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Biomedical subjects

R Hall

Publications and source records attributed to R Hall.

At least 55 records · Page 3Linked to original sources

A systematic approach to erectile dysfunction in the cardiovascular patient: a consensus statement.

Sexual activity is no more stressful to the heart when compared with a number of other natural daily activities, e.g. walking one mile on the level in 20 minutes. The cardiac risk of sexual activity in patients diagnosed with cardiovascular disease is minimal in properly assessed and advised patients. Erectile dysfunction (ED) is common, affecting 10% of men aged 40-70 years and increases in frequency with age. ED and cardiovascular disease share many of the same risk factors and often coexist. ED in the diagnosed cardiovascular patient should be identified by routine questioning in general practice. Modern therapies can restore a sexual relationship in the majority of patients with ED and can lead to a substantial improvement in quality of life. The majority of patients assessed to be at low or intermediate cardiac risk, as defined later in this paper (Table 4), can be effectively managed in primary care. Primary care treatment for ED in patients defined as high risk can be initiated following a specialist opinion and/or confirmation that the patient's cardiovascular condition is stabilised. There is no evidence that currently licensed treatments for ED add to the overall cardiovascular risk in patients with or without diagnosed cardiovascular disease.

Adult↗

Pyrimidinylimidazole inhibitors of CSBP/p38 kinase demonstrating decreased inhibition of hepatic cytochrome P450 enzymes.

Pyrimidine analogs of the pyrimidinylimidazole class of CSBP/p38 kinase inhibitors were prepared in an effort to reduce the potent inhibition of hepatic cytochrome P450 observed for the pyridinyl compounds. The substitution of pyrimidin-4-yl, 2-methoxypyrimidin-4-yl, or 2-methylaminopyrimidin-4-yl for pyridin-4-yl effectively dissociates CSBP/p38 kinase from P450 inhibition for this series and furthermore achieves an increase in oral activity.

Animals↗

DNA-based and alphavirus-vectored immunisation with prM and E proteins elicits long-lived and protective immunity against the flavivirus, Murray Valley encephalitis virus.

The immunogenicity and protective efficacy of DNA-based vaccination with plasmids encoding the membrane proteins prM and E of the flavivirus Murray Valley encephalitis virus (MVE) were investigated. Gene gun-mediated intradermal delivery of DNA encoding the prM and E proteins elicited long-lived, virus-neutralising antibody responses in three inbred strains of mice and provided protection from challenge with a high titer inoculum of MVE. Intramuscular DNA vaccination by needle injection also induced MVE-specific antibodies that conferred resistance to challenge with live virus but failed to reduce virus infectivity in vitro. The two routes of DNA-based vaccination with prM and E encoding plasmids resulted in humoral immunty with distinct IgG subtypes. MVE-specific IgG1 antibodies were always prevalent after intradermal DNA vaccination via a gene gun but not detected when mice were immunised with DNA by the intramuscular route or infected with live virus. We also tested a Semliki Forest virus replicon as vector for a flavivirus prM and E protein-based subunit vaccine. Single-cycle infections in mice vaccinated with packaged recombinant replicon particles elicited durable, MVE-specific, and virus-neutralising antibody responses.

Animals↗

Upregulation of Jun and Fos family members and permanent JNK activity lead to constitutive AP-1 activation in Theileria-transformed leukocytes.

Theileria parasitises bovine leukocytes and transforms them into proliferating, metastatic tumours, where the infection resembles a leukaemia-like disease. We have studied the signal transduction pathways leading to activation of the transcription factor AP-1 in different transformed leukocytes. Parasite infection leads to an up-regulation of all members of the Jun/Fos family of proteins and surprisingly, this occurs in the absence of any detectable ERK, or p38 MAP kinase activity. In the parasitised B-sarcoma TBL3, AP-1 induction occurs in the absence of any JNK activity. In contrast, in infected macrophage and B-cell lines, AP-1 transcriptional activity is strictly associated with the parasite-induced constitutive activation of JNK and subsequent c-Jun N-terminal phosphorylation. Thus, constant AP-1 transcriptional activity involves both an upregulation in the levels of Jun and Fos proteins and constitutive JNK activation.

Animals↗

Pertussis in South Australia 1893 to 1996.

This study describes trends in reports of pertussis in South Australia. Data were analysed from three sources: mortality data since 1893 from South Australian yearbooks, notification data from 1917, and hospitalisation data for pertussis or related complications since July 1985. Crude and age-specific rates of mortality, notifications and hospitalisation were compared. Pertussis peaked in 3 to 5 yearly cycles. The mortality and notification rates have generally declined over time. However, since 1993 the notification rate has remained high. The median age for pertussis notifications increased from 4 years in 1984 to 15 years in 1996. Serological testing for pertussis was included in 15% of notifications in 1985 and 90% in 1996. The age specific hospitalisation rate for pertussis was highest in infants < or = 6 months. Since the turn of the century, mortality and notification rates due to pertussis have declined. Over the past decade the major burden of severe disease resulting in hospitalisation has been borne by infants < or = 6 months. These infants are too young to be afforded protection from three primary immunisations against pertussis. Despite no substantial increase in mortality nor hospitalisation for pertussis in South Australia, the notification rate has remained high since 1993. This increase may be attributable to the use of more sensitive tests for pertussis, such as serology.

Adolescent↗

A comparison of sucralfate and ranitidine for the prevention of upper gastrointestinal bleeding in patients requiring mechanical ventilation. Canadian Critical Care Trials Group.

BACKGROUND: Critically ill patients who require mechanical ventilation are at increased risk for gastrointestinal bleeding from stress ulcers. There are conflicting data on the effect of histamine H2-receptor antagonists and the cytoprotective agent sucralfate on rates of gastrointestinal bleeding, ventilator-associated pneumonia, and mortality. METHODS: In a multicenter, randomized, blinded, placebo-controlled trial, we compared sucralfate with the H2-receptor antagonist ranitidine for the prevention of upper gastrointestinal bleeding in 1200 patients who required mechanical ventilation. Patients received either nasogastric sucralfate suspension (1 g every six hours) and an intravenous placebo or intravenous ranitidine (50 mg every eight hours) and a nasogastric placebo. RESULTS: The patients in the two groups had similar base-line characteristics. Clinically important gastrointestinal bleeding developed in 10 of 596 (1.7 percent) of the patients receiving ranitidine, as compared with 23 of 604 (3.8 percent) of those receiving sucralfate (relative risk, 0.44; 95 percent confidence interval, 0.21 to 0.92; P=0.02). In the ranitidine group, 114 of 596 patients (19.1 percent) had ventilator-associated pneumonia, as compared with 98 of 604 (16.2 percent) in the sucralfate group (relative risk, 1.18; 95 percent confidence interval, 0.92 to 1.51; P=0.19). There was no significant difference between the groups in mortality in the intensive care unit (ICU) (23.5 percent in the ranitidine group and 22.9 percent in the sucralfate group) or the duration of the stay in the ICU (median, nine days in both groups). CONCLUSIONS: Among critically ill patients requiring mechanical ventilation, those receiving ranitidine had a significantly lower rate of clinically important gastrointestinal bleeding than those treated with sucralfate. There were no significant differences in the rates of ventilator-associated pneumonia, the duration of the stay in the ICU, or mortality.

Aged↗

Identification of a Theileria annulata antigen expressed in multiple stages of the parasite life cycle.

In order to identify sporozoite surface molecules which may be involved in invasion and could act as potential vaccine candidates, a number of Mabs were raised in mice against T. annulata sporozoites. These were assayed for their ability to block sporozoite invasion of bovine peripheral blood mononuclear (PBM) cells in vitro. One of these, Mab 4B11, was found to neutralize sporozoite invasion to a high degree and to recognize a group of sporozoite antigens on Western blots. A T. annulata lambdagt11 genomic expression library was screened with Mab 4B11 and a positive clone containing a 900-bp insert (KP8) analysed further. Data from Southern and Northern blotting indicated that the gene containing the KP8 sequence, termed sporozoite and macroschizont gene 2 (spm2), was expressed both in T. annulata sporozoites and in later parasite life-cycle stages, macroschizont-infected leucocytes and piroplasms. The KP8 sequence was expressed in E. coli as a fusion protein with glutathione-S-transferase (GST) using the vector pGEX1lambdaT. Bovine antiserum raised against GST-KP8 recognised a single high molecular weight molecule on Western blots corresponding to one of the antigens recognised by Mab 4B11, expressed in sporozoites, macroschizont-infected leucocytes, and piroplasms. While our evidence suggests that the spm2 molecule alone is not responsible for sporozoite neutralization, it is a multistage antigen likely to function both in T. annulata sporozoites and in subsequent parasite life-cycle stages.

Amino Acid Sequence↗

Principles for the safety evaluation of flavouring substances.

This paper reviews efforts by various organizations to develop principles and procedures for the safety evaluation of flavouring substances. Critical factors considered in safety evaluation of these substances include their level of human intake, ease of metabolism to innocuous end-products and the margin of safety between no-observed-effect levels in animal studies and human intakes. These factors form the basis for the principles and criteria laid out in this paper.

Animals↗

An approach to the treatment of psychogenic parasitosis.

BACKGROUND: Patients with psychogenic parasitosis typically seek help from nonpsychiatric physicians and can be difficult and time-consuming to treat. Pimozide has been promoted as the treatment of choice but is not indicated for every patient presenting with this symptom. Our purpose was to develop a realistic treatment protocol for the nonpsychiatric physician faced with these patients. METHODS: Using what is known about this problem through review of the literature and our own experience with 20 patients, a practical treatment strategy is suggested. RESULTS: It is proposed that dermatologists and primary care professionals seeing these patients determine (1) whether or not the patient's belief in infestation is shakable and (2) whether or not the patient is depressed, in order to chose a therapeutic plan. CONCLUSIONS: Dermatologists and psychiatrists can work together to develop treatment protocols that minimize risk and maximize therapy for patients with psychogenic parasitosis.

Adult↗

The impact of rubella immunisation on the incidence of rubella, congenital rubella syndrome and rubella-related terminations of pregnancy in South Australia.

OBJECTIVES: To describe the impact of rubella immunisation on the incidence of rubella, congenital rubella syndrome and rubella-related terminations of pregnancy in South Australia, and to identify factors associated with a re-emerging problem. DESIGN AND METHODS: A population-based descriptive study using data from South Australian notifications of disease, births and terminations of pregnancy, the rubella immunisation programme, antenatal rubella antibody screening and paediatric hospital case records. SETTING: South Australia (population 1.48 million people; 20,000 births per year). MAIN OUTCOME MEASURES: Incidence of rubella (age-sex specific), congenital rubella syndrome and rubella-related terminations of pregnancy; antenatal rubella sero-positive rates; rubella immunisation uptake rates. RESULTS: Rubella notification rates in 1990-1996 were significantly higher for males than females for ages 15-34 years. There were five cases of congenital rubella syndrome notified in 1980-1996 compared with at least 20 confirmed or compatible cases in 1965-1979. Rubella-related terminations of pregnancy are now rare, with the last termination for maternal rubella being in 1993. The antenatal rubella sero-positive rate in 1995 was 96.7%, but was significantly lower among Asian women born overseas (78.6% among those 30 years or older). Vaccination uptake rates in schoolgirls decreased between 1990 and 1994 (91.2% to 86.9%). CONCLUSIONS: Since the introduction of rubella immunisation, the incidence of rubella infection among women of reproductive age, and of rubella-related terminations, has fallen. Congenital rubella syndrome has not been notified since 1990 but its risk persists with a recent increase in rubella notifications, a fall in school immunisation rates, a relatively low antenatal sero-positive rate among older Asian women born overseas and the trend towards giving birth at older ages. Effective immunisation programmes must be maintained, particularly in schools and for young children and migrant women.

Abortion, Induced↗

Calcium- and hydroxyapatite-binding properties of glucuronic acid-rich and iduronic acid-rich glycosaminoglycans and proteoglycans.

This study describes the interaction of a small chondroitin sulphate proteoglycan and the glycosaminoglycans chondroitin 4-sulphate, dermatan sulphate and heparan sulphate with hydroxyapatite. All macromolecules possessed a high affinity, with the iduronic acid-rich dermatan sulphate and heparan sulphate displaying higher adsorption maxima than the glucuronic acid-rich chondroitin 4-sulphate. At similar concentrations, dermatan sulphate produced a 30% inhibition of hydroxyapatite-induced crystal growth, whilst chondroitin 4-sulphate yielded 50% inhibition. Estimation of the calcium binding capacity of these glycosaminoglycans using equilibrium dialysis indicated that chondroitin 4-sulphate bound five times more calcium than dermatan sulphate at a calcium concentration similar to that of serum. The data indicate a possible important role for chondroitin 4-sulphate in dentinogenesis where it is the dominant glycosaminoglycan, since it could act as a capture point for calcium ions during mineralisation, with the leucine-rich domain of its parent proteoglycan acting as anchor points to type I collagen.

Adsorption↗

Remifentanil and propofol total intravenous anaesthesia for thymectomy in myasthenia gravis.

We report a case of trans-sternal thymectomy for myasthenia gravis using a non relaxant, total intravenous technique with propofol and remifentanil. This afforded excellent control of heart rate and pressor responses during surgery while allowing early return of spontaneous ventilation and extubation within nine minutes of termination of anaesthesia. Advantages and disadvantages of this approach versus relaxant and volatile techniques are discussed with particular reference to preservation of neuromuscular function.

Adolescent↗

The measurement of intervention effects in developmental phonological disorders.

The effectiveness of speech and language therapy for developmental phonological disorders has typically been measured in terms of the diminution of the application of phonological processes. Often substantial amounts of intervention and time may be needed to show up such changes. Shorter and more clinically realistic intervention regimes can result in small but significant changes in speech production which represent positive developments in the phonological system. In order to measure progress in this sort of therapy a sensitive instrument of measurement is required. In this paper we describe a research measurement tool, the probe scoring system, which was designed to detect small changes in the child's phonological system following therapy and contrast it to some of the instruments selected for use in other efficacy studies. The potential for wider clinical application is also considered.

Child↗

Systolic and diastolic effects of variable atrioventricular delay in patients with complete heart block and normal ventricular function.

This study was designed to demonstrate the effects of varying the atrioventricular delay (AVD) on ventricular diastolic filling dynamics and the resultant stroke volume in patients with complete heart block and normal cardiac function. We studied 7 patients with normal cardiac function in whom a dual chamber pacemaker had been implanted because of complete heart block. Doppler and M-mode echocardiography was performed at 70, 100, 140, 180, and 220 ms, AVD with the device in DDD mode at a rate of 80 beats/min. The effects of these variable intervals on the contribution of the E and A waveform to the diastolic filling, on the stroke volume, and on the systolic intervals were evaluated. Optimization of this interval, with a 19% increase in stroke volume was achieved in the group of patients at an AVD of 140 ms. When considered individually, the AVD associated with the largest stroke volume, was 100 ms in 2 patients and 140 ms in the remaining 5. At this individual optimal AVD the ventricular septal contraction occurred 31 +/- 14 ms, before the end of the transmitral flow. The optimal AVD is, therefore, the one which synchronizes the ventricular and atrial systole so that the first ventricular septal contraction occurs after the peak of the A wave, just before the end of the transmitral flow. Because of the different functional cardiovascular status of the single patient, this parameter should be individualized; this can be clinically important as it may lead, in this patient population, to an improvement of the stroke volume up to 42%.

Adult↗

Concurrent outbreaks of Salmonella Typhimurium in South Australia.

The Communicable Disease Control Branch of the South Australian Health Commission received 45 laboratory notifications of Salmonella between 23 December 1996 and 17 January 1997. A rapid screening test, undertaken by the Institute of Medical and Veterinary Sciences, Adelaide, was the first indication that this was more than one outbreak, prompting the establishment of separate investigations. Three Salmonella Typhimurium (S. Typhimurium) phage types were subsequently identified. Investigations are continuing into an outbreak of S. Typhimurium phage type (PT) 64, while investigations failed to identify any association between four cases of PT 44. As of 12 February 1997, 71 notifications had been confirmed as S. Typhimurium PT 135. Epidemiological investigations found this outbreak was associated with consumption of bread rolls with a meat filling distributed through local Asian grocery stores from a home-based manufacturer. The product was voluntarily withdrawn and there have been no new cases of PT 135.

Bacterial Typing Techniques↗

Postoperative elevation of creatine kinase (CK-MB): does it contribute to diagnosis of myocardial infarction?

PURPOSE: This retrospective study sought to determine the benefit of measurement of changes in plasma creatine kinase-myocardial band (CK-MB) levels in elective postoperative high risk surgical patients beyond that obtained from the surface 12 lead ECG. METHODS: The charts of 111 patients admitted to the surgical intensive care unit (SICU) of a tertiary level university teaching hospital were reviewed. They were screened using predetermined definitions of myocardial infarction (MI) (as reflected by changes in the 12 lead surface ECG (Minnesota code) or elevations in CK-MB) for complications such as pulmonary oedema, congestive heart failure, arrhythmias, or cardiogenic shock. Four groups were identified based on changes in the ECG indicative of MI (Present-ECG+ or Absent-ECG-) and elevations of CK-MB (Present-CKMB+ or Absent-CKMB-) and compared for the incidence of complications. RESULTS: No patient with ECG- findings had a complication. Fifteen patients with ECG+ findings were identified and all had complications. Fourteen of these patients had CKMB+ results. In contrast, 29 patients with CKMB+ results alone (i.e., ECG-) had no complications. CONCLUSION: Clinically important (i.e., requiring therapeutic intervention) postoperative myocardial infarction was detected by ECG changes. The benefit of determining changes in CK-MB was minimal from a therapeutic perspective.

Adult↗