Long-term denosumab treatment restores cortical bone loss and reduces fracture risk at the forearm and humerus: analyses from the FREEDOM Extension cross-over group.

Upper limb fractures (including wrist, forearm, and humerus) represent a significant burden among postmenopausal women with osteoporosis. Up to 7 years of treatment with denosumab resulted in an increase in bone mineral density and decrease in fractures in upper limb sites. INTRODUCTION: Upper limb (wrist, forearm, and humerus) fractures are a significant burden in osteoporosis, associated with significant morbidity and mortality. Denosumab, a monoclonal antibody against RANK ligand, increases bone mineral density (BMD) and decreases vertebral, nonvertebral, and hip fractures. Here, we evaluated the long-term effect of denosumab treatment on upper limb fracture risk and BMD. METHODS: In the FREEDOM trial, subjects were randomized 1:1 to receive every-6-month denosumab 60 mg or placebo subcutaneously for 3 years, after which all subjects could receive denosumab for up to 7 years (Extension). Among placebo subjects who completed FREEDOM and enrolled in the Extension, wrist, forearm, humerus, and upper limb fracture rates and rate ratios between different time periods (FREEDOM years 1-3, Extension years 1-3, and Extension years 4-7) were computed. BMD at the ultradistal radius, 1/3 radius, and total radius was analyzed in a subset of subjects in a BMD substudy. RESULTS: This analysis included 2207 subjects (116 in the BMD substudy). Fracture rates decreased over the 7-year Extension; fracture rate ratios between Extension years 4-7 (denosumab) and FREEDOM years 1-3 (placebo) reduced significantly for the wrist (0.57), forearm (0.57), humerus (0.42), and upper limb (0.52; p < 0.05 for all). Percentage increase in BMD from Extension baseline at the ultradistal radius, 1/3 radius, and total radius was significant by Extension year 7 (p < 0.05 for all). CONCLUSIONS: Long-term treatment with denosumab decreases upper limb fracture risk and increases forearm BMD, suggesting beneficial effects on both cortical and trabecular bone accruing over time.

Safety and efficacy of insulin degludec/insulin aspart with bolus mealtime insulin aspart compared with standard basal-bolus treatment in people with Type 1 diabetes: 1-year results from a randomized clinical trial (BOOST® T1).

AIMS: To evaluate the long-term safety and efficacy of a simplified basal-bolus regimen of once-daily insulin degludec/insulin aspart (IDegAsp) with additional IAsp vs. a standard basal-bolus insulin regimen of insulin detemir (IDet) with IAsp in adults with Type 1 diabetes. METHODS: This was an open-label trial comprising a 26-week core phase followed by a 26-week extension phase. Participants were randomized to IDegAsp once daily at the main meal and IAsp at remaining meals (IDegAsp+IAsp), or IDet (once or twice daily) and IAsp at all meals (IDet+IAsp). Insulins were titrated to target plasma glucose of < 5 mmol/l (< 90 mg/dl) at pre-breakfast (IDegAsp and IDet) and at pre-meal (IAsp). RESULTS: After 52 weeks, the overall confirmed hypoglycaemia rate was 31.8 episodes/patient-years of exposure (PYE) with IDegAsp+Asp and 36.7 episodes/PYE with IDet+IAsp, and the rate of nocturnal confirmed hypoglycaemia was significantly lower with IDegAsp+Asp than with IDet+IAsp (3.1 vs. 5.4 episodes/PYE, respectively; P < 0.05). Adverse event rates were comparable between groups. Mean HbA1c decreased from baseline by 0.7% (IDegAsp+IAsp) and 0.6% (IDet+IAsp), achieving 60 or 61 mmol/mol (7.6% or 7.7%, respectively), at Week 52. The mean total daily insulin dose was lower with IDegAsp+IAsp than with IDet+IAsp (ratio: 0.87; 95% CI 0.79-0.95; P = 0.0026). CONCLUSIONS: Once-daily treatment with IDegAsp and IAsp as bolus insulin for remaining meals was associated with significantly lower risk of nocturnal confirmed hypoglycaemia, improved glycaemic control and showed non-inferiority compared with IDet+IAsp, the standard of care in Type 1 diabetes.

LEADER 5: prevalence and cardiometabolic impact of obesity in cardiovascular high-risk patients with type 2 diabetes mellitus: baseline global data from the LEADER trial.

BACKGROUND: Epidemiological data on obesity are needed, particularly in patients with type 2 diabetes mellitus (T2DM) and high cardiovascular (CV) risk. We used the baseline data of liraglutide effect and action in diabetes: evaluation of CV outcome results-A long term Evaluation (LEADER) (a clinical trial to assess the CV safety of liraglutide) to investigate: (i) prevalence of overweight and obesity; (ii) relationship of the major cardiometabolic risk factors with anthropometric measures of adiposity [body mass index (BMI) and waist circumference (WC)]; and (iii) cardiometabolic treatment intensity in relation to BMI and WC. METHODS: LEADER enrolled two distinct populations of high-risk patients with T2DM in 32 countries: (1) aged ≥50 years with prior CV disease; (2) aged ≥60 years with one or more CV risk factors. Associations of metabolic variables, demographic variables and treatment intensity with anthropometric measurements (BMI and WC) were explored using regression models (ClinicalTrials.gov identifier: NCT01179048). RESULTS: Mean BMI was 32.5 ± 6.3 kg/m(2) and only 9.1 % had BMI <25 kg/m(2). The prevalence of healthy WC was also extremely low (6.4 % according to International Joint Interim Statement for the Harmonization of the Metabolic Syndrome criteria). Obesity was associated with being younger, female, previous smoker, Caucasian, American, with shorter diabetes duration, uncontrolled blood pressure (BP), antihypertensive agents, insulin plus oral antihyperglycaemic treatment, higher levels of triglycerides and lower levels of high-density lipoprotein cholesterol. CONCLUSIONS: Overweight and obesity are prevalent in high CV risk patients with T2DM. BMI and WC are related to the major cardiometabolic risk factors. Furthermore, treatment intensity, such as insulin, statins or oral antihypertensive drugs, is higher in those who are overweight or obese; while BP and lipid control in these patients are remarkably suboptimal. LEADER confers a unique opportunity to explore the longitudinal effect of weight on CV risk factors and hard endpoints.

Twice-daily insulin degludec/insulin aspart provides superior fasting plasma glucose control and a reduced rate of hypoglycaemia compared with biphasic insulin aspart 30 in insulin-naïve adults with Type 2 diabetes.

AIM: To evaluate the efficacy and safety of twice-daily insulin degludec/insulin aspart vs. twice-daily biphasic insulin aspart 30 in people with Type 2 diabetes mellitus who were naïve to insulin. METHODS: In this 26-week, multinational, open-label, controlled, two-arm, parallel-group, treat-to-target trial, participants [mean (± sd) age 58.9 (±8.9) years, duration of diabetes 9.5 (±5.9) years, HbA1c 68 (±8.7) mmol/mol or 8.4 (±0.8)% and BMI 31.2 (±4.2) kg/m(2) ) were randomized (1:1) to insulin degludec/insulin aspart (n = 197) or biphasic insulin aspart 30 (n = 197), administered with breakfast and the main evening meal, titrated to a self-monitored plasma glucose target > 3.9 and ≤ 5.0 mmol/l. RESULTS: The mean HbA1c was reduced to 49 mmol/mol (6.6%) with insulin degludec/insulin aspart and 48 mmol/mol (6.5%) with biphasic insulin aspart 30. Insulin degludec/insulin aspart achieved the prespecified non-inferiority margin (estimated treatment difference 0.02%; 95% CI -0.12, 0.17). Insulin degludec/insulin aspart was superior in lowering fasting plasma glucose (estimated treatment difference -1.00 mmol/l; 95% CI -1.4, -0.6; P < 0.001) and reducing overall and nocturnal confirmed hypoglycaemia at a similar overall insulin dose compared with biphasic insulin aspart 30. Similar proportions of participants in each arm experienced severe hypoglycaemia. Adverse events were equally distributed. CONCLUSIONS: Consistent with previous findings, insulin degludec/insulin aspart twice daily effectively improved long-term glycaemic control, with superior reductions in FPG, and significantly less overall and nocturnal confirmed hypoglycaemia compared with biphasic insulin aspart 30 in people with Type 2 diabetes who were insulin-naïve.

Randomized, double-blind clinical trial comparing basal insulin peglispro and insulin glargine, in combination with prandial insulin lispro, in patients with type 1 diabetes: IMAGINE 3.

AIMS: To compare the efficacy and safety of basal insulin peglispro (BIL), which has a flat pharmacokinetic and pharmacodynamic profile and a long duration of action, with insulin glargine (GL) in patients with type 1 diabetes. MATERIALS AND METHODS: In this phase III, 52-week, blinded study, we randomized 1114 adults with type 1 diabetes in a 3 : 2 distribution to receive either BIL (n = 664) or GL (n = 450) at bedtime, with preprandial insulin lispro, using intensive insulin management. The primary objective was to compare glycated haemoglobin (HbA1c) in the groups at 52 weeks, with a non-inferiority margin of 0.4%. RESULTS: At 52 weeks, mean (standard error) HbA1c was 7.38 (0.03)% with BIL and 7.61 (0.04)% with GL {difference -0.22% [95% confidence interval (CI) -0.32, -0.12]; p < 0.001}. At 52 weeks more BIL-treated patients reached HbA1c <7% (35% vs 26%; p < 0.001), the nocturnal hypoglycaemia rate was 47% lower (p < 0.001) and the total hypoglycaemia rate was 11% higher (p = 0.002) than in GL-treated patients, and there was no difference in severe hypoglycaemia rate. Patients receiving BIL lost weight, while those receiving GL gained weight [difference -1.8 kg (95% CI -2.3, -1.3); p < 0.001]. Treatment with BIL compared with GL at 52 weeks was associated with greater increases from baseline in levels of serum triglyceride [difference 0.19 mmol/l (95% CI 0.11, 0.26); p < 0.001] and alanine aminotransferase (ALT) levels [difference 6.5 IU/l (95% CI 4.1, 8.9), p < 0.001], and more frequent injection site reactions. CONCLUSIONS: In patients with type 1 diabetes, treatment with BIL compared with GL for 52 weeks resulted in a lower HbA1c, more patients with HbA1c levels <7%, and reduced nocturnal hypoglycaemia, but more total hypoglycaemia and injection site reactions and higher triglyceride and ALT levels.

The effect of 8 or 5 years of denosumab treatment in postmenopausal women with osteoporosis: results from the FREEDOM Extension study.

UNLABELLED: The FREEDOM study and its Extension provide long-term information about the effects of denosumab for the treatment of postmenopausal osteoporosis. Treatment for up to 8 years was associated with persistent reduction of bone turnover, continued increases in bone mineral density, low fracture incidence, and a favorable benefit/risk profile. INTRODUCTION: This study aims to report the results through year 5 of the FREEDOM Extension study, representing up to 8 years of continued denosumab treatment in postmenopausal women with osteoporosis. METHODS: Women who completed the 3-year FREEDOM study were eligible to enter the 7-year open-label FREEDOM Extension in which all participants are scheduled to receive denosumab, since placebo assignment was discontinued for ethical reasons. A total of 4550 women enrolled in the Extension (2343 long-term; 2207 cross-over). In this analysis, women in the long-term and cross-over groups received denosumab for up to 8 and 5 years, respectively. RESULTS: Throughout the Extension, sustained reduction of bone turnover markers (BTMs) was observed in both groups. In the long-term group, mean bone mineral density (BMD) continued to increase significantly at each time point measured, for cumulative 8-year gains of 18.4 and 8.3 % at the lumbar spine and total hip, respectively. In the cross-over group, mean BMD increased significantly from the Extension baseline for 5-year cumulative gains of 13.1 and 6.2 % at the lumbar spine and total hip, respectively. The yearly incidence of new vertebral and nonvertebral fractures remained low in both groups. The incidence of adverse and serious adverse events did not increase over time. Through Extension year 5, eight events of osteonecrosis of the jaw and two events of atypical femoral fracture were confirmed. CONCLUSIONS: Denosumab treatment for up to 8 years was associated with persistent reductions of BTMs, continued BMD gains, low fracture incidence, and a consistent safety profile.

A double blind randomized controlled trial investigating efficacy and safety of varenicline for smoking cessation in patients with type 2 diabetes: study protocol.

Reducing exposure to cigarette smoke is an imperative for public health and for diabetic patients. Patients with diabetes who continue to smoke face challenges at quitting and the delivery of effective smoking cessation interventions is a major unmet need. The high-affinity α4ß2 nicotinic acetylcholine receptor partial agonist varenicline in combination with counseling is effective for smoking cessation, but evidence in patients with diabetes is limited. A clinical trial of varenicline targeted specifically at smokers with T2DM is warranted. This randomized, double blind, placebo-controlled trial will be the first study to test efficacy and safety of varenicline in smokers with type 2 diabetes mellitus (T2DM) over the course of 52 weeks. We hypothesize that varenicline treatment (1 mg BID, administered for 12 weeks) would increase quit rates, maintain smoking abstinence up to 1 year after treatment, and be well-tolerated in T2DM smokers intending to quit. Efficacy end points will include carbon monoxide-confirmed continuous abstinence rate (CAR) and 7-day point prevalence of abstinence. The results of this RCT will help inform medical/health authorities and physicians worldwide whether an optimally varenicline-treated cohort of T2DM patients who smoke will experience significant success rates, without significant side effects.Trial registration NCT01387425 ( https://clinicaltrials.gov/ct2/show/NCT01387425 ).

Serum 1-84 and 7-84 parathyroid hormone concentrations and bone in patients with primary hyperparathyroidism.

BACKGROUND AND AIMS: Parathyroid hormone (PTH) acts on bone as both anabolic and catabolic factor. It includes two fractions: 1-84 (cyclase activating PTH, CAP) which increases bone turnover and serum calcium, and 7-84 (cyclase inactivating PTH, CIP) acting the opposite way. The aim of this study was to establish whether bone mineral density (BMD) and turnover in patients' primary hyperparathyroidism (HPT) are dependent on CAP and CIP concentrations. PATIENTS/METHODS: Thirty-one patients with HPT and 29 appropriately matched controls were examined. Parameters of calcium-phosphate homeostasis and BMD were estimated. RESULTS: BMD of radius shaft was lower in patients with HPT as compared with controls, whereas BMD of spine and ultradistal radius were similar. Serum calcium, bone alkaline phosphatase, total PTH, 1-84 PTH, and 7-84 PTH were higher in HPT patients, whereas serum phosphate was lower and beta cross-laps similar. Both total PTH and CAP correlated significantly with BMD of radius shaft and serum calcium concentration, but not with other examined parameters. CONCLUSION: Total and 1-84 PTH are similarly associated with examined parameters in patients with HPT. Thus, determination of serum CAP concentration does not seem to have advantages over total PTH with regard to bone mineral density and bone turnover assessment in those patients.

Immunoablation and autologous hematopoietic stem cell transplantation in the treatment of new-onset type 1 diabetes mellitus: long-term observations.

The activity of the autoimmune mechanism underlying type 1 diabetes mellitus (T1DM) can be suppressed when immunoablation and autologous hematopoietic stem cell transplantation (AHSCT) are applied early in the course of the disease. We report here a single centre experience with this treatment modality. Twenty-four patients underwent a AHSCT preceded by immunoablative conditioning with high-dose cyclophosphamide and anti-thymocyte globulin. During the 52-month median time of follow-up 20 out of 23 patients (87%) remained for at least 9.5 months without the use of exogenous insulin. The median time of T1DM remission for these patients was 31 months (range of 9.5-80 months). Among the patients available for follow-up (n=20), four remain insulin free (for 80, 61, 42 and 34 months). The average glycated hemoglobin (HbA1c) concentrations were 10.9% at diagnosis, 5.9% at 1 year, 6.4% at 2 years, 6.8% at 3 years and 7.1% at 4 years after AHSCT. No severe complications of diabetes were seen, however one of the patients died of pseudomonas sepsis in the course of neutropenia after AHSCT. AHSCT leads to a remission of T1DM with good glycemic control in the vast majority of patients, with the period of remission lasting over 5 years in some patients.

Effect of isobaric hyperoxemia on erythropoietin secretion in hypertensive patients.

We assessed the influence of hyperoxemia on erythropoietin secretion in patients with various etiological forms of arterial hypertension (essential, n = 15; renoparenchymal, n = 16; renovascular, n = 15) and in 15 healthy subjects. On the first day of the study, blood was withdrawn at 1-hour intervals for the estimation of erythropoietin during a total of 6 hours and at 2-hour intervals for the assessment of PO2. Three days later the same parameters were assessed again at identical time intervals, but the subjects were breathing pure oxygen during the first 2 hours. Breathing with pure oxygen resulted in a significant increase of blood PO2 (184.85 +/- 4.47 versus 85.92 +/- 2.28 in essential, 185.21 +/- 5.52 versus 84.55 +/- 3.04 in renoparenchymal, and 181.7 +/- 3.14 versus 87.49 +/- 2.25 in renovascular hypertension groups and 189.84 +/- 5.2 versus 85.89 +/- 1.73 mm Hg in healthy subjects; P < .001 in all groups). Baseline plasma erythropoietin was not different among the groups (29.33 +/- 4.14 in essential, 24.56 +/- 3.09 in renoparenchymal, and 27.77 +/- 3.29 in renovascular hypertension groups and 24.23 +/- 2.70 mU/mL in the control group). The pattern of erythropoietin decline was different in the groups of hypertensive patients. In patients with essential hypertension, unlike in healthy subjects and patients with other etiological forms of arterial hypertension, only a very short-term suppression of erythropoietin levels was observed during hyperoxemia. No significant changes in blood pressure during breathing with pure oxygen were found in any of the studied groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Altered action of angiotensin II in patients with type 2 diabetes mellitus of recent onset.

OBJECTIVE: Angiotensin II (Ang II) increases insulin sensitivity in healthy volunteers. This effect is thought to be mediated, at least in part, by an increase in skeletal muscle blood flow. In the past it had been documented that some biological actions of Ang II are altered in diabetes. We addressed the issue of whether this is also true for its action on insulin sensitivity. DESIGN AND METHODS: Twelve healthy volunteers (aged 43+/-9 years) and 15 patients with type 2 diabetes mellitus (NIDDM) of recent onset (aged 45+/-9 years) were allocated in random order in a double-blind placebo-controlled design to be administered a sham infusion or an infusion of 2 ng Ang II/kg per min. Insulin-stimulated glucose uptake (the M value) was measured with the euglycaemic clamp technique, leg muscle blood flow (MBF) with plethysmography, blood pressure with a Dinamap device, and glomerular filtration rate and effective renal plasma flow with the steady-state inulin (Cin) and p-aminohippurate (CPAH) clearance methods, respectively. RESULTS: In volunteers the mean M-value after Ang II infusion (10.1+/-1.5 mg/kg per min) was significantly higher (P < 0.01) than that after sham infusion (8.2+/-0.9 mg/kg per min). In contrast, in diabetic patients it was not significantly different with Ang II (6.1+/-1.3 mg/kg per min) and sham infusion (5.5+/-1.2 mg/kg per min). The difference in the mean absolute increase in the M value (deltaM) between groups was significant (P< 0.02). The Ang II-induced increase in MBF under euglycaemic conditions was attenuated in diabetic patients (from 15.0+/-3.5 to 15.5+/-3.9 ml/100 ml per min, NS) compared with volunteers (from 16.8+/-3.3 to 19.1+/-3.7 ml/100 ml per min, P< 0.01). Again, the difference between the mean absolute increases in MBF (deltaMBF) in the groups was significant (P < 0.01). A significant correlation was found between deltaMBF and deltaM (r= 0.62, P<0.01). The absolute acute increase in mean arterial blood pressure with Ang II was similar in diabetic patients and volunteers. Mean Cin, CPAH and fractional sodium excretion values were significantly lower and renal vascular resistances and filtration fractions higher during the Ang II than they were during the placebo clamp period. This was observed in patients as well as in healthy subjects, but the effects of Ang II on renal haemodynamics and sodium handling were more pronounced in diabetic patients. CONCLUSIONS: In patients with NIDDM of recent onset the stimulatory effect of Ang II on insulin sensitivity and on skeletal muscle blood flow is attenuated. In contrast, the effects of Ang II on renal perfusion and sodium handling are more pronounced in patients with NIDDM than they are in healthy subjects.

Renal reserve in the elderly.

The increase in glomerular filtration rate after an amino acid load, the so-called renal reserve, was found to be impaired in the aged rat. Renal diseases progress more rapidly in the elderly. Whether the renal reserve predicts progression of renal disease is controversial, however, and generally little information on renal reserve in elderly subjects is available. We examined renal hemodynamics before and after an amino acid infusion in 15 healthy normotensive subjects of young age (median age, 26 years [23 to 32]) and in 10 of old age (70 years [61 to 82]). Median basal inulin (Cin) and paraaminohippurate (Cpah) steady-state clearances were significantly lower in the elderly (102 and 339 mL/min/1.73 m2) than in the young subjects (122 and 647 mL/min/1.73 m2), but virtually all GFR values of the elderly were still within the normal range. The median percent rise of Cin was +16% in young and +17% elderly subjects (independent of gender). A well-preserved renal reserve was also confirmed by two other studies; one in chronically ill elderly patients treated for various nonnephrological diseases using an amino acid load and the other in healthy elderly volunteers in which renal reserve was tested with a protein (meat) meal. The mean absolute renal reserve in the three cohorts studied was between 16 and 26 mL/min/1.73 m2, the oldest patient studied was 89 years. The results of these studies document that in humans renal functional reserve is preserved at least until age 90 years in women and men.

Influence of acetate and bicarbonate hemodialysis on the plasma erythropoietin concentration in patients with chronic renal failure.

The present study aimed to assess the influence of acetate (AC) and bicarbonate (BI) hemodialysis with a cuprophane membrane on plasma erythropoietin (EPO) levels in 30 patients with chronic renal failure (CRF). Fifteen patients were severely anemic with an Hct below 30%, while 13 were moderately anemic with an Hct equal to or more than 30%. None had received rHuEPO or ACE inhibitors before the study. Blood samples for EPO and pO2 estimation were withdrawn before and after 1, 2 and 5 h of AC dialysis. In 11 of the patients with an Hct < 30% the same protocol was repeated during BI dialysis. In spite of a significant decrease in pO2 during the first hour of AC dialysis, the plasma EPO concentration decreased significantly in both severely and moderately anemic CRF patients from 35.4 +/- 2.6 to 23.6 +/- 3.5 mU/ml after 5 h of hemodialysis (p = 0.0001 by paired t-test) and from 39.5 +/- 8.6 to 27.5 +/- 8.9 mU/ml (p < 0.01) respectively. In contrast to AC dialysis, Bi dialysis failed to change the plasma EPO concentration (from 32.3 +/- 4.1 to 30.3 +/- 4.7 mU/ml after 5 h of hemodialysis). Conclusions AC but not BI hemodialysis shows a significant suppressive effect on plasma EPO levels in anemic CRF patients in spite of a significant decline in pO2. Factors other than pO2 seem to be involved in the regulation of EPO secretion in CRF patients during AC dialysis.

Abnormal function of renal tubules in patients with simple renal cysts.

The present study aimed to assess the function of proximal and distal tubules in patients with simple renal cysts. Thirty-one patients with simple renal cysts and 10 healthy subjects were examined. Based on the cyst fluid/plasma sodium ratio, 25 cysts were found to be of proximal origin and 6 of undetermined origin. In all patients cyst fluid and plasma concentrations of beta-2-microglobulin (beta-2-MG), sodium, potassium, calcium, phosphorus and total protein were assessed. Urinary excretions of sodium, potassium, calcium, phosphorus, beta-2-MG and Tamm-Horsfall protein (THP) were also estimated. Fractional excretion of beta-2-MG was calculated. The concentrations of beta-2-MG in fluid obtained from cysts of proximal origin were significantly higher than in fluid from cysts of undetermined origin (2.26 +/- 0 36 vs. 0.65 +/- 0.13 mg/l, p = 0.0004). Concentrations of THP (6.85 +/- 1.21 vs. 3.14 +/- 1.06 micrograms/ml, p < 0.05), and potassium (4.39 +/- 0.07 vs. 3.13 +/- 0.44 mmol/l, p < 0.05) were also higher in fluid from proximal cysts than in fluid from cysts of undetermined origin. Plasma beta-2-MG concentration was significantly higher in patients with proximal and undetermined cysts than in the control group (4.35 +/- 0.34 and 4.11 +/- 0.74 vs. 1.89 +/- 0.1 mg/l, p < 0.001). Urinary beta-2-MG excretion was also significantly higher in both groups of patients than in healthy subjects (474.8 +/- 165.9 and 346 +/- 94 vs. 100.2 +/- 19.6 micrograms/24 h, p < 0.05). Urinary THP excretion was significantly higher in patients with proximal cysts than in healthy subjects (31.0 +/- 5.1 vs. 16.3 +/- 2.5 mg/24 h, p < 0.05). From the results obtained in this study it seems that patients with simple renal cysts of proximal origin are characterized by abnormal tubular handling of beta-2-MG, and calcium and THP excretion. Thus, in patients with proximal cysts presence of a latent renal tubulopathy seems to be likely.

[Erythropoietin secretion in patients with chronic obstructive lung diseases during normobaric oxygen inhalation]. / Sekrece erytropoetinu u nemocných s chronickou obstrukcní chorobou plicní po normobarické inhalaci kyslíku.

BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) are characterized by compensatory polycythaemia probably induced by increased erythropoietin (EPO) secretion in the kidneys. METHODS AND RESULTS: As the regulatory mechanisms of erythropoietin secretion in chronic obstructive pulmonary disease are scarcely known we studied plasma EPO levels in 14 patients with COPD (pO2 = 61.9 +/- 1.4 mm Hg, Hct = 47.8 +/- 1.1%) under basal conditions, after two hours of isobaric oxygen breathing and two and four hours after discontinued oxygen breathing. The control group consisted of 12 healthy subjects (pO2 = 87.5 +/- 2.2 mm Hg, Hct = 43.7 +/- 1.6%). Under basal conditions patients with COPD showed significantly higher plasma erythropoietin levels as compared with healthy controls. Oxygen breathing was followed by a significant decline of plasma EPO levels both in patients with COPD as in the control group. This decline was significantly more marked and of longer duration in COPD patients than in healthy controls. CONCLUSIONS: 1. Patients with chronic obstructive pulmonary disease are characterized by significantly higher plasma EPO levels as compared with healthy subjects. 2. The renal oxygen sensor function involved in the regulation of EPO secretion seems to be altered in COPD patients.

[Electrically enhanced damaged tissues healing. Part I: direct current in bone healing]. / Elektryczne wspomaganie gojenia uszkodzonych tkanek. Czesc I: Prad staly i pulsujacy w leczeniu kosci.

The reasons of investigators' interest of damaged tissues healing with electrical current in concise form are represented by the authors. The nonunions and pseudarthroses healing with direct current through negative polarized electrode is described in this article. Hypothetic biological healing mechanisms (as piezoelectric activity, streaming potentials, electric properties of glycosaminoglycan etc.) are discussed. Technical data of currents and their antibacterial properties are described.

[Electrically enhanced damaged tissues healing. Part II: direct and pulse current in soft tissue healing]. / Elektryczne wspomaganie gojenia uszkodzonych tkanek. Czesc II. Prad staly i pulsujacy w leczeniu tkanek miekkich. Leczenie tkanek pradem zmiennym.

Methodology of soft tissues wounds, ulcers and pressure sores healing with direct current is described by the authors. Results of clinical trials and animal experiments are represented, as well as technical and using data. Electrical properties of damaged tissues (e. i. skin battery, vascular-interstitial closed circuits etc.) and probable electrical healing mechanisms are discussed. Effects of electrical current on batteries are described. Inductive and capacitive coupling of electric and magnetic fields, and high voltage electrostimulation for enhance tissue healing are also described in the article.

[Erectile dysfunction in patients with diabetes]. / Zaburzenia erekcji u chorych na cukrzyce.

Erectile dysfunction is present in approximately 50% of diabetic men. It is most often caused by diabetic neuropathy and angiopathy but psychogenic factors are also of importance. Treatment includes: elimination of risk factors, psychotherapy, pharmacologic treatment and implantation of penile prosthesis.

[Half-time of erythropoietin in patients with chronic obstructive pulmonary diseases]. / Czas polowiczego znikania erytropoetyny u chorych z przewlekla zaporowa choroba pluc.

Presence of elevated plasma levels of erythropoietin (EPO) has been reported both in polycythaemic and normocythaemic patients with chronic obstructive pulmonary disease (COPD). The present study aimed to elucidate in what extent prolonged erythropoietin half-life time (T1/2EPO) is involved in the pathogenesis of elevated plasma EPO levels in patients with COPD. Seven normocythaemic patients (5 men and 2 women) with CODP and 6 healthy controls (4 males and 2 females) were examined. In all examined subjects half-life time of erythropoietin was determined after i.v. administration of EPO in a dose of 50 U/kg b.m. In COPD patients the T1/2EPO value was 5.98 +/- 0.67 hours and did not differ from that found in healthy controls (5.87 +/- 0.35 h). Results obtained in this study suggest participation of factors other than prolonged half-time of erythropoietin in the pathogenesis of polycythaemia in patients with COPD.