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Biomedical subjects

A Nichols

Publications and source records attributed to A Nichols.

At least 55 records · Page 3Linked to original sources
PubMed1994

Ablation of islet endocrine cells by targeted expression of hormone-promoter-driven toxigenes.

Ontogenic relationships between the different types of endocrine cells in the islets of Langerhans were explored by generating transgenic mouse embryos in which cells transcribing the glucagon, insulin, or pancreatic polypeptide genes were destroyed through the promoter-targeted expression of the diphtheria toxin A chain. Embryos lacking glucagon- or insulin-containing cells did not exhibit alterations in the development of the nontargeted islet cell types, whereas embryos lacking pancreatic polypeptide gene-expressing cells also lacked pancreatic insulin- and somatostatin-containing cells. These results show that neither glucagon nor insulin gene-expressing cells are essential for the differentiation of the other islet endocrine-cell types. These results also suggest that pancreatic polypeptide gene-expressing cells are indispensable for the differentiation of islet beta and delta cells because the former produce a necessary paracrine or endocrine factor and/or operate through a cell-lineage relationship.

Animals↗
PubMed1994

Training for rural general practice.

OBJECTIVE: To identify requirements for vocational training and continuing education programs in rural general practice. DESIGN: A questionnaire was sent to all 487 rural doctors and 140 metropolitan and 140 provincial city general practitioners (GPs) in Queensland. A sample of medical educators, health professional and consumer representatives and rural doctors was also interviewed. Responses were compared by geographical area, practice characteristics and level of postgraduate training. RESULTS: There are significant differences between rural and urban practice profiles. Rural doctors have to practise a range of clinical skills in an environment with restricted access to health professional support, although the need for advanced training in procedural or other skills depends on the type of rural practice. Rural and urban doctors want more influence in determining continuing medical education (CME) programs. Interactive learning methods were rated as the most effective education methods by both rural and urban GPs. Rural doctors were less likely to consider that they spent enough time on CME. CONCLUSION: Vocational training programs should accommodate various rural career objectives, including those requiring advanced levels of procedural work. There is a significant unmet demand for CME tailored to the needs of individual doctors, both rural and urban, but distance and isolation may make this more critical in rural practice. These issues need to be addressed as training opportunities can contribute to improved retention of the rural medical workforce.

Australia↗
PubMed1994

The value of hysteroscopy.

This study is a report of the first 200 diagnostic hysteroscopic procedures undertaken on 191 patients, in the GynaecoIogical Outpatient Department of a busy general hospital. One hundred and sixty examinations were conducted successfully. The study demonstrated that outpatient hysteroscopy is valuable to the patient by avoiding hospitalization and general anaesthesia, valuable to the nursing and medical staff by increasing job satisfaction and valuable to the hospital by reducing expensive inpatient costs. The potential reduction to the Australian national health budget, by the adoption of outpatient hysteroscopy instead of inpatient dilatation of the cervix and curettage, is calculated to be in excess of $60,000,000 per annum.

Cost-Benefit Analysis↗
PubMed1994

A sampling framework for rural and remote doctors.

A pilot survey by telephone interview, followed by a questionnaire of all rural doctors identified in Queensland, was used develop both a definition of rural practice that distinguishes it from urban general practice and a classification of rural and remote practice which assists in sampling of rural doctors. Questionnaire responses in specific geographic areas were compared using chi-square and Mantel-Haenszel chi-square tests. Several factors were found to differentiate rural from urban general practice consistently, thereby enabling a functional definition of rural practice to be developed. Within the broad group of rural doctors, gradients in practice characteristics were found to differentiate doctors in larger rural centres from those in smaller, more remote communities. These gradients were related to the distance and time of travel from support services. They formed the basis of a complex classification of rural and remote general practice. This functional definition of rural and remote medical practice should be considered by researchers of rural medicine issues when sampling rural and remote doctors. The strategies used in this study could be adapted for use in considering practice characteristics of other rural health professions.

Humans↗
PubMed1994

TGF-beta 1 influences the relative development of the exocrine and endocrine pancreas in vitro.

Pancreatic rudiments from E12.5 mouse embryos undergo extensive development and differentiation when cultured in three-dimensional gels of extracellular matrix proteins for up to 12 days. Whereas collagen gels promote the formation of numerous exocrine acini and relatively small clusters of endocrine cells, in basement membrane (EHS) matrices the development of endocrine cells is dramatically favoured over that of acinar tissue. Buds embedded in a collagen gel contiguous to an EHS gel also fail to develop acini, suggesting the involvement of diffusible factor(s). Addition of cytokines to cultures of pancreatic buds in collagen gels modifies the relative proportions of the epithelial components of the gland. In the presence of EGF the proportion of the tissue occupied by ducts overrides that of acinar structures, whereas the endocrine portion of the tissue is not significantly modified. TGF-beta 1 partially mimicks the effect of EHS matrix in inhibiting the development of acinar tissue without decreasing the amount of ducts and mesenchyme; TGF-beta 1 also promotes the development of endocrine cells, in particular of insulin-containing beta cells and of cells expressing genes of the PP-fold family. These results show that cytokines can modulate the development of the pancreas and suggest a role for TGF-beta 1 in regulating the balance between the acinar and endocrine portions of the gland in vivo. More generally, they are compatible with the notion that, during organogenesis, cytokines act as paracrine factors responsible for the development and maintenance of appropriate proportions of different tissue constituents.

Animals↗
PubMed1993

Modulation of vitronectin receptor-mediated osteoclast adhesion by Arg-Gly-Asp peptide analogs: a structure-function analysis.

This study details the investigation of induction of retractile shape change in the osteoclast through inhibition of adhesion between osteoclasts and matrix with (1) peptide analogs bearing an Arg-Gly-Asp (RGD) sequence, (2) antibodies to the integrin alpha V beta 3 vitronectin receptor, and (3) the RGD-containing snake venom peptide echistatin. Osteoclast retraction on dentin has been demonstrated for GRGDSP peptide, in contrast to the inactivity of the analog containing the conservative RGE sequence modification. An osteoclast adhesion assay employing rat or chick bone cells and serum-coated glass coverslips as substrate was developed for routine evaluation of inhibition of adhesion. Antibodies F4 and F11 to the beta 3 chain of rat vitronectin receptor were effective at submicromolar concentrations in rat osteoclasts (IC50 0.29 and 0.05 microM, respectively), whereas MAb 23C6 to human/chick vitronectin receptor was somewhat less effective against chick osteoclasts (IC50 1.6 microM). A rank order of RGD analog activity (mean IC50, microM) in the serum-coated glass adhesion assay was derived for the linear peptides GRGDSP (201 microM), GRGDTP (180 microM), Ac-RGDS-NH2 (84 microM), Ac-RGDV-NH2 (68 microM), RGDV (43 microM), GRGDS (38 microM), and RGDS (26 microM). The two most potent short peptides were the cyclic analog SK&F 106760 Ac-S,S-cyclo-(Cys-(N alpha Me)Arg-Gly-Asp-Pen)-NH2 (IC50 7.0 microM), and the Telios peptide H-Gly-S,S-cyclo-(Pen-Gly-Arg-Gly-Asp-Ser-Pro-Cys)-Ala-OH (IC50 6.6 microM). The snake venom peptide echistatin was the most potent substance evaluated in the serum-coated glass assay (IC50 0.78 nM) employing either rat or chick osteoclasts.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1993

Training curricula in surgery, anaesthesia and obstetrics for rural GPs.

These three curricula for advanced training practice represent the first significant progress towards the development of specific vocational training for rural general practice. They have been created by rural doctors in consultation with their rural specialist colleagues and with the support of the learned colleges and educationists. Dedicated and enthusiastic project management with a clear understanding of the issues and context of rural general practice was also an essential element for the success of this project. Following implementation and evaluation of the curricula in accredited training posts throughout 1993 and 1994, opportunities will arise to develop further curricula in other medical disciplines and to use the methodology developed for other health fields both in Australia and overseas.

Anesthesiology↗
PubMed1992

Investigation of conformational specificity at GPIIb/IIIa: evaluation of conformationally constrained RGD peptides.

RGD-containing proteins and peptides are known to bind to the platelet GPIIb/IIIa receptor and inhibit platelet aggregation. That a conformational component to the specificity exists is suggested by significantly lower activity of linear RGD analogs relative to closely related cyclic peptides and small proteins containing the RGD sequence. Recently, conformations for a suite of RGD containing cyclic peptides have been defined by NMR-based methods and, for one molecule, by X-ray diffraction. We report here the NMR-based conformational analysis of an additional cyclic peptide, cyclo(Pro-Arg-Gly-Asp-D-Pro-Gly), and compare the conformational variations in the suite of peptides and related analogs. Biological activity data for these peptides shows a preference of the platelet GPIIb/IIIa receptor for one conformation of the RGD sequence, but suggests its ability to bind a second, distinct conformation.

Amino Acid Sequence↗
PubMed1992

Analysis of strike-through contamination in saturated sterile dressings.

The method of saturating gauze sponges directly in their wrapper was tested to determine strike-through contamination. Contamination occurred in 100% of the uncoated-wrapper sponges, regardless of exposure to Staphylococcus epidermidis or Escherichia coli. Among coated-wrapper sponges, 80% exposed to Staphylococcus epidermidis and 20% exposed to Escherichia coli demonstrated strike-through contamination. Coated-wrapper sponges had a significantly lower rate of contamination than uncoated-wrapper sponges when exposed to Escherichia coli. Occurrence of contamination of all sponges was significantly higher from Staphylococcus epidermidis. The findings render the popular practice of saturating gauze sponges in their wrapper unacceptable.

Bandages↗
PubMed1991

High-performance liquid chromatographic analysis of the (cyanoaquo) stereoisomers of several putative vitamin B12 precursors.

The cyanoaquo and aquocyano stereoisomers of several putative vitamin B12 precursors are reversibly formed and can be separated using analytical high-performance liquid chromatographic methods. The behavior of these stereoisomers varies somewhat depending on the type of column used and the chromatographic conditions employed. Both reversed-phase and ion-exchange columns can be used to observe the reversible formation and separation of the stereoisomers of (H2O,CN)cobyric acid, cobinamide and the cobinic acid pentaamide-1, -2 and -3 structural isomers. The greatest differences in retention times are seen when the pH of the eluting buffer is less than 4.0 and the buffer contains no KCN.

Chromatography, High Pressure Liquid↗
PubMed1991

Separation and study of corrinoid cobalt-ligand isomers by high-performance liquid chromatography.

Vitamin B12 belongs to a group of complex organo-cobalt compounds, the corrinoids. "Complete" corrinoids, such as B12, contain a nucleotide as the cobalt alpha-(lower)ligand. This nucleotide is also connected to the periphery of the corrin ring. The "incomplete" corrinoids, in contrast, contain simple cobalt alpha-ligands, such as water or cyanide. Using analytical reversed-phase and anion-exchange high-performance liquid chromatography (HPLC), we have been able to study the behavior of several aquocyano-"incomplete" corrinoids: three isomeric cobinic acid pentaamides, cobinamide, and cobyric acid, all of which exist as thermally unstable isomers, which separate during HPLC. All but one of these corrinoids gave isomer mixtures of 1:1, the exception giving mixtures of 2:1 to 3:1. The separated stereoisomers had different retention times and were collected from analytical columns for further study.

Chromatography, High Pressure Liquid↗
PubMed1991

The preparation and characterization of the diaquo- forms of several incomplete corrinoids: cobyric acid, cobinamide, and three isomeric cobinic acid pentaamides.

The preparation of the diaquo- forms of the incomplete corrinoids, cobyric acid, cobinamide, and three isomeric cobinic acid pentaamides, from the corresponding aquocyanocorrinoids has been accomplished. The compounds were characterized by electronic absorption spectra, pka values, and HPLC/TLC behavior. Upon titration, the acids exhibited three pKa values, but only the pKa corresponding to the carboxylic acid involved the transfer of a full equivalent of protons. In addition, the progress of diaquo- to dihydroxo-titration, and the spectrum of the final products indicated a complex process. These diaquocorrinoids appear to be unstable, and should be stored in solution, frozen, under an inert atmosphere.

Chromatography, High Pressure Liquid↗
PubMed1991

Patient and staff acceptance of robotic technology in occupational therapy: a pilot study.

While the majority of applications of robotics in the field of rehabilitation focus on the development of smart aids for people without upper extremity function, there is also potential for the robot as a therapy "aide." We designed, built, and pilot-tested hardware and software that used a robot to provide muscle reeducation movement patterns after stroke. This is a report on a field trial, in which 11 occupational therapists used the system with 22 patients; each patient averaged 2.2 sessions. Based on information contained in the system database, a log, patient interviews, and therapist questionnaires, we evaluated safety, system utility, and patient and therapist acceptance. The results suggest that robotic treatment is safe and accepted (if not welcomed) by patients. The therapists expressed a qualified acceptance, suggesting several modifications to increase utility. The potential for the application of robotics in rehabilitation therapy is discussed in light of these findings.

Attitude of Health Personnel↗
PubMed1990

Altered rheological properties of blood following administrations of tissue plasminogen activator and streptokinase in patients with acute myocardial infarction.

Tissue blood flow is determined by rheological properties of blood as well as by vascular resistance. In acute myocardial infarction patients who participated in the TIMI I trial, we compared the effects of recombinant tissue plasminogen activator (rt-PA) and streptokinase (SK) on blood rheological properties and plasma fibrinogen concentration. Blood viscosity was determined by using a coaxial cylinder viscometer at shear rates, gamma, of 0.01-200 sec-1. Red blood cell (RBC) deformability was studied by filtration through polycarbonate microsieves with pore size of 3 and 5 microns. Therapy with rt-PA resulted in slight decreases but statistically significant in blood viscosity from 5.2 +/- 0.5 to 4.9 +/- 0.4 cP (gamma = 52 sec-1), plasma viscosity from 1.36 +/- 0.09 to 1.32 +/- 0.06 cP, and plasma fibrinogen from 0.26 +/- 0.04 to 0.21 +/- 0.03 g/dl. SK therapy resulted in reductions in blood viscosity from 5.1 +/- 0.5 to 4.6 +/- 0.3 cP, plasma viscosity from 1.26 +/- 0.10 to 1.16 +/- 0.03 cP, and fibrinogen from 0.26 +/- 0.06 to 0.10 +/- 0.05 g/dl. Changes observed with SK were significantly greater than those observed with rt-PA (all p less than 0.05), and the differences persisted at 10 days after thrombolytic therapy. RBC deformability was similar in the two groups. The greater reduction of blood viscosity after SK than rt-PA suggests that, for a given degree of arterial patency, myocardial blood flow may be better maintained with SK than rt-PA in patients with acute myocardial infarction.

Blood Proteins↗