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Exercise-induced changes in the plasma levels of propranolol and noradrenaline were determined in nine volunteers. Total plasma propranolol levels were increased during submaximal treadmill exercise, with exercise-induced increments of 13 +/- 4% at 4 h after the last dose, 18 +/- 7% at 9 h and 41 +/- 5% at 16 h. Exercise-induced increments in plasma propranolol were observed after single as well as repeated doses. During exercise, increments in plasma propranolol were correlated temporally with changes in plasma noradrenaline. Exercise- induced increments in plasma noradrenaline were greater during propranolol administration than during placebo periods. The changes in plasma propranolol concentration during exercise may reflect a redistribution of propranolol at its site(s) of action. [ABSTRACT FROM AUTHOR]

Purpose of Review: Idiopathic intracranial hypertension (IIH) is a chronic headache disorder with increasing prevalence. Although characterized by raised intracranial pressure causing papilledema with a risk of visual impairment, psychological symptoms such as depression, anxiety, and cognitive impairment are frequently seen but are understudied and under-reported. Together, these can negatively affect quality of life. These were explored through a systematic PRISMA scoping review. OVID, EMBASE, Cochrane, and PubMed databases were searched in April 2023, limited to those in English and published during January 2000-March 2023. PROSPERO ID CRD42023399410., Recent Findings: From 454 identified studies, 24 relevant articles were identified from a range of countries including the United Kingdom, the United States, Israel, Egypt, Canada, Germany, and Brazil. Data on study design, participants, tests performed, and outcomes were collated. There is a considerable burden of psychiatric, affective, and cognitive conditions, as well as impaired quality of life, in adult patients with IIH. Notably, these were independently correlated with the presence of headache in a number of studies and with obesity in others., Summary: Aside from optimizing symptom control, including reducing the severity of headaches and protecting visual function, clinicians should be mindful of the biopsychosocial difficulties and potential cognitive impairments patients with IIH face. Assistance may be required with managing concurrent depression and anxiety, as well as optimizing cognitive function. Incorporating neuropsychological assessment and individualized management strategies may be beneficial at the point of diagnosis and throughout the illness., Competing Interests: The authors report no relevant disclosures. Full disclosure form information provided by the authors is available with the full text of this article at Neurology.org/cp., (© 2024 American Academy of Neurology.)

Glioblastoma is an aggressive brain tumor that carries a poor prognosis. The tumor's molecular and cellular landscapes are complex, and their relationships to histologic features routinely used for diagnosis are unclear. We present the Ivy Glioblastoma Atlas, an anatomically based transcriptional atlas of human glioblastoma that aligns individual histologic features with genomic alterations and gene expression patterns, thus assigning molecular information to the most important morphologic hallmarks of the tumor. The atlas and its clinical and genomic database are freely accessible online data resources that will serve as a valuable platform for future investigations of glioblastoma pathogenesis, diagnosis, and treatment., (Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

The transcriptional underpinnings of brain development remain poorly understood, particularly in humans and closely related non-human primates. We describe a high-resolution transcriptional atlas of rhesus monkey (Macaca mulatta) brain development that combines dense temporal sampling of prenatal and postnatal periods with fine anatomical division of cortical and subcortical regions associated with human neuropsychiatric disease. Gene expression changes more rapidly before birth, both in progenitor cells and maturing neurons. Cortical layers and areas acquire adult-like molecular profiles surprisingly late in postnatal development. Disparate cell populations exhibit distinct developmental timing of gene expression, but also unexpected synchrony of processes underlying neural circuit construction including cell projection and adhesion. Candidate risk genes for neurodevelopmental disorders including primary microcephaly, autism spectrum disorder, intellectual disability, and schizophrenia show disease-specific spatiotemporal enrichment within developing neocortex. Human developmental expression trajectories are more similar to monkey than rodent, although approximately 9% of genes show human-specific regulation with evidence for prolonged maturation or neoteny compared to monkey.

The anatomical and functional architecture of the human brain is mainly determined by prenatal transcriptional processes. We describe an anatomically comprehensive atlas of the mid-gestational human brain, including de novo reference atlases, in situ hybridization, ultra-high-resolution magnetic resonance imaging (MRI) and microarray analysis on highly discrete laser-microdissected brain regions. In developing cerebral cortex, transcriptional differences are found between different proliferative and post-mitotic layers, wherein laminar signatures reflect cellular composition and developmental processes. Cytoarchitectural differences between human and mouse have molecular correlates, including species differences in gene expression in subplate, although surprisingly we find minimal differences between the inner and outer subventricular zones even though the outer zone is expanded in humans. Both germinal and post-mitotic cortical layers exhibit fronto-temporal gradients, with particular enrichment in the frontal lobe. Finally, many neurodevelopmental disorder and human-evolution-related genes show patterned expression, potentially underlying unique features of human cortical formation. These data provide a rich, freely-accessible resource for understanding human brain development.

This study examined the relationship between sensory processing difficulties, parental stress, and behavioral problems in a clinical sample of young children with developmental and behavioral difficulties. We hypothesized that a high rate of sensory processing difficulties would be found, that there would be a high rate of comorbidity between sensory processing difficulties and behavioral problems, and that children's sensory processing difficulties and parental stress would be highly correlated. Parents of 59 children ages two to five who attended an out-patient clinic in a low income, urban community completed the Child Behavior Checklist, Parental Stress Inventory-Short Form and the Short Sensory Profile. Children in this clinical population showed a high prevalence (55.9%) of sensory processing difficulties, a significantly higher rate than previously reported. Sensory processing deficits were correlated with behavioral difficulties and parental stress levels-suggesting that as sensory processing difficulties increase, so do behavioral difficulties and parental stress. Parents of children with sensory processing deficits had significantly higher levels of parental stress than parents of children without sensory deficits. Parenting stress levels were also clinically elevated for the cohort of children in which sensory processing difficulties and behavioral concerns co-existed. These findings suggest that treatment outcomes might improve and parental stress could be reduced if mental health clinicians were trained to identify and address sensory problems. This could result in more children being screened and treated for sensory processing difficulties and an eventual reduction in the rates of parental stress.

The authors performed a chart review to determine the frequency with which neurologists detect cognitive and psychiatric symptoms in patients with cerebellar degeneration. Psychopathology, including depression, personality change, cognitive impairment, anxiety, and psychosis was noted in 51% of 133 patients.

A provocative double-blind study of headache was performed using chocolate as the active agent and carob as the placebo. The chocolate and carob samples were formulated to duplicate products used in an earlier study (1) in which strong differential effects between the ability of chocolate and carob to trigger headache in migraine were shown. Sixty-three women with chronic headache (50% migraine, 37.5% tension-type, 12.5% combined migraine and tension-type) participated in the study. After 2 weeks of following a diet that restricted vasoactive amine-rich foods, each subject underwent double-blinded provocative trials with two samples of chocolate and two of carob presented in random order. Diaries were maintained by the subjects throughout the study, monitoring diet and headache. The results demonstrated that chocolate was not more likely to provoke headache than was carob in any of the headache diagnostic groups (chi2(2)=0.36, p=0.83). Interestingly, these results were independent of subjects' beliefs regarding the role of chocolate in the instigation of headache (chi2(1)=0.73, p=0.39). Headache diagnosis and the concomitant use of additional vasoactive amine-containing foods were also not associated with chocolate acting as a headache trigger. Thus, contrary to the commonly held belief of patients and physicians, chocolate does not appear to play a significant role in triggering headaches in typical migraine, tension-type, or combined headache sufferers.

The association between the consumption of preserved foods in infancy, childhood and adulthood and the risk of nasopharyngeal carcinoma was investigated in a case-control study among Singapore Chinese: 200 cases (73% male) were compared with 406 hospital controls (71% male). Significantly increased risks were observed in association with frequent adult consumption of salted soy beans (OR 7.3 for consumption 4 or more times per week, compared with never), canned pickled vegetables (p = 0.01; OR 4.5 for 4 or more times per week), "sze chuan chye", a salted Chinese tuber, (OR 2.4 for 4 or more times per month) and "kiam chye", salted mustard greens (OR 2.7 for 4 or more times per week). A protective effect of high vitamin-E intake in adulthood was observed (OR 0.5 for the highest third of the control range, as compared with the lowest).

The purpose of this study was to determine whether patients whose blood pressure failed to normalize while receiving monotherapy with atenolol would experience further blood pressure lowering by adding the angiotensin-converting enzyme (ACE) inhibitor benazepril hydrochloride to their treatment regimen. Seventy-four of the original 127 patients treated with atenolol met the criteria for entry into the 4-week, double-blind phase of the study, in which either benazepril 10 mg twice daily (increased after 1 week, if necessary, to 20 mg twice daily) or placebo was added to atenolol. At end point, 46% of the benazepril group had achieved an excellent or good response (ie, diastolic blood pressure [DBP] < 90 mm Hg or a decrease of > or = 10 mm Hg below the baseline) compared with 14% of the placebo group (P < 0.01). The mean fall in DBP at end point was -5.6 mm Hg in the benazepril group and -3.7 mm Hg in the placebo group. Because six patients in the benazepril group experienced an increase of blood pressure that offset the fall observed in the responders, the difference in DBP response between the benazepril group and the placebo group was not statistically significant. We conclude that adding benazepril to the regimen of patients whose blood pressure is inadequately controlled while receiving atenolol monotherapy can produce an additional decrease in blood pressure in almost half the patients.

Background: Although digoxin is effective in the treatment of patients with chronic heart failure who are receiving diuretic agents, it is not clear whether the drug has a role when patients are receiving angiotensin-converting-enzyme inhibitors, as is often the case in current practice., Methods: We studied 178 patients with New York Heart Association class II or III heart failure and left ventricular ejection fractions of 35 percent or less in normal sinus rhythm who were clinically stable while receiving digoxin, diuretics, and an angiotensin-converting-enzyme inhibitor (captopril or enalapril). The patients were randomly assigned in a double-blind fashion either to continue receiving digoxin (85 patients) or to be switched to placebo (93 patients) for 12 weeks. Otherwise, their medical therapy for heart failure was not changed., Results: Worsening heart failure necessitating withdrawal from the study developed in 23 patients switched to placebo, but in only 4 patients who continued to receive digoxin (P < 0.001). The relative risk of worsening heart failure in the placebo group as compared with the digoxin group was 5.9 (95 percent confidence interval, 2.1 to 17.2). All measures of functional capacity deteriorated in the patients receiving placebo as compared with those continuing to receive digoxin (P = 0.033 for maximal exercise tolerance, P = 0.01 for submaximal exercise endurance, and P = 0.019 for New York Heart Association class). In addition, the patients switched from digoxin to placebo had lower quality-of-life scores (P = 0.04), decreased ejection fractions (P = 0.001), and increases in heart rate (P = 0.001) and body weight (P < 0.001)., Conclusions: These findings indicate that the withdrawal of digoxin carries considerable risks for patients with chronic heart failure and impaired systolic function who have remained clinically stable while receiving digoxin and angiotensin-converting-enzyme inhibitors.

A case-control study was conducted among Singapore Chinese women, comprised of 200 histologically confirmed cases of breast cancer and 420 hospital controls. Subjects were interviewed on family history of breast cancer, social and demographic characteristics, reproductive history, and diet one year prior to interview. Differences in risk factors were observed according to menopausal status. In the premenopausal group, the most consistently significant nondietary effect was an increased risk with late age at first birth. In postmenopausal women, the most consistent nondietary effects were increased risks with nulliparity, tall stature, high educational status, and a family history of breast cancer. In premenopausal women, the strongest dietary effects were low risks with high intakes of polyunsaturated fatty acids (PUFA), beta-carotene, soya protein as a proportion of all protein, and a high risk with high red-meat intake. No dietary effects were observed in postmenopausal women. Examination of effects by 10-year age groups suggested that the differences in the effects of age at first birth, nulliparity, height, education, beta-carotene intake, and PUFA intake between premenopausal and postmenopausal women were at least partly attributable to age-related differences in the baseline distributions of these variables. The variation in the effects of red meat and soya protein appeared to be attributable mainly to menopausal status itself, which is consistent with the hypothesis that these factors operate on risk by way of hormonal mechanisms.

This study evaluated the blood pressure effects of administration of once daily oral benazepril hydrochloride, a new angiotensin-converting enzyme (ACE) inhibitor, for mild-to-moderate hypertension. After a 2 to 4 week placebo baseline period, patients with diastolic blood pressure between 95 and 114 mm Hg, were randomized to receive either placebo or benazepril hydrochloride, 5, 10, 20, or 40 mg, once daily in double-blind fashion for 28 days. Blood pressure was measured predose and at 1, 2, 3, 4, 6, 8, 12, 16, 20, and 24 hours after the dose during inpatient observation days at the end of the placebo baseline period, and on the first and last day of the double-blind treatment period; and 24 hours after the dose at weekly outpatient visits. All doses of benazepril hydrochloride resulted in clinically important reductions in diastolic and systolic blood pressures that lasted between 12 and 24 hours after both the first dose, and following the last dose after 4 weeks of treatment. The findings indicate that benazepril hydrochloride may be clinically useful as once-daily monotherapy in many patients with hypertension.

A survey of 40 Singapore Chinese households was performed, obtaining information on major perishable foods purchased for home consumption in the previous week, extent of home consumption (eating in), household dietary habits and housing type, the last as a measure of affluence. Eating out was very common: nine (23 per cent) households ate less than 50 per cent of meals at home. Excluding these nine households, consumption and habits were compared between more affluent and less affluent households. The more affluent households purchased more red meat/offal (P = 0.001), poultry (P = 0.002), vegetables other than green leafy (P = 0.04), fruit (P = 0.007) and eggs (P = 0.04); they also differed significantly in various dietary habits. Significant differences were also observed between English-speaking and Chinese-speaking households. The results suggest that increasing affluence may have brought about substantial dietary change in Singapore, thus meriting further study of the role of diet in changing disease patterns in Singapore.

The effects of single oral and intravenous doses of propranolol on blood pressure and hemodynamics were measured in normal volunteers. Systolic and diastolic blood pressure decreased 10% within 3 hours after the oral dose and by 3%-5% after the intravenous dose. Cardiac output decreased 16% after the intravenous dose and 10% after the oral dose. Total peripheral resistance transiently increased by 23% after the intravenous, but not after the oral dose. Change in mean arterial pressure was positively correlated with change in total peripheral resistance after both the oral and intravenous doses. In contrast, change in mean arterial pressure was negatively correlated with change in cardiac output after the intravenous dose. Single oral and intravenous doses of propranolol lowered blood pressure within 3 hours after administration, and the reduction was correlated with change in total peripheral resistance and not with change in cardiac output. At least part of the adaptation in peripheral resistance occurs within the first 3 hours after both oral and intravenous single doses of propranolol.

Data on fat and fibre content in the Singapore diet are presented. Food availability data show an upward trend in per capita fat and fibre supplies over the last 25 years. However, food availability is usually an overestimate of actual consumption. Data on food consumption levels show that fat intake in Singapore is in reality relatively lower than the corresponding intake in Western countries. Fibre intake is also lower than in the West. At the same time, the incidence of colorectal cancer is increasing. This provides an interesting opportunity for analytical studies to further elucidate the likely role of diet in the aetiology of colorectal cancer in Singapore.

Treatment with beta-adrenoceptor blocking drugs may result in augmented plasma concentrations of noradrenaline during exercise. The effect of propranolol on exercise heart rate and its relationship to plasma concentrations of propranolol and noradrenaline were examined in 10 hospitalized volunteers following treatment with propranolol, in doses of 80 mg and 320 mg daily. Responses to submaximal treadmill exercise during propranolol treatment and following discontinuation of the higher dose were compared to pre-drug and post drug placebo values. Exercise noradrenaline was increased by 67% over baseline values by treatment with the 320 mg daily dose of propranolol; this increment was present at 4 h and returned to baseline by 16 h after drug administration. Augmentation of exercise noradrenaline was correlated with plasma propranolol concentrations; the threshold concentration for this effect was 10-fold higher than the threshold for reduction in exercise heart rate. The effect of propranolol on heart rate was blunted in relation to the augmentation of exercise noradrenaline (P less than 0.001). These relationships suggest that, in patients taking high doses of propranolol, drug induced augmentation of plasma levels of noradrenaline during exercise may have physiologic importance. Enhanced effects on adrenergic receptors could have clinical relevance in certain groups of patients.

The effects of a standardized mixed meal, a self-selected meal and a sham meal on heart rate, arterial pressure, cardiac output, total systemic resistance and echocardiographic indexes of left ventricular performance were examined in normal volunteers. Supine heart rate and cardiac output increased after the meals (p less than 0.07 to 0.001), but not after the sham meal. Supine diastolic blood pressure and total systemic resistance decreased after the meals but not after the sham meal (p less than 0.05 to 0.001). Ejection fraction and mean velocity of circumferential fiber shortening increased after the standard meal (p less than 0.01) and tended to increase after the self-selected meal, but did not increase after the sham meal. Meals of normal size may induce splanchnic vasodilation and a decrease in total systemic resistance. Ingestion of food also significantly affects heart rate, blood pressure, cardiac output and echocardiographic indexes of left ventricular performance. Patients should not eat during short-term evaluation of cardiovascular interventions because the cardiovascular effects of a meal may compromise interpretation of the cardiovascular effects of the primary intervention. The hemodynamic effects of food may also interact with the effects of cardiovascular disease processes.