Impact of severe diabetic kidney disease on the clinical outcome of autologous cell therapy in people with diabetes and critical limb ischaemia.

AIM: To assess the impact of autologous cell therapy on critical limb ischaemia in people with diabetes and diabetic kidney disease. METHODS: A total of 59 people with diabetes (type 1 or type 2) and critical limb ischaemia, persisting after standard revascularization, were treated with cell therapy in our foot clinic over 7 years; this group comprised 17 people with and 42 without severe diabetic kidney disease. The control group had the same inclusion criteria, but was treated conservatively and comprised 21 people with and 23 without severe diabetic kidney disease. Severe diabetic kidney disease was defined as chronic kidney disease stages 4-5 (GFR <30 ml/min/1.73 m²). Death and amputation-free survival were assessed during the 18-month follow-up; changes in transcutaneous oxygen pressure were evaluated at 6 and 12 months after cell therapy. RESULTS: Transcutaneous oxygen pressure increased significantly in both groups receiving cell therapy compared to baseline (both P<0.01); no significant change in either of the control groups was observed. The cell therapy severe diabetic kidney disease group had a significantly longer amputation-free survival time compared to the severe diabetic kidney disease control group (hazard ratio 0.36, 95% CI 0.14-0.91; P=0.042); there was no difference in the non-severe diabetic kidney disease groups. The severe diabetic kidney disease control group had a tendency to have higher mortality (hazard ratio 2.82, 95% CI 0.81-9.80; P=0.062) than the non-severe diabetic kidney disease control group, but there was no difference between the severe diabetic kidney disease and non-severe diabetic kidney disease cell therapy groups. CONCLUSIONS: The present study shows that autologous cell therapy in people with severe diabetic kidney disease significantly improved critical limb ischaemia and lengthened amputation-free survival in comparison with conservative treatment; however, the treatment did not influence overall survival.

Severe Epidermal Nerve Fiber Loss in Diabetic Neuropathy Is Not Reversed by Long-Term Normoglycemia After Simultaneous Pancreas and Kidney Transplantation.

Whether nerve fiber loss, a prominent feature of advanced diabetic neuropathy, can be reversed by reestablishment of normal glucose control remains questionable. We present 8-year follow-up data on epidermal nerve fiber (ENF) density and neurological function in patients with type 1 diabetes after simultaneous pancreas and kidney transplantation (SPK) with long-term normoglycemia. Distal thigh skin biopsies with ENF counts, vibration perception thresholds (VPTs), autonomic function testing (AFT) and electrophysiological examinations were performed at time of SPK and 2.5 and 8 years after SPK in 12 patients with type 1 diabetes. In comparison to controls, baseline ENF density, VPT and AFT results of patients indicated severe neuropathy. At follow-up, all SPK recipients were insulin independent with excellent glycemic control and kidney graft function; however, the severe ENF depletion present at baseline had not improved, with total ENF absence in 11 patients at 8-year follow-up. Similarly, no amelioration occurred in the VPT and AFT results. Numerical improvement was seen in some electrophysiological parameters; however, statistical significance was achieved only in median motor nerve conduction velocity. ENF loss and functional deficits in advanced diabetic peripheral neuropathy are rarely reversible, even by long-term normoglycemia, which underscores the importance of neuropathy prevention by early optimal glycemic control.

Portal versus systemic venous drainage of the pancreatic graft: the effect on glucose metabolism in pancreas and kidney transplant recipients.

Two different methods of graft venous drainage are used in pancreas transplantation: portal (PVD) and systemic (SVD). PVD is considered to be more physiologic due to its similarity to venous outflow of the native pancreas. The aim of our study was to compare glucose metabolism in Type 1 diabetic recipients of kidney and pancreatic grafts with PVD versus SVD by intravenous glucose tolerance test (IVGTT). We examined 28 insulin-independent patients after simultaneous pancreas and kidney transplantation: 14 recipients with PVD of the pancreatic graft and 14 with SVD after a mean post-transplant period of 1 year. All recipients had stable good function of the kidney graft. Fasting glycemia, insulin levels, glycosylated hemoglobin (HbA1c), and standard IVGTT with coefficient of glucose assimilation (KG) calculation were assessed. Insulin sensitivity and production were evaluated using the homeostasis model assessment (homeostasis model assessment of insulin resistance [HOMA-IR], homeostasis model assessment of B-cell function [HOMA-B]). Total C-peptide and insulin secretions were calculated as areas under the curves (AUCs) from the serum levels during the IVGTT. PVD and SVD groups did not differ in age, body mass index (BMI) and duration of post-transplantation period (P ≥ .05). We did not find any significant difference in fasting glycemia, HbA1c, KG, HOMA-IR, parameters of C-peptide level, fasting insulin level, and response during IVGTT. HOMA-B and AUC of insulin level were higher in the SVD group (45.1 ± 35.1 versus 19.8 ± 15.5, P =.03 and 1075 ± 612 versus 1799 ± 954 mIU/L/60 minutes, P < .03, respectively). In the PVD group, 1 patient had an abnormal response to the glucose stimulus, 8 patients had an impaired glucose tolerance, and 5 patients had a normal glucose tolerance. In the SVD group, an abnormal response was present in none, impaired glucose tolerance in 4, and normal glucose tolerance in 10 recipients. Athough this was not a prospectively randomized trial, we conclude that the change of surgical technique from SVD to PVD did not lead to any substantial change in terms of glucose tolerance.

Effect of tacrolimus versus cyclosporine on glucose metabolism of pancreas and kidney recipients in the late (> 8 years) posttransplant period.

Diabetogenic effects of immunosuppressive agents are of great importance in pancreas or islet transplantation. The aim of our study was to compare the glucose metabolism in type 1 diabetic kidney and pancreas recipients on tacrolimus (Tacro) versus cyclosporine-based (Cyclo) immunosuppression in the late posttransplant period. We examined 26 insulin-independent patients with stabile good renal function. They were at least 7 years after simultaneous pancreas and kidney transplantation and with unchanged immunosuppressive therapy for at least 6 years. The mean follow-up in Tacro (n = 13) and Cyclo (n = 13) groups were 9.7 ± 1.9 and 10.9 ± 1.3 years, respectively (P = .08). Fasting glycemia, insulin levels, glycosylated hemoglobin (HbA(1c)), a standard intravenous glucose tolerance test (IVGTT) with coefficient of glucose assimilation (K(G)) calculation and trough Tacro/Cyclo levels were assessed. Insulin sensitivity and insulin secretion were evaluated using the homeostasis model assessment (HOMA-IR, HOMA-B). Total C-peptide and insulin secretions were calculated as areas under the curves (AUC) from the serum levels during the IVGTT. Tacro and Cyclo groups did not differ in age and body mass index. We did not find any significant difference in any examined parameters of glucose metabolism (fasting glycemia, insulin and C-peptide levels, HbA(1c,) IVGTT with K(G), HOMA-IR, HOMA-B, AUC of C-peptide and AUC of insulin; P > .05). Two patients in the Tacro group and none in the Cyclo group had K(G) <0.8%/min. Seven recipients in the Tacro group and eight in the Cyclo group had the normal glucose tolerance with K(G) ≥ 1.2%/min. Trough Tacro or Cyclo levels did not correlate with any of examined parameters. The use of different types of calcineurin inhibitors in type 1 diabetic pancreas and kidney recipients had no effect on glucose metabolism in the late posttransplant period.

The influence of vascular endothelial growth factor (VEGF) polymorphism on the progression of chronic glomerulonephritides.

Vascular endothelial growth factor is an important mediator in maintaining normal kidney functions. In addition, several lines of evidence show that up-regulation of this mediator in glomeruli may be associated with or may directly cause renal dysfunction. We tried to assess the influence of the -2578 C/A and -1154 G/A polymorphisms in the regulatory region of the vascular endothelial growth factor gene upon progression of three primary chronic glomerulonephritides (minimal change disease/focal and segmental glomerulosclerosis, membranous nephropathy, immunoglobulin A nephropathy). We studied a cohort of 213 patients compared to 311 unrelated healthy controls. Analysis of the C/A polymorphism of vascular endothelial growth factor revealed an increased prevalence of CC genotype in the minimal change disease/focal and segmental glomerulosclerosis group in comparison with the other groups. A balanced distribution of G and A alleles among the respective types of chronic glomerulonephritides was shown in the analysis of -1154 G/A polymorphism. Finally, we have not proved any significant influence of the polymorphisms at positions -2578 C/A and -1154 G/A of the vascular endothelial growth factor gene promoter on the progression of chronic glomerulonephritides even though our study suggests a negative effect of CC genotype of -2578 C/A polymorphism on the clinical course of minimal change disease/focal segmental glomerulosclerosis.

Biventricular pacing in the early postoperative period after cardiac surgery.

Cardiac resynchronization therapy is not commonly used in the early postoperative period in patients undergoing cardiac surgery who have left ventricular (LV) dysfunction and a history of heart failure. We performed a prospective randomized clinical trial to compare atrial synchronous right ventricular (DDD RV) and biventricular (DDD BIV) pacing within 72 hours after cardiac surgery in patients with an EF ≤35 %, a QRS interval longer than 120 msec and who had LV dyssynchrony detected by real-time three-dimensional echocardiography (RT3DE). Epicardial pacing was provided by a modified Medtronic INSYNC III pacemaker. An LV epicardial pacing lead was implanted on the latest activated segment of the LV based on RT3DE. The study included 18 patients with ischemic heart disease, with or without valvular heart disease (14 men, 4 women, average age 71 years). Patients undergoing DDD BIV pacing had a statistically significant greater CO and CI (CO 6.7±1.8 l/min, CI 3.4±0.7 l/min/m(2)) than patients undergoing DDD RV pacing (CO 5.5±1.4 l/min, CI 2.8±0.7 l/min/m(2)), p<0.001. DDD BIV pacing in the early postoperative period after cardiac surgery corrects LV dyssynchrony and has better hemodynamic results than DDD RV pacing.

[Treatment of critical limb ischemia and diabetic foot disease by the use of autologous stem cells]. / Terapie kritické koncetinové ischemie u pacientu se syndromem diabetické nohy pomocí autologních kmenových bunek.

AIM: The aim of our study was to assess safety and effectiveness of therapy of critical limb ischaemia by autologous stem cells and evaluation of potential adverse events. METHODS: Fourteen patients were included into the study (11 men, 3 women, mean age 61.9 +/- 9.6 years, mean diabetes duration 23.5 +/- 11.1 years, mean glycated hemoglobin 6 +/- 1%). Eight patients were treated by bone marrow stromal cells, 6 patients by peripheral blood progenitor cells after stimulation by filgrastim. The suspension of stem cells was then applied into the muscles of ischemic limbs. We evaluated transcutaneous oxygen tension (TcPO2), subjective pain sensation assessed by Visual Analog Scale (VAS) and wound healing. RESULTS: TcPO2 significantly increased in all patients from 10 +/- 8.7 mm Hg before the treatment to 39.4 +/- 9.5 mm Hg after 6 months (p = 0.0005) after stem cell therapy. We also observed significant area defect reduction and pain decrease during the follow-up period. Median of area defect was reduced from 4.3 (0.7 - 31.7) before the treatment to 0.06 (0 - 0.5) cm2 after 6 months from the treatment (p = 0.0078). Decrease in rest pain was observed in all patients, mean VAS decreased from 5.3 +/- 1.8 to 1.1 +/- 1.3 after 6 months (p = 0.002). CONCLUSION: Our study suggests that stem cell therapy of diabetic foot disease is an effective therapeutic option with no adverse events for patients with severe peripheral arterial disease. This treatment leads to increase of transcutaneous oxygen tension, improves wound healing and decreases the rest pain.

Th1/Th2 cytokine gene polymorphisms in patients with uterine fibroid.

Uterine fibroid or leiomyoma is a frequent non-malignant tumour with unknown aetiology and pathogenesis. The aim of our study was to look for possible genetic markers which could be used as prognostic tools for evaluation of an increased risk for development of uterine fibroid. A large spectrum of Th1/Th2 cytokine gene polymorphisms in 102 patients with uterine leiomyoma was compared with 145 healthy controls. An association between polymorphisms of the IL4 gene promotor at positions -590 C/T and -33 C/T, and the risk of leiomyoma was observed. The CC genotype of IL4 -590 and at position -33 was less frequent in the patient group than in the control group (P = 0.03). Besides IL-4, we observed different genotype distribution of the TNFA gene -308 A/G. The frequency of genotype AA was higher in the younger (≤ 35 years) patient group (P = 0.02). Our study thus suggests that certain cytokine gene polymorphisms, especially of the IL4 and TNFA genes, may be associated with increased risk for development of uterine fibroid. Further investigation would be needed to elucidate the mechanisms responsible for these associations.

Cytokine gene polymorphisms in sarcoidosis.

BACKGROUND: Sarcoidosis is a disease characterized by granuloma formation in many organs, but mostly in lung and lymph nodes. The immunopathogenic background of the disease is probably based on disregulation of immune response to different antigens. The imbalance of immune reactivity might be influenced by genetic background. In our study, we have investigated cytokine genetic polymorphisms in sarcoidosis group and compared the results with that of a group of healthy volunteers. METHODS: Thirty one sarcoidosis patients were enrolled to our study. Basic demographic data were collected. Polymorphisms in the promoter regions of the IL-1alpha, IL-1beta, IL-1R, IL-1RA, IL-2, IL-4, IL-6, IL-10, IL-12, TNF-alpha, IFN-gamma and in the translated regions of the TGF-beta, IL-1 beta, IL-2, IL-4 and IL-4RA genes were characterized. RESULTS: For IL-10, the (-819) and (-592) CC homozygosity was statistically more frequent in the sarcoidosis group compared to healthy controls. According to the haplotypes, the majority of sarcoidosis patients had IL-10 (-1082)(-819)(-592) ACC haplotype 2 compared to controls with ATA in most of the cases. CONCLUSIONS: The results of our study support the hypothesis of a genetically encoded immune regulation imbalance in sarcoidosis. The high-producer IL-10 (-819) and (-592) CC genotypes and intermediate- producer IL-10 (-1082) (-819) (-592) ACC haplotype 2 present in the majority of our sarcoidosis patients could support the role of genetically encoded disregulation of cell- mediated immune response to an unknown antigen.

[Incidence of congenital heart defects in the Czech Republic--current data]. / Incidence vrozených srdecních vad v Ceské republice--aktuální data.

AIM OF STUDY: An analysis of incidence of congenital heart defects (CHD) in the Czech Republic in the 1994 - 2008 period. An assessment of absolute numbers, frequencies and incidences for particular selected diagnoses according to 10th decennial revision of International Classification of Diseases (ICD-10). An analysis of pre- and postnatal incidences of selected diagnoses and of a secondary prevention measures efficiency in the Czech Republic. TYPE OF STUDY: A retrospective epidemiological analysis of congenital anomalies from the database of the National Register of Birth Defects (NRBD) of the Czech Republic. MATERIAL AND METHODS: Data from the NRBD from the 1994 - 2008 period were used. In our study, CHD incidences (ICD-10 Q20-Q28 Congenital malformations of the circulatory system group) in the Czech Republic were analyzed. First, CHD incidences in births were assessed - absolute numbers, frequencies and incidences for particular selected diagnoses. Second, absolute numbers, frequencies and incidences of particular selected diagnoses in prenatally diagnosed fetuses and a secondary prevention measures efficiency in selected CHD were evaluated. In a third part, survival of babies with CHD during the first year of their life was analyzed. RESULTS: In the period under the study, there were a total of 1 472 610 life births in the Czech Republic. Congenital malformations of the circulatory system (Q20-Q28) present more than 40% of all registered congenital anomalies and are themselves the most frequent birth defect group in births in the Czech Republic. As a whole, 29 133 CHD were diagnosed (197.83 per 10 000 live births) in 18 811 children (127.53 per 10 000 live births) in this period, which presents more than 36% of children born with a congenital anomaly in the Czech Republic during 1994 - 2008. CHD most frequently diagnosed in births were congenital malformations of cardiac septa (total 16 428, 145.05 per 10 000 live births, more than 55% of all CHD) and congenital malformations of great arteries (total 5389, 47.58 per 10 000 live births, more than 18% of all CHD). Further, prenatally diagnosed CHD were analyzed. Incidences for particular diagnoses as well as percentage of pregnancy termination were assessed. A rate of prenatally diagnosed was 11.35% in discordant ventriculoarterial connection (Q20.3), 8.35% in discordant atrioventricular connection (Q20.5), 49.41% in hypoplastic left heart syndrome (Q23.4), 7.64% in coarctation of aorta (Q25.1) and 9.71% in tetralogy of Fallot (Q21.3). These anomalies were parts of chromosomal syndromes in 42.58% and non-chromosomal syndromes in 9.33%. There were also associated malformations (from other systems than circulatory one). The most frequent were congenital malformations of the nervous system (Q00-Q07) - 14.59%, congenital malformations and deformations of the musculoskeletal system (Q65-Q79) - 12.44%, cleft lip and cleft palate (Q35-Q37) - 7.42% and congenital malformations of the urinary system (Q60-Q64) - 6.70%. In children born with a CHD, 84.53% were associated with other anomaly, out of which more than 70% were CHD only. Only about 14% were associated with anomalies from other (non-circulatory system) groups. Perinatal mortality was highest in hypoplastic left heart syndrome (Q23.4) - 327.103 per thousand and in tetralogy of Fallot (Q21.3) - 6.565 per thousand. CONCLUSIONS: The study presents current results of analysis of CHD incidences in the Czech Republic in the 1994 - 2008 period. Children born with a CHD make more than 36% out of all children born with a congenital anomaly. CHD themselves represents an important part (more than 40%) of all diagnosed congenital anomalies in the Czech Republic. Over the period of the study there was a slight increase of diagnosed CHD during 1994 - 1999 followed by a slight decrease from 2000 with an exception of 2007 year. The most frequent of diagnosed CHD were ventricular septal defect (Q21.0) and atrial septal defect (Q21.1). Both defects incidences changes influence not only a total CHD but also a total congenital anomalies incidence. An influence of prenatal diagnostics among the five selected CHD was most important in hypoplastic left heart syndrome (Q23.4), less so in others. In prenatal diagnostics group, it is necessary to distinguish between those anomalies, which led to pregnancy termination (parts of both chromosomal and non-chromosomal syndromes and/or association with other severe anomalies) and those in which pregnancy leads to a delivery (late diagnostics, operabile defects, parental decision). CHD can be a part of chromosomal syndromes. In our study, in prenatally diagnosed CHD it was more than 42%. A presence of other associated diagnoses of congenital anomalies in births will significantly influence infant mortality and morbidity.

Hepatocyte growth factor and antibodies to HLA and MICA antigens in heart transplant recipients.

Recent unconfirmed literature data suggest that elevated concentrations of the multifunctional cytokine hepatocyte growth factor (HGF) might be a marker of increased incidence of acute rejection after organ transplantation. The aim of this study was to test the hypothesis that HGF levels may correlate with the rejection and/or with the production of HLA and MHC Class I chain-related antigens A (MICA) specific antibodies. Sixty-three heart transplant recipients were included into the study. Hundred and eighty-five endomyocardial biopsies (EMB) obtained up to 6 months after transplantation were retrospectively analyzed for signs of cellular (CR) and antibody-mediated rejection (AMR). Pre- and post-transplant sera were tested for HGF concentrations and antibodies to HLA class I, class II and MICA antigens by xMap technology (Luminex). Pre-transplant HGF did not correlate with the incidence of CR or AMR. However, higher HGF concentrations correlated significantly with HLA antibody production before and after transplantation (P = 0.006 and P < 0.0001 respectively). Patients with both HLA class I and class II antibodies before transplantation had significantly lower AMR-free survival. Furthermore, recipients with pre-transplant donor-specific antibodies (DSA) had significantly lower AMR-free survival (50%) than recipients without pre-transplant HLA antibodies (90%) and patients with antibodies not specific to donor antigens (92%) (P = 0.005). Post-transplant MICA antibodies tended to be more frequent in patients with AMR (P = 0.063). In conclusion, elevated HGF concentrations in our study were not associated with the incidence of CR and/or AMR but with the presence of HLA-specific antibodies. Testing for DSA before heart transplantation by Luminex may be helpful for the identification of patients with increased risk of AMR.

Fetuin-A early after renal transplantation.

BACKGROUND: Fetuin-A is a major inhibitor of ectopic calcium phosphate precipitation and an acute phase reactant. Its deficiency, common in end-stage renal disease, has been suggested to be associated with cardiovascular complications. The aim of this study was to monitor fetuin-A levels in the early period after renal transplantation. METHODS: 30 deceased donor kidney recipients treated with calcineurin inhibitor-based immunosuppression were followed prospectively for the first 3 months and the association of fetuin-A levels with clinical and laboratory parameters was evaluated. RESULTS: Despite a correlation of fetuin-A levels with creatinine clearance (r = 0.348, p < 0.01) and estimated GFR (r = 0.331, p < 0.01), no significant increase in fetuin-A levels over the first 3 months was observed. Moreover, a significant decrease in serum fetuin-A levels was noted at 2 weeks (p < 0.001). Subsequently, fetuin-A levels increased (p < 0.001) reaching pretransplant values at month 3. CONCLUSIONS: In this study there was no increase of fetuin-A levels during the first 3 months, but a decrease 2 weeks after transplantation was observed.

[Birth defects in the Czech Republic in 1994--2007]. / Vrozené vady v Ceské republice v období 1994-2007.

AIM OF STUDY: An analysis of occurrence of birth defects in the Czech Republic in 1994-2007. An assessment of total numbers and relative incidences of birth defects in births according to Tenth Revision of International Classification of Diseases (ICD-10). TYPE OF STUDY: Retrospective epidemiological analysis of birth defects incidences from the Czech National Birth Defects Register database. MATERIAL AND METHODS: Data from the National Birth Defects Register (Institute for Health Information and Statistics) in the Czech Republic in the 1994-2007 period were used. In this study, particular diagnoses--as they were registered in the National Register--were analyzed. The diagnoses in study were divided into following eleven birth defects groups according to ICD-10 classification: (Q00-Q07) nervous system, (Q10-Q18) eye, ear, face and neck, (Q20-Q28) circulatory system, (Q30-Q34) respiratory system, (Q35-Q37) cleft lip and cleft palate, (Q38-Q45) digestive system, (Q50-Q56) genital organs, (Q60-Q64) urinary system, (Q65-Q79) musculoskeletal system, (Q80-Q89) other defects and (Q90-Q99) chromosomal abnormalities, not elsewhere classified. Prenataly diagnosed cases are not included. RESULTS: During 1994-2007 period, totally 1,353,040 children were born on the area of the Czech Republic, out of which 44,343 with a birth defect. The diagoses in study were divided into eleven groups according to ICD-10 classification. Further, particular diagnoses according to ICD-10 and their verbal descriptions are presented in tables. Each group is accompanied by data on its total number and a relative incidence (per 10,000 live births) with a 95% C.I.. A relative frequency of the birth defects groups in study (in % from the total number of birth defects) is as follows: (Q00-Q07) nervous system 2.10, (Q10-Q18) eye, ear, face and neck 4.76, (Q20-Q28) circulatory system 39.63, (Q30-Q34) respiratory system 1.03, (Q35-Q37) cleft lip and cleft palate 3.67, (Q38-Q45) digestive system 4.05, (Q50-Q56) genital organs 10.93, (Q60-Q64) urinary system 7.08, (Q65-Q79) musculoskeletal system 18.90, (Q80-Q89) other defects 5.55 and (Q90-Q99) chromosomal abnormalities 2.28. CONCLUSIONS: The study gives updated results of incidences analysis of postnatally diagnosed birth defects (available on the date of August 31, 2008) in the Czech Republic in the 1994-2007 period. Data on birth defects were collected in the National Birth Defects Register (Institute for Health Information and Statistics). Birth defects registration is a compulsory process and is a part of the National Health Information System. The diagnoses in study were divided into eleven groups according to ICD-10 classification. Total numbers, relative incidences (per 10 000 live births, with a 95% C.I.) and relative frequencies of the birth defects groups are presented.

Bronchoalveolar lavage fluid cellular characteristics, functional parameters and cytokine and chemokine levels in interstitial lung diseases.

Idiopathic pulmonary fibrosis (IPF), hypersensitivity pneumonitis (HP) and sarcoidosis belong to interstitial lung diseases (ILD) where an imbalance of regulatory, profibrotic and antifibrotic cytokines is hypothesized. The relationship of bronchoalveolar lavage (BAL) fluid (BALF) cytokines, BALF cell profile and ILD course is supposed. The aim of our study was to correlate BALF cytokine and chemokine levels with BALF cellular characteristics and lung function parameters in different ILD. Twenty-two sarcoidosis, seven IPF and 11 HP patients underwent lung function tests and BAL. The BALF differential cell counts and superficial cell markers were characterized, and MCP-1, MIP-1alpha, MIP-1beta, RANTES, epithelial neutrophil-activating protein (ENA)-78, FGF, G-CSF, GM-CSF, IFN-gamma, interleukin (IL)-1alpha, IL-1RA, IL-1beta, -2beta, -4beta, -5beta, -6beta, -8beta, -10beta, -17beta, tumour necrosis factor (TNF)-alpha, thromobopoietin (Tpo) and vascular endothelial growth factor (VEGF) values measured. The BALF VEGF values were highest in sarcoidosis (P = 0.0526). IL-1RA values were higher in IPF and HP compared with sarcoidosis (P = 0.0334). IL-8/ENA-78 ratio positively correlated with BALF neutrophil counts in IPF (r = 0.89, P = 0.04). Vital capacity and TL(CO) values positively correlated with VEGF and negatively with IL-8 BALF levels in all ILDs but the correlations were most significant in sarcoidosis group. We suppose that VEGF plays a role in ILDs' early phases and has rather angiogenic than profibrotic effect. On the contrary, IL-8 is probably upregulated in advanced ILDs with prominent fibrosis and marked lung functions decline. We state that BALF VEGF, IL-8 and ENA-78 levels and IL-8/ENA-78 ratio could become useful markers of ILDs' phase, activity and prognosis. They might also be helpful in treatment modality choice.

[Birth defects incidence in children from single and twin pregnancies in the Czech Republic--current data]. / Incidence vrozených vad u detí z jednocetných a dvojcetných gravidit v Ceské republice--aktuální data.

AIM OF STUDY: An analysis of occurrence of birth defects in children from single and twin pregnancies in the Czech Republic in 1994-2007. An assessment of total numbers and relative incidences of birth defects in births according to Tenth Revision of International Classification of Diseases (ICD-10). TYPE OF STUDY: Retrospective epidemiological analysis of birth defects incidences from the Czech National Birth Defects Register database. MATERIAL AND METHODS: Data from the National Birth Defects Register (Institute for Health Information and Statistics) in the Czech Republic in the 1994-2007 period were used. In this study, particular diagnoses--as they were registered in the National Register--were analyzed. Birth defects were analyzed separetely for children from single and twin pregnancies. The diagoses in study were divided into following eleven birth defects groups according to ICD-10 classification: (Q00-Q07) nervous system, (Q10-Q18) eye, ear, face and neck, (Q20-Q28) circulatory system, (Q30-Q34) respiratory system, (Q35-Q37) cleft lip and cleft palate, (Q38-Q45) digestive system, (Q50-Q56) genital organs, (Q60-Q64) urinary system, (Q65-Q79) musculoskeletal system, (Q80-Q89) other defects and (Q90-Q99) chromosomal abnormalities, not elsewhere classified. Total numbers and mean incidences of birth defects separetely for children from single and twin pregnancies were assessed for all these 11 groups. RESULTS: In the Czech Republic during 1994-2007 period, totally 1,312,930 children were born (live births and stillbirts) from single pregnancies, whereas 42,448 from twin pregnancies. A twin rate (out of a total number of births) increased from 2.33% in 1997 to 4.17% in 2004. An overall incidence of diagnosed birth defects was 436.03 per 10,000 live births in singletons and 598.38 in twins. Birth defects incidence (per 10,000 livebirths)in singletons and twins in each of 11 birth defects groups under the study was during the 1994-2007 period as follows: (Q00-Q07) nervous system 9.45 in sigletons and 17.20 in twins, (Q10-Q18) eye, ear, face and neck 21.69 in singletons, and 18.38 in twins, (Q20-Q28) circulatory system 154.16 in singletons and 272.57 in twins, (Q30-Q34) respiratory system 4.92 in singletons and 5.65 in twins, (Q35-Q37) cleft lip and cleft palate 16.79 in singletons and 20.02 in twins, (Q38-Q45) digestive system 18.97 in singletons and 28.74 in twins, (Q50-Q56) genital organs 52.07 in singletons and 56.30 in twins, (Q60-Q64) urinary system 34.21 in singletons and 56.78 in twins, (Q65-Q79) musculoskeletal system 87.49 in singletons and 90.93 in twins, (Q80-Q89) other defects 26.06 in singletons and 22.14 in twins and (Q90-Q99) chromosomal abnormalities 10.20 in singletons and 9.66 in twins. CONCLUSIONS: The study gives differentiated results of incidences of selected types of birth defects in births according to pregnancy multiplicity. A statistically significant difference (p<0.001) in total birth defects incidence in twins compared to singletons was confirmed. Same statistical significance (p<0.001) was also found (twins compared to singletons) in following birth defects or their groups: (Q00-Q07) nervous system, Q20-Q28) circulatory system, (Q38-Q45) digestive system, (Q60-Q64) urinary system, congenital hydrocephalus, some congenital heart defects, cleft lip and/or palateoesophageal atresia, anorectal malformation, hypospadia, congenital hydronefrosis, polydactyly and syndactyly. A statistically significant difference (p<0.01) was found in spina bifida, hypoplastic left heart syndrome, duodenal atresia/stenosis, diaphragmatic hernia and Down syndrome.

[Liver transplantation and peri-operative changes to renal function]. / Transplantace jater a perioperacní zmeny renálních funkcí.

THE AIM OF THE STUDY: Was to analyze in detail perioperative changes of renal function during orthotopic liver transplantation (OLT) and to identify risk factors, that were associated with the need of renal replacement therapy (RRT) during the first week after liver transplantation. METHODS: Prospective study of 50 consecutive patients undergoing OLT was performed. Selected laboratory and clinical parameters were monitored prior to the procedure, after reperfusion, at the end of the procedure, and at 12 hours after the procedure. In the first post-transplant week, necessity to use RRT in the presence of acute kidney injury was monitored and the analysis of risk factors for the need for RRT was performed. Patient survival, graft function, need for dialysis and selected laboratory parameters were assessed at one year post-transplant. RESULTS: During OLT, there was an increase in S(cr) and S(urea), which persisted as late as 12 hours post-transplant. There was a decrease in U(cr) and U(urea) and an increase in S(Na) and S(K). During the procedure any increase in S(cyst) were observed, increase the values were recorded 12 hours after surgery. S(bili) level decreased. There was a rise in the urinary levels of total protein, albumin and beta2-microglobulin. U(prot)/U(cr) increased significantly after reperfusion, with a peak after the procedure. At 12 hours after the procedure, there was a decrease in U(prot)/U(cr), but the values were still many times higher than those seen preoperatively. RRTwas necessary in 14% cases. Risk factors for acute kidney injury requiring RRT included a higher APACHE score, higher BMI, higher preoperative S(cr) and S(urea), hepatorenal syndrome pretransplant, blood loss and intraoperative hemodynamic instability, postoperative complications and dysfunction of the liver graft. One year after OLT, there was no difference in followed laboratory values between patients requiring postoperative RRT and others; no patient was treated with dialysis. CONCLUSION: OLT has a major impact on glomerular and tubular renal functions. Our data suggest that patients surviving acute renal injury treated with RRT in the early postoperative period have a high chance of restoring renal function. A sensitive marker of renal injury during OLT seems to be perioperative proteinuria.

[Biological and non-biological elimination therapy of acute liver failure. Experimental study on large laboratory animal]. / Biologická a nebiologická eliminacní lécba akutního selhání jater experimentální práce na velkém laboratorním zvíreti.

BACKGROUND: Development of biological and non-biological artificial liver devices in the previous 20 years enabled effective treatment of acute liver failure (ALF) of patients waiting for liver transplantation or for spontaneous liver parenchyma regeneration. Aim of the study was the evaluation of the effectiveness of biological (BAL - bioartificial liver) and non-biological (FPSA - Fractionated plasma separation and adsorption) methods in the treatment of experimental ALF on large laboratory animal. METHODS AND RESULTS: Surgical model of ALF with liver devascularization in pigs (weight 25-40 kg) was provided following monitoring of ALF markers (AST, ALT, bilirubin, ammoniac, glycaemia, INR) including intracranial pressure (ICP). Control group included animals without treatment of ALF. Results of both experimental groups were compared and statistically worked-out with that of controls by T-test and Mann-Whitney non-parametric test by EXCEL and QUATRO. BAL group: 10 pigs (weight 30 +/- 5 kg) with ALF were treated by BAL with isolated hepatocytes. When plasma bilirubin was compared, significant differences (p < 0.05) in 6 and 9 hours interval were found favouring BAL group (18.1 vs. 13.1, 22.9 vs. 13.2 mmol/l). The value of ICP in both groups was no significant. Prometheus group: 14 pigs weight 35 kg (35 +/- 5 kg) with the identical ALF were treated by Prometheus (FPSA). Level of serum bilirubin in experimental group when compared to control group was significantly lower (p < 0.01) at 6 hour interval 12.81 +/- 6.54 vs. 29.84 +/- 9.99 at 9 hour 11.94 +/- 4.14 vs. 29.95 +/- 12.36 and at 12 hour 13.88 +/- 6.31 vs. 26.10 +/- 12.23 mmol/l. No significant difference in serum ammonia level was found. ICP was significantly different from 9 hour to 12 hour interval in favour of FPSA group (p < 0.01): 9 hour 19.1 +/- 4.09 vs. 24.1 +/- 2.85, 10 hour 21.9 +/- 3.63 vs. 25.1 +/- 2.19, 11 hour 22.5 +/- 3.98 vs. 26.3 +/- 3.50 and 12 hour 24.0 +/- 4.66 vs. 29.8 +/- 5.88 mm Hg. CONCLUSIONS: Significant improvement of bilirubin and ICP levels resulting from the treatment with fractionated plasma separation and adsorption (Prometheus) were observed in the case of experimental ALE Except the bilirubin levels, bioartificial liver provided by O. liver Performer with isolated hepatocytes did not bring any significant improvement of laboratory markers, including ICP.

Self-expandable stent placement in infrapopliteal arteries after unsuccessful angioplasty failure: one-year follow-up.

The purpose of this prospective study was to evaluate whether stent placement in infrapopliteal arteries is helpful in failed percutaneous transluminal angioplasty (PTA). Infrapopliteal PTA was performed in 70 arteries of 66 patients with chronic critical lower limb ischemia. The group comprised 55 males and 11 females, with an average age of 63.4 (range, 42-82) years. Diabetes mellitus was present in 92.4% of patients. Only the palpable anterior tibial and posterior tibial arteries were evaluated. Stents (Xpert stent; Abbot Vascular, Redwood City, CA, USA) were placed in 16 arteries where PTA was not successful (the failure was defined as residual stenosis >30% after PTA). In 54 arteries simple PTA was performed and was technically successful. Twenty-four nondilated arteries with no significant stenosis served as a comparison group. The 12-month patency rate was evaluated according to a combination of palpation and Doppler ultrasound. In all cases stent placement restored the flow in the artery immediately after unsuccessful PTA. Twelve-month follow-up showed a patency rate of 82% in the PTA group, 78% in the stent group, and 69% in the comparison group. We conclude that stent placement in the case of unsuccessful infrapopliteal PTA changed technical failure to success and restored flow in the dilated artery. At 12-month follow-up the patency rate of infrapopliteal arteries stented for PTA failure did not differ significantly either from nonstented arteries with an optimal PTA result or from a comparison group of nonintervened arteries.

TRH test in patients with diabetes mellitus type 1 and/or autoimmune thyroiditis. Changes in the pituitary-thyroid axis, reverse T3, prolactin and growth hormone levels.

The response of the pituitary- thyroid axis, reverse triiodothyronine (rT3), prolactin, and growth hormone (GH) levels following TRH stimulus (Relefact TRH 200 microg 2 amp. i.v.) was examined in patients with autoimmune diabetes type 1 (DM1, n=30), with autoimmune thyroiditis (AT, n=25), and with concurrent DM1 and AT (n=22) to evaluate the influence of DM1 and AT of autoimmune pathogenesis on the above-mentioned hormonal parameters. Statistical analysis (ANOVA) showed that: a) the response of TSH did not differ from control groups (C); b) free triiodothyronine (fT3), free thyroxine (fT4) and their ratio in DM1, DM1+AT and C rose in 120 and 180 min, while a similar increase was not seen in AT (p<0.000001); c) rT3 was not present in any group, with rT3 levels higher in AT (p<0.00002) and lower in DM1 (p<0.02); d) the response of GH had a paradoxical character in some patients in all groups, most often in DM1 (52 %, DM1 vs C, p <0.01). The characteristic response difference was not in the peak GH level, but the delayed return to basal levels in DM1 (p<0.0001) and an abrupt one in AT (p<0.0001). The major findings in DM1 were the differences in GH response, while significant impairment of pituitary-thyroid axis and PRL response to TRH was absent. AT was associated with impairment of TRH stimulated fT3, fT4, fT3/fT4 response and changes in rT3 levels, in spite of preserved TRH-stimulated TSH secretion. GH response in AT patients was also altered.

Weight, body composition and fat distribution of Czech women in relation with reproductive phase: a cross-sectional study.

A sample of 213 healthy Czech women was classified into four groups according to their reproductive phase: fully reproductive, premenopausal, menopausal and postmenopausal women. Changes in body weight, body composition and fat distribution were studied in those four groups using the classical anthropometric method. Body weight rises till the menopause with no further increase. A decrease in relative contribution of muscle and bone mass was observed. The progressive increase in fat mass with age was clearly demonstrated, both the fat mass weight (r = 0.38, p < 0.001) and its percentage contribution (Matiegka r = 0.40, p < 0.001, Parízkovi r = 0.42, p < 0.001). There is a stronger correlation of central fat indices as WHR (r = 0.57, p < 0.001), abdominal (r=0.56, p < 0.001) and waist circumference (r = 0.50, p < 0.001) than for hip circumference (r = 0.27, p < 0.001) to the age. WHR and waist increase most when fully reproductive and premenopausal women were compared (p < 0.001); less when premenopausal to menopausal women are compared (NS) and the least when menopausal to postmenopausal women were compared (NS). The mean values of 14 skinfolds thickness are shown, the skinfold at the abdomen shows the strongest correlation to the age (r = 0.49, p < 0.001). The results are consistent with the hypothesis of progressive fat centralisation.