Relative Change in NT-proBNP Level: An Important Risk Predictor of Cardiovascular Congestion in Haemodialysis Patients.

BACKGROUND: Cross-sectional studies have shown that B-type natriuretic peptide (BNP) and its N-terminal fragment (NT-proBNP) are predictive of cardiovascular death in haemodialysis (HD) patients. In the present study, we tested the hypothesis that monitoring NT-proBNP measurements adds further prognostic information, i.e. predicts congestive heart failure (CHF) events. METHODS: In a prospective cohort of 236 HD patients, NT-proBNP levels were measured monthly during 18 months. Patients were divided according to the occurrence of CHF events. In a nested case-control study, we assessed the evolution of NT-proBNP levels. RESULTS: On average, the 236 HD patients were followed up for 12.5 months, a period during which 44 patients developed a CHF event (half requiring hospitalisation). At baseline, patients who developed a CHF event had significantly more dilated cardiomyopathy and/or altered left ventricular ejection fraction and higher NT-proBNP levels compared with patients who did not develop a CHF event. During follow-up, we observed a significant increase in NT-proBNP levels preceding the CHF event. At a 20% relative increase of NT-proBNP, the sensitivity of NT-proBNP as a predictor of CHF events was 0.57 and the specificity 0.77. CONCLUSION: The relative change in NT-proBNP levels is a significant risk predictor of a CHF event.

Individualized mycophenolate mofetil dosing based on drug exposure significantly improves patient outcomes after renal transplantation.

Efficacy and safety of mycophenolate mofetil (MMF) may be optimized with individualized doses based on therapeutic monitoring of its active metabolite, mycophenolic acid (MPA). In this 12-month study, 137 renal allograft recipients from 11 French centers receiving basiliximab, cyclosporine A, MMF and corticosteroids were randomized to receive either concentration-controlled doses or fixed-dose MMF. A novel Bayesian estimator of MPA AUC based on three-point sampling was used to individualize doses on posttransplant days 7 and 14 and months 1, 3 and 6. The primary endpoint was treatment failure (death, graft loss, acute rejection and MMF discontinuation). Data from 65 patients/group were analyzed. At month 12, the concentration-controlled group had fewer treatment failures (p = 0.03) and acute rejection episodes (p = 0.01) with no differences in adverse event frequency. The MMF dose was higher in the concentration-controlled group at day 14 (p < 0.0001), month 1 (p < 0.0001) and month 3 (p < 0.01), as were median AUCs on day 14 (33.7 vs. 27.1 mg*h/L; p = 0.0001) and at month 1 (45.0 vs. 30.9 mg*h/L; p < 0.0001). Therapeutic MPA monitoring using a limited sampling strategy can reduce the risk of treatment failure and acute rejection in renal allograft recipients 12 months posttransplant with no increase in adverse events.

Homocysteine, vitamin B12, and folic acid in age-related macular degeneration.

PURPOSE: Hyperhomocysteinemia is considered an independent risk factor for atherosclerosis and thrombosis. The purpose of this study was to evaluate plasma homocysteine, red blood cell folate, plasma folate, and plasma vitamin B12 concentration in patients with exudative age-related macular degeneration (ARMD). METHODS: The participants of this study included 30 patients aged 60 to 71 years (mean age 66.2+/-3.6) with exudative ARMD. Plasma homocysteine levels were determined by high performance liquid chromatography (HPLC). Red blood cell folate, plasma folate, and plasma vitamin B12 concentration were determined using a standard kit (Dualcount Solid Phase No Boill radioassay kit for B12/folic acid, DPC Diagnostic, USA) by radioassay method. RESULTS: The plasma concentration of Hcy (14.88+/-6.23 micromol/L) in ARMD patients was significantly increased (p<0.0001) compared with the control group (8.72+/-3.34 micromol/L). We found not a significant decrease of the plasma vitamin B12 concentration in the ARMD group (476.88+/-220.91 pg/mL) compared with the control group (527.08+/-208.97 pg/mL). Red blood cell folate (158.44+/-56.30 ng/mL) and plasma folate (6.5+/-3.4 ng/mL) in ARMD patients were also not significantly decreased when compared with the control group (183.86+/-59.33 ng/mL and 7.93+/-5.05 ng/mL). CONCLUSIONS: Hyperhomocysteinemia might be one of the risk factors for the exudative form of ARMD.

Changes in lipid metabolism in women with age-related macular degeneration.

Age-related macular degeneration (AMD) is one of the leading causes of visual loss among people aged 65 and older. At present the origin of AMD still remains unknown. The objective was to evaluate the chosen lipid and lipoprotein concentrations in blood of patients with AMD. Sixty women aged 55-71 (mean age 65.1+/-5.7) were treated in the outpatient ophthalmological clinic for more than two years because of AMD. We evaluated total serum cholesterol (TCH), triglycerides (TG), HDL-cholesterol (HDL), LDL-cholesterol (LDL), lipoprotein (a) (Lp(a)), apolipoprotein AI (Apo AI) and apolipoprotein B (Apo B) by direct spectrophotometry (Human and Randox standard kits, USA). We found a significant increase of TCH, LDL and TG (224.36+/-41.67 mg/dl, 159.02+/-39.66 mg/dl and 120.92+/-42.64 mg/dl), and a significant decrease of HDL (38.68+/-6.36 mg/dl) in the AMD patients when compared with the control group. We have not found a significant difference in the average TG level between the studied groups. The concentration of Apo B was markedly increased (164.66+/-46.46 mg/dl) and Apo AI concentration was markedly decreased (128.9+/-17.01 mg/dl) in the AMD patients when compared with the control group. There was no significant difference in the concentration of the Lp(a) between the two groups. The results of our present study could point to the fact that changes in the lipid metabolism could be one of the very important risk factors involved in the pathogenesis of AMD.

Homocysteine, vitamin B12, and folic acid in age-related macular degeneration.

PURPOSE: Hyperhomocysteinemia is considered an independent risk factor for atherosclerosis and thrombosis. The purpose of this study was to evaluate plasma homocysteine, red blood cell folate, plasma folate, and plasma vitamin B12 concentration in patients with exudative age-related macular degeneration (ARMD). METHODS: The participants of this study included 30 patients aged 60 to 71years (mean age 66.23.6) with exudative ARMD. Plasma homocysteine levels were determined by high performance liquid chromatography (HPLC). Red blood cell folate, plasma folate, and plasma vitamin B12 concentration were determined using a standard kit (Dualcount Solid Phase No Boill radioassay kit for B12/folic acid, DPC Diagnostic, USA) by radioassay method. RESULTS: The plasma concentration of Hcy (14.886.23 micronmol/L) in ARMD patients was significantly increased (p<0.0001) compared with the control group (8,.723,.34 micronmol/L). We found not a significant decrease of the plasma vitamin B12 concentration in the ARMD group (476.88220.91 pg/mL) compared with the control group (527.08208.97 pg/mL). Red blood cell folate (158.4456.30 ng/mL) and plasma folate (6.53.4 ng/mL) in ARMD patients were also not significantly decreased when compared with the control group (183.8659.33 ng/mL and 7.935.05 ng/mL). CONCLUSIONS: Hyperhomocysteinemia might be one of the risk factors for the exudative form of ARMD.

Detection of ganciclovir resistance after valacyclovir-prophylaxis in renal transplant recipients with active cytomegalovirus infection.

Whether valaciclovir (VCV) prophylaxis could be responsible for ganciclovir (GCV)-resistance of Human cytomegalovirus (HCMV) in transplantation has never been documented. A multicentric retrospective pilot study was undertaken to detect GCV-resistance through mutations within the UL97 gene in renal transplant recipients who experienced active HCMV infection and received valacyclovir prophylaxis. Twenty-three patients who experienced HCMV antigenaemia or DNAemia during or at the end of prophylaxis were included. UL97 genotyping was carried out on peripheral blood samples, using a nested in-house PCR, which amplified the full-length UL97 gene. One patient has a resistance-related mutation (M460I); the major risk factor for emergence of resistance in this patient was the presence of early and persistent antigenaemia. GCV-resistance during VCV-prophylaxis was rare after renal transplantation. However, special attention must be paid to patients developing early active HCMV infection under prophylaxis.

Circadian rhythm of androstendione and free testosterone in asthmatic women with postmenopausal hormone therapy.

OBJECTIVE: of this study was to assess daily rhythm of androstendione (delta4alpha) and free testosterone (FT) levels in postmenopausal asthmatic women before and after hormonal replacement therapy and the influence of inhaled glucocorticosteroids (GC). METHODS: 54 asthmatic and 20 healthy postmenopausal women (aged 48-59) before and after 6 months of estrogen plus progestin therapy (EPT) were studied. Hormone concentrations in serum (delta4alpha and FT) were assessed with the use of RIA method. Statistical analysis of the circadian rhythm was performed with the use of cosinor test according to Halberg et al RESULTS: Cosinor analysis of delta4alpha and FT secretion during the day showed existence of daily rhythm in three studied groups before as well as after postmenopausal hormone therapy (HT). A statistically significant decrease of circadian concentrations of delta4alpha and FT in groups of patients treated with GC was observed. Changes in amplitude of delta4alpha and FT rhythm between studied groups were not observed. However, displacement of rhythm acrophase of studied hormones in asthmatic women in comparison to control group before and after HT was shown. No significant differences in circadian values of delta4alpha and FT concentrations before HT use compared to values after HT were shown. CONCLUSIONS: Postmenopausal asthmatic women show diminished circadian concentrations of androstendione and free testosterone in serum caused among other things by inhalative GC. Postmenopausal hormone therapy did not influence any changes in function of studied endocrine organs.

Serum adiponectin in women with polycystic ovarian syndrome and its relation to clinical, metabolic and endocrine parameters.

UNLABELLED: Several studies have demonstrated that low levels of serum adiponectin are present in obesity, insulin resistance, hypertension and hyperlipidemias. The aim of our study was to determine whether serum adiponectin level is different between patients with polycystic ovarian syndrome (PCOS) and control subjects. We also investigated relationships between various cardiovascular risk factors, levels of serum adiponectin and other hormones, such as androstendione, testosterone, estradiol, DHEAS, sex hormone binding globulin (SHBG), and leptin. We also analysed the correlation between serum adiponectin and free androgen index. Ninety-one women with clinical diagnosed PCOS and 53 healthy control subjects, carefully matched by body mass index (BMI) and age, were enrolled in the study. The fasting blood samples were obtained and all participants underwent an oral 75 g glucose tolerance test. The prevalences of impaired glucose tolerance (IGT), hypertension and hypertriglyceridemia were higher in the PCOS group. PCOS women had increased androgen concentrations and higher free androgen index and decreased level of serum SHBG. Lower serum adiponectin concentrations were observed among cases than in controls (median 13.7 microg/ml vs 17.8 microg/ml, p<0.001) despite being matched by BMI. In the PCOS group adiponectin levels correlated significantly with: BMI (r=-0.32, p=0.002), waist circumference (r=-0.32, p=0.003), waist-to-hip ratio (WHR, r=-0.38, p=0.001), triglycerides (r=-0.31, p=0.007), SHBG (r=0.30, p=0.003) and free androgen index (r=-0.29, p=0.02). In contrast, the adiponectin level does not appear to be related to total testosterone, DHEAS and leptin levels. The adiponectin and SHBG levels were found to be decreased in PCOS women with IGT compared to PCOS women with normal glucose tolerance, but after adjustment by BMI or WHR, the differences were no longer statistically significant. To exclude a possible confounding effect due to a higher prevalence of IGT in the PCOS group, this comparison was repeated for the subgroup of 58 PCOS women and 48 control women after excluding those with IGT. Neither adiponectin nor SHBG were significantly different between those subgroups. Multiple regression analysis revealed that serum adiponectin concentrations were best predicted by WHR, free androgen index and presence of IGT when all patients were considered. In PCOS subjects, the only independent predictor of adiponectin concentrations was glucose tolerance status. CONCLUSIONS: Lower adiponectin levels were observed in PCOS group than in control women, and these differences were probably due to higher prevalence of IGT in these cases.

Thrombotic microangiopathy and digital necrosis: two unrecognized toxicities of gemcitabine.

We report one new case of hemolytic-uremic syndrome (HUS) and one case of digital necrosis after treatment with gemcitabine (Gemzar). Case 1, a 34-year-old man, was given first-line metastatic treatment with gemcitabine for a adenocarcinoma of the pancreas. After a cumulative dose of 10 000 mg/m2 gemcitabine, the onset of subacute renal failure associated with hemolytic anemia of mechanical origin was observed. A diagnosis of probable gemcitabine-induced thrombotic microangiopathy was arrived at. Symptoms resolved after stopping the chemotherapy, in spite of the progression of the disease. Case 2, a 61-year-old man, was administered a combination of gemcitabine and a platinum salt as first-line metastatic treatment for carcinoma of the bladder urothelium. Following a cumulative dose of 10 000 mg/m2 of gemcitabine, the patient suffered from bilateral peripheral vascular disease of somewhat acute onset with hemorrhagic lesions of the finger pads that became necrotic. The work-up was negative and a causal relationship was attributed to gemcitabine. The patient made good progress when given an i.v. infusion of Ilomedine (iloprost trometamol) and chemotherapy was withdrawn. We conclude that gemcitabine must be added to the list of drugs that cause HUS and necrotizing vasculitis.

Changes in blood antioxidants and several lipid peroxidation products in women with age-related macular degeneration.

PURPOSE: The aim of this study was to evaluate the ferric reducing ability of plasma (FRAP), selected enzymatic and non-enzymatic components of the antioxidative system, and the intensity of peroxidative processes in the blood of patients with age-related macular degeneration (AMD). METHODS: In the peripheral blood, we evaluated FRAP; concentrations of vitamins C, A, and E; and of thiols. We assayed the activity of enzymatic components of the antioxidative system-superoxide dismutase, catalase, ceruloplasmin and the concentration of reduced glutathione as an indicator of glutathione peroxidase activity. In order to determine the intensity of lipid peroxidation, we measured the concentrations of malondialdehyde and hydroxyalkenales (MDA-HNA) and conjugated diens (CD). RESULTS: We found a significant increase in FRAP in patients with AMD compared with the control group. The average concentrations of vitamins A and C were low and vitamins E and GSH were significantly higher in AMD than in the control group. The activity of almost all the antioxidative enzymes was high. We found a significant increase in MDA-HNA but no difference in CD. CONCLUSIONS: The significantly higher concentration of lipid peroxidation products in patients with AMD indicates an important pathogenic role of oxido-reduction disturbance. The high FRAP concentration may be one of the protective mechanisms in oxidation stress. The adaptive increase of the antioxidant barrier mostly involves the enzymatic components.

Plasma levels and metabolism of AcSDKP in patients with chronic renal failure: relationship with erythropoietin requirements.

N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP) is a physiological inhibitor of hematopoiesis that is maintained at stable levels in normal plasma. Its degradation in vivo and in vitro by angiotensin-converting enzyme (ACE) accounts for the high plasma concentrations of AcSDKP in patients treated with ACE inhibitors. Because ACE inhibitors can induce anemia in some patients, we measured plasma AcSDKP concentrations in 176 patients with chronic renal failure: 120 hemodialysis (HD) and 56 nondialysis (nD) patients, 39 of whom were administered ACE inhibitors. We studied the relationships between AcSDKP levels, hematologic parameters, and recombinant human erythropoietin (rHuEPO) requirements in these patients. AcSDKP levels were significantly greater in HD (10.3 +/- 3.9 pmol/mL) and nD (3.1 +/- 1.8 pmol/mL) patients not administered ACE inhibitors than controls (1.8 +/- 0.2 pmol/mL). In all patients, treatment with ACE inhibitors significantly increased these levels fourfold. HD sessions significantly decreased AcSDKP concentrations by 66% and reduced the predialysis in vitro half-life of AcSDKP (270 +/- 109 minutes) to values (182 +/- 67 minutes) not significantly different from those of controls or nD patients. Most HD patients treated with ACE inhibitors had AcSDKP levels greater than 24 pmol/mL (the greatest concentration found in other nD and HD patients). Only in this group of patients did weekly doses of rHuEPO correlate with AcSDKP levels. Our results show that renal function is essential to maintain stable AcSDKP plasma levels, and at high levels, AcSDKP acts as a uremic toxin causing partial resistance to erythropoietin and inhibiting erythropoiesis.

Plasma transforming growth factor beta1 in breast cancer patients treated with CMF chemotherapy.

BACKGROUND: In early breast cancer patients the transformed epithelial cells are thought to be sensitive to transforming growth factor beta1 (TGFbeta1)-mediated growth arrest. TGFbeta1 may therefore act as an anti-tumour promoter. However, in advanced breast cancer resistance to such TGFbeta1 action develops. Neoplastic cells produce TGFbeta1, which may enhance tumour invasion and metastasis, mainly by intensifying angiogenesis, which is an immunosuppressive action. In the light of the potential role of TGFbeta1 in breast cancer pathogenesis, an understanding of the effect of applied therapeutic methods on plasma TGFbeta1 concentration is essential. OBJECTIVE: To investigate the effect of adjuvant chemotherapy on plasma transforming growth factor beta1 (TGFbeta1) concentration in breast cancer patients with metastases to axillary lymph nodes. METHOD: Fifteen stage II breast cancer patients on adjuvant chemotherapy with cyclophosphamide, methotrexate and 5-fluorouracil (CMF) were studied along with 15 healthy premenopausal women. RESULTS: Plasma TGFbeta1 concentration (determined by the ELISA method) in the breast cancer patients did not differ significantly from that of the healthy women. Adjuvant CMF chemotherapy significantly decreased plasma TGFbeta1 concentration in those pre-menopausal breast cancer women with metastases to axillary lymph nodes. CONCLUSION: The possible pathogenic action of this growth factor in stage II breast cancer disease warrants further investigation to elucidate whether the induced decrease of blood TGFbeta1 concentration is essential to successful chemotherapy.

Estradiol and progesterone release form biodegradable d,l-lactide and epsilon-caprolactone copolymer.

A study on the release of 17 beta-estradiol and progesterone from d,l-lactide and epsilon-caprolactone copolymer was performed. The copolymer was used in the form of microsphere, d,l-lactide content in the copolymer was 83%. It was found that nearly constant rate of hormone release during 100 days of experiment can be achieved by using this biodegradable material as a drug carrier.

Activity of liver cytochrome P-450-dependent monooxygenase system in morphine-dependent rats.

Young female Wistar rats were injected intraperitoneally with increasing doses of morphine (9-45 mg/kg b.w. twice a day) for 14 days. The activities of the cytochrome P-450-dependent monooxygenase system and microsomal electron transport chain I were determined. Long-term morphine treatment decreased significantly cytochrome P-450 content, while it did not affect microsomal electron transport chain I. A decrease in cytochrome b5 content was accompanied by a compensatory increase in the activity of NADH-cytochrome b5 reductase. Both 4-aminopyrine N-demethylase activity and aniline hydroxylase activity decreased after morphine treatment (48% and 70%, respectively, when compared with controls).

Central adrenergic system does not contribute to morphine stimulated pineal secretion of melatonin.

The effect of long-term morphine treatment of rats subjected to central chemical sympathectomy (CCS) was studied. The experiment was performed on 7-week-old male Wistar rats. CCS was performed with 6-hydroxydopamine injected into the lateral ventricle of the brain. The serum concentration of melatonin was assayed by specific RIA. The study showed that morphine alone significantly increased melatonin concentrations in serum. CCS alone significantly decreased melatonin concentrations in serum at the time of highest secretory activity of the pineal gland. Long-term morphine treatment of rats subjected to CCS significantly increased the serum concentration of melatonin. Therefore, it may be concluded that the central adrenergic system does not take part in the morphine-stimulated secretion of melatonin.

[Evaluation of selected parameters of collagen metabolism in rats after implantation of copolymer d,l-lactide and E-caprolacton with cortisol and progesterone]. / Ocena wybranych parametrów metabolizmu kolagenu u szczurów po implantacji d,l-laktydu i E-kaprolaktonu z kortyzolem i progesteronem.

Tests were carried out on the possibility of biodegradable copolymer d, l-lactide and E-caprolacton as a carrier system for a long-term substitution of progesterone and cortisole. During 120 days of the experiment almost linear profile of freeing of progesterone with average rate 0.5% of the initial amount of hormone (24 hours, what indicates a practical possibility of its application in hormonal substitution) was obtained. Simultaneously the influence of copolymer implants on the metabolism of collagen was tested marking the concentrations P I CP and P III NP in particular periods of the experiment. We did not notice any permanent changes of metabolism of collagen under the influence of the tested carrier system of the hormonal medicaments and the obtained changes of concentrations P I CP and P III NP are probably caused by the hormones freeing from the subgrade.

[Delaire's facial mask in the treatment of anterior prognathic anomalies]. / Maska twarzowa Delaire'a w leczeniu wad doprzednich.

The authors present the technique of treatment of pseudo Class III malocclusion using an orthopedic Delaire's face mask. The use of the method is illustrated with 3 clinical cases.

[Evaluation of the effects of various fluoride concentrations in drinking water and atmospheric air on permanent teeth eruption in children aged 12 years]. / Ocena wplywu róznych stezen fluoru w wodzie pitnej i powietrzu atmosferycznym na wyrzynanie zebów stalych u dzieci w wieku 12 lat.

Dental age was evaluated in 382 children aged 12 +/- 6 years in four Silesian localities differing in the content of fluorine in drinking water and air: in Milicz--without fluoride, in Wroclaw where artificial Fluoridation of drinking water is conducted to levels regarded as optimal--from 0.8 to 1.2 mg/l, in Gryfów where the mean annual pollution of atmospheric air with fluorides was from 0.044 to 0.059 mg/m3 in Nysa where drinking water contains an excess of fluorides 4.0 to 7.0 mg/l. In the light of these studies fluoride was found to retard teeth age. The greater dose of fluorine is taken up by the organism in the period of development the longer is the retardation of dental age.