Post-operative benefits of Tisseel(®)/Tissucol (®) for mesh fixation in patients undergoing Lichtenstein inguinal hernia repair: secondary results from the TIMELI trial.

PURPOSE: The Tisseel/Tissucol for mesh fixation in Lichtenstein hernia repair (TIMELI) study showed that mesh fixation with human fibrin sealant during inguinal hernia repair significantly reduced moderate-severe complications of pain 12 months post-operatively compared with sutures. Further analyses may assist surgeons by investigating predictors of post-surgical complications and identifying patients that may benefit from Tisseel/Tissucol intervention. METHODS: Univariate and multivariate analyses identified risk factors for combined pain, numbness and groin discomfort (PND) visual analogue scale (VAS) score 12 months post-operatively. Variables tested were: fixation method, age, employment status, physical activity, nerve handling, PND VAS score at pre-operative visit and 1 week post-operatively. The effect of fixation technique on separate PND outcomes 12 months post-surgery was also assessed. Analyses included the intention-to-treat (ITT) population and a subpopulation with pre-operative PND VAS > 30 mm. RESULTS: 316 patients were included in the ITT, with 130 patients in the subpopulation with pre-operative PND VAS > 30. Multivariate analysis identified mesh fixation with sutures, worsening pre-operative PND and worsening PND 1 week post-surgery as significant predictors of 12-month PND in the ITT population; mesh fixation with sutures was a significant predictor of 12-month PND in the pre-operative PND VAS > 30 subpopulation (p < 0.05). Mesh fixation with Tisseel/Tissucol resulted in significantly less numbness and a lower intensity of groin discomfort compared with sutures at 12 months; there was no difference in pain between the treatment groups. CONCLUSIONS: Pre-operative discomfort may be an important predictor of post-operative pain, numbness and discomfort. Tisseel/Tissucol may improve long-term morbidity over conventional sutures in these patients.

Penetration of telithromycin (HMR 3647), a new ketolide antimicrobial, into inflammatory blister fluid following oral administration.

The penetration of telithromycin (HMR 3647), a novel ketolide antimicrobial, has been assessed in an open, single-dose study in eight healthy male subjects. Following a single, oral, 600 mg dose the mean ratio of the concentration of telithromycin in blister fluid over plasma was 1.38. Significant blister fluid concentrations were maintained up to 24 h post-dose. These results indicate that telithromycin penetrates well into inflammatory extracellular fluid, achieving high and sustained concentrations in this medium.

Pharmacokinetics of the new ketolide telithromycin (HMR 3647) administered in ascending single and multiple doses.

Telithromycin (HMR 3647) is a novel ketolide antimicrobial with good activity against both common and atypical respiratory pathogens, including many resistant strains. This randomized, three-period crossover study determined the dose proportionality of telithromycin pharmacokinetics after single and multiple dosing in healthy subjects. In each treatment period, subjects received a single oral dose of 400, 800 or 1,600 mg of telithromycin followed 4 days later by the same dose once daily for 7 days. Blood and urine samples were taken throughout the study for determination of pharmacokinetic parameters for telithromycin and RU 76363, its main metabolite. Telithromycin and RU 76363 achieved steady state within 2 to 3 days of once-daily dosing. A slight accumulation of telithromycin was observed after 7 days of therapy, with values of the area under the concentration-time curve from 0 to 24 h approximately 1.5 times higher than those achieved with the single dose. The pharmacokinetics of telithromycin and RU 76363 deviated moderately from dose proportionality. At a dose of 800 mg/day, telithromycin attained mean maximal and trough plasma concentrations of 2.27 and 0. 070 mg/liter respectively. Elimination was biphasic; initial and terminal half-lives were 2.87 and 9.81 h for the 800-mg dose. Study medication was well tolerated, although adverse events tended to be more frequent at the 1,600-mg dose. This study showed that telithromycin was generally well tolerated and suggests that a once-daily 800-mg oral dose of telithromycin maintains an effective concentration in plasma for the treatment of respiratory tract infections involving the key respiratory pathogens.

Total esophagectomy by right anterior thoracotomy and immediate esophageal reconstruction for carcinoma of the esophagus.

In the past 11 months we treated 12 cases of squamous-cell carcinoma of the esophagus with single-stage total esophagectomy via an anterior thoracotomy and esophageal reconstruction. The stomach was utilized as esophageal substitute in nine patients and the left colon in three, in whom stomach was not available. One patient died. The single fistula from the esophagogastric anastomosis closed spontaneously within two weeks. We believe total esophagectomy to be more successful than partial resection in squamous-cell carcinoma of the esophagus. The right anterior approach in the thorax permits two surgical teams to work simultaneously. As the patient is supine throughout the operation, the cervical, thoracic and abdominal approaches can be effectively checked. The operating time is also shortened.