Patterns, predictors and prognostic relevance of high-grade hematotoxicity after temozolomide or temozolomide-lomustine in the CeTeG/NOA-09 trial.

PURPOSE: In the randomized phase III trial CeTeG/NOA-09, temozolomide (TMZ)/lomustine (CCNU) combination therapy was superior to TMZ in newly diagnosed MGMT methylated glioblastoma, albeit reporting more frequent hematotoxicity. Here, we analyze high grade hematotoxicity and its prognostic relevance in the trial population. METHODS: Descriptive and comparative analysis of hematotoxicity adverse events ≥ grade 3 (HAE) according to the Common Terminology of Clinical Adverse Events, version 4.0 was performed. The association of HAE with survival was assessed in a landmark analysis. Logistic regression analysis was performed to predict HAE during the concomitant phase of chemotherapy. RESULTS: HAE occurred in 36.4% and 28.6% of patients under CCNU/TMZ and TMZ treatment, respectively. The median onset of the first HAE was during concomitant chemotherapy (i.e. first CCNU/TMZ course or daily TMZ therapy), and 42.9% of patients with HAE receiving further courses experienced repeat HAE. Median HAE duration was similar between treatment arms (CCNU/TMZ 11.5; TMZ 13 days). Chemotherapy was more often discontinued due to HAE in CCNU/TMZ than in TMZ (19.7 vs. 6.3%, p = 0.036). The occurrence of HAE was not associated with survival differences (p = 0.76). Regression analysis confirmed older age (OR 1.08) and female sex (OR 2.47), but not treatment arm, as predictors of HAE. CONCLUSION: Older age and female sex are associated with higher incidence of HAE. Although occurrence of HAE was not associated with shorter survival, reliable prediction of patients at risk might be beneficial to allow optimal management of therapy and allocation of supportive measures. TRIAL REGISTRATION: NCT01149109.

A large multicenter cohort on the use of full-thickness resection device for difficult colonic lesions.

BACKGROUND: Introduction of the full-thickness resection device (FTRD) has allowed endoscopic resection of difficult lesions such as those with deep wall origin/infiltration or those located in difficult anatomic locations. The aim of this study is to assess the outcomes of the FTRD among its early users in the USA. METHODS: Patients who underwent endoscopic full-thickness resection (EFTR) for lower gastrointestinal tract lesions using the FTRD at 26 US tertiary care centers between 10/2017 and 12/2018 were included. Primary outcome was R0 resection rate. Secondary outcomes included rate of technical success (en bloc resection), achievement of histologic full-thickness resection (FTR), and adverse events (AE). RESULTS: A total of 95 patients (mean age 65.5 ± 12.6 year, 38.9% F) were included. The most common indication, for use of FTRD, was resection of difficult adenomas (non-lifting, recurrent, residual, or involving appendiceal orifice/diverticular opening) (66.3%), followed by adenocarcinomas (22.1%), and subepithelial tumors (SET) (11.6%). Lesions were located in the proximal colon (61.1%), distal colon (18.9%), or rectum (20%). Mean lesion diameter was 15.5 ± 6.4 mm and 61.1% had a prior resection attempt. The mean total procedure time was 59.7 ± 31.8 min. R0 resection was achieved in 82.7% while technical success was achieved in 84.2%. Histologically FTR was demonstrated in 88.1% of patients. There were five clinical AE (5.3%) with 2 (2.1%) requiring surgical intervention. CONCLUSIONS: Results from this first US multicenter study suggest that EFTR with the FTRD is a technically feasible, safe, and effective technique for resecting difficult colonic lesions.

Study of IRF6 and 8q24 region in non-syndromic oral clefts in the Brazilian population.

OBJECTIVES: We investigated the association between non-syndromic oral cleft and variants in IRF6 (rs2235371 and rs642961) and 8q24 region (rs987525) according to the ancestry contribution of the Brazilian population. SUBJECTS AND METHODS: Subjects with oral cleft (CL, CLP, or CP) and their parents were selected from different geographic regions of Brazil. Polymorphisms were genotyped using a TaqMan assay and genomic ancestry was estimated using a panel of 48 INDEL polymorphisms. RESULTS: A total of 259 probands were analyzed. A TDT detected overtransmission of the rs2235371 G allele (P = 0.0008) in the total sample. A significant association of this allele was also observed in CLP (P = 0.0343) and CLP + CL (P = 0.0027). IRF6 haplotype analysis showed that the G/A haplotype increased the risk for cleft in children (single dose: P = 0.0038, double dose: P = 0.0022) and in mothers (single dose: P = 0.0016). The rs987525 (8q24) also exhibited an association between the A allele and the CLP + CL group (P = 0.0462). These results were confirmed in the probands with European ancestry. CONCLUSIONS: The 8q24 region plays a role in CL/P and the IRF6 G/A haplotype (rs2235371/rs642961) increases the risk for oral cleft in the Brazilian population.

Antimicrobial management of septic arthritis of the hand and wrist.

PURPOSE: The optimal antimicrobial treatment for patients with hand or wrist septic arthritis is unknown. We report the treatment outcomes in patients with these infections. METHODS: The medical records of 40 consecutive adult patients with hand or wrist septic arthritis treated at our institution from 2000 to 2008 were retrospectively reviewed. The primary outcome measure was treatment failure (histopathologic or microbiologic evidence of relapsed infection from the same joint or a contiguous anatomic area). RESULTS: Involved joints were the wrist (n = 10, 25 %), metacarpal-phalangeal (n = 11, 27.5 %), proximal interphalangeal (n = 8, 20 %), distal interphalangeal (n = 10, 25 %), and thumb interphalangeal (n = 1, 2.5 %). Methicillin-sensitive (n = 15, 45 %) and -resistant (n = 7, 17.5 %) Staphylococcus aureus were the most common pathogens. Surgical therapies included open arthrotomy with debridement (n = 33, 82.5 %), arthroscopic debridement (n = 2, 5 %), and aspiration alone (n = 5, 12.5 %). Most patients (23/40, 58 %) received less than 1 week of parenteral antimicrobial therapy. Only two patients developed definite antimicrobial treatment failure, one of whom had an atypical mycobacterium infection. Patients with subacute to chronic infections were at high risk for finger amputation. CONCLUSIONS: When combined with surgical debridement, relatively short courses of parenteral antimicrobial treatment (<1 week) supplemented with oral therapy for an additional 2-3 weeks is usually sufficient antimicrobial therapy for hand or wrist septic arthritis.

Oral antibiotic treatment and long-term outcomes of Lyme facial nerve palsy.

PURPOSE: To study the long-term functional outcomes of patients with Lyme facial nerve palsy treated with oral antibiotics. METHODS: We conducted a retrospective double-cohort study involving patients with Lyme facial nerve palsy treated with oral antibiotics matched to three controls with early localized Lyme disease. Chart review was completed and an SF-36 health questionnaire and standardized symptom questionnaire administered. RESULTS: Lyme facial nerve palsy patients were treated with oral antibiotics for a median duration of 21 days (range 7-30 days). Only three patients underwent lumbar puncture and each demonstrated lymphocytic pleocytosis. Fourteen of 15 patients with Lyme facial nerve palsy completely regained nerve function. The long-term outcomes were similar between patients with Lyme facial nerve palsy and controls after a median follow-up duration of 4.6 years. Patients with Lyme facial nerve palsy had significantly higher reported rates of fatigue (60%) than controls (27%) (p = 0.019), but similar energy and vitality scores on the SF-36 questionnaire (55.0 vs. 58.4, p = 0.621). SF-36 social functioning domain scores were significantly lower in patients with Lyme facial nerve palsy (77.5) than in controls (88.6) (p = 0.044). There were no other significant differences noted between the two cohorts. CONCLUSIONS: For patients with Lyme facial nerve palsy in North America, treatment with oral doxycycline appears to be an effective therapeutic strategy.

Self-expanding plastic esophageal stents versus jejunostomy tubes for the maintenance of nutrition during neoadjuvant chemoradiation therapy in patients with esophageal cancer: a retrospective study.

In patients undergoing chemoradiotherapy for esophageal cancer, the inability to eat may severely impair nutritional status. We conducted a retrospective study to compare the efficacy of the Polyflex self-expanding silicone stent (PS) versus a jejunostomy tube (JT) for maintaining nutrition during neoadjuvant chemoradiation therapy in patients with esophageal cancer who were scheduled for resectional surgery. Thirty-six patients were treated either with PS placement (12 patients) or JT placement (24 patients) prior to receiving an 8-week course of chemoradiation therapy. Patients were interviewed weekly until cessation of therapy. Patient data were collected on procedural success and complication rates, nutritional status, and dysphagia scores. PS placement was successful in 11 of 12 patients (92%), and those 11 patients were able to resume oral nutrition. Dysphagia scores improved from a mean of 3 to 1 in the PS group (P < 0.005) but did not change significantly in the JT group. PS were removed endoscopically without complications prior to the esophagectomies. Albumin levels and weight increased significantly in both the PS and JT groups. There were no significant differences between groups in the procedural success rates (PS 92% vs. JT 100%, P = 0.33), complication rates (PS 22% vs. JT 4%, P = 0.11), mean increase in weight (PS 4.4 kg vs. JT 4.2 kg, P = 0.59), and mean increase in serum albumin (PS 0.62 g/dL vs. JT 0.44 g/dL, P = 0.05). PS is a safe and effective alternative to a surgical JT for maintaining nutrition in this subset of patients.

The effect of combined therapy on activity of cathepsin D and alpha-1-antitrypsin in the blood serum of women with cervical cancer.

PURPOSE OF INVESTIGATION: The aim of the study was to determine the activity of cathepsin D (CTSD) and alpha-1-antitrypsin (AAT) in the blood serum of women with cervical carcinoma treated with different modes of therapy. METHODS: The study was conducted on 68 women suffering from carcinoma of the uterine cervix, that were irradiated intracavitarily by a Selectron LDR brachytherapy unit. Additionally, all patients were treated with different therapy methods according to clinical stage. RESULTS: In women with cervical cancer, CTSD activity was higher while AAT activity was lower both before and after brachytherapy sessions as compared to controls. Six months after the end of therapy, the activity of CTSD and AAT reverted back to the values characteristic for healthy women. CONCLUSION: The estimation of cathepsin D and alpha-1-antitrypsin activity during the course of cervical cancer management may be useful in early detection of potential recurrence and/or widespread metastasis formation.

Follow-up MR imaging in patients with pyogenic spine infections: lack of correlation with clinical features.

BACKGROUND AND PURPOSE: Follow-up MR imaging examinations are increasingly used to monitor response to treatment in patients with spine infection. We aim to describe follow-up MR imaging examination findings 4-8 weeks after diagnosis and initiation of treatment of spine infections and to compare with clinical findings. MATERIALS AND METHODS: Thirty-three patients with spinal infection and available baseline and 4-8-week follow-up MRIs were included in this retrospective cohort study. Baseline and follow-up MR imaging were graded by 2 neuroradiologists blinded to clinical characteristics and outcome. Clinical findings and outcomes were independently obtained by retrospective review of the medical record. RESULTS: Compared with baseline MR imaging examinations, follow-up MR imaging more frequently demonstrated vertebral body loss of height (26/33 [79%] versus 14/33 [47%]; P < .001) and less frequently demonstrated epidural enhancement (19/32 [59%] versus 29/33 [88%]; P = .008), epidural canal abscess (3/32 [9%] versus 15/33 [45%]; P = .001), and epidural canal compromise (10/32 [31%] versus 19/33 [58%]; P = .008). Most follow-up MR imaging examinations demonstrated less paraspinal inflammation and less epidural enhancement compared with baseline. However, vertebral body enhancement, disk space enhancement, and bone marrow edema more often were equivocal or appeared worse compared with baseline. Twenty-one of 32 (66%) follow-up MR imaging examination overall grades were considered improved, 5 (16%) were equivocal, and 6 (19%) were worse. No single MR imaging finding was associated with clinical status. CONCLUSION: Soft tissue findings, not bony findings, should be the focus of clinicians interpreting follow-up MR imaging results. No single MR imaging parameter was associated with the patients' clinical status.

Effects of expiratory muscle activation via high-frequency spinal cord stimulation.

In persons with spinal cord injury, lower thoracic low-frequency spinal cord stimulation (LF-SCS; 50 Hz, 15 mA) is a useful method to restore an effective cough. Unfortunately, the high-stimulus-amplitude requirements and potential activation of pain fibers significantly limit this application in persons with intact sensation. In this study, the mechanism of the expiratory muscle activation, via high-frequency SCS (HF-SCS; 500 Hz, 1 mA) was evaluated in dogs. In group 1, the effects of electrode placement on airway pressure generation (P) was evaluated. Maximal P occurred at the T9-T10 level with progressive decrements in P at more rostral and caudal levels for both LF-SCS and HF-SCS. In group 2, electromyographic (EMG) latencies of internal intercostal muscle (II) activation were evaluated before and after spinal root section and during direct motor root stimulation. Onset time of II EMG activity during HF-SCS was significantly longer (3.84 ± 1.16 ms) than obtained during direct motor root activation (1.61 ± 0.10 ms). In group 3, P and external oblique (EO) EMG activity, before and after sequential spinal section at the T11-T12 level, were evaluated. Bilateral dorsal column section significantly reduced EO EMG activity below the section and resulted in a substantial fall in P. Subsequent lateral funiculi section completely abolished those activities and resulted in further reductions in P. We conclude that 1) activation of the expiratory muscles via HF-SCS is dependent entirely on synaptic spinal cord pathways, and 2) HF-SCS at the T9 level produces a comparable level of muscle activation with that achieved with LF-SCS but with much lower stimulus amplitudes. NEW & NOTEWORTHY The findings in the present study suggest that lower thoracic high-frequency spinal cord stimulation with low stimulus currents results in sufficient activation of the expiratory muscles via spinal circuitry to produce large positive airway pressures sufficient to generate an effective cough mechanism. This method, therefore, may be applied in patient populations with intact sensation such as stroke and amyotrophic lateral sclerosis to restore an effective cough.

Endoscopic sphincterotomy with or without cholecystectomy for choledocholithiasis in high-risk surgical patients: a decision analysis.

BACKGROUND: Laparoscopic cholecystectomy (LC) is recommended for patients with choledocholithiasis after ERCP with sphincterotomy (ES) and stone extraction. AIM: We designed a decision model to address whether ES alone versus ES followed by LC (ES + LC) is the optimal treatment in high-risk patients with choledocholithiasis. METHODS: Our cohort were patients with obstructive jaundice who have undergone an ES with biliary clearance. Recurrent biliary complications over a 2-year period stratified by gallbladder status (in/out) and age-stratified surgical complication rates were obtained from the literature. Failure of therapy was defined as either recurrent symptoms or death attributed to biliary complications. RESULTS: For age 70-79 years, ES failed in 15% whereas ES + LC failed in 17% of cases. Mortality in the EC + LC group was 3.4 times that of the ES alone cohort. For age 80+ years, ES was dominant with an incremental success rate of 8%. Mortality in the ES + LC was 7.6 times that of ES. For age <70, ES + LC was the dominant strategy with an incremental success rate 5%. Sensitivity analysis in the groups confirmed our conclusions. CONCLUSIONS: Management of choledocholithiasis by ES and stone clearance, but without cholecystectomy, should be considered for patients aged 70+. For low-risk patients, ES + LC should be performed to prevent recurrent biliary complications.

A survey of oesophageal cancer: pathology, stage and clinical presentation.

BACKGROUND: Oesophageal adenocarcinoma is the sixth leading cause of cancer-related mortality worldwide. Previously, oesophageal cancer was mainly squamous cell, presenting late with dysphagia and weight loss. AIMS: To examine the distribution of oesophageal cancer histopathology at a large, urban hospital; to determine the tumour stage and symptoms at presentation; and to evaluate the impact of endoscopic surveillance in Barrett's oesophagus. METHODS: From 1999 to 2004, all patients diagnosed with oesophageal cancer were evaluated retrospectively for demographics and tumour stage at presentation using endoscopic ultrasonography and computerized tomography. RESULTS: A total of 131 patients were included. 81% of tumours were adenocarcinomas; most localized to the distal oesophagus (97%). Patients presented with dysphagia (56%), pain (30%) and/or weight loss (16%). Irrespective of histology, locally advanced lesions accounted for most cases. Thirteen patients had lesions detected in Barrett's surveillance; these were early or intermediate stage in nine patients, but late stage in four patients. CONCLUSIONS: Adenocarcinoma has become the dominant histologic subtype, comprising 81% of proven malignancies. Despite a change in histopathology, most cancers are diagnosed at an advanced stage, presenting with dysphagia, pain and/or weight loss. Endoscopic surveillance of Barrett's oesophagus allows earlier diagnosis of cancer in most, but not all, patients.

High frequency spinal cord stimulation-New method to restore cough.

Spinal cord stimulation (SCS, 50Hz) is a useful method to restore an effective cough in persons with spinal cord injury (SCI). However, high stimulus amplitudes and potential activation of pain fibers, significantly limits this application. It is our hypothesis that high frequency SCS (HF-SCS), with low stimulus amplitudes may provide the same level of expiratory muscle activation. In 6 dogs, the effects of SCS, with varying stimulus parameters on positive pressure (P) generation was evaluated. At any given level of stimulus current, mean P was largest at 500Hz, compared to all other stimulus frequencies. For example, with stimulation at 1mA and frequencies of 200, 500 and 600Hz, P were 25±3, 58±4, 51±6cmH2O, respectively. By comparison, P achieved with conventional SCS parameters was 61±5cmH2O. HF-SCS results in a comparable P compared to that achieved with conventional stimulus parameters but with much lower stimulus amplitudes. This method may be useful to restore cough even in subjects with intact sensation.

Transgenic complementation of leptin-receptor deficiency. I. Rescue of the obesity/diabetes phenotype of LEPR-null mice expressing a LEPR-B transgene.

Mice homozygous for the Leprdb3J (db3J) mutation are null for all known isoforms of the leptin receptor (LEPR). These animals are obese, hyperphagic, cold intolerant, insulin resistant, and infertile. Mice homozygous for the Leprdb (db) mutation (lacking the B isoform only) have the same phenotype as db3J animals. To better understand the function(s) of the LEPR isoforms in vivo, we generated db3J/db3J and db/db mice bearing a transgene (neuron-specific enolase [NSE]-Rb) expressing the B isoform of LEPR, the isoform capable of activating the signal transducer and activator of transcription (STAT) pathway, under the control of the neuron-specific enolase enhancer/promoter. The NSE-Rb transgene was expressed in the brain, with low levels of expression in adrenals, testis, and white adipose tissue. LEPR-B transgene expression in NSE-Rb db3J/db3J mice partially corrected the increased fat mass, hyperphagia, and glucose intolerance while restoring fertility in males and rescuing the cold intolerance in both sexes. The body weights of NSE-Rb transgenic mice that possessed the full complement of short LEPR isoforms (NSE-Rb db/db mice) were similar to those of NSE-Rb db3J/db3J mice, suggesting that the short LEPR isoforms play little role in body weight regulation. Based on quantitative analysis of hypothalamic neuropeptide gene expression in the transgenic animals, we infer full restoration of leptin sensitivity to proopiomelanocortin (POMC) neurons, partial correction of leptin sensitivity in agouti gene-related protein (AGRP)/neuropeptide Y (NPY) neurons, and a lack of effect on leptin sensitivity of melanin concentrating hormone neurons. Thus, hypothalamic POMC and AGRP/NPY neurons are primary candidates as the mediators of the effects of the NSE-Rb transgene on energy homeostasis, ingestive behavior, the neuroendocrine system, and glucose metabolism.

Transgenic overexpression of neuromedin U promotes leanness and hypophagia in mice.

Recent work has shown that neuromedin U (NmU), a peptide initially identified as a smooth muscle contractor, may play a role in regulating food intake and energy homeostasis. To further evaluate this putative function, we measured food intake, body weight, energy expenditure and glucose homeostasis in transgenic mice that ubiquitously overexpress murine proNmU. NmU transgenic mice were lighter and had less somatic and liver fat, were hypophagic, and had improved insulin sensitivity as judged by an intraperitoneal insulin tolerance test. Transgenic mice had higher levels of hypothalamic NPY, POMC and MCH mRNA. There was no difference in O2 consumption between genotypes; however, NmU transgenic mice displayed a modest increase in respiratory quotient during food deprivation and refeeding. There were no behavioral disturbances in the NmU transgenic mice that could account for the results (e.g. changes in locomotor activity). When placed on a high-fat diet, transgenic mice remained lighter than wild-type mice and ate less, but gained weight at a rate similar to wild-type mice. Despite the increased weight gain with high-fat feeding, glucose tolerance was significantly improved in the transgenic mice. These findings support the hypothesized role of NmU as an endogenous anorexigenic peptide.

Mapping auditory cortex in the La Plata dolphin (Pontoporia blainvillei).

This study deals with the mapping of the primary and secondary auditory cortex. Due to their important role in echolocation they were the first areas to be examined [P.J. Morgane, M.S. Jacobs, in: R.J. Harrison (Ed.), Functional Anatomy of Marine Mammals, Comparative Anatomy of the Cetacean Nervous System, vol. 1, Academic Press, London, 1972, pp. 117-144]. We analysed the brain of a La Plata dolphin (Pontoporia blainvillei), which had been fixed in formaldehyde, embedded in paraffin, cut in sections of 20mum thickness and stained with cresyl violet. The experimental approach being impossible, we used cytoarchitectonic variations in the neocortex. Former electrophysiological data [T.F. Ladygina, A.Y. Supin, Localization of the projectional sensory areas in the cortex of the porpoise Tursiops truncates, Zh. Evol. Biokhim. Fiziol. 13 (1978) 712-718] [Sokolov, T.F. Ladygina, A.Y. Supin, Location of sensory zones in cerebral cortex of dolphin, Dokl. Biol. Sci., Russian Original 202 (1-6) (1972)] provided the framework for the exact determination of borders between functional cortical areas. We used a stereological observer-independent procedure based on changes in volume density of cell bodies throughout the neocortex [A. Schleicher, et al., Stereological approach to human cortical architecture: Identification and delineation of cortical areas, J. Chem. Neuroanat. 20 (2000) 31-47]. Due to the computer program's high sensitivity to changes in volume density it was possible to analyse the poorly laminated dolphin cortex. The 3D-reconstruction of the auditory cortex was processed using the AMIRA 3.0 Graphics software package comparing the main primary gyri in the histological sections with those in coronal magnetic resonance imaging scans of another intact Pontoporia brain.

Quantitative architectural analysis: a new approach to cortical mapping.

Recent progress in anatomical and functional MRI has revived the demand for a reliable, topographic map of the human cerebral cortex. Till date, interpretations of specific activations found in functional imaging studies and their topographical analysis in a spatial reference system are, often, still based on classical architectonic maps. The most commonly used reference atlas is that of Brodmann and his successors, despite its severe inherent drawbacks. One obvious weakness in traditional, architectural mapping is the subjective nature of localising borders between cortical areas, by means of a purely visual, microscopical examination of histological specimens. To overcome this limitation, more objective, quantitative mapping procedures have been established in the past years. The quantification of the neocortical, laminar pattern by defining intensity line profiles across the cortical layers, has a long tradition. During the last years, this method has been extended to enable a reliable, reproducible mapping of the cortex based on image analysis and multivariate statistics. Methodological approaches to such algorithm-based, cortical mapping were published for various architectural modalities. In our contribution, principles of algorithm-based mapping are described for cyto- and receptorarchitecture. In a cytoarchitectural parcellation of the human auditory cortex, using a sliding window procedure, the classical areal pattern of the human superior temporal gyrus was modified by a replacing of Brodmann's areas 41, 42, 22 and parts of area 21, with a novel, more detailed map. An extension and optimisation of the sliding window procedure to the specific requirements of receptorarchitectonic mapping, is also described using the macaque central sulcus and adjacent superior parietal lobule as a second, biologically independent example. Algorithm-based mapping procedures, however, are not limited to these two architectural modalities, but can be applied to all images in which a laminar cortical pattern can be detected and quantified, e.g. myeloarchitectonic and in vivo high resolution MR imaging. Defining cortical borders, based on changes in cortical lamination in high resolution, in vivo structural MR images will result in a rapid increase of our knowledge on the structural parcellation of the human cerebral cortex.

A large multicenter study analysis of adverse events associated with single operator cholangiopancreatoscopy.

AIM: Cholangiopancreatoscopy (CP) is an endoscopic technique that allows for direct visualization of the biliary and pancreatic ducts using a narrow caliber endoscope that passes through the working channel of a duodenoscope directly into the bile and/or pancreatic ducts. Little data is available on the safety of CP. We performed a multicenter retrospective study to evaluate the frequency and severity of adverse events with single operator CP. METHODS: A multicenter retrospective study was conducted. RESULTS: A total of 282 single operator peroral CP procedures were performed in 224 patients (128 M, 96 F). Most procedures involved the performance of therapeutic maneuvers, with most cases including multiple therapeutic maneuvers. Cholangioscopic or pancreatoscopic-assisted tissue sampling was performed in 222 procedures. Thirty-seven patients underwent electrohydraulic lithotripsy (EHL) for the treatment of common bile duct stones. Adverse events in patients undergoing single cholangioscopy and pancreatoscopy included post-ERCP pancreatitis (N.=11, 3.9%, all mild), post-ERCP cholangitis (N.=4, 1.4%), bleeding (N.=3, 1%), and perforation (N.=2, 0.7%). CONCLUSION: Overall, our data shows that ERCP performed with single operator cholangioscopy or pancreatoscopy is safe with adverse events similar to that seen in large studies of ERCP performed without these additional techniques. Of note, vigorous irrigation of the bile ducts was not associated with increased rates of post-procedure cholangitis in our study.

Bioinformatics -- a patenting view.

The use of bioinformatics in the biological sciences has brought about a change in the way that biological inventions can be protected by patent laws. Using approaches developed in the fields of computer science and business, patent applicants now seek to protect certain aspects of their inventions, which include software, methods of doing business and uses of information as well as more traditional biotechnological products and processes. These approaches are useful in resolving some of the difficulties now faced in prosecuting patent applications directed to biological inventions that are claimed in more conventional terms.

Vitamin A hepatotoxicity: a cautionary note regarding 25,000 IU supplements.

Vitamin A hepatotoxicity has been reported at doses exceeding 50,000 IU/day. At 25,000 IU vitamin A per day, although elevated liver enzymes may be seen, hepatotoxicity is rare. We report a case of severe hepatotoxicity associated with the habitual daily ingestion of 25,000 IU of vitamin A bought as an over-the-counter dietary supplement. With the general availability of high-dose supplements and recent literature emphasizing the importance of vitamin A adequacy, the potential for vitamin A hepatotoxicity may increase. Health professionals should remain aware of the potential for vitamin A hepatotoxicity and elicit a vitamin A history in all patients being evaluated for liver dysfunction.

Oral antibiotic treatment of right-sided staphylococcal endocarditis in injection drug users: prospective randomized comparison with parenteral therapy.

PURPOSE: To compare the efficacy and safety of inpatient oral antibiotic treatment (oral) versus standard parenteral antibiotic treatment (intravenous) for right-sided staphylococcal endocarditis in injection drug users. PATIENTS AND METHODS: In a prospective, randomized, non-blinded trial, febrile injection drug users were assigned to begin oral or intravenous (IV) treatment on admission, before blood culture results were available. Oral therapy consisted of ciprofloxacin and rifampin. Parenteral therapy was oxacillin or vancomycin, plus gentamicin for the first 5 days. Antibiotic dosing was adjusted for renal dysfunction. Administration of other antibacterial drugs was not permitted during the treatment or follow-up periods. Bacteremic subjects having right-sided staphylococcal endocarditis received 28 days of inpatient therapy with the assigned antibiotics. Test-of-cure blood cultures were obtained during inpatient observation 6 and 7 days after the completion of antibiotic therapy, and again at outpatient follow-up 1 month later. Criteria for treatment failure and for drug toxicity were prospectively defined. RESULTS: Of 573 injection drug users who were hospitalized because of a febrile illness and suspected right-sided staphylococcal endocarditis, 93 subjects (16.2%) had two or more sets of blood cultures positive for staphylococci; 85 of these bacteremic subjects (14.8%) satisfied diagnostic criteria for at least possible right-sided staphylococcal endocarditis (no other source of bacteremia was apparent) and entered the trial. Forty-four (oral, 19; IV, 25) of these 85 subjects completed inpatient treatment and evaluation including test-of-cure blood cultures. There were four treatment failures (oral, 1 [5.2%]; IV, 3 [12.0%]; not significant, Fisher's exact test). Drug toxicity was significantly more common in the parenterally treated group (oral, 3%; IV, 62%; P < 0.0001), consisting largely of oxacillin-associated increases in liver enzymes. CONCLUSIONS: For selected patients with right-sided staphylococcal endocarditis, oral ciprofloxacin plus rifampin is effective and is associated with less drug toxicity than is intravenous therapy.