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Biomedical subjects

W L Wiser

Publications and source records attributed to W L Wiser.

At least 55 records · Page 3Linked to original sources

Human ovarian 17 beta-hydroxysteroid oxidoreductase activity: a comparison of normal and polycystic ovarian tissues.

Ovarian tissue and ovarian venous blood were obtained from women undergoing wedge resection, and ovarian tissue was obtained from normally menstruating women who had an oophorectomy for medical reasons. A morphological evaluation was made of the wedged tissue. 17 beta-Hydroxysteroid oxidoreductase levels were determined as the 17-ketoreductase (17-KR) and 17 beta-dehydrogenase activities in both normal and wedged tissue. Plasma androstenedione (A) and testosterone (T) levels were measured in the ovarian venous blood. Low, but measurable, 17 beta-hydroxysteroid oxidoreductase activity was found in the mitochondria, microsomes, and cytosol. With whole, cell-free homogenates, mean 17-KR activity was not significantly different in normal tissues and polycystic tissues; mean 17-KR activity of corpora lutea was significantly greater than that of the other tissues. Mean 17 beta-dehydrogenase activity was not significantly different from 17-KR activity in the tissues studied. Ovarian venous A levels were higher than the reported mean ovarian venous A levels of normal women with only one exception; approximately half of the ovarian venous T levels were higher than reported mean ovarian venous T levels of normal women. The morphology of the wedge sections did not correlate well with the biochemical data.

17-Hydroxysteroid Dehydrogenases↗

Fetal health assessment in pregnancies complicated by sickle hemoglobinopathies.

The contraction stress test (CST) and nonstress test (NST) are used as fetal health assessments. Severe sickle hemoglobinopathies in the parturient have been shown to place the fetus significantly at risk. This study correlates these fetal health assessment tests with outcome data in 58 pregnancies occurring in women with sickle cell disease. There were 30 patients with homozygous sickle cell anemia (HbS-S), 19 with hemoglobin S-C disease (HbS-C), and nine with hemoglobin S-thalassemia (HbS-Thal). All received prophylactic partial exchange transfusions as part of their antepartal care. At 34 weeks' gestation, NSTs followed by CSTs were begun in each patient. A total of 255 tests were performed. Of these, 19 NSTs and 24 CSTs were unsatisfactory or questionably abnormal and were repeated. There were no nonreactive NSTs, and no patient demonstrated a positive CST. The neonatal outcome revealed one infant who was small for gestational age and two infants who were of low birth weight but appropriate for gestational age. All infants survived and were normal. These data suggest that the fetal reactivity and placental reserve among these parturients with severe sickle hemoglobinopathies were uncompromised, as these tests have been shown to be relatively sensitive assessments of fetal well-being in other maternal disorders.

Anemia, Sickle Cell↗

The lecithin/sphingomyelin ratio in cases associated with fetomaternal disease.

The efficacy of correlating the L/S ratio in the amniotic fluid with fetal lung maturity has been substantiated in normal pregnancies. In gestations complicated by fetomaternal diseases, however, the assay is less reliable. This study involves 555 pregnancies in which there was a significant maternal, fetal, or placental disorder. The L/S ratio was related to fetal respiratory maturity as measured by Dubowitz criteria and the occurrence of RDS. The results show that pre-eclampsia, chronic hypertension, diabetes (Class D, E, F), significant cardiovascular disease, severe hemoglobinopathies, various congenital anomalies, chronic placental insufficiency, and prolonged ruptured membranes accelerated the L/S ration. Conversely, mild diabetes (Class B, C), intrinsic renal disease, hepatitis, collagen disease, hydrops fetalis, syphilis, and toxoplasmosis were associated with a delay in the L/S ratio. A significant increase in erroneous responses was noted in these patients when the L/S ratio was correlated to infant maturity and to the incidence of RDS. Possible mechanisms for these findings are discussed.

Amniotic Fluid↗

Amniotic fluid tests for fetal maturity in normal and abnormal pregnancies.

The lecithin-sphingomyelin (L/S) ratio is acknowledged to be superior to most procedures for predictinf fetal lung maturity in normal pregnancy. In complicated gestations, however, errors have been reported. This study involves 686 normal gestations and 389 pregnancies complicated by fetomaternal diseases. The L/S ratio, creatinine level, and percent of fat-staining cells were measured in samples of amniotic fluid from these patients. The results showed good correlation of all three tests with fetal maturity as measured by weight, Dubowitz criteria, and incidence of respiratory distress syndrome in the normal patients. In the complicated pregnancies, however, the creatinine was unacceptable in up to 30% of the cases. The L/S ratio likewise decreased in accuracy for all parameters of fetal maturity measured. The Nile blue staining of the fetal cells appeared to be the most consistent technic in these cases. A fetal maturity battery comprised of these three assays and other methods of assessing fetal health is advocated in pregnancies complicated by certain disease states.

Amniocentesis↗

Nile blue and fetal maturity. Further investigations.

The consistency of results using Nile blue staining of fetal cells in amniotic fluid to estimate fetal maturity has been demonstrated. Recently, evidence to support this method has been published from this laboratory. Several biochemical and technical factors were cited as important to the success of the method. This report deals with further testing of several Nile blue dyes (hydrochloride and sulfate) necessitated by changes in production and federal regulation of this compound. The results show Nile blue hydrochloride (HCl) to be the most superior dye regardless of color index. Buffered solutions (6.6) of Nile blue A (sulfate) improve its performance, but not to levels demonstrated by the HCl preparation. Storage at room temperature adversely affects each dye; however, the sulfate variety appears to be the most unreliable under these circumstances. For best results, it is recommended that Nile blue HCl be used and the solution (buffered or normal) be kept refrigerated.

Amniotic Fluid↗

Metabolites of meperidine in the fetal and maternal serum.

Although meperidine appears to be the safest obstetric analgesic agent, it has been associated with infant respiratory depression in certain situations. It would appear that the incidence of fetal depression related to meperidine is dependent on the time of injection prior to delivery, the quantity of drug administered, and the rate of maternal metabolism of the analgesic. Previous work showed that meperidine is metabolized in the maternal system by one of three patterns. The present study demonstrates that the particular maternal serum pattern is characteristic for the individual, regardless of whether the patient is pregnant or not, and that the fetal depression, although usually mild, can be correlated with fetal pH data as well as Apgar scores. In addition, this study supports indirectly the contention that metabolites of meperidine rather than the parent compound cause fetal depression. It would appear, therefore, that in certain obstetric cases with a higher probability for infant depression, other analgesic agents might be considered, especially if the serum pattern indicates meperidine is being metabolized.

Apgar Score↗

Fluctuation of fetal hemoglobin in sickle-cell anemia.

A reduction of morbidity and mortality rates in homozygous sickle-cell patients was found in those with high fetal hemoglobin (HbF) levels. This factor would lead one to believe that an adequate amount of this substance would be protective to a patient with this hemoglobinopathy. This study utilizing pregnant and nongravid females, as well as males, followed for long periods of time indicates that the HbF level fluctuates with crisis. Some patients had low HbF levels with many crises and others had high amounts of HbF with no crises. However, many patients with high levels on one occasion demonstrated a decrease in HbF levels when crisis occurred. More importantly, no patient had high levels of HbF during a crisis although the amount was elevated before and after the episodes. The possible explanation and ramifications of this finding are discussed.

Anemia, Sickle Cell↗

Response of the binding capacity of plasma testosterone-estradiol-binding globulin to norethindrone, 2 mg., and mestranol, 0.1 mg., in polycystic ovarian disease.

The binding capacity of plasma testosterone-estradiol-binding globulin (TeBG) and testosterone (T) levels were measured in four women with proved polycystic ovaries and three women with a clinical diagnosis of polycystic ovarian disease before, during, and after administration of norethindrone, 2 mg., and mestranol, 0.1 mg. (N + M)...

Carrier Proteins↗

The effectiveness of two oral contraceptives in suppressing plasma androstenedione, testosterone, LH, and FSH, and in stimulating plasma testosterone-binding capacity in hirsute women.

The effectiveness of two oral contraceptives in suppressing plasma androstenedione (A), testosterone (T), LH, and FSH and in stimulating testosterone-estradiol-binding globulin (TeBG) was evaluated in 39 hirsute women. Twenty-seven hirsute women received norethindrone 2 mg.-mestranol 0.1 mg. (Group I) and 12 received norgestrel 0.5 mg.-ethinyl estradiol 0.05 mg. (Group II). Hormone assays were performed before treatment and at the end of 3 weeks of therapy. Ninety percent of the women in both groups had an elevated plasma A and/or T. During treatment, plasma A,T, LH, and FSH were significantly reduced in both groups (p less than 0.01). In Group I, 78% of the women had a normal plasma A and T during treatment. In Group II, 83% of the women had a normal A and T during treatment. There was a greater increase in TeBG in Group I (p less than 0.01). It is concluded that these two oral contraceptives effectively suppressed the hyperandrogenism of most of the hirsute women.

Adolescent↗

The effect of maternal partial exchange transfusion on the infants of patients with sickle cell anemia.

The reproductive outcome of pregnancies complicated by severe sickle cell hemoglobinopathies is not usually satisfactory. In this study, prophylactic partial exchange transfusions have been used in 35 patients with sickle hemoglobinopathies. There was significant improvement in results, both maternal and neonatal, as compared to those in 29 pregnancies complicated by similar disease processes who did not receive this therapy. The former group was also compared to 61 normal pregnant patients and 31 patients with sickle cell trait, none of whom received blood as part of their therapy. The results were similar in the group receiving transfusions and in the group with sickle cell trait. There was a decrease in perinatal wastage, prematurity, and incidence of low-birth-weight infants in the transfusion group when compared to the patients with hemoglobinopathies who were treated conservatively.

Anemia, Sickle Cell↗

Clinical findings and hormonal responses in patients with polycystic ovarian disease with normal versus elevated LH levels.

The clinical features, ovarian pathology, and hormonal responses to dexamethasone (Dex), Dex + ethinyl estradiol (EE), and Dex + hCG were compared in 5 women with polycystic ovarian disease (PCOD) who have normal 24-hr urinary luteinizing hormone (LH levels to 5 who had elevated urinary LH levels. No differences were noted in the clinical features. There was no correlation between ovary size and LH levels. Three in the normal-LH group had hyperthecosis. Plasma androstenedione (A) was more frequently elevated in the high-LH group. Dex + EE markedly increased LH secretion in the high-LH group, suggesting increased responsiveness of the positive feedback control mechanism of LH secretion in the high-LH group. There was a greater response of A, testosterone (T), and 17-ketosteroids to Dex + hCG in the normal-LH group. Those with high-LH levels did not exhibit a significant increase in A, T, and 17-KS with hCG. The limitations and usefulness of the Dex + hCG test are discussed. The hypothesis is advanced that the increased LH secretion in the high-LH group is due at least in part to positive feedback resulting from the increased A levels. The amount of 17beta-oxidoreductase activity in the ovary may influence LH secretion in PCOD.

17-Ketosteroids↗

The use of prophylactic partial exchange tranfusion in pregnancies associated with sickle cell hemoglobinopathies.

Sickle cell anemia is associated with an alarming attrition rate during pregnancy. The maternal morbidity rate, perinatal wastage rate, and the incidence of severe morbidity in both mother and child are elevated above acceptable limits. In most cases, these statistics have been compiled using conservative therapeutic modalities. In contrast, this report utilizes prophylactic partial exchange transfusion therapy in patients with severe sickle cell hemoglobinopathies. The protocol involves the introduction of 750-1000 cc of buffy coat, poor washed red cells exchanged with 1000-1500 cc whole blood during phlebotomy at 28 weeks' gestation and again prior to term. Thirty-six consecutive pregnant patients with sickle cell anemia have been managed in this fashion. The one maternal mortality occurred in a patient who did not complete the protocol. Major maternal morbidity and perinatal wastage rates were significantly decreased. Two cases of serum hepatitis occurred. It appears from these data that the use of prophylactic partial exchange transfusion in pregnant patients with severe sickle cell hemoglobinopathies can be of benefit. Further trials of this method seem justified by these results to assess completely the benefit-risk ratio of this procedure.

Anemia, Sickle Cell↗

Features of Turner's syndrome in women with polycystic ovaries.

Four women with phenotypic features of Turner's syndrome and with poly cystic ovaries (PCO) are describe. In addition to the phenotypic features, Case 1 had primary amenorrhea and small PCO, Case 2 had a 46, XX/45, X karyotype (lumphocytes), Case 3 had enlarged PCO which contained a decreased number of oocytes, and Case 4 had enlarged PCO and was short in statute. These cases support the concept of a relation between PCO and the X chromosome. Some PCO may represent an intermediate condition in a spectrum that extends from the streak gonad of Turners syndrome to the normal ovary. Evidience for X chromosome involvement in PCO is summarized. The concept is advanced that at least some cases of OCO may be due to X chromosomal factors causing an abnormal follicular appartus.

Adolescent↗

Adrenal function in hirsutism I. Diurnal change and response of plasma androstenedione, testosterone, 17-hydroxyprogesterone, cortisol, LH and FSH to dexamethasone and 1/2 unit of ACTH.

ACTH dependency of plasma androstenedione (A) and testosterone (T) was determined in normal and hirsute women by measuring the magnitude of change of A and T between the time of the cortisol (F) peak and F nadir in a diurnal study. There was a significant diurnal rhythm of A synchronous with F in both normal and hirsute women (P less than 0.01). Five of 12 hirsute women had a greater than normal diurnal swing of A (P less than 0.05), but only 2 of the 12 had a greater than normal diurnal swing of T. Responsiveness of A and T to 1/2 unit of intravenous ACTH was determined after dexamethasone 1 mg was given the night before. Plasma A and T were elevated in most of the hirsute women during acute ACTH suppression by dexamethasone, indicating ACTH-independent hypersecretion of androgens. Nine of 17 hirsute women had a greater than normal A response to ACTH (P less than 0.05). Those who had an exaggerated diurnal swing of A also had hyper-responsiveness of A secretion to ACTH. Only 2 hirsute women had an exaggerated T response to ACTH. Some T levels were decreased by ACTH. Seven of the 9 hiruste women who had an exaggerated A response to ACTH had a normal maximum F response, but a greater than normal 17-hydroxy-progesterone (17-OHP) response to ACTH with a high 17-OHP to F ratio, suggesting they have a mild but compensated reduction in 21-hydroxylase or 11beta-hydroxylase activity. Two women with hyper-responsiveness of A secretion had low F and 17-OHP responses to ACTH suggesting reduced C21 but intact C19 3beta-hydroxysteroid dehydrogenase-delta-5,-4 isomerase activity. These apparent reduced enzyme activity may not be congenital, but induced by an altered hormonal milieu such as an abnormal androgen-estrogen ratio. It is concluded that ACTH uniformly stimulated A secretion but not T secretion and that approximately 50% of the hirsute women had ACTH-dependent hypersecretion of A, but most of these also had concurrent ACTH-independent hypersecretion of androgens.

Adrenal Glands↗

A testosterone-secreting, gonadotropin-responsive pure thecoma and polycystic ovarian disease.

UNLABELLED: A 31-yr-old hirsute female with oligoamenorrhea since menarche had markedly elevated peripheral plasma testosterone (T) concentrations of 250-255 ng/100 ml (normal 20-60 ng/100 ml), which lacked a diurnal rhythm, were not suppressed by dexamethasone, were decreased by ACTH, and were massively increased to 2,530 ng/100 ml by human chorionic gonadotropin (hCG). The binding capacity of T-binding globulin (TeBG) was 0.2 mug/100 ml (normal = 1.1-3.3 mug/100 ml). Plasma delta 4-androstenedione (A) was elevated at 374-681 ng/100 ml (normal = 90-135 ng/100 ml). Plasma estrone (E1) and estradiol (E2) were normal. The endometrium was proliferative. A T-secreting tumor was suspected because the plasma T levels were higher than those observed in polycystic ovarian disease. Exploratory surgery revealed bilateral polycystic ovaries and a pure thecoma in the right ovary which was not visible on surface examination. The thecoma did not contain granulosa cells. Plasma T in the right ovarian vein, draining the tumor, was 28,200 ng/100 ml and in the left ovarian vein was 2,600 ng/100 ml. Plasma A was elevated in both ovarian veins: 11,170 ng/100 ml on the left and 8,360 ng/100 ml on the right. The thecoma contained 1.35 mug/g of T and only 0.014 mug/g and 0.007 mug/g of E2 and E1, respectively. Plasma A and T after bilateral oophorectomy and removal of the thecoma were normal at 184 ng/100 ml and 40 ng/100 ml, respectively. CONCLUSIONS: 1) This pure thecoma produced primarily T rather than E1 OR E2 and was gonadotropin-responsive. 2) A very high plasma androgen level in a female is an important clue to the presence of a tumor. A T-secreting tumor should be ssupected when the peripheral plasma T is over 250 ng/100 ml and when plasma T increases to over 1,000 ng/100 ml following hCG stimulation. 3) Tumors cannot be classified as estrogenic or androgenic on the basis of the character of the endometrium.

Adult↗