Search

The purpose of this article was to report a case of unilateral late-onset nontuberculous mycobacterial keratitis after small incision lenticule extraction (SMILE).This was a case report.A 27-year-old woman presented with Mycobacterium chelonae keratitis 3 weeks after uncomplicated SMILE with a solitary interface infiltrate. The keratitis worsened after an initial response to topical fortified and interface antibiotic irrigation. Despite repeated interface irrigation and topical and oral antibiotics, progressive, diffuse stromal infiltrates followed by melting of the cap ensued over the next 6 weeks. Cap amputation and intrastromal antibiotic injection followed by prolonged topical and oral antibiotics usage for the following 5 weeks led to infiltrate resolution and re-epithelization of the residual stromal bed. All medications were tapered off over 6 months after initial presentation without recurrence, but anterior stromal scarring and corneal neovascularization persisted.Cap amputation and intrastromal antibiotic injection for intractable post-SMILE keratitis can prevent the need for therapeutic keratoplasty.

Recently, the International Endocervical Adenocarcinoma Criteria and Classification (IECC) has reorganized the classification of endocervical adenocarcinomas (ECAs), separating them into human papilloma virus (HPV)-associated (HPVA) and HPVA independent (HPVI) categories. In this study, we sought to revalidate the IECC clinical findings in an independent cohort and assess the mutational differences between HPVA and HPVI ECAs using next generation sequencing. Consecutive cases of ECAs were reclassified under the IECC. Clinicopathologic information was collected and tissue was sent for targeted next-generation sequencing in 33 genes. Associations between HPV status, clinicopathologic parameters and mutation status, with survival were evaluated. The series comprised of 85/100 HPVA (63 HPVA-usual type, 4 villoglandular, 3 mucinous intestinal, 15 mucinous not otherwise specified) and 15/100 HPVI (9 gastric, 4 mesonephric, 1 clear cell, 1 not otherwise specified). HPVA ECAs presented at a lower age (P=0.001), smaller tumor sizes (P=0.011), less margin positivity (P=0.027), less Silva pattern C (P=0.002), and lower FIGO stages (P=0.020). HPVA had superior survival compared with HPVI ECA [overall survival (P=0.0026), disease-specific survival (P=0.0092), and progression-free survival (P=0.0041)]. Factors that correlated with worse prognosis irrespective of HPV status were FIGO stage, positive margins and lymphovascular invasion (P

Purpose:The Urinary Tract Dilation classification system was designed to be more objective and reproducible than currently available grading systems. We evaluated the reliability and consistency of...

The diagnosis of clear cell (CC) carcinoma of the endometrium can be challenging, especially when endometrioid (EC) and serous (SC) endometrial cancers exhibit nonspecific clear cell changes, in carcinomas with mixed histology and in the setting of Arias-Stella reaction (ASR). In this study, classic CC immunohistochemical markers (Napsin A, HNF-1β, and ER) and 2 recent novel markers, cystathionine gamma-lyase (CTH) and arginosuccinate synthase (ASS1), are assessed for their utility in distinguishing CC from its morphologic mimics. Tissue microarrays containing 64 CC, 128 EC, 5 EC with clear cell change, 16 SC, 5 mixed carcinomas, and 11 whole ASR sections were stained, with 12 additional examples of ASR stained subsequently. A cutoff of 70% and moderate intensity were used for HNF-1β, 80% of cells and strong intensity were used for CTH, and any staining was considered positive for the remaining markers. For differentiating CC from pure EC and SC, HNF-1β, Napsin A, and CTH all performed well. HNF-1β had higher specificity (99.3% vs. 95.1%) but lower sensitivity (55.8% vs. 73.1%) compared with Napsin A. CTH did not substantially outperform HNF- 1β or Napsin A (sensitivity 51.9%, specificity 99.3%). ASS1 and ER were not helpful (specificities of 60.1% and 22.6%). For differentiating CC from ASR, HNF-1β, Napsin A, and CTH stained a large proportion of ASR and were not useful. However, ER positivity and ASS1 negativity were helpful for identifying ASR (specificity 88.2% and 95.1%, respectively). EC with clear cell changes exhibited immunohistochemical patterns similar to pure EC (HNF-1β-, ER+, and CTH-). No markers were useful in confirming the CC components in mixed carcinomas.

PurposeThe importance of cardiorespiratory fitness versus adiposity in determining heart rate variability (HRV) is unclear.MethodsFrom the Coronary Artery Risk Development in Young Adults study, an observational cohort study, we included 2316 participants (mean age = 45.2 ± 3.6 yr at year 20

Introduction: The WHO defines overweight and obesity as abnormal or excessive fat accumulation that may impair health. However, for population and clinical classification of overweight and obesity BMI is most commonly used as a proxy for adiposity. Despite the strength of the association between higher BMI and cardiometabolic disease risk across populations, and minimal direct comparison of BMI v. BF%, BMI draws significant criticism as a metric to classify obesity and screen for cardiometabolic risk. Hypothesis: BF% defined obesity classification categories have higher underlying cardiometabolic risk compared to equivalent BMI categories. Methods: We analyzed data from CARDIA study participants from the year 20 exam with concurrent measures of BMI, and BF% measured by Dual-energy X-ray absorptiometry (DXA), plus clinical measures. Sex specific BF% obesity classification categories were defined by evidence-based diagnostic and classification performance measures vs. standard BMI cut points. Underlying cardiometabolic risk was defined by a continuous metabolic syndrome risk score (MetS), consisting of the averaged standardized deviates of the 5 ATP III components. Higher MetS z-scores indicate higher overall risk. MetS z-scores between categories (e.g. obesity defined by BMI v. BF%) were compared by z-tests. Results: The figure reports the distribution of obesity classification categories by the different metrics and underlying cardiometabolic risk. The MetS risk score was significantly higher in BMI defined overweight and obesity compared to BF% defined categories; and BF% defined obesity categories classify a greater prevalence of the population as obese compared to BMI. Results for MetS risk did not differ by race/sex or when including prevalent cardiometabolic disease. Conclusions: Physiologically defined BF% obesity categories classify a greater prevalence of obesity in CARDIA at year 20, whereas there was higher underlying cardiometabolic risk in BMI defined obesity classification categories.

Little is known about anorectal function and quality of life after chemoradiation followed by local excision, which is an alternative to total mesorectal excision for selected patients with early rectal cancer.The purpose of this study was to prospectively assess anorectal function and health-related quality of life of patients with T2N0 rectal cancer who were treated with an alternative approach.This was a prospective, phase II trial.The study was multicentric (American College of Surgeons Oncology Group trial Z6041).Patients with stage cT2N0 rectal adenocarcinomas were treated with an oxaliplatin/capecitabine-based chemoradiation regimen followed by local excision.Anorectal function and quality of life were assessed at enrollment and 1 year postoperatively with the Fecal Incontinence Severity Index, Fecal Incontinence Quality of Life scale, and Functional Assessment of Cancer Therapy-Colorectal Questionnaire. Results were compared, and multivariable analysis was performed to identify predictors of outcome.Seventy-one patients (98%) were evaluated at enrollment and 66 (92%) at 1 year. Compared with baseline, no significant differences were found on Fecal Incontinence Severity Index scores at 1 year. Fecal Incontinence Quality of Life results were significantly worse in the lifestyle (p0.001), coping/behavior (p0.001), and embarrassment (p = 0.002) domains. There were no differences in the Functional Assessment of Cancer Therapy overall score, but the physical well-being subscale was significantly worse and emotional well-being was improved after surgery. Treatment with the original chemoradiation regimen predicted worse depression/self-perception and embarrassment scores in the Fecal Incontinence Quality of Life, and male sex was predictive of worse scores in the Functional Assessment of Cancer Therapy overall score and trial outcome index.Small sample size, relatively short follow-up, and absence of information before cancer diagnosis were study limitations.Chemoradiation followed by local excision had minimal impact on anorectal function 1 year after surgery. Overall quality of life remained stable, with mixed effects on different subscales. This information should be used to counsel patients about expected outcomes.

Background and Purpose: Intracerebral hemorrhage (ICH) expansion is an independent predictor of mortality and functional outcome with each milliliter of expansion increasing the chance of functional dependence by up to 7%. Unfortunately, detection of ICH expansion is often subjective, inaccurate, and may misguide treatment pathways. Artificial intelligence with convolutional neural networks (CNNs) represents a powerful new technology for image analysis and quantification. This study compares the accuracy, sensitivity, and specificity between a CNN optimized for ICH volume quantification and a traditional ABC/2 method. Materials and Methods: We performed a retrospective analysis of ICH patients who have had at least one follow-up non-contrast head CT (NCCT) within 24 hours. ICH expansion was defined as >33% volume of expansion, corresponding to a 10% increase in diameter. Each ICH was manually segmented, which served as ground truth measurements. Comparison of ICH expansion was made using (1) a traditional ABC/2 estimative approach and (2) a previously validated hybrid 3D/2D mask ROI-based CNN for ICH evaluation, which was trained previously on over 10,000 patients. Accuracy, sensitivity, and specificity of the CNN and ABC/2 approaches were then compared. Results: A total of 230 patients were included for a total of 460 NCCTs. The average ICH volume was 44.8 mL. The average ICH volume for the CNN was 45.3 mL (Pearson 0.99) and for ABC/2 was 60.4 mL (Pearson 0.81). Accuracy, sensitivity, and specificity for ICH expansion detection was 100%, 100%, and 100% for the CNN and 93.0%, 74.2%, and 96.0% for ABC/2. On visual inspection, cases of false positives by ABC/2 approaches tended to demonstrate eccentric expansion (Figure 1). Conclusions: A customized deep learning tool is highly accurate in the detection of ICH expansion. This may have important implications clinically for management and surveillance as well as in a clinical trial setting.

Epithelial ovarian cancer consists of 5 major histotypes: high-grade serous carcinoma (HGSC), endometrioid carcinoma (EC), clear cell carcinoma (CCC), mucinous carcinoma (MC) and low-grade serous (LGSC). Each can have a broad spectrum of morphological appearances, and one histotype can closely mimic histopathological features more typical of another. Historically, there has been a relatively high frequency of mixed, defined by 2 or more distinct histotypes present based on routine histopathological assessment, histotype carcinoma diagnoses (3–11%), however recent immunohistochemical studies identifying histotype specific markers and allowing more refined histotype diagnoses suggests a much lower incidence. We reviewed hematoxylin and eosin stained slides from 871 cases of epithelial ovarian cancer and found the frequency of mixed carcinomas to be 1.7% when modern diagnostic criteria are applied. Through international collaboration, we established a cohort totaling 22 mixed epithelial ovarian cancers, consisting of 9 EC/CCC, 4 EC/LGSC, 3 HGSC/CCC, 2 CCC/MC and 4 other combinations. We interrogated the molecular differences between the different components of each case using immunohistochemistry, gene expression and hotspot sequencing analyses. Immunohistochemical data alone suggested 9 of the 22 cases were not mixed tumors as they presented a uniform immuno-phenotype throughout, and these cases most probably represent morphological mimicry and variation within tumors of a single histotype. Synthesis of molecular data further reduces the incidence of mixed carcinomas. Based on these results, true mixed carcinomas with both morphological and molecular support for the presence of more than one histotype within a given tumor represent less than 1% of epithelial ovarian cancers.

There are few guidelines and little data on imaging after urinary tract infections in older children. We determined the clinical yield of renal and bladder ultrasound, and voiding cystourethrogram in older children and adolescents after urinary tract infection.We analyzed findings on voiding cystourethrogram, and renal and bladder ultrasound as well as the clinical history of patients who underwent the 2 studies on the same day between January 2006 and December 2010. We selected for study patients 5 to 18 years old who underwent imaging for urinary tract infection. Those with prior postnatal genitourinary imaging or prenatal hydronephrosis were excluded from analysis.We identified a cohort of 153 patients, of whom 74% were 5 to 8 years old, 21% were 8 to 12 years old and 5% were 12 to 18 years old. Of the patients 77% were female, 78% had a febrile urinary tract infection history and 55% had a history of recurrent urinary tract infections. Renal and bladder ultrasound findings revealed hydronephrosis in 7.8% of patients, ureteral dilatation in 3.9%, renal parenchymal findings in 20% and bladder findings in 12%. No patient had moderate or greater hydronephrosis. Voiding cystourethrogram showed vesicoureteral reflux in 34% of cases and bladder or urethral anomalies in 12%. Reflux was grade I, II-III and greater than III in 5.9%, 26% and 2% of patients, respectively. For any voiding cystourethrogram abnormality the sensitivity and specificity of any renal and bladder ultrasound abnormality were 0.49 (95% CI 0.37-0.62) and 0.76 (95% CI 0.66-0.84), respectively. Positive and negative predictive values were 0.58 (95% CI 0.44-0.71) and 0.69 (0.59-0.77), respectively.In older children with a history of urinary tract infection the imaging yield is significant. However, imaging revealed high grade hydronephrosis or high grade vesicoureteral reflux in few patients. Renal ultrasound is not reliable for predicting voiding cystourethrogram findings such as vesicoureteral reflux.

Fitness decline, high body mass index (BMI), and insulin resistance (IR) are associated with worsening cardiometabolic risk factors prospectively; modification of the fitness change effect by BMI and IR remains unknown.Participants from the Coronary Artery Risk Development in Young Adults study without diabetes at year 0 (Y0) (n = 2048, 43.4% men; mean age, 25 yr) had fitness quantified by treadmill at Y0 and Y20. Y0 BMI was normal (nBMI25 kg·m) or high (hBMI ≥25 kg·m). Y0 IR status was insulin sensitive (IS) (homeostatic model assessment IR1.84 (75th percentile)) or insulin resistant (IR) (homeostatic model assessment IR ≥1.84). Four groups were established: nBMI/IS, hBMI/IS, nBMI/IR, and hBMI/IR. Y0 fitness was low (33rd percentile for sex) or average high (≥33rd percentile for sex). Fitness change (treadmill time: Y20-Y0) was maintained (increase or decline ≤20th percentile for sex) or decreased (decline20th percentile for sex). The outcomes were incident diabetes and percentage change over 25 yr in weight, waist girth, blood pressure, and lipid profile. Analysis was by multiple linear regression and proportional hazards regression with adjustment for individual characteristics.Maintained fitness after 20 yr was associated with greater increase in HDL cholesterol and less increase in weight, waist girth, blood pressure, and triglycerides than decreased fitness, similarly for the groups defined by BMI and IR. Maintained fitness reduced the rate of incident diabetes in IS but not IR participants.Maintained fitness after 20 yr was associated with more favorable middle-age cardiometabolic risk factors than decreased fitness; this benefit might be blunted by baseline IR.

Introduction: Whether trajectories in fasting glucose (FG) and insulin resistance (HOMA-IR) during young adulthood, before the onset of diabetes, are associated with cardiac function and structure in middle adulthood is unclear. Hypothesis: We tested the hypothesis that as compared to low-stable trajectory of FG and HOMA-IR, an increasing trajectory for each would be associated with worse cardiac structure and function in middle adulthood. Methods: We determined FG and HOMA-IR for 2,198 CARDIA participants, age 18-30 years, at baseline (1985-1986) and 7, 10, 15, 20, and 25 year follow-up exams who fasted for >8 hours and were not pregnant and were free from diabetes at all exams. At year 30 (2016), Doppler echocardiography and 2D-guided M-mode echocardiography was performed, measuring left atrial dimension, relative wall thickness, left ventricular (LV) mass, LV mass indexed to height, LV ejection fraction percentage, LV end-diastolic and systolic volume, and LV mass to volume ratio. Trajectories were determined using latent class analysis (SAS Proc Traj). We used multivariable linear regression to estimate adjusted means for echo measures according to FG and HOMA-IR trajectory group after adjustment for potential confounding factors. Results: For individuals free from diabetes in midlife, we identified three trajectory groups for both FG and HOMA-IR, low-stable to increasing, moderate-increasing, and high-increasing. Compared to low-stable trajectory for FG, increasing trajectory was associated with greater LV end-diastolic volume, whereas for HOMA-IR increasing trajectory was associated with lower LV end-diastolic volume ( Table ). Increasing FG trajectory was also associated with greater left atrial dimension, while HOMA-IR was not. Conclusion: Trajectory of both FG and HOMA-IR during young adulthood, in the absence of diabetes, was most prominently and differentially associated with LV end-diastolic volume. Future research should elaborate on differential associations of FG and HOMA-IR trajectory.

OBJECTIVE Magnetic resonance imaging is the gold standard in retrocochlear imaging; however, its role in management of inner ear diseases remains poorly defined. In this study, we investigate the utility of MRI in defining the nature of intracochlear pathology. STUDY DESIGN A retrospective review of 11 patients with inner ear abnormalities on MRI between 2010 and 2013. Patients' diagnosis included cholesteatoma, labyrinthitis, meningitis, and intralabyrinthine schwannoma. SETTING Tertiary care hospital. MAIN OUTCOME MEASURES T1, T2, and postcontrast signal intensities were measured within the lesion and normalized in reference to the contralateral normal cochlea. The following ratios were calculated: T1 postgadolinium lesion/contralateral cochlea, T2 lesion/contralateral cochlea and T1 lesion/contralateral cochlea. Statistical analysis was conducted using the unpaired Student's t test using IBM SPSS Statistics version 20.0.0. RESULTS The relative intensity ratios were useful in defining the nature of inner ear lesion. Normalized T1 postgadolinium lesion intensities were significantly higher in the tumor group (3.98 ± 0.880 versus 1.71 ± 0.370, p < 0.0002). Normalized T1 precontrast signal intensities were higher in tumors (1.33 ± 0.200 versus 0.842 ± 0.426, p < 0.0626), and T2 values were lower in tumors (0.838 ± 0.491 versus 1.10 ± 0.305, p < 0.317); however, these did not reach significance. CONCLUSION Intensity of gadolinium enhancement on MRI is useful in differentiation of inflammation from tumors; normalized T1 postgadolinium intensity ratio greater than 3 is strongly suggestive of intralabyrinthine tumor.

After prospective measurement of radiation exposure during pediatric ureteroscopy for urolithiasis, we identified targets for intervention. We sought to systematically reduce radiation exposure during pediatric ureteroscopy.We designed and implemented a pre-fluoroscopy quality checklist for patients undergoing ureteroscopy at our institution as part of a quality improvement initiative. Preoperative patient characteristics, operative factors, fluoroscopy settings and radiation exposure were recorded. Primary outcomes were the entrance skin dose in mGy and midline dose in mGy before and after checklist implementation.We directly observed 32 consecutive ureteroscopy procedures using the safety checklist, of which 27 were done in pediatric patients who met study inclusion criteria. Outcomes were compared to those in 37 patients from the pre-checklist phase. Pre-checklist and postchecklist groups were similar in patient age, total operative time or patient thickness. The mean entrance skin dose and midline dose were decreased by 88% and 87%, respectively (p0.01). Significant improvements were noted among the major radiation dose determinants, total fluoroscopy time (reduced by 67%), dose rate setting (appropriately reduced dose setting in 93% vs 51%) and excess skin-to-intensifier distance (reduced by 78%, each p0.01).After systematic evaluation of our practices and implementation of a fluoroscopy quality checklist, there were dramatic decreases in radiation doses to children during ureteroscopy.

Background Meningiomas are slow-growing tumors that may present in pregnancy because of accelerated growth. We present the case of a recurrent meningioma in two separate pregnancies in the same woman. Case A 35-year-old woman presented at 30 weeks of gestation with limb weakness, vomiting, and a progressive decreased level of consciousness with an enlarging forehead mass. Imaging revealed a massive extra-axial exophytic tumor. An emergency craniotomy was performed, complicated by massive blood loss. Final pathology showed a grade I meningioma positive for progesterone receptors. Maternal-fetal outcome was good, with return of normal neurologic status and elective delivery at 38 weeks of gestation. Conclusion Pregnancy is associated with accelerated meningioma growth and recurrence. Treatment during pregnancy is possible and requires a multidisciplinary approach.

Canonical Wnt/β-catenin signaling plays important roles during vertebrate heart development and inhibition of this pathway has been shown to improve injured heart repair by promoting cardiac progenitor cells’ differentiation. Despite extensive research, to date, no approved Wnt inhibitors are available in clinic. Triptonide is a key bioactive small molecule identified in a traditional Chinese medicine named Tripterygium wilfordii Hook F., and its cellular target has not been identified. Here we showed that triptonide effectively inhibited canonical Wnt/β-catenin signaling by targeting a very downstream nuclear component associated with c-termini-transaction domain of β-catenin. Tripterygium wilfordii Hook F., which contains triptonide, has been traditionally used in clinic in China, suggesting that triptonide may have ideal drug properties. Our discovery of triptonide as an effective Wnt inhibitor may represent an important step in identification of bioactive small molecule drugs to stimulate endogenous cardiac progenitor cells for cardiac repair.

Accurate measurement of anterior urethral stricture length is critical to determine the appropriate surgical approach. Retrograde urethrogram is often used to determine stricture location and length. However, the adult literature shows that retrograde urethrogram may underestimate stricture length. We investigated the role of sonographic urethrogram in the preoperative evaluation of adolescent urethral stricture disease.Between June 2008 and February 2009 we retrospectively evaluated 12 pediatric patients with urethral stricture disease using retrograde and sonographic urethrogram. Stricture length was categorized by 2 radiologists as I-less than 1, II-1 to 3 and III-greater than 3 cm. On sonographic urethrogram stricture length was measured as the longest extent of the urethral abnormality.Mean patient age was 16.9 years (range 9.5 to 20.8). Retrograde urethrogram classified 7 cases as category I, 4 as category II and none as category III stricture, and 1 with no evidence of stricture. Sonographic urethrogram revealed strictures greater than 1 cm in all 7 category I cases and 2 of the 4 category II cases had strictures longer than 3 cm. One patient in whom retrograde urethrogram showed a category II stricture was stricture-free on sonographic urethrogram. One patient with a negative retrograde urethrogram had a stricture on sonographic urethrogram. Sonographic urethrogram upgraded stricture length in 10 of the 12 patients and outperformed retrograde urethrogram in 11.Sonographic urethrogram is effective for evaluating adolescent urethral stricture disease. It may provide more accurate measurement of stricture length and improve preoperative planning.

We prospectively evaluated the precision of ultrasound and computerized tomography to diagnose urinary stones in children and determined whether these differences in radiological findings have any impact on clinical management.A total of 50 consecutive patients with suspected urolithiasis underwent computerized tomography and ultrasound. Two radiologists reviewed each study independently in blinded fashion. When a difference in findings was detected, 8 pediatric urologists reviewed the case. Clinical management was based on the results of each radiological test independently. Statistical analysis was performed using Fisher's exact test.Compared to computerized tomography ultrasound had 76% sensitivity and 100% specificity. In 8 patients stone(s) seen on computerized tomography was not seen on ultrasound. The average size of missed stones was 2.3 mm. In 7 patients computerized tomography showed stones bilaterally but stone was seen on only 1 side on ultrasound. When evaluating the clinical impact, the ultrasound/computerized tomography discrepancy did not result in any significant change in clinical management except in 4 cases. In these cases ultrasound findings suggested that additional imaging was required and, thus, stone(s) in the distal ureter would have been identified on subsequent imaging.Although computerized tomography is more sensitive for detecting urolithiasis than ultrasound, the difference in usefulness between the 2 radiological tests may not be clinically significant. Given concerns for the potentially harmful cumulative long-term effect of radiation, ultrasound should be considered the first imaging test in children with suspected urolithiasis.

To the Editors:Curcumin is a polyphenolic molecule that comprises approximately 5% of turmeric, giving the spice its color but not flavor. It is used in processed foods as a yellow coloring. 1 Because of its anti-inflammatory and antioxidant properties, curcumin has been tested in animal models of A

Ginkgo biloba was found to exert a significant inductive effect on CYP2C19 activity. This study was designed to investigate the potential herb-drug interaction between G. biloba and omeprazole, a widely used CYP2C19 substrate, in subjects with different CYP2C19 genotypes.Eighteen healthy Chinese subjects previously genotyped for CYP2C19 were selected. All subjects received a single omeprazole 40 mg at baseline and then at the end of a 12-day treatment period with G. biloba (140 mg, bid). Multiple blood samples were collected over 12 h, and 24 h urine was collected post omeprazole dosing. Plasma and urine concentrations of omeprazole and its metabolites, 5-hydroxyomeprazole and omeprazole sulfone, were determined, and their pharmacokinetics calculated non-compartmentally.Plasma concentrations of omeprazole and omeprazole sulfone were significantly decreased, and 5-hydroxyomeprazole significantly increased following G. biloba administration in comparison to baseline. A significant decrease in the ratio of area under the plasma concentration-time curve (AUC) of omeprazole to 5-hydroxyomeprazole was observed in the homozygous extensive metabolizers, heterozygous extensive metabolizers, and poor metabolizers, respectively. The decrease was greater in PMs than EMs. No significant changes in the AUC ratios of omeprazole to omeprazole sulfone were observed. Renal clearance of 5-hydroxyomeprazole was significantly decreased after G. biloba, but the change was not significantly different among the three genotype groups.Our results show that G biloba can induce omeprazole hydroxylation in a CYP2C19 genotype-dependent manner and concurrently reduce the renal clearance of 5-hydroxyomeprazole. Co-administration of G. biloba with omeprazole or other CYP2C19 substrates may significantly reduce their effect, but further studies are warranted.

OBJECTIVE AND IMPORTANCE: An unusual foreign body traversing the spinal canal at the foramen magnum level is described. Interesting radiological findings and a review of nonmissile penetrating injuries are presented. This case demonstrates the importance of a thorough physical examination and the use of neurodiagnostic imaging in an inebriated, uncooperative patient with neurological dysfunction. CLINICAL PRESENTATION: The patient presented with quadriparesis confounded by cocaine intoxication. A physical examination revealed only a small punctate lesion in the posterior occipital region. INTERVENTION: After detection of the foreign body, the patient underwent immediate surgical exploration and removal of the object. The dura was repaired primarily, and the patient was maintained on intravenous antibiotics for 7 days. CONCLUSION: With physical therapy, the patient was walking with assistance at 2 weeks postsurgery. Upper extremity strength, especially intrinsic hand movement, was most severely affected. At 10 months' follow-up, the patient's only deficits were mild intrinsic hand weakness and incoordination with fine finger movements. Immediate surgical exploration is indicated for patients with retained fragments and progressive neurological dysfunction.

Defibrillation energy requirements may be altered by antiarrhythmic agents. We investigated the effects of moricizine on the defibrillation threshold (DFT) in 18 pentobarbital-anesthetized pigs. The animals were randomized, in a blinded fashion, to moricizine or control (0.9% saline) treatment groups. Each group underwent three treatment phases: baseline, drug infusion (moricizine or saline), and drug infusion combined with lidocaine. Moricizine (2 mg/kg loading dose, 1.5 mg/kg/h infusion) and lidocaine (5 mg/kg loading dose, 4 mg/kg/h infusion) were dosed to achieve therapeutic concentrations. After 5 s of induced ventricular fibrillation, defibrillation was performed using a cardiac defibrillator interfaced with two epicardial electrode patches. DFTs were determined at baseline, during the drug phase, and during the combination of lidocaine with moricizine or saline. DFT values in the animals randomized to the control group were 15.2 +/- 4.2, 14.0 +/- 3.3, and 17.8 +/- 8.7 J at baseline, saline infusion, and saline combined with lidocaine, respectively. No significant differences were observed among the treatment phases. DFT values in the animals randomized to moricizine group were 12.1 +/- 2.8, 13.8 +/- 5.2, and 22.9 +/- 7.1 J at baseline, moricizine infusion, and moricizine combined with lidocaine, respectively. The DFT values during the lidocaine-moricizine combination treatment phase were significantly greater than baseline and moricizine alone (p < 0.002). The mean change in the DFT from baseline to moricizine (14% increase) was significantly different than the mean change in the DFT from baseline to saline (8% decrease) (p = 0.03). Lidocaine added to moricizine increased the DFT by 84%, which was significantly different from the 27% increase in the DFT when lidocaine was added to saline (p = 0.02). We conclude that moricizine minimally increases the DFT, but the combination of moricizine with lidocaine results in a synergistic rise in the DFT that may have detrimental clinical implications.

Objective To describe and analyse the factors affecting the pregnancy rate of laparoscopic ovarian drilling for polycystic ovarian syndrome in women with anovulatory infertility. Design A retrospective study. Setting A specialist infertility clinic based at a teaching hospital in England. Population One hundred and eighteen women, for whom hospital records and follow up data were available, with polycystic ovarian syndrome who underwent laparoscopic ovarian surgery for anovulatory infertility over a five year period, between January 1991 and December 1995. Main Outcome measures Ovulation and pregnancy rate. Results The cumulative conception rate 12 months after the treatment was 54%. Women who conceived following the surgery had a shorter duration of infertility, were treated with diathermy (rather than laser), had higher pre-operative luteinising hormone levels, were younger and were more likely to have ultrasonographic evidence of polycystic ovarian disease. Logistic multiple regression analysis showed that the duration of infertility, modality used in treatment (laser or diathermy) and the preoperative levels were the main determinants of the outcome. Conclusion Women with polycystic ovarian syndrome respond favourably to laparoscopic ovarian drilling. The success rate in women with infertility duration of less than three years, treated with diathermy, in whom the pre-operative level was more than 10 IU/L reached 79%.

Using quantitative and qualitative methodology, a study was conducted on the process of case management performed by nurse case managers on a group of 45 post-discharged frail elderly patients in 2001-2002. The quantitative data provided the common reasons for client-initiated telephone calls to nurse case managers and the nurse case managers' interventions to these calls. Qualitative data yielded 9 major themes on which a sequential and dynamic process model of case management was conceptualized. Another 7 thematic descriptions on essential factors for the successful implementation of case management were configured in a dual-dimensional framework of staff and structural factors.

Previous CPR studies from our laboratory have shown that a standard iv dose of lidocaine (2 mg/kg) has a rapid antifibrillatory effect, while a standard dose of bretylium (5 mg/kg) produces a delayed but more pronounced effect. In order to determine the optimal doses, we investigated the antifibrillatory effects of a) high dose bretylium (10 mg/kg) and b) a combination of lidocaine (2 mg/kg) and bretylium (5 mg/kg) during CPR in two groups of anesthetized dogs. Ventricular fibrillation threshold (VFT) was determined using a train method and CPR was performed by a pneumatic device. During both a control and drug phase, the VFT was determined in each dog before CPR, and after each of three consecutive 3-min CPR periods. The combination of lidocaine and bretylium (11 dogs) caused a significant increase in VFT compared to the control phase after each of the 3-min CPR periods and maintained this effect for greater than 2 h. Bretylium 10 mg/kg (eight dogs) significantly elevated the VFT only after the third 3-min CPR period. We conclude that the combination of standard doses of lidocaine and bretylium produces a rapid and prolonged antifibrillatory effect and may be the optimal regimen in the CPR setting. High dose bretylium has a delayed onset of effect and appears to produce no greater effect than standard doses of the drug.

To investigate the interaction of cyclosporine nephrotoxicity and renal ischemia, an animal model in rats with bilateral renal artery clamping was used. Rats given cyclosporine had a lower rate of recovery from ischemia. However, the percentages of reduction in glomerular filtration rate in vehicle and cyclosporine groups were the same in sham-operated or ischemically treated group. This suggests a superimposition of cyclosporine nephrotoxicity on the recovering kidneys rather than synergistic potentiation between ischemia and cyclosporine nephrotoxicity.