Topical lidocaine does not limit autonomic dysreflexia during anorectal procedures in spinal cord injury: a prospective,double-blind study

BACKGROUND AND AIMS: Autonomic dysreflexia is a common and potentially dangerous response in patients with spinal cord injury at T6 or above. Acute blood pressure elevation may be precipitated by rectosigmoid distention and anal manipulation. Topical anesthetics are widely recommended to minimize the incidence and severity of autonomic dysreflexia, although no scientific evidence supports or refutes this practice. This study tested whether topical lidocaine would prevent or limit anorectal procedure-associated autonomic dysreflexia. PATIENTS AND METHODS: We enrolled patients with chronic, complete spinal cord injury scheduled for anoscopy and/or flexible sigmoidoscopy. In a double-blind fashion they were randomized to receive either 2% lidocaine jelly (n = 18) or nonmedicated lubricant (control; n = 32) just prior to the procedure. We measured blood pressure before, during, and after procedures. RESULTS: Mean maximal systolic blood pressure increased 35 +/- 25 mmHg in the lidocaine group vs. 45 +/- 30 mmHg in the control group (NS). However, there was a significant difference between anoscopic procedures and flexible sigmoidoscopies without anoscopy (49 +/- 29 vs. 25 +/- 20 mmHg). CONCLUSION: Topical lidocaine did not significantly limit or prevent autonomic dysreflexia in susceptible patients. Both anoscopy and flexible sigmoidoscopy caused significant blood pressure elevation. Anoscopy, which involves stretching of the anal sphincters, was a more potent stimulus for autonomic dysreflexia than flexible sigmoidoscopy, which involves gaseous distention of the rectosigmoid. Anal sphincter stretch and rectosigmoid distention, rather than a mucosal stimulus, are likely nociceptive triggers for procedure-associated autonomic dysreflexia.     

Treatment of occluded central venous catheters with alteplase: results in 1,064 patients

PURPOSE: Thrombosis of central venous access devices (CVADs) is a relatively frequent complication. Alteplase (tissue plasminogen activator) has been used to salvage dysfunctional devices. The purpose of this study was to analyze the safety and efficacy of alteplase after administration of a maximum of two 2-mg/2-mL doses to thrombosed CVADs. MATERIALS AND METHODS: A combined analysis was performed of two pivotal prospective phase-III clinical trials (Cardiovascular thrombolytic to Open Occluded Lines [COOL] Trials) involving 80 centers enrolling patients from November 1999 through December 2000. Patients 2 years of age or older (with body weights >10 kg) with dysfunctional nondialysis CVADs were eligible, including those with peripherally inserted central catheters, apheresis catheters, and ports. Alteplase (2 mg/2 mL) was instilled into the lumen of the central venous catheter and allowed to dwell for as long as 120 minutes. For patients with body weights of 10-30 kg, 110% of the internal lumen volume of alteplase (2 mg/2 mL) was administered. If the device was still occluded after a maximum of 120 minutes, a second alteplase dose was given and allowed to dwell for as long as 120 minutes. The primary efficacy endpoint was designated as restored function after a maximum of two doses. The primary safety endpoint was intracranial hemorrhage (ICH) within 5 days. RESULTS: A total of 1,064 patients (465 men, 599 women; mean age, 50.7 y; range, 2-91 y) with dysfunctional catheters were treated. After alteplase administration, function was restored in 798 patients (75.0%; 95% CI: 72.3%, 77.6%) after one dose and 905 (85.1%; 95% CI: 82.8%, 87.2%) after two doses. Efficacy rates were similar among catheter types (single-, double-, and triple-lumen catheters, and ports). Serious adverse events monitored within 30 days of treatment included ICH (0.0%), embolic events (0.0%), gastrointestinal bleeding (0.3%), thrombosis (0.3%), and sepsis (0.4%). One event (fever) was attributed to the study drug. Efficacy was independent of age, sex, body weight, and catheter type. CONCLUSION: A regimen of as many as two 2-mg doses of alteplase is safe and effective for restoring flow to occluded central venous access devices.     

A Study of Changes in Uterine Leucocytes During Early Pregnancy in the Mouse-vole Interspesific Pregnancies

Mouse and vole embryos were allogeneically and xenogeneically transferred into pseudopregnant CD.1 and immunodeficient (seid)female mice,and we investigated the distribution of uterine leucocytes cells in the implantation sites on days 5,6,and 7 of pregnancy. Maerophages were evenly distributed in the endometrium on days 5-7.Neutrophils were rarely seen on days 5-7,but lymphocytes were found throughout the endometrium,often in groups associated with glands or the luminal epithelium.The number of uNK cells increased markedly at the mesometrial uriangle and the outer decidual area in the CD-1 uteri containing vole embryos;by contrast,seid uteri having vole embryos showed almost the same number as those having mouse embryos.Mast cells were present in large numbers at the myometrium,but rarely in the decidua in all types of pregnant uteri.Cells at the myometrium were more numerous in xenogeneic than in allogeneic transfer.Maay mast cells appeared in the inner decidua where xenogeneically transferred vole embryos were dead and aborted.These results suggest the possibility that uterine leucocytes mediate various immunological events in the mouse-vole interspesific pregnancies.     

C-peptide, IGF-I, sex-steroid hormones and adiposity: a cross-sectional study in healthy women within the European Prospective Investigation into Cancer and Nutrition (EPIC)

Objectives: The risk of some cancers is positively associated with body weight, which may influence circulating levels of sex-steroid hormones, insulin and IGF-I. Interrelationships between these hormones and the associations with adiposity were evaluated in healthy women participating in the European Prospective Investigation into Cancer and Nutrition (EPIC).Methods: A cross-sectional analysis was performed on anthropometric and hormonal data from 743 pre- and 1217 postmenopausal women. Body mass index (BMI) and waist circumference were used as indicators of adiposity. C-peptide, Insulin Growth Factor (IGF)-I, Insulin Growth Factor binding protein (IGFBP)-3, androgens, estrogens and sex hormone binding globulin (SHBG) were measured by immunoassays; free sex steroid concentrations were calculated.Results: BMI and waist circumference were positively correlated with estrogens in postmenopausal women and with C-peptide, free testosterone and inversely with SHBG in all women. C-peptide and IGF-I were inversely correlated with SHBG, and positively with free sex steroids in postmenopausal women. IGF-I was positively associated with postmenopausal estrogens and androgen concentrations in all women.Conclusions: Sex-steroid concentrations appear to be regulated along several axes. Adiposity correlated directly with estrogens in postmenopausal women and with insulin, resulting in lower SHBG and increased levels of free sex steroids. Independent of adiposity and insulin, IGF-I was associated with decreased SHBG levels, and increased concentrations of androgens and postmenopausal estrogens.     

Lidocaine Anal Block Limits Autonomic Dysreflexia During Anorectal Procedures in Spinal Cord Injury: A Randomized, Double-Blind, Placebo-Controlled Trial

PURPOSE Autonomic dysreflexia is a common and potentially dangerous hypertensive response to stimulation below the level of injury that occurs in patients with spinal cord injury at T6 or above. Rectosigmoid distention and anal manipulation are among the stimuli that may precipitate autonomic dysreflexia. Instillation of topical local anesthetic into the rectum is the recommended prophylaxis against autonomic dysreflexia of anorectal origin. However, a previous randomized, double-blind, placebo-controlled trial showed that topical lidocaine in the rectum does not blunt the autonomic dysreflexia response to anorectal procedures. The purpose of this study was to determine whether lidocaine anal sphincter block would be effective in limiting anorectal procedure-associated autonomic dysreflexia.METHODS We enrolled patients with chronic, complete spinal cord injury above T6, who were having anorectal procedures (flexible sigmoidoscopy and/or anoscopic hemorrhoid ligation). In a double-blind fashion, patients were randomized for intersphincteric anal block with 1 percent lidocaine or normal saline (placebo) before the procedure. Blood pressure was measured before, during, and after the block and procedure.RESULTS Thirteen patients received lidocaine, and 13 received placebo. The groups were similar in age, level of injury, duration of spinal cord injury, type of procedure, and procedure duration. The mean maximal systolic blood pressure increase for the lidocaine group was 22 ± 14 mmHg, significantly lower than the placebo group’s 47 ± 31 mmHg (P = 0.01).CONCLUSIONS Lidocaine anal block significantly limits the autonomic dysreflexia response in susceptible patients undergoing anorectal procedures.     

Developmental pathways in musculoskeletal neoplasia: involvement of the Indian Hedgehog-parathyroid hormone-related protein pathway

There are many crucial genes and signaling pathways in the proper development of an organism. Pathologies may arise from a deregulation of these pathways. The Indian Hedgehog-PTH-related protein (Ihh-PTHrP) pathway is vital in the proper development of endochondral bones, such as the long bones. The Ihh-PTHrP pathway regulates the rate at which chondrocytes within the growth plate proliferate and differentiate. Thus, this pathway allows for the longitudinal growth of bones. However, a disruption in this pathway may lead to enchondromas and osteochondromas, which are both childhood cartilaginous neoplasms. Recently, our lab identified a mutant receptor for PTHrP in enchondroma samples. Mice expressing this mutant receptor and mice with increased Ihh activity develop conditions similar to human enchondromatosis. Linkage analysis shows an association between EXT genes and osteochondromas in hereditary multiple exostoses syndrome. Studies in Drosophila and mice suggest EXT gene products play a role in the diffusion of hedgehog proteins. A mutation in EXT genes may result in an abnormal Ihh diffusion pattern leading to an osteochondroma. There are agents that inhibit Hedgehog signaling. These agents may be useful in the treatment of enchondromas and osteochondromas. This review will discuss the discovery of the Ihh-PTHrP pathway and its involvement in neoplasia, and will suggest possible novel therapeutic agents in the treatment of these cartilaginous neoplasms.     

Calculus of variations approach for state and parameter estimation in switched 1D hyperbolic PDEs

This paper proposes the use of calculus of variations to solve the problem of state and parameter estimation for a class of switched 1‐dimensional hyperbolic partial differential equations coupled with an ordinary differential equation. The term “switched” here refers to a system changing its characteristics according to a switching rule, which may depend on time, parameters of the system, and/or state of the system. The estimation method is based on a smooth approximation of the system dynamics and the use of variational calculus on an augmented Lagrangian cost functional to get the sensitivity with respect to the initial state and some (possibly distributed) parameters of the system. Those sensitivities or variations, together with related adjoint systems, are used as inputs for an optimization algorithm to identify the values of the variables to be estimated. Two examples are provided to demonstrate the effectiveness of the proposed method. The first one is concerned with a switched overland flow model, developed from Saint‐Venant equations and Green‐Ampt law; the second example deals with a switched free traffic flow model based on the Lighthill‐Whitham‐Richards representation, modified by the presence of a relief route.