Pharyngeal diverticula

A series of 73 hypopharyngeal (Zenker's) diverticula is reported and the choice of treatment and technique of excision are discussed. The problems of excision include operation on an infected site with limited access but few patients are unfit for the procedure. Preoperatively the sac should be packed and the oesophagus stented. The side of approach is unimportant as the condition is essentially midline. Cricopharyngeal myotomy appears to reduce the recurrence rate, possibly by improving coordination of pharyngeal contraction and upper oesophageal relaxation. The use of electrocoagulation is not recommended as 20% of patients require repeated general anaesthesia and the procedure fails in 13%. For all but the smallest pouches, excision is the treatment of choice.     

Instrumental activation of bid by caspase-1 in a transgenic mouse model of ALS

Transgenic expression of mutant superoxide dismutase-1 (SOD1) produces an animal model of amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disorder. We have previously shown that the mitochondrial-dependent programmed cell death (PCD) pathway, including the redistribution of Bax, the cytosolic release of cytochrome c, and the activation of caspase-9, is recruited during neurodegeneration in spinal cords of transgenic mutant SOD1 mice. Herein, we show that the pro-PCD protein Bid is highly expressed in spinal cords of both wild-type and transgenic mutant SOD1 mice. While full-length Bid is found in the spinal cord of the two groups of mice, its cleaved form is only seen in transgenic mutant SOD1 mice, as early as the beginning of symptoms. In contrast, activated caspase-8, which is known to cleave Bid, is detected only at the end-stage of the disease. We also found that the expression of a dominant negative mutant of caspase-1 attenuates Bid cleavage as well as the mitochondrial release of cytochrome c, and the ensuing activation of caspase-9 and -3 in spinal cords of transgenic mutant SOD1 mice. These findings suggest that Bid cleavage may occur in this model by a pathway other than caspase-8 and shed light onto the molecular correlates of the previously reported beneficial effect of caspase-1 inhibition in transgenic mutant SOD1 mice.     

Energy intake deficit and physical performance at altitude

BACKGROUND: Physical performance of sea-level (SL) residents acutely exposed to altitude (ALT) is diminished and may improve somewhat with ALT acclimatization. HYPOTHESIS: A large reduction in lean body mass (LBM), due to severe energy intake deficit during the first 21 d of ALT (4300 m) acclimatization, will adversely affect performance. METHODS: At ALT, 10 men received a deficit (DEF) of 1500 kcal x d(-1) below body weight (BW) maintenance requirements and 7 men received adequate (ADQ) kcal x d(-1) to maintain BW. Performance was assessed by: 1) maximal oxygen uptake (VO2max); 2) time to complete 50 cycles of a lift and carry task (L+C); 3) number of one-arm elbow flexions (10% BW at 22 flexions x min(-1); and 4) adductor pollicis (AP) muscle strength and endurance time (repeated 5-s static contractions at 50% of maximal force followed by 5-s rest, to exhaustion). Performance and body composition (using BW and circumference measures) were determined at SL and at ALT on days 2 through 21. RESULTS: At SL, there were no between-group differences (p > 0.05) for any of the performance measures. From SL to day 21 at ALT, BW and LBM declined by 6.6 +/- 3 kg and 4.6 kg, respectively, for the DEF group (both p < 0.01), but did not change (both p > 0.05) for the ADQ group. Performance changes from day 2 or 3 to day 20 or 21 at ALT were as follows (values are means +/- SD): VO2max (ml x min(-1)): DEF = +97 +/- 237, ADQ = +159 +/- 156; L + C (s): DEF = -62 +/- 35*, ADQ = -35 +/- 20* (*p < 0.05; improved from day 3); arm flex (reps): DEF = -2 +/- 7, ADQ = +2 +/- 8; AP endurance (min): DEF = +1.4 +/- 2, ADQ = + 1.9 +/- 2; AP strength (kg): DEF = -0.7 +/- 4, ADQ = -1.2 +/- 2. There were no differences in performance between groups. CONCLUSIONS: A significant BW and LBM loss due to underfeeding during the first 21 d of ALT acclimatization does not impair physical performance at ALT.     

Oxaliplatin and axonal Na+ channel function in vivo.

PURPOSE: The aim of the study was to investigate the pathophysiology of oxaliplatin-induced neurotoxicity using clinical nerve excitability techniques that provide information about axonal ion channel function. EXPERIMENTAL DESIGN: Excitability studies were combined with standard nerve conduction studies and clinical assessment in 22 patients undergoing treatment with oxaliplatin. RESULTS: Excitability studies recorded before and immediately after oxaliplatin infusion for 89 treatment cycles revealed significant increases in refractoriness and relative refractory period postinfusion in all patients, consistent with an effect of oxaliplatin on axonal Na(+) channels. However, those patients that developed chronic neuropathy had significantly greater changes. Following cessation of oxaliplatin treatment, 41% of patients had persistent symptoms and nerve conduction abnormalities consistent with the development of chronic neuropathy. CONCLUSION: The present study provides evidence that oxaliplatin-induced neurotoxicity is mediated through an effect on axonal Na(+) channels. Clinical nerve excitability techniques may prove beneficial in monitoring for early signs of neurotoxicity and in the assessment of future prophylactic therapies.     

Use of fibrin sealant for prosthetic mesh fixation in laparoscopic extraperitoneal inguinal hernia repair

OBJECTIVE: To evaluate the efficacy of mesh fixation with fibrin sealant (FS) in laparoscopic preperitoneal inguinal hernia repair and to compare it with stapled fixation. SUMMARY BACKGROUND DATA: Laparoscopic hernia repair involves the fixation of the prosthetic mesh in the preperitoneal space with staples to avoid displacement leading to recurrence. The use of staples is associated with a small but significant number of complications, mainly nerve injury and hematomas. FS (Tisseel) is a biodegradable adhesive obtained by a combination of human-derived fibrinogen and thrombin, duplicating the last step of the coagulation cascade. It can be used as an alternative method of fixation. METHODS: A prosthetic mesh was placed laparoscopically into the preperitoneal space in both groins in 25 female pigs and fixed with either FS or staples or left without fixation. The method of fixation was chosen by randomization. The pigs were killed after 12 days to assess early graft incorporation. The following outcome measures were evaluated: macroscopic findings, including graft alignment and motion, tensile strength between the grafts and surrounding tissues, and histologic findings (fibrous reaction and inflammatory response). RESULTS: The procedures were completed laparoscopically in 49 sites. Eighteen grafts were fixed with FS and 16 with staples; 15 were not fixed. There was no significant difference in graft motion between the FS and stapled groups, but the nonfixed mesh had significantly more graft motion than in either of the fixed groups. There was no significant difference in median tensile strength between the FS and stapled groups. The tensile strength in the nonfixed group was significantly lower than the other two groups. FS triggered a significantly stronger fibrous reaction and inflammatory response than in the stapled and control groups. No infection related to method of fixation was observed in any group. CONCLUSION: An adequate mesh fixation in the extraperitoneal inguinal area can be accomplished using FS. This method is mechanically equivalent to the fixation achieved by staples and superior to nonfixed grafts. Biologic soft fixation with FS will prevent early graft migration and will avoid the complications associated with staple use.     

Ageing and the mismatch repair system

Age-related accumulation of mutations has been extensively documented, and it has been proposed as one of the prominent causes of malignancies in old age. The present review is focused on the particular case of DNA mismatch repair system (MMR), that has drawn increased attention for its possible relevance to malignancy. We also report on our own observations on an age-associated genomic instability that develops with age in the MMR system. Our study was performed on DNA samples that were prepared from peripheral blood cells, obtained at a 10-year interval from young and old human subjects. The two DNA samples from each individual were examined comparatively. The older individuals showed a significantly higher rate of microsatellite instability (MSI) in several loci examined, whereas no difference was found between the paired samples of any of the young subjects. We suggest that this increase in MSI with age may indicate an overall genomic instability in the elderly.     

Investigation of loss of heterozygosity at specific loci on chromosomes 3p, 6q, 11p, 17p and 17q in ovarian cancer

In an attempt to further define the genetic events in the pathogenesis and progression of human ovarian cancer, an analysis of constitutional and ovarian carcinoma DNA samples revealed loss of heterozygosity (LOH) at specific loci on chromosomes 3p (38%), 6q (23%), 11p (33%), 17p (82%) and 17q (62%). In contrast, LOH was not observed in benign or borderline tumors. No significant association could be demonstrated between LOH at the loci studied and tumor stage, histologic subtype, grade or patient outcome. Further analyses of large tumor panels are now required to determine the relationship between LOH at these loci and the clinicopathological behavior of ovarian tumors.     

Current management of epithelial ovarian carcinoma: a review

Epithelial carcinoma of the ovary is the most lethal of gynaecological malignancies and it affects about one in 70 women in developed countries. Over 75% of women with the disease have tumour spread beyond the pelvis at the time of diagnosis, and their treatment requires the appropriate use of surgery and chemotherapy. The strategies used in the treatment of ovarian cancer are constantly evolving. An overview of current treatment regimens and their evolution is provided, with particular emphasis on the interdependence of surgery and chemotherapy in the optimal management of the disease.