Search PubMed⌕ Search

Biomedical subjects

J A Finkelstein

Publications and source records attributed to J A Finkelstein.

At least 55 records · Page 3Linked to original sources

Quality of care for preschool children with asthma: the role of social factors and practice setting.

OBJECTIVE: To determine whether patient race or source of payment is associated with differences in the quality of inpatient and outpatient treatment for young children with asthma. DESIGN: Structured medical record review. SETTING: Tertiary care pediatric hospital. PATIENTS: We studied 354 patients aged 1 to 6 years discharged with asthma between October 1, 1989 and September 30, 1990. MEASURES: We developed indicators of the quality of asthma care provided before and during hospitalization and planned after discharge. Outpatient indicators were the use of inhaled beta-agonists and the use of preventive anti-inflammatory medications (inhaled steroids or cromolyn sodium) before admission. In-hospital indicators were the intensity of inhaled beta-agonist therapy in the emergency department and length of stay. Planning for post-hospital care was assessed by the prescription of a nebulizer for home use. We examined associations between these indicators and patient race and source of payment, and explored the influence of primary-care practice type on these associations. RESULTS: After adjustment for potential confounders, we found that Hispanic patients were less likely than white patients to have taken inhaled beta-agonists before admission. Both black and Hispanic patients were less likely than white patients to have taken anti-inflammatory medications. When we adjusted for the patients' primary-care practice type, the effect of patient race did not persist for these indicators of outpatient care. We found no differences by patient race in emergency department care or length of hospital stay. However, black and Hispanic patients were much less likely to be prescribed a nebulizer for home use upon discharge. After adjustment for confounders, there were no differences in the quality of asthma care by source of payment. CONCLUSIONS: We found that young children of racial minorities admitted for an asthma exacerbation were less likely to have received maximally effective preventive therapy. We also identified marked differences in the quality of care planned after hospital discharge for black and Hispanic patients, compared with white patients. Particularly in an era of health reform, attention should focus on barriers to high-quality care for underserved children, who are already at high risk for asthma-related morbidity.

Adrenergic beta-Agonists↗

The serotonin syndrome associated with paroxetine, an over-the-counter cold remedy, and vascular disease.

There is a new, potentially fatal disorder that is infrequently reported. The apparent rareness may be because of a lack of recognition of the syndrome or its predisposing factors. Fluoxetine (Prozac, Dista Products Co, Division of Eli Lilly Co, Indianapolis, IN), sertraline (Zoloft, Roerig Division, Pfizer Inc, New York, NY), and paroxetine (Paxil, SmithKline Beecham Pharmaceuticals, Philadelphia, PA) belong to a new class of antidepressant medication: the serotonin reuptake-inhibitors (SRIs). The relative safety profile of the SRIs has led to their widespread use. However, a syndrome of excessive serotonergic activity, the "serotonin syndrome" (SS), has recently been recognized. It is characterized by changes in mental status, hypertension, restlessness, myoclonus, hyperreflexia, diaphoresis, shivering, and tremor. A high index of suspicion is required to make the diagnosis in these acutely ill patients. The most common agents implicated in SS are the monoamine oxidase inhibitors in combination with L-tryptophan or fluoxetine. A case of a patient with significant peripheral vascular disease who developed SS while taking paroxetine and an over-the-counter cold medicine is reported. There have been no prior reports of this interaction. Discontinuation of the offending agents, sedation, and supportive care are the mainstays of treatment. The interactions of serotonin with platelets and vascular endothelium are also discussed.

Acetaminophen↗

Rapid infusion of magnesium sulfate obviates need for intubation in status asthmaticus.

Rapid infusion of intravenous magnesium sulfate (MgSO4) was given to two young adults with impending respiratory failure caused by status asthmaticus. The infusion of 2 g of MgSO4 during a 2-minute period was associated with an immediate, dramatic reversal of their severe bronchospasm. This treatment obviated the need for intubation. Continuous beta 2-agonist therapy was performed simultaneously, taking advantage of the MgSO4-induced bronchodilation to deliver the beta 2-agonist to the target tissues. Rapid infusion of intravenous MgSO4 has been documented as safe in standard obstetric literature. Previous reports of MgSO4 therapy for acute asthma have used slow infusion. This is the first report of rapid infusion of MgSO4 for the emergency department management of asthma. In both cases, this therapy obviated the need for endotracheal intubation and mechanical ventilation.

Administration, Inhalation↗

A study of micromotion and appositional bone growth to a canine madreporic-surfaced femoral component.

A canine total hip arthroplasty model was used to examine micromotion and bone apposition to a proximally two-thirds madreporic-surfaced femoral prosthesis. Micromotion was also measured following initial press-fit implantation into canine cadaveric femora. After initial press-fit fixation and either 6 or 24 months of biologic fixation, micromotion was less than 23 microns in the proximal and midstem regions, a magnitude consistent with bone apposition. Bone apposition was greatest near the junction of the madreporic and smooth surfaces and was not significantly different between 6 and 24 months (51% at 6 months and 47% at 24 months). The quality of the interface tissue appears to be conductive to long-term fixation.

Animals↗

Hormonal control of growth in the genetically obese Zucker rat. I. Linear growth, plasma insulin-like growth factor-I (IGF-I) and IGF-binding proteins.

The genetically obese Zucker rat is a widely used model of early-onset obesity. Like obese children, these obese rats are hyperinsulinemic and have low GH secretion. However, data on linear growth and insulin-like growth factor-I (IGF-I) levels in this model are scanty and contradictory. In the present study, we investigated linear growth and its hormonal control in Zucker rats (male and female) from 4-20 weeks of age. In the obese animals, compared to their lean littermates, the naso-anal length was normal or slightly greater, whereas the tails and femurs were shorter. The plasma concentration of IGF-I increased between 4-20 weeks of age, and IGF-I levels were normal or slightly higher in the obese animals. The serum level of IGF-binding protein-3 (IGFBP-3) measured by Western ligand blotting was not significantly different in lean vs. obese rats. To assess the IGF-I response to GH, bovine GH was administered (250 micrograms/100 g BW, ip, daily for 3 days) to 16- to 20-week-old female Zucker rats; plasma IGF-I concentrations increased more in the obese (percent increase over baseline, 347 +/- 44% vs. 194 +/- 31%; P < 0.01). These results show that despite low GH secretion, genetically obese Zucker rats have 1) normal linear (nasoanal) growth, 2) normal or increased circulating levels of IGF-I and IGFBP-3, and 3) increased plasma IGF-I responses to exogenous GH. These results suggest that the GH-independent growth in this model could result from direct effects of hyperinsulinism on circulating IGF-I and IGFBP-3 levels and/or indirect effects through increased GH receptor function.

Animals↗

Potent nonpeptide angiotensin II receptor antagonists. 2. 1-(Carboxybenzyl)imidazole-5-acrylic acids.

The further evolution of the imidazole-5-acrylic acid series of nonpeptide angiotensin II receptor antagonists is detailed (for Part 1, see: J. Med. Chem. 1992, 35, 3858). Modifications of the N-benzyl ring substitution were undertaken in an effort to mimic the Tyr4 residue of angiotensin II. Introduction of a p-carboxylic acid on the N-benzyl ring resulted in the discovery of compounds with nanomolar affinity for the receptor and good oral activity. SAR studies of these potent antagonists revealed that the thienyl ring, the (E)-acrylic acid, and the imidazole ring in addition to the two acid groups were important for high potency. Also, overlay comparisons of the parent diacid with both angiotensin II and a representative biphenylyltetrazole nonpeptide angiotensin II receptor antagonist are presented. The parent diacid analog, SK&F 108566 or (E)-3-[2-butyl-1-(4-carboxybenzyl)-1H-imidazole-5-yl]-2-[(2- thienyl)methyl]propenoic acid, is currently in clinical development for the treatment of hypertension.

Acrylates↗

Obesity-associated decrease in growth hormone-releasing hormone gene expression: a mechanism for reduced growth hormone mRNA levels in genetically obese Zucker rats.

The secretion of growth hormone (GH) is impaired in the genetically obese Zucker rat where GH gene expression and plasma GH levels are depressed; however, the underlying mechanism of this abnormality remains unclear. We have evaluated the potential causative role of hypothalamic GH-releasing hormone (GHRH) and somatostatin (SRIH) gene expression in the onset of the decreased GH mRNA levels by studying both GHRH and SRIH mRNA and peptide levels in obese and lean rats at 5 weeks of age when the decrease in GH mRNA is first detected. At that age both GHRH content and GHRH mRNA were significantly reduced in obese rats as compared to lean controls; hypothalamic SRIH content was also decreased in obese rats, but SRIH mRNA levels did not differ. Since GHRH is capable of stimulating GH gene expression, the decreased GHRH mRNA level could be a critical factor in causing the attenuation in GH gene expression and consequent diminution of circulating plasma GH.

Animals↗

Imidazole-5-acrylic acids: potent nonpeptide angiotensin II receptor antagonists designed using a novel peptide pharmacophore model.

A series of novel nonpeptide angiotensin II receptor antagonists containing a substituted (E)-acrylic acid has been developed. The overlay of 1, an imidazole-5-acetic acid found in the patent literature, on a novel pharmacophore model of AII suggested that extension of the acid side chain and attachment of a second aryl residue to mimic the C-terminal phenylalanine region of AII would lead to increased activity. A study of extended acid side chains at C-5 of the imidazole nucleus led to the discovery of the (E)-acrylic acid 5 as a promising starting point for further exploration. As predicted by the modeling, substitution of a benzyl group on the acrylic acid side chain to mimic the phenylalanine gave increased potency. An extensive study of the SAR of the newly introduced aromatic ring revealed that electron-rich heteroaryl rings provided improved activity, most notably in the in vivo rat models. Compound 40, (E)-3-[2-butyl-1- [(2-chlorophenyl)methyl]imidazol-5-yl]-2-[(2-thienyl)methyl]-2- propenoic acid, has been shown to be a potent, competitive, and orally active small molecule AT-1 receptor antagonist. It exhibits a 2 orders of magnitude increase in binding affinity and a 10-fold improvement in in vivo potency as compared to compound 1 and represents an important milestone in the development of even more potent nonpeptide angiotensin II receptor antagonists.

Acrylates↗

In situ hybridization study of obesity-associated alteration in growth hormone mRNA levels.

In order to investigate whether the impaired GH secretion associated with obesity is due to a pituitary disorder we studied GH mRNA levels by in situ hybridization in genetically obese and lean Zucker rats. The levels of GH mRNA were at least two fold lower in obese rats in comparison to that in lean controls as quantified by both the scanning of autoradiographs of tissue sections and Northern blot analysis. Quantification of somatotrophs revealed no significant difference in their number between lean and obese rat pituitaries. It is therefore likely that the attenuated GH mRNA levels in genetically obese Zucker rats are due to a decrease in GH transcripts per somatotroph rather than a result of a pituitary defect involving a preferential decrease in somatotroph population.

Animals↗

Alteration of somatostatin but not growth hormone-releasing factor pituitary binding sites in obese Zucker rats.

The present study was designed to determine whether the diminution of growth hormone (GH) secretion that occurs in obese Zucker rats is related to alterations of GH-releasing factor (GRF) or somatostatin (SRIF) pituitary binding sites. Cold saturation studies were performed in pituitary homogenates of 4-month-old lean and obese rats, using [125I-Tyr10]hGRF(1-44)NH2 as radioligand and [127I-Tyr10]hGRF-(1-44)NH2 as competitor, and in pituitary membrane preparations, using [125I-Tyr0, D-Trp8]SRIF14 as radioligand and [127I-Tyr0, D-Trp8]SRIF14 as competitor. In lean rats, analysis of the curves by the Ligand program revealed the presence of two distinct classes of GRF binding sites, the first being of high affinity (0.74 +/- 0.11 nM) and low capacity (118 +/- 31 fmol/mg protein), the second being of lower affinity (880 +/- 240 nM) and higher capacity (140 +/- 35 pmol/mg protein), and of a single class of SRIF binding sites (affinity: 0.40 +/- 0.12 nM; capacity: 24 +/- 6 fmol/mg protein). In obese rats, no difference was observed in GRF binding parameters for both classes of sites, but the concentration of somatostatin binding sites was reduced by 67% when compared to their lean littermates. These findings suggest that the SRIF pituitary receptors are down-regulated in obese Zucker rats and indicate that no alteration of GRF pituitary binding sites contribute to the blunted GH secretion observed in this model of obesity.

Animals↗

A survey of the health of homeless children in Philadelphia shelters.

We conducted a random-sample survey of homeless children and their mothers residing in Philadelphia (Pa) shelters. One hundred forty-six families were included in the final sample, resulting in an 80% response rate. The aims of the survey were to characterize the child's current and past health status, to determine access to and use of medical services, and to determine the serum erythrocyte protoporphyrin levels and tuberculin skin test status of the children. In addition, psychological tests were administered to both child and parent to assess developmental level and psychological problems. Finally, detailed questions were asked concerning the reasons for the homeless condition. The important reasons for homelessness cited in the survey included physical abuse, substance abuse, disagreements with landlords, and poor living conditions. The children's health problems included a high incidence of reported accidents and injuries, burns, and lead toxicity; the parents suffered from depression, physical abuse, and substance abuse. School-aged children tended to have low scores on tests of expressive vocabulary and word decoding, and preschoolers seemed to be below age expectations in receptive vocabulary and visual motor skills. The findings of this study suggest that homeless children tend to score poorly on developmental and psychological tests and tend to sustain serious burns and accidents. Policy implications of the survey include suggestions for health screening, rehabilitation, and education.

Accidents↗

Higher alpha-noradrenergic receptors in paraventricular nucleus of obese Zucker rats: decline after food deprivation.

Norepinephrine (NE), acting through alpha 2-noradrenergic receptors in the hypothalamic paraventricular nucleus (PVN), has been implicated in the control of feeding behavior and body weight gain. To determine whether this hypothalamic receptor system is disturbed in genetically obese rats, the binding of radioligands to alpha 2-noradrenergic, as well as to alpha 1-noradrenergic, receptors was examined in seven hypothalamic nuclei of obese Zucker rats relative to their lean littermates. Receptor binding procedures, using the alpha 2-noradrenergic agonist [3H]p-aminoclonidine ([3H]PAC) and the alpha 1-noradrenergic antagonist [3H]prazosin, demonstrated that the obese rats, compared to the lean rats, had significantly greater alpha 2-noradrenergic and alpha 1-noradrenergic receptor binding, specifically in the PVN as opposed to other hypothalamic areas examined. Moreover, the obese rats, compared to the lean rats, exhibited greater responsiveness to the effects of food deprivation (48 h), which caused a significant decline in radioligand binding to both alpha 2 and alpha 1 receptors, specifically in the PVN. A decrease in alpha 2-receptor binding after deprivation in the obese rats was also seen in two basal hypothalamic areas, namely, the supraoptic nucleus and arcuate nucleus-median eminence. The possibility exists that these disturbances in hypothalamic alpha-receptors may be involved in the development and/or maintenance of the genetic obesity.

Adrenergic alpha-Agonists↗

Polyethylene synovitis following canine total hip arthroplasty. Histomorphometric analysis.

The synovial membrane response to polyethylene wear debris was analyzed in canine total hip arthroplasties (THA). Fifty-four THAs were performed in healthy, mature dogs. None of the arthroplasties demonstrated clinical or radiographic signs of loosening. Synovial membrane biopsies were harvested 4 (n = 13), 6 (n = 5), 8 (n = 8), 12 (n = 15), and 24 (n = 6) months after surgery and were scored for inflammation, polyethylene (PE) wear debris, histiocyte density, and membrane thickness. The amount of PE wear debris tended to increase with time. However, the inflammatory changes within the joint capsule and synovial membrane did not progress, and the total thickness of the alveolar and surface layers decreased (P = .008). It appears that the amount of wear debris at 2 years in canine hip arthroplasties, without evidence of loosening, is well tolerated by the joint capsule.

Animals↗