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Biomedical subjects

R Morice

Publications and source records attributed to R Morice.

At least 19 recordsLinked to original sources
PubMed2006

[Acquired long QT syndrome: a dominant problem?].

QT prolongation is essentially of pharmacologic origin. It is principally linked to a block of the outward potassium current Ikr, with as a consequence a prolongation of the repolarisation causing early after potentials and re-entry. The term "repolarisation reserve" expresses the variable risk of arrhythmia among individuals under the same drug blocking Ikr. This reserve can be altered under various pathologic or genetic conditions. A series of risk factors (bradycar-Torsades de pointes} were described in 1966 by Dessertenne. They are due to a perturbation of ventricular repolarisation causing QT prolongation on surface ECG. Acquired dia, electrolytic disorders, cardiac disease, neurologic disorders, nutrition troubles, female gender) can play a role as well as the metabolic processing of pharmacological agents by Cytochrome P450 and various inhibitors or inductors of this system which can influence the half life of drugs. The list of drugs involved is continuously increasing: antiarrhythmics, antihistamines, psychotropics, anti-infectious are the main categories involved. Risk prediction is difficult particularly for non cardiovascular drugs and a low risk incidence. An other risk is to exclude patients from the benefit of an efficient drug for a serious but not frequent risk, at last an industrial risk for the manufacturer when a drug is withdrawn lately when important quantities of money have already been invested for its development. The diagnosis of torsades is easy on standard ECG although QT measurement and its heart rate variation remain uneasy. The treatment of the arrhythmias is based on heart rate acceleration by Isoprenaline or intravenous pacing and on intravenous administration of magnesium.

Adrenergic beta-Agonists↗
PubMed1998

Expression of heterogeneous nuclear ribonucleoprotein A2/B1 in bronchial epithelium of chronic smokers.

The monoclonal antibody 703D4, which binds heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNP A2/B1), has been reported to detect lung cancer more than a year earlier than routine chest X-ray or cytomorphology. To explore the biological basis of this detection, we studied the expression of this antigen in the central airways of smokers with evidence of bronchial metaplasia using specimens from a previously reported, randomized retinoid chemoprevention trial. By analyzing 1078 available biopsy specimens from 147 individuals at baseline and 68 individuals who completed the intervention, we frequently detected overexpression of hnRNP A2/B1 in normal and abnormal bronchial epithelium (i.e., in 41% of normal and 37% of squamous metaplasia samples). There was no correlation between hnRNP A2/B1 overexpression and the different histological changes. In cases with hnRNP A2/B1 overexpression, immunoreactivity was homogeneously expressed in all biopsied sites. For the 68 cases with serial biopsies, there was no significant modulation of hnRNP expression by retinoid intervention or smoking status. With lung cancer cell lines, 0.5-4 microM concentrations of 13-cis-retinoic acid reduced hnRNP A2/B1 overexpression by immunocytochemistry. We conclude that hnRNP A2/B1 overexpression is frequently found in central airways of chronic smokers, consistent with the pattern of expression that we reported previously in airways surrounding resected primary lung cancers. Oral 13-cis-retinoic acid at a dose of 1 mg/kg has no demonstrable effects on modulating hnRNP A2/B1 expression in proximal bronchial epithelium.

Biomarkers, Tumor↗
PubMed1996

Frontal/executive impairments in schizophrenia.

A study of frontal/executive impairments in schizophrenia is reported. Schizophrenia patients and controls were not significantly different with respect to age, sex, and premorbid IQ. The schizophrenia group demonstrated significant impairments in cognitive flexibility and forward planning, replicating results from a 1990 study by Morice. Impairment prevalence figures of 65 and 76 percent for cognitive flexibility and forward planning, respectively, were demonstrated. Several tests for short-term memory were administered. Schizophrenia patients were not found to be impaired on tests of simple, or primary, short-term memory as measured by Digits Span Forward and Words Span Forward, but they were found to be significantly impaired compared with controls on two tests of working memory, Alphabet Span and Sentence Span. Using a cutoff derived from the mean score for the controls, 65 percent of schizophrenia patients proved to be impaired on Sentence Span. A total of 16 (94%) were impaired on one or more of the three tests of executive functioning used. The effects of IQ on test results were examined, and impairment of cognitive flexibility and forward planning seemed to occur regardless of whether premorbid IQ had been preserved or had deteriorated. However, working memory impairments occurred in the subgroup of schizophrenia patients demonstrating a substantial fall in IQ from premorbid levels. The ability to process increasingly complex information was addressed by a more detailed examination of the Tower of London results. There were no differences in performance between groups for the first three levels of complexity (1-3 moves), but significant, and increasing, differences emerged for the last three levels (4-6 moves). These results were taken to support the hypothesis that schizophrenia represents a loss of, or a failure to acquire, the ability to process complex information. Impairments of executive functions that could affect complex information processing could have implications for schizophrenia rehabilitation.

Adult↗
PubMed1996

Rehabilitation of frontal/executive impairments in schizophrenia.

OBJECTIVE: A relatively high prevalence of deficits in cognitive flexibility, working memory and planning ability has been reported in schizophrenia patients. The objective was to develop a rehabilitation training program in an attempt to improve these specific cognitive functions. METHODS: The deficits in cognitive flexibility, working memory and planning ability were interpreted as reflecting executive cognitive processing impairments secondary to prefrontal neural system dysfunction. Following the 'process specific' approach, it was considered important to develop tasks that hypothesised the exercise of these cognitive abilities and the more molecular information processes thought to be fundamental to these abilities. Care was taken to ensure that all tasks involved the practice of processes thought to activate frontal/prefrontal neural systems. Attentional, visual, verbal, conceptual, motor and fine motor tasks were considered important for each process area in order to involve as many functional modalities as possible. RESULTS: A program comprising cognitive shift, working memory and planning modules was developed. Conducted over 11 weeks, four modules were of 2 weeks' duration, and the fifth of 3 weeks' duration. Four individual 1 hour training sessions were conducted each week. Core elements of the modules are described. CONCLUSION: Consisting predominantly of pencil and paper information processing exercises, all of the training exercises are presented in the volumes of the Frontal/Executive Program. The program appears to be user-friendly with therapists now successfully delivering the program, in its entirety, to schizophrenia patients. Should future studies replicate preliminary findings of improved neurocognitive performance following training with the program, such findings would have important implications for the treatment of schizophrenia.

Cognition Disorders↗
PubMed1994

Effects of dobutamine on oxygen transport and consumption in the adult respiratory distress syndrome.

OBJECTIVE: To determine if oxygen consumption (VO2) in patients with adult respiratory distress syndrome (ARDS) is dependent on, and thus limited by, oxygen transport (TO2) rather than O2 demand. DESIGN: Prospective study. SETTING: Intensive care unit of a tertiary referral center. PATIENTS: 12 patients with ARDS and sepsis syndrome. INTERVENTIONS: Routine intensive care unit monitoring including pulmonary and radial artery catheters. MEASUREMENTS: Dobutamine was used to increase cardiac output, thereby directly varying TO2 under conditions of constant O2 demand. After baseline measurements of TO2 and VO2, dobutamine was infused intravenously at progressively increasing doses of 5, 10, 15 and 20 micrograms/kg/min and measurements of TO2 and VO2 were repeated after 30 min at each dose. RESULTS: Dobutamine increased TO2 in 8 of the 12 patients, by 29% at 5 micrograms/kg/min and by 45% (net) at 10 micrograms/kg/min, but not at higher doses. In these 8 patients dobutamine also increased VO2 by 15% at 5 micrograms/kg/min, but did not further increase VO2 at higher doses. There was no correlation between baseline blood lactate concentration and the response of either TO2 or VO2 to dobutamine. CONCLUSIONS: In some but not all patients with ARDS and sepsis syndrome, short-term infusion of low-dose dobutamine can increase both TO2 and VO2. Achievement of a TO2-independent level of VO2 could not be convincingly demonstrated in any individual patient. The response of TO2 and VO2 to dobutamine could not be predicted from baseline blood lactate concentration. Determination of the impact on patient outcome of a more prolonged infusion of dobutamine requires further study.

Adult↗
PubMed1993

Specific cognitive flexibility rehabilitation in schizophrenia.

A Cognitive Shift neurocognitive training module was developed in the attempt to ameliorate cognitive flexibility deficits in chronic schizophrenic patients. A procedural training approach hypothesized the exercise of specific neural network processes, identified from theories of frontal and prefrontal lobe functioning. Three male patients who underwent the intensive program demonstrated significant gains in Wisconsin Card Sorting Test performance, gains that were maintained at a six month reassessment. Expanded Brief Psychiatric Rating Scale (a measure of symptomatology) and Life Skills Profile (a measure of daily functioning) measures showed smaller improvements. The ability to improve cognitive flexibility could have important implications for the treatment of schizophrenia.

Adult↗
PubMed1993

Squamous metaplasia of the bronchial mucosa and its relationship to smoking.

We performed flexible fiberoptic bronchoscopy (FFB) on 106 heavy cigarette smokers. Six bronchial biopsy specimens, obtained from the carina and five major bronchi, were screened for squamous metaplasia. Individual biopsy specimens were sectioned into 4-microns sections, and a metaplasia index (MI), or percentage of sections containing squamous metaplasia, was determined. Metaplasia was noted at one or more biopsy sites in 66 of 99 subjects (seven were excluded from the analysis). Twenty-five percent of the subjects showed metaplasia at three or more biopsy sites, and one subject had metaplasia on all six biopsy specimens. The presence of squamous metaplasia varied from 40.4 percent in the right lower lobe to 15.3 percent in the left upper lobe. The subjects were grouped into simple categories based on the number of packs smoked per day and the pack-year history of smoking. Subjects who smoked more than two packs per day (n = 11) had the highest MI (37.4 +/- 4.9 percent, mean +/- SEM). Fifty-seven subjects smoked more than one pack per day but fewer than or equal to two packs per day, and they had a mean MI of 22.3 +/- 2.9 percent. Subjects who smoked one pack per day or less (n = 31) had a mean MI of only 12.9 +/- 2.8 percent. The MI of those who smoked more than two packs per day was significantly greater than the MI of those who smoked one pack per day or less (p < or = 0.003). While the MI varied from 12.9 +/- 3.5 percent in subjects who had smoked less than 20 pack-years to a maximum of 29.1 +/- 4.5 percent in those who had smoked greater than 60 pack-years, no statistically significant difference was detected between these two groups. Thus, we conclude that heavy tobacco use is associated with important alterations of bronchial mucosa. Furthermore, the intensity of tobacco use (packs per day) rather than the number of pack-years appears to be the more important factor in promoting squamous metaplasia of the bronchial mucosa.

Adult↗
PubMed1992

A phase II study of interleukin-2 and interferon-alpha in head and neck cancer.

The capacity to modulate host response against metastatic head and neck cancer may eventually lead to improved survival. This phase II study in patients with advanced head and neck cancer evaluated the efficacy of combination systemic recombinant interleukin-2 (IL-2) and interferon-alpha (INF-a) and evaluated laboratory correlates between tumor response and a) tumor differentiation and b) NK cell activation. Five of fourteen patients responded; two had partial responses and three had transient responses (one complete and two partial, each lasting less than four weeks). Patients that responded had relatively lesser tumor burden and poorly-differentiated metastases. No response was observed in those few individuals in whom natural immune function was only minimally enhanced by therapy. Major toxicity, including but not limited to fever, fatigue and pulmonary compromise, allowed only 3 of 14 patients to complete three cycles of therapy. This preliminary phase II study shows that combination IL-2/INF-a therapy has clinical anti-tumor activity and that the level of NK cell activation and the degree of tumor differentiation may correlate with response.

Adult↗
PubMed1991

Miliary pulmonary infection caused by Mycobacterium terrae in an autologous bone marrow transplant patient.

A 64-year-old woman with ovarian carcinoma that had been treated with high-dose chemotherapy and autologous bone marrow transplantation presented with a maculopapular rash on the extremities and miliary infiltrates evident on chest roentgenogram. Transbronchial biopsy specimens revealed caseating granulomas, and cultures grew Mycobacterium terrae. Six weeks after therapy with isoniazid, rifampin, and pyrazinamide was begun, her rash and pulmonary infiltrates had cleared, despite the in vitro resistance to these drugs and continued spread of her carcinoma. This case suggests that spontaneous resolution may be part of the natural history of M terrae infections.

Bone Marrow Transplantation↗
PubMed1990

Cognitive inflexibility and pre-frontal dysfunction in schizophrenia and mania.

The ability to shift cognitive set, which is probably subserved, at least in part, by the pre-frontal cortex, was determined for schizophrenic, bipolar (manic) and control subjects, using the Wisconsin Card Sorting Test (WCST). The schizophrenic and manic subjects both demonstrated poor performance on the WCST, suggesting that cognitive inflexibility and/or pre-frontal dysfunction, is not specific to schizophrenia (although laterality differences could exist). Moderate levels of poor performance in the non-psychiatric control group suggest the need for a review of the cut-off figures in the WCST currently used for predicting 'brain damage' and 'focal frontal involvement', especially given the trend for the increasing use of cognitive assessment and rehabilitation in the major psychoses.

Adult↗
PubMed1986

Language changes in schizophrenia: a limited replication.

Similar changes in the spoken language of schizophrenic patients were demonstrated in two separate studies. Schizophrenic patients used less depth of clausal embedding and fewer reduced relative clauses; they uttered more semantically deviant sentences and were more dysfluent than either manic patients or control subjects. They appeared to demonstrate a language impairment characterized especially by reduced syntactic complexity. Four linguistic variables in a discriminant analysis produced an overall diagnostic confidence for schizophrenia in "grouped" subjects of 87 percent, replicating at 83 percent for "ungrouped" subjects from a separate study. These results demonstrate the stability of language changes in schizophrenia, together with acceptable levels of diagnostic sensitivity and specificity. Currently, the possible diagnostic utility of language analysis is constrained by its time-consuming nature. The issue of whether the language changes represent a specific (linguistic) or general cognitive impairment is being addressed in a second phase of the current study.

Adult↗
PubMed1986

Beyond language--speculations on the prefrontal cortex and schizophrenia.

Changes to the structural complexity of the spoken language of schizophrenic patients have been demonstrated in three recent studies. The speculation is offered that these changes could result from dorsolateral prefrontal cortical dysfunction. Impairment of the executive functions of this part of the brain could theoretically explain both the varied symptomatology of schizophrenia and its unique pattern of ages of onset.

Age Factors↗
PubMed1985

The comprehension and production of complex syntax in schizophrenia.

A new and syntactically more complex version of the Token Test was developed to investigate the comprehension of complex syntax in schizophrenia. Results suggested that schizophrenic patients as a group demonstrated an impairment of comprehension proportionate to a reduction in the syntactic complexity of their spoken language, which had been demonstrated in two separate studies. While manic patients also recorded poorer results on the new Token Test than control subjects, there were no significant correlations between their comprehension and production measures as there were for the schizophrenic patients. The speculation is made that manic patients may perform poorly because of state factors such as distractibility, while schizophrenic patients may do so because of an underlying language impairment.

Bipolar Disorder↗
PubMed1985

The Premorbid Adjustment Scale (PAS): its use in an Australian study.

The Premorbid Adjustment Scale (PAS) is a new premorbid scale for use in schizophrenia, developed by the National Institute of Mental Health. Its use in a recent Australian study is described. While total scores clearly discriminated schizophrenic from manic patients, and good test-retest reliability was demonstrated for the schizophrenic patients, the scores did not predict duration of hospitalisation for the schizophrenic group, as reported in the North American study. It is concluded that more research on the PAS is necessary before it can be accepted as a useful instrument in schizophrenia research and clinical practice.

Adult↗