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Biomedical subjects

B Levy

Publications and source records attributed to B Levy.

At least 235 records · Page 13Linked to original sources
PubMedDate not supplied

Fixed-dose combination diuretics in congestive heart failure: an evaluation.

Thirty-two patients with congestive heart failure were studied for their clinical and biochemical responses to the administration of two combination diuretic products (hydrochlorothiazide/spironolactone and hydrochlorothiazide/triamterene) and the single entity diuretic furosemide. Data from these studies revealed the following: 1. Comparison of the patients on furosemide with those receiving the combination products showed no difference in serum potassium or 24-hour potassium excretion. 2. Significant changes in blood urea nitrogen, plasma renin activity, and urinary aldosterone excretion were noted with both fixed-combination medications but not with furosemide. 3. The combination diuretics offered no clinical benefits over the single agent furosemide. 4. Therapy is best served by the use of a single effective diuretic agent for the treatment of most patients with congestive heart failure.

Blood Urea Nitrogen↗
PubMedDate not supplied

In utero fetal liver cell transplantation without toxic irradiation alleviates lysosomal storage in mice with mucopolysaccharidosis type VII.

Lysosomal storage diseases, such as Mucopolysaccharidosis type VII (MPS VII), cause progressive loss of mobility and intellect and result in early death. Treatment of progressive diseases must occur before the blood-brain barrier closes. In MPS VII mice, normal donor hematopoietic cells secrete the missing enzyme beta-glucuronidase (GUSB) that reverses disease manifestations. Correction of lysosomal storage is limited to the visceral organs unless transplantation is preceded by high-dose irradiation. We hypothesize that irradiation opens the blood-brain barrier allowing passage of corrective cells. Here we transplanted genetically myeloablated MPS VII fetuses to determine whether earlier treatment without toxic irradiation is systemically corrective. Cells with a selective advantage in utero were identified. Donor fetal liver cells (FLC), a substitute for difficult to obtain murine cord blood cells, were increased 10-fold in the host peripheral blood over equivalent numbers of adult marrow cells injected simultaneously and were stable long term in both primary and secondary hosts. GUSB- MPS VII fetuses injected with GUSB+ FLC were assessed longitudinally after birth. Donor FLC replaced host stem cell descendants, prolonged life dramatically, and reduced bone dysplasia and lysosomal storage in all tissues long term. GUSB, donor leptomeningeal cells, and microglia were present in the brain at 11 months postinjection. Lysosomal storage in cortical neurons and glia, although not completely corrected, was reduced. We conclude that in utero intervention without toxic pretreatment in this model reduces the storage disease long term and improves the length and quality of life despite exerting only minor effects on the brain.

Animals↗
PubMedDate not supplied

Effect of vasopressin on phasic coronary blood flow.

The effects of vasopressin on the coronary circulation have been studied with regard to its general hemodynamic effects. Aortic blood pressure (BP), left ventricular pressure (LVP), aortic blood flow (AoBF), and circumflex blood flow (CBF), were measured in 12 open-chest dogs, under control conditions and during vasopressin infusion (25 mU/kg/min). During vasopressin infusion, the mean aortic blood pressure (MBP) was increased from 104 +/- 23 mm Hg to 161 +/- 23 mm diastolic blood pressure (DBP) was more increased (+55%) than the systolic blood pressure (SBP) (+40%). AoBF was decreased from 2.169 +/- 0.408 l/min to 1.118 +/- 0.303 l/min; and the heart rate was decreased by 18%. The total combined left ventricular power did not change significantly. The increase in total peripheral resistance (TPR) (+200%) was the main change in impedance spectrum. The mean circumflex coronary blood flow (MCBF) was decreased from 48 +/- 8.6 ml/min to 33.4 +/- 9.7 ml/min. This decrease was more important in the diastolic circumflex blood flow (DCBF) (-33%) than in the systolic one (-0.8%). The diastolic pressure time index (DPTI) was more increased than the systolic pressure time index (SPTI). The DPTI/SPTI ratio was increased from 0.91 to 1.3. Long diastoles, induced by vagus nerve stimulation, have permitted to characterise the relationship between pressure and coronary blood flow during diastole. This relationship was linear under basal condition, and during vasopressin perfusion. This made it possible to determine the critical closing pressure (Pf0), and the coronary conductance (the slope of the regression curve). Vasopressin induced an increase in Pf0, from 33.7 +/- 95 to 77.4 +/- 16.07 mm Hg (p less than 0.001), and a decrease in coronary conductance, from 0.8 +/- 0.32 to 0.5 +/- 0.1 ml/min/mm Hg. The effect of an acute change in perfusion pressure on the coronary flow, under control conditions and during vasopressin infusion was studied by opening a large arteriovenous fistula. Unclamping of the fistula, under control conditions, allowed to realize an acute fall in DBP from 82.5 +/- 6.36 to 35.5 +/- 9.19 mm Hg, and in DCBF, from 58.5 +/- 9.2 to 20 +/- 9.8 ml/min. During vasopressin infusion, a similar fall in perfusion pressure lead to a zero diastolic circumflex blood flow, for a diastolic aortic blood pressure of 56 +/- 12 mm Hg. However, vasopressin did not affect the delayed active coronary vasodilatation.

Animals↗
PubMedDate not supplied

Murine mucopolysaccharidosis VIL: impact of therapies on the phenotype, clinical course, and pathology in a model of a lysosomal storage disease.

The mucopolysaccharidoses are a group of lysosomal storage diseases caused by deficiency of an enzyme required for the normal degradation of glycosaminoglycans. Patients with mucopolysaccharidosis typically have widespread lysosomal storage, skeletal and central nervous system disease, and hepatosplenomegaly. Some patients with mucopolysaccharidosis may benefit from enzyme replacement therapy or bone marrow transplantation. Animal models of mucopolysaccharidosis have proven valuable for the evaluation of the effectiveness of potential treatments for patients with lysosomal storage disease. A murine model of MPS VII (Sly syndrome) has proven particularly useful because of its well-defined genetics and its well-characterized clinical, pathologic, and biochemical alterations, which resemble those seen in patients with mucopolysaccharidosis. Correction of these alterations forms the basis for evaluation of the effectiveness of novel treatments. A wide range of therapies have been tested using this model, including enzyme replacement therapy, bone marrow, stem cell, and neural progenitor cell transplantation, and a variety of viral-mediated gene therapies. The inferences drawn from these therapeutic studies using the murine MPS VII model are likely generalizable to other lysosomal storage diseases.

Animals↗
PubMedDate not supplied

Intrathecal enzyme replacement therapy reduces lysosomal storage in the brain and meninges of the canine model of MPS I.

Enzyme replacement therapy (ERT) has been developed for several lysosomal storage disorders, including mucopolysaccharidosis I (MPS I), and is effective at reducing lysosomal storage in many tissues and in ameliorating clinical disease. However, intravenous ERT does not adequately treat storage disease in the central nervous system (CNS), presumably due to effects of the blood-brain barrier on enzyme distribution. To circumvent this barrier, we studied whether intrathecal (IT) recombinant human alpha-L-iduronidase (rhIDU) could penetrate and treat the brain and meninges. An initial dose-response study showed that doses of 0.46-4.14 mg of IT rhIDU successfully penetrated the brain of normal dogs and reached tissue levels 5.6 to 18.9-fold normal overall and 2.7 to 5.9-fold normal in deep brain sections lacking CSF contact. To assess the efficacy and safety in treating lysosomal storage disease, four weekly doses of approximately 1 mg of IT rhIDU were administered to MPS I-affected dogs resulting in a mean 23- and 300-fold normal levels of iduronidase in total brain and meninges, respectively. Quantitative glycosaminoglycan (GAG) analysis showed that the IT treatment reduced mean total brain GAG to normal levels and achieved a 57% reduction in meningeal GAG levels accompanied by histologic improvement in lysosomal storage in all cell types. The dogs did develop a dose-dependent immune response against the recombinant human protein and a meningeal lymphocytic/plasmacytic infiltrate. The IT route of ERT administration may be an effective way to treat the CNS disease in MPS I and could be applicable to other lysosomal storage disorders.

Animals↗
PubMedDate not supplied

Endothelium-dependent changes in arterial diameter in old normotensive rats.

1. In normotensive rats, removal of carotid artery endothelium results in an acute increase in diameter. This finding, observed in young animals, has not been investigated in old animals. The present study was undertaken to assess the contribution of endothelial function in the regulation of arterial stiffness in aged rats. 2. In normotensive female WAG/Rij rats, isobaric (100 mmHg transmural pressure) carotid diameter was measured in vitro in situ, using a previously described arterial preparation associated with a high-resolution echotracking technique allowing non-invasive diameter measurements under baseline conditions, after removal of the endothelium and after total relaxation of vascular smooth muscle by potassium cyanide. Histomorphometry of the carotid wall was studied after pressure fixation (100 mmHg) of the arteries. 3. Compared with younger animals (10 months), older animals (30 months) had the same baseline carotid isobaric diameter but significantly higher values of wall thickness and collagen content. In older animals, whereas total relaxation by potassium cyanide was associated with a slight but significant increase of isobaric diameter, no increase was observed after endothelium removal. 4. The results of the presnt study provide evidence that, in old normotensive rats, endothelium-dependent increases in isobaric carotid diameter are blunted. This endothelium alteration may contribute to the age-dependent increase in isobaric carotid stiffness observed in old rats.

Aging↗
PubMedDate not supplied

The maturation and aging of the vertebrae of marmosets.

This study deals with the growth, maturation, and age changes to the cartilaginous end-plates of vertebrae from marmosets (Callithrix jacchus) varying in age from birth to 10 years. The cartilaginous end-plate is divided into an inner growth layer and an outer articular zone that abuts against the intervertebral disc. The growth cartilage gradually narrows and disappears by 1 year of age, when the animal reaches physical maturity. The articular cartilage undergoes changes in collagen and ground substance that leads to its calcification. There was a progressive resorption of the calcified articular cartilage beginning at 3 years of age and continuing throughout the aging period. In the vertebrae of 8- and 10-year-old animals, only a thin layer of calcified cartilage separates the disc from the underlying bone.

Aging↗
PubMedDate not supplied

Clinical applications of comparative genomic hybridization.

PURPOSE: Comparative genomic hybridization (CGH) is a powerful DNA-based cytogenetic technique that allows the entire genome to be scanned for chromosomal imbalances without requiring the sample material to be mitotically active. During the past 2 years we received many requests from various medical centers around the country to use CGH to resolve the identity of aberrant chromosomal material. METHODS: We report the use of CGH for the evaluation of 12 clinical postnatal cases in which traditional cytogenetic analysis yielded ambiguous results. This series consisted of five marker chromosomes, five unbalanced translocations, and two intrachromosomal duplications. RESULTS: Identification and characterization of the additional unknown chromosomal material was achieved with use of CGH. All CGH findings were validated by traditional fluorescence in situ hybridization and other specialized staining techniques. CONCLUSLONS: These results demonstrate the effective use of CGH as a focused, single-step method for the identification of chromosomal material of unknown origin.

Adolescent↗
PubMedDate not supplied

To be or not to be: the effects of aging stereotypes on the will to live.

This study examined whether stereotypes of aging might contribute to decisions the elderly make about when to die. Old and young participants (N=64) were subliminally primed with either negative or positive stereotypes of old age and then responded to hypothetical medical situations involving potentially fatal illnesses. Consistent with our prediction, the aged participants primed with negative stereotypes tended to refuse life-prolonging interventions, whereas the old participants primed with positive age stereotypes tended to accept the interventions. This priming effect did not emerge among the young participants for whom the stereotypes were less relevant. The results suggest that societally-transmitted negative stereotypes of aging can weaken elderly people's will to live.

Age Factors↗
PubMedDate not supplied

Elevated virulence of Newcastle disease virus strains following serial passages in kidney cells in vitro.

Serial passage of two lentogenic Newcastle disease virus (NDV) strains in kidney cell lines increased virulence and changed viral biological properties. In two cell lines (BHK and MDBK), elevation in virulence was demonstrated by plaque formation under an overlay with no additives, decrease in mean death times, elevated intracerebral pathogenicity index, and cytopathic effect in chicken embryo fibroblasts. Some other markers not directly correlated to virulence, such as heat inactivation of hemagglutinin and neuraminidase, were not influenced by passage in kidney cells. In addition, all strains were slow eluters. This observation emphasizes the importance of preventing the virus from reaching the viscera.

Animals↗