Smoking delays chondrogenesis in a mouse model of closed tibial fracture healing.

Smoking delays the healing process and increases morbidity associated with many common musculoskeletal disorders, including long bone fracture. In the current study, a murine model of tibial fracture healing was used to test the hypothesis that smoking delays chondrogenesis after fracture. Mice were divided into two groups, a nonsmoking control group and a group exposed to cigarette smoke for 1 month prior to surgical tibial fracture. Mice were euthanized at 7, 14, and 28 days after surgery. The outcomes measured were immunohistochemical staining for type II collagen protein expression as a marker of cartilage matrix and proliferating cell nuclear antigen (PCNA) staining to measure proliferation at the site of injury. Toluidine blue staining and histomorphometry were used to quantify areas of cartilaginous and noncartilaginous fracture callus. Radiographs were analyzed for evidence of remodeling after injury. At day 7 after injury, mice exposed to cigarette smoke had a smaller fracture callus with less cartilage matrix compared to controls. Proliferation was present at high levels in both groups at this time point, but proliferating cells had a more immature morphology in the smoking group. At day 14, chondrogenesis was more active in smokers compared to controls, while a higher percentage of bone was present in the control animals. At day 28, X-ray analysis revealed a larger fracture callus remaining in the smoking animals. Together, these findings show that the chondrogenic phase of tibial fracture healing is delayed by smoking. This study represents, to our knowledge, the first analysis of molecular and cellular mechanisms of healing in a smoking mouse fracture model.     

The urodynamic characteristics of different ileal reservoirs: an experimental study in dogs.

Using adult mongrel dogs, the urodynamic characteristics of three types of ileal reservoirs were studied and compared. Segments of ileum of the same length were utilized to construct simple loop pouches (five dogs), DeKlerk pouches (five dogs) and Kock pouches (five dogs). Six to eight weeks after surgery, urodynamic evaluation was carried out. This included determination of the volume/pressure relationship and measurement of the contractions of the circular and longitudinal muscle fibers. Results indicate that the Kock pouch offers the best features in terms of the volume capacity, the volume/pressure relationship and contractile activity. Detubularization abrogated the muscle tone but it did not affect the phasic contractile activity of the circular muscle layer.     

Dose-response analysis of the behavioral effects of diazepam: II. Psychomotor performance,cognition and mood

The psychomotor, cognitive, and mood effects of orally administered diazepam and placebo were measured over 3.5 h. A total of 120 volunteers were assigned to 12 groups of 10 each, representing the combination of four treatments (placebo, 0.1, 0.2, and 0.3 mg/kg diazepam) and three testing sessions (7 AM, 1 PM, and 7 PM). A variety of cognitive tasks, tapping and postural stability tests, and a mood evaluation scale were used. Psychomotor and cognitive functions showed consistent dose-response effects, while for subjective evaluations, the only effect of dose level was in the duration of sedation. The pattern of impairment of cognitive functions suggests that the drug affects speed rather than accuracy, and it primarily blocks acquisition of new information or skills. Use of repeated testing may therefore be necessary to detect subtle drug effects. Subjects reported no tranquilization, which suggests that the anxiolytic action of the drug cannot be studied in healthy volunteers. There was no circadian influence on the actions of the drug.     

Optimization of uretero-intestinal anastomosis in urinary diversion: an experimental study in dogs

Summary A new antireflux uretero-ileal reimplantation technique suitable for use with bladder substitutes is presented. This procedure entails creation of a serouslined extramural tunnel. Following detubularization of the bowel segment, the adjacent flaps are approximated by continuous 4/0 non-absorbable sutures 1.5 cm from the cut edges. The ureters are laid in the trough thus fashioned. Button-holes are created in the bowel flaps and a mucosa-to-mucosa uretero-ileal anastomosis is carried out. The mucosal edges of the flaps are then approximated by one layer of continuous 4/0 (PGA) suture resulting in closure of this artificial tunnel. The feasibility and functional outcome of this technique were experimentally investigated in 8 dogs. Follow-up was carried out up to 30 weeks. Assessment by intravenous urography and ascending studies showed that the procedure is an efficient method of providing an unobstructed unidirectional flow of urine.     

Numerical chromosomal aberrations in muscle invasive squamous cell and transitional cell cancer of the urinary bladder: an alternative to classic prognostic indicators?

OBJECTIVES: To evaluate the prognostic value of chromosomal aberrations in muscle invasive bladder cancer, because they are of diagnostic and prognostic significance in superficial bladder cancer. METHODS: One hundred ninety patients, who underwent radical cystectomy because of squamous cell carcinoma (SCC) of the urinary bladder in 94 cases and transitional cell carcinoma (TCC) in 96 cases, were studied retrospectively. Numerical aberrations of chromosomes 7, 9, and 17, p53 positivity, histologic stage and grade, histologic tumor type, lymph node status, and the presence of bilharzial eggs were investigated as possible prognostic factors. RESULTS: Univariate analysis demonstrated the prognostic significance of all parameters analyzed, excluding chromosome 9. Multivariate analysis revealed only T category (P = 0.01095266), lymph node involvement (P = 0.00054877), and p53 positivity (P = 0.0316974) to be independent prognostic factors in muscle invasive SCC and TCC. CONCLUSIONS: Although chromosomal aberrations are associated with progression-free survival, they are not independent prognostic factors and give the clinician no additional information on patients with muscle invasive bladder cancer.     

Classical conditioning during nitrous oxide treatment: influence of varying the interstimulus interval

Classical conditioning of the rabbit nictitating membrane response (NMR) was accomplished by presenting a 75-ms tone conditioned stimulus (CS) at intervals of 0, 100, 200, 400, and 800 ms before the presentation of a 100-ms shock unconditioned stimulus. Following every four paired trials (tone followed by shock), the occurrence of conditioned responses (CRs) was tested on every fifth trial in which only tone was presented (test trials). Three doses of nitrous oxide in oxygen (0, 33, and 67%) were used during conditioning. Nitrous oxide produced dose-dependent decrements of learning. Conditioned responding was related to the interstimulus interval (ISI) by a concave-down function. The higher dose of nitrous oxide caused more decrements of learning at several ISIs compared to the other two doses, changing the shape of the curve. Trace conditioning, which was examined in the present study, was more impaired under the influence of nitrous oxide than conditioning in a previous study, which used the standard delay paradigm. Thus, the drug impairs explicit memory more than implicit memory.     

Studies on human memory: The interactions of diazepam,scopolamine, and physostigmine

Seventy volunteers were injected with diazepam (0.3 mg/kg), scopolamine (8 g/kg), or placebo, followed 70 min later by another injection of physostigmine, physostigmine and methscopolamine (in case of diazepam treatment), or placebo. Physostigmine was given in two doses, 16 and 32 g/kg; methscopolamine, 8 and 16 g/kg. Subjects (Ss) were tested in groups of 5 in a double blind procedure with treatments distributed according to a Latin square design. Prior to treatment, Ss heard a series of lists of words, followed by an immediate recall test. Following the first injection, delayed free recall and recognition tests were given. The second drug was then injected, followed by a presentation of another two sets of lists which were tested similarly. Subjective feelings were also evaluated with a rating questionnaire.Diazepam and scopolamine did not affect recall of information which had been learned prior to drug injection. However, both drugs impaired the learning or acquisition of new information. Physostigmine, especially in its high dose, antagonized most of the memory deficits produced by scopolamine while those of diazepam remained. This is a strong indication that scopolamine acts centrally through an anticholinergic mechanism while diazepam may act through a different system.     

Short bowel syndrome: clinical guidelines for nutrition management.

Intestinal failure is a condition in which inadequate digestion or absorption of fluid, electrolytes, and nutrients leads to dehydration or malnutrition. The most common cause of intestinal failure is short bowel syndrome (SBS) defined as <200 cm of functional small intestine. SBS may result from congenital abnormalities or from surgical resection. For the past 3 decades, patients with severe SBS were managed with home parenteral nutrition (HPN). With the emergence of new therapies, the clinician now has multiple options to treat these patients. These include intestinal rehabilitation regimens whereby patients are treated with specialized oral diets, soluble fiber, oral rehydration solutions (ORS), and trophic factors to enhance absorption. There are also a variety of surgical techniques available to preserve intestinal length. Small bowel and multivisceral transplantation has evolved during the last decade to be a valid therapeutic option for those patients who cannot be rehabilitated or who fail HPN. These are interrelated services designed to offer the patient the best therapeutic options to meet their individual needs. This article reviews the principles associated with the nutrition management of this very complex and diverse group of patients.