Relationship of arterial compliance and glycosylated haemoglobin as a predictor of vascular damage in diabetic patients

Accelerated arterial stiffness has been linked in diabetes to hyperglycaemia, hyperinsulinaemia, and impaired glucose tolerance. In this work, we studied two groups: Normotensive diabetic patients Group [A] and non diabetic age and gender matched controls group Group [B]. We excluded those with hypertension, hypercholesterolemia, smokers or ex-smokers and patients with history of or complaining of peripheral vascular disease or coronary artery disease. The aim of work was to study the relationship between arterial compliance and diabetic status in normotensive diabetic patients. The two groups [A and B] were compared as regards the clinical data, laboratory investigations, echocardiographic studies, carotid duplex evaluation [intima-media thickness and incidence of atherosclerotic plaques], pulse wave velocity measurements. On comparing both groups we found that diabetic patients had average pulse wave velocity, higher incidence of diastolic dysfunction and had lower fractional shortening values and E/A ratio on echocardiographic evaluation. Correlation of glycosylated haemoglobin with the other study parameters showed a significantly positive correlation with pulse wave velocity [PWV] among the whole population and with mean intima-media thickness [Mean IMT] among the whole population and in diabetics. Correlation of pulse wave velocity with the study parameters revealed a statistically significant positive correlation with mean-intima media thickness among the total population as well as in diabetics. In this study we concluded that early vascular damage and arterial stiffness is independently related to glycaemic status in diabetic patients even before evident clinical manifestations of macrovascular affection such as hypertension, increase in intima-media thickness, development of atherosclerotic plaques, symptoms or signs of peripheral vascular disease or coronary artery disease. We don't know if tight glycaemic control could reverse these early changes of vascular compliance or not and that needs further investigation. Pulse wave velocity is a non invasive, inexpensive and feasible method for early detection of vascular damage and impaired arterial function, so that therapeutic interventions can be evaluated, in order to reduce future cardiovascular complications and thereby increase both duration and quality of life.

Evaluation of different biochemical markers of bone turnover as a diagnostic tool for osteoporosis in postmenopausal women

Osteoporosis is a major global health problem affects mainly elderly and postmenopausal women with increased risk of bone fractures. The value of different biochemical markers of bone turnover as diagnostic tool for osteoporosis is still debated. The aim of this study is to assess the value of different biochemical markers of bone turnover as a diagnostic tool for osteoporosis in postmenopausal women. We measured fasting urinary calcium [Uca], total ALP, inorganic phosphorus [Pi], urinary deoxypyridino-line [DPD], carboxyterminal telopeptide of collagen type I [ICTP] and serum N-terminal telopeptide [NTX] in 40 postmenopausal females [diagnosed by DEXA as osteoporotic, | mean age, 60.2 years], 16 preimenopausal non-osteoporotic females [mean age, 39.1 years] and 24 healthy controls [mean; age, 29.2 years]. The postmenopausal osteoporotic group showed significantly higher levels of ALP, DPD, NTX and ICTP compared to controls [p<0.001] and only ALP was significantly higher in preimenopausal group compared to controls [p<0.001]. However, there was no significant difference of Uca and Pi among the three groups. On comparing peri and postmenopausal groups together, DPD, NTX and ICTP were the only markers that clearly discriminate the two groups being higher in the osteoporotic postmenopausal group. There were significant negative correlations between bone mineral density [BMD] and each of ALP, DPD, NTx, and ICTP. The clinical utility of DPD, NTx and ICTP in identifying patients with osteoporosis was assessed by ROC [receiver operating characteristic] curve analysis. This revealed that the best diagnostic cut-off level for DPD was 6.8nM DPD/mM creatinine. This gave a diagnostic sensitivity of 100% and specifity 100%, whereas NTx at a level 17.0 nM BCE had a diagnostic sensitivity of 100% and specifity of 98%. Regarding ICTP at cut-off level of 3.6 microg/L its sensitivity was 88% and specifity was 65% which considered the lesser better sensitivity and specifity among the three studied parameters

Role of thrombopoietin in thrombocytopenic patients with chronic viral hepatitis with and without liver cirrhosis

Thrombocytopenia is a common hematological defect among patients with chronic liver diseases. Thrombocytopenia secondary to liver cirrhosis and portal hypertension is a well known complication of advanced stage liver disease, but theories about the underlying pathogenetic mechanisms, mostly concentrating on splenic sequestration i.e. hypersplenism and destruction of platelets, have failed to solve the problem so far. Thrombopoietin [TPO] was recently cloned and identified as the primary cytokine involved in the megakaryocyte maturation and formation of platelets. The predominant site of TPO-production is the liver, where parenchymal cells are the TPO-producing cells. Therefore, thrombocytopenia in chronic liver disease may be related to deficient production of thrombopoietin. Thus, altered TPO production in patients with chronic liver disease may in part explain the thrombocytopenia found in these patients. To evaluate the relationship between serum TPO concentrations, circulating platelet count, and the state of liver pathology in patients with chronic viral hepatitis with and without liver cirrhosis, this study included ninety subjects divided into two main groups. Group A included sixty chronic hepatitis patients and group B included thirty apparently normal age- and sex-matched subjects taken as a control group. Etiology of the chronic hepatitis patients was either HBV or HCV. Group A was further subdivided into subgroup AI including thirty chronic hepatitis patients with liver fibrosis, while subgroup AII included thirty chronic hepatitis patients with liver cirrhosis, who were all of Child A group according to Child score. Ultrasonography as well as liver biopsy were used to differentiate the two subgroups. Thorough history taking, full physical examination, as well as biochemical blood tests in the form of serum albumin and total bilirubin were done. Prothrombin time, platelet counts, as well as serum TPO concentrations were all determined in addition to abdominal ultrasonography to evaluate the splenic size. Our data showed that serum albumin level was decreased and serum bilirubin level was increased in both subgroups AI fibrosis and AII cirrhosis compared to group B controls. Prothrombin time was prolonged in subgroup AII cirrhosis patients compared to both subgroup Al fibrosis and to group B controls. Splenic size was highly significantly increased in subgroup AII cirrhosis patients compared to subgroup AI fibrosis patients who showed larger spleen compared to group B controls as well. Serum TPO levels were significantly increased in subgroup Al fibrosis patients and significantly decreased in subgroup All cirrhosis patients compared to group B controls, moreover, TPO levels were highly significantly decreased in subgroup All patients compared to subgroup Al patients. Thus, our study clarified that decreased serum TPO levels parallel the increased serum biliruhin levels, the deterioration of the protein producing liver ability, as well as the prolonged prothrombin time. Thus, TPO concentrations decreased with the progression of liver disease and the reduction in the functional hepatic mass indicating that thrombocytopenia in chronic liver disease might highly be correlated with the hepatocellular damage. Our study also detected a negative correlation between the spleen size and the platelet counts, meanwhile we also demonstrated that the spleen size does not correlate with the TPO levels. In addition we demonstrated a significant positive correlation between TPO concentrations and platelet counts and a negative correlation between TPO concentrations and prothrombin time. Thus, we denoted that TPO concentration is an independent factor affecting positively the platelet counts in chronic viral hepatitis patients regardless of the splenic size, which is also partially implicated, also it is negatively related to the prothrombin time, which is an indicator of the functioning liver mass. This study concluded that serum TPO concentrations are increased above control levels in chronic viral hepatitis patients with liver fibrosis, but as the condition progresses to cirrhosis, the functioning liver mass decreases and so the TPO concentrations fall. Thus, the impaired TPO synthesis by the diseased liver may contribute to the development of thrombocytopenia in liver cirrhosis. Therefore, TPO deficiency due to reduced production, seems to be a major factor for thrombocytopenia in chronic liver disease although increased splenic sequestration of platelets in the enlarged spleen may also have an additional role. Our findings may suggest that recombinant TPO could possibly be an effective drug to treat patients with liver cirrhosis and severe thrombocytopenia during bleeding episodes or when undergoing surgical procedures. Moreover, it may decrease the incidence of splenectomy, with all its intraand postoperative hazards, done in such conditions

Role of non invasive biomarkers in the assessment of liver condition in chronic hepatitis C Egyptian patients and if they correlate with the severity of liver affection

Hepatitis C virus [HCV] is considered the most common etiology of chronic liver disease in Egypt. Anti-HCV-positive patients are more likely to have elevated liver enzymes, liver cirrhosis, portal hypertension and spleen enlargement. Schistosomal liver disease in Egypt is commonly associated with HCV infection. Concurrent infection results in much more severe liver affection than that seen in either disease alone. Chronic hepatitis C is a slowly progressive inflammatory disease that can lead to cirrhosis with all its complications. Thus, repeated assessment of liver condition is always required. Assessment of liver damage has been primarily done by liver function tests as well as by histological evaluation. Meanwhile, assessment of liver affection is mainly done by liver biopsy with histological analysis which always remains the "reference standard" used by physicians to assess the presence as well as the degree of liver fibrosis in patients with chronic liver diseases and also to determine the appropriate management. However, many physicians are cautious to perform liver biopsy because of the relative risks associated with this procedure, particularly in patients with coagulation abnormalities. Among the possible alternatives, imaging is informative mainly for cirrhosis but not for lesser stages of fibrosis. In addition, it is nonquantitative and thus cannot track progression. Unfortunately, there are few reliable noninvasive methods for detecting liver fibrosis and its progression. Thus, a noninvasive test detecting hepatic fibrosis has become a priority in the context of hepatitis C evaluation and treatment. Therefore, identifying hepatic biomarkers that correlate with the severity of the liver pathology is an important issue in the follow up of such cases. Few serum markers such as hyaluronic acid, ferritin, and soluble interleukin-2 receptor [sIL-2R] have been reported to be useful in detecting fibrosis in liver disease. The aim of this study is to clarify the diagnostic value of serum hyaluronic acid, ferritin, and soluble interleukin-2 receptor levels as non-invasive biomarkers in the assessment of the liver condition in chronic hepatitis C Egyptian patients with and without concurrent Bilharzial affection and moreover, to evaluate whether their serum levels correlate with the histological severity of the related liver injury. One hundred and twenty Egyptian subjects were included in this study. They were divided into three main groups. Group A [n=30] included patients with chronic hepatitis C and with liver fibrosis as assessed by abdominal ultrasonography, Group B [n = 60] included patients with chronic hepatitis C and with liver cirrhosis and/or history of antibilharzial treatment and positive rectal snips for bilharzial ova, and Group C [n = 30] included apparently normal age and sex-matched subjects taken as a control group. Group B was further subdivided into two subgroups according to liver cirrhosis staging as performed by abdominal ultrasonography, where Subgroup B1 [n = 30] included patients with early cirrhotic changes while Subgroup B2 [n = 30] included patients with advanced cirrhotic changes. Patients were diagnosed as having hepatitis C by detecting HCV antibodies using a third generation enzyme immunoassay, ELISA. Biochemical blood tests were carried out to evaluate liver functions in the form of serum transaminases [AST and ALT], alkaline phosphatase [ALP], gamma glutamate [GGT], total bilirubin, as well as serum albumin. In addition, serum hyaluronic acid, ferritin, as well as sIL-2R levels were measured by EL1SA. Our study detected impaired liver functions in all patient groups compared to the controls. Liver functions were also detected to be more impaired in each of subgroup B1 early cirrhosis as well as in B2 advanced cirrhosis patients compared to group A fibrosis patients and this was statistically significant. Meanwhile, our study also demonstrated statistically significant difference on comparing both subgroups B1 and B2 together showing more impairment in subgroup. B2 advanced cirrhosis patients. The above findings denote that as the liver condition progresses from fibrosis to early then to advanced cirrhosis, the liver enzymes as well as the bilirubin concentrations increase progressively and the serum albumin concentrations decrease progressively, thus indicating more deterioration in liver functions and more liver injury. Not only this, but also our study detected more deterioration in liver functions occurring in the presence of bilharzial infection concurrent with hepatitis C infection than without it. This was shown clearly from comparing group B patients, whether subgroup B1 or B2, with history of bilharziasis to group A patients without, denoting that concurrent bilharzial infection adds more to the liver affection. As regarding the hepatic biomarkers, namely, serum hyaluronic acid, ferritin, and sIL-2R, our study detected statistically increased serum levels in each of the patient groups compared to the controls. A progressive increase in their serum levels was detected as the liver condition progressively deteriorates. Meanwhile, more serum level elevations occurred with the presence of bilharzial infection concurrent with hepatitis C infection than without it. In addition, our study reported that in advanced cirrhosis subgroup B2 patients; there was a significant positive correlation detected between each of serum hyaluronic acid, ferritin, and sIL-2R and each of ALT and GGT serum levels. A positive correlation was also detected between serum hyaluronic acid and ALP. Meanwhile, a significant negative correlation was detected between each of the above three biomarkers and serum albumin level. In conclusion, our study reported that in chronic hepatitis C Egyptian patients, as the liver affection progresses, the liver functions deteriorate progressively, thus indicating more liver injury. Not only this, but also more deterioration in liver functions was detected in the presence of concurrent bilharzial infection than without it. As regarding the serum biomarkers: serum hyaluronic acid, ferritin, and sIL-2R, a progressive increase in their serum levels was detected as the liver condition progressively deteriorates. In addition, more elevations occurred in the presence of concurrent bilharzial infection. Moreover, our study detected that in advanced cirrhosis, these biomarkers correlate significantly with the liver functions denoting not only their diagnostic value as non-invasive biomarkers in the assessment of the liver condition, but also that their levels correlate with the histological severity of the related liver injury, and thus can be used in the prognostic follow up to assess the degree of liver pathological progression especially when liver biopsy is contraindicated, thus, protecting the patient from its hazards especially in cases of hepatic coagulopathy which is well known to occur in this category of patients

Hyperhomocysteinemia in end stage renal disease: a risk factor for atherosclerotic and/or thromboembolic complications?

To clarify the association of hyperhomocysteinemia with the increased risk of atherosclerotic and thromboembolic vascular complications in patients with end stage renal disease [ESRD] independent of other traditional risk factors, this study was performed. It included 150 patients with established ESRD scheduled on chronic ambulatory peritoneal dialysis [CAPD] or regular hemodialysis using high-flux membrane. All patients were supplemented with multivitamins including B12, B6 and folic acid. These patients were divided into two groups: Group A included 26 patients with clinically documented peripheral vascular events [ten with deep venous thrombosis and 16 with peripheral arterial disease] and group B included 124 patients without any clinically or laboratory documented vascular disease. In addition, 30 apparently healthy individuals were included as a control group. Total fasting plasma homocysteine as well as other risk factors were determined including hypertension, obesity, smoking, diabetes mellitus, hyperuricemia, dyslipidemia, prolonged recumbency and recent operations or trauma. Biochemical analyses were done including blood glucose levels [fasting and 2-hour postprandial], lipid profile [total cholesterol, triglycerides, HDL, LDL], serum uric acid, BUN and creatinine. Hematological analyses were also done including complete blood count, prothrombin time and concentration, aPTT, protein C, protein S, antithrombin III as well as fibrinogen. Imaging was also performed in the form of duplex ultrasound for peripheral arterial and/or venous systems and/or angiography in the selected cases. It was concluded that hyperhomocysteinemia is frequently seen in ESRD patients and it represents an independent risk factor for the atherosclerotic and thrombotic vascular disorders which occur frequently in these patients. It is higher in hemodialysis patients than in those on chronic ambulatory peritoneal dialysis [CAPD]

Anticardiolipin antibodies in chronic hepatitis C virus infection: is there an aetiopathogenetic link to antiphospholipid syndrome?

Chronic hepatitis c virus [HCV] has always been linked to extrahepatic autoimmune phenomena and found to be associated with various diseases known as extrahepatic manifestations of HCV. In addition, a variety of autoantibodies are detected in HCV patients. Recently HCV has been implicated as a cause of antiphospholipid syndrome [APS] which is usually defined by the association of clinical manifestations that comprise venous and/or arterial thrombosis, recurrent fetal losses, and thrombocytopenia, along with the presence of anticardiolipin [ACL] antibodies and/or lupus anticoagulant. Anticardiolipin antibodies can be induced by various infections diseases, however, they are not associated with thrombotic events as in the case of autoimmune diseases in which they are b2-glycoprotein I dependent and produce thrombotic events. To clarify whether an aetiopathogenesis exists between HCV and APS and meanwhile to study the prevalence, nature, and clinical significant of ACL auto antibodies in serum samples of HCV patients, the present study included one hundred and thirty subjects divided into three groups: a included 50 patients with chronic HCV infection, group b included 30 patients with APS [15 patients with primary and 15 with secondary type], and group c included 50 apparently normal age and sex-matched subjects taken as a control group. Clinical events as well as proper history of APS manifestations were recorded. The prevalence of ACL antibodies was detected by Elisa as well as its IgG and IgM isotypes, its B2-glycoprotein dependence was also evaluated. The present of cryoglobulins and other autontibodies as lupus anticoagulant [LA] and antinuclear antibodies [ANA] were determined as well, using indirect immunofkuorescence. HcVRNA and its viraemia titre were determined by RT-PCR and its quantitative testing. Our data showed that the prevalence of ACL antibodies in chronic HCV patients was found to be 42% which proved to be more than that in the normal controls [0%] but, its presence had no clinical significance. Our study clarified also that there is no significant association between a ACL antibodies and the presence of other auto antibodies or cryoglobulins in those patients. Furthermore, all HCV patients with positive ACL antibodies in our study were B-2 glycoprotein I independent. We concluded that the presence of ACL antibodies in chronic HCV patients seem to be an epiphenomenon and their presence has neither a clinical nor a laboratory significance in this category of patients. Thus, testing for HCV infection in APS patients or follow-up for the possibility of APS development in HCV patients might not be recommended. Thus, our study failed to implicate HCV as an aetiopathogeinc factor for APS