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Biomedical subjects

J Schwartz

Publications and source records attributed to J Schwartz.

At least 217 records · Page 12Linked to original sources
PubMed1995

Controlled study of the putative interaction between famotidine and theophylline in patients with chronic obstructive pulmonary disease.

The effects of famotidine (80 mg per day), cimetidine (1600 mg per day), and placebo on theophylline pharmacokinetic parameters in chronic obstructive pulmonary disease (COPD) patients were compared. This was an open-label, randomized, three-period cross-over study, in which each subject first underwent a seven-day theophylline washout period, and thereafter received three single intravenous doses of theophylline (5 mg/kg infused over 30 minutes) during the study. Each of the experimental treatments was administered orally every 12 hours for a total of 9.5 days (19 doses). Theophylline was infused after the 17th dose of each treatment. Fourteen serial blood samples were collected before the start of each infusion, and for 30 hours after the end of each infusion. Plasma samples were assayed for theophylline, pharmacokinetic parameters were estimated, and treatment effects on each parameter were compared. Fourteen COPD patients completed all three periods of the investigation. Famotidine treatment had virtually no effect on any of theophylline's pharmacokinetic parameters. In contrast, cimetidine treatment significantly altered every pharmacokinetic parameter of theophylline as follows: Cimetidine decreased theophylline geometric mean CL from 2.74 L/h to 2.07 L/h (P < .001), and prolonged theophylline harmonic mean half-life from 6.6 to 9.6 hours (P < .001) and mean residence time from 10.8 to 15.0 hours (P < .001). Cimetidine treatment slightly increased theophylline volume of distribution by approximately 10%, and that change also was statistically significant (P = .032). The authors conclude that the treatment effects of cimetidine on theophylline pharmacokinetic parameters were in accord with those reported by others, and that famotidine treatment had no effect on any of theophylline's pharmacokinetic parameters in COPD patients.

Adult↗
PubMed1995

Clinical pharmacology of estrogens: cardiovascular actions and cardioprotective benefits of replacement therapy in postmenopausal women.

The use of estrogens in postmenopausal women has been the subject of much controversy regarding hormone formulation, dosage, use in combination with progestins, duration of treatment, and contraindications. Estrogens have been prescribed to relieve menopausal symptoms for more than three decades. The hormones reduce the gynecologic and psychologic changes associated with menopause while inhibiting bone resorption and possibly reducing the risk of cardiovascular disease. Their use however has been complicated by an increased risk of endometrial cancer and possibly breast cancer. The use of estrogens as cardioprotective agents is discussed and the clinical experiences and the possible mechanisms of action are reviewed. The clinical pharmacology of estrogens and the various formulations that are available as monotherapy or in combination with progestins will also be reviewed.

Adult↗
PubMed1995

Safety and efficacy of controlled-release mesalamine for maintenance of remission in ulcerative colitis. Pentasa UC Maintenance Study Group.

This 12-month, double-blind, placebo-controlled study randomized 205 ulcerative colitis patients in remission to placebo or controlled-release mesalamine at 4 g/day for 12 months. Patients were stratified to either pancolitis or left-sided disease, based on previous diagnosis. Maintenance of remission was defined as a sigmoidoscopic index of < 5, less than five stools per day, and the absence of rectal bleeding. A significantly greater number of patients maintained remission on mesalamine 4 g/day than on placebo at each of five study visits, following the first one-month visit (P < 0.05). The estimated 12-month remission rates for the mesalamine group were 64% (38% for placebo, P = 0.0004). Baseline subgroups (disease location, time since last flare of active disease, and previous response to oral/rectal steroids or sulfasalazine) did not influence remission rates. Treatment-related adverse events were rare. Controlled-release mesalamine is a safe and efficacious single agent for maintaining remission of ulcerative colitis.

Adult↗
PubMed1995

Structure--function studies of vasopressin analogues with D-3 pyridyl-alanine in position 2.

A number of analogues of vasopressin, incorporating the substitution of D-3'-(pyridyl)-alanine in position 2, were synthesized and tested for antidiuretic (V2), vasoconstrictor (V1a) and ACTH secretory (V1b; pituitary) activities. One analogue, deamino-[D-3'-(pyridyl)-alanine2]arginine-vasopressin (abbreviated d[D-3Pal]VP) was a potent pituitary agonist, weaker antidiuretic agonist, and weak vasoconstrictor antagonist. Another analogue, [D-3'-(pyridyl)-alanine2]arginine-vasopressin, had very weak pituitary activity but no measurable antidiuretic or vasoconstrictor activity. Other D-3'-(pyridyl)-alanine-substituted analogues had only very weak activity in one or two of the bioassays. In further examination of the relationship between the actions of vasopressin on generation of cyclic AMP and secretion of ACTH in pituitary cells, the cyclic AMP responses to d[D-3Pal]VP, to another analogue of vasopressin ([Val4,D-Arg8]VP) with potent agonist activity at pituitary and renal (V2) receptors, and to CRF were compared to that of vasopressin. At the prescribed concentrations, the ACTH secretory responses to vasopressin, d[D-3Pal]VP, and [Val4,D-Arg8]VP were comparable; but only ([Val4,D-Arg8]VP) and CRF, which did not change ACTH secretion, increased intracellular cyclic AMP. These results indicate the possibility of synthesizing analogues of vasopressin with selective activity for the pituitary response and the potential for further study of vasopressin receptor subtypes, using the D-3'-(pyridyl)-alanine substitution. They are also consistent with the concept that the ACTH secretory response to vasopressin by itself is not linked to cyclic AMP, although adenylate cyclase may be activated.

Adenylyl Cyclases↗
PubMed1995

Anterior pituitary cells: getting to know their neighbors.

We review in this article recent findings on the effects of cell proximity (nearness to each other) on anterior pituitary cell function in vitro. Important cellular processes, including protein synthesis, basal hormone release, response to hypothalamic regulatory factors and signal transduction can change as a function of the distance between adjacent cells. These findings, together with a growing body of evidence on intrapituitary intercellular interactions, form a basis for proposing a model of anterior pituitary cell regulation. In this scheme extrapituitary, intracellular and intercellular signaling pathways all contribute and interact to control secretory processes in cells.

Animals↗
PubMed1995

Effect of fluoxetine on anger in symptomatic volunteers with borderline personality disorder.

Clinical data and uncontrolled observations have suggested that fluoxetine is helpful in some patients with borderline personality disorder. This article describes the results of a 13-week double-blind study of volunteer subjects with mild to moderately severe borderline personality disorder. Thirteen fluoxetine recipients and nine placebo recipients received treatment. Pretreatment and posttreatment measures were obtained for global mood and functioning, anger, and depression. The most striking finding from this study was a clinically and statistically significant decrease in anger among the fluoxetine recipients. This decrease was independent of changes in depression. These data support previous observations that fluoxetine may reduce anger in patients with borderline personality disorder. The number of subjects in this study was small, the placebo responsiveness was high, and the clinical characteristics of the patients were in the mild to moderate range of severity. The data cannot be extrapolated to more severely ill borderline patients, but further study of fluoxetine and other selective serotonin reuptake inhibitors is indicated in this population.

Adult↗
PubMed1995

Short term fluctuations in air pollution and hospital admissions of the elderly for respiratory disease.

BACKGROUND: Several recent studies have reported associations between short term changes in air pollution and respiratory hospital admissions. This relationship was examined in two cities with substantially different levels of sulphur dioxide (SO2) but similar levels of airborne particles in an attempt to separate the effects of the two pollutants. Significant differences in weather between the two cities allowed the evaluation of that potential confounder also. METHODS: Daily counts of admissions to all hospitals for respiratory disease (ICD 9 460-519) were constructed for persons aged 65 years and older in two cities - New Haven, Connecticut and Tacoma, Washington. Each city was analysed separately. Average daily concentrations of SO2, inhalable particles (PM10), and ozone were computed from all monitors in each city, and daily average temperature and humidity were obtained from the US weather service. Daily respiratory admission counts were regressed on temperature, humidity, day of the week indicators, and air pollution. A 19 day weighted moving regression filter was used to remove all seasonal and subseasonal patterns from the data. Possible U-shaped dependence of admissions on temperature was dealt with using indicator variables for eight categories each of temperature and humidity. Each pollutant was first examined individually and then multiple pollutant models were fitted. RESULTS: All three pollutants were associated with respiratory hospital admissions of the elderly. The PM10 associations were little changed by control for either ozone or SO2. The ozone association was likewise independent of the other pollutants. The SO2 association was substantially attenuated by control for ozone in both cities, and by control for PM10 in Tacoma. The magnitude of the effect was small (relative risk 1.06 in New Haven and 1.10 in Tacoma for a 50 micrograms/m3 increase in PM10, for example) but, given the ubiquitous exposure, this has some public health significance. CONCLUSIONS: Air pollution concentrations within current guidelines were associated with increased respiratory hospital admissions of the elderly. The strongest evidence for an independent association was for PM10, followed by ozone. These results are consistent with other studies and suggest that lowering air pollution concentrations would have some impact on public health.

Aged↗
PubMed1995

Biological activity of adrenocorticotropic hormone precursors on ovine adrenal cells.

Adrenocorticotropic hormone (ACTH) is synthesized in the corticotrophs as a precursor, pro-opiomelanocortin (POMC), which is processed via proACTH to ACTH. Both precursors and ACTH are secreted. Although the steroidogenic activity of ACTH is well characterized, that of the precursors is not. This study assessed the capacity of POMC and proACTH to alter cortisol synthesis. POMC and proACTH were prepared by subjecting medium, conditioned by exposure to DMS-79 cells, to Sephadex chromatography, and the bioactivity was assessed in cultured-dissociated ovine adrenal cells. Alone neither POMC (< or = 2.6 nM) nor proACTH (< or = 0.7 nM) showed any consistent acute (6 h) stimulatory or inhibitory action on cortisol in either fetal or adult cells. In contrast, in fetal cells the precursors inhibited steroidogenic response to ACTH-(1-24). POMC at 2.6 nM, but not lower concentrations, decreased the cortisol responses to 0.01, 0.1, and 1 nM ACTH by at least 50%. ProACTH (0.70 and 0.23 nM) decreased the responses to ACTH at 0.01 nM by 89 and 67%, respectively, and at 0.1 nM by 49 and 34%, respectively. At 1 nM ACTH only 0.7 nM proACTH decreased the response to ACTH (by 69%). In contrast, in adult adrenal cells, the precursors did not significantly reduce the response to ACTH (range 0.01-1 nM). Therefore, these data indicate that POMC and proACTH can inhibit the cortisol response to ACTH in fetal adrenal cells, an effect that is concentration dependent. The data suggest that precursors may play a physiological role, possibly regulating fetal plasma cortisol concentrations.

Adrenal Glands↗
PubMed1995

Regulation of bioactive and immunoreactive ACTH secretion by CRF and AVP in sheep fetuses.

The purpose of this study was to determine the effects of corticotropin-releasing factor (CRF) or arginine vasopressin (AVP) on the secretion of bioactive adrenocorticotropic hormone (bACTH) and immunoreactive ACTH (iACTH), the latter being measured by radioimmunoassay and separate two-site immunoradiometric assays for ACTH-(1-39) and ACTH precursors. Experiments were performed on chronically catheterized fetal sheep at 0.70 (n = 9) and 0.90 (n = 8) gestation. Each fetus received a 15-min infusion of CRF, AVP, or saline on 3 consecutive days. Blood was obtained before and 15 and 60 min after the infusion began. CRF significantly increased iACTH at 15 (younger group) and 60 min (both groups). CRF significantly increased bACTH and the bACTH-to-iACTH ratio (bACTH/iACTH) in both groups at 15 and 60 min. AVP significantly increased iACTH, bACTH, and bACTH/iACTH in both groups at 15 min. In two subgroups (n = 4/subgroup), CRF significantly increased ACTH-(1-39) and ACTH precursors at 15 and 60 min. CRF increased the ratio of ACTH-(1-39) to ACTH precursors [ACTH-(1-39)/ACTH precursors] at 15 (younger group) and 60 min (both groups). AVP increased ACTH-(1-39), ACTH precursors, and ACTH-(1-39)/ACTH precursors in both groups at 15 min. These findings show that both CRF and AVP can stimulate the secretion of bACTH, ACTH-(1-39), and ACTH precursors at 0.70 and 0.90 gestation. The proportional increments in bACTH/iACTH and ACTH-(1-39)/ACTH precursors suggest that CRF and AVP evoke selective increases in bACTH and ACTH-(1-39).

Adrenocorticotropic Hormone↗
PubMed1995

Is removal of the tube mandatory after coagulation in ectopic pregnancies.

Laparoscopic treatment of ectopic pregnancy is gaining wide acceptance. We report a new simple laparoscopic technique involving grasping the tube with forceps and coagulating on both sides of the ectopic pregnancy site, leaving the fertilized ovum in situ. This method is suitable for multiparous women and women who request tubal sterilization. Sixteen patients (mean age 32.6 +/- 4.4 years) were treated by using this method. The mean duration of hospitalization was 1.94 +/- 1.12 days. No complications occurred.

Adult↗
PubMed1995

Relationship of skin test reactivity to decrements in pulmonary function in children with asthma or frequent wheezing.

We examined the relationship between skin test reactivity and level of FEV1 in a stratified random sample of U.S. children 6 to 12 yr of age with asthma or frequent wheezing, studied as part of the Second National Health and Nutrition Survey (NHANES II). Subjects were considered symptomatic if they reported asthma or wheezing. Spirometry was performed according to ATS standards. Skin test reactivity to Alternaria, Bermuda grass, cat, dog, house dust, mixed long and short ragweed, oak, and rye grass allergens was determined. House dust mite (-17% FEV1; 95% CI, -9 to -25), dog (-28% FEV1; 95% CI, -11 to -42), and oak (-26% FEV1, 95% CI, -16 to -35) were associated with the greatest decrements in FEV1. In general, indoor allergens (-13% FEV1; 95% CI, -6 to -20) were associated with greater effects than outdoor allergens (-5% FEV1; 95% CI, -2 to -13). The association of indoor allergens with reduced FEV1 was greater in girls (-16% FEV1; 95% CI, -5 to -25) than in boys (-8% FEV1; 95% CI, -3 to -13). Sensitization to indoor allergens among symptomatic children 6 to 12 yr of age was associated with decrements in level of FEV1.

Allergens↗
PubMed1995

Ovine anterior pituitary production of follistatin in vitro.

Rat pituitary cells express messenger RNA for the activin-binding protein, follistatin (FS), and rat and bovine pituitary cell cultures secrete FS into the medium. In the present study, a previously validated, heterologous RIA for ovine FS was employed to investigate FS synthesis, secretion, and regulation in cultures of ovine anterior pituitary cells. The validity of the RIA was confirmed by the finding that FS immunoreactivity in ovine pituitary cell culture-conditioned medium diluted in parallel with purified bovine FS, and fractionation of the conditioned medium resulted in the coelution of activin-binding activity with the FS immunoactivity. The concentration of endogenous ovine FS achieved in the culture medium (0.08-0.6 nM) was in the range over which bovine FS suppresses FSH secretion in these cultures (IC50 = 0.5 nM). To characterize the relationship between endogenous FS and FSH secretion, dispersed ovine pituitary cells were preincubated with 10% fetal bovine serum for 2 days, then cultured between days 2-5 in the presence of a chemically defined serum substitute. Under these conditions, FS was continuously secreted at a rate of 12.1 +/- 1.8 ng/10(6) cells.day (mean +/- SEM; n = 18), whereas FSH was secreted at 64 +/- 13 ng/10(6) cells.day (n = 7). The secretion of FS and FSH changed in a reciprocal way as culture conditions were altered either by maintaining exposure of the cells to fetal bovine serum or by plating the cells at a 6- to 10-fold higher seeding density. Under the latter circumstance, for instance, FS secretion during the 3-day test period decreased to 47 +/- 14% (n = 10) and FSH secretion increased to 137 +/- 6% (n = 6) of the respective values in cultures of dispersed cells. FS secretion was increased nearly 3-fold (P < 0.05) in a dose-dependent manner by continuous exposure of ovine pituitary cells between days 2-5 to recombinant human activin A (1-10 nM), which concomitantly increased FSH secretion. Recombinant human inhibin A (0.003-10 nM); the synthetic glucocorticoids, RU28362 and dexamethasone (each 1-100 nM); the sex steroids, testosterone (1-100 nM), 17 beta-estradiol (0.001-5 nM), and progesterone (4-2500 nM); and the vitamin A derivative, retinoic acid (0.3-32 microM), each inhibited FSH secretion from these cultures, but only the last agent significantly (P < 0.05) increased FS secretion. Inhibin prevented the stimulation of FSH secretion by activin A without affecting its stimulation of FS secretion.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1995

Development of adrenocorticotropin-(1-39) and precursor peptide secretory responses in the fetal sheep during the last third of gestation.

Although it is known that concentrations of immunoreactive ACTH increase during late gestation in fetal sheep plasma, the nature of the ACTH has not been well characterized. We used two-site immunoradiometric assays to separately measure high mol wt ACTH precursors (POMC and pro-ACTH) and ACTH-(1-39) in plasma of fetal sheep with chronic arterial and venous catheters. We compared the ratio of these peptides as a function of gestational age under basal conditions and in response to exogenous vasopressin and/or corticotropin-releasing hormone. Under basal conditions, the concentration of precursors was not changed throughout the last third of gestation; however, ACTH-(1-39) increased significantly approaching term. The molar ratio of precursors to ACTH-(1-39), therefore, decreased from 15.8 +/- 1.0 at 110 days to 7.9 +/- 0.6 at 140 days gestation. At all gestational ages, vasopressin and corticotropin-releasing hormone increased ACTH-(1-39) and precursors, albeit with different time courses. At 120 days gestation, arginine vasopressin plus CRH produced synergistic increases in ACTH-(1-39) and precursors, whereas the response was only additive at other ages. The present results indicate that the elevation in the resting plasma immunoreactive ACTH concentration that occurs near term is constituted by an increase in the concentration of ACTH-(1-39) relative to those of POMC and pro-ACTH, which may have further physiological significance. Also, CRH and AVP are potent stimulators of both ACTH-(1-39) and ACTH precursors.

Adrenocorticotropic Hormone↗
PubMed1995

Increasing gestational age and cortisol alter the ratio of ACTH precursors:ACTH secreted from the anterior pituitary of the fetal sheep.

We have used a perifusion system and slices of the anterior pituitary of the fetal sheep combined with specific immunoradiometric assays to investigate the effect of increasing gestational age and cortisol infusion on the output of ACTH(1-39) and the ACTH precursors, pro-ACTH and pro-opiomelanocortin, from the fetal sheep pituitary. Two slices from each fetal anterior pituitary at 106-113 days (n = 3), 120-136 days (n = 5) and 140-143 days (n = 5) of gestation were used. Slices from each anterior pituitary were perifused with the perifusion buffer for at least 120 min prior to the infusion of cortisol (100 nM) for 30 min or buffer alone (control). The anterior pituitary output (fmol/5 min per mg pituitary) of ACTH(1-39) and the ACTH precursors were measured using specific immunoradiometric assays. There was a significant increase in the anterior pituitary secretion rate of ACTH(1-39) between 120 and 136 days (1.04 +/- 0.23 fmol/5 min per mg) and between 140 and 143 days of gestation (3.08 +/- 0.33 fmol/5 min per mg). In contrast, there was no change in the secretory rate of the ACTH precursors between 105 and 143 days of gestation. The ratio of the anterior pituitary output of the ACTH precursors:ACTH(1-39) therefore decreased between 120 and 143 of days gestation from 19.10 +/- 2.05 to 6.36 +/- 0.58. There was no effect of cortisol infusion on the anterior pituitary secretion of either ACTH(1-39) or the ACTH precursors before 116 days of gestation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗