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Biomedical subjects

B Kirkpatrick

Publications and source records attributed to B Kirkpatrick.

15 recordsLinked to original sources
PubMed1992

Plasma prolactin as a predictor of relapse in drug-free schizophrenic outpatients.

A low plasma prolactin concentration has been reported to be associated with an increased risk of subsequent relapse in patients with schizophrenia. Prolactin concentration was measured in samples from stable schizophrenic men who were outpatients just prior to neuroleptic withdrawal. No relationship between prolactin concentration and time to subsequent relapse was found. Prolactin concentration may predict time to relapse only in populations characterized by specific demographic features or medication history.

Administration, Oral↗
PubMed1992

Clinical predictors of relapse following neuroleptic withdrawal.

The validity of previously hypothesized predictors of elapse following neuroleptic discontinuation was examined. One hundred sixty-two outpatients, with either Research Diagnostic Criteria schizophrenia or schizoaffective disorder, were discontinued from neuroleptic medication for a 28-day period or until judged to be relapsed. Pre-discontinuation neuroleptic dosage level, the severity of psychotic symptoms, and the presence of dyskinetic movements prior to neuroleptic discontinuation were the predictor variables. Of the 162 patients, 62.7% did not relapse during the study period. There were no differences in the survival rates between the patients withdrawn from oral versus depot neuroleptics. Neuroleptic dosage, but not severity of psychotic symptoms or dyskinetic movements, predicted relapse. These results support the hypothesis that pre-withdrawal neuroleptic dosage level predicts relapse, but fail to validate either severity of psychotic symptoms or presence of dyskinetic movements as predictors of relapse.

Administration, Oral↗
PubMed1992

Limbic system abnormalities identified in schizophrenia using positron emission tomography with fluorodeoxyglucose and neocortical alterations with deficit syndrome.

A hypothesis of psychosis localization in schizophrenia was derived from studying metabolic alterations in rat brain in response to phencyclidine hydrochloride administration. Since phencyclidine and its selective agonist dizocilpine maleate (MK801) induced overlapping and long-lasting metabolic alterations predominantly in limbic areas, the hypothesis developed that schizophrenic patients with psychosis would evidence functional abnormalities in limbic circuits compared with normal controls. Accordingly, 12 actively psychotic, drug-free patients with schizophrenia and matched normal controls underwent functional brain scans using positron emission tomography and fluorodeoxyglucose. Regions of interest were identified on five matched axial slices in each patient and control subject, and average metabolic rates were calculated. Patients with schizophrenia showed a significantly lower regional cerebral metabolic rate of glucose in the hippocampus and the anterior cingulate cortex than did normal controls, but not in neocortical areas or in the extrapyramidal system. When the group of schizophrenic patients was divided into deficit and nondeficit types, a preliminary exploratory analysis suggested thalamic, frontal, and parietal cortical hypometabolism in the deficit subgroup, with normal metabolism in the nondeficit patient group in those areas; in contrast, hippocampal and anterior cingulate cortical metabolism was reduced in both deficit and nondeficit subtypes. These results suggest that the limbic system, especially the hippocampus, is functionally involved in schizophrenic psychosis and that different manifestations of schizophrenia may involve different neuronal circuits.

Adolescent↗
PubMed1992

Brain morphology and schizophrenia. A magnetic resonance imaging study of limbic, prefrontal cortex, and caudate structures.

We used magnetic resonance imaging to examine the morphologic characteristics of the amygdala/hippocampus, prefrontal cortex, and caudate nucleus in 29 healthy volunteers matched for age, gender, and head of household socioeconomic status and 44 patients with chronic schizophrenia. Total volumes of these structures were determined from 3-mm contiguous coronal sections. Schizophrenic patients, compared with healthy controls, had significantly smaller right and left amygdala/hippocampal complex volumes, smaller right and left prefrontal volumes, and larger left caudate volumes. A secondary analysis revealed reductions in the right and left amygdala and the left hippocampus. In addition, prefrontal white matter, but not gray matter, was reduced in the schizophrenic patients. Moreover, the right white matter volume in schizophrenic patients was significantly related to right amygdala/hippocampal volume (r = .39), data that provide preliminary support for a hypothesis of abnormal limbic-cortical connection in schizophrenia. We studied the implications of these data for the pathophysiology of schizophrenia.

Adult↗
PubMed1992

The concept of supersensitivity psychosis.

The hypothesis that chronic neuroleptic treatment may induce relapse in some schizophrenic patients has received considerable attention. This effect, usually called supersensitivity psychosis, has been attributed to neuroleptic-induced changes in mesolimbic or mesocortical dopaminergic receptors. However, research has not established that neuroleptics cause the proposed effect, and considerations of mechanism have not been separated from those of causation. The focus of research in this area should be the establishment or refutation of a causal relationship between chronic neuroleptic use and psychotic relapse.

Antipsychotic Agents↗
PubMed1991

Carbamazepine maintenance treatment in outpatient schizophrenics.

A double-blind crossover trial was used to evaluate carbamazepine as the sole maintenance treatment of chronic, nonmanic schizophrenic outpatients whose conditions had been stabilized with the use of neuroleptics prior to study. Criteria of treatment effectiveness included the number of patients relapsing and time to relapse over a 95-day neuroleptic-free period during which either carbamazepine or placebo was administered. Relapse was determined by the concordance of psychiatric ratings and independent clinical judgements indicating significant worsening. Results for 27 patients (13 receiving carbamazepine and 14 receiving placebo) involved in the first phase of this treatment comparison were nondifferentiating. Corroborating descriptive findings in the second phase were available for 14 of these patients. There was no evidence supporting the existence of a treatment-relevant subgroup defined by episodic dyscontrol phenomena.

Adult↗
PubMed1979

Soluble proteins in the human atherosclerotic plaque. With spectral reference to immunoglobulins, C3-complement component, alpha 1-antitrypsin and alpha 2-macroglobulin.

A number of soluble proteins contained in human aortic intimal tissue was extracted into buffered saline (pH 7.4) and identified and quantitated by immunoelectrophoresis and immunodiffusion. The proteins included IgA, IgG, IgM, B1C (C3), alpha 1-antitrypsin, alpha 2-macroglobulin, fibrinogen, albumin, LDL, HDL, alpha 1-acid glycoprotein, beta 2-glycoprotein, transferrin and ceruloplasmin. The concentration of soluble proteins was significantly higher in the atherosclerotic intima than in the normal intima. The diseased intima also contained a small amount of tissue-bound IgG, IgA and B1C which was extractable with citrate buffer at pH 3.2. The vascular band IgG, and B1C were shown by enzymatic and immunohistochemical studies to be closely associated with the collagenous tissue of the plaque. The Ig contained in the atherosclerotic plaque may be derived in part from the biosynthesis of Ig by the artery, since the incorporation of 14C-labeled leucine into IgG by the atheromatous plaque was demonstrable by radioimmunoelectrophoresis. In contrast to the diseased artery, the normal artery did not synthesize IgG and did not contain vascular bound IgG or complement. However, the normal artery was capable of fixing IgG and B1C eluted from the diseased artery. The present studies suggested that the IgG contained and synthesized by the plaque might represent an immune response to an endogenous or exogenous antigen closely associated with plaque collagen. IgG and B1C either alone or in the form of an immune complex also may play an important role in phagocytosis in the plaque and thereby influence the course of atherosclerosis. The proteolytic inhibitors, alpha 1-antitrypsin and alpha 2-macroglobulin, found in relatively high concentrations in the plaque, could enhance fibrosis of the lesion because of thier known inhibitory effects on collagenase and elastase.

Aorta↗
PubMed1979

Effects of anticalcifying and antifibrobrotic drugs on pre-established atherosclerosis in the rabbit.

The effects of the anticalcifying drug, ethane-hydroxydiphosphonate (EHDP) and the inhibitors of collagen biosynthesis, colchicine, penicillamine and azetidine were studied in the rabbit with pre-established atherosclerosis. The drugs were administered with a cholesterol-free diet (regression diet) for 8 weeks following the induction of atherosclerosis by feeding a hypercholesterolemic diet containing 2% cholesterol and 8% peanut oil for 8 weeks. The extent and severity of aortic atherosclerosis, as revealed by the morphological and biochemical findings, increased significantly during the regression period. In rabbits treated with EHDP (5 mg/kg/day) the aorta had fewer gross lesions and contained significantly less cholesterol, collagen and elastin than did the aorta of the rabbits fed the regression diet alone. These changes were associated with a significant reduction in aortic calcium caused by EHDP. The aortic content of cholesterol, collagen and elastin in the EHDP-treated rabbits, although less than that of the rabbits fed the regression diet alone, was about the same as that of the rabbits fed a high cholesterol diet for 8 weeks. Both colchicine (0.2 mg/kg/day) and penicillamine (100 mg/kg/day) had a selective action on the induced plaques in that they suppressed the fibrous proliferation in the lesions without preventing lipid and calcium accumulation in the lesions. Neither colchicine nor penicillamine reduced the extent of aortic atherosclerosis as determined by gross examination of the vessel. Azetidine had no significant effect on the pre-established atherosclerotic lesions. The lipid, fibrous protein and calcium content of the aorta of the azetidine-treated animals was not significantly different from that of the untreated animals. The biochemical findings in the aorta were consistent with the microscopic changes.

Animals↗
PubMed1978

The benzodiazepines.

The benzodiazepines are remarkably effective anxiolytic drugs. However, they are prone to misuse by both physicians and patients. They should be used in clearly defined clinical situations for short periods, at the lowest possible dosages. Although rare, toxicity can be severe. These agents should be used with caution in persons likely to abuse medication, in the elderly, in patients with glaucoma and in patiens with known hepatic impairment. Sudden cessation may be followed by a withdrawal state.

Anti-Anxiety Agents↗
PubMed1977

Role of hypertension in ischemic heart disease and cerebral vascular disease in the cynomolgus monkey with coarctation of the aorta.

The role of hypertension in cardiovascular disease was studied in the hypertensive coarcted monkey during the feeding of an atherogenic and nonatherogenic diet. During the 15-month period of observation, half of the hypertensive coarcted monkeys developed cardiovascular disease which included heart failure, ischemic heart disease, stroke, and sudden death. There were no cardiovascular complications in the control normotensive monkeys except for one cholesterol-fed animal. The incidence of ischemic heart disease and sudden cardiac death was higher in monkeys with both hypertension and hypercholesterolemia than in those with hypertension or hypercholesterolemia alone. Postmortem studies revealed that the former monkeys had both hypertensive and atherosclerotic heart disease, whereas the monkeys with hypertension or hypercholesterolemia had either hypertensive or atherosclerotic heart disease. Hypertensive heart disease was characterized not only by hypertrophy of the left ventricle but also by focal myocardial degeneration and fibrosis and by focal thickening and narrowing of the small coronary arteries, particularly the sinus node artery and the atrioventricular node artery. The finding of transmural myocardial infarction in two monkeys with patient coronary arteries suggests a possible role of coronary artery spasm in ischemic heart disease in hypertension. The cerebral vascular complications of hypertension included hypertensive encephalopathy, transient "ischemic" attacks, and hemorrhagic stroke. The complications were associated with severe hypertension and with hypertensive vascular disease or hypertensive and atherosclerotic vascular disease of the cerebral arteries.

Animals↗
PubMed1976

Aggravation of atherosclerosis by hypertension in a subhuman primate model with coarctation of the aorta.

The interrelationships between hypertension and atherosclerosis were investigated in a subhuman primate model (cynomolgus monkey) with hypertension produced by surgically coarcting the miathoracic aorta. The hypertensive coarcted monkey fed a low cholesterol diet for 6 months did not develop complicating atherosclerosis but did develop focal intimal lesions as well as marked thickening of the musculoelastic media of both the large and small arteries. Fibrocellular thickening of the intima and media occurred in the vessels proximal to the coarctation but not distal to the coarctation suggesting that a high level of blood pressure with resulting increase in arterial wall tension is responsible for these changes. The hypertensive coarcted monkey fed a hypercholesterolemic diet (2% cholesterol and 10% butter) for 6 months developed severe coronary atherosclerotic disease with fibrous plaque formation. The disease produced over 65% luminal narrowing of the major coronary arteries and their extramural and intramural branches. In contrast the noncoarcted normotensive animal fed the same diet developed mild atherosclerosis of only the major coronary arteries which caused an average luminal narrowing of 12%. Aggravation of atherosclerosis by hypertension also appeared to occur in the other arteries above the coarctation particularly the cerebral arteries. When the hypertensive coarcted monkey with preestablished coronary atherosclerosis was treated with a low cholesterol diet and a combination of antihypertensive drugs (hydrochlorothiazide, hydralazine, and reserpine), the progression of the disease was arrested. There also was evidence that treatment caused some regression of the coronary lesions which appeared to "heal" by fibrosis. The treatment of both hyperlipidemia and hypertension appeared to be more effective than the treatment of hyperlipidemia, alone.

Animals↗
PubMed1976

Effects of phototherapy on platelet counts in low-birthweight infants and on platelet production and life span in rabbits.

The effects of conventional phototherapy on platelets in vivo were studied in rabbits and in low-birthweight infants. Rabbits were divided into three groups and individually treated continuously for 96 hours, with blue light, daylight, or no phototherapy. Incorporation of selenomethionine Se75 was used to evaluate platelet production and life span. Platelet turnover was significantly increased in the blue-light phototherapy group, and was also increased in the daylight group but to a lesser degree. Daily platelet counts and hematocrits were performed in infants weighing less than 2,000 gm at birth randomized at 24 +/- 12 hours of life to receive daylight phototherapy continuously for 96 hours (31 infants) or no phototherapy (26 infants). In 12 treated infants (38.7%) platelet counts fell below 150,000/cu mm whereas this occurred in only 3 (11.5%) of the controls. These two lower platelet count subgroups differed significantly in mean gestational age and birthweight with the phototherapy group being the more mature. Pre-phototherapy, the mean platelet count of these 12 infants was lower than the mean of the entire control group, suggesting that these infants had borderline marrow reserve before phototherapy was given. These results suggest that phototherapy increases the rate of platelet turnover. When bone marrow compensation is inadequate, the platelet count may fall.

Animals↗