Normalization of pregnancy outcome in pregestational diabetes through functional insulin treatment and modular out-patient education adapted for pregnancy.

AIM: To investigate whether modular out-patient group education for flexible, Functional Insulin Treatment (FIT) adapted for pregnancy can eliminate diabetes-associated neonatal complications in pregestational diabetes. RESEARCH DESIGN AND METHODS: Outcome analysis of the modular out-patient group education and FIT based on separate insulin dosages for fasting, eating or correcting hyperglycaemia in 76 consecutive pregnancies (in 20 cases first after conception) of 59 patients with pregestational diabetes (Type 1 diabetes, n = 54). CONTROLS: (a) diabetic pregnancies: historical controls; (b) non-diabetic pregnancies: retrospective case-controlled study; (c) population-based data of all Austrian newborns registered within the respective time period. RESULTS: HbA1c of 113 +/- 18% of mean value (= 100%) of non-diabetic, non-pregnant population (103 +/- 14% during the last pregnancy trimester), and self-monitored blood glucose of 5.6 +/- 0.7 mmol/l (5.3 +/- 0.7 mmol/l during the last trimester) was achieved throughout all FIT pregnancies. Severe hypoglycaemia occurred in 14 pregnancies. The gestational age at delivery was 39.2 +/- 1.5 weeks (four cases (5.4%) < 37 weeks) with a birth weight of 3305 +/- 496 g. Four newborns (5.3%) were above the 90th, and nine (11.8%) below the 10th percentile for weight of reference population-based data. Hypoglycaemia was recorded in six newborns (8%). Malformations were found in two infants whose mothers booked for diabetes FIT education only after conception. The caesarean delivery rate was 25%. In comparison with historical diabetic pregnancy controls we demonstrated a reduction in major complications, and compared with non-diabetic women, a lowering of diabetes-related neonatal complication rates to general population levels. CONCLUSIONS: Structured, comprehensive, modular out-patient group education promoting self-choice of insulin dose for flexible, normal eating prior to conception normalizes pregnancy outcome in diabetes.

A case of myocardial infarction complicating pregnancy--a role for prostacyclin synthesis stimulating plasma factor and lipoprotein (a)?

Coronary heart disease and myocardial infarction (MI) is rarely seen in women below the age of 40 years and even more rarely during pregnancy. The first case of MI during pregnancy was described by Katz in 1992 (1). Current literature reviewed by Samara et al. 1989 (2) listed only 62 cases of proven MI during pregnancy or in the puerperium, the maternal mortality rate being as high as 24%. In this paper we are going to report on a 26-year old pregnant woman suffering from MI, probably as a result of a haemostatic imbalance caused by a lack of prostacyclin synthesis stimulating plasma factor (PF) and elevated lipoprotein (a) (Lp (a)). The potentially deleterious thromboembolic complications in patients with PF-deficiency, especially in combination with elevated Lp (a), should be carefully considered.

[Modular education in diabetes and pregnancy: analysis of results of 58 pregnancies in diabetic patients with functional insulin treatment]. / Modulare Schulung bei Diabetes und Schwangerschaft: Ergebnis-Analyse in 58 Schwangerschaften von Diabetikerinnen unter funktioneller Insulinbehandlung.

Functional insulin treatment based on the patient's education for selective use of insulin for fasting, eating or correction of hyperglycaemia was used between 1985 and 1994 prospectively in 58 pregnancies (in 18 cases after conception) in 47 pregnant diabetic patients. We hypothesised that near-normalisation of glycaemia is possible throughout pregnancy by modular outpatient group education, individual counselling and functional insulin treatment. We wanted to investigate to which degree it might eliminate classical diabetes-associated neonatal complications. To avoid hospitalisation if possible and premature induction of labour, patients were taught both the primary adjustment (immediate correction of hyperglycaemia) and the secondary adjustment of the insulin dosages: correction of individual algorithms for insulin use according to daily insulin consumption and mean blood glucose MBG. A target metabolic control (HbA1c levels in the normal range, MBG < 100 and < 90 mg/dl after the 28th week of gestation respectively) was achieved in the majority of the 58 pregnancies. Severe hypoglycaemia occurred in 12 patients (21%). The gestational age at delivery was 39.0 +/- 1.6 (34-41; in 3 cases only [5%] < 37) weeks with an average birth weight of 3335 +/- 521 (1950-4450) g. The birth weight of only 5 newborn (9%) was above the 90th percentile and no one below the 10th percentile for weight of a comparable population. No cases of respiratory distress were observed. Hypoglycaemia was recorded in only 4 newborn (7%) and was comparable also to that of offsprings in non-diabetic women. Malformations were found in two offsprings whose mothers had presented first for diabetes education after conception, pregnancy being terminated in one case of meningomyelocele. Caesarean section (n = 15; 26%) was primarily due to maternal reasons. Functional insulin treatment prior to conception, modular diabetes group education, specific patient motivation for a near-normal glycaemia throughout pregnancy as well as interdisciplinary care allow pregnancy outcome in diabetic patients similar to that in non-diabetic women and thus the realisation of the 5-year targets of the WHO Declaration of St. Vincent 1989.

Treatment with biologic response modifiers in patients with ovarian cancer.

The therapeutic and immunomodulating potential of biological response modifiers (BRM) such as OK-432 (a streptococcal preparation) and recombinant interferon gamma (rIFN-gamma) has been evaluated in 15 patients with advanced chemotherapy resistant ovarian cancer, presenting malignant ascites and/or pleural effusions. OK-432 was injected intracavitary in 10 patients in increasing doses from 0.2 up to 7.5 mg weekly. Five women were treated intracavitary with rIFN-gamma twice a week. The initial dose was 0.1 mg/m2 which was raised up to 12 mg/m2 over 6 weeks. With OK-432 a complete response was achieved for 14.1 + 8.9 months in 4 patients, a partial response for 1.7 + 0.3 months in 3 patients. The survival time of the 4 responders was significantly longer (21.1 + 8.3 months) than the survival time of the patients with partial or no response (4.9 + 2.7,4.1 + 2.3 months, respectively). In the rIFN-gamma therapy group, we found a partial response in one and no response in 4 patients. Toxicity observed under OK-432 and rIFN-gamma was minimal in all patients, suggesting a lack of systemic effect of intracavitary-applied BRM. With both agents, augmentation of certain immune responses, especially in the peritoneal cavity and to a lesser extent in the peripheral blood, has been documented. In 5 patients treated with OK-432, we found an overall augmentation of the effusion macrophage killer activity. rIFN-gamma augmented natural killer activity in 2 of 3 patients.

Use of CA 125 monoclonal antibody to monitor patients with ovarian cancer.

The monoclonal antibody (mAb) OC 125 reacts with an antigen on human ovarian carcinoma (OVCA) cells that is also shed into the body fluids and can be detected in patients' sera and/or ascites with a radioimmunometric assay. For the present study, serum CA 125 levels of patients (n = 36) with different stages of OVCA were investigated. Serum levels seem to correlate with tumor burden. In stages I and II (n = 12), 33% of patients were CA 125 positive, whereas 70% of stage III and IV patients (n = 24) were CA 125 positive. Mean serum levels were in 93 U/ml (stages I, II) and 279 U/ml (stages III, IV). CA 125 levels in ascites and in pleural effusions were manyfold higher than serum levels of the same patients (P less than 0.0001). Immunohistochemical investigations of CA 125 in different ovarian tumors (n = 91) revealed that 85% of malignant and 75% of borderline serous cystadenocarcinomas had detectable CA 125 surface expression. Furthermore, 71% of benign tumors showed the CA 125 epitope, whereas mucinous tumors were negative for this marker. One of six ovarian cancer cell lines was CA 125 positive, whereas in 6 of 11 patients, ascites-derived ovarian cancer cells (fresh and gradient isolated) were positive for this marker. The proportion of positive cells ranged from 10 to 90% in these samples. Intraperitoneal recombinant interferon-gamma (rIFN-gamma) therapy resulted in an increase in the number of cells reacting with CA 125. The results of monitoring in patients receiving different therapeutic regimens and/or agents demonstrate the usefulness of this marker.

[Assessment of edema in pregnancy]. / Die Bewertung von Odemen in der Schwangerschaft.

The clinical evaluation of oedemata during pregnancy is more or less subjective and not reproducible. There is no common factor to the relevance of its presence. The aim of this investigation was to check systematically the frequency and degree of generalised Oedemata and their clinical relevance. 184 pregnant women were examined for their finger circumference between the 16th and 36th week of gestation. According to the change in the circumference, three significantly different groups of oedemata were found. The group with strongly marked oedemata showed increased hypertensive complications and the highest rate of growth retarded children. This objective and simple method of measuring the finger circumference, is suggested for antenatal care.

MCA, a monoclonal-antibody-defined breast-tumor-associated antigen and its relation to CA 15.3.

A mucin-like carcinoma-associated antigen (MCA) was recently identified on the surface of established breast cancer cell lines by several monoclonal antibodies. The antibody b-12 was used in a sandwich enzyme immunoassay to measure MCA concentrations in serum samples and other biological fluids. The upper limit for noncancerous women and men was 14 U/ml. MCA levels were independent of estrogen or prolaction secretion, 63% of patients with metastatic breast cancer had elevated serum concentrations of MCA. Elevated MCA levels were also associated with cervical, ovarian or endometrial cancer and carcinoma of the prostate. In metastatic breast cancer, MCA and CA 15.3 showed similar sensitivity. Carcinoembryonic antigen levels did not correlate with MCA. Serum concentrations of MCA increased during pregnancy and remained elevated in nursing mothers. Amniotic fluid was found to be rich in MCA. In contrast, CA 15.3 showed only small changes during pregnancy and was low in amniotic fluid. From binding tests with antibodies used in the MCA and CA 15.3 assays, we conclude that the monoclonal antibodies b-12 as well as 115-D8 and DF3 (CA 15.3 assay) recognize coexisting epitopes on mucin-like antigens, which belong to a polymorphic family of glycoproteins suitable for tumor monitoring. Differences in the behavior of MCA and CA 15.3 may emerge from the complexity and heterogeneity of these mucin-like antigens.

[Proteinuria in normal pregnancy and in EPH gestosis]. / Proteinurie bei normaler Schwangerschaft und bei EPH-Gestose.

EPH-gestosis (pre-eclampsia-eclampsia) characterized by edema, proteinuria and hypertension occurs primarily in the nullipara, usually after the 20th gestational week. As in normal pregnancy there is striking change in both renal blood flow and glomerular filtration rate a slight increase in urinary protein secretion is not considered abnormal until it exceeds 300 mg/day. Abnormal proteinuria commonly accompanies pre-eclampsia and may be minimal, moderate or severe (even exceeding greater than 25 g/l). Proteinuria was typed mainly of nonselective glomerular origin by using the SDS-disc-electrophoresis. Additionally the clearance ratio of IgG to transferrin in all patients with abnormal proteinuria was evaluated. In none of the patients studied the ratio was less than 0.1 (highly selective). As severe proteinuria is associated with fetal growth retardation, preterm deliveries and prenatal mortality the quantitation and typing of early proteinuria is essential for considering patients who are at risk for developing EPH-gestosis.

[Characteristics of peripheral rheograms following thermal provocation in normal and pathologic pregnancy]. / Charakteristik der peripheren Rheogramme nach thermischer Provokation in der normalen und pathologischen Schwangerschaft.

Using the impedance plethysmographic method of rheography it is possible to ascertain the tone of the peripheral resistance vessels directly by simple means. Previous studies have shown that there is a close relationship between peripheral vasodilatation at rest and normal course of pregnancy. In the present study, rheographic changes were studied in patients with normal pregnancy (n = 27, Group 1), diabetes mellitus (n = 18, Group 2), "pregnancy-induced hypertension" (n = 10, Group 3), and chronic placental insufficiency (n = 16, Group 4) during and following a low-temperature stimulus. After exposure to icy water, the Group 1 subjects showed a 40% reduction in rheographic amplitude, Groups 2 and 3 a 25% reduction, while Group 4 patients showed no signs of vasoconstriction going beyond the resting state (p less than 0.001). The four groups also differed considerably as regards vessel wall behavior in the recovery phase. The study confirms that the amplitude of the peripheral rheogram is a good indicator for detecting high-risk pregnancies. The amplitude pattern under thermal stimulation also provides further information on the dynamic behavior of the resistance vessels in normal and pathologic pregnancies.

Successful outcome of a complicated pregnancy in a renal transplant recipient taking cyclosporine A.

The successful outcome of a pregnancy complicated by reversible renal failure secondary to total ureteral obstruction caused by a pregnant uterus and treated temporarily with nephrostomy is reported. The cyclosporine A (CsA) and prednisone treated female recipient of a cadaveric renal allograft gave birth to a male child, which at 2080 grams was small for gestational age (35 weeks of pregnancy). The child presented neither signs of congenital anomalies or chromosome aberrations nor nephrotoxicity, hepatotoxicity or anemia. Simultaneous measurement of trough CsA blood levels (CsA RIA, Sandoz) displayed reduced values in the child's blood (mother 864 ng/ml-4 hours after oral CsA intake; son 312 ng/ml). Beside postrenal failure the patient's pregnancy was complicated by 7 rejection episodes treated with high doses of methylprednisone (total dose 5 g) with reversible damage of the transplant function, two episodes of a urinary tract infection and increasing anemia necessitating blood transfusions. The HIV negative patient had developed a Kaposi's sarcoma 6 weeks after grafting. The progression of infiltrating skin lesions during pregnancy was not seen.