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.      

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.     

Mouse and rat placental cell lines express abundant amounts of laminin

Placental cell lines derived from midgestation placentae of outbred mice and rats were evaluated for the expression of the extracellular matrix protein laminin. The murine cell line, which has not been previously reported, demonstrates morphological characteristics similar to those of the rat cell line. Placental cell lines grow vigorously both in vitro and when transplanted to the peritoneum of allogeneic hosts. When transplanted, placental cells form cyst-like structures (with acellular cores) suspended in the peritoneal fluid, and invade abdominal structures forming solid masses. Using immunohistology, laminin was identified within in vitro cultured cells, within cyst-like structures and their acellular cores, and as a major component of the extracellular matrix of solid masses. Laminin was also identified in the normal rat chorioallantoic placenta. Evaluation of extracts from in vitro cultured placental cells, transplanted placental cells, and the normal chorioallantoic placenta by electrophoresis and immunoblotting demonstrated that laminins were composed of two species with molecular weights of 400,000 (A-chain) and 200,000 (B-chains). Mouse and rat placental cell lines may be valuable for studying laminin biosynthesis and function in the developing placenta.     

Serum copper and zinc levels in the preterm infant. A longitudinal study of the first year of life

Serial determinations were carried out on 27 male and 21 female preterm infants (gestational age 28-36 weeks) throughout the first year of life. Serum copper at birth was 0.33 +/- 0.20 micrograms/ml (n equal 8); at 9 weeks, 0.77 +/- 0.19 micrograms/ml (n = 22); at 24 weeks, 1.00 +/- 0.27 micrograms/ml (n = 31), and at 52 weeks 1.21 +/- 0.27 micrograms/ml (n = 40). Serum zinc at birth was 1.03 +/- 0.16 micrograms/ml (n = 9); at 9 weeks, 0.71 +/- 0.11 micrograms/ml (n = 17); at 24 weeks, 1.02 +/- 0.20 micrograms/ml (n = 20), and at 52 weeks, 1.19 +/- 0.34 micrograms/ml (n = 33). The results of this study compare well with values previously reported for infants studied at selected age points.     

Glucose-induced oxidative stress in mesangial cells

BACKGROUND: Hyperglycemia is a well-recognized pathogenic factor of long-term complications in diabetes mellitus. Hyperglycemia not only generates reactive oxygen species but also attenuates antioxidant mechanisms creating a state of oxidative stress. METHODS: Porcine mesangial cells were cultured in high glucose (HG) for ten days to investigate the effects on the antioxidant defenses of the cell. RESULTS: Mesangial cells cultured in HG conditions had significantly reduced levels of glutathione (GSH) compared with those grown in normal glucose (NG). The reduced GSH levels were accompanied by decreased gene expression of both subunits of gamma-glutamylcysteine synthetase (gamma-GCS), the rate-limiting enzyme in de novo synthesis of GSH. Elevated levels of intracellular malondialdehyde (MDA) were found in cells exposed to HG conditions. HG also caused elevated mRNA levels of the antioxidant enzymes CuZn superoxide dismutase (SOD) and MnSOD. These changes were accompanied by increased mRNA levels of extracellular matrix proteins (ECM), fibronectin (FN) and collagen IV (CIV). Addition of antioxidants to high glucose caused a significant reversal of FN and CIV gene expression; alpha-lipoic acid also up-regulated gamma-GCS gene expression and restored intracellular GSH and MDA levels. CONCLUSIONS: The results demonstrate the existence of glucose-induced oxidative stress in mesangial cells as evidenced by elevated MDA and decreased GSH levels. The decreased levels of GSH are as a result of decreased mRNA expression of gamma-GCS within the cell. Antioxidants caused a significant reversal of FN and CIV gene expression, suggesting an etiological link between oxidative stress and increased ECM protein synthesis.     

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.