Time trends for alendronate prescription practices in women with chronic obstructive pulmonary disease and women exposed to systemic glucocorticoids.

UNLABELLED: Chronic obstructive pulmonary disease (COPD) and systemic glucocorticoid exposure are well-known risk factors of osteoporosis. We evaluated alendronate prescription practices related to COPD and exposure to systemic corticosteroids from 1996 to 2008 and showed an increasing targeting of alendronate treatment in patients with COPD and patients with systemic corticosteroid exposure. INTRODUCTION: COPD and systemic glucocorticoid exposure are well-known risk factors of osteoporosis and fragility fracture, but osteoporosis is often underdiagnosed and undertreated in these patients. This study aims to evaluate alendronate prescription practices related to COPD and/or to exposure to systemic glucocorticoids among Danish women. METHODS: A total of 388,314 female subjects >50 years old, 64,719 of whom initiated treatment with alendronate, and 323,595 age- and gender-matched controls were retrospectively identified between 1996 and 2008 from national health registers. Multivariate logistic regression was used for examining prescription practices, specifically if these risk factors (COPD or glucocorticoid exposure) increased or decreased the likelihood of beginning alendronate therapy. RESULTS: A diagnosis of COPD was associated with an increased likelihood of using alendronate (odds ratio (OR) 1.4, 95 % confidence interval (CI) 1.4-1.5, p < 0.001). Further, a diagnosis of COPD was associated with an increasing tendency of initiating alendronate treatment in the study period (OR 1.3 (95 % CI 1.1-1.5, years 1996-1999) to 1.5 (95 % CI 1.4-1.6, years 2006-2008), p < 0.01). Exposure to systemic glucocorticoids was associated with a significantly increasing (OR 3.6, 95 % CI 3.3-3.9 to OR 5.5, 95 % CI 5.3-5.8) probability of receiving alendronate treatment in the same observation period. CONCLUSION: This nationwide register-based study on alendronate prescription practices in Denmark shows an increasing targeting of alendronate treatment in patients with COPD and an even stronger trend for patients with systemic glucocorticoid exposure, perhaps indicating increased awareness of well-known and associated conditions.

Osteoporosis pharmacotherapy following bone densitometry: importance of patient beliefs and understanding of DXA results.

SUMMARY: Persistence with osteoporosis therapy remains low and identification of factors associated with better persistence is essential in preventing osteoporosis and fractures. In this study, patient understanding of dual energy X-ray absorptiometry (DXA) results and beliefs in effects of treatment were associated with treatment initiation and persistence. INTRODUCTION: The purpose of this study is to examine patient understanding of their DXA results and evaluate factors associated with initiation of and persistence with prescribed medication in first-time users of anti-osteoporotic agents. Self-reported DXA results reflect patient understanding of diagnosis and may influence acceptance of osteoporosis therapy. To improve patient understanding of DXA results, we provided written information to patients and their referring general practitioner (GP), and evaluated factors associated with osteoporosis treatment initiation and 1-year persistence. METHODS: Information on diagnosis was mailed to 1,000 consecutive patients and their GPs after DXA testing. One year after, a questionnaire was mailed to all patients to evaluate self-report of DXA results, drug initiation and 1-year persistence. Quadratic weighted kappa was used to estimate agreement between self-report and actual DXA results. Multivariable logistic regression was used to evaluate predictors of understanding of diagnosis, and correlates of treatment initiation and persistence. RESULTS: A total of 717 patients responded (72%). Overall, only 4% were unaware of DXA results. Agreement between self-reported and actual DXA results was very good (κ = 0.83); younger age and glucocorticoid use were associated with better understanding. Correctly reported DXA results was associated with treatment initiation (OR 4.3, 95% CI 1.2-15.1, p = 0.02), and greater beliefs in drug treatment benefits were associated with treatment initiation (OR 1.4, 95%CI 1.1-1.9, p = 0.006) and persistence with therapy (OR 1.8, 95% CI 1.2-2.7, p = 0.006). CONCLUSION: Our findings suggest that written information provides over 80% of patients with a basic understanding of their DXA results. Communicating results in writing may improve patient understanding thereby also improve osteoporosis management and prevention.

Plasma levels of interleukin-6 and C-reactive protein are associated with physical inactivity independent of obesity.

It is recognized that the path from physical inactivity and obesity to lifestyle-related diseases involves low-grade inflammation, indicated by elevated plasma levels of inflammatory markers. Interestingly, contracting skeletal muscle is a major source of circulating interleukin-6 (IL-6) in response to acute exercise, but with a markedly lower response in trained subjects. As C-reactive protein (CRP) is induced by IL-6, we hypothesized that basal levels of IL-6 and CRP reflect the degree of regular physical activity when compared with other markers of inflammation associated with lifestyle-related morbidity. Fasting plasma/serum levels of IL-6, IL-18, CRP, tumur necrosis factor-alpha (TNF-alpha), soluble TNF receptor II (sTNF-RII), and adiponectin were measured in healthy non-diabetic men and women (n=84). The amount of leisure-time physical activity (LTPA) was assessed by interview. Obesity was associated with elevated insulin, C-peptide, triglycerides, low-density lipoprotein, IL-6, CRP, and adiponectin (all P<0.05). Importantly, physical inactivity was associated with elevated C-peptide (P=0.036), IL-6 (P=0.014), and CRP (P=0.007) independent of obesity, age, gender, and smoking. Furthermore, the LTPA score was inversely associated with IL-6 (P=0.017) and CRP (P=0.005), but with neither of the other markers. The results indicate that low levels of IL-6 and CRP - not IL-18, TNF-alpha, sTNF-RII, or adiponectin - reflect regular physical activity.

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.

Bone mineral density and biochemical markers of bone turnover in patients with predialysis chronic renal failure.

BACKGROUND: Metabolic bone disease might commence early in the course of renal failure. This study therefore examined the frequency and severity of the skeletal changes in predialysis chronic renal failure by measurements of bone mineral density (BMD), biochemical markers of bone turnover (osteocalcin, bone-specific alkaline phosphatase, carboxy terminal propeptide of type I collagen, and carboxy-terminal telopeptide of type I collagen), parathyroid hormone (PTH), ionized calcium (Ca++), phosphate (P), and vitamin D metabolites. METHODS: The study was performed in 113 patients (male/female: 82/31) with chronic renal diseases [mean glomerular filtration rate (GFR) of 37 ml/min] and in 89 matched, normal control subjects. RESULTS: The patients had significantly (P<0.05) reduced BMD in the spine (-6.3%), the femur (-12.1%), the forearm (-5.7%), and the total body (-4.2%) as compared with the control subjects. Dividing the patients into quartiles according to GFR revealed that BMD decreased with the gradual decline in renal function at all the measured skeletal sites, but was most pronounced in the femur: 0.63+/-0.03, 0.74+/-0.02, 0.77+/-0.02, and 0.82+/-0.03 g/cm2 in each quartile from lowest to highest GFR compared with 0.82+/-0.02 g/cm2 in the control group (P<0.0001). All of the measured bone markers showed increasing plasma levels with the more advanced stages of renal failure. Serum PTH and serum P levels increased, whereas serum Ca++ and 1,25-dihydroxyvitamin D decreased. BMD Z-scores of the femur and of the forearm correlated to the biochemical markers and to PTH (P<0.05 to P<0.0001). The biochemical markers all showed strong correlations to PTH, also when corrected for the effect of the decline in GFR (r = 0.40 to 0.92, P<0.01 to P< 0.0001). CONCLUSION: Skeletal changes are initiated at an early stage of chronic renal failure, as estimated from reduced BMD and elevated levels of PTH and from the biochemical markers of both bone formation and bone resorption.

Impact of peripheral neuropathy on bone density in patients with type 1 diabetes.

OBJECTIVE: To investigate whether peripheral neuropathy (PN), as part of the microangiopathic complex, affects bone mineral density (BMD) of the peripheral or the axial skeleton in patients with type 1 diabetes. RESEARCH DESIGN AND METHODS: Three study groups were examined. Group 1 comprised 21 males with type 1 diabetes and severe PN with a mean (range) duration of diabetes of 28 (9-59) years and an HbA1c of 8.2% (6.3-10.4). Group 2 comprised 21 male type 1 diabetic patients with absent or mild PN matched to patients of group 1 regarding age, weight, and duration of diabetes. Group 3 comprised 21 control subjects. BMD was measured by dual-energy x-ray absorptiometry (DEXA) and by quantitative ultrasound of the calcaneus. PN was determined by biothesiometry. Levels of physical activity were assessed through guided questionnaires. RESULTS: In group 1, BMD was significantly reduced at all measured sites, compared with an expected Z score of 0 (spine, -1.01 +/- 0.34; femur, -0.94 +/- 0.25; forearm, -1.10 +/- 0.36). To a lesser extent, but still significantly, group 2 also showed reduced BMD values (spine, -0.60 +/- 0.26; femur, -0.55 +/- 0.25; forearm, -1.05 +/- 0.36), whereas group 3 had normal BMD values (-0.23 +/- 0.25, -0.10 +/- 0.21, -0.07 +/- 0.25, respectively). Group 1 had lower mean BMD levels than group 2 and group 3 at all measured sites, but a significant difference was found only between groups 1 and 3 at the site of the femur (analysis of variance, P < 0.05). Broadband ultrasound attenuation (BUA) of the calcaneus was significantly reduced in group 1 compared with groups 2 and 3 (108 +/- 3 vs. 115 +/- 2 and 115 +/- 2). Significant correlations between all DEXA measurements and BUA were demonstrated in both groups 1 and 2 (r values between 0.54 and 0.75). No significant differences in physical activity levels or body composition were demonstrated between the two patient groups. CONCLUSIONS: The present results suggest that in patients with type 1 diabetes, PN may be an independent risk factor for reduced BMD in the affected limbs as well as in the skeleton in general.

[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.

Regulators of calcium homeostasis and bone mineral density in patients with Crohn's disease.

BACKGROUND: Several papers have reported on vitamin D, parathyroid hormone (PTH), and other regulators of calcium metabolism in patients with Crohn's disease, but results have been conflicting. Bone mineral density (BMD) has been found to be reduced in several papers. A recent study from our laboratory suggested that the expected reduction in BMD disappears when the patients are compared with sex-, age-, and weight-matched healthy controls. The relationship between BMD and regulators of calcium homeostasis is not well established in patients with Crohn's disease. METHODS: BMD and biochemical regulators of calcium metabolism were measured in 115 unselected patients with Crohn's disease, most of whom were in remission. RESULTS: Vitamin D deficiency (25-OHD < or = 10 pg/ml) was present in 44% of patients. Secondary hyperparathyroidism was present in 2% of unoperated patients and in 18% of patients subjected to bowel operations. CONCLUSIONS: 1) Vitamin D deficiency is common in patients with Crohn's disease even when the disease is in remission and regardless of the location of the disease. 2) Secondary hyperparathyroidism is most frequently seen in patients who have undergone intestinal resection(s). 3) PTH correlates with BMD in a large group of unselected patients with Crohn's disease; 25-OHD only correlates with BMD of the forearm.

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.