Experimental model of pudendal nerve innervation of a skeletal muscle neosphincter for faecal incontinence

BACKGROUND: Faecal incontinence is difficult to treat. A variety of reconstructive procedures has been described, but none is entirely satisfactory. This study evaluated the feasibility of cross-innervating a skeletal muscle neosphincter with the pudendal nerve in a canine model. METHODS: Thirty dogs were rendered surgically incontinent (the pudendal nerve was cut and the external sphincter was partially excised). A neosphincter was then created using the semitendinosus muscle. In ten dogs pudendal nerve transposition (PNT) to the nerve to the semitendinosus muscle was performed. Ten dogs were given a dynamic neosphincter by inserting a pulse generator at 6 weeks. The remaining ten dogs served as controls with passive semitendinosus wraps. Anal manometry was performed before operation and monthly for 5 months. Muscle biopsies, performed at the initial operation and at 5 months, were stained for slow- and fast-twitch fibres, and were examined histologically. RESULTS: At 1 month, mean sphincter function was 32 per cent of the preoperative value in the control animals, 34 per cent in the PNT group and 27 per cent in the electrostimulation group; all dogs were incontinent. At 5 months the mean recovery of sphincter function was 42 per cent of the preoperative value in controls, 100 per cent in dogs with PNT (P < 0.001) and 63 per cent in dogs having electrostimulation (stimulator on) (P = 0.02). Six dogs with PNT had squeeze pressures equal to or greater than preoperative levels. At 5 months the ratio of slow to fast fibres was significantly greater in all dogs (control P = 0.01, PNT P < 0.005, electrostimulation P < 0.001). CONCLUSION: Use of the pudendal nerve to innervate a canine skeletal muscle anal wrap produced a functional anal sphincter that was superior to electrically stimulated and passive wraps.     

Resistance to vasopressin action on the kidney in patients with Cushing's disease

OBJECTIVE: To assess the plasma levels and action of arginine vasopressin (AVP) in patients with Cushing's disease. There are many reports that patients with Addison's disease have increased AVP levels associated with hyponatraemia and hypoosmolality, but none on the dynamics of secretion of this neurohormone during osmolality-based stimulation in patients with chronic hypercortisolism. DESIGN AND SUBJECTS: The plasma AVP concentration and the urinary and plasma osmolality after a 7.5-h water deprivation test (WDT) were evaluated in 13 patients with Cushing's disease and 15 normal (control) individuals. In patients with Cushing's disease we also assessed the urinary osmolality in response to 10 micrograms i.v. desmopressin (DDAVP) administered at the end of the WDT. RESULTS: At the end of the WDT, urinary osmolality was significantly lower in patients with Cushing's disease (511.5 +/- 148.5 mOsm/l) than in the normal subjects (981.1 +/- 107.1 mOsm/l, P < 0.001), whereas plasma osmolality did not differ between the two groups. Consequently, the urine/plasma osmolality ratio (Uosm/Posm) was lower in patients with Cushing's disease than in normal individuals (1.8 +/- 0.5 compared with 3.4 +/- 0.4, P < 0.001). The AVP concentration also was greater (7.3 +/- 3.1 pmol/l) in those with Cushing's disease than in the controls (3.9 +/- 2.3 pmol/l, P < 0.005). After administration of DDAVP to the hypercortisolaemic patients, the urinary osmolality attained (718.0 +/- 200.0 mOsm/l) was still lower than that in the normal group at the end of WDT (P < 0.005). CONCLUSIONS: Patients with Cushing's disease presented higher AVP levels and smaller Uosm/Posm ratios than normal subjects. After DDAVP, the patients with Cushing's disease were unable to concentrate the urine adequately. These data suggest that the kidney shows resistance to the action of both endogenous and exogenous AVP in patients with Cushing's disease.     

Postmortem analysis of bone growth into porous-coated acetabular components

Microradiography, backscattered electron microscopy, and histological analysis were used to conduct a quantitative postmortem study of seven consecutively retrieved anatomical porous replacement acetabular components that had been inserted during total hip arthroplasties. Screws had been used for the initial fixation of six components. The microradiographic analysis of all seven components showed that an average (and standard deviation) of 84 +/- 9 per cent (range, 72 to 93 per cent) of the porous coating was in direct apposition to the periprosthetic bone. The backscattered electron images demonstrated that an average of 12 +/- 6 per cent (range, 4 to 21 per cent) of the space available in the porous coating was occupied by ingrown bone. The amount of bone ingrowth was not significantly different among the three zones delineated by DeLee and Charnley. Uniformity of bone growth into the porous coating suggests that the preferential loading that occurs in the superior region did not differentially affect the bone ingrowth. The present study showed that consistent bone growth into anatomical porous replacement acetabular components can be achieved.     

Health On the Net automated database of health and medical information

With the number of World Wide Web sites growing every day, the problem is not just to find information, but to locate the right piece of information. Current World Wide Web search engines have not resolved this problem as they most often return a long list of documents. The search result is then unusable because of the large number of answers from different domains and topics. Only complex queries may, in a given situation, produce a limited number of potentially relevant documents. To make searches more efficient and usable by common users, we now need intelligent and specialised search engines on the Net [1,2]. Health On the Net Foundation and the Molecular Imaging and Bioinformatics Laboratory at Geneva University Hospital have developed Multi-Agent Retrieval Vagabond on Information Networks (MARVIN), a robot that searches sites and documents specifically related to a given specialised field. One such robot has already been implemented and used for the medical and the 2D electrophoresis domains. Health On the Net Foundation has implemented the corresponding search engines, MedHunt (http://www.hon.ch/cgi-bin/find) for the medical field and 2DHunt (http://www.hon.ch/cgi-bin/2DHunt/find) for the 2D electrophoresis field.     

Pharmacokinetics of rocuronium during the three stages of liver transplantation

BACKGROUND: Little is known about the influence of liver transplantation on the pharmacokinetics of most anesthetic drugs. The authors determined the pharmacokinetics of rocuronium during liver transplantation and examined whether variability in pharmacokinetics could explain variability in recovery of neuromuscular function. METHODS: Twenty patients undergoing liver transplantation were given rocuronium, 600 microg/kg, after induction of anesthesia and again after perfusion of the transplanted liver. Plasma was sampled to determine rocuronium concentrations. Pharmacokinetic models were fit to rocuronium concentrations versus time data using a mixed-effects population approach. Various models permitted changes in clearance (Cl) or central compartment volume to account for changes in hepatic function and circulatory status during the paleohepatic, anhepatic, and neohepatic periods. Time to initial recovery of four twitches of the orbicularis oculi was determined. RESULTS: During the paleohepatic and anhepatic periods, the typical value of Cl was 2.47 ml x kg(-1) x min(-1) and was not influenced by the magnitude of preexisting liver disease (as evidenced by prothrombin time, bilirubin, serum albumin, alanine transaminase [ALT], and aspartate transaminase [AST]). During the neohepatic period, the typical value of Cl varied as a function of the duration of warm ischemia of the hepatic allograft and was 2.72 ml x kg(-1) x min(-1) for a patient with an average 60-min period of warm ischemia; time to neuromuscular recovery varied as a function of Cl. CONCLUSIONS: Despite prolonged hypothermic ischemia, the newly transplanted liver eliminates rocuronium as well as the diseased native liver (and comparably with historical control values). However, some patients had decreased rocuronium Cl during the neohepatic period, apparently a result of prolonged graft warm ischemia. The authors' finding of preservation of hepatic drug elimination in the hepatic allograft is consistent with limited data for other drugs evaluated during anesthesia.     

R-phenylisopropyladenosine attenuates noise-induced hearing loss in the chinchilla

Reactive oxygen species, which are cytotoxic to living tissues, are thought to be partly responsible for noise-induced hearing loss. In this study R-phenylisopropyladenosine (R-PIA), a stable non-hydrolyzable adenosine analogue which has been found effective in upregulating antioxidant enzyme activity levels, was topologically applied to the round window of the right ears of chinchillas. Physiological saline was applied to the round window of the left ears (control). The animals were then exposed to a 4 kHz octave band noise at 105 dB SPL for 4 h. Inferior colliculus evoked potential thresholds and distortion product otoacoustic emissions (DPOAE) were measured and hair cell damage was documented. The mean threshold shifts immediately after the noise exposure were 70-90 dB at frequencies between 2 and 16 kHz. There were no significant differences in threshold shifts at this point between the R-PIA-treated and control ears. By 4 days after noise exposure, however, the R-PIA-treated ears showed 20-30 dB more recovery than saline-treated ears at frequencies between 4 and 16 kHz. More importantly, threshold measurements made 20 days after noise exposure showed 10-15 dB less permanent threshold shifts in R-PIA-treated ears. The amplitudes of DPOAE also recovered to a greater extent and outer hair cell losses were less severe in the R-PIA-treated ears. The results suggest that administration of R-PIA facilitates the recovery process of the outer hair cell after noise exposure.     

Anti-inflammatory action of dapsone: inhibition of neutrophil adherence is associated with inhibition of chemoattractant-induced signal transduction

Dapsone has clinical utility as an anti-inflammatory agent but the mechanism of this action remains unknown. We have previously reported that dapsone inhibits beta2 integrin (CD11b/CD18)-mediated adherence of human neutrophils in vitro and now describe studies designed to discover how dapsone-mediated inhibition of this neutrophil function occurs. Results indicate that dapsone interferes with the activation or function of the G-protein (Gi type) that initiates the signal transduction cascade common to chemotactic stimuli. They also show that dapsone-mediated suppression of this pathway inhibits the generation of second messengers essential to the activation of beta2 integrin molecules, as well as respiratory and secretory functions of neutrophils exposed to chemoattractants. We propose that the inhibition of chemoattractant-induced signal transduction by dapsone suppresses neutrophil recruitment and local production of toxic respiratory and secretory products in the affected skin of dermatitis herpetiformis and other neutrophilic dermatoses.     

Carbohydrate-deficient transferrin and alcohol dependency: variation in response to alcohol intake among different groups of patients

1. The effects of rilmakalim, a potassium channel opener, were studied on rabbit cardiac Purkinje, ventricular muscle and atrial fibers, with the use of conventional microelectrode techniques. 2. Rilmakalim (0.24-7.2 microM) shortened, in a concentration-dependent manner, the action potential duration (APD) in Purkinje and ventricular muscle without affecting other parameters of the action potential. Pinacidil (30-300 microM) also decreased the APD of Purkinje fibers. 3. Rilmakalim (2.4 microM) and cromakalim (100 microM) hyperpolarized and abolished abnormal automaticity of cardiac Purkinje fibers pretreated with barium (0.2-0.3 mM). Glibenclamide (5 microM) blocked the hyperpolarizing effect. 4. Stable early afterdepolarizations induced in Purkinje fibers by berberine (100 microM) were reversibly blocked by rilmakalim (2.4 microM), which also suppressed late afterdepolarizations induced in Purkinje fibers treated with ouabain (0.3-0.5 microM). 5. The rate of spontaneous discharges of the rabbit sinoatrial node was not affected by rilmakalim (7.2 microM) or by pinacidil (100 microM). Both agents were also unable to affect the APD of atrial muscle fibers. 6. In cardiac Purkinje fibers, tetraethylammonium (TEA; 20 mM) significantly reduced the effects of rilmakalim (2. 4 microM) on the APD. However, neither TEA nor glibenclamide (100 microM) reduced the shortening of the APD induced by dinitrophenol (30 microM) or by salicylate (1 mM).