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J H Lewis

Publications and source records attributed to J H Lewis.

At least 37 records · Page 2Linked to original sources
PubMed1999

Solution structure of potassium channel-inhibiting scorpion toxin Lq2.

Lq2 is a unique scorpion toxin. Acting from the extracellular side, Lq2 blocks the ion conduction pore in not only the voltage- and Ca2+ -activated channels, but also the inward-rectifier K+ channels. This finding argues that the three-dimensional structures of the pores in these K+ channels are similar. However, the amino acid sequences that form the external part of the pore are minimally conserved among the various classes of K+ channels. Because Lq2 can bind to all the three classes of K+ channels, we can use Lq2 as a structural probe to examine how the non-conserved pore-forming sequences are arranged in space to form similar pore structures. In the present study, we determined the three-dimensional structure of Lq2 using nuclear magnetic resonance (NMR) techniques. Lq2 consists of an alpha-helix (residues S10 to L20) and a beta-sheet, connected by an alphabeta3 loop (residues N22 to N24). The beta-sheet has two well-defined anti-parallel strands (residues G26 to M29 and residues K32 to C35), which are connected by a type I' beta-turn centered between residues N30 and K31. The N-terminal segment (residues Z1 to T8) appears to form a quasi-third strand of the beta-sheet.

Amino Acids↗
PubMed1999

An outbreak of Escherichia coli O157:H7 infection from unpasteurized commercial apple juice.

BACKGROUND: Escherichia coli O157:H7 infections have traditionally been associated with animal products, but outbreaks associated with produce have been reported with increasing frequency. In fall 1996, a small cluster of E. coli O157:H7 infections was epidemiologically linked to a particular brand (brand A) of unpasteurized apple juice. OBJECTIVE: To define the extent of the outbreak, confirm the source, and determine how the apple juice became contaminated. DESIGN: Descriptive epidemiologic study and traceback investigation. SETTING: Western United States and British Columbia, Canada. PATIENTS: Patients with E. coli O157:H7 infection who were exposed to brand A apple juice. MEASUREMENTS: Clinical outcome and juice exposure histories of case-patients, pulsed-field gel electrophoresis of case and juice isolates, and juice production practices. RESULTS: Seventy persons with E. coli O157:H7 infection and exposure to brand A unpasteurized apple juice were identified. Of these persons, 25 (36%) were hospitalized, 14 (20%) developed the hemolytic uremic syndrome, and 1 (1%) died. Recalled apple juice that was produced on 7 October 1996 grew E. coli O157:H7 with a pulsed-field gel electrophoresis pattern indistinguishable from that of case isolates. Apple juice produced on 7 October 1996 accounted for almost all of the cases, and the source of contamination was suspected to be incoming apples. Three lots of apples could explain contamination of the juice: Two lots originated from an orchard frequented by deer that were subsequently shown to carry E. coli O157:H7, and one lot contained decayed apples that had been waxed. CONCLUSIONS: Standard procedures at a state-of-the-art plant that produced unpasteurized juices were inadequate to eliminate contamination with E. coli O157:H7. This outbreak demonstrated that unpasteurized juices must be considered a potentially hazardous food and led to widespread changes in the fresh juice industry.

Adolescent↗
PubMed1999

Drug- and chemical-induced cholestasis.

Cholestasis resulting from drugs is an increasingly recognized cause of liver disease. It produces a broad clinical-pathologic spectrum of injury that includes simple jaundice, cholestatic hepatitis, and bile duct injury that can mimic extrahepatic biliary obstruction, primary biliary cirrhosis, and sclerosing cholangitis. Although the risk of drug-induced cholestasis leading to a fatal outcome is quite rare, knowledge and recognition of the various forms of cholestatic injury assumes an importance whenever clinicians are confronted with jaundice or other manifestations of liver disease in patients receiving medicinal or chemical agents.

Anti-Bacterial Agents↗
PubMed1999

Drug-induced liver disease.

The past year has seen several additions to the list of drugs that cause hepatic injury. Many of these agents produce fulminant hepatic necrosis and, in some cases, were withdrawn from the market (eg, bromfenac). Other drugs had warnings placed in their labeling along with stringent monitoring guidelines to alert physicians and patients alike to the potential for severe hepatic injury (eg, troglitazone, tolcapone). New reports of hepatoxicity continued to appear for many older agents, in some cases expanding the hepatotoxic spectrum for the drugs. Vanishing bile duct syndrome has drawn increasing attention and is now associated with more than 30 drugs. Ibuprofen is among those drugs newly described as causing this syndrome. Hepatitis C virus infection was reported as a possible risk factor for ibuprofen hepatotoxicity, raising the issue of safe use of nonprescription as well as prescription drugs in patients with underlying liver disease. Reports have appeared about acetaminophen-induced hepatotoxicity in several dozen children from unintentional overdoses, in addition to cases of therapeutic misadventure in adults.

Journal Article↗
PubMed1999

Insights into the management of erectile dysfunction: Part I.

It is estimated that as many as 30 million men in the United States suffer from erectile dysfunction (ED). Because ED is so widespread, especially among the older population, it is imperative that this disorder be recognized as an important and manageable health problem.

Erectile Dysfunction↗
PubMed1997

cash4, a novel achaete-scute homolog induced by Hensen's node during generation of the posterior nervous system.

In vertebrate embryos, the precursor cells of the central nervous system (CNS) are induced by signaling from the organizer region. Here we report the isolation of a novel vertebrate achaete-scute homolog, cash4, which is expressed in the presumptive posterior nervous system in response to such signaling. cash4 is first expressed in epiblast cells flanking the late-phase organizer (Hensen's node), which retains its ability to induce cash4 during regression to the caudal end of the embryo. We show that these node-derived signals can be mimicked in vivo by the activity of fibroblast growth factor (FGF). We demonstrate that cash4 can substitute for the achaete/scute genes in the fly and that it also has proneural activity in vertebrate embryos. Together these results suggest that cash4 functions as a proneural gene downstream of node-derived signals (including FGF) to promote the formation of the neural precursors that will give rise to the posterior CNS in the chick embryo.

Amino Acid Sequence↗
PubMed1997

Tolerance and efficacy of oral ribavirin treatment of chronic hepatitis C: a multicenter trial.

Hepatitis C is a common cause of chronic liver disease that may progress to cirrhosis. We conducted a multicenter double-blind placebo-controlled trial of ribavirin 600 mg given orally twice daily for 36 weeks with follow-up off therapy for an additional 16 weeks. Fifty-nine patients with compensated chronic hepatitis C were entered. Efficacy was measured at the end of therapy and after follow-up by normalization of alanine aminotransferase (ALT), improvement in liver histology, reduction in hepatitis C virus (HCV) RNA level and improvement of symptoms. Among the ribavirin recipients, 12 of 29 (41.4%) had normal ALT values at 36 weeks compared with only 1 of 30 (3.3%) placebo recipients (P < .001). No patient maintained a normal ALT when therapy was stopped. No significant decrease in level of HCV RNA was observed during the study. Histological improvement among subjects who normalized ALT (-1.67 Knodell index) was significantly greater than that in other treated patients (+0.33 Knodell index; P < .05). Fatigue improved in 19.2% of ribavirin-treated subjects and in 8.3% of placebo recipients whereas no worsening of fatigue was reported by ribavirin recipients compared with 16.7% of controls. This difference in fatigue was significant at weeks 36 and 52 (P < .05; .02, respectively). Adverse events were generally comparable between treatment groups except for a reversible hemolytic anemia experienced by ribavirin recipients. Chest pain was noted in four patients on ribavirin. Ribavirin was well tolerated and improved aminotransferase values and reduced fatigue in patients with hepatitis C viral infection while treatment was being administered. Because this action was produced without change in viral level, the mechanism of action of this agent requires further investigation.

Administration, Oral↗
PubMed1997

A new system for defining endoscopic complications emphasizing the measure of importance.

BACKGROUND: Currently, there are no satisfactory systems for defining, classifying, and/or scoring endoscopic complications, although it would be important for quality assurance, comparative studies, and outcomes research. Recently the term "negative outcomes" was proposed rather than "complications," and an approach that incorporates "measures of importance" was added to compare negative outcomes. METHODS: A system was developed that defines, classifies, and grades negative outcomes with a scoring system based on measures of importance. Information was recorded on a Morbidity and Mortality (M & M) form, which was used at a monthly quality assurance (M & M) conference. Several measures of importance related to the immediate negative outcome (O) were quantified (effect of the complication on completion of the endoscopy, change in level of care, change in number of hospital days, necessity for new invasive procedures). The disability (D), defined as a residual or chronic negative outcome caused by the complication, was characterized and scored. Death (D) was also characterized, the value varying with circumstances. As a quantitative measure, an overall ODD score was used. RESULTS: One hundred twenty-three negative outcomes were retrospectively classified using the new M & M form and the ODD score was applied for 117 complications. Complications were ranked according to the ODD score. CONCLUSION: A system for defining, classifying, and grading negative outcomes of endoscopic procedures is proposed with a quantitative scoring system that emphasizes measures of importance. The ODD score looks at the immediate negative outcome and also the separate long-term issues of disability and death.

Documentation↗
PubMed1997

Prevalence of hepatitis C virus associated cryoglobulinemia at a veterans hospital.

OBJECTIVE: To prospectively evaluate the prevalence and clinical spectrum of cryoglobulinemia in a population infected with the hepatitis C virus (HCV). METHODS: Inpatients and outpatients at the Veterans Affairs (VA) Medical Center were recruited for study. Sixty-nine patients with HCV and 68 anti-HCV negative, age and sex matched controls were evaluated for the prevalence of cryoglobulinemia. Clinical and laboratory profiles were obtained in all patients and rheumatologic complaints were sought in 58 anti-HCV positive patients. RESULTS: Twenty-nine (42%) of 69 anti-HCV positive patients and no controls had cryoglobulinemia (p < 0.001). A history of intravenous drug abuse and excessive alcohol ingestion was more prevalent in the anti-HCV positive group compared to controls, (p < 0.001 and p = 0.02, respectively), but was unrelated to the presence or absence of cryoglobulinemia. Of 58 anti-HCV positive patients evaluated for rheumatologic complaints, 12 (21%) reported symptoms; 9 (41%) of 22 with cryoglobulinemia and 3 (8%) of 36 without cryoglobulinemia (p < 0.01). No patient had vasculitis. Antinuclear antibody (ANA) and rheumatoid factor (RF) were evaluated in 19 anti-HCV positive patients with cryoglobulinemia. About one-half were positive for ANA or RF, fewer than 50% of whom had rheumatologic symptoms. Nineteen of the 29 patients with cryoglobulinemia were available for followup after one year. Ten of 19 revealed only trace (< 5%) cryoglobulinemia; 7 were type III, one type I, and none were type II. The character of the remaining 2 cryoglobulins was unknown. Twenty-five liver biopsy specimens were available for review; there were no histological differences between patients with and without cryoglobulinemia. CONCLUSION: The prevalence of HCV related cryoglobulinemia at a VA hospital was 42% and was most often of the type III variety. Although mild rheumatologic symptoms were common in HCV infected patients with cryoglobulinemia, no specific syndrome denoted its presence. The absence of any specific rheumatologic disease in this cohort implies that the pathogenesis of diseases such as essential mixed cryoglobulinemia is multifactorial and that low levels of type III cryoglobulinemia in HCV infected patients are not specific for the diagnosis.

Biopsy↗
PubMed1996

Pattern formation by lateral inhibition with feedback: a mathematical model of delta-notch intercellular signalling.

In many developing tissues, adjacent cells diverge in character so as to create a fine-grained pattern of cells in contrasting states of differentiation. It has been proposed that such patterns can be generated through lateral inhibition--a type of cell-cell interaction whereby a cell that adopts a particular fate inhibits its immediate neighbors from doing likewise. Lateral inhibition is well documented in flies, worms and vertebrates. In all of these organisms, the transmembrane proteins Notch and Delta (or their homologues) have been identified as mediators of the interaction--Notch as receptor, Delta as its ligand on adjacent cells. However, it is not clear under precisely what conditions the Delta-Notch mechanism of lateral inhibition can generate the observed types of pattern, or indeed whether this mechanism is capable of generating such patterns by itself. Here we construct and analyse a simple and general mathematical model of such contact-mediated lateral inhibition. In accordance with experimental data, the model postulates that receipt of inhibition (i.e. activation of Notch) diminished the ability to deliver inhibition (i.e. to produce active Delta). This gives rise to a feedback loop that can amplify differences between adjacent cells. We investigate the pattern-forming potential and temporal behaviour of this model both analytically and through numerical simulation. Inhomogeneities are self-amplifying and develop without need of any other machinery, provided the feedback is sufficiently strong. For a wide range of initial and boundary conditions, the model generates fine-grained patterns similar to those observed in living systems.

Animals↗
PubMed1996

Flumazenil reversal of psychomotor impairment due to midazolam or diazepam for conscious sedation for upper endoscopy.

BACKGROUND: Flumazenil is a competitive benzodiazepine antagonist that acts to reverse their sedative and hypnotic effects. It is indicated in the management of benzodiazepine overdose, but its role in the routine reversal of endoscopic conscious sedation has not been defined. METHODS: Patients undergoing diagnostic upper endoscopy who received sedation with either diazepam or midazolam alone were given flumazenil 0.2 mg incrementally immediately following the procedure until awake. They were then asked to repeat three psychomotor tests measuring cognitive and motor skills, with their baseline scores compared with postprocedure scores over a 3-hour period. RESULTS: Full psychomotor function was restored to baseline values within 30 minutes after flumazenil in 79% of patients, with no differences in the reversal of psychomotor skill impairment observed between diazepam and midazolam sedation. There was no evidence of rebound sedation seen for up to 3 hours. No significant anterograde amnesia was evident in 78% of individuals. CONCLUSIONS: These results demonstrate that flumazenil's effects on reversing psychomotor impairment are similar when midazolam or diazepam are used for conscious sedation. However, the potential usefulness of routine flumazenil reversal of conscious sedation will require further evaluation of specific psychomotor performance skills (such as driving a car) before we lift the admonition against leaving the endoscopic suite unattended, driving a vehicle, or operating complicated machinery for several hours.

Adult↗
PubMed1996

Spatial localization of the K+ channel selectivity filter by mutant cycle-based structure analysis.

The structurally well-characterized scorpion toxin Agitoxin2 inhibits ion permeation through Shaker K+ channels by binding to the external pore entryway. Scanning mutagenesis identified a set of inhibitor residues critical for making energetic contacts with the channel. Using thermodynamic mutant cycle analysis, we have mapped channel residues relative to the known inhibitor structure. This study constrains the position of multiple channel residues within the pore-forming loops; in one stretch, we have been able to map five out of seven contiguous residues to the inhibitor interaction surface, including those involved in ion selectivity. One interaction in particular, that of K27M on the inhibitor with Y445F on the channel, is unique in that it depends on the K+ ion concentration. These results reveal a shallow vestibule formed by the pore loops at the K+ channel entryway. The selectivity filter is located at the center of the vestibule close to (approximately 5 A) the extracellular solution.

Amino Acid Sequence↗
PubMed1996

High-resolution chromoendoscopy for the diagnosis of diminutive colon polyps: implications for colon cancer screening.

BACKGROUND & AIMS: A visual, nonbiopsy technique that could reliably determine the histology of diminutive colorectal polyps could greatly reduce the cost of colon cancer screening. This study was designed to report our experience using a high-resolution colonoscope combined with indigo carmine dye to diagnosis diminutive colorectal polyps. METHODS: Colonoscopy using a Fujinon EC-400 HM/HL was performed in 36 patients with polyps <10mm in diameter. Polyps from the first 12 patients (phase 1) were sprayed with 10 mL of 0.2% indigo carmine dye, and a biopsy was performed or a specimen removed and submitted for histological analysis. The morphological data were used to predict polyp histology in the subsequent 24 patients (phase 2). RESULTS: Hyperplastic polyps had a characteristic surface "pit pattern" of orderly arranged "dots" that resembled the surrounding, nonpolypoid mucosa. Adenomatous polyps had surface "grooves" or "sulci." Sensitivity and specificity of our techniques in distinguishing adenomatous from nonadenomatous colorectal polyps were 93% and 95% respectively. CONCLUSIONS: High-resolution chromoendoscopy provides morphological detail of diminutive colorectal polyps that correlates well with polyp histology. If incorporated into colon cancer screening, these techniques may limit the need for biopsy and/or subsequent colonoscopy and ultimately decrease costs.

Adult↗
PubMed1996

Report of a multicenter clinical evaluation of the Dura-II penile prosthesis.

PURPOSE: Information was collected during the first 2 years of an ongoing, prospective, multi-institutional evaluation of the Dura-II penile prosthesis. Evaluation included data on clinical outcomes and a patient satisfaction survey, and will continue for 5 years after implantation for each patient. MATERIALS AND METHODS: To date 196 patients have been evaluated. Surgical data, adverse events and information from satisfaction surveys are reported. RESULTS: At a followup of 13.4 +/- 8.4 months postoperatively, adverse events occurred in 8.2% of the patients, resulting in reoperation in 5.1%. There have been no mechanical failures. Overall satisfaction rates were 85% at 3 months, 83% at 1 year and 91% at 2 years after implantation, and levels of sexual functioning were correspondingly high. A majority of patients assigned high scores to rigidity, concealability, ability to have intercourse and erection size, although satisfaction with erection size ranked lower than the other measures. CONCLUSIONS: The Dura-II penile prosthesis provides a satisfactory result and has an acceptable level of complications associated with its use. Further followup will assess temporal changes in satisfaction rates and sexual functioning for these patients.

Adult↗
PubMed1995

Molecular epidemiology of a fast-food restaurant-associated outbreak of Escherichia coli O157:H7 in Washington State.

We studied the molecular epidemiology of the recent fast-food restaurant chain-associated Escherichia coli O157:H7 outbreak in Washington State. Genomic DNAs prepared from strains isolated from 433 patients were probed with radiolabelled Shiga-like toxin (SLT) I and SLT II genes and bacteriophage lambda DNA and were subsequently analyzed for their restriction fragment length polymorphism (RFLP) patterns. The SLT RFLP and lambda RFLP profiles of an E. coli O157:H7 strain isolated from the incriminated beef and prototype patient were compared with those of the patient isolates for determination of the concordance between patterns. Of the 377 patients with primary and secondary cases of infection epidemiologically linked to the outbreak, isolates from 367 (97.3%) of the patients displayed SLT RFLP and lambda RFLP profiles identical to those of the outbreak strains. Isolates from 10 of the 377 (2.6%) patients possessed SLT RFLP and lambda RFLP profiles different from those of the outbreak strains, and the patients from whom those isolates were obtained were subsequently characterized as having non-outbreak-related infections. The E. coli O157:H7 strains isolated from 31 of 44 (70.4%) patients who were epidemiologically excluded from the outbreak were linked to the outbreak by RFLP typing. Our results indicate that SLT RFLP and lambda RFLP analyses are stable and sensitive methods, and when they are used in conjunction with an epidemiological investigation they could result in an earlier recognition of outbreaks and their sources, hence prompting measures to prevent the continued transmission of E. coli O157:H7.

Animals↗