The Role of the Local Bone Marrow Renin-Angiotensin System in Multiple Myeloma

Objective: Angiotensin II promotes growth and angiogenesis via type 1 receptors (AGTR1) in certain tumors. In this study, we examine the bone marrow AGTR1 expression in multiple myeloma (MM) and its relationship with the regulation of angiogenesis and prognostic factors. Materials and Methods: Bone marrow AGTR1 mRNA levels of 39 MM patients and 15 healthy controls were analyzed with quantitative RT-PCR. Immunohistochemical staining of the tissue vascular endothelial growth factor (VEGF), CD34, and factor VIIIrAg (fVIIIrAg) was used to assess bone marrow angiogenesis. Results: Bone marrow samples of the patients showed increased VEGF, fVIIIrAg, and CD34 staining and higher AGTR1 expression levels when compared to controls. Patients with severe-diffuse bone marrow infiltration showed higher bone marrow VEGF, fVIIIrAg, CD34, and AGTR1 mRNA levels when compared to other patients. Conclusion: AGTR1 expression was found positively correlated with plasma ß2-microglobulin level and patients with increased AGTR1 expression showed increased bone marrow CD34 levels.

Limited utility of adipokine levels in the diagnosis of malnutrition in the elderly.

BACKGROUND AND AIMS: Adipokine levels may have a role in the diagnostic and prognostic evaluation of malnutrition. The aim of the present study was to evaluate the correlation between malnutrition score and leptin, other biological markers, and body mass index (BMI) in the diagnosis of malnutrition in the elderly. METHODS: In this cross-sectional observational study, we enrolled subjects over 70 years. Exclusion criteria were diabetes mellitus, obvious thyroid disorders, significant edema, renal dysfunction, chronic liver disease, symptomatic cardiovascular diseases, and malignity. Patients' demographic and medical data were recorded and anthropometric measurements were performed. Laboratory parameters including leptin, IGF-1, IGFBP-3, IL-6, TNF-α were measured. We defined malnutrition according to mini nutritional assessment (MNA) scale. Patients were divided into four groups according to BMI quartiles. RESULTS: Average age of the patients was 81.9 ± 4.8 years, 68.2 % female and 31.8 % male. According to their MNA scores, 103 (66.9 %) were well nourished, 33 (21.4 %) were under malnutrition risk and 18 (11.7 %) were malnourished. MNA total and screening scores were positively correlated with albumin, BMI, high-density lipoprotein cholesterol and estimated glomerular filtration rate. Serum leptin levels (ng/ml) were 18.9 ± 22.6, 22.3 ± 21.9, 51.9 ± 85.5, and 61.7 ± 56.1 in BMI groups 1-4, respectively. BMI was positively correlated with leptin and triglyceride levels. Leptin levels were similar among nutritional state groups. Neither BMI nor MNA scores had any significant correlation with adiponectin, ghrelin, IGF-1, or IGFBP-3. CONCLUSIONS: Adipokine levels do not seem to give relevant information in nutritional state assessment.

Malnutrition in the elderly and its relationship with other geriatric syndromes.

BACKGROUND & AIMS: Age related decline in food intake is associated with various physiological, psychological and social factors. Our aim was to assess the nutritional status of our elderly patients and its association with other geriatric syndromes. METHODS: In this cross-sectional population based study, Mini Nutritional Assessment (MNA) test was used to evaluate nutritional status of 413 elderly patients who were admitted to our outpatient clinic in the last 12 months. MNA test results were compared with the laboratory findings and established geriatric syndromes. RESULTS: Poor nutritional status was found in 44% of the patients (n=181: 13% malnutrition, 31% malnutrition risk). Malnutrition rate was higher among those with subsequent hospitalization (n=122, 25% vs 8%). Patients with poor nutritional status had lower blood haemoglobin, serum total protein and albumin, and revealed more chronic diseases and geriatric syndromes (6 ± 2 vs 3 ± 2, p<0.0001). Patients with depression, fecal incontinence, decreased cognitive function and functional dependence showed poor nutritional status according to MNA test results. CONCLUSIONS: Malnutrition rate of our patients was comparable with the previous data. Malnutrition risk showed positive correlation with the number of existing geriatric syndromes. Depression, dementia, functional dependence and multiple co-morbidities were associated with poor nutritional status.

Plasma nitrate/nitrite and endothelin-1 in patients with liver cirrhosis.

The aims of this study were to examine the plasma nitrate/nitrite (NOx; two end products of nitric oxide metabolism) and endothelin-1 (ET-1) concentrations in patients with liver cirrhosis, and to investigate whether there is a relationship between these two vasoactive parameters and the course of disease. Twenty-eight patients with liver cirrhosis (11 HBV-related, four HCV-related, four alcohol-related, and nine with idiopathic etiology) and 25 healthy subjects (controls) were included in the study. The venous plasma concentrations of NOx and ET-1 were significantly higher (P<0.01 and P<0.001) in the patients with cirrhosis than in the controls. A significant increase in ET-1 was observed in the Child B subgroup vs. Child A (P<0.05), and in the Child C subgroup vs. either subgroup A or B (P<0.05). There were no statistical differences between study subgroups (Child A-C) in the mean of NOx values. Plasma NOx and ET-1 were significantly increased in patients with ascites compared to those without ascites (P<0.05 and P<0.01). Increased nitric oxide synthesis may be a compensation mechanism against endothelial injury. The highest ET-1 levels in Child C and moderately increased ET-1 levels in Child B, and the lower increase of ET-1 levels in Child A patients suggest that plasma ET-1 increases with the progression of the disease. The fact that NOx and ET-1 levels were higher in patients with decompensated cirrhosis (patients with ascites) than in those with compensated cirrhosis (patients without ascites), and the presence of a strong correlation between ET-1, NOx, and the degree of varices, supports the suggestion that there is a relationship between NOx, ET-1, and portal hypertension. Our study demonstrates that increased ET and nitric oxide metabolism is associated with the hemodynamic alterations induced by portal hypertension.

Non-invasive evaluation of endothelial function in hypertensive elderly patients.

Impaired endothelium-dependent vasomotion is a diffuse disease process resulting in abnormal regulation of blood vessel tone and loss of several atheroprotective effects of the normal endothelium. The aim of the present study was to investigate the effects of aging and hypertension on endothelial function. Sixty-six geriatric subjects with ages over 60 (48 hypertensive and 18 healthy) and 40 middle-aged subjects (16 hypertensive and 24 healthy) were included in the study. Systemic vascular endothelial function was evaluated through measuring brachial arterial vasodilation, a physiologic answer to reactive hyperemia occured with increased blood flow in the vessel after transient ischemia (flow-mediated dilation, FMD%), and with carotid artery intima-media thickness (IMT) measurement, using high-resolution ultrasonography. Endothelial independent vasodilation was also measured after administration of sublingual isosorbide dinitrate (isosorbide dinitrate mediated dilation, IDNMD%). FMD% was significantly decreased in elderly and/or hypertensive (HT) patients (geriatric HT: 9.5 +/- 4.7%, geriatric non-HT: 12.7 +/- 5.5%, middle-aged HT: 12.9 +/- 4.3% and middle-aged non-HT: 18.9 +/- 8.1%) (geriatric HT versus geriatric non-HT (P = 0.02), geriatric HT versus middle-aged HT (P = 0.01), geriatric non-HT versus middle-aged non-HT (P = 0.008)). Both FMD% and IDNMD% were inversely correlated with age, baseline vessel diameter and carotid artery intima-media thickness. FMD% was also inversely correlated with diastolic blood pressure. No correlation was found between FMD% and systolic blood pressure, serum cholesterol and triglyceride levels. Endothelium dependent (EDD) and independent dilatation of large arteries decreased with aging even in the healthy elderly, and FMD further declined in HT elderly patients, indicating that age and hypertension independently impair endothelial function. Positive correlations with age and hypertension, and significant inverse correlation with FMD, makes carotid artery IMT a possible indicator of endothelial function.

The predictive and diagnostic values of procalcitonin and C-reactive protein for clinical outcome in febrile neutropenic patients.

BACKGROUND: Procalcitonin (PCT) represents a new marker of systemic inflammatory reactions to bacterial infections. The main aim in this study was to determine the diagnostic value of PCT in predicting the clinical severity of febril neutropenic attacks, compare it with that of C-reactive protein (CRP), and clarify its importance in culture-positive attacks. METHODS: Between February 2001 and April 2002, 36 patients who were neutropenic due to various hematologic disorders and febrile were entered into the study. Blood samples were obtained on the first day of fever for the measurement of serum PCT and CRP levels. RESULTS: In clinically severe neutropenic fever attacks, means of serum PCT and CRP levels were measured as 0.93+/-1.33 ng/mL and 67+/-24 mg/L, while they were 0.37+/-0.23 ng/mL and 32+/-19 mg/L in clinically mild ones (p = 0.033 and p < 0.001). On the other hand, no statistical significance was found between culture-positive and negative attacks when either serum PCT or CRP levels were taken into consideration (p = 0.133 and p = 0.141). The specificity and positive predictive value of the serum PCT test for severe febrile neutropenia was higher than that of the serum CRP test (0.80 vs. 0.57 and 0.50 vs. 0.39). However, sensitivity and negative predictive value for CRP were higher than the values for PCT (1.00 vs. 0.40 and 1.00 vs. 0.73). Diagnostic value and positive likelihood ratio of CRP for severe febrile neutropenia were higher than those of PCT (71 vs. 67 and 2.32 vs. 2.00). CONCLUSIONS: PCT and CRP are comparable with each other in prediction of the clinical severity of febrile neutropenic attacks. Furthermore, serum CRP levels correlate with the duration of fever.

Catastrophic secondary antiphospholipid syndrome with peripheral nervous system involvement: a case report.

A 34-year-old woman was admitted to our emergency room with a high fever, abdominal pain, dyspnea and confusion. High fever and abdominal pain had first occured after a cystocele operation 5 months earlier. Later, congestive heart failure with mural thrombus formation, peripheral polyneuropathy and ischemic cerebrovascular accident were identified in clinical follow-ups, and multiple arterial and venous thromboses were seen on cranial and abdominal magnetic resonance imaging angiography. The patient's symptoms improved with anticoagulant treatment. Antiphospholipid syndrome with elevated serum anticardiolipin IgG levels was diagnosed, and ischemic peripheral polyneuropathy with axonal degeneration was determined by sural nerve biopsy. In antiphospholipid syndrome, elevated anticardiolipin antibodies appear to be the most common acquired blood protein defect causing thrombosis. Disseminated vascular thrombosis in catastrophic antiphospholipid syndrome can result in multiorgan failure with increased morbidity and mortality. It rarely occurs secondary to various infections as in the case of our patient, who suffered postoperative intraabdominal infection. It is important to note that peripheral nervous system involvement is rare in antiphospholipid syndrome.

Takayasu arteritis presenting with Fever of unknown origin: two case reports.

Two patients with Takayasu arteritis are reported who presented with fever of unknown origin. Takayasu arteritis was diagnosed at the prepulseless period after stenotic lesions of the aorta, and its branches were seen with imaging methods. In the first month of steroid treatment, hypertension developed in both patients that was related to fibrosis in stenotic lesions in renal arteries. Both patients were treated with percutaneous transfemoral renal angioplasty. Takayasu arteritis should be considered in the differential diagnosis of fever of unknown origin, especially in young women. Absence of the physical findings related to vasculitic lesions will not rule out the disease, which can be seen in the prepulseless period.

The in vitro effect of interferon-alpha 2a on CD95 expression of T cells in hepatitis B.

BACKGROUND/AIMS: In chronic hepatitis B, apoptotic rate of peripheral cytotoxic T cells may be related with hepatocyte injury. We aimed to investigate Fas (CD95) expression of peripheral cytotoxic T cells and to show the in vitro effect of interferon-alpha 2a on Fas expression and apoptosis. METHODOLOGY: The study group consisted of 17 patients with chronic hepatitis B and control group consisted of 10 healthy subjects. Apoptotic cells were identified by flow-cytometric assay using Annexin V and propidium iodide. We used monoclonal antibodies stained by direct immunofluorescent method to show surface molecules. CH-11 monoclonal antibodies were used as anti-Fas antibodies. RESULTS: Basal expressions of CD95 and CD8+ CD95+ in the peripheral mononuclear cells were higher in chronic hepatitis B patients than controls. In vitro treatment with interferon-alpha 2a increased the percentage of CD8+ 95+ peripheral mononuclear blood cells in controls; this effect was less remarkable in patients with chronic B hepatitis, and the difference was not statistically significant. The number of apoptotic cytotoxic T cells also increased in 5 subjects of the study group and 3 subjects of controls; the percentage of CD95+ cells increased in 7 of 17 patients and 8 of 10 controls. The percentage of CD8+ 95+ cells and the apoptotic rate of CD8+ cells were not different between study group and controls after combined treatment with interferon-alpha 2a and monoclonal stimulating anti-Fas antibodies. CONCLUSIONS: We suggest that interferon-alpha 2a does not induce Fas-dependent apoptosis in CD8+ peripheral T cells of the patients with chronic hepatitis B, and CD95 molecules on peripheral cytotoxic T cells might be defective.

Relationship between insulin-like growth factor 1 and bone mineral density in men aged over 65 years.

OBJECTIVE: To determine the association between insulin growth factor 1 (IGF-1) and bone mineral density (BMD) in men over 65 years of age. SUBJECTS AND METHODS: Forty-one male patients aged 65-88 years without a history of drug use or illness which is known to affect BMD were enrolled in the study. The control group consisted of 20 healthy men (19-62 years old). An immunoradiometric assay was used to measure IGF-1 levels. Dual-energy X-ray absorptiometry was used to determine BMD at the proximal femur and lumbar spine. A detailed questionnaire was used to assess the epidemiological findings. RESULTS: The men over 65 years of age had a lower mean IGF-1 level (102.04 +/- 36.65 vs. 196.62 +/- 84.86 ng/ml) and a lower mean BMD at the femoral neck, trochanter and intertrochanteric zones, Ward's triangle and total hip than the controls. No statistically significant association was observed in the BMD of the lumbar vertebrae between the patients and controls. IGF-1 levels were strongly and negatively correlated with age (p < 0.0001, r = -0.82). Logistic regression analysis showed that low IGF-1 levels were strongly associated with osteopenia of the total hip, femoral neck, trochanter and intertrochanteric zone. CONCLUSION: The finding shows that low serum IGF-1 levels were associated with an increased risk of hip osteopenia and, hence, at least partly responsible for the osteopenia observed in men aged 65 years or over.

Ptosis caused by pachydermoperiostosis.

A 39-year-old man with pachydermoperiostosis is presented. He had enlarged, thickened upper eyelids that made it difficult for him to open his eyes. Eyelid correction was performed by resecting the excessive skin and orbicularis muscle in a fusiform shape and shortening the levator aponeurosis by plication. A wedge resection of the lateral third of the upper lid shortened the horizontal width and also changed the unpleasant fan shape to a better shape, with a natural curvature of the lid. The authors also performed a 5-mm transconjunctival tarsectomy. Visual impairment was corrected with a satisfactory aesthetic outcome.

Acute wood or coal exposure with carbon monoxide intoxication induces sister chromatid exchange.

OBJECTIVE: The object of this study was to investigate the genotoxic effect of acute overexposure to combustion products originating from coal or wood stoves in patients presenting with acute carbon monoxide intoxication. STUDY DESIGN: In a prospective study, we analyzed the frequency of sister chromatid exchange and the carboxyhemoglobin concentration in 20 consecutive patients without a history of smoking or drug use who had been treated in the Emergency Care Unit of Istanbul Medical Faculty due to acute carbon monoxide intoxication. All of these cases were domestic accidents due to dysfunctioning coal or wood stoves. The results were compared with a control group of 20 nonsmoking, nondrug-using healthy individuals matched for age, sex, and absence of other chemical exposure. RESULTS: The mean sister chromatid exchange frequency per metaphase was significantly higher in the study group compared to the control group: 8.11 +/- 2.39 vs. 6.33 +/- 1.60 (p = 0.008). We found that there was no positive correlation between the blood carboxyhemoglobin concentration and sister chromatid exchange frequency. CONCLUSIONS: These results suggest that acute exposure to combustion products of wood or coal is genotoxic to DNA. Potential causes of genotoxicity include known mutagenic compounds present in coal or wood smoke and ash, oxygen radicals formed during combustion, as well as hypoxic and reperfusion injury mechanisms initiated by carbon monoxide intoxication. Additional studies on separate carbon monoxide exposure from smoke and ash are needed to understand individual genotoxic contributions and mechanisms.