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Biomedical subjects

L Schwartz

Publications and source records attributed to L Schwartz.

At least 109 records · Page 6Linked to original sources
PubMed1995

Antithrombotic therapy in patients with saphenous vein and internal mammary artery bypass grafts.

In most studies, aspirin has been shown to be effective for a period of 1 year in reducing the frequency of saphenous vein bypass graft occlusion when begun 1 day before surgery, on the day of surgery, or the day after surgery. Effective doses of aspirin range from 100 to 975 mg/d. Aspirin in combination with dipyridamole is effective in the prevention of saphenous vein bypass graft occlusion if aspirin and dipyridamole therapy is started 1 or 2 days before surgery or aspirin therapy is started on the day of surgery but dipyridamole therapy is started before surgery or if treatment with both aspirin and dipyridamole is started 1 day after surgery. Aspirin in combination with dipyridamole is not more effective than aspirin alone in the prevention of saphenous vein graft occlusion. Bleeding is higher among patients treated with aspirin alone than among controls if aspirin therapy is started 1 day before surgery. Bleeding is not greater in comparison to controls if aspirin therapy is started the day of surgery or 1 day after surgery. When aspirin and dipyridamole are used in combination, bleeding is higher than in controls, and bleeding is higher than with aspirin alone. The continued use of aspirin for 2 additional years after an initial year of aspirin therapy for the prevention of saphenous vein bypass graft occlusion showed no additional long-term benefit on graft patency at the end of the third year.

Clinical Trials as Topic↗
PubMed1995

Renal sodium handling with cyclosporin A and FK506 after orthotopic liver transplantation.

Hypertension is common after orthotopic liver transplantation and may be due, in part, to cyclosporin A-induced renal dysfunction and/or enhanced proximal tubular sodium reabsorption. To determine whether enhanced proximal tubular sodium reabsorption is central to the development of posttransplant hypertension, measurements of renal hemodynamics and fractional clearances of lithium and sodium were compared 1 month after orthotopic liver transplantation in previously normotensive patients receiving either cyclosporin A (N = 24) or FK506 (N = 18), an immunosuppressive agent that is structurally unlike cyclosporin A and that has a lower reported incidence of hypertension. Median prednisone doses were 20 and 13 mg/day in the cyclosporin A and FK506 groups, respectively (P < 0.05). At 1 month, mean arterial blood pressure was higher in the cyclosporin A versus the FK506 group: 108 +/- 2 versus 95 +/- 3 mm Hg (P < 0.05). GFR, RBF, and renal vascular resistance were not different between the two groups: 59 +/- 4 and 53 +/- 5 mL/min per 1.73 m2, 439 +/- 28 and 440 +/- 41 mL/min per 1.73 m2, and 22,429 +/- 1,822 and 22,977 +/- 3,506 dyne s/cm5 per 1.73 m2, respectively. Fractional lithium excretion was similar in the cyclosporin A and FK506 groups: 19.9 +/- 2.2 and 19.4 +/- 2.0% (P = not significant) although both values were lower than those of normal controls (25.5 +/- 1.1%) (P < 0.05). Fractional sodium excretion was 2.7 +/- 0.3 and 2.3 +/- 0.4% in the cyclosporin A and FK506 groups, respectively (P = not significant).(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Pressure↗
PubMed1995

Paclitaxel in germ cell cancer.

The teratocarcinoma cell line 833K and its relatively cisplatin-resistant subline 833K/63CP 10 were used to assess the cytotoxicity of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ), cisplatin, and 4-hydroxyperoxycyclophosphamide quantitatively. The results showed that paclitaxel had marked cytotoxicity against teratocarcinoma, particularly in the cells that were relatively cisplatin resistant. These studies suggested synergy in cytotoxicity for paclitaxel, cisplatin, and 4-hydroxyperoxycyclophosphamide. A phase II trial of paclitaxel was conducted in patients with previously treated germ cell tumors with restricted prior treatment. The paclitaxel dose was 250 mg/m2 given by 24-hour continuous infusion. In 31 patients treated with paclitaxel, eight (26%) achieved a major (complete or partial) response. The antitumor activity of paclitaxel in the phase II trial has led us to further study it as a part of combination therapy. Since the in vitro studies showed synergistic cytotoxicity, combination studies of paclitaxel, ifosfamide, and platinum are under way as salvage treatment for patients with germ cell tumors.

Adolescent↗
PubMed1995

[Motivations of volunteers for participation in an interventional study in the field of nutritional prevention: results of a pilot study of the SU.VI.MAX project].

In this paper, we try to understand the motivations and characteristics of people susceptible to be volunteers for the SU.VI.MAX study. The objective of this study will be to recruit and to follow during 8 years, a cohort of 15,000 subjects at a national level, for an intervention trial in the field of nutritional prevention. A short media campaign has been organised to recruit "1,000 volunteers to help to test and to validate tools specifically developed for the SU.VI.MAX study". In total, 15,789 subjects matching selection criteria answered to our invitation. All received a short questionnaire; 10,984 sent back correctly filled up questionnaires (70%) and 1005 were selected at random for a complete analysis. A lexical analysis of motivations disclosed 6 different groups organised in two poles. The pole of true altruists with a speech relative to notions such as "volunteers-benevolent" (7% of subjects), wishes to participate to a "humane task" (9% of subjects) or to progress of medical research (27% of subjects). The other pole corresponds to people interested personally by the theme of the project with 3 kinds of speech: personal past history (13% of subjects), interest for foods fortified with vitamins and/or minerals (19% of subjects) or for relationships between food consumption and health (22% of subjects).

Adult↗
PubMed1995

Hypertension after liver transplantation.

Hypertension developing after liver transplantation is nearly universal and likely reflects several pathogenic mechanisms. Foremost among these are altered vascular reactivity and vasoconstriction related to CSA, and probably FK506, administration, impaired GFR and sodium excretion, and the effects of steroids. This disorder is of both theoretical and practical importance in understanding blood pressure regulation in humans. Most importantly, it poses a considerable long-term cardiovascular risk for the transplant recipient. Recognition of acquired hypertension and timely intervention are among the primary management challenges for the transplant clinician.

Animals↗
PubMed1994

Purification of human basophils by density and size alone.

Basophils typically account for approximately 1% of the white cells in peripheral blood. We have developed a unique method for purifying basophils from whole blood of normal subjects to at least 95% purity. Basophils are separated from other cell types by density-dependent sedimentation in Percoll and cell sorting, based solely on their size and granularity. The mean overall yield ranged from 5% to 28%. The procedure is typically completed within 4 h. The highly purified basophils obtained are functionally competent and morphologically intact. They release histamine in response to Fc epsilon RI-mediated stimulation, express Fc epsilon RI and BSP-1 ligand as analyzed by flow cytometry, and exhibit the known characteristic ultrastructural features of basophils by electron microscopy. This procedure avoids positive-selection antibodies that might perturb receptors on basophils or negative-selection antibodies that might activate other cell types, and can be used to obtain basophils for studies in vitro.

Basophils↗
PubMed1994

Cardiac L-type Ca2+ channel triggers transmitter release in PC12 cells.

Among the various voltage-sensitive Ca2+ channels present in PC12 cells are the dihydropyridine (DHP)-sensitive L-channel, the omega-conotoxin (omega-CgTx)-sensitive N-channel, and an atypical omega-CgTx/DHP-insensitive Ca2+ channel. Depolarization-evoked Ca2+ entry and [3H]dopamine release is mediated by L-type Ca2+ channels determined by the use of Ca2+ channel antagonists, and a single protein of 250 kDa is recognized by L-type-specific antibodies. Screening of a PC12 cDNA library revealed two types of Ca2+ channels which were identified by partial sequencing. A pc12-L clone displayed virtually identical sequence homology to the cardiac L-type channel. The identical sequence homology of the single alternative splicing region confirmed clone pc12-L as the rbC-I transcript, a cardiac-neuronal alpha 1 subunit expressed in rat brain. Clone pc12-N displayed identical sequence homology to rbB-I, a neuronal alpha 1 subunit of the N-type Ca2+ channel expressed in rat brain; Northern blot analysis identified RNA of a size similar to that previously described for rat brain.

Animals↗
PubMed1994

Caffeine-induced transmitter release is mediated via ryanodine-sensitive channel.

An isolated clone PC12-37 of rat pheochromocytoma PC12 cells, which lacks ryanodine-sensitive Ca2+ channel, responds to depolarization and to agonist activation and triggers [3H]dopamine ([3H]DA) release. A caffeine-stimulated transmitter release, while present in the parental PC12 cell line, is completely abolished in PC12-37 cells. In contrast, caffeine-induced Ca2+ influx in PC12-37 cells is similar to that observed in PC12 cells, indicating that caffeine-induced CA2+ influx is neither mediated by caffeine-induced Ca2+ release nor contributes to the caffeine-induced secretion. These results show (a) a tight coupling between caffeine activation of a ryanodine-sensitive Ca2+ store and transmitter release, (b) no significant involvement of the ryanodine-sensitive Ca2+ channel in depolarization- and agonist-mediated transmitter release, and (c) exclude a major role for caffeine-mediated Ca2+ entry in the caffeine-activated secretion.

Animals↗
PubMed1994

Interpersonal stress and pain behaviors in patients with chronic pain.

This study was designed to empirically evaluate the role of interpersonal stress in eliciting pain behavior. Thirty-four married male patients with chronic back pain (CBP) and their wives participated in a randomized between-groups study examining the effects of 2 interactional conditions (i.e., maritally focused stress interview and neutral talking control task) on subsequent persistence in a physically demanding task and with self-reports of pain. Results indicated that a significantly greater proportion of patients in the stress interview group terminated the physical activity task prematurely, compared with controls. The findings provide some of the first experimental support for the notion that uncomfortable interpersonal interactions may increase the likelihood of subsequent pain behavior in patients with CBP. Clinical implications and directions for future research are addressed.

Adult↗
PubMed1994

Systemic and renal effects of nifedipine in cyclosporine-associated hypertension.

Cyclosporine induces hypertension and wide-spread vasoconstriction after transplantation in addition to reducing kidney function. We studied hemodynamic, renal, and hormonal effects of monotherapy with nifedipine XL (n = 37) in liver transplant recipients within a year after transplant (median, 4.4 months). Systemic hemodynamics were determined with thoracic electrical bioimpedance. Blood pressure before therapy was 172 +/- 4/108 +/- 2 mm Hg. Sixty-four percent of recipients achieved blood pressures less than 140/90 mm Hg mediated by a fall in systemic vascular resistance index (2427 +/- 245 dyne.s.cm-5.m-2 in responders versus 2905 +/- 281 in nonresponders, P < .01). Despite the fall in systemic vascular resistance, glomerular filtration rates were not changed during nifedipine therapy, as measured by both creatinine and iothalamate clearances. Urinary prostacyclin (6-ketoprostaglandin F1 alpha) was suppressed below normal from 2468 +/- 323 ng/d before transplant to 1103 +/- 99 ng/d (P < .01) after transplant and did not change during nifedipine therapy. Urinary thromboxane B2 and plasma renin activity also fell after transplant and remained low during nifedipine. These data demonstrate that nifedipine can reverse systemic vasoconstriction associated with hypertension after transplantation. Systemic effects were not transmitted to the kidney sufficiently to improve glomerular filtration rate or reverse hormonal changes within the kidney. Hence, vascular and functional regulation of the kidney was dissociated from the systemic circulation during nifedipine administration after transplantation.

6-Ketoprostaglandin F1 alpha↗
PubMed1994

Resolution of posttransplant hypertension after liver transplantation despite impaired glomerular filtration.

Hypertension developing after transplantation is characterized by widespread vasoconstriction including the kidney. Late resolution (mean, 29 +/- 4 months) of posttransplant hypertension has been observed in 15 (Group I) of 278 subjects monitored after liver transplantation. These studies were undertaken to define the systemic and renal changes associated with resolution, as compared with a group matched for age, sex, and time after transplant who remained hypertensive (Group II; N = 15) or a group who never developed hypertension (Group III; N = 23). Blood pressure during resolution paralleled changes in the systemic resistance index, which fell from 3,052 +/- 548 to 1,872 +/- 205 dyne/s.cm5/m2 (P < 0.01). GFR and RBF remained low, despite the resolution of hypertension, and renal vascular resistance did not change. Circulating endothelin levels remained above normal in all transplant recipients (Group I, 11.9 +/- 3.0 versus normal subjects, 7.0 +/- 1.1 pg/mL; P < 0.05), and urinary prostacyclin excretion was suppressed (880 +/- 120 versus 2,247 +/- 187 ng/day; P < 0.01). No hormonal differences were apparent between transplant groups. These results demonstrate the capacity for systemic vasodilation to occur after transplantation, independent of vascular tone in the kidney. They further suggest that renal vasoconstriction and impaired GFR alone are not sufficient to explain de novo hypertension after transplantation.

Adult↗
PubMed1994

Conjunctival leukocyte infiltration evoked by leukotrienes: differing responses among rodent species.

Application of leukotrienes (LT) B4 or D4 to the guinea-pig eye evokes conjunctival eosinophil infiltration, providing an in vivo model of tissue eosinophilia. To determine if other rodent species would respond similarly, LTB4 or LTD4 were applied to the right eye of male mice and rats (three per group) at doses of 250, 1000 or 5000 ng/eye (mice) and 1000 or 5000 ng/eye (rats). Left eyes received the same volume (mice, 5 microliters; rats, 20 microliters) of vehicle (isotonic saline). Conjunctivae were evaluated histologically 6 h after application. In mice, 1000 or 5000 ng/eye LTB4 resulted in mild conjunctival neutrophilia, but no leukocyte response to LTD4 was observed. In rats, no leukocyte responses, either to LTB4 or to LTD4, were observed. The results illustrate interspecies differences in leukocyte responsiveness to LT and indicate specifically that, unlike the guinea pig, neither mouse nor rat responds to LT with conjunctival eosinophilia.

Animals↗
PubMed1993

Detection and measurement of an endogenous clonidine-displacing substance in human cerebrospinal fluid.

Clonidine-displacing substance (CDS) is a novel endogenous ligand for clonidine receptors previously detected in bovine brain and human serum. We examined for the first time whether CDS can be detected and measured in human cerebrospinal fluid (CSF). Using the [3H]clonidine displacement assay, we found that CDS could be identified and quantified in each of the CSF samples obtained from 81 patients with various neurological disorders. Mean level of CDS in CSF was 4.66 units/ml. Exceedingly high levels were observed in the CSF of patients with neoplastic meningitis (mean, 36.75 units/ml) and stroke (mean, 19.5 units/ml) (P < 0.0001). No correlation was found between CDS levels in CSF and age, gender, CSF protein or number of cells. CDS levels in CSF were higher than those in the serum (P < 0.01). We conclude that CDS is present and can be measured in human CSF. High CDS levels in CSF from patients with leptomeningeal metastases may serve as a tumor marker for malignant infiltration of the meninges. Additional studies in stroke patients will determine whether this endogenous ligand plays a role in the pathogenesis of cerebral ischemia.

Adolescent↗
PubMed1993

cAMP-specific phosphodiesterase inhibitor, rolipram, reduces eosinophil infiltration evoked by leukotrienes or by histamine in guinea pig conjunctiva.

The effect of rolipram, an isozyme IV-selective inhibitor of cAMP-specific phosphodiesterase, was evaluated in a guinea pig eye model of tissue eosinophilia. (R)-rolipram was administered by gavage to guinea pigs 1 h prior to topical ocular challenge with a mixture of leukotrienes (LTs) (10 ng LTB4 + 1000 ng LTD4/eye) or with histamine dihydrochloride (1 mg/eye). Conjunctivae were evaluated histologically 6 h after challenge. Eosinophil counts per millimeter of conjunctival epithelium in LT-challenged animals that received (R)-rolipram at dosages of 0.1, 0.3, 1, 3, or 10 mg/kg were reduced by 63, 63, 84, 81 and 90% respectively, compared to LT-challenged controls. Reduction was statistically significant (P < 0.05) at all dosages. Eosinophil counts per millimeter of epithelium in histamine-challenged animals that received 10 mg/kg (R)-rolipram were reduced by 79% compared to histamine-challenged controls (P < 0.01). The results indicate that (R)-rolipram inhibits the response to two distinct classes of mediator in this model of eosinophil infiltration, adding support to the contention that isozyme IV-selective cAMP phosphodiesterase inhibitors offer therapeutic potential for human asthma.

3',5'-Cyclic-AMP Phosphodiesterases↗