Mycophenolate mofetil without antibody induction in cadaver vs. living donor pediatric renal transplantation

Mycophenolate mofetil (MMF) is a new immunosuppressive agent that blocks de novo purine synthesis in T and B lymphocytes via a potent selective inhibition of inosine monophosphate dehydrogenase. MMF has been shown to significantly reduce the incidence of acute rejection in both adult and pediatric renal transplantation. The impact of MMF on routine antibody induction therapy in pediatric renal transplantation has not been defined. Remarkably, a recent North American Pediatric Transplant Cooperative Study concluded that T-cell antibody induction therapy was deleterious for patients who received MMF. Our study examines the use of MMF in an evolving immunosuppressive strategy to avoid antibody induction in both living (LD) and cadaver (CAD) donor pediatric renal transplantation. We retrospectively analyzed the records of 43 pediatric renal transplants that received MMF-based triple therapy without antibody induction therapy between November 1996 and April 2000. We compared CAD (n = 17) with LD (n = 26). The two groups were similar demographically except that CAD had significantly younger donors than LD, 26.1 +/- 13.7 vs. 36.2 +/- 9.2 yr (p = 0.006). All the patients received MMF at 600 mg/m2/b.i.d. (maximum dose of 2 g/d) and prednisone with cyclosporine (86%) or tacrolimus (14%). Mean follow-up was >36 months for each group. Acute rejection rate at 6 months was 11.8% (CAD) vs. 15.4% (LD) (p = 0.999) and at 1 yr was 23.5% (CAD) vs. 26.9% (LD) (p = 0.999). Mean estimated glomerular filtration rate (ml/min/1.73 m2) at 6 months was 73.3 +/- 15.3 (CAD) vs. 87.6 +/- 24.2 (LD) (p = 0.068). Patient survival at 1, 2, and 3 yr was 100, 100, and 100% for CAD vs. 100, 96, and 96% for LD, respectively. Graft survival at 1, 2, and 3 yr was 100, 100, and 94% for CAD vs. 96, 88, and 71% for LD, respectively. Graft loss in CAD was because of chronic rejection (n = 2) while in LD it was because of non-compliance (n = 6), post-transplant lymphoproliferative disorder (n = 1), and sepsis (n = 1). In conclusion, MMF without antibody induction in both CAD and LD pediatric renal transplantation provides statistically similar and effective prophylaxis against acute rejection at 6 months and 1 yr post-transplant. The short-term patient and graft survival rates are excellent, however, non-compliance remains a serious challenge to long-term graft survival. Additional controlled studies are needed to define the role of MMF without antibody induction therapy in pediatric renal transplantation.     

Parasympathetic extrinsic reflex: role in defecation mechanism

The rectum has an intrinsic nervous mechanism represented by the enteric nervous plexus (ENP) and an extrinsic one mediated by the parasympathetic nerves. Rectal distension evokes the rectoanal inhibitory reflex, which acts through the ENP and is considered the main mechanism responsible for defecation. However, the role of the parasympathetic innervation compared to the role of the intrinsic mechanism of the defecation act has so far not been sufficiently addressed in the literature. The current study investigated this point. Twelve dogs were anesthetized. The anal and rectal pressures were recorded during rectal balloon distension with normal saline in 10 ml increments until the balloon was expelled to the exterior. The test was repeated after ENP block with a (phentolamine) and b (propranolol) adrenoceptor blocking agents and then after rectal denervation by bilateral pelvic ganglionectomy. The rectal balloon was expelled to the exterior at rectal balloon distension with 30 to 40 ml. After separate administration of phentolamine and propranolol, it was dispelled at a distending volume of 50 to 60 ml, and after rectal denervation at a volume of 80 to 90 ml. The results were reproducible. The balloon expulsion test suggests that the intrinsic defecation reflex is weaker than the extrinsic one for inducing defecation, although the two reflexes appear to be complementary. The difference between them in inducing defecation might be significant to our understanding the defecation act in the neurogenic rectum, a point that needs further study.     

Vaginal response to clitoral stimulation: identification of the clitorovaginal reflex

OBJECTIVE: To investigate the hypothesis that glans clitoris (GC) penile buffeting effects contraction of the vaginal musculature and seems to increase arousal of the penis during coitus. STUDY DESIGN: The response of the vaginal wall to GC electrical and mechanical stimulation was recorded in 26 healthy women (aged 36.8 +/- 6.7 years). The test was repeated after individual anesthetization of the GC and vagina using lidocaine gel and after application of bland gel instead of lidocaine. RESULTS: The 2 vaginal electrodes recorded, at rest, slow waves followed or superimposed by action potentials. Wave parameters were similar from the 2 electrodes. Electrical or mechanical GC stimulation effected a significant increase in vaginal electromyographic (EMG) activity and pressure (p < 0.01). GC stimulation, while the vagina or GC had been separately anesthetized, produced no significant change, but there was a response following application of bland gel. CONCLUSION: GC stimulation effected an increase in vaginal EMG activity and pressure and presumably indicated vaginal wall contraction. This action seems to be a reflex and is mediated through the clitorovaginal excitatory reflex. Vaginal wall contraction during coitus appears to effect penile arousal and, consequently, female sexual stimulation.     

Interstitial cells of cajal in patients with constipation due to total colonic inertia.

Colonic wall contains interstitial cells of Cajal. In view of studies demonstrating that Cajal cells generate electric waves which are presumably responsible for colonic motor activity, and that these waves are absent in total colonic inertia, we investigated the hypothesis that colonic Cajal cells might be disordered in patients with total colonic inertia. The study comprised 28 patients (age 41.6 +/- 8.2 SD years, 19 women, 9 men) with total colonic inertia in whom total colectomy was performed. Colonic specimens obtained from normal segments of the excised colon of 24 cancer patients acted as controls. Specimens were subjected to c-kit immunohistochemistry. Controls for antisera specificity consisted of tissue incubated with normal rabbit serum that had been substituted for the primary antiserum. C-kit-positive branched Cajal-like cells were detected in the musculature of the normal colonic segments. They were distinguishable from the C-kit-negative smooth muscle cells and the C-kit-positive but unbranched mast cells. No Cajal cells were detected in colon of total colonic inertia patients. The absence of Cajal cells in patients with total colonic inertia can be assumed to explain the absence of electric waves and motile activity previously reported in these patients. Further studies are needed to investigate the cause of Cajal-cell absence.     

Uterine effect of cervical buffeting: role of the cervicouterine reflex in coitus

OBJECTIVE: To investigate the hypothesis that cervical buffeting during coitus effects reflex relaxation and dilatation of the corpus uteri (CorU) smooth muscle; that mechanism acts to suck the ejected semen into the CorU. STUDY DESIGN: The CorU response to electrical and mechanical stimulation of the CU was recorded in 22 healthy women (mean age, 38.2 +/- 7.6 SD years). Cervical electrical stimulation was effected by an electromyographic needle electrode and mechanical stimulation by pencil electrode. The test was repeated after individual anesthetization of the CU and CorU and after normal saline injection. RESULTS: Slow waves, superimposed or followed by action potentials, were recorded at rest from the CorU electrode. Electrical or mechanical stimulation of the CU effected a significant reduction of the electric wave parameters and pressure in the CorU; this response was reproducible. Separate stimulation of the anesthetized CU or CorU did not evoke the response, while saline infiltration did. CONCLUSION: CU stimulation resulted in diminished CorU electrical activity and pressure; that presumably indicates uterine wall relaxation. Repeated CU buffeting apparently leads to an intermittent uterine pressure decline, with resulting semen siphonage from the vagina to the uterus. Diminished CorU electrical activity and pressure on cervical stimulation or buffeting might be mediated through the cervicouterine inhibitory reflex. This reflex seems to be evoked by penile thrusting during coitus and may prove of diagnostic significance in sexual disorders.     

Specialized pacemaking cells in the human Fallopian tube

It is postulated that the propagated electric activity of the gut is generated by the interstitial cells of Cajal (ICCs). We investigated the hypothesis of the presence of ICCs in the Fallopian tube (FT) as initiators of the tubal electric activity. Specimens from various parts of the FT were obtained from 21 female cadavers (mean age 38.2 +/-10.9 years) from the PostMortem Department of the Cairo University, Faculty of Medicine. Fixed sections were prepared and stained for c-kit. Controls for antisera specificity consisted of tissue incubated with normal rabbit serum substituted for the primary antiserum. Dendritic, c-kit-positive, ICC-like cells were detected in the tubal musculature of the studied specimens. They were distinguishable from the c-kit-positive nonbranching mast cells and from the c-kit-negative smooth muscle cells (SMC). Immunoreactivity was absent in the negative controls. We have for the first time identified cells in the FT with morphologic and immunologic phenotypes similar to the ICCs of the gut. These cells may be responsible for initiating the slow waves (SWs) recorded from the SMC of the FT. This is a preliminary study, and further studies are needed to investigate the functional role of these cells.     

The effect of terrain on foot pressures during walking

BACKGROUND: High plantar pressures are associated with the development of foot ulcers in people with diabetic neuropathy. The effect of terrain on plantar pressures during walking has not been fully explored. METHODS: Twenty 23- to 40-year-old subjects with no known musculoskeletal pathology walked across three terrains: padded carpet (R), grass (G), and concrete (C) while wearing Novel Pedar (Novel Electronics Inc. GMBH, Munich, Germany) insoles with and without shoes. Pressures were collected at 50 Hz. The sole of the foot was divided into: heel (H), lateral midfoot (LM), medial midfoot (MM), big toe and first metatarsal head (BT), and lateral toes and metatarsal heads (LT). Repeated measures ANOVA identified differences in pressures, forces, and contact areas across terrains. Post hoc Bonferroni adjustments were used to accept an overall alpha level of 0.05. RESULTS: Peak pressure (PP), maximal mean pressure (MMP) and pressure time integral (PTI) were significantly higher (p < 0.01) when walking barefoot on concrete than on grass or carpet for all foot regions except MM and LM. The percent increase in the three pressure variables ranged from 21% to 43%. Grass and carpet PP, MMP, and PTI were similar for the BT and LT. Wearing shoes significantly increased contact area and decreased all pressure variables on all three terrains. CONCLUSION: Walking barefoot, especially on concrete was associated with higher plantar pressure variables. Wearing shoes eliminated terrain differences in pressure except under the lesser toes. Persons with insensate feet should avoid walking barefoot on hard surfaces to avoid excessive plantar pressures. Wearing shoes and covering hard floors with nonslip, padded rugs may decrease plantar pressures and the risk of ulceration.     

Inguinal herniorrhaphy under monitored anesthesia care with ilioinguinal-iliohypogastric block: the impact of adding clonidine to ropivacaine

There is no information concerning the association of ropivacaine and clonidine for ilioinguinal-iliohypogastric block. In this prospective, double-blind study, we randomly assigned 40 adult patients scheduled for inguinal herniorrhaphy under monitored anesthesia care to receive either 225 mg ropivacaine (7.5 mg/mL) alone (control group) or combined with 75 mug clonidine (clonidine group) for preoperative ilioinguinal-iliohypogastric block. After completion of surgery, patients were transferred to the postanesthesia care unit and were asked to stand up and walk around at the second postoperative hour. After leaving the postanesthesia care unit, patients could take oral propacetamol (500 mg) and codeine (30 mg) on request. Pain intensity was assessed with a 100 mm visual analog scale. Time to first request of supplemental analgesics (median [95% confidence interval]) was 10 h (7.1-14.5 h) and 9 h (6.4->24 h) respectively in the clonidine and control groups (P = 0.83). Pain at rest did not differ between groups whereas pain at motion was reduced on the third postoperative day in the clonidine group. More patients who received clonidine experienced orthostatic hypotension upon standing up within the first postoperative hours (6 of 20 versus 1 of 20 in the control group; P < 0.05). In conclusion, the benefit of adding clonidine 75 mug to ropivacaine for ilioinguinal-iliohypogastric block for motion pain on the third postoperative day must be balanced with an increasing risk of orthostatic hypotension in the immediate postoperative period.     

On the pathogenesis of gastroesophageal reflux: the concept of gastroesophageal dyssynergia

OBJECTIVES: The cause of lower esophageal sphincter incompetence in gastroesophageal reflux disease is not clearly understood. We investigated the hypothesis that the esophagogastric junction incompetence results from failure of the gastric distention to produce the lower esophageal sphincter and crural diaphragm contraction caused by a disordered reflex action. METHODS: The study was performed in 19 subjects (mean age, 42.6 +/- 7.2 years; 11 men and 8 women) who had reflux esophagitis and hiatus hernia and were scheduled for a fundoplication operation. Eight control volunteers (mean age, 41.8 +/- 6.9; 5 men and 3 women) who had huge supraumbilical ventral hernia but no reflux esophagitis or hiatus hernia were studied during operative hernia repair. The electromyographic activity and pressure response of the lower esophageal sphincter and crural diaphragm to separate esophageal and gastric distention were recorded. RESULTS: In the control subjects (volunteers) esophageal distention caused diminished electromyographic activity of the crural diaphragm and lower esophageal sphincter with decreased esophagogastric junction pressure, whereas gastric distention increased the electromyographic activity of the crural diaphragm and lower esophageal sphincter with increased esophagogastric junction pressure. In the patients the crural diaphragm and lower esophageal sphincter showed diminished resting electromyographic activity, with either no response or a paradoxical response to esophageal or gastric distention. CONCLUSION: The current study has demonstrated that the lower esophageal sphincter and crural diaphragm in patients with gastroesophageal reflux disease exhibited a diminished resting electric activity and either did not respond or reacted paradoxically to esophageal and gastric distention, constituting what we call esophagosphincteric and gastroesophageal paradox or dyssynergia. The cause of lower esophageal sphincter and crural diaphragm dysfunction is not known; a neurogenic cause was proposed. Further studies are required to investigate this point.