The rate of MEFV gene mutations in hematolymphoid neoplasms.

The aim of this study was to determine the rate of MEFV gene mutations, the gene responsible for familial Mediterranean fever (FMF), in patients with hematolymphoid neoplasm. The rate of the five most common MEFV gene mutations (M694V, M680I, V726A, M694I and E148Q) was determined in 46 patients with hematolymphoid neoplasm. We found a high frequency of carriers in patients with multiple myeloma (60%) and acute lymphocytic leukaemia (33.3%), whereas patients with chronic lymphocytic leukaemia (9%) and non-Hodgkin lymphoma (5%) had a low mutation carrier rate. There is no MEFV gene mutation in patients with Hodgkin lymphoma. Furthermore, the statistically significant predominance of strong heterozygous mutations such as M694V and M680I in patients with hematolymphoid neoplasm; none had own and/or family history compatible with FMF, is interesting. In conclusion, we found a high frequency of carriers for MEFV gene in patients with multiple myeloma and acute lymphocytic leukaemia. The data of our study may provide some new insights in understanding of individual genetic differences in susceptibility to these neoplasms.

Efficacy of deferoxamine, N-acetylcysteine and selenium treatments in rats with Adriamycin-induced nephrotic syndrome.

BACKGROUND: Various experimental models related to Adriamycin (ADR)-induced nephropathy have been reported. The purpose of the present study was to evaluate the efficacy of N-acetylcysteine (NAC), deferoxamine (DFO) and selenium in protection against renal injury in ADR nephropathy. METHODS: The study included 53 Sprague Dawley male rats. Nephrotic syndrome was induced by injection of ADR 5 mg/kg intravenously (n=46). Control rats (n=7) were injected with an equal volume of isotonic saline. After ADR administration, they were divided into a group given only ADR (n=17) and 3 antioxidant treatment groups: (i) NAC (n=10), (ii) DFO (n=10) and (iii) selenium (n=9). In both renal tissue and erythrocytes, oxidative system parameters and trace elements were determined. RESULTS: Nephrotic syndrome was proven in ADR-injected rats 4 weeks after injections, with proteinuria, higher blood lipids and hypoalbuminemia. All of the antioxidant agents used in the present study to prevent the development of nephrotic syndrome provided benefits for the nephrotic state. Of them, selenium seemed to offer relatively lower and statistically insignificant efficacy for preventing proteinuria compared with the others. CONCLUSIONS: Our results showed that concomitant administration of some antioxidants with ADR injections seems to have beneficial effects on clinical parameters even if antioxidants were given in a single dose. NAC and DFO are more effective than selenium to prevent renal injury.

Persistent mediastinal and axillary lymph node tuberculosis in a renal transplant patient with successful outcome.

Tuberculosis is an opportunistic infection that carries substantial morbidity and mortality in renal transplant recipients. We report here about a 21 year-old man with a living related renal transplant from his mother who developed persistent extra-pulmonary tuberculosis. The disease showed aggressive invasion to the axillary and mediastinal regions with abscess formations, despite standard antituberculosis treatment. During the course of the disease, immunosuppressive therapy was stopped, and the patient received extraordinary doses of multiple antituberculosis drugs. The patient then showed an uneventful course with good clinical and radiological responses.

Plasma melatonin concentration before and during testosterone replacement in Klinefelter's syndrome: relation to hepatic indolamine metabolism and sympathoadrenal activity.

The mechanisms leading to alterations in plasma melatonin (MT) levels with testosterone replacement in Klinefelter's syndrome (KS) remain elusive. We investigated early morning plasma MT levels, urinary 6-sulfatoxymelatonin (6-SM) levels, and urinary catecholamine levels before and 6 months after testosterone treatment in 31 patients with KS and 20 healthy males to demonstrate whether alterations in plasma MT levels in such patients are due to subtle changes in sympathoadrenal activity and/or alterations in the hepatic indolamine metabolism influenced by testosterone replacement. The plasma MT level was measured by RIA. The sensitivity of the test was 10.7 pmol/L. The 6-SM level was measured by enzyme-linked immunosorbent assay. Urinary catecholamines were determined by high performance liquid chromatography. The pretreatment mean plasma MT level was insignificantly higher in the patient group than in the control group (72.57 +/- 74.82 vs. 42.37 +/- 29.02 pmol/L; z = -1.218; P = 0.223). The pretreatment urinary 6-SM and norepinephrine (NE) levels were significantly lower and, the epinephrine (E) and dopamine levels were insignificantly lower in the patient group than those in the control group [6-SM, 76.54 +/- 31.92 vs. 125.49 +/- 50.16 nmol/L (z = -3.727; P < 0.001); NE, 120.79 +/- 58.33 vs. 178.84 +/- 81.61 nmol/day (z = -2.585; P = 0.01); E, 31.27 +/- 27.42 vs. 34.65 +/- 28.33 nmol/day (z = -0.39; P: = 0.692); dopamine, 1577.02 +/- 863.02 vs. 1812.32 +/- 677.59 nmol/day (z = -1.03, P = 0.308)]. After testosterone replacement, plasma MT levels were significantly decreased (72.57 +/- 74.82 vs. 24.73 +/- 23.61 pmol/L; z = -4.29; P < 0.001), and urinary 6-SM, NE, E, and dopamine levels were significantly increased [6-SM, 25.04 +/- 10.44 vs. 40.05 +/- 17.65 ng/mL (z = -4.78; P < 0.001); NE, 120.78 +/- 58.33 vs. 154.08 +/- 61.35 nmol/day (z = -4.27; P < 0.001); E, 31.27 +/- 27.42 vs. 40.74 +/- 30.04 nmol/day (z = -4.22; P < 0.001); dopamine, 1577.02 +/- 863.02 vs. 2162.67 +/- 823.15 (z = -6.127; P < 0.001)]. There was no relation between plasma MT levels, urinary 6-SM, and catecholamine levels and levels of gonadotropins or gonadal steroids either before or after treatment. We demonstrate that in untreated KS, plasma MT levels tend to be higher than those in normal controls, whereas those of the melatonin metabolite 6-SM and those of NE in urine tend to be lower. After testosterone treatment, however, plasma MT levels fall significantly, whereas urinary levels of 6-SM and NE rise. Our data show that the effect of testosterone is mediated by enhanced metabolism of melatonin, not by any effect on net sympathetic outflow, and that the increase in plasma melatonin in untreated KS patients also results from an alteration in the rate of melatonin metabolism and not from increased net sympathetic activity.

Gonadotropin treatment increases homocysteine levels in idiopathic hypogonadotropic hypogonadism: an indirect effect mediated by changes in body composition.

The main objective of the present study was to examine the alterations in plasma total homocysteine (tHcy) concentrations during a testosterone-deficient state and after gonadotropin treatment for 6 Months in patients with idiopathic hypogonadotropic hypogonadism (IHH). Thirty-five newly diagnosed male patients with IHH (mean age 21.34+/-1.53 years) and 29 age- and body mass index-matched healthy males (mean age 21.52+/-1.77 years) were recruited into the study. Pretreatment levels of free testosterone (1.51+/-0.66 pg/ml), estradiol (21.37+/- 4.37 pg/ml), FSH (0.91+/-0.24 IU/l) and LH (1.25+/- 0.53 IU/l) were lower than controls (25.17+/-3.06 pg/ml, 31.00+/-4.96 pg/ml, 3.14+/-1.62 IU/l and 4.83+/-1.65 IU/l respectively) (P<0.001). They increased significantly after treatment (18.18+/-1.59 pg/ml, 27.97+/- 4.25 pg/ml, 2.41+/-0.27 IU/l and 2.79+/-0.19 IU/l respectively) (P<0.001). Patients with IHH had lower tHcy levels than controls (10.14+/-1.34 and 12.58+/- 2.29 micro mol/l respectively) (P<0.001). Plasma tHcy concentrations increased significantly (12.63+/-1.44 micromol/l) after 6 months of treatment (P<0.001). As compared with the controls, pretreatment levels of serum creatinine (63.54+/-13.01 vs 82.84+/-16.69 micromol/l), hemoglobin (12.98+/-0.56 vs 13.83+/-0.71 g/dl) and hematocrit (39.29+/-2.01 vs 41.38+/-1.95%) were significantly lower (P<0.001), and they increased significantly following treatment (80.24+/-11.93 micromol/l, 13.75+/-0.49 g/dl and 41.26+/-1.78% respectively) (P<0.001). The pretreatment folic acid and vitamin B(12) levels were significantly higher in patients when compared with controls (14.87+/-5.68 vs 12.52+/-4.98 nmol/l, P=0.034 and 289.75+/-92.34 vs 237.59+/-108.17 pmol/l, P=0.002 respectively). They decreased significantly after treatment (11.29+/-3.31 nmol/l and 228.51+/-54.33 pmol/l respectively) (P<0.001). The univariate and multivariate regression analysis results showed that only changes in creatinine, creatinine clearance, vitamin B12 and folic acid were independently associated with changes in tHcy levels in patients with IHH. In conclusion, the increase in plasma tHcy concentrations following gonadotropin treatment seems to be largely independent of changes in androgen levels.

Octreotide administration in diabetic rats: effects on renal function and morphology.

The effects of synthetic somatostatin analogue, octreotide, on fractional kidney weight (FKW), urinary protein excretion (UPE), creatinine clearance (Cl(cre)) and renal morphological changes were studied in alloxan-diabetic and non-diabetic rats comparatively. Diabetic rats were treated with twice daily s.c. injections of octreotide (2x2.5 microg) for 90 days. Untreated diabetic and non-diabetic animals were used as reference. The body weights and blood glucose levels of the animals were followed-up throughout the study period. After 90 days, FKW and renal morphology were evaluated. When compared to octreotide-treated diabetic group (O-D: 1.96+/-0. 23), normal control rats (NC: 1.24+/-0.05) showed a lower FKW (P<0. 05) and the FKW value of non-treated diabetic controls (DC: 2.74+/-0. 17) were significantly higher (P<0.05). Cl(cre) values were calculated at 45th and 90th days. At the 45th day, Cl(cre) values (ml/min) of O-D group (0.75+/-0.06) and NC group (0.56+/-0.09) were significantly lower than non-treated DC group (1.05+/-0.1) (P<0.05). However, at the 90th day no significant difference in Cl(cre) was observed. At the 45th day, UPE (mg/dl/day) was significantly higher in non-treated DC group (1000.45+/-392.38) when compared to NC group (236+/-36.59) (P<0.005) and UPE levels of O-D group were only slightly lower than that of non-treated diabetic group. At the 90th day, no significant beneficial effect of octreotide on UPE was observed. Octreotide did not prevent the histopathological changes related to diabetes. In conclusion, 5 microg/day octreotide administrations to diabetic rats for 90 days prevented renal weight increase but this treatment were insufficient to decrease the histopathological changes, UPE and increased Cl(cre).

Iodine and zinc, but not selenium and copper, deficiency exists in a male Turkish population with endemic goiter.

Although endemic goiter has been shown to have a high prevalence in Turkey, little is known about the concentration of urinary iodine, plasma selenium (Se), copper (Cu), and zinc (Zn) in these patients. We studied on 140 male patient with endemic goiter (mean age: 22.2 +/- 0.19 yr) and 140 healthy male subjects (mean age: 21.8 +/- 0.28 yr). Daily urinary iodine excretion was determined by the ionometric method. Plasma Se, Zn, and Cu were determined by using atomic absorption spectrometry. Daily urinary iodine excretion was found to be significantly lower in the patient group (38.7 +/- 2.26 microg/d) than that of controls (50.73 +/- 2.56 microg/day, p = 0.001). Plasma Zn concentrations were also found to be significantly lower in the patient group (1.04 +/- 0.03 microg/mL) than that of controls (1.16 +/- 0.02 microg/mL, p = 0.001). No significant difference was determined in Se and Cu concentrations between the patient and control groups. Our study shows that a moderate iodine deficiency exists in both patients with endemic goiter and control subjects, which indicates the important role of iodine deficiency in the etiopathogenesis of endemic goiter in Turkey. Zinc deficiency may also contribute to the pathogenesis of endemic goiter. However, Se and Cu do not seem to have any role in the etiopathogenesis of endemic goiter in Turkey. A community-based iodine fortification program throughout the country may be proposed to take over the problem, which also can prevent the contributing effects of other element deficiencies that occur when iodine deficiency is the prevailing factor.

Craniofacial anomalies, ocular findings, pigmented nevi, camptodactyly, and skeletal changes: a possible new autosomal recessive disorder.

A 20-year-old male is described with craniofacial anomalies, ocular findings, pigmented nevi, camptodactyly and skeletal changes. On the basis of the clinical and radiological differences with syndromes previously described we classify the present case as a new faciothoracoskeletal syndrome. Parental consanguinity supports autosomal recessive inheritance.

Detection of source of haematuria after extracorporeal shock wave lithotripsy (ESWL) by automated measurement of urinary red cell volume.

Midstream urine samples taken from 35 patients with secondary haematuria due to nephrolithiasis and 31 patients with haematuria after ESWL were compared using a red cell analyser (RCA) to differentiate the source of haematuria. Urine samples obtained from both groups were examined by RCA for urinary red cell mean corpuscular volume (UMCV) and urinary red cell volume distribution curves (RCVDC). To rule out the influence of blood MCV (BMCV), BMCVs were determined separately and the ratio of UMCV/BMCV (R) was calculated. Although our findings showed no difference between haematurias after ESWL and nephrolithiasis, we cannot exclude a direct effect of shock waves on renal tissue.

Infectious complications in 135 Turkish renal transplant patients.

Infections are the emerging causes of mortality and morbidity due to lifelong immunosuppressive therapy in renal transplant patients (1, 4). Here, we report infectious complications of 135 renal allograft recipients who were followed up in the last 20 years in Gülhane Military Medical Academy, Ankara, Turkey. Of them, 83 (61.4%) had a transplant from living related donors, 18 (13.3%) from living non-related HLA matched donors and 34 (25.1%) from cadaveric matched donors. Immunosuppression was achieved in 42 (31.1%) recipients by azathioprine plus corticosteroid (AZA + CS) and in 93 (68.8%) by AZA + CS + cyclosporin A (CsA). Encountered infections were classified according to three different periods of the transplantation procedure [early (first month), intermediate (2-6th months) and late (after the 6th month)]. Bacterial infections were the leading infections in all three periods and the most affected system was the urinary tract. Each recipient had at least one episode of urinary tract infection (UTI) and E. coli was the most common urinary pathogen. On the other hand, HCV was the leading viral pathogen (14.3%). The total mortality rate was 7.4%, and septic shock was the most common cause of death (80%).

Plasma osteoprotegerin concentrations in type 2 diabetic patients and its association with neuropathy.

BACKGROUND AND AIMS: To investigate the association of plasma osteoprotegerin (OPG) levels with diabetic neuropathy. METHODS: Forty-two diabetic patients (21 female and 21 male) and twenty-four non-diabetic healthy control subjects (12 female and 12 male) were included in the study. All consecutive diabetic patients who came for routine follow-up at our outpatient clinic were invited to participate in this clinical study. We studied EMG and neuropathy symptom score in all study subjects. Fasting plasma glucose, HbA1 C, hs-CRP, OPG levels and lipid profile were measured for each subject. RESULTS: Serum fasting glucose, HbA1c, HOMA-IR, total cholesterol, triglyserid, LDL-Cholesterol, HDL-Cholesterol, lipoprotein (a), apolipoprotein-b, hs-CRP, OPG levels, and neuropathy symptom score were statistically higher in diabetic patients than in healthy control subjects. Plasma OPG levels was statistically higher in diabetic patients than it was in nondiabetic control subjects. However, plasma OPG levels were not significantly different between diabetic patients without neuropathy and healthy control subjects. On the other hand, OPG levels were statistically higher in diabetic patients with neuropathy than in patients without neuropathy. In addition to that serum fasting glucose, HbA1c, hs-CRP, diabetes duration, neuropathy symptom score were statistically higher in diabetic patients with neuropathy than they were in patients without neuropathy. In total group of subjects, plasma OPG levels were correlated significantly with age, diabetes duration, HbA1c, total cholesterol, HDL-cholesterol, lipoprotein (a), apolipoprotein b, hs-CRP. In diabetic patients, plasma OPG correlated significantly with age, diabetes duration, neuropathy symptom score, HbA1c, lipoprotein (a), apolipoprotein b levels. CONCLUSIONS: The major findings of this study were that the plasma OPG concentrations were higher in type 2 diabetic patients than OPG concentrations in healthy control subjects and they were positively correlated with diabetic neuropathy. This finding supports the growing concept that OPG acts as an important regulator in the development of vascular dysfunction in diabetes.

Detrimental effects of N-acetylcysteine plus desferoxamine combination in an experimental nephrotic syndrome model.

The aim of this study was to evaluate the effects of N-acetylcysteine (NAC) and desferoxamine (DFO) administered alone or in combination together in rats with doxorubicin (DOX)-induced nephrotic syndrome, by monitoring oxidative stress parameters and trace elements in renal tissue and erythrocytes. Fifty-four male Sprague-Dawley rats were included the study. Equal volume of isotonic saline was injected to control rats. After DOX administration, the animals were divided into four experimental groups: (a) rats given only DOX; (b) rats treated with NAC; (c) rats treated with DFO; (d) rats treated with NAC plus DFO. The combination of N-acetylcysteine and DFO has no beneficial effect on reducing proteinuria in experimentally nephrotic rats, although both of these agents ameliorate the condition when administered separately. It seems likely that detrimental effects of NAC plus DFO could be secondary to its effects on erythrocyte selenium levels demonstrated here. Consequently, the results may propose caution to the use of antioxidant therapeutic strategies such as NAC plus DFO against nephropathy.

ADMA, proteinuria, and insulin resistance in non-diabetic stage I chronic kidney disease.

The rationale of this study is based on the fact that, both proteinuria and elevated asymmetric dimethyl arginine (ADMA) levels have been linked to the progression of vascular disease. Currently, there is not enough knowledge about any association between the levels of proteinuria and ADMA levels. Seventy-eight non-diabetic patients (42 men, 36 women, mean age of 26.1+/-5.2 years) with proteinuria having normal glomerular filtration rate were enrolled along with 38 healthy subjects (20 men, 18 women, mean age of 26.9+/-5.9 years). Proteinuria was below 3.5 g/day in 40 patients and above 3.5 g/day in 38 patients. Both groups had similar age, gender, and body mass index distributions. Serum ADMA, symmetric dimethyl arginine (SDMA), immunoreactive insulin, and high sensitivity C reactive protein (hsCRP) levels were measured. Insulin resistance was determined by homeostasis model assessment (HOMA). Serum ADMA, SDMA, insulin, hsCRP levels, and HOMA indexes were significantly higher in patients than in healthy control subjects. The above parameters were higher in the nephrotic range proteinuria group when compared to patients having protein levels below 3.5 g/day. There were significant correlations between the levels of proteinuria and the above parameters. According to the regression analysis, levels of proteinuria and hsCRP were significant determinants of serum ADMA levels. Our results indicate that, independent of other risk factors, ADMA is directly associated with proteinuria. Further studies are recommended to find out whether elevated ADMA levels are implicated in the high cardiovascular risk of proteinuric nephropathies.

Leptin, soluble interleukin-6 receptor, C-reactive protein and soluble vascular cell adhesion molecule-1 levels in human coronary atherosclerotic plaque.

The aim of the present study was to explore the relationship between tissue levels of leptin, soluble interleukin-6 receptor (sIL-6R), high-sensitive-C-reactive protein (hs-CRP) and soluble vascular cell adhesion molecule-1 (sVCAM-1) in atherosclerotic plaques, and traditional risk factors. Coronary artery specimens were obtained from 35 consecutive patients (26 men and nine women) who underwent coronary artery bypass grafting procedure. The mean tissue levels of leptin, hs-CRP and sIL-6R were significantly higher in patients with diabetes mellitus than without diabetes mellitus. When patients were classified according to the smoking status, the mean tissue levels of leptin, hs-CRP and sIL-6R were significantly higher in current smokers than both former smokers and non-smokers. In addition, the mean tissue levels of leptin and sIL-6R were significantly higher in former smokers than non-smokers. There was a positive association between leptin and hs-CRP, sIL-6R and plasma glucose in all patients. Plasma HDL levels were associated negatively with atherosclerotic tissue levels of leptin. Tissue levels of sIL-6R were associated significantly in a positive manner with leptin, hs-CRP and plasma glucose, while tissue levels of hs-CRP were associated with both leptin and sIL-6R. In conclusion, it is attractive to speculate that hs-CRP, sIL-6R and leptin could act synergistically in course of local inflammatory activity and those molecules may not be just markers of inflammation and cardiovascular risk but are also likely to play a pathogenic role in atheromatous plaque. In addition, atherosclerotic tissue levels of CRP, sIL-6R and leptin were significantly higher in current smokers and patients with diabetes.

Renal magnesium wasting, hypomagnesemic hypocalcemia, hypocalciuria and osteopenia in a patient with glycogenosis type II.

We describe a patient with late-onset glycogenosis type II with renal magnesium wasting, hypomagnesemic hypocalcemia, hypocalciuria and osteopenia. He was admitted to our hospital for evaluation of lower limb weakness and mild deterioration of liver function. Serum magnesium and calcium were low with low-to-normal levels of PTH in the patient. Echocardiogram revealed marked concentric hypertrophy of the left ventricle. An X-ray film of his spine showed a thoracic (Th12) vertebral compression fracture. Bone mineral density of the lumbar spine L2-L4 showed a reduced value. Kidney, liver and muscle biopsies were performed. These were found to have histologic features consistent with glycogenosis type II. In addition, accumulation of PAS-positive material in the cytoplasmic vacuoles of the tubular epithelium was present only in the distal tubules. An oral magnesium supplement was useful in helping to correct the hypomagnesemia, despite the presence of renal magnesium wasting in our patient. Magnesium supplement was also sufficient to maintain normal serum calcium concentrations. However, the hypocalciuria persisted in our patient despite correction of hypomagnesemia. In conclusion, the consistent association between the glycogen accumulation in distal tubules, renal magnesium wasting, hypomagnesemic hypocalcemia and hypocalciuria, in the absence of other identifiable reasons, suggests a cause-and-result relationship. Also, the combination of renal magnesium wasting, hypomagnesemia and hypocalciuria is a picture similar to that of Gitelman's syndrome in our patient. The glycogen accumulation in distal tubules may cause renal magnesium wasting and hypocalciuria through tubular injury. Therefore, we may speculate that the present case has glycogenosis type II-associated Gitelman's-like syndrome.

The effects of metformin and diet on plasma testosterone and leptin levels in obese men.

OBJECTIVE: The aim of this study was to investigate the effects of combined hypocaloric diet and metformin on circulating testosterone and leptin levels in obese men with or without type 2 diabetes. RESEARCH METHODS AND PROCEDURES: Twenty obese men with type 2 diabetes (mean body mass index [BMI]: 35.5 +/- 1.1 kg/m(2)) and 20 nondiabetic obese men were enrolled in the study. We measured serum follicle-stimulating hormone, luteinizing hormone (LH), total testosterone (TT), free testosterone (FT), sex-hormone-binding globulin (SHBG), dehydroepiandrosterone sulfate (DHEAS), and plasma leptin levels before and 3 months after metformin treatment. Both groups were placed on a hypocaloric diet and 850 mg of metformin taken orally twice daily for 3 months. RESULTS: Metformin and hypocaloric diets led to decreases in BMI and waist and hip circumferences in both groups. A significant decrease in TT levels in the diabetic group and FT levels in the control group was found, whereas follicle-stimulating hormone, LH, and DHEAS levels were not changed significantly. A significant increase in SHBG levels was observed in the control group but not in the patient group. Leptin levels also decreased after treatment in both groups. Decreased testosterone levels were not correlated to changes in waist and hip circumference, waist-to-hip ratio, BMI, and levels of fasting blood glucose, leptin, SHBG, or DHEAS in the diabetic group. However, a decrease in FT was correlated to changes in the levels of SHBG (r = -0.71, p = 0.001) and LH (r = 0.80, p = 0.001) but not to other parameters. DISCUSSION: We conclude that metformin treatment combined with a hypocaloric diet leads to reduced FT levels in obese nondiabetic men and to reduced TT levels in obese men with type 2 diabetes. Increased SHBG levels may account for the decrease in FT levels in the former group.