Search PubMed⌕ Search

Biomedical subjects

A Hogan

Publications and source records attributed to A Hogan.

At least 55 records · Page 3Linked to original sources

Short direct repeats mediate spontaneous high-frequency deletions in DNA of minute virus of mice.

Previous work (E. A. Faust and D. C. Ward, J. Virol. 32:276-292, 1979) revealed a remarkably high rate of spontaneous deletion in viral DNA during lytic infection of cultured murine cells with minute virus of mice (MVM), an autonomous parvovirus. In the present study, we have isolated plasmid and phage recombinants containing MVM DNA inserts bearing deletions and we have determined the DNA sequence spanning three deletion junctions. The deletions, which average 3 kilobases in length, occur between pairs of perfectly homologous 4- to 10-base-pair direct repeats, such that one copy of the repeated sequence is lost, whereas the other remains behind at the deletion junction. When compared, the three sets of direct repeats exhibit no apparent sequence homology and have an A + T content of between 50 and 80%. These results indicate that 4- to 10-base-pair homologies mediate spontaneous deletion formation in the MVM genome and highlight parvoviruses as novel model systems for studies of this ubiquitous pathway of genetic variation.

Base Sequence↗

Aggregation patterns of bile salts: crystal structure of calcium cholate chloride heptahydrate.

Crystals of calcium cholate chloride heptahydrate, CaC24H39O7Cl . 7H2O, are monoclinic, space group P2(1), with a = 11.918(2), b = 8.636(1), c = 15.302(3) A, beta = 97.93(3) degrees, V = 1559.9(8) A3, and Z = 2. A trial structure was obtained by Patterson and Fourier techniques and was refined by full-matrix least-squares calculations using absorption corrected CuK-alpha diffractometer data. The final R index is 0.047. The crystal structure contains bilayer-type arrangements, with hydrophobic portions of cholate rings sandwiched between layers of polar groups that are interacting with calcium ions and water molecules. The calcium ion is coordinated to five water molecules and to the two carboxylate oxygen atoms of the cholate residue. Two additional water molecules are involved only in crystal packing through the formation of hydrogen bonds. Cholate-cholate hydrophobic interactions involve contacts between the hydrocarbon portions of the carboxylate sidechains and the A and B rings. This results in a staggered packing pattern that is nearly identical to that found in crystals of sodium cholate and rubidium deoxycholate. Similar bilayer aggregation patterns may also be involved in the formation of bile salt micelles in aqueous media. The characteristic bilayer packing arrangement can accommodate a variety of cation-binding patterns, as evidenced by the finding that calcium, sodium, and rubidium ions interact with the polar faces of the bilayers in different ways. The carboxylate sidechain displays two different conformations in the crystal structure of calcium cholate chloride heptahydrate. Variation in sidechain conformation may be of importance in the adjustment required to accommodate different cation coordination schemes.

Bile Acids and Salts↗

Cost-effectiveness analysis in heart disease, Part II: Preventive therapies.

Cost-effectiveness analysis of preventive therapies are reviewed in the following categories: lipid lowering, hypertension, smoking cessation, exercise, and anticoagulation. From review of 8 analyses, cost-effectiveness of primary prevention via cholesterol lowering drugs is generally expensive, whereas that of secondary prevention generally is favorable. However, targeting by age, coexisting risk factors, and gender strongly influence results that are also sensitive to drug costs. Treatment of hypertension (5 analyses) is cost-effective in virtually all patient populations and circumstances and for a wide variety of drugs. It is more so with coexisting risk. Issues relating to compliance and drug costs are important. Smoking cessation (4 analyses) is highly cost-effective and worthwhile. However, data on recidivism are incomplete, and cessation may be more difficult to achieve in the general population versus study patients. In one analysis, an exercise program was found to be cost-effective in prevention of coronary heart disease. Anticoagulants have been analyzed in various circumstances. Their cost-effectiveness is favorable for prosthetic valves, although sensitive to imprecision in monitoring. It is also favorable for mitral stenosis in the presence of atrial fibrillation but not normal sinus rhythm. Cost-effectiveness of heparinization for prosthetic valve patients undergoing surgery is rather variable and depends on type of surgery (major versus minor) and type of valve. Many topics in anticoagulant therapy remain to be explored from a cost-effectiveness point of view.

Adult↗

Cost-effectiveness analysis in heart disease, Part III: Ischemia, congestive heart failure, and arrhythmias.

Cost-effectiveness analyses were reviewed in the following diagnostic and treatment categories: acute myocardial infarction (MI) and diagnostic strategies for coronary artery disease (CAD), coronary artery bypass graft (CABG) surgery, percutaneous transluminal coronary angioplasty (PTCA), congestive heart failure (CHF), and arrhythmias. In the case of acute MI, coronary care units, as presently used, are rather expensive but could be made much more efficient with more effective triage and resource utilization; reperfusion via thrombolysis is cost-effective, as are beta-blockers and angiotensin-converting enzyme (ACE) inhibitors post-MI in appropriate patients. Cost-effectiveness of CAD screening tests depends strongly on the prevalence of disease in the population studied. Cost-effectiveness of CABG surgery depends on targeting; eg, it is highly effective for such conditions as left-main and three-vessel disease but not for lesser disease. PTCA appears to be cost-effective in situations where there is clinical consensus for its use, eg, severe ischemia and one-vessel disease, but requires further analysis based on randomized data; coronary stents also appear to be cost-effective. In preliminary analysis, ACE inhibition for CHF dominates, ie, saves both money and lives. Cardiac transplant appears to be cost-effective but requires further study. For arrhythmias, implantable cardioverter defibrillators are cost-effective, especially the transvenous device, in life-threatening situations; radiofrequency ablation is also cost-effective in patients with Wolff-Parkinson-White syndrome apart from asymptomatic individuals; and pacemakers have not been analyzed except in the case of biofascicular block, where results were variable depending on the situation and preceding tests.

Angioplasty, Balloon, Coronary↗

Perceptions of psychosocial adjustment to acquired communication disorders: applications of the Code-Müller Protocols.

The 'Code-Müller protocols' (CMP) were introduced in 1983 and originally aimed to compare perceptions of psychosocial adjustment to aphasia and related disorders from the separate perspectives of patients, relatives and speech and language therapists as a basis for counselling. In later studies the items of the CMP were also used to examine perceptions of their importance as possible therapy targets in the rehabilitation of people with communication disorders. This paper describes the development of the CMP and presents an overview of their application in aphasia, laryngectomy and acquired deafness and discusses some clinical implications. Studies published in the past 15 years show that aphasic people and their relatives or significant others are significantly more optimistic concerning psychosocial adjustment than their therapists. Furthermore, optimism changes during the course of illness. The relative weightings given for therapy or rehabilitation targets significantly differ between different professional groups concerned with aphasia rehabilitation (speech and language therapists/pathologists, physiotherapists, occupational therapists, psychologists and physicians) and are influenced by clinical experience.

Clinical Protocols↗

Evaluation of the effectiveness of following up laboratory reports of elevated blood leads in adults.

The usefulness of a statewide laboratory-based blood lead surveillance system to initiate workplace enforcement inspections was studied. In particular, the effectiveness of inspection of companies in which at least one worker had a blood lead level (BLL) 30-39 microg/dL but no greater than 39 microg/dL was considered. The surveillance system identified all individuals who had been tested for blood lead. Adults with BLLs > or =30 microg/dL were interviewed. Companies where lead exposures occurred were identified and enforcement inspections performed there. Companies were grouped into four categories: one or more employees with BLL > or =50 microg/dL; one or more employees with highest BLL of 40-49 microg/dL; one or more employees with highest BLL of 30-39 microg/dL; and companies that used lead but from which no blood lead reports were received. The number of citations and amounts of penalties, and BLLs before and after, were compared among the three blood lead groups and with a control group of no lead-using companies. A cost-benefit analysis was performed. Citations and penalties did not differ among the three blood lead groups but were markedly increased compared with the lead using but no blood lead group. Violations of specific lead standard components were similar among the three blood lead groups. Blood lead companies had increased citations and penalties as compared with nonusing lead control companies. No significant decrease in blood leads was seen postinspection. Total cost to identify lead-exposed workers at problem work sites was $125 ($53-$459) per lead-exposed worker. Followup of companies identified through the surveillance system was an effective method to target workplace inspections. It is recommended that routine inspection be instituted for all companies in which an employee is reported to have a blood lead of 30 microg/dL or greater.

Adult↗

A four-year longitudinal investigation of the social skills and behavior problems of students with learning disabilities.

This longitudinal, prospective study investigated the social skills and behavior problems of three groups of students (10 students per group) from kindergarten through third grade: learning disabilities (LD), low achievement (LA), and average/high achievement (A/HA). Social skills and behavior problem rating scales were completed by teachers on all students during kindergarten through third grade. Students in the LD and LA group exhibited significantly lower social skills and higher levels of behavior problems than their A/HA peers, but no significant differences for either measure were found between the LD and LA groups. Scores on the cooperating/responding factor of the social skills rating scale increased over time, but scores on the outgoing/initiating factor of the social skills rating scale did not change significantly over time. Discussion focused on the finding that students in the LD and LA groups did not differ significantly on social skills or behavior problems over time, though both groups demonstrated more behavior problems and lower social skills than the A/HA students.

Child↗

Confidence intervals for cost-effectiveness ratios.

The problem of variability in computed cost-effectiveness ratios (CERs) is usually addressed by performing sensitivity analyses to determine the effects on these ratios of plausible ranges of values of input parameters. However, the sampling variation that exists in these estimated parameters can be utilized to obtain confidence intervals for cost-effectiveness ratios. As cost-effectiveness analysis becomes more widely used, new techniques need to be developed for establishing when a difference in strategies evaluated is meaningful. A first step is to establish the precision of the CER itself. The authors estimate the precision of a CER in the context of a statistical model in which the primary outcome is survival, with cost and effectiveness defined in terms of the underlying survival distribution (S). Effectiveness (alpha) is measured by life expectancy, restricted to a finite time horizon and discounted at a fixed rate r, alpha = integral of e-rtS(t)dt. Cumulative cost (beta) per patient is regarded as resource utilization and incurred randomly over time depending on the survival experience of the patient, beta = integral of e-rtS(t)dC(t), where C(t) is the total potential resources utilized up to time t. Average cost-effectiveness (ACE) of a single strategy is beta/alpha, and when comparing two strategies, the CER is delta beta/delta alpha, the ratio of the incremental cost to the difference in mean survival. Utilizing the sampling distribution of the Kaplan-Meier estimate of S yields standard errors and confidence intervals for ACE and CER. The technique is applied to survival data from 218 previously studied patients to assess 95% confidence intervals for the CER and ACE of the implantable cardioverter defibrillator as compared with electrophysiology-guided therapy.

Confidence Intervals↗