Bioavailability of calcium: comparison of calcium carbonate and milk and the effect of vitamin D, age, and sex using 24-hour urine calcium as a method.

The aim of the present study was to compare the bioavailability of calcium from calcium carbonate and milk and to investigate if 1,200 IU of cholecalciferol a day increased intestinal absorption of calcium. Both young women and a group of older persons of both sexes were included to study the influence of age and sex. In total, 53 healthy women and men were included: a group of 23 younger women (median age 30) and an older group of 15 women and 15 men (median age 66). The study period was 4 weeks; each participant completed four treatment regimens randomly: CaCO(3), CaCO(3 )+ 1,200 IU of cholecalciferol, milk, and placebo. All regimens were distributed three times a day and consisted of 1,200 mg of elementary calcium. The 24-hour urine calcium excretion was used as a method. Total urinary calcium excretion rates (mmol/day) were as follows (mean +/- SD): placebo 4.41 +/- 2.17, milk 5.17 +/- 2.33, CaCO(3) 5.83 +/- 2.03, and CaCO(3 )+ D 6.06 +/- 2.46. All regimens compared to placebo were significant. Addition of cholecalciferol to the CaCO(3) regimen increased calcium excretion but insignificantly: 0.27 +/- 2.84 mmol/day. The increase in calcium excretion during the milk regimen was significant only for the old group: 0.96 vs. 0.28 mmol/day. No other difference was found according to age and sex. The bioavailability of calcium carbonate and milk was demonstrated. Additional cholecalciferol (1,200 IU) to individuals in positive calcium balance with serum 25(OH)D levels >50 nmol/L only marginally increased calcium absorption in a short-term intervention.

Impaired vascular reactivity is present despite normal levels of von Willebrand factor in patients with uncomplicated Type 2 diabetes.

BACKGROUND: Type 2 diabetes is associated with an increased risk of cardiovascular disease. Endothelial dysfunction is thought to be an early marker of atherosclerosis. The purpose of this study was to assess whether endothelial function, judged by measurements of flow-mediated vasodilatation (FMD) and nitroglycerine (NTG)-induced vasodilatation as well as serum levels of von Willebrand factor, was affected in patients with uncomplicated Type 2 diabetes and normal levels of urinary albumin excretion (UAE). SUBJECTS AND METHODS: Twenty-three patients with Type 2 diabetes, normal UAE and no vascular complications were examined. Twenty-three healthy subjects matched for age, gender, body mass index and resting vessel size served as controls. All participants were non-smokers. Endothelial function was assessed by high-resolution ultrasound which measures changes in diameter of the brachial artery during flow-mediated and NTG-induced vasodilatation. We also measured serum levels of von Willebrand factor. RESULTS: In Type 2 diabetic patients FMD (3.2 +/- 0.5% vs. 4.8 +/- 0.5%, P = 0.019) as well as NTG-induced vasodilatation (15.9 +/- 0.6% vs. 18.5 +/- 0.9%, P = 0.021) were significantly reduced compared with controls. Levels of von Willebrand factor were not different between groups (0.88 +/- 0.07 vs. 0.88 +/- 0.07 in patients and controls, respectively) and were not correlated to FMD or NTG-induced vasodilatation. CONCLUSION: Impaired vascular reactivity is present in uncomplicated Type 2 diabetes and seems to be a more sensitive marker of vascular dysfunction than von Willebrand factor.

US-guided fine needle aspiration versus coarse needle biopsy of thyroid nodules.

OBJECTIVE: The aim of this study was retrospectively to evaluate ultrasound (US) guided fine-needle aspiration (FNA), in combination with US-guided coarse-needle biopsies, (CNB) from solitary or dominant thyroid nodules routinely performed during a 2 year period. METHODS: Seventy seven patients were biopsied using US-guided FNA and CNB. FNA was performed using a 21-Gauge needle and CNB using a 18-Gauge single action spring-activated needle biopsy system. The biopsies were performed with local anaesthesia. The Department of Pathology routinely examined the biopsy specimens. The retrieval rate in obtaining material for diagnostic evaluation was FNA (97%), CNB (88%), FNA and CNB (100%). RESULTS: In all, 41 of the 77 patients underwent neck-surgery. The surgical specimens were used to determine the results of diagnosing neoplasia. The accuracy, sensitivity and specificity for FNA were 80, 83, and 77%. For CNB 86, 78, and 94%. For both FNA and CNB 80, 89 and 73%. The diagnostic value of the two methods showed no significant difference (P < 0.05). CNB revealed contrary to FNA, however, one additional cancer. Also a higher number of false positive findings was noticed using FNA. No serious complications were registered. Adequate biopsies were obtained in all the patients using the combination of US-guided FNA and CNB. No patient underwent rebiopsy. CONCLUSIONS: The study demonstrated that neither US-guided CNB nor the combination of US-guided FNA and CNB were superior to US-guided FNA. US-guided CNB is only recommended in few selected patients.

[Markers for risk of IDDM in children of Danish patients with IDDM. A population-based, historical prospective study]. / Markører for IDDM-risiko hos børn af danske IDDM-patienter. En populationsbaseret, historisk prospektiv undersøgelse.

To assess the offspring IDDM recurrence risk in a Danish population-based study and to investigate parental and offspring related biological variables that might influence this risk, we identified 2726 IDDM probands and their 2826 offspring from a background population of 1.725 million people (33% of the Danish population). Proband current age was 20-60 years and age at IDDM onset was 30 years or less. Offspring data were obtained by a questionnaire. The cumulative IDDM risk up to age 30 years was found significantly decreased in maternal offspring compared to paternal offspring (2.3 +/- 0.6% and 5.7 +/- 0.9%, RR = 2.40, 95% CI 1.30-4.47; Mantel Cox: p = 0.004) only if parents were diagnosed with IDDM before offspring birth. However, due to a low number of diabetic offspring of probands diagnosed with IDDM after offspring birth, this observation need to be confirmed in a larger population. Using the Cox proportional hazards model we found that among several biological variables tested separately on offspring of male and female probands, all diagnosed with IDDM before pregnancy, paternal age at IDDM onset was the only statistically significant predictor of IDDM risk in offspring. Our findings may be important for counselling families in which one parent has IDDM.

Predictors of IDDM recurrence risk in offspring of Danish IDDM patients. Danish IDDM Epidemiology and Genetics Group.

It has previously been observed that offspring of mothers with insulin-dependent diabetes mellitus (IDDM) have a lower risk of IDDM than offspring of IDDM affected fathers. To assess the offspring IDDM recurrence risk in a Danish population-based study and to investigate parental and offspring-related biological variables that might influence this risk, we identified 2726 IDDM probands and their 2826 offspring from a background population of 1.725 million people (33% of the Danish population). Current age of probands was 20-65 years and their age at IDDM onset was 30 years or less. Sixty-nine offspring (2.4%) were affected with IDDM. The sex difference in the parental-offspring IDDM transmission rate was confirmed. The cumulative IDDM risk up to age 30 years was found to be significantly decreased in maternal offspring compared to paternal offspring (2.3 +/- 0.6 and 5.7 +/- 0.9 %, RR = 2.40, 95% CI 1.30-4.47; p = 0.004) only if parents were diagnosed with IDDM before birth of the offspring. However, due to the low number of diabetic offspring of probands diagnosed with IDDM after offspring birth, this observation needs to be confirmed in a larger population. In a subpopulation of the 2380 offspring, whose parents were all diagnosed with IDDM before offspring birth, the recurrence risk was significantly increased in offspring of male probands diagnosed up to age 17 years compared to offspring of fathers diagnosed at older ages (8.5 +/- 1.8 and 3.6 +/- 1.0%; RR = 2.27, 95% CI 1.21-4.25; p = 0.006). No such relation was found in maternal offspring. Using the Cox proportional hazards model on this offspring subpopulation we found that paternal age at IDDM onset was the only statistically significant predictor of IDDM recurrence risk. Our findings may be important for counselling families in which one parent has IDDM.

Diabetic ketoacidosis in Denmark: epidemiology, incidence rates, precipitating factors and mortality rates.

The epidemiology of uncontrolled diabetes mellitus was studied in an 11.2% sample of the Danish population (574,696 inhabitants) during a 24-month period. Some 175 admissions in ketoacidosis (heavy ketonuria and plasma bicarbonate below 21 mmol/l) were recorded. Based on prevalence rates from a socio-economically and ethnically comparable Danish county, the annual incidence rate was calculated to be 0.045 per diabetic. The incidence rate of moderate and severe episodes (bicarbonate less than 16 mmol/l) was 0.032 and of severe episodes only (bicarbonate less than 10 mmol/l) 0.017 per diabetic. The major risk group was female teenagers. The total annual frequency of recurrence was 8.7%: 48% of the male episodes were ketoacidosis (DKA) associated with onset of diabetes, against 30% of the female episodes (P = 0.02). All Danish diabetics were at the time of the survey (1978-79) treated with conventional insulin treatment. Annual incidence rate in these established diabetics was 0.028, i.e. three to five times less than reported during treatment with continuous subcutaneous insulin infusion. Mortality of DKA was low, 3.4%, and dependent upon age and precipitating factor but not upon the degree of acidosis. The overall annual mortality rate was 1.5 per 100 diabetics.

The pituitary-thyroid axis in patients with pituitary disorders.

The pituitary-thyroid axis of 12 patients, exposed to transsphenoidal pituitary microsurgery because of nonfunctioning adenomas (6), prolactinomas (3) and craniopharyngioma (1), or to major pituitary injury (1 apoplexy, 1 accidental injury), was controlled more than 6 months following the incidents. The patients did not receive thyroid replacement therapy and were evaluated by measurement of the serum concentration of thyroxine (T4), 3,5,3'-triiodothyronine (T3), 3,3',5'-triiodothyronine (rT3), T3-resin uptake test and thyrotropin (TSH, IRMA method) before and after 200 micrograms thyrotropin releasing hormone (TRH) iv. The examination also included measurement of prolactin (PRL) and cortisol (C) in serum. Apart from 1 patient with pituitary apoplexy all had normal basal TSH levels and 9 showed a significant TSH response to TRH. Compared to 40 normal control subjects the 12 patients had significantly decreased levels of T4, T3 and rT3 (expressed in free indices), while the TSH levels showed no change. Five of the patients, studied before and following surgery, had all decreased and subnormal FT4I (free T4 index) after surgery, but unchanged FT3I and TSH. The levels of FT4I were positively correlated to both those of FT3I and FrT3I, but not to TSH. The TSH and thyroid hormone values showed no relationship to the levels of PRL or C of the patients exposed to surgery. It is concluded that the risk of hypothyroidism in patients exposed to pituitary microsurgery is not appearing from the TSH response to TRH, but from the thyroid hormone levels.

The pituitary-thyroid axis in acromegaly.

The pituitary-thyroid axis of 12 acromegalic patients was evaluated by measurement of the serum concentrations (total and free) of thyroxine (T4), triiodothyronine (T3) and reverse T3 (rT3) and thyrotropin (TSH), growth hormone (GH) and prolactin (PRL) before and after iv stimulation with thyrotropin releasing hormone (TRH). Using an ultrasensitive method of TSH measurement (IRMA) basal serum TSH levels of the patients (0.76, 0.07-1.90 mIU/l) were found slightly, but significantly (P less than 0.01), lower than in 40 healthy controls (1.40, 0.41-2.50 mIU/l). The total T4 levels (TT4) were also reduced (84, 69-106 nmol/l vs 100, 72-156 nmol/l, P less than 0.01) and significantly correlated (P less than 0.02, R = 0.69) to the TSH response to TRH, suggesting a slight central hypothyroidism. The acromegalics had, however, normal serum levels of TT3 (1.79, 1.23-2.52 nmol/l vs 1.74, 0.78-2.84 nmol/l, P greater than 0.10), but significantly decreased levels of TrT3 (0.173, 0.077-0.430 nmol/l vs 0.368, 0.154-0.584 nmol/l, P less than 0.01) compared to the controls. The serum concentration of the free iodothyronines (FT4, FT3, FrT3) showed similar differences between acromegalics and normal controls. All the acromegalics showed a rise of serum TSH, GH and PRL after TRH. Positive correlation (P less than 0.05, R = 0.59) was found between the TSH and GH responses, but not between these two parameters and the PRL response to TRH. These findings may be explained by the existence of a central suppression of the TSH and GH secretion in acromegalic subjects, possibly exerted by somatostatin. Euthyroidism might be maintained by an increased extrathyroidal conversion of T4 to T3.

Renal handling of iodothyronines in acromegaly.

Measurement of the free serum concentration, the 24-h urinary excretion and the renal clearance of T4, T3, 3,3',5'-tri-iodothyronine (rT3), 3',5'-diiodothyronine (3',5'-T2) and 3,3'-di-iodothyronine (3,3'-T2) was performed in 13 patients with active acromegaly and in 18 healthy controls. The acromegalic patients had normal serum levels of the free iodothyronines, whereas the urinary excretion of T4 and T3 was increased approximately two-fold in the patients with acromegaly. The creatinine clearance, reflecting the glomerular filtration rate (GFR), was increased in the acromegalic patients, in median 133 ml/min versus 87 ml/min (p less than 0.01) in the controls. Compared to the creatinine clearance the clearance of T3 and 3,3'-T2 was higher (p less than 0.01) in acromegalics as well as in controls. The patients with acromegaly had higher renal clearance of T4 and T3 than controls, in median 81 ml/min versus 33 ml/min, and 269 ml/min versus 137 ml/min, respectively (p less than 0.01). These differences were not due to changes in creatinine clearance. The renal clearance of 3',5'-T2 tended to be enhanced in acromegalic patients (8.2 ml/min versus 3.9 ml/min, p less than 0.10), both before and after correction for creatinine clearance. The data suggest that in acromegaly, as in normal condition, iodothyronines are subject to both glomerular filtration and active tubular transport mechanisms. Further, active acromegaly results not only in increased GFR, but also in changes of the net tubular transport in favour of secretion of at least T4 and T3, and possibly also of 3',5'-T2.

Fatal septicaemia caused by DF-2 in a previously healthy man.

A case of fatal septicaemia caused by DF-2, a fastidious gram-negative rod is presented. Attention is drawn to the connection between DF-2 septicaemia and dog bites or contacts, not only in patients with impaired host defence but also in previously healthy individuals. As the organism is difficult to subculture, infections with DF-2 may easily be overlooked.

The influence of thyroid disorders on the dopaminergic regulation of prolactin, thyrotropin and growth hormone.

In order to clarify if hyper- and hypothyroidism change by feed-back mechanisms the dopaminergic controlled release of PRL, TSH and GH, the serum values of these hormones were measured before and following iv administration of 5 mg metoclopramide in 10 hyperthyroid, 11 euthyroid and 10 primary hypothyroid age-matched females, all consecutively investigated. The secretion pattern, as well as the quantitated response (area under the curve - AUC) of PRL were identical for the three groups, and uninfluenced by thyroid status. By contrast the TSH responses (AUC) were significantly and positively correlated to the basal TSH, suggesting that the effect of metoclopramide was dependent on the secretory capacity of the thyrotropic cells. The serum GH level was found to decrease in all three groups following metoclopramide, probably due to the inhibition of release. Stimulation of the same subjects with 200 micrograms TRH iv resulted in response curves of serum PRL and TSH, which were significantly and positively correlated to the basal serum TSH. The serum values of GH increased following TRH in the hypothyroid group, while the values of the hyperthyroid were depressed and unchanged. The present results suggest that the dopaminergic tonus on PRL, TSH and GH secretion is unaffected by thyroid feed-back mechanisms. The TRH-induced release of each of the three hormones is, however, dependent on thyroid status.

Release of prolactin, thyrotropin, and growth hormone in women with cyclical mastalgia and fibrocystic disease of the breast.

Prolactin (PRL), thyroid stimulating hormone (TSH) and growth hormone (GH) response to metoclopramide and TRH was investigated in seven women with fibrocystic disease and cyclical mastalgia, in eight similar patients without mastalgia, and in six normal controls. The basal PRL level was significantly elevated in patients with cyclical mastalgia (P less than 0.025). PRL and TSH response to metoclopramide did not differ significantly between the three groups, indicating that decreased dopaminergic tone is not the cause of elevated basal PRL level in cyclical mastalgia. PRL and TSH response to TRH and the abscent GH response to both metoclopramide and TRH further indicate that the hypothalamicpituitary axis is not primarily disturbed in cyclical mastalgia. The basal GH level was elevated in patients with fibrocystic disease with or without mastalgia. The increased basal GH secretion is not believed to be directly involved in cyclical mastalgia, but may be of importance in fibrocystic disease.

The effect of a new ergoline derivative, CU 32-085, in the treatment of acromegaly. A controlled study.

The effect of a new dopamine agonist, CU 32-085 (8 alpha-amino-ergoline), on pituitary function in acromegaly was evaluated by a controlled, single blind study of 12 acromegalics. The study included a single dose placebo/drug (0.5 mg CU 32-085) trial and a long-term crossover trial with 3 month periods (placebo/CU 32-085 8 mg daily). The patients were evaluated clinically and biochemically (oral glucose tolerance (OGTT), TRH- and LHRH-tests) before and after each 3 month period. Nine patients completed this long-term trial; one died from myocardial infarction during the placebo period, and two dropped out because of side effects. The release of GH, judged from more than 9 h suppression of serum GH following the single dose, and from the response to OGTT after the long-term treatment, was significantly inhibited by CU 32-085. Serum GH reached normal values in 4 of 9 patients. Serum PRL was also markedly suppressed, to subnormal values after the 3 months in all but one hyperprolactinemic patient. Serum TSH, cortisol, FSH and LH were generally unaffected. Glucose tolerance was not significantly altered, although an improvement was found in six of nine patients. A semiquantitative evaluation of subjective symptoms showed a significant improvement following the long-term treatment, while objective signs of acromegaly were unaffected. The blood pressure was slightly lowered, both after a single dose and after 3 months' treatment. Seven patients experienced nausea and dizziness, two of them with vomiting, after a single dose of the drug. Four of these had similar symptoms initially during the long-term treatment, which forced two to interrupt the trial. We conclude that CU 32-085 caused a marked suppression of the release of GH and PRL and an improvement of the major symptoms of acromegaly, a therapeutic effect that is comparable to the previous experience with bromocriptine.

A comparative study of atenolol and metoprolol in the treatment of hypertension.

1 In an open, randomized cross-over investigation of thirteen patients (nine and four women, aged 37-67 years) with mild or moderate essential hypertension a comparison between atenolol and metoprolol was carried out in order to study the effects of 50, 100 and 200 mg given once daily on blood pressure and heart rate at rest and during exercise. 2 Before one beta-adrenoceptor blocking drug was replaced by the other in a patient an intervening drug-free interval of sufficient length was secured to allow an increase in the blood pressure to pretreatment levels. 3 A maximal fall in blood pressure was achieve with 50 mg atenolol once daily, with no further reduction when the dose was increased to 100 mg or 200 mg. Maximal blood pressure reduction was achieved with 100 mg metoprolol daily, while the hypertensive effect of 50 mg once daily was not consistent. Significant reductions in heart rate in all test situations were observed with 50 mg atenolol, while 200 mg metoprolol 100 was necessary to reduce exercise-induced tachycardia. 4 Atenolol 50 mg and metoprolol 100 mg once daily are efficient in treating mild or moderate hypertension and doses beyond these may not reduce the blood pressure further. On the contrary lower doses than generally recommended may be effective in the individual patient.

Calcium and vitamin D metabolism in acromegaly.

Acromegalic subjects were found to have elevated serum levels of both 1,25-dihydroxyvitamin D (1,25-(OH)2D), 67 +/- 22 (SD) pg/ml) and 24.25-dihydroxyvitamin D (24.25-(OH)2D), (6.9 +/- 1.5 (SD) ng/ml). The serum concentration of 1,25-(OH)2D correlated positively (P less than 0.02, R = 0.56) to the 24 h urinary excretion of growth hormone, but not to the serum levels of parathyroid hormone, prolactin, thyroid hormones or the urinary excretion of free cortisol. Fourteen patients were treated with bromocriptine at doses from 15-45 mg/day for a period of about 6 months. This was accompanied by a significant decrease in the urinary excretion of growth hormone and calcium and in the serum concentrations of 1,25-(OH)2D and 24.25-(OH)2D. A relationship was demonstrated between the decrease in urinary calcium excretion and the decrease in serum 1,25-(OH)2D (P less than 0.02, R = 0.64). It is concluded that the serum concentration of 1,25-(OH)2D is elevated in acromegaly, perhaps as a consequence of a direct action of growth hormone on the renal 1 alpha-hydroxylase activity.

Serum prolactin and thyrotropin responses to thyrotropin-releasing hormone in men with alcoholic cirrhosis.

The serum concentrations of prolactin (PRL) and thyrotropin (TSH) in 12 males with alcoholic cirrhosis during basal condition and after stimulation with thyrotropin-releasing hormone (TRH) were compared with the concentrations in ten thiazide-treated hypertensive and nine normal men. The basal as well as the TRH-stimulated increase in serum PRL was significantly elevated in the cirrhotic males, while the increase in serum TSH was unchanged, compared with hypertensive and normal men. No correlation between clinical or laboratory parameters and serum PRL was found. Serum estradiol was equal in cirrhotic and control subjects and no correlation was found between serum PRL and serum estradiol. These findings favour the concept that raised serum PRL in cirrhotic patients might be caused by a diminished dopaminergic neurotransmission.

Ovarian and placental hormones during prolactin suppression and stimulation in early human pregnancy.

Twenty-seven healthy females referred for legal abortion between the sixth and ninth week of pregnancy were treated for 1 week with either bromocriptine, metoclopramide or placebo. Serum prolactin was significantly (P < 0.01) elevated by metoclopramide and suppressed by bromocriptine. Despite a more than tenfold difference in circulating prolactin levels among these two groups, no significant difference was found in serum levels of progesterone, oestradiol, human chorionic gonadotrophin (hCG) human placental lactogen (hPL) or pregnancy specific B1-glycoprotein (SP1). These data suggest that circulating levels of prolactin below 150 ng/ml are without effect on either luteal or placental hormone secretion during early human pregnancy.