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Biomedical subjects

D Goff

Publications and source records attributed to D Goff.

At least 19 recordsLinked to original sources

Cognitive therapy for psychosis in schizophrenia: an effect size analysis.

We conducted a meta-analysis using all available controlled treatment outcome studies of cognitive therapy (CT) for psychotic symptoms in schizophrenia. Effect sizes were calculated for seven studies involving 340 subjects. The mean effect size for reduction of psychotic symptoms was 0.65. The findings suggest that cognitive therapy is an effective treatment for patients with schizophrenia who have persistent psychotic symptoms. Follow-up analyses in four studies indicated that patients receiving CT continued to make gains over time (ES=0.93). Further research is needed to determine the replicability of standardized cognitive interventions, to evaluate the clinical significance of cognitive therapy for schizophrenia, and to determine which patients are most likely to benefit from this intervention.

Cognition Disorders↗

Clozapine-associated reduction in arrest rates of psychotic patients with criminal histories.

OBJECTIVE: The authors examined the relationship between treatment with clozapine and rates of arrest of psychotic outpatients with criminal histories. METHOD: Patients who had been given a DSM-IV psychotic diagnosis were selected from an urban outpatient clinic database. Background checks performed on 360 patients identified 165 (45.8%) with positive criminal histories in Massachusetts. The authors reviewed the charts of these patients to determine several variables, including whether and when they had received clozapine. A Poisson regression model was used to regress arrest rates against the variables of age, sex, onset of illness, birth cohort, and clozapine treatment. Risk ratios (i.e., percent change in arrest rates) were then calculated by computing the exponential of the Poisson regression coefficients. RESULTS: The 165 patients included in the analysis had a total of 1,126 arrests. The mean number of arrests was 6.8. Differences were found between the 65 patients who received clozapine and the 100 patients who did not in number of arrests, sex, and onset of illness. The regression revealed significantly higher arrest rate estimates associated with more recent birth cohort (4.8%) and with onset of illness (64.6%) and lower arrest rate estimates associated with higher levels of education (11.6%), receiving clozapine (32.6%), and receiving clozapine during specific periods of time (68.9%). CONCLUSIONS: Clozapine's effect on arrest rates in this group of patients is large enough to warrant further investigation. The data indicate that clozapine may reduce recidivism in subjects with criminal histories who are in need of antipsychotic medication.

Adult↗

Abnormalities in the thalamus and prefrontal cortex during episodic object recognition in schizophrenia.

BACKGROUND: Many patients with schizophrenia demonstrate memory deficits. We studied patterns of brain activity during episodic recognition of new and previously seen three-dimensional objects. METHODS: We used (15)O positron emission tomography to study regional cerebral blood flow in eight normal subjects and nine patients with schizophrenia during a visual object recognition task. RESULTS: In comparison with control subjects, patients with schizophrenia showed less regional cerebral blood flow increases in the pulvinar region of the right thalamus and the right prefrontal cortex during the recognition of new objects and significantly greater left prefrontal cortex regional cerebral blood flow increases during the recognition of previously seen objects. Patients with schizophrenia exhibited alarm rates to new objects similar to those of control subjects, but significantly lower recognition rates for previously seen objects. CONCLUSIONS: Schizophrenia is associated with attenuated right thalamic and right prefrontal activation during the recognition of novel visual stimuli and with increased left prefrontal cortical activation during impaired episodic recognition of previously seen visual stimuli. This study provides further evidence for abnormal thalamic and prefrontal cortex function in schizophrenia.

Adult↗

Cardiovascular fitness in premenarcheal girls and young women.

Maximal oxygen uptake (VO2max) in females, expressed as ml x kg(-1) x min(-1), declines steadily during the first three decades of life. The contribution of diminished cardiovascular function to this apparent fall in aerobic fitness is unknown. Cardiac responses to maximal cycle exercise were compared in 24 premenarcheal females (mean age 11.7 years) and 17 young adult women (mean age 27.4 years) using Doppler echocardiography. Mean VO2max was 40 ml x kg(-1) x min(-1) and 34.7 ml x kg(-1) x min(-1) in the girls and women, respectively (p < 0.05). When VO2max was expressed relative to allometrically-derived mass(0.52), however, no significant difference was observed in aerobic fitness between the two groups. Similar allometric analyses revealed no significant differences in average maximal cardiac output (10.50 vs 10.07 L x min(-1) BSA(-1.11) for girls and women, respectively) nor maximal stroke volume (53 vs 56 ml BSA(-1.13) respectively). These findings suggest that 1) allometric scaling is important in eliminating the effects of body size on VO2max, 2) body dimension differences can account for variations in VO2 in young females, and 3) cardiac functional reserve is similar in premenarcheal girls and young adult women.

Adolescent↗

Cardiac responses to progressive exercise in normal children: a synthesis.

UNLABELLED: The cardiac responses to exercise are influenced by a complex interplay of changes in diastolic filling, intrinsic myocardial contractility, heart rate, and ventricular afterload. PURPOSE: To characterize these responses in children, findings are reported from two studies utilizing Doppler echocardiographic assessment of stroke volume and cardiac output during maximal upright and semisupine cycle exercise. METHODS: In study 1, stroke volume, heart rate, and peak aortic velocity were assessed during upright cycle exercise to exhaustion in 39 sixth-grade boys. In study 2, similar methods were used to examine cardiac responses to semisupine exercise with measurement of left ventricular dimensions by two-dimensional echocardiography. RESULTS: The findings support patterns similar to that previously described in adults, with an initial rise in stroke volume reaching a plateau at mild-moderate exercise intensities. CONCLUSIONS: The observations in these two studies also suggest 1) peripheral vasodilatation plays an important role in the early rise in stroke volume, 2) increasing heart rate acts to maintain a stable stroke volume and left ventricular diastolic dimension at high workloads, and 3) improvements in contractility serve to maintain stroke volume as the systolic ejection period shortens.

Adolescent↗

Age and sex differences in presentation of symptoms among patients with acute coronary disease: the REACT Trial. Rapid Early Action for Coronary Treatment.

BACKGROUND: There are few data on possible age and sex differences in presentation of symptoms for patients with acute coronary disease. OBJECTIVE: To investigate demographic differences in presentation of symptoms at the time of hospital presentation for acute myocardial infarction (AMI) and unstable angina. METHODS: The medical records of patients who presented with chest pain and who also had diagnoses of AMI (n = 889) or unstable angina (n = 893) on discharge from 43 hospitals were reviewed as part of data collection activities of the Rapid Early Action for Coronary Treatment trial based in 10 pair-matched communities throughout the USA. RESULTS: Dyspnea (49%), arm pain (46%), sweating (35%), and nausea (33%) were commonly reported by men and women of all ages in addition to the presenting complaint of chest pain. After we had controlled for various characteristics through regression modeling, older persons with AMI were significantly less likely than were younger persons to complain of arm pain and sweating, and men were significantly less likely to report vomiting than were women. Among persons with unstable angina, arm pain and sweating were reported significantly less often by elderly patients. Nausea and back, neck, and jaw pain were more common complaints of women. CONCLUSIONS: Results of this study suggest that there are differences between symptoms at presentation of men and women, and those in various age groups, hospitalized with acute coronary disease. Clinicians should be aware of these differences when diagnosing and managing patients suspected to have coronary heart disease.

Adult↗

Influence of cardiac functional capacity on gender differences in maximal oxygen uptake in children.

OBJECTIVE: To examine the role of gender differences in cardiac functional capacity in explaining higher mean values for maximal oxygen uptake (VO(2)max) in boys than in girls. DESIGN: Comparative group exercise testing. SETTING: Pediatric exercise testing laboratory. SUBJECTS: Twenty-five prepubertal boys (mean [+/- SD] age, 12 +/- 0.4 years) and 24 premenarcheal girls (mean age, 11.7 +/- 0.5 years). INTERVENTIONS: Maximal incremental upright cycle exercise. MEASUREMENTS AND RESULTS: Mean values for VO(2)max were the following: boys, 47.2 +/- 6.1 mL/kg/min; and girls, 40.4 +/- 5.8 mL/kg/min (16.8% difference; p < 0.05). The average maximal stroke index with Doppler echocardiography was 62 +/- 9 mL/m(2) for boys and 55 +/- 9 mL/m(2) for girls (12.7% difference; p < 0.05). No significant gender differences were seen in maximal heart rate or arterial venous oxygen difference. When VO(2)max and maximal stroke volume (SV) were expressed relative to lean body mass, gender differences declined but persisted, falling to 6.2% and 5.2%, respectively. CONCLUSIONS: These findings indicate that differences in SV as well as in body composition contribute to gender-related variations in VO(2)max during childhood. Whether this reflects small gender differences in relative heart size or dynamic factors influencing ventricular preload and contractility during exercise is unknown.

Body Composition↗

One-mile run performance and cardiovascular fitness in children.

BACKGROUND: Endurance run tests are administered in schools to assess cardiovascular fitness, defined in the laboratory as maximum oxygen consumption. OBJECTIVE: To examine the validity of this concept, assessing the influences of body fat and maximum values of oxygen consumption per unit time, stroke volume, heart rate, and arteriovenous oxygen difference on 1-mile (1.6-km) run time in healthy sixth-grade boys. STUDY DESIGN: Subjects were 36 boys with a mean (SD) age of 12.2 (0.5) years. The relationship was examined between body fat content (estimated by skinfold measurements) and maximum oxygen consumption per kilogram and cardiac variables (during maximum cycle testing) with 1-mile run velocity. RESULTS: Body fat content and maximum oxygen consumption per kilogram (independent of body fat) accounted for 31% and 28% of the variance in run velocity, respectively. Stroke volume was the only component of maximum oxygen consumption that related to run performance. CONCLUSIONS: These findings suggest that cardiovascular fitness and body fat content contribute equally to 1-mile run time in healthy boys and together account for only 60% of the variance in performance on this endurance fitness test. Consequently, 1-mile run performance in children may not serve as a strong indicator of cardiovascular fitness.

Adipose Tissue↗

Functional imaging of memory retrieval in deficit vs nondeficit schizophrenia.

BACKGROUND: Neuroimaging studies have provided evidence of abnormal frontal and temporal lobe function in schizophrenia. Frontal cortex abnormalities have been associated with negative symptoms and temporal lobe abnormalities with positive symptoms. The deficit and nondeficit forms of schizophrenia were predicted to differ in prefrontal cortical activity, but not in medial temporal lobe activity. METHODS: Regional cerebral blood flow was studied using oxygen 15 positron emission tomography during 3 different memory retrieval conditions in 8 control subjects, 8 patients with the deficit syndrome, and 8 patients without the deficit syndrome. Behavioral and positron emission tomography data were analyzed using a mixed-effects model to test for population differences. RESULTS: In all memory conditions, frontal cortex activity was higher in patients without the deficit syndrome than in patients with the deficit syndrome. During the attempt to retrieve poorly encoded words, patients without the deficit syndrome recruited the left frontal cortex to a significantly greater degree than did patients with the deficit syndrome. The 2 schizophrenia subtypes did not differ in the activity or recruitment of the hippocampus during memory retrieval. CONCLUSION: Frontal cortex function during memory retrieval is differentially impaired in deficit and nondeficit schizophrenia, whereas hippocampal recruitment deficits are not significantly different between the 2 schizophrenia groups.

Adult↗

LDL size in African Americans, Hispanics, and non-Hispanic whites : the insulin resistance atherosclerosis study.

The prevalence of cardiovascular disease (CVD) and atherosclerosis varies among several minority ethnic groups in the United States. Recently, small, dense low density lipoprotein (LDL) particle size has been recognized as a risk factor for CVD. We examined LDL size as a possible explanation for differences in CVD rates in 1571 subjects from the Insulin Resistance Atherosclerosis Study (IRAS), a multiethnic study of insulin resistance and cardiovascular risk factors. LDL size (A) was significantly different by ethnic group (African Americans 262.1+/-0.6, Hispanics 257.6+/-0.6, and non-Hispanic whites 259.2+/-0.4, P<0.001). Ethnic differences in LDL size continued to be statistically significant after adjustment for upper body adiposity, insulin resistance, and glucose tolerance status. However, after further adjustment for other cardiovascular risk factors, especially ethnic differences in triglyceride and high density lipoprotein (HDL) cholesterol levels, the ethnic differences in LDL size were markedly attenuated and in general no longer statistically significant. The relation of triglyceride, HDL cholesterol, insulin resistance, and adiposity to LDL size in each ethnic group was similar. LDL size differs by ethnic group, which is independent of obesity or insulin resistance. These ethnic differences appear to be due to ethnic variations in dyslipidemia (especially differences in triglyceride levels); ethnic differences in LDL size are not consistent with previously reported ethnic dissimilarities in CVD or atherosclerosis.

Adipose Tissue↗

Relationships between insulin resistance and lipoproteins in nondiabetic African Americans, Hispanics, and non-Hispanic whites: the Insulin Resistance Atherosclerosis Study.

The study purpose was to explore the association between dyslipidemia and insulin resistance in three ethnic groups. The Insulin Resistance Atherosclerosis Study (IRAS) is a multicenter epidemiologic study conducted at four clinical centers in California, Texas, and Colorado. The study population for this analysis consisted of 931 non-Hispanic white, African American, and Hispanic men and women (aged 45 to 64 years) without diabetes. The IRAS clinical examinations included lipoprotein measures, a 75-g glucose tolerance test, and the frequently sampled intravenous glucose tolerance (FSIGT) test. The results show a consistent relationship between insulin-mediated glucose disposal and dyslipidemia in African American, Hispanic, and non-Hispanic white men and women. Further, LDL size was inversely associated with insulin resistance in all three ethnic groups. These findings indicate that dyslipidemia is a fundamental part of the insulin resistance syndrome in all of the ethnic groups studied.

Adult↗

Impaired recruitment of the hippocampus during conscious recollection in schizophrenia.

Poor attention and impaired memory are enduring and core features of schizophrenia. These impairments have been attributed either to global cortical dysfunction or to perturbations of specific components associated with the dorsolateral prefrontal cortex (DLPFC), hippocampus and cerebellum. Here, we used positron emission tomography (PET) to dissociate activations in DLPFC and hippocampus during verbal episodic memory retrieval. We found reduced hippocampal activation during conscious recollection of studied words, but robust activation of the DLPFC during the effort to retrieve poorly encoded material in schizophrenic patients. This finding provides the first evidence of hippocampal dysfunction during episodic memory retrieval in schizophrenia.

Adult↗

Cardiac responses to exercise in child distance runners.

Cardiovascular responses to exercise in trained endurance child athletes have been largely unexplored. Doppler echocardiography was utilized to compare cardiac variables during progressive upright cycle exercise to exhaustion in trained male prepubertal distance runners (n = 8) and untrained control boys (n = 14). Athletes demonstrated a greater maximal stroke index and cardiac index. Stroke volume rose progressively with increasing workloads in the runners but remained stable beyond low intensities in the non-athletes. No significant differences in stroke volume were observed between the two groups at rest. This contrasts with the greater resting stroke volumes typically seen in adult endurance athletes compared to non-athletes. Likewise, values for maximal stroke index were less in the child runners than those typically seen in trained adults. This study demonstrated that the stroke volume response to exercise differs in boy runners compared to non-athletes. The findings also suggest quantitative differences in such responses between prepubertal and young adult athletes.

Adolescent↗

Cardiac effects of a competitive road race in trained child runners.

BACKGROUND: Animal studies and investigations of adult endurance athletes indicate a transient depression of myocardial function after prolonged high-intensity exercise. PURPOSE: To determine whether a similar decrease is observed in child distance runners after a 4-km competitive road race. METHODS: Anthropometric measures, resting M-mode echocardiograms, maximal cycle exercise tests with estimation of cardiac output, and electrocardiograms were performed before a 4-km road race in nine run-trained boys (mean age, 12.2 years). Weight and resting echocardiogram and electrocardiogram were assessed immediately after the race. The entire test battery was repeated 24 hours later. RESULTS: Small but significant decreases in mean body weight and left ventricular end-diastolic dimension were observed immediately after the race, but there were no changes in shortening fraction. These findings are consistent with the effects of dehydration. Measurements returned to prerace values by 24 hours of recovery. Peak work capacity, maximal stroke volume, and maximal cardiac output were similar on prerace and 24-hour-postrace testing. No electrocardiographic abnormalities were observed. CONCLUSIONS: No adverse cardiac effects were observed from a competitive 4-km road race in male child distance runners.

Adolescent↗

Differential expression of myogenic regulatory genes and Msx-1 during dedifferentiation and redifferentiation of regenerating amphibian limbs.

An amputated limb of an adult urodele amphibian is capable of undergoing regeneration. The new structures form from an undifferentiated mass of cells called the regenerative blastema. The cells of the blastema are believed to derive from differentiated tissues of the adult limb. However, the exact source of these cells and the process by which they undergo dedifferentiation are poorly understood. In order to elucidate the molecular and cellular basis for dedifferentiation we isolated a number of genes which are potential regulators of the process. These include Msx-1, which is believed to support the undifferentiated and proliferative state of cells in the embryonic limb bud; and two members of the myogenic regulatory gene family, MRF-4 and Myf-5, which are expressed in differentiated muscle and regulate muscle-specific gene activity. As anticipated, we find that Msx-1 is strongly up-regulated during the initiation of regeneration. It remains expressed throughout regeneration but is not found in the fully regenerated limb. The myogenic gene MRF-4 has the reverse expression pattern. It is expressed in adult limb muscle, is rapidly shut off in early regenerative blastemas, and is only reexpressed at the completion of regeneration. These kinetics are paralleled by those of a muscle-specific Myosin gene. In contrast Myf-5, a second member of the myogenic gene family, continues to be expressed throughout the regenerative process. Thus, MRF-4 and Myf-5 are likely to play distinct roles during regeneration. MRF-4 may directly regulate muscle phenotype and as such its repression may be a key event in dedifferentiation.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

Potentiation of cytotoxic therapies by TNP-470 and minocycline in mice bearing EMT-6 mammary carcinoma.

The ability of the antiangiogenic agents TNP-470 and minocycline, singly or in combination, to potentiate the antitumor effects of several cytotoxic therapies was assessed in the murine EMT-6 mammary carcinoma as well as in two drug resistant sublines of that tumor designated EMT-6/CTX and EMT-6/CDDP. The antiangiogenic agents alone or in combination did not alter the growth of the tumors. However, their administration along with cyclophosphamide, CDDP, or thiotepa substantially increased the tumor growth delay produced by these cytotoxic therapies in tumors responsive to the drugs--the increase was about 2-fold for TNP-470 and minocycline together. In drug resistant tumors, treatment with the antiangiogenic agents did not reverse drug resistance but did increase the effect of the cytotoxic drugs. Treatment with TNP-470/minocycline also increased the oxygenation of each of the three tumors. Thus, TNP-470/minocycline administration increased the efficacy of fractionated radiation therapy, especially when used along with a perflubron emulsion oxygen delivery agent/carbogen. These results indicate that treatment regimens including therapies directed toward the proliferating normal cells within a tumor mass as well as therapies directed toward the malignant cells can produce improved outcomes.

Animals↗

Membrane-interactive phospholipids inhibit HIV type 1-induced cell fusion and surface gp160/gp120 binding to monoclonal antibody.

Membrane-interactive phospholipids (PLs), previously evaluated for activity against HIV-1 in vitro, are known to affect late steps in viral replication. Studies were done to determine the effects of PL analogs on post-translational processing of HIV-1 proteins, binding of viral surface gp160/gp120 to CD4 receptor, and HIV-1-induced cell fusion. Results of this investigation indicated that PL alone (1-octadecanamido-2-ethoxypropyl-rac-3-phosphocholine, CP-51) and PL-AZT conjugate (1-octadecanamido-2-ethoxypropyl-rac-3-phospho-3'- azido-3'-deoxythymidine, CP-92) have no effect on HIV-1-induced syntheses or processing of gp160/gp120, pr51, p24, or p17 (including myristoylation) in infected cells. Progeny HIV-1 particles made in CP-92-treated H9IIIB cells contained gp120, pr51, and p24; however, these virus particles had reduced capacity to bind to CD4+ cells. Both CP-51 and CP-92 inhibited syncytium (cell fusion) formation between treated HIV-1-infected cells and uninfected CD4+ cells, and, they reduced HIV-1 gp160/gp120 binding to CD4+ cells and monoclonal antibody. These results suggest that anti-HIV-1 activity of PL compounds involves alteration of cell surface membranes and viral envelopes. Phospholipid compounds are a novel class of membrane interactive compounds with potential use in blocking the spread of HIV-1 infection and pathogenesis in AIDS.

Antibodies, Monoclonal↗