Yahya Sagliker

Effect of tempol (4‐hydroxy tempo) on gentamicin‐induced nephrotoxicity in rats

We investigated the effects of tempol (4‐hydroxy tempo), a membrane‐permeable radical scavenger, on gentamicin‐induced renal failure in rats. The rats were given gentamicin (100 mg/kg/day, i.p., once a day); and gentamicin (100 mg/kg/day, i.p.) and tempol (3.5, 7 or 14 mg/kg/day, i.p., once a day). At the end of 7 days, the gentamicin group produced the remarkable nephrotoxicity, characterized by a significantly decreased creatinine clearance and increased serum creatinine, blood urea nitrogen (BUN) and daily urine volume when compared with controls. In control the BUN value was 21.2 ± 0.07 (mg/100 mL); in comparison, it was 96.9 ± 6.03 in gentamicin group (P < 0.05). Renal histopathologic examination confirmed acute tubular necrosis in this group. In rats treated with gentamicin and tempol a partial improvement in biochemical and histologic parameters was observed. BUN values were 96.9 ± 6.03 and 36.3 ± 2.39 in gentamicin, and gentamicin plus tempol (14 mg/kg) treated groups, respectively (P < 0.05). These results suggest that the administration of tempol may have a protective effect on gentamicin‐induced nephrotoxicity in rats.

Heart Rate Variability, Left Ventricular Functions, and Cardiac Autonomic Neuropathy in Patients Undergoing Chronic Hemodialysis

Objective. Autonomic neuropathy and impairment of left ventricular functions (LVF) have been frequently encountered in chronic renal failure (CRF). The aim of the present study was to evaluate the relationship of cardiac autonomic modulation impairments, as assessed by means of heart rate variability (HRV), with clinical characteristics, and left ventricular function in the patients with CRF undergoing hemodialysis (HD). Methods. Twenty control subjects (Group I) and 22 comparable by age and gender patients with CRF undergoing hemodialysis (Group II) were enrolled in the study. After routine clinical and biochemical evaluations, electrocardiography, and 2 Dimensional, M Mode echocardiography were performed in all participants. Frequency domain HRV analysis was studied by using Kardiosis System. The powers (P1 and P2) and the central frequencies (F1 and F2) of low and of high frequency spectral bands were recorded. Results. End systolic (ESV) and end diastolic volumes (EDV) were significantly higher in Group II (59.3 ± 21.1 mL vs. 34.0 ± 14.3 mL and 131.5 ± 37.3 mL vs. 96.9 ± 18.9 mL, p<0.01, p<0.05, respectively) when compared to those of Group I. Ejection fraction (EF) and fractional shortening (FS) were significantly lower in Group II than in control subjects (52.3 ± 2.4% vs. 63.7 ± 10.1% and 0.29 ± 0.01 vs. 0.34 ± 0.07, p<0.001, p<0.05, respectively). P1 and P2 were decreased in Group II than in Group I (136.2 ± 173.9 m s2 vs. 911.0 ± 685.5 and 96.5 ± 149.6 vs. 499.7 ± 679.5, p<0.001, p<0.01, respectively). Significant correlations were found between high frequency spectral power and dialysis duration (DD), ESV, EDV, EF, FS (r = 0.52 p<0.01, r = 0.68 p<0.001, r = 0.65 p<0.002, r = 0.66 p<0.02, and r = 0.69 p<0.01). Conclusion. As a result, the dependence of cardiac autonomic neuropathy on the disease duration and degree of left ventricular function impairment was shown in the patients undergoing chronic hemodialysis.

Wegener's Granulomatosis Complicated by Pericardial Tamponade and Renal Failure

Prof. Saime Paydaş, Çukurova University, Faculty of Medicine, Dep. of Internal Medicine, TR-013 30 Adana (Turkey) Dear Sir, A 50-year-old woman was admitted to hospital on March 30, 1994, because of coughing and uremia. She had a history of coughing, white mucoid sputum of small volume, weakness, anorexia and pleuritic chest pain. There was nothing in her past and family history. Her physical examination revealed a temperature of 36 °C, pulse 80/min and regular, blood pressure 100/60 mm Hg, respiration 22/min. She was pale. Cardiac examination was normal. The breath sounds were heard less on the basal segments of the right lung. We could not find any organomegaly and LAP. Laboratory findings were as follows: hemoglobin 8.1 g/dl, WBC 9,600/mm3, platelets 147,000/mm3, ESR 120mm/h, BUN 145 mg/dl, creatinine 13.6mg/dl, Na 142 mEq/dl, K 6.1 mEq/dl, Cl 102mEq/dl, Ca 5.6 mg/dl, P 6.1 mg/dl, serum protein 6.6 g/ dl, albumin 2.7 g/dl; blood smear and bone marrow were normal, microscopic analysis of urine revealed 15-20 RBC, fine granular casts and 10-15 leukocytes/high-power field; ANF, RF and anti-DNA were negative, ANCA was not tested. C3 and C4 were normal; daily proteinuria 1 g. HBsAg and antiHCV were negative; computed tomography of the lung revealed patchy infiltrates and bilateral hilar lymphadenopathy, X-ray examination of paranasal sinuses revealed left maxillar sinusitis. In abdominal ultrasonog-raphy, the sizes of the left and right kidneys were 98 × 37 and 97 × 34 mm, respectively. Abdominal computed tomography revealed no further pathology. In renal biopsy, in the glomerular compartment, there were segmental changes, excessive polymorpho-nuclear leukocyte (PMNL) infiltration, nuclear debris, plasma cells and attachments on Bowman’s capsules; in the interstitial compartment, granulomas which revealed necrosis in the inner zones, some fibrosis, atrophy of some tubules, leukocyte and hyaline casts in tubule lumens were seen. In the vessel walls, thickening, necrosis that consisted of PMNL, plasma cells and lymphocytes and in some areas occlusion were seen. Immunohistochemically, IgM was localized in the glomerular tufts and along the capillaries, IgG and IgA were found positive in the glomerulus and vessel walls, locally. Amyloid was negative. Pathologic examination of pericardial biopsy was necrotizing vasculitis that suggested Wegener’s granulomatosis (WG). Epidermal hyperkeratosis and atrophy, collagenous degeneration in band form and mononuclear inflammatory cell infiltration around vessels in the upper dermis were observed in a dermal

International evaluation of unrecognizably uglifying human faces in late and severe secondary hyperparathyroidism in chronic kidney disease. Sagliker syndrome. A unique catastrophic entity, cytogenetic studies for chromosomal abnormalities, calcium-sensing receptor gene and GNAS1 mutations. Striking and promising missense mutations on the GNAS1 gene exons 1, 4, 10, 4.

Hypotheses explaining pathogenesis of secondary hyperparathyroidism (SH) in late and severe CKD as a unique entity called Sagliker syndrome (SS) are still unclear. This international study contains 60 patients from Turkey, India, Malaysia, China, Romania, Egypt, Tunisia, Taiwan, Mexico, Algeria, Poland, Russia, and Iran. We examined patients and first degree relatives for cytogenetic chromosomal abnormalities, calcium sensing receptor (Ca SR) genes in exons 2 and 3 abnormalities and GNAS1 genes mutations in exons 1, 4, 5, 7, 10, 13. Our syndrome could be a new syndrome in between SH, CKD, and hereditary bone dystrophies. We could not find chromosomal abnormalities in cytogenetics and on Ca SR gene exons 2 and 3. Interestingly, we did find promising missense mutations on the GNAS1 gene exons 1, 4, 10, 4. We finally thought that those catastrophic bone diseases were severe SH and its late treatments due to monetary deficiencies and iatrogenic mistreatments not started as early as possible. This was a sine qua non humanity task. Those brand new striking GNAS1 genes missense mutations have to be considered from now on for the genesis of SS.

A controlled study of psychiatric manifestations and electroencephalography findings in chronic kidney disease patients with Sagliker syndrome.

Sagliker syndrome (SS) is a novel syndrome that was described in 2004 in patients with chronic kidney disease (CKD). The aim of this study was to assess psychiatric evaluations and electroencephalography (EEG) findings of patients with CKD and SS to compare them with patients with CKD having characteristics similar to that of the study group, in terms of age and gender. The study group comprised 13 patients with CKD and SS. The control group included 13 patients with CKD. Psychiatric diseases were diagnosed using the Structure Clinical Interview. Beck Depression Inventory, Beck Anxiety Inventory, Social Comparison Scale, Hopelessness Scale, and Mini Mental State Examination (MMSE) were administered to the groups. Moreover, EEG recording for all the patients was performed. According to the results obtained from the Structure Clinical Interview, 69.2% of patients with CKD and SS were diagnosed with a mental disease, as compared with only 3 (23.1%) patients with CKD. There was a significant difference between the study and the control group (P < .001). As compared with the control group, patients with CKD and SS had significantly higher scores on the Beck Depression Inventory, the Beck Anxiety Inventory, and the Hopelessness Scale. However, patients with CKD and SS had significantly lower scores on the Social Comparison Scale. The MMSE scores were not significantly different between the 2 groups. When the 2 groups were evaluated separately, no significant differences were found between the EEG abnormalities and psychiatric diagnosis of both the groups. However, an evaluation of EEG abnormalities in all cases with CKD suggested a statistically significant difference between them. In the EEG recordings, electrical seizures activity was not enrolled in any of the cases. In the present study, psychiatric morbidity for patients with CKD and SS was worse than for patients with only CKD. These results indicate a need to develop an effective psychologic strategy for dealing with psychiatric disorders among patients with CKD and SS.

Audiological Findings in Chronic Kidney Disease Patients With Sagliker Syndrome

Potential hearing loss was found to be high in a 10 patients with chronic kidney disease and Sagliker syndrome. The cause of hearing loss in these subjects remains unknown. We do not know whether those are the results of preexisting renal disease, hemodialysis, or other factors. Thus, future studies will include more subjects with Sagliker syndrome to determine the frequency of hearing loss and to investigate the etiologic factors that cause loss of hearing.

Low Blood Pressure and Amyloidosis

Yahya Saḡliker, MD, Professor of Medicine, Head, Department of Medicine, Çukurova University School of Medicine, TR01330 Adana (Turkey) Dear Sir, Amyloidosis is a complex disease entity caused by deposition of amyloid substance in various organs or systems with resultant derangement in bodily functions. The symptomatology of the disease depends on the organ involved. Kidneys are known to be primarily affected and proteinuria due to glomerular permeability increase is usually the leading symptom in the patient with systemic amyloidosis. As the disease progresses renal functions further deteriorate and death is usually caused by renal complications [1-4]. Cardiovascular involvement is another frequent feature and cause of death in amyloidosis patients [1,5,6]. Hypotension is reported to be a common feature of the disease though the exact mechanism is not established. Autonomic neuropathy, suppression of the renin-angiotensin-aldosterone system due to juxtaglomerular apparatus involvement, adrenal insufficiency, low-cardiac output and secondary reasons like dehydration and malnutrition are some factors that are held responsible [ 1 ‚ 7-9]. For elucidating the incidence and etiology of low blood pressure in systemic amyloidosis, we conducted a study on 30 systemic amyloidosis patients diagnosed by renal biopsies. Two of the patients had primary, 16 patients had reactive and 12 patients had FMFrelated heredofamilial amyloidosis. The mean age of the patients was 35.6 ± 15.0 years. Sixteen of the patients were newly diagnosed while 14 had had the disease for an average duration of 42 + 33 months. The presenting symptoms were edema in 26, uremic complications in 2, gastrointestinal bleeding in 1 and restrictive cardiac failure in 1 of the patients. After a complete physical examination, blood pressure and heart rate was taken. Laboratory tests like a hemogram, biochemical tests and urinalysis were performed. Electrocardiographic, echocardiographic, ultrasono-graphic examinations were done. Blood pressure while standing was measured and autonomic tests like Valsalva maneuver, sub-maximal handgrip test were performed for evaluating the autonomic system involvement. The results of cardiac and autonomic tests were compared to those of a control group of 15 subjects. Average mean arterial blood pressure was 80.6 ± 13.7 mm Hg in the patients while it was 89.2 ± 12.7 mm Hg in the control group, the difference being statistically significant (p < O.02).

Systemic Lupus erythematosus-Nephrotic Syndrome and Mediastinal Lymphadenopathy Mimicking Lymphoma

Prof. Yahya Sağliker, Cukorava University, Faculty of Medicine, Department of Internal Medicine, TR-01330 Adana (Turkey) Dear Sir, Systemic lupus erythematosus (SLE) is a chronic inflammatory disease that may affect the skin, joints, kidneys, lungs, nervous system, and serous membranes and/or other organs. Lymphadenopathy is common in SLE. It has been reported that lymph node enlargement is observed in 25-67% of SLE patients [1-3]. But hilar and mediastinal lymph node enlargement due to SLE is rare [4]. We report a 15-year-old young girl with SLE, involving the cardiovascular, central nervous, pulmonary, renal and hematologic systems and the skin with cervical, axillary, inguinal and mediastinal lymph nodes. The patient was admitted to the nephrology ward with generalized edema, ascites, fever and lymphadenopathy and suspicion of lymphoma. Blood pressure was 140/90 mm Hg, temperature was 37.5 °C, multiple lymph nodes measuring from 0.5 cm to several centimeters were detected in the cervical, axillary and inguinal areas. Bilateral optic atrophy was detected. Laboratory findings on admission showed: hemoglobin 5.9 g/dl, hematocrit 19.6%, white blood count 3,700/ mm3, platelets 186,000/mm3, sedimentation rate 80 mm/h, BUN 64 mg/dl, creatinin 2.2 mg/dl, total serum protein 5.4 g/dl, albumin 1.9 g/dl, cholesterol 335 mg/dl, total serum lipid 825 mg/dl, LDL cholesterol 216 mg/dl, triglyceride 439 mg/dl. Daily pro-teinuria was 9.6 g. Urine sediment contained 15-20 white blood cells, 20-25 red blood cells and granular casts. Antinuclear antibody and anti-smooth muscle antibody were positive and serum C3 level decreased. Thoracic and abdominal computerised tomography (CT) scan showed mediastinal, left axillary and retroperitoneal lymph node enlargement and pleural effusion. Pericardial effusion was detected by echocardiography. Cervical node biopsy and renal biopsy showed follicular hyperplasia and mesangiocapillary glomerulonephritis, respectively. She received a 5-day pulse of methyl-prednisolone (25 mg/kg/day). And then 1 mg/kg/day methylprednisolone and dipyri-damole (225 mg/day). One month later, full evaluation was negative for mediastinal, cervical and axillary lymph nodes. But 15 days later, she was admitted with generalized convulsion and supraventricular tachycardia. Blood pressure was 200/120 mm Hg. Uremia and electrolyte imbalance were not detected. Magnetic resonance imaging and CT of

Helicobacter pylori Antibodies in Patients on Chronic Hemodialysis

Prof. Yahya Sagliker, Department of Internal Medicine, Cukurova University, Faculty of Medicine, TR-01330 Adana (Turkey) Table 1. Characteristics of hemodialysis patients Hp(-) Dear Sir, A variety of gastrointestinal tract disorders are seen in uremic patients and gastritis, gastroduodenal ulceration, and bleeding are frequent complications of uremia [1]. Reduced gastric motility, changes in gastric morphology and histology, and increased gastrin levels may induce gastroduodenal lesions [2]. Helicobacter pylori (HP), a gram-negative spiral bacterium, has been shown to be strongly associated with gastritis, peptic ulcer disease and nonulcer dyspepsia, to be increased with gastritis, peptic ulcer disease and nonulcer dyspepsia [3]. Increased urea content of the gastric mucus could be a risk factor for HP in patients with chronic renal failure [4]. We measured the prevalence of HP in 91 hemodialysis (HD) patients and the results were correlated with dialysis duration, blood urea levels, receiving antacids or not. Ninety-one HD patients, 55 males and 36 females, aged between 16 and 70 years (mean age 41.4 ± 1.4 years) were studied. The mean duration of HD was 22.9 ± 2.2 months (range: 6-120 months). Sixty-eight HD patients (74.7%) were receiving aluminium antacids and calcium carbonate as phosphate binders. Serum samples for blood urea and Hp were taken before dialysis. Thirty-five age-matched healthy subjects with normal renal function were used as controls. Patients who had received antibiotics and colloidal bismuth preparations prior to blood sampling were excluded. IgG antibodies against HP were measured by using the IgG ELISA test where the sensitivity and specificity of this technique was near 95%. The χ2 test and the t test were used for statistical analysis. NS = Not significant. HP was detected in 13 (14.3%) of 91 patients undergoing regular HD. The mean predialysis serum urea in HP positive (+) and HP negative (-) patients was 127.3 ± 16.1 and 108.6 ± 19.8mg/dl, respectively, the difference being significant at p < 0.001. There were no difference between HP (+) and HP (-) patients with respect to sex, age, and HD duration. The receiving

The Frequencies of Hepatitis B Virus Markers and Hepatitis C Virus Antibody in Patients with Glomerulonephritis

Hepatitis B virus markers and hepatitis C virus (HCV) antibody were assayed in 72 patients with glomerulonephritis (GN) at the time of biopsy. The patients, 41 males and 31 females, were aged between 16 and 68 years. The frequency of positivity for HbsAg, anti-Hbs, and anti-Hbe, anti-Hbc and anti-HCV antibody was 5.5, 20.8, 2.8, 16.6 and 1.4% respectively. At the same time, HbsAg and anti-HCV positivity were 8.5 and 0.95% in blood donors. We can say that morbidity and prognosis may be affected by hepatitis infection. Infections of hepatitis B and C have to be evaluated in patients with GN, especially in endemic areas. In our study group the frequencies of HbsAg positivity and anti-HCV positivity were not higher in patients with GN than in blood donors.