bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevalence of type 2 Diabetes in Sweden
Authors: Sartor Gunnar
Published: October 2009

ABSTRACT. Studies on the prevalence of diabetes mellitus, type 1 and type 2, in Sweden covering four decades give figures ranging from 0.35 % to 2.3 %. Figures are assumed to reflect type 2 diabetes in the majority of cases. In the most recent study the prevalence is 2.08 % for males and 1.95 % for females after standardization to total Swedish population. The disease becomes very common above the age of 60 (5.7 % or more). High risk groups suitable for screening are reviewed.

Key words:

diabetes mellitus, type 2

prevalence

risk group

screening procedure
A genetic marker for non-insulin-dependent diabetes and atherosclerosis
Authors: Owerbach D. , Johansen K. , Billesbølle P. , Poulsen S. , Schroll M. , Nerup J.
Published: October 2009

ABSTRACT. The human insulin gene has been localized to the short arm of chromosome 11. The length of a segment of DNA associated with the human insulin gene is polymorphic. In patients with non-insulin-dependent diabetes mellitus (NIDDM) the proportion of subjects homozygous for DNA restriction fragments of a large size class (U alleles) in the polymorphic region was significantly higher than in normal controls. The U allele is thus associated with at least one type of NIDDM. The U-alleles were also strongly associated with macroangiopathy in diabetic as well as in non-diabetic subjects.

Key words: DNA polymorphism, chromosome 11, genetic marker, human insulin gene, non-insulin-dependent diabetes, glucose regulation, atherosclerosis, macroangiopathy.
Insulin secretion in type II diabetes
Authors: Faber Ole K. , Damsgaard Else Marie
Published: October 2009

ABSTRACT: Beta-cell function was studied in young (20–30 years old, n=10) and old non-diabetic subjects (n=305), newly detected (n=87) as well as established (n=101) non-insulin dependent diabetic subjects, aged 60–75 years.

Fasting plasma insulin concentrations were 0.04 ± 0.01, 0.07 ± 0.04, 0.11 ± 0.07 and 0.11 ± 0.07 pmol/ml (mean ± sd) in the different groups. The corresponding C-peptide values were 0.36 ± 0.07, 0.63 ± 0.36, 0.98 ± 0.40 and 0.95 ± 0.45 pmol/ml, respectively. The relative changes in insulin and C-peptide concentrations were identical despite different kinetics of the metabolism of the peptides, indicating, that the elevated insulin levels of old as opposed to young non-diabetics and diabetic as opposed to non-diabetic subjects are caused by hypersecretion rather than decreased metabolic clearance of insulin.
Insulin Secretagogues. Possible Modulators of Glucose and Non-Glucose Stimuli
Authors: Lundquist Ingmar , Ahrén Bo , Scherstén Bengt
Published: October 2009

ABSTRACT: A short overview is given concerning different insulin secretagogues and possible peptidergic modulators capable of acting on theβ-cell through the paracrine, the neurocrine or the gastro-intestinal endocrine pathway. Model experiments in animals have shown that peptidergic modulation of insulin secretion elicited by glucose stimulation, cholinergic stimulation or β-adrenergic stimulation seems to vary with the nature of the secretory stimulus. Several peptides influence only one type of secretory stimulus other may even display opposite effects with different stimuli. Generally, members of the secretin-glucagon family seem to be more insulinogenic than members of the gastrin-CCK family. Studies in man have shown that the insulin secretory defect in type II diabetes is mainly due to an abnormality of glucose recognition in the β-cell. Recent evidence seems to favour the idea that impairment of the complex system of non-glucose insulin secretagogues and modulators may be of additional importance in the heterogenous pathogenesis of type II diabetes. The sulfonylurea drugs may have beneficial effects not only on glucose-induced insulin release, but also on insulin secretion induced by nonglucose stimuli such as β-adrenergic stimulation which was found to be most sensitive to these drugs.

Key words: Insulin secretion, glucose and non-glucose stimuli, peptidergic modulation, type II diabetes, sulfonylurea.
Diabetes and arterial hypertension
Authors: Fagerberg Sven-Erik
Published: October 2009

ABSTRACT. The epidemiology, pathogenesis, significance and management of hypertension i diabetic subjects are discussed. The frequency of hypertension in the diabetic population is about 20 %. Microangiopathy which leads to increased peripheral resistance and subsequently to impaired kidney function is probably the most important factor in the pathogenesis of hypertension in diabetes. All antihypertensive drugs have particular limitations in the diabetic patient. However the blood pressure must be treated more aggressively than in nondiabetics. Today we know that complications in well controlled diabetics occur later and to a lesser degree than in poorly controlled diabetics. Drugs that have an unfavourable effect on the metabolic processes in diabetes should, if possible, be avoided.

Key words: Hypertension, Type 1 diabetes, Type 2 diabetes, diabetic complications, nephropathy, retinopathy, obesity, antihypertensive drugs.
Diabetic patients and myocardial infarction
Authors: Rytter Lene , Beck-Nielsen Henning , Troelsen Svend
Published: October 2009

ABSTRACT. The investigation comprised 832 consecutive hospitalized patients with acute myocardial infarction (AMI). The prevalence of diabetes mellitus among the AMI-patients was 9.7 % and is significantly higher than in an age-matched population where the prevalence is about 6.1 % (p<0.05). The prevalence was higher for women than for men (14.9 % versus 7.6 %). The risk of AMI was found to be about 4 times higher among IDDM than among nondiabetics(p<0.05), whereas the risk for non-insulin dependent diabetics was only slightly increased (p<0.05).

The mortality rate from AMI within the first month was 20.2 % for non-diabetics while 42 % of the diabetics died from their myocardial infarction (p<0.001). A specially high mortality rate of 51.6% was found among non-insulin dependent women. The investigation show further that patients in a poor diabetic state, both in the years prior to the AMI and at the time of hospitalization in the coronary care unit, had a significantly higher mortality rate (p<0.05).

We therefore conclude that diabetes mellitus disposes to AMI and that the mortality rate of AMI is significantly increased among diabetics. A poor metabolic regulation of the diabetes seems to aggravate the prognosis of AMI.

Key words: diabetes mellitus, acute myocardial infarction, coronary sclerosis.
Dietary treatment of patients with noninsulin-dependent diabetes mellitus
Authors: Pedersen Oluf
Published: October 2009

ABSTRACT. The dietary recommendations for noninsulin-dependent diabetics recently published by several national diabetes associations are reviewed and commented upon. In obese diabetics the emphasis is on an energy restriction. Moreover, all organizations agree on the advice of a decrease of the saturated fat content and an increase in the amount of starch and watersoluble, nondigestible carbohydrates in diabetic diets. Epidemiological, experimental and clinical evidences suggest that consumption of this type of diet may be less atherogenic and may improve the action of insulin on carbohydrate metabolism.

Key words: Noninsulin-dependent diabetes, diet, carbohydrates, fat, fibres, weight reduction.
Exercise in the treatment of type II diabetes
Authors: Koivisto Veikko A. , DeFronzo Ralph A.
Published: October 2009

ABSTRACT. There are only a few studies evaluating the role of physical exercise in the treatment of type II diabetes. These data indicate that during acute exercise, plasma glucose levels decline more in type II diabetics than in healthy subjects and hyperinsulinemia is dimenished. During physical training, insulin sensitivity is enchanced, hyperinsulinemia can be reduced and serum lipid profile is changed to a more antiatherogenic direction. An improvment in oral glucose tolerance is shown to occur in some, but not in all patients after training. In obese type II diabetics physical training with dietary therapy can help to reduce weight. Based on these potential benefits, physical exercise can be recommended to type II diabetic patients bearing in mind that the exercise program should be adjusted according to the physical fitness of the patient.
Experimental work with anabolics in autoimmunity models
Authors: Schuurs A. H. W. M. , Verheul H. A. M. , Schot L. P. C.
Published: October 2009

Abstract. 19-nortestosterone (nandrolone) or its decanoate was tested in six animal models for autoimmune disease. The compound was found capable of inhibiting the development of disease symptoms or the deterioration of certain immune parameters in three out of five models of spontaneous autoimmune disease: NZB/NZW F1 (NZB/W) mice (lupus glomerulonephritis, Sjögren's disease-like syndrome), NZB (lupus glomerulonephritis, autoimmune haemolytic anaemia) and OS chickens (thyroiditis). No effect of the compound was seen in MRL lpr/lpr mice (lupus glomerulonephritis, lymphoproliferative disease) and in BB rats (insulin-dependent diabetes mellitus; IDDM). Nandrolone decanoate also seems to be active in myasthenia gravis evoked in rats immunised with acetylcholine receptor but further experiments are necessary to confirm this. In a first experiment also ethylestrenol was found to give favourable effects in the model.
Pancreatic transplantation in diabetes mellitus: Present status
Authors: Östman J. , Lundgren G. , Tydén G. , Gunnarsson R. , Groth C-G.
Published: October 2009

Between December 1966 and June 1982, 269 transplantations of vascularized pancreas (whole or segmental) were undertaken in 254 diabetic patients throughout the world. Most of the transplantations were performed in patients with end-stage renal disease who also received kidney grafts; a few patients received pancreatic grafts only. About 25% of the pancreatic grafts are still functioning after periods of various lenghts, the longest being five years.

To the problem of how to handle the exocrine secretion there are two main approaches: 1) occlusion of the duct with a synthetic polymer and 2) pancreatico-enterostomy. A disadvantage of the former procedure is late fibrosis and atrophy of the endocrine tissue. With the latter method duct leakage and fistula development cannot be completely prevented. In either case, vascular complications cause graft failure in about 20% of the operations. The risk of rejection of the graft seems not to differ significantly from that concerning other allogeneic organs, including the kidney and heart.

Most of the patients with a functioning pancreatic graft are normoglycemic: they have a normal or near-normal oral or intravenous glucose tolerance and an early insulin response to intravenous glucose tolerance and an early insulin response to intravenous glucose challenge. Whether the improvement of the motor and sensory nerve conduction velocities observed in some patients whose graft has functioned for a long time is due to the reversal of renal insufficiency or to insulin deficiency cannot yet be determined. At present, pancreas transplantation at Huddinge Hospital is performed only in conjunction with renal transplantation in patients with end-stage diabetic renal disease.

The metabolic disturbances in animals with experimental or spontaneous diabetes mellitus can be corrected by the transplantation of either a vascularized pancreatic graft or a suspension of more or less purified islets. In insulin-dependent patients only vascularized pancreatic allografts have led to sustained normoglycemia; the results of transplanting suspensions of adult or fetal human pancreas have so far been discouraging (Sutherland, 1981b). This presentation will deal only with the transplantation of vascularized pancreatic allografts, which has proved increasingly successful in recent years. Since the first systematic clinical trial started in December, 1966, in Minnesota more than 300 pancreatic transplantations have been performed, according to the new Human Pancreas and Islet Transplant Registry (Sutherland, 1984). During the last few years the annual number of pancreas transplantations carried out in the world has greatly increased (Fig. 1), and more than 40 centers have now reported to the Registry.
Beta-cell function and diabetic control in insulin dependent diabetes melletus
Authors: Faber Ole K.
Published: October 2009

Beta-cell function, as evaluated from plasma C-peptide measurements, is found in all insulin dependent diabetic patients the first months of disease and in about 15% of patients with more than 15 years of treatment.

The beta-cells are capable of modulating their secretory activity in response to changes in blood glucose.

Even a minimal residual insulin secretion is of metabolic significance.

Key words: insulin dependent diabetes mellitus, beta-cell function, C-peptide metabolic control.
Endocrine pancreatic function in insulin-dependent diabetic pregnant women
Authors: Fiore R. , Maldonato A. , Zicari D. , Pimpinella G. , Gargiulo P. , Tinelli F. P. , Arachi S. , Pachi A. , Fallucca F.
Published: October 2009

Abstract. In order to better understand the role of A-and B-cell function in diabetic pregnancy, we studied four groups of pregnant women at week 34–36 of gestation. Seventeen were healthy controls (C), 24 had gestational diabetes (GD), 16 had type 2 diabetes (NIDD) and 37 had type 1 diabetes (IDD). At times —20, 0, 20, 30, 45, 60, 90 and 120 min from the beginning of a 30 min infusion of 30 g of arginine intravenously, plasma glucose, glucagon (IRG) and C-peptide (CPR) were measured.

Plasma glucose was higher in diabetic than in control subjects. IRG values were also higher in the GD and the NIDD women. CPR values were similar to, or slightly higher than control values in the GD and the NIDD and were much lower in the IDD women. All three variables increased during the arginine infusion in all groups, with the exception that CPR remained unchanged in the IDD. The CPR/IRG molar ratio was similar in control, GD and NIDD women; in the IDD, it was much smaller than in the other groups and was not affected by arginine. In all the diabetic patients, IRG was negatively correlated with the maternal weight gain and in the IDD IRG was positively correlated with the increase in the insulin need and with the CPR levels.

In conclusion diabetes appeared to enhance the A-cell function also in pregnancy, possibly impairing the 'facilitated anabolism' and stressing the 'accelerated starvation' which are typical of normal pregnancy. Glucagon was confirmed as one possible determinant of the insulin resistance seen in diabetic pregnancy.
Growth hormone releasing factor and somatomedin C production: Extrahypothalamic localization and possible functional significance
Authors: Thorner Michael O. , Vance Mary Lee , Evans William S. , Ho Ken , Rogol Alan D. , Blizzard Robert M. , Furlanetto Richard , Rivier Jean , Vale Wylie
Published: October 2009

Abstract. Growth hormone-releasing factor (GRF) is found in the highest concentration (albeit lower compared to other hypothalamic regulatory hormones) in the hypothalamus. There is mounting evidence that GRF-like immunoreactivity is found in other sites in the CNS and in the periphery. The role of GRF, other than to stimulate growth hormone secretion by the somatotroph, is unknown. In addition generation of IGF-1 in response to GRF appears to be dependent on an intact pituitary.
Intensified treatment of pregnant insulin-dependent diabetic women
Authors: Jovanovic L. , Peterson C. M.
Published: October 2009

Abstract. Intensified treatment of glycaemic excurtions has become the standard of care for all insulindependent diabetic women. This paper reviews the rationale for intensified insulin treatment programs and offers the algorithms of one approach to achieve and maintain normoglycaemia throughout pregnancy.
Preconceptional treatment with insulin infusion pumps in insulin-dependent diabetic women with particular reference to prevention of congenital malformations
Authors: Jensen Bente Møller , Kühl Claus , Mølsted-Pedersen Lars , Saurbrey Nina , Fog-Pedersen Jan
Published: October 2009

Abstract. Severe congenital malformations occur more often in infants of diabetic mothers than in infants of non-diabetic mothers. Fetuses exhibiting early fetal growth delay are in increased risk to be malformed and the early fetal growth rate seems to be related to the degree of metabolic control around the time of conception and in the early pregnancy.

Nine insulin-dependent diabetic women (White classes B–F) were treated by means of continuous subcutaneous insulin infusion (CSII) initiated at least two months prior to conception and continued throughout pregnancy in order to evaluate the influence of optimized metabolic control on the course and outcome of diabetic pregnancy. Eleven conventionally treated pregnant diabetics (White classes B–D) served as controls. In the pump group the mean blood glucose values in the 4 weeks immediately before and after the conception were 7.7 ± 0.2 mmol/l and 8.0 ± 0.3 mmol/l, respectively, the HbA1c was 7.3 ± 0.5% at the time of conception and 6.9 ± 0.2% 6–10 weeks later. In the control group the HbA1c 6–10 weeks after conception was 7.2 ± 0.5%. In the pump group two fetuses exhibited early growth delay while all of the 11 fetuses in the control group were of normal early growth. There were no malformations in either group. All pregnancies were uncomplicated except for one case of toxaemia in the control group.

Thus, during CSII treatment the metabolic control was improved in all patients. A possible beneficial effect of this improved control on the early fetal growth delay was not demonstrated. Both groups are, however, still small and definite conclusions must await further results.
Methods of fetal monitoring and assessment of placental function in diabetic pregnancy
Authors: Sutherland Hamish W.
Published: October 2009

Abstract. The clinical usefulness and limitations of the methods available for monitoring fetal well-being and assessing placental function in diabetic pregnancy are reviewed.
Glycosylated proteins in normal and diabetic pregnancy
Authors: Peterson C. M. , Jovanovic L.
Published: October 2009

Abstract. The methods available for and the clinical usefulness of measuring glycosylated proteins in pregnancy complicated by diabetes is reviewed. The need for standardization of reference ranges for pregnancy and for highly accurate and precise methods of measurement is emphasized. Measurement of glycosylated proteins is useful in patients with established diabetes to identify pregnancies at risk for complications known to be associated with significant hyperglycaemia. These include spontaneous abortion and malformations, foetal loss due to premature labour or intrauterine death, and macrosomia and other neonatal morbidities. The use of glycosylated protein measurements as a diagnostic test for gestational diabetes appears limited.
Contraception in diabetic women
Authors: Skouby Sven O. , Mølsted-Pedersen Lars , Kühl Claus
Published: October 2009

Abstract. In diabetic women investigations have been performed covering the clinical consequences of intrauterine contraception and the influence on glucose and lipid metabolism of oral contraceptives. Insertion of copper-T intrauterine contraceptive devices in insulin-dependent diabetic women resulted in accidental pregnancy rates and total continuation rates after 12 months which were at the same levels as in non-diabetic women. No differences were observed in the maximum depth of corrosion or in the constitution of the corrosion products. The glucose tolerance as well as the serum lipoprotein levels remained unchanged when low-dose hormonal compounds were administered to women with a previous gestational diabetes. In insulin-dependent diabetic women it was found, that the use of oral contraceptives containing natural oestrogen may not give rise to difficulties with the diabetes control or disturbancies in the lipid metabolism.
The development and function of the endocrine pancreas of fetuses and infants born to normal and diabetic mothers
Authors: Grasso Sebastiano , Palumbo Giuseppe , Fallucca Franco , Lanzafame Salvatore , Indelicato Barbara , Sanfilippo Silvana
Published: October 2009

Abstract. The development of the human endocrine pancreas is described. The hormone content and islet responsiveness of foetal and neonatal pancreases of diabetic and non-diabetic pregnant women are reported.
The control of catch-up growth
Authors: MOSIER H. DAVID
Published: October 2009

Catch-up (compensatory) growth following transient growth retardation due to illness or starvation has long been recognized in biology and in clinical medicine. This report summarizes work utilizing experimental models in rats in efforts to elucidate the control of catch-up growth. The results support the hypothesis that the catch-up growth mechanism includes a set-point or reference for body size appropriate for age and that the control resides in the central nervous system. Growth hormone (GH ) secretion is increased during catch-up growth, although the results also show that increased GH secretion is not required for catch-up growth acceleration. Environmental light modulates the effect of catch-up growth on GH secretion. The mechanisms for sensing a deficit in body size and for stimulating catch-up growth acceleration remain unknown.
Remarkable catch-up growth in a boy with steroid-responsive nephrotic syndrome
Authors: STEENDIJK R.
Published: October 2009

A boy is described who was followed from 4 to 21.5 years of age, during which time he was treated with high doses of corticosteroids for a steroid-responsive nephrotic syndrome. For the first 10 years therapy was mainly continuous and height decreased from -0.5 to -4.5 SDS. Later discontinuous treatment without a reduction in the total weekly dose was accompanied by rapid catch-up growth. Final height was -1.0 SDS. During most of the time skeletal age was severely retarded and a discrepancy between the development of the short bones of the hand and the carpal bones was noted.
Effect of steroids on cartilage metabolism "in vitro"
Authors: DU CAJU Marc V.L. , ROOMAN Raoul P.
Published: October 2009

Conditions characterized by high levels of glucocorticoids are associated with poor growth. Serum somatomedin or insulin-like growth factor activity measured by cartilage bioassay systems is low, but is generally not accompanied by a fall in somatomedin concentration. Hydrocortisone and a synthetic analogue, dexamethasone, impaired the serum stimulated "in vitro" 35S sulphate and 3H-thymidine incorporation in porcine rib cartilage at physiological concentrations. Hydrocortisone added at a concentration of 0,1 μg/ml decreased the potency of normal serum to 50 % of controls. Dexamethasone was at least 10 times more potent. Removal of "in vitro" or "in vivo" administered hydrocortisone with dextran-coated charcoal restored the sulphate and thymidine activity to normal. We conclude that physiological amounts of glucocorticoids inhibit the "in vitro" porcine cartilage metabolism. Glucocorticoid administration "in vivo" does not abolish the activity of the cartilage stimulating effect of serum but affects cartilage metabolism directly or by the induction of locally produced inhibitors of cartilage metabolism.
Some comparative aspects of a longitudinal growth study in normal spanish children and other longitudinal studies
Authors: FERRANDEZ A. , MAYAYO E. , RODRIGUEZ M. , ARNAL J.M. , CARO J. , PUGA B. , ATARES M.
Published: October 2009

The differences existing among some european longitudinal growth studies make it necessary to be cautious in the use of standards constructed on different populations. The improvement of the environmental conditions during the last 20 years is probably the most important cause of the "catch-up" phenomenon of the spanish stature. It is probable that racial characteristics also play a role, even in the same country as can be appreciated on comparing two spanish longitudinal studies based on children originary from different regions. All of wich indicates the need to use own standards in those countries wich, like ours, have lived through a period of intenses changes. Even exploratory studies of regional differences in the same country seem necesary.
Longitudinal study of testosterone and luteinizing hormone (LH) in relation to spermarche, pubic hair, height and sitting height in normal boys
Authors: NIELSEN C. THØGER , SKAKKEBÆK N.E. , DARLING JANET A.B. , HUNTER W.M. , RICHARDSON D.W. , JØRGENSEN MERETE , KEIDING N.
Published: October 2009

In a 7-year longitudinal study of 40 normal boys, initially aged 8.6-11.7 years, 24-h urine samples were collected every 3 months and analysed for LH and testosterone as well as for the presence of spermatozoa (spermaturia). Spermarche (onset of the release of spermatozoa) was estimated on the basis of age at the first observed spermaturia. Physical examination, including measurements of height and sitting height and staging of pubic hair (Tanner stage) was performed every 6 months. Spermarche occurred early in puberty when the median pubic hair stage was 2.5. Urinary testosterone did not reach maximum levels until approximately 2 years after spermarche. Peak height velocity occurred when urinary testosterone levels were low, 1-2 years before adult levels of testosterone were attained. Our results support the proposition that low levels of testosterone have a predominantly growth-promoting effect, whilst higher concentrations have an inhibitory effect on height spurt.
Single and repeated testing of growth hormone secretory capacity in hypopituitarism using growth hormone releasing factor
Authors: BUTENANDT O. , EMMLINGER M. , DOERR H.
Published: October 2009

38 patients with proven growth hormone deficiency (GHD) and 19 children with familial short stature received an iv GRF-bolus injection of 1 ug/kg body weight. Whereas in all control children plasma growth hormone rose significantly (mean of maximal values 36 ng/ml), only 7 out of 38 patients with GHD reached peak values of 8 ng/ml or more. GRF-priming by 1 ug GRF/kg BW given once daily s.c. for 5 days in 19 patients improved the response of the pituitary gland in 11. Thus, following the first GRF test, only 21 % of patients demonstrated function of the pituitary gland whereas 45 % did so when all test results are combined.

To evaluate the pituitary function in patients with GHD correctly, GRF tests following a GRF priming period seems to be necessary to reactivate atrophic somatotropic cells of the pituitary gland.
Testosterone treatment of constitutional delay in growth and development: effect of dose on predicted versus definitive height
Authors: MARTIN MALCOLM M. , MARTIN ARLINE L. A. , MOSSMAN KENNETH L.
Published: October 2009

Abstract. The outcome of treatment in 3 groups of boys with constitutional delay in growth and development given monthly intramuscular injections of testosterone enanthate 200 mg (22 subjects) 100 mg (10 subjects) and 50 mg (12 subjects) was compared with the outcome in a control group (14 subjects) without treatment. The 4 groups were similar in chronological age, height, height age, bone age, height age/bone age ratio, pubertal development and had similar predicted adult heights. All treated subjects achieved an excellent growth response with growth velocities reflecting androgen dose. Bone age advanced commensurate with height age in all the treated groups and Δ height age/Δ bone age ratios at the end of therapy did not differ significantly. Nor was there a significant difference in the height prediction by the RWT method before and at the end of treatment. However, the year following treatment, growth velocities reversed so that those who received the largest steroid dose and had grown the fastest, decelerated the most and eventually ended up significantly shorter than their predicted adult height. In contrast the control group and those treated with smaller doses of testosterone achieved their predicted heights. The present study confirms that large doses of androgens compromise adult height and are contraindicated in the treatment of constitutional delay in growth and development. Testosterone enanthate 50 mg/mo did not affect predicted adult height adversely, but to the contrary, permitted it to be fully realised. The data caution against drawing conclusions based on changes observed during androgen therapy in the absence of extended follow-up.
Oestrogen treatment of adolescent tall girls; short term side effects
Authors: TRYGSTAD OLAV
Published: October 2009

In 1980-1985 680 preadolescent tall girls were treated with pharmacological doses of oestrogen to reduce final height. Indications for the therapy were predicted final height >+2.5 SD (180.75 cm), idiopathic scoliosis, and psychosocial problems. Until 1976 141 girls were given diethyl stilboestrol 5 mg daily. By advice of Prader this was then replaced by ethinyl oestradiol and a progestin was given on days 5-10 each month. The mean duration of therapy was close to 2 years. The observed short-term unwanted effects were due to the pharmacological actions of the drugs, (11 girls had galactorrhoea at the end of therapy; no pituitary prolactionoma was observed) or events happening by chance.
Hypothalamic GnRH-like bioactivity and immunoreactivity in prepubertal and adult male rats
Authors: BOURGUIGNON J.P. , FRANCHIMONT P.
Published: October 2009

In prepubertal (21-days old) and adult (50-days old) male rats, the immunological and biological properties of GnRH-like material extracted from the hypothalamus were studied. At both ages, hypothalamic material and synthetic GnRH resulted in a parallel inhibition of the binding of labelled GnRH to 2 different anti-GnRH antisera (As I and As II). Using both antisera, a similar amount of immunoreactivity was measured in several extracts from 50-day hypothalami. In contrast, hypothalamic extracts obtained at 21 days contained a greater immunoreactivity using As II than using As I. This discrepancy was only observed with the hypothalamic content whereas the immunoreactivity released in vitro was similar with the two antisera at both ages studied. Filtration of hypothalamic extracts on biogel P2 revealed two immunoreactive fractions, the major one being eluted as the synthetic decapeptide and showing a similar immunoreactivity using both antisera. A high molecular weight fraction was proportionally predominant in 21-day extracts and showed a greater immunoreactivity using As II than using As I. The biopotency of the hypothalamic extracts upon rat pituitary cells in vitro was similar at the two ages but around 30 times higher than the bioactivity expected for the immunoreactivity. We conclude that the heterogeneous physicochemical and immunological nature of hypothalamic GnRH is different before and after sexual maturation in the male rat, whereas the bioactivity, although much greater than expected, is similar at both ages.
Frequency of hypoglycemia in children with adrenal insufficiency
Authors: Artavia-Loria E. , Chaussain J.L. , Bougnères P.F. , Job J.C.
Published: October 2009

The frequency of hypoglycemia in 165 children with primary adrenal insufficiency, 118 of whom had Congenital Adrenal Hyperplasia and 47 Addison's Disease, was 18 %. Half of the hypoglycemic episodes occurred in the neonatal period. Hypoglycemia was isolated in 13 children, revealing the disease in 4 newborns with Congenital Adrenal Hypoplasia and in a boy with 11 B Hydroxylase deficiency.

Basal plasma cortisol levels were significantly lower in those of subjects who experienced hypoglycemia ( 47.1 ± 28.6 ng/ml vs. 106.0 ± 86.6 ng/ml, p< 0.001). A significant correlation ( p < 0.001) was found between the plasma concentration of glucose and cortisol at time of hypoglycemia.
Primary adrenocortical insufficiency in childhood
Authors: RONGEN-WESTERLAKEN C. , DROP S.L.S. , VAN DEN ANKER J.N.
Published: October 2009

Seven patients with primary glucocorticoid or glucocorticoid and mineralocorticoid deficiency are described with emphasis on the clinical presentation and laboratory investigations. Two patients presented with irreversible shock and at autopsy adrenal tissue was recognized only microscopically. In 3 patients adrenal antibodies were present. One girl had the polyglandular autoimmune disorder type I and one boy had glucocorticoid deficiency only. The histories of the patients illustrate that the presenting symptoms of primary adrenocortical insufficiency are very insiduous and that it may take several years before the correct diagnosis is made and hydrocortisone substitution therapy is instituted.
Compensatory growth after HLA-typing revelation of incorrect diagnosis of 21-hydroxylase deficiency
Authors: Sobel Edna H. , Hahm Sue Y.E.
Published: October 2009

A 9 1/2 year old boy had been treated for complete 21-hydroxylase deficiency from infancy. That diagnosis was excluded by HLA-typing of family members who wished to know their carrier status. Withdrawal of replacement therapy was very well tolerated. The patient showed distinct compensatory growth and for the first time was free of crises of adrenal insufficiency.

This instance demonstrates an unexpected application of HLA-typing. It also shows that an amount of hydrocortisone too small to give any clinical evidence of overdose can impede growth. Furthermore, it provides reassurance that adrenocortical function can recover completely after many years of treatment with exogenous steroids.
Why do children with diabetes die?
Authors: Scibilia J , Finegold D , Dorman J , Becker D , Drash A
Published: October 2009

While the treatment of children with Type I diabetes mellitus has dramatically improved since the introduction of insulin in 1922, significant acute mortality still remains. To better ascertain the causes of death in younger children and adolescents with diabetes mellitus, a retrospective review was undertaken of diabetes associated mortality in the patient population followed at the Children's Hospital of Pittsburgh between the years 1950 and 1985. Fifty-five deaths were identified of which 20 occurred during the initial presentation of diabetes and 35 occurred between 2 months and 11 years following the diagnosis of diabetes mellitus. Diabetic ketoacidosis (DKA) was associated with 64% of the total mortality with 85% of the early onset and 54% of the late onset deaths being ketoacidosis related. Of these ketoacidosis associated deaths, cerebral edema was documented in 31%, or 20% of the total group mortality. Non ketoacidosis deaths in both early and late onset groups were caused by heterogeneous events. There were no deaths associated with the traditional late vascular complications of diabetes mellitus. Since diabetic ketoacidosis is a potentially preventable acute complication of diabetes mellitus and represented a predominant cause of mortality in these children, early recognition and prompt treatment might substantially reduce childhood mortality in patients with Type I diabetes mellitus.
Sixty children with congenital hypothyroidism detected by neonatal thyroid: Mental development at 1,4, and 7 years: a longitudinal study
Authors: ILLIG R. , LARGO R.H. , WEBER M. , AUGSBURGER TH. , LIPP A. , WISSLER D. , PERRENOUD A.E. , TORRESANI T.
Published: October 2009

A prospective study of mental development has been carried out in 60 unselected children with congenital hypothyroidism (C.H.) detected between 1976 and February 1985. Treatment with 1-thyroxin was initiated at the age of 10.4 + 2.5 days and supervised by T4 and TSH monitoring in 3-6 monthly intervals. Although clinical signs were mild or missing, skeletal maturation was prenatal in more than half. Developmental testing was carried out at 1, 4 and 7 years by the Brunet-Lezine (n=60), the non-verbal Snijders-0omen (n=40), and the german version of the Wechsler intelligence test (n=20), respectively. The global DQ/IQ in all but a few children at each age group are within the 3rd and 97th percentile of the DQ/IQ distribution in a control group tested during the same period of time. The mean values of all global and subscores, however, are lower than that one in the control group, differences being highly significant at 1 year. In 21 of our 60 children, associated findings and/or risk factors were present. The DQ/IQ in children without risk factors are identical to that of the control group. There are no significant DQ/IQ differences neither between athyroidism and ectopic thyroid glands, nor between prenatal bone age and normal skeletal maturation at diagnosis. We assumethat the favourable results in our children with C.H. may be ascribed to the early onset of thyroid hormone replacement and the strictly controlled compliance.
Prostaglandin excretion in pseudohypoaldosteronism type I
Authors: WERDER E.A. , HILBE W. , VALLOTTON M.B.
Published: October 2009

In an infant with pseudohypoaldosteronism type I increased urinary excretion of PGE2 (1.32 ng/mg creatinine; normal mean ± SE: 0.50 ± 0.10) and PGF2α (6.15 ng/mg creatinine; normal mean ± SE: 2.93 ± 0.91) was found. Prostaglandin excretion as well as the typical hyperkalemia, hyperreninemia and hyperaldosteronism normalized with adequate dietary salt supplementation. An abnormally high excretion of the renal prostaglandins was again present at age 4.4 years when the child was thriving although additional salt was withheld. These abnormalities are considered to be secondary to this condition's basic defect which remains to be elucidated.
Evidence against growth hormone-releasing factor deficiency in children with idiopathic obesity
Authors: VAN VLIET G. , BOSSON D. , RUMMENS E. , ROBYN C. , WOLTER R.
Published: October 2009

The mechnisms whereby growth hormone (GH) secretion is decreased in human obsity remain obscure. We studied the response of plasma GH and prolactin (PRL) to an I.V. dose of 0.5 mcg/kg of growth hormone releasing factor (GRF) in three groups of children: lean (N=12), obese (N=15) and GRF-deficient, i.e. children with complete GH deficiency on the basis of conventional provocative testing and evidence of hypothalamic dyfunction on the basis of thyrotropin-releasing hormone testing (N=7).

Mean (±SEM) peak plasma GH after GRF was blunted to the same extent in obese and in GRF deficient children (11.1 ± 2.2 and 8.3 ± 2.8 mg/ml) as compared to lean control children (34.7 ± 4.7 mg/ml).

The pattern of PRL response to GRF was however different in GRF after GRF injection, and in obese and lean children, who had no acute change in PRL levels after GRF.

Baseline plasma somatomedin C concentrations were low for age in GRF deficient children and tended to be high for age in obese children.

On the basisi of these discrepant patterns of response of PRL to GRF and plasma somatomedin C concentration, we conculde that GRF defeciency does not account for the decreased GH secreation observed in obese children.
Serum insulin-releasing activity and the Prader-Willi syndrome
Authors: LAUTALA PENTTI , KNIP MIKAEL , AKERBLOM HANS K. , KOUVALAINEN KAUKO , MARTIN JULIO M.
Published: October 2009

Pathogenesis and etiology of the various clinical features of the Prader-Willi syndrome (PWS) are not completely understood. There is evidence suggesting a hypothalamic abnormality leading to hypogonadism in this syndrome. To test the possible hypothalamic involvement in the pathogenesis of obesity in these patients we studied the sera of 5 patients with PWS for insulin-releasing activity of possible hypothalamic origin. In addition 4 patients with a PWS-like syndrome and 6 obese patients with signs of central nervous system damage were studied. All five patients with PWS showed significant insulin-releasing activity in their sera. Of the four patients with PWS-like symptoms three showed similar activity while three of the obese patients with central nervous system damage had this activity in their sera. Serum insulin-releasing activity has been shown earlier to be associated with childhood obesity and it could play a role in the pathogenesis of obesity in PWS.
The functional response to furosemide in a case of de Toni-Debre-Fanconi disease
Authors: SANTOS-ATHERTON DAVID , FRENK SILVESTRE
Published: October 2009

The case of a 13-year-old boy with the advanced clinical picture of the idiopa thic DeToni-Debré-Fanconi syndrome is described, on whom acute studies of proximal tubular functions and of the effect of furosemide thereon were performed. Sodium bicarbonate loading corrected the hyperchloremic acidosis, but induced an increase of urinary bicarbonate loss of over 20 % of the filtered amount. Furosemide corrected bicarbonate reabsorption in spite of the presence of metabolic alkalosis. The urinary excretion of alpha-amino nitrogen, glucose, and phosphates decreased and tubular reabsorption of the two latter increased under furosemide. On a chronic treatment with furosemide and dietary sodium chloride restriction, correction of hyperchloremic acidosis, hypophosphatemia and rickets was achieved.
Modulation of class-II antigen expression in human thyroid epithelial cell cultures
Authors: Wenzel B. E. , Arnholdt H. , Grammerstorf S. , Gutekunst R. , Scriba P. C.
Published: October 2009

Abstract. The modulation of HLA-D expression of thyroid epithelial cells (TEC) was studied in vitro by means of immunofluorescence. Under serum-free culture conditions, TSH and TSH-receptor antibodies induce HLA-D on TECs derived from GD-patients. Serum-free culture conditions provide a higher availability of TSH-receptors by a 'right side right' polarity of the cellular morphology. There was no evidence for IFN-γ producing cell contaminations on GD-TECs. TSH in contrast to IFN-γ does not induce HLA-DQ on TECs. HLA-DQ is not displayed by spontaneously class-II antigen expressing GD-TECs. Methimazole as well as perchlorate do not suppress HLA-D expression of TECs.
Dendritic cells in autoimmune thyroid disease
Authors: Kabel P.J. , Voorbij H. A. M. , van der Gaag R. D. , Wiersinga W. M. , de Haan M. , Drexhage H. A.
Published: October 2009

Abstract. Dendritic cells form a morphologically distinct class of cells characterized by shape, reniform nucleus, absent to weak acid-phosphatase activity and strong Class II MHC determinant positivity. Functionally they are the most efficient cells in antigen presentation to T-lymphocytes which indicates their role in the initiation of an immune response. Using immunehistochemical techniques we studied the presence of dendritic cells in normal Wistar rat and human thyroids, in thyroids of BBW rats developing thyroid autoimmunity and in Graves' goitres. Dendritic cells could be identified in all thyroids studied and were positioned underneath the thyrocytes in between the follicles. Skin dendritic cells travel via lymphatics to draining lymph nodes, thus forming an antigen presenting cell system. It is likely that a similar cell system exists on the level of the thyroid for dendritic cells have also been detected in thyroid draining lymph nodes. In normal thyroid tissue of both human and rat dendritic cells were relatively scarce. During the initial phases of the thyroid autoimmune response in the BBW rat (before the appearance of Tg-antibodies in the circulation) numbers of thyroid dendritic cells increased. Intrathyroidal T-helper cells, B-cells or plasma cells could not be found. The thyroid draining lymph node contained large numbers of plasma cells. During the later stages of the thyroid autoimmune response in the BB/W rat (after the appearance of Tg-antibodies in the circulation) and in Graves' goitres dendritic cells were not only present in high number, but 20–30% were seen in contact with now-present intrathyroidal T-helper lymphocytes. The so-formed lymphoid cell aggregates were predominantly small (< 10 cells), but very large aggregates could also be detected. These large accumulations were highly organized and composed of T-cell zones, B-cell zones and numerous plasma cells. Such accumulations are reminiscent of secondary lymphoid organs. In view of these morphological data it is conceivable that thyroid dendritic cells are of prime importance in the presentation of autoantigen in thyroid autoimmune disease. Throughout the process of autosensitization in the BB/W rat thyroid epithelial cells stayed negative for Class II MHC determinants. This shows that Class II expression on thyrocytes is not prerequisite for thyroid autoimmunity to develop.
Cellular localization of the microsomal antigen and the thyroid peroxidase antigen
Authors: Pinchera A. , Mariotti S. , Chiovato L. , Vitti P. , Lopez G. , Lombardi A. , Anelli S. , Bechi R. , Carayon P.
Published: October 2009

Abstract. Evidence has been accumulated that human thyroid microsomal/microvillar autoantigen (M) is expressed both in the cytoplasm and on the surface of thyroid follicular cells. The availability of this autoantigen to the immune system, possibly associated with abnormally expressed HLA-DR antigens may be relevant both to the triggering and to maintenance of thyroid autoimmune reactions. Preliminary biochemical characterization of M suggested that it was a glycoprotein with a mol. wt. of about 100–110 kD. recent studies carried out in our laboratories taking advantage of monoclonal antibodies provided evidence that the structure presently referred as M-Ag is represented by thyroid peroxidase (TPO). The identity between TPO and M is further supported by four-layer immunofluorescence analysis showing a complete overlap of the two antigens both in the surface and in the cytoplasm of thyroid cells and by the observation that the expression of M and TPO is similarly modulated by TSH, possibly through a cAMP-dependent mechanism.
Transplantation of human endocrine tissues to nude mice:
Authors: Usadel K. H. , Teuber J. , Paschke R. , Junker M. , Schwedes U.
Published: October 2009

Abstract. After transplantation of human tissue to nu/nu mice the human lymphocytes disappear. In this context, interestingly, the DR-expression is not detectable anymore after transplantation of the tissues from patients with autoimmune thyrotoxicosis and cancer.

Neopterin release was only demonstrable when T-lymphocytes from patients with autoimmune thyrotoxicosis or PHA-stimulated lymphocytes were added, independently of the presence of DR-expression in the used culture tissues.

These results seem to exclude a functional role of DR-expression as a trigger mechanism of autoimmunity. It is supposed that DR-priming on epithelial cells is mediated by kinine production of activated T-lymphocytes or macrophages.