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Biomedical subjects

G Morgan

Publications and source records attributed to G Morgan.

At least 91 records · Page 5Linked to original sources
PubMed1998

Confidential inquiry into quality of care before admission to intensive care.

OBJECTIVE: To examine the prevalence, nature, causes, and consequences of suboptimal care before admission to intensive care units, and to suggest possible solutions. DESIGN: Prospective confidential inquiry on the basis of structured interviews and questionnaires. SETTING: A large district general hospital and a teaching hospital. SUBJECTS: A cohort of 100 consecutive adult emergency admissions, 50 in each centre. MAIN OUTCOME MEASURES: Opinions of two external assessors on quality of care especially recognition, investigation, monitoring, and management of abnormalities of airway, breathing, and circulation, and oxygen therapy and monitoring. RESULTS: Assessors agreed that 20 patients were well managed (group 1) and 54 patients received suboptimal care (group 2). Assessors disagreed on quality of management of 26 patients (group 3). The casemix and severity of illness, defined by the acute physiology and chronic health evaluation (APACHE II) score, were similar between centres and the three groups. In groups 1, 2, and 3 intensive care mortalities were 5 (25%), 26 (48%), and 6 (23%) respectively (P=0.04) (group 1 versus group 2, P=0.07). Hospital mortalities were 7 (35%), 30 (56%), and 8 (31%) (P=0.07) and standardised hospital mortality ratios (95% confidence intervals) were 1.23 (0.49 to 2.54), 1.4 (0.94 to 2.0), and 1.26 (0.54 to 2.48) respectively. Admission to intensive care was considered late in 37 (69%) patients in group 2. Overall, a minimum of 4.5% and a maximum of 41% of admissions were considered potentially avoidable. Suboptimal care contributed to morbidity or mortality in most instances. The main causes of suboptimal care were failure of organisation, lack of knowledge, failure to appreciate clinical urgency, lack of supervision, and failure to seek advice. CONCLUSIONS: The management of airway, breathing, and circulation, and oxygen therapy and monitoring in severely ill patients before admission to intensive care units may frequently be suboptimal. Major consequences may include increased morbidity and mortality and requirement for intensive care. Possible solutions include improved teaching, establishment of medical emergency teams, and widespread debate on the structure and process of acute care.

Adult↗
PubMed1998

Long-term immune reconstitution and outcome after HLA-nonidentical T-cell-depleted bone marrow transplantation for severe combined immunodeficiency: a European retrospective study of 116 patients.

We have performed a retrospective analysis of the development of T- and B-cell functions after HLA-nonidentical T-cell-depleted bone marrow transplantation (BMT) performed in 193 patients with severe combined immunodeficiency (SCID) at 18 European centers between December 1982 and December 31, 1993. One hundred sixteen of 193 patients were alive with evidence of engraftment 6 months after BMT. Development of T-cell function occurred earlier than B-cell function and was achieved more frequently up to the time of last follow-up. The median time to achieve normal T-cell function was 8.7 months, whereas the median time to achieve normal B-cell function was 14.9 months. Twenty-four patients died later than 6 months post-BMT, mainly due to chronic graft-versus-host disease (cGVHD) and/or viral infection. Absence of T-cell reconstitution 6 months after BMT, unlike absence of B-cell reconstitution, was associated with a poor outcome. Two additional factors were associated with a poor outcome: presence of cGVHD 6 months after BMT and B- SCID versus B+ SCID. However, two of these three factors remained as significant prognostic factors in a multivariate analysis: the absence of T-cell function and the presence of cGVHD 6 months after BMT. Analysis of the factors influencing the development of immune reconstitution showed that T- and B-cell functions occurred earlier and more frequently in B+ SCID versus B- SCID patients. Acute GVHD was associated with a slower development of T-cell function at 6 months, and cGVHD had a negative influence on the development of T-cell function afterwards, but neither acute nor chronic GVHD was found to influence the development of B-cell function. Once engraftment occurred, whether patients had or had not received Busulfan in the conditioning regimen did not influence the kinetics and quality of T-cell function development. In a multivariate study, two factors were found to influence the T-cell function 6 months after BMT: type of SCID and acute GVHD. The results of this retrospective analysis should lead to new protocols adapted to SCID disease, considering that disease-related as well as BMT-related parameters influence the development of immune function and thereby long-term outcome after HLA-nonidentical T-cell-depleted BMT.

B-Lymphocytes↗
PubMed1998

Early VEP and ERG evidence of visual dysfunction in autosomal recessive osteopetrosis.

Autosomal recessive (AR) osteopetrosis has a rapid course and manifests in the first months of life. Visual loss occurs because of optic nerve compromise, and more rarely retinal dysfunction (which may be a part of a primary neurodegeneration). The only curative treatment currently available is bone marrow transplantation (BMT). It has been suggested that BMT is contraindicated if AR osteopetrosis is associated with a primary neurodegeneration. Visual impairment tends to be irreversible after BMT. The young age of the patients makes reliable, objective tests of visual function especially important. We have reviewed the flash electroretinograms (ERGs) and flash and pattern visual evoked potentials (VEPs) recorded without sedation from 15 patients with AR osteopetrosis, 11 of whom were recorded longitudinally. The most frequent, early indication of visual dysfunction was a delay in the pattern or flash VEP latency. This first affects the pattern reversal VEP to small checks. Importantly this often preceded fundal changes of optic disc pallor, and evidence of optic nerve compression on neuroimaging. Only two patients had ERG evidence of retinal dysfunction affecting both rods and cones. One of these patients had a distinctive fundal appearance, but did not have evidence of associated neuronal degenerative disease. The other patient was lost to follow-up. In the patients reviewed in this study successful BMT and optic nerve decompression did not result in VEP improvement. Fundoscopy, VEP and ERG testing are indicated when the diagnosis of AR osteopetrosis is suspected and provide a useful means of monitoring visual involvement.

Bone Marrow Transplantation↗
PubMed1998

Barrett's oesophagus, oesophageal cancer and colon cancer: an explanation of the association and cancer chemopreventive potential of non-steroidal anti-inflammatory drugs.

Barrett's oesophagus is associated with an increased risk of oesophageal adenocarcinoma. In 1985, Sontag et al reported an association between Barrett's oesophagus and colorectal cancer. This association has become controversial owing to conflicting evidence. Two recent papers indicate that although the prevalence of colon adenomas is the same in persons with Barrett's oesophagus as in the rest of the population, patients have an increased risk of developing colon cancer. A biologically plausible hypothesis is presented which explains the predisposition to both oesophageal and colon cancers. This hypothesis discusses the contribution of environmental factors such as alcohol, smoking and diet. In addition, it is proposed that the increased expression of the cyclo-oxygenase 2 enzyme is central to the predisposition to both oesophageal and colon cancers. Since this enzyme is inhibited by non-steroidal anti-inflammatory drugs such as aspirin and sulindac, these drugs hold promise as cancer chemopreventive agents in Barrett's oesophagus patients. Sulindac is the most promising of these agents owing to its efficacy in regressing colon polyps in patients with familial adenomatous polyposis.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1998

Peripheral T-cell activation in non-segmental vitiligo.

Vitiligo is a hypopigmentary dermatosis of probable autoimmune origin. Previously reported aberrations in peripheral blood mononuclear cells (PBMC), especially T cells and T cell subsets, have been inconsistent. Lymphocyte subpopulations were examined using flow cytometry and monoclonal antibodies against CD4, CD8, CD20, CD25, CD45RA, and HLA-DR in 34 patients with non-segmental vitiligo. Twelve patients had not received any previous treatment and 22 had previously received at least one course of PUVA therapy that was discontinued at least four months prior to our study. Compared to matched controls, we found significant increases in CD25 and HLA-DR in vitiligo patients (p = 0.000). An inverse correlation was observed between HLA-DR and patient status with regard to treatment (p = 0.001). These results suggest a role for T cells in the pathogenesis of vitiligo and imply that previous PUVA therapy may be reflected by an alteration in circulating DR +ve cells.

Adult↗
PubMed1998

How should we introduce high-dose chemotherapeutic strategies into the adjuvant management of high-risk breast cancer in Australasia?

BACKGROUND: Development of bone marrow support techniques has altered the standard chemotherapeutic management of haematological malignancies, and these techniques are now being increasingly utilized in solid tumours. In breast cancer, survival benefits have resulted from conventional dose adjuvant chemotherapy, but outcomes remain poor in many women with high-risk disease. Improved response rates with high-dose chemotherapy (HDC) in metastatic disease have led to the investigation of these techniques in adjuvant therapy of high-risk localized disease. In some high-risk patient subgroups survival is extremely poor, with 5-year rates below 30%. Improved adjuvant strategies for patients in these subgroups are therefore urgently required. In Australasia, oncology departments are currently considering accrual of women with high-risk disease into the International Breast Cancer Study Group (IBCSG) 15-95 Trial investigating HDC/stem cell transplantation. METHODS: The present paper reviews the available data on the efficacies and toxicities of currently available high-dose chemotherapeutic strategies; discussing methodological considerations relevant to their introduction and safe use in the adjuvant setting in Australia and New Zealand. RESULTS: Although response rates with HDC in metastatic disease are encouraging, the clinical effectiveness of current HDC regimens in adjuvant management has not been established and is limited by significant toxicity. CONCLUSIONS: The introduction of HDC strategies for high-risk breast cancer in Australia encounters difficulties both in trial design and potential clinical practice.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1998

Immunocytochemical and In situ hybridization studies of the distribution of calbindin D9k in the bovine placenta throughout pregnancy.

The fetus must transport considerable and increasing amounts of calcium across the placental trophoblast epithelium to support growth and development and bone formation. Active calcium transport across epithelia has been shown to correlate with calbindin D9k or 28k content. This study examined the distribution of calbindin D9k (9CBP) protein and mRNA during pregnancy in the bovine placenta to determine its possible role in calcium transport in this system. The immunocytochemical results show 9CBP in an increasing percentage of interplacentomal uninucleate trophoblast cells until, at term, all show a level at least eight times that of any other placental cell. There is a similar, although smaller, rise in their 9CBP mRNA content. The mature interplacentomal binucleate cell ( approximately 5% of the total) contains no 9CBP at any stage of pregnancy. In interplacentomal uterine epithelium, 9CBP protein and mRNA decrease to zero in late pregnancy but the glands maintain constant low levels throughout. In the placentome trophoblast, uninucleate cells show insignificant amounts but binucleate cells (15-20% of the total trophoblast cells) contain considerable levels of both 9CBP protein and mRNA, as do all the uninucleate uterine epithelial cells. The placentomal binucleate cells show peak values at mid-pregnancy; the placentomal uterine epithelium shows only small changes in levels in the second half of pregnancy. Increase in fetal calcium demand in the second half of pregnancy therefore correlates with a major increase in 9CBP only in the interplacentomal trophoblast, as we have also shown in the sheep and goat, indicating an important role for this region in active calcium transport by the ruminant placenta. The 9CBP is distributed uniformly in the cytosol and nucleoplasm, supporting a role in facilitated diffusion of calcium through the cell rather than a vesicular shuttle system.

Animals↗
PubMed1998

Cervical radiculopathy and coexisting distal entrapment neuropathies: double-crush syndromes?

The double-crush hypothesis (DCH) proposes that a proximal lesion along an axon predisposes it to injury at a more distal site along its course through impaired axoplasmic flow. Although this hypothesis has been accepted, it has anatomic and pathophysiologic restrictions that limit its application as an explanation for coexisting cervical root lesions (CRLs) and carpal tunnel syndrome (CTS) or ulnar neuropathy at the elbow (UN-E). We retrospectively surveyed all electrodiagnostic (EDX) reports of coexisting CTS or UN-E and CRL for anatomic correlation, if any, between the proximal root lesion and the distal entrapment neuropathy. In the period between January 1982 and August 1995 there were 12,736 limbs with CTS or UN-E. In 435 of these limbs (3.4%) there was a coexisting CRL, but only 98 (0.8%) had an association that was anatomically appropriate. Moreover, only 69 (0.5%) of the 98 cases demonstrated axon loss at the distal lesion site on EDX examination. Therefore, cumulatively, only 69 of our 12,736 cases of CTS and UN-E satisfied the pathophysiologic and one of the anatomic requirements of the DCH. Our data thus suggest that a CRL can seldom serve as the proximal lesion with these entrapment neuropathies in the DCH.

Axonal Transport↗
PubMed1998

Air pollution and hospital admissions in Sydney, Australia, 1990 to 1994.

OBJECTIVES: This study examined the effects of outdoor air pollutants on daily hospital admissions in Sydney, Australia. METHODS: A time-series analysis of counts of daily hospital admissions and outdoor air pollutants (1990 to 1994) was performed, by means of Poisson regression that allowed for overdispersion and autocorrelation. RESULTS: An increase in daily maximum 1-hour concentration of nitrogen dioxide from the 10th to the 90th percentile was associated with an increase of 5.29% (95% confidence interval = 1.07, 9.68) in childhood asthma admissions and 4.60%(-0.17,9.61) in chronic obstructive pulmonary disease (COPD) admissions. A similar increase in daily maximum 1-hour particulate concentration was associated with an increase of 3.01% (-0.38, 6.52) in COPD admissions. An increase from the 10th to the 90th percentile in daily maximum 1-hour nitrogen dioxide, daily maximum 1-hour ozone, and daily mean particulate was associated with an increase in heart disease admissions among those 65 years and older of 6.71% (4.25, 9.23), 2.45% (-0.37, 5.35), and 2.82% (0.90, 4.77), respectively. Heart disease and childhood asthma were primarily associated with nitrogen dioxide; COPD was associated with both nitrogen dioxide and particulates. CONCLUSIONS: Current levels of air pollution in Sydney are associated with increased hospitalization for respiratory and heart disease.

Adolescent↗
PubMed1998

Air pollution and daily mortality in Sydney, Australia, 1989 through 1993.

OBJECTIVES: This study examined the effects of outdoor air pollutants in Sydney, Australia, on daily mortality. METHODS: Time-series analysis was performed on counts of daily mortality and major outdoor air pollutants (particulates, ozone, and nitrogen dioxide) in Sydney (1989 to 1993) with adjustment for seasonal and cyclical factors. Poisson regression was calculated with allowance for overdispersion and autocorrelation. The effects of lagging exposure by 0 to 2 days were assessed with single- and multiple-pollutant models. RESULTS: An increase in daily mean particulate concentration from the 10th to the 90th centile was associated with an increase of 2.63% (95% confidence interval 0.87 to 4.41) in all-cause mortality and 2.68% (0.25 to 5.16) in cardiovascular mortality. An increase in daily maximum 1-hour ozone concentration from the 10th to the 90th centile was associated with an increase of 2.04% (0.37 to 3.73) in all-cause mortality and 2.52% (-0.25 to 5.38) in cardiovascular mortality. An increase in the daily mean nitrogen dioxide concentration from the 10th to the 90th centile was associated with an increase of 7.71% (-0.34 to 16.40) in respiratory mortality. Multiple-pollutant models suggest that the effects of particulates and ozone on all-cause and cardiovascular mortality, and of nitrogen dioxide on respiratory mortality, are independent of the effects of the other pollutants. CONCLUSIONS: Current levels of air pollution in Sydney are associated with daily mortality.

Air Pollutants↗
PubMed1998

Tumor necrosis factor-alpha inhibits epithelial differentiation and morphogenesis in the mouse metanephric kidney in vitro.

Tumor necrosis factor-alpha (TNF-alpha), an inflammatory cytokine, has diverse actions both within and outside the immune system and has been implicated in the etiology of a wide range of pathological conditions. Evidence is accumulating that it may also have important roles in the normal development of the embryo. In this study we demonstrated that the addition of recombinant TNF-alpha to metanephric organ culture induced a dose dependent and reversible decrease in growth and development, with inhibition of ureteric bud branching and nephron formation beyond the condensate stage and despite appropriate expression of the transcription factor pax-2. TNF-alpha also increased the point prevalence of apoptosis after only 1 day of culture. We also noted that macrophages were present in renal rudiments at the inception of nephrogenesis and their numbers significantly increased during the culture period. This effect was enhanced by TNF-alpha. We have also demonstrated expression of mRNAs for TNF-alpha and its receptors in whole mouse metanephroi from the inception of renal development. TNF-alpha protein was also detected, predominantly at mesenchymal/epithelial interfaces. In addition, TNF-alpha mRNA and protein were expressed by clonal renal mesenchymal cells in vitro, suggesting that these cells are a source of TNF-alpha in vivo.

Animals↗
PubMed1997

KLP38B: a mitotic kinesin-related protein that binds PP1.

We have identified a new member of the kinesin superfamily in Drosophila, KLP38B (kinesin-like protein at 38B). KLP38B was isolated through its two-hybrid interaction with the catalytic subunit of type 1 serine/threonine phosphoprotein phosphatase (PP1). We demonstrate that recombinant KLP38B and PP1 associate in vitro. This is the first demonstration of direct binding of a kinesin-related protein to a regulatory enzyme. Though most closely related to the Unc-104 subfamily of kinesin-related proteins, KLP38B is expressed only in proliferating cells. KLP38B mutants show cell proliferation defects in many tissues. KLP38B is required for normal chromatin condensation as embryos from KLP38B mutant mothers have undercondensed chromatin at metaphase and anaphase. This is the first time that a kinesin-related protein has been shown to have such a role. Incomplete lethality of a strong KLP38B allele suggests partial redundancy with one or more additional kinesin-related proteins.

Amino Acid Sequence↗