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Biomedical subjects

R Hillman

Publications and source records attributed to R Hillman.

At least 19 recordsLinked to original sources
PubMed2006

Clinical, enzymatic and molecular characterization of nine new patients with malonyl-coenzyme A decarboxylase deficiency.

We report nine new patients with malonic aciduria associated with enzyme-confirmed malonyl-CoA decarboxylase (MCD) deficiency in eight. Clinical details were available on eight, and molecular genetic characterization was obtained for nine. As for 15 previously described patients, cardinal clinical manifestations included developmental delay and cardiomyopathy; metabolic perturbations (e.g. acidosis) and seizures, however, were infrequent or not observed in our patients. For all, detection of elevated malonic acid in urine (+/- increased C3DC acylcarnitine by analysis employing tandem mass spectrometry) led to pursuit of enzyme studies. MCD activities (nmol/h PER mg protein) revealed: control (n = 22), 16.2 +/- 1.8 (SEM; range 5.7-46.2); patients (n = 8, assayed in duplicate), 1.7 +/- 0.3 (10% of parallel control; range 0.6-2.8). Molecular characterization by DNA sequence analysis and multiplex ligation-dependent probe amplification revealed nine novel mutations (c.796C>T; p.Gln266X, c.481delC; p.Leu161CysfsX18, c.1367A>C; p.Tyr456Ser, c.1319G>T; p.Ser440Ile, c.1430C>T; p.Ser477Phe, c.899G>T; p.Gly300Val, c.799-1683_949-1293del3128, and two other large genomic deletions comprising exons 1 or the complete gene) and two known mutations in the MLYCD gene. Our findings increase the number of enzyme-confirmed MCD-deficient patients by >50%, and expand our understanding of the phenotypic and molecular heterogeneity of this rare disorder.

Adolescent↗
PubMed2003

Sex in the suburbs.

BACKGROUND: Many suburban sexual health clinics exist in Australasia. However, sexual health research has hitherto been restricted to populations from major metropolitan centres. OBJECTIVE: To describe the demographic, sexual characteristics and presenting diagnoses of 6521 new patients attending a sexual health clinic in the western suburbs of Sydney (New South Wales). DISCUSSION: Patients originated from over 50 different countries. Postcode analysis suggested the clinic sample was representative of the socioeconomic distribution of the area, but there were notable ethnic disparities. The classic bacterial sexually transmitted infections constituted only a small proportion of presentations, with asymptomatic infections and those requiring complex therapies more commonly encountered. This has resource implications for general practitioners and specialist clinics alike. Improved liaison between specialist sexual health clinics and GPs, together with a raised awareness of sexual health services in general, has the potential to significantly improve overall public health.

Adolescent↗
PubMed2002

[Physical and technical elements of short-interval, color-filtered double strobe flash-stroboscopy].

INTRODUCTION: Quantitative measurement of vocal fold movements can be done either with high-speed imaging or with short interval, color-filtered double strobe flash-stroboscopy. The physical and technical elements of this new technique are described. METHODS: Two special strobe units (KAY Elemetrics RLS 9100) are used in a master-slave configuration. In this way an adjustable interval of 0.1-2.0 ms between flashes is introduced. The strobe flashes are color filtered and are separated by a brief interval. By this means a double exposure is created in each video frame.Real-time visualization of opening and closing velocities over the entire length of the vocal fold from anterior to posterior is possible. Quantification is possible off-line after image calibration. CONCLUSION: Short-interval, color-filtered double-strobe flash stroboscopy allows quantitative measurement of the velocity of vocal fold movements during vibration at different pitches and sound pressure levels (SPL). Images gained with this new technique provide information about a dynamic property (velocity) of the vocal fold within a single image.Therefore, its use could be helpful from the aspect of clinical documentation.

Artifacts↗
PubMed2001

A phase III study of recombinant human interferon gamma to prevent opportunistic infections in advanced HIV disease.

The efficacy and safety of recombinant human interferon gamma (rIFN-gamma) in the reduction of opportunistic disease in patients with advanced HIV-1 infection are assessed. A 12-month double-blind, placebo-controlled, multicenter, Phase III trial of rIFN-gamma in HIV-positive patients with CD4 < 100 x 10(9)/liter on stable antiretroviral therapy. Eighty-four patients were allocated treatment on a 1:1 basis to rIFN-gamma or placebo. Patients received rIFN-gamma 0.05 mg/m(2) or 0.9% saline subcutaneously three times weekly for 48 weeks (optional extension to 18 months). The primary end point was the incidence of opportunist infections (CDC categories B/C). Secondary end points included mortality, immunological, and virological parameters. Patients on placebo had a mean of 3.45 opportunist infections (OIs) in the first 48 weeks. Patients treated with rIFN-gamma had a mean of 1.71 OIs (p = 0.04). However, the model showed overdispersion and the inclusion of a dispersion factor raised the p value to 0.13. rIFN-gamma appeared to have a particular effect on the incidence of Candida, herpes simplex, and cytomegalovirus infections. Three-year survival in the rIFN-gamma arm was 28% compared to 18% in the placebo group (not significant). rIFN-gamma-associated side-effects of headache, fatigue, rigors, influenza-like symptoms, depression, myalgia, and granulocytopenia were reversible. There was no evidence for HIV activation. Although not significant, the trend towards decreased opportunistic infections and increased survival warrants consideration of further trials of rIFN-gamma. The study gives additional information on the safety profile of this cytokine.

AIDS-Related Opportunistic Infections↗
PubMed2001

A modified population analysis profile (PAP) method to detect hetero-resistance to vancomycin in Staphylococcus aureus in a UK hospital.

One hundred methicillin-resistant Staphylococcus aureus (MRSA) strains, isolated between 1983 and 1999, were tested alongside the vancomycin hetero-resistant S. aureus (hVRSA) strain Mu 3, and vancomycin-resistant S. aureus (VRSA) strain Mu 50, for their resistance to vancomycin. This was achieved using the screening method described by Hiramatsu, gradient plates, agar incorporation, standard Etest, macrodilution Etest and a modified population analysis. Using Hiramatsu's screening method, 5% of the 100 MRSA were identified as VRSA and 5% identified as hVRSA, the gradient plates identified 7% hVRSA, and the standard and macrodilution Etests identified no hVRSA. Mu 3 appeared to be vancomycin-susceptible using both the agar incorporation and standard Etest methods, but was classified as hVRSA using the macrodilution Etest. The modified population analysis reliably detected vancomycin hetero-resistance in Mu 3 and identified no hVRSAs within the 100 MRSA sample.

Hospitals↗
PubMed1999

Knowledge of Chlamydia trachomatis genital infection and its consequences in people attending a genitourinary medicine clinic.

OBJECTIVES: To assess knowledge of Chlamydia trachomatis infections, with a comparison of knowledge of Neisseria gonorrhoeae infections. METHODS: A cross sectional survey, by self completed questionnaire, of 200 subjects attending a genitourinary outpatient clinic. RESULTS: The response rate was 82% (90 male and 73 female). 51% of men (60% of females) had heard of chlamydia. 65 (82%) were unaware of the potential consequences of infection. 66% were unaware that the disease could be asymptomatic. Significantly more men (77%) than women (60%) had heard of gonorrhoea. Most participants (68%-82%) knew little of the possible consequences of this infection, and only 26% were aware that it could be asymptomatic. Knowledge was higher regarding fertility topics. There was no correlation between knowledge and either age or socioeconomic status. However, greater knowledge was displayed by those who read health information leaflets always or often. For both men and women, the preferred source of health information was the doctor. Other popular sources were health information leaflets, women's magazines, and television. CONCLUSIONS: Barely half the participants had heard of chlamydia and gonorrhoea. Further knowledge of either infection was very poor. There are serious implications for public health. The reasons for this are unclear and require exploration before targeted health promotion. Doctors and the popular media are acceptable, and potentially effective, sources of information. Acquisition of knowledge is important, both to reduce sexual risk taking behaviour and its consequences, and to allow for informed consent for chlamydia screening programmes.

Adolescent↗
PubMed1997

Effect of recombinant human erythropoietin on transfusion risk in coronary bypass patients.

BACKGROUND: Patients having a cardiac operation frequently require allogeneic blood transfusions despite surgical blood-conservation techniques. Recombinant human erythropoietin (Epoetin alfa) may augment this conservation by stimulating erythropoiesis. The safety and efficacy of perioperative use of Epoetin alfa to reduce the need of allogeneic transfusion was studied. METHODS: A multicenter double-blind, placebo-controlled, parallel-group study involved 182 patients having coronary artery bypass grafting and randomized to receive Epoetin alfa (300 or 150 IU/kg) or placebo subcutaneously for 5 days before, on the day of, and for 2 days after operation. RESULTS: Perioperative Epoetin alfa resulted in greater increases in baseline to preoperative hemoglobin levels and hematocrit (300 IU/kg) and in presurgery to postsurgical day 1 reticulocyte counts versus placebo (p < or = 0.05). However, there was no significant difference in transfusion requirements. Incidences of adverse events were similar in all study groups. CONCLUSIONS: Lower incidences of allogeneic blood exposure were observed in both Epoetin alfa-treated groups; however, the differences between all treatment groups were not significant. This was probably due to the relatively short 5-day preoperative course of Epoetin alfa therapy. There were no significant differences between the three groups relative to safety. Epoetin alfa was well tolerated in this population.

Antibodies↗
PubMed1997

The relationship between the supply of cardiac catheterization laboratories, cardiologists and the use of invasive cardiac procedures in northern New England.

OBJECTIVES: Utilization rates of coronary angiography and cardiac revascularization have been found to vary between areas. This study addresses the relationship between resource supply and procedure rates. METHODS: We compared the association of per capita catheterization laboratories, per capita cardiologists and multi-provider markets (where more than one hospital offers coronary angiography services) with the utilization rates for angiography and cardiac revascularization in northern New England, USA. Administrative data were used to capture invasive cardiac procedures. Small area analyses were used to create coronary angiography service areas. Linear regression methods were used to measure associations between the resource supply and utilization rates. RESULTS: Variation in the use of invasive cardiac procedures was strongly associated with the population-based availability of catheterization facilities and multi-provider markets and unrelated to cardiologist supply or need (as reflected in the hospitalization rates for myocardial infarction). In the multivariate model, an increase of 1 catheterization laboratory per 100,000 population was associated with an increase in the angiography rate of 1.62 per 1000 population; those service areas with multi-provider markets were associated with an additional increase in the angiography rate of 1.27 per 1000 population (R2 = 0.84, P = 0.0006). There was a moderately strong relationship between the catheterization laboratories per capita and the revascularization rates (R2 = 0.43, P = 0.029). Angiography rates were highly associated with cardiac revascularization rates: an increase in the angiography rate of 1 per 1000 population was associated with a 0.46 per 1000 increase in the cardiac revascularization rate (R2 = 0.85, P = 0.0001). CONCLUSIONS: Our work suggests that current efforts to address variation in cardiac procedures through activities such as appropriateness criteria, guidelines and utilization review are misdirected and should be redirected towards capacity, in this case the supply of catheterization facilities.

Cardiac Catheterization↗
PubMed1996

Decreased bone mineralization in children with phenylketonuria under treatment.

Children with phenylketonuria (PKU) obtain a great deal of their protein and mineral intakes from synthetic elemental formulae devoid of phenylalanine. To assess the effect of such diets and/or the disease on bone mineralization, children with PKU were compared to normal children for many parameters of mineral homeostasis and bone mineralization. A total of 11 children with PKU of mean age 10.9 +/- 4.2 years were compared to a large group of normal control children mean age 11.4 +/- 4.2, and an age and sex matched subset (n = 11). Children with PKU had lower serum calcium (9.1 +/- 0.9 vs 10.4 +/- 1.9 mg/dl P < 0.01) amd magnesium (1.67 +/- 1.4 vs 2.07 +/- 0.16 mg/ dl, P < 0.001) but normal values for phosphorus, zinc, and copper. The percentage tubular reabsorption of phosphorus was increased in PKU (93 +/- 3% vs 88 +/- 6%, P < 0.05) suggesting a lower phosphorus intake and/or absorption. Serum 25-hydroxyvitamin D, parathyroid hormone and 1,25 dihydroxyvitamin D were similar in PKU and control children. Serum albumin and lean body mass by dual energy X-ray absorption were not different suggesting that protein intake was adequate. In the 11 pairs, a decreased bone mineral density was seen for the lumbar spine (0.61 +/- 0.15 vs 0.72 +/- 0.24 P < 0.05), and lower extremities (1.56 +/- 0.30 vs 1.87 +/- 0.56 P < 0.05) by paired t-test. Compared to the total controls and the paired controls, decreases were seen in markers of bone formation; bone alkaline phosphatase, (72 +/- 30 vs 126 +/- 43 P < 0.001), osteocalcin (10.7 +/- 3.4 vs 13.1 +/- 2.0 P < 0.05) and procollagen type I carboxyterminal propeptide. No differences were seen in the bone resorption markers tartrate resistant acid phosphatase and urine Ca/Cr. The changes noted could not be related after age correction to serum phenylalanine levels, protein intake, or mineral intakes. It is unclear whether deficits in bone mineralization relate to the disease process itself or its treatment.

Adolescent↗
PubMed1996

Reproduction and development in Drosophila are dependent upon catecholamines.

Drosophila melanogaster, maintained on culture media containing alpha-methyl-p-tyrosine (alpha-MT) at millimolar levels for 7 days, fail to produce viable progeny. Lesser concentrations delay development. This effect of alpha-MT, an inhibitor of tyrosine hydroxylase (TH), is partially reversible by co-administration of L-dihydroxyphenylalanine, the product of TH. Potent inhibitors of other steps in the pathway for catecholamine biosynthesis are inactive except for a partial effect with dopamine B-hydroxylase inhibition. the effect of alpha-MT is due to a combination of ovulation suppression coupled with decreases in embryonic and larval viability. Effects similar to those of alpha-MT are found with millimolar levels of reserpine, prazosin and to a lesser extent, rauwolscine. No significant effects are found with propranolol, chlorpromazine, sulpiride and SK&F 83566. Mutant alleles of the gene coding for TH are known to be lethal at the embryonic stage when homozygous in both Drosophila and mice. Taken together, these results indicate that in addition to their established roles in the nervous system catecholamines function in animal development via an action mediated through alpha-adrenoceptors.

Animals↗
PubMed1994

Project 2000 and the replacement of the traditional student workforce.

This paper reports on part of a 4-year study monitoring the implementation of Project 2000 in one health authority. Its focus is on the consequences for the nursing service of replacing traditional, pre-Project 2000 students with permanent staff. It is argued that the Department of Health, who have been responsible for funding the replacement programme, have underestimated the numbers of permanent staff required to replace the traditional student workforce, and that the Project 2000 replacement exercise has contributed to a deterioration in staffing levels and skill mix.

Delivery of Health Care↗
PubMed1991

Platelet activation and aggregation during cardiopulmonary bypass.

Increases in plasma concentrations of platelet granule products such as platelet factor 4 and beta-thromboglobulin during cardiopulmonary bypass suggest that platelets are activated during extracorporeal circulation. Subsequent circulation of these activated platelets may be responsible for the ubiquitous platelet dysfunction associated with cardiopulmonary bypass. Using flow cytometry and a monoclonal antibody directed against an alpha-granule membrane protein, granule membrane protein 140 (GMP-140), which is expressed on the platelet surface membrane after activation, we directly measured the percentage of circulating activated platelets in 41 patients before, during, and after cardiopulmonary bypass. In addition, we compared the GMP-140 expression with platelet aggregation in response to adenosine diphosphate (ADP). Cardiopulmonary bypass produced a significant increase in the percentage of GMP-140-positive platelets persisting in the circulation; the percentage peaked at a mean of 29% (range 10-58%) before separation from extracorporeal circulation. A significant percentage of these activated platelets continued to circulate in the early postoperative period. Simultaneous measurement of platelet aggregation in response to ADP demonstrated an aggregation defect that had a time course distinct from platelet activation and whose magnitude did not correlate with the degree of platelet activation in individual patients. We conclude that cardiopulmonary bypass causes a complex constellation of platelet defects, which include alpha-granule release, prolonged circulation of activated, "spent" platelets, and impaired platelet aggregation.

Adenosine Diphosphate↗
PubMed1991

The natural history of dilated cardiomyopathy--a community study.

The incidence, clinical features and natural history of dilated cardiomyopathy within a clearly defined population of Scotland was studied retrospectively. From 1982 to 1986, 57 cases were recorded in a population of 145,00, representing an annual incidence of 7.9 per 100,000 per year. This incidence rate is higher than that reported from other centres, and the overall survival rates were poorer.

Aged↗
PubMed1990

Surveillance for persistent bovine viral diarrhea virus infection in four artificial insemination centers.

Four large bovine artificial insemination centers implemented a program of surveillance of resident and newly acquired bulls for persistent bovine viral diarrhea virus infection. Infection was identified in 12 of 1,538 bulls. Several clinical abnormalities, including acute and chronic mucosal disease, were evident among the persistently infected bulls. Semen produced by such bulls consistently contained bovine viral diarrhea virus, and such contamination was not always accompanied by diminished seminal quality. Infected bulls were detected by means of virus isolation tests performed on blood specimens, but not by use of serologic testing. Ten of the 12 persistently infected bulls were results of embryo transfer. Virologic surveillance of breeding herds, artificial insemination and embryo transfer centers, and the cattle trade is necessary to prevent spread of this virus by modern cattle breeding practices. Attention is also necessary to prevent contamination by this virus of the fluids used for recovery, in vitro manipulation, and transfer of bovine embryos.

Animals↗