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Biomedical subjects

D Lewis

Publications and source records attributed to D Lewis.

At least 37 records · Page 2Linked to original sources
PubMed1994

Impact of nutritional rehabilitation on gastroesophageal reflux in neurologically impaired children.

The impact of nutritional rehabilitation on gastroesophageal reflux (GER) in 10 malnourished neurologically impaired children (NIC) was studied (mean age, 9.1 +/- 3.1 years). None of the children had an antireflux procedure (ARP), and all were fed exclusively through a percutaneous endoscopic gastrostomy (PEG). Malnutrition was defined as triceps skin fold thickness (TSF) below the fifth percentile for age and sex. GER was established using standard criteria for a 24-hour pH probe study. All children were treated with an H2 antagonist and a prokinetic agent, along with aggressive nutritional rehabilitation. When TSF was > or = 50th percentile, medications were stopped, and the 24-hour pH probe study was repeated. The mean weight gain was 8.8 +/- 3.7 kg over 8.4 +/- 2.3 months. The 24-hour pH probe study showed marked improvement after nutritional rehabilitation in six of 10 children. These children remained asymptomatic throughout long-term follow-up, without the use of medications. Two children had abnormal pH probe results and worsening clinical symptoms when taken off medications after nutritional rehabilitation. They were reexamined after reinstituting the prokinetic drug; results of the pH probe study were normal, and there was no clinical symptomatology. The patients were then given long-term medication. Two children (one with erosive esophagitis and one with persistent symptoms) underwent ARP. We conclude that despite accompanying GER, successful nutritional rehabilitation can be achieved in malnourished NIC, using PEG feeding and antireflux medication. Although some NIC with GER may need an ARP or long-term medication, in most malnourished NIC nutritional rehabilitation is associated with resolution of GER.

Adolescent↗
PubMed1994

Maternal cocaine use without evidence of fetal exposure.

We report a case of lack of fetal exposure to cocaine and benzoylecgonine as evidenced by meconium and hair analysis, but exposure to nicotine and its metabolite cotinine, after extensive maternal use of cocaine and nicotine. These data suggest that the mode of maternal use of cocaine and individual differences in placental handling of the drug may protect some fetuses, and highlight the need to address interpatient variability.

Adult↗
PubMed1994

Pharmacokinetics and tissue distribution of recombinant human transforming growth factor beta 1 after topical and intravenous administration in male rats.

Recombinant human transforming growth factor beta (rhTGF-beta 1) enhances the healing process after topical application to various animal wound models. A detailed pharmacokinetic and tissue distribution study was performed to support the clinical development of rhTGF-beta 1 for wound healing indications. Rats received radioiodinated or unlabeled rhTGF-beta 1 as an intravenous (iv) bolus or as a topical formulation applied to a full thickness wound. Plasma concentrations of TGF-beta 1 were estimated from TCA-precipitable radioactivity or were measured by ELISA. Following iv administration, the initial half-life was rapid (< 11 min), regardless of whether radiolabeled or unlabeled rhTGF-beta 1 was used. The terminal half-life was long (163 min) when the test material was radioiodinated and administered as a trace dose and relatively short (< or = 61 min) when given at high doses and assayed by ELISA. Analysis of plasma radioactivity by SDS-PAGE revealed a time-dependent clearance of the 25-kDa parent molecule without a significant appearance of lower molecular weight radiolabeled metabolites. The majority of the radioactivity was associated with highly perfused organs, known iodide elimination pathways, and the thyroid at 1 and 8 hr after iv injection. After topical administration of a high dose (0.8 mg/kg), no immunoreactive TGF-beta 1 was detectable in plasma samples taken over a 48-hr period. However, trace amounts (< or = 0.05 ng/mL) of acid-precipitable radioactivity were detected in plasma after topical application of [125I]rhTGF-beta 1 (1 microgram/kg, 126 microCi/kg).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Topical↗
PubMed1994

The use of untreated bednets and malaria infection, morbidity and immunity.

The effect of bednet use was investigated, without undertaking a specific intervention, in four cross-sectional community-based surveys in 10 villages of a highly endemic area of Papua New Guinea. Over half (55%) of the villagers interviewed reported that they had used a bednet on the previous night. In general and after adjustment for age, village and housing characteristics, bednet users, particularly children, had lower parasite prevalences and spleen rates and less enlarged spleens than non-users. However, users were similar to non-users in terms of fever reported for the previous week, axillary temperature, parasite density and haemoglobin level. The prevalence of antibody to the ring erythrocyte surface antigen and the major merozoite surface antigen 2 was lower in users than non-users. The association with malariometric indices and immune responses remained significant when bednet users were compared with non-users in houses without bednets. Thus, untreated bednets do not reduce malaria transmission sufficiently to decrease morbidity. They might paradoxically increase the risk of clinical malaria by lowering the development of humoral immunity.

Adolescent↗
PubMed1994

The comparative analgesic efficacy of transcutaneous electrical nerve stimulation and a non-steroidal anti-inflammatory drug for painful osteoarthritis.

Thirty-six non-hospitalized subjects with chronic pain from OA of the knee participated in an evaluation of transcutaneous electrical nerve stimulation (TENS) and naproxen, an NSAID. All pre-experiment treatment was withdrawn. Each subject experienced in some order three 3-week treatment phases: NSAID plus placebo TENS; TENS plus placebo drug; and double placebo. A broad range of pain measures was used, including daily diary ratings, and four-times-per-day ratings entered into a small electronic data logger (the PIPER) worn by the subject. A substantial placebo response occurred across all conditions, which may have masked treatment differences. Broad comparisons across subjects, combining the four main measures of pain, found no significant differences among the three experimental treatments. Analysis of diary and PIPER data for individuals suggested that, in a small minority of subjects, the NSAID plus placebo TENS combination may be more effective than double placebo. The PIPER ratings seemed to tap aspects of the pain experience different from those captured by conventional measures, suggesting the value of very frequent pain assessments, such as those entered by a subject into the PIPER, in the study of chronic pain.

Adult↗
PubMed1994

Transposition of IS2 into the hemB gene of Escherichia coli K-12.

Genetic studies of the hemB gene in Escherichia coli have resulted in the recovery of both stable and unstable mutant strains. The stable strains have been shown to result from large deletions. This study demonstrates that unstable strains result from the insertion of transposable element IS2 primarily into the 5' region of the structural gene; the instability results from precise excision of the element, producing strains with both high and low frequencies of reversion. This first report of IS2 insertion into hemB suggests that this gene may be a preferred target for insertion of this transposable element.

Aldehyde Oxidoreductases↗
PubMed1994

Relationship between humoral response to Plasmodium falciparum merozoite surface antigen-2 and malaria morbidity in a highly endemic area of Papua New Guinea.

The prevalence and concentration of antibodies to merozoite surface antigen-2 (MSA-2) were measured in blood samples collected during a cross-sectional survey. Antibodies were measured by enzyme-linked immunosorbent assay using two recombinant proteins that closely approximated the full-length mature MSA-2 polypeptides expressed by the Plasmodium falciparum isolate FC27 and the cloned line 3D7 and that were representative of the dimorphic forms of MSA-2. Antibodies were also measured to a form of the 3D7 MSA-2 lacking the central repetitive sequences (d3D7). High antibody prevalence was observed to all three antigens: the overall prevalence of IgG to FC27, 3D7, and d3D7 was 91%, 90%, and 90%, respectively. The majority of individuals > or = 5 years of age had antibodies to both forms of MSA-2. The geometric mean antibody units increased with age with a plateau being reached by 15-20 years of age. There was a significant positive association of antibody prevalence with both the presence of the parasite and an enlarged spleen in children. This study provides the first evidence that antibodies against nonrepeat regions of MSA-2 are associated with fewer fever episodes and less anemia, both known to be indicators of malaria morbidity.

Adolescent↗
PubMed1994

Comparison of approximate and iterative methods to calculate the efficiency of haemodialysis as KT/V.

Dialysis dose is given by the index KT/V, where K is the dialyser urea clearance, T the duration of dialysis and V the notional urea distribution volume. KT/V may be calculated using the single pool model and an iterative calculation which requires a computer program. Three estimates of KT/V, each based on simple correction of the log ratio in (C0/C1), where C0, C1 denote the pre- and post-dialysis blood urea concentrations in mg/ml, were developed and compared with the values of KT/V given by iteration. The first estimate was given by adding two terms to the log ratio to account for the effect of ultrafiltration and urea generation while the second and third estimates were given by increasing the log ratio by 12.5% and 15% respectively. All estimates gave good agreement when compared with the iterative technique by Bland-Altman analysis for 27 patients on standard 4 hour dialysis treatment using 4 different dialysers (0.71 < KT/V < 1.62). The mean difference in all cases was less than 0.025 and the differences were not clinically significant. The use of these approximate formulae to estimate dialysis efficiency avoids the need for complex calculation or additional blood samples.

Adult↗
PubMed1994

Neurosonographic abnormalities associated with maternal history of cocaine use in neonates of appropriate size for their gestational age.

PURPOSE: To determine whether increased incidence of neurosonographic abnormalities (predominantly of the basal ganglia and thalamus) in cocaine-exposed neonates who are small for their gestational age is attributable to the cocaine or to neonatal size. METHODS: Neonates whose sizes were appropriate for their gestational age with no evidence of hypoxia or respiratory distress were identified prospectively by a maternal history of cocaine use. Scans were performed within 72 hours of birth using a 7.5-MHz transducer following a standard protocol. The images were analyzed without access to patient information. Forty study neonates were compared with 34 control subjects who were appropriate in size for their gestational age, scanned using the same protocol. Comparisons were made using Fisher Exact Test, t test, and logistic regression. RESULTS: No control infant had neurosonographic abnormalities. In the study group, gestational age ranged from 27 to 41 weeks. Of the 40 study neonates, 14 (35%) had one neurosonographic abnormality; two had two abnormalities. The predominant lesion was focal echolucencies, mainly in the area of the basal ganglia (10 of 40, 25%). Other findings were caudate echogenicity (3 of 40, 7.5%), ventricular dilation (2 of 40, 5%) and one "moth-eaten" appearance of the thalamus. Lesions were more likely approaching term and were not related to prematurity or alcohol use. CONCLUSION: Apparently normal neonates with a maternal history of cocaine use are likely to have degenerative changes or focal infarctions in their basal ganglia attributable to cocaine. Neurosonography should be used to evaluate these neonates. The long-term significance of these lesions needs further evaluation.

Alcohol Drinking↗
PubMed1994

Family matters.

There are many more 'family matters' issues worthy of reflection, but the examples represent some of the more common personal dilemmas facing medical practitioners, and in particular women doctors, based on both my own experience and conversations with colleagues. There are no simple or universally appropriate answers to any of the scenarios; I have not attempted to suggest solutions to any of the issues raised, but hope that some situations outlined will evoke empathy and promote thought, discussion or debate about ways that individual doctors could deal with such matters.

Family↗
PubMed1993

High sensitivity to site directed mutagenesis of the peptide segment connecting phosphorylation and Ca2+ binding domains in the Ca2+ transport ATPase.

Nine residues (Leu321, Lys329, Asn330, Val333, Arg334, Leu336, Pro337, Val339 and Glu340), within the peptide segment intervening between the catalytic domain and the Ca2+ binding domain of the sarcoplasmic reticulum (SERCA 1) ATPase, were individually mutated to Ala. The mutated proteins were recovered in the microsomal fraction of COS-1 cells following transient expression, and exhibited inhibition of Ca2+ uptake and ATPase hydrolytic activity, while forming discernable levels of phosphorylated intermediate. Mutation of Glu340 to Gln (rather than to Ala) was much less effective, suggesting that the functional consequence of the mutation is related to structural perturbation, rather than loss of the acidic side chain. The high sensitivity of this peptide segment to single mutations suggests that its structural integrity is required for functional linkage of the phosphorylation and Ca2+ binding domains.

Animals↗
PubMed1993

Veterans Affairs congestive heart failure antiarrhythmic trial. CHF STAT Investigators.

This is a prospective, double-blind, placebo-controlled trial to determine the effect of antiarrhythmic drug therapy on mortality in patients with congestive heart failure and ventricular arrhythmia. Patients will be assigned to receive either amiodarone or placebo. Eligible patients include those with ischemic and nonischemic congestive heart failure and with > or = 10 ventricular premature beats per hour. All patients must have shortness of breath with minimal exertion or paroxysmal nocturnal dyspnea, a left ventricular internal dimension (LVIDd) by echocardiogram of > or = 55 mm or a cardiothoracic ratio of > 0.5 and an ejection fraction of < or = 40%. All patients will receive vasodilator therapy, unless they find it intolerable. Patients will be entered into the study for 2.5 years and followed for an additional 2 years. Drug therapy will be continued for all patients throughout the entire study unless adverse reactions occur that necessitate individualized treatment. The expectation is that 674 patients will be entered into the study from 25 participating centers. This sample size will allow for the detection of a 33% decrease in 2-year mortality (20% vs 30%) in the treated patients compared with those in the placebo group, with a power of 0.90 and a 2-sided alpha level of 0.05. Intermittent Holter monitoring, radionuclide ventriculograms, pulmonary function tests, echocardiograms, and blood tests, including arterial blood gases, will be required for each patient.(ABSTRACT TRUNCATED AT 250 WORDS)

Amiodarone↗
PubMed1993

Detection and characterization of a novel bisegmented double-stranded RNA virus (picobirnavirus) from rabbit faeces.

In two separate studies rabbits were fed orally with human and rabbit "picobirnaviruses". Polyacrylamide gel electrophoresis (PAGE) of nucleic acid extracted from faecal samples collected from inoculated rabbits revealed the presence of discrete equimolar bands, typical of picobirnaviruses, in several specimens. The genome profiles detected in both studies differed significantly from that of the inoculum suggesting that passage of the inoculated picobirnaviruses had not taken place and that the bands were a co-incidental finding. The presence of rabbit picobirnaviruses was confirmed by characterization of the genome bands, as dsRNA by enzyme digestion and by their co-sedimentation in caesium chloride (CsCl) gradients with 32 nm virus particles at a buoyant density of 1.39 g/ml. Picobirnavirus genome segments varied in size in a range between 2.3-2.6 kilo base pairs (kbp) and 1.6-1.9 kbp for the slow and fast migrating bands, respectively. Immune electron microscopy of the picobirnavirus particles revealed round or slightly hexagonal particles with a smooth surface and a mean diameter of 30.7 nm. In one rabbit, an immune response, temporally associated with picobirnaviruses excretion, was demonstrated by immune electron microscopy (IEM) supporting the view that picobirnaviruses may be vertebrate viruses. Two antigenically distinct picobirnavirus strains were defined by IEM.

Animals↗
PubMed1993

Doramectin--a potent novel endectocide.

Doramectin, 25-cyclohexyl-5-O-demethyl-25-de(l-methylpropyl)avermectin A1a, was selected as the best of a series of novel avermectins prepared by mutational biosynthesis. The primary evaluation of its in vivo antiparasitic activity was carried out using a rat Trichostrongylus colubriformis model and a rabbit Psoroptes cuniculi model. In each case the new avermectin performed favourably relative to dihydroavermectin B1a (DHAVM), the major component of ivermectin. Doramectin was extensively evaluated in cattle using an experimental micelle formulation, proving highly effective in cattle infected with Ostertagia ostertagi, Cooperia oncophora and Dictyocaulus viviparus when administered subcutaneously at 200 micrograms kg-1. The plasma pharmacokinetic characteristics of doramectin in cattle following intravenous administration revealed a plasma half-life of approximately 89 h. In the micelle formulation, doramectin administered subcutaneously at 400 micrograms kg-1 provided persistent activity against infection of cattle with C. oncophora and O. ostertagi for at least 8 and 12 days respectively.

Administration, Oral↗
PubMed1993

Effect of formulation on the pharmacokinetics and efficacy of doramectin.

The pharmacokinetics of doramectin, a novel avermectin, were evaluated following parenteral administration in a range of oil-based formulations in an attempt to optimise the formulation. Therapeutic and persistent efficacies against Cooperia oncophora were also evaluated. This approach led to the identification of formulations based upon sesame oil and ethyl oleate which gave more prolonged doramectin plasma concentrations with no loss in therapeutic efficacy and improved persistent efficacy following subcutaneous administration to cattle at a dosage of 200 micrograms kg-1. The importance of using both pharmacokinetic and efficacy end points to distinguish between formulations is discussed. All formulations were well tolerated as evidenced by the absence of any reaction to injection either in the form of behavioural responses, injection site swelling or postmortem lesions. Sesame oil with ethyl oleate was the best parenteral vehicle tested for doramectin, allowing the expression of a high level of therapeutic and persistent efficacy and offering the benefit of excellent injection site toleration.

Analysis of Variance↗
PubMed1993

Effect of standard-dose versus high-dose epinephrine on myocardial high-energy phosphates during ventricular fibrillation and closed-chest CPR.

STUDY OBJECTIVE: To evaluate the effects of standard-dose versus high-dose epinephrine on myocardial high-energy phosphate metabolism during resuscitation from cardiac arrest. DESIGN: Prospective, nonrandomized, controlled study using a swine model of cardiac arrest and resuscitation. INTERVENTIONS: After anesthesia, intravascular pressure instrumentation, and ten minutes of ventricular fibrillation arrest, closed-chest CPR was begun. After three minutes of CPR, animals were allocated to receive either 0.02 mg/kg i.v. standard-dose epinephrine (eight) or 0.2 mg/kg i.v. high-dose epinephrine (nine). The animals underwent thoracotomy and rapid-freezing transmural myocardial core biopsy for high-energy phosphate analysis 3.5 minutes after epinephrine administration. High-energy phosphate values were blindly determined using high-pressure liquid chromatography. RESULTS: Intravascular pressure (mm Hg) and high-energy phosphate (nmol/mg protein) results for standard-dose epinephrine versus high-dose epinephrine are, respectively, coronary perfusion pressure, 15.3 +/- 7.8 versus 23.7 +/- 5.5 (P = .0009); phosphocreatine, 0.4 +/- 0.8 versus 6.2 +/- 4.4 (P = .0003); adenosine triphosphate, 9.8 +/- 4.8 versus 12.7 +/- 5.7 (P = .30); adenosine diphosphate, 5.4 +/- 2.1 versus 6.1 +/- 1.3 (P = .41); and adenylate charge, 0.68 +/- 0.12 versus 0.72 +/- 0.12 (P = .87). CONCLUSION: High-dose epinephrine does not deplete myocardial high-energy phosphate when given in this model of prolonged ventricular fibrillation. High-dose epinephrine increases coronary perfusion pressure compared with standard-dose epinephrine. High-dose epinephrine administration repletes phosphocreatine during closed-chest CPR, thereby increasing myocardial energy stores.

Adenosine↗
PubMed1993

Norwalk-like viruses: demonstration of genomic diversity by polymerase chain reaction.

A reverse transcription-polymerase chain reaction (RT-PCR) amplification procedure was developed for the detection of Norwalk-like viruses in fecal specimens. Ninety-nine fecal specimens collected in the United Kingdom and containing small round-structured virus particles as determined by electron microscopy were tested. They came from 50 outbreaks and 16 sporadic cases of viral gastroenteritis. RT-PCR products of the appropriate size for Norwalk virus RNA were detected in 15 specimens from three outbreaks, suggesting that viruses closely related to Norwalk virus have not been circulating widely in the United Kingdom in recent years. From four isolates, the RT-PCR amplification products of two genomic regions were sequenced and the degree of genomic variation was compared. DNA sequencing of the PCR products revealed strong similarities among strains from the United Kingdom (approximately 97% for both regions amplified) but significant differences from Norwalk virus (67 to 78%). All of the viruses detected by RT-PCR were classified as serotype UK2 by solid-phase immune electron microscopy or enzyme-linked immunosorbent assay. These findings provide evidence of a genomic relationship between Norwalk virus and serotype UK2 small round-structured viruses.

Base Sequence↗