Combination therapy with ciprofloxacin and third-generation cephalosporin versus third-generation cephalosporin monotherapy in Escherichia coli meningitis in infants: a multicentre propensity score-matched observational study.

OBJECTIVES: Escherichiacoli is the second cause of bacterial meningitis in neonates. Despite the use for 35 years of third-generation cephalosporins (3GCs), high morbidity and mortality rates with E. coli meningitis continue to occur. Because ciprofloxacin has good microbiologic activity against E. coli and good penetration in cerebrospinal fluid and brain, some authors have suggested adding ciprofloxacin to a 3GC regimen. The objective of this study was to assess combining 3GCs with ciprofloxacin versus 3GCs alone in a cohort of infants with E. coli meningitis. METHODS: We included all cases of E. coli meningitis diagnosed in infants <12 months of age that were prospectively collected through the French paediatric meningitis surveillance network between 2001 and 2016. The main outcome was the proportion of short-term neurologic complications with versus without ciprofloxacin. The analysis was conducted retrospectively by multivariable regression and propensity score (PS) analysis. RESULTS: Among the 367 infants enrolled, 201 (54.8%) of 367 had ciprofloxacin and 3GC cotreatment and 166 (45.2%) of 367 only a 3GC. Median age and weight were 15 days (range, 1-318 days) and 3.42 kg (range, 0.66-9.4 kg). A total of 86 (23.4%) of 367 infants presented neurologic complications (seizures, strokes, empyema, abscesses, hydrocephalus, arachnoiditis); 57 received ciprofloxacin cotreatment. Complications were associated with ciprofloxacin cotreatment on multivariable analysis (odds ratio (OR) = 1.9; 95% confidence interval (CI), 1.1-3.4) and PS analysis (OR = 1.9; 95% CI, 1.1-3.3). Mortality rate did not differ with and without ciprofloxacin: 22 (10.9%) of 201 versus 16 (9.6%) of 166 deaths (OR = 0.7; 95% CI, 0.3-1.6; PS analysis). CONCLUSIONS: Ciprofloxacin added to 3GCs at least offers no advantage for neurologic outcome and mortality in infants with E. coli meningitis.

Lack of effect of sacral nerve stimulation for incontinence in patients with systemic sclerosis.

AIM: Systemic sclerosis (SSc) is a multisystem disorder of unknown aetiology leading to the deposition of excessive connective tissue in the skin, blood vessels and internal organs. Gastrointestinal involvement occurs in 90% of cases and the prevalence of faecal incontinence (FI) is 38%. This study comprises the largest case series assessing the efficacy of sacral nerve stimulation (SNS) treatment for incontinence in this patient group. METHOD: A retrospective analysis on prospectively collected data was performed on all SSc patients from our two centres who had undergone SNS for FI. RESULTS: Ten female patients of mean age of 54 (37-72) years had temporary SNS performed. The mean duration of FI was 13 (2-25) years. All had passive FI. Each patient had preprocedure anorectal physiology and endoanal ultrasound examinations documenting internal sphincter atrophy/fragmentation or reduced anal resting pressure. Overall there was no statistically significant difference (P = 0.57) in the total Wexner incontinence scores before (mean 15.1 ± 2.6 SD) and during temporary SNS procedures (mean 13.1 ± 3.6 SD). Two patients with a significant improvement went on to have permanent SNS with only one achieving a favourable outcome at 1 year. CONCLUSION: This study showed that SNS failed to reduce episodes of leakage in nine out of 10 patients with systemic sclerosis affected with incontinence.

Quality of life in major depressive disorder before/after multiple steps of treatment and one-year follow-up.

OBJECTIVE: This study examines the impact of major depressive disorder (MDD) and its treatment on quality of life (QOL). METHOD: From the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial, we analyzed complete data of 2280 adult MDD out-patients at entry/exit of each level of antidepressant treatments and after 12 months of entry to follow-up. QOL was measured using the QOL Enjoyment and Satisfaction Questionnaire (Q-LES-Q). The proportions of patients scoring 'within-normal' QOL (within 10% of Q-LES-Q community norms) and those with 'severely impaired' QOL (>2 SD below Q-LES-Q community norms) were analyzed. RESULTS: Before treatment, no more than 3% of MDD patients experienced 'within-normal' QOL. Following treatment, statistically significant improvements were detected; however, the proportion of patients achieving 'within-normal' QOL did not exceed 30%, with >50% of patients experiencing 'severely impaired' QOL. Although remitted patients had greater improvements compared with non-remitters, 32-60% continued to experience reduced QOL. 12-month follow-up data revealed that the proportion of patients experiencing 'within-normal' QOL show a statistically significant decrease in non-remitters. CONCLUSION: Symptom-focused treatments of MDD may leave a misleading impression that patients have recovered when, in fact, they may be experiencing ongoing QOL deficits. These findings point to the need for investigating specific interventions to ameliorate QOL in MDD.

[Management of severe invasive group A streptococcal infections]. / Prise en charge des infections invasives et graves à streptocoque du groupe A.

The group A streptococcus (GAS) is the 5(th) responsible pathogen of invasive infections in children in France. These particularly severe diseases are dominated in children by soft tissue infection, isolated bacteremia but also osteoarthritis. Other complications are rare in France such as lung infections, necrotizing fasciitis (NF) and streptococcal toxic shock syndrome (STSS). More unusual localizations such as meningitis, neonatal infections, severe ear and throat and gastrointestinal infections and vascular disorders are also described. Based on published series, mortality ranging from 0-8 % of cases, is high but still lower than that observed in adults. Probabilistic antibiotherapy includes a ß-lactam with anti-SGA but also anti-staphylococcal (predominantly methi-S in France) activity such as clavulanic acid- amoxicillin followed by amoxicillin as soon as identification of SGA is performed. The addition of an anti-toxin antibiotic such as clindamycin is recommended particularly in NF or STSS or clinical signs suggestive of toxin production by the SGA (rash, gastrointestinal signs, hemodynamic disorders). The use of intravenous polyvalent immunoglobulins must also be discussed in NF and STSS. In all cases surgery should be discussed. The prognosis of these potentially very severe infections is related to their early diagnosis and treatment. A better understanding of the pathophysiology of these infections may optimize their management but also their prevention.

Sympathomimetic amine therapy found effective for treatment of refractory chronic complex regional pain syndrome (reflex sympathetic dystrophy).

PURPOSE: To determine if treatment with sympathomimetic amines could improve the pain from complex regional pain disorder (CRPD) which was keeping a woman from trying to conceive her second child. MATERIALS AND METHODS: Dextroamphetamine sulfate was prescribed. RESULTS: Within a short length of time the woman's wrist pain considerably improved to the point that she is ready to try in vitro fertilization once again to have a second baby. CONCLUSIONS: Though sympathomimetic amines are used by some reproductive endocrinologists for unexplained infertility and unexplained recurrent miscarriages, the most common use by the gynecologist is for pelvic pain. Despite the thought by some clinicians and researchers that the etiology for CRPD may be related to sympathetic nervous system hyperactivity (and thus sympathomimetic amines could theoretically exacerbate the symptoms), in fact, the treatment with dextroamphetamine sulfate may turn out to be a new and possibly the most effective, least risky, and least expensive treatment to date for CRPD.

Predictors of CNS injury as measured by proton magnetic resonance spectroscopy in the setting of chronic HIV infection and CART.

The reasons for persistent brain dysfunction in chronically HIV-infected persons on stable combined antiretroviral therapies (CART) remain unclear. Host and viral factors along with their interactions were examined in 260 HIV-infected subjects who underwent magnetic resonance spectroscopy (MRS). Metabolite concentrations (NAA/Cr, Cho/Cr, MI/Cr, and Glx/Cr) were measured in the basal ganglia, the frontal white matter, and gray matter, and the best predictive models were selected using a bootstrap-enhanced Akaike information criterion (AIC). Depending on the metabolite and brain region, age, race, HIV RNA concentration, ADC stage, duration of HIV infection, nadir CD4, and/or their interactions were predictive of metabolite concentrations, particularly the basal ganglia NAA/Cr and the mid-frontal NAA/Cr and Glx/Cr, whereas current CD4 and the CPE index rarely or did not predict these changes. These results show for the first time that host and viral factors related to both current and past HIV status contribute to persisting cerebral metabolite abnormalities and provide a framework for further understanding neurological injury in the setting of chronic and stable disease.

Mer or Axl receptor tyrosine kinase inhibition promotes apoptosis, blocks growth and enhances chemosensitivity of human non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) is a prevalent and devastating disease that claims more lives than breast, prostate, colon and pancreatic cancers combined. Current research suggests that standard chemotherapy regimens have been optimized to maximal efficiency. Promising new treatment strategies involve novel agents targeting molecular aberrations present in subsets of NSCLC. We evaluated 88 human NSCLC tumors of diverse histology and identified Mer and Axl as receptor tyrosine kinases (RTKs) overexpressed in 69% and 93%, respectively, of tumors relative to surrounding normal lung tissue. Mer and Axl were also frequently overexpressed and activated in NSCLC cell lines. Ligand-dependent Mer or Axl activation stimulated MAPK, AKT and FAK signaling pathways indicating roles for these RTKs in multiple oncogenic processes. In addition, we identified a novel pro-survival pathway-involving AKT, CREB, Bcl-xL, survivin, and Bcl-2-downstream of Mer, which is differentially modulated by Axl signaling. We demonstrated that short hairpin RNA (shRNA) knockdown of Mer or Axl significantly reduced NSCLC colony formation and growth of subcutaneous xenografts in nude mice. Mer or Axl knockdown also improved in vitro NSCLC sensitivity to chemotherapeutic agents by promoting apoptosis. When comparing the effects of Mer and Axl knockdown, Mer inhibition exhibited more complete blockade of tumor growth while Axl knockdown more robustly improved chemosensitivity. These results indicate that Mer and Axl have complementary and overlapping roles in NSCLC and suggest that treatment strategies targeting both RTKs may be more effective than singly-targeted agents. Our findings validate Mer and Axl as potential therapeutic targets in NSCLC and provide justification for development of novel therapeutic compounds that selectively inhibit Mer and/or Axl.

Properties of nanoparticles prepared from NdFeB-based compound for magnetic hyperthermia application.

Nanoparticles were prepared from a NdFeB-based alloy using the hydrogen decrepitation process together with high-energy ball milling and tested as heating agent for magnetic hyperthermia. In the milling time range evaluated (up to 10 h), the magnetic moment per mass at H = 1.59 MA m(-1) is superior than 70 A m(2) kg(-1); however, the intrinsic coercivity might be inferior than 20 kA m(-1). The material presents both ferromagnetic and superparamagnetic particles constituted by a mixture of phases due to the incomplete disproportionation reaction of Nd(2)Fe(14)BH(x) during milling. Solutions prepared with deionized water and magnetic particles exposed to an AC magnetic field (H(max) ~ 3.7 kA m(-1) and f = 228 kHz) exhibited 26 K ≤ ΔT(max) ≤ 44 K with a maximum estimated specific absorption rate (SAR) of 225 W kg(-1). For the pure magnetic material milled for the longest period of time (10 h), the SAR was estimated as ~2500 W kg(-1). In vitro tests indicated that the powders have acceptable cytotoxicity over a wide range of concentration (0.1-100 µg ml(-1)) due to the coating applied during milling.

No evidence to support the concept that low serum dehydroepiandrosterone (DHEA) sulfate (s) levels are associated with less oocyte production or lower pregnancy rates.

PURPOSE: To determine if in a population of women with diminished oocyte reserve as evidenced by day 3 serum follicle stimulating hormone (FSH) levels > 12 mIU/ml women with lower dehydroepiandrosterone sulfate (DHEA-s) levels produce fewer oocytes or have lower pregnancy rates following in vitro fertilization-embryo transfer (IVF-ET) compared to women with higher levels. METHODS: The women were divided into poor responders (producing < or = 4 oocytes) following oocyte retrieval or good responders (> or = 5 oocytes). Mean DHEA-s levels were compared in poor vs good responders and in the subgroups of those who conceived vs those who did not conceive. RESULTS: The data clearly showed no association with low DHEA-s levels and response to controlled ovarian hyperstimulation or pregnancy rates. CONCLUSIONS: In women with elevated serum FSH low DHEA levels do not suggest that supplementation with DHEA would improve response or pregnancy rate. These data do not preclude the possibility that there is a small subset of women with normal oocyte reserve who also fail to respond to controlled ovarian hyperstimulation for some unknown reason and the problem could be remediable by DHEA supplementation.

Chronic pelvic pain--traditional and novel therapies: part II medical therapy.

PURPOSE: To describe medical therapeutic options for chronic pelvic pain. Furthermore to describe some new concepts in the etiology of chronic pelvic pain leading to some novel therapies. METHODS: The benefits and risks of various medical treatments for chronic pelvic pain including central pain, cyclic pain, vulvar pain and bladder pain are discussed. RESULTS: Among various conventional therapies the medical therapy with the most benefit with the least risks are low-dose impeded androgens, oral contraceptives, or low dosage progesterone/progestins. CONCLUSIONS: The various types of pelvic pain may all be different manifestations of a common etiology related to defects in the sympathetic nervous system. Sympathomimetic amine therapy may be the most effective therapy with the least side-effects. However, at the moment this schedule II drug has not been approved for this use and thus must be used off-label.

Spontaneous caloric restriction associated with increased leptin levels in obesity-resistant αMUPA mice.

BACKGROUND: αMUPA mice carry as a transgene the cDNA encoding urokinase-type plasminogen activator, a member of the plasminogen/plasmin system that functions in fibrinolysis and extracellular proteolysis. These mice spontaneously consume less food when fed ad libitum and live longer compared with wild-type (WT) control mice. αMUPA mice are obesity resistant and they share many similarities with calorically restricted animals. However, extensive metabolic characterization of this unique transgenic model has never been performed. METHOD: Metabolism of αMUPA mice was analyzed by measuring hormone, lipid and glucose levels in the serum, as well as gene and protein expression levels in the liver, hypothalamus and brainstem. RESULTS: αMUPA mice were found to be leaner than WT mice mainly because of reduced fat depots. Serum analyses showed that αMUPA mice have high levels of the anorexigenic hormones insulin and leptin, and low levels of the orexigenic hormone ghrelin. Analyses of brain neuropeptides showed that the transcript of the anorexigenic neuropeptide Pomc is highly expressed in the brainstem, whereas the expression of the orexigenic neuropeptides Npy, Orexin and Mch is blunted in the hypothalamus of αMUPA mice. In addition, adenosine monophosphate (AMP)-activated protein kinase (AMPK) levels were higher in the liver and lower in the hypothalamus, thus promoting simultaneously central reduction in appetite and peripheral loss of fat. The levels of SIRT1 were low in the liver, but high in the hypothalamus, a feature that αMUPA mice share with calorically restricted animals. CONCLUSION: Taken together, αMUPA mice exhibit a unique metabolic phenotype of low-calorie intake and high leptin levels, and could serve as a model for both spontaneous calorie restriction and resistance to obesity.

Elimination of symbiotic Aeromonas spp. from the intestinal tract of the medicinal leech, Hirudo medicinalis, using ciprofloxacin feeding.

The use of the medicinal leech (Hirudo medicinalis) in promoting venous drainage in tissues whose vitality is threatened by venous congestion and obstruction, especially in plastic and reconstructive surgery, has been complicated by infections caused by Aeromonas spp. These are leech endosymbionts for which patients undergoing hirudotherapy frequently receive systemic chemoprophylaxis. In order to evaluate the possibility of rendering leeches safe for use on patients, H. medicinalis were fed artificially with a 2 g/L arginine solution (used as a phagostimulant) supplemented with ciprofloxacin (100 mg/L). Aeromonads were detected in 57 out of 80 control leeches (71.3%), but in none of the 56 leeches treated with ciprofloxacin (p <0.001). Treated leeches survived for up to 4 months. Tested weekly, 61% of these leeches took human blood for at least 4 weeks after treatment and all remained negative for aeromonads. All water samples in which leeches were kept before treatment were contaminated with Aeromonas spp.; none were detected in any of the NaCl/arginine solutions with which treated animals were fed. Molecular characterization of two phenotypically distinct isolates using gyrB sequencing showed that one clustered tightly with A. veronii and the other was closely related to A. media. Other environmental bacteria and fungi were isolated from 26.5% of treated leeches that had taken a blood meal 1-4 weeks after treatment. Ciprofloxacin reduced the number of leech-associated aeromonads to undetectable levels for extended periods. Most treated leeches were ready to take a blood meal after treatment, suggesting the possibility of using ciprofloxacin-treated leeches instead of chemoprophylaxis in patients undergoing hirudotherapy.

Sequential therapy for the locally advanced larynx and hypopharynx cancer subgroup in TAX 324: survival, surgery, and organ preservation.

BACKGROUND: Locally advanced laryngeal and hypopharyngeal cancers (LHC) represent a group of cancers for which surgery, laryngectomy-free survival (LFS), overall survival (OS), and progression-free survival (PFS) are clinically meaningful end points. PATIENTS AND METHODS: These outcomes were analyzed in the subgroup of assessable LHC patients enrolled in TAX 324, a phase III trial of sequential therapy comparing docetaxel plus cisplatin and fluorouracil (TPF) against cisplatin and fluorouracil (PF), followed by chemoradiotherapy. RESULTS: Among 501 patients enrolled in TAX 324, 166 had LHC (TPF, n = 90; PF, n = 76). Patient characteristics were similar between subgroups. Median OS for TPF was 59 months [95% confidence interval (CI): 31-not reached] versus 24 months (95% CI: 13-42) for PF [hazard ratio (HR) for death: 0.62; 95% CI: 0.41-0.94; P = 0.024]. Median PFS for TPF was 21 months (95% CI: 12-59) versus 11 months (95% CI: 8-14) for PF (HR: 0.66; 95% CI: 0.45-0.97; P = 0.032). Among operable patients (TPF, n = 67; PF, n = 56), LFS was significantly greater with TPF (HR: 0.59; 95% CI: 0.37-0.95; P = 0.030). Three-year LFS with TPF was 52% versus 32% for PF. Fewer TPF patients had surgery (22% versus 42%; P = 0.030). CONCLUSIONS: In locally advanced LHC, sequential therapy with induction TPF significantly improved survival and PFS versus PF. Among operable patients, TPF also significantly improved LFS and PFS. These results support the use of sequential TPF followed by carboplatin chemoradiotherapy as a treatment option for organ preservation or to improve survival in locally advanced LHC.

[Bacterial diarrheas and antibiotics: European recommendations]. / Diarrhées bactériennes et antibiotiques : les recommandations européennes.

The need to limit unnecessary antibiotic treatments and recent studies with unusual antibiotics in pediatrics (fluoroquinolones) or in digestive tract infections (azithromycin) have led to update the treatment of acute gastro-enteritis. In 2007, the European Society for Pediatric Infectious Diseases and the European Society for Gastroenterology Hepatology and Nutrition have issued guidelines. The proven shigellosis as well as the strong suspicion have to be treated promptly with antibiotics, mainly azithromycin. There is no argument to treat moderate salmonella gastroenteritis or carriage. However, the severe cases and those occurring in high risk patient must be treated (ciprofloxacin or ceftriaxone). It is recommended to treat diarrhoea due to Campylobacter jejuni in case of early diagnosis. The presumptive antibiotic treatment should be limited but can not be dismissed, in invasive cases gastro-enteritis, especially in traveller children.

Mild traumatic brain injury to the infant mouse causes robust white matter axonal degeneration which precedes apoptotic death of cortical and thalamic neurons.

The immature brain in the first several years of childhood is very vulnerable to trauma. Traumatic brain injury (TBI) during this critical period often leads to neuropathological and cognitive impairment. Previous experimental studies in rodent models of infant TBI were mostly concentrated on neuronal degeneration, while axonal injury and its relationship to cell death have attracted much less attention. To address this, we developed a closed controlled head injury model in infant (P7) mice and characterized the temporospatial pattern of axonal degeneration and neuronal cell death in the brain following mild injury. Using amyloid precursor protein (APP) as marker of axonal injury we found that mild head trauma causes robust axonal degeneration in the cingulum/external capsule as early as 30 min post-impact. These levels of axonal injury persisted throughout a 24 h period, but significantly declined by 48 h. During the first 24 h injured axons underwent significant and rapid pathomorphological changes. Initial small axonal swellings evolved into larger spheroids and club-like swellings indicating the early disconnection of axons. Ultrastructural analysis revealed compaction of organelles, axolemmal and cytoskeletal defects. Axonal degeneration was followed by profound apoptotic cell death in the posterior cingulate and retrosplenial cortex and anterior thalamus which peaked between 16 and 24 h post-injury. At early stages post-injury no evidence of excitotoxic neuronal death at the impact site was found. At 48 h apoptotic cell death was reduced and paralleled with the reduction in the number of APP-labeled axonal profiles. Our data suggest that early degenerative response to injury in axons of the cingulum and external capsule may cause disconnection between cortical and thalamic neurons, and lead to their delayed apoptotic death.

[Pharmacokinetics and pharmacodynamics of antimicrobial therapy used in child osteoarticular infections]. / Pharmacocinétique et pharmacodynamique sériques des antibiotiques utilisés dans les infections ostéoarticulaires de l'enfant.

The progress in the knowledge of antibiotic action mechanisms have led to determine phamacodynamic/pharmacokinetic (PK/PD) parameters predictive of antibiotic efficacy in bacterial infections. According to the antibiotic compound, the implicated bacterial specie, the localization of the infection, the severity of the disease, these parameters could vary. The PK/PD parameters described in this paper focus only on blood compartment and S. aureus, (main bacteria implicated in bone and joint tissue infections). All beta-lactamase resistant beta-lactam compounds given by IV route, if they are prescribed at the good dosage and frequency, fulfill these PK/PD parameters. In contrast, by oral route, M penicillins and cefuroxime-axetil should not be considered as acceptable regimens. Only amoxicillin-clavulanate and some first generation cephalosporin compounds fulfill the PK/PD parameters predictive of clinical efficacy if S. aureus strains are methicillin susceptible and dosages of cephalosporins are increased. Clindamycin is a very interesting alternative, if the strains are susceptible to macrolides.

High-precision guidance of ablation catheters to arrhythmic sites using electrocardiographic signals.

Hemodynamically unstable ventricular arrhythmias are frequently untreatable with radio-frequency ablation due to the difficulty of rapidly and accurately localizing the site of origin of an arrhythmia with current technologies. We demonstrate a new catheter guidance method that will direct the tip of an ablation catheter to the site of origin of an arrhythmia and reduce the time needed to locate the site such that a patient need only be maintained in the arrhythmia for a few beats. The algorithm, based on a single-equivalent moving dipole (SEMD) model, is used to identify the bioelectric dipole corresponding to a site of origin of an arrhythmia. If a current dipole is produced at the ablation catheter tip, the tip position may also be calculated using this algorithm, and the catheter can be guided towards the site of origin of the arrhythmia. We present a method to compensate for the effect of systematic non-idealities, such as boundary effects, on the accuracy of this algorithm. In simulations, this method is able to guide the catheter tip to within 1.5 mm of the arrhythmic site at any location within the model torso with almost 100% success and with a realistic number of movements of the ablation catheter. These results suggest that this method has great potential to direct radio-frequency ablation procedures, especially in the significant patient population that is currently untreatable.

Sacral nerve stimulation for faecal incontinence due to systemic sclerosis.

BACKGROUND: Faecal incontinence occurs in over one third of patients with systemic sclerosis. The aetiology is multifactorial. Conventional treatment is often unsuccessful. Sacral nerve stimulation is a new effective treatment for resistant faecal incontinence. AIMS: To evaluate sacral nerve stimulation in patients with systemic sclerosis. PATIENTS: Five women, median age 61 years (30-71), with scleroderma associated faecal incontinence were evaluated. All had failed maximal conventional treatment. Median number of preoperative weekly episodes of incontinence was 15 (7-25), median duration of incontinence was five years (5-9), and scleroderma 13 years (4-29). METHODS: All patients were screened with temporary stimulation. Those who benefited underwent permanent implantation. At baseline and after stimulation a bowel diary, the SF-36 quality of life assessment, endoanal ultrasound, and anorectal physiology were performed. RESULTS: Four patients were continent at a median follow up of 24 months (6-60). One patient failed temporary stimulation and was not permanently implanted. The weekly episodes of incontinence decreased from 15, 11, 23, and 7 to 0. Urgency resolved (median time to defer <1 minute (0-1) v 12.5 minutes (5-15)). Quality of life, especially social function, improved. Endoanal ultrasound showed an atrophic internal anal sphincter (median width 1.0 mm (0-1.6)). Anorectal physiology showed an increase in median resting pressure (37 pre v 65 cm H(2)O post) and squeeze pressure (89 v 105 cm H(2)O). Stimulation produced enhanced rectal sensitivity to distension. There were no major complications. CONCLUSIONS: Sacral nerve stimulation is a safe and effective treatment for resistant faecal incontinence secondary to scleroderma. The benefit is maintained in the medium term.

Permanent sacral nerve stimulation for treatment of idiopathic constipation.

BACKGROUND: Constipation can usually be managed using conservative therapies. A proportion of patients require more intensive treatment. Surgery provides variable results. This paper describes an alternative approach, in which the neural control of the bowel and pelvic floor is modified, using permanent sacral nerve stimulation. METHODS: Four women (aged 27-36 years), underwent temporary and then permanent stimulation. All had idiopathic constipation, resistant to maximal therapy, with symptoms for 8-32 years. Clinical evaluation, bowel diary, Wexner constipation score, symptom analogue score, quality of life questionnaire and anorectal physiology were completed. RESULTS: There was a marked improvement in all patients with temporary, and in three with permanent, stimulation. Median follow-up was 8 (range 1-11) months. Bowel frequency increased from 1-6 to 6-28 evacuations per 3 weeks. Improvement occurred, at longest-follow-up, in median (range) evacuation score (4 (0-4) versus 1 (0-4)), time with abdominal pain (98 (95-100) versus 12 (0-100) per cent), time with bloating (100 (95-100) versus 12 (5-100) per cent), Wexner score (21 (20-22) versus 9 (1-20)), analogue score (22 (16-32) versus 80 (20-98)) and quality of life. Maximum anal resting and squeeze pressures increased. Rectal sensation was altered. Transit time normalized in one patient. CONCLUSION: Permanent sacral nerve stimulation can be used to treat patients with resistant idiopathic constipation.