Bone mineral density in human immunodeficiency virus-1 infected men with hypogonadism prior to highly-active-antiretroviral-therapy (HAART).

Alterations of bone metabolism have been observed in numerous studies of HIV-infected patients. Sex steroids are known to profoundly influence bone mass and bone turnover. Hypogonadism is common in HIV-infection. Therefore, we performed a cross sectional study of 80 male HIV-infected patients without wasting syndrome, and 20 healthy male controls, in whom we analyzed urine and serum samples for both calciotropic hormones and markers of bone metabolism and of endocrine testicular function. Bone mineral density (BMD) was assessed by dual-energy X-ray absorptiometry both in the lumbar spine and Ward's triangle of the left hip. None of the patients received highly-active-antiretroviral-therapy (HAART). Compared to eugonadal HIV-infected patients, subjects with hypogonadism (n = 32; 40%) showed statistically significant decrease of serum osteocalcin (p < 0.05) and elevated urinary excretion of crosslinks (p < 0.05). However, we found 13 and 15, respectively, patients with osteopenia (t-score -1.0 to -2.5 SD below normal) of the lumbar spine. The dissociation between bone formation and resorption and the reduction of of BMD (p < 0.05) is stronger expressed in patients with hypogonadism. Habitual hypogonadism appears to be of additional relevance for bone metabolism of male HIV-positive patients prior to HAART.

Parathormone levels and Vitamin D metabolism in female patients with various grades of fecal elastase 1 deficiency.

BACKGROUND: There are still too few conclusive reports about conspicuous parathormone (PTH) and Vitamin D metabolism in patients with fecal elastase 1 deficiency or any connection of the calcium metabolism to the severity of exocrine pancreas insufficiency. METHODS: Between March 1998 and September 2002, we investigated on 240 female patients with fecal elastase 1 deficiency at an average age of approx. 56.4 years and suffering from meteorism and weight loss as well as on age matched 80 healthy female controls. Serum levels of PTH, total calcium, D subset3-vitamins, calcitriol and calcefediol, as well as the concentration of fecal elastase 1 were determined in patients and controls. RESULTS: In 240 female patients with deficiency of fecal elastase 1 only two patients show milder cases of new diagnosed primary hyperparathyroidism. Calcitriol was markedly decreased (14.3 +/- 6.1 and 20.7 +/- 9.4 pg/ml) compared to controls (41.8 +/- 8.3 pg / ml) ( p < 0.01). Calcefediol was not significantly different within the various elastase-groups (p = 0.07). Nevertheless, vitamin D subset3 and fecal elastase 1 in patients correlated significantly (p < 0.01) and, compared to controls, both were extremely low (means in patients. Both D subset3-vitamins in patients were significantly lower when elastase 1 in feces was under 200 microg/g compared to the others (for calcitriol p < 0.05, for calcefediol p < 0.05). CONCLUSION: In female patients elastase 1 in feces confirm the grade of vitamin D supply, and thus show a vitamin D subset3-deficiency, depending on the loss of stool content. There seems to be a connection here between the loss of exocrine function and may be even the characteristic of sterol-binding of elastase 1 in the pancreas, which seems to be relevant for vitamin D-supply.

Benfotiamine in diabetic polyneuropathy (BENDIP): results of a randomised, double blind, placebo-controlled clinical study.

AIM: Efficacy and safety of benfotiamine in treatment of diabetic polyneuropathy. METHODS: Double blind, placebo-controlled, phase-III-study. 181 patients were screened. 165 patients with symmetrical, distal diabetic polyneuropathy were randomised to one of three treatment groups entering the wash-out phase and 133/124 patients were analysed in the ITT/PP analysis: Benfotiamine 600 mg per day (n=47/43), benfotiamine 300 mg per day (n=45/42) or placebo (n=41/39). RESULTS: After 6 weeks of treatment, the primary outcome parameter NSS (Neuropathy Symptom Score) differed significantly between the treatment groups (p=0.033) in the PP (per protocol) population. In the ITT (intention to treat) population, the improvement of NSS was slightly above significance (p=0.055). The TSS (Total Symptom Score) showed no significant differences after 6 weeks of treatment. The improvement was more pronounced at the higher benfotiamine dose and increased with treatment duration. In the TSS, best results were obtained for the symptom "pain". Treatment was well tolerated in all groups. CONCLUSION: Benfotiamine may extend the treatment option for patients with diabetic polyneuropathy based on causal influence on impaired glucose metabolism. Further studies should confirm the positive experiences.

Growth hormone and bone mineral densitiy in HIV-1-infected male subjects.

The aim of this study was to characterize the GH-IGF-I axis of patients with HIV-1-infection without any symptoms of AIDS-associated wasting. A special emphasis was placed on determine bone mineral density (BMD) and biochemical markers of bone metabolism. Therefore 42 male fasting HIV-1-infected outpatients were included and estimation of serum GH, IGF-I, IGFBP-1 and 3, osteocalcin, TNF-alpha, 1,25dihydroxycholecalciferol, and endocrine markers of the gonad function by commercially available RIA's performed. DEXA-measurements of the lumbar spine and the Ward's triangle of the left hip were done. The GH, IGF-1, IGFBP-1 and 3 serum levels were within the normal range Performing Spearman-correlation test, we established significance between IGF-I serum levels and BMD lumbar spine and Ward's triangle (p < 0.01, p < 0.05), CD4 cell-count (p < 0.05), 1,25dihydroxycholecalciferol (p < 0.05), osteocalcin (p < 0.05), TNF-alpha (p < 0.05), body mass index (BMI) (p < 0.05) and total testosterone (p < 0.01). IGFBP-1 correlates both inversely significantly with CD4 cell-count (p < 0.05) and serum-calcium (p < 0.05). The IGFBP-3 correlates with BMI (p < 0.05) and serum osteocalcin (p < 0.05). Correlation both with markers of bone metabolism and vitamin D metabolites showed the important role of GH/IGF-I axis in modulating the availability of calcium in chronic conditions. This axis may be in a part responsible for the manifestation of the HIV-associated osteopenia.

Fecal elastase 1 and vitamin D3 in patients with osteoporotic bone fractures.

BACKGROUND AND AIMS: The aim of the present study was to clarify if patients with osteoporotic bone fractures have exocrine pancreatic insufficiency, especially reduced fecal elastase 1, connected with lowered serum levels of vitamin D3 that could be relevant for predominant osteoporosis. METHODS: Between October 1999 and September 2001, we investigated on 167 patients with an average age of approx. 69 years suffering from typical osteoporotic bone fractures, as well as 20 healthy controls with an average age of 53 years. A standardized osteodensitometry via dual energy X-ray absorptiometry (DEXA) was performed in all participants. Levels of PTH, 1,25(OH)(2) Vitamin D(3), 25(OH) Vitamin D(3), calcium and phosphate in serum, elastase 1 in feces as well as the body mass index were determined in all patients and controls. RESULTS: In patients 25(OH)D3 was more than 60% and 1,25(OH)(2)D(3) was more than 53% decreased compared to controls. Fecal elastase 1 was lower than the lowest reference of 200 microg/g feces in more than 34% of the patients and it was more than 65% reduced in comparison to healthy controls (fecal elastase 1 patients: 240.7 +/- 96.3 microg/g; controls 694.9 +/- 138.6 microg/g). Separation of the patients in accordance with the elastase 1 contend in feces into four groups (below 100 microg/g, between 100 and 200 microg/g, between 201 and 300 microg/g and above 300 microg/g) resulted in significant variations for 25(OH)D(3), 1,25(OH)(2)D(3), calcium and PTH between these groups (p < 0.01). Furthermore 25(OH)D(3), 1,25(OH)(2)D(3), calcium and PTH correlated significantly with elastase 1 in feces (p < 0.01) the way, that lower fecal elastase 1 was connected with lower levels of the other parameters. BMI shows no relevant differences within the patients or between patients and controls. CONCLUSION: Exocrine pancreatic insufficiency, especially lowered fecal elastase 1, may be much more frequent in patients with osteoporotic bone fractures than suggested so far. Lowered exocrine pancreatic function with lowered fecal elastase 1 seems to be relevant as a reason for reduced levels of circulating vitamin D3 metabolites being an appropriate additional cause for predominant osteoporosis.

Neural interactions within and beyond the critical band elicited by two simultaneously presented narrow band noises: a magnetoencephalographic study.

Neural activities elicited in the auditory system are systematically organized according to the frequency characteristics of corresponding sound inputs. This systematic frequency alignment, called 'tonotopy,' plays an important role in auditory perception. By means of magnetoencephalography (MEG) we investigated here interactions between neural groups activated by two simultaneously presented narrow-band noises (NBNs) within the human cortical tonotopic map. Auditory evoked fields indicated that the neural interactions activated by these NBNs depended on the frequency difference between them: the amplitude of the N1m-response systematically increased with increasing frequency difference between the NBNs until the critical bandwidth was reached. In contrast, the N1m decreased with frequency difference exceeding the critical bandwidth. The different N1m-response patterns within and beyond the critical band seem to result from the combination of inhibitory and excitatory neural processes in the auditory pathway and may contribute to the perception of complex sound patterns like speech and music.

Alterations of vitamin D3 metabolism in young women with various grades of chronic pancreatitis.

BACKGROUND: There are still too few conclusive reports about conspicuous vitamin D-deficiency in young female patients with chronic pancreatitis, or any connection of the deficiency to the severity of the disease. Therefore the aim of this study was to examine marker of vitamin D3 metabolism in female patients with episode of biliary pancreatitis to determine if increased severity of the disease would correlate with impaired vitamin D3 metabolism. METHODS: Between 1996 and 2003, we investigated 53 premenopausal patients with an average age of approximately 33 years suffering from an episode of chronic pancreatitis, as well as 30 female healthy controls with an average age of 32.4 years. The severity of chronic pancreatitis in patients was determined via endoscopic retrograde cholangiopancreaticography (ERCP) and assigned to 1 of 3 grades based on the Cambridge classification. Additional parameter assessed were demographics, smoking, consumption of alcohol and CD-transferrin, fasting metabolic parameters, biochemical markers of vitamin D3 metabolism and fecal elastase 1. None of the patients received hormone replacement therapy, Vitamin D or Calcium-supplementation. RESULTS: The serum levels of 1,25-dihydroxyvitamin D [1,25(OH2)D] were significantly reduced compared to female healthy controls. Fecal elastase 1 correlated with this classification of severity of chronic pancreatitis (p < 0.01). Furthermore, fecal elastase 1 of patients correlated the same way with both D-vitamins (p <0.01). The level of both D3 vitamins in patients were significantly lowered when the content of fecal elastase 1 was under 200 microg/g compared to the others [for 1,25-(OH2)D3 p < 0.01; 25-OH- D3 p < 0.01]. CONCLUSION: Premenopausal patients with chronic pancreatitis are at risk of developing decreased levels of 1,25(OH2)D3. This fact may contribute to a negative calcium balance and alteration of bone metabolism. Therefore, ERCP and fecal elastase 1 verify the severity grade of a chronic pancreatitis, and thus show a vitamin D3 deficiency in young women, depending on the progress of disease.

High prevalence of vitamin D deficiency, secondary hyperparathyroidism and generalized bone pain in Turkish immigrants in Germany: identification of risk factors.

INTRODUCTION: The aim of the study was to determine the prevalence of vitamin D deficiency, secondary hyperparathyroidism (sHPT), generalized bone pain and predictors of vitamin D deficiency in a cohort of 994 healthy adult urban residents (589 males, 405 females; age range: 16-69 years) consisting of 101 Germans, 327 Turkish residents of Turkey and 566 Turkish immigrants living in Germany. METHODS: The mean (+/- standard deviation) for 25-hydroxyvitamin D [25(OH)D] and biointact parathyroid hormone (BioPTH) for the German men and women was 68.4 nmol/l and 26.7 pg/ml, respectively. Turkish residents of Turkey had a mean 25(OH)D and BioPTH of 40.6 nmol/l and 27.5 pg/ml, respectively, whereas Turkish residents of Germany had a 25(OH)D of 38.1 nmol/l and a BioPTH of 35.6 pg/ml. RESULTS: Vitamin D insufficiency was common among Turkish nationals independent of whether they lived in Turkey or Germany; 75% had 25(OH)D levels of <50 nmol/l. Turkish females had a higher prevalence of 25(OH)D deficiency (<25 nmol/l) than Turkish males: 30 and 19% of Turkish females living in Germany and Turkey were severely vitamin D deficient compared to 8% and 6% of Turkish males living in Germany and Turkey, respectively. With respect to BioPTH levels, 31% of Turkish females and 21% of Turkish males had elevated BioPTH levels in contrast to only 15% of females and 4% of males living in Turkey. Unconditional logistic regression analysis identified the most important predictors for low 25(OH)D levels as sex, body mass index, lack of sun exposure and living at a higher latitude. Additionally, wearing a scarf and number of children were found to be an independent risk factor for vitamin D deficiency in Turkish women living in Turkey and Germany. A strong correlation between low 25(OH)D levels and higher rates and longer duration of generalized bone and/or muscle aches and pains (often diagnosed as fibromyalgia) was observed. CONCLUSION: Secondary hyperparathyroidism and vitamin D deficiency was found to be common among Turkish immigrants living in Germany, especially in veiled women. Therefore, the monitoring of vitamin D status--i.e. 25(OH)D and PTH--in Turkish immigrants is warranted and once a deficiency is identified, it should be appropriately treated.

[Osteoporosis in patients under oral anticoagulant treatment]. / Osteoporose bei Patienten unter oraler Antikoagulantien-Therapie.

BACKGROUND AND OBJECTIVE: Osteoporosis is thought to be one possible side-effect of oral anticoagulant therapy, especially after long-term treatment. Nevertheless, data concerning this problem only exist from earlier years. Therefore, we decided to look for the incidence of osteoporosis in patients under long-term oral anticoagulant treatment. PATIENTS AND METHODS: 30 patients (15 female, 15 male) - age between 38 and 77 years (average age 65,1+/-11,2 years) were examined. Group A: 10 patients with a capture time between 0,5 - 5 years, Group B: 10 patients with a capture time between 6 - 11 years, Group C: 10 patients with a capture time more than 11 years. The control group consisted 30 healthy persons - age between 39 and 81 years (18 female, 12 male, average age 61,5 +/- 12 years). RESULTS: In 21 out of 30 patients (9 female, 12 male) osteoporosis was found due to results of x-ray and bone-density-measurements. In 9 patients (6 female, 3 male) no osteoporosis was detected. No correlation between appearance of osteoporosis and duration of oral anticoagulant treatment was detected. Nevertheless, the number of patients presenting with osteoporosis in comparison with the control group was highly unexpected and astonishing. CONCLUSION: While treating patients with oral anticoagulants the possibility of appearing osteoporosis should be kept in view. In those circumstances the therapy should be supported by calcium and vitamin D.

Vitamin D receptor genotypes are not associated with rheumatoid arthritis or biochemical parameters of bone turnover in German RA patients.

OBJECTIVE: Vitamin D is known to exert immunomodulatory effects. An overrepresentation of the b allele of the vitamin D receptor (VDR) has been detected in autoimmune diseases as type-1-diabetes and multiple sclerosis. VDR polymorphisms have been shown to influence bone metabolism and bone density. The aim of the present study was to examine the distribution of VDR alleles in German rheumatoid arthritis (RA) patients and their relation to bone turnover parameters. METHODS: 62 German RA patients were included and compared to 40 controls. Three VDR alleles were examined (Bsm I, Taq I and Fok I). In addition, serum intact osteocalcin (OC), parathyroid hormone, bone specific alkaline phosphatase (B-ALP), the carboxyterminal extension peptide of type I procollagen, 25-OH-vitamin D and urinary deoxypyridinoline (DPD) excretion were measured. Furthermore, C-reactive protein, erythrocyte sedimentation rate and rheumatoid factor were measured. RESULTS: We found a slightly higher frequency of the bB and tT-genotype in RA patients compared to controls, which was not statistically significant. OC and B-ALP were found to be significantly higher in RA patients with positive correlations between bone formation and resorption parameters indicating higher bone turnover in RA patients with maintained coupling. CRP in RA patients correlated with DPD and inversely with PTH. VDR genotype showed no association with bone turnover, family history or the presence of rheumatoid factor. CONCLUSIONS: Our results suggest that VDR polymorphisms do not play a major role in RA predisposition in Germans.

Osteopenia in HIV-infected women prior to highly active antiretroviral therapy.

BACKGROUND AND OBJECTIVES: Multiple endocrine and metabolic consequences of human immunodeficiency (HIV) infection exist that alter bone metabolism in patients with acquired immune deficiency syndrome (AIDS). Osteopenia in AIDS patients has been associated with antiretroviral therapy particularly with protease inhibitors. However, there is very little data on bone metabolism in female subjects with AIDS prior to highly active antiretroviral therapy. METHODS: Bone mineral density (BMD) was assessed by dual-energy X-ray absorptiometry (DEXA) in 50 HIV-infected female outpatients (mean age 37 years) both in the lumbar spine and the Ward's triangle of the left hip. Additional parameter assessed were demographics, smoking, CD4 counts, fasting metabolic parameters and biochemical markers of bone metabolism. None of the patients received reverse transcriptase inhibitors or protease inhibitors, vitamin D or calcium-supplementation. RESULTS: The serum levels of parathyroid hormone and 1,25-dihydroxyvitamin D (1,25(OH2)D) were significantly reduced compared to 50 age-matched female healthy controls. Urinary calcium and pyridinium crosslinks-excretion corrected for creatinine excretion were elevated (P<0.01) and were likewise significantly correlated with the loss of CD4 cells (P<0.05). Serum osteocalcin was significantly lowered (P<0.01). Reduced BMD of the lumbar spine (t -score <-2.5 SD below normal) was found in seven patients (14%) and osteopenia (t -score -1.0 to -2.5 SD below normal) was diagnosed in 31 (62%). No patient had a fracture since being infected with HIV. The BMD was reduced both in lumbar spine and the hip measured in the left Ward's triangle. There were significant positive correlation between the CD4 counts and 1,25(OH2)D (P<0.05). Neither the CD4 counts nor the duration of disease correlated with BMD. The reduced bone formation rate was linked to progressive loss of CD4-cell count. CONCLUSION: Osteopenia in HIV-infected female subjects is commonly manifested both in lumbar spine and Ward's triangle of the hip. There is a dissociation between lowered markers of bone formation rate and the increased bone resorption expressed as elevated urinary crosslinks and calcium excretion. Furthermore, the decreased levels of 1,25(OH2)D may contribute to a negative calcium balance and inhibition of bone formation. Our results suggest that further research is necessary to determine, whether low levels of 1,25(OH2)D lead to an accelerated inflammatory process in AIDS, since 1,25(OH)2D is known as an endogenous immune modulator suppressing formation of activated T cells and cell proliferation.

Vitamin D3 in patients with various grades of chronic pancreatitis, according to morphological and functional criteria of the pancreas.

There are still too few conclusive reports about conspicuous vitamin D deficiency in patients with chronic pancreatitis, or any connection of the deficiency to the severity of the disease. Between October 1999 and September 2000, we investigated 42 patients at an average age of 53 years, suffering from chronic pancreatits, as well as 20 healthy male controls at an average age of 49 years. Serum levels of D3 vitamins, 1,25-(OH)2-vitamin D3 and 25-(OH)-vitamin D3, as well as the concentration of fecal elastase 1 were determined in patients and controls. Furthermore, the severity of chronic pancreatitis in patients was determined via endoscopic retrograde cholangiopancreatography (ERCP) into 3 grades, based on the Cambridge classification. Elastase 1 in feces revealed sensitivities of 14%, 87%, and 95% for Cambridge-grades I, II, and III, respectively, and correlated significantly with this classification of severity of chronic pancreatitis (P < 0.01). In patients with Cambridge-grade II and III 1,25-(OH)2-D3 was markedly decreased (26.7 +/- 7.7 pg/ml and 27.6 +/- 9.0 pg/ml) compared to those with Cambridge-grade I (38.0 +/- 10.5 pg/ml; between I and II P = 0.027, between I and III P = 0.033). 25-(OH)-D-3 did not differ significantly within the various Cambridge-grade groups (P = 0.07). Nevertheless, vitamin D3 and fecal elastase 1 in patients correlated significantly (P < 0.01) and, compared to controls, both were extremely low (means in patients: fecal elastase 1 140.7 +/- 75.7 microg/g, 1,25-(OH)2-D3 29.9 +/- 9.5 pg/ml, 25-(OH)-D3 26.7 +/- 9.7 nmol/liter; controls: fecal elastase 1 694.9 +/- 138.6 microg/g, 1,25-(OH)2-D3 67.5 +/- 4.3 pg/ml, 25-(OH)-D3 69.5 +/- 13.5 nmol/liter). The amounts of both D3 vitamins in patients were significantly lower when the content of fecal elastase 1 was under 200 microg/g compared to the others [for 1,25-(OH)2-D3 P < 0.01, for 25-(OH)-D3 P < 0.05]. Therefore, ERCP and fecal elastase 1 verify the severity grade of a chronic pancreatitis, and thus show a vitamin D3 deficiency, depending on the progress of the disease. There seems to be a connection between inflammatory pancreas destruction (Cambridge classification), exocrine insufficiency (fecal elastase 1), and perhaps even the characteristics of sterol-binding of pancreatic elastase 1, which seems to be relevant for vitamin D supply.

Alterations of bone mineral density and bone metabolism in patients with various grades of chronic pancreatitis.

The aim of this study was to examine bone mineral density (BMD) and bone metabolism in patients with chronic pancreatitis to determine if increased severity of the disease would correlate with increased bone loss. Between October 1999 and September 2000, we investigated 42 patients with an average age of approximately 53 years suffering from chronic pancreatitis, as well as 20 healthy male controls with an average age of 49 years. Dual energy x-ray absorptiometry (DEXA) was performed on patients and controls, and serum levels of parathyroid hormone (PTH), osteocalcin (OC), carboxy-terminal propeptide of type I procollagen (CICP), bone-specific alkaline phosphatase (BAP), 1,25(OH)(2) vitamin D(3) and 25(OH) vitamin D(3), as well as fecal elastase 1 were also determined. The severity of chronic pancreatitis in patients was determined via endoscopic retrograde cholangiopancreatography (ERCP) and assigned to 1 of 3 grades based on the Cambridge classification. BMD of patients with chronic pancreatitis was markedly decreased compared to controls (means in patients: DEXA lumbar vertebra anterior/posterior (LV ap) 96.8% +/- 4.2%, DEXA Ward's triangle (WARD) 92.2% +/- 5.2%; controls: DEXA LV ap 98.7% +/- 3.7%, DEXA WARD 97.1% +/- 3.1%; P <.05 and P <.0001) and correlated with the various Cambridge-grades (DEXA LV ap and DEXA WARD, P <.01). Fecal elastase 1 showed sensitivities of 14%, 87%, and 95% for the Cambridge-grades I, II, and III, respectively, and correlated with this classification of severity of chronic pancreatitis (P <.01). Furthermore, fecal elastase 1 of patients correlated the same way with both D(3)-vitamins (P <.01), as well as with parameters of BMD (P <.01). If fecal elastase 1 in patients was below 200 micro g/g, then the BMD and vitamin D(3) values were also significantly decreased compared to those with fecal elastase 1 above 200 micro g/g. In patients with Cambridge grades II and III 1,25(OH)(2)D(3) was markedly decreased (26.7 +/- 7.7 pg/mL and 27.6 +/- 9.0 pg/mL) compared to those with Cambridge grade I (38.0 +/- 10.5 pg/mL; between I and II, P =.027; between I and III, P =.033). 25(OH)D(3) was not significantly different within the various Cambridge groups (P =.07). Compared to controls, both D(3) vitamins, as well as fecal elastase 1, were extremely low (means in patients: fecal elastase 1, 140.7 +/- 75.7 micro g/g; 1,25(OH)(2)D(3), 29.9 +/- 9.5 pg/mL; 25(OH)D(3), 26.7 +/- 9.7 nmol/L; controls: fecal elastase 1, 694.9 +/- 138.6 micro g/g; 1,25(OH)(2)D(3), 67.5 +/- 4.3 pg/mL; 25(OH)D(3), 69.5 +/- 13.5 nmol/L). A significant correlation was observed between increased severity of chronic pancreatitis based on both endoscopic retrograde cholangiopancreatography and levels of fecal elastase 1, with decreased circulating levels of vitmain D(3) and decreased BMD. This supports a connection between the inflammatory destruction of the pancreas (Cambridge classification), exocrine pancreatic insufficiency (fecal elastase 1), altered levels of vitamin D metabolites, and loss of skeletal mass.

Longitudinal evaluation of serum estradiol and estrone in male patients infected with the human immunodeficiency virus.

In patients with human immunodeficiency virus (HIV) infection alteration of various endocrine functions have been described. However, there is limited information available on estrogens and their function in these patients. The aim of this study was to evaluate the pituitary and testicular endocrine markers: 14 HIV-positive men were included into the longitudinal study with a follow up to of 18 month period. None of the patients had a history or clinical evidence of endocrine dysfunction. Follicle stimulating hormone (FSH), luteinizing hormone (LH), prolactin, estrone, estradiol, and testosterone were measured in serum by commercially available radioimmunoassays. Prolactin levels were not affected in the patients. LH and FSH remained within normal range, but at the end of the study period we observed a significant increase of LH (p < 0.05). In addition, testosterone levels were normal with a slight reduction at the end of the 18-month observation period (p <0.05). Both estrone and estradiol were significantly increased with a further rise at the end of the study (p <0.05). In summary, the elevation of the serum estrone and estradiol in HIV-afflicted patients correlated with the progress of the HIV-disease, being paralleled by a decrease in testosterone. The altered relation of estrogens and testosterone may in a part be responsible for the complaints of decreased libido and increased impotence often observed in HIV-infected men.

VDR gene polymorphisms are overrepresented in german patients with type 1 diabetes compared to healthy controls without effect on biochemical parameters of bone metabolism.

Type 1 diabetic individuals are known to develop disorders of bone metabolism resulting in osteopenia. Previous studies have suggested an influence of vitamin D receptor alleles on bone metabolism and susceptibility for type 1 diabetes mellitus. The present study was initiated to investigate the distribution of vitamin D receptor alleles in Caucasian type 1 diabetic patients and their relation to bone turnover parameters. 75 patients were included and compared to 57 healthy controls. Three vitamin D receptor alleles were examined (BsmI, TaqI and FokI); serum levels of intact osteocalcin, parathyroid hormone, bone specific alkaline phosphatase, the carboxy terminal extension peptide of type I procollagen, 25-OH-vitamin D levels, HbA1c and urinary deoxypyridinoline excretion were measured. We observed a higher frequency of the TT genotype in diabetic patients, but no difference in markers of bone turnover between diabetics and non-diabetics in either sex. Bone turnover was different in men and in women without any association with vitamin D receptor genotype. No association was found between diabetes duration, age of onset or metabolic control and bone turnover parameters. In summary, our results show an association between the TT genotype and diabetes in Germans, but no difference in bone turnover markers between diabetics and non-diabetics.

Efficacy of benfotiamine versus thiamine on function and glycation products of peripheral nerves in diabetic rats.

In rats with streptozotocin (STZ) induced diabetes the effect of (watersoluble) thiamine nitrate and of (lipidsoluble) benfotiamine on peripheral nerve function (motor nerve conduction velocity) as well as on the formation of advanced glycation end-products in peripheral nerve tissue was studied. In one group of animals drug administration was started immediately after diabetes induction (prevention study) and in another group two months after diabetes induction (treatment study). Motor nerve conduction velocity (NCV) dropped by 10.5% in diabetic animals, carboxymethyl-lysine (CML) rose to a 3.5fold concentration, deoxyglucosone (3DG)-type AGE formation was increased 5.1fold compared with controls. After three months preventive administration of both vitamin B(1) preparations NCV had increased substantially compared with results in diabetic controls. It was nearly normal after six months with benfotiamine, while the administration of thiamine nitrate resulted in no further amelioration. NCV was nearly normalized after six months of benfotiamine application but not with thiamine. Furthermore, benfotiamine induced a major inhibition of neural imidazole-type AGE formation and completely prevented diabetes induced glycoxidation products (CML). Treatment with thiamine did not significantly affect AGE or cmL levels. Unlike treatment with water-soluble thiamine nitrate timely administration of liposoluble prodrug benfotiamine was effective in the prevention of functional damage and of AGE and cmL formation in nerves of diabetic rats.

Thyroid function, thyroid immunoglobulin status, and urinary iodine excretion after enteral contrast-agent administration by endoscopic retrograde cholangiopancreatography.

BACKGROUND AND STUDY AIMS: The aim of this study was to examine the occurrence of clinically relevant changes in thyroid function after enteral administration of contrast agent by endoscopic retrograde cholangiopancreatography (ERCP). PATIENTS AND METHODS: In this study 70 patients without a history of thyroid disease who had not recently undergone thyroid-specific or thyroid-influencing therapy were examined. Patients were examined on two or three occasions using a standardized questionnaire regarding symptoms of hypothyroidism and hyperthyroidism. The parameters of thyroid function (TT3, TT4, FT4, thyroid-stimulating hormone (TSH)) and urinary iodine excretion were measured on day 0 and on day 21 post-ERCP, and in 23 patients additionally on day 42 post-ERCP. Based on ultrasonographic results, four groups differing in thyroid morphology were distinguished. RESULTS: The data show that an average amount of only 4.7 g of enterally applied iodine is associated with a lasting decrease of TSH, especially in patients with enlarged organs with nodular transformation. As far as TT3 is concerned, there was a significant increase in all patient groups; regarding FT4 we only observed a marked increase in the group with enlarged, nodular thyroid glands. There was a notable increase in urinary iodine excretion on day 21, and a further increase on day 42 post-ERCP. Clinical symptoms of hyperthyroidism did not occur. CONCLUSIONS: We conclude that before administration of iodine-containing contrast agent for ERCP in patients without a history of thyroid disease, thyroid ultrasonographic examination, rather than TSH measurements, should be performed, in order to identify patients already at risk for hyperthyroidism before diagnostic enteral contrast-medium application.

Risk of new vertebral fracture in the year following a fracture.

CONTEXT: Vertebral fractures significantly increase lifetime risk of future fractures, but risk of further vertebral fractures in the period immediately following a vertebral fracture has not been evaluated. OBJECTIVE: To determine the incidence of further vertebral fracture in the year following a vertebral fracture. DESIGN AND SETTING: Analysis of data from 4 large 3-year osteoporosis treatment trials conducted at 373 study centers in North America, Europe, Australia, and New Zealand from November 1993 to April 1998. SUBJECTS: Postmenopausal women who had been randomized to a placebo group and for whom vertebral fracture status was known at entry (n = 2725). MAIN OUTCOME MEASURE: Occurrence of radiographically identified vertebral fracture during the year following an incident vertebral fracture. RESULTS: Subjects were a mean age of 74 years and had a mean of 28 years since menopause. The cumulative incidence of new vertebral fractures in the first year was 6.6%. Presence of 1 or more vertebral fractures at baseline increased risk of sustaining a vertebral fracture by 5-fold during the initial year of the study compared with the incidence in subjects without prevalent vertebral fractures at baseline (relative risk [RR], 5.1; 95% confidence interval [CI], 3.1-8.4; P<.001). Among the 381 participants who developed an incident vertebral fracture, the incidence of a new vertebral fracture in the subsequent year was 19.2% (95% CI, 13.6%-24.8%). This risk was also increased in the presence of prevalent vertebral fractures (RR, 9.3; 95% CI, 1.2-71.6; P =.03). CONCLUSION: Our data indicate that women who develop a vertebral fracture are at substantial risk for additional fracture within the next year.

[Thyroid function after iodine-containing contrast agent administration in coronary angiography: a prospective study of euthyroid patients]. / Schilddrüsenfunktion nach Gabe jodhaltigen Röntgenkontrastmittels bei Koronarangiographie--eine prospektive Untersuchung euthyreoten Patienten.

In a prospective study, thyroid metabolism in 102 patients undergoing diagnostic coronary angiography was investigated, stratified for thyroid morphology. The thyroid function serum parameters "TT3, rT3, TT4, fT4 and TSH" and the urinary iodine excretion were measured before and three weeks after diagnostic intraarterial administration of the iodine-containing contrast agent. Only patients with euthyroid function were included in order to answer the questions whether or not the administration of non-ionic iodine containing contrast medium leads to significant thyroid function changes in euthyroid patients and whether thyroid morphology is a prognostic factor for the risk of developing hyperthroidism. Serum concentrations of thyroid autoantibodies (TPO-Ab, Tg-Ab, TSH-receptor-Ab) were measured and thyroid ultrasound was performed. According to the ultrasound findings, 4 morphologic groups were formed: normal thyroid glands (n = 37), normal sized but nodular glands (n = 16), diffuse goiter (n = 15) and nodular goiter (n = 34). Twenty-five patients were positive for Tg-Ab; TPO-Ab were found in 13 patients. TSH-receptor-Abs were not detected in all patients. TT3 levels did not significantly change after iodine application (p = 0.30). TT4 and fT4 levels showed significantly different alterations in the 4 groups (fT4 p < 0.001). The amount of iodine given did not influence alteration of serum concentrations of TSH (p = 0.67), TT3 (p = 0.68), TT4 (p = 0.37), fT4 (p = 0.92) and rT3 (p = 0.81). Elevated levels of urinary iodine excretion correlated with the amount of contrast medium given (p = 0.087). Albeit there was a high number of nodular transformed glands and goitrous patients included, and our cohort was recruited in an iodine deficient area, we did not observe hyperthyroidism in any patient. However, thyroid function parameters are significantly altered after coronary angiography independent of antibody status and the amount of contrast agent given, but dependent on thyroid morphology.

Serum levels of immunoreactive bone sialoprotein in osteoporosis: positive relations to established biochemical parameters of bone turnover.

Bone Sialoprotein (BSP), synthesized by osteoblasts and osteoclasts, is a highly glycosylated and phosphorylated protein, accounting for approximately 5-10% of noncollagenous proteins of bone extracellular matrix. The present study investigates possible correlations between serum values of immunoreactive Bone Sialoprotein in relation to established bone turnover markers like osteocalcin (OC), bone alkaline phosphatase (B-ALP) and the c-terminal extension peptide of type-I-Procollagen (PICP) in 170 osteoporosis patients (female n = 144, male n = 26) in order to evaluate the usefulness of BSP in the diagnosis of bone disease. Fasting venous blood samples were collected from our osteoporosis outpatients in the morning and stored at -80 degrees C until processing. Serum levels of BSP were determined by RIA, OC and B-ALP were measured by IRMA, and PICP was assessed employing an ELISA technique. A significant correlation was found between BSP serum values and B-ALP (r = 0.532, p = 0.0001). Median serum BSP levels were 8.0 micrograms/l, median B-ALP values were 22.39 U/ml in these patients. Also a significant correlation was observed between BSP and OC (r = 0.588, p = 0.0001), more pronounced in the female patient group (r = 0.632, p < 0.0001). A weak association between BSP and PICP in the female group was detected (r = 0.398, p = 0.0001). In the female group BSP was inversely related to serum estradiol levels (r = -0.274, p = 0.002) as to BMD (DEXA) at the lumbar spine and femoral neck. In conclusion, BSP might be a useful marker of non-collagenous organic bone matrix in laboratory assessment of bone turnover, being inversely related to BMD at lumbar spine and femoral neck and showing significant correlations to established markers of bone turnover like B-ALP and OC.