Spectrum of looping disturbances in stage 34 chicken hearts after retinoic acid treatment

Background: In a recently developed chick model the teratogen retinoic acid has appeared to induce a spectrum of double outlet right ventricle, which needs further detailed evaluation. It is known that retionic acid is able to induce cardiac malformations. Although the exact mechanism is not known, an interaction with neural crest cell function is thought to exist. Methods: After treatment with 1 μg all-trans retinoic acid at Hamburger and Hamilton stage 15 and reincubation until stage 34 of development 41 chicken embryos were evaluated macroscopically and microscopically, supported by graphic reconstructions. These retinoic acid treated embryos were compared with a control group (n = 8). Results: The retinoic acid treated embryos could be divided in three groups. Group 1 (23/41) had an intact septum, group 2 (11/41) had an isolated ventricular septal defect (VSD), and group 3 (7/41) had a double outlet right ventricle (DORV). Besides, in the group with an intact septum 11 hearts showed an abnormal course of the subaortic outflow tract. In the group with DORV a straddling tricuspid orifice (7/8) and a double inlet left ventricle (1/8) could be distinguished. Considering the external contour, the hearts in the DORV group all showed a dextroposed arterial pole. Malformed pharyngeal arch arteries were found in all three groups (11/41) and with a great diversity. Conclusions: The present cardiac malformations in the chicken as a result of retinoic acid treatment are part of a continuous spectrum, varying from hearts with an intact ventricular septum and a normal course of the subaortic outflow tract to a double outlet right ventricle with a straddling tricuspid orifice or even a double inlet left ventricle. A remarkable observation in this spectrum concerns the correlation of malformations of the inflow and outflow tracts, which is explained as a cardiac looping disturbance. The disturbance of the looping process seems to lead to malalignment of septal components, although, in the chick, retinoic acid does not in general interfere with the formation of these septal components themselves. © 1995 Wiley-Liss, Inc.     

User satisfaction with a real-time automated feedback system for general practitioners: a quantitative and qualitative study.

OBJECTIVE: The GRIF automated feedback system produces real-time comments on the appropriateness of diagnostic tests ordered by general practitioners (GPs) based on recommendations from accepted national and regional practice guidelines. We investigated the experiences of GPs with this system and, more specifically, with the recommendations produced by the system as well as their views on using this system in daily practice. SETTING: We tested the GRIF system in an experiment in a laboratory setting and in a daily practice trial. STUDY PARTICIPANTS: General practitioners. INTERVENTION: In the laboratory experiment, GPs used the GRIF system to assess the appropriateness of 30 request forms. Each of the GPs was confronted with requests they had submitted to the diagnostic unit of the hospital in the past. In the field trial, the GRIF system was applied during patient consultations for 1 year. MAIN OUTCOME MEASURES: We measured GPs' satisfaction with the system using a questionnaire, and also conducted group discussions (in the laboratory experiment) and in-depth interviews (in the field trial) to elicit GPs' opinions of and experiences with the system. In addition, we explored GPs' reasons for not accepting the comments offered by the GRIF system. RESULTS: The results show that the GPs in the laboratory experiment had more positive attitudes towards the system compared with participants in the field trial. All discussion groups and most of the GPs in the field trial regarded receiving the immediate feedback during the test ordering process as an important advantage. The most frequently mentioned reason to reject the recommendation was disagreement with the content and/or the recommendations in the practice guidelines. CONCLUSION: Apart from securing agreement on guideline content, a prerequisite for using GRIF in daily practice on a large scale is that more attention is paid to promotion of the guidelines and their adoption, and stimulation of a positive attitude towards the practice guidelines among the users.     

Adenoma malignum (minimal deviation adenocarcinoma) of the cervix responsive to hormonal treatment

Adenoma malignum (AM) is a rare variant of cervical adenocarcinoma with an unfavorable prognosis despite radiation therapy, surgery, or chemotherapy either alone or in combination. Hitherto, however, the effectiveness of hormonal therapy for this condition has not been evaluated. We report on a patient with cervical AM treated with progesterone before surgery. The progesterone therapy resulted in a complete clinical response and partial surgical response. Later on the treatment was changed to tamoxifen because of side effects of the progesterone treatment. The patient is still without evidence of disease 42 months after the start of the hormonal therapy. The progesterone receptor analysis on the biopsy was clearly positive. This is, to our knowledge, the first case of an AM responsive to hormonal treatment. Furthermore, this is the first case of an AM with bone metastases at the time of primary diagnosis.     

Humoral and cellular effects of the K+-channel activator cromakalim in man

Summary The effect of cromakalim, a K⁺-channel activator, on the plasma renin-angiotensin-aldosterone system, catecholamines and -atrial natriuretic peptide, and on the intraerythrocyte concentration and transmembrane fluxes of Na⁺ and K⁺ has been investigated in 18 normal male subjects, in a double-blind parallel study. After a run-in period on placebo for 1 week, the subjects were treated either with placebo (n=6) or cromakalim (n=12) for 1 week.Plasma renin activity was significantly increased during cromakalim. No effect of cromakalim on plasma angiotensin II, aldosterone, adrenaline, noradrenaline and -atrial natriuretic peptide was demonstrated. The intra-erythrocyte K⁺ concentration was decreased during cromakalim administration and Ca²⁺-dependent K⁺-channels in red blood cells were increased.     

Short limbed dwarfism,genital hypoplasia,sparse hair,and vertebral anomalies: a variant of Ellis-van Creveld syndrome?

A male newborn with acromesomelic short limbed dwarfism, genital hypoplasia, and vertebral anomalies is reported. As the child had an important number of clinical and radiological symptoms seen in patients with Ellis-van Creveld syndrome, we raise the question of whether he may represent a variant example of this syndrome despite the absence of cardinal symptoms such as postaxial polydactyly and ectodermal changes (nail hypoplasia).     

Congenital muscular dystrophy associated with lethal arthrogryposis multiplex congenita

Summary Two unrelated patients with severe arthrogryposis multiplex congenita (AMC) who died perinatally, are presented. In both, postmortem examination revealed an intact nervous system and striking dystrophic muscle changes, consistent with congenital muscular dystrophy (CMD). Few similar cases have been reported before, but since the condition is not well known, it seems probable that in the past many have been labeled as mere multiple malformations. The possibility of an underlying muscular disorder, either primary myopathic or neurogenic should be considered in any patient with early lethal AMC. Our findings confirm that the fetal akinesia-arthrogryposis sequence is a nonspecific clinical syndrome resulting from various causes of muscular inactivity in utero. The main objective of this report is to provide reasonable guidelines on how to approach the problem of classification. We favor a pathogenetic approach, depending upon careful sampling of the central nervous system and skeletal muscles at autopsy.     

In-vitro adhesion of endometrium to autologous peritoneal membranes: effect of the cycle phase and the stage of endometriosis

BACKGROUND: Endometrium can adhere to autologous peritoneum. This study was undertaken to determine the effect of the menstrual cycle phase and the presence and stage of endometriosis on in-vitro adhesion of endometrium onto autologous peritoneum. METHODS: This was performed in an academic medical research centre. Sixty-seven subfertile women with a visually normal pelvis (n = 18) and with biopsy-proven endometriosis (n = 49) were included. Endometrial and peritoneal biopsies were obtained at laparoscopy during menstrual, follicular and luteal phase. Endometrium was cultured in vitro with autologous peritoneum, followed by fixation, paraffin embedding, serial sectioning, hematoxylin-eosin and immunohistochemical staining. Endometrial-peritoneal adhesion was evaluated using light microscopy. RESULTS: Endometrial-peritoneal adhesion was observed in approximately 80% of the adhesion assays and was not affected by the phase of the cycle, or by the presence and stage of endometriosis. The continuity of the mesothelial layer was disrupted at the attachment sites. Epithelialization was observed along the edges to integrate the endometrial implant. After adhesion, histological changes were observed within and below the implant. CONCLUSIONS: Endometrium obtained during menstrual, follicular or luteal phase appears to have a similar potential to implant in vitro on autologous peritoneum, and this adhesion process is not affected by the stage of endometriosis.     

Membrane filtration test for rapid presumptive differentiation of four Candida species

A rapid enzymatic two-step test for the presumptive differentiation of four Candida species commonly occurring in various clinical samples is described. The technique involves membrane filtration of a liquid sample, followed by preincubation of the membrane filter on Sabouraud glucose agar supplemented with ticarcillin-clavulanic acid to yield microcolonies. In a separate assay step, parts of the filter are placed on absorbent pads impregnated with fluorogenic 4-methylumbelliferyl (4-MU) enzyme substrates (4-MU-N-acetyl-beta-D-galactosaminide, 4-MU-phosphate, 4-MU-pyrophosphate, and 4-MU-beta-D-galactoside) in combination with 0.1% digitonin acting as a membrane permeabilizer. The membrane filter in contact with the assay medium is incubated to allow cleavage of the enzyme substrate, resulting in fluorescent microcolonies under long-wavelength UV light. This approach, tested on 301 clinical samples, is able to presumptively differentiate C. albicans, C. glabrata, C. krusei, and C. tropicalis and to distinguish them from other Candida spp. in about 9 to 11 h. Overall agreement with the conventional methods of 94.4% (one Candida species present in the sample) to 83.8% (multiple Candida spp. present) was obtained. The false-negative rates with reference to identification by traditional methods were 1.3% (single species) and 3.8% (multiple species).     

How the COVID-19 pandemic can distort risk adjustment of health plan payment

The European Journal of Health Economics - The COVID-19 pandemic has led to disruptions in healthcare utilization and spending. While some changes might persist (e.g. substitution of specialist...