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Biomedical subjects

C Hughes

Publications and source records attributed to C Hughes.

At least 145 records · Page 8Linked to original sources

Oral propafenone for rapid conversion of recent onset atrial fibrillation--a review.

OBJECTIVE: To review comparative studies evaluating oral propafenone for restoring sinus rhythm in recent onset atrial fibrillation. DATA SOURCES: A MEDLINE search of the English-language literature (1966 to 1996) along with any referenced articles not identified by MEDLINE. STUDY SELECTION: Because intravenous propafenone is not marketed in Canada, only studies evaluating oral propafenone were included. Studies were selected if they compared oral propafenone with placebo or other antiarrhythmic agents for converting recent onset atrial fibrillation to normal sinus rhythm. DATA SYNTHESIS: Propafenone is often used as a first-line agent for pharmacological cardioversion of atrial fibrillation. In earlier studies, the efficacy of propafenone in restoring sinus rhythm was reported to be low with conversion rates of 6% to 62%. Many of these studies were noncomparative and often included patients with refractory, chronic atrial fibrillation or employed suboptimal doses of propafenone. More recently propafenone has been evaluated in the treatment of recent onset atrial fibrillation by using a single 600 mg oral loading dose. Success rates of 76% at 8 h and 83% at 12 h following the loading dose are reported. The incidence of atrial flutter during active treatment was similar to that with placebo, with the majority exhibiting 2:1 or greater atrioventricular conduction ratios and heart rates 150 beats/min or less. CONCLUSIONS: A single 600 mg oral dose of propafenone is highly effective at restoring sinus rhythm in patients with acute onset atrial fibrillation with few adverse effects. The small studies reviewed cannot lead to definitive conclusions about the safety of propafenone without prior administration of agents for rate control.

Administration, Oral↗

Comparison of ondansetron, metoclopramide, and placebo in the prevention of postoperative emesis in children undergoing ophthalmic surgery.

A common and distressing adverse effect following general anesthesia is nausea and vomiting. Pediatric ophthalmic surgery is associated with a high (50%-80%) incidence of postoperative emesis. Vomiting postoperatively may cause a prolonged hospital stay, and if it is persistent, may lead to unanticipated hospital admission after ambulatory surgery. The purpose of the present study was to compare the effectiveness of prophylactic antiemetic treatment with ondansetron, metoclopramide, and placebo in a study population of pediatric patients scheduled to undergo ophthalmic surgery. One hundred and one patients were included in this double-blinded study. The incidence of emesis and adverse effects were observed in the postanesthesia care unit and documented for 24 hours postoperatively. Analysis of variance showed that ondansetron significantly decreased (P = .05) the incidence of emesis in the postanesthesia care unit and during the first 24 hours postoperatively (P = .049). Additionally, parents of children in the ondansetron group reported a high degree (94%) of satisfaction with the experience.

Adolescent↗

BRCA1 testing in families with hereditary breast-ovarian cancer. A prospective study of patient decision making and outcomes.

OBJECTIVES: To identify predictors of utilization of breast-ovarian cancer susceptibility (BRCA1 gene) testing and to evaluate outcomes of participation in a testing program. DESIGN: Prospective cohort study with baseline interview assessment of predictor variables (eg, sociodemographic factors, knowledge about hereditary cancer and genetic testing, perceptions of testing benefits, limitations, and risks). BRCA1 test results were offered after an education and counseling session in a research setting. Outcome variables (including depression, functional health status, and prophylactic surgery plans [follow-up only]) were assessed at baseline and 1-month follow-up interviews. PARTICIPANTS: Adult male and female members (n=279) of families with BRCA1-linked hereditary breast-ovarian cancer (HBOC). RESULTS: Of subjects who completed a baseline interview (n=192), 60% requested BRCA1 test results (43% of all study subjects requested results). Requests for results were more frequent for persons with health insurance (odds ration [OR], 3.74; 95% confidence interval [CI], 2.06-6.80); more first-degree relatives affected with breast cancer (OR, 1.59; 95% CI, 1.16-2.16); more knowledge about BRCA1 testing (OR, 1.85; 95% CI, 1.36-2.50); and indicating that test benefits are important (OR, 1.45; 95% CI, 1.13-1.86). At follow-up, noncarriers of BRCA1 mutations showed statistically significant reductions in depressive symptoms and functional impairment compared with carriers and nontested individuals. Individuals identified as mutation carriers did not exhibit increases in depression and functional impairment. Among unaffected women with no prior prophylactic surgery, 17% of carriers (2/12) intended to have mastectomies and 33% (4/12) to have oophorectomies. CONCLUSIONS: Only a subset of HBOC family members are likely to request BRCA1 testing when available. Rates of test use may be higher in persons of a higher socioeconomic status and those with more relatives affected with breast cancer. For some high-risk individuals who receive test results in a research setting that includes counseling, there may be psychological benefits. More research is needed to assess the generalizability of these results and evaluate the long-term consequences of BRCA1 testing.

Adult↗

Transverse (Harris) lines in Irish archaeological remains.

Transverse lines were examined in 633 long bones from 73 individuals exhumed from two burial sites in the Republic of Ireland: Waterford City and Tintern Abbey. The burials cover four distinct periods between the 11th and 17th centuries. Lines were most numerous in the tibia, especially in the distal segment, and were not seen in the humerus nor the proximal part of the femur. The number of lines varied between the proximal and distal segments of each long bone, and though apparently equal in number across the midline, there were significant differences in the incidence of lines between corresponding pairs of bones. Thus, it is unwise to rely on the results of a single bone or one type of long bone alone either to indicate the health status of an individual, or as the basis for assessing the health status of a small population. Such results should be used only in association with other indicators.

Adult↗

Ethnic differences in risk perception among women at increased risk for breast cancer.

There has been increasing interest in the role of cultural and ethnic factors in breast cancer risk perceptions and screening practices. This study examined ethnic differences in breast cancer risk perception in 112 African American and 224 white women ages 35 and older who had at least one first-degree relative diagnosed with breast cancer. These samples were matched for education and age. Data on breast cancer risk factors, risk perceptions, breast cancer worries, and breast cancer screening practices were collected through structured telephone interviews. The results show that African American women were significantly less likely than white women to report heightened perceptions of personal risk after their relative was diagnosed with breast cancer (61% vs 82%; p < .001). Despite this, African American women had significantly greater concerns about their personal risk of breast cancer and worries about their affected relative. African American women also scored significantly higher than white women on a measure of avoidance of breast cancer-related thoughts and feelings. These psychological variables were associated independently with breast cancer risk perception in multivariate models, taking precedence over demographic and risk factor predictors. Observed ethnic differences in breast cancer risk perceptions and psychological distress may be attributable to the influence of cultural factors particular to people of African descent, such as the importance of interpersonal relationships, spirituality, and time orientation. An Africentric perspective is used to interpret these findings and to provide suggestions for delivering effective breast cancer risk counseling to African American women.

Adult↗

Epithelial ovarian cancer risk among women with polycystic ovary syndrome.

OBJECTIVE: To investigate the relationship between polycystic ovary syndrome (PCOS) and ovarian cancer, and to present three hypotheses regarding hormonal factors and the risk of ovarian cancer in women. METHODS: Data were analyzed from a population-based, case-control study, the Cancer and Steroid Hormone Study, to test the hypotheses. Four hundred seventy-six subjects with histologically confirmed epithelial ovarian cancer were identified from eight tumor registries of the Surveillance Epidemiology and End Results program. The study included 4081 controls ascertained via random-digit telephone dialing. All subjects and controls were aged 20-54 years. RESULTS: Seven subjects with ovarian cancer and 24 controls reported that they had been diagnosed with PCOS before the study period. Ovarian cancer risk was found to increase 2.5-fold (95% confidence interval [CI] 1.1-5.9) among women with PCOS. This association is found to be stronger among women who never used oral contraceptives (odds ratio [OR] 10.5, 95% CI 2.5-44.2) and women who were in the first quartile of body mass index (13.3-18.5 kg/m2) at age 18 (OR 15.6, 95% CI 3.4-71.0). CONCLUSION: The data suggest that the hormonal status of women with PCOS featuring abnormal patterns of gonadotropic secretion (enhanced levels of LH) in lean women may be a mitigating factor for the observed association between PCOS and ovarian cancer. We hope that our preliminary data stimulate further investigation of the testable hypotheses.

Adult↗

Suppression of transcription polarity in the Escherichia coli haemolysin operon by a short upstream element shared by polysaccharide and DNA transfer determinants.

Expression of the Escherichia coli hlyCABD operon encoding synthesis, maturation and export of haemolysin toxin was strongly dependent upon a 35 bp DNA sequence, spanning the element GGCGGTAG, located 2 kbp upstream. When the hly operon was placed under the control of the inducible tac promoter, expression remained dependent upon this element, when transcribed in its native orientation 3' of the promoter. The increase in ptac-directed transcription was strongest for the distal, export genes of the hly operon, and was particularly striking when ptac and the element were placed far upstream. The element did not influence transcript stability, and we suggest that it is a key component of a novel regulatory mechanism may suppresses transcription polarity within operons. The mechanism that be of widespread importance in bacterial gene expression because the 8 bp element is present in many Gram-negative species as an upstream component of operons encoding the production of toxins and the surface assembly of polysaccharides and components required for the conjugal transfer of DNA. We name it the ops element for operon polarity suppressor.

Bacterial Proteins↗

Increased distal gene transcription by the elongation factor RfaH, a specialized homologue of NusG.

The Escherichia coli RfaH protein is required for the expression of operons directing synthesis and export of the toxin haemolysin, the lipopolysaccharide core, and the F-factor sex pilus. Mutation of rfaH increases transcriptional polarity along all three operons. By demonstrating strong RfaH-dependent suppression of transcription polarity in vitro, we have established RfaH as a novel transcriptional activator, and we reveal that RfaH is a homologue of the essential protein NusG that modulates general transcriptional pausing and termination in prokaryotes. Full transcription of the distal genes from an upstream promoter required RfaH and the 5' cls-acting ops element, both in vivo and in vitro. In vivo the requirement for the ops element was suppressed by overexpressing RfaH, and in vitro the presence of ops lowered the concentration of RfaH required to stimulate transcript elongation. We suggest that RfaH directs transcript elongation in an analogous way to NusG, but does so in a subset of bacterial operons primarily engaged in the production of extracellular components required for virulence and fertility.

Amino Acid Sequence↗

A comparative analysis of pharmacokinetics of ceftriaxone in serum and pleural fluid in humans: a study of once daily administration by intramuscular and intravenous routes.

Pleural fluid and serum pharmacokinetics of ceftriaxone were performed in thirteen patients with pleural effusion. One gram of ceftriaxone was administered once daily intravenously in six patients and intramuscularly in seven patients. Ceftriaxone concentrations were measured in serum and pleural fluids in both groups on the first day of administration and in four patients of the intramuscular group on the fourth day of administration. The mean serum peak concentration at 1 h was 199 mg/L (S.E.M. 63.2) in the iv group and 80.5 mg/L (S.E.M. 12.0) in the im group. The mean serum trough concentrations in the two groups at 24 h were 27.5 mg/L (S.E.M. 12.6) and 29.7 mg/L (S.E.M. 5.2) respectively. In the pleural fluid, mean peak concentration was 20.1 mg/L (S.E.M. 4.7) at 6 h in the iv group and 15.3 mg/L (S.E.M. 5.1) at 12 h in the im group. The mean trough concentration was 9.6 mg/L (S.E.M. 1.9) and 13.3 mg/L (S.E.M. 3.1) at 24 h in the two groups respectively. On the fourth day of intramuscular administration the serum and pleural fluid peak and trough concentrations were higher when compared with the first day, consistent with a cumulative effect. The serum and pleural fluid concentrations of ceftriaxone following intravenous and intramuscular administration were well above the MIC90 of most common respiratory pathogens indicating good penetration into extracellular spaces. Further, these serum and pleural fluid antibiotic concentrations could be maintained even after a single intramuscular injection of the drug, thus indicating its usefulness as a parenteral mode of therapy on a domicilliary basis with a significant cost-saving potential. In conclusion, intramuscular administration of ceftriaxone would appear to be a convenient method of administering parenteral therapy in lower respiratory tract infections in the hospital and community, with pharmacokinetics very similar to those exhibited by the intravenous route.

Adult↗

Independent interaction of the acyltransferase HlyC with two maturation domains of the Escherichia coli toxin HlyA.

The apparently unique fatty acylation mechanism that underlies activation (maturation) of Escherichia coli haemolysin and related toxins is further clarified by investigation of the interaction of protoxin with the specific acyltransferase HlyC. Using deleted protoxin variants and protoxin peptides as substrates in an in vitro maturation reaction dependent upon HlyC and acyl-acyl carrier protein, two independent HlyC recognition domains were identified on the 1024-residue protoxin, proA, and they were shown to span the two target lysine residues K564 (KI) and K690 (KII) that are fatty acylated. Each domain required 15-30 amino acids for basal recognition and 50-80 amino acids for wild-type acylation. The two domains (FAI and FAII) competed with each other in cis and in trans for HlyC. The affinity of FAI for HlyC is approximately four times greater than that of FAII resulting in an overall 80% acylation at KI and 20% acylation at KII in both whole toxin and peptide derivatives. No other proA sequences were required for toxin maturation, and excess Ca2+ prevented acylation of both lysines. The lack of primary sequence identity between FAI and FAII domains in proA and among corresponding sites on related protoxins currently precludes an explanation of the basis of HlyC recognition by proA.

Acylation↗

Control of action and thought: normal development and dysfunction in autism: a research note.

Thirty-six children with autism, 24 children with learning difficulties (matched with the autistic group for sentence comprehension), and 41 normally-developing preschoolers were given two simple tasks: a hand-game requiring inhibitory control, and a delayed-reward situation tapping metacognitive awareness of strategies for coping with the delay period. For both clinical groups, performance on the two tasks was correlated, even when the effect of comprehension level was partialled out. However, no such correlation was observed for the preschoolers, once age was taken into account. The results are discussed in terms of potential links between executive-function and mental-state awareness.

Adolescent↗

Plantar pressure measurements during ambulation in weightbearing conventional short leg casts and total contact casts.

Total contact casts have been shown to be effective in healing plantar neuropathic ulcerations. The proposed mechanism of action is reduction of pressure over the ulcer during ambulation. However, there is little information to support this contention. Plantar pressure distribution was studied using standard short leg casts and total contact casts in normal feet. Both types of casts reduced forefoot pressure in study subjects. This occurred because of an increase in plantar surface area exposed to weightbearing forces. While increased force was shifted to the midfoot, there was no increase in pressure due to a corresponding increase in midfoot surface area exposed to this force. No significant difference was noted between standard short leg casts and total contact casts.

Adult↗

Self-instructional intervention for teaching generalized problem-solving within a functional task sequence.

Effects of an intervention that combined self-instruction with multiple exemplar training on the generalized problem solving of five high school students with severe mental retardation were examined. Innovative features of the intervention included (a) preteaching self-instruction to proficiency with one exemplar before introducing multiple exemplars and (b) embedding problem situations within a functional task sequence. Findings indicated that all students learned to perform five trained problem responses and five generalized responses while self-instructing. The self-instructional intervention appeared to decrease training time required to self-instruct as well as to decrease variability with which participants verbalized their self-instructions.

Adolescent↗