Neuroprotective effects of a novel kynurenic acid analogue in a transgenic mouse model of Huntington’s disease

Huntington’s disease (HD) is a progressive neurodegenerative disorder, the pathomechanism of which is not yet fully understood. Excitotoxicity is known to be involved in the development of HD and antiglutamatergic agents may, therefore, have beneficial neuroprotective effects. One of these agents is the tryptophan metabolite kynurenic acid (KYNA), which is an endogenous NMDA receptor antagonist. However, its pharmacological properties rule out its systemic administration in CNS disorders. We have tested a novel KYNA analogue, N-(2-N,N-dimethylaminoethyl)-4-oxo-1H-quinoline-2-carboxamide hydrochloride, in the N171-82Q transgenic mouse model of HD. The analogue exhibited several significant effects: it prolonged the survival of the transgenic mice, ameliorated their hypolocomotion, prevented the loss of weight and completely prevented the atrophy of the striatal neurons. The beneficial effects of this KYNA analogue are probably explained by its complex anti-excitotoxic activity. As it did not induce any appreciable side-effect at the protective dose applied in a chronic dosing regime in this mouse model, it appears worthy of further thorough investigations with a view to eventual clinical trials.     

State-of-the-art of intrauterine contraception

Despite its nearly 100-year history, intrauterine contraception is a modern method even in the 21st century and its development is still going on. The aim of innovations is to optimize the contraceptive efficacy and to suppress as much as possible side effects and unwanted events (e.g. menstrual irregularities, expulsion). It is important that this method be made available to all those who could not resort to it earlier (young women, nulligravidae, nulliparae). Currently three areas are more particularly being investigated: (1) flexible, frameless intrauterine implants, (2) levonorgestrel-releasing intrauterine systems, and (3) metal alloy intrauterine devices. Partly relying on the author's own clinical experience and based on the literature of recent years, this article reviews the present state and possibilities with regard to further development of intrauterine contraceptive devices.     

Characteristic distribution of interictal brain electrical activity in idiopathic generalized epilepsy

PURPOSE: To demonstrate the anatomic localization of the cortical sources of the interictal EEG activity in human idiopathic generalized epilepsy (IGE). METHODS: Multiple cortical and hippocampal sources of the interictal spontaneous EEG activity were investigated by low-resolution electromagnetic tomography in 15 untreated IGE patients and in 15 healthy controls. EEG activity (current density) in four frequency bands (delta: 1.5-3.5 Hz, theta: 3.5-7.5 Hz, alpha: 7.5-12.5 Hz, beta: 12.5-25.0 Hz) was computed for 2,397 voxels. Voxel-by-voxel group comparison was done between the patient and the control group. Voxels with p < 0.01 differences (between the two groups) were correlated with cortical anatomy. RESULTS: Areas of significantly increased or decreased activity were characterized by their anatomical extension and the frequency bands involved. Five areas of bilaterally increased activity were found: rostral part of the prefrontal cortex (delta, theta); posterior part of the insula (delta); hippocampus and mediobasal temporal cortex (all frequency bands); medial parietooccipital cortex (theta, alpha, beta); dorsal and polar parts of the occipital cortex (alpha). Bilaterally decreased delta, theta, alpha activity was found in the majority of the frontal and anterior parietal cortex on the lateral surface, and in parts of the medial surface of the hemispheres. The area of decreased beta activity was less extensive. The right lateral and laterobasal temporal cortex showed decreased delta, theta, alpha, and beta activity, while its left counterpart only showed decreased delta and alpha activity in a limited part of this area. CONCLUSIONS: (1) Pathological interictal EEG activity is not evenly distributed across the cortex in IGE. The prefrontal area of increased activity corresponds to the area that is essential in the buildup of the ictal spike-wave paroxysms (absence seizures). The existence of the posterior "center of gravity" of increased EEG activity in IGE was confirmed. The frontal area of decreased activity might be related to the cognitive deficit described in IGE patients. (2) Increased activity in a lot of ontogenetically older areas (including the hippocampi) and decreased activity in the majority of the isocortex is a peculiar pattern that argues for a developmental hypothesis for IGE.     

X-linked myotubular myopathy: report of a case with novel mutation

Myotubular myopathy is a well-defined entity within the centronuclear myopathy subgroup of congenital myopathies. The authors present a patient with the most severe X-linked recessive type (XLMTM). A baby boy presented at birth with severe hypotonia, weak spontaneous movements, arthrogryposis, and respiratory insufficiency. Muscle biopsy showed features of myotubular myopathy. The diagnosis was confirmed and further specified by genetic analysis, revealing a novel frameshift mutation (1314-1315insT) of the myotubularin-coding MTM1 gene. This case underlines the importance of interdisciplinary analysis of congenital muscle diseases, including histomorphological and genetic investigations.     

Massive gastrointestinal bleeding in Henoch-Schoenlein purpura in an adult

Henoch-Schoenlein syndrome in an adult patient, localised only to the gastrointestinal system is very rare. A 50 year old male was treated in our Intensive Department because of acute respiratory distress syndrome (ARDS) and renal failure. After temporary improvement massive gastrointestinal bleeding developed with shock. Blood was found in the descending duodenum without evident pathology at endoscopy. Angiogram showed bleeding at the hepatic flexure of the colon, which was successfully treated by a coil and bleeding was also present in the terminal part of the small intestine. The catheter was left in situ and the bleeding part of the bowel was painted intraoperatively, so we could resect the stained part of the intestine. Because of rebleeding, bowel resection was performed an other two occasions in the same way. The histology of the bowel showed Henoch-Schoenlein syndrome in each specimen. Our patient was totally non-responsive to treatment, which is usually successful in this disease. After the resections the bleeding stopped temporarily, but as the underlying disease was unmanageable the patient died but we have not found any surgical complication at autopsy. We think that this method in the surgical treatment of massive intestinal bleeding is very useful and effective.     

Surgical treatment for primary and secondary tumors of the liver

We performed liver resection for focal liver disease in 266 patients between January 1, 1992 and December 31, 2001 at the University of Debrecen Medical and Health Science Center, Medical School of Medicine, 2nd Department of Surgery in Debrecen, Hungary. The indication was primary liver cancer in 35 cases, liver metastasis in 97 cases. The primary tumour and its liver metastases were removed synchronously in 28 patients (29.9%). Comparing the results of different operating methods we found the need of transfusion significantly less in "anterior" liver resections. Regarding operating time, complications and survival time there were no significant differences between the different operations. One patient died in the perioperative period because of cardiac failure and one because of DIC (1.5%). There were 4 complications which needed reoperation in the early postoperative period. Eighty of the patients were treated with systemic adjuvant chemotherapy (Mayo protocol), with added chemoembolisation in another 26 patients. This has not increased life expectancy significantly. Thirty-two patients are still alive, their average survival time is 21.2 (5 to 59) months. The average survival time of the 78 patients' who died is 16.5 (3 to 58) months. Twenty-two patients were lost out of our follow-up.     

Results of laparoscopic repair of ventral hernias--a case-control study

The surgical treatment of ventral hernias has changed in the last decade. Conventional methods involve tightening of the abdominal fascias is the reason for high recurrence rate. While the use of mesh reduces the recurrence rate, it does not change the rate of other complications, in particular, the risk of infection. We report the results of laparoscopic repair of ventral hernias performed in 15 patients (10 female, 5 male). The average age of patients was 59.5 years (39-79). Indications included 7 recurrent incisional hernias (3 patients had second recurrence, 4 patients had first recurrence operated on without mesh in the first operation); 5 patients with primary incisional hernias; and 3 primary umbilical hernias. The mean size of the defect was 66.2 cm2 (16-130 cm2). Average operation time was 101 minutes (64-190 min). In the postoperative period 1 patient developed seroma, and 4 patients developed ileus each was successfully treated conservatively. In one patient a second-look laparoscopy was performed because of neuralgia. Length of hospital stay varied between 3 and 10 days (median: 6 days); the length of follow-up period was 5-22 months (median: 12.4 months). We believe that laparoscopic treatment of ventral hernias reduces the complication rate, and reduces hospital stay.     

Etiology, pathogenesis and clinical course of unstable coronary artery disease

The clinical presentations of ischemic heart disease comprises the term of acute ischaemia syndromes, that include unstable angina pectoris, non-Q-wave myocardial infarction, Q-wave-myocardial infarction and sudden death. Among the different presentations of acute ischemic syndromes, tha unstable angina and non-Q-wave myocardial infarction can be regarded together. In both pathologic entity, the plaque rupture, or erosion signifies the primary event, which is the source of the highly thrombogenic substances coming out from the core of the atherosclerotic plaque and entering to the coronary and systemic circulation. They cause a thrombocyte-rich "white" intracoronary thrombus, that is not fully obstructive, or there is adequate collateral circulation, being the pathogenetic substrate that prevents the development of transmural necrosis. The nosologically-bound two clinical entity can be called as "unstable coronary artery disease" (UCAD), since they have uniform etiologic, risk stratification and therapeutic backgrounds and also therapeutic targets that are basically distinct, they are admitted for transmural "ST-elevation" infarction. The review is discussing the etiology, pathophysiology, the role of inflammation factors, the problems of diagnostics, as well as risk stratification of the disease in the light of the recent guidelines of the European Society of Cardiology and multicenter evidence based studies.     

Determination of serum semicarbazide-sensitive amine oxidase activity in diabetic retinopathy in type-2 diabetes

INTRODUCTION: Recent data suggest that the copper-containing semicarbazide-sensitive amine oxidase enzyme (SSAO) may play a role in vascular endothelial damage through conversion of certain endogenous monoamines, like methylamine into cytotoxic aldehydes, hydrogen peroxide and ammonia. SSAO is present in various human tissues and in the serum. Elevated SSAO activities have been reported in patients with both types of diabetes mellitus. The purpose of this study was to examine the possible association between serum SSAO activity and the different severity stages of diabetic retinopathy. PATIENTS AND METHODS: A prospective study was performed on a defined group of Type 2 diabetic patients (n = 93) compared to non-diabetic control subjects (n = 42). All participants underwent a detailed ocular examination (slit lamp, colour retinal photography, fluorescein angiography) and standard laboratory investigations. Age at diagnosis, duration of diabetes, presence of systemic hypertension, medication and BMI were recorded. Serum SSAO activity was determined by a radiometric procedure using [14C]-benzylamine as substrate. RESULTS: In the total group of Type 2 diabetic patients SSAO activity (mean +/- SD) was significantly elevated compared to non-diabetic controls (n = 93, 131.72 +/- 53.07 vs. n = 42, 89.56 +/- 26.89 pmol.mg-1 protein.hour-1, p < 0.0001). After dividing patients to four subgroups according to the severity of diabetic retinopathy, serum SSAO activity was significantly higher in patients with high-risk proliferative diabetic retinopathy (n = 16, 166.96 +/- 70.56 pmol.mg-1 protein.hour-1) compared to those without retinopathy (n = 42, 119.54 +/- 50.49 pmol.mg-1 protein.hour-1, p < 0.02). CONCLUSION: The results support the hypothesis that elevated SSAO activity may be involved in the pathogenesis of microvascular diabetic late complications, such as retinopathy. The pharmacological manipulation of SSAO activity might be an interesting new concept for prevention and treatment of diabetic retinopathy.