H. M. H. Hofmann

Cervical pregnancy: case reports and current concepts in diagnosis and treatment.

SummaryCervical pregnancy produces profuse but painless vaginal bleeding. After ultrasound diagnosis early in pregnancy, preservation of the uterus is possible. After the 12th week, hysterectomy is almost always necessary. We review current concepts in the diagnosis and management of cervical pregnancy.

Fetal outcome in gestational diabetes with elevated amniotic fluid insulin levels: Dietary versus insulin treatment

Of 228 women with gestational diabetes between 28 and 32 gestational weeks, 195 had a normal amniotic fluid insulin level (4.8 +/- 3.6 microU/ml) while 33 (14.5%) had an elevated level (23.1 +/- 10 microU/ml). Women with a normal amniotic fluid insulin level were treated by diet alone. Fourteen of the women with an elevated level were treated by diet alone; 19 received insulin treatment additionally. The fetal outcome of patients with a normal amniotic fluid insulin level and dietary therapy and of those with an elevated level and insulin treatment was similar to that of metabolically healthy women. The newborns of gestational diabetics with elevated amniotic fluid insulin treated by diet alone showed a significantly higher incidence of neonatal hyperinsulinism, hypoglycemia, hyperbilirubinemia, high birth weight, respiratory distress syndrome and hypocalcemia. While 2/14 (14%) of the neonates in the dietary group had fatal respiratory distress syndrome, there were no deaths in the group with elevated amniotic fluid insulin and insulin treatment. The data demonstrate that in gestational diabetics with normal amniotic fluid insulin (low-risk group), dietary therapy is sufficient while insulin therapy is required to ensure healthy offspring in patients with elevated amniotic insulin (high-risk group).

Diagnosis and Treatment of Gestational Diabetes According to Amniotic Fluid Insulin Levels

SummaryIn spite of dietary treatment, the infants of pregnant patients with abnormal glucose tolerance have hyperinsulinism and diabetogenic fetopathy in 10 to 36% of cases. Those patients, who require insulin to prevent from fetopathy cannot be reliably selected by maternal parameters such as blood glucose and glycosylated hemoglobin values. We recommend the measurement of amniotic fluid insulin between the 28 and 32 weeks of pregnancy to differentiate whether the fetus is compromised or not. Subjects with values above the 97th centile require insulin therapy. Inadequate insulin dosage or delayed fetal hyperinsulinism can be discovered by checking the amniotic fluid insulin level at 33 to 36 weeks. In a total of 88 gestational diabetic patients 19 had raised amniotic fluid insulin levels indicating the onset of diabetic fetopathy at an early stage. Diabetic patients with raised amniotic fluid insulin levels needed large doses of insulin, namely 64.6 ± 29.5 (Mean ± SD) U/24 h. This treatment reduced mean blood glucose levels from 98 ± 9 (Mean ± SD) mg/dl to 82 ± 10 mg/dl and was sufficient to prevent from diabetic fetopathy.

Serum fructosamine and amniotic fluid insulin levels inpatients with gestational diabetes and healthy control subjects

Summary Gestational diabetic pregnancies with fetal hyperinsulinism should be identified because these casesrequire insulin therapy. To determine the relationship between the serum fructosamine and amniotic fluid insulin concentrations, these substances were measured in 87 pregnant women with impaired glucose tolerance. Fructosamine was also measured in 678 healthy pregnant control subjects, in 113 of whom amniotic fluid insulin levels were available. Fetal hyperinsulinism was rare at serum fructosamine levels of

Interactions between insulin and insulin-like growth factor I in the pathogenesis of polycystic ovarian disease.

Concentrations of growth factors were examined in 28 patients with clinical and endocrinologic signs of polycystic ovarian disease (PCOD). Elevated levels of total insulin-like growth factor I (IGF-I) and decreased levels of the human growth hormone (HGH) were found. Studies of carbohydrate metabolism and of insulin receptors on erythrocytes indicated insulin resistance in all PCOD patients. Elevated insulin and IGF-I levels seem to play a pathogenetic role in PCOD by influencing the development and steroid production of ovarian follicles. Interactions between insulin and IGF-I could be shown at different levels. A positive correlation between elevated insulin and IGF-I concentrations was demonstrated in patients with different classes of gestational diabetes. Hyperinsulinemia seems to be the trigger mechanism and therefore the key to the pathogenetic loop of polycystic ovarian disease.

Fructosamine in relation to maternofetal glucose and insulin homeostasis in gestational diabetes

SummaryThe problem in screening for gestational diabetes is recognizing fetuses endangered by hyperinsulinism. 21.8% of patients with gestational diabetes (defined as a glucose peak exceeding 160 mg/dl after an oral glucose load of 1 g per kg body weight) develop fetal hyperinsulinism. Thus, is indicated by an elevated amniotic fluid insulin (AFI) concentration and requires insulin treatment. Since fetal hyperinsulinism can be neither predicted nor ruled out by single parameters of materal metabolism, every patient with gestational diabetes had to undergo amniocentesis for amniotic fluid analysis. In 110 gestational diabetics and 822 controls, fetal hyperinsulinism was predicted by the combination of the oGTT (≥160 mg/dl) and maternal serum fructosamine (≥2.6 mmol/l) with a sensitivity of 95.8% and a specificity of 91.8%. Thus, 73% of gestational diabetics need not undergo amniocentesis. With a sensitivity of 20.8%, the combination of the oGTT and HbA1c is not useful in identifying hyperinsulinemic fetuses.

Insulin Treatment of Gestational Diabetes. The Basal Bolus Concept

Gestational diabetes mellitus is caused primarily by peripheral insulin resistance and by a relative lack of the hormone. The gestational diabetic’s insulin production can cover her basal insulin requirement — as evident in the often normal fasting blood glucose level-but insulin secretion after carbohydrate intake (bolus production) is delayed and decreased. The resulting pulsatile hyperglycemia causes an oversupply of glucose to the fetus, which eventually reacts to even slight glucose elevations by overproducing insulin. As a result of the maternofetal concentration gradient, even more glucose is metabolized by the fetus. Because of this syphoning (the extent of which is not known), the fetal glucose turnover can no longer be estimated by the maternal blood glucose level. Hyperstimulation of the fetal pancreas, fetal hyperinsulinism, and biochemical fetopathy (see p. 18 f.) can occur even at seemingly normal maternal blood glucose values.

Maternal serum fructosamine and maternofetal glucose and insulin homeostasis in normal pregnancy

SummaryWell-defined normal values are necessary to identify pregnancies complicated by gestational diabetes (GD) and thus further reduce perinatal morbidity and mortality from this condition. The present study defined the range for the oral glucose tolerance test (oGTT) in 2578 pregnancies. After exclusion of abnormal results 822 randomized patients were used to define normal values for fructosamine, HbA1c, insulin, glucose and C-peptide in the maternal serum; insulin, glucose and fructosamine in the amniotic fluid; and insulin, glucose, C-peptide and fructosamine in the cord blood.

In vitro chemosensitivity testing in the treatment of ovarian carcinoma.

SummaryIn vitro chemosensitivity to cisplatinum, adriamycin, cyclophosphamide, and 5-fluorouracil was investigated in 58 cases of ovarian carcinoma using Volms short-term test. These in vitro results were retrospectively correlated with the relapse-free interval. Operative treatment in all patients (FIGO stage I (5), III (43), IV (10)) comprised maximum debulking procedure including hysterectomy, adnexectomy, omentectomy, pelvic and in most cases additionally paraaortic lymphadenectomy. Subsequently, all patients were treated with the cisplatinum-epirubicin-cyclophosphamide regimen. 33/58 tumors (66%) were sensitive in vitro (inhibition of nucleic acid precursor incorporation of more than 45% as compared to untreated controls). The median relapse-free interval of patients with sensitive tumors was significantly longer than that of those with resistant carcinomas (30.3 versus 22.6 months, respectively;P<0.05). Histopathological evaluation showed the majority of serous cystadenocarcinomas to be sensitive (26/33=79%,P<0.05).

Insulin receptor binding to erythrocytes in the first half of pregnancy is increased in healthy pregnant women as compared with non-pregnant or gestational diabetic women

Insulin binding to erythrocytes was measured longitudinally by a competitive radioreceptor assay in 21 healthy pregnant (HP) and 20 well-controlled gestational diabetic women (GD) in 4-week intervals throughout pregnancy and at day 4 post-partum. Maximum insulin binding (maxbdg) at weeks 8-14 was increased (P < 0.001) in HP (median: 6.0%) but not in GD (median: 2.7%) as compared with non-pregnant control subjects (C) (median: 3.6%; previously reported: Clin. Chim. Acta 1992;207:57-71) due to an increased number of high-affinity insulin receptors. Throughout gestation the binding decreased continuously, to reach at term the levels found in C. In GD maxbdg remained close to the level of C throughout pregnancy. Binding differences between HP and GD were independent of the body mass index. Maxbdg did not differ between diet- and insulin-treated patients. It was higher in women whose offspring had low umbilical cord insulin levels (< 10 mu units/ml). The findings suggest that (a) higher insulin binding in HP could contribute to the improved glucose tolerance in early pregnancy and (b) the lack of increase in insulin binding during early pregnancy in gestational diabetes might be one factor leading to the manifestation of the disease in late pregnancy. However, it must be kept in mind that insulin receptors on erythrocytes do not necessarily resemble those on the major target tissues of insulin.