The effect of metformin on mean platelet volume in diabetic patients.

Diabetes mellitus (DM) is an independent risk factor for cardiovascular diseases. Metformin, the most commonly used antidiabetic, also has an antiatherogenic effect. Mean platelet volume (MPV) is increased in patients with high thrombogenic activation and also at risk for atherosclerosis. The purpose of this study was to examine the effects of metformin on MPV values in newly diagnosed type II DM patients on metformin monotherapy. In this study, 60 newly diagnosed type II DM patients (45 females, 15 males), who had applied to the Kocaeli University School of Medicine Endocrinology outpatient clinic, and 47 healthy individuals (35 females, 12 males) were included. The two groups have similarity for age, sex and body mass index. The patients with additional disease, nephropathy, smoking and using drugs that may affect the MPV were excluded. At baseline and 6 months after metformin treatment, patient demographics and laboratory values were compared. MPV was higher among type II DM patients than the control group (p < 0.001). After 6 months of metformin treatment, MPV values were significantly decreased (p < 0.001). HbA1c and mean platelet mass were also significantly decreased (p = 0.022 and 0.001, respectively). There was no correlation between MPV and HbA1c values (r = -0.13, p = 0.926). Metformin, which has been shown to exhibit antiatherogenic effect through positive effects on cholesterol levels, inflammatory markers and vascular adhesion molecules, decreased MPV values that appear to play a crucial role at the beginning of atherosclerosis development. We conclude that our result may contribute to the explanation for antiatherogenic effect of metformin.

Evaluation of the efficacy of aprepitant on the prevention of chemotherapy-induced nausea and vomiting and quality of life with functional living index emesis.

OBJECTIVE: Functional Living Index Emesis (FLIE) is developed to evaluate the relationship between emesis and it's effects on patient's daily life and is far more relevant to detect the effectiveness of antiemetic treatment compared with self-diary reports. In this study, the efficacy of oral neurokinin-1 antagonist aprepitant on the prevention of chemotherapy-induced nausea and vomiting and quality of life is evaluated with FLIE. STUDY DESIGN: Cross sectional study. MATERIAL AND METHODS: Sixty patients with Non-Small Cell Lung Cancer (NSCLC) receiving a chemotherapy regimen consisting of Cisplatin and Docetaxel were evaluated. The patients were prospectively randomized to two groups before the first cycle of chemotherapy. Patients in Group A (31 patients) received 3 daily doses of aprepitant along with oral ondansetron and dexamethasone. The patients in group B (29 patients) received only ondansetron and dexamathasone. The efficacy of both regimens was evaluated by a modified Turkish version of FLIE scale consisting of 18 questions. RESULTS: The number of patients with complete response was 31 in the whole group. Of these 18 patients (58%) were in Group A (Aprepitant) and 13 patients in group B (42%). Median FLIE score in group A was 24.97 (±12.45) while it was 38.1 (±26.987) in group B and the difference was statistically significant (p=0.022). Total score >20 was seen in only 5 of 31 patients in aprepitant group (16%) showing the significant efficiency of aprepitant on quality of life, while in group B, 13 of 29 patients (44%) had total scores >20 (p=0.02). CONCLUSION: Regarding these findings, it is certain to state that aprepitant in combination with other drugs optimizes protection against both nausea and vomiting compared to the prior standard of care, and must be recommended as first-line therapy for patients who are treated with moderately or highly emetogenic chemotherapy.

Anti-proteinuric effects of combination therapy with enalapril and losartan in patients with nephropathy due to type 2 diabetes.

The benefits of angiotensin-converting enzyme inhibitors and angiotensin II (ATII) receptor antagonist therapy of diabetic nephropathy (DNP) are thought to be largely the result of attenuation of ATII effects on proteinuria. The aim of the study was to ascertain whether there is the additive anti-proteinuric effect of enalapril plus losartan in DNP. Twenty-two patients with DNP were studied. Patients were randomly assigned to enalapril 10 mg/day (11 patients) or losartan 50 mg/day (11 patients) administered in a single oral dose in the morning for 12 weeks. and then, in 10 patients (five patients from enalapril group and five patients from losartan group), combination therapy (10 mg/day enalapril and 50 mg/day losartan) was started and continued for 12 weeks. In 12 patients, initial drugs dosages were doubled (six patients 20 mg/day enalapril and six patients 100 mg/day losartan), and monotherapy was continued for 12 weeks. Blood pressure and proteinuria were measured before and after therapy. Adverse effects were recorded at every visit. Proteinuria decreased by 33% with enalapril and losartan administered alone (p < 0.05). Co-administration of enalapril and losartan decreased proteinuria by a greater extent compared with enalapril and losartan administered alone (51%, p<0.05). This proteinuria level was significantly lower than the proteinuria level of 12 weeks therapy with enalapril and losartan alone. The decrease of proteinuria was 37% in double-dose monotherapy group (p < 0.05). Reduction of mean arterial blood pressure (MAP) in co-administration of enalapril and losartan was higher than enalapril and losartan administered alone (p < 0.05). Combination of enalapril and losartan decreased proteinuria and MAP by a greater extent compared with enalapril and losartan administered alone. We have found that proteinuria reduction induced by combined therapy is maintained throughout short-term follow-up; a greater anti-proteinuric response was observed in the patients with DNP.

The effect of high dose losartan on erythropoietin resistance in patients undergoing haemodialysis.

AIM: In some of the patients undergoing haemodialysis, (HD) resistance might develop against recombinant human erythropoietin (rHuEPO) used for treatment of anaemia. Recently, angiotensin-converting enzyme (ACE) inhibitors that are used to treat hypertension and congestive heart failure in HD patients have been suggested to contribute to anaemia as well by inhibiting erythropoiesis. Our purpose in this study is to investigate whether or not losartan, an angiotensin II (ATII) receptor antagonist, is causing rHuEPO resistance. METHODS: In this prospective study of 12 months, we compared the effects of high dose losartan (100 mg/day) and amlodipine (10 mg/day) on rHuEPO requirement in 40 hypertensive patients receiving rHuEPO for more than 12 months on maintenance HD. Twenty normotensive rHuEPO dependent patients served as control group. Iron deficiency, hyperparathyroidism, aluminium intoxication, infections and inflammations were excluded in all patients. RESULTS: The mean haemoglobin level was found >8 g/dl in all groups. The mean weekly rHuEPO dose increased in the losartan group (p<0.0001 vs before) and remained constant in the other groups. No significant differences were found with PTH, iron status, aetiologies of renal failure in all groups. CONCLUSION: High-dose losartan increases rHuEPO requirement and should be reserved for dialysis patients with hypertension uncontrollable with other antihypertensive medications.

Clinical and biochemical outcome of renal amyloidosis.

AA amyloidosis is a relatively rare disease which complicates chronic inflammatory diseases, chronic infections, familial Mediterranean fever (FMF) and malignant diseases. Although amyloid deposition may be found in many organs, renal involvement dominates the clinical picture. We reviewed 63 patients with AA amyloidosis who presented to our nephrology department between 1995 and 2000. Prognostic markers, detailed history, physical examination and laboratory tests were evaluated. The causes of AA amyloidosis were as follows: FMF 42 (66.6%), pulmonary tuberculosis 9 (14.2%), chronic osteomyelitis 4 (6.3%), bronchiectasia 4 (6.3%), rheumatoid arthritis 1 (1.5%), juvenile idiopathic arthritis 1 (1.5%), inflammatory abdominal aortic aneurysm 1 (1.5 %), unknown aetiology 1 (1.5%). The diagnosis was made on renal biopsies in 63.4% of the patients, while the remaining 36.6% were diagnosed as a result of rectal biopsies. Sixteen patients died. A low serum albumin, high creatinine and high 24-hour urine albumin excretion were associated with high mortality.

Increased serum ferritin levels in active Behçet's disease.

There is no routine test to evaluate the activity of Behçet's disease (BD). Ferritin as a serum predictor of iron storage is an important acute phase reactant. In this study, we assessed serum ferritin levels in patients with active BD and compared them with those of patients with inactive BD. We aimed to show the relationship between ferritin and BD. The patients with BD were subdivided into two groups according to disease activity: active (24 patients; 18 men and 6 women, average age 36.5 +/- 4.9 [28-45] years), and inactive (20 patients; 16 men and 4 women, average age 37.2 +/- 5.2 [30-49] years). Twenty healthy volunteers (15 men and 5 women; average age 38.2 +/- 4.6 [30-47] years) served as controls. Patients with active BD had significantly higher serum ferritin levels (p=0.0001) than the inactive and control groups. Ferritin levels in patients with inactive BD did not differ significantly from healthy control subjects (p=0.687). We concluded that in patients with active BD, serum ferritin levels are increased and do not reflect serum iron levels.

Alkaptonuria: a case report.

Alkaptonuria is a rare, autosomally recessive, metabolic disorder caused by a deficiency in homogentisic acid oxidase. It results in accumulation and deposition of homogentisic acid in cartilage, eyelids, forehead, cheeks, axillae, genital regions, nail beds, buccal mucosa, larynx, tympanic eardrum, and the tendons. We report a 33-year-old woman who presented with alkaptonuria and ochronotic pigment deposited in articular cartilage and cartilage of the ear and sclera.

Effect of losartan treatment on the proteinuria in normotensive patients having proteinuria due to secondary amyloidosis.

Secondary amyloidosis (AA amyloidosis) is a well known cause of nephrotic syndrome and renal failure. Several studies in patients with nephrotic syndrome have suggested a beneficial effect of angiotensin-converting enzyme inhibitors (ACEI). Angiotensin II (ATII) receptor antagonists effect on the long term is not known. In this study, we intended to study the effect of losartan, as an ATII receptor antagonist, on proteinuria and renal functions in patients with normotensive secondary amyloidosis. In total 44 patients with biopsy proven AA amyloidosis associated with nephrotic proteinuria were included. The first group of patients (n=22) was treated with losartan 50 mg/day. The second group of patients (n=22) did not receive any specific antiproteinuric treatment. Urinary protein loss was effectively lowered by losartan from 4.38 +/- 1.0 to 2.8 +/- 0.61 g/day (p<0.0001), whereas the control group showed a slight fall in proteinuria as 4.21 +/- 1.06 to 4.12 +/- 1.07 g/day (p = 0.176). Hypoalbuminemia improved significantly from 2.52 +/- 0.69 to 2.78 +/- 0.46 g/dl (p = 0.004), in the losartan group, whereas serum albumin had fallen in the control group from 2.44 +/- 0.57 to 2.27 +/- 0.41 (p = 0.041). Serum creatinine increased in the control group from 1.52 +/- 0.42 to 2.39 +/- 0.51 mg/dl (p<0.0001), and in the losartan group from 1.59 +/- 0.50 to 1.84 +/- 0.6 mg/dl (p<0.001), after 24 months of treatment. The ATII receptor blocker losartan is effective in protecting against the progression of nephropathy due to AA amyloidosis. Symptomatic treatment of proteinuria with losartan is therefore to be considered, especially with severe proteinuria even in normotensive patients.

Severe and prolonged febrile myalgia in familial Mediterranean fever.

Familial Mediterranean fever (FMF) is characterized by recurrent attacks of fever and serositis. Typical attacks of FMF last 3 to 5 days. Fever and myalgia are not always improved by colchicine therapy and sometimes require steroid therapy. We present two cases of severe prolonged febrile myalgia where steroid therapy was needed.

Plasma atrial natriuretic peptide and its relation to the renin-angiotensin-aldosterone system in patients with chronic renal failure.

To determine the relationship between plasma immunoreactive atrial natriuretic peptide (i-ANP) and renin-angiotensin-aldosterone system (RAAS), plasma i-ANP, plasma renin activity (PRA) and plasma aldosterone (PA) were assayed in 29 patients (19 hypertensive and 10 normotensive) with chronic renal failure (CRF), and in 10 healthy subjects. Hypertensive patients had higher i-ANP values than normotensive patients and controls (P less than 0.05 and P less than 0.01 respectively). There was no significant correlation between plasma i-ANP and creatinine concentrations in hypertensive patients, whereas this correlation was statistically significant in normotensive patients (r = 0.70, P less than 0.01). Other positive correlations were between plasma i-ANP and systolic blood pressure in hypertensive patients (r = 0.69, P less than 0.01) and between plasma ANP and mean arterial pressure in normotensive patients (r = 0.63, P less than 0.01). There was significant negative correlation between plasma ANP and fractional sodium excretion (FENa) in hypertensive patients (r = -0.47, P less than 0.05), though there was significant positive correlation in normotensive patients (r = 0.80, P less than 0.01). Hypertensive patients, with the exception of one anuric patient and another with atrial fibrillation, had a significant negative correlation between FENa and systolic arterial blood pressure (r = 0.64, P less than 0.01). The patient group had increased PRA and PA values (P less than 0.01 and P less than 0.001 respectively) and showed positive correlation with mean arterial pressure (MAP) (r = 0.71, P less than 0.001 and r = 0.58, P less than 0.01 respectively). These results show that increased concentrations of immunoreactive ANP circulate in CRF together with activated RAAS. We demonstrate that elevated ANP cannot affect blood pressure and natriuresis in hypertensive patients with CRF, whose RAAS is activated.

Spontaneous bilateral rupture of kidneys in a patient with polyarteritis nodosa. A case report.

A previously well 42-year-old man presented with a three-hour history of pain in the right flank of acute onset. At laparotomy he was found to have a ruptured right kidney which was treated by nephrectomy. Eight days later he developed similar symptoms on the left: at operation 21 of blood were drained and nephrostomy and catheterisation carried out. He recovered after a complicated postoperative course, and histological examination of the removed kidney, and biopsy specimens, showed classic polyarteritis nodosa. This is a rare cause of spontaneous rupture of the kidney but must be considered whenever a patient presents with renal haemorrhage of unknown cause.