Search PubMed⌕ Search

Biomedical subjects

M E Lewis

Publications and source records attributed to M E Lewis.

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

Replacement of the proximal aorta and aortic valve using a composite bileaflet prosthesis and gelatin-impregnated polyester graft (Carbo-Seal): early results in 143 patients.

OBJECTIVE: We report the combined early results from two centers in the United Kingdom using a composite conduit consisting of a bileaflet mechanical valve incorporated into a gelatin-impregnated, ultra-low porosity, woven polyester graft (Carbo-Seal; Sulzer Carbomedics, Inc, Austin, Tex). METHODS: Between August 1992 and March 1997, 143 patients underwent aortic root replacement with the Carbo-Seal composite prosthesis. The indication for surgery was acute type A dissection in 31 (22%), chronic type A dissection in 9 (6%), ascending aortic aneurysm without dissection in 100 (70%), and false aneurysm of the ascending aorta in 3 (2%). Twenty-seven patients (19%) had undergone previous sternotomy, and 40 (28%) were seen as emergencies. Concomitant procedures were performed in 38 (27%), including 18 aortic arch or hemiarch replacements. Total follow-up is 270 patient-years. Follow-up is 100% complete. RESULTS: The early (30-day) mortality was 7% (10 patients). Permanent neurologic events occurred in 2%. At a mean follow-up of 23 months, 94% of survivors were in New York Heart Association functional class I. Freedom from reoperation was 97.2% +/- 1.6% (1 standard error [1 SE]) at 12 months and 95.7% +/- 2.2% at 48 months. Including early mortality, survival was 90.1% +/- 2.6% at 12 months and 83.1% +/- 3. 5% at 48 months. CONCLUSIONS: Aortic root replacement with use of the Carbo-Seal prosthesis can be undertaken with a relatively low early mortality and morbidity. A low reoperation rate and high intermediate-term survival can be expected, but continued follow-up is needed to determine the long-term efficacy of this prosthesis.

Aged↗
PubMed1999

Infections, vaccinations, and the risk of childhood leukaemia.

A nationwide case-control study was conducted in New Zealand, to test hypotheses about the role of infections in the aetiology of childhood leukaemia. Children aged 0-14 years with leukaemia were matched on age and sex to controls selected from birth records. Case ascertainment was virtually complete and 121 (92%) of 131 eligible case families took part. The participation rate among the 303 first-choice eligible controls was 69%. Home interviews and serological tests were conducted. Adjusted relative risks were estimated by logistic regression. There was an increased risk of leukaemia in relation to reported influenza infection of the child during the first year of life (adjusted odds ratio 6.8, 95% confidence interval 1.8-25.7). This could be a chance finding due to multiple comparisons, and it should be tested elsewhere. Some key variables relevant to Greaves' hypothesis were not associated with B-cell precursor acute lymphoblastic leukaemia (numbers of infections and vaccinations, firstborn status, attendance at preschool groups), although a small effect could not be ruled out with a study of this size. Leukaemia risk was higher among children in poorer social circumstances, and this was true for all eligible children as well as for the participants.

Adolescent↗
PubMed1999

Lipid and lipoprotein analysis of cats with lipoprotein lipase deficiency.

BACKGROUND: We have previously described a colony of domestic cats with a naturally occurring mutation in the lipoprotein lipase (LPL) gene. We have now further characterized cats homozygous for LPL deficiency (LPL -/-, homozygotes), and have contrasted these with heterozygotes (LPL +/-) and normal cats (LPL +/+). MATERIALS AND METHODS: Density gradient ultracentrifugation with subsequent lipid analysis, agarose and polyacrylamide gel electrophoresis was used to examine detailed liproprotein differences between the genotypes. Oral fat loading studies and breast milk fatty acid analysis were also performed to further characterize the phenotypic expression of LPL deficiency in this model system. RESULTS: Several lipid abnormalities associated with homozygosity for LPL deficiency were evident. Triglyceride-rich lipoprotein-triglycerides (TRL-TG) and cholesterol (TRL-C) were higher (TRL-TG 2.09 +/- 1.14 vs. 0.15 +/- 0.04 mmol L-1, P < 0.001; TRL-C 0.42 +/- 0.30 vs. 0.11 +/- 0.16 mmol L-1, P < 0.05) in male -/- than in male +/+ cats, as was HDL-cholesterol (HDL-C, 1.75 +/- 0.24 vs. 1.41 +/- 0.14 mmol L-1, P < 0.05). LDL-C levels were lower in homozygous cats than in control cats, similar to what is seen in human LPL deficiency. Oral fat loading studies revealed that homozygous cats have a marked reduced ability to clear plasma TGs in terms of peak time (7 h vs. 3 h), peak height (9.36 vs. 1.1 mmol L-1), area under the TG clearance curve (AUC, 280.3 vs. 2.2 h mmol L-1) and time to return to baseline. Fasting lipid and lipoprotein levels were not significantly different between heterozygous and normal cats. However, oral fat loading in heterozygotes revealed an intermediate phenotype (peak of 2.35 mmol L-1 at 5 h, AUC 13.1 h mmol L-1), highlighting the impaired TG clearance in these animals. CONCLUSION: Thus, LPL deficiency in the cat results in a lipid and lipoprotein phenotype that predominantly parallels human LPL deficiency, further validating the use of these animals in studies on the pathobiology of LPL.

Animals↗
PubMed1999

Childhood cancer in New Zealand 1990 to 1993.

An epidemiological study of childhood cancer in New Zealand identified 409 children aged 0 to 14 years with malignant neoplasms newly diagnosed between 1990 and 1993 inclusive. The original microscopic material on which the diagnoses were based was reviewed in 398 cases and the neoplasms were allocated into the 12 major groupings and 48 further subcategories of the International Classification of Childhood Cancer (ICCC). The pathology reviewers agreed with group and subcategory classification of the confirmed cancers in all but one case of acute leukemia and three cancers of the central nervous system. Changes were also made in the FAB classification of three cases of acute non-lymphocytic leukemia and in the further subcategorisation of three Hodgkin's lymphomas and ten astrocytomas. The results show a high level of diagnostic accuracy for confirmed childhood neoplasms in that time period. Nine of 15 cases of malignant melanoma notified to the study were not confirmed for various reasons, which included a change in the pathological diagnosis in four cases. Compared with Victoria (Australia), New Zealand has a high incidence rate of lymphomas in boys and an unusual female preponderance of Wilms' tumor cases.

Adolescent↗
PubMed1999

Coronary revascularisation for postischaemic heart failure: how myocardial viability affects survival.

OBJECTIVE: To assess the impact of revascularisation of viable myocardium on survival in patients with postischaemic heart failure. METHODS: 35 patients (mean (SD) age 58 (7) years) with severe heart failure (New York Heart Association (NYHA) functional class > or = III), mean left ventricular ejection fraction (LVEF) 24 (7)% (range 10-35%), and limited exercise capacity (peak oxygen consumption (VO(2)) 15 (4) ml/kg/min) were studied. 21/35 patients had no angina. Myocardial viability was assessed with quantitative positron emission tomography and the glucose analogue (18)F-fluorodeoxyglucose (FDG) (viable segment = FDG uptake > or = 0.25 micromol/min/g) in all patients before coronary artery bypass grafting. Patients were divided into two groups: group 1, > or = 8 viable dysfunctional segments (mean 12 (2), range 8-15); and group 2, < 8 viable dysfunctional segments (mean 3.5 (3), range 0-7). The two groups were comparable for age, sex, NYHA class, LVEF, and peak VO(2). RESULTS: Two patients died perioperatively and seven patients died during follow up (mean 33 (14) months). All deaths were from cardiac causes. Kaplan-Meyer survival analysis showed 86% survival for group 1 patients versus 57% for group 2 (p = 0.03). Analysis by Cox proportional hazard model revealed three independent factors for cardiac event free survival: presence of > or = 8 viable segments (p = 0.006); preoperative LVEF (p = 0.002); and patient age (p = 0.01). CONCLUSION: Revascularisation for postischaemic heart failure can be associated with good survival, which is critically dependent upon the amount of viable myocardium.

Adult↗
PubMed1998

Prototypes of intrafamily homicide and serious assault among insanity acquittees.

Public concern with societal violence is intensified when persons who have been found not guilty by reason of insanity (NGRI) of having committed a homicide or serious assault are returned to the community. Successful management of such acquittees in the community requires a sophisticated understanding of the person and the illness within the larger context of the violent incident, the family, the community, and the culture. In this article, we present an analysis of psychotic violence within a family context. A qualitative study of 64 subjects who were found NGRI of killing or seriously injuring a family member resulted in four prototypes of intrafamilial homicide/assault: Till Death Us Do Part; Overwhelming Burden, Elimination of the Limit Setter; and Family-Focused Delusional Killing. The prototypes are presented as a model for developing management strategies both for future risk assessment and for successful transition of the insanity acquittee into the community.

Adolescent↗
PubMed1997

Insulin-like growth factor-I prevents development of a vincristine neuropathy in mice.

Vincristine is a commonly used antitumor agent whose major dose-limiting side-effect is a mixed sensorimotor neuropathy. To assess whether insulin-like growth factor-I (IGF-I), a neurotrophic agent that supports the survival of motoneurons and enhances regeneration of motor and sensory neurons, could prevent the peripheral neuropathy produced by vincristine, mice were treated with both vincristine (1.7 mg/kg, i.p., 2 x /week) and/or IGF-I (0.3 or 1 mg/kg, s.c. daily) for 10 weeks. In mice treated with vincristine alone, there was evidence of a mixed sensorimotor neuropathy as indicated by changes in behavior, nerve conduction and histology. Caudal nerve conduction velocity was significantly slower in mice treated with vincristine alone as compared with vehicle-treated mice. Vincristine treatment alone also significantly increased hot-plate latencies and reduced gait support and stride length, but not toe spread distances. The effects of vincristine were accompanied by degeneration of sciatic nerve fibers and demyelination, indicating a peripheral neuropathy. IGF-I (1 mg/kg, s.c.) administered to vincristine-treated mice prevented the neurotoxic effects of vincristine as measured by nerve conduction, gait, response to noxious stimuli and nerve histology. At a lower dose of 0.3 mg/kg administered s.c., IGF-I partially ameliorated the neuropathy induced by vincristine as this dose only prevented the change in nerve conduction and hot-plate latencies. IGF-I administered alone had no effect on any of these parameters. These results suggest that IGF-I prevents both motor and sensory components of vincristine neuropathy and may be useful clinically in preventing the neuropathy induced by vincristine treatment.

Animals↗
PubMed1997

Novel case of del(17)(q23.1q23.3) further highlights a recognizable phenotype involving deletions of chromosome (17)(q21q24).

We report on a girl with a phenotype and developmental profile initially suggestive of Angelman syndrome. Subsequently she was shown to have an interstitial deletion of the long arm of chromosome 17; [del(17)(q23.1q23.3)], the smallest unique cytogenetic deletion in this region documented to date. These findings and those of 4 others from the literature, with overlapping deletions of 17q and breakpoints between 17q21-17q24, are reviewed and compared. Similar phenotypic findings include growth retardation, global developmental delay, and specific musculoskeletal and craniofacial anomalies. The size of the specific deletion, and the proximal and distal breakpoints at this region of chromosome 17q, appear to be important in determining morbidity from cardiac involvement and may affect the extent of developmental delay.

Angelman Syndrome↗
PubMed1997

Efficient adenovirus-mediated ectopic gene expression of human lipoprotein lipase in human hepatic (HepG2) cells.

Gene therapy to deliver and express a corrective lipoprotein lipase (LPL) gene may improve the lipid profile and reduce the morbidity and potential atherogenic risk from hypertriglyceridemia and dyslipoproteinemia in patients with complete or partial LPL deficiency. We have used an E1-/E3- adenoviral vector, with an RSV-driven human LPL cDNA expression cassette (Ad-RSV-LPL), to achieve high ectopic LPL gene expression in the human hepatoma cell line HepG2, an accepted hepatocellular model of lipoprotein metabolism. Ad-RSV-LPL transduction of HepG2 cells with a multiplicity of infection (moi) between 12.5 and 100 yielded dose-dependent increments in LPL mass and activity. Peak levels of LPL protein of 2,032.1 +/- 274.5 ng/10(5) cells per ml (mol 100) correlated with increased activity of 92.7 +/- 22.6 mU/10(5) cells per ml relative to negligible LPL levels in Ad-RSV-LacZ (beta-galactosidase) controls. Exogenous LPL expression over a 5-day period peaked at day 3. Susceptibility to inhibition by 1 M NaCl and an anti-LPL monoclonal antibody confirmed that lipase activity was indeed derived from human LPL. Hydrolysis, by LPL-overexpressing HepG2 cells, of TG carried in very-low-density lipoprotein (VLDL) showed that greater than 50% of the triglycerides (TG) disappeared after 4 hr of incubation. These results were compatible with FPLC evidence of a marked reduction in VLDL-TG. These results provide strong in vitro evidence that adenoviral-mediated ectopic expression of the human LPL gene could render hepatic cells capable of VLDL catabolism and thus support the possibility for in vivo adenoviral vector-mediated liver-targeted LPL gene therapy.

Adenoviridae↗
PubMed1997

The accuracy and completeness of childhood cancer registration in New Zealand.

The New Zealand Cancer Registry (NZCR) is the main source of data on cancer incidence in New Zealand. The accuracy and completeness of registration of childhood cancers (ages zero to 14 years) were assessed during the conduct of a case-control study. Newly diagnosed children (1990-93) were ascertained from three sources: the NZCR; the Patient Management System (hospital admissions and discharges); and the separate Children's Cancer Registry. Pathology reviews were conducted to verify the diagnoses. Capture-recapture methods were used to assess the completeness of ascertainment. During the four-year period, 409 incident cases of childhood cancer were confirmed, giving an age-standardized incidence rate of 131 per million person-years (95 percent confidence interval = 119-144). The NZCR ascertained 395 (97 percent) of these children. In addition, the NZCR notified us of 43 other 'childhood cancer' registrations which were not confirmed as new cases of childhood cancer according to our eligibility criteria. The main reasons for these were coding errors (20 registrations), duplicates (seven), and a change in the pathological diagnosis as a result of the pathology review (seven). The capture-recapture estimate of the total number of incident cases was 410. Overall, the NZCR had good completeness for childhood cancers, but the number of unconfirmed registrations was larger than expected.

Adolescent↗
PubMed1997

Correction of hypertriglyceridemia and impaired fat tolerance in lipoprotein lipase-deficient mice by adenovirus-mediated expression of human lipoprotein lipase.

Humans homozygous or heterozygous for mutations in the lipoprotein lipase (LPL) gene demonstrate significant disturbances in plasma lipoproteins, including raised triglyceride (TG) and reduced HDL cholesterol levels. In this study we explored the feasibility of adenovirus-mediated gene replacement therapy for LPL deficiency. A total of 5 x 10(9) plaque-forming units (pfu) of an E1/E3-deleted adenovirus expressing either human LPL (Ad-LPL) or the bacterial beta-galactosidase gene (Ad-LacZ) as a control were administered to mice heterozygous for targeted disruption in the LPL gene (n = 57). Peak expression of total postheparin plasma LPL activity was observed at day 7 in Ad-LPL mice versus Ad-LacZ controls (834 +/- 133 vs 313 +/- 89 mU/mL, P < .01), and correlated with human-specific LPL activity (522 +/- 219 mU/mL) and mass (9214 +/- 782 ng/mL), a change that was significant to 14 and 42 days, respectively. At day 7, plasma TGs were significantly reduced relative to Ad-LacZ mice (0.17 +/- 0.07 vs 1.90 +/- 0.89 mmol/L, P < .01) but returned to endogenous levels by day 42. Ectopic liver expression of human LPL was confirmed by in situ hybridization analysis and from raised LPL activity and mass in liver homogenates. Analysis of plasma lipoprotein composition revealed a marked decrease in VLDL-derived TGs. Severely impaired oral and intravenous fat-load tolerance in LPL-deficient mice was subsequently corrected after Ad-LPL administration and closely paralleled that observed in wild-type mice. These findings suggest that liver-targeted adenovirus-mediated LPL gene transfer offers an effective means for transient correction of altered lipoprotein metabolism and impaired fat tolerance due to LPL deficiency.

Adenoviridae↗
PubMed1997

Diet-induced atherosclerosis in the domestic cat.

The domestic cat has not been used in studies of atherosclerosis, with the exception of a single study published in 1970. We have further evaluated the susceptibility of the domestic cat to diet-induced atherosclerosis, the ultimate intent being to discern the atherogenic risk due to lipoprotein lipase deficiency in an affected feline kindred with a phenotype very similar to that of the human form of this condition. We subjected a group of normal domestic cats to a moderately high-fat, cholesterol-enriched diet (30% fat and 3% cholesterol) for a period of 2 to 8 months. Plasma lipid levels were monitored monthly. At the time of killing, all organs and the entire vascular tree were removed, sectioned, processed, and stained with hematoxylin and eosin. The entire vascular tree was also stained with Movat's pentachrome and oil red O (ORO) and assessed semiquantitatively (0 to 5+/5+) and quantitatively (mean intimal area and ORO positivity, mm2). Both blood lipid measurements (total cholesterol, high-density lipoprotein-cholesterol, triglycerides, and low-density lipoprotein-cholesterol) and vessel wall lesion assessment (intimal area, mm2) were statistically elevated (p < 0.05) in the cholesterol-fed cats as compared to those on a normal diet. The highest correlations obtained between blood lipid components and vessel wall measures were the percent increase in triglyceride from base line versus the ORO measurement or foam cell grade (r = 0.86), and percent increase in triglycerides versus the intimal area in the lower abdominal aorta (r = 0.91). Similar relationships were found when the intimal area in the brachiocephalic/subclavian vessels was correlated with the absolute triglyceride values (r = 0.85) or with the percent increase in triglycerides (r = 0.83). Thus, we produced atherosclerotic lesions in the cat within 2 to 4 months on a cholesterol-enriched diet; blood lipid levels were highly correlated with lesional measurements in the vessel wall. This study will provide the basis for evaluation of the susceptibility of New Zealand lipoprotein lipase-deficient cats to diet-induced atherosclerosis.

Animal Feed↗
PubMed1996

Accumulation of xylitol in the mammalian lens is related to glucuronate metabolism.

Cataract remains the major cause of blindness worldwide and a common complication of diabetes. Polyol accumulation in the lens is associated with cataract formation. Here we present evidence for a novel pathway for xylitol production in the lens involving glucuronate metabolism. Xylitol can be produced in rat and bovine lens from glucose, via the enzymes myo-inositol-oxygen oxidoreductase, D-glucuronate reductase, L-gulonate NAD(+)-3-oxidoreductase and L-iditol-NAD(+)-5-oxidoreductase, which have been found in the mammalian lens for the first time. Glucuronate reductase has been purified and was inhibited by thiol quenching reagents. UDP-glucuronyl transferase is also present in mammalian lenses; this enzyme may be an anti-toxic defense mechanism in the lens.

Animals↗
PubMed1996

A mutation in the lipoprotein lipase gene is the molecular basis of chylomicronemia in a colony of domestic cats.

Members of a domestic cat colony with chylomicronemia share many phenotypic features with human lipoprotein lipase (LPL) deficiency. Biochemical analysis reveals that these cats do have defective LPL catalytic activity and have a clinical phenotype very similar to human LPL deficiency. To determine the molecular basis underlying this biochemical phenotype, we have cloned the normal and affected cat LPL cDNAs and shown that the affected cat has a nucleotide change resulting in a substitution of arginine for glycine at residue 412 in exon 8. In vitro mutagenesis and expression studies, in addition to segregation analysis, have shown that this DNA change is the cause of LPL deficiency in this cat colony. Reduced body mass, growth rates, and increased stillbirth rates are observed in cats homozygous for this mutation. These findings show that this LPL deficient cat can serve as an animal model of human LPL deficiency and will be useful for in vivo investigation of the relationship between triglyceride rich lipoproteins and atherogenic risk and for the assessment of new approaches for treatment of LPL deficiency, including gene therapy.

Amino Acid Sequence↗
PubMed1995

Comparative study of the prevalence of maxillary sinusitis in later Medieval urban and rural populations in northern England.

Six hundred sixty-three Medieval individuals from Wharram Percy, a rural settlement in the Yorkshire Wolds, and 1,042 individuals from St. Helen-on-the-Walls, a poor parish in the Medieval city of York, were examined in order to test the hypothesis that maxillary sinusitis would be more prevalent in an urban population due to social and environmental conditions characteristic of an industrialized settlement. The results showed that the individuals from St. Helen-on-the-Walls, living in the urban environment, had a greater prevalence of maxillary sinusitis than the rural population; 39% (106) of the individuals from Wharram Percy had evidence of sinusitis compared to 55% (134) of the individuals from St. Helen-on-the-Walls. It is suggested that this pattern may be attributed to occupation and industrial air pollution in the Medieval city of York.

England↗
PubMed1995

Retroviral-mediated gene transfer and expression of human lipoprotein lipase in somatic cells.

Lipoprotein lipase (LPL) is an enzyme responsible for the hydrolysis of triglyceride-rich circulating lipoproteins. Humans with complete defects in LPL activity present from infancy with failure to thrive, eruptive xanthomas, pancreatitis, and lactescent plasma. In addition, heterozygous carriers for this disorder may be at increased risk for the development of coronary artery disease. In view of a potential strategy for correcting complete or partial LPL deficiency, a 1.56-kb human LPL cDNA was inserted into a series of recombinant myeloproliferative sarcoma virus (MPSV)-based retroviral vectors under transcriptional control of the constitutive MPSV long terminal repeat (LTR). Stable gene transfer and enhanced expression of human LPL was observed at both the RNA and protein level in a variety of somatic cell types in vitro. Genetically modified cell populations included mouse NIH-3T3 fibroblasts and C2C12 myoblasts, primary human fibroblasts, and established human hematopoietic cell lines of erythroid (K562), myelocytic (HL60), and monocytic (U937,THP-1) type. The achieved levels of bioactive human LPL were found to vary widely between the different transduced cell lines, which may be critical to an approach to gene therapy. Transduced primary human fibroblasts yielded maximal elevation of LPL immunoreactive mass and activity of at least 24- and 50-fold, respectively, above constitutively expressed levels for this cell type. Human fibroblasts, therefore, appear to accommodate in vitro the complex processes readily leading to the maturation and secretion of bioactive human LPL and may serve as an effective cellular vehicle for LPL gene delivery and expression in human LPL deficiency.

3T3 Cells↗