Prolonged duration of anesthesia in a patient with multiple sclerosis following paravertebral block

PURPOSE: To explore the possibility that the prolonged duration of anesthesia following paravertebral block was related to the presence of multiple sclerosis in a patient undergoing elective inguinal hernia repair. CLINICAL FEATURES: A healthy 33-yr-old female presented for elective inguinal hernia repair. The procedure was performed under general anesthesia and a paravertebral block was performed at the end of the procedure for postoperative pain relief, whilst the patient was still anesthetized. Upon recovering from general anesthesia it was noted that the patient had a flaccid paralysis of both lower extremities. She was also very nauseated and required antiemetics and vasopressors for hypotension. A differential diagnosis of subarachnoid, subdural or epidural spread was considered. The presence of an epidural hematoma was also considered. The block regressed very slowly with full return of function in 12.5 hr. The duration of action of the block was far longer than one would expect following spinal, epidural or subdural spread of a local anesthetic. Urinary catheterization was performed electively to prevent urinary retention. The patient was discharged home late that evening. Prior to discharge she volunteered that she was being investigated for multiple sclerosis. One month later the diagnosis of multiple sclerosis was confirmed. CONCLUSION: In conclusion the extended duration of central neural blockade following paravertebral block, may have been related to an abnormal uptake of local anesthetics into the spinal cord in the presence of demyelination.     

Delphinidin,a dietary antioxidant,induces human epidermal keratinocyte differentiation but not apoptosis: studies in submerged and three‐dimensional epidermal equivalent models

Delphinidin (Del), [3,5,7,3'‐,4'‐,5'‐hexahydroxyflavylium], an anthocyanidin and a potent antioxidant abundantly found in pigmented fruits and vegetables exhibits proapoptotic effects in many cancer cells. Here, we determined the effect of Del on growth, apoptosis and differentiation of normal human epidermal keratinocytes (NHEKs) in vitro in submerged cultures and examined its effects in a three‐dimensional (3D) epidermal equivalent (EE) model that permits complete differentiation reminiscent of in vivo skin. Treatment of NHEKs with Del (10–40 μm ; 24–48 h) significantly enhanced keratinocyte differentiation. In Del‐treated cells, there was marked increase in human involucrin (hINV) promoter activity with simultaneous increase in the mRNA and protein expressions of involucrin and other epidermal differentiation markers including procaspase‐14 and transglutaminase‐1 (TGM1), but without any effect on TGM2. Del treatment of NHEKs was associated with minimal decrease in cell viability, which was not associated with apoptosis as evident by lack of modulation of caspases, apoptosis‐related proteins including Bcl‐2 family of proteins and poly(ADP‐ribose) polymerase cleavage. To establish the in vivo relevance of our observations in submerged cultures, we then validated these effects in a 3D EE model, where Del was found to significantly enhance cornification and increase the protein expression of cornification markers including caspase‐14 and keratin 1. For the first time, we show that Del induces epidermal differentiation using an experimental system that closely mimics in vivo human skin. These observations suggest that Del could be a useful agent for dermatoses associated with epidermal barrier defects including aberrant keratinization, hyperproliferation or inflammation observed in skin diseases like psoriasis and ichthyoses.     

Lens opacities in adults in Pakistan: prevalence and risk factors

PURPOSE: To investigate the prevalence and risk factors for lens opacity (LO) amongst a nationally representative sample of the adult population of Pakistan. METHODS: This national study of blindness and visual impairment (adults > or =30 years) used multistage, stratified, cluster random sampling. Grading of LO was conducted using the Mehra/Minassian classification system. LO, partly or wholly obscuring the red reflex, or previous cataract surgery were indicators of opacity. RESULTS: 16,402 (94.7%) adults were included in this analysis (study conducted 2002-2003). A total of 4,096 (standardized prevalence 20.9%, 95%CI: 20.3, 21.5%) adults were found to have LO. The highest prevalence of LO was found in Punjab province (22.2%), the lowest in Balochistan Province (18.0%). Significant positive associations were increasing age (multivariable odds ratio (OR) 3.2: 95%CI: 3.1, 3.4), hypertension (OR 1.2, 95%CI: 1.1, 1.3), history of diabetes (OR 2.6: 95%CI 2.0, 3.2) and smoking (OR 1.3: 95%CI: 1.1, 1.5). Higher body mass index (BMI) (OR 0.8: 95%CI 0.7, 0.9, heavy vs. normal BMI) and attendance to school (OR 0.6: 95%CI: 0.5, 0.8) were associated with lower risk of LO. Individuals in districts classified as hot were at significantly increased risk (OR 1.3: 95%CI: 1.1, 1.5), and those in wet districts (> 600 mm annual rainfall) had lower odds than individuals living in dry districts (OR 0.7: 95%CI: 0.6, 0.8). CONCLUSIONS: Almost a fifth of the adult population had LO. Significant positive associations were age, smoking status, hypertension, diabetes, and increased deprivation level. Protective factors included high BMI and educational achievement. The climatic associations offer novel hypothesis for further research into cataractogenesis.     

Clinical Evaluation of the Cook Advance Enforcer 35 Focal-Force PTA Balloon Catheter for Treatment of Hemodialysis Fistula Stenoses: A Feasibility Study

Purpose

A prospective, single-center, single-arm feasibility study evaluated procedural and short-term performance of the Advance Enforcer 35 focal-force percutaneous transluminal angioplasty (PTA) balloon catheter in treating stenoses of mature native arteriovenous (AV) hemodialysis access circuits.

Association of gray matter volumes with general and specific dimensions of psychopathology in children

Childhood is an important time for the manifestation of psychopathology. Psychopathology is characterized by considerable comorbidity which is mirrored in the underlying neural correlates of psychopathology. Both common and dissociable variations in brain volume have been found across multiple mental disorders in adult and youth samples. However, the majority of these studies used samples with broad age ranges which may obscure developmental differences. The current study examines associations between regional gray matter volumes (GMV) and psychopathology in a large sample of children with a narrowly defined age range. We used data from 9607 children 9–10 years of age collected as part of the Adolescent Brain Cognitive Development^SM Study (ABCD Study^®). A bifactor model identified a general psychopathology factor that reflects common variance across disorders and specific factors representing internalizing symptoms, ADHD symptoms, and conduct problems. Brain volume was acquired using 3T MRI. After correction for multiple testing, structural equation modeling revealed nearly global inverse associations between regional GMVs and general psychopathology and conduct problems, with associations also found for ADHD symptoms (p_fdr-values ≤ 0.048). Age, sex, and race were included as covariates. Sensitivity analyses including total GMV or intracranial volume (ICV) as covariates support this global association, as a large majority of region-specific results became nonsignificant. Sensitivity analyses including income, parental education, and medication use as additional covariates demonstrate largely convergent results. These findings suggest that globally smaller GMVs are a nonspecific risk factor for general psychopathology, and possibly for conduct problems and ADHD as well.Subject terms: Human behaviour, Risk factors, Neuroscience     

Comorbidities Do not Influence Primary Fistula Success in Incident Hemodialysis Patients: A Prospective Study

Background and objectives: Concern about primary fistula failure may contribute to the underuse of arteriovenous fistula. The objective of this study was to investigate the baseline clinical parameters associated with primary fistula success.Design, setting, participants, & measurements: Consecutive incident patients who commenced dialysis during a 28-mo period in a regional renal program were studied. Data on patient-related variables and on surgical approach (e.g., whether the surgeons routinely assess vessel size during the operation) were collected. Primary fistula success was defined as an arteriovenous fistula that was able to afford successful dialysis for 3 h with blood pump speed of ≥300 ml/min for three consecutive sessions.Results: A total of 205 (69%) patients had an AVF attempted as their first vascular access. The overall primary success rate was 64% and was similar for radiocephalic and brachiocephalic fistula. Logistic regression was done separately for patients with the two types of fistula because of the presence of statistical interaction. For radiocephalic fistula, male gender was the only parameter associated with primary fistula success (odds ratio 3.57; P = 0.01). The presence of comorbidity was not significantly associated with primary fistula failure.Conclusions: Despite significant patient comorbidity, there was a high primary fistula success rate among this incident hemodialysis cohort. Given that vessel size may be the ultimate determinant of fistula success, if surgeons assess vessel size perioperatively, then the presence of significant comorbidity might not preclude arteriovenous fistula from being attempted as the initial access.Given the well-documented advantages of arteriovenous fistula (AVF) over arteriovenous graft and central venous catheter (CVC), the current Kidney Disease Outcomes Quality Initiative (K/DOQI) guidelines suggest that AVF should be attempted as the initial vascular access in at least 50% of incident patients and that at least 40% of prevalent hemodialysis (HD) patients should undergo dialysis with an AVF (1–5). Despite these recommendations, it is clear that AVF are underused in many centers in North America, especially when compared with European centers (6,7). Recent data suggest that only 32% of prevalent US HD patients undergo dialysis with an AVF (8). In Canada, AVF are used by 53% of prevalent and only 26% of incident HD patients (7).One of the fears that may reduce the use of AVF is the high primary fistula failure rate (i.e., failure of AVF to mature) (9). Identifying risk factors that contribute to primary fistula failure may help clinicians and patients make an informed decision as to for whom to attempt an AVF. Only a few studies have prospectively examined the risk factors associated with primary fistula failure, which has been reported in 20 to 50% of patients (9–12).Most studies that have evaluated factors that are associated with primary fistula failure have typically used a retrospective design. For instance, Miller et al. (10) reported higher primary fistula failure rate in older and female patients with diabetes, although small numbers and a highly selected patient population limit the generalizability of these results. Feldman et al. (13) published data from a larger cohort (348 patients), reporting a primary success rate of 54%. Preexisting cerebrovascular disease, older age, and commencement of dialysis before access creation were noted to be associated with higher primary fistula failure in their study. Ravani et al. (11) noted that cardiovascular disease and late referral to nephrologists were associated with lower primary AVF success in patients from northern Italy.More recently, Lok et al. (14) studied a cohort of 422 HD patients who were undergoing their first AVF placement to identify preoperative clinical characteristics that are predictive of fistula failure to mature and to use this information to develop a prediction rule to estimate the risk for fistula failure to mature. This prediction rule was validated in an external data set from five North American centers. Age, peripheral vascular disease, coronary artery disease, and white race all were associated with fistula failure to mature in their study; however, in this and the previously mentioned studies, it is not clear whether there was any consistent surgical assessment performed perioperatively to guide fistula placement; as such, the results may not be applicable to programs that use pre- or intraoperative surgical assessment to guide fistula placement.Given these uncertainties, we sought to determine the association of various baseline clinical parameters with primary fistula success in a cohort that consisted of all incident dialysis patients between July 1, 1999, and November 1, 2001, in Calgary, Alberta, Canada, the majority of whom had an indirect assessment of vessel diameter intraoperatively to guide the location of fistula placement.     

The efficacy of proton pump inhibitors in nonulcer dyspepsia: a systematic review and economic analysis

BACKGROUND AND AIMS: The evidence that proton pump inhibitor (PPI) therapy affects symptoms of nonulcer dyspepsia is conflicting. We conducted a systematic review to evaluate whether PPI therapy had any effect in nonulcer dyspepsia and constructed a health economic model to assess the cost-effectiveness of this approach. METHODS: Electronic searches were performed using the Cochrane Controlled Trials Register, MEDLINE, EMBASE, CINAHL, and SIGLE until September 2002. Dyspepsia outcomes were dichotomized into cured/improved versus same/worse. Results were incorporated into a Markov model comparing health service costs and benefits of PPI with antacid therapy over 1 year. RESULTS: Eight trials were identified that compared PPI therapy with placebo in 3293 patients. The relative risk of remaining dyspeptic with PPI therapy versus placebo was .86 (95% confidence interval, .78-.95; P = .003, random-effects model) with a number needed to treat of 9 (95% confidence interval, 5-25). There was statistically significant heterogeneity between trials (heterogeneity chi(2) = 30.05; df = 7; P < .001). The PPI strategy would cost an extra US dollar 278/month free from dyspepsia if the drug cost US dollar 90/month. If a generic price of US dollar 19.99 is used, then a PPI strategy costs an extra US dollar 57/month free from dyspepsia. A third-party payer would be 95% certain that PPI therapy would be cost-effective, provided they were willing to pay US dollar 94/month free from dyspepsia. CONCLUSIONS: PPI therapy may be a cost-effective therapy in nonulcer dyspepsia, provided generic prices are used.     

Concomitant 5-Aminosalicylate Therapy in Moderate-to-Severe Ulcerative Colitis Patients Escalated to Infliximab Is Not Beneficial

Digestive Diseases and Sciences - While there is recent literature to support the discontinuation of 5-aminosalicylate (5-ASA) upon the initiation of biologics, continuing 5-ASA after treatment...