[Changes in the arterial wall in aging].
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Aging↗
Biomedical subjects
B Levy
Publications and source records attributed to B Levy.
Does pulse lavage reduce hip hemiarthroplasty infection rates?
This paper reports a prospective randomized trial involving four hospitals in the south of England, in which every hemiarthroplasty (American Association of Anaesthetists grade IV and above) was randomized to one of two limbs. In the first group, the patients received a 2-L pulse lavage normal saline washout; in the second group, they received a 2-L normal saline washout via a jug or a syringe. All wounds were reviewed during their time in hospital up to 30 days post surgery or discharge (using criteria from the Nosocomial Infection National Surveillance Survey). Any re-admissions for infection were recorded. The pulse lavage group had a significantly lower total infection rate and, specifically, a decreased 'joint space' or deep infection rate.
Arthroplasty, Replacement, Hip↗
Detection of an interstitial deletion of 2q21-22 by high resolution comparative genomic hybridization in a child with multiple congenital anomalies and an apparent balanced translocation.
Various molecular cytogenetic techniques are currently available to accurately characterize chromosome rearrangements in patients with multiple congenital anomalies. Among these is comparative genomic hybridization (CGH) whose main advantage is the ability to perform a whole genome scan without prior knowledge of the underlying chromosome abnormality. It has been used mostly in the area of cancer cytogenetics, but its role in clinical genetics is now expanding to even include preimplantation genetic diagnosis. We have used this method to reveal an interstitial deletion in a patient with multiple anomalies, who had for years been thought to have a de novo balanced translocation involving chromosomes 1 and 2. A review of published reports suggests that there is significant phenotypic and genetic heterogeneity in the small group of patients including our own with interstitial deletions of 2q21-q22.
Abnormalities, Multiple↗
N(carboxymethyl)lysine as a biomarker for microvascular complications in type 2 diabetic patients.
AIMS: Hyperglycemia is linked to vascular dysfunction in patients with diabetes mellitus, either directly or through advanced glycation end product (AGE) formation. Experimental evidence has indicated the possible involvement of AGEs in the genesis of vascular complications. We investigated whether serum levels of AGEs and of the glycoxidation compound carboxymethyl-lysine (CML) were increased and correlated with vascular complications in type II diabetes mellitus. METHODS: Serum levels of AGEs and CML-human serum protein (CML-HSP) were measured by a specific immunoassay in 51 men and 26 women aged 58 +/- 6.1 years (mean +/- SD) who had been treated for type II diabetes mellitus for 11 +/- 8 years, and in a non-diabetic control group consisting of 39 men and 21 women aged 55.5 +/- 7.5 years. Patients with macroalbuminuria or abnormal creatinine clearance were excluded from the study. RESULTS: The serum levels of AGEs were significantly increased in patients with type II diabetes compared to controls (P<0.001). Blood levels of CML-HSP were significantly increased in diabetic patients compared to normal subjects [35.3 +/- 27.4 and 9.3 +/- 7.2 (mean +/- SD) pmol/mg of protein, respectively; P<0.0001]. In diabetic patients with retinopathy or microalbuminuria (urinary albumin excretion: UAE > 30 mg/24 h), CML-HSP levels were significantly higher (P<0.02), and even more elevated in patients with both complications. CONCLUSION: In patients with type II diabetes, CML-HSP levels that are at variance with the HbA(1c) index for blood glucose may be a biomarker of glycoxidation, and related to the development of microvascular complications.
Biomarkers↗
Efficacy and safety of sibutramine for weight loss in obese patients with hypertension well controlled by beta-adrenergic blocking agents: a placebo-controlled, double-blind, randomised trial.
Sibutramine is a serotonin-noradrenaline reuptake inhibitor that is effective for long-term weight reduction and maintenance in obese patients when used as an adjunct to dietary and behavioural measures. Because the inhibition of noradrenaline reuptake may be expected to increase systolic and diastolic blood pressure (SBP and DBP) and pulse rate (PR), a 12-week multi-centre, placebo-controlled, double-blind study was designed to evaluate the efficacy and tolerability of sibutramine for weight loss in obese patients whose hypertension was well controlled (DBP < or = 95 mm Hg) by beta-adrenergic blocking agents (beta-blockers), with or without concomitant thiazide diuretics. Of the 61 patients randomised to sibutramine 20 mg once daily or placebo, 55 patients (90%) completed the study. After 12 weeks, sibutramine-treated patients lost significantly more weight than placebo-treated patients: mean weight reductions were 4.2 kg (4.5%) in the sibutramine group vs 0.3 kg (0.4%) in the placebo group (P<0.001). Greater weight reduction on sibutramine was accompanied by trends for greater mean reductions in serum triglycerides and very low density lipoprotein cholesterol. Sibutramine was well tolerated, and most adverse events were mild or moderate in severity. No sibutramine patient discontinued treatment because of an adverse event. Mean supine and standing DBP and SBP were not statistically significantly different between the sibutramine group and the placebo group at any post-baseline visit during the 12-week trial. At week 12, mean increases from baseline supine SBP and DBP, respectively, were 1.6 and 1.7 mm Hg for the sibutramine group vs increases of 0.4 and 1.3 mm Hg for the placebo group. At week 12, mean increases from baseline standing SBP and DBP, respectively, were 1.5 and 1.8 mm Hg for the sibutramine group vs an increase of 0.3 and a decrease of 0.8 mm Hg for the placebo group (P > 0.05 for treatment comparison). A statistically significant mean increase of 5.6 bpm (+/-8.25, s.d.) in supine PR from a baseline of 62 bpm was reported in sibutramine-treated patients at week 12, whereas placebo-treated patients had a mean supine PR decrease of 2.2 bpm (+/-6.43) (P < 0.001). In summary, sibutramine was well tolerated and effective in weight reduction. The addition of sibutramine did not result in an increase in BP in obese patients whose hypertension was well controlled by a beta-blocker. However, based on the potential for changes in BP and PR, obese patients being treated with sibutramine should be monitored periodically for changes in BP and PR and managed appropriately.
Adrenergic beta-Antagonists↗
Biodistribution, kinetics, and efficacy of highly phosphorylated and non-phosphorylated beta-glucuronidase in the murine model of mucopolysaccharidosis VII.
Enzyme replacement therapy (ERT) has been shown to be effective at reducing the accumulation of undegraded substrates in lysosomal storage diseases. Most ERT studies have been performed with recombinant proteins that are mixtures of phosphorylated and non-phosphorylated enzyme. Because different cell types use different receptors to take up phosphorylated or non-phosphorylated enzyme, it is difficult to determine which form of enzyme contributed to the clinical response. Here we compare the uptake, distribution, and efficacy of highly phosphorylated and non-phosphorylated beta-glucuronidase (GUSB) in the MPS VII mouse. Highly phosphorylated murine GUSB was efficiently taken up by a wide range of tissues. In contrast, non-phosphorylated murine GUSB was taken up primarily by tissues of the reticuloendothelial (RE) system. Although the tissue distribution was different, the half-lives of both enzymes in any particular tissue were similar. Both preparations of enzyme were capable of preventing the accumulation of lysosomal storage in cell types they targeted. An important difference in clinical efficacy emerged in that phosphorylated GUSB was more efficient than non-phosphorylated enzyme at preventing the hearing loss associated with this disease. These data suggest that both forms of enzyme contribute to the clinical responses of ERT in MPS VII mice but that enzyme preparations containing phosphorylated GUSB are more broadly effective than non-phosphorylated enzyme.
Animals↗
Complex cytogenetic rearrangement of chromosome 8q in a case of Ambras syndrome.
Ambras syndrome (AMS) is a unique form of congenital universal hypertrichosis. The syndrome has been found in association with rearrangements of chromosome 8 in two isolated cases. One of these patients was reported to have an apparently balanced paracentric inversion of chromosome 8, inv(8)(q12q22). Our cytogenetic analysis on this patient showed that the rearrangement of chromosome 8 is more complex than initially reported. We detected an insertion of the q23-q24 region into a more proximal region of the long arm of chromosome 8 as well as a large deletion in 8q23:46,XX, rea(8)(8pter-->8q13::8q23.2-->8q24.1::8q13-->8q23.1::8q24.1-->8qter). Given the large number of breakpoints and the presence of a substantial deletion, it is surprising that the proposita did not show anomalies other than these characteristic of Ambras syndrome.
Child, Preschool↗
[Aclotine (antithrombotic].
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Drug Costs↗
Nonablative neonatal marrow transplantation attenuates functional and physical defects of beta-glucuronidase deficiency.
The toxicity of preparative regimens render neonatal bone marrow transplantation (BMT) for progressive childhood diseases a controversial treatment. Ablative BMT in neonatal mice with or without the lysosomal storage disease mucopolysaccharidosis type VII (MPS VII) show high morbidity and developmental disruption of both brain and bone structure. In this investigation, BMT was performed with a high dose of congenic, normal bone marrow into nonablated newborn mice. Recipients had lifelong, multilineage, peripheral blood chimerism with the donor beta-glucuronidase-positive (GUS(+)) cells that was both well tolerated and therapeutic. Three daily injections of normal adult marrow increased the average life span by at least 6 months and corrected the functional breeding deficits typical of the MPS VII mice. Twelve months after injection, several structural features of femurs were more like that of normal mice than of untreated MPS VII mice. Periosteal circumference and bone cortical thickness were significantly improved in males and cortical density did not differ significantly from values in normal females. Significant reduction of lysosomal glycosaminoglycan storage corresponded directly with GUS enzyme activity and percentage of histochemically GUS(+) cells in visceral organs and hematopoietic tissues such as thymus, spleen, peripheral blood, and bone marrow. By all criteria tested, BMT into neonatal MPS VII mice in the absence of any preparative regimen is a successful therapy.
Adult↗
Intracranial injection of recombinant adeno-associated virus improves cognitive function in a murine model of mucopolysaccharidosis type VII.
Mucopolysaccharidosis type VII (MPS VII) is a lysosomal storage disease caused by the lack of beta-glucuronidase (GUSB) activity. GUSB deficiency leads to the progressive accumulation of undegraded glycosaminoglycans (GAGs) in cells of most tissues, including the brain, and is associated with mental retardation. Reduction of lysosomal storage in the central nervous system and prevention of cognitive dysfunction may require intracranial delivery of a therapeutic agent during the newborn period that provides a continuous source of GUSB. Therefore, we injected recombinant adeno-associated virus encoding human GUSB into both the anterior cortex and the hippocampus of newborn MPS VII mice. Total GUSB activity in the brain approached normal levels by 18 weeks. Although GUSB activity was concentrated near the injection sites, lysosomal distension was reduced in most areas of the brain. In addition to histopathologic evidence of GAG reduction, the previously undescribed accumulation of GM2 and GM3 gangliosides in the brain was also prevented. Furthermore, GUSB expression and reduced lysosomal distension correlated with improvements in cognitive function as measured in the Morris Water Maze test. These findings indicate that localized overexpression of GUSB has positive effects on the pathology and cognitive function and does not have overt toxicity.
Animals↗
Evaluation of renal arteries with use of gadoterate meglumine-, CO(2)-, and iodixanol-enhanced DSA measurements versus histomorphometry in renal artery restenosis in rabbits.
PURPOSE: To experimentally evaluate gadolinium (Gd)-, carbon dioxide (CO(2))-, and iodixanol-enhanced digital subtraction angiography (DSA) versus histomorphometry in the assessment of renal artery stenosis. MATERIALS AND METHODS: Fifteen male New Zealand White rabbits weighing 4.0 kg underwent percutaneous catheterization. Renal artery stenosis was induced by bilateral overdilation-deendothelialization (balloon diameter = 2 mm). The percentage of artery overdilation was 33%. After 4 weeks, the rabbits were randomized into two groups: group A underwent right-sided therapeutic percutaneous transluminal renal angioplasty (PTRA) (balloon diameter = 1.5 mm). After another 4 weeks, the renal arteries were evaluated by gadoterate-, iodixanol-, and CO(2)-enhanced selective quantitative DSA. The rabbits were then killed and renal arteries were perfusion-fixed for 60 minutes. Serial orcein-stained 4-um-thick slices were prepared for histomorphometry. RESULTS: Based on morphometric data of single-stenosis versus post-PTRA restenosis lesions, no significant difference was observed between Gd- and iodixanol-enhanced quantitative DSA (r(2) > 0.95), although the iodine/Gd density ratio was equal to 3.5. Carbon dioxide less reliably allowed quantitative DSA (r(2) < 0.75). CONCLUSION: Gd-based contrast agents represent a highly reliable alternative in experimental quantitative DSA evaluation of renal artery restenosis.
Angiography, Digital Subtraction↗
Familial clustering and myopia progression in Singapore school children.
BACKGROUND: Familial factors may be related to the progression of myopia in children. A cohort study was conducted to determine the relationship between familial factors and myopia progression in children. METHODS: From a larger clinical trial (n = 311), 153 Singapore children aged 6--12 years were recruited to participate in a cohort study of the risk factors for myopia progression. An in-person interview was conducted whereby information on the history of myopia in first-degree relatives was obtained. Other information collected included housing type, parental education and income. Cycloplegic refractive error as measured by subjective refraction and autorefraction were ascertained every six months. The average length of follow-up was 28 months. RESULTS: The adjusted mean rate of progression of myopia was -0.60 (95% confidence interval -0.66, -0.55) diopters per year. The average rate of progression of myopia for children with a parental history of myopia was -0.63 (95% confidence interval -0.69, -0.56) diopters per year compared to -0.42 (95% confidence interval -0.57, -0.27) diopters per year for children whose parents were not myopic. The different measures of family history of myopia were related to rate of change in refractive error and refractive error in the final visit. There was no association between close work and myopia progression. CONCLUSIONS: A positive family history is related to the progression of myopia and final refractive error in Singapore children, thus supporting evidence that hereditary factors may play an important role in myopia progression.
Child↗
Ageism is a major problem in our society.
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Humans↗
A novel model of murine mucopolysaccharidosis type VII due to an intracisternal a particle element transposition into the beta-glucuronidase gene: clinical and pathologic findings.
We describe the clinical and pathologic findings in a murine model of mucopolysaccharidosis VII (Sly disease) that arose spontaneously in the C3H/HeOuJ mouse strain. Affected gus(mps2J)/gus(mps2J) mice are deficient in beta-glucuronidase because of insertion of an intracisternal A particle element into intron 8 of the gus structural gene. This is the first model of a human lysosomal storage disease caused by an intracisternal A particle element insertion. Mice with the gus(mps2J)/gus(mps2J) genotype have < 1% of normal beta-glucuronidase activity and secondary elevations of other lysosomal enzymes. The phenotype includes shortened life-span, dysmorphic features, and skeletal dysplasia. Lysosomal storage of glycosaminoglycans is widespread and affects the brain, skeleton, eye, ear, heart valves, aorta, and the fixed tissue macrophage system. Thus the phenotypic and pathologic alterations in gus(mps2J)/gus(mps2J) mice are similar to those in patients with mucopolysaccharidosis VII. The finding of antibodies to beta-glucuronidase in some older gus(mps2J)/gus(mps2J) mice suggests the mice produce sufficient enzyme to elicit an immune response. The gus(mps2J)/gus(mps2J) model provides another well-defined genetic system for the study of the pathophysiology of mucopolysaccharidosis and for evaluation of experimental therapies for lysosomal storage diseases. The disease in gus(mps2J)/gus(mps2J) mice is less severe than that seen in the previously characterized B6.C-H2(bm1)/ByBir-gus(mps)/gus(mps) mouse model. Furthermore, unlike gus(mps)/gus(mps) mice, gus(mps2J)/gus(mps2J) mice are fertile and breed to produce litters, all of which are mucopolysaccharidosis VII pups. This feature makes them extremely useful for testing intrauterine therapies.
Animals↗
Common medical terminology comes of age, Part One: Standard language improves healthcare quality.
It has become abundantly clear that standards of recording clinical terms in human-readable, computer-processable format are indispensable. Controlled medical terminology is the missing link in health information standards (in fact, medical terminology can be viewed as the mother of all standards); its absence interferes with the business of healthcare and impedes the core processes of healing and maintaining health. Medicine has lacked the controlled common medical vocabulary that would enable universal sharing of data at the point of care and ensure reliable information for determining health intervention effectiveness. Simple clinical and code content alone has proven insufficient for healthcare enterprises to successfully manage the terminology problem; the "lexical runtime engine," formerly called a vocabulary server (VOSER), which manages the vocabulary ontology and serves up the relevant vocabulary to users of applications in the clinical environment, has recently become a reality.
Database Management Systems↗
Common medical terminology comes of age, Part Two: Current code and terminology sets--strengths and weaknesses.
A number of clinical coding and vocabulary schemes are in use in healthcare enterprises today. Most of them are weak in light of the qualities that characterize adequate controlled medical terminologies, as outlined in Part One of this review. Here we look at the major code and terminology sets with a critical eye, as well as suggest practical steps to enable health industry information system purchasers and users to move forward with their effort to use common terminology to improve the quality, service, and knowledge in their enterprise.
Abstracting and Indexing↗
Use of hormone replacement therapy (Hrt) And detection of human papillomavirus (Hpv) Dna in postmenopausal women.
PURPOSE: This study investigated the association between detection of HPV DNA among current and past HRT users compared to never HRT users, duration of HRT use, and type of HRT (estrogen, estrogen/progestin).METHODS: Postmenopausal women (n = 390) were recruited from a university hospital and completed a questionnaire regarding 1) HRT use, duration, and type, 2) reproductive and sexual history, 3) smoking and alcohol use, and 4) HPV-related diseases. Cervical specimens were obtained for Pap smears, and for the presence of HPV using PCR/dot blot and DNA sequencing, and Southern blot or SSCP. Age-adjusted odds ratios (OR), 95% confidence intervals (CI), and logistic regression examined the association between HRT use and risk of HPV detection.RESULTS: The frequency of HPV was 10%, with 2.8% oncogenic types. Compared to Never Users, Current (adj. OR = 1.50, 95% CI = 0.55, 4.07) and Past (OR = 1.96, CI = 0.56, 6.86) HRT users had an elevated risk of HPV detection. Although HRT duration among Current Users was not statistically significant (OR = 1.01, 95% CI = 0.95, 1.07), duration among Past Users was significantly associated with an increased risk of HPV detection (OR = 1.30, CI = 1.06, 1.61). In addition, Past Users of estrogen/cyclic progestin HRT regimens were significantly more likely to be detected with HPV (OR = 1.82, CI = 1.11, 2.97) compared to Never Users.CONCLUSIONS: These findings indicate that risk of HPV detection is increased among users of HRTs, particularly among Past Users associated with longer duration and among those taking HRT regimens that included a progestin. Results suggest a latency or duration effect may be important in elevating the risk. They also support previous in vitro studies of progestin effects on HPV gene regulation.
Journal Article↗
Cloning, characterization, and expression of the human TIN-ag-RP gene encoding a novel putative extracellular matrix protein.
The human gene encoding a novel tubulointerstitial nephritis antigen (TIN-ag)-related protein (TIN-ag-RP) was isolated, and its genomic organization was determined. BLAST searches revealed the highest degree of homology to several mammalian TIN-ag orthologues, and a weak homology to cathepsin B-like proteases. The 12 kb gene was mapped by fluorescence in situ hybridization to chromosome 1p34.2-3, a locus neither related to that of the human TIN-ag (6p11.2-12) nor to that of cathepsin B (8p22-23.1). The TIN-ag-RP is encoded in ten exons with introns ranging from 83 bp to 4 kb. In addition, the gene contained one exon in the 5'UTR, but none in the 3'UTR. Five of the 10 splice sites of the TIN-ag-RP gene were fully conserved when compared to a related gene of C. elegans, whereas only one splice site was identical to those found in cathepsin B genes. Furthermore, human TIN-ag-RP tagged with the T7-epitope, was expressed in HeLa cells, and was found to be localized in vesicular compartments as well as secreted into the medium suggesting the involvement of the endosomal trafficking pathway. Based on the high degree of homology of the amino acid sequences and genomic organization between TIN-ag-RP and TIN-ag, we suggest that both molecules may form a distinct group or family of TIN-ag-like proteins.
Amino Acid Sequence↗