Disposition of 9-beta-D-arabinofuranosyl-2-fluoroadenine in mice, dogs, and monkeys

The metabolic disposition of 9-beta-D-arabinofuranosyl-2-fluoroadenine (2-F-AraA) has been studied in mice, dogs, and monkeys after iv administration. Following injection of 2-F-AraA (30 mg/m2) into mice, serum levels fell with apparent half-lives of 17 min for the alpha-phase and 72 min for the beta-phase. For dogs given the same dose, these values were less than 5 and 112 min, and, for monkeys, 26 and 125 min, respectively. A higher concentration of metabolites was present in the serum of dogs than in the serum of mice and monkeys. Phosphorylated derivatives of 2-F-AraA were present in each of several mouse tissues examined; liver contained the highest concentration. In 24 hr, mice excreted more than half of the administered compound in the urine as unchanged 2-F-AraA. For dogs given a dose of 400 mg/m2, a single phase of disappearance of the drug (t1/2 = 130 min) was observed. For a single monkey, there were two phases, with half-lives of 15 min and 6.7 hr. In the urine, monkeys excreted about half of either dose as parent compound; but dogs excreted only about one-fourth as unchanged drug. These data indicate that 2-F-AraA is extensively metabolized by dogs but less so by mice and monkeys.     

Results of valvuloplasty for Ebstein's anomaly

Sixteen patients, 8 males and 8 females were referred for surgery with the diagnosis of Ebstein's malformation of the tricuspid valve. The intervention was necessary because of deterioration of the clinical status. The age of the patients at the time of surgery ranged from 4 to 51 years. In 11 patients valvuloplasty was performed, in 5 patients the tricuspid valve was replaced with a bioprosthesis. One patient, with end-stage disease prior to surgery, died 2 days postoperatively rendering total mortality at 6.25%. Subsequent follow-up ranging from 8 months to 8 years was uneventful in the 15 survivors. Only 2 patients showed evidence of dysrhythmias, and demonstrated cardiothoracic ratios greater than 0.65. Cardiac catheterization in 3 patients, at one or 5 months postoperatively revealed normal pressure in the right heart. Provided the anterior tricuspid leaflet is of adequate size, surgical repair of Ebstein's anomaly through valvuloplasty appears to be feasible. The valvuloplasty consists of forming a monocusp valve with the anterior leaflet and plicating the atrialized portion of the right ventricle.     

Paediatric trainees and the transportation of critically ill neonates: experience, training and confidence

AIM: To study the experience of, training in, and confidence in the transportation of critically ill neonates amongst paediatric trainees in one UK region. DESIGN: An anonymized questionnaire was sent to all middle grades with paediatrics National Training Numbers from the Trent region. RESULTS: The response rate was 78%. Less than half (45%) of the respondents reported receiving any training in the transportation of neonates, either in the UK or abroad; 45% (30/66) of the trainees reported having performed 10 or fewer neonatal transfers. The self-perceived confidence for transporting neonates was scored on a 10-point scale, to produce a "confidence score", the median score being 7 (IQ range 5, 8). Both as a group and individually, the trainee paediatricians were more confident in transporting neonates than older infants or children (p < 0.0001). Using multiple analysis of covariance, it was found that the most important and significant variables affecting the "confidence scores" for the inter-hospital transportation of critically ill neonates were receipt of any relevant transport training, and the current frequency of transports performed. CONCLUSIONS: Many training-grade paediatricians lack both the experience and training in transporting critically ill neonates, factors that were found to affect their confidence in transferring sick neonates. As the overwhelming majority of neonatal transports in the UK are still arranged by individual units and performed by training-grade paediatricians, concerns regarding both the safety and effectiveness of the current service provision for the inter-hospital transfer of critically ill neonates remain valid.     

Ventral hernia repair: a study of current practice

Ventral wall hernias are common; despite this, there are no guidelines on the best surgical management. The aim of this study was to examine the types of repair in use for abdominal wall hernias in the West of Scotland over a 3-month period. Data were gathered on 120 patients. There were 60 incisional, 32 umbilical, and 28 epigastric hernias. The main indication for repair was pain (78%), while 12 patients (10%), presented acutely with incarceration or strangulation. The most common method of repair was sutured (55%), followed by mesh (29%) and Mayo repair (16%). There was no correlation between use of mesh and hernia size or whether repair was for a recurrent hernia. Surgical practice varies widely in the repair of ventral wall hernias. Clinical trials are required to establish the best method of repair for this common condition. Electronic Publication     

D2 lymphadenectomy in the management of gastric cancer

Background Gastric carcinoma is a significant cause of death in Ireland. Surgery offers the best option of cure, but the five-year survival following resection remains dismal at 10–15%. Experience from Japan and from some Western units suggest that an extended (D2) lymphadenectomy in association with gastrectomy increases the prospect of cure, but concern about the morbidity and mortality of this operation and lack of evidence from randomised studies has limited its acceptance. Aims This study reports the experience of a specialist upper gastrointestinal unit with D2 gastrectomy in a four-year audit. Methods Sixty-two resections were performed for gastric cancer. Results Nineteen patients were deemed unsuitable for the D2 procedure and underwent a more limited lymphadenectomy (DO or D1). Forty-three patients underwent D2 resection, 12 with an oesophagogastrectomy, 22 with total gastrectomy and nine with a sub-total distal resection. Eight patients undergoing D2 resection had extended resections, five with splenectomy and three with a distal pancreatectomy. Post-operative complications occurred in 31% of patients. Thirty-day and 90-day mortality were zero. Median survival was 822 days in the D2 group (range 120–1,320). Conclusions These results show that a D2 gastrectomy can be performed with a low morbidity and mortality and a median survival of greater than two years.     

Effect of tumour and chemoradiotherapy on oesophageal motility

Background The contribution of dysmotility to dysphagia in oesophageal cancer is unclear. Aim To examine oesophageal motility in patients with oesophageal carcinoma and to assess the effect of chemoradiotherapy on motility. Methods Stationary manometry and 24-hour pH-metry were performed in 12 patients with oesophageal carcinoma and one week following completion of chemoradiotherapy using 5-fluorouracil (5-FU), cisplatin and 40Gy radiotherapy. Results All patients had abnormal motility prior to treatment. Peristalsis was impaired in 11 patients with a mean (SD) of 25% (9) of waves normally propagated. Eight patients had 20% or more simultaneous waves. Following chemoradiotherapy, the percentage of waves normally propagated increased from 25% (9) to 52% (10) (p < 0.03) and normal peristalsis was restored in four patients. The percentage of simultaneous waves decreased from 38% (11) to 21.6% (10) (p=0.129) while the percentage of dropped or increased waves decreased from 20% (11) to 8.3% (4) (p=0.264). Conclusions Oesophageal motility is disturbed in oesophageal cancer. Dysphagia in oesophageal cancer may be partly explained by oesophageal dysmotility. This is improved by chemotherapy.     

Human lens cells in culture. I. Isolation of adult lens epithelial cells from lens capsule preparations and reactivation of nucleus-containing fiber cells

BACKGROUND: Bovine lens epithelial cells in culture revealed a high sensitivity against micromolar concentrations of linoleic acid. To prove the assumption that unsaturated free fatty acids are risk factors for cataractogenesis, human lens cell lines are needed. Furthermore, the reactivation of nucleus-containing fiber cells to mitotic growth may hint at their role in after cataract genesis. MATERIAL AND METHODS: Epithelium-capsule-preparations obtained by capsulorhexis were cultured in serum containing medium. Subculturing of these adult human lens epithelial cells was done by trypsinization. Fiber cell bundles from the equator region of a fetal human lens were transferred into culture medium. Aggregates of nucleus containing fiber cells were isolated from floating fiber cell bundles by trypsinization. Subculturing and cryoconservation of suitable cell lines. RESULTS: Primary culture of epithelium-capsule-preparations results in flattening, migration and proliferation of adult human lens epithelial cells. Nucleus containing fiber cells were reactivated to mitotic growth after adhesion to a suitable substratum. Established cell lines were received from adult human lens epithelial cells and fetal human fiber cells after repeated subculturing. CONCLUSIONS: Lens-capsule-preparations available from cataract surgery are well suited for the isolation of human lens cell lines, which were needed for testing cytotoxicity of drugs and for tracing of cataractogenic risk factors. The finding that nucleus containing fiber cells from the equator of human lenses can be reactivated to proliferating cells let us suppose, that these cells, which can not be removed easily from the posterior lens capsule, contribute to the after cataract formation.