Abstract Purpose of the study To evaluate if renal angioplasty (PTRA) in patients with transplanted kidney and renal artery stenosis (TRAS) can have long-term effect on hypertension and renal ...function. Materials and methods Within a 24-year time period, 58 PTRAs in 55 adults (three times Re-PTRA) with transplanted kidney were performed. The group included 34 males and 21 females, average age 41 ± 10.6 (18–72) years. After exclusion of 7 technical failures, 51 PTRAs were followed at 1 week, 6 months and 1–3 years after PTRA. Hypertension improvement was defined as mean arterial pressure (MAP) decrease of at least 15% from the pre-PTRA value. Graft function was evaluated by serum creatinine (Scr) and creatinine clearance (Ccr) levels, and the improvement was defined as a 20% change. Clinical FU was 3 years. Results PTRA technical success was 88.4%. In 51 kidney recipients at the end of FU, blood pressure improved in 65.2% of patients (MAP decreased from 123 ± 13.1 to 107 ± 12.1 mmHg), but no patient remained normotensive medication free. Graft function improved in 44.8% of patients and was stabilized in 20.7% of them (average Ccr before PTRA: 0.48 ± 0.29, after PTRA: 0.78 ± 47 ml/s). PTRA complications were observed in 25.5% of procedures, most often with no clinical sequel. Thirty days mortality was 1.8% (one patient). Conclusions PTRA results in kidney recipients are valuable mainly in preserving graft function.
Pregnancy-associated plasma protein A (PAPP-A) and soluble receptor for advanced glycation end products (sRAGE) are new markers related to vascular damage.
Thirty-one patients who had undergone ...kidney transplantation (TX) in the year 2005 under tacrolimus-based immunosuppression were included in this prospective single-center study. PAPP-A and sRAGE were determined before TX and 2 and 6 weeks and 3 months after TX. The results were correlated with the 3-month protocol kidney graft biopsy findings.
Both PAPP-A and sRAGE decreased after TX (mean values in serum: PAPP-A 20.8, 13.7, 12.1, and 10.7 mIU/l, respectively, before and 2 and 6 weeks and 3 months after TX, p < 0.001; sRAGE 4,403.4, 2,512.7, 1,909.0, and 1,817.6 pg/ml, respectively, before and 2 and 6 weeks and 3 months after TX, p < 0.001) and were correlated with the graft function (PAPP-A vs. modification of diet in renal disease formula r = -0.52, p < 0.001; sRAGE vs. modification of diet in renal disease formula r = -0.54, p < 0.001). Additionally, the PAPP-A levels correlated with interstitial inflammation (r = 0.57, p < 0.05) and vascular intimal thickening (r = 0.47, p < 0.05), while sRAGE correlated with arteriolar hyalinosis (r = 0.49, p < 0.05).
Our study demonstrates the role of the kidney in the metabolism and/or the removal of PAPP-A and sRAGE. After successful TX, these substances decrease, and, on the contrary, early chronic vascular changes in the kidney TX are associated with elevation of their serum levels.
Abnormal immune functions of polymorphonuclear (PMN) cells occur in a variety of pathophysiological conditions. There exists a close link between glucose metabolism and PMN functions. The aim of this ...study was to assess the effect of short-term hyperglycemia and/or hyperinsulinemia on phagocytosis and respiratory burst of PMN cells in healthy subjects in vivo. The study was performed on 12 healthy subjects (mean age, 26.9 ± 1.6 years; body mass index, 24.4 ± 0.84 kg/m
2). Acute hyperglycemia and/or hyperinsulinemia was induced by three 4-hour-long clamp studies—hyperglycemic hyperinsulinemic clamp (HHC), hyperinsulinemic euglycemic clamp (HEC), and isolated hyperglycemic clamp with insulin secretion blockade (HGC). Polymorphonuclear cell phagocytosis and PMN cell respiratory burst (mean percentage and mean fluorescent intensity of phagocyting/activated PMN cells, phagocytic, and respiratory burst indexes) were evaluated by flow cytometry under basal and stimulated conditions. Results detected during clamp studies were compared with those found during a control study with saline infusion. Significant reductions in the mean percentage of phagocyting cells measured under basal conditions after the HHC (6.7% ± 1.3% vs 12.1% ± 4.3%;
P < .05) and HGC (4.5% ± 1.8% vs 9.9% ± 2.1%;
P < .05) were found in comparison with the preclamp study period; however, these results did not differ significantly from those detected during the control clamp (CC) study. Significantly higher phagocytic (115.1 ± 65 vs 35.8 ± 18.6;
P < .05) and respiratory burst indexes (16.5 ± 3 vs 10.1 ± 1.4;
P < .05) measured under basal conditions were found after HEC in comparison with the preclamp data. However, these data did not differ significantly from those found after the CC study. No significant differences in other parameters of detected PMN cell immune functions were found after HHC, HEC, and HGC. In conclusion, immune functions of PMN cells were not significantly influenced by short-lasting hyperglycemia and/or hyperinsulinemia induced in vivo by clamp techniques in healthy subjects compared to changes induced by the CC study. Further studies on the short-term effect of glucose metabolism on PMN functions in diabetic patients should be considered necessary.
The aim of this study was to compare the serum levels of the anti-angiogenic factor endostatin (S-endostatin) as a potential marker of vasculogenesis after autologous cell therapy (ACT) versus ...percutaneous transluminal angioplasty (PTA) in diabetic patients with critical limb ischemia (CLI). A total of 25 diabetic patients with CLI treated in our foot clinic during the period 2008–2014 with ACT generating potential vasculogenesis were consecutively included in the study; 14 diabetic patients with CLI who underwent PTA during the same period were included in a control group in which no vasculogenesis had occurred. S-endostatin was measured before revascularization and at 1, 3, and 6 months after the procedure. The effect of ACT and PTA on tissue ischemia was confirmed by transcutaneous oxygen pressure (TcPO2) measurement at the same intervals. While S-endostatin levels increased significantly at 1 and 3 months after ACT (both P < 0.001), no significant change of S-endostatin after PTA was observed. Elevation of S-endostatin levels significantly correlated with an increase in TcPO2 at 1 month after ACT (r = 0.557; P < 0.001). Our study showed that endostatin might be a potential marker of vasculogenesis because of its significant increase after ACT in diabetic patients with CLI in contrast to those undergoing PTA. This increase may be a sign of a protective feedback mechanism of this anti-angiogenic factor.
Developmental language disorder (DLD) is frequently associated with other developmental diseases and may lead to a handicap through adolescence or adulthood. The aim of our retrospective study was to ...characterize DLD subgroups, their etiological factors and clinical comorbidities, and the role of epileptiform discharges in wake and sleep recordings. Fifty-five children (42 male, mean age 6.2 ± 1.4 years, range 4-9 years) were included in the present study and underwent phoniatric, psychologic, neurologic, as well as wake and nocturnal electroencephalography (EEG) or polysomnography (PSG) examinations. A receptive form of DLD was determined in 34 children (63.0%), and an expressive form was found in 20 children (37.0%). Poor cooperation in one child did not permit exact classification. DLD children with the receptive form had significantly lower mean phonemic hearing (79.1% ± 10.9) in comparison with those with the expressive form (89.7% ± 6.2,
< 0.001). A high amount of perinatal risk factors was found in both groups (50.9%) as well as comorbid developmental diseases. Developmental motor coordination disorder was diagnosed in 33 children (61.1%), and attention deficit or hyperactivity disorder was diagnosed in 39 children (70.9%). Almost one half of DLD children (49.1%) showed abnormalities on the wake EEG; epileptiform discharges were found in 20 children (36.4%). Nocturnal EEG and PSG recordings showed enhanced epileptiform discharges, and they were found in 30 children (55.6%,
= 0.01). The wake EEG showed focal discharges predominantly in the temporal or temporo-parieto-occipital regions bilaterally, while in the sleep recordings, focal activity was shifted to the fronto-temporo-central areas (
< 0.001). Almost all epileptiform discharges appeared in non-rapid eye movement (NREM) sleep. A close connection was found between DLD and perinatal risk factors, as well as neurodevelopmental disorders. Epileptiform discharges showed an enhancement in nocturnal sleep, and the distribution of focal discharges changed.
Insulin resistance affecting skeletal muscle metabolism is present in the prehypertensive state. The aim of our study was to test the hypothesis that blood pressure value is related to skeletal ...muscle composition, measured by
31P magnetic resonance (MR) spectroscopy, and to insulin sensitivity in the offspring of hypertensive parents (OH) and healthy controls. Study groups consisted of 10 healthy young lean OH with normal glucose tolerance, confirmed with oral glucose tolerance test, and 13 controls matched for age, sex, and body mass index. Insulin action was estimated as glucose disposal (M), glucose metabolic clearance rate (MCR), and insulin sensitivity index (M/I) during a 10-hour hyperinsulinemic euglycemic clamp. The sum of immunoreactive insulin values from the oral glucose tolerance test was calculated.
31P MR spectroscopy was performed on a whole-body MR scanner (Siemens Vision, Erlangen, Germany) operating at 1.5 T and equipped with actively shielded gradient coils. There were no differences in common metabolic and anthropometric parameters between OH and controls except for the blood pressure, which was in the range of normal to high-normal level in OH. Mean blood pressure was significantly higher in OH (95.73 ± 4.39 vs 83.76 ± 3.95 mm Hg;
P < .001). Trend toward insulin resistance was registered in OH with significantly lower M/I (0.74 ± 0.47 vs 1.42 ± 0.65 mg · kg
−1 · min
−1 · mIU
−1 · L
−1;
P < .05). There were no significant differences in total serum magnesium (sMg) levels between OH and controls, although a positive correlation exists between sMg and insulin sensitivity expressed as M (
r = 0.63,
P < .01), MCR (
r = 0.54,
P < .01), and M/I (
r = 0.51,
P < .05). No differences in signal intensities of phosphocreatine (PCr), phosphomonoesters, phosphodiesters, inorganic phosphates (Pi), adenosine triphosphates (Patp and
βATP), and calculated concentrations of intracellular ionized magnesium (Mgi) and H
+ ions between the groups were detected. Systolic blood pressure correlates positively with PCr/Patp (
r = 0.43,
P < .05), Pi/Patp (
r = 0.413,
P < .05), and Pi/
βATP (
r = 0.48,
P < .05). Diastolic blood pressure correlates positively only with the ratio Pi/
βATP (
r = 0.42,
P < .05). The sum of immunoreactive insulin values correlates with PCr/
βATP (
r = 0.53,
P < .01) and with Pi/
βATP (
r = 0.6,
P < .01). In conclusion, increase in blood pressure and insulin resistance were confirmed in offspring of OH. Insulin sensitivity is related to sMg and the elevation of blood pressure is associated with the activation of energy metabolism in skeletal muscle. The relationship between muscle energetic characteristics and markers of insulin resistance suggests that the alteration of energy metabolism may be present in early stages of metabolic syndrome.
Fatigue, depression, and sleep inertia are frequently underdiagnosed manifestations in narcolepsy and idiopathic hypersomnia. Our cross-sectional study design included diagnostic interview ...accompanied by assessment instruments and aimed to explore how these factors influence disease severity as well as to elucidate any sex predisposition. One hundred and forty-eight subjects (female 63%) were divided into narcolepsy type 1 (NT1; n = 87, female = 61%), narcolepsy type 2 (NT2; n = 22, female = 59%), and idiopathic hypersomnia (IH; n = 39, female = 69%). All subjects completed a set of questionnaires: Epworth Sleepiness Scale (ESS), Hospital Anxiety and Depression Scales (HADS), Fatigue Severity Scale (FSS), and Sleep Inertia Questionnaire (SIQ). In narcoleptic subjects, questionnaire data were correlated with the Narcolepsy Severity Scale (NSS), and in subjects with idiopathic hypersomnia, with the Idiopathic Hypersomnia Severity Scale (IHSS). The highest correlation in narcoleptic subjects was found between NSS and ESS (r = 0.658; p < 0.0001), as well as FSS (r = 0.506; p < 0.0001), while in subjects with idiopathic hypersomnia, the most prominent positive correlations were found between IHSS and SIQ (r = 0.894; p < 0.0001), FSS (r = 0.812; p < 0.0001), HADS depression scale (r = 0.649; p = 0.0005), and HADS anxiety scale (r = 0.528; p < 0.0001). ESS showed an analogic correlation with disease severity (r = 0.606; p < 0.0001). HADS anxiety and depression scores were higher in females (p < 0.05 and p < 0.01), with similar results for FSS and SIQ scales (p < 0.05 for both), and a trend toward higher ESS values in females (p = 0.057). Our study illustrates that more attention should be focused on pathophysiological mechanisms and associations of fatigue, depression, as well as sleep inertia in these diseases; they influence the course of both illnesses, particularly in women.
Extrinsic allergic alveolitis (EAA) patients form heterogenous group with different clinical manifestation and different prognosis. We aimed to determine how to phenotype distinct EAA subgroups. ...Predictive role of the bronchoalveolar lavage fluid (BALF) IL-4Rα concentration at the time of diagnosis with regard to the clinical behavior in EAA patients was studied.
Concentrations of MMP-7, IL-4Rα, TNF-α, and PAR-2 were measured in the BALF od 71 EAA patients at the time of diagnosis. Lung functions and outcome data were assessed at 12 months after the diagnosis. Correlations between the BALF protein concentration, cell profile, lung functions and patient outcome were determined.
We found positive correlations between BALF IL-4Rα concentration and BALF eosinophils (
= 0,006), negative correlation between IL-4Rα BALF concentration and diffusing capacity (DLco) (
= 0,003), negative correlation between IL-4Rα BALF concentration and forced vital capacity (FVC) (
= 0,004) and negative correlation between IL-4Rα concentration and BALF lymphocytes (
= 0,04). The BALF concentration of IL-4Rα was significantly higher in acute exacerbation patients (
= 0,0032) and in patients progressing despite corticosteroid treatment (
= 0,04). We observed a positive correlation between MMP-7 BALF concentration and the BALF lymphocytes (
= 0.05), negative correlation between the PAR-2 BALF concentration and DLco (
= 0.04) and a negative correlation between the BALF TNF-α concentration and DLco (
= 0.03).
Specific subgroup of EAA patients with more severe functional impact, distinct BALF cell profile and higher IL-4Rα BALF concentration can be differentiated. Correlations between the BALF concentrations of PAR-2, MMP-7 and TNF-α with clinical parameters may reflect the role of inflammation in the pathogenesis of EAA.
Low dehydroepiandrosterone sulfate (DHEAS) levels and a high cortisol/ DHEAS ratio are associated with higher mortality in elderly, dialyzed, and immunocompromised patients. The role of these ...hormones in patients with hypoglycemia unawareness (hypo) or in pancreas or islet recipients treated by glucocorticoid-free immunosuppressive regimen (IS) has not been studied.
The aim of this study was to determine the effects of IS and of recurrent hypoglycemia on DHEAS and adrenocorticotropic hormone (ACTH) levels in patients with type-1 diabetes (T1DM).
A case control, cross-sectional analysis of patients in a prospective database enrolled 84 patients with T1DM. They were divided into 4 groups of 21 subjects each: 1) islet or pancreas recipients with hypoglycemia who are IS (hypo +, IS +); 2) pancreas and kidney transplant recipients without insulin or hypoglycemia (hypo -, IS +); 3) T1DM patients with hypoglycemia (hypo +, IS -); and 4) T1DM patients without hypoglycemia (hypo -, IS -).
DHEAS and ACTH levels were significantly decreased in patients with hypoglycemia (P = 0.0002 and P = 0.0001, respectively) as well as in those with IS (P = 0.0497 and P < 0.001, respectively) compared to those without hypoglycemia or IS. The influence of hypoglycemia unawareness on DHEAS levels was stronger than that of immunosuppression (P < 0.10).
Low DHEAS and ACTH levels represent an additional component of hypoglycemia unawareness syndrome and they remain low in patients receiving glucocorticoid-free immunosuppression. DHEAS may serve as a marker, the importance of which remains unclear, but deserves attention.
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