Rhabdomyosarcoma of middle ear-mastoid

Embryonal Rhabdomyosarcoma is relatively uncommon of the Paediatric Tumours. In this paper a rare case of Embryonal Rhabdomyosarcoma of the middle ear/mastoid is presented with relevant review of literature.     

Nimodipine-induced changes in the distribution of carotid blood flow and cardiac output in pentobarbitone-anaesthetized pigs.

In view of the claimed effectiveness of nimodipine in migraine and its possible selectivity for cerebral vessels, we investigated the effects of nimodipine in anaesthetized pigs on the fractionation of carotid arterial blood flow into non-nutrient (arteriovenous anastomoses; AVAs) and nutrient (capillary) parts, and on regional tissue blood flows and vascular conductances. Intracarotid infusions of nimodipine (0.05-1.25 microgram kg-1 min-1) redistributed carotid blood flow in favour of its nutrient compartment, particularly to the skeletal muscles and tongue. Vascular conductance in the non-nutrient (AVAs) compartment decreased (40%), most likely, as a result of 'steal' following profound (5.5 fold) arteriolar dilatation. Intravenous infusions of nimodipine (0.05-6.25 micrograms kg-1 min-1) caused hypotension, bradycardia, a decrease in conduction in the non-nutrient fraction, and an increase in conduction in the nutrient fraction (mostly in the skeletal muscles, but also in the gastrointestinal tract, cerebral hemispheres, heart and adrenals). Probably due to the hypotensive effect, only skeletal muscle blood flow increased. The nimodipine-induced increase in vascular conductance in the skeletal muscles showed regional variation; the effect was most pronounced in the cheek muscles, followed by the muscles of the chest, abdominal, trunk and gluteal regions. We conclude that: AVA flow seems to represent a 'reserve' perfusion which can be readily diverted to tissues in the case of increased metabolism and/or vasodilatation, though the overall response to nimodipine of carotid blood flow distribution qualitatively resembles that to some antimigraine drugs, the relevance of such acute effects in the prophylactic usefulness of nimodipine in migraine remains to be ascertained, and nimodipine lacks a selective cerebral vasodilator action in the anaesthetized pig.     

Histopathological changes induced in rat tissues by oral intake of lead acetate

In the present study an attempt has been made to observe the pathological alterations brought about in the intestine, liver, and kidney of lead-intoxicated rats. A short-term exposure to a sublethal dose of lead (44 mg/kg body wt/day) is seen to cause conspicuous degenerative changes in the three tissues. The intestinal mucosal epithelium is affected which leads to malabsorption, while in the kidney proximal tubular cells degenerate causing secretion of essential materials such as glucose, amino acids, etc., in the urine.     

Symptoms of classic migraine attacks: Modifications brought about by metoprolol

There is little information available concerning whether, and to what extent, migraine-prophylactic agents interfere with the symptoms of migraine attacks. The present study is a placebo-controlled, double-blind study concerning metoprolol in classic migraine. The data refer to the symptoms of single migraine attacks. During metoprolol treatment more attacks were characterized as mild (p = 0.002), and mean global rating (an integrated estimate of headache intensity and of other discomfort) was lower (4.2 versus 5.2, p = 0.003). The mean headache intensity per attack (1.97 versus 2.15) and the mean duration (5.5 versus 6.8 h) were not significantly different. Consumption of analgesics per attack was lower during metoprolol treatment (0.6 versus 1.1; p = 0.02). Attacks with associated symptoms accompanying the headache were fewer during metoprolol treatment (p = 0.014). Total visual and non-visual aura symptoms occurred with similar frequency, but scintillations and paraesthesia were more frequent during metoprolol treatment, whereas speech disturbances were less frequent. In spite of lower consumption of analgesics, the symptoms appeared milder during metoprolol than during placebo. The pattern of changes indicates that metoprolol exerts its action via the sympathetic nervous system; peripheral vasoconstriction is hardly the underlying mechanism of action.     

Session 10a Long-acting contraception

Abstract

Session 10a Long-acting contraception     

5-Hydroxytryptamine-induced contractions of the human isolated saphenous vein: involvement of 5-HT2 and 5-HT1D-like receptors,and a comparison with grafted veins

Summary The receptors mediating the contractile effect of 5-hydroxytryptamine (5-HT) on the human isolated saphenous vein, obtained from 42 patients undergoing coronary bypass surgery, have been further characterized using a number of 5-HT-related drugs. The rank order of agonist potency was 5-carboxamidotryptamine (5-CT) 5-HT > methysergide sumatriptan -methyl-5-HT 5-methoxy-3-(1,2,3,6-tetrahydropyridin-4-yl)-1-Hindolesuccinate (RU 24969) 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride (DOI) > 2-methyl-5-HT > 8-hydroxy-2(di-n-propylamino)tetralin (8-OH-DPAT). Flesinoxan was inactive as an agonist. Ketanserin (1 mol/l) hardly affected sumatriptan-induced contractions but it caused a rightward shift of the upper part of the concentration-response curve of 5-HT and 5-CT. The same concentration of ketanserin caused a parallel rightward shift of the concentration-response curves of -methyl-5-HT and DOI with pK_B values of 7. 1 and 7.1, respectively. The responses to sumatriptan were antagonized by methiothepin (0.1 mol/l), metergoline (0.1 and 1 mol/l), rauwolscine (1 mol/l) and cyanopindolol (1 mol/l); the calculated pK_B values were 7.3, 6.9, 7.3, 6.7 and 6.5, respectively. Contractions to 5-HT were antagonized by methysergide (1 mol/l), methiothepin (0.1 mol/l; pKB = 7.1), ICS 205-930 (1 mol/l; pK_B = 5.9) and flesinoxan (30 mol/l; pK_B = 5.3). Remarkably, the contractions elicited by 2-methyl-5-HT were not attenuated by ICS 205-930, but were antagonized by methiothepin (0.1 mol/l) and, more markedly, by ketanserin (1 mol/l).There was a high correlation between the functional pD₂ values of 5-HT₁-like receptor agonists (5-CT, 5-HT, methysergide, sumatriptan, RU 24969 and 8-OH-DPAT) and their reported binding affinities for the 5-HT_1D receptor in human or calf brain membranes. Such a correlation for the antagonism of sumatriptan-induced responses was less marked than for the agonists, but of the 5-HT₁-like receptor subtypes it was the highest for the 5-HT_1D receptor identified in human or calf brain membranes.In 3 patients, undergoing heart transplantation, saphenous vein which had previously functioned as a graft for 6–11 years, was dissected out from the heart. Though the contractions to potassium were significantly smaller in the grafted veins, the pD₂ and E_max values (calculated as percentage of potassium-induced contractions) for 5-HT and sumatriptan were similar to those found in the veins obtained directly from the lower leg.It is concluded that contractions in the human isolated saphenous vein induced by 5-HT are mediated by 5-HT₂ receptors as well as by a 5-HT₁-like receptor resembling the 5-HT_1D subtype found in brain membranes. It is also to be noted that 2-methyl-5-HT, considered selective for the 5-HT₃ receptor, contracts the saphenous vein mainly via 5-HT₂ receptors.This study was supported by the Netherlands Heart Foundation, grant 89.252 Send offprint requests to W. A. Bax at the above address     

A Novel Technique to Treat Hallux Rigidus in Athletic Patients With Central Osteochondral Defects: Preliminary Report on 12 Cases

Osteochondral defects, often caused by traumatic injuries, are focal areas of articular damage resulting in joint pain and stiffness ultimately leading to degenerative joint disease. This has not been well studied in the first metatarsal head, but is an often encountered problem in the active population in other joints. In this study, we prospectively evaluated the results of 12 patients who received autogenous bone grafting for repair of osteochondral defects of the first metatarsal head. Clinical outcomes were evaluated by the visual analog scale for pain and the Roles and Maudsley (RM) score. Between the years of 2009 and 2016, 12 patients received treatment for this particular surgical intervention and their outcomes were measured. The patients’ average age was 43.5 ± 10.6 years and were followed from 52.3 ± 26.7 months postoperatively. Average return to activity was 4.7 ± 1.1 months. The average preoperative RM score was 4.0 ± 0.0 and postoperative RM score was 1.4 ± 0.7 (p = .0001). The encouraging outcomes of this study suggest that autogenous bone grafting for osteochondral defects of the first metatarsal head is an effective treatment to help restore the function of the first metatarsophalangeal joint.     

Semaphorin-5A maintains epithelial phenotype of malignant pancreatic cancer cells

Background

Pancreatic cancer (PC) is a highly aggressive disease, and the lethality of this disease stems from early metastatic dissemination where surgical removal cannot provide a cure. Improvement of the therapeutic outcome and overall survival of PC patients requires to understand the fundamental processes that lead to metastasis such as the gain of cellular migration ability. One such family of proteins, which are essential players of cellular migration, is Semaphorin. Previously, we have identified one of the Semaphorin family member, Semaphorin-5A (SEMA5A) to be involved in organ-specific homing during PC metastasis. We have also demonstrated that SEMA5A has a constitutive expression in PC cell lines derived from metastatic sites in comparison with low endogenous expression in the primary tumor-derived cell line. In this study, we examined whether constitutive SEMA5A expression in metastatic PC cells regulates tumor growth and metastatic potential.

Methods

We generated SEMA5A knockdown in T3M-4 and CD18/HPAF cells and assessed their phenotypes on in vitro motility, tumor growth, and metastatic progression.

Results

In contrary to our initial expectations, orthotopic injection of SEMA5A knockdown cells into nude mice resulted in a significant increase in both tumor burden and liver metastases in comparison with the Control cells. Similarly, we observed higher in vitro migratory potential with pronounced morphological changes associated with epithelial-mesenchymal transition (EMT), a decrease in the expression of epithelial marker E-cadherin (E-Cad), increase in the expression of mesenchymal markers N-cadherin (N-Cad) and Snail and the activation of the Wnt-signaling pathway in SEMA5A knockdown cells. Furthermore, re-establishing SEMA5A expression with a knockdown resistant mouse Sema5A in SEMA5A knockdown cells resulted in a reversion to the epithelial state (mesenchymal-epithelial transition; MET), as indicated by the rescue of E-Cad expression and a decrease in N-Cad and Snail expression.

Conclusions

Collectively, our data suggest that SEMA5A expression maintains epithelial phenotype in the metastatic microenvironment.