Identification of MEN1 gene mutations in sporadic carcinoid tumors of the lung

Lung carcinoids occur sporadically and rarely in association with multiple endocrine neoplasia type 1 (MEN1). There are no well defined genetic abnormalities known to occur in these tumors. We studied 11 sporadic lung carcinoids for loss of heterozygosity (LOH) at the locus of the MEN1 gene on chromosome 11q13, and for mutations of the MEN1 gene using dideoxy fingerprinting. Additionally, a lung carcinoid from a MEN1 patient was studied. In four of 11 (36%) sporadic tumors, both copies of the MEN1 gene were inactivated. All four tumors showed the presence of a MEN1 gene mutation and loss of the other allele. Observed mutations included a 1 bp insertion, a 1 bp deletion, a 13 bp deletion and a single nucleotide substitution affecting a donor splice site. Each mutation predicts truncation or potentially complete loss of menin. The remaining seven tumors showed neither the presence of a MEN1 gene mutation nor 11q13 LOH. The tumor from the MEN1 patient showed LOH at chromosome 11q13 and a complex germline MEN1 gene mutation. The data implicate the MEN1 gene in the pathogenesis of sporadic lung carcinoids, representing the first defined genetic alteration in these tumors.      

High throughput parallel analysis of hundreds of patient samples for more than 100 mutations in multiple disease genes

As more mutations are identified in genes of known sequence, there is a crucial need in the areas of medical genetics and genome analysis for rapid, accurate and cost-effective methods of mutation detection. We have developed a multiplex allele-specific diagnostic assay (MASDA) for analysis of large numbers of samples (> 500) simultaneously for a large number of known mutations (> 100) in a single assay. MASDA utilizes oligonucleotide hybridization to interrogate DNA sequences. Multiplex DNA samples are immobilized on a solid support and a single hybridization is performed with a pool of allele-specific oligonucleotide (ASO) probes. Any probes complementary to specific mutations present in a given sample are in effect affinity purified from the pool by the target DNA. Sequence-specific band patterns (fingerprints), generated by chemical or enzymatic sequencing of the bound ASO(s), easily identify the specific mutation(s). Using this design, in a single diagnostic assay, we tested samples for 66 cystic fibrosis (CF) mutations, 14 beta-thalassemia mutations, two sickle cell anemia (SCA) mutations, three Tay-Sachs mutations, eight Gaucher mutations, four mutations in Canavan disease, four mutations in Fanconi anemia, and five mutations in BRCA1. Each mutation was correctly identified. Finally, in a blinded study of 106 of these mutations in > 500 patients, all mutations were properly identified. There were no false positives or false negatives. The MASDA assay is capable of detecting point mutations as well as small insertion or deletion mutations. This technology is amenable to automation and is suitable for immediate utilization for high-throughput genetic diagnostics in clinical and research laboratories.      

Education initiative improves the evidence‐based use of metoclopramide following morphine administration in the emergency department

Objective: We aimed to evaluate a multifaceted education initiative designed to reduce the prophylactic use of metoclopramide. Methods: This was a pre‐ and post‐intervention trial undertaken in a single ED. All ED doctors and nurses were targeted. The intervention comprised a specifically designed, 19‐slide ‘e‐learning module’, accessible via the ED intranet, supplemented by in‐service training and a range of reminder techniques (posters, emails and drug room flyers). The primary end‐point was the proportion of patients administered metoclopramide prophylactically with their initial morphine dose. Data were collected on random samples of patients who received morphine, using explicit medical chart review. Results: Both pre‐ and post‐intervention periods were of 3 month duration. The charts of 146 cases were reviewed in each period. In the post‐intervention period: ? The proportion of patients administered metoclopramide prophylactically decreased from 22.6% to 4.1% (difference 18.5% [95% CI 10.3–26.7], P < 0.001) ? The proportion of patients administered metoclopramide appropriately (for known morphine sensitivity, established nausea and rescue anti‐emesis) rose marginally from 28.8% to 32.9% (difference 4.1% [95% CI ?7.2–15.4], P = 0.53) ? There was a 12.7% decrease in the number of ampoules of metoclopramide issued to the ED without a concurrent rise in the issue of other anti‐emetic drugs Conclusion: The education initiative resulted in a significant improvement in the evidence‐based use of metoclopramide.     

Neurohydatidosis

Early and non‐invasive evaluation of hydatid infestation of brain and spine is of paramount importance, especially in endemic areas. We present a spectrum of imaging findings in neurohydatidosis with a brief review of literature.     

An ultrasonographic study of Peyronie's disease

A study was undertaken to determine the usefulness of ultrasonography as an investigative tool, and its role in deciding the management of Peyronie's disease. Fifteen patients with Peyronie's disease were studied by ultrasonography. The plaque could be demonstrated in all patients. The dimensions of the plaque varied from less than 1 cm to more than 7cm in length and 2-4mm in thickness. The disease was active in 26% of the patients, as indicated by the presence of hypoechoic areas around a central region of hyperechoism. Ultrasonogram was more accurate than clinical assessment in delineating the extent of lesions. In one-third of the patients, sonography demonstrated the plaques to be more extensive than had been detected by clinical examination. Calcification and activity of disease (which are clearly defined by ultrasonogram) are determining factors in the management of Peyronie's disease. This information allows the surgeon to select the modality of treatment, the timing of surgery and extent of excision. Thus, ultrasonography plays a vital role in the preliminary investigation and management of Peyronie's disease.     

Preoperative embolization of a large vaginal leiomyoma: Report of a case and review of the literature

Leiomyoma of the vagina is a very rare tumour of the lower urogenital tract. These slow‐growing masses may be asymptomatic or present with pain, dyspareunia or urinary symptoms. Rarely, these tumours may present with life‐threatening haemorrhage. These hypervascular tumours are treated by surgical excision. Preoperative embolization therefore may aid in devascularization of these tumours before surgical excision. We present the MRI features of a case of vaginal leiomyoma, which was managed by preoperative embolization and was then excised in toto. To the best of our knowledge, this is the first report where preoperative embolization was performed before excision of a vaginal leiomyoma with minimal peroperative blood loss.     

Paracetamol use, availability, and knowledge of toxicity among British and American adolescents

Paracetamol is the commonest agent employed in self poisoning, however it is not clear whether adolescents possess insight into the serious complications associated with its misuse. Using a one page questionnaire, the availability, usage, and knowledge of toxicity of paracetamol among 1147 American and British adolescents was assessed. Although 90% of all students recognised that paracetamol could kill, the great majority of students overestimated the lethal dose. In addition, while knowledge regarding side effects of paracetamol was poor the drug was widely available to, and used by, the study population. It is proposed that gross overestimation of the number of tablets required to kill, poor understanding of paracetamol side effects, and wide availability of the drug contribute to its frequent use in adolescent suicidal behaviour. The inclusion of some over-the-counter medications in school drug education programs in addition to tighter control of the availability of paracetamol may help reduce the problem of adolescent self poisoning.