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PubMed2003

Corpus callosum atrophy, white matter lesions, and frontal executive dysfunction in normal aging and Alzheimer's disease. A community-based study: the Tajiri Project.

BACKGROUND AND OBJECTIVES: Cerebral MRIs of normal aging and Alzheimer's disease (AD) frequently reveal corpus callosum (CC) atrophy, white matter hyperintensity (WMH), and hippocampal atrophy. However, their relationship or the relationship between these findings and cognitive function has not been fully studied. We investigated the relationship between CC atrophy, WMH, and hippocampal atrophy, together with frontal executive dysfunction in both normal aging and AD. METHOD: We examined 170 randomly selected residents from a designated community: 99 Clinical Dementia Rating (CDR) 0 (healthy, control group, HC) participants, 54 CDR 0.5 (very mild AD) patients, and 17 CDR 1 & 2 (probable AD) patients. By means of MRI, WMH and CC atrophy were visually rated. Four portions of the CC and the hippocampal width were measured. A Mini-Mental State Examination and Cognitive Abilities Screening Instrument (CASI) were performed to assess global function. For the frontal function, the CASI subitems of attention and word fluency, letter-based fluency, the Digit Symbol test of the WAIS-R, and Trail Making Tests were performed. RESULTS: Those patients with CDR 1 & 2 had both hippocampal and CC atrophy, whereas the CDR 0.5 patients had only hippocampal atrophy. Frontal executive dysfunction was associated with CC atrophy in both the HC and AD groups. Significant Spearman correlations were noted between CC atrophy and WMH in both groups. The combined effect of CC atrophy and WMH was noted only in the verbal fluency test in the HC group. CONCLUSION: In both groups, CC atrophy was associated with frontal executive dysfunction. The combined effect of CC atrophy and WMH in normal aging was probably due to subclinical ischemic conditions.

Aged↗

PubMedDate not supplied

Evolution of depressive symptoms in Alzheimer disease: one-year follow-up.

The current longitudinal study analyzes the natural course of depressive symptoms in patients with Alzheimer disease (AD). The goals were to identify the clinical and sociodemographic variables related to depressive symptoms, to assess the effect of depressive symptoms on the course of cognitive and functional impairment and on associated neuropsychiatric disorders, and to identify which factors are associated with remission, persistence, and emergence of depressive symptoms at 12 months. A sample of 150 patients with mild or moderate severity was assessed at baseline and at 12 months using the neuropsychologic battery Cambridge Cognitive Examination. The Neuropsychiatric Inventory and Rapid Disability Rating Scale were administered to the caregiver. Prevalence, persistence, and emergence of depressive symptoms at baseline were 51%, 55%, and 20%, respectively. Remission of depressive symptoms at 12 months leads to a decreased frequency of other noncognitive disorders and to a slight improvement in the assessment of global function. The presence of depressive symptoms does not affect the course of cognitive impairment at 12 months, and a psychiatric history of the patient and the number of depressive symptoms at baseline are risk factors for the emergence and persistence of depressive symptoms at 12 months.

Aged↗

PubMed2001

Angiogenesis by endothelial cell transplantation.

PURPOSE: Myocardial angiogenesis may improve regional perfusion and perhaps function after cardiac injury. We evaluated the effect of endothelial cell transplantation into a myocardial scar on angiogenesis and ventricular function, as an alternative to angiogenic gene or protein therapy. METHODS AND RESULTS: A transmural myocardial scar was created in the left ventricular free wall of rat hearts by cryoinjury. Allogeneic aortic endothelial cells were injected into the scar 2 weeks after cryoinjury. A cluster of transplanted cells was identified at the site of injection 1 day and 1 week after transplantation, but not after 2 weeks. The size of this cluster of transplanted cells decreased as vascular density in the transplanted scar tissue increased with time. Six weeks after transplantation, vascular density was significantly greater in transplanted hearts than in control hearts. Regional blood flow, by microsphere analysis, was greater in the transplanted rats. Systolic and diastolic ventricular function was similar between groups. In a second series of experiments, syngeneic aortic endothelial cells labeled with bromodeoxyuridine were transplanted 2 weeks after cryoinjury. Vascular density in the transplanted scar was greater than in controls. Labeled transplanted endothelial cells were identified forming part of the newly developed blood vessels. No difference in vascular density was found between allogeneic and syngeneic cell transplantation. Vascular endothelial growth factor was not expressed at greater levels in the transplanted cells or the myocardial scar. CONCLUSION: Transplanted endothelial cells stimulated angiogenesis, were incorporated into the new vessels, and increased regional perfusion in myocardial scar tissue, but did not improve global function in this cryoinjury rat model.

Animals↗

PubMedDate not supplied

Interrelationship of hepatic function, thyroid activity and mood status in alcohol-dependent individuals.

BACKGROUND: Alcohol-induced changes in thyroid function may contribute to the development of mood disorders such as depression and anxiety that almost invariably coexist in alcohol-dependent individuals. The aim of the present study was to investigate the severity of liver dysfunction and thyroid activity in correlation with anxiety and depressive-like symptomatology before and after a detoxification period. PATIENTS AND METHODS: In a sample of 100 alcohol-abusing/dependent subjects treated on an in-patient basis according to a standard detoxification protocol, measurements of the serum levels of hepatic enzymes (ASAT, ALAT, gammaGT) and thyroid hormones (T3, T4, TSH) as well as measures of anxiety, depression and global functioning were obtained at baseline and at weekly intervals over the period of 4-5 weeks. RESULTS: After completion of the alcohol detoxification, most measurements returned to normal levels and correlations were observed between the levels of hepatic enzymes and thyroid hormones. Additionally, a significant correlation was obtained between the levels of thyroid hormones and the mood status scales. CONCLUSION: Our results indicated a dysfunction of the hypothalamic-pituitary-thyroid axis in alcohol dependence with possible implications in the diagnosis and treatment of mood disorders associated with alcohol abuse.

Adult↗

PubMed2003

Prospective study of adult mental disturbance in offspring of women with psychosis.

BACKGROUND: The high-risk method is an important strategy for studying the antecedents and causes of schizophrenia and other psychoses. The Swedish High-Risk Project is a prospective longitudinal study of offspring of women with a history of schizophrenic, schizoaffective, affective, or unspecified functional psychoses and control women with no history of psychosis. The offspring and their environments were studied beginning before birth, and again during childhood. This article reports the mental outcome results from the first adult follow-up at age 22 years. METHODS: Of 178 offspring, 166 (93%) were followed up and blindly assessed using standardized methods, including a self-report scale for mental symptoms and the Structured Clinical Interview for DSM-III-R. RESULTS: Compared with controls (n = 91), the offspring of mothers with schizophrenia (n = 28) showed a significantly increased frequency of DSM-III-R Axis I and Axis II disorders, poor global functioning, high Symptom Checklist-90 scores, and a history of mental health care and psychopharmacologic medication use. Offspring of mothers with affective disorders (n = 22) showed high Symptom Checklist-90 scores, more frequent poor functioning, and receipt of mental health care, with a significant increase in Axis I depressive disorders and no increase in Axis II disorders. The extension of schizophrenia and affective risk groups to include additional maternal "spectrum cases" (10 and 15 individuals, respectively) generally yielded similar results. CONCLUSIONS: Maternal schizophrenia is associated with widespread increases in offspring mental disturbance in adolescence and young adulthood, differing from offspring disturbance associated with maternal affective disorder.

Adolescent↗

PubMed1996

Pathogenesis of mitral regurgitation in acute myocardial infarction: importance of changes in left ventricular shape and regional function.

The pathogenesis of mitral regurgitation (MR) was determined by quantitative echocardiography in 188 patients with acute myocardial infarction (AMI) within 48 hours after admission. MR was classified, by using color Doppler, as significant (grades 3 to 4) or trivial (grades 0 to 2). Left ventricular (LV) function (global and regional), volume, and shape, as well as mitral valvular features, were measured and analyzed by stepwise logistic regression. Significant MR occurred in 25 (13%) patients. Univariately, recurrent infarction (p < 0.01), LV dilation (p < 0.001) and sphericity (p < 0.001), inferoposterolateral asynergy (p < 0.001), mitral annular dilatation (p < 0.005), and mitral leaflet restriction (p < 0.05) were associated with significant MR. In regression analysis, only recurrent infarction (odds ratio 5.08), LV sphericity index (odds ratio 1.12), and inferoposterolateral asynergy (odds ratio 6.07) were independently associated with significant MR, whereas none of the mitral valvular features examined had an independent association. In conclusion, changes in LV shape and regional function and not mitral valvular changes are prime determinants of significant MR after AMI.

Aged↗

PubMed1987

Cardiovascular function during controlled hypotension induced by adenosine triphosphate or sodium nitroprusside in the anesthetized dog.

The present study was undertaken to compare the hemodynamic effects of adenosine triphosphate (ATP) and sodium nitroprusside (NP) given in equieffective doses to induce hypotension during halothane anesthesia. Eight dogs, instrumented with pressure and ultrasonic dimension transducers for assessment of left ventricular (LV) performance, were given both NP and ATP. Regional blood flow was measured by radioactive microspheres. After 20 min of infusion, both drugs decreased systemic arterial pressure by 36% with minimal changes in cardiac index (CI), LV end-diastolic pressure, or heart rate. However, hypotension produced by ATP was associated with a greater CI (3.84 +/- 0.32 vs 2.97 +/- 0.35 L X min-1 X m-2) than was NP and also associated with a further decrease in systemic vascular resistance (14.4 +/- 1.4 vs 17.7 +/- 2.2 mm Hg X L-1 X min X m2). Left ventricular global function, measured by the slope of the linear regression line of the LV end-systolic pressure-diameter relation (Ees), did not change significantly after either drug. Blood flow to the coronary bed was significantly greater with ATP than with NP (231.6 +/- 30.6 vs 81.7 +/- 6.1 ml X min-1 X 100 g-1). Except for an increase in hepatic arterial blood flow with NP, neither ATP nor NP significantly altered blood flow to the brain, spinal cord, spleen, kidney, jejunum, muscle, and skin. Controlled hypotension by ATP was stable and rapidly reversible without rebound hypertension. The results of this study indicate that ATP is a rapidly acting, effective hypotensive agent that compares favorably with NP.

Adenosine Triphosphate↗

PubMed2003

Empirical analysis of transcriptional activity in the Arabidopsis genome.

Functional analysis of a genome requires accurate gene structure information and a complete gene inventory. A dual experimental strategy was used to verify and correct the initial genome sequence annotation of the reference plant Arabidopsis. Sequencing full-length cDNAs and hybridizations using RNA populations from various tissues to a set of high-density oligonucleotide arrays spanning the entire genome allowed the accurate annotation of thousands of gene structures. We identified 5817 novel transcription units, including a substantial amount of antisense gene transcription, and 40 genes within the genetically defined centromeres. This approach resulted in completion of approximately 30% of the Arabidopsis ORFeome as a resource for global functional experimentation of the plant proteome.

Arabidopsis↗

PubMed2005

Cell transplantation improves ventricular function after a myocardial infarction: a preclinical study of human unrestricted somatic stem cells in a porcine model.

BACKGROUND: Cell transplantation offers the promise in the restoration of ventricular function after an extensive myocardial infarction, but the optimal cell type remains controversial. Human unrestricted somatic stem cells (USSCs) isolated from umbilical cord blood have great potential to differentiate into myogenic cells and induce angiogenesis. The present study evaluated the effect of USSCs on myocardial regeneration and improvement of heart function after myocardial infarction in a porcine model. METHOD AND RESULTS: The distal left anterior descending artery of Yorkshire pigs (30 to 35 kg) was occluded by endovascular implantation of a coil. Four weeks after infarction, single-photon emission computed tomography technetium 99m sestamibi scans (MIBI) and echocardiography were performed. USSCs (100 x 10(6)) or culture media were then directly injected into the infarcted region (n=8 per group). Pigs were immunosuppressed by daily administration of cyclosporin A. At 4 weeks after transplantation, MIBI and echocardiography were repeated and heart function was also assessed with a pressure-volume catheter. The infarcted myocardium and implanted cells were studied histologically. MIBI showed improved regional perfusion (P<0.05) and wall motion (P<0.05) of the infarct region in the transplant group compared with the control. Ejection fraction evaluated by both MIBI and echocardiography decreased in the control group but increased in the transplant group (P<0.01). Scar thickness of the transplant group was higher than the control. The grafted cells were detected 4 weeks after transplantation by both immunohistochemistry and in situ hybridization. CONCLUSIONS: Engrafted USSCs were detected in the infarct region 4 weeks after cell transplantation, and the implanted cells improved regional and global function of the porcine heart after a myocardial infarction. This study suggests that the USSC implantation will be efficacious for cellular cardiomyoplasty.

Animals↗

PubMed2002

Tissue Doppler imaging and long axis left ventricular function: hypertrophic cardiomyopathy versus athlete's heart.

BACKGROUND: The different diagnosis between hypertrophic cardiomyopathy and athlete's heart has important clinical implications. The assessment of long axis left ventricular function with tissue Doppler imaging in hypertrophic cardiomyopathy (showing systolic and diastolic dysfunction with heterogeneity and asynchrony), may be useful in the differentiation of these situations. AIM: To study, with tissue Doppler imaging, long axis left ventricular function in a population of athletes (rowers) and to compare it with a population of non-obstructive hypertrophic cardiomyopathy patients. METHODS: In 24 patients with non-obstructive hypertrophic cardiomyopathy and in 20 competitive rowers with similar age, blood pressure and heart rate, we analyzed mitral annulus motion with pulsed tissue Doppler imaging in the 4 sides of the annulus (septal, lateral, inferior, anterior), in apical views. In each wave (systolic, rapid filling and atrial contraction) we measured velocities, time intervals and velocity-time integrals, and calculated heterogeneity and asynchrony indices. Data were compared between the groups, between the different sides in each group ("parallel analysis") and with conventional indices of global function. RESULTS: Hypertrophic cardiomyopathy patients showed: systolic function: lower velocities and integrals, shorter ejection time and shorter systolic time. These abnormalities occurred even in annular sites contiguous to walls without hypertrophy. DIASTOLIC FUNCTION: Much lower rapid filling velocities and integrals, lower atrial contraction velocities and integrals, lower e/a, longer isovolumic relaxation time and time to peak rapid filling wave. These abnormalities occurred even in annular sites adjacent to walls without hypertrophy. In the athletes group, the e/a ratio was never < 1, in any annular site. In hypertrophic cardiomyopathy patients this ratio was < 1 in 27% of the sites. CONCLUSIONS: 1--Systolic and diastolic long axis left ventricular function is different in hypertrophic cardiomyopathy and in athletes, in all mitral annulus sides. 2--The presence of these abnormalities in annular sites contiguous to walls without hypertrophy suggests that this technique may be useful in the differential diagnosis between these groups, particularly in the "gray zone" of Maron.

Adolescent↗

PubMed2004

The platelet function defect of paroxysmal nocturnal haemoglobinuria.

Paroxysmal nocturnal haemoglobinuria (PNH) is a rare, acquired stem cell disorder, characterised by an abnormal susceptibility of red blood cells to complement induced lysis, resulting in repeated episodes of intravascular haemolysis and haemoglobinuria, thromboembolic events at atypical locations and, to a much lesser extent, bleeding complications. Platelet function is assumed to be abnormal, however, a defect has not yet been characterised and underlying mechanisms remain elusive. To explore these issues, we investigated platelet function in PNH patients using assays for clot formation under low and high shear force (thrombelastography and PFA100 device), adhesion to glass beads in native whole blood (Hellem method), aggregometry using various agonists (Born method), and flow cytometric assays for baseline and agonist-induced surface expression density of alpha-granule (CD62P) and lysosomal granule proteins (CD63), ligand binding to surface receptors (thrombospondin), and expression density of activation-induced neoepitopes of the fibrinogen receptor complex (PAC-1). Platelet PNH clone size determined by CD55 and CD59 labelling was compared to the clone sizes of granulocytes, monocytes, erythrocytes, and reticulocytes. A profound reduction of platelet reactivity was observed in PNH patients for all "global function" assays (clot formation, adhesion, aggregation). Platelet hyporeactivity was confirmed using flow cytometric assays. Whereas baseline levels of flow cytometrically determined platelet activation markers did not differ significantly between controls and PNH patients, agonist-induced values of all markers were distinctly reduced in the PNH group. Moreover, significantly reduced white blood cell counts (3.1/nl vs. 5.9/nl), haemoglobin values (9.5 vs. 14.3/g per dl), and platelet counts (136 vs. 219/nl) delineate profound tricytopenia in PNH patients. The fraction of particular cell types lacking the surface expression of GPI-anchored glycoproteins is referred to as the respective PNH clone; median PNH clone sizes of cells with short life spans (reticulocytes, platelets, granulocytes) was 50-80% of total cell populations compared to 20% of red blood cells. The results of our laboratory investigations show, that in PNH, reduced platelet counts coincide with reduced platelet reactivity. The foremost clinical complication in PNH, however, is venous thromboembolism, very probably induced by an activated and dysregulated plasmatic coagulation system. From these seemingly contradictory findings we infer, that part of the platelet hyporeactivity is probably due to reactive downregulation of platelet function in response to chronic hyperstimulation. The overall result is thought to be an unsteady balance, associated with thromboembolism in a larger proportion of patients, and with bleeding in a smaller proportion.

Adolescent↗

PubMed2001

A genome-wide analysis of transcriptional effect of Gal11 in Saccharomyces cerevisiae: an application of "mini-array hybridization technique".

The Gal11 protein is a subunit of the Mediator complex. Biochemical as well as genetic studies have strongly suggested that Gal11 is a positive global regulator of transcription. Some reports argue that Gal11 is a negative regulator, however. Here we have adopted the "Mini-array membrane hybridization" to analyze the effect of Gal11 in a genome-wide fashion. This technique has been demonstrated to be reliable to identify genes whose expression is controlled by a specific set of genetic and/or physiological signals. Our experiments indicate that this technique is applicable to profile the gene expression in yeast grown in rich medium. Thus mRNAs of 40% of significantly expressed genes are reduced more than two fold in gal11null yeast, in which only 3% of mRNAs are increased more than two fold. These results strongly suggest that Gal11 functions globally as a positive regulator in vivo.

Fungal Proteins↗

PubMed2006

Cognitive reserve, age, and neuropsychological performance in healthy participants.

The first aim of this study was to explore the relation between cognitive reserve, age, and neuropsychological functioning in a healthy sample; and second, to determine the risk of showing cognitive deficits as a function of cognitive reserve. One hundred forty-six healthy participants between the ages of 20 and 79 were submitted to neuropsychological assessment, focusing on attention, memory, visuo-construction, conceptualization and reasoning. Premorbid IQ as measured with the Wechsler Adult Intelligence Scale Vocabulary subtest was used as a proxy of cognitive reserve. Multivariate regression analysis with age and premorbid IQ as explanatory factors revealed a significant effect in all neuropsychological tests. Logistic regression revealed that participants with low cognitive reserve were more likely to obtain deficient scores (< or =1.5 SD below the mean) in the cognitive domains of attention (odds ratio [OR], 3.13; 95% confidence interval [CI], 1.059.29), memory (OR, 6.17; 95% CI, 1.69-22.61) and global functioning (OR, 6.44; 95% CI, 2.56-16.22) than participants with high cognitive reserve. Results suggest that cognitive reserve acts as a protective factor against the expression of cognitive decline related to age in healthy individuals.

Adult↗

PubMed1990

Significance of collateral circulation in reversible left ventricular asynergy by nitroglycerin in patients with relatively recent myocardial infarction.

To evaluate the functional role of coronary collateral circulation in reversible asynergy of the left ventricle, cineventriculography was performed before and after the administration of sublingual nitroglycerin in 19 patients with complete occlusion of the proximal part of the left anterior descending coronary artery. In nine patients who had significant collateral circulation to the infarct-related coronary artery (group A), there was significant improvement in both the left ventricular ejection fraction (53% to 60%, p less than 0.05) and regional wall motion in the infarct zone (8% to 18%, p less than 0.01 in the anterolateral area) with administration of nitroglycerin. In contrast, in the remaining 10 patients without significant collateral perfusion (group B), there were no detectable changes in either global function (49% versus 50%) or regional wall motion (6% versus 8% in the anterolateral area) before and after nitroglycerin. Changes in heart rate and left ventricular peak systolic and end-diastolic pressures with nitroglycerin were comparable in both groups. These results suggest that angiographically demonstrable collaterals preserve viable myocardium, which can improve its contraction when the supply-demand relationship is favorably affected because of increased collateral flow and/or more favorable loading conditions produced by nitroglycerin.

Cineradiography↗

PubMed1986

Left ventricular function during lethal and sublethal endotoxemia in swine.

Our previous studies suggested that after a median lethal dose (LD50) of endotoxin, cardiac contractility was depressed in nonsurviving dogs. The canine cardiovascular system is unlike humans in that dogs have a hepatic vein sphincter that is susceptible to adrenergic stimulation capable of raising hepatic and splanchnic venous pressures. We retested the hypothesis that lethality after endotoxin administration is associated with cardiac contractile depression in pigs, because the hepatic circulation in this species is similar to that of humans. We compared cardiac mechanical function of pigs administered a high dose (250 micrograms/kg) or a low dose (100 micrograms/kg) endotoxin by use of the slope of the end-systolic pressure-diameter relationship (ESPDR) as well as other measurements of cardiac performance. In all the pigs administered a high dose, ESPDR demonstrated a marked, time-dependent depression, whereas we observed no significant ESPDR changes after low endotoxin doses. The other cardiodynamic variables were uninterpretable, due to the significant changes in heart rate, end-diastolic diameter (preload), and aortic diastolic pressure (afterload). Plasma myocardial depressant factor activity accumulated in all endotoxin-administered animals, tending to be greater in the high-dose group. In this group, both subendocardial blood flow and global function were depressed, whereas pigs administered the low dose of endotoxin demonstrated slight, but nonsignificant, increases in flow and function. These observations indicate that myocardial contractile depression is associated with a lethal outcome to high doses of endotoxin. One possible mechanism for this loss of contractile function may be a relative hypoperfusion of the subendocardium.

Animals↗

PubMed2000

Depot bromperidol decanoate for schizophrenia.

BACKGROUND: Anti-psychotic drugs are the mainstay treatment for schizophrenia. Long-acting depot injections of drugs such as bromperidol decanoate are extensively used as a means of long-term maintenance treatment. OBJECTIVES: To assess the effects of depot bromperidol versus placebo, oral anti-psychotics and other depot antipsychotic preparations for people with schizophrenia in terms of clinical, social and economic outcomes. SEARCH STRATEGY: Relevant trials were identified by searching Biological Abstracts (1982-1999), Cochrane Library (Issue 2, 1999), Cochrane Schizophrenia Group's Register (May 1999), EMBASE (1980-1999), MEDLINE (1966-1999) and PsycLIT (1974-1999). References of all identified trials were inspected and Janssen Cilag contacted in order to identify more trials. SELECTION CRITERIA: All randomised trials focusing on people with schizophrenia where depots bromperidol, oral anti-psychotics or other depot preparations were sought. Primary outcomes were death, clinically significant change in global function, mental state, relapse, hospital admission, adverse effects and acceptability of treatment. DATA COLLECTION AND ANALYSIS: Studies were reliably selected, quality rated and data extracted. For dichotomous data Peto odds ratios (OR) with the 95% confidence intervals (CI) were estimated. The number needed to treat statistic (NNT) was to have been calculated. Analysis was by intention-to-treat. MAIN RESULTS: Four controlled clinical trials were found (total n=117). Smeraldi 1990 (n=20) compared bromperidol decanoate to placebo and found that more people in the latter group left the study by six months duration (50% versus 20%, OR 0.3 CI 0.05-7). There were no clear differences between bromperidol decanoate and placebo for a list of side effects. Ratings of global impression, mental state and needing additional antipsychotic medication all tended to favour the control depots (fluphenazine decanoate and haloperidol decanoate) and people consistently left the bromperidol decanoate group more frequently than those allocated other depots (n=97, OR 2.6 CI 0.8-9). There was no clear pattern in the occurrence of adverse effects. REVIEWER'S CONCLUSIONS: Currently, extrapolating from minimal trial data suggests that bromperidol decanoate may be better than a placebo injection but less valuable than fluphenazine or haloperidol decanoate. If bromperidol decanoate is available to the clinician it may be a viable choice, especially when there are reasons not to use fluphenazine or haloperidol decanoate. Well-conducted and reported randomised trials are urgently needed to inform practice in Belgium, Germany, Italy and the Netherlands.

Antipsychotic Agents↗

PubMed1992

Long-term survivors of leukemia treated in infancy: factors associated with neuropsychologic status.

PURPOSE: Because of concerns about late toxicities of treatment among infants diagnosed with acute lymphoblastic leukemia (ALL), and especially the effects of cranial radiation therapy (CRT), we compared the functional and neuropsychologic status of 26 long-term survivors of ALL who were diagnosed in the first 24 months of life versus 26 children who were treated previously for Wilms' tumor. PATIENTS AND METHODS: Of the children with ALL, CNS prophylaxis included no CRT in six, 18 Gy CRT in five, 20 Gy CRT in seven, and 24 Gy CRT in five. Three additional children experienced CNS relapse and received total CRT doses of 24, 40, and 44 Gy. All children received neuropsychologic testing; children with ALL also participated in diagnostic imaging studies. RESULTS: As a group, the children who were treated for ALL did not differ significantly from those who were treated for Wilms' tumor on objective measures of global functional status. However, children treated for ALL had a significantly lower mean intelligence quotient (IQ) (87 v 96), poorer performance on four of six measures of visual and auditory memory, lower achievement with regard to arithmetic skills, and a greater frequency of special educational intervention than those who were treated for Wilms' tumor. IQ and auditory memory performance in the ALL group was correlated inversely with time since the completion of therapy and total CRT dose. CONCLUSIONS: These results reinforce the contemporary trend of prophylactic CRT omission in very young children except for those who are at risk for CNS relapse. For infants and very young children who require CRT, evidence is presented that supports the approach for the delay of CRT until the child is older.

Adolescent↗

PubMed1985

Clinical and hemodynamic evaluation of propranolol in combination with verapamil, nifedipine and diltiazem in exertional angina pectoris: a placebo-controlled, double-blind, randomized, crossover study.

The clinical and hemodynamic effects of propranolol, propranolol-verapamil (P-V), propranolol-nifedipine (P-N) and propranolol-diltiazem (P-D) were studied in 19 patients with chronic exertional angina pectoris. A placebo-controlled, double-blind, randomized, crossover study design was used in which patients took each treatment for a 4-week period. The 3 combinations equally reduced the incidence of angina attacks and decreased ST-segment depression. Left ventricular hypokinesia during exercise was lessened and end-systolic volume during exercise decreased with all combinations. Because of a corresponding reduction of normokinetic segmental function, global ejection fraction during exercise remained unchanged. Heart size increased (p less than 0.05) and the PR interval lengthened (p less than 0.001) with P-V and P-D compared to P-N. The largest number of adverse clinical reactions occurred with P-V, whereas the fewest occurred with P-D. Almost all patients preferred combined therapy over propranolol and many favored 1 combination over the others. In summary, when therapy with combined beta- and calcium channel-blocking drugs is planned, P-D should be considered the combination of first choice because of its low incidence of adverse clinical effects. In the presence of possible or definite abnormalities of atrioventricular nodal conduction or decreased left ventricular function, P-N should be considered. Although P-V is associated with frequent adverse reactions, a trial may be warranted if the other combinations are unsuccessful.

Adult↗