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T M Goodwin

Publications and source records attributed to T M Goodwin.

72 records · Page 4Linked to original sources

Thyrotropic activity of basic isoelectric forms of human chorionic gonadotropin extracted from hydatidiform mole tissues.

hCG is known to have thyroid-stimulating activity and may cause hyperthyroidism in patients with trophoblastic diseases. hCG occurs in normal and molar pregnancy with breaks or nicks in the alpha- or beta-subunit peptide linkage and with substantial heterogeneity in the composition and degree of branching within the oligosaccharide side-chains. The bioactivity of hCG is markedly influenced by these structural variations. We purified hCG from five hydatidiform moles, using chromatofocusing separation after gel filtration. The hCG molecules were fractionated according to their isoelectric points, with a linear pH gradient from 3.2-6.1 and a final 1.0 mol/L NaCl step elution. The hCG immunoreactivity of each fraction was measured by RIA, and the thyroid-stimulating activity of hCG was determined by means of the cAMP response in Chinese hamster ovary cells expressing functional human TSH receptors (Chinese hamster ovary-JP09 cells). The chromatofocusing profile showed that hCG from the moles was eluted in six or seven major peaks at pH 6.1, 5.5, 5.3, 4.8, 3.8, and 3.2 and with 1.0 mol/L NaCl, whereas hCG extracted from serum of hydatidiform moles and standard hCG preparation CR-127 extracted from pregnancy urine showed only small peaks at pH greater than 5.3. Each fraction increased cAMP production significantly in Chinese hamster ovary-JP09 cells. The relative bioactivity/immunoreactivity, represented as the ratio of cAMP/hCG (picomoles per IU), was significantly higher in basic components (pI 6.1, 6.2 +/- 1.2; pI 5.5, 4.4 +/- 2.7; pI 5.3, 5.8 +/- 0.3) than in hCG CR-127 (bioactivity/immunoreactivity, 0.42; P < 0.05). The difference in pI of each hCG isoform was attributable to the extent of sialylation; basic hCG isoforms contained less sialic acid by immunological detection using lectins. These results indicate that isoforms of hCG with more thyrotropic activity were produced by trophoblastic tissues in patients with hydatidiform mole. We speculate that these isoforms of hCG may be responsible for the hyperthyroidism in some patients with hydatidiform moles.

Adult↗

Increased concentration of the free beta-subunit of human chorionic gonadotropin in hyperemesis gravidarum.

OBJECTIVE: The amount of free beta subunit hCG (free beta) has been reported to be increased in trophoblast disease and Down's syndrome, conditions also associated with high total hCG. Increased total hCG has been reported in hyperemesis gravidarum. We sought to determine if sera from singleton gestations with hyperemesis gravidarum contained a higher proportion of free beta hCG compared to controls of comparable gestational age. METHODS: Sera from 39 patients with hyperemesis gravidarum was compared with that from 23 control subjects of comparable gestational age with respect to beta hCG and its subunits (free beta and free alpha). RESULTS: Hyperemesis patients and controls were comparable with respect to age, weight and gestational age. The concentration of hCG was greater in hyperemesis patients (9237 +/- 3613 ng/ml, mean +/- s.d.) compared to controls (5543 +/- 2290, p < 0.005) as was the concentration of free beta hCG (101 +/- 70 ng/ml vs. 31 + 31, p < 0.001). Free alpha did not differ between hyperemesis patients and controls (399 +/- 231 ng/ml vs. 377 +/- 214). A percent free beta greater than 0.6 was found in 33/39 hyperemesis patients (85%) compared to 5/23 controls (22%), p < 0.001. CONCLUSION: Increased free beta hCG is found in hyperemesis gravidarum. This finding strengthens the association of hyperemesis with abnormal metabolism of hCG.

Adult↗

Increased in vitro thyrotropic activity of partially sialated human chorionic gonadotropin extracted from hydatidiform moles of patients with hyperthyroidism.

The intrinsic thyrotropic activity of hCG purified from normal pregnancy urine has been demonstrated in several laboratories. hCG has a specific thyrotropic potency of about 0.04-0.5 microU bovine (b) TSH/IU hCG, depending on the bioassay system. The corresponding potency for hCG derived from pathological sources, such as hydatidiform moles and choriocarcinoma tissue, or from the serum of these patients has not been studied as extensively. Since the biological activity of glycoproteins can be strongly influenced by variations in the oligosaccharide side-chain composition, we have investigated the effect of anion exchange chromatography on the thyrotropic potency of hCG derived from the hydatidiform mole and serum of three hyperthyroid patients with molar pregnancy. The activity for the fraction of total molar hCG immunoreactivity that was not retained by an anion exchange column (0.18-0.90 microM bTSH/IU hCG) was about twice that of the corresponding serum and molar hCG fraction eluting during the NaCl gradient elution (0.08-0.40 microU bTSH/IU hCG). The unretained hCG fraction corresponds to a previously described hCG precursor that is partially desialated in the C-terminal region of the beta-subunit.

Adult↗

Asphyxial complications in the term newborn with severe umbilical acidemia.

OBJECTIVE: Our purpose was to determine the relationship of umbilical acid-base status and Apgar score to neonatal asphyxial sequelae in infants with severe acidemia (pH < 7.00). STUDY DESIGN: The obstetric and neonatal course of 129 term, nonanomalous singleton infants with umbilical pH < 7.00 was reviewed. RESULTS: There were three stillbirths (failed resuscitation). Seventy-two of 126 (57%) were admitted to the neonatal intensive care unit. Thirty-eight percent had pulmonary dysfunction, 26% renal dysfunction, 31% cardiac dysfunction, and 31% hypoxic ischemic encephalopathy (seizures and hypotonia, n = 29; seizures only, n = 3; hypotonia only, n = 10). There were five neonatal deaths. In 109 cases umbilical arterial values were available, and among these infants there was a significant increase in the incidence of seizures with declining pH from 9% (5/57), with a pH of 6.90 to 6.99, to 80% (8/10), with a pH of 6.61 to 6.70. Respiratory acidemia (PCO2 > 65, base deficit < 10) was identified in 28 of 109 (26%), all but six occurring in the pH range above 6.90. Compared with infants with comparable umbilical artery pH, infants with respiratory acidemia did not differ significantly with respect to asphyxial end-organ injury in general (8/35 vs 6/22), but there was a trend toward a lower incidence of hypoxic ischemic encephalopathy (6/35 vs 1/22, p = 0.06). All infants with definite abnormal outcome (five neonatal deaths and 10 severe neurologic deficit) had seizures, hypotonia, and at least one other organ system dysfunction. Twenty-four of 29 infants (83%) who developed seizures had a 5-minute Apgar score < 7, but only 12 of 29 (41%) had a 5-minute Apgar score of < or = 3. Two infants with Apgar scores of 6 and 7 at 5 minutes and no evidence of nonasphyxial comorbidity subsequently manifested profound neurologic deficit. CONCLUSIONS: Infants with severe umbilical acidemia can be separated with regard to risk of hypoxic ischemic encephalopathy and abnormal neurologic outcome by consideration of the severity and composition of the acidemia and evidence of other end-organ dysfunction. Even in this pH range the Apgar score is not highly predictive of asphyxial complications.

Acids↗

Transient hyperthyroidism and hyperemesis gravidarum: clinical aspects.

OBJECTIVES: Our objectives were to describe the presentation and course of hyperemesis gravidarum with respect to thyroid function and to test the hypothesis that patients with biochemical hyperthyroidism differ in clinical presentation from euthyroid hyperemesis patients. STUDY DESIGN: Sixty-seven patients seen at Los Angeles County Women's Hospital over a 10-month period with hyperemesis gravidarum were studied prospectively with respect to thyroid function. RESULTS: Forty-four patients (66%) had biochemical hyperthyroidism (increased free thyroxine index [n = 39] or suppressed thyroid-stimulating hormone [n = 40]) that was self-limited, resolving by 18 weeks' gestation. Hyperthyroid patients were more likely than euthyroid patients to have abnormal electrolyte levels (23/39 [59%] vs 6/28 [21%] and increased liver enzyme levels (23/59 [59%] vs 5/28 [18%], p less than 0.01). The severity of hyperemesis was found to vary directly with the degree of hyperthyroidism. CONCLUSIONS: Hyperthyroidism is a common, self-limited finding in hyperemesis. The cause of the hyperthyroidism may be linked to the cause of hyperemesis itself.

Adolescent↗

The role of chorionic gonadotropin in transient hyperthyroidism of hyperemesis gravidarum.

Biochemical evidence of hyperthyroidism is frequently encountered in hyperemesis gravidarum, but its relationship to the cause of hyperemesis is unknown. We studied the relationship of serum hCG, thyroid function, and severity of vomiting among 57 hyperemesis patients and 57 controls matched for gestational age. TSH was suppressed in 60% of hyperemesis patients and 9% of controls. hCG correlated directly with free T4(r = 0.45, P < 0.001) and inversely with TSH (r = -0.48, P < 0.001). Hyperemesis patients had significantly greater mean serum hCG, free T4, total T3, and estradiol, and lesser serum TSH compared to controls. Hyperemesis patients with suppressed TSH had significantly greater free T4 and hCG compared to those with TSH in the normal range. Control and hyperemesis subjects were divided into four groups based on the severity of vomiting. The degree of biochemical hyperthyroidism and hCG concentration varied directly with the severity of vomiting. Unextracted serum was tested for thyrotropic activity by measuring its effect on iodide uptake in cultured FRTL-5 rat thyroid cells. Thyrotropic activity correlated with serum hCG (r = 0.50, P < 0.001). These data show that biochemical hyperthyroidism is a common finding in patients with hyperemesis gravidarum and suggest that hCG is the thyroid stimulator in this state. The increased estradiol concentration in patients with hyperemesis gravidarum may be attributed to the effects of hCG on steroidogenesis.

Acute Disease↗

Pregnancy outcome and fetomaternal hemorrhage after noncatastrophic trauma.

Two hundred five consecutive cases of noncatastrophic trauma occurring during the second half of pregnancy were evaluated prospectively. Pregnancy complications as a result of trauma occurred in 18 of 205 patients (8.8%): premature labor (n = 10), placental separation (n = 5), fetal injury (n = 1), and fetal death (n = 2). Multiple regression analysis of the data base showed obstetric findings (contractions, uterine tenderness, and bleeding) on presentation to be highly associated with complications (17/88; 19.3%). In their absence complications were rare (1/117; 0.9%). Detectable fetomaternal hemorrhage was significantly more common in trauma patients (18/205) than in control subjects (2/110) (p less than 0.01), but its role in managing trauma patients was limited to detection of rare massive hemorrhage (1/205) and detection of rare hemorrhage exceeding that covered by the standard Rho (D) immune globulin dose (2/205). Fetomaternal hemorrhage need not be quantitated in patients who lack obstetric findings on presentation. Despite rare reports of delayed abruptio placentae, it is doubtful that prolonged observation (greater than 2 to 3 hours) in the hospital is necessary in patients who lack obstetric findings on initial presentation.

Accidents, Traffic↗

Congenital hypofibrinogenemia in pregnancy.

A new case of congenital hypofibrinogenemia in pregnancy is reported and the literature is reviewed from an obstetric perspective. An association with spontaneous abortion, abruption, and postpartum hemorrhage is documented and management options are presented.

Abortion, Spontaneous↗

Chromosome subband 17p11.2 deletion: a minute deletion syndrome.

Interstitial deletion of the short arm of chromosome 17 was detected in three unrelated patients with mental retardation and multiple congenital malformations. These patients were identified at a single centre over a six month period suggesting that del(17) (p11.2p11.2) is not a rare constitutional chromosome rearrangement. Comparison of the phenotypic features in a total of 19 patients with del(17)(p11.2p11.2) shows a consistent clinical phenotype with moderate to severe mental retardation, microbrachycelphaly, prominent forehead, broad face, flat midface, prognathism, short, broad hands, and behavioural anomalies such as self-mutilation. The sex ratio is unremarkable, parental ages are normal, and survival is usually unimpaired. Chromosome resolution of at least 500 bands appears necessary to detect this deletion.

Abnormalities, Multiple↗

Toluene abuse and renal tubular acidosis in pregnancy.

Five gravidas presented with severe renal tubular acidosis from paint sniffing. Normal acid-base balance returned within 72 hours with cessation of toluene abuse and standard supportive measures. Fetal heart tracings and dynamic ultrasound parameters were normal in four of five cases. Three of five infants were growth-retarded at birth; two showed anomalies and neonatal hyperchloremic acidosis. These and previous cases of renal tubular acidosis in pregnancy suggest that toluene is teratogenic.

Acidosis↗

A haemogregarine from the American alligator (Alligator mississippiensis).

Haemogregarina crocodilinorum Börner 1901 is redescribed from the blood of the American Alligator (Alligator mississippiensis). Gametocytes occurred in erythrocytes and erythrocytic schizonts contained about eight merozoites (range, 6--12). Gametogony and sporogony occurred in the gut of the leech, Placobdella multilineata and intracellular, unisporocystic oocysts were found within epithelial cells of the leech's intestinal wall. Presumed sporozoites were present in the intestinal contents. Attempts to transmit the parasite via leeches failed. The haemogregarine was widely distributed in southern United States and was found in 77 (59%) of 130 alligators examined. A comparison of this parasite is made with other haemogregarines reported from crocodilian reptiles.

Alligators and Crocodiles↗

Significance of antinuclear antibody testing in unexplained second and third trimester fetal deaths.

The purpose of this study was to determine if a group of patients with unexplained second or third trimester fetal demise have an increased prevalence of antinuclear antibodies (ANA) when compared to controls. During a 5-year period from January 1989 through December 1993, the records of all fetal deaths > or = 500 g or > or = 20 weeks of gestation that occurred at our institution were reviewed. In these women the ANA titers were checked at the discretion of the physician. The proportion of positive ANA tests in the group of women with explained fetal deaths was compared to that in women with unexplained fetal deaths. These results were then compared to a control group of healthy gravidas presenting to labor and delivery in the third trimester. During this time period, 848 fetal deaths were recorded. Our study population consisted of 286 patients who had an unexplained second or third trimester fetal demise with a record of having an ANA drawn. Of the 376 explained fetal deaths, 190 had an ANA assayed. The control group included 299 healthy third trimester gravidas. In the group of patients with unexplained fetal death, 11.5% (33/286) had a positive ANA, whereas 16% (31/190) of ANA tests were positive in cases of explained fetal death (P = 0.17). In the control group, 14% (43/299) had a positive ANA. There were three distinct immunofluorescence patterns: nucleolar, speckled, and homogeneous. The first two were seen more often in the control group, whereas the latter was seen more frequently in those patients with fetal death (P = 0.10). The incidence of a significant circulating ANA titer was similar in patients and controls. Moreover, there was no significant association between circulating antinuclear antibody titers and fetal outcome. More patients with a fetal death had a homogeneous nuclear fluorescence pattern when compared to controls; however, this finding was not statistically significant. Therefore, we do not recommend routine testing for ANA in women with unexplained second or third trimester fetal death.

Adolescent↗

Ballantyne syndrome: is placental ischemia the etiology?

Ballantyne syndrome is a condition in which the gravid patient essentially "mirrors" the in utero state of the hydropic fetus. The exact pathophysiological mechanism, however, is unclear. At 25 weeks gestation, a 28-year-old G3P2 presented with acute onset lower extremity edema, hyperuricemia, polyhydramnios, generalized pruritus, hemodilutional anemia, and pre-term labor. The human chorionic gonadotrophin (hCG) level was markedly elevated, at 570,020 mIU/ml. Postpartum, she developed a pre-eclampsia-like syndrome with oliguria and pulmonary effusions. Associated placental findings included a 8 x 7 x 7 cm chorangioma. Underlying placental ischemia, reflected by a hyperproliferative trophoblast, increased hCG secretion, and increased placental resistance may account for the maternal findings of Ballantyne syndrome.

Adult↗

Efficacy of azithromycin in reducing lower genital Ureaplasma urealyticum colonization in women at risk for preterm delivery.

OBJECTIVE: The purpose of this study was to determine if azithromycin is effective in reducing lower genital colonization of Ureaplasma urealyticum in women with preterm labor or preterm premature rupture of membranes (PROM). METHODS: A randomized, double-blinded, placebo-controlled prospective study of 60 pregnancies was carried out between 22 and 34 weeks. Genital mycoplasma cultures were performed at the time of admission. Patients were randomized to receive either a single dose of azithromycin (four 250 mg capsules) or a placebo in addition to prophylactic intravenous ampicillin. Repeat cultures were done on undelivered patients 7 days after enrollment. The study had power to detect a 50% decrease in colonization. RESULTS: Overall, lower genital colonization was 47/59 (79.7%) for U. urealyticum. Seven days after enrollment, U. urealyticum was isolated in 14/15 (93.3%) of the azithromycin-treated cases and in 11/14 (78.6%) of the controls (RR = 1.19, 95% CI = 0.88-1.61). Vertical transmission of U. urealyticum was 3/15 (20%) in the azithromycin-treated cases and 5/10 (50%) for the controls (RR = 0.40, 95%, CI = 0.12-1.31). CONCLUSION: These data suggests that a single 1 g dose of azithromycin is ineffective in reducing lower genital colonization with U. urealyticum.

Adult↗

Massive fetomaternal hemorrhage and fetal death: are they predictable?

OBJECTIVE: To report the incidence of massive fetomaternal hemorrhage (FMH) associated with fetal death and to test the hypothesis that FMH is more likely to occur in those with risk factors for FMH. STUDY DESIGN: All cases of fetal death of infants weighing > 500 gm between January 1, 1990 and December 31, 1994 were reviewed for evidence of massive FMH (> or = 2% fetal cells in the maternal circulation as measured by the Betke-Kleihauer test). Women with risk factors were compared with those without risk factors with respect to the occurrence of massive FMH. RESULTS: The prevalence of massive FMH was 14 of 319 (4.4%) cases, occurring in 4 of 102 (3.9%) of those with risk factors and 10 of 217 (4.6%) of patients without risk factors (p = 0.78). Otherwise unexplained fetal death was associated with massive FMH in 5 of 141 (3.5%). Major fetal anomalies were present in 5 of 14 (35.7%) cases of massive FMH. CONCLUSION: Clinical risk factors do not predict an increased likelihood of massive FMH. Massive FMH is associated with fetal anomalies. Betke-Kleihauer testing should be performed in all cases of fetal death, including those with anomalies regardless of the presence or absence of risk factors for FMH.

Adolescent↗

Pharmacokinetic and pharmacodynamic evaluation of atenolol during and after pregnancy.

STUDY OBJECTIVE: To evaluate changes due to pregnancy on atenolol's pharmacokinetics, response of maternal heart rate to atenolol, and the drug's effect on fetal heart rate. DESIGN: Prospective study. SETTING: Large university teaching hospital. PATIENTS: Fourteen pregnant women who were receiving oral atenolol for cardiac disease were enrolled and 10 completed the study. INTERVENTIONS: Patients were studied for 12 hours during the third trimester (TT) and again 6 weeks postpartum (PP). MEASUREMENTS AND MAIN RESULTS: Fetal heart rates, and maternal heart rates at rest and during exercise were recorded. Maternal plasma and urine atenolol concentrations were measured. Average resting heart rates (TT 68+/-10, PP 62+/-9 beats/min) and maximum heart rate during exercise (TT 100+/-6, PP 87+/-7 beats/min) were significantly higher in the third trimester than postpartum (p<0.05). The 12-hour atenolol area under the curve (TT 0.208+/-0.061, PP 0.215+/-0.089 ng/ml/day) and maximum plasma concentrations during the time of exercise tests (TT 1.07+/-0.39, PP 1.14+/-0.53 mmol/L) were not significantly different. Individual and population pharmacokinetics did not differ significantly between study periods. The fetal heart rate did not correlate with maternal atenolol concentration. CONCLUSION: Constant dosages of atenolol result in higher heart rates during pregnancy compared with the postpartum period. This lack of heart rate control is not due to significant changes in atenolol's pharmacokinetics or plasma concentrations.

Adrenergic beta-Antagonists↗