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Biomedical subjects

B Levy

Publications and source records attributed to B Levy.

At least 109 records · Page 6Linked to original sources

Complications of rigid gas permeable lenses for extended wear.

A retrospective study of 174 patients wearing rigid gas permeable lenses for a period of 2 years was carried out to determine the success rate and types of complications which typically occur. The results indicate that these types of lenses are a viable modality for extended wear, as the majority of signs which may lead to serious complications can be detected relatively early. When these signs were detected the patients were switched to daily wear and most were able to wear these lenses uneventfully. However, the results also indicate that unexpected problems can occur, and thus frequent follow-up is essential in these patients in order to avoid the potentially sight-threatening problems which have come to be associated with extended wearing of contact lenses.

Cohort Studies↗

Vascular effects of perindopril: from experimental to clinical investigation.

Vascular remodeling is central to the pathophysiology of hypertension and atherosclerosis. The effects of antihypertensive drugs on this process are important to consider from a mechanistic and a pathogenetic point of view in relation to vascular complications of hypertension, e.g., decrease in vascular reserves, shift in cerebral blood flow autoregulation and atherosclerosis development. There is now evidence that, in addition to several other growth factors, vasoactive peptides such as angiotensin II may act as vascular smooth muscle growth promoting substances. Based on these data, the effects of perindopril, a potent and long-lasting angiotensin-converting enzyme (ACE) inhibitor, on structural and mechanical properties of the arterial wall, have been studied in animal models of hypertension as well as in humans. Perindopril completely reversed aortic medial hypertrophy and arterial stiffening observed in renovascular hypertensive rats. Similar benefits were reported in mesenteric resistance vessels of spontaneously hypertensive rats. The effect of perindopril was totally in keeping with potent inhibition of vascular ACE and emphasized the potential role of angiotensin II as a vascular growth modulator. Clinical studies confirmed animal experiments; both suggest that increases in arterial compliance and distensibility following perindopril is likely to be related to drug-induced modification of the arterial wall, at least partially independently of blood pressure reduction. The increase in arterial compliance was associated with a selective decrease in pulse pressure, a finding that is important, not only for the arterial wall, but also for the structure and function of the hypertensive heart.

Angiotensin-Converting Enzyme Inhibitors↗

[Evaluation of arterial compliance in renal insufficiency].

The pulse wave velocity (PWV) of the aorta, of the arm, of the leg, was measured in 90 normal subjects (N) and 92 dialysis patients (D) of the same age and blood pressure status. All patients underwent blood biochemistry, especially serum liquid concentrations, and aortic ultra-sonography. Aortic calcifications were diagnosed by echo and radiologic examination. Aortic PWV was significantly higher in D (1,113 +/- 319 cm/s) than in N (965 +/- 216 cm/s) (p = 0.0016). The aortic diameters were greater in D both at the aortic root and at the bifurcation. The pulse pressure was higher in D (76.6 +/- 23.7 vs 63.9 +/- 2 mmHg, p = 0.007). In both populations, the PWV increased with age and blood pressure but aortic calcification was only weakly correlated with this increase. These results indicate that the compliance of the aortic wall is reduced in D and leads to an increase in the pulsatile component of the blood pressure and thereby to an increase in left ventricular afterload.

Adult↗

[Neurovascular sequelae related to the removal of forearm fasciocutaneous free flaps with radial pedicle. Preliminary study].

The authors study the consequences of amputation of the radial artery in order to create a Chinese forearm graft on the blood supply and innervation of the upper limb. After a brief review of the anatomy, the haemodynamics of the upper limb are studied in detail. Preoperative assessment by Hallen's test is generally sufficient. Postoperatively, pulsed Doppler studies provide the most useful information. Compensatory development of the interosseous artery is always observed and, in seven out of nine cases, this is associated with a marked increase in the blood flow in all of the arteries of the upper limb, especially in the hand. Of all of the methods of investigation available, this examination is able to demonstrate the safety of forearm grafts in the very great majority of cases.

Arm↗

Pathophysiological role of the vascular smooth muscle cell.

The vascular smooth muscle cell of the arterial media plays a predominant role in functional and structural alterations of the arterial wall in pathophysiological processes such as arterial hypertension, atheroma, or normal aging. The observed alterations are related to the three activities of the vascular smooth muscle cell, namely contractility, secretion of proteins from the extracellular matrix, and proliferation and migration. In arterial hypertension, vascular smooth muscle cells are functionally more contracted and structurally hypertrophic, and more collagen is secreted than under normal conditions. Similar structural changes are observed in the normal aging process. With respect to vascular smooth muscle cells, atheroma is characterized by their subintimal migration and proliferation, and by excessive excretion of collagen associated with other phenotypic modifications that are expressed in their regression to a myofibroblastic state. Regardless of the pathophysiological context, these phenotypic modifications of the vascular smooth muscle cell are always linked to an activation of the phosphoinositol pathways and to calcium accumulation. The activation of the phosphoinositol pathways seems to be a common feature of the different types of arterial hypertension. This activation can be associated with an increase in vasoactive peptides such as angiotensin II, vasopressin, or endothelin as in the secondary types of hypertension or directly related to an increase in vasoconstriction; or, as an exception, it can be spontaneously active in vivo and in vitro, as in the model of cultured vascular smooth muscle cells of the spontaneously hypertensive rat (SHR).(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

A murine model of mucopolysaccharidosis VII. Gross and microscopic findings in beta-glucuronidase-deficient mice.

This report describes the clinical and pathologic alterations found in mice that have a recessively inherited, essentially complete deficiency of the lysosomal enzyme beta-glucuronidase. Affected animals have a shortened life span and are dysmorphic and dwarfed. Abnormal gait and decreased joint mobility correlate with glycosaminoglycan accumulation in articular tissue and cartilaginous and bony lesions result in extensive skeletal deformation. In these enzyme-deficient animals, lysosomes, distended by fine fibrillar and granular storage material, are particularly prominent in the macrophage system but also occur in other tissues including the skeletal and central nervous systems. The clinical and pathologic abnormalities in these mutant mice closely parallel those identified in humans with mucopolysaccharidoses (MPS). Therefore, these mice provide a well-defined genetic system for the analysis of the pathophysiology of mucopolysaccharidosis type VII, which has many features in common with the other MPS. The mutant mice provide an attractive animal model to test potential therapies for lysosomal storage disease.

Animals↗

[Hemodynamic effects of perindopril].

1. The effects of prolonged infusion of perindopril (1 mg/kg/d) were studied on Goldblatt rats and spontaneously hypertensive SHR rats compared to control animals. Perindopril increased significantly the arterial compliance in treated animals. Mechanical parameters of the carotid artery are normalized with perindopril infusion in renovascular hypertensive rats and improved in SHR rats. Perindopril reversed the thickness of aortic media in treated rats. After three months treatment the ratio elastine/collagen of the aortic media increased significantly. Perindopril reversed the majority of vascular alteration in both hypertensive groups. 2. Twenty one hypertensive patients received for 30 minutes an infusion of perindoprilat either at 1 mg/kg/min, or at 2.5 mg/kg/min, or dihydralazine at 4 mg/kg/min. It was shown that perindoprilat significantly reduced the blood pressure in the three groups. However the increase in arterial diameter and compliance were only recorded with perindoprilat (2.5 mg/kg/min) infusion. The results of this study pointed out that for the same antihypertensive effect, with two different antihypertensive drugs, the vascular effects can be different. Blood pressure, forearm hemodynamic parameters, echocardiography values were recorded on 16 sustained hypertensive patients before and after one year of perindopril treatment. The results showed that perindopril decreased significantly the SBP, DBP and the MBP, increased diameter and arterial compliance of the brachial artery, and decreased cardiac mass. Three months later, the treatment was stopped for four weeks: blood pressure and hemodynamic values returned toward basal values, whereas mass cardiac didn't increase significantly; then the treatment was continued over 9 months; during this period. The arterial compliance increased again on the cardiac mass remained reduced. (ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Tumor necrosis factor alpha stimulates the growth of the clonogenic cells of acute myeloblastic leukemia in synergy with granulocyte/macrophage colony-stimulating factor.

TNF-alpha has been shown to antagonize the proliferative effects of growth factors present in crude conditioned media from PHA-stimulated leukocytes or cell lines on the clonogenic cells of acute myeloblastic leukemia (AML) (19,21). In the present study, we investigated the responses of AML blasts to TNF-alpha in the presence of defined growth factors (recombinant granulocyte/macrophage-CSF [rGM-CSF], recombinant granulocyte-CSF [rG-CSF], rIL-3, and rIL-1) and under conditions described for autocrine stimulation (32). While TNF-alpha antagonized the stimulatory effects of G-CSF and IL-3 on blast progenitors, TNF-alpha did not affect blast colony formation in the presence of IL-1. Unexpectedly, TNF-alpha significantly enhanced blast proliferation in the presence of GM-CSF. Further, TNF-alpha also acted synergistically with an endogenous source of growth stimulatory signal to promote proliferation of blast clonogenic cells. Thus, on human leukemic cells, TNF-alpha appears to be a molecule that is at least bifunctional, having the ability to either support or inhibit cell proliferation, depending on the other growth factors present. It is postulated that the proliferative response of blast progenitors to TNF-alpha under conditions that favor autocrine stimulation may represent one property that allows the cells to escape from negative regulation and proliferate in AML.

Blotting, Northern↗

Atrial natriuretic factor gene expression in rat ventricle during experimental hypertension.

Activation of atrial natriuretic factor (ANF) gene expression has been reported in the rat ventricle in several models of hemodynamic overload, including hypertension. However, nothing is known about the potential trigger(s) and the time course of this activation during the development of hypertension. We measured aortic blood pressure, left ventricular hypertrophy (LVH), and left ventricular ANF mRNA concentration (LV ANF mRNA) in a first group of rats (study A) killed at 5 and 18 h and 2, 4, 6, 9, 15, and 30 days after suprarenal coarctation of the abdominal aorta. Coarctation induced a progressive rise in aortic blood pressure and left ventricular mass. We observed a biphasic accumulation of ANF mRNA in the left ventricle with a peak at day 4 averaging 20 times the control value long before stable hypertension and hypertrophy were achieved, followed by a decrease until day 9. This decrease was followed by a new rise, which stabilized around 10 times the control value seen during stable hypertension and hypertrophy. In a second group of rats killed at days 4 and 30 (study B), we determined, in addition to the previous parameters, left ventricular end-diastolic pressure (LVEDP), plasma renin (PRC), and plasma ANF concentrations. LVEDP and PRC were markedly increased at day 4, but at day 30, during stable hypertension and hypertrophy, these parameters returned to control values, whereas plasma ANF was increased. Using immunocytochemistry, we looked in a third group of rats (study C) for the presence of the immunoreactive peptide at days 4 and 30.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Long-term cardiac effects of hypotensive agents in normotensive mature rats: comparison of beta-blocking agent and converting enzyme inhibition.

The hemodynamic and myocardial effects of chronic treatment (5 months) with converting enzyme inhibitor (CEI, enalapril, group T1, n = 10) or a beta 1 blocker (atenolol, group T2, n = 13) of normotensive mature male Wistar rats were studied and compared to untreated younger rats (group C0, 11 months old, n = 14) and to untreated age-matched controls (group C1, 16 months old, n = 14). Heart rate was significantly decreased in T2 rats but unchanged in the T1 group. There was a significant decrease in systolic and diastolic arterial blood pressure (BP) in both treated groups (systolic T1:90 +/- 17, T2: 87 +/- 10, vs. C1: 102 +/- 11 mm Hg, and diastolic T1: 60 +/- 17, T2: 59 +/- 9, vs. C1: 73 +/- 13 mm Hg). Cardiac output was unchanged by therapy but stroke volume was significantly increased in the T2 group (0.24 +/- 0.03 vs. 0.19 +/- 0.04 cm3 in C1). Total peripheral resistance was significantly decreased in T1 and T2 groups. Left ventricular weight to body weight ratio (LVW/BW) was significantly decreased in T1 (1.74 +/- 0.11 vs. 2.02 +/- 0.22 in C1) but unchanged in T2 (1.90 +/- 0.15 vs. 2.02 +/- 0.22). The left ventricular passive pressure-volume curve was significantly rightward shifted by beta-blocker therapy (T2) but unchanged by CEI (T1). This corresponds to a decrease of chamber stiffness k in the T2 group compared to C1 and T1 groups. A significant fibrosis was seen in group T2 (mean collagen fiber thickness of 3.03 +/- 0.24 vs. 2.8 +/- 0.15 micron) but not in the T1 group (2.94 +/- 0.14 vs. 2.8 +/- 0.15 micron). Thus, despite the similar decrease in BP induced by the CEI and the beta blocker, the cardiac effects of the two drugs were opposite: CEI decreased LVW/BW with no change in the left ventricular pressure-volume curve and myocardial fibrosis whereas beta blocker did not change the LVW/BW, but induced a left ventricular dilation associated with a decrease in chamber stiffness and an increase in subendocardial fibrosis.

Adrenergic beta-Antagonists↗

Use of fluoxetine, a selective serotonin-uptake inhibitor, in the treatment of obesity: a dose-response study (with a commentary by Michael Weintraub).

Pharmacologic measures which increase serotonergic activity in the brain decrease food consumption and lead to decreased weight in animals. Fluoxetine, an inhibitor of serotonin reuptake, decreases food intake in animals and is associated with weight loss in depressed and otherwise healthy obese patients. To determine the most effective daily fixed dose which causes weight loss in nondepressed obese patients, fluoxetine (10, 20, 40 or 60 mg) or placebo was administered once daily for 8 weeks to 655 patients consisting primarily of women (mean age 40 years, mean weight 95 kg). Diet and activity were not controlled. The placebo-treated patients lost 0.6 +/- 2.3 kg. With the 60-mg fluoxetine dose, patients lost an average of 4.0 +/- 3.9 kg (P less than 0.001), with intermediate responses at the lower doses. Weight loss was proportional to the initial body mass index (weight/height squared). There were no statistically significant differences between any fluoxetine treatment group and placebo for discontinuations from the study. There were statistically significant dose-dependent increases in reports of asthenia, somnolence and sweating. Thus, fluoxetine 60 mg daily appears to be potentially effective for use in weight reduction.

Adolescent↗

Neurohypophysial hormones of the 1-month-old bovine fetus: absence of vasotocin during mammal development.

The neurohypophysial hormones of the 1-month-old bovine fetus have been identified by their positions in ion-exchange chromatography and their retention times in high-pressure reverse-phase partition chromatography. Arginine vasopressin and oxytocin have been recognized. The molar ratio vasopressin/oxytocin in neurohypophysis is about 6 in the 1-month-old fetus compared with 4 in the 3-month-old fetus, 2.7 in the 7-month-old fetus and 1 in the adult. Vasotocin is virtually absent even in the early fetus (less than 0.1% of arginine vasopressin). The occurrence of a vasotocin gene expressed in the fetus but silent in the adult appears unlikely.

Animals↗

Noninvasive study of cardiac structure and function after rilmenidine for essential hypertension.

The hemodynamic effects of rilmenidine (S 3341) were evaluated noninvasively by aortic Doppler velocimetry, M-mode echocardiography and phonocardiography in hypertensive patients treated for 28 days. After a 2-week placebo run-in period, patients with mild hypertension (group I, n = 8, mean diastolic blood pressure [BP] = 97.18 +/- 0.65 mm Hg) received 1 mg of rilmenidine each morning and patients with moderate hypertension (group II, n = 6, mean diastolic BP = 107.62 +/- 1.18 mm Hg) received 1 mg twice daily. The hemodynamic variations in both groups after the first administration (day 1) showed that during the first 3 hours, mean arterial pressure and cardiac index (CI) were significantly reduced, whereas total peripheral resistance (TPR) was increased. From the third to the fifth hour, the decrease in mean arterial pressure was maintained, CI was higher than initial values and TPR decreased, indicating a persistent vasodilator effect. On day 28, hemodynamic variations were similar but of a lower amplitude. Before administration on day 28, a significant decrease in systolic and diastolic BP was observed, demonstrating that the antihypertensive activity of 1 mg was maintained for 24 hours, with a significant reduction in TPR and no modification of CI or stroke index. The M-mode and phonocardiographic left ventricular function indexes remained unchanged. Rilmenidine has a prolonged antihypertensive activity with a chronic vasodilator effect and no negative inotropic effect.

Adrenergic alpha-Agonists↗