Results from a national survey on the management of primary hyperparathyroidism.

BACKGROUND: Management of primary hyperparathyroidism (PHPT) continues to be challenging. At the Third International Workshop on PHPT, recent data on this disease were reviewed and new clinical recommendations were developed. There are few data on the influence of new guidelines in clinical practice. AIM: We designed an online survey that was sent to all Spanish hospital endocrinology services. METHODS: The questionnaire included 28 questions about diagnosis and management of PHPT. Ninety-nine of 131 sites (76%), giving health coverage to 70% of Spanish population, completed the survey. RESULTS: The reported incidence of PHPT was 9.95/100,000 person-years. Heighty percent of patients were asymptomatic. Each center performed a median (Q1, Q3) of 12 (6, 20) parathyroidectomies/year. The median (Q1, Q3) percentage of curative interventions (at first trial) was 90% (80, 95). The main reasons for not performing surgery were, by decreasing frequency: surgery contraindication, patient's refusal, loss of monitoring, limited surgery experience. Localization techniques were used in 83% of cases. The main criteria for parathyroidectomy in asymptomatic patients were Ca≥2.875 mmol/l (79%), Tscore ≤-2.5 SD at any site (91%), age <50 yr (80%) and glomerular filtration rate <60 ml/min/1.73 m 2 (82%). Minimally invasive surgery was performed in 42% of centers. Frequency of biochemistry and bone density determinations for non-surgically managed patients was in accordance with international guidelines. CONCLUSIONS: The clinical practice of Spanish endocrinologists is consistent with the recommendations of the guidelines from the Third International Workshop for the management of PHPT.

Association of ACACB polymorphisms with obesity and diabetes.

Acetyl-CoA carboxylase beta, encoded by the ACAB gene, plays an important role in the oxidation of fatty acids. The aim of this study was to check the hypothesis that allelic variants of ACACB influence the risk of obesity and type 2 diabetes mellitus. Twenty five tagging single nucleotide polymorphisms (SNPs) capturing common variants of the ACACB gene were selected and analyzed in two cohorts including 1695 postmenopausal women of the general population and in 161 women with severe obesity (BMI>35). In vitro binding of transcription factors was explored by electrophoretic mobility shift assays (EMSA). T alleles at the rs2268388 locus were overrepresented in women with severe obesity (18% vs. 10% in controls; OR 1.74 [95% confidence interval 1.30-2.47]), which was statistically significant after multiple-test adjustment (p=0.0004). Likewise, T alleles at the rs2268388 locus and C alleles at the rs2239607 locus were associated with diabetes, in the discovery as well as in the replication cohorts, even after women with severe obesity were excluded (OR 3.6 and 2.8, for TT and CC homozygotes, respectively). Allelic differences in the binding affinity for nuclear proteins were revealed in vitro by EMSA and competition experiments were consistent with the binding of glucorticoid receptor and serum response factor. In conclusion, common polymorphisms of ACACB gene are associated with obesity and, independently, with type 2 diabetes in postmenopausal women, suggesting that the activity of acetyl-CoA carboxylase beta plays an important role in these disorders related to energy metabolism.

Value of soluble CD30 in liver transplantation.

INTRODUCTION: CD30 is a membrane glycoprotein that belongs to the tumor necrosis factor superfamily. It is expressed on activated T cells. After activation of CD30(+) T cells, a soluble form of CD30 (sCD30) released into the bloodstream, can be measured in the serum. The aim of our study was to investigate the time course of serum levels of sCD30 during hepatic allograft rejection. MATERIALS AND METHODS: Serum levels of sCD30 were determined in 30 healthy subjects and 50 hepatic transplant recipients. These patients were divided into two groups: group I, 35 patients without rejection; and group II, 15 patients with acute rejection. Samples were collected on day 1 and 7 after transplantation and on the day of liver biopsy. RESULTS: The concentrations of sCD30 were similar in the rejection (40.4 +/- 16.5 U/mL) and nonrejection groups (43.0 +/- 18.2 U/mL) on postoperative day 1. We observed a significant increase in sCD30 levels in the rejection group on postoperative day 7 (76.3 +/- 61.8 U/mL vs 46.8 +/- 20.5 U/mL; P = .01). The difference increased when a diagnosis of acute rejection had been established: namely 133.0 +/- 113.5 U/mL versus 40.1 +/- 22.0 U/mL; (P = .001). These levels were also significantly higher during the entire postoperative period in all the patients, with or without rejection, than those observed in healthy controls (26.6 +/- 5.3 U/mL; P = .005). CONCLUSIONS: The release of circulating sCD30 is a prominent feature coinciding with the first episode of hepatic allograft rejection. So, monitoring of sCD30 levels may be useful for the early diagnosis of an acute rejection episode.

Fasting plasma ghrelin levels increase progressively after biliopancreatic diversion: one-year follow-up.

BACKGROUND: The role of ghrelin in weight control after surgery is not clear. We examined plasma ghrelin and leptin levels in patients with morbid obesity undergoing biliopancreatic diversion (BPD) of Scopinaro. METHODS: 30 adult patients (27 females, 3 males), undergoing elective BPD were recruited from the Hospital Surgery Service. Fasting blood samples for biochemical determinations were drawn before surgery and 1, 3 and 12 months after BPD. Human plasma ghrelin was measured by RIA. RESULTS: During the study period, weight, BMI and serum leptin levels decreased significantly at all sample points compared to preoperative values. Ghrelin plasma levels increased during the study, with statistical significance at 3 months and 1 year after surgery compared with preoperative levels. While leptin changes correlated with changes in BMI, no correlation was found between ghrelin and leptin or BMI changes. CONCLUSION: Plasma ghrelin levels could be decreased in obese patients as a compensatory mechanism to their nutritional state, but our results do not support the postulated beneficial role of ghrelin in the 1-year weight loss after BPD. They rather suggest that weight loss somehow stimulates ghrelin secretion, even in the absence of part of the stomach.

Levels of plasma total adrenomedullin are related with two acute phase inflammatory reactants (fibrinogen and sialic acid) but not with markers of endothelial dysfunction in Type 1 diabetes Adrenomedullin and vascular risk factors in Type 1 DM.

Adrenomedullin (AM), an ubiquitous regulatory peptide with different actions, is known to be elevated in different clinical situations, including diabetes mellitus (DM), but its potential role in the pathogenesis of diabetic vascular complications is not clear. In the present study, we examined plasma total AM levels, and their association with different markers of endothelial dysfunction and with other established risk factors for cardiovascular diseases, in patients with Type 1 DM. We studied a total of 155 patients, 117 patients without any kind of vascular complications, 24 patients with retinopathy only, and 14 patients with retinopathy and microalbuminuria but normal renal function. None of them had clinical evidence of atherosclerotic disease. Compared with the control group (64 healthy participants), patients had raised fibrinogen, soluble E-selectin ((s)E-selectin), vascular cellular adhesion molecule (VCAM), angiotensin converting enzyme (ACE), and von Willebrand factor (vWf) (P<.001 in all cases), but plasma total AM, endothelin (ET), sialic acid, and homocysteine were not raised. In the diabetic group, AM levels correlated significantly with sialic acid (r=.16; P<.05), but a more significant correlation was found with fibrinogen (r=.30; P<.001). No correlation was found with the other parameters studied. In summary, plasma total AM levels seem to correlate with inflammatory markers but not with endothelial dysfunction markers in Type 1 diabetic patients without atherosclerotic disease.

Low levels of intraplatelet cGMP in IDDM.

OBJECTIVE: To determine the levels of intraplatelet cGMP, an index of activity of the antiaggregatory nitric oxide pathway, in IDDM patients. RESEARCH DESIGN AND METHODS: We measured intraplatelet and plasmatic cGMP levels in 22 IDDM patients and 22 age- and sex-matched control subjects. RESULTS: Intraplatelet cGMP levels decreased in the IDDM patients (0.32 +/- 0.16 pmol/10(9) platelets) when compared with the control group (0.52 +/- 0.32 pmol/10(9) platelets), P = 0.032. Plasmatic cGMP levels were not significantly different between groups. Intraplatelet cGMP levels correlated negatively with the duration of the disease (r = -0.43, P < 0.05). CONCLUSIONS: IDDM patients have lower levels of intraplatelet cGMP, which may be responsible in part for their platelet hyperactivity.

Plasma adrenomedullin levels in type 1 diabetes. Relationship with clinical parameters.

OBJECTIVE: To assess the relationship between plasma adrenomedullin (AM) levels and the presence of microvascular complications in type 1 diabetic patients. RESEARCH DESIGN AND METHODS: We measured plasma AM and cAMP levels in 103 type 1 diabetic patients (46 without complications, 24 with retinopathy only, 14 with microalbuminuria but normal kidney function, and 19 with renal insufficiency) and 41 matched healthy control subjects. RESULTS: Patients with renal insufficiency had higher levels of AM and cAMP than all other groups. Patients with only retinopathy showed a trend to have higher levels than patients without complications. There were no differences among all other groups. There was a significant correlation between AM and cAMP in the total diabetic group (rs = 0.36, P < 0.001) but not in the control group. In multiple regression analysis, plasma AM demonstrated significant relationships with creatinine clearance (beta = -0.31, P = 0.004) and duration of the disease (beta = 0.28, P = 0.008). CONCLUSIONS: Plasma AM and cAMP are increased in type 1 diabetic patients with renal insufficiency. Creatinine clearance (CrClc) and duration of the disease are related to plasma AM levels in these patients.

(18)F-sodium fluoride PET/CT for the in vivo visualization of Mönckeberg's sclerosis in a diabetic patient.

Diabetes is a major frequent cause of atherosclerosis vascular disease. Arterial calcification in diabetic patients is responsible for peripheral vascular involvement. Molecular imaging using (18)F-sodium fluoride ((18)F-NaF) positron emission tomography (PET)/computed tomography (CT) has been recently proposed as a marker to study the in vivo mineralization process in the atheroma plaque. A 69-year-old man with a history of type 2 diabetes and no clinical evidence of peripheral arterial disease underwent an (18)F-NaF PET/CT scan. A linear, well-defined (18)F-NaF uptake was detected along the femoral arteries. In addition, the CT component of the PET/CT identified an unsuspected "tram-track" calcification in his femoral arteries, suggestive of medial calcification (Mönckeberg's sclerosis). In other vascular territories, focal (18)F-NaF uptake was also detected in carotid and aorta atheroma plaques. Molecular imaging with (18)F-NaF PET/CT might provide new functional information about the in vivo vascular calcification process in diabetic patients.

Seasonal deficiency of vitamin D in children: a potential target for osteoporosis-preventing strategies?

Peak bone mass attained after skeletal growth is a major determinant of the risk of developing osteoporosis later in life, hence the importance of nutritional factors that contribute to bone mass gain during infancy and adolescence. An adequate supply of vitamin D is essential for normal bone homeostasis. This study was undertaken to determine what the levels are of 25-hydroxyvitamin D (25(OH)D) that may be considered desirable in children and to assess if normal children maintain these levels throughout the year. Vitamin D metabolites and parathyroid hormone (PTH) serum levels were measured in 21 children in March and October, prior to and after the administration of a daily supplement of 25(OH)D (40 microg for 7 consecutive days). There were inverse correlations between basal 25(OH)D levels and supplementation-induced changes in serum 1,25(OH)2D (r = 0.57, p < 0.05) and PTH (r = 0.41, p < 0.05). When basal levels of 25(OH)D were below 20 ng/ml, the supplement induced an increase in serum 1,25(OH)2D; with basal 25(OH)D under 10-12 ng/ml, the supplement also decreased serum PTH. The lowest serum level of 25(OH)D in 43 normal children studied in summer was 13 ng/ml. Those results suggested that the lowest limit for desirable levels of 25(OH)D in children was somewhere between 12 and 20 ng/ml. However, 31% of 51 normal children studied in winter had levels below 12 ng/ml, and 80% had levels lower than 20 ng/ml. Those children are likely to have suboptimal bioavailability of vitamin D, which might hamper their achievement of an adequate peak bone mass. Since cutaneous synthesis of vitamin D is rather limited in winter, oral vitamin D supplementation should be considered.

Expression and functional role of nitric oxide synthase in osteoblast-like cells.

Nitric oxide synthases (NOS) are enzymes that produce nitric oxide (NO) from L-arginine in a reaction yielding citrulline as a coproduct. Nitric oxide modulates the activity of a wide variety of cells, but little is known about its effects on bone cells. In the present study we report that the NOS inhibitor NG-monomethyl-L-arginine (NMMA) induced a dose-dependent inhibitory effect on the proliferation of the osteoblast-like cell lines MG63 and ROS 17/2.8. The inhibitory effect was prevented by increasing L-arginine concentrations in the medium and by the NO donor sodium nitroprusside. Likewise, NMMA inhibited interleukin-6 secretion, independently of its effect on cell number. NOS expression by MG63 cells was confirmed by measuring their ability to metabolize radiolabeled L-arginine to citrulline. NOS bioactivity was detected in unstimulated cells, but was markedly increased by stimulating the cells with cytokines, lipopolysaccharide, or 1,25-dihydroxyvitamin D3. NOS activity was partially dependent upon the presence of calcium in the medium. Furthermore, constitutive-type NOS (c-NOS) and inducible-type NOS (i-NOS) mRNA expression was detected in ROS 17/2.8 cells after reverse transcription and polymerase chain reaction amplification. In conclusion, osteoblast-like cells express c-NOS and i-NOS, and NOS activity seems to play an important role in the regulation of cell proliferation and function.

Sex and age distribution of 1,25(OH)2D3 receptors in peripheral blood mononuclear cells from normal human subjects.

Specific receptors for 1,25 Dihydroxyvitamin D3 have been described in human peripheral blood mononuclear cells (PBMC). We have tried to find out whether these receptors could show any difference in sex or age distribution. Twenty two healthy men aged 21-66 yr (mean +/- SD 41.0 +/- 13.6) and nineteen healthy women aged 22-60 yr (38.9 +/- 13.9) have been studied. The mean dissociation constant (Kd) was similar in both sexes (1.35 +/- 0.70 x 10(-10) M in males, 1.13 +/- 0.66 x 10(-10) M in females), but the concentration of binding sites (Nmax) was significantly lower in females (2.32 +/- 0.92 fmol/10(7) PBMC vs 4.43 +/- 1.38 fmol/10(7) PBMC in males; p = 0.0001). Neither Kd nor Nmax were significantly correlated with age. No difference was found between pre and postmenopausal women. Further studies are needed to elucidate if this sex difference in PBMC receptors for 1.25 Dihydroxyvitamin D3 is of any pathophysiological relevance.

Effect of calcitriol on the secretion of prostaglandin E2, interleukin 1, and tumor necrosis factor alpha by human monocytes.

Cells of the monocyte/macrophage lineage express specific receptors for calcitriol (1,25-dihydroxyvitamin D3) and secrete prostaglandins and several cytokines with potent effects on bone metabolism. The aim of this study was to determine the effect of calcitriol on the secretion of prostaglandin E2 (PGE2), interleukin-1 (IL-1), and tumor necrosis factor (TNF alpha). Monocyte-enriched peripheral blood mononuclear cells (PBMC) from healthy subjects were cultured in the presence or absence of calcitriol (10(-11)-10(-7) M) and several stimulating agents. After 24 h, PGE2, IL-1, and TNF alpha were measured in the culture supernatants or lysates with specific immunoassays. Calcitriol induced a biphasic effect on PGE2 production by unstimulated cells and increased PGE2 synthesis by cells stimulated with either endotoxin or tau-interferon (IFN-tau). On the other hand, calcitriol inhibited the production of TNF alpha by monocytes stimulated with either IFN-tau or phorbol esters. This effect was not prevented by the addition of indomethacin, IL-1, or IL-2. Under the conditions used, we observed no effect of calcitriol on IL-1 alpha or IL-1 beta production. These results indicate that calcitriol induces in vitro marked changes in the secretion of monocyte products with known activity on bone cells. Further studies are needed to elucidate whether some effects of calcitriol on bone metabolism are mediated by the interaction of the sterol with cells of the immune system.

Vitamin D metabolism and serum binding proteins in anorexia nervosa.

Serum vitamin D metabolites and other parameters of mineral metabolism were measured in 12 patients with anorexia nervosa. Serum concentrations of calcium, phosphate, albumin, alkaline phosphatase, parathyroid hormone, calcitonin, osteocalcin, and 24-hours calcium excretion were normal. Serum 25-hydroxyvitamin D (25OHD) concentration was similar in patients and normal subjects, whereas 1,25-dihydroxyvitamin D (1,25(OH)2D) levels were significantly reduced in patients (62 +/- 17 vs 82 +/- 17 pmol/l); p less than 0.05). The concentration of vitamin D-binding protein (DBP) in patients was normal, but serum binding capacity (Nmax) was diminished in anorectic patients (2.05 +/- 0.50 vs 2.53 +/- 0.51 mumol/l; p less than 0.05). The diminished serum binding capacity, in spite of normal concentrations of albumin and DBP, reflects the presence of qualitative rather than quantitative defects in serum transport proteins. Since the reduction in 1,25(OH)2D and serum binding capacity was quantitatively similar, it is likely that free 1,25(OH)2D levels would be normal.

Effects of radiation on endothelial function.

PURPOSE: The response of endothelium to ionizing radiation was studied. METHODS AND MATERIALS: The abdominal aorta in different experimental groups of rats was irradiated, and the response of arterial rings from the irradiated segments to norepinephrine, acetylcholine (ACh), and nitroglycerin (NTG) was studied. Nonirradiated thoracic segments in the same experimental animals were used as as a control for comparisons. Two age-matched nonirradiated control groups were also studied. RESULTS: A poor endothelium-dependent vasodilator response was obtained with ACh in the irradiated rings and also in those not directly irradiated; the endothelium-independent vasodilator response to NTG was preserved during the first 3 days after irradiation. By 6 months, both the endothelium-dependent response and endothelium-independent response were impaired. CONCLUSIONS: Alterations in nitric oxide synthesis and/or release by the endothelium were observed during the early phase of radiation in irradiated and nonirradiated segments. In the delayed phase of radiation, endothelium-independent muscular relaxation was also affected.

Different time course of circulating adhesion molecules and hyaluran during hepatic allograft rejection.

BACKGROUND: Inducible adhesion molecules are involved in cell-mediated allograft rejection. In addition, the endothelium is the main target of this process. This study investigated, whether soluble (s) forms of vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) are elevated during cellular rejection and whether hyaluran is a useful marker of endothelial function in liver transplantation. METHODS: Serum levels of sICAM-1, sVCAM-1, and hyaluran were determined in 24 controls and 27 hepatic transplant recipients. These patients were divided in two groups: group I, 14 patients without rejection; and group II, 13 patients with rejection. Samples were collected on day 1 and 7 after transplantation, on the day of liver biopsy, and after treatment of the rejection. RESULTS: We found a significant increase in sICAM-1 levels in the postoperative period in the rejection group compared with the non rejection group. It persisted significantly elevated until the diagnosis of rejection was made. In contrast, sVCAM-1 was only significantly elevated in the rejection group when diagnosis of rejection was evident. Hyaluran levels were also significantly elevated in the rejection group at diagnosis of rejection. We noticed a significant decline in sICAM-1, sVCAM-1, and hyaluran levels after successful treatment of rejection. In addition, we observed in the non-rejection group a stable lower levels of hyaluran during the entire postoperative period. CONCLUSIONS: The release of circulating adhesion molecules is a prominent feature coinciding with the first episode of hepatic rejection. Differential patterns of sICAM-1 and sVCAM-1 exist during rejection. In addition, hyaluran levels may be a sensitive marker of liver endothelial cell function in the postoperative period of liver transplantation.

Blood levels of cytokines in brain-dead patients: relationship with circulating hormones and acute-phase reactants.

We hypothesized that increased levels of blood cytokines occur in brain-dead patients, and that these cytokines are responsible for some of the endocrine and/or acute-phase reactant abnormalities found in these patients. We measured blood levels of cytokines, hormones, and acute-phase reactants in 18 brain-dead potential organ donors at the moment of establishing the legal diagnosis of brain death and compared them with levels found in a control group. Although interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) levels were within the normal range, interleukin-6 (IL-6) levels were clearly above the normal range in all patients (median, 1,444 pg/mL; range, 75 to 11,780). In the brain-dead group, total thyroxine (tT4), free T4 (fT4), triiodothyronine (T3), thyrotropin (TSH), dehydroepiandrosterone sulfate (DHEA-S), testosterone, albumin, Zn, and osteocalcin levels were decreased, T3 resin uptake index (T3 RUI), corticotropin (ACTH), cortisol, 11-deoxycortisol (11-DOC), 17-hydroxyprogesterone (17-OHPr), aldosterone, luteinizing hormone, and follicle-stimulating hormone levels were normal, and reverse T3 (rT3), renin, and C-reactive protein (CRP) levels were increased. Multiple regression analysis demonstrated significant interrelations between IL-6 and T4, T3, testosterone, and CRP. We also studied the evolution of some of these parameters in four patients with severe head injury who finally developed brain death. IL-6 levels on admission to the intensive care unit (ICU) were above the normal limits, as in other patients with cranial trauma, but when the patients developed brain death, there was a pronounced increase in IL-6 levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Parathyroidectomy in dialysis patients.

Subtotal parathyroidectomy or total parathyroidectomy (PTx) with autotransplantation are surgical procedures considered while the patient is included on the waiting list for renal transplantation. Total PTx alone is based in the possibility that a fragment of tissue (nodular hyperplasia in particular) left in the same pathophysiological environment of long term dialysis would show the same behavior and reproduce in time the same clinicopathological picture. The persistence of uremia induces a continued growth stimulus developing residual hyperplasia and consequently a very high risk of recurrence. We performed total PTx alone in 15 uremic patients excluded for renal transplantation 10 patients with undetectable iPTH serum concentration and were followed up for 37 to 144 months. There was no evidence of clinical bone disease (bone pain or fractures). Bone mineral lumbar spine and hip density was measured at the end of follow-up. The z score data showed that all patients had a bone mass similar than that expected for their age. Bone biopsies performed in four patients showed a uniform picture of low turnover without aluminium staining. Calcification of small arteries (digital and arcade vessels in hands and feet) were evaluated pre and post total PTx alone in nine out of the 10 patients with undetectable PTH levels. The small vessel calcification was present in five patients at the moment of PTx. At the end of the long term follow-up only one patient showed progression. In conclusion, total PTx without autotransplantation is a very effective and adequate treatment for refractory severe hyperparathyroidism in patients excluded for renal transplantation. Aluminium related osteopathy post PTx is a risk to be controlled with aluminium "free" dialysis water and avoiding aluminium containing phosphate binders.

Induction of nitric oxide synthase in human mammary arteries in vitro.

This study investigated whether human mammary arteries express an inducible nitric oxide (NO) synthase and, if so, what its effects are on vascular tone. In human mammary artery pre-contracted with phenylephrine there was a gradual time-dependent loss of tone over an 8 h period. L-Arginine and lipopolysaccharide enhanced the rate but not the magnitude of this loss in tone, whereas NG-nitro-L-arginine, NG-monomethyl-L-arginine, dexamethasone, and polymyxin B inhibited these effects. These findings indicate that incubation of human mammary artery with lipopolysaccharide resulted in the expression of an inducible NO synthase. The induction of this enzyme in human vessels may be important in the pathogenesis of septic shock.

Venous endothelial function in postmenopausal women who are receiving long-term estrogen and progestagen therapy.

OBJECTIVE: To test venous endothelial function during long-term hormone replacement therapy (HRT) and after treatment withdrawal. DESIGN: Measurement of dorsal hand-vein diameter by venous occlusion plethysmography during infusion of norepinephrine, bradykinin, NG-monomethyl L-arginine, and sodium nitroprusside. SETTING: Plethysmography and menopause units, University Hospital Marqués de Valdecilla, Santander, Spain. PATIENT(S): Twenty postmenopausal women, of whom 10 were assigned to receive no hormone replacement therapy (HRT) for 6 months after plethysmography (group A) and 10 were assigned to receive HRT for 6 months (group B). After 6 months, HRT was administered to group A and withdrawn from group B for another 6 months. INTERVENTION(S): Plethysmography at baseline and at 6 and 12 months. MAIN OUTCOME MEASURE(S): Dorsal hand-vein diameter measured by venous occlusion plethysmography during infusion of norepinephrine, bradykinin, NG-monomethyl L-arginine, or sodium nitroprusside. RESULT(S): At 6 months, the maximum dilation obtained with bradykinin was 48.8 +/- 7.58% in group A and 76.7 +/- 12.9% in group B. At 12 months, maximum bradykinin dilation increased to 74.3 +/- 14.2% in group A and decreased to 54.0 +/- 15.9% in group B. CONCLUSION(S): Long-term HRT with estrogen plus progestin improves endothelium-dependent vasodilation, but this effect is lost in a relatively short time. Endothelial function in dorsal hand veins is an easy-to-use plethysmography model that can be used in serial studies.

Decreased plasma endothelin-1 levels in asymptomatic type I diabetic patients with regional cerebral hypoperfusion assessed by Spect.

The prevalence of stroke is increased in diabetic patients. The vasoconstrictor peptide endothelin-1 (ET-1) has been implicated in the development of cerebral vasospasm after stroke but its role in the physiological regulation of cerebral blood flow (CBF) is not well known. Our aim was to assess the relationship between CBF and plasma ET-1 levels in type I diabetic patients. Regional CBF was assessed semi-quantitatively by 99Tc(m)-hexamethylpropylene-amine-oxime (99Tc(m)-HMPAO) single photon emission computed tomography (SPECT) in 50 cerebral "regions of interest" (ROIs) of 19 type I diabetic patients without clinical evidence of cerebral disease, and 10 healthy control subjects. In both groups, plasma ET-1 levels were measured. Results showed that type I diabetic patients had significantly more hypoperfusion ROIs than control subjects. While up to 68.4% of the type I diabetic patients showed 3 or more hypoperfusion ROIs, only 10% of the control subjects did. Plasma ET-1 levels were lower in the type I diabetes subgroup with 3 or more hypoperfusion ROIs than in the type I diabetes subgroup with less than 3 hypoperfusion ROIs and in the control group. Moreover, an inverse correlation between the number of hypoperfusion ROIs and plasma ET-1 levels (r = 0.47, p = 0.04) was found in the type I diabetes group. It is concluded that plasma ET-1 is decreased in type I diabetic patients with subclinical abnormalities of regional CBF assessed by cerebral SPECT. This fact may reflect a compensatory response to the reduction of the brain perfusion in order to prevent ischemic events in these patients.