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Biomedical subjects

A M Golichowski

Publications and source records attributed to A M Golichowski.

At least 19 recordsLinked to original sources

A randomized comparison of home uterine activity monitoring in the outpatient management of women treated for preterm labor.

OBJECTIVE: The aim of the study was to evaluate home uterine activity monitoring as an intervention in reducing the rate of preterm birth among women treated for preterm labor. STUDY DESIGN: A total of 186 women were treated in the hospital with magnesium sulfate for preterm labor and were prospectively randomly assigned to study groups; among these, 162 were ultimately eligible for comparison. Eighty-two of these women were assigned to the monitored group and 80 were assigned to an unmonitored control group. Other than monitoring, all women received identical prenatal follow-up, including daily perinatal telephone contact and oral terbutaline therapy. Outcome comparisons were primarily directed toward evaluation of preterm birth at <35 weeks' gestation. Readmissions for recurrent preterm labor and observations lasting <24 hours were evaluated in monitored and unmonitored groups. Compliance with monitoring was also evaluated in the monitored group. RESULTS: The monitored and control groups were demographically similar. According to a multivariate logistic regression model, women with cervical dilatation of >/=2 cm were 4 times more likely to be delivered at <35 weeks' gestation (P <.05). Gestational ages at delivery were similar in the monitored and control groups. There was no significant difference in the overall rate of preterm delivery at <35 weeks' gestation between the monitored group (10.9%) and the control group (15.0%). The overall rates of delivery at <37 weeks' gestation were high (48.8% and 60.0% for monitored and control groups, respectively), and the difference was not significant. The numbers of women with >/=1 instance of readmission and treatment for recurrent preterm labor were equal in the monitored and control groups. The numbers of women with >/=1 hospital observation lasting <24 hours were not different between the groups. Compliance with monitoring did not significantly differ for women who were delivered at <35 weeks' gestation, women with >/=2 cm cervical dilatation at enrollment, or for African American women. CONCLUSION: A reduction in the likelihood of preterm delivery at <35 weeks' gestation was not further enhanced by the addition of home uterine monitoring to the outpatient management regimens of women treated for preterm labor.

Adolescent↗

Tocolytic treatment for preterm contractions with and without cervical changes.

Our purpose was to evaluate the impact of intravenous and oral tocolysis on prolongation of gestation for women with preterm uterine contractions and/or labor. Candidates for evaluation and treatment including women with contractions between 24 and 35 weeks. Two hundred women (group I) without cervical changes met the protocol criteria and 175 women (group II) who presented with or developed cervical changes were treated by protocol. A representative sample of both groups received oral terbutaline maintenance therapy until 37 weeks' gestation. Primary outcome variables included the length of gestation obtained following initial treatment and the preterm birth rate. Women in group II were twice as likely to deliver before 35 weeks, 23% versus 9.5%, respectively, and to have a delivery before 37 weeks' gestation, 45% versus 22%, respectively, (p < 0.05). There was no significant difference in days gained in utero for women on oral terbutaline for either group. Women in group II on oral therapy were more likely to be readmitted and retreated with parenteral tocolysis. In conclusion, oral maintenance tocolysis has no significant impact on further prolongation of pregnancy after intravenous tocolysis.

Administration, Oral↗

Glucose and amino acid turnover in untreated gestational diabetes.

OBJECTIVE: Although gestational diabetes affects as many as 3% of all pregnant women, specific aspects of glucose and protein metabolism in this population have not been clearly delineated. We tested the hypothesis that gestational diabetes mellitus (GDM) results in increased glucose production and proteolysis during fasting. RESEARCH DESIGN AND METHODS: Using tracer isotope infusions, the rate of appearance (Ra) of glucose, leucine, phenylalanine and tyrosine, phenylalanine hydroxylation, leucine oxidation, and urea nitrogen excretion were determined after an overnight fast in 10 GDM subjects, within 2 weeks of diagnosis and before initiation of treatment, and in a matched control group of nine healthy nondiabetic pregnant women. RESULTS: Fasting glucose Ra was similar in GDM patients and control subjects (GDM, 12.8 +/- 1.1 vs. control subjects, 12.8 +/- 0.9 mumol . kg-1 . min-1). Leucine and phenylalanine Ra (reflecting proteolysis) also were not different between GDM patients and control subjects (GDM leucine Ra, 128 +/- 14 vs. control subjects, 124 +/- 5; phenylalanine Ra GDM, 35 +/- 4 vs. control subjects, 40 +/- 2 mumol . kg-1 . h-1). Furthermore, leucine oxidation and phenylalanine hydroxylation were not increased in GDM subjects, urea nitrogen excretion was actually lower in GDM patients. However, fasting insulin concentrations were significantly elevated in GDM subjects (GDM, 165 +/- 35 vs. control subjects, 30 +/- 5 pmol/l; P < 0.01). CONCLUSIONS: Hepatic glucose release and whole-body proteolysis in GDM patients were remarkably similar to matched pregnant control subjects. This was achieved with insulin concentrations three- to fivefold higher than normal, suggesting significant insulin resistance for both glucose and protein metabolism in GDM.

Adult↗

Cutaneous mastocytosis complicating pregnancy.

BACKGROUND: Telangiectasia macularis eruptiva perstans, a rare form of cutaneous mastocytosis associated with elevated histamine excretion, has not previously been reported to complicate pregnancy. CASE: A woman presented in the late second trimester with an anaphylactoid reaction, rash, uterine contractions, and vaginal bleeding. Skin biopsy revealed perivascular mast-cell infiltration. Her urinary histamine excretion was markedly elevated. She was treated successfully with tocolytics and antihistamines. CONCLUSION: Elevated histamine excretion in biopsy-proven cutaneous mastocytosis may be associated with preterm labor.

Adult↗

Prenatal ultrasound detection of isolated neural tube defects: is cytogenetic evaluation warranted?

OBJECTIVE: To determine the value of cytogenetic evaluation in fetuses with isolated neural tube defects diagnosed by prenatal ultrasound. METHODS: Fifty-five thousand two hundred sixty obstetric ultrasounds performed for various indications at the Indiana University Prenatal Diagnostic Center from July 1988 to March 1994 were reviewed using a computerized data base. Excluding all cases of anencephaly, fetuses with isolated neural tube defects were identified. Maternal demographic data, pregnancy outcomes, level of defect, and fetal karyotype when available were obtained. Statistical analysis was performed using the chi 2 test, when appropriate. P < or = .05 was considered statistically significant. RESULTS: Seventy-seven medical record charts of women with prenatally diagnosed isolated fetal neural tube defects were reviewed. Nineteen pregnancies were terminated, 42 pregnancies were delivered, and 16 pregnancies were lost to follow-up. Karyotypes were available in 43 of the 77 cases (55.8%). The theoretical risk of chromosomal anomalies in this sample population based solely on maternal age was 0.3%. Of the 43 documented karyotypes, seven chromosomal anomalies were discovered (16.3%). The difference was statistically significant (P = .012). Detected chromosomal anomalies included two trisomy 18, two triploid 69,XXX, one triploid 69,XXY, one balanced Robertsonian translocation t(13q,14q), and one inversion in the q arm of the X chromosome. CONCLUSION: The prevalence of karyotypic abnormalities is significantly increased in fetuses with isolated neural tube defects; therefore, prompt antenatal genetic evaluation should be considered in such cases.

Adult↗

Multiple defects in the adipocyte glucose transport system cause cellular insulin resistance in gestational diabetes. Heterogeneity in the number and a novel abnormality in subcellular localization of GLUT4 glucose transporters.

Mechanisms causing cellular insulin resistance in gestational diabetes mellitus are not known. We, therefore, studied isolated omental adipocytes obtained during elective cesarean sections in nondiabetic (control) and GDM gravidas. Cellular insulin resistance was attributed to impaired stimulation of glucose transport; compared with control subjects, basal and maximally insulin-stimulated transport rates (per surface area) were reduced 38 and 60% in GDM patients, respectively. To determine underlying mechanisms, we assessed the number, subcellular distribution, and translocation of GLUT4, the predominant insulin-responsive glucose transporter isoform. The cellular content of GLUT4 was decreased by 44% in GDM patients as assessed by immunoblot analysis of total postnuclear membranes. However, GDM patients segregated into two subgroups; half expected profound (76%) cellular depletion of GLUT4 and half had GLUT4 levels in the normal range. Cellular GLUT4 was negatively correlated with adipocyte size in the control subjects and GDM patients with normal GLUT4 (r = 0.60), but fell way below this continuum in GDM patients with low GLUT4, indicating that heterogeneity was not caused by differences in obesity. All GDM. distribution. In basal cells, increased amounts of GLUT4 were detected in membranes fractionating with (such that the plasma membrane GLUT4 level in GDM (such that the plasma membrane GLUT4 level in GDM patients was equal to that observed in insulin-stimulated cells from control subjects). Furthermore, insulin stimulation induced translocation of GLUT4 from low-density microsomes to plasma membranes in control subjects but did not alter subcellular distribution in GDM patients. In other experiments, cellular content of GLUT1 was normal in GDM patients, and GLUT1 did not undergo insulin-mediated recruitment to plasma membranes in either control subjects or GDM patients. A faint signal was detected for GLUT3 only in low-density microsomes and only with one of two different antibodies. In GDM, we conclude that insulin resistance in adipocytes involves impaired stimulation of glucose transport and arises from a heterogeneity of defects intrinsic to the glucose transport effector system. GLUT4 content in adipocytes is profoundly depleted in approximately 50% of GDM patients, whereas all patients are found to exhibit a novel abnormality in GLUT4 subcellular distribution. This latter defect is characterized by accumulation of GLUT4 in membranes cofractionating with plasma membranes and high-density microsomes in basal cells and absence of translocation in response to insulin. The data suggest that abnormalities in cellular traffic or targeting relegate GLUT4 to a membrane compartment from which insulin cannot recruit transporters to the cell surface and have important implications regarding skeletal muscle insulin resistance in GDM and NIDDM.

Adipocytes↗

Gene expression of GLUT4 in skeletal muscle from insulin-resistant patients with obesity, IGT, GDM, and NIDDM.

In obesity, impaired glucose tolerance (IGT), non-insulin-dependent diabetes mellitus (NIDDM), and gestational diabetes mellitus (GDM), defects in glucose transport system activity, contribute to insulin resistance in target tissues. In adipocytes from obese and NIDDM patients, we found that pretranslational suppression of the insulin-responsive GLUT4 glucose transporter isoform is a major cause of cellular insulin resistance; however, whether this process is operative in skeletal muscle is not clear. To address this issue, we performed percutaneous biopsies of the vastus lateralis in lean and obese control subjects and in obese patients with IGT and NIDDM and open biopsies of the rectus abdominis at cesarian section in lean and obese gravidas and gravidas with GDM. GLUT4 was measured in total postnuclear membrane fractions from both muscles by immunoblot analyses. The maximally insulin-stimulated rate of in vivo glucose disposal, assessed with euglycemic glucose clamps, decreased 26% in obesity and 74% in NIDDM, reflecting diminished glucose uptake by muscle. However, in vastus lateralis, relative amounts of GLUT4 per milligram membrane protein were similar (NS) among lean (1.0 +/- 0.2) and obese (1.5 +/- 0.3) subjects and patients with IGT (1.4 +/- 0.2) and NIDDM (1.2 +/- 0.2). GLUT4 content was also unchanged when levels were normalized per wet weight, per total protein, and per DNA as an index of cell number. Levels of GLUT4 mRNA were similarly not affected by obesity, IGT, or NIDDM whether normalized per RNA or for the amount of an unrelated constitutive mRNA species. Because muscle fibers (types I and II) exhibit different capacities for insulin-mediated glucose uptake, we tested whether a change in fiber composition could cause insulin resistance without altering overall levels of GLUT4. However, we found that quantities of fiber-specific isoenzymes (phopholamban and types I and II Ca(2+)-ATPase) were similar in all subject groups. In rectus abdominis, GLUT4 content was similar in the lean, obese, and GDM gravidas whether normalized per milligram membrane protein (relative levels were 1.0 +/- 0.2, 1.3 +/- 0.1, and 1.0 +/- 0.2, respectively) or per wet weight, total protein, and DNA. We conclude that in human disease states characterized by insulin resistance, i.e., obesity, IGT, NIDDM, and GDM, GLUT4 gene expression is normal in vastus lateralis or rectus abdominis. To the extent that these muscles are representative of total muscle mass, insulin resistance in skeletal muscle may involve impaired GLUT4 function or translocation and not transporter depletion as observed in adipose tissue.

Adult↗

Enhancement of binding of the dihydropyridine calcium antagonist PN200-110 to human myometrial sarcolemma by the heterologous calcium antagonist diltiazem.

Binding of the dihydropyridine calcium antagonist PN200-110 was studied in human myometrial membranes. PN200-110 bound reversibly and with high affinity to membrane fragments. The highest concentration of binding sites was found in the sarcolemma. The benzothiazepine calcium antagonist diltiazem stimulated PN200-110 binding by increasing the amount bound at equilibrium. Kinetic studies detected a fast and slow rate of dissociation in the presence of diltiazem.

Calcium Channel Blockers↗

Tocolytic and hemodynamic effects of nifedipine in the ewe.

The ability of the calcium antagonist nifedipine to inhibit uterine contractions during labor and in the postpartum period was measured in the ewe. The hemodynamic effects of tocolytic doses of this drug were measured and compared with the hemodynamic effects of equivalent doses of ritodrine. Intravenous nifedipine was found to be a potent tocolytic agent that completely inhibited uterine activity even in advanced labor when administered at infusion rates that resulted in only mild hemodynamic effects. At tocolytically similar infusion rates nifedipine produced significantly less increase in maternal heart rate than did ritodrine.

Animals↗

Binding of the calcium antagonist [3H] nitrendipine to human myometrial plasmalemma.

Membrane fragments were prepared from nonpregnant human myometrium and fractionated by differential and sucrose gradient centrifugation. Reversible high-affinity binding sites of the dihydropyridine calcium antagonist nitrendipine were identified in highest density in that membrane fraction most enriched in markers for plasmalemma. In determinations done on several preparations, the equilibrium dissociation constant for nitrendipine at 37 degrees C was found to be 0.3 to 0.8 nM and was the same for each fraction. The maximum binding capacity was found to be 400-500 fmol/mg protein in the plasmalemma fraction.

Calcium↗

Fetal hydrothorax and bilateral pulmonary hypoplasia. Ultrasonic diagnosis.

Bilateral pulmonary hypoplasia associated with hydrothorax is an unexplained entity. The purpose of this study was to evaluate an ultrasonic diagnostic approach towards this problem. Antenatal screening of pregnancies at risk for fetal hydrothorax, early detection of suspected hypoplasia and active management might afford the fetus adequate pulmonary function to support extra-uterine life.

Adult↗

Effect of prostaglandins on immune complex interaction with glomerular cells in vitro.

Previous studies demonstrated that prostaglandins of the E1 (PGE1) series reduced immune complex (IC) accumulation and inflammation in murine glomeruli in IC glomerulonephritis (GN). This study examines the effect of PGE1 on IC interaction with cultured rabbit glomerular cells and heparan sulfate synthesis by the cells. IC were formed with antigen chemically modified to produce a cationic (CAT) charge or left unmodified (UM). CAT IC binding to cells was greater than UM IC in the absence of PGE1. CAT IC binding to cells was increased by PGE1 while UM IC interaction was not affected. Prolonged exposure of cells to PGE1 enhanced CAT IC binding. Heparan sulfate synthesis by the cells was not affected by the concentrations of PGE1 employed. The findings suggest the benefit provided by PGE1 in murine IC GN may not be due to a direct effect on glomerular cells which reduces glomerular IC accumulation.

Alprostadil↗

A clinical evaluation of chlorhexidine gluconate spray as compared with iodophor scrub for preoperative skin preparation.

In a prospective, randomized study, 737 patients who were evaluated had the operative site prepared preoperatively by either a 0.5 per cent chlorhexidine gluconate spray or povidone-iodine scrub. The wound infection rate in these two comparable groups was not statistically different, although slightly favoring the spray technique (6.0 versus 8.1 per cent). The spray technique challenges the conventional preoperative scrub and offers further advantages of increased effectiveness while also offering savings of time and expense.

Aerosols↗

Respiratory distress following elective repeat cesarean section.

The clinical course and chest radiographs of 47 infants with respiratory distress after elective cesarean section were reviewed. The mean difference between the gestational age determined prenatally and that postnatally was 2.6 +/- 1.6 weeks. However, 14 of the infants were delivered at term. All 47 infants required more than 40% oxygen, and 18 infants required a respirator. Fifteen infants developed a pneumothorax; one, a pneumopericardium; one, bronchopulmonary dysplasia; and one infant died. Chest radiographs and the clinical course were consistent with hyaline membrane disease in 17 patients; respiratory distress syndrome type II in 24; and in three the radiographic findings were normal. These data suggest that some of the respiratory morbidity subsequent to elective repeat cesarean section is not secondary to iatrogenic delivery of a premature infant, and that much of it is not due to hyaline membrane disease. These data emphasize that respiratory distress in an infant delivered by elective cesarean section does not necessarily suggest poor prenatal care in regard to the timing of delivery.

Cesarean Section↗

Pregnancy-related changes in rat cervical glycosaminoglycans.

Non-pregnant and pregnant rats of known gestational age were killed at intervals and their uterine cervices were excised and digested with papain. Glycosaminoglycans thus extracted were separated by cellulose acetate electrophoresis and stained with Alcian Blue. Glycosaminoglycans were identified by comparison with standards and by serial degradation with chondroitin ABC lyase, butyl nitrite and leech hyaluronidase. Dermatan sulphate, hyaluronic acid and heparan sulphate were identified and quantitative determined by densitometry. The overall concentration of glycosaminoglycans changed little during pregnancy. A 3-fold total increase in uronic acid paralleled the increase in cervical weight. Hyaluronate content, however, increased 17-fold, and rose from 6% of total glycosaminoglycans in the non-pregnant state to 33% at term. Furthermore, the ratio of hyaluronate to hydroxyproline increased 10-fold. These changes are consistent with an accumulation of hyaluronate in the interstices between collagen fibres, resulting in the softening of this tissue that is seen in late pregnancy.

Animals↗