Biomechanical strength of two laparoscopic herniorrhaphy techniques in a cadaveric diaphragm and in a neoprene model.

OBJECTIVES: Our objectives were to 1) Biomechanically compare two laparoscopic repair techniques; an automated suturing device and a stapling device to conventional open suturing, and 2) Evaluate a model for canine diaphragmatic tissue by comparisons to similar constructs in fresh diaphragms. We hypothesized that automated suturing is biomechanically superior to laparoscopic stapling in dogs, and that neoprene defect repair is an acceptable model for experimental cadaveric diaphragm herniorrhaphy. MATERIALS AND METHODS: Samples of diaphragm pars costalis were prepared with defects mimicking radial muscular tears. Defects were repaired using conventional open suturing, laparoscopic automated suturing, and laparoscopic stapling techniques. Similar defects were created in 6.35 mm thick single-sided neoprene. Samples were biomechanically tested across a biaxial loading machine. Site and mode of failure were noted for all samples. RESULTS: In both the diaphragm muscle and neoprene, the laparoscopic stapling technique was significantly weaker. The neoprene model showed a similar failure load as the diaphragm in both laparoscopic techniques, and a similar stiffness in an open-sutured and stapled diaphragm compared to the neoprene samples. Site and mode of failure in neoprene were similar to cadaveric diaphragmatic tissue, but the overall median load-to-failure was higher for the neoprene. CONCLUSION: The strength of laparoscopically repaired simulated diaphragmatic hernias was higher with an automated suture technique than with a stapling technique. Neoprene defect repair is an acceptable model of canine diaphragmatic herniorrhaphy for biomechanical testing.

Persistent changes in gene expression induced by estrogen and progesterone in the rat mammary gland.

Epidemiological studies have consistently shown that an early full-term pregnancy is protective against breast cancer. We hypothesize that the hormonal milieu that is present during pregnancy results in persistent changes in the pattern of gene expression in the mammary gland, leading to permanent changes in cell fate that determine the subsequent proliferative response of the gland. To investigate this hypothesis, we have used suppression subtractive hybridization to identify genes that are persistently up-regulated in the glands of E- and progesterone (P)-treated Wistar-Furth rats 28 d after steroid hormone treatment compared with age-matched virgins. Using this approach, a number of genes displaying persistent altered expression in response to previous treatment with E and P were identified. Two markers have been characterized in greater detail: RbAp46 and a novel gene that specifies a noncoding RNA (designated G.B7). Both were persistently up-regulated in the lobules of the regressed gland and required previous treatment with both E and P for maximal persistent expression. RbAp46 has been implicated in a number of complexes involving chromatin remodeling, suggesting a mechanism whereby epigenetic factors responsible for persistent changes in gene expression may be related to the determination of cell fate. These results provide the first support at the molecular level for the hypothesis that hormone-induced persistent changes in gene expression are present in the involuted mammary gland.

Effect of hyperoxia on aerobic and anaerobic performances and muscle metabolism during maximal cycling exercise.

The hyperoxia-improved tolerance to maximal aerobic performance was studied in relation to exercising muscle metabolic state. Five students were submitted to four different tests on a cycle ergometer, each being conducted under normoxia and hyperoxia (60% FiO2) on separate days: Test 1, a progressive exercise until exhaustion to determine the maximal work load (Wmax) which was unchanged by hyperoxia; Test 2, an exercise at Wmax (287 +/- 12 W) until exhaustion to determine the performance time (texh) which was elevated by 38% under hyperoxia but exhaustion occurred at the same arterial proton and lactate concentrations; Test 3 (S-Exercise test) consisted of cycling at Wmax for 90% normoxic-texh (4.8 +/- 0.5 min under both O2 conditions) then followed by a 10-s sprint bout during which the total work output (Wtot) was determined; Wtot was elevated by 15% when exercising under hyperoxia; Test 4 (M-Exercise test) consisted also of cycling at Wmax for 4.8 +/- 0.5 min with blood and muscle samples taken at rest and at the end of the exercise to compare the level of different metabolites. During hyperoxic M-Exercise test, glycogen was twice more depleted whereas glucose-6-phosphate and lactate were less accumulated when compared with normoxia. No significant differences were observed for pyruvate, phosphocreatine and muscle/blood lactate ratio between the two conditions. Conversely to normoxia, levels of ATP, ADP and total NADH were maintained at their resting level under 60% FiO2. These data lead us to suppose a higher oxidation rate for pyruvate and NADH in mitochondria, thereby lowering the metabolic acidosis and allowing a better functioning of the glycolytic and contractile processes to delay the time to exhaustion.

Bcl-2 expression delays mammary tumor development in dimethylbenz(a)anthracene-treated transgenic mice.

Bcl-2 is known to have dual antiproliferative and antiapoptotic roles. Overexpression of Bcl-2 in the mammary gland using a whey acidic protein (WAP) promoter-driven Bcl-2 transgene inhibits apoptosis in the mammary gland during pregnancy, lactation, and involution, and also counteracts apoptosis induced by overexpression of a mutant p53 transgene (WAP-p53 172 R-L). WAP-Bcl-2 mice and nontransgenic controls were treated with the carcinogen dimethylbenz(a)anthracene (DMBA). Surprisingly, the nontransgenic mice developed mammary tumors with decreased latency. Tumors arising in WAP-Bcl-2 mice displayed substantially reduced levels of proliferation relative to those seen in nontransgenic mice (P < 0.015), perhaps resulting in the observed increase in tumor latency following carcinogen treatment. This WAP-Bcl-2 mouse tumor model reflects the situation seen in some human breast cancers overexpressing Bcl-2, where expression of Bcl-2 has been shown to correlate with a lower proliferative index in tumors.

Effects of pentoxifylline on circulating cytokine concentrations and hemodynamics in patients with septic shock: results from a double-blind, randomized, placebo-controlled study.

OBJECTIVE: To determine whether a continuous intravenous infusion of pentoxifylline, a methylxanthine derivative, alters the serum cytokine concentrations and/or hemodynamic measurements in patients with septic shock. DESIGN: A prospective, randomized, double-blind, placebo-controlled study. SETTING: Medical intensive care unit in a university hospital. PATIENTS: Sixteen patients with septic shock. INTERVENTIONS: Patients were randomly assigned to receive either pentoxifylline (1 mg/kg) followed by an infusion of 1.5 mg/kg/hr for 24 hrs (n = 8), or placebo (n = 8). MEASUREMENTS AND MAIN RESULTS: Tumor necrosis factor (TNF) and interleukin (IL)-6 concentrations were measured by radioimmunoassays; IL-8 concentrations by an enzyme-linked immunosorbent assay (ELISA) and pentoxifylline concentrations by high-performance liquid chromatography at 0, 3, 6, 12, 18, 24 and 48 hrs after study entry. Pulmonary artery catheter-derived hemodynamics were measured at 0, 0.75, 3, 6, 12, 18, and 24 hrs. In pentoxifylline-treated patients, at 24 hrs, serum concentrations of TNF were significantly lower compared with controls (12 +/- 2 vs. 42 +/- 12 pg/mL, respectively, p = .04). Serum concentrations of IL-6 and IL-8 did not differ between the two treatment groups. There were also no significant differences in any hemodynamic and oxygenation measurements comparing the two treatment groups. Pentoxifylline concentrations were 1,544 +/- 241 ng/mL after the initial dose, and 5,776 +/- 1,781 ng/mL at the end of the 24-hr infusion. Five patients in the pentoxifylline group and four patients in the placebo group died. CONCLUSIONS: Pentoxifylline is able to decrease serum TNF but not IL-6 or IL-8 serum concentrations during septic shock. Pentoxifylline was well tolerated by all eight patients with no adverse effect. Further studies are needed to determine if pentoxifylline's ability to lower circulating TNF concentration without altering hemodynamics will improve outcome in septic shock.

[Study of serum kinetics of vancomycin during the "antibiotic-lock" technique]. / Etude de la cinétique sérique de la vancomycine au décours de la technique de "blocage in situ".

The serum kinetics of vancomycin was studied in two patients aged 3 and 15 years during antibiotic therapy for catheter related sepsis associated with Staphylococcus epidermidis. Vancomycin was administered, simultaneously, by parenteral conventional doses (30 mg/kg/day div q 8 h) and using the antibiotic-lock technique in the infected catheter at a high concentration (150 mg/ml) during one hour, 3 hours after each infusion. Pharmacokinetics data did not show any significant change in the serum kinetics of the antibiotic. The results suggest that delivering a high concentration of vancomycin in the infected catheter using the lock technique may be useful to sterilize infected catheter without toxic effect.

Effects of moderate exercise on the pharmacokinetics of caffeine.

The effect of moderate exercise on the kinetics of caffeine in 12 healthy volunteers-6 heavy coffee drinkers (HD) and 6 light coffee drinkers (LD) has been studied. Kinetics at Rest was measured first (R): the subjects remained at rest for 8 h after a single 250 mg dose of caffeine. One week later, the Exercise Kinetics (E) was measured under the same conditions, but with the subjects performing moderate exercise (30% of VO2 max) during the first hour of the study. Exercise raised the maximal plasma caffeine concentrations (R: 7.28: E: 10.45) and reduced both the half-life (R 3.99 h: E 2.29 h) and the volume of distribution (R 37 l: E 20.9 l). Both during exercise and at rest. HD had a greater half-life elimination and volume of distribution than LD. The results suggest potentiation of the effects of caffeine during exercise and an increase in its distribution due to regular heavy coffee intake.