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Biomedical subjects

E D Newman

Publications and source records attributed to E D Newman.

15 recordsLinked to original sources
PubMed1992

P-31 magnetic resonance spectroscopy in polymyositis and dermatomyositis. Altered energy utilization during exercise.

OBJECTIVE: To explore alterations in energy utilization as a potential etiology for weakness in polymyositis and dermatomyositis (PM/DM). METHODS: P-31 magnetic resonance spectroscopy studies were performed in patients with acute and treated PM/DM and in normal controls, at rest and with exercise. RESULTS: Patients with acute and treated PM/DM showed increased ratios of inorganic phosphate to phosphocreatine (PCr) during exercise, with loss of ATP disproportional to loss of PCr. CONCLUSION: This study demonstrates changes in energy utilization in PM/DM, thus supporting the notion of a metabolic etiology for the weakness associated with these diseases.

Adenosine Triphosphate↗
PubMed1992

Seronegative inflammatory arthritis in the myelodysplastic syndromes.

The myelodysplastic syndromes (MDS) are a group of therapeutically refractory anemias resulting from a clonal stem cell disorder often associated with cytogenetic abnormalities. Immunologic abnormalities and occasionally vasculitis have been reported although no series has characterized an associated arthritis. All cases of MDS diagnosed in 1990 by bone marrow biopsy and followed up at the authors' institution were reviewed. Of the 28 consecutive patients, 8 had acute seronegative inflammatory arthritis temporally related to the initial discovery of cytopenia. Five patients had a symmetric polyarthritis resolving only with use of steroids or upon evolution to leukemia, and 3 had episodes of oligoarthritis with systemic features including fever, pleuritis, pericarditis, and hemolytic anemia. Arthrocenteses in 2 cases did not show crystals or infection. Serological studies were nondiagnostic. The arthritis and systemic features responded to steroids in all 5 treated patients. Inflammatory arthritis appears to be common in MDS. Most compelling is the apparent bone marrow response to steroids in 2 cases, possibly identifying a treatable subgroup.

Aged↗
PubMed1992

Clinical liver disease in patients with rheumatoid arthritis taking methotrexate.

Between 1981 and 1989, 3 of 134 patients with rheumatoid arthritis (RA) treated with methotrexate (MTX) developed clinically significant hepatic dysfunction and showed histologic evidence of severe liver disease (fibrosis and cirrhosis). Factors identified in these patients that may have been linked to liver toxicity included diabetes, congestive heart failure and Felty's syndrome. In the patient group that received a post-MTX liver biopsy, pulmonary fibrosis and obesity were significantly associated with hepatic fibrosis/cirrhosis. Severe liver disease may occur in patients with RA treated with low dose MTX (less than 3%). Early liver biopsy is recommended in selected cases.

Aged↗
PubMed1991

Forskolin and methotrexate induce an intermediate trophoblast phenotype in cultured human choriocarcinoma cells.

The human placenta and its associated membranes are vital to the maintenance, nutrition, and protection of the developing fetus. During placental development some cytotrophoblasts give rise to the chorionic membrane whereas others fuse to form a differentiated syncytium of cells that are responsible for placental protein and steroid hormone production. The mechanisms involved in the differentiation of the trophoblasts are unknown; however, an intermediate stage with a characteristic phenotype has been documented in vivo. We have observed that chemically dissimilar xenobiotic agents induced BeWo choriocarcinoma cells to change their usual cytotrophoblastic phenotype and acquire morphologic and functional characteristics typical of intermediate trophoblast. Incubation of BeWo cell cultures in the presence of 1 mumol/L methotrexate for 48 hours stimulated human chorionic gonadotropin secretion (2.3-fold) and aromatase activity (4.9-fold). Morphologic findings associated with these hormonal changes, including increased nuclear size and cytoplasmic expansion, were also observed. With the use of a computer-interfaced image analyzer, planimetric morphometry of the nuclear area of the cells revealed a 1.8-fold increase after incubation with methotrexate. The effect of forskolin, a direct activator of adenylyl cyclase, was also evaluated by means of this model of cytotrophoblast differentiation. The addition of 10 mumol/L forskolin to BeWo cultures also resulted in dramatic changes in trophoblast cell phenotype. Increases in human chorionic gonadotropin synthesis (7.3-fold), aromatase activity (13.5-fold), and nuclear area (3.0-fold) were induced over those of untreated cells. In addition, increases in [3H]thymidine incorporation (1.7-fold) were afforded by both treatments. These results suggest that biochemical and cytologic changes associated with human trophoblast differentiation can be induced in vitro via activation of the adenylyl cyclase pathway by forskolin and through unknown and apparently independent signals by methotrexate.

Cell Differentiation↗
PubMed1991

Endothelin increases the synthesis and secretion of atrial natriuretic peptide in neonatal rat cardiocytes.

Endothelin (ET) effected a dose-dependent increment in atrial natriuretic peptide (ANP) secretion and ANP mRNA accumulation in neonatal rat atrial and ventricular cardiocytes but had no effect on the processing of the ANP prohormone to the mature ANP product. The secretagogue effect was not limited by cell density. Both basal and ET-dependent secretory activity were abrogated by the calmodulin antagonist calmidazolium but were unaffected by meclophenamate or pertussis toxin. The magnitude of the ET-dependent increment in ANP secretion was amplified by culturing the cells in a dynamically pulsating (vs. static) environment, implying an interaction between mechanical and agonist-mediated secretory stimuli in this system. ET also promoted immunoreactive ANP release from primary cultures of fetal rat hypothalamic cultures, suggesting that this regulatory function may be generally employed in ANP gene-expressing cells. These findings demonstrate that ET has parallel effects on ANP synthesis and secretion and support a role for this peptide in the regulation of local and circulating levels of the natriuretic hormone.

Animals↗
PubMed1991

Estradiol down-regulation of the rat uterine estrogen receptor.

We have previously shown that neonatal exposure of rats to pharmacologic doses of diethylstilbestrol via daily injections resulted in a significant decrease in the estrogen-binding capacity of the uterine estrogen receptor (ER). In this study, we examined the effects of physiologic and pharmacologic doses of estradiol (E2) administered to adult ovariectomized rats via Silastic implants. Two days after implantation, uteri were removed, weighted, and homogenized, and ER levels were determined in the supernatant (hydroxylapatite assay) and low-speed pellet (nuclear exchange assay). Implants containing E2 concentrations of 0.005 or 0.05 mg/ml increased cytosolic but not total ER-binding capacity, whereas 0.5 or 5.0 mg of E2/ml implants decreased the binding capacity of cytosol ER to 40% and total ER to 50% of control values. The 0.005-mg/ml dose increased cytosol ER without increasing uterine weight; all higher doses significantly increased uterine weight. Determination of ER protein by an ER radioimmunoassay showed the same extent of reduction of ER concentration as the binding assays, demonstrating that the loss in E2 binding capacity is homologous down-regulation. The down-regulation of ER was maximal at 24 hr and was completely reversible after implant removal, although the time required to recover from down-regulation was dose dependent. Uterine weight also returned to control levels slowly after implant removal. Neither the sedimentation rate of the down-regulated ER nor the Kd of the cytosolic ER changed following long-term implantation; however, the Kd of the nuclear ER decreased significantly. This is the first demonstration of in vivo homologous down-regulation of uterine ER. ER down-regulation may play a role in several biologic processes.

Animals↗
PubMed1991

Sulfasalazine therapy in psoriatic arthritis: clinical and immunologic response.

Sulfasalazine therapy has been shown effective in rheumatoid arthritis and ankylosing spondylitis. We treated 10 patients with active polyarticular psoriatic arthritis with 2 g/day of sulfasalazine for 16 weeks. Significant improvement was seen in joint count score, morning stiffness, and patient/physician assessment of disease activity. Toxicity requiring drug cessation was seen in only 1 patient. Patients with psoriatic arthritis had elevated B cells and immunoglobulin levels which fell with sulfasalazine therapy. Minimal changes were seen in T cell subsets. Sulfasalazine appears to be an effective second line agent for the treatment of psoriatic arthritis. Its mechanism of action may in part relate to alteration of B cell number and function.

Adult↗
PubMed1989

Suppurative extensor tenosynovitis caused by Staphylococcus aureus.

Suppurative tenosynovitis is a rare infection, occurring almost exclusively in the flexor tendon sheath as a posttraumatic event. We report the case of a systemically ill woman with suppurative tenosynovitis of the extensor tendons caused by Staphylococcus aureus. Early recognition of this unusual infection may prevent unnecessary morbidity.

Female↗
PubMed1988

Septic arthritis due to gram negative bacilli: older patients with good outcome.

Previous studies of gram negative bacillary septic arthritis conclude it is an uncommon disease of older patients with poor outcome, or of younger patients with good outcome. We reviewed 22 cases of gram negative bacillary septic arthritis in a rural population. The mean age was 61 years, symptoms were of short duration (6.5 days mean), and a chronic illness was frequently present (77%). The knee was involved in 73% and E. coli was the usual causative organism (32%). Antibiotics plus aspiration was a successful initial therapy. Overall survival was 95% and a good outcome was achieved in 68%. Gram negative bacillary septic arthritis affects older patients, and the outcome appears good.

Aged↗
PubMed1984

Multiple simultaneous determinations of hemodynamics and flow distribution in conscious rat.

A method for multiple simultaneous determinations of cardiocirculatory dynamics, regional blood flow, and total cardiac output distribution in the conscious rat preparation is described. The preparation allows for intravenous administration of agents and can be performed on animals either at rest or during treadmill exercise. Instrumentation procedures involve placement of fluid-filled catheters in the left ventricle, right atria, right jugular vein, and caudal artery. Left ventricular pressures are recorded via a modified 4F Millar transducer-tipped manometer containing a 10-cm extension of fluid-filled PE 50 placed into the left ventricle via the right carotid artery. Radionuclide-labeled microspheres (15 +/- 5 mu) are injected into the left ventricle through the fluid-filled PE 50 at selected times for determination of cardiac output and regional blood flows using the caudal artery catheter as the source of the reference blood sample. Details and selected validation data for procedures involving anesthesia, instrumentation, recovery from anesthesia, data gathering, and data analysis are presented. Emphasis is placed on the procedures required for use of the radioactive microsphere technique in this model with special attention given to quality control of the microsphere stock, counting procedures, and computer analysis of these data.

Animals↗
PubMedDate not supplied

Effects of intravenous diltiazem on cardiocirculatory dynamics and cardiac output distribution in conscious spontaneously hypertensive rats.

The effects of the calcium channel blocker, diltiazem hydrochloride (DZ), on conscious, resting spontaneously hypertensive rats (SHR) were evaluated and compared with results from parallel studies on Wistar-Kyoto (WKY) controls. DZ was administered as a continuous, cumulative infusion at rates equal to 0.40, 2.00, and 10.00 mg/kg/h (each dose was administered for 15 min). Parallel volume infusion (saline) controls were simultaneously conducted using volume infusion rates identical to those used in DZ studies (0.015, 0.100, and 0.500 ml/min). Three hours prior to study, animals were instrumented under halothane anesthesia for measurement of left ventricular, arterial, and central venous pressures; heart rate and arterial blood gases; and for injection of radioactive microspheres and subsequent determination of cardiac output, regional blood flows, and cardiac output distribution. All data were collected at control (C) before initiation of infusion, and at the end of each 15-min infusion period in each animal. At C and compared with WKY, SHR had increased heart rate (392 vs. 280 beats/min), mean arterial pressure (155 vs. 100 mm Hg), left ventricular peak systolic pressure (200 vs. 132 mm Hg), and systemic vascular resistance (0.3 vs. 0.2 mm Hg/ml/min/kg), and reduced stroke volume (1.8 vs. 2.2 ml/beat/kg); but no difference in cardiac output, left ventricular end diastolic pressure, or central venous pressure was found. At C, SHR tended to have increased blood flow and reduced vascular resistance in the coronary circulation and increased vascular resistance in the cutaneous, renal, bronchial arterial, hepatic arterial, testicular, and cerebral circulations. Infusion of DZ increased cardiac output and stroke volume and decreased heart rate, left ventricular and arterial pressures, and systemic vascular resistance in SHR. Similar changes of substantially smaller magnitude were observed in WKY. DZ increased flow and reduced resistance in the coronary and skeletal muscle circulations of SHR to a greater extent than in WKY. DZ also normalized vascular resistance in previously elevated regions. These results suggest that acute intravenous infusion of DZ at doses ranging between 2 and 5 mg/kg is capable of normalizing cardiovascular hemodynamics and regional blood flow distribution in SHR.

Animals↗