Oncogene-mediated propagation of tracheal epithelial cells from two cystic fibrosis fetuses with different mutations. Characterization of CFT-1 and CFT-2 cells in culture

Abstract. Primary tracheal epithelial cells obtained from two fetuses with cystic fibrosis (CF) were successfully transfected with a plasmid vector recombined with the large T oncogene of SV40. The resulting tracheal cells were propagated in culture for up to 25 passages and retained the mutations of the CF genes carried by the two fetuses, one heterozygous for the S549N and N1303K substitutions (CFT-I cells), and the other homozygous for the most common deletion ΔF508 (CFT-2 cells). The transfected cells: (a) expressed the SV40 large T oncogene, as determined by immunofluorescence and Northern blot analysis; (b) retained typical epithelial morphology, as assessed by the presence of microvilli, desmosomes, gap junctions, and cytokeratin expression; (c) were fully responsive to the cAMP-stimulating agents isproterenol, forskolin and vasoactive intestinal peptide for cAMP production and PKA activation; (d) do not produce any tumour in the athymic nude mice; (e) were diploid and tetraploid with a normal chromosomal complement at early passages, and (f) exhibited the abnormal regulation of chloride conductance characteristic of CF.
These results indicate that CFT-1 and CFT-2 cells constitute a suitable model for: (a) comparison of the maturation and function of the CFTR protein mutated in the two nucleotide-binding domains; (2) analysis of the biochemical defect in CF epithelial airway cells, (c) development of new therapeutic agents, and correction of the CF defect by gene replacement therapy in vitro .     

The effect of antibody against TNF alpha on cytokine response in Jarisch-Herxheimer reactions of louse-borne relapsing fever

Severe Jarisch Herxheimer reaction (J-HR) precipitated by antibiotic treatment of louse-borne relapsing fever (LBRF) is associated with a transient, marked rise in circulating tumour necrosis factor alpha (TNF alpha), interleukin 6 (IL-6) and interleukin 8 (IL-8). Ovine polyclonal anti-TNF alpha antibody fragments (Fab) were used in a randomized double blind placebo controlled trial in an attempt to prevent this reaction. Within 4 h after penicillin, in controls (n = 29), a several- fold rise in cytokines occurred, concomitant with a fall in spirochaetes and maximal clinical manifestations of the J-HR. An intravenous infusion of anti-TNF alpha Fab, 30 min before penicillin in 20 patients reduced peak plasma levels of IL-6 and IL-8 (but not IL-1 beta) compared with controls (p = 0.01 and < 0.001, respectively) and the incidence of the J-HR, indicating some neutralization of TNF alpha. An apparent fall in TNF alpha reflected interference of anti-TNF alpha in the immunoassay.      

Major complications after 400 continuous popliteal sciatic nerve blocks for post‐operative analgesia

Background: A continuous popliteal sciatic nerve block (CPSNB) has been performed with increasing frequency for post‐operative analgesia after foot surgery. Major complications associated with the placement of a perineural catheter remain rarely studied. The aim of this study was to prospectively determine the incidence of major complications (neurological and infectious) in post‐operative adult patients with a continuous popliteal catheter inserted by the anatomical posterior approach for analgesia after foot surgery. Methods: All popliteal catheters were placed pre‐operatively under sterile conditions with the aid of a nerve stimulator technique. The primary outcome measure was the incidence of major complications including infection and neuropathy. As a secondary outcome, adverse effects as well as other complications were also evaluated. Data were expressed as median [25th–75th percentiles]. Results: A total of 400 patients were included in the study during a 2‐year period. The median time the catheter remained indwelling was 47 h [23, 54]. Major complications included three events (0.75%) with one infection (0.25%) and two neuropathies (0.50%). Three blocks were unsuccessful and the catheter insertion was difficult in 12 patients (3%). During the CPSNB procedure, one patient reported slight paraesthesia during stimulation. Patient satisfaction was scored at 4 for 89%, 3 for 6% and 2 for 5% on the analogue scale. Conclusions: Major complications after the use of CPSN are not in fact rare. The incidence of severe neuropathy or infection complications is, respectively, 0.50% and 0.25%. However, the insertion of CPSN could be considered effective and is associated with only a few minor complications.     

胃重复畸形并胃胰腺损伤1例

1临床资料患儿,女性,4岁。因间断性腹痛1月加重伴黑便15d,呕吐2d入院。患儿病前无明确外伤史,其母于入院前15d发现左膝部有损伤痕,已愈合,行腹部B超检查,提示肝胆肾正常,胰大小正常,边界清,实质回声均匀,主胰管不扩张,肝前区肝肾夹角及脾肾夹角可见53mm的液性暗区,内见肠管蠕动     

Weight loss and incretin responsiveness improve glucose control independently after gastric bypass surgery

Background: The aim of the present study was to determine the mechanisms underlying Type 2 diabetes remission after gastric bypass (GBP) surgery by characterizing the short‐ and long‐term changes in hormonal determinants of blood glucose. Methods: Eleven morbidly obese women with diabetes were studied before and 1, 6, and 12 months after GBP; eight non‐diabetic morbidly obese women were used as controls. The incretin effect was measured as the difference in insulin levels in response to oral glucose and to an isoglycemic intravenous challenge. Outcome measures were glucose, insulin, C‐peptide, proinsulin, amylin, glucagon, glucose‐dependent insulinotropic polypeptide (GIP), glucagon‐like peptide‐1 (GLP‐1) levels and the incretin effect on insulin secretion. Results: The decrease in fasting glucose (r = 0.724) and insulin (r = 0.576) was associated with weight loss up to 12 months after GBP. In contrast, the blunted incretin effect (calculated at 22%) that improved at 1 month remained unchanged with further weight loss at 6 (52%) and 12 (52%) months. The blunted incretin (GLP‐1 and GIP) levels, early phase insulin secretion, and other parameters of β‐cell function (amylin, proinsulin/insulin) followed the same pattern, with rapid improvement at 1 month that remained unchanged at 1 year. Conclusions: The data suggest that weight loss and incretins may contribute independently to improved glucose levels in the first year after GBP surgery.     

An echocardiographic assessment of cardiac morphology and common ECG findings in teenage professional soccer players: reference ranges for use in screening

OBJECTIVE—To assess physiological cardiac adaptation in adolescent professional soccer players.
SUBJECTS AND DESIGN—Over a 32 month period 172 teenage soccer players were screened by echocardiography and ECG at a tertiary referral cardiothoracic centre. They were from six professional soccer teams in the north west of England, competing in the English Football League. One was excluded because of an atrial septal defect. The median age of the 171 players assessed was 16.7 years (5th to 95th centile range: 14-19) and median body surface area 1.68 m² (1.39-2.06 m²).
MAIN OUTCOME MEASURES—Standard echocardiographic measurements were compared with predicted mean, lower, and upper limits in a cohort of normal controls after matching for age and surface area. Univariate regression analysis was used to assess the correlation between echocardiographic variables and the age and surface area of the soccer player cohort. ECG findings were also assessed.
RESULTS—All mean echocardiographic variables were greater than predicted for age and surface area matched controls (p < 0.001). All variables except left ventricular septal and posterior wall thickness showed a modest linear correlation with surface area (r = 0.2 to 0.4, p < 0.001); however, left ventricular mass was the only variable that was significantly correlated with age (r = 0.2, p < 0.01). Only six players (3.5%) had structural anomalies, none of which required further evaluation. All had normal left ventricular systolic function. Sinus bradycardia was found in 65 (39%). The Solokow-Lyon voltage criteria for left ventricular hypertrophy were present in 85 (50%) and the Romhilt-Estes points score (five or more) in 29 (17%). Repolarisation changes were present in 19 (11%), mainly in the inferior leads.
CONCLUSIONS—Chamber dimensions, left ventricular wall thickness and mass, and aortic root size were all greater than predicted for controls after matching for age and surface area. Sinus bradycardia and the ECG criteria for left ventricular hypertrophy were common but there was poor correlation with echocardiographic left ventricular hypertrophy. The type of hypertrophy found reflected the combined endurance and strength based training undertaken.


Keywords: cardiac morphology; professional soccer players; echocardiography; ECG findings     

Left‐sided Partial Anomalous Pulmonary Venous Communication in a Patient with Turner's Syndrome

Congenital defects of the aortic valve and thoracic aorta are well recognised in patients with Turner's syndrome. Anomalous pulmonary venous connections that were previously considered rare in patients with Turner's syndrome have been detected in up to one in ten patients with the advent of cardiac magnetic resonance imaging. We describe an instance of partial anomalous pulmonary venous drainage in a patient with Turner's syndrome, discuss the clinical indicators of these anomalies, and briefly mention the management options in such patients.