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Biomedical subjects

M Moran

Publications and source records attributed to M Moran.

At least 73 records · Page 4Linked to original sources

Predictors of outcome after anterior temporal lobectomy: the intracarotid amobarbital test.

The intracarotid amobarbital test (IAT) examines hemispheric memory and language. We set out to determine whether memory performance on the IAT correlated with seizure relief after anterior temporal lobectomy in 117 patients with refractory epilepsy. The IAT assessed recognition memory performance for nine items with correction for false-positive recognitions. We then compared performance of one hemisphere with that of the other, defining a correctly lateralized memory deficit as worse performance when using the hemisphere containing the operated temporal lobe than when using the other hemisphere. The analysis included concurrent factors that might also affect outcome, such as age at first risk for epilepsy, presence or absence of tumor, and Full Scale IQ. A discriminant function analysis demonstrated that patients with a correctly lateralized memory deficit on the IAT had an increased probability of being seizure-free following surgery after controlling for other predictors. The performance of the nonoperated temporal lobe related to outcome, although less strongly. The magnitude of the difference in performance between the two hemispheres and the performance of the operated hemisphere did not relate to outcome. Patients who became seizure-free had an earlier age at first risk than did those with persistent seizures, and tumor presence weakly correlated with postoperative outcome. IQ did not correlate with outcome. We conclude that the IAT predicts seizure relief after anterior temporal lobectomy independent of other known risk factors we examined.

Adolescent↗

Leishmania major-like parasite, a pathogenic agent of cutaneous leishmaniasis in Paraguay.

Leishmania parasites isolated from two patients with cutaneous leishmaniasis from geographically different localities in Paraguay have been characterized by enzyme electrophoresis (zymodeme) and digestion profiles of kinetoplast DNA with restriction enzymes (schizodeme). Both Paraguayan isolates showed identical zymodeme profiles to each other using 14 enzymes (glutamic pyruvate transaminase, glutamic oxaloacetic transaminase, enolase, fumarate hydratase, glucose phosphate isomerase, glucose-6-phosphate dehydrogenase, malate dehydrogenase, malic enzyme, mannose phosphate isomerase, nucleoside phosphorylase, peptidase-D, 6-phosphogluconate dehydrogenase, phosphoglucomutase, and pyruvate kinase). Although two Paraguayan isolates showed different zymodeme profiles from those of six Leishmania reference strains of Old and New World Leishmania species, they showed identical zymodeme profiles to those of an L. major-like parasite from Ecuador. These observations were confirmed by schizodeme analysis using three restriction endonucleases (Msp I, Hae III, and Taq I). These results indicate that Leishmania parasites isolated in Paraguay are identified as an L. major-like parasite, and it is necessary to consider the existence of L. major-like parasites when classifying Leishmania isolates from the New World.

Alanine Transaminase↗

Clozapine in tardive dyskinesia: observations from human and animal model studies.

Clozapine has long been considered a useful treatment in patients who have schizophrenia with the neuroleptic-induced delayed-onset side effect tardive dyskinesia. We present data in support of the clinical impression using both an animal model of the disorder and dyskinetic patients themselves. Clozapine produces a lower rate of oral dyskinesia in laboratory rats after 6 months of chronic treatment than does haloperidol (8.6 +/- 1.3 vs. 13.6 +/- 1.4 vacuous chewing movements every 5 minutes, respectively), suggesting a lower propensity to cause tardive dyskinesia. In the human, when clozapine was compared with haloperidol in the treatment of patients with tardive dyskinesia, clozapine produced significantly greater benefit for motor symptoms after 12 months of treatment than did haloperidol (p < .001). Moreover, the dyskinesia rebound, which occurred equally in both drug groups at the beginning of the study, was sustained in the haloperidol group but lost in the clozapine-treated patients. These data suggest that dyskinetic patients lose their symptoms of tardive dyskinesia, along with dopaminergic hypersensitivity, with long-term clozapine treatment.

Adult↗

Continuous passive motion stimulates repair of rabbit knee articular cartilage after matrix proteoglycan loss.

Continuous passive motion facilitates repair of full-thickness defects in the articular cartilage in rabbits. Studies were conducted to determine whether continuous passive motion would similarly affect the repair process after injection of chymopapain into the rabbit knee. Adolescent rabbits were injected with chymopapain and then given intermittent active motion in the form of free cage activity or continuous passive motion of the injected knee. After injection of either 0.2 or 2 mg chymopapain into the knee, serum keratan sulfate levels rose sharply, indicating proteoglycan loss, and, in all cases, peaked at 24 hours between 200-800% of preinjection levels. Importantly, serum keratan sulfate levels were significantly elevated within 1 hour when joints were submitted to immediate continuous passive motion after the injection. As shown previously, injection of either 0.2 or 2 mg chymopapain into the knee, followed by intermittent active motion, resulted in a pronounced loss of proteoglycans by Day 2, partial restoration of proteoglycans by Day 9, continued proteoglycan synthesis by Day 21 in animals receiving the lower dose, and severe degenerative changes by Day 21 in animals receiving the higher dose. In all animals that received either high or low doses of chymopapain, as well as 2 days of intermittent active motion and then continuous passive motion, the articular cartilage surface was intact by Day 9, and replenishment of proteoglycans had occurred in pericellular and interterritorial areas. By Day 21, the surface of the articular cartilage was still intact, and replenishment of proteoglycans in loaded regions continued in all animals receiving either dose of chymopapain. These results indicate that a period of intermittent active motion followed by continuous passive motion of a chymopapain injected knee may protect and stimulate repair of the articular cartilage matrix after chymopapain-induced injury.

Animals↗

Biologic resurfacing of a major joint defect with cryopreserved allogeneic periosteum under the influence of continuous passive motion in a rabbit model.

Periosteal autografts have been widely used for biologic resurfacing of full-thickness articular cartilage defects in rabbits. This study examined the effect of donor and recipient age on biologic joint resurfacing using fresh and cryopreserved periosteal allografts in a rabbit model. The study also assessed the ability of cryopreserved periosteal allografts to undergo neochondrogenesis. Eighty New Zealand rabbits were divided into six groups receiving combinations of fresh or cryopreserved allografts. After all the grafts were secured with fibrin glue, the animals were subjected to two weeks of continuous passive motion followed by four weeks of cage activity or intermittent active motion. The rabbit knees were analyzed at six weeks by gross examination, histochemical staining, and collagen typing. No significant difference in chondrogenic potential between fresh and cryopreserved periosteal allografts was observed. Grafts obtained from adult donors were much less chondrogenic than those from adolescents, but adults recipients experienced reasonably good results when they received allografts from young donors. No evidence of rejection was found in any of the samples as late as six weeks after transplantation.

Aging↗

Effects of administration of ciliary neurotrophic factor on normal motor and sensory peripheral nerves in vivo.

Ciliary neurotrophic factor (CNTF) has a variety of effects on different neuronal populations in vitro, but little has been reported concerning its effects in vivo. This study examined the effects of CNTF administration on peripheral nerves both in young growing rats and in more mature animals. In both young and fully grown rats, CNTF stimulated levels of substance P and calcitonin gene related peptide in sensory spinal ganglia. In immature rats, CNTF increased compound nerve conduction velocity and motor nerve conduction velocity. By contrast, electrophysiological measurements were not affected in fully grown animals. There was a biphasic dose response to CNTF for the electrophysiologic changes with larger changes noted at a dose of 0.1 micrograms/g body weight than at a dose of 0.25 micrograms/g. There were no behavioral changes noted at either dose of the factor. These observations indicate that CNTF administration in vivo can influence neural physiology, and suggest that the factor may be useful for the treatment of disorders involving either sensory or motor peripheral nerves.

Aging↗

Psychosis proneness scales in schizophrenia spectrum personality disorders: familial vs. nonfamilial samples.

The authors evaluated the extent of overlap between DSM-III-R schizophrenia spectrum personality diagnoses (SSPD) and the Psychosis Proneness Scales of Chapman and his associates. The subjects were recruited from the family members of schizophrenic patients ("familial" subjects; n = 45) and members of the community with negative family histories for schizophrenia ("nonfamilial" subjects; n = 60). Clinical interviews were performed to obtain DSM-III-R Axis I and II diagnoses. In 105 individuals with no Axis I diagnosis, the five Chapman Scales were administered. The results suggest that the nonfamilial subjects with diagnoses of SSPD (n = 24) scored significantly higher on the Chapman Scales of Magical Ideation, Perceptual Aberration, and Impulsive Nonconformity compared with the familial SSPD subjects and the other non-SSPD groups. The familial SSPD subjects (n = 17) scored significantly higher than the nonfamilial, non-SSPD groups on the Physical Anhedonia Scale. Scores on the Social Anhedonia Scale were highest in the SSPD subjects, but only scores for the nonfamilial SSPD subjects were statistically different from those for the other non-SSPD groups. The data were reanalyzed by first dividing the scores from the Chapman Scales into high and low scores based on different cutoff points. Sensitivities, specificities, and predictive powers of the "high" Chapman scores for SSPD diagnoses were then calculated. These were done because the Chapman Scales are often used to identify individuals with schizophrenia-related personality disorders on the basis of scores that exceed arbitrary cutoff points. The results suggest that the Chapman Scales (other than the Physical Anhedonia Scale) and DSM-III-R criteria identified mostly the same subjects, when only nonfamilial subjects were considered (with sensitivities and specificities of about 0.70). However, the overlap between these two constructs was poor when only schizophrenia spectrum subjects recruited from the family members of schizophrenic patients were considered.

Adult↗

Effects of systemic indomethacin, meclizine, and BW755C on chronic ultraviolet B-induced effects in hairless mouse skin.

Chronic exposure of hairless mice to ultraviolet B (UVB) radiation is associated with inflammation as well as an altered macromolecular composition of the dermis. This study was designed to determine whether or not various systemic anti-inflammatory agents inhibit chronic UVB-induced changes in the macromolecular content of the dermis and, if so, whether each agent had the same or different effects. The agents and doses were chosen for their ability to inhibit the changes induced by a single exposure to UVB radiation (increased vasopermeability, neutrophil accumulation, and skin-fold thickness). Indomethacin, a cyclooxygenase inhibitor, and meclizine, an H1 histamine receptor antagonist, were administered from slow-release pellets. BW755C, a combined cyclooxygenase and lipoxygenase inhibitor, was administered intraperitoneally 30 min prior to UVB exposure. Animals were exposed to UVB three times per week for 20-26 weeks or were unirradiated. The elastin, glycosaminoglycan and collagen content of the skin were determined by measuring the desmosine, uronic acid, and hydroxyproline levels, respectively. The amount of each macromolecule per area of skin increased after chronic UVB exposure. The increase in desmosine was inhibited by indomethacin; the increase in hydroxyproline was inhibited by meclizine and BW755C. None of the agents inhibited the uronic acid increase. These results suggest that chronic inflammation contributes to the dermal changes seen in chronically UVB-exposed skin and that different inflammatory mediators are involved in the increases observed in elastin, glycosaminoglycans, and collagen.

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗

Psychiatric illnesses in families of subjects with schizophrenia-spectrum personality disorders: high morbidity risks for unspecified functional psychoses and schizophrenia.

OBJECTIVE: The authors determined morbidity risks for psychiatric illnesses in the families of probands with schizophrenia-spectrum personality disorders. METHOD: Subjects were recruited from the community through newspaper advertisements. Subjects were identified as having schizophrenia-spectrum personality disorders (N = 30) if they met at least three, four, or three DSM-III-R criteria for schizoid (N = 14), schizotypal (N = 20), and/or paranoid (N = 15) personality disorder, respectively. The comparison subjects had no psychiatric diagnoses (N = 8) or had other personality disorders (N = 12); none of the subjects in either group had any DSM-III-R axis I diagnosis. Trained interviewers collected family history information about the relatives of the two groups; the interviewers were blind to the probands' diagnoses. RESULTS: The risks for schizophrenia, other functional psychoses, and schizophrenia-spectrum personality disorders were significantly higher in the relatives of subjects with schizophrenia-spectrum personality disorders than in the families of the comparison subjects. CONCLUSIONS: The high rate of schizophrenia in the families of probands with schizophrenia-spectrum personality disorders is consistent with the previous findings of higher than normal rates of these personality disorders in the biological relatives of schizophrenic patients. The significance of the high rate of unspecified functional psychoses is unclear. Use of the family study method, by which valid differential diagnosis of psychoses is possible, is indicated. The results from the current study do not rule out the possibility that the schizophrenia-spectrum personality disorders are related to psychoses in general rather than specifically to schizophrenia.

Adult↗

GABA agonist-induced changes in motor, oculomotor, and attention measures correlate in schizophrenics with tardive dyskinesia.

Saccadic distractibility, Stroop color-word scores, and serial dyskinesia assessments were obtained on 10 schizophrenic patients with tardive dyskinesia during a pharmacologic challenge with placebo or 7 mg muscimol, a potent, direct-acting GABA agonist. Although no significant difference in the measures was evident between conditions, a significant correlation was found between GABA agonist-induced changes in saccadic distractibility and dyskinesia scores where no correlation existed between these measures on placebo. Improvement in saccadic distractibility was also correlated with reduction in attention performance, as measured by Stroop. These effects are not due to sedation. The correlation between dyskinesia and saccadic distractibility is consistent with a model of parallel motor and oculomotor cortico-striatal-thalamic circuits in humans. This work supports the hypothesis that a dysfunction in GABA-mediated neurotransmission may be the basis for tardive dyskinesia.

Adult↗

Between the lines.

Germany's successful healthcare system avoids the problems of rationing, access and patient choice which afflict both state and market-dominated systems. But problems of accountability, cost, and equity need to be tackled--the purchaser/provider split has been a recipe for expensive care, argues Michael Moran.

Ambulatory Care↗

Effect of the prostaglandin E1 analog enisoprost on glucose and lipid metabolism in patients with type II diabetes mellitus.

Short-term studies have suggested that analogs of prostaglandin E may have favorable effects on the carbohydrate and lipid metabolism in patients with type II diabetes mellitus. The present study was undertaken to investigate the long-term effects of a prostaglandin E1 analog on the regulation of glycemic control and plasma lipids. Twenty patients with type II diabetes received enisoprost, 300 mcg/day, for three months. Fasting serum glucose, glycosylated hemoglobin, insulin and C-peptide levels as well as triglyceride, total cholesterol, high density lipoprotein cholesterol and its subfractions, apolipoproteins B and AI and post-heparin lipoprotein lipase and hepatic triglyceride lipase activities were determined. During the first month, enisoprost treatment caused significant decreases in plasma glucose (baseline = 8.72 +/- 0.39 mmol/L, 4 week = 7.78 +/- 0.5 mmol/L, change = -0.94 +/- 0.28 mmol/L, p less than 0.01) and total cholesterol (baseline = 5.30 +/- 0.23 mmol/L, 4 week = 5.01 +/- 0.26 mmol/L, change = -0.28 +/- 0.06 mmol/L, p less than 0.05). The decrease in cholesterol level was due to a reduction in high density lipoprotein, specifically in high density lipoprotein2 fraction (baseline = 1.29 +/- 0.1 mmol/L, 4 week = 1.12 +/- 0.08 mmol/L, change = -0.018 +/- 0.04 mmol/L, p less than 0.05 for the former and baseline = 0.40 +/- 0.06 mmol/L, 4 week = 0.27 +/- 0.03 mmol/L, change = -0.12 +/- 0.03 mmol/L, p less than 0.05 for the latter): All of these values returned to the pretreatment levels despite continuation of enisoprost.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Abnormal electroretinography in schizophrenic patients with a history of sun gazing.

Electroretinographic (ERG) measurements were performed in 9 schizophrenic patients and in 13 control subjects. The measurements of schizophrenic patients as a group did not differ from those of normals. However, 6 schizophrenic patients who had a past history of sun gazing showed a decrease in retinal responsiveness under conditions of light adaptation. These results suggest that a subgroup of schizophrenic patients, who show deviant light-related behavior, have abnormal ERG. We postulate that an abnormality in retinal dopaminergic neurons, which are known to reduce light responsiveness of horizontal and ganglion cells, is the underlying pathophysiology of this clinical finding.

Adaptation, Ocular↗

A prospective evaluation of distal margins in carcinoma of the rectum.

The controversy regarding the ideal distal margin after a "curative" anterior resection is currently unresolved. To clarify this issue, a prospective study was undertaken. Two hundred and forty-three patients who underwent "curative" anterior resection were included in this study. Patients were divided into 1 centimeter groups based upon the length of the distal margin (from 0.0 to 8.0 centimeters), and recurrence, local and distant, and survival were analyzed. There was no significant difference in local or distant recurrence or survival when each centimeter interval was studied to 1 centimeter. Patients with a distal margin of less than 0.8 centimeter (group 1) had more frequent anastomotic recurrences (30 percent) when compared with patients (group 2) with a distal margin greater than 0.8 centimeter (10.5 percent; p = 0.01). Both groups were well matched for age, gender, tumor size, length of proximal margin, number of positive lymph nodes, histologic factors, grade of differentiation, Dukes' classification, type of operation, preoperative and postoperative radiotherapy, follow-up evaluation and surgeon. Both groups had a similar pelvic area recurrence (5.0 versus 8.7 percent, p = NS) and distance recurrence rates (10.0 versus 14.2 percent, p = NS). The five year survival rate was adversely affected by a distal margin of less than 0.8 centimeter (49.3 percent in group 1 and 67.5 percent in group 2; p = 0.01). The data suggest that a distal margin of 1 centimeter in the pathologic specimen is adequate distal clearance for most carcinomas of the rectum.

Adenocarcinoma↗

The growth hormone response to clonidine in acute and remitted depressed male patients.

The growth hormone (GH) response to clonidine was evaluated in 28 acutely depressed male patients, 17 remitted depressed patients, and 26 normal control subjects. The GH response to clonidine was blunted (delta less than 4 ng/ml) in a significantly increased proportion of both acute and remitted patients compared to control subjects. Covarying for age effects, the GH response to clonidine (as area-under-the-curve) was not significantly different between any of the three groups, but was significantly diminished in both the acute and remitted depressed patients who were ever hospitalized for an episode of depression, compared to control subjects. Six patients studied in both the acute and remitted states were blunted in both states. These findings could not be accounted for by other clinical and demographic variables including weight, time off antidepressants, severity of current depressive symptoms, and subtype of depression. These results raise the possibility that the blunted GH response to clonidine may represent a state-independent correlate of some forms of severe depression. Issues regarding the specificity and interpretation of this finding require further clarification.

Acute Disease↗

Magnetic resonance imaging in diagnosis of transient osteoporosis of the hip.

The results of magnetic resonance (MR) imaging in six patients with transient osteoporosis of the hip were reviewed. Short TR/TE (repetition time/echo time) images demonstrated diffusely decreased signal intensity in the femoral head and intracapsular region of the femoral neck. Increased signal intensity was noted with progressive T2 weighting. Bone biopsies were performed in four patients. Histologic findings were nonspecific and included fat necrosis, marrow edema, increased bone resorption, and reactive bone formation. Repeat MR scans in two patients, performed six and eight months after the initial scans, showed an almost complete return to normal marrow signal. All patients became asymptomatic without bony deformity. In the appropriate clinical setting, MR scanning can aid in the diagnosis of transient osteoporosis as the cause of a painful hip.

Acute Disease↗

Onchocercacidal effects of amocarzine (CGP 6140) in Latin America.

An open clinical trial of amocarzine was carried out in onchocerciasis patients in Ecuador and Guatemala. Administration after food was more effective than that during fasting. The most effective and best tolerated regimen, 3 mg/kg twice daily after food for 3 days (in 312 patients), killed 73% of 1477 female worms at nodulectomy 4 months after treatment. The mean microfilarial skin count was greatly reduced within a week (6-11% Of day 0 value on day 8) and it remained low at least 6 months (14-18% on day 180). Follow-up of a higher dose 3 day regimen taken while fasting showed microfilaridermia of 7-9% of the day 0 value 2 years after treatment.

Adult↗