Method for Dissection of Mesenteric Metastases in Mid-gut Carcinoid Tumors

With adequate medical management the midgut carcinoid tumor generally is an indolent malignancy associated with substantial life expectancy and appreciable life quality, even in the presence of liver metastases and significant tumor burden. Abdominal complications may occur in this entity of carcinoids owing to entrapment of intestines and encasement of mesenteric vessels by mesenteric metastases and associated marked mesenteric fibrosis. This may be the cause of abdominal pain, disabling diarrhea, weight loss to the extent of malnutrition, and eventually the risk of death with acute or chronic intestinal obstruction or intestinal gangrene. Operative removal of the mesentericointestinal lesion is often indicated to prevent or treat these complications but may be technically difficult when mesenteric metastases extend in the vicinity of major vessels in the mesenteric root. At laparotomy 56 patients with advanced midgut carcinoids underwent removal of the mesenteric tumor with a method for preserving the mesenteric vessels. This was feasible by mobilizing and releasing the right colon and mesenteric root from posterior adhesions, identifying the mesenteric artery below the pancreas, and free-dissecting this artery on the tumor capsule in the mobilized mesentery. Dissection was successful even with tumors initially judged inoperable unless tumor growth completely surrounded the mesenteric vessels or extended retroperitoneally. One patient was subjected to distal intestinal artery bypass. Symptom relief was been substantial and often of long duration after mesenteric tumor removal in patients who prior to surgery often had threatening intestinal ischemia. Patients with advanced midgut carcinoids may benefit markedly from dissectional removal of mesenteric tumors, which (conceivably better than conventional wedge resection) preserves the length of the remaining intestine.     

Urogenital injuries in childhood: A strong association of bladder trauma to bowel injuries

We analysed the inter-relationships of the cause and the type of trauma, the presence of pelvic fracture, the associated intraabdominal organ injuries,and the morbidity and mortality rates in 154 patients presenting and being treated for UGT between 1983 and 1997.The cause of injury was blunt in 77% of cases and penetrating in 13%. The most frequently injured organs were kidney followed by urethra and bladder. Bowels, liver and spleen were the most frequently associated injured organs. Moreover, bladder injuries were strongly associated with bowel injuries (p < 0.0001). Hemodynamically normal 49 children with minor or major kidney injuries were managed conservatively. Hemodynamically non-stable 11 patients were explored.The majority of urogenital injuries can be managed conservatively evenwhen associated with intraabdominal organ injuries. Solid genitourinary organ injuries may accompany more frequently to intraperitoneal solidorgan injury. Whereas, non-solid genitourinary organ injuries may more frequently associated with injuries of intraperitoneal hollow viscus. This revised version was published online in August 2006 with corrections to the Cover Date.     

Absence of p53 Overexpression and Favorable Response to Cisplatin-based Neoadjuvant Chemotherapy in Urothelial Carcinomas

It has been controversial whether cancer cells harboring loss or inactivation of the tumor suppressor p53 are resistant or sensitive to DNA-damaging agents including cisplatin and doxorubicin. Overexpression of mdm2 oncoprotein, a negative regulator of p53, is assumed to be an alternative to p53 dysfunction. Archival urothelial carcinoma specimens obtained from 60 patients prior to cisplatin-based chemotherapy were immunohistochemically studied for overexpression of p53 and mdm2. Thirty-two patients (group I) were treated with chemotherapy in the neoadjuvant setting, while 28 patients (group II) underwent chemotherapy for distant metastases or inoperable locoregional tumors. In group I, the responsiveness was correlated with staining status of p53 ( P =0.0225) and the combination of p53 and mdm2 ( P =0.0497). Negative staining of p53 and negative for both p53 and mdm2 could have predicted favorable response to chemotherapy in 16 of 18 (88.9%) and in 12 of 13 (92.3%) tumors, respectively. On the other hand, p53-positive and p53 and/or mdm2-positive staining could have predicted poor response only in 7 of 14 (50.0%) and 8 of 19 (42.1%) tumors, respectively. Disease-specific survival of the p53-negative group was significantly superior to that of the p53-positive group ( P =0.0086). Difference in survival did not become more significant when overexpression of mdm2 was taken into consideration ( P =0.0456). In contrast, in group II, there was no correlation of responsiveness to chemotherapy or survival with p53- or p53/mdm2-staining status. The patients with urothelial carcinomas negative for overexpression of p53 will benefit from neoadjuvant chemotherapy. From clinical viewpoint, however, p53 status alone or the combination of p53 and mdm2 status is not enough to identify those patients who will not benefit from the treatment.     

Neuroprotective and symptomatological action of memantine relevant for alzheimer’s disease — a unified glutamatergic hypothesis on the mechanism of action

The involvement of glutamate mediated neurotoxicity in the pathogenesis of Alzheimer's disease is finding increasingly more acceptance in the scientific community. Central to this hypothesis is the assumption that in particular glutamate receptors of the N-methyl-D-aspartate (NMDA) type are overactivated in a tonic rather than a phasic manner. Such continuous mild activation leads under chronic conditions to neuronal damage. Moreover, one should consider that impairment of plasticity (learning) may result not only from neuronal damage per se but also from continuous activation of NMDA receptors. To investigate this possibility we tested whether overactivation of NMDA receptors using either non-toxic doses/concentrations of a direct NMDA agonist or through an indirect approach--decrease in magnesium concentration--produces deficits in plasticity. In fact NMDA both in vivo (passive avoidance test) and in vitro (LTP in CA1 region) impaired learning and synaptic plasticity. Under these conditions memantine which is an uncompetitive NMDA receptor antagonist with features of "improved magnesium" (voltage dependence, affinity) attenuated the deficit. The more direct proof that memantine can act as a surrogate for magnesium was obtained in LTP experiments under low magnesium conditions. In this case as well, impaired LTP was restored in the presence of therapeutically relevant concentrations of memantine (1 microM). In vivo, doses leading to similar brain/serum levels produce neuroprotection in animal models relevant for neurodegeneration in Alzheimer's disease such as neurotoxicity produced by inflammation in the NBM or beta-amyloid injection to the hippocampus. Hence, we postulate that if in Alzheimer's disease overactivation of NMDA receptors occurs indeed, memantine would be expected to improve both symptoms (cognition) and slow down disease progression because it takes over the physiological function of magnesium.     

COX-inhibiting nitric oxide donators (CINODs) -- a new paradigm in the treatment of pain and inflammation

The clinical utility of non-selective non-steroidal anti-inflammatory drugs (NSAIDs) for pain relief is tempered by their propensity to cause gastrointestinal toxicity. Cyclooxygenase (COX)-inhibiting nitric oxide donators (CINODs) are a new class of drugs designed to provide analgesic efficacy through COX inhibition and gastrointestinal safety through the protective effects of controlled nitric oxide donation. Pre-clinical studies assessing the pharmacology, efficacy and gastrointestinal safety of AZD3582 [4-(nitrooxy)butyl-(2S)-2-(6-methoxy-2-naphthyl)propanoate] support this concept. Based on these studies, AZD3582 was the first CINOD to enter clinical development for the treatment of acute and chronic pain. The potential clinical utility of this new class is illustrated by a study of AZD3582 in healthy volunteers in which it caused significantly less acute gastrointestinal toxicity than an equimolar dose of naproxen. The results of the animal studies and the initial clinical study warrant long-term tolerability studies of AZD3582 along with evaluation of its anti-inflammatory and analgesic effects in humans.     

Mean Platelet Volume is Associated with Diabetic Macular Edema in Patients with Type-2 Diabetes Mellitus

Aim: To evaluate the effect of the platelet indices on the stage of diabetic retinopathy (DR) and diabetic macular edema (DME). Methods: In this retrospective study, the mean platelet valume (MPV), Plateletcrit (PCT), platelet (PLT), and platelet distribution width (PDW) of 199 diabetic patients and 76 healthy subjects were enrolled. The participants were divided into four groups. The first group was healthy control; the second group consisted of diabetic patients without DR; the third group was nonproliferative DR (NPDR); and the fourth group was proliferative DR (PDR). Results: Significant differences were found only in MPV and PCT values between patients with diabetes and healthy participants (8.6±0.96 fL vs 8.32±0.9 fL, P=0.011, 0.216± 0.58 vs 0.202±0.52, P=0.038). Comparing the groups, a statistically significant difference in MPV values was found between groups 4 and 1 (8.91±.7 fL vs 8.32±0.9 fL P=0.001) and between groups 4 and 3 (8.91±.7 fL vs 8.42±0.9 fL P=0.014). The MPV values of patients with DME were significantly higher than those of diabetic patients without DME (8.87±0.80 fL vs 8.45±0.97 fL). Conclusion: High MPV values may be an important risk factor for the development of PDR and DME in patients with diabetic retinopathy.     

The evaluation of Chronic Progressive External Ophthalmoplegia with computerized tomography

Introduction: Chronic progressiveexternal ophthalmoplegia is characterisedby limitation of ocular motility in alldirections of gaze and ptosis.Innervational or myogenic factors wereclaimed to be responsible for thismotility disorder. The aim of thisstudy was toinvestigate the extraocular muscles inCPEO with computerized tomography in an attemptto distinguish extraocular musclemorphology caused by this disorderfrom that occurring in normal individuals.Methods: Eighteen orbits from 9patients diagnosed with CPEOwere included in the study. Axialand coronal scans were obtained for CTevaluation of extraocular muscles and thedimensions of extraocular muscles were measured.The control group consisted of40 orbits belonging to 20 individuals and,the results were compared with a student'st test.Results: The thickness (the verticaldimension of vertical recti and thehorizontal dimension of horizontal recti)of all rectus muscles wassignificantly decreased in comparison with the controlgroup, whereas the width (the horizontal dimensionof vertical recti and the verticaldimension of horizontal recti) was similar inboth the diseased and normal orbits.In all the rectus musclesof the diseased orbits,the normal fusiform shape was lost and the muscles appeared asthin bands.Discussion: The differentiation ofCPEO from other myogenic and neurogenicdisorders may present difficulty,and a cluster of criteria are required fora final diagnosis. CT has provento be a valuable tool in assessing extraocularmuscles [1, 2]. In this study, an extremeatrophy of all rectus muscles wasdemonstrated by means of CT. This diagnostic method mayconsequently contribute to a properdiagnosis of CPEO.     

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