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Biomedical subjects

J Donovan

Publications and source records attributed to J Donovan.

At least 55 records · Page 3Linked to original sources
PubMed2000

An ordered comparative map of the cattle and human genomes.

A cattle-human whole-genome comparative map was constructed using parallel radiation hybrid (RH) mapping in conjunction with EST sequencing, database mining for unmapped cattle genes, and a predictive bioinformatics approach (COMPASS) for targeting specific homologous regions. A total of 768 genes were placed on the RH map in addition to 319 microsatellites used as anchor markers. Of these, 638 had human orthologs with mapping data, thus permitting construction of an ordered comparative map. The large number of ordered loci revealed > or =105 conserved segments between the two genomes. The comparative map suggests that 41 translocation events, a minimum of 54 internal rearrangements, and repositioning of all but one centromere can account for the observed organizations of the cattle and human genomes. In addition, the COMPASS in silico mapping tool was shown to be 95% accurate in its ability to predict cattle chromosome location from random sequence data, demonstrating this tool to be valuable for efficient targeting of specific regions for detailed mapping. The comparative map generated will be a cornerstone for elucidating mammalian chromosome phylogeny and the identification of genes of agricultural importance."Ought we, for instance, to begin by discussing each separate species-in virtue of some common element of their nature, and proceed from this as a basis for the consideration of them separately?" from Aristotle, On the Parts of Animals, 350 B.C.E.

Animals↗
PubMed1999

Population requirement for primary hip-replacement surgery: a cross-sectional study.

BACKGROUND: There has been a long-standing failure in many countries to satisfy the demand for several elective surgical treatments, including total hip replacement. We set out to estimate the population requirement for primary total hip replacement in England. METHODS: We undertook a cross-sectional study of a stratified random sample of 28,080 individuals aged 35 and over from 40 general practices in inner-city, urban, and rural areas of Avon and Somerset, UK. Prevalent disease was identified through a two-stage process: a self-report screening questionnaire (22,978 of 26,046 responded) and subsequent clinical examination. Incident disease was estimated from the point prevalence by statistical modelling. The requirement for total hip replacement surgery was estimated on the basis of pain and loss of functional ability, with adjustment for evidence of comorbidity and patients' treatment preferences. FINDINGS: 3169 people reported hip pain on the screening questionnaire. 2018 were invited for clinical examination, and 1405 attended. The prevalence of self-reported hip pain was 107 per 1000 (95% CI 101-113) for men and 173 per 1000 (166-180) for women. The prevalence of hip disease severe enough to require surgery was 15.2 (12.7-17.8) per 1000 aged 35-85 years. The corresponding annual incidence of hip disease requiring surgery was estimated as 2.23 (1.56-2.90), which suggests an overall requirement in England of 46,600 operations per year for patients who expressed a preference for, and were suitable for, surgery; the recent actual provision in England was about 43,500. INTERPRETATION: This research suggests that the satisfaction of demand for total hip replacement, given agreed criteria for surgery, is a realistic objective.

Adult↗
PubMed1999

Calcified plaque cross-sectional area in human arteries: correlation between intravascular ultrasound and undecalcified histology.

BACKGROUND: The purpose of this investigation was to quantify the amount of intralesional calcium detected by intravascular ultrasound (IVUS) compared with undecalcified histology in human arteries. This method preserves intralesional calcium and reduces sectioning artifacts, thereby providing an accurate measure of calcium plaque morphology. METHODS AND RESULTS: Ten arterial segments (5 coronary, 5 iliac) were obtained at autopsy. IVUS imaging was performed with a 4.9F catheter at an automated pullback rate of 1.0 mm/s. The undecalcified arteries were dehydrated in ascending alcohol and polymerized in glycol methylmethacrylate. The arteries were cut into 200-microm sections with an Isomet low-speed saw and stained with Goldner's trichrome. The lumen cross-sectional area, the calcium plaque cross-sectional area, the calcium plaque depth, length, and angle of arc of calcified plaque were measured from the IVUS images and histologic sections. In 24 selected cross sections, there were 38 separate calcium plaques. An independent observer correctly identified 34 of 38 calcified plaques for a sensitivity of 89% and specificity of 97%. The total mean calcified plaque cross-sectional area measured from histology was 4.6 +/- 4.1 mm2 compared with 2.8 +/- 2.3 mm2 by IVUS (P =.002). Plaque depth measured by histology was 1.2 +/- 0.4 mm versus 0.7 +/- 0.2 mm by IVUS (P =.001). The length of calcium plaques measured by histology was 3.6 +/- 1.78 mm versus 3.6 +/- 1.5 mm for IVUS (r = 0.79). CONCLUSIONS: IVUS accurately depicts circumferential calcified lesions with high sensitivity (89%) and specificity (97%). However, IVUS underestimates the total calcified plaque cross-sectional area by 39%. This is mainly because of the inability of the ultrasound to penetrate intralesional calcium, which leads to an underestimation of the depth of calcium by 45%.

Adult↗
PubMed1999

Mutations of glutamate-84 at the putative potassium-binding site affect camphor binding and oxidation by cytochrome p450cam.

Cytochrome P450cam (CYP101) from Pseudomonas putida is unusual among P450 enzymes in that it exhibits co-operative binding between the substrate camphor and a potassium ion. This behaviour has been investigated by mutagenesis of Glu84, a surface residue which forms part of the cation-binding site. Substitutions that neutralize or reverse the charge of this side chain are shown to disrupt the co-operativity of potassium and camphor binding by P450cam, and also to influence the catalytic activity. In particular, replacement of Glu84 by positively charged residues such as lysine results in increased high-spin haem fractions and camphor turnover activities in the absence of potassium, along with decreased camphor dissociation constants. However, in the presence of potassium the camphor dissociation constants of these mutants are significantly increased compared with the wild-type, although the camphor turnover activities remain marginally higher. In contrast, substitution by aspartate results in tighter binding of both potassium and camphor, but has little effect on the enzymatic activity. In all cases the reaction remains essentially 100% coupled and gives 5-exo-hydroxycamphor as the only product. These results suggest that an anionic side chain at the 84 position is crucial for the co-operativity of camphor and cation binding, and that the physiological role for potassium binding by cytochrome P450cam is to promote camphor binding even at the expense of turnover rate, thus allowing the organism to utilize low environmental concentrations of this substrate for growth.

Amino Acid Substitution↗
PubMed1999

Transurethral resection or incision of the prostate and other therapies: a survey of treatments for benign prostatic obstruction in the UK.

OBJECTIVE: To establish the current usage of transurethral incision of the prostate (TUIP) and other forms of treatment for benign prostatic obstruction (BPO). METHODS: The Prostate Trial Office (PROTO) sent a survey questionnaire to all 376 consultant urologists in the UK which asked for estimates of their clinical practice in treating BPO. The survey had three principle aims: to assess the role that the determination of prostate size has in clinical practice, to determine the nature and frequency of use of a range of therapies including TUIP, and to examine the feasibility of conducting a randomized controlled trial comparing transurethral resection of the prostate (TURP) and TUIP. RESULTS: Of the 376 urologists, 349 replied (response rate 93%); most respondents used prostate size as a determinant when deciding on therapy for BPO (60%). Of their patients with BPO who were treated, 38% received surgical treatment, 33% drug therapies and 29% conservative management. Of the types of surgical treatment, the most commonly used procedure was TURP, in 79% of patients, with only 15% undergoing TUIP. When compared with TURP, TUIP tended to be used for patients with a mean prostate volume of </=25 mL. Only 6% of surgical patients were treated using minimally invasive techniques. CONCLUSION: This survey provides some evidence that prostate size plays an important role in determining the treatment; TUIP appeared to be under-used and other minimally invasive techniques are rarely used in the UK.

Adult↗
PubMed1999

Inhibition of protein kinase C activity promotes heat-induced apoptosis in RIF-1 but not in TR-4 cells.

PURPOSE: Inhibition of protein kinase C (PKC) activity has been demonstrated to reduce thermotolerance (TT), presumably by decreasing heat shock protein (HSP) production. Therefore, the interest was in evaluating this relationship further in two isogenic murine tumour cell lines: RIF-1 and its thermoresistant TR-4 selectant. MATERIALS AND METHODS: TT was induced in RIF-1 and TR-4 cells (45 degrees C for 15 min, then 37 degrees C for 6 h) with or without Ro31-8220, a specific inhibitor of PKC. PKC activity was assayed by determining the catalytic transfer of ATP to a specific substrate peptide. Survival was determined using the clonogenic assay. Apoptosis was quantitated by counting the number of cells demonstrating apoptosis after staining with acridine-orange/ ethidium bromide. Production of the inducible form of HSP70 was assessed using Western blot. RESULTS: At 2 microM Ro31-8220, >80% of PKC activity was inhibited in both cell lines, which was associated with no cytotoxicity at 37 degrees C. Basal HSP70 level was approximately 10-fold higher in the TR-4 compared with the RIF-1 cells. Upon TT induction, HSP70 level increased significantly in both cell lines, which was suppressed in the presence of Ro31-8220, but the relative amount of HSP70 remained high in the TR-4 cells. At 24 h, heat-induced apoptosis increased from 4 to 38% in RIF-1 cells in the presence of Ro31-8220, which was associated with a 26% reduction in clonogenic survival after thermotolerant heating. In contrast, <1% of TR-4 cells demonstrated apoptosis even with the highest dose of Ro31-8220, and no effect on survival was observed. CONCLUSION: Inhibition of PKC activity reduces HSP70 induction, which in turn is associated with promotion of heat-induced apoptosis in RIF-1 cells. However, the survival signals in the TR-4 cells are so strong, that even 80% inhibition of PKC activity has minimal impact on heat-induced apoptosis and survival in this thermoresistant cell line.

Animals↗
PubMed1999

Comparison of bispectral index, 95% spectral edge frequency and approximate entropy of the EEG, with changes in heart rate variability during induction of general anaesthesia.

We have compared bispectral index (BIS), 95% spectral edge frequency (SEF) and approximate entropy (ApEn) in 37 patients during induction and recovery from a short general anaesthetic. Heart rate variability (HRV) was also compared during induction only. These indices were noted at the start of induction, when a syringe held between the thumb and fingertips was dropped, at insertion of a laryngeal mask or tracheal tube (tube insertion), at incision, at the end of surgery, on return of the gag reflex and when the patient could follow a verbal command. When indices at the start of induction were compared with those at tube insertion, all four decreased significantly. BIS decreased from a mean of 95.38 (SEM 1.02) to 44.22 (1.05), mean SEF from 20.91 (1.19) to 14.14 (0.70) Hz, mean HRV from 37.1 (7.75) to 17.9 (3.6) bpm2 and ApEn from 0.90 (0.06) to 0.65 (0.04). Using logistic regression, the indices were compared both individually and in combination as to the power of distinguishing awake (at pre-induction) from asleep (at tube insertion) states. BIS had the best predictive power, with a sensitivity of 97.3%, specificity 94.4%, positive predictive value 94.7% and negative predictive value 97.1%. A combination of the indices conferred no additional predictive advantage.

Adolescent↗
PubMed1999

Parent-child relationships, child temperament profiles and children's alcohol use norms.

OBJECTIVE: The purpose of this study was to examine the contributions of child temperament, parents' alcohol use norms for their children and parent-child relationship quality to children's alcohol use norms. METHOD: Observational and self-report data on these variables were gathered from mothers, fathers and target children during home visits to a purposive random sample of 171 intact white families with a 10- to 12-year-old child, 85 with girls and 86 with boys. RESULTS: Liberality in children's norms was associated with active, sensation-seeking temperament, liberality in parents' norms and poor parent-child relationship quality. Positive parent-child, particularly father-child, relationships were associated with less liberal child norms even when parents' norms were liberal and children's temperaments were active and sensation oriented. CONCLUSIONS: Positive parent-child relationships have a conventionalizing effect on children's alcohol use norms that moderates the effects of temperament and parental norms. The development of alcohol use norms is best described by transactional models.

Alcohol Drinking↗
PubMed1999

Utility of hepatitis C virus serotypes in predicting response to treatment of chronic hepatitis C. Consensus Interferon Study Group.

Hepatitis C virus (HCV) genotyping has been shown to predict response to interferon, but is expensive. HCV serotyping is less expensive and simpler, and may be similarly useful. Using data from a large, randomized trial comparing consensus interferon (CIFN) and interferon alfa-2b (IFN alfa-2b) in patients with chronic HCV, we evaluated response rates based on HCV serotypes versus genotypes. Patients included in this analysis received subcutaneous injection of 9 microg CIFN (n = 232) or 3 MU IFN alfa-2b (n = 240) three times weekly for 24 weeks followed by 24 weeks of observation. Serum HCV RNA concentrations were measured regularly during treatment and at the end of both the treatment and post-treatment periods. Response to interferon was similar for HCV antibody types and their corresponding genotypes. The end-of-treatment HCV RNA rate of response (defined as undetectable serum on two consecutive assessments) was 29% for serotype 1 versus 24% for genotype 1 after CIFN; and 14% versus 15%, respectively, after IFN alfa-2b. Independently of treatment, patients infected with serotype or genotype 2 or 3 had a better therapeutic response than those infected with serotype or genotype 1. Similar results were obtained based on HCV antibody typing and genotyping, suggesting the potential of the former for predicting response to interferon.

Antiviral Agents↗
PubMed1998

Reporting on quality of life in randomised controlled trials: bibliographic study.

OBJECTIVES: To examine the frequency and quality of reporting on quality of life in randomised controlled trials. DESIGN: Search of the Cochrane Controlled Trials Register 1980 to 1997 to identify trials from all disciplines, from oncology, and from cardiovascular medicine that reported on quality of life. Assessment of abstracts from articles published from 1993 to 1996. Assessment of a sample of full reports with a standardised instrument. MAIN OUTCOME MEASURES: Prevalence of reporting on quality of life. Conditions and interventions studied in trials reporting on quality of life. Quality of reporting on quality of life. RESULTS: During 1980-97 reporting on quality of life increased from 0.63% to 4.2% for trials from all disciplines, from 1.5% to 8.2% for cancer trials, and from 0.34% to 3.6% for cardiovascular trials. Of 364 abstracts, 65% reported on drug interventions. Of a sample of 67 full reports, authors of 48 (72%) used 62 established quality of life instruments. In 15 reports (22%) authors developed their own measures, and in 2 (3%) methods were unclear. Response rates were given in 38 (57%), and complete reporting on all items and scales occurred in 31 (46%). CONCLUSIONS: Less than 5% of all randomised controlled trials reported on quality of life, and this proportion was below 10% even for cancer trials. A plethora of instruments was used in different studies, and the reporting of methods and results was often inadequate. Standards for the measurement and reporting of quality of life in clinical trials research need to be developed.

Data Collection↗
PubMed1998

Significance of early aminotransferase elevation after liver transplantation.

BACKGROUND: We retrospectively reviewed 213 consecutive patients who received their first liver allograft between January 1 and December 31, 1993, in order to study the impact of ischemia/preservation/reperfusion injury (IPRI) on patient and graft outcome. METHODS: The extent of IPRI was assessed by the peak value of aspartate aminotransferase (ASTmax) observed within the first 72 hr after transplant. For the purpose of univariate analysis, categorical classification of recipients was done based upon ASTmax as follows: group 1, ASTmax<600 U/L (n=46); group 2, ASTmax=600-2000 U/L (n=97); group 3, ASTmax>2000-5000 U/L (n=50), and group 4, ASTmax>5000 U/L (n=17). For multivariate analysis, stepwise Cox regression was performed with age, ASTmax, and United Network for Organ Sharing (UNOS) status as covariates. RESULTS: Groups were comparable with respect to age, UNOS status at the time of transplantation, and diagnostic case mix. Median follow-up was 644 days. The overall incidence of primary graft nonfunction (PNF) was 7.6%. PNF incidence was significantly correlated with the severity of IPRI (0%, 4%, 10%, and 41% for groups 1 to 4, respectively, P < 0.0001), but this impact was confined to the respective rates of retransplantation as early patient survival was unaffected. The 1-year survival of patients whose initial grafts manifested extreme IPRI (group 4) was significantly inferior to recipients in the three other groups (77%, 71%, 73%, and 52% for groups 1 to 4, respectively, P=0.03). This increased mortality was confined to patients who never achieved discharge from their initial hospitalization, with no significant differences between groups being detected in the survival of those patients who were discharged (84%, 80%, 85%, and 81% for groups 1 to 4, respectively, P=NS). Although overall 1-year graft survival was strongly correlated with the extent of IPRI (77%, 67%, 62%, and 41% for groups 1 to 4, respectively, P=0.001), this correlation was abolished when survival of grafts not lost to PNF was examined at 1 and 2 years. Stepwise Cox regression analysis confirmed the independent association between ASTmax and patient and graft survival. The long-term quality of allograft function as well as the incidence of chronic rejection and biliary complications were unrelated to the extent of IPRI. CONCLUSIONS: We conclude that: (1) patient survival is influenced by IPRI only when it is extreme (ASTmax>5000 U/L), provided parameters of graft function are used in conjunction with aminotransferase values to assess the need for prompt retransplantation; (2) short-term graft survival is proportional to the extent of IPRI, but grafts that are not lost to PNF have equivalent 1- and 2-year survival irrespective of the magnitude of IPRI; (3) 40% of grafts with extreme IPRI are lost to PNF, but the same proportion also provide long-term function; and (4) for surviving grafts, long-term biochemical function as well as the incidence of biliary complications and of chronic rejection are unrelated to the extent of IPRI.

Adult↗
PubMed1998

Low risk for tuberculosis in a regional pediatric hospital: nine-year study of community rates and the mandatory employee tuberculin skin-test program.

OBJECTIVE: To assess the risk of Mycobacterium tuberculosis infection and disease among patients and workers in a regional pediatric hospital. DESIGN: Descriptive epidemiological study of the mandatory tuberculin skin testing program of hospital employees at hire and during annual reevaluation, pediatric patients with tuberculosis (TB), efficacy of hospital infection control measures, and community rates of TB. SETTING: 361-bed, university, pediatric hospital serving Cincinnati (1.7 million population). RESULTS: During 1986 through 1994, 2,275 to 4,356 employees were compliant with Mantoux skin testing and screening each year. This represented >97% of the population who were eligible for screening. The cumulative rate of M tuberculosis infection from a previous positive tuberculin skin test was 10% to 12% per year during 1986 through 1994. Among new Mantoux skin-test converters in employees at annual reevaluation, the risk of TB infection was 0.3% in 1993 and 1994. There were no active cases of TB identified during new employee screening or annual reevaluation. Of 62 new Mantoux skin-test converters in 9 years, 23% were foreign-born, 13% were Asian, 23% were African American, 11% received the bacillus of Calmette-Guérin vaccine, and 60% had direct patient care or indirect patient contact. A cluster of five converters occurred in a department with no patient care or contact. Mantoux conversion rates were 1.9 per 1,000 employee patient-care or contact-years and 2.2 per 1,000 employee non-patient-contact years. Twenty pediatric patients with active TB were identified during 1991 to 1994, with < or =6 cases per year, placing this hospital in the low-risk category for M tuberculosis disease. Three children with pulmonary TB were admitted without immediate respiratory isolation, possibly exposing 9 patients and 42 employees; none converted their Mantoux skin tests on retesting. Rates of active TB in Cincinnati were stable during the period (eg, 8/100,000 population in 1994). CONCLUSIONS: Despite intense active surveillance among thousands of hospital employees with >97% annual compliance, tuberculin conversion rates were low, and no cases of active TB were identified during 9 years of follow-up. There was no evidence of transmission of M tuberculosis from infected patients to employees during uncontrolled exposures. Rates of TB in the community were low. These data suggest that rigorous application of the Centers for Disease Control and Prevention guidelines and Occupation Safety and Health Administration regulations for preventing nosocomial TB in pediatric hospitals may be excessive and costly. Special provisions should be made for pediatric hospitals with a proven low risk of transmission of M tuberculosis.

Adult↗
PubMed1998

Comparison of the use of a foot pump with the use of low-molecular-weight heparin for the prevention of deep-vein thrombosis after total hip replacement. A prospective, randomized trial.

We conducted a prospective, randomized trial to compare the safety and effectiveness of the A-V Impulse System foot pump with that of low-molecular-weight heparin for reducing the prevalence of deep-vein thrombosis after total hip replacement. Of 290 patients who were to have a primary total hip replacement, 143 were randomized to receive enoxaparin (forty milligrams daily) for seven days after the operation and 147, to use the foot pump for seven days. The primary outcome measure was the prevalence of deep-vein thrombosis, as determined by venography on the sixth, seventh, or eighth postoperative day. Secondary outcome measures included transfusion requirements, intraoperative blood loss, postoperative drainage, blood-loss index, appearance of the site of the wound according to a subjective visual-analog scale, and swelling of the thigh. The patients' compliance with the regimen for use of the foot pump was monitored with an internal timing device, and their acceptance of the device was assessed with a questionnaire. Symptoms consistent with pulmonary embolism were investigated with ventilation-perfusion scanning. The patients were contacted later for detection of symptoms of venous thromboembolism that may have occurred during the first three months after discharge from the hospital. Venography was performed on 274 patients: 136 who used the foot pump and 138 who received enoxaparin. Deep-vein thrombosis was detected in twenty-four (18 per cent) of the patients who used the foot pump compared with eighteen patients (13 per cent) who received enoxaparin (95 per cent confidence interval for the difference in proportions, -3.9 to +13.0 per cent). Thrombosis in the calf was found in seven patients (5 per cent) in the former group compared with six patients (4 per cent) in the latter (95 per cent confidence interval for the difference, -4.2 to +5.8 per cent), and proximal thrombosis was observed in seventeen patients (13 per cent) in the former group compared with twelve patients (9 per cent) in the latter (95 per cent confidence interval for the difference, -3.5 to +11.1 per cent). None of these differences was significant. No patient in either group had major proximal deep-vein thrombosis; all proximal thrombi were isolated entities involving the femoral valve cusp and were of unknown importance. One patient who used the foot pump had a non-fatal pulmonary embolism. One patient who received enoxaparin had a symptomatic deep-vein thrombosis during hospitalization. Two patients (one from each group [0.7 per cent]) were readmitted to the hospital because of a symptomatic deep-vein thrombosis despite normal venographic findings at the time of discharge. There was no difference in the transfusion requirements or the intraoperative blood loss between the two groups. There were more soft-tissue side effects in the patients who received enoxaparin than in those who used the foot pump: there was more bruising of the thigh and oozing of the wound (p < 0.001 for each), postoperative drainage (578 compared with 492 milliliters; p = 0.014), and swelling of the thigh (twenty compared with ten millimeters; p = 0.03). Of 124 patients who used the foot pump and were asked about the acceptability of the device, fourteen (11 per cent) said that it was uncomfortable, twenty-one (17 per cent) reported sleep disturbance, and four (3 per cent) stated that they had stopped using the device. Conversely, ten (8 per cent) found it relaxing. We concluded that the foot pump is a suitable alternative to low-molecular-weight heparin for prophylaxis against thromboembolism after total hip replacement and that it produces fewer soft-tissue side effects. Tolerance of the device is a problem for some patients.

Aged↗
PubMed1997

A question of community: at not-for-profit hospitals health is a local affair.

For-profit hospitals' entrepreneurial status, big business climate, and adherence to market discipline mandate that their services be considered akin to any other market commodity, to be bought and sold at the highest margin to the largest audience. Investor owned healthcare's primary allegiance must be a reasonable return to its stockholders and as a result it must avoid unprofitable services and unprofitable patients, by displacing their costly burdens onto the rest of the healthcare system.

Capital Financing↗