Pathologic explanation for postoperative obstipation in Hirschsprung's disease revealed with monoclonal antibody staining

Until now, no pathologic explanation could be found for the postoperative obstipation occurring in some patients with intestinal aganglionosis. Twenty-two of 108 infants treated for intestinal aganglionosis suffered from postoperative obstipation. Resected material from these 22 patients and from 17 control subjects was investigated with monoclonal anti-neurofilament antibody staining. An abnormal staining pattern was revealed in 18 of the constipated patients. Consequently, this new immunohistochemical staining technic has revealed a hitherto unsuspected cause for postoperative obstipation in aganglionosis. The monoclonal antibody may provide early warning of such postoperative constipation.     

Dose-effect relations in time-limited combined psycho-pharmacological treatment for depression

BACKGROUND: A limited number of psychotherapy sessions in combination with medication is preferable to pharmacotherapy only in the treatment of ambulatory patients with major depression. Whether there is a relation between the number of sessions and the efficacy of the treatment is uncertain. METHOD: Randomized clinical trial comparing two treatment conditions in outpatients with major depression. All patients studied had a baseline score of at least 14 points on the 17-item Hamilton Depression Rating Scale. The two conditions consist of 8-session or 16-session Short Psychodynamic Supportive Psychotherapy, both in combination with pharmacotherapy. Efficacy was assessed using the 17-item HDRS, the CGI of Severity and of Improvement, the depression subscale of the SCL-90 and the Quality of Life Depression Scale. RESULTS: The rate of change would seem to indicate that eight sessions are preferable for both moderately and severely depressed patients, although the results converged again at the end. Furthermore, in terms of satisfaction with the number of sessions and drop-out percentages during treatment, no differences were found between the conditions. CONCLUSION: In the light of the outcome analysis (faster remission after fewer sessions), a short version of the psychotherapy treatment in a combined course of treatment seems to be justified.     

Primitive neuroectodermal tumors of the central nervous system. Patterns of expression of neuroendocrine markers, and all classes of intermediate filament proteins

Snap-frozen samples from 22 primitive neuroectodermal tumors (PNETs) primary in the central nervous system were studied with antibodies to synaptophysin, bombesin, somatostatin, substance P, vasoactive intestinal polypeptide, all classes of intermediate filaments, and desmoplakins I and II. Frozen sections were immunostained by the avidin-biotin peroxidase complex and indirect immunofluorescence microscopy methods. Selected cases were also studied by double and triple label immunofluorescence microscopy, and by two-dimensional gel electrophoresis and immunoblot analysis. We found that all 22 PNETs expressed synaptophysin extensively. Focal expression of 2 or more neuropeptides was noted in 10 samples studied. All PNETs expressed vimentin, 21 of 22 expressed glial filament protein (GFP), 16 of 22 expressed neurofilament proteins (NFP), 4 of 22 expressed desmin, and 3 of 22 expressed cytokeratins. In only one case were focal and questionable reactions with desmoplakin antibodies seen. Immunoblots confirmed the presence of desmin. Double and triple immunofluorescence revealed a number of antigenic coexpressions in individual cells including: synaptophysin with vimentin, GFP, NFP and desmin, vimentin-GFP, vimentin-NFP, vimentin-cytokeratin, vimentin-desmin and desmin-NFP; similarly, combinations of vimentin-GFP-NFP, vimentin-GFP-desmin, and vimentin-GFP-cytokeratin were found. The consistent expression of synaptophysin and 2 or more neuropeptides indicates that central nervous system PNETs have significant phenotypic features in common with neuroendocrine tumors. Their complex and variable intermediate filament complement patterns combined with their consistent expression of specific neuroendocrine differentiation markers, suggest that central nervous system PNETs comprise a distinct, albeit heterogeneous group of neoplasms.     

Localization of (-)-[125I]cyanopindolol binding in guinea-pig heart: characteristics of non-beta-adrenoceptor related binding in cardiac pacemaker and conducting regions.

Receptor autoradiography was used in guinea-pig heart to locate binding sites for the beta-adrenoceptor ligand (-)[125I]cyanopindolol (CYP) resistant to blockade by the beta-adrenoceptor antagonist (-)-propranolol (1 microM). Highly localized binding was observed to regions closely associated with the sinoatrial node, atrioventricular node and bundle of His but was not observed on myocardial, pacemaker, conducting cells or adipose tissue. Free [125I] also bound to identical sites. Binding was enhanced in the presence of ascorbic acid but was completely inhibited by (-)-isoprenaline (100 microM), serotonin (5-HT) (10 microM) and phentolamine (10 microM).     

The influence of molecular structure on the affinity and efficacy of some β-adrenoceptor agonists

Summary The affinity and efficacy of a number of sympathomimetic amines structurally related to prenalterol and the selective ₁-adrenoceptor agonist RO 363 were determined using a combination of radioligand binding and organ bath techniques. Affinity of the molecules (pK _D) was calculated from their ability to displace the radioligand [¹²⁵I]iodocyanopindolol ([¹²⁵I]CYP) from -adrenoceptor sites in left atrial (₁) and uterine (₂) membrane homogenates. These pK _D values were used to calculate efficacy from the positive inotropic and uterine relaxant responses elicited by the drugs in organ bath experiments. The drugs studied were either arylethanolamines i.e., (–)-isoprenaline (ISO), p-hydroxyisoprenaline (pOH-ISO), compounds XIV and XVI or aryloxypropanolamine-derivatives, i.e., oxymethylene-isoprenaline (OM-ISO), prenalterol and Compound XI which possessed ap-phenol or catechol ring and an isopropyl or a homoveratryl amine substituent. Only ISO, OM-ISO, pOH-ISO and Compound XVI were active as agonists in both tissue preparations. These drugs were partial agonists which exhibited a wide range of pD₂ values and did not display any marked selectivity for either -adrenoceptor subtype. Compound XI and prenalterol were inactive as agonists and together with the partial agonists behaved as competitive antagonists to ISO in the two preparations. All drugs tested displaced [¹²⁵I]CYP from -adrenoceptor sites, however, there was also a wide range of potency amongst the drugs.Analysis of the structure-affinity and structure-efficacy relationships indicated that removal of the 3-hydroxyl group from the catechol ring reduces both affinity and efficacy without altering the selectivity of the drug for either -adrenoceptor subtype. While aryloxypropanolamine derivatives have generally higher affinities than arylethanol-amines, especially at -adrenoceptor sites, their efficacies are generally reduced at both -adrenoceptors. The presence of a homoveratryl group in aryloxypropanolamines enhances slightly the affinity for ₁- and reduces affinity for ₂-adrenoceptors. With this amine group, efficacy is markedly reduced at ₂- as opposed to ₂-adrenoceptor sites.Thus for prenalterol, the small degree of cardioselectivity can be attributed to the oxymethylene group whilst its lack of agonist activity (i.e., efficacy) reflects a combined action of this group and the absence of the 3-hydroxyl group on the phenyl ring. In RO363 it can be deduced that the oxymethylene group, together with the homoveratryl substituent are responsible for the observed selective affinity of the drug for ₁- as opposed to ₂-adrenoceptors.     

Effects of Advertising: A Qualitative Analysis of Young Adults’ Engagement with Social Media About Food

Young adults are constantly exposed to energy-dense, nutrient-poor food and beverages, particularly through advertising. Exposure can influence poor food choices and negatively impact health. This study aimed to understand young adults’ attitudes and experiences associated with food-related advertisements, particularly on social media. This qualitative analysis involved n = 166 Australian 18 to 24-year-olds who were involved in a four-week online conversation on different areas relating to health, social media, and eating. Inductive thematic analysis was utilised on two forums on the recall and perceptions of food-related advertisements. Young adults commonly mentioned aspects of the marketing mix (promotion, product, price, and place) in food advertisements. Participants were more readily able to recall energy-dense, nutrient-poor food advertisements compared to healthy food-related advertisements. Digital advertisements were often discussed alongside the use of ad-blockers and algorithms which tailored their social media viewing to what they like. Participants felt constant exposure to unhealthy food advertisements hindered their ability to realise healthy eating behaviours and created feelings of guilt. This current analysis highlights the need to provide an advertising environment that appropriately motivates healthy eating and a food environment that allows healthy food to be the affordable and convenient option.     

Psycho-Behavioural Segmentation in Food and Nutrition: A Systematic Scoping Review of the Literature

Inadequate dietary intakes are a key modifiable risk factor to reduce the risk of developing non-communicable diseases. To encourage healthy eating and behaviour change, innovative public health interventions are required. Social marketing, in particular segmentation, can be used to understand and target specific population groups. However, segmentation often uses demographic factors, ignoring the reasons behind why people behave the way they do. This review aims to explore the food and nutrition related research that has utilised psycho-behavioural segmentation. Six databases from were searched in June 2020. Inclusion criteria were: published 2010 onwards, segmentation by psycho-behavioural variables, outcome related to food or nutrition, and healthy adult population over 18 years. 30 studies were included; most were quantitative (n = 28) and all studies used post-hoc segmentation methods, with the tools used to segment the population varying. None of the segments generated were targeted in future research. Psycho-behavioural factors are key in understanding people’s behaviour. However, when used in post-hoc segmentation, do not allow for effective targeting as there is no prior understanding of behaviours that need to change within each segment. In future, we should move towards hybrid segmentation to assist with the design of interventions that target behaviours such as healthy eating.     

Early fetal acquisition of the chromaffin and neuronal immunophenotype by human adrenal medullary cells. An immunohistological study using monoclonal antibodies to chromogranin A, synaptophysin, tyrosine hydroxylase, and neuronal cytoskeletal proteins

The development of chromaffin and neuronal features in the adrenal medulla was studied in normal human fetuses with gestational ages (GAs) of 6-34 weeks. Monoclonal antibodies specific for chromogranin A, synaptophysin, and tyrosine hydroxylase; for different subunits and phosphoisoforms of neurofilament (NF) proteins; and for microtubule-associated proteins were applied. Morphologically, two major cell types could be distinguished, i.e., "large" cells with pale nuclei and ill-defined cytoplasm, which were present from 9 weeks GA on, and clusters of "small," primitive appearing cells, present from 14 weeks GA on. The large cells were immunoreactive for chromogranin A, synaptophysin, tyrosine hydroxylase, and NF proteins, similar to adult chromaffin cells. In contrast, small cells expressed NF proteins and tyrosine hydroxylase, but not chromogranin A or synaptophysin, more resembling ganglion cells in the adult adrenal medulla. At the latest developmental stages large cells were observed in the center of the clusters of "small" cells, which morphologically resembled immature ganglion cells and expressed NF proteins in their perikarya. These observations indicate that chromaffin and ganglion cells establish their immunophenotype early in embryogenesis. They suggest that "large" and "small" cells are progenitors of the chromaffin and the ganglion cells, respectively, of the mature adrenal medulla.