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At least 361 records · Page 20Linked to original sources

Effects of an exercise intervention for older heart failure patients on caregiver burden and emotional distress.

BACKGROUND: The impact of exercise programmes for heart failure on those close to the patient is largely unknown. We examined the effect of a hospital and home-based exercise intervention on burden, anxiety and depression of informal caregivers. DESIGN: The study was a randomized, controlled trial. Heart failure patients were randomized to a seated 12-week hospital-based exercise programme. Caregiver measures were gathered at baseline, 3 months later and 6 months following baseline. METHODS: Sixty caregivers (mean age 63.4 years, 65% female) of heart failure patients (n = 82, mean age 80.5 years, 44% female) participating in a trial of an exercise intervention were recruited. Caregiver burden, anxiety and depression were assessed. RESULTS: There were no differences in caregiver burden, depression or anxiety between the two groups of caregivers at baseline (caregiver burden, patient control 33.1 versus patient exercise 34.1; anxiety 4.1 versus 5.5; depression 2.8 versus 3.8). At 3 months there were no differences between caregivers in the two groups on outcomes. At 6-month follow-up caregivers of heart failure patients in the exercise group had burden scores that were significantly worse than the control group. There were no differences between the carers of exercise and control groups in anxiety and depression. Levels of anxiety and depression in the entire carer sample were marginally higher than reference values in a healthy non-clinical sample. CONCLUSION: The present exercise interventions for frail older patients did not benefit caregivers and was associated with an increase in caregiver burden. We suggest that future exercise interventions for heart failure patients should actively incorporate informal caregivers into research designs.

Aged↗

The association of weight gain and olanzapine plasma concentrations.

Atypical antipsychotics, including olanzapine, have been associated with clinically significant weight gain in some patients. The purpose of this study was to determine if weight gain was associated with increasing plasma concentrations during olanzapine treatment in subjects with schizophrenia. This study included 39 acutely ill subjects with schizophrenia, schizoaffective disorder, or schizophreniform disorder (DSM-III-R or DSM-IV). Assessments included the Brief Psychiatric Rating Scale (BPRS), the Scale for Assessment of Negative Symptoms (SANS), and weight measurements. Olanzapine was titrated to a dose of 5 to 20 mg/d for 2 to 6 weeks. A 24-hour plasma concentration was obtained after 6 weeks of treatment. Analysis using a receiver operator characteristic curve identified a threshold dose-weighted plasma concentration of 20.6 ng/mL being associated with an increased likelihood of clinically significant weight gain (> or =7% baseline weight) during olanzapine treatment. The associations remained significant after adjusting for age, gender, baseline body mass index, baseline symptom severity, and symptom improvement (OR = 10.1; 95% CI, 1.3-75.0; P = 0.024). Similar analysis determined that a threshold olanzapine dose of 13.3 mg/d was associated with > or =7% weight gain. However, after adjusting for potential confounders, the results did not remain significant. The association of weight gain with plasma concentrations during treatment with olanzapine may support the utilization of plasma drug concentration as a marker for antipsychotic-induced weight gain in the treatment of schizophrenia.

Adult↗

Therapy of NAFLD: insulin sensitizing agents.

Insulin resistance is an integral part of the underlying pathophysiology in most patients with nonalcoholic fatty liver disease (NAFLD). Insulin-sensitizing agents are therefore likely to be of key importance in the treatment of this disorder, especially in the histologically more severe form known as nonalcoholic steatohepatitis. Here we have reviewed the current literature on the two major insulin-sensitizing agents that have been studied in patients with NAFLD: the thiazolidinediones (or PPAR-gamma agonists) and metformin, the only available biguanide. Thiazolidinedione administration in human NAFLD has been shown to decrease hepatic fat by several different global measures and to decrease evidence of cellular injury, but it has also been associated with increased peripheral fat and weight gain. In contrast, metformin has been shown to improve biochemical markers without weight gain, but with more variable improvement in histology. Neither agent has been FDA approved for treating NAFLD, but existing studies have provided much hope for incorporating these medications into NAFLD management strategies in selected patients.

Fatty Liver↗

Therapy of NAFLD: antioxidants and cytoprotective agents.

Lipid peroxidation and secondary cellular injury are the dominant mechanism in the transition from relatively stable hepatic steatosis to potentially progressive steatohepatitis in nonalcoholic fatty liver disease (NAFLD). Oxidation of excessive fatty acids generates free radicals (reactive oxygen species) that damage organelles and stimulate signaling pathways leading to fibrosis and cellular injury. Both antioxidant agents (by breaking the chain reaction of lipid peroxidation) and cytoprotective agents (by stabilizing cellular and organelle phospholipid membranes) may be effective agents in treating an active steatohepatitis through amelioration of the driving force and attenuation of the secondary effects. Here we have reviewed the existing studies on such therapies, including vitamin E, S-adenosylmethionine (SAMe), betaine, and ursodeoxycholic acid. Small trials suggest possible improvement in liver enzymes with the use of these agents in NAFLD. However, controlled studies have not uniformly demonstrated benefit from these agents when compared with control groups treated with diet and weight loss alone, and measurement of reliable histologic endpoints is limited. These agents may show benefit in NAFLD through future larger controlled studies. Particular promise may exist in the use of these agents in combination therapy with ones that target other aspects in the pathogenesis of NAFLD, such as insulin-sensitizing agents.

Acetylcysteine↗

Effect of structural modifications on the assembly of a glycinin subunit.

A Gy4 glycinin cDNA was modified and used to produce structurally altered 11S storage protein subunits. We evaluated these modified subunits for their ability to assemble into oligomers. Alterations made in the acidic polypeptide changed the subunit solubility characteristics but did not eliminate assembly. Modifications in the basic polypeptide usually eliminated assembly of subunits into trimers. A region exhibiting high natural variability located at the COOH terminus of the acidic polypeptide that we have designated the hypervariable region was also studied. Extensive deletions and insertions were tolerated in the hypervariable region without perturbing subunit assembly. Some of the insertions significantly increased the methionine content in the Gy4 glycinin subunit. Together, our results indicated that the structure of the basic polypeptide was more critical for assembly of trimers than that of the acidic polypeptide, an observation that implies that the basic polypeptides direct trimer formation. The assembly assays described here will be useful in efforts to improve seed quality. Using them, the effects of modifications to the storage protein subunits can be rapidly evaluated before introducing the mutated genes into plants.

Base Sequence↗

Reliability of atomic displacement parameters in protein crystal structures.

Mean standard errors in atomic displacement parameters (ADPs) resulting from protein crystal structure determinations are estimated by comparing the ADPs of protein-chain pairs of identical sequence within the same crystal or within different crystals displaying the same or different space groups. The estimated ADP standard errors increase nearly linearly as the resolution decreases - an unexpected result given the nonlinear dependence of the resolution on the amount of diffraction data. The estimated ADP standard errors are larger for side-chain and solvent-exposed atoms than for main-chain and buried atoms and, surprisingly, are also larger for residues in the helical secondary structure relative to other local backbone conformations. The results allow an estimate of the influence of crystallographic refinement restraints on ADP standard errors. Such corrections should be applied when comparing different protein structures.

Crystallography, X-Ray↗

Amino acid distribution in protein secondary structures.

The compositional distribution of the twenty amino acids was examined for particular positions within secondary structures (alpha-helices, beta-strands, and turns) taken from a 44-protein sample. Correlation coefficients calculated between positional composition of the amino acids and various of their physico-chemical characteristics indicated considerable asymmetry in the properties of the residues comprising regions within and adjacent to secondary structures, modes of helix formation, physical parameters most sensitive to the buriedness of residues in beta-strands, and possible improvements in the accuracy of secondary structure prediction methodologies.

Amino Acids↗

Residue contacts in protein structures and implications for protein folding.

The preferential association of amino acid side groups with specific side chain atoms are examined in 44 known protein structures. The resulting association potentials among residue side groups are used to detect structural homology in proteins displaying little or no homology in their primary sequences. Suggestions are also made regarding the nature of the protein folding process. They are based on statistical observations that delineate the extent of short and long range interactions and that display side group bias in association with other side chain atoms on their N-terminal side.

Amino Acid Sequence↗

Prediction of secondary structural elements in glycerol-3-phosphate dehydrogenase by comparison with other dehydrogenases.

The secondary structure of glycerol-3-phosphate dehydrogenase was predicted from its amino acid sequence. The pattern of helices and sheets within the first half of the polypeptide as well as specific marker residues were consistent with the properties of the NAD binding domain in other dehydrogenases. The second half of the sequence shows similarities with the catalytic domain of glyceraldehyde-3-phosphate dehydrogenase. The resulting two-domain structure of glycerol-3-phosphate dehydrogenase allows the correct environment for the B specificity of the nicotinamide ring and the L-glycerol 3-phosphate substrate.

Alcohol Oxidoreductases↗

Structural prediction of membrane-bound proteins.

A prediction algorithm based on physical characteristics of the twenty amino acids and refined by comparison to the proposed bacteriorhodopsin structure was devised to delineate likely membrane-buried regions in the primary sequences of proteins known to interact with the lipid bilayer. Application of the method to the sequence of the carboxyl terminal one-third of bovine rhodopsin predicted a membrane-buried helical hairpin structure. With the use of lipid-buried segments in bacteriorhodopsin as well as regions predicted by the algorithm in other membrane-bound proteins, a hierarchical ranking of the twenty amino acids in their preferences to be in lipid contact was calculated. A helical wheel analysis of the predicted regions suggests which helical faces are within the protein interior and which are in contact with the lipid bilayer.

Amino Acid Sequence↗

Structural homology of lens crystallins. A method to detect protein structural homology from primary sequences.

The X-ray crystallographic structure of bovine gamma-crystallin shows four similar folding motifs each composed of about 42 residues arranged as four topologically sequential, anti-parallel beta-strands. Since the beta and gamma-crystallin sequences show good homology, proposals for a four-motif beta-crystallin model have been made. The other bovine eye-lens protein species, alpha-crystallins, are not homologous to beta or gamma-crystallin in primary structure. In the present work, smoothed plots of amino acid sequence number versus a residue characteristic (e.g. hydrophobicity) were calculated for the various crystallins. Cross-correlation coefficients were then determined between pairs of crystallin plots for various registers of the curves. The correlation plots were then combined for several characteristics and for pairwise comparisons between beta or gamma-crystallin and the alpha-crystallins. The resulting plots showed four peaks separated by about 42 residues for the alpha-crystallins, suggesting that they also possess a four-motif beta-barrel structure. The physical parameter comparison technique appears generally applicable in suggesting a structural and functional relationship amongst proteins that show no primary sequence homology.

Amino Acid Sequence↗

Homologies and anomalies in primary structural patterns of nucleotide binding proteins.

In searches for homology among nucleotide binding proteins, recent reports have described primary structure alignments for stretches of 30 or so amino acid residues among a variety of proteins including the ras and src oncogene products. The significance of these sequence matches has been tested by searching in available data banks for certain conserved residue patterns resulting from the alignments. The tests suggest that alignments over these limited stretches are not necessarily justifiable and any implications for residues involved in nucleotide binding must be viewed with caution.

Amino Acid Sequence↗

A double-blind placebo controlled study of a 5% lidocaine/prilocaine cream (EMLA) for topical anesthesia during thermolysis.

BACKGROUND: Electrolysis and thermolysis are commonly used electrosurgical methods for the permanent destruction of unwanted hair. However, patient fear of pain during treatment may interfere with or even prevent desired treatment of hirsutism on sensitive areas such as the upper lip. OBJECTIVE: This study was conducted to assess the efficacy of EMLA (Eutetic Mixture of Local Anesthetics), a 5% lidocaine/prilocaine cream, as a topically applied local anesthetic during thermolysis on the upper lip. METHODS: A double-blind placebo control study was conducted by the University of Texas Medical Branch thermolysis clinic. Thirty women with idiopathic hirsutism of the upper lip were studied. Pain was measured with a 100 mm visual analog scale (VAS). RESULTS: Total paired VAS score differences comparing the placebo VAS scores to the EMLA VAS scores were significant by paired t-test (P = .0001). Adverse reactions were mild and transient. CONCLUSION: EMLA cream may have multiple applications to the practice of dermatologic surgery, including topically achieved local anesthesia during thermolysis and electrolysis.

Adolescent↗

The association of alcohol-induced blackouts and grayouts to blood alcohol concentrations.

The primary aim of this study was to investigate the association between measured blood alcohol concentration (BAC) and the presence and degree of amnesia (no amnesia, grayout, or blackout) in actively drinking subjects. A secondary aim was to determine potential factors other than BAC that contribute to the alcohol-induced memory loss. An interview questionnaire was administered to subjects regarding a recent alcohol associated arrest with a documented BAC greater than 0.08 g/dL for either public intoxication, driving under the influence, or under age drinking was administered. Demographic variables collected included drinking history, family history of alcoholism, presence of previous alcohol-related memory loss during a drinking episode, and drinking behavior during the episode. Memory of the drinking episode was evaluated to determine if either an alcohol-induced grayout (partial anterograde amnesia) or blackout (complete anterograde amnesia) occurred. Differences in (1) mean total number of drinks ingested before arrest, (2) gulping of drinks, and (3) BAC at arrest were found for those having blackouts compared with no amnesia; while differences in drinking more than planned were found between the no amnesia and grayout groups. A strong linear relationship between BAC and predicted probability of memory loss, particularly for blackouts was obvious. This finding clinically concludes that subjects with BAC of 310 g/dL or greater have a 0.50 or greater probability of having an alcoholic blackout.

Adult↗

A tissue-equivalent phantom series for mammography dosimetry.

A breast tissue-equivalent series (BRTES) of phantoms is manufactured to mimic both the attenuation and the density of the range of glandular and adipose tissue compositions encountered in mammography. The BRTES simulates breast tissues across the range of 20% to 70% glandularity and can be assembled in a variety of thicknesses to represent a compressed breast thickness corresponding to glandularity to simulate various patient demographics. The fabrication techniques are presented, and the physical properties of the completed series of phantoms are described. The BRTES phantoms provide a dosimetry comparison with commonly used phantoms, including the American College of Radiology accreditation phantom and BR12, a 50% glandularity tissue-equivalent material. The comparison shows that the average glandular dose is a strong function of compressed breast thickness and tissue composition. Patient doses measured using photo-timed exposures with the BRTES phantoms can be up to a factor of 3 greater than or less than the doses predicted using conventional phantoms.

Equipment Design↗