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Biomedical subjects

M Carter

Publications and source records attributed to M Carter.

At least 37 records · Page 2Linked to original sources
PubMed1999

Acute promyelocytic leukaemia: a retrospective analysis of patients treated at St. Bartholomew's Hospital 1969-1995.

Seventy-two patients with acute promyelocytic leukemia (APML) were treated at St.Bartholomew's Hospital (SBH) over a 25-year period. Improvements in supportive care and the use of more intensive chemotherapy have led to an increase in the complete remission rate from 14 to 58%. Similarly, the median survival has increased from 3 weeks to 2 years; the median duration of remission, which was 7 months in 1974, has not yet been reached. There was also a significant difference in survival from first recurrence, compared with that of patients with other subtypes of acute myeloid leukemia. RT-PCR analysis on bone marrow samples from 14 patients confirmed the presence of the PML/RARA fusion; 13 of the 14 patients achieved 'molecular remission' after therapy. The one patient who remained persistently positive experienced recurrence within 4 months. In seven of the eight patients in whom the disease recurred, the translocation was identified by RT-PCR at the time of relapse, whilst in one patient it was noted 4 months prior to morphological recurrence. These results illustrate the improvement in prognosis that occurred over a 25-year period in patients with APML treated at a single centre.

Adult↗
PubMed1999

Renilla luciferase as a vital reporter for chloroplast gene expression in Chlamydomonas.

The use of luciferases as reporters of gene expression in living cells has been extended to the chloroplast genome. We show that the luciferase from the soft coral Renilla reniformis (Rluc) can be successfully expressed in the chloroplast of Chlamydomonas reinhardtii. Expression of the rluc cDNA was driven by the promoter and 5' untranslated regions of the atpA gene. Western analysis with an anti-Rluc antibody detected a single polypeptide of 38 kDa in the luminescent cells. This is 3 kDa larger than native Rluc, and suggests that translation of the chimeric mRNA begins at the atpA start codon, 29 codons upstream from the rluc start site. We also show that the luminescence of the transformants was sufficient to enable imaging of colonies using a cooled CCD camera.

5' Untranslated Regions↗
PubMed1999

Crooked tail (Cd) models human folate-responsive neural tube defects.

Genetic correlation of human neural tube defects (NTDs) with NTD genes identified in mouse may unravel predisposing complex traits for assessment of individual risk and treatment in clinical settings. Folic acid (FA) can reduce the recurrence of NTDs in human populations by as much as 50-70%, though the mechanism of this rescue is unknown. We examined whether Crooked tail ( Cd ), a mouse strain prone to exencephaly, could provide a genetic animal model for folate-responsive NTDs. The Cd locus was localized to a 0.2 cM interval of the Mouse Genome Database genetic map, identifying tightly linked markers for genotyping prior to phenotypic expression. In a controlled diet study, Cd was found to mimic closely the clinical response to FA. FA supplementation reduced the recurrence risk of Cd exencephaly by as much as 55%. This rescue was dose dependent and did not require subjects to be inherently folate deficient. Like the female predominance of NTDs in humans, female Cd embryos were most likely to display exencephaly and were more responsive than males to the FA rescue. Importantly, FA supplementation shifted the severity of Cd phenotypic expression from early embryonic lethality to longer survival, and reduced the incidence of NTDs. The Cd locus is distinct from the known genes associated with neurulation defects, and isolation of this gene will assist identification of biochemical, genetic and gender-dependent factors contributing to folate-responsive NTDs.

Animals↗
PubMed1999

Does acid suppression by antacids and H2 receptor antagonists increase the incidence of atrophic gastritis in patients with or without H. pylori gastritis?

Currently there is controversial evidence that suggests that the accepted incidence of atrophic gastritis of 1.2 to 3.3% in patients with Helicobacter pylori gastritis may be increased by the long-term suppression of acid by a proton pump inhibitor (omeprazole). The purpose of this study is to show whether lesser forms of acid suppression by antacids or H2 receptor antagonists may have an influence on the development of atrophic gastritis. The authors recently reported a study in which a cohort of 36 patients with symptoms of dyspepsia were followed clinically for a period of 7 to 19 years. In that report all subjects underwent upper endoscopy with two biopsy specimens each from the antrum and fundus, on at least two occasions, 7 to 19 years apart. A diagnosis of atrophic gastritis was based on the interpretation of these biopsies by two gastrointestinal pathologists. The presence of H. pylori colonization was determined by tissue sampling and by a campylobacter-like organisms test of the antrum. Of the 36 patients in the authors' previous report, 33 had adequate baseline and follow-up data on medications consumed throughout the period of the study. In their current report they now present the findings of a retrospective review in which they correlate the presence of atrophic gastritis with the sole use of antacids and H2 receptor antagonists throughout the period of the study. In the cohort of 33 patients evaluated from the previous report, the authors found that atrophic gastritis had developed in all 28 patients positive for H. pylori, and in none of the 5 patients negative for H. pylori (p < 0.0001). A retrospective analysis of this previously studied cohort of 33 patients revealed that the use of antacids and H2 receptor antagonists did not predict the development of atrophic gastritis in either H. pylori-negative or -positive subjects. In a retrospective analysis of a cohort of 33 patients followed for an average of 11.7 years, atrophic gastritis developed in H. pylori-positive but not in H. pylori-negative subjects, irrespective of the use and duration of antacids or H2 receptor antagonists.

Aged↗
PubMed1998

Analysis of ClC-2 channels as an alternative pathway for chloride conduction in cystic fibrosis airway cells.

Cystic fibrosis (CF) is a lethal inherited disease that results from abnormal chloride conduction in epithelial tissues. ClC-2 chloride channels are expressed in epithelia affected by CF and may provide a key "alternative" target for pharmacotherapy of this disease. To explore this possibility, the expression level of ClC-2 channels was genetically manipulated in airway epithelial cells derived from a cystic fibrosis patient (IB3-1). Whole-cell patch-clamp analysis of cells overexpressing ClC-2 identified hyperpolarization-activated Cl- currents (HACCs) that displayed time- and voltage-dependent activation, and an inwardly rectifying steady-state current-voltage relationship. Reduction of extracellular pH to 5.0 caused significant increases in HACCs in overexpressing cells, and the appearance of robust currents in parental IB3-1 cells. IB3-1 cells stably transfected with the antisense ClC-2 cDNA showed reduced expression of ClC-2 compared with parental cells by Western blotting, and a significant reduction in the magnitude of pH-dependent HACCs. To determine whether changes in extracellular pH alone could initiate chloride transport via ClC-2 channels, we performed 36Cl- efflux studies on overexpressing cells and cells with endogenous expression of ClC-2. Acidic extracellular pH increased 36Cl- efflux rates in both cell types, although the ClC-2 overexpressing cells had significantly greater chloride conduction and a longer duration of efflux than the parental cells. Compounds that exploit the pH mechanism of activating endogenous ClC-2 channels may provide a pharmacologic option for increasing chloride conductance in the airways of CF patients.

Cell Line↗
PubMed1998

Recovery of function processes in human amnesia: evidence from transient global amnesia.

There are few clues as to the processes that underlie recovery of function from human amnesia. Evidence is offered from the perspective of a study of recovery of function during an episode of transient global amnesia (TGA) that occurred as a complication of a cerebral angiographic procedure being carried out in a neurosciences centre, and where there was therefore a unique opportunity to examine acute changes in memory function. This allowed us to conduct the first quantitative study where shrinkage of anterograde and retrograde memory loss was plotted at four separate intervals throughout the acute recovery process, and also 24 hr later. Recovery of retrograde amnesia preceded recovery from anterograde amnesia. Resolution of a naming deficit more closely paralleled recovery from retrograde amnesia rather than anterograde amnesia. Within retrograde amnesia for public events, there was a temporal gradient of memory loss, with more recent events affected to a greater degree than earlier events. Within anterograde amnesia, picture recognition memory preceded recovery of story recall memory. On the basis of these findings, and related observations in the published literature, it is proposed that recovery from some types of human amnesia, such as that associated with TGA, follows a 'lateral-to-medial' rule--lateral inferotemporal areas that play a major role in retrograde amnesia recover first from hypometabolism related to the TGA attack, followed by 'interface' areas such as the rhinal and parahippocampal cortices that are considered to have a role in both anterograde and retrograde memory functioning, with the last areas to recover physiological integrity being discrete limbic-diencephalic structures such as the hippocampus.

Adult↗
PubMed1998

Association of sensitization to Alternaria allergens with asthma among school-age children.

BACKGROUND: Molds in the Alternaria genus, normally found on outdoor vegetation, produce some of the most common fungal allergens to elicit a skin test response. OBJECTIVES: The objectives of this study were to evaluate a serum assay for IgE antibodies to Alternaria allergens and to establish the prevalence of sensitization to Alternaria allergens among children and adults enrolled in epidemiologic studies of asthma. In addition, the significance of sensitization to Alternaria allergens as a risk factor for asthma was compared with that of sensitization to indoor allergens or pollens. METHODS: Using the Pharmacia Capsulated Hydrophobic Carrier Polymer (CAP) system, we have evaluated the significance of Alternaria allergens by using sera from several epidemiologic studies of asthma. RESULTS: Comparisons between serum assays and skin test results suggest that this in vitro assay yields results similar to those for traditional RASTs and is as sensitive as skin prick testing. In each of the groups studied, sensitization to Alternaria allergens was more common among asthmatic than control subjects, and in two studies the relationship was highly significant. Alternaria allergens were significantly associated with asthma in middle schools in Charlottesville, Virginia and Los Alamos, New Mexico but not in Albemarle County, Virginia. Logistic regression analysis of the results for the three schools identified an association between sensitization to Alternaria allergens and asthma independent of, but not as strong as, that found between sensitization to indoor allergens and asthma (p < 0.001). CONCLUSIONS: The Pharmacia CAP system is a useful tool for measuring specific IgE to Alternaria allergens. Although not as important as sensitization to dominant local indoor allergens, sensitization to Alternaria allergens appears to be a significant independent risk factor for asthma in children in some locations of the United States.

Adolescent↗
PubMed1998

A strategic information system to facilitate the use of performance indicators in hospitals.

Hospital management teams receive voluminous data from a wide variety of sources, but are unable to distill the essential data they require to make good decisions. We have used a methodology which helps teams define and use important management data coupled with an information system that makes this data accessible. Results of our evaluation indicate that the process of developing a balanced scorecard (BSC) indicator system helps management teams to define meaningful strategic objectives and measurable performance indicators. The framework combined with the information acts as an integrating force, providing a shared understanding of the unit's goals. We conclude that a customized decision support system which integrates multiple measures in a BSC framework is a powerful tool for enabling complex decision making by a management team.

Canada↗
PubMed1998

Grip strengths and required forces in accessing everyday containers in a normal population.

OBJECTIVE: A commonly adhered to operating principle in occupational therapy clinics is that a person must exhibit 20 lb of grip strength before his or her hand is considered "functional." This study examined the relationship between hand and finger grip performances with the forces required to open common household containers. METHOD: The grip and pinch strengths of 49 college students were obtained using dynamometry. The forces required to open six common household containers were measured using Force Sensing Resistors attached to each container. RESULTS: Weak correlations were found (r = -.179 to r = .333) between grip and pinch strength performances and the forces used to operate the accessing mechanisms of the containers. Analyses of variances demonstrated significantly greater grip and pinch strength performances in men than in women (ps < .05) but no significant difference between the genders in the forces generated to open the containers (ps > .05). CONCLUSIONS: In a normal population of college students, the premise that greater hand strength affords greater performance in accessing everyday household containers was not supported. Implications suggest that grip and pinch dynamometry are not conclusive evaluative tools for predicting hand function while opening a select group of containers. The relationship between traditional dynamometry and hand performance during a variety of functional tasks needs to be examined in clinical populations as well.

Activities of Daily Living↗
PubMed1998

Hospital management decision support: a balanced scorecard approach.

Hospital management teams receive voluminous data from a wide variety of sources, but are unable to distill the essential data they require to make good decisions. We have used a methodology, which helps teams define and use important management data coupled with an information system that makes this data accessible. Results of our evaluation indicate that the process of developing a Balanced Scorecard indicator system helps management teams to define meaningful strategic objectives and measurable performance indicators. The framework combined with the information acts as an integrating force, providing a shared understanding of the unit's goals. We conclude that a customized decision support system, which integrates multiple measures in a balanced Scorecard framework, is a powerful tool for enabling complex decision making by a management team.

Cardiovascular Diseases↗
PubMed1997

Human type I cytokeratin genes are a compact cluster.

A YAC clone (211F11) containing approximately 0.5 Mb of human DNA was isolated from a human genomic library by PCR-based screening with cytokeratin (KRT) 13-specific primers. The YAC clone was mapped by FISH to the long arm of chromosome 17 (17q12-->q21), a region to which several other type I KRT genes had been mapped previously. We now show by Southern blot hybridization and PFGE analyses that KRT13, 14, 15, and 16 are all contained within YAC clone 211F11. Long-range restriction mapping analysis of clone 211F11 and of two smaller YAC clones that were also isolated with KRT13-specific primers, suggests that KRT13, 14, 15, 16 and their linked type I genes KRT17 and 19, are contained in less than 150 kb of genomic DNA. According to our reconstruction it then appears that at least six type I KRT genes are arranged in a highly compact cluster. The three YACs reported in this study represent a new tool to dissect the molecular structure of the locus of the human type I KRT genes.

Base Sequence↗
PubMed1997

Three-year trials of personal therapy among schizophrenic patients living with or independent of family, I: Description of study and effects on relapse rates.

OBJECTIVE: The study of individual psychotherapeutic approaches to the treatment of schizophrenia has yielded equivocal findings, partly because of methodologic problems. Further, the ability of psychosocial treatments to prevent psychotic relapse appears to lessen over time. The authors' goal was to develop and test a demonstrably effective individual therapy for schizophrenia. METHOD: Using a study design that addressed previous methodologic issues, the authors evaluated personal therapy specifically designed to forestall late relapse in patients with schizophrenia. They evaluated the effectiveness of personal therapy over a period of 3 years after hospital discharge among 151 patients with schizophrenia or schizoaffective disorder diagnosed according to Research Diagnostic Criteria. The patients were randomly assigned to receive either personal therapy or contrasting therapies in one of two concurrent trials. One trial studied patients who were living with family (N = 97); the other studied patients who were living independent of family (N = 54). RESULTS: All of the patients had extensive psychiatric histories, but only 44 (29%) experienced recurrent psychotic episodes over the 3-year study period, and only 27 (18%) prematurely terminated the study; most of those who left the study were in the no-personal-therapy conditions. Among patients living with family, personal therapy was more effective than family and supportive therapies in preventing psychotic and affective relapse as well as noncompliance. However, among patients living independent of family, those who received personal therapy had significantly more psychotic decompensations than did those who received supportive therapy. CONCLUSIONS: Personal therapy had a positive effect on adverse outcomes among patients who lived with family. However, personal therapy increased the rate of psychotic relapse for patients living independent of family. The application of personal therapy might best be delayed until patients have achieved symptom and residential stability.

Adolescent↗
PubMed1997

Three-year trials of personal therapy among schizophrenic patients living with or independent of family, II: Effects on adjustment of patients.

OBJECTIVE: Previous analyses of the personal and social adjustment of outpatients with schizophrenia have either relied on the assessment of unrepresentative patients who survived without relapse or used analyses that included relapse assessments, a potential confound when different rates of relapse existed among treatment conditions. The authors' goal was to conduct a study of the effects of personal therapy on outcome that was designed to take into consideration the effects of relapse. METHOD: They evaluated the effectiveness of personal therapy over 3 years after hospital discharge among 151 patients with schizophrenia or schizoaffective disorder. The patients were randomly assigned to receive personal therapy or contrasting therapies in one of two concurrent trials. One trial included patients who were living with family (N = 97); the other included patients who were living independent of family (N = 54). Patients were assessed at 6-month intervals over 3 years of treatment on measures of personal and social adjustment; patients who relapsed and restabilized and those who did not relapse were included. RESULTS: Personal therapy had positive effects on broad components of social adjustment (role performance) but had few differential effects on symptoms, and patients receiving personal therapy remained more anxious than patients who received family or supportive therapy. For patients who were living with family, personal therapy led to better outcomes in overall performance than did the other treatments. Although family therapy had only one positive effect on patients' social adjustment, the personal adjustment (residual symptoms) of patients who received family therapy appeared to improve more than that of patients receiving personal or supportive therapy. For patients not living with family, personal therapy was more successful than supportive therapy in improving work performance and relationships out of the home. Longitudinal effects of personal therapy on symptoms were similar to those of family and supportive therapies, particularly in the first 2 years, but personal therapy effect sizes increased over time on measures of social adjustment. CONCLUSIONS: Personal therapy has pervasive effects on the social adjustment of patients with schizophrenia that are independent of relapse prevention. Supportive therapy, with or without family intervention, produces adjustment effects that peak at 12 months after discharge and plateau thereafter. However, personal therapy, a definitive psychosocial intervention, continues to improve the social adjustment of patients in the second and third years after discharge. Brief treatment would appear to be less effective than a long-term, disorder-relevant intervention for schizophrenia.

Adaptation, Psychological↗
PubMed1997

Differentiation of achalasia from pseudoachalasia by computed tomography.

OBJECTIVES: The purpose of this study was to determine the computed tomography (CT) findings in idiopathic achalasia and in the pseudoachalasia of malignancy. METHODS: We identified 12 patients with the manometric diagnosis of achalasia who also had CT scans available for review: eight had idiopathic achalasia, and four had pseudoachalasia. As controls, we selected nine patients with endoscopically obvious esophageal cancer who also had CT scans. The CT scans were blindly reviewed to determine esophageal wall thickness, symmetry of the esophageal wall, presence of esophageal dilation or mass, and a radiological diagnosis. RESULTS: Six of the eight patients with achalasia had a dilated esophagus. Five had symmetric wall thickening >5 mm (range 7-10 mm) at the gastroesophageal junction. One patient with a 10-mm wall thickening was incorrectly diagnosed with a mass. All others were correctly diagnosed with achalasia. Three of the four patients with pseudoachalasia had esophageal dilation. Two had an obvious esophageal mass. The other two were given an indefinite diagnosis: one had asymmetric wall thickening (11 mm) at the gastroesophageal junction, and the other had symmetric thickening of 18 mm. Eight of the nine patients with obvious esophageal cancer had a mass on CT; the other patient had asymmetric wall thickening of 6 mm at the gastroesophageal junction and was given an indefinite diagnosis. CONCLUSIONS: Most achalasia patients have CT findings of esophageal dilation and mild, symmetric wall thickening. Therefore, symmetric esophageal wall thickening (<10 mm) should not dissuade one from the diagnosis of achalasia. Most pseudoachalasia patients have CT findings of esophageal dilation, more marked and/or asymmetric wall thickening, or mass. In this group, asymmetric or marked thickening (>10 mm) indicated pseudoachalasia. Therefore, CT can be helpful in differentiating between achalasia and the pseudoachalasia of malignancy.

Adenocarcinoma↗
PubMed1997

Experiences of a nursing ethics forum. Case studies and outcomes.

Nursing staff members should need few rules and should focus on using critical thinking to guide nursing practice and care. Nurses are decision makers participating in collaborative practice. A high degree of professionalism, responsibility, and accountability is expected. We feel that this program has succeeded not only in meeting the mission and vision of the department of nursing but also that of the hospital. It also has developed to promote the philosophy that nurses must be committed to providing excellence in patient care. In addition to developing this group concept as a model, our intention is to assist staff members with the continued expansion of the group and its tenets. As Uustal asserted, the knowledge of ethical theories and principles can stimulate the nurse's thinking, and ethical decision making can offer direction; however, only you can make ethical decisions. We hope to continue the development of clinical, ethical decision-making skills and to promote the value of this program to the ongoing growth and development of professionalism in nursing.

Decision Making↗
PubMed1996

Intensive chemotherapy for adult acute lymphoblastic leukaemia given with or without granulocyte-macrophage colony stimulating factor.

Twenty-six patients with newly diagnosed ALL (age range 15-49 years, median 32 years) received treatment comprising: cycles 1 and 2: adriamycin 30 mg/m2 days 1-3, vincristine: 2 mg days 1, 8, and 15, with prednisolone 40 mg daily, given until complete remission (CR). L-asparaginase 10000 units/m2, days 1-14, was given only with the first cycle. Cycle 3 consisted of 100 mg/m2 etoposide orally, days 1-5, and 1 gm/m2 bd cytosine arabinoside (ara-C) days 1-5. Cycles 1-3 were then repeated. Intrathecal methotrexate (MTX) 12.5 mg was given on day 1 of each treatment cycle. The first 12 consecutive patients received this chemotherapy alone, the subsequent 14 received, in addition, 3 micrograms/kg GM-CSF subcutaneously, from day 4 of cycles 1,2,4 and 5 (and from day 6 of cycles 3 and 6) until the absolute neutrophil count had reached 0.5 x 10(9)/1. All patients in whom CR was achieved then received prophylactic cranial irradiation. With the exception of those with T-ALL, this was followed by oral maintenance therapy consisting of 6-mercaptopurine, MTX, and cyclophosphamide for 3 years. Patients receiving GM-CSF did not have shorter intercycle times or a lower incidence of documented infections than those who did not receive it. The CR rate was 89% overall-uninfluenced by GM-CSF, but higher than that achieved previously at St Bartholomew's Hospital in an equivalent age-group.

Adolescent↗
PubMed1995

Mutagenesis of the H-ras p21 at glycine-60 residue disrupts GTP-induced conformational change.

The function of Gly-60, the conserved glycine in the DXXG domain of v-H-ras, was examined by site-directed mutagenesis. It was found that while the G60A (Gly-60 to Ala substitution) mutation has little effect on the interaction of H-ras with guanine nucleotides, it completely abolishes the biological activity of v-H-ras. The G60A mutation also exerts little effect on the interaction of H-ras with SDC25C (a guanine nucleotide exchange factor) and GAP. However, the G60A mutation does lower the ability of H-ras to bind Raf. GTP induces an enhancement of fluorescence emission in complexes consisting of H-ras and the fluorescent dye 8-anilino-1-naphthalenesulfonic acid. This enhancement is blocked by the G60A mutation. On the basis of these observations, we propose that the GTP-induced conformational change of H-ras, a process required for H-ras activities, is impaired by the G60A mutation.

3T3 Cells↗