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Biomedical subjects

J Walsh

Publications and source records attributed to J Walsh.

At least 19 recordsLinked to original sources

Regional variation in coronary mortality within Tasmania.

OBJECTIVE: To measure regional rates of mortality from ischaemic heart disease (IHD) within Tasmania and to analyse factors associated with regional differences. DESIGN: Descriptive epidemiological study. SETTING: Community-based study. SUBJECTS: Male residents of Tasmania aged 30-69 years dying from IHD between 1986 and 1989. MAIN OUTCOME MEASURES: Coronary death as coded by the Australian Bureau of Statistics and place of death validated by hospital and community data. RESULTS: This study identifies substantial differences in coronary death rates among the three Health Regions of Tasmania. These differences are real and are not caused by variations in diagnostic or coding practices between regions. The two northern Health Regions, which represent approximately 52% of the total population, account for 98% of the excess mortality from IHD in Tasmania compared with the national rate. More detailed analysis of these differences suggests that variation in the number of deaths occurring in hospital contributes significantly to the regional differences in death rate from IHD. CONCLUSION: Rates of coronary mortality in Tasmania have been significantly higher than in all other Australian States for much of the past decade because of a higher death rate within the population of the northern half of Tasmania. Differences in mortality rates between regions in Tasmania provide a focus for further study into the causes of the unacceptably high rates of death from IHD in Tasmania and underline the need for the funding of a coronary register in Tasmania.

Adult

Colour Doppler ultrasonography studies of benign and malignant breast lesions.

Colour Doppler scanning was carried out on 53 patients with solid, discrete breast masses. Twenty-five of 32 breast cancers and none of 21 benign lesions gave a positive scan, giving a sensitivity of 78 per cent for association with malignancy, a specificity of 100 per cent and a positive predictive value of 100 per cent. Tumours less than 1 cm in diameter and invasive lobular cancers were least likely to give a positive scan. Axillary node scans were performed in 31 of 32 patients with breast cancer with 29 undergoing an axillary staging procedure. Nine patients had a positive axillary scan and all nine had involved axillary nodes. Three patients had involved axillary nodes, but a negative axillary scan. The sensitivity of colour Doppler scanning for axillary node involvement was 75 per cent, with a specificity of 100 per cent and a positive predictive value of 100 per cent.

Adolescent

Methods of psychoeducational program evaluation in mental health settings.

Psychoeducational programs for families of the mentally ill became widespread during the 1980s as a means of providing a forum for the relevant education and mutual support of participants. While these programs are thought to be extremely useful as interventions, very little emphasis has been placed on evaluation as a means of demonstrating their effectiveness in achieving goals. There is a possibility, then, that psychoeducation will continue to flourish with little direct evidence of positive outcomes for its family participants. This article consists of a literature review of existing methods of psychoeducational program evaluation, both quantitative and qualitative, all of which may be applicable in certain circumstances. The process by which an evaluation instrument was developed for a program with families of the mentally ill is then presented in some detail.

Family

Modulation of tissue factor on human monocytes by cisplatin and adriamycin.

Coagulation disorders have been associated with the use of chemotherapeutic drugs. Pharmacological doses of cisplatin and adriamycin directly induced low levels of procoagulant on normal human blood monocytes and on a human myelomonocytic cell line, RC2a. Activity was maximal after 24 h and was not due to cell lysis as increasing drug doses which decreased cell viability were less effective. Procoagulant induction was markedly enhanced in the presence of bacterial lipopolysaccharide (LPS), with as little as 10-100 pg/ml LPS potentiating the cisplatin response by 2-5-fold and more than doubling the adriamycin response. Greater than 90% of the procoagulant activity was membrane-bound tissue factor as indicated by the factor VII-dependent generation of factor Xa by viable cells and by the neutralization of this activity by a monoclonal antibody to tissue factor. Tissue factor antigen was measured simultaneously by immunohistochemical staining and by cell ELISA. Blood monocytes activated with LPS expressed high levels of tissue factor antigen; by contrast, adriamycin and cisplatin did not appear to induce antigen expression, but to enhance the specific activity of that already present. Results suggest that membrane alterations which occur following treatment with DNA/RNA intercalating drugs, may result in a highly active form of monocyte/macrophage tissue factor which may contribute to the complications caused by activated coagulation. Secondary Gram-negative infection or cytokines released by an active immune response to a tumour may contribute to the procoagulant potential of these cytotoxic drugs.

Cisplatin

Prophylactic cerclage: a method of preventing femur fracture in uncemented total hip arthroplasty.

The incidence of femur fracture in non-cemented hip arthroplasty has been reported to be between 4.1% and 27.8%. To quantitate the hoop stress generated during insertion of a femoral broach in total hip arthroplasty and determine the effect of cerclage with both braided cable and wire, we harvested 14 pairs of embalmed cadaver femurs. These were reamed and broached to duplicate the surgical technique of inserting a straight non-cemented femoral component. Group one consisted of eight matched cadaver femurs which were tested using a single 2.0 mm chrome-cobalt cable placed around the calcar of one femur, with the other serving as a control. Group two consisted of five matched cadaver femurs which were tested using a single 18 gauge cerclage wire in the same manner. In group one, the femurs serving as controls were found to have a mean microstrain of (1425.00 +/- 1180.19). The eight femurs tested with a 2 mm cable were determined to have a mean microstrain of (4179 +/- 2853.89). In group two, the femurs serving as controls were found to have a mean microstrain of (962.60 +/- 956.78). The five femurs in group two tested with a cerclage wire were determined to have a mean microstrain of (1112.00 +/- 975.66). Using a paired t-test, statistical significance was achieved with a confidence level of P less than or equal to .01 in group one. Prophylactic wiring of the proximal femur with 2 mm cable increases the hoop stress resistance and, therefore, should decrease the incidence of intraoperative femur fractures in uncemented total hip arthroplasty.

Bone Cements

Non-haematological toxicity limiting the application of sequential high dose chemotherapy in patients with advanced breast cancer.

A programme of repeated high dose chemotherapy for advanced breast cancer was developed using (1) cyclophosphamide 4 g/m2 followed by autologous peripheral blood stem cell (PBSC) collection; (2) three cycles of conventional dose chemotherapy; (3) high dose cyclophosphamide, cisplatin, and carmustine with PBSC rescue; and (4) high dose etoposide and melphalan with PBSC rescue. Fifteen eligible patients had advanced poor prognosis breast cancer either at initial diagnosis (one patient) or at relapse (14 patients). During the course of the protocol, there were three treatment related deaths, two patient withdrawals due to debilitating toxicity, five patient withdrawals due to disease progression, and one patient withdrawal due to inadequate collection of PBSC. The remaining four patients did not complete the planned protocol as the programme was terminated because of the unacceptable morbidity and mortality. They were treated with an alternative high dose chemotherapy protocol which was well tolerated. This study highlights the significant problems associated with a complex sequential high dose chemotherapy regimen. Cyclophosphamide mobilized PBSC infused following high dose chemotherapy enables rapid haematological recovery. However the non-haematological toxicity following high dose chemotherapy regimens is often severe and may limit the application of certain sequential high dose chemotherapy combinations in patients with breast cancer.

Adult

Moving Out Services for Education and Support (MOSES): a model program for individuals with spinal cord injury.

A comprehensive educational, social, and community integrated program for individuals with spinal cord injury (SCI) was established at Mount Sinai Medical Center. The need for this program was evident from patients' responses to mailed questionnaires and staff's direct observations of the difficulties encountered by SCI patients when they left the hospital's protected environment and began to cope with living in their communities. The program, Moving Out Services for Education and Support (MOSES), provides relevant information and support to individuals with spinal cord injury as they make the transition from patient to community member. The goal of the program is to foster independence and initiative and to develop leadership skills which enhance successful community reintegration. This article describes the program development, content and training requirements for implementation of these services.

Activities of Daily Living

Comparison of independent aura, ictal and interictal cerebral perfusion.

Technetium-HMPAO cerebral SPECT was performed interictally, immediately after an independent aura and ictally in a patient with complex partial seizures. Interictally there was a left inferior frontoparietal region of decreased perfusion. Ictally there were a number of foci of increased perfusion. The aura study showed focal hyperperfusion in the left frontal region and decreased perfusion in the adjacent cortex posteriorly, suggesting a zone of suppression. This may be the cause or effect of the nonprogression of the aura. The case raises the possibility that cerebral perfusion studies performed immediately after independent auras may localize seizure foci if ictal studies are nonfocal.

Adult

TraT: a powerful carrier molecule for the stimulation of immune responses to protein and peptide antigens.

A number of integral membrane proteins (Imps) isolated from Escherichia coli have been examined for their ability to generate serum antibody responses in the absence of adjuvant. These proteins were found to stimulate high titers of serum antibody when injected into rabbits or mice in saline. The antibody titers elicited were not significantly increased by the addition of a powerful adjuvant such as IFA. Covalent conjugation of BSA, of the DNP group, and of a peptide Ag from Plasmodium falciparum to these protein carriers resulted in a significant enhancement of the immune response to the conjugated material in comparison with the response elicited when the immunogen was injected without adjuvant or was not conjugated to Imps. The antibody response to these conjugates could not be significantly increased by the addition of IFA. Thus, the Imps of E. coli represent powerful carrier molecules which, when injected into mice and rabbits, are not only capable of generating high titers of antibody to themselves, but also to molecules conjugated to them. Immunization with immunogens coupled to these proteins results in the production of high titers of antibody without the need for oil-based adjuvants, thereby avoiding the unwanted side effects of such adjuvants.

Adjuvants, Immunologic

Molecular mapping of the mouse ob mutation.

The mouse ob mutation has been mapped relative to a series of RFLPs among the progeny of three separate mouse crosses: an intraspecific backcross, an intraspecific intercross, and an interspecific intercross. Genotypic assignment at the ob locus was made by making use of measurements of body mass index and the plasma concentrations of glucose and insulin. These data have suggested that the development of diabetes in these animals is a consequence of unlinked polygenes. There was also evidence that unlinked Mus spretus alleles can diminish the obesity of ob/ob mice. From these data we have mapped several markers on chromosome 6 with the following order: cen-Cola-2-Met-ob-Cpa-Tcrb. The homologs of markers that flank ob map to human chromosome 7q, suggesting that if there is a human homologue of ob, it maps to 7q31.

Animals

Immunogold labelling of dystrophin in human muscle, using an antibody to the last 17 amino acids of the C-terminus.

Immunolabelling with a 10 nm gold probe was used to localize dystrophin at the ultrastructural level in human skeletal muscle. The primary antibody was raised against a synthetic peptide containing the last 17 amino acids at the C-terminus of dystrophin. Using this antibody, labelling was almost entirely confined to a narrow band enclosing 40 nm either side of the plasma membrane and including the membrane itself. Histograms of the position of the gold probe relative to the plasma membrane showed modes lying over the membrane itself or the extracellular face of the membrane. One interpretation of these results is that the C-terminus of dystrophin is inserted in the plasma membrane alongside the glycoproteins with which it is tightly associated. Histograms of the distances between gold probes displayed modes at approximately 120 nm in both transverse and longitudinal sections suggesting that dystrophin forms a lattice-like network adjacent to the plasma membrane.

Amino Acid Sequence

Consequences of person-environment incongruence: absenteeism, frustration, and stress.

Two correlational studies using English nurses and working adults are reported that examined the relationship between the three measures of person-environment (P-E) fit as derived from Holland's (1973) theory and three dependent work-related variables. In the first study, the P-E fit measures of congruence, consistency, and differentiation were correlated with two measures of absenteeism, frustration, and various demographic variables. Contrary to predictions, two measures of absenteeism were positively correlated with congruence and consistency. In accordance with the hypothesis, however, frustration was highly negatively correlated with congruence and consistency. In the second study, consistency, but not congruence or differentiation, was significantly negatively correlated with stress, as predicted. These studies provide some support for Holland's theses, although not all hypotheses were supported, both for methodological and theoretical reasons. It is argued that P-E fit measures are useful predictors of occupational behavior in conjunction with other major determinants.

Absenteeism

Ultrastructural localization of dystrophin in human muscle by using gold immunolabelling.

Immunolabelling with a 5 nm gold probe was used to localize dystrophin at the ultrastructural level in human muscle. The primary antibody was monoclonal, raised against a segment (amino acids 1181-1388) from the rod domain of dystrophin. The antibody (Dy4/6D3) is specific for dystrophin and shows no immunoreactivity with any protein from mdx mouse muscle or from patients with a gene deletion spanning part of the molecule recognized by the antibody (Nicholson et al. 1989 a; England et al. 1990). Using this antibody, labelling was almost entirely confined to a narrow 75 nm rim at the periphery of the muscle fibres. Histograms of the distance from the gold probe to the cytoplasmic face of the plasma membrane and of the distance between gold probes (nearest neighbour in a plane parallel with the plasma membrane) displayed modes at approximately 15 nm and 120 nm, respectively. The distribution of the probe was the same in longitudinal and transverse sections of the muscle. These observations suggest that the rod portion of the dystrophin molecule is normally arranged close to the cytoplasmic face of the plasma membrane and that the molecules form an interconnecting network. Labelling was not associated with the transverse tubular system.

Cell Membrane

A new computed tomographic sign of pancreatitis.

Computed body tomography has become useful in the diagnosis of pancreatic disease. Pancreatitis frequently results in lateral and posterior extension of inflammatory tissue into the pararenal fat planes, which can be visualized by CT. In our series it was associated with clinically diagnosed pancreatitis. Of 100 cases studied for abdominal pathology where pancreatic visualization was optimum, 10 had enlargement of the pancreas with destruction of soft tissue planes extending into the left pararenal space and clinical findings of pancreatitis. Carcinoma of the pancreas was identified in 12; no abnormality was identified in 49; the remaining cases were mixed intraabdominal and retroperitoneal pathology. The value of this sign lies in separating inflammatory processes from neoplastic disease; the sign was not found in normals.

Acute Disease

The application of prolonged EEG telemetry and videotape recording to the study of seizures and related disorders.

The clinical application of prolonged monitoring by the combined EEG and videotape recording of patients was evaluted. This test was found to be useful in diagnosing epileptic seizures in patients in whom both the history and diurnal EEG studies were unhelpful, and it assisted with the accurate classification of seizure types. It enabled seizure focus lateralisation in medically intractable epileptic who were being evaluated for surgery, and it also provided an objective estimate of minor seizure frequency. Prolonged EEG telemetry and videotape recording was especially useful in assessing additional seizures that develop in known epileptics. In some patients with syncope and drop attacks this technique helped to exclude atonic epileptic seizures and intermittent cardiac tachy-brady-arrhythmia as the underlying cause. As a method for identifying sleep disorders it has greater merits than conventional methods of polygraphic recordings.

Adolescent