Differential expression of alpha-smooth muscle actin and vascular endothelial growth factor in skin biopsy of patients with systemic sclerosis: a histological and immunohistochemical study

Vasculopathy is a hallmark of systemic sclerosis [SSc]. It contributes to many of its clinical manifestations and precedes fibrosis. The aim of this study was to investigate the expression of alpha-smooth muscle actin [alpha-SMA] in skin biopsy of patients with SSc and correlate it with other manifestations of vasculopathy, including those seen on fundus fluorescein angiography and tissue vascular endothelial growth factor [VEGF] expression. This study included 25 patients with SSc and 10 healthy individuals. Patients underwent full history taking and a clinical examination. All participants underwent fundus fluorescein angiography. Skin biopsy was examined by H and E staining, Mallory triple staining, and immunohistochemical staining for alpha-SMA and VEGF. Histological examination showed loss of dermal papillae, hypovascularity of the dermis, and subepidermal fibrosis. Immunohistochemical staining of the vessel wall in skin biopsy samples showed a statistically highly significant increase in VEGF and a highly significant decrease in alpha-SMA in patients as compared with controls. There was a highly significant positive correlation between VEGF and duration of illness, Raynaud's phenomenon, digital ulcers, disease activity score, and modified Rodnan Skin Score. As regards alpha-SMA, there was a highly significant negative correlation with Raynaud's phenomenon, disease activity score, modified Rodnan Skin Score, and VEGF, whereas there was a significant negative correlation with digital ulcers. The strongest correlation [r] for the duration of illness was found with alpha-SMA, followed by VEGF. alpha-SMA was found to be correlated to different manifestations of vasculopathy in SSc. It was found to be one of the early markers of vasculopathy among the other studied variables. Besides its diagnostic role in SSc vasculopathy, it could play a role in impaired vasculogenesis, making it a potential therapeutic target in the management of SSc

Results of early probing in cases of congenital nasolacrimal duct obstruction

To evaluate the efficacy of early intervention in cases of congenital NasoLacrimal Duct Obstruction [NLDO]. Also, to find the possibility of occurrence of additional side effects. The study involved thirty-three patients diagnosed as nasolacrimal duct obstruction of congenital origin between 2003 to 2005. These patients were submitted to early intervention by probing and irrigation under general anaesthesia between the age of 6 to 9 months. The success of the procedure was defined as complete resolution of signs and symptoms. The follow up period ranged from six to 18 months postoperatively. The success rate was 90.48%, out of thirty-three patients, thirty patients showed complete cure after first attempt of probing and did not need any further interference or additional treatment. No serious complications were noticed to occur in this age group. Probing is highly successful in the younger age group and proved to be a safe procedure. This encourages us to use probing as first line of treatment starting from six months of age in cases of congenital nasolacrimal duct obstruction

Cognitive dysfunction in patients with chronic hepatitis C: a psychometric and magnetic resonance spectroscopic study

Patients with chronic hepatitis C virus [HCV] infection frequently describe neuropsychological symptoms and there is a growing body of literature on cerebral dysfunction occurring at an early stage of chronic HCV infection. The aim of the present study was to elucidate whether patients' subjective impression of cognitive impairment was accompanied by objective evidence of cerebral dysfunction. 12 Patients with chronic hepatitis C virus infection with compensated liver function were recruited from Ain-Shams university hospitals. Another 8 healthy controls matched for age and sex were recruited from available hospital staff or patients relatives. Patients with potential risk factors for cognitive impairment were excluded. All patients and controls underwent clinical assessment, laboratory test, abdominal ultrasound, neuropsychological assessment, digital electroencephalography [DEEG], brain MRI and MR spectroscopy [MRS]. DEEG of all 12 patients revealed normal background with well formed alpha waves with no focal or generalized slowing and no epileptic activity. Psychometric assessment revealed that attention and sustained attention was affected in 6 patients [50%], short term memory was affected in 4 patients [33.5%], psychomotor speed and learning ability was affected in 4 patients [33.5%] and immediate verbal and visual memories were affected in 6 patients [50%]. Depression was absent in all patients. The MRI brain of all patients revealed no abnormalities. On intermediate echo sequence of MRS, the HCV group showed significant decrease in N-acetylaspartate/creatine ratios [NAA/Cr ratio] in frontal white matter [P < 0.05]. Mild, statistically non significant, elevation of choline/creatine ratios predominantly in basal ganglionic [BG] region was noted on both short and intermediate echo sequences. On short echo sequence of MRS, the HCV group showed a mild, statistically non significant, increase in myoinositol/creatine in frontal white matter region as compared to controls. Thus, there is a suggested reduction of normal neurons and accentuation of gliosis in frontal white matter together with membrane degradation in BG in patients with hepatitis C virus infection. Agreement between psychometry and MRS revealed a significant agreement between decreased NAA/Cr and impaired attention and sustained attention, immediate verbal memory and immediate visual memory [P < 0.05]. HCV infection itself is associated with changes in the brain, even in the absence of hyperammonemia. Specifically, HCV-infected individuals may have deficits in cognitive functions such as attention, working memory, and speed of information processing. They also have abnormalities on magnetic resonance spectroscopy [MRS] that favor the organic explanation of the patients' mental symptoms

Resistive index as a predictor of kidney dysfunction and hepatorenal syndrome in different stages of liver cirrhosis

Renal hemodynamic changes begin early in the course of liver disease-related functional kidney failure The hallmark - change is intense intra-renal vasoconstnction associated with reduced renal blood flow and elevated renal arterial vascular resistance. Nitric oxide has been proposed to constitute a mediator of both the hyperdynamic circulation and renal failure in patients with advanced hepatic disease. The aim of this study was to evaluate the renal hemodynamic changes by renal duplex Doppler ultrasound and nitric oxide as predictors of kidney dysfunction and hepatorenal syndrome [HRS] in patients with liver cirrhosis. Twenty five patients with liver cirrhosis without ascites, 25 patients had liver cirrhosis with ascites, 25 patients with HRS and, 25 patients with end stage renal disease [ESRD] without liver disease, and 25 normal subjects as control group were enrolled in this study, they were age and sex matched. All the participants were subjected to lull medical history clinical examination, routine investigations, in addition to duplex Doppler ultrasound on the intra-renal arteries to detect the resistive index [RI] and measurement of the stable end product of nitric oxide [serum nitrate]. The highest values of RI of intra renal arteries and serum nitric oxide were found in patients with ESRD. RI of intra-renal arteries and serum nitric oxide levels were significantly higher in patients with HRS than in cirrhotic patients [ascitic and non ascitic] and control group. Also our study revealed that RI and serum nitric oxide were significantly higher in the non ascitic phase of liver cirrhosis than normal control group but increased more with the development of ascites, and reached higher value in patients with HRS. The study revealed a highly significant direct correlation between serum nitric oxide and RI of intra-renal arteries among the studied cirrhotic patients. An increased renal RI can predict development of HRS independent of liver disease severity and is better predictor than the individual parameters of the child-Pugh classifications

Paclitaxel-carboplation in advanced ovarian cancer

This study included 85 female patients with advanced ovarian epithelial cancer. Fifty patients were subjected to primary optimal debulking surgery, followed by adjuvant combination chemotherapy either cisplatin-cyclophosphamide or paclitaxel-carboplatin with comparable treatment outcome. The other 35 cases were not amenable to optimal surgery. They received primary chemotherapy, either cisplatin-cyclophosphamide or paclitaxel-carboplatin. The overall median duration of response and survival in this subgroup was 12 and 28 months, respectively, which was significantly lower than in those subjected to primary optimal debulking surgery [22 and 35 months, respectively]. However, in the subgroup of patients who received primary chemotherapy [paclitaxel-carboplatin], the median duration of response and survival was significantly higher than those received cisplatin-cyclophosphamide and comparable with those patients subjected to primary debulking surgery and adjuvant chemotherapy. Also, the treatment related toxicity was significantly higher among the patients receiving cisplatin-cyclophosphamide

Activity of single agent oxaliplatin in recurrent ovarian cancer, previously treated with cisplatin or carboplatin

This study included 28 females with recurrent ovarian cancer previously treated with combination chemotherapy including cisplatin or carboplatin. The platinum free interval was >6 - <12 months in 11 patients and >12 months in 17 patients. Oxaliplatin was prescribed in a dose of 130 mg/m2 administered over 2 hours every 21 days with an average of 5 cycles/patient. An overall response was achieved in ten patients with a median time to tumor progression and overall survival of 11 and 17 months, respectively. A favorable response was observed in the platinum sensitive group [platinum free interval of >12 months] as well as those cases with non-bulky recurrent disease. Oxaliplatin administration was associated with an accepted level of drug related toxicity

diagnostic value of Von Willibrand factor and circulating adhesion molecules in arteriopathic vascular patients: Relationship to lipid profile and risk factors

The present study was conducted on a group of seldom arteriopathic hyperlipidemic patients to investigate the availability of adhesion molecules measurement [ICAM-1, E-selectin] as well as vWF as markers of endothelial dysfunction, assisting in diagnosis or as indicators of disease progression. This study included 73 hyperlipidemic patients [43 males and 30 females] suffering from arterial occlusive disease. They were subdivided into group I [25 patients with mild hypercholesterolemia, group II [28 patients with severe hypercholesterolemia and group III [20 patients with hypercholesterolemia]. Control group consisted of 20 apparently healthy normolipidemic subjects, age and gender matching. Both patients and controls were subjected to the laboratory investigations [total cholesterol [TC], LDL-C, HDL-C, triglycerides, soluble intracellular adhesion molecule-1 [sICAM-1], soluble endothelial leukocyte adhesion molecule [sELAMs-sE-selectin] and von Willebrand factor [vWF]]. The level of sICAM-1, E-selectin and vWF were significantly higher in group with mild or severe hypercholesterolemia while the increase was nonsignificant in hypertriglyceridemia as regards ICAM-1 and E-selectin compared with the control group. The correlation between vWF and TC, LDL-C, sICAM or sE-selectin were significant, while sICAM showed significant correlation with only LDL-C. sE-selectin had no correlation with the lipid profile parameter. These results support the suggestion that vWF could serve as a marker of diagnosis, prognosis and follow-up of disease severity, while E-selectin is an indicator of early endothelial cell disturbance. sICAM could be also taken as an evidence of the atherosclerotic process. Hypertriglyceridemia seemed to be noninjurious to the endothelial wall

Study of significance of immunethrombocytopenia and platelet associated IgG in patients with chronic hepatitis Cand patients with liver cirrhosis

Background: Chronic hepatitis C virus infection are often associated with extra hepatic imrnunological manifestations including various autoimmune disorders . The aim of this study was to evaluate the significance of immune thrombocytopenia and platelet associated IgG in patients with chronic hepatitis C and patients with liver cirrhosis .Forty patients with chronic hepatitis C virus infection were chosen for this study . They were divided according to platelet cotmt into thrombocytopenic group and non thrombocytopenic group matched for age and sex .all patients were subjected to liver function tests , renal function tests , complete blood picture, bone marrow biopsy ,abdominal ultrasonography , liver biopsy with histopathological examination and platelet Ig G assay[PA Ig G]

Results: PA IgG was significantly high in thrombocytopenic group [15 out of 20 ; 75%] compared with non thrombocytopenic group [3 out of 20 ,15%][p< 0.01] . Moreover , in the thrombocytopenic group,when we compared PAIgG and child's grades we found that PAIgG was significantly high in patients with child's C grade [6 out- of 6 100%], when compared to child's B'[4 out of 7 ; 57%], and those with child's A [0 out of 7Also PAIgG was significantly high in patients with child's B when compared with those with child's A grade[p<0.05]. As regards histopathology index , we found that in the thrombocytopenic group , PAIgG was significantly high in patients with liver cirrhosis [8. out of 10;.80%] compared with chronic active hepatitis[2 out of 10 ;20%][p< 0.01]. Moreover , we found that histopathological activity index was significantly high in the thrombocytopenic group [9.1+ 2.5] comparing with non-thrombocytopenic group [7.35 +2.5][p,0.05] . Also fibrosis stage was significantly high in the thrombocytopenic group [2.5+0.96] , comparing to non thrombocytopenic group [2.05+0.876][p< 0.05]. the study

Concluded: that It is vitally important not to immediately conclude that the thrombocytopenia encountered in patients with chronic hepatitis C indicates cirrhosis with portal hypertension andhypersplenism, but autoimmune mechanisms may be the cause. PAIgG and immune thrombocytopenia can be used as prognostic marker from the clinical and pathological point of view in patients with chronic hepatitis C virus infection and in patients with liver cirrhosis passing from one stage to another