Tumour cords in 52 human bronchial and cervical squamous cell carcinomas: inferences for their cellular kinetics and radiobiology

Tumour cords have been measured in 33 cases of squamous cell carcinoma (SCC) of the bronchus and 19 cases of SCC of the uterine cervix. The overall mean cord radius for SCC in both sites was 104 microns, similar to the overall mean for various tumours in rodents. For tumour cells adjacent to blood vessels in cords of SCC, the mean Mitotic Index was 2.1% and from this value a rapid potential doubling time could be inferred (approximately 31 to 66 h). The proportion of dead cells within cords of cervical SCC was higher than in animal tumours. Using measured values for cord radius and published equations that describe the diffusion and consumption of oxygen in metabolising tissue, an attempt was made to calculate the oxygen partial pressure in vessels of cords of these SCC.     

Excimer laser surface ablation: a review of recent literature

The aim was to review the recently published literature on excimer laser surface ablation procedures, including photorefractive keratectomy (PRK), laser sub‐epithelial keratomileusis (LASEK), microkeratome‐assisted PRK (epi‐LASIK) and trans‐epithelial (laser‐assisted) PRK, to help elucidate where and how surface ablation may best fit into current refractive surgical practice. The emphasis was on publications within the last three years and included systemic reviews, meta‐analyses and randomised controlled trials. Where such evidence did not exist, selective large series cohort studies, case‐controlled studies and case series with follow‐up preferably greater than six months were examined and included. Refractive and visual outcomes are excellent and comparable to those after LASIK even in complex cases after previous corneal surgery. Indeed, surface ablation combined with corneal collagen cross‐linking may be used in selected eyes with biomechanical instability, where LASIK is contraindicated. In addition, there is evidence to suggest that there may be less induction of higher order aberrations with surface techniques. Long‐term stability and safety appear to be extremely satisfactory. The literature supports the use of modern excimer laser surface treatments, with outcomes comparable to those after LASIK and evidence of less induction of higher‐order aberrations. Follow‐up studies at 10 to 20 years indicate excellent stability and safety.     

Failure to recapture cardioprotection with high-dose atorvastatin in coronary artery bypass surgery: a randomised controlled trial

The acute administration of atorvastatin has been reported to reduce myocardial infarct size in animal studies. However, this cardioprotective effect is lost with the chronic administration of atorvastatin, although it can be recaptured by administering an acute high-dose of atorvastatin. We hypothesised that pre-treatment with high-dose atorvastatin, on a background of chronic standard 'statin' therapy, would reduce myocardial injury in patients undergoing elective coronary artery bypass graft (CABG) surgery. One hundred and one consenting patients undergoing elective CABG surgery at a single tertiary cardiac centre were recruited into two randomised controlled, single-blinded clinical studies. Study 1: 45 patients were randomised to receive either 160?mg of atorvastatin 2?h preoperatively and 24?h following surgery or their standard statin therapy. Study 2: 56 patients were randomised to receive either 160?mg of atorvastatin 12?h preoperatively and 24?h following surgery or their standard statin therapy. Blood samples for troponin T and creatine kinase were taken prior to surgery and then at 6, 12, 24, 48 and 72?h post-surgery. Cardiac enzyme levels at each time point and the total area-under curve (AUC) were calculated. The group characteristics and surgical methods were well matched. High-dose atorvastatin was not associated with any significant side effects. There was no significant difference in serum troponin T or creatine kinase in either study at each time point or over 72?h. Study 1: AUC, troponin T: atorvastatin 29.6?±?34.8?μg/L versus control 25.0?±?22.0?μg/L:P?>?0.05. Creatine kinase: atorvastatin 33,544?±?20,063?IU/L versus control 30,620?±?10,776?IU/L:P?>?0.05. Study 2: AUC, troponin T: atorvastatin 21.8?±?14.3?μg/L versus control 20.9?±?8.7?μg/L:P?>?0.05. Creatine kinase: atorvastatin 36,262?±?28,821?IU/L versus control 33,448?±?14,984:P?>?0.05. There were no differences in postoperative outcomes. We report that the administration of high-dose atorvastatin to low risk patients undergoing elective CABG surgery, who are already on standard dose 'statin' therapy is safe, but does not further reduce perioperative myocardial injury.     

Localization by chromosome microdissection of a recurrent breakpoint region on chromosome 6 in human B-cell lymphoma

Deletion of the long arm of chromosome 6 (6q) is one of the most common chromosomal alterations in human B-cell lymphomas. Conventional cytogenetic banding analysis and loss-of-heterozygosity (LOH) studies have detected several common regions of deletion ranging across the entire long arm (6q), with no defined recurrent breakpoint yet identified. We describe here a strategy combining chromosome microdissection and fluorescence in situ hybridization (Micro-FISH) to determine a minimal region of deletion along chromosome 6. Seven clinical cases and one cell line of follicular lymphoma containing a t(14;18) and one case of diffuse lymphoma, also with a t(14;18), were used for this study. All nine cases had previously defined abnormalities of chromosome 6 determined by cytogenetic analysis. The results of chromosome dissection were unexpected and in contrast to the suggestion of disparate breakpoints by conventional chromosome banding. Specifically, Micro-FISH analysis provided evidence for a common breakpoint at 6q11 in seven of nine cases. After Micro-FISH analysis, all of the presumed simple deletions of chromosome 6 were carefully reanalyzed and shown to actually represent either nonreciprocal translocations (three cases), interstitial deletions (five cases), or isochromosome (one case). The recurrent proximal breakpoint (6q11) was detected in seven of nine cases, with the minimal region of deletion encompassing 6q11 to 6q21. By analogy to other tumor systems, the identification of recurring breakpoints within 6q11 may suggest that a gene(s) important to the genesis or progression of follicular lymphoma can be localized to this band region.     

Beneficial effects of insulin-like growth factor I on epithelial structure and function in parenterally fed rat jejunum

BACKGROUND & AIMS: The functional significance of intestinal hyperplasia stimulated by insulin-like growth factor (IGF)-I is unclear and has not been studied in a model of mucosal atrophy induced by total parenteral nutrition (TPN). The aim of this study was to determine how IGF-I affects intestinal structure and epithelial function in the absence of luminal nutrition caused by TPN. METHODS: Rats were maintained with TPN with or without IGF-I (800 micrograms/day), and jejunal histology and epithelial ion transport were measured after 5 days. In a third TPN group without IGF-I, a short-term dose of IGF-I was added during in vitro flux chamber experiments. RESULTS: Rats given TPN with IGF-I had greater jejunal mucosal weight, greater protein and DNA content, and increased villus height and crypt depth compared with rats given TPN only. TPN increased ionic permeability and ion transport responses to secretory and absorptive agents. IGF-I in vivo reversed most of these changes; IGF-I in vitro enhanced sodium-dependent glucose absorption but had no other effects. CONCLUSIONS: Coinfusion of recombinant human IGF-I with TPN solution stimulates intestinal hyperplasia and attenuates transport changes induced by TPN. The latter effect seems to be primarily associated with the growth state of the epithelium. (Gastroenterology 1996 Dec;111(6):1501-8)