from coronary heart disease (CHD). There is substantial evidence that oxidative injury plays a major role in the atherosclerotic process. Thus, antioxidants may protect against development of atherosclerosis. Glutathione, an intracellular tripeptide with antioxidant properties, may be protective. METHODS AND RESULTS: This case-control study compared total serum glutathione (tGSH) in 81 adolescent male offspring of parents with premature CHD (ie, before 56 years of age) and 78 control male offspring of parents without known or suspected CHD. Case offspring had significantly lower tGSH than control offspring. In multiple logistic regression with parental CHD status as the dependent variable, age entered as a covariate, and other CHD risk factors competing to enter the model as significant independent predictor variables, LDL cholesterol (odds ratio [OR], 2.15 [units=1.5 SD]; 95% CI, 1.21 to 3.82), tGSH (OR, 0.40; 95% CI, 0.22 to 0.71), HDL cholesterol (OR, 0.42; 95% CI, 0.22 to 0.78), and total serum homocysteine (OR, 2.6; 95% CI, 1.35 to 5.02) entered the model as significant predictors of parental CHD status. CONCLUSIONS: Low tGSH in adolescent boys is a significant independent predictor of parental CHD, in addition to elevated LDL cholesterol, low HDL cholesterol, and elevated total serum homocysteine concentrations.

Adolescent↗

Reduction of homocysteine levels in coronary artery disease by low-dose folic acid combined with vitamins B6 and B12.

An increased plasma homocysteine concentration is a risk factor for atherosclerosis. Folic acid lowers homocysteine but the optimal dose in patients with coronary artery disease (CAD) is unclear. This placebo-controlled, single-blind, dose-ranging study evaluates the effect of low-dose folic acid on homocysteine levels in 95 patients aged 61 +/- 11 years (mean +/- SD) with documented CAD. Patients in each group were given either placebo or 1 of 3 daily supplements of folic acid (400 microg, 1 mg, or 5 mg) for 3 months. Each active treatment arm also received 500 microg vitamin B12 and 12.5 mg vitamin B6. Total plasma homocysteine levels were measured after 30 and 90 days. Folic acid 400 microg reduced homocysteine levels from 13.8 +/- 8.8 to 9.6 +/- 2.0 micromol/L at 90 days (p = 0.001). On 1- and 5-mg folic acid, levels decreased from 13.0 +/- 6.4 to 9.8 +/- 4.0 micromol/L (p = 0.001) and from 14.8 +/- 6.9 to 9.7 +/- 3.3 micromol/L (p < 0.001), respectively. The decrease was similar in all treatment groups. There was no significant change with placebo. Although the sample size is small, these findings suggest that daily administration of 400 microg/day folic acid combined with vitamin B12 and vitamin B6 may be equivalent to higher doses in reducing homocysteine levels in patients with CAD.

Coronary Disease↗

Homocysteine and coronary risk.

Hyperhomocysteinemia has recently emerged as a potentially major risk factor in the pathogenesis of coronary artery disease. Various genetic and nongenetic factors influence plasma homocysteine status. The mechanism associating hyperhomocysteinemia with atherosclerosis, if any, is still unclear, but homocysteine may have an adverse effect on vascular endothelium. Folic acid in low doses may ameliorate this process. Several studies are examining the influence of homocysteine-lowering therapy with folic acid on the risk of atherosclerotic vascular disease.

Age Factors↗

Mouse very low-density lipoprotein receptor (VLDLR): gene structure, tissue-specific expression and dietary and developmental regulation.

The very low density lipoprotein receptor (VLDLR) is a multifunctional apolipoprotein (apo) E receptor that shares a common structural feature as well as some ligand specificity to apo E with members of the low density lipoprotein receptor gene family. We have isolated and characterized the mouse VLDLR gene. The mouse VLDLR gene contains 19 exons spanning approximately 50 kb. The exon-intron organization of the gene is completely conserved between mouse and human. Since the 5'-flanking region of the mouse VLDLR gene contains two copies of a sterol regulatory element-1 like sequence (SRE-1), we next studied regulation of the VLDLR mRNA expression in heart, skeletal muscle and adipose tissue in C57BL/6, LDLR-/-, apo E-/- and LDLR-/-apo E-/- mice fed normal chow or atherogenic diet. The VLDLR mRNA expression was down-regulated 3-fold by feeding atherogenic diet in heart and skeletal muscle only in LDLR-/- mice. In contrast, VLDLR mRNA expression was up-regulated by atherogenic diet in adipose tissue in all animal models except double knockout mice. These results suggest that SRE-1 may be functional and VLDLR plays a role in cholesterol homeostasis in heart and skeletal muscle when LDLR is absent and that apo E is required for this modulation. Developmental regulation of the VLDLR mRNA expression was also tissue-specific. VLDLR mRNA expression in heart displayed significant up and down regulation during development. Maximal level was detected on post-natal day 3. However, the VLDLR mRNA levels in skeletal muscle remained relatively constant except a slight dip on post-natal day 7. In kidney and brain, VLDLR mRNA also peaked on post-natal day 3 but remained relatively constant thereafter. In liver, VLDLR mRNA expression was very low; it was barely detectable at day 19 of gestation and was decreased further thereafter. In adipose tissue, the VLDLR mRNA level showed an increase on post-natal day 13, went down again during weaning and then continued to increase afterwards. This developmental pattern as well as dietary regulation in adipose tissue supports the notion that VLDLR plays a role in lipid accumulation in this tissue. Although the primary role of VLDLR in heart, muscle and adipose tissue is likely in lipid metabolism, developmental pattern of this receptor in other tissues suggests that VLDLR has functions that are unrelated to lipid metabolism.

Adipose Tissue↗

Increased oxidative stress brought on by pro-inflammatory cytokines in neurodegenerative processes and the protective role of nitrone-based free radical traps.

Nitrone-based free radical traps (NFTs) have been shown to be protective in several neurodegenerative models. Our research has strongly implicated that: A) several neurodegenerative conditions exhibit increased levels of pro-inflammatory cytokines which consequently result in increased levels of oxidative stress and B) that NFTs act in part by suppressing oxidative stress through suppression of the action of the cytokine cascade. Acquired Immune Deficiency Syndrome (AIDS) dementia complex (ADC) is one of several conditions where the data collected helped to develop these concepts. Novel observations include demonstration that IL-1beta acts on cultured brain glia cells to invoke protein nitration and oxidative stress and that low levels of PBN (alpha-phenyl tert-butyl nitrone) inhibit this effect. We interpret these data as indicating that PBN prevents IL-1beta mediated peroxynitrite formation. Additionally, we have found that the AIDS viral envelope protein gp120 upregulates mRNA for the cytokines TNF alpha and TNF beta in rat neonatal brain, and that PBN prevents this. Western blots of protein extracts showed upregulation of inducible nitric oxide synthase (iNOS) in gp120 treated neonatal rat brains, and that PBN prevented induction of this enzyme as well. These observations underscore the general concept that PBN inhibits the induction of genes which produce neurotoxic products, one of which is peroxynitrite formed by the reaction of nitric oxide with superoxide, and may act also by inhibiting the induction of cytokines which mediate pro-inflammatory conditions in the brain.

Acquired Immunodeficiency Syndrome↗

Homocysteine metabolism in cardiovascular cells and tissues: implications for hyperhomocysteinemia and cardiovascular disease.

We have determined the activity and protein levels of CBS in a number of cardiovascular cells and tissues by direct enzyme assay and Western blot analysis, respectively. We have also determined the activity of BHMT in these same tissues and cells and have come to the conclusion that neither enzyme is expressed. This results suggests that in the human cardiovascular system homocysteine metabolism is limited to the remethylation pathway catalyzed by MS. Thus, hyperhomocysteinemia in conjunction with a limited metabolic capacity for homocysteine in the cardiovascular system could result in cellular dysfunction.

Animals↗