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Biomedical subjects

G Roberts

Publications and source records attributed to G Roberts.

At least 127 records · Page 7Linked to original sources

Practice-based training in nurse management development: a case study.

One hundred and twenty nurse managers within the Central Sydney Area Health Service completed a program designed to concurrently strengthen professional skills and management systems. The program was based on functional review of work practices. It required consultation with the unit staff and collaboration with other sections of the organisation in designing and implementing quality improvement projects. The success of the program supports the idea that adult learners benefit from the opportunity to reflect on their experience at work. The program demonstrated that nurse managers will make major contributions to improvements in an organisation when the review process is legitimised, when they can participate in developing a framework for the review, and when organisational support is provided.

Education, Nursing, Continuing↗

An analysis of a melanoma epidemic.

Between 1986 and 1988 the annual incidence of invasive melanoma in the Hunter area of New South Wales, Australia, almost doubled to 52.5 per 100,000 in men and 42.9 per 100,000 in women. These rates have been maintained and are similar to those reported for 1987 in Queensland, Australia, which are the highest in the world. Most of the increase in incidence was in melanomas less than 1.50 mm in thickness, and adults of both sexes and all ages were affected. Thicker melanomas also increased in incidence but only in adults 45 years and older, and mainly in men. An analysis of health insurance data on treatment of skin lesions and data from a histopathology laboratory suggested that diagnosis and treatment of skin lesions generally in the Hunter area had increased almost 2-fold over this period. Advancement of the time of diagnosis and a real increase in incidence were likely explanations for some of the observed trends. Increasing diagnosis of a non-metastasising form of thin melanoma, consequent upon increasing removal of pigmented skin lesions by medical practitioners, may also explain some of the observed increase in the incidence of the disease. This possibility has important implications for proposed population screening programs, and methods are needed to distinguish such lesions, if they exist, from potentially fatal melanoma.

Adult↗

Medical education.

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Education, Medical, Undergraduate↗

Review of research leading to new anti-herpesvirus agents in clinical development: valaciclovir hydrochloride (256U, the L-valyl ester of acyclovir) and 882C, a specific agent for varicella zoster virus.

Research leading to the new anti-herpesvirus compounds discussed here has come from three approaches. The first approach was directed towards improving the bioavailability of acyclovir by examining the potential of a variety of prodrugs, leading to the new compound valaciclovir hydrochloride. The second approach was to examine a large number of 5-substituted pyrimidines for activity against those viruses which were not as potently inhibited by acyclovir as are herpes simplex viruses, i.e., varicella zoster virus (VZV) and human cytomegalovirus (HCMV). This research led to the new chemical entity 882C for VZV. A third approach has been to examine drug combinations with acyclovir. This research led to the compound 348U, an inhibitor of herpes simplex virus ribonucleotide reductase which acts synergistically in combination with acyclovir. This manuscript will focus on the first two approaches leading to new compounds valaciclovir hydrochloride and 882C since Dr. Safrin details such background for 348U/acyclovir. Attempts to improve the bioavailability of acyclovir began a decade ago. Early prodrugs were compounds with alterations in the 6-substituent of the purine ring of acyclovir. The 6-amino congener required the cellular enzyme adenosine deaminase for conversion to acyclovir and the 6-deoxycongener was dependent on cellular xanthine oxidase for conversion. Neither of these prodrugs had a chronic toxicity profile in laboratory animals as good as acyclovir. Efforts were directed towards simpler esters and 18 amino acid esters were made. The pharmacokinetic profile of each prodrug was determined in rats by measuring the recovery of acyclovir in urine after oral dosing.(ABSTRACT TRUNCATED AT 250 WORDS)

Acyclovir↗

A single amino acid substitution abolishes the heterogeneity of chimeric mouse/human (IgG4) antibody.

Human immunoglobulin G4 (IgG4) exists in two molecular forms due to the heterogeneity of the inter-heavy chain disulphide bridges in the hinge region in a proportion of secreted human IgG4. This heterogeneity is only revealed under denaturing, non-reducing conditions in which an HL "half antibody" is detected, a phenomenon not seen in other human IgG isotypes. In native conditions noncovalent interactions hold the antibody together as the H2L2 tetramer. Analysis of the hinge sequences of human IgG heavy chains suggested that the presence of serine at residue 241 might be the cause of this heterogeneity. We therefore changed the serine at 241 to proline (found at that position in IgG1 and IgG2) in a mouse/human chimeric heavy chain. This single residue substitution leads to the production of a homogeneous antibody. Further, the variant IgG4 has significantly extended serum half-life and shows an improved tissue distribution compared to the original chimeric IgG4.

Amino Acid Sequence↗

Mucopolysaccharidosis VII as cause of fetal hydrops in early pregnancy.

We report on fetal hydrops presenting at 18 weeks of gestation and diagnosed as beta-glucuronidase deficiency. The parents were first cousins and there were 2 previous similar fetal deaths. beta-Glucuronidase was absent in cultured fetal fibroblasts and lymphoblasts but was normal in the tested relatives. The activities of other lysosomal enzymes were normal.

Adult↗

Scintigraphic evaluation of tissue viability after gunshot injury in a dog.

Triple-phase bone scintigraphy was used to evaluate tissue viability in the forelimb of a dog after gunshot injury. This technique was reliable, noninvasive, and easily performed. It was used to complement radiography by providing functional, rather than structural, assessment of tissues on the basis of regional vascular patterns. In this dog, vascular impairment caused by trauma appeared as photopenic or "cold" spots during immediate (vascular), soft tissue and bone phases of the scintigraphic study. On the basis of gross morphologic and scintigraphic findings, forelimb amputation was performed.

Amputation, Surgical↗

Development of an ovine collagen-based composite biosynthetic vascular prosthesis.

The search for an ideal vascular prosthesis to bypass peripheral vascular obstructive lesions is necessary where autologous tissues are either unavailable or unsuitable. This paper will outline the development and use of vascular conduits, principally of biological origin. The clinical benefits and limitations of these materials are discussed. The development of a composite biosynthetic prosthesis (Omniflow¿) is described, together with the testing methods used to determine and predict its suitability for use as an arterial substitute. The ovine biosynthetic prosthesis has significantly improved surface and mural properties over previous attempts at producing prostheses for vascular reconstruction. Immunohistological studies on samples recovered from dogs after 4 years show that the original ovine collagen is still present after 4 years, and it is further augmented by the deposition of new, host-derived connective tissue.

Animals↗

The Worcester Development Project.

"The philosophy of Community Care has resulted in the closure of several mental hospitals in this country. The ethos of the Worcester Development Project saw the closure of St Wulstan's and Powick Hospitals, and their replacement by a community-based service. This paper briefly describes the outcome of a three-year retrospective study completed in 1988 following the closure of both hospitals. The findings provide a comparison of the two hospitals, including details of the destination of all the patients. It is suggested that the term 'hospital replacement' might be preferable to 'hospital closure'." "The Worcester Development Project began in 1968 when the Department of Health and Social Security brought together the Worcester and Kidderminster Hospital Management Committee and the County Council in a co-ordinated joint planning venture. Powick Hospital was chosen as the location for testing the hypothesis that closing a mental hospital and replacing it with general hospital psychiatric units, supported by a variety of community facilities, would provide a more economical and better service. This paper describes the outcome of this unique opportunity to study the problems involved in closing a mental hospital and its replacement with other facilities."

Activities of Daily Living↗

The origins of delusion.

Although delusion remains one of the basic problems in psychopathology, attempts to understand its pathogenesis have been dominated by unsubstantiated speculation. Previous psychodynamic formulations have recently given way to increasing interest in measurement, and testing of models derived from cognitive psychology. However, the formation, elaboration, and persistence of delusional beliefs may be an expression of the convergence of numerous causal influences, each exerting an effect at a different stage in the evolution of the belief. This review takes a structured overview of the literature, placing the numerous part theories and scant experimental findings within a general model of delusional development. It argues for a return to systematic research on symptoms rather than complex diagnostic formulations to facilitate better understanding of the development of delusional disorders and stimulate further interest in therapeutic intervention.

Delusions↗

Some properties of the H-ATPase activity present in root plasmalemma of Avena sativa L. Two different enzymes or one enzyme with two ATP sites?

The effects of Mg2+, K+ and ATP on a H-ATPase activity from a native plasmalemma fraction of oat roots were explored at 20 degrees C and pH 6.5. In the presence of 3 mM ATP and no K+, H-ATPase activity vs. [Mg2+] approached a monotonic activation but it became biphasic, with a decline above 3 mM Mg2+, in the presence of 20 mM K+. Mg2+ inhibition occurred also in K-free solutions when [ATP] was lowered to 0.05 mM. Also, an apparent monotonic H-ATPase activation by [K+] at 3.0 mM ATP was transformed in biphasic (inhibition by high [K+]) when [ATP] was reduced to 0.05 mM. The best fits of the ATP stimulation curves of hydrolysis satisfied the sum of two Michaelian functions where that with higher affinity had lower Vmx. Taking into consideration all conditions of activity assay, the high-affinity component (1) had a Km about 11-16 microM and a Vmx around 0.14-0.28 mumol Pi/mg per min whereas that with lower affinity (2) had a Km of 220-540 microM and a Vmx of 0.5-1.0 mumol Pi/mg per min. Km2 was markedly affected by the [K+] and [Mg2+]; at optimal concentrations of these cations (1 mM Mg2+ and 10 mM K+) it had a value of 235 +/- 24 microM which was increased to 540 +/- 35 microM at 20 mM [Mg2+] and 60 mM [K+]. In addition, Vmx1 was reduced to about a half when the concentrations of Mg2+ and K+ were increased to inhibitory levels. These results could be explained by the existence of two different enzymes or one enzyme with two ATP sites. In the second case, we could not tell at this stage if both are catalytic or one is regulatory.

Adenosine Triphosphatases↗

The effect of indomethacin on basal and saline-stimulated plasma atrial natriuretic factor levels in normal man.

Surprisingly inappropriately high levels of plasma atrial natriuretic factor (ANF) in subjects with Bartter's syndrome are lowered by indomethacin therapy. Indomethacin in normal man causes sodium retention. One might therefore expect plasma ANF to increase in subjects taking indomethacin as a secondary phenomenon. On the other hand a decrease of plasma ANF in normal man similar to that reported in Bartter's subjects may explain the sodium retention caused by the drug in normals. We have studied plasma ANF before and during a two litre, four hour normal saline infusion in eight healthy male subjects both before and following five days of oral indomethacin. Plasma ANF basally was 4.2 +/- 0.9 pmol/l (mean +/- SEM) on no drug and 5.2 +/- 0.6 pmol/l on indomethacin (NS). It increased in response to saline in both studies (7.8 +/- 1.5 pmol/l after two litres of saline on control day; 10.6 +/- 1.5 pmol/l on the drug at the equivalent time, both p less than 0.05 vs basal value). Overall response to saline as assessed by the area under the curve above the basal value of hourly measurements, was not different in the two studies. Basal serum aldosterone and plasma renin activity were reduced by indomethacin. Urinary sodium excretion was not different between groups during the 12 hours before, four hours during and eight hours after the infusion. We have shown that indomethacin does not alter basal or saline stimulated plasma ANF in normal man, a finding in contrast to that reported in subjects with Bartter's syndrome. The sodium retention caused by indomethacin in normal man is not therefore due to a decrease of plasma ANF.

Administration, Oral↗

Serum keratan sulphate level following chemonucleolysis.

In chemonucleolysis, accuracy of injection can be in doubt if the patient fails to respond. Discography preceding chemonucleolysis is associated with increased neurologic complications. Biplane fluoroscopy may fail to provide a clear picture on many occasions. The serum keratan sulphate levels were estimated in patients undergoing chemonucleolysis to ascertain if this could be used as a biochemical indicator to confirm accurate needle placement and to predict outcome. Serum keratan sulphate levels rose significantly following chemonucleolysis during the first 3 days (P less than 0.01). The rise was not significantly different, however, in patients who had improvement in their leg pain from those who did not improve (P = 0.35). Serum keratan sulphate level estimation before chemonucleolysis and at 24 or 48 hours following the procedure can be used to confirm accuracy of needle placement, but the rise in keratan sulphate is not predictive of the clinical outcome of the procedure.

Adult↗

Basal and stimulated plasma atrial natriuretic factor in patients with type 1 diabetes with and without nephropathy.

Hypertension is linked to the development of nephropathy in Type 1 diabetes. Total exchangeable sodium is elevated in patients with Type 1 diabetes in good metabolic control, and correlates with blood pressure. Atrial natriuretic factor has been shown to have effects on sodium and blood pressure homeostasis in man. Basal and NaCl-stimulated plasma atrial natriuretic factor was therefore studied in 33 patients with Type 1 diabetes. Seventeen had no evidence of nephropathy, 11 had incipient nephropathy (albumin excretion rate 20-199 micrograms min-1) and five had overt nephropathy. Seventeen age- and sex-matched normal control subjects were also studied. Subjects fasted from 2200 h, rose at 0745 h and remained ambulant until 0945 h. After 15 min supine, 2 l 0.15 mmol l-1 NaCl was infused over 4 h. Basal erect (0945 h) plasma atrial natriuretic factor was 4.2 +/- 0.5, 3.5 +/- 0.4, 2.5 +/- 0.2, and 2.5 +/- 0.3 pmol l-1 in the control, non-nephropathic, incipient-nephropathic, and overt nephropathic diabetic groups, respectively (all NS). Levels in all groups increased in response to NaCl infusion, and the responses were not different between groups. Urinary sodium excretion for 12 h before NaCl infusion was not different between groups, but during the 12 h after the start of the infusion was significantly (p less than 0.05) less in the Type 1 diabetic group without nephropathy than in the control group. These results suggest that atrial natriuretic factor does not play a major role in the development of changes in sodium balance which are associated with Type 1 diabetes and nephropathy.

Adult↗

Basal and saline-stimulated plasma atrial natriuretic hormone in Cushing's syndrome.

The pathogenesis of hypertension associated with Cushing's syndrome is incompletely understood. We have studied basal and saline-stimulated levels of plasma atrial natriuretic hormone in 10 subjects with active Cushing's syndrome (8 F: 2 M), aged 43 +/- 4 years (mean +/- SEM). Ten age- and sex-matched normal control subjects were also studied. Subjects fasted from 22.00 h, rose at 07.45 h, and remained ambulant until 09.45 h when blood was taken for plasma ANH, plasma renin activity and serum aldosterone. Subjects then rested supine until 10.00 h when blood was again taken, and blood pressure recorded. Then, while subjects remained supine, 21 of 0.9% NaCl were infused between 10.00 and 14.00 h. Blood was taken hourly. Basal plasma ANH was 8.0 +/- 0.9 pmol/l in Cushing's subjects and 6.9 +/- 2.5 pmol/l in controls. Levels increased in response to saline in both groups, and became significantly higher in the group of patients with Cushing's syndrome (14.00 h level 21.3 +/- 3.9 vs 10.4 +/- 1.9 pmol/l; p less than 0.05). Serum aldosterone and plasma renin activity were not different between groups. Mean blood pressure was higher in patients (114 +/- 4 vs 91 +/- 7 mmHg; p less than 0.05). Urinary sodium excretion was not different between groups before saline, but during the four hours of saline was higher in Cushing's subjects (133 +/- 12 vs 67 +/- 11 mmols; N = 6; p less than 0.05). Our results suggest that during salt loading the exaggerated natriuresis seen in the Cushing's group may have been caused by ANH.

Adult↗

Structural stability of long-term implants of a collagen-based vascular prosthesis.

Samples of an ovine collagen-polyester composite device suitable for peripheral revascularization, the Omniflow Vascular Prosthesis, have been retrieved for morphological and immunohistological analyses during and up to 4 years of implantation in a dog aortoiliac by-pass model. At the various sample times, the prosthesis explants were shown to retain their structural integrity, with no aneurysm formation and with little thrombus accumulation. Immunohistological studies on samples of the prosthesis showed that the original ovine collagen was still present after 4 years, and that there had been augmentation by the deposition of new, host-derived connective tissue.

Animals↗