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Biomedical subjects

J Morris

Publications and source records attributed to J Morris.

At least 343 records · Page 19Linked to original sources

Persistence of supply dependency of oxygen uptake at high levels of delivery in adult respiratory distress syndrome.

OBJECTIVE: To identify any plateau in oxygen consumption (VO2) when oxygen delivery (DO2) is increased in patients with the adult respiratory distress syndrome (ARDS). DESIGN: Clinical prospective study; multiple regression analysis was done to assess the relationship between VO2 and DO2 for pooled data and for each individual patient. SETTING: University hospital ICU. PATIENTS: Twenty consecutive patients aged 18 to 78 yrs (mean 43.5) in whom ARDS was present during their ICU stay. INTERVENTIONS: Multiple measurements were obtained in individual patients (mean number of measurements 40, range 20 to 83) and mathematical models were fitted to both pooled and individual patient data. DO2 ranged from 212 to 1550 mL/min.m2 with a maximum of 758 to 1550 mL/min.m2 (mean 1136). Because of the large variations between patients, it was not justifiable to describe a relationship for the pooled data and each case was analyzed individually. MEASUREMENTS AND MAIN RESULTS: We found the optimal regression model to be linear in 13 patients, cubic in four, and either cubic or linear in one. Two patients demonstrated no significant relationship. The relationship for the group was determined from each patient's data and was best described by linear regression. CONCLUSIONS: In no patient was there evidence of a plateau, despite high levels of DO2 being achieved in all patients.

Adolescent↗

The sharing of injecting equipment among drug users attending prescribing clinics and those using needle-exchanges.

Three groups of injecting drug-users were defined in terms of their experience of methadone treatment: treatment for periods longer than 6 months, treatment for shorter periods, and no treatment. Methadone treatment and the use of needle exchanges were related in subsequent analysis to the sharing of injecting equipment. Comparisons between groups were made on other variables believed to be associated with sharing. Significant differences were observed between treatment groups in the recency of sharing and in the use of needle-exchanges. Age and length of drug use were important factors in sharing, which was least prevalent among older respondents in long-term treatment. Regular use of needle-exchanges was associated with the passing on of used equipment to others. Subsequent analysis of regular users suggested respondents in long-term treatment were less likely to pass on their equipment than those in the other two groups.

Adolescent↗

The haematology of homozygous sickle cell disease after the age of 40 years.

Haematological indices have been studied in 181 patients with homozygous sickle cell (SS) disease aged 40-73 years. Cross-sectional analyses in 5-year age bands indicated age-related decreases in HbF (males only), total haemoglobin and platelet counts. Longitudinal studies within individuals confirmed the downward age-related trend in haemoglobin and platelets and also revealed a falling reticulocyte count, most significant when expressed as absolute values. Total nucleated cells also fell although the decline was significant only in females. These observations are consistent with a progressive bone marrow failure which is not explained by the commonly occurring renal impairment in older SS patients since the changes persisted in analyses confined to patients with normal creatinine levels. The mechanism of this bone marrow failure is currently unknown.

Adult↗

The red cell distribution width in sickle cell disease--is it of clinical value?

The red cell distribution width (RDW) has been studied during the clinical steady state in 1121 patients with homozygous sickle cell (SS) disease, 344 with sickle cell-haemoglobin C (SC) disease, 68 with sickle cell-beta+ thalassaemia, 49 with sickle cell beta 0 thalassaemia and in 130 control subjects with a normal (AA) genotype. The mean RDW was moderately increased in S beta + thalassaemia and SC disease and markedly increased in S beta 0 thalassaemia and SS disease. In SS, SC and S beta 0 thalassaemia genotypes, lower RDW values occurred in females and with alpha thalassaemia. The RDW correlated negatively with total haemoglobin, mean cell haemoglobin concentration, mean cell volume, and fetal haemoglobin (HbF) and positively with reticulocyte count in SS disease. A low RDW was associated with higher weight and less frequent dactylitis, painful crisis, acute chest syndrome, acute splenic sequestration, and hospital admissions. A low RDW in SS disease is consistent with a high total haemoglobin, high HbF, low reticulocyte count, alpha thalassaemia, and a more mild clinical course.

Adolescent↗

Gender differences in the incidence of definite schizophrenia and atypical psychosis--focus on negative symptoms of schizophrenia.

In a catchment area study of 101 first inceptions of schizophrenia, mania and atypical psychoses, women were significantly more likely to have atypical psychosis and men were more likely to have definite schizophrenia. Negative symptoms such as affective flattening and poverty of speech were already present in many cases, and were significantly increased in patients with definite schizophrenia (geometric mean 5.6) compared with those with atypical psychosis (geometric mean 3.2) and mania (geometric mean 1.5). Negative symptoms were also twice as severe in men (geometric mean 5.5) than women (geometric mean 2.6). There was a significant increase in negative symptom severity with longer illness and greater depression, but the diagnosis and the sex effects were not caused by these factors. We suggest that our findings are further support for the hypothesis that men have a greater biological vulnerability to negative symptoms and consequent social disability in the face of psychosis, particularly a schizophrenic psychosis, and that this may be one explanation for the apparently greater risk of definite schizophrenia and its poorer prognosis in men.

Adult↗

Contribution of leukotriene B4 to airway inflammation and the effect of antagonists.

Inhalation of aerosols of ovalbumin in sensitized guinea pigs produced a marked, bronchoalveolar eosinophilia 24 hr after challenge. The lung eosinophilia was not prevented by the cyclooxygenase inhibitors, indomethacin or PAF antagonists (WEB-2086 and L-652731) but was inhibited by methylprednisolone, the 5-LO inhibitor, U-66858 and a series of structural analogs of LTB4, U-75302, U-77692, U-75485 and U-78489. The effectiveness of LTB4 antagonists but not PAF antagonists in vivo was consistent with in vitro studies in which LTB4 was shown to be far more chemotactic than PAF for guinea pig eosinophils. LTB4 elicited maximal directional migration of guinea pig eosinophils at concentrations from 10(-7) M to 10(-9) M while PAF showed no effect over the same concentration range. The structural analogs of LTB4 were shown to inhibit LTB4 induced chemotaxis of guinea pig eosinophils and produced a dose-related inhibition of binding of LTB4 to guinea pig eosinophil membranes. To add further proof to the hypothesis that LTB4 contributed to the antigen-induced lung eosinophilia we attempted to measure LTB4 release into BAL fluid immediately after and at various time points up to 24 hr after antigen inhalation. However, using a sensitive radioimmunoassay (detection limit 10 pg/ml) very low levels of LTB4 (24.9-67.9 pg/ml) or its metabolite, 20-OH LTB4 (24.9-98.2 pg/ml) were detected in BAL fluid and these levels did not increase significantly following antigen provocation. Inhalation of LTB4 aerosols in unsensitized Brown-Norway rats or inhalation of aerosols of ovalbumin in sensitized Brown-Norway rats also produced a marked "late-phase" eosinophil-rich influx of inflammatory cells into the lungs. The lung eosinophilia in the rat was prevented by two structurally unrelated leukotriene B4 (LTB4) antagonists, U-75302 and Ly255283. These data implicate LTB4 as a mediator of allergen-induced bronchopulmonary eosinophilia. Leukotriene B4 antagonists may provide leads for the development of compounds which inhibit the chronic airway inflammation associated with asthma in man.

Aerosols↗

More accurate diagnosis of irritable bowel syndrome by the use of 'non-colonic' symptomatology.

The criteria now used in an attempt to distinguish irritable bowel syndrome from organic gastrointestinal disease rely almost entirely on symptoms of colonic origin. 'Non-colonic' symptoms, however, arising either from elsewhere in the gut or of a more general nature, are common in irritable bowel syndrome and may have even better diagnostic potential. The prevalence of these non-colonic features was assessed in 107 patients with the irritable bowel syndrome and 295 subjects with other gut disorders. Gastrointestinal type non-colonic symptoms are useful in differentiating irritable bowel syndrome from inflammatory bowel disease but, with the exception of early satiety, are not helpful when there is gastro-oesophageal or biliary disease. More general 'non-colonic' features, such as lethargy and backache, are much commoner in irritable bowel syndrome than in all the organic gastrointestinal diseases studied and have good discriminant function. Multiple logistic regression analysis identified certain features that had a particularly significant independent risk for irritable bowel syndrome. Those were lethargy (relative risk 6.7), incomplete evacuation (RR 5.2), age under 40 (RR 2.1), backache (RR 2.0), early satiety (RR 1.8), and frequency of micturition (RR 1.8). These relative risks can be multiplied together to give an overall risk when more than one of these features is present in a patient. Until a diagnostic test is available more confident diagnosis of irritable bowel syndrome can be achieved by identifying symptoms that have good discriminant function. The results of this study indicate that the non-colonic features of irritable bowel syndrome may be especially valuable in this respect.

Adult↗

Negative symptoms in chronic schizophrenia. Relationship to duration of illness.

The frequency and distribution of negative symptoms in a sample of 40 patients admitted to hospital with RDC-definite schizophrenia were examined. There was a highly significant positive correlation between negative symptom scores obtained using three different rating scales, but the presence of negative symptoms was not significantly related to duration of illness or number of episodes of illness. These findings do not support a model of negative symptoms being the consequence of schizophrenic relapse, but are in favour of their being an integral component of the schizophrenic syndrome, as salient in the first as in later episodes.

Adolescent↗

A phase II trial of intraperitoneal cisplatin and etoposide as salvage treatment for minimal residual ovarian carcinoma.

We conducted a phase II study of intraperitoneal (IP) cisplatin (CDDP) and etoposide (VP-16) as salvage therapy in patients with ovarian cancer who had persistent disease or who had relapsed after primary systemic chemotherapy and had residual disease of less than 2 cm. Two hundred eleven courses of IP chemotherapy consisting of CDDP 200 mg/m2 and VP-16 350 mg/m2 were administered. All patients received intravenous (IV) thiosulfate protection. Treatment was given once every 4 weeks for a median of six cycles. Twenty-four of 37 assessable patients were clinically free of disease at the end of treatment (normal physical exam, computed tomographic [CT] scan, CA-125 and peritoneal cytology); one patient had a partial response. Ten of these 24 patients consented to reexploration at the end of treatment, and nine were in pathologic complete remission, while one patient had positive peritoneal washings as her only evidence of persistent disease. The median survival of the 37 patients was 26 months from the first day of IP treatment and 51 months from diagnosis. The major toxicity was myelosuppression, with median nadir WBC, granulocyte, and platelet counts of 2,400, 684, and 134,000/mm3, respectively. There was no cumulative renal damage, hypomagnesemia, or chemical peritonitis. We conclude that IP CDDP and VP-16 can produce pathologic complete remissions when used as a second-line regimen for patients with ovarian cancer who have received systemic cisplatin-based therapy and have less than 2 cm disease.

Adult↗

Antibodies to non-beta regions of the beta-amyloid precursor protein detect a subset of senile plaques.

A central unresolved issue in Alzheimer's disease is the origin of the extracellular amyloid beta protein (A beta P) found in senile plaques and its relationship to the dystrophic neurites that intimately surround it. Here the presence and distribution within senile plaques of various epitopes of the beta-amyloid precursor protein (APP) are compared with the distribution of A beta P itself and markers for plaque neurites. Several principal findings emerge: 1) antibodies to regions of APP outside of A beta P ('APP antibodies') recognize only a subgroup of senile plaques; 2) within these plaques, APP antibodies label discrete globular and granular structures morphologically resembling neurites; 3) virtually all of the plaques labeled by APP antibodies also contain neurites reactive with antibodies to tau; 4) double labeling with anti-tau and an APP antibody shows that the neuritelike profiles stained by the APP antibody are always closely associated with tau-positive neurites within the same plaque and that a minority of profiles appear to be labeled by both antibodies; and 5) antibodies to different regions throughout APP label the same profiles within plaques, suggesting the presence of the full-length precursor. The authors conclude that only a subgroup of senile plaques contain APP epitopes and that the immunostained structures are neurites. Because many A beta P-containing plaques in neocortex, cerebellum, and striatum were found to be devoid of any APP labeling, as were vascular A beta P deposits, it is unlikely that the extracellular A beta P is principally derived from the APP found within dystrophic neurites. The immunodetection of apparently full-length APP, an axonally transported protein, in selected plaque neurites provides yet another protein marker of neuritic dystrophy, possibly indicative of an aberrant regenerative response.

Alzheimer Disease↗

Occupational-health training at the University of Hawaii.

Occupational-health training at the University of Hawaii School of Public Health (UH-SPH) is a graduate-level program focusing on industrial hygiene; it also offers courses of interest to other health professionals, particularly physicians and nurses. The current training at the UH-SPH is designed primarily to prepare occupational-health practitioners at the master's degree level. The occupational-health program elective is considered to be an area of emphasis within a broader program of study in public health. The program offers special opportunities for occupational-health training and research in cross-cultural and international settings. Post-graduate and continuing-education occupational-health training in the community is also discussed.

Curriculum↗

Effects of tracer blood measurement noise on glucose metabolic rate estimation.

Tracer kinetic modeling with Positron Emission Tomography (PET) requires measurements of the time-activity curves in both plasma (PTAC) and tissue (TTAC) to estimate physiological parameters. However, the estimation usually ignores the measurement noise in plasma tracer activity curves. The accuracy and reliability of the physiological parameters estimated by ignoring such noise are not well understood. In this paper, computer simulations were performed to investigate the influence of input measurement noise on the accuracy of estimates. The results show that input measurement noise causes considerable variability in the parameter estimates.

Blood Glucose↗

A bovine homolog to the human myogenic determination factor myf-5: sequence conservation and 3' processing of transcripts.

A bovine cDNA library from fetal skeletal muscle myoblasts. was screened with a 274 bp probe to a conserved region of the mouse MyoD1 cDNA. One positive recombinant, designated bmyf, was found to contain a 1931 bp insert with an open reading frame encoding a predicted protein highly related to the human myogenic factor myf-5 Human and bovine factors are 96% homologous in their predicted amino acid sequences. At the nucleotide level, bmyf and myf-5 are 92% identical in the coding region and 74 and 80% homologous in their 5'- and 3'-untranslated regions, respectively. The bmyf cDNA, nevertheless, extends 475 nucleotides beyond a polyadenylation signal common to both cDNAs. Bmyf transcripts are expressed exclusively in skeletal muscle where three transcripts of 1.5, 2 and 3 kb were detected. While the 1.5 kb transcript lacks sequences 3' to the polyadenylation signal at nt 1415 in the bmyf cDNA, both the 2 and 3 kb RNAs contain these sequences suggesting that bmyf transcripts are alternatively polyadenylated. Bmyf cDNA can activate the expression of the myogenic program in C3H10T1/2 fibroblasts as assayed by stable and transient transfection experiments.

Amino Acid Sequence↗

Monocyte adherence results in selective induction of novel genes sharing homology with mediators of inflammation and tissue repair.

Adherence of monocytes to endothelial cells or extracellular matrices is likely to play a critical role in triggering monocyte activation in extravascular sites of infection, chronic inflammatory disorders, tissue damage and neoplastic growth. We have constructed a cDNA library from monocytes adhered for 30 min on plastic and have screened it by differential hybridization for mRNA rapidly induced by adherence. Two of the cDNA isolated have been identified as IL-1 beta and superoxide dismutase. Sequence data from three other adherence specific clones demonstrates the presence of ATTTA mRNA instability sequences in their 3' untranslated regions signifying inflammation-associated genes. The deduced amino acid sequences indicate the presence of open reading frames with sequence homologies to a family of host defense cytokines, one of them being identified as IL-8. Of the 14 clones initially identified, 4 have been analyzed for induction of mRNA expression. Although 3 of the 4 clones were equally induced by PMA and LPS under nonadherent conditions, all 4 cDNA showed distinct patterns of induction with adherence to extracellular matrix components or endothelial cells. The deduced amino acid sequence homologies indicate that we have isolated cDNA that code for three unique gene products. These cDNA belong to a gene family of early host defense cytokines involved in inflammation and cell growth, but which are differentially regulated by adherence to different surfaces.

Amino Acid Sequence↗

Phenotypic and functional properties of B lymphocytes from aged mice.

Phenotypic and functional properties of B lymphocytes from individual young and old mice of different inbred strains were studied. B lymphocyte subpopulations defined by the ratios of the densities of cell surface IgM and IgD were found to be altered with age. However, such alterations in B cell subsets were found only in 30-40% of the old mice. B cell mitogenic responses to anti-mu and anti-Lyb2 antibodies were decreased in a majority of DBA/2 mice. Proliferative responses to LPS and anti-mu were reduced only in a minority of CBA/Ca mice but there was a very good correlation in the responsiveness of the old mice to LPS and anti-mu. The anomalous properties of the individual old mice of these inbred strains may be due to a heterogeneity in the effects of aging or due to environmental influences.

Aging↗