Risk of recurrence in major central nervous system malformations between 1976 and 2005

OBJECTIVE: The goal of the current publication is to review isolated central nervous system malformations (CSMs) using a database in excess of 75 000 cases, with special regard to the risk of recurrence of these malformations alone or in combination. METHODS: In the period between 1 January 1976 and 31 December 2005, among the 75 320 documented cases, consultations were requested due to earlier isolated CSMs in the patients' histories in 3030 cases (4.2%). Processing the data we only considered disorders of genetic origin, and that was why we excluded the cases due to intrauterine infection. Monogenically inherited malformations were also excluded from the analysis. The diagnosis of the malformations was based on the prenatal diagnosis of ultrasonography as well as the findings of the foetopathological examination. RESULTS: In 65% of the cases, the couples sought counselling because of malformation in a previous pregnancy. In these cases, the risk of recurrence was thought to be 5.2%, while in the case of two affected children this figure stood at 21.9%. Analysing the values for the risk of recurrence in 5-year periods, neural tube defects (NTDs) (particularly anencephaly and spina bifida) showed a detectable decrease, which could be attributed to a growing use of folic acid supplementation around the time of conception and during pregnancy. CONCLUSION: There is a clear decrease of risk of recurrence of NTDs, while in the case of the other CSMs in this study, there is no noteworthy chronological change in their risk of recurrence.     

Congenital lung malformations in the second trimester: prenatal ultrasound diagnosis and pathologic findings

PURPOSE: To correlate prenatal sonographic diagnosis of cystic lung malformations with fetopathologic findings after termination of pregnancy. METHODS: We retrospectively analyzed the data of 16 terminated cases in which a cystic lung lesion was diagnosed pre- or postnatally. RESULTS: On average, prenatal diagnosis was established on the 21(st) gestational week (range, 19-26 weeks). The cause of termination was severe polyhydramnios in 4 cases, nonimmune fetal hydrops in 4 cases, other congenital malformation in 5 cases (renal malformation, 2 cases; congenital diaphragmatic hernia, 3 cases), and obstetrical conditions (intrauterine death, placental abruption, spontaneous abortion) in 3 cases. In 11 cases, congenital cystic adenomatoid malformation (CCAM) was the presumptive prenatal diagnosis. Autopsy confirmed the prenatal diagnosis in 6 of them, while in the other 5 cases, an enteric cyst, a laryngeal atresia, an unidentified tumor, a pulmonary hypoplasia, and an extralobar pulmonary sequestration were found on histologic examination. On the other hand, the autopsy revealed CCAM in those 5 cases in which other malformations were suggested prenatally. CONCLUSION: The prenatal sonographic diagnosis of CCAM is difficult. Our cases emphasize the important role of fetopathology even today in the verification of prenatal diagnosis based on sonographic examinations.     

Surgical aspects of histologically unproven space-occupying lesions of the pancreas head

A suspected, but unproved malignant tumor in the head of the pancreas is a fairly common problem for surgeon. Even intraoperatively, differentiation between chronic pancreatitis and carcinoma is difficult. We try to give guidelines about what can be done with a pancreas head mass intraoperatively without previous cytology or histology. When do we have to achieve definite diagnosis at all costs, and how can we achieve it? Results of 40 intraoperative aspiration cytologies, performed for suspected pancreatic cancer were analysed. All of them were controlled by histology in the resected specimen. Intraoperative biopsy was false negative in 12.5% and the diagnosis was uncertain in 35%. These data show that a benign result by itself never excludes the presence of malignancy. If pathology will alter our decision about resection, all efforts should be made to confirm the diagnosis. On the other hand, in a case of a mass lesion with obstructive symptoms, cytology does not alter the need for surgical decompression, and some kind of resection is a reasonable option, even in case of chronic pancreatitis. Nihilistic approach in the case of pancreatic head mass with suspected but unproved malignancy is not justified. Pancreatoduodenectomy should be performed for all tumors even without histologic confirmation if an experienced team can perform it with low postoperative morbidity and mortality.     

Sphincter of Oddi dysfunction--prolonged medical therapy or early endoscopic sphincter ablation

INTRODUCTION: Sphincter of Oddi dysfunction is a real challenge from both diagnostic and therapeutic point of view. PATIENTS AND METHODS: In the last two years the authors have performed ERCP and EST in 29 patients with positive evocative test results, who had important enzyme elevations and/or did not respond to prolonged medical treatment. RESULTS: Endoscopic findings were positive in 25/29 patients (86.2%): 8 adenoma of p. Vateri, 17 papillitis were identified, and in 4 cases the papilla was intact. Histopathology obtained in 12 patients supported the diagnosis. In 6 patients, who underwent a postpapillotomy evocative test, after an average of 10 months follow up the results have been converted from positive to negative response in all but two cases. The two patients continued to have abdominal symptoms with persistent positive provocation tests because of restenosis, were treated with repapillotomy. CONCLUSIONS: The Debray and Nardi tests are useful screening tests for hypertonic biliary or pancreatic dyskinesia. Structural endoscopic and histological findings are frequent already in the functional cases. Early sphincter ablation should be considered in failure of medical therapy for preventing the transformation of this functional disorder into an organic, potentially precancerous state.     

Distinct localization of GABA(B) receptors relative to synaptic sites in the rat cerebellum and ventrobasal thalamus

Metabotropic gamma-aminobutyric acid receptors (GABA(B)Rs) are involved in modulation of synaptic transmission and activity of cerebellar and thalamic neurons. We used subtype-specific antibodies in pre- and postembedding immunohistochemistry combined with three-dimensional reconstruction of labelled profiles and quantification of immunoparticles to reveal the subcellular distribution of pre- and postsynaptic GABA(B)R1a/b and GABA(B)R2 in the rat cerebellum and ventrobasal thalamus. GABA(B)R1a/b and R2 were extensively colocalized in most brain regions including the cerebellum and thalamus. In the cerebellum, immunoreactivity for both subtypes was prevalent in the molecular layer. The most intense immunoreactivity was found in Purkinje cell spines with a high density of immunoparticles at extrasynaptic sites peaking at around 240 nm from glutamatergic synapses between spines and parallel fibre varicosities. This is in contrast to dendrites at sites around GABAergic synapses where sparse and random distribution was found for both subtypes. In addition, more than one-tenth of the synaptic membrane specialization of spine-parallel fibre synapses were labelled at pre- or postsynaptic sites. Weak immunolabelling for both subtypes was also seen in parallel fibres but only rarely in GABAergic axons. In the ventrobasal thalamus, immunolabelling for both receptor subtypes was intense over the dendritic field of thalamocortical cells. Electron microscopy demonstrated an extrasynaptic localization of GABA(B)R1a/b and R2 exclusively in postsynaptic elements. Quantitative analysis further revealed the density of GABA(B)R1a/b around GABAergic synapses was higher than glutamatergic synapses on thalamocortical cell dendrites. The distinct localization of GABA(B)Rs relative to synaptic sites in the cerebellum and ventrobasal thalamus suggests that GABA(B)Rs differentially regulate activity of different neuronal populations.     

Fermented wheat germ extract induces apoptosis and downregulation of major histocompatibility complex class I proteins in tumor T and B cell lines

The fermented wheat germ extract (code name: MSC, trade name: Avemar), with standardized benzoquinone content has been shown to inhibit tumor propagation and metastases formation in vivo. The aim of this study was to understand the molecular and cellular mechanisms of the anti-tumor effect of MSC. Therefore, we have designed in vitro model experiments using T and B tumor lymphocytic cell lines. Tyrosine phosphorylation of intracellular proteins and elevation of the intracellular Ca2+ concentration were examined using immunoblotting with anti-phosphotyrosine antibody and cytofluorimetry by means of Ca2+ sensitive fluorescence dyes, Fluo-3AM and FuraRed-AM, respectively. Apoptosis was measured with cytofluorimetry by staining the DNA with propidium iodide and detecting the cell population. The level of the cell surface MHC class I molecules was analysed with indirect immunofluorescence on cytofluorimeter using a monoclonal antibody to the non-polymorphic region of the human MHC class I. MSC stimulated tyrosine phosphorylation of intracellular proteins and the influx of extracellular Ca2+ resulted in elevation of intracellular Ca2+ concentration. Prominent apoptosis of 20-40% was detected upon 24 h of MSC treatment of the cell lines. As a result of the MSC treatment, the amount of the cell surface MHC class I proteins was downregulated by 70-85% compared to the non-stimulated control. MSC did not induce a similar degree of apoptosis in healthy peripheral blood mononuclear cells. Inhibition of the cellular tyrosine phosphatase activity or Ca2+ influx resulted in the opposite effect increasing or diminishing the Avemar induced apoptosis as well as the MHC class I downregulation, respectively. A benzoquinone component (2,6-dimethoxi-p-benzoquinone) in MSC induced similar apoptosis and downregulation of the MHC class I molecules in the tumor T and B cell lines to that of MSC. These results suggest that MSC acts on lymphoid tumor cells by reducing MHC class I expression and selectively promoting apoptosis of tumor cells on a tyrosine phosphorylation and Ca2+ influx dependent way. One of the components in MSC, 2,6-dimethoxi-p-benzoquinone was shown to be an important factor in MSC mediated cell response.     

Signaling pathways of mechanotransduction in arteriolar endothelium and smooth muscle cells in hypertension

Hypertension, a disease with a high incidence in the population, affects all parts of the cardiovascular system. Studying the alteration of vasomotor responses of microvessels of hypertensive animals or responses of vessels following short-term increases in hemodynamic forces helps us to better understand the underlying cellular signaling events responsible for their functional adaptation. These adaptations are likely to precede the structural remodeling of arterioles, resulting in irreversible increases in peripheral vascular resistance in hypertension. Although malfunction of several mechanisms can lead to the development of hypertension, hemodynamic forces (such as pressure and shear stress) are increased in all forms of hypertension. Thus, local mechanisms that sense the level of these forces and transduce the signals into vasomotor responses must be affected in all forms of hypertension. The endothelium has a central role in the early functional adaptations. Pressure-induced myogenic constriction is enhanced due to the augmented release of endothelium-derived constrictor factors that modulate arteriolar smooth muscle sensitivity to Ca(2+). In contrast, flow/shear stress-induced dilation of arterioles is reduced in hypertension, due to the impaired mediation of the response by nitric oxide (NO). The magnitude of impairment is gender specific, primarily due to an estrogen-dependent enhancement of NO release in females. It is proposed that the elevated hemodynamic forces present in hypertension may themselves initiate these alterations, probably by enhancing the release of reactive oxygen species (ROS; produced by xanthine oxidase, NAD(P)H oxidoreductase, eNOS, etc.), which then interfere with the synthesis and/or action of endothelium-derived mediators. Interfering early on with these mechanisms may prevent the development of irreversible structural changes of the microcirculation observed in hypertension.     

Serum CA-125 and inhibin B levels in the prediction of ovarian response to gonadotropin stimulation in in vitro fertilization cycles.

There is much controversy about the relationship between serum CA-125 levels during in vitro fertilization (IVF) cycles and ovarian function. To evaluate the prognostic value of serum CA-125 and inhibin B measurements in predicting ovarian response to gonadotropin stimulation, we compared the CA-125 and inhibin B levels of poor and normal responders on the first day of ovarian stimulation, on the day of ovulation induction (OI) and at oocyte pick-up. Sixteen patients with poor ovarian response (3 oocytes, serum estradiol (E2) 900 pg/ml at OI) in IVF/intracytoplasmic sperm injection cycles were matched with normal responders (6 oocytes, E2 1800 pg/ml) by age, spontaneous cycle day-3 follicle-stimulating hormone level and cause of infertility. Inhibin B concentrations were significantly lower at all three time points in poor responders, but CA-125 levels were not. No statistically significant correlation was found between CA-125 levels and any of the clinical or laboratory parameters examined. Thus, CA-125 measurements during stimulation are not useful in predicting or identifying poor ovarian response to gonadotropin stimulation in IVF cycles. The lack of difference in CA-125 concentrations between poor and normal responders and lack of correlation with E2 or inhibin B levels suggest that ovarian steroidogenesis and other granulosa cell functions do not influence the production of CA-125. Inhibin B, however, seems to predict ovarian response as early as at the start of stimulation.     

Failure of diagnosing pancreatic tumors in the course of laparoscopic cholecystectomy: surgical lessons

INTRODUCTION: In Hungary surgeons perform approximately 24000 cholecystectomies per year. Nowadays the choice of treatment of uncomplicated cholelithiasis is laparoscopic cholecystectomy. The advantages and popularity of the procedure are well known; otherwise the exploration of the abdominal cavity is not so complete than during open surgery. In the course of laparoscopic surgery the surgeon has minimal chance to find the preoperatively not diagnosed tumour. AIMS: In our retrospective study we analysed those complains and clinical signs, when we suspect the presence of a pancreas tumour. PATIENTS AND METHODS: We analysed the clinical data of patients who were operated on with pancreatic tumor and before the surgery, laparoscopic cholecystectomy had been performed in the previous 24 month. RESULTS: In the period of 1996-2003 we operated 1515 patients with pancreatic tumor, at our clinic. 21 patients (1.39%) had laparoscopic cholecystectomy in the last 24 month, before the surgery. The age of the patients was between 50-78 (average age 65), the rate of the female and male patients was 15/6. Most of the patients had weight loss (in 11 cases it was considerable, 5.4 kg in one month) and the uncertain abdominal pain, feeling of discomfort, meteorism was also characteristic of these patients. In 16 cases (76%) the blood glucose level had been elevated. The ultrasound examination before the cholecystectomy in these cases was focused to the gall bladder. After the cholecystectomy, complains did not disappear definitely and further diagnostic steps verified the pancreatic tumour. The average time between the laparoscopic cholecystectomy and the open surgery was 10 month. In 4 cases we were able to remove the tumor, but in 17 cases only palliative operation was performed. CONCLUSIONS: If the patient is over the age of 50, especially if he is male, has weight loss and if the symptoms are not characteristic of gallbladder disease, further diagnostic steps are necessary before cholecystectomy. Complains remaining after laparoscopic cholecystectomy must be indication for urgent diagnostic steps. The life expectancy of patients with advanced pancreatic tumor is very poor.