bluuebunny/crossref_metadata_2025 huggingface dataset:
CONCEPTS AND METHODS IN IMMUNOLOGY APPLICABLE TO THE CONTROL OF HUMAN FERTILITY
Authors: Celada Franco
Published: October 2009

The reproductive event has been operationally subdivided into three periods, respectively including gametogenesis, fertilization and pregnancy: the feasibility of manipulating each period is discussed.

A note of caution arises from our present incomplete understanding of the nature of the materno-foetal immunological relationship, and from the danger of producing irreversible effects or of leading to autoimmunity.
II. MANIFESTATION OF THE ANTI-ANDROGENIC ACTION OF A STEROID ESTER TSAA-330 (16β-ETHYL-17β-HYDROXY-4-OESTREN-3-ONE CAPROATE) AND ELUCIDATION OF ITS LONG-LASTING MECHANISM USING A SIMPLE STEROID DETERMINATION TECHNIQUE
Authors: Masuoka Michio , Shikata Mutsushi , Fuziwara Reiko , Nakayama Ryo
Published: October 2009

Using a simple steroid determination technique, in situ steroid absorption from a subcutaneously injected sesame oil solution in rats was pursued following the time-course changes in the steroid concentration. Based on the knowledge thus obtained, the antiandrogenic effect of a steroidal compound, TSAA-330*, could be manifested in the subcutaneous route.

(1) Anti-androgenic steroid TSAA-291* and its esters in the subcutaneously injected sesame oil solution were selectively absorbed into the general circulation at different rates according to their chemical nature and structures, while the oil itself remained at the injected site for a considerably long period. At the injected site where subcutaneous doses of steroids molar equivalent to 50 mg of TSAA-291 were administered in 5 ml/rat of sesame oil, TSAA-291 decreased to the level of 10% of the initial concentration on the 4th day. TSAA-328* decreased slowly to the 50% and 20% levels on the 7th and 21st day, respectively. TSAA-335* decreased more slowly to the 50% level on the 14th day. TSAA-330 decreased most slowly only to the 70% level on the 49th day.

(2) A single subcutaneous administration of 200 mg of TSAA-330 suppressed the weight increase of the accessory sex organs caused by a single subcutaneous injection of testosterone caproate (10 mg) in the immature orchiectomized rat. The suppressive effect was obvious from 2 weeks after the administration, and seemed to last for more than two weeks. The levator ani weight was not affected by the administration of TSAA-330. (3) Dose-dependent inhibitions of the accessory sex organs were obtained three weeks after a single subcutaneous administration of 50 to 400 mg of TSAA-330 in the adult male rat. (4) Daily oral administrations of 50 mg of TSAA-291 or TSAA-330 to the adult male rat for 8 days resulted in depression of the accessory sex organs to almost the same extent obtained with either agent. One week after the last administration, however, the weight of the accessory sex organs of the TSAA-291-administered animals recovered to almost the comparable level with the control, whereas a significant after-effect of the inhibition was still evident in the TSAA-330-administered animals.
IV. EFFECTS OF THE ANTI-ANDROGEN TSAA-291 (16β-ETHYL-17β-HYDROXY-4-OESTREN-3-ONE) ON THE SECRETION OF GONADOTROPHINS
Authors: Sudo Katsuichiro , Yamazaki Iwao , Masuoka Michio , Nakayama Ryo
Published: October 2009

Effects of the anti-androgen TSAA-291 on the gonadotrophin secretion were studied.

(1) A single subcutaneous or oral administration of TSAA-291 and its caproate induced the ovulation in the proestrous rat of which the spontaneous ovulation was blocked by the treatment with chlorpromazine. (2) A single subcutaneous administration of TSAA-291 at 2.4 mg/kg to the adult male rat induced only a slight elevation in the serum LH and FSH levels at 30 min after the administration. Successive intramuscular administrations of TSAA-291 to the adult male rat for 2 or 4 weeks resulted in significant decreases in the serum LH and FSH levels at high dose levels. A dose-dependent decrease in the serum LH level but not FSH level was observed in the orchiectomized rat. (3) Successive intramuscular adminstrations of TSAA-291 at high dose levels to the male rat suppressed the plasma testosterone level in the testicular venous blood and general circulation.
The diagnosis of diabetes mellitus
Authors: Scherstén Bengt , Bitzén Per-Olof
Published: October 2009

ABSTRACT. The procedure for diagnosing diabetes mellitus when accompanied by classical symptoms is based on random blood glucose levels of 7 mmol/l or more. Problem of diagnosing diabetes in the asymptomatic subject remains difficult. A procedure based on fasting blood glucose levels below 5.5 mmol/l in normals and reproducible values at or above 7 mmol/l in diabetics is proposed. In cases with fasting blood glucose values between 5.5 and 7 mmol/l standardized oral glucose tolerance test is recommended. The diagnostic criteria for normality, impaired glucose tolerance and for diabetes are evaluated against the results of a 10–14 years prospective study.
Prevalence and incidence of diabetes in Norway
Authors: Midthjell Kristian
Published: October 2009

ABSTRACT. There are limited data on the prevalence of Type 2 diabetes in Norway, since most studies conducted have not tried to separate between Type 1 and Type 2 diabetes. The prevalence of known diabetes in patients over 14 years was reported as 0.7 % in 1956. The present prevalence of known diabetes probably is about twice this percentage. This will be estimated in a planned study.

The treatment behaviour of Norwegian physicians has been analysed in a preliminary study. Based on this, 90 % of the patients at hospital outpatients clinics used insulin compared with only 16 % in general practice. The criteria applied for definition of diabetes varied considerably among the physicians, only 50 % of them using the WHO criteria. Age related prevalence data will be determined in a future screening project.

Key words: prevalence, incidence, Type 1 diabetes, Type 2 diabetes, treatment, Norway.
Natural history of non-insulin dependent diabetes mellitus
Authors: Beck-Nielsen Henning , Sørensen N. Schwartz
Published: October 2009

ABSTRACT. The prevalence of NIDDM is about 1.5 %. Allready at birth the subjects developing NIDDM seem to be genetically primed. Environmental factors are able to precipitate the disease. Most subjects seem to run through a phase of IGT, before developing frank diabetes. The glucose homeostasis deteriorates with time resulting in complications, especially in the form of macrovascular diseases. The mortality from CHD is for NIDDM doubled compared with non-diabetics.

Diet treatment is of great importance for NIDDs but is not sufficient in all diabetics. Therefore, antidiabetic drugs, or in severe cases (secondary failures) insulin may be necessary. Insulin treatment seems to be preferable in diabetics not obtaining a near normal glucose homeostasis during diet and/or oral antidiabetic treatment as the mortality rate seems to increase in subjects with a poor glucose homeostasis.
Prevalence and incidence of type 2 diabetes in Finland
Authors: Reunanen Antti
Published: October 2009

ABSTRACT. The prevalence and incidence of type 2 diabetes in Finland was evaluated on the basis of three large population surveys and the national register of diabetics receiving drug therapy. The prevalence of type 2 diabetes was 16 per 1000 in persons aged 30 years and over in a survey conducted in 1966–72,29 per 1000 in a survey conducted in 1976 and 32 in a survey from the years 1979–80. The secular increase in the prevalence rates seemed to be particularly evident in diabetics treated by diet only. According to the drug-recipient register the prevalence of type 2 diabetes is higher in eastern and northern parts of the country. The mean annual incidence of type 2 diabetes estimated on the basis of data from drugrecipient register and the latest of the three population surveys was in Finland in 1970s about 4 per 1000 in pesons aged 30 and over.

Key words: Diabetes mellitus, epidemiology
How to screen for diabetes mellitus
Authors: Bitzén Per-Olof , Melander Arne , Scherstén Bengt
Published: October 2009

ABSTRACT. In an attempt to compare and evaluate different screening methods for diabetes mellitus in primary health care, urine and blood samples from 1082 consequtive patients were collected without any relation to meal or time of day. Urine glucose was determined by strip tests and quantitatively by the hexokinase method. Venous blood glucose was analysed by the hexokinase method and semiquantitatively by Dextrostix-Eyetone reflectance meter. 89 patients fulfilling the criteria for a positive screen were subjected to further diagnostic examination.

38 patients were classified as diabetics and 13 as having impaired glucose tolerance. In a control group randomly selected from negatively screened patients, all 30 patients had a normal glucose tolerance.

It was found that random blood glucose measurement using 7.0 mmol/l as screening level had significantly higher sensitivity than all other screening methods with comparable specificity.

Key words: Screening, diabetes mellitus, primary health care, methods, validity.
Insulin resistance in obesity, type II diabetes and stress
Authors: Smith Ulf
Published: October 2009

ABSTRACT. Insulin resistance plays a major role for the reduced glucose tolerance in obesity, type II diabetes and stress. Both in vivo and in vitro studies strongly support the major importance of post-receptor perturbations as the cause of the insulin resistance in these conditions. One likely level for the post-receptor alterations is the reported reduction in glucose transport.

Key words: Insulin resistance, diabetes, obesity, insulin receptors, glucose transport.
Chlorpropamide-alcohol flushing and diabetes
Authors: Lyngsøe J.
Published: October 2009

SUMMARY. Chlorpropamide alcohol flushing (CPAF) has been suggested as a genetic marker for a type of non-insulin dependent diabetes mellitus characterized by a strong genetic disposition and a low frequency of retinopathy. This theory has not been supported by later investigations.

Studies indicate that the most likely primary event in the CPAF phenomenon is an increased blood acetaldehyde level as a consequence of decreased acetaldehyde degradation. Probably the decreased elimination of acetaldehyde is elicited through an inhibitory effect of chlorpropamide on acetaldehyde dehydrogenase, the effect being most pronounced in subjects who have a genetically determined low activity of this enzyme.

Key words: Diabetes, chlorpropamide, ethanol, acetaldehyde.
Macroangiopathy in type II diabetes
Authors: Aro Antti
Published: October 2009

ABSTRACT. Macroangiopathy is the most important cause of mortality and morbidity in type II diabetes. The atherosclerotic process in diabetes is similar to that found in non-diabetic subjects, but the laesions are more extensive and the clinical manifestations are more common in diabetic subjects than in the non-diabetic population. In diabetic patients from different populations, the prevalence of macroangiopathy is variable, and the relative frequency follows the pattern found in the respective non-diabetic populations. The relative risk of large vessel disease is in most populations higher for female than for male diabetics. Coronary heart disease is the most important manifestation of macroangiopathy while cerebrovascular disease and peripheral vascular disease are less frequent, although all these manifestations occur at increased frequency among middle-aged diabetic subjects. The incidence of peripheral vascular disease seems to increase with increasing duration of diabetes in middle-aged subjects, whereas coronary heart disease is particularly frequent in type II diabetes already at the time of the diagnosis.

Key words: atherosclerosis, complications, diabetes mellitus, macroangiopathy, mortality.
Utilization of antidiabetic drugs in the Nordic Countries
Authors: Andrew Marit , Jervell Jak
Published: October 2009

ABSTRACT. Remarkable differences exist in the consumption of antidiabetic drugs in the Nordic countries. The overall sales vary by a factor of 5 between the country with the lowest consumption, Iceland, and those with the highest consumption, Finland and Sweden. The differences are greater for oral antidiabetics than for insulin. There are also marked differences in the use of the different oral antidiabetic drugs.
Clinical pharmacology of oral antidiabetic agents
Authors: Melander Arne , Wåhlin-Boll Elisabeth
Published: October 2009

ABSTRACT. Currently available antidiabetic agents for oral intake are sulfonylureas (SU) and biguanides (BG). All SU seem to have the same mechanism(s) of action, including an enhanced release of pancreatic insulin, modulation of the release of other pancreatic hormones, and an enhanced peripheral sensitivity to insulin. Nevertheless, SU have different clinical effects, due to differences in intrinsic activity and pharmacokinetics. Thus, glipizide and glibenclamide are much more potent than tolbutamide and chlorpropamide, and should hence be preferred. Glipizide has the most rapid absorption and onset of action, and a shorter half-life and effect duration than glibenclamide, Accordingly, glibenclamide can exert a slightly better effect on fasting blood glucose but also involves a greater risk of long-lasting and sometimes fatal hypoglycemia. Thus, from the safety point of view, glipizide is to be preferred. Both glipizide and glibenclamide can be given once daily, and their efficacy may be improved if they are administered before, rather than together with, breakfast. The claim that SU enhance cardiovascular morbidity and mortality seems to be unfounded.

BG do not release insulin and do not provoke hypoglycemia but they may induce lactic acidosis, which is often fatal. This risk is most prominent with phenformin, partly beause this drug is eliminated by metabolic hydroxylation, which is greatly impaired in about 5 % in a Western population. In contrast, metformin is eliminated by renal excretion without preceding metabolic transformation; accordingly, the risk of lactic acidosis can be minimized if only metformin is used and is not given to subjects with impaired renal function. It remains to be established whether or not metformin can provoke permanent malabsorption of vitamin B12. From a theoretical point of view, the combination of SU and BG should be rational, but the clinical value of such combination therapy remains to be assessed.
Treatment failures: A common problem in the management of patients with type II diabetes
Authors: Groop Leif , Pelkonen Risto
Published: October 2009

ABSTRACT. Secondary failure is a common problem in the treatment of patients with type II diabetes. The underlying mechanisms are reviewed, and special interest is focused on the assessment of insulin secretion and insulin sensitivity. Impaired beta-cell function seems to be the major cause of secondary drug failure in patients with normal weight, whereas insulin resistance is of greater importance in obese patients. The importance of Cpeptide determinations to detect patients needing insulin is emphasized. The concept of progressive deterioration of beta-cell function with time in type II diabetes is challenged.

Different treatment modalities for the management of patients with secondary drug failure are discussed and special interest is focused on the combination of insulin and sulfonylureas in the management of secondary failure patients with slightly impaired insulin secretion.

Key words: secondary drug failure, type II diabetes, Cpeptide, insulin sensitivity, oral antidiabetic drugs, insulin therapy.
The influence of strict control on diabetic complications
Authors: Hanssen Kristian F. , Dahl-Jørgensen Knut , Brinchmann-Hansen Olaf , _ _
Published: October 2009

Abstract. We studied 45 IDDM without c-peptide response, duration 7-22 years, without proliferative retinopathy. After 2 months run-in period, they were randomly assigned to: (P) 15 received CSII: (C) 15 received muliple s.c. injections via butterfly 5-6x daily;: (M) 15 received twice daily mixed rapid and long acting insulin.

All groups improved blood glucose control in the run-in period (p<0.0001). After change of treatment (P) and (M) improved further (p<0.01) but (C) was unchanged.

GFR was supranormal and decreased in (P) and (M). No regression of retinopathy was shown in any group. One in (P) had transient florid pre-proliferative retinopathy which regressed spontaneously without laser treatment.

We conclude that retinal response to strict control is complex. A transient deterioration may been seen.
Role of plasma C-peptide determination in the management of type II diabetes.
Authors: Aro Antti
Published: October 2009

The classification of diabetes may be sometimes difficult, particularly in persons with non-ketotic diabetes becoming manifest in middle age. The plasma C-peptide concentration, determined either in the fasting state or, preferably, after stimulation with iv. glucagon, gives a reliable estimate of the endogenous insulin secretion capacity of the individual. The C-peptide determination has improved the facilities for classification of diabetes and for appropriate choice of therapy. Patients showing stimulated plasma C-peptide values less than 0.6 nmol/l are definitely insulin-dependent, whereas values above the limit indicate that the patients can probably be managed without exogenous insulin (non-insulin-dependent diabetes). The C-peptide determination alone does not definitely indicate the therapy of choice. Conventional indicators of energy balance and glucose control together with regular follow-up of patients are still essential, particularly in the management of patients showing relatively low plasma C-peptide levels (between 0.6 and 1.1 nmol/l.). The stimulated plasma C-peptide concentration should be determined always before stopping insulin therapy in any diabetic patient or before instituting insulin therapy in a non-ketotic patient. In addition, plasma C-peptide determinations will certainly prove valuable in the classification of adult onset diabetic patients for the purposes of epidemiologic studies.
Treatment of non insulin-dependent diabetic women during pregnancy
Authors: Bompiani G. D. , Botta R. M.
Published: October 2009

Abstract. From 1981 to 1984 90 cases of diabetic pregnancy were seen at the Palermo Center. Twentynine patients (32%) had prepregnancy type 2 diabetes, 20 (69%) of these were obese and were studied further.

The patients were divided into 2 groups of 13 and 7 patients. The first group was given a diet of 30 kcal/kg ideal prepregnancy weight. The second group was prescribed a low energy diet of on average 1200 kcal/day.

In the diet-restricted group, weight gain was less pronounced (7.9 ± 1.2 sd vs. 12.7 ± 8.6 kg), insulin requirement was lower (0.56 ± 0.22 vs. 1.00 ± 0.34 U/kg body weight) and the metabolic control was better than observed in the group given 30 kcal/kg body weight. The weight gain during pregnancy was proportional to the fetal weight index at birth (r = 0.72, P < 0.0005).

It is concluded that obese type 2 diabetic women are best treated by a low caloric diet and, when necessary, small doses of insulin. To establish the optimal caloric intake for obese pregnant type 2 diabetic women, the following formula is proposed: (30 kcal/kg prepregnancy ideal body weight/24 h) – X, where X is the % of prepregnancy obesity exceeding 120.
Gastrointestinal hormones and cortisol in normal pregnant women and women with gestational diabetes
Authors: Hornnes Peter J. , Kühl Claus
Published: October 2009

Abstract. In pregnancy the secretion of a number of gastro-enteropancreatic hormones is considerably altered. These changes might be involved in the gestational modification of gastrointestinal physiology. The enteral stimulation of insulin secretion (the incretin effect) is diminished in pregnancy – both when determined indirectly and when the gastric inhibitory polypeptide (GIP) response to glucose ingestion is considered. Whether this is important for the deterioration of glucose tolerance in pregnancy is uncertain. In gestational diabetics similar findings as in normal pregnant women were obtained except that the GIP response to glucose ingestion was smaller and the GIP response to lipid ingestion greater than in normal women. It is, however, unlikely that these differences are responsible for the development of gestational diabetes. Significant positive correlations were found between the increase of plasma cortisol levels during normal pregnancy and the concomitant decrease in glucose tolerance indicating that the increased cortisol levels might be involved in the development of the insulin resistance found in normal pregnancy.
Gastro-entero-pancreatic hormones in amniotic fluid from normal and diabetic pregnant women
Authors: Fallucca F. , Gargiulo P. , Troili F. , Zicari D. , Pimpinella G. , Sciullo E. , Gori G. , Gerlini G. , Pachi A.
Published: October 2009

Abstract. Clinical applications of analyses of hormones in amniotic fluid (AF) have recently been increased. In diabetic pregnancy, determinations of insulin and C-peptide in AF have been suggested as good indicators of the status of the foetus. We have investigated the pancreatic alpha and beta cell function by measuring insulin (IRI), C-peptide (CPR), glucagon (IRG), somatostatin (SLI), and gastric inhibitory polypeptide (GIP) in amniotic fluid collected during basal conditions or 2 h after an arginine test in 92 diabetic and 32 nondiabetic pregnant women. During basal conditions, in diabetic pregnant women, IRI, CPR and the insulin: glucagon molar ratio (I/G) were all significantly higher while amniotic fluid-IRG was significantly lower than in the controls. After arginine stimulation, IRI increased in AF of the diabetic pregnant women but not in AF of the controls while no differences were observed in AF-GIP and AF-SLI concentrations. Higher IRI and CPR, as well as lower IRG values were significantly related to poor maternal metabolic control. The occurrence of neonatal morbidity including macrosomia was significantly associated with increased AF, IRI and CPR concentrations after an arginine challenge and these factors were the most sensitive predictors of neonatal morbidity in infants of diabetic mothers. Increased AF glucose concentrations and I/G ratios were related to neonatal hypoglycaemia; jaundice and respiratory distress syndrome were associated to low concentrations of SF-IRG.
CRF: its regulation of ACTH and pro-opiomelanocortin peptide release and its extra hypothalamic occurrence
Authors: Lowry P. J. , Estivariz F. E. , Gillies G. E. , Kruseman A. C. N. , Linton E. A.
Published: October 2009

Abstract. CRF-41 and vasopressin are the major part of the hypothalamic complex responsible for the release of ACTH. The potentiated response of the corticotroph to mixtures of the peptides and their co-localization in the same neurosecretory vesicles would indicate their obligatory co-secretion in many stress situations. The occurrence of CRF at peripheral sites especially in the placenta and in the plasma of women in their third trimester of pregnancy is suggestive of further roles for this peptide although care should be exercised in interpreting simple immunohistochemical staining in certain tissues. When ACTH is released from the pituitary several other peptides which form part of its precursor are co-released. The effect of these peptides on the adrenal gland and the way their activity is expressed has led to a post-secretional proteolytic control mechanism being proposed.
Treatment of diabetic pregnant women with monocomponent insulins
Authors: Gargiulo P. , Di Mario U. , Zuccarini O. , Troili F. , Tiberti C. , Nicolini U. , Pachi A. , Gerlini G. , Fallucca F.
Published: October 2009

Abstract. Very little immunological research has been undertaken in pregnant diabetic women in relation to insulin therapy.

We investigated the relations between treatment with insulins of varied immunogenic character and the presence of immune factors such as insulin antibodies, immune complexes and insulin antiinsulin complexes as well as some maternal and neonatal complications of diabetic pregnancy.

128 insulin treated diabetic pregnant women and 121 of their newborns were included in the study.

The incidence of insulin antibodies, immune complexes and insulin antiinsulin complexes was lower in patients treated with highly purified insulins than in those treated with conventional insulins.

The insulin antibody levels were significantly related to the occurrence of maternal and neonatal morbibity.

The presence of insulin antiinsulin complexes in the cord blood of infants of diabetic mothers was related to the presence of these complexes in their mothers.

Our results seem to indicate that the use of highly purified insulin could favour the outcome of diabetic pregnancy.
Fetal lung maturation in diabetic pregnancy
Authors: Tydén Olof , Eriksson Ulf J. , Berne Christian
Published: October 2009

Abstract. The increased incidence of the idiopathic respiratory distress syndrome (IRDS) in infants of diabetic mothers may be explained by preterm delivery and asphyxia but the metabolic derangement per se may also be responsible for the inadequate production of surfactant.

Experimental studies of the underlying mechanisms in the lungs of fetuses of pregnant diabetic rats have shown a decreased formation of the two major surfactant phospholipids disaturated phosphatidyl choline and phosphatidyl glycerol. In addition, the activities of key enzymes responsible for the production of these phospholipids are decreased in the fetal lung tissue. Inadequate utilization of pulmonary glycogen for surfactant biosynthesis has also been observed. Furthermore, experimental studies support that other changes than fetal hyperinsulinaemia are needed to produce a state of disturbed surfactant production.

In human diabetic pregnancy strict metabolic control allows the fetal lungs to mature in a near-normal fashion. The presence of phosphatidyl glycerol in the amniotic fluid seems to be the best available predictor of lung maturity in diabetic pregnancy, in which both the lecithin/sphingomyelin ratio and amniotic fluid cytology may result in false-positive and false-negative values. The trend towards extension of delivery to term will undoubtedly diminish the need for estimation of fetal lung maturity by amniocentesis. Avoiding preterm delivery and adhering to strict metabolic control of the maternal diabetes would be expected to decrease the neonatal respiratory problems in diabetic pregnancy.
Metabolic adaptations during the neonatal period in infants of diabetic mothers
Authors: Hertel Jens , Kühl Claus
Published: October 2009

Abstract. Infants of diabetic mothers (IDM's) are prone to develop severe but usually asymptomatic hypoglycaemia during the first postnatal hours. High maternal plasma glucose concentrations at the time of delivery increase this risk, especially if the mode of delivery is cesarean section. Newborn IDM's are hyperinsulinaemic and the neonatal hypoglycaemia seems to result from this together with a retarded increase in plasma glucagon levels. Despite very high plasma insulin concentrations, lipolysis, as indicated by a rise in plasma glycerol concentrations, appears to be normal in IDM's. The IDM's are able to respond to both physiologic and metabolic stress with an increased catecholamine secretion during the first hours of life, and the catecholamines seem to counteract the inhibitory effect of insulin on lipolysis and, at least partly, to oppose the blood glucose lowering effect of insulin.
Relationship between ultrasound findings in pregnancy and neonatal morbidity
Authors: Pachi A. , Fallucca F. , Gerlini G. F. , Maggi E. , Torre R. La
Published: October 2009

Abstract. In 142 diabetic pregnancies fetal biparietal diameter (BPD), transverse abdominal diameter (TAD) and abdominal circumference (AC) were estimated by means of serial ultrasound examinations. An accurate evaluation of fetal growth was obtained in 85% of the cases. AC was found to have the highest degree of reliability in predicting macrosomia (71%) followed by TAD (60%) and BPD (17%).

Placental morphology was estimated at the last scanning before delivery in 85 of the patients. In pregnancies resulting in macrosomic infants the placental maturation seemed to be retarded.

In 26 patients a third trimester amniocentesis was performed. A mature (grade III) placenta was always associated with a lecithin-sphingomyelin (L/S) ratio> 2, indicating fetal lung maturity but there was no constant relation between placental maturity and the L/S ratio.

In conclusion, ultrasound examination during diabetic pregnancy offers valuable information concerning the prenatal diagnosis of macrosomia and could serve as a guidance in the determination of the optimal time and route of delivery. The grading of placental maturity might help to identify fetuses at risk, but further studies in this area are needed before final conclusions can be drawn.
Treatment of emergency cases in newborn infants of diabetic mothers
Authors: Reitano G.
Published: October 2009

Abstract. Some of the most common complications seen in newborn infants of diabetic mothers are reported in this paper. These include hypoglycaemia, hypocalcaemia, hyperbilirubinaemia, polycythaemia, respiratory distress syndrome and cardiac failure. Recent pathogenetic views and therapeutic schedules are discussed.
Growth hormone response to thyrotropin-releasing hormone in children and adolescents: a reappraisal
Authors: THEINTZ G.E. , TANG J.Z. , MARTI C. , BISCHOF P. , SIZONENKO P.C.
Published: October 2009

In normal subjects, thyrotropin-releasing hormone (TRH) is not involved in the control of growth hormone secretion. Paradoxical growth hormone (GH) responses to TRH have been described in acromegalic subjects and, recently, in some constitutionnally tall children. To confirm this finding, we have examined the GH response to combined LHRH-TRH tests performed to assess the pituitary function of children with GH deficiency, tall stature before and during bromocriptine therapy, precocious or delayed puberty as well as in a group of patients of average height and normal bone age. Unlike prolactin, the GH "response" to TRH, in children followed longitudinally, is particularly heterogeneous with an unpredictable pattern of secretion in repeated tests. Over 90% of children display peaks of GH (≥5ng/ml), of which 38% occur twice during the test period. Amplitude and frequency of GH peaks appear to be independent of height, chonological age or bromocriptine therapy. Secretory rate estimated by integrated surface area increases in parallel to sex steroids impregnation. The pattern of GH secretory episodes, the increase in mean GH secretion in parallel to the production of gonadal sex steroids and the failure of bromocriptine to affect GH secretion in constitutionnally tall children allow to speculate that what is measured after TRH injection is normal spontaneous GH rhythm rather than a direct effect of TRH on GH secretion.
Sex hormone priming prior to the combined hypoglycaemia test
Authors: HAMILTON WILLIAM , KHATTAB MOHSEN M.
Published: October 2009

The insulin hypoglycaemia test (IHT) was performed on 3 groups of short statured children. One group was unprimed with sex steroid hormones, a second group received 17β-oestradiol, while a third group received testosterone. The dosage of insulin was adjusted to produce a nadir in blood glucose of ⇋ 1 mmol/L. When this level is achieved plasma growth hormone (GH) responses less than 10 mU/L are not improved by either priming procedure. It is suggested from the data that there is no place for a diagnosis of a partial GH deficiency state.

When the IHT is combined with Gn-RH and TRH infusion the data derived may indicate GH-RH deficiency alone or additionally a CRF deficiency. Alternatively a pituitary insensitivity to these releasing substances or a pituitary synthetic failure of all trophic hormones may be adduced. Unless a releasing hormone is deficient and the pituitary is shown to be able to respond to its synthetic analogue, treatment with the available analogues will fail to give the desired clinical response.
Treatment of Silver-Russell type dwarfism with human growth hormone: Effects on serum somatomedin-C levels and on longitudinal growth studied by knemometry
Authors: PARTSCH C.-J. , HERMANUSSEN M. , SIPPELL W. G.
Published: October 2009

Abstract. Two patients, aged 5 and 12 years, with Silver-Russell type dwarfism are presented. As shown by standard tests and examination of the spontaneous nocturnal hGH secretion, there was only mild regulative hGH deficiency. HGH treatment was started with daily subcutaneous injections at age 5.5 years (height 90.3 cm, −6.1 SDS, bone age 2.75 years) and 12.6 years (height 125.7 cm, −3.7 SDS, bone age 8.75 years), respectively. Treatment was monitored by serial somatomedin-C (SM-C) determinations and by knemometry (lower leg measurement).

SM-C values increased in both patients by 10.5 and 4.8 fold, respectively, and remained above the prepubertal range (>2.5 U/ml) during the treatment periods of 1.5 years. Pretreatment knemometric growth rate was high (after a somatomedin generation test) in patient 1 (0.7 mm/week) and low in patient 2 (0.31 mm/week). It remained at the same level in patient 1 (0.67 mm/week) and increased markedly in patient 2 (0.46 mm/week). During a treatment interruption, in both patients, knemometric growth rates fell to 0.33 and 0.30 mm/week, respectively. After resumption of treatment, now with biosynthetic hGH, growth rates increased again in patients 1 and 2 to 0.64 and 0.48 mm/week, respectively. This lower leg growth pattern was parallelled by similar changes in total body growth velocity. Even after the relatively short treatment period of 14 to 16 months, a slight net gain in statural height could be observed, as standard deviation scores for bone age increased.
Observations on the role of GH/IGF-1 and sex hormone binding globulin (SHBG) in the pubertal development of growth hormone deficient (GHD) children
Authors: RUDD B.T. , RAYNER P.H.W. , THOMAS P.H.
Published: October 2009

SHBG concentrations in GHD and non GHD children of both sexes were studied in relation to their weight and androgen status. SHBG was inversely related to age in short and control children, but not for GHD. Correction for body weight restored the inverse relationship in these children and improved the correlation for the other groups. DHAS concentrations were similar in GHD and short children, suggesting GH per se does not influence adrenal androgen synthesis. The mean free testosterone in GHD children 12.7 pmol/L, was similar to that in short children, 14.3 pmol/L, and lower than controls 21.2 pmol/L, but consistent with their pubertal status.

The Linear regression of SHBG on IGF-1 was r = -0.605 (P <0.01). It was postulated that IGF-1 and free testosterone may regulate SHBG synthesis.

Administration of native and synthetic GH to prepubertal GHD children lowered SHBG without a significant change in TBG, albumin or free testosterone.

The fall in SHBG concentration after HGH in GHD children is suggested as a selective mechanism which may lead to improved pubertal development.

It is now recognised that many of the biochemical actions of administered human growth hormone (HGH), notably linear growth, protein synthesis and turnover, recorded in the classical studies of Prader et al. (1964), Hubble (1966) and Brown et al. (1967) are mediated by the generation of somatomedin C (IGF-1) (Van Wyk et al., 1974). Less certain is the role that IGF-1 may play in the timing of the growth spurt and subsequent pubertal development. It is documented however, (Laron and Sarel, 1970), that clinical signs of poor genital development in male patients with growth hormone deficiency may be reversed by HGH therapy, but the mechanism is unknown.

A specific carbohydrate rich dimeric binding protein, sex hormone binding globulin, with a high Ka for testosterone and oestradiol-17β is present in serum (Anderson, 1974). Levels are raised prepubertally and fall progressively in both sexes as puberty advances (Lee et al., 1985).

This fall is a trigger for increased levels of free testosterone and oestradiol-17β which may play a part in the activation of the hypothalamic-pituitary-gonadal axis. Preliminary reports (Rudd et al., 1985), have shown that some GHD children had raised SHBG values for chronological and bone age.

These observations suggested that concentrations of non-protein bound sex steroids may be inappropriately low because of a raised In this paper, the weight and the androgen status of GHD SHBG. children is studied in relation to compared to similar data for short addition, the effect of native and Sweden) GH on SHBG and non-protein GHD patients, is examined. their SHBG concentrations and is children and controls. In synthetic (Somatonorm S - Kabi, bound testosterone in the serum of
Growth, growth hormone secretion and somatomedin C after cranial irradiation for acute lymphoblastic leukemia
Authors: BRAUNER R. , PREVOT C. , ROY MP. , RAPPAPORT R.
Published: October 2009

In a large group of 74 patients irradiated with 2400 rad for acute lymphoblastic leukemia an unusually high frequency of complete GH deficiency was observed (40 %). Only 11 out of 46 prepubertal children had growth retardation and seven children received hGH treatment. On the contrary 11 other prepubertal cases had normal growth rates in spite of lack of response to AITT. Plasma SmC values were correlated with growth rates but were discrepant with GH responses to AITT in somecases. Because of this high frequency of GH dysregulation further growth at time of puberty should be carefully documented.
Endogenous opioid inhibitory tone on LH secretion in normal puberty and in several pubertal disturbances
Authors: BERNASCONI S. , PETRAGLIA F. , IUGHETTI L. , FACCHINETTI F. , MARCELLINI C. , GIOVANNELLI G. , GENAZZANI A.R.
Published: October 2009

To further evaluate the role exerted by endogenous opioids on LH secretion a naloxone challenge (0.08 mg/Kg b.w. i.v.) was performed in 23 healthy children at different stages of puberty, in 5 adolescents in different period of menstrual cycle, in 3 case of idiopathic precocious puberty (PP), in 7 cases of delayed puberty (DP), in 4 females affected by hypogonadotropic hypogonadism (HH) and in 6 patients affected by polycystic ovary disease (PCOD). Naloxone does not induce any significant change on LH plasma levels in prepubertal helathy children and in all the cases of PP and DP. Similarly there was no LH response in healthy adolescents neither in HH nor in PCOD, the response to naloxone appears only in preovulary and luteal phases. These data indicate that the central opioid system regulating LH secretion in humans is active only at more advanced stages of puberty and it does not seem to play a role in the beginning of sexual maturation. Moreover gonadal steroids seem to play a fundamental modulatory role on opioid-controlled LH secretion.
Gynaecomastia and premature thelarche in a schoolchildren population of northern Italy
Authors: Nizzoli G , Del Corno G , Fara G M , Chiumello G
Published: October 2009

The prevalence and incidence of gynaecomastia and thelarche have been studied in pre-school children and school children belonging to different socio economical classes in two Northern Italian Cities: Milano and Mantova. The child ren selected underwent three clinical examinations in their own school by the same examinator. The highest prevalence (36.6%) of breast enlargement was observed in nursery children until 2 years of age in Milano. Age and sex specific incidence rates were higher in Milano than in Mantova except in boys 11-14 years old. Assumption of drugs which might induce gynaecomastia thelarche was excluded. Relative risks calculated for veal and chicken must suggest that these are not relevant in the ethiology of breast enlargement.
Is heterozygosity for the steroid 21-hydroxylase deficiency responsible for hirsutism, premature pubarche, early puberty, and precocious puberty in children?
Authors: KNORR D. , BIDLINGMAIER F. , HÖLLER W. , KUHNLE U. , MEILER B. , NACHMANN A.
Published: October 2009

We applied the ACTH-stimulation test developed in our laboratory for the detection of heterozygous carriers of the 21-hydroxylase deficiency gene to patients suffering from hirsutism (n=89), premature pubarche (n=75), early puberty (n=37), and precocious puberty (n=22). While, in the general population, this test is positive in less than 2%, we found in 33% of hirsute patients, in 41% of patients with premature pubarche, and in 33% of patients with early puberty a hormonal response similar to the one seen in heterozygous carriers for the 21-hydroxylase defect. In contrast, only 18% of patients with precocious puberty responded abnormally. Thus we speculate that, at least in some patients with hirsutism, premature pubarche, and early puberty, heterozygosity for the 21-hydroxylase defect plays a major role in the pathogenesis of these disorders.
Annual progression of retinopathy in conventionally treated children and adolescents with type I diabetes mellitus
Authors: BURGER W. , WEBER B. , HARTMANN R. , HÖVENER G.
Published: October 2009

In a cohort of 268 type I diabetic patients, aged 19.6 ± 4.1 years (Mean ± 1 SD), with a diabetes duration of 10.4 ± 4.9 years, treated by the same team, using the same conventional treatment regime during the total observation period, the progression rate of early retinopathy within the first two decades of diabetes was deduced from observed transitions of the retinal status from one stage of retinopathy (as defined by fluorescein angiography) to a higher one (Malone et al., 1977) within one year. A total number of 83 such events were evaluated.

After a gradual development of earliest changes within the fifth year of diabetes, the median annual rate of progression was found to be 12 - 13%, independent of the previous duration of diabetes and the actual retinal state.
Long-term treatment with diazoxide in childhood hyperinsulinism
Authors: GRANT D. B. , DUNGER D. B. , BURNS E. C.
Published: October 2009

This paper reviews the outcome in 12 children with hyperinsulinaemic hypoglycaemia who first developed symptoms between the ages of 2 and 8 months and who were treated with diazoxide (5 - 20 mg/kg/day) for 2-13 years. Two cases required subtotal pancreatectomy at the ages of 5 and 10 years because of recurrent hypoglycaemia and one girl with severe retardation died at the age of 6 years while still on diazoxide therapy. Two patients aged 3.5 and 9 years are still on treatment and in 7 cases diazoxide was discontinued between the ages of 2.5 and 14 years, indicating that spontaneous remission can be expected in a high proportion of children with post-neonatal hyperinsulinaemic hypoglycaemia. Of the 9 children who started diazoxide within 3 months of the onset of symptoms, 5 are of normal intelligence and 4 are moderately retarded (IQs 63-71). In 3 children diazoxide was started 8 months to 3 years after the onset of symptoms; two are retarded (IQs 60-70) and the third was severely retarded and died aged 6 years.
Juvenile thyrotoxicosis
Authors: PETER F.
Published: October 2009

The incidence of juvenile thyrotoxicosis has not exceeded one case per 100,000 population per year in Hungary during the past decades. From more than 200 simultaneous determinations of serum thyroid hormones (T3, T4, FT4) it was concluded that increased FT4 concentrations are the most frequent findings in thyrotoxicosis, even when both or one of the other thyroid hormone concentrations (T3, T4) are normal,-TSH and prolactin responses to TRH were studied in 18 patients; TSH remained always undetectable whereas prolactin increased in half of the patients. A significant negative relationship was found between the prolactin response and the level of circulating thyroid hormone. Although the pituitary lactotrophin is controlled by thyroid hormones, thyrotrophin is more sensitive to thyroid hormone levels in juvenile thyrotoxicosis.-In 56 TRH tests during antithyroid drug therapy this test was not found to be useful in predicting the likelihood of long-term remission. - The low maintenance dose of antithyroid treatment (2.5-5.0 mg/day) without thyroid hormone addition seems to be a favourable mode of therapy in juvenile thyrotoxicosis.
The subcellular defects in the androgen insensitivity syndrome
Authors: SWOBODA W. , HERKNER K.
Published: October 2009

The androgen insensitivity syndrome (AIS) was studied with consideration of the complexity of mechanisms involved on the intracellular level: testosterone (T) and dihydrotestosterone (DHT) receptors and the androgen-5α-reductase (A5R). Five children with "normal" female external genitalia (group A) and three patients with variable forms of ambiguity (group B), ages 1 to 18 years, were studied. Tissue specimens from genital skin were analysed for the Kd- and Nmaxvalues of the cytosolic and nuclear T- and DHT-receptors, as well as for the Km- and Vmax-data of the tissue specific A5R. The enzyme analyses were performed with a kinetic method.

Results show that patients from group A mainly lack action of the nuclear DHT receptor, combined with reduces binding capacity in the cytosol. T binding was poor in both, cytosolic and nuclear fractions, respectively. Results of group B proved to be more inhomogenous, ranging from total absence of a DHT receptor to normal binding capacities in the nuclear fractions, accompanied by decreased cytosolic Nmax values for that ligand. T binding was poor in all patients of group B in the cytosolic and nuclear fractions, respectively. A5R was qualitatively normal in all patients examined, except one, but decreased enzyme activities could be observed in a wide range. In summary, the study confirms the complex mechanisms, presenting as AIS clinically. Moreover a close relationship between abnormalities of androgen receptor function and changes in A5R activity could be evaluated, thus confirming the recent theories about intracellular androgen action.
The role of regulatory peptides in postnatal metabolic adaptation
Authors: Aynsley-Green A
Published: October 2009

Major changes occur after the umbilical cord is cut at birth in the structure and function of several physiological systems which enable the newborn baby to adapt from an intrauterine milieu of continuous intravenous nutrition via the placenta to a postnatal environment of intermittent enteral feeding with milk. The secretion of regulatory peptides from the gut and pancreas in response to enteral milk feeding may have a fundamental role in initiating and regulating the cascade of developmental changes needed for the utilization of food which occur after birth.
Urinary arginine-vasopressin (AVP) excretion in cystic fibrosis (CF)
Authors: Stegner H. , Caspers S. , Niggemann B. , Commentz J.
Published: October 2009

Free water handling is impaired in chronic obstructive lung disease (COLD). We studied the role of AVP in this mechanism with a sensitive urinary AVP radioimmunoassay (RIA) in 13 patients with CF. The mean age was 14.7 ± 1.27 SE years. The control group was age and sex matched. While the 24-hour urine volume was not significant different in both groups, urine osmolality was higher in CF (788 mosmol/kg ± 182 SE vs. 622 mosmol/kg ± 218 SE; p = 0.05).

The 24-hour urinary AVP excretion in CF patients was found to be significantly elevated (174 ng/day ± 99 SE vs. 74 ng/day ± 48 SE; p = 0.01). This difference becomes even greater if these values are corrected for body weight (4.4 ng/(kg × day) ± 2.1 SE vs. 1.5 ng/(kg × day) ± 0.9 SE; p = 0.005).

Lung function studies were available in 8 patients. We used a body plethysmograph to measure FEV1 (1 sec forced exspiratory volume) and MEF25 (forced exspiratory flow at 25% of vital capacity) as sensitive indices of airway obstruction. There was a significant negative correlation between urinary AVP excretion and MEF25 (r =.76) and FEV1 (r =.65): the more pronounced the airway obstruction the higher the AVP excretion. We conclude that AVP plays a major role in the impaired water handling in COLD. Increased AVP secretion is already present under clinically stable conditions and is dependent on the degree of airway obstruction. In treating those patients one has to be aware of the possibility of water intoxication.