Does choice of anesthesia during stage 1 sacral neuromodulation testing influence outcomes?

INTRODUCTION: Staged sacral neuromodulation (SNM) testing has been shown to have a high rate of progression to permanent implantation for the management of voiding dysfunction. Stage 1 lead placement (SNM-I) can be performed under monitored anesthesia care (MAC) or general anesthesia (GA). MAC allows for interpretation of sensory and motor responses to optimize lead placement while GA only permits for motor assessment. However, patient discomfort and movement can make lead placement challenging during MAC. Herein we evaluate whether the anesthesia type impacts the progression rate to permanent implantation (SNM-II). MATERIALS AND METHODS: A retrospective chart review was performed for patients who underwent SNM-I in the operating room for wet overactive bladder between 2005 and 2023. Patients were divided into two groups based on the type of anesthesia used, MAC or GA. Clinical variables and progression to SNM-II were compared between cohorts. Progression to SNM-II was based on ≥50% symptomatic improvement during a 1-2 week trial period following SNM-I. RESULTS: Of 121 patients included in the study, 95 (79%) underwent MAC and 26 (21%) GA for SNM-I. No difference in the progression rate to SNM-II was noted between groups (MAC, 68/95 patients, 72%; GA, 19/26, 73%; p = 0.39). We also found no difference when comparing the GA group to the 26 most recent MAC patients (MAC, 20/26 patients, 77%; GA, 19/26, 73%; p = 0.48). CONCLUSION: Types of anesthesia for SNM-I did not affect rate of progression to SNM-II. The result lends support to the reliance on motor responses alone for lead placement during SNM-I.

Effects of the Toxic Non-Protein Amino Acid ß-Methylamino-L-Alanine (BMAA) on Intracellular Amino Acid Levels in Neuroblastoma Cells.

The cyanobacterial non-protein amino acid (AA) ß-Methylamino-L-alanine (BMAA) is considered to be a neurotoxin. BMAA caused histopathological changes in brains and spinal cords of primates consistent with some of those seen in early motor neuron disease; however, supplementation with L-serine protected against some of those changes. We examined the impact of BMAA on AA concentrations in human neuroblastoma cells in vitro. Cells were treated with 1000 µM BMAA and intracellular free AA concentrations in treated and control cells were compared at six time-points over a 48 h culture period. BMAA had a profound effect on intracellular AA levels at specific time points but in most cases, AA homeostasis was re-established in the cell. The most heavily impacted amino acid was serine which was depleted in BMAA-treated cells from 9 h onwards. Correction of serine depletion could be a factor in the observation that supplementation with L-serine protects against BMAA toxicity in vitro and in vivo. AAs that could potentially be involved in protection against BMAA-induced oxidation such as histidine, tyrosine, and phenylalanine were depleted in cells at later time points.

Is a 50% improvement threshold adequate to justify progression from sacral neuromodulation testing to implant?

PURPOSE: A ≥50% subjective improvement in urinary symptoms during sacral neuromodulation testing (SNM-I) is currently used as the indication for progression to second-stage implantation (SNM-II). While most patients will have successful SNM-I and proceed to SNM-II, deterioration in efficacy over time has been reported. It remains unclear if the durability of efficacy is related to the initial symptom reduction. We sought to determine if the degree of improvement after SNM-I is sufficient to predict long-term success. METHODS: The records of all patients who underwent sacral neuromodulation (SNM) for overactive bladder were reviewed. Subjects were divided into those who reported 50%-75% improvement (Group 1) and more than 75% improvement (Group 2) after SNM-I. Differences in clinical variables and long-term device efficacy were compared between groups. RESULTS: Of 213 patients who underwent SNM-I, 137 underwent permanent device implantation. A total of 76 (55%) and 61 (45%) patients reported 50%-75% (Group 1) and more than 75% (Group 2) symptomatic improvement, respectively. With a mean follow-up of 46 months, 44% of Group 1 patients and 68% of Group 2 patients still had a functioning device providing the symptomatic benefit (p = 0.007). Univariate analyses identified the presence of stress urinary incontinence at baseline and having a more than 75% improvement after SNM-I as predictors of long-term functional success. CONCLUSIONS: Compared to patients reporting 50%-75% symptomatic reduction after SNM-I, individuals with a more than 75% improvement during SNM-I were more likely to maintain device efficacy over time. Additional study is warranted to determine if the improvement threshold for progression to SNM-II should be increased.

Microbial production and consumption of hydrocarbons in the global ocean.

Seeps, spills and other oil pollution introduce hydrocarbons into the ocean. Marine cyanobacteria also produce hydrocarbons from fatty acids, but little is known about the size and turnover of this cyanobacterial hydrocarbon cycle. We report that cyanobacteria in an oligotrophic gyre mainly produce n-pentadecane and that microbial hydrocarbon production exhibits stratification and diel cycling in the sunlit surface ocean. Using chemical and isotopic tracing we find that pentadecane production mainly occurs in the lower euphotic zone. Using a multifaceted approach, we estimate that the global flux of cyanobacteria-produced pentadecane exceeds total oil input in the ocean by 100- to 500-fold. We show that rapid pentadecane consumption sustains a population of pentadecane-degrading bacteria, and possibly archaea. Our findings characterize a microbial hydrocarbon cycle in the open ocean that dwarfs oil input. We hypothesize that cyanobacterial hydrocarbon production selectively primes the ocean's microbiome with long-chain alkanes whereas degradation of other petroleum hydrocarbons is controlled by factors including proximity to petroleum seepage.

High-Fat Diet and Antibiotics Cooperatively Impair Mitochondrial Bioenergetics to Trigger Dysbiosis that Exacerbates Pre-inflammatory Bowel Disease.

The clinical spectra of irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD) intersect to form a scantily defined overlap syndrome, termed pre-IBD. We show that increased Enterobacteriaceae and reduced Clostridia abundance distinguish the fecal microbiota of pre-IBD patients from IBS patients. A history of antibiotics in individuals consuming a high-fat diet was associated with the greatest risk for pre-IBD. Exposing mice to these risk factors resulted in conditions resembling pre-IBD and impaired mitochondrial bioenergetics in the colonic epithelium, which triggered dysbiosis. Restoring mitochondrial bioenergetics in the colonic epithelium with 5-amino salicylic acid, a PPAR-γ (peroxisome proliferator-activated receptor gamma) agonist that stimulates mitochondrial activity, ameliorated pre-IBD symptoms. As with patients, mice with pre-IBD exhibited notable expansions of Enterobacteriaceae that exacerbated low-grade mucosal inflammation, suggesting that remediating dysbiosis can alleviate inflammation. Thus, environmental risk factors cooperate to impair epithelial mitochondrial bioenergetics, thereby triggering microbiota disruptions that exacerbate inflammation and distinguish pre-IBD from IBS.

InTone: a novel pelvic floor rehabilitation device for urinary incontinence.

INTRODUCTION: InTone(TM) (InControl Medical) is a nonimplanted vaginal device providing biofeedback and electrical stimulation of pelvic floor muscles. The purpose of this study was to assess its efficacy and usability for treating urinary incontinence (UI). METHODS: Women with UI (stress, urge, mixed) were recruited for this pilot trial. InTone was used 5-6 days a week for 12 weeks. Patients were assessed at baseline and monthly with symptom questionnaires [Urinary Distress Index (UDI6), Incontinence Impact Questionnaire (IIQ7)], bladder diaries. and 24-h pad-weight testing (PWT). Efficacy was assessed by comparing 12-week results to baseline values using chi-square and Wilcoxon rank-sum tests. Usability was assessed with a device-usage log and the System Usability Scale (SUS), which evaluates patients' global impression of usability. RESULTS: Thirty-three women were enrolled; five patients withdrew and were excluded. Median age was 50 years (range 35-69). After 12 weeks of InTone therapy, median UDI6 and IIQ7 scores improved from 50.0 to 29.2 (p < 0.001) and from 42.9 to 14.3 (p < 0.001), respectively. Statistically significant reductions in median PWT (35.5-4.6 g, p < 0.001), median daily pad use (4.0-2.0, p < 0.001), and median daily incontinence frequency (4.3-1.0, p < 0.001) were noted; 68 % of patients achieved a > 50 % reduction in daily pad usage and PWT. Device usability was good, with a median SUS of 86.3 and a median expected use of 107 % (33-140 %). CONCLUSIONS: Twelve weeks of InTone usage resulted in significant objective and subjective reductions in UI. Device usability was very good.

Structured care of diabetes in general practice: a qualitative study of the barriers and facilitators.

This qualitative study explored general practitioner's and practice nurse's perceptions of barriers and facilitators to the proposed transfer of diabetes care to general practice. Qualitative data were collected through five focus groups. Participants included GPs (n = 55) and practice nurses (n = 11) representing urban (44%), rural (29%) and mixed (27%) practices, in the Irish Mid-West region. Barriers and facilitators were mentioned 631 times (100%). Barriers were mentioned 461 times (73%), facilitators 170 times (27%). The most frequently identified barriers were lack of financial incentive (119/631; 19%), lack of access to secondary resources (93/631; 15%), lack of staff and increased workload (59/631; 9%) and time constraints (52/631; 8%). Identified facilitators were access to secondary care (49/631;7.8%), the holistic nature of general practice and continuity of care (48/631;7.6%). Although many are enthusiastic, there remains significant reluctance among GPs and practice nurses to take responsibility for diabetes care without addressing these barriers.

Towards the development of integrated epilepsy services: an audit of documented epilepsy care.

Effective chronic disease management (CDM) requires the ready availability and communication of accurate, clinical disease specific information. Using epilepsy as a probe into CDM, we report on the availability and reliability of clinical information in the primary care records of people with epilepsy (PWE). The medical records of 374 PWE from 53 general practices in the Mid-West region of Ireland were examined. Confirmation of an epilepsy diagnosis by a neurologist was documented for 132 (35%) patients. 282 (75%) patients had no documented evidence of receiving specialist neurology review while 149 (40%) had not been reviewed by their GP in the previous two years for their epilepsy. Significant variation in documentation of epilepsy specific information together with an inadequacy and inconsistency of existing epilepsy services was highlighted.

Comparative bioenergetic assessment of transformed cells using a cell energy budget platform.

The aberrant expression and functional activity of proteins involved in ATP production pathways may cause a crisis in energy generation for cells and compromise their survival under stressful conditions such as excitation, starvation, pharmacological treatment or disease states. Under resting conditions such defects are often compensated for, and therefore masked by, alternative pathways which have significant spare capacity. Here we present a multiplexed 'cell energy budget' platform which facilitates metabolic assessment and cross-comparison of different cells and the identification of genes directly or indirectly involved in ATP production. Long-decay emitting O(2) and pH sensitive probes and time-resolved fluorometry are used to measure changes in cellular O(2) consumption, glycolytic and total extracellular acidification (ECA), along with the measurement of total ATP and protein content in multiple samples. To assess the extent of spare capacity in the main energy pathways, the cells are also analysed following double-treatment with carbonyl cyanide p-(trifluoromethoxy)phenylhydrazone and oligomycin. The four-parametric platform operating in a high throughput format has been validated with two panels of transformed cells: mouse embryonic fibroblasts (MEFs) lacking the Krebs cycle enzyme fumarate hydratase (Fh1) and HeLa cells with reduced expression of pyrimidine nucleotide carrier 1. In both cases, a marked reduction in both respiration and spare respiratory capacity was observed, accompanied by a compensatory activation of glycolysis and consequent maintenance of total ATP levels. At the same time, in Fh1-deficient MEFs the contribution of non-glycolytic pathways to the ECA did not change.

Unilateral versus bilateral stage I neuromodulator lead placement for the treatment of refractory voiding dysfunction.

AIMS: To determine if bilateral S3 lead placement during the stage I trial period improves the "success" rate for advancing to stage II (permanent) sacral neuromodulator placement. METHODS: A retrospective chart review of 124 (20 male and 104 female) patients undergoing stage I sacral neuromodulation (InterStim, Medtronic, Minneapolis, Minnesota) implantation for the treatment of refractory voiding dysfunction was performed. Patients were divided into two cohorts based on unilateral versus bilateral stage I lead placement in the S3 foramina. Both groups were then evaluated and compared with regards to overall "success", defined as progression from stage I to stage II placement. RESULTS: Fifty-five (44%) patients underwent unilateral stage I lead placement and 69 (56%) received bilateral S3 leads. Successful stage I trials were reported in 32/55 (58%) and 53/69 (76%) of unilateral and bilateral cohorts, respectively (P = 0.03). Five wound infections were reported-2 (3.6%) following unilateral and 3 (4.3%) after bilateral stage I lead placement. No other complications were encountered. CONCLUSIONS: Bilateral stage I neuromodulation trial provides a significantly higher rate of improvement in refractory voiding symptoms to allow for the progress to stage II implantation.

Sacral neuromodulation for urinary retention after pelvic plexus injury.

Injury to the pelvic plexus with resultant urinary retention is a known complication of colectomy. We describe a case of urinary retention after colectomy successfully treated with the insertion of a pelvic neuromodulator.

Characteristics of infections in patients undergoing staged implantation for sacral nerve stimulation.

OBJECTIVES: To review clinical and surgical factors in patients who have undergone staged sacral nerve stimulator implantation and to determine whether there are any identifiable risk factors for infection. METHODS: A retrospective chart review was performed on 76 consecutive patients undergoing staged implantation for sacral nerve stimulation for voiding dysfunction. Patients with postprocedural wound infections (after Stage 1 or Stage 2) were compared with those without infections with regard to demographic factors and surgical characteristics, such as operative time and duration of exposed lead wire. Organisms cultured were also documented. RESULTS: Lead infection occurred in 9 of 76 patients (12%). All cultures grew Staphylococcus aureus. Of 9 patients with lead infection, 6 had organisms sensitive to their perioperative antibiotic. Forty-five patients had an implantable pulse generator implanted, and 5 infections occurred (11%). Four cultures grew S. aureus (all sensitive to the perioperative antibiotic given), whereas one grew Pseudomonas. The only significant difference in clinical/surgical characteristics between infected and noninfected patients was a longer operative time for Stage 2 in infected patients. In addition, 3 patients with infection had one or more known risk factors for wound infection (steroid use, severe psoriasis, recurrent skin abscess). CONCLUSIONS: Apart from known risk factors for surgical wound infections, the only variable we could identify that might increase the risk for infection is a longer operative time for Stage 2. S. aureus was the organism most commonly cultured. Often it was sensitive to the perioperative antibiotic prophylaxis.

Long-term blood cholesterol-lowering effects of a dietary fiber supplement.

BACKGROUND: The study evaluated the blood cholesterol-lowering effects of a dietary supplement of water-soluble fibers (guar gum, pectin) and mostly non-water-soluble fibers (soy fiber, pea fiber, corn bran) in subjects with mild to moderate hypercholesterolemia (LDL cholesterol, 3.37-4.92 mmol/L). METHODS: After stabilization for 9 weeks on a National Cholesterol Education Program Step 1 Diet, subjects were randomly assigned to receive 20 g/d of the fiber supplement (n = 87) or matching placebo (n = 82) for 15 weeks and then receive the fiber supplement for 36 weeks. The efficacy analyses included the 125 subjects (58 fiber; 67 placebo) who were treatment and diet compliant. One hundred two (52 fiber; 50 placebo) completed the 15-week comparative phase. Of these subjects 85 (45 fiber; 40 placebo) elected to continue in the 36-week noncomparative extension phase. RESULTS: The mean decreases during the 15-week period for LDL cholesterol (LDL-C), total cholesterol (TC), and LDL-C/HDL-C ratio were greater (P < 0.001) in the fiber group. The mean changes from pre-treatment values in LDL-C, TC, and LDL-C/HDL-C ratio for subjects in the fiber group were -0.51 mmol/L (-12.1%), -0.53 mmol/L (-8.5%), and -0.30 (-9.4%), respectively. The corresponding changes in the placebo group were -0.05 mmol/L (-1.3%), -0.05 mmol/L (-0.8%), and 0.05 (1.5%), respectively. The fiber supplement had no significant effects (P > 0.05) on HDL cholesterol (HDL-C), triglyceride, iron, ferritin, or vitamin A or E levels. Similar effects were seen over the subsequent 36-week noncomparative part of the study. CONCLUSIONS: The fiber supplement provided significant and sustained reductions in LDL-C without reducing HDL-C or increasing triglycerides over the 51-week treatment period.

EMS systems and managed care integration.

Emergency medical services systems and MCOs must cooperate and educate each other in order to effect delivery of reliable, high-quality emergency health care to the entire community. Shared goals are rapid access, medically appropriate care, and operational efficiency. An integrated approach is necessary in order to maintain the integrity of EMS systems. EMS systems serve as a safety net for patients with perceived emergencies. Changes in form and function should be guided by outcome studies that ensure the continued delivery of quality emergency health care services.

Respiratory arrest after local anesthesia for outpatient cataract surgery: a dramatic but transient complication.

Retrobulbar injection of anesthetic agents is common practice before ophthalmologic procedures. Rare but life-threatening complications of this procedure include respiratory depression and coma. We present the case of a woman with complete respiratory arrest and unresponsiveness who was brought into our emergency department from a local freestanding surgical center after preoperative retrobulbar anesthetic injection. Subsequently, the pathogenesis, clinical features, and supportive treatment for this dramatic but transient complication are discussed.

Surface to nuclear distances in human bronchial epithelium: relationships to penetration by Rn daughters.

Lung cancer in U miners is thought to be related to the inhalation of particulate Rn daughters. Since the depth of penetration by alpha particles is short, the thickness of the epithelium lining the bronchial tree may be a critical factor in the development of cancers at specific sites in the lung. The objectives of the study were to measure the thickness of the epithelium at all levels of the human bronchial tree, to determine the distances of epithelial nuclei from the mucociliary surface, and to compare these parameters in smokers and nonsmokers. Twenty-nine surgically removed specimens were examined; 26 were from smokers. No significant differences were found between smokers and nonsmokers, allowing us to treat the 29 cases as a homogeneous group. With progressive divisions of the bronchi, the epithelium decreases in thickness, and distances of nuclei from the surface are also less in the peripheral bronchi. Allowing for artefacts of tissue preparation, the mean distance from the mucociliary surface to the underlying nuclei varies between 17 and 38 microns.

Effect of internal microblasting on retention of cemented cast crowns.

Microblasting of cast mental crowns is considered a standard procedure in most laboratories and an effective alternative to acid pickling. During the process of devesting and finishing, the surfaces of cast restorations are microblasted with an abrasive agent. This investigation measured the retention of type III cast gold crowns after cleansing with pickling solution (group I) or microblasting with 50-micron aluminum oxide (group II) or 50-micron glass beads (group III). Microblasting the internal surface of cast crowns with 50-micron aluminum oxide significantly improved the retention of castings luted with zinc phosphate cement.

Glutathione protects against exogenous oxidant injury to rabbit renal proximal tubules.

Glutathione, comprising a major portion of cellular nonprotein thiols, plays a central role in a diverse group of cell metabolic functions. Glutathione and related enzyme systems have been shown to protect against both toxin and oxidant-induced injury in several organ systems. The role of glutathione in protecting renal epithelia against oxidant stress has not been investigated previously. We report here the response of enriched, isolated rabbit renal proximal tubule segments to oxidant stress induced by tert-butyl hydroperoxide. In addition, the effects of glutathione depletion by various biochemical means and of exogenous glutathione supplementation on the response of tubule segments to tert-butyl hydroperoxide exposure are described. Depletion of cell glutathione by several distinct methods potentiates oxidant-induced injury. Augmentation of cellular glutathione affords significant protection against exogenous oxidant stress. The protective effect of glutathione may reside in its ability, in conjunction with glutathione peroxidase, to arrest the propagation of lipid peroxidation and, therefore, to minimize alterations in plasma membrane permeability. The results of this study do not exclude the possibility that glutathione prevents tert-butyl hydroperoxide induced oxidation of critical sulfhydryl groups of catalytic or structural proteins associated with control of cell cation homeostasis. These results confirm the important role of glutathione in protecting renal tubular epithelia against oxidant stress.