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.      

Bromodeoxyuridine incorporation and Ki 67 expression in oral hairy leukoplakia

OBJECTIVES: Oral hairy leukoplakia (HL) is an acan-thotic, hyperparakeratotic lesion characterised by the presence of a replicative Epstein-Barr virus (EBV) infection in the superficial and adjoining layers of the epithelium. EBV or its gene products are capable of modifying epithelial differentiation. The aim of this study was to establish whether the presence of EBV was associated with an alteration in cell turnover by assessing bromodeoxyuridine (BrdU) incorporation and Ki 67 expression in lesional tissue and control mucosa.
METHODS: Biopsies of HL together with age, site and sex matched controls ( n = 7 and 8 respectively) were incubated in 200 μM BrdU in vitro , fixed in methacarn and processed to paraffin wax. Following acid hydrolysis, incorporated BrdU and Ki 67 were identified in serial 5 fim sections using a three-stage immunoperoxidase technique and cell density expressed as the number of positive cells per mm basement membrane length.
RESULTS: Overall, there was no difference in the number of BrdU positive cells per mm basement membrane length between control and HL tissue. However, within HL alone, the presence'of focal EBV replication was associated with a significant reduction in the number of basal cells incorporating BrdU compared to adjacent EBV free areas (P < 0.05). There was no significant difference between Ki 67 positive cells in control and HL tissue and no evidence of a reduction of Ki 67 positive cells in areas associated with EBV replication.
CONCLUSIONS: These results suggest that there is no evidence of a generalised alteration of the proliferative capacity of basal cells in HL, although the focal reduction in BrdU incorporation may reflect subtle changes on cell turnover by EBV infection.     

Emergency surgery comparison of right versus left acute colonic diverticulitis: A 10-year outcome analysis

IntroductionThe difference in outcome between right (RCD) and left colonic diverticulitis (LCD) is not well established. The aim of this study was to analyse the presentation and surgical outcome of RCD versus left-sided disease following emergency surgery.MethodWe conducted a retrospective review of patients presenting with acute diverticulitis over a 10-year period from 2004 to 2014 to a tertiary unit. Patient demographics, Hinchey classification, need for emergency surgery, perioperative outcome and recurrence were evaluated.ResultsIn total 360 patients presented with acute diverticulitis, 218 (61%) were right-sided and 142 (39%) were left-sided. The mean age (57 yrs vs 68 yrs) and median length of stay (4 days vs 5 days) were significantly less in RCD (p < 0.001). The need for emergency surgery was similar between RCD and LCD (30.7% vs 23.2%, p = 0.12). Sixty-seven (31%) patients with RCD required emergency surgery, 42 (62.7%) of these were based on a presumptive diagnosis of appendicitis and underwent laparoscopic appendicectomy only. Operative morbidity (10.4% vs 51.5%, p < 0.001) and mortality were significantly higher in LCD (1.5% v 15.2%, p = 0.007). Subgroup analysis of non-appendicectomy, RCD patients, showed LCD were more likely to require surgery (11.5% vs 23.2%, p = 0.003). There was no difference in recurrence (p = 0.6).ConclusionRight colonic diverticulitis patients are younger and disease course is more benign compared to LCD. Presentation can be confused with appendicitis without proper imaging. In the rare cases where emergency surgery is required, RCD is associated with a lower operative morbidity and mortality compared to left-sided disease.     

Strangulation in child abuse: CT diagnosis

The central nervous system is commonly affected in child abuse. Between April 1985 and July 1986 three infants were identified in whom the primary mode of injury had been strangulation. In each case computed tomography (CT) demonstrated a large cerebral infarction confined to vascular territories associated with small subdural hematomas. There was no history or visible evidence of significant head trauma. Autopsy of one infant confirmed the presence of a hemispheric infarct, thin subdural hematoma, and an area of subintimal hemorrhage in the carotid artery ipsilateral to the infarct. The remaining two patients survived with residual hemiparesis. CT findings of a large cerebral infarction with an associated subdural hematoma in an infant without a history of a significant trauma should suggest the possibility of child abuse and may be the primary manifestation of abuse in some patients.     

Proximal femoral focal deficiency: radiologic analysis of 49 cases

Proximal femoral focal deficiency, an uncommon congenital anomaly, necessitates early radiologic classification for surgical planning and treatment. Objective radiographic criteria, including femoral length index, acetabular depth index, acetabular angle index, and shape of the proximal femur were determined in 49 patients before cartilaginous ossification of the femoral capital epiphysis; final classification was based on follow-up radiographs or findings at arthrography or surgery. These parameters were analyzed to determine the accuracy and contributions of each in classification. Correct classification into one of three groups was possible in 86% of cases with use of three of the parameters: femoral length index, acetabular depth index, and shape of the proximal femur. The acetabular angle was found to contribute insignificantly to classification. Magnetic resonance imaging, used in only one case, depicted the nonossified cartilaginous femoral capital epiphysis, thus obviating the need for invasive diagnostic procedures and facilitating early classification.     

Comparison of the structure of human intervertebral discs in the cervical,thoracic and lumbar regions of the spine

Posterior and anterior heights, cross-sectional area and shape were measured for all the intervertebral discs in four spines from elderly human cadavers. Disc height was a minimum at the T4-5 level; thoracic discs were less wedge-shaped than those in the cervical and lumbar regions. Cross-sectional area increased from the cranial to caudal extremity; at the L5-S1 level the nucleus pulposus occupied a high proportion of this area. Cervical discs tended to have an elliptical cross-sectional shape, thoracic discs were more circular and lumbar discs tended to have an elliptical cross-section which was flattened or re-entrant posteriorly. This shape distribution was quantified by defining a shape index which had a maximum value of 1 for a circular cross-section. Orientations of the reinforcing fibres in the outer lamellae of the anterior annulus fibrosus were measured from 27 discs by X-ray diffraction. For these measurements, C3-4, T7-8 and L2-3 were chosen as representative of cervical, thoracic and lumbar discs. The fibre tilt, with respect to the axis of the spine, was significantly less in the cervical discs (at 65 degrees) than in the thoracic and lumbar discs (about 70 degrees). These findings are interpreted in relation to differing functional requirements and possible mechanisms of failure in the cervical, thoracic and lumbar regions of the spine in the light of current knowledge on the biomechanics of the intervertebral disc.