Lebanese women׳s awareness and attitude toward epidural anesthesia during labor.

Women׳s choice to use epidural anesthesia (EA) for relief of labor pain varies from one culture to another. A descriptive cross-sectional design was used to gather data from a sample of 200 women in childbearing age. Data was gathered from general population in Lebanon. Demographic data, knowledge and attitudes questionnaires towards EA were used to gather data for this study. The data in this article provides demographic data about Lebanese women and their awareness and attitudes towards epidural anesthesia. The analyzed data is provided in the tables included in this article.

BRCA1 and BRCA2 mutation testing in Cyprus; a population based study.

This paper presents the largest study in Cyprus evaluating the frequency and distribution of BRCA1/2 mutations in a high risk patient cohort. Deleterious mutations in the BRCA1/2 genes were identified in 68 of the 527 patients tested (13%). It is of interest that a quarter of those tested positive, did not have an extensive family history of breast/ovarian cancer but were diagnosed with early onset breast cancer, ovarian cancer under the age of 60 or triple negative breast cancer. The spectrum of mutations identified in our patient cohort is different compared to other Mediterranean countries. Furthermore, several of the mutations detected are novel and have not been identified in other ethnic populations. This highlights the importance of operating a national reference center for cancer genetic diagnosis which offers services tailored to the needs of the Cypriot population.

Genetic background modifies amyloidosis in a mouse model of ATTR neuropathy.

Penetrance and age of onset of ATTRV30M amyloidotic neuropathy varies significantly among different populations. This variability has been attributed to both genetic and environmental modifiers. We studied the effect of genetic background on phenotype in two lines of transgenic mice bearing the same ATTRV30M transgene. Amyloid deposition, transthyretin (TTR), megalin, clusterin and disease markers of endoplasmic reticulum stress, the ubiquitin-proteasome system, apoptosis, and complement activation were assessed with WB and immunohistochemistry in donor and recipient tissue. Our results indicate that genetic background modulates amyloid deposition by influencing TTR handling in recipient tissue and may partly account for the marked variability in penetrance observed in various world populations.

Anti-SOX1 antibodies in patients with paraneoplastic and non-paraneoplastic neuropathy.

Anti-SOX1 antibodies have been described to be positive in patients with paraneoplastic Lambert-Eaton myasthenic syndrome and, in a lower amount, in patients with anti-Hu positive paraneoplastic neurological syndromes, and with SCLC alone, respectively. We found 5/32 patients with paraneoplastic neuropathy and, surprisingly, 4/22 patients with neuropathy of unknown origin positive for anti-SOX1 antibodies, whereas no patient with inflammatory neuropathy and no healthy controls showed any reactivity (p=0.007). All patients with neuropathy of unknown origin where followed up for four years without diagnosis of a tumour so far. Anti-SOX1 antibodies are associated with paraneoplastic neuropathies and may define another group of non-paraneoplastic, immune-mediated neuropathies.

Novel germline mutations in the APC gene of Cypriot patients with familial and sporadic adenomatous polyposis.

Familial adenomatous polyposis (FAP) is one of the two commonest familial syndromes that predispose to colorectal cancer. FAP is caused by mutations in the adenomatous polyposis coli (APC) tumour suppressor gene that has a high penetrance. The disease is characterized by the occurrence of hundreds to thousands of colorectal polyps, which if left untreated give rise to colorectal cancer. In Cyprus, there are no molecular data available as yet on families with FAP. This work presents the results of APC analysis in our population for the first time. The APC gene was analyzed in 33 DNA samples from 20 individuals belonging to four FAP families and 13 patients with sporadic polyposis. We identified three truncating mutations, four missense mutations and 11 polymorphisms. It is of interest that two of the three truncating mutations, 2307delA and Q1242X, are novel, which supports the existence of a unique genetic pool in the Cypriot population. This ethnic molecular study in addition to highlighting population heterogeneity also contributes to phenotype-genotype associations that are essential for the clinical management of FAP families in Cyprus.

Sox1-deficient mice suffer from epilepsy associated with abnormal ventral forebrain development and olfactory cortex hyperexcitability.

Mutations in several classes of embryonically-expressed transcription factor genes are associated with behavioral disorders and epilepsies. However, there is little known about how such genetic and neurodevelopmental defects lead to brain dysfunction. Here we present the characterization of an epilepsy syndrome caused by the absence of the transcription factor SOX1 in mice. In vivo electroencephalographic recordings from SOX1 mutants established a correlation between behavioral changes and cortical output that was consistent with a seizure origin in the limbic forebrain. In vitro intracellular recordings from three major forebrain regions, neocortex, hippocampus and olfactory (piriform) cortex (OC) showed that only the OC exhibits abnormal enhanced synaptic excitability and spontaneous epileptiform discharges. Furthermore, the hyperexcitability of the OC neurons was present in mutants prior to the onset of seizures but was completely absent from both the hippocampus and neocortex of the same animals. The local inhibitory GABAergic neurotransmission remained normal in the OC of SOX1-deficient brains, but there was a severe developmental deficit of OC postsynaptic target neurons, mainly GABAergic projection neurons within the olfactory tubercle and the nucleus accumbens shell. Our data show that SOX1 is essential for ventral telencephalic development and suggest that the neurodevelopmental defect disrupts local neuronal circuits leading to epilepsy in the SOX1-deficient mice.

Complications following percutaneous endoscopic gastrostomy and subsequent catheter replacement in children and young adults.

BACKGROUND: Percutaneous endoscopic gastrostomy has gained wide acceptance for patients who require prolonged tube feeding support. We sought to identify complications and associated risk factors of endoscopic gastrostomy and subsequent catheter replacement in pediatric patients. METHODS: Medical records were reviewed for 137 patients. Odds ratios were calculated for complications related to patient age, weight, weight-for-age Z score, and principal diagnosis. RESULTS: Seventeen patients (12.4%) developed significant complications after gastrostomy: cellulitis occurred in 10 patients (7.3%); other complications included gastrocolic fistula (2), duodenal hematoma (1), complicated pneumoperitoneum (1), necrotizing fasciitis (1), gastric perforation (1), and catheter migration (1). Patients with cancer had significantly greater odds for developing a wound infection, and patients with AIDS had significantly greater odds for total complications. A trend toward increased wound infection was observed in patients with cardiac disease. Age, weight, and weight-for-age Z score were not associated with adverse outcome. Two complications occurred in 85 patients (2.4%) after gastrostomy catheter replacement. CONCLUSIONS: Pediatric patients with cancer and AIDS are at increased risk for complications after endoscopic gastrostomy regardless of age, weight, or nutritional status. Infrequent yet life-threatening complications may occur after replacement of initial gastrostomy catheter.

Radiotherapy for stage I and II testicular seminoma after orchidectomy.

A retrospective study was undertaken to evaluate the effect of irradiation on 65 patients with stage I, or II testicular seminomas treated at Hillbrow Hospital with irradiation following orchidectomy. Forty-seven patients presented with stage 1 and 9 with stage II disease. All patients received infradiaphragmatic irradiation. In addition 4 patients with stage II disease received prophylactic supradiaphragmatic irradiation. The 5-year overall and disease-free survival rate for all stages and for stage I and II compared favourably with other reports in the literature. The irradiation was well tolerated and severe long-term toxicity was rare. Seminomas were uncommon in black patients, of whom only 3 were seen in the 12-year period of this study.

Toxicity in patients with testicular seminoma treated with radiotherapy. Different dose levels and treatment fields.

The aim of this study was to evaluate the acute and late effects of irradiation in 56 patients with stage I and II testicular seminomas. A retrospective study of patients' records was performed paying attention to the acute and late toxicity of radiation in relation to treatment fields and radiation doses. Treatment groups were compared using the chi squared-test. Mild to moderate nausea and/or vomiting was seen in 66% of patients and occurred equally independent of the treatment volume or radiation dose. Increased bowel frequency was seen in 59% and was more common when a larger treatment volume was used. Skin reactions increased with increase in treatment volume and dose (p = 0.046). Severe late complications were recorded in two patients (myocardial damage-1/4 at risk, duodenal ulcer-1/56 at risk). These could not be attributed solely to the irradiation as other contributing factors might play a role. Overall the data suggest that the risk of major posttreatment morbidity is minimal for patients with testicular seminoma treated with postoperative radiotherapy.

Carotid body tumour--a case for radiotherapy?

Carotid body tumours are rare tumours in the head and neck region. Treatment has been surgery with little or no role for radiotherapy. We describe 5 patients with carotid body tumours seen in our department in the last 10 years. Two patients were treated with postoperative radiotherapy after incomplete surgery, 2 had inoperable tumours and were treated with radiotherapy alone, and 1 had a complete excision and required follow-up only. In the 4 patients who received radiotherapy, the disease was stable in 1 patient at 1,1 years and progressive in 2 at 0,6 and 5,6 years respectively; 1 patient did not complete treatment. The patient who had surgery alone for a small tumour was free of disease at 1 year. Small carotid body tumours should be treated with surgery alone. When the tumour is large or the patient is older we propose radiotherapy as initial treatment because of the high morbidity of surgery. A review of the literature and the results with radiotherapy alone in varying doses support this view.

Von Recklinghausen's disease associated with a primary malignant schwannoma of the breast.

A case of a primary malignant schwannoma of the breast is reported. This case and the review of the literature illustrate the problems of diagnosing and treating this rare malignancy.

Initial experience with telebrachytherapy treatment in palliation of advanced oesophageal cancer.

Ten patients with advanced metastatic squamous cell carcinoma of the middle third of the oesophagus were treated with palliative external radiotherapy and intraluminal brachytherapy. All patients had long lesions, 8-15 cm in length, and narrow lumens that did not allow the passage of a guidewire for dilatation. Improvement in dysphagia by more than 2 grades was seen in 9 of 10 patients. This finding was correlated with an increase in the size of the oesophageal lumen at the end of 6 weeks following treatment by barium swallow. No complications of treatment were noted in any patient. Low doses of external beam radiotherapy and high-dose-rate intraluminal brachytherapy can provide quick and effective palliation in advanced metastatic oesophageal carcinoma.

Two loci for tuberous sclerosis: one on 9q34 and one on 16p13.

32 families informative for the segregation of Tuberous sclerosis (TSC) have been examined for genetic markers on chromosomes 9, 11, 12 and 16. In one large family there was clear evidence of linkage to markers on chromosome 16p13.3 (lodscore with D16S291 of 4.7 at theta = 0) but other families were too small to give individually convincing lodscores. Combined results for all families gave positive results with ABO/DBH on chromosome 9 (max lod 2.63) and with D16S291 on chromosome 16 (max lod 3.98) at values of theta of 0.2 in each case. Further analysis showed strong evidence for heterogeneity with approximately half the families linked to a locus TSC1 on chromosome 9 between ASS and D9S298 and half to TSC2 on chromosome 16 close to D16S291. There was no definite support for a third locus although in many families this could not be excluded. In three families the segregation pattern of TSC remains unexplained. In two of these the family apparently segregates for TSC1 but in each case a single affected individual appeared to exclude the whole of the candidate region. Preliminary analysis of clinical features did not reveal any definite differences in incidence of mental handicap between individuals in different linkage groups or with different sex of the parent of origin. The frequencies of periungual fibromas and facial angiofibromas were also similar in both linkage groups. The difficulties of detecting linkage in small families where there is locus heterogeneity are discussed. The program ZZ was found to be helpful in this respect.

Linkage mapping around the ragged (Ra) and wasted (wst) loci on distal mouse chromosome 2.

Mice that are heterozygous for the ragged (Ra) mutation, which is semidominant, have ragged coats caused by an absence of certain hair types. Ra/Ra homozygous mice usually die soon after birth, are naked, and have edema. Mice that are homozygous for the recessive mutation wasted (wst) appear normal until soon after weaning, but then develop tremors and ataxia, undergo atrophy of the thymus and spleen, and die by around 28 days of age. The Ra and wst loci map to distal mouse chromosome 2, but have never been positioned with respect to molecular markers. We have now mapped each of these genes in interspecific backcrosses that were also typed for available molecular markers. The results show that Ra maps very close to D2Mit74 and Acra-4, with no recombinants in 165 mice, whereas wst maps 3 cM distal to the most telomeric molecular marker on mouse chromosome 2, Acra-4.