Bacterial DNA and its consequences in patients with cirrhosis and culture negative, non neutrocytic ascites

The detection of bacterial DNA [BactDNA] in serum and ascitic fluid [AF] from patients with liver cirrhosis and ascites is interpreted as molecular evidence of intestinal bacterial translocation [BT] and considered sufficient to activate the cellular immune response leading to greater cytokine synthesis. In the present work we study whether BactDNA and Tumor necrosis factor-alpha [TNF- alpha] in cirrhotic patients with culture negative, non neutrocytic ascites have been implicated in various complications of cirrhosis such as hepatorenal syndrome [HRS], spontaneous bacterial peritonitis [SBP] and mortality. We studied 34 patients with liver cirrhosis and culture negative, non neutrocytic ascites [22 patients without BactDNA [group I] aged [48.3 +/- 7.85y] and 12 patients with BactDNA [group II], aged [49.7 +/- 6.5y]]. Full history and complete clinical examination were done with the following investigations in the first admission and subsequent admissions during follow up for 24 weeks: complete blood picture, S. creatinine, S. bilirubin, S. albumin, S. transaminases [AIT and AST], AF and plasma TNF-alpha, AF protein and polymorphnuclear leucocytes [PMNL], both blood culture and AF aerobic and anaerobic cultivation, and detection of blood and ascitic fluid BactDNA using PCR. Plasma and ascitic TNF-alpha were significantly higher in cirrhotic patients with compared to those without BactDNA during first admission [54.5 +/- 22.56 vs 35.2 +/- 17.97; 123.2 +/- 49.32 vs 82.6 +/- 29.58 pg/ml respectively, P<0.05]. These changes became highly significant at the end of follow up of both groups [119.3 +/- 27.19 vs 40.2 +/- 16.08; 518.8 +/- 91.11 vs 97.6 +/- 17.81 pg/ml respectively, P<0.001]. There is non significant change of plasma and ascitic TNF-alpha in group I at first admission compared to those at the end of follow up [P>0.05]. However, in group II, there is highly significant increase in both plasma and ascitic TNF-alpha at the end of follow up compared to those at the first admission [P<0.001]. The relative risk of deaths, HRS and SBP were higher in patients with compared to those without BactDNA after follow up for 24 weeks [2.73, 27.37 and 18.18 respectively]. There were significant positive correlation between both plasma and ascitic TNF-alpha and each of serum creatinine and PMNL in the studied patients at the end of follow up. [r= 0.590, p= 0.002 ; r= 0.535, p= 0.005 ; r=0.499, p=0.009 ; r= 0.589, p= 0.002, respectively]. -Patients with BactDNA had more advanced liver disease after 24 weeks follow up compared to patients without BactDNA. We conclude that cirrhotic patients with culture negative, non neutrocytic ascites and BactDNA have significant higher level of AF and plasma TNF-alpha and higher risk of HRS, SBP and morality compared to those without BactDNA during follow up for 24 weeks which could suggest that both BactDNA and TNF-alpha have been implicated in these complications of liver cirrhosis

Proinflammatory cytokines and endothelial dysfunction in obese subjects: effect of weight reduction

Obesity is associated with an increased risk of developing atherosclerosis, which may be mediated, at least in part, by increased secretion of proinflammatory cytokines by adipose tissue. The aim of present study was to determine whether circulating levels of inflammatory cytokines and intercellular adhesion molecule-1 [sICAM-1] are elevated in obese subjects and whether they could be reduced by a substantical decrease in body weight. Forty-two healthy obese subjects [22 females and 20 males, age range 25 to 40 years, body mass index 35.2 +/- 3.64 Kg/m2, waist to hip ratio 0.883+0.085, and 20 age and sex matched normal weight controls were studied. Compared with nonobese subjects, obese subjects had increased basal concentrations of tumor necrosis factor-alpha [TNF-alpha]. [P<0.001], interleukin-6 [IL-6], [P<0.001] and sICAM-1 [P<0.001]. Flow mediated dilatation [FMD] was impaired in obese subjects when compared to lean controls [7.52% +/- 3.05 Vs 10.28% +/- 1.64, P<0.001]. Concentrations of TNF-alpha and lL-6 were related [P<0.001] to visceral obesity, as well as to slCAM-1 levels and FMD. After one year of a multidisciplinary program of weight reduction [diet, exercise, behavioral counseling], all obese women lost at least 10% of their original weight. Compared with baseline, sustained weight loss was associated with reduction of cytokines [TNF-alpha, IL-6] [P<0.001] and sICAM-1 [P = 0.001] concentrations in addition to improvement of FMD [P<0.001]. In obese subjects, endothelial activation and dysfunction correlates with visceral body fat, possibly through inappropriate secretion of cytokines. Weight loss represents a safe method for downregulating the inflammatory state and ameliorating endothelial dysfunction in obese subjects

Relationship between plasma homocysteine level and some cardiovascular risk factors in patients with type 2 diabetes

High plasma homocysteine [Hcy] concentration is risk factor for cardiovascular disease. Insulin resistance has been hypothesized to play an important role in the development of atherosclerotic disease. The information on the association between insulin resistance, other cardiovascular risk factors and plasma Hcy in type 2 diabetes is limited. The aim of our study was to assess the impact of insulin resistance and other cardiovascular risk factors on plasma total Hcy levels in patients with type 2 diabetes. The study included 40 patients with type 2 diabetes [aged 42.0 +/- 4.1 years] and 15 healthy controls, matched in age and sex with the patients. The following parameters were assessed: fasting plasma glucose [FPG], fasting plasma insulin [FPI], homeostasis model assessment of insulin resistance [HOMA-IR], serum total cholesterol, triglycerides, HDL-C, LDL-C and plasma total Hcy. Our study revealed significant increase in SBP, FPG, FPI, HOMA-IR, and total Hcy in type 2 diabetic patients compared to control group [137 +/- 4 vs 123 +/- 5 mmHg, 103 +/- 10.1 vs 83.2 +/- 6.9 mg/dl; 20.1 +/- 4.1 vs 8.8 +/- 3.1 mu/L, 5.8 +/- 0.8 vs 1.93 +/- 0.26, 13.6 +/- 1.2 vs 7.6 +/- 0.8 umol/L, respectively, all P<0.001]. As regard serum lipids our results revealed significant increase in total cholesterol, triglycerides and LDL-C but significant decrease in HDL-C in type 2 diabetic patients compared to control group [210 +/- 39 vs 160 +/- 21 mg/dl, 220 +/- 29 vs 106 +/- 10 mg/dl, 129 +/- 28 vs 88 +/- 21 mg/dl, 40 +/- 11 vs 52 +/- 16 mg/dl, respectively, all P<0.05]. In patients with type 2 diabetes there was significant positive correlation between total Hcy and SBP, FPG, FPI, HOMA-IR, total cholesterol and LDL-C [r = 327, P = 0.005, r = 240, P = 0.049, r = 0.513, P<0.001; r = 0.601, P<0.001, r = 0.241, P = 0.048; r = 0.250, P = 0.040 respectively], but there was significant negative correlation between total Hcy and HDL-C [r = -0.301, P = 0.009]. Increases in total homocysteine levels in type 2 diabetes are associated with insulin resistance and other cardiovascular riskfactors. Thus insulin resistance may be an important determinant of Hcy levels in those patients

Renal impairment and mortality in cirrhotic patients with spontaneous bacterial peritonitis: role of proinflammatory cytokines and a possible role of intercellular adhesion molecule-1

This study included 32 cirrhotic patients with spontaneous bacterial peritonitis [SBP] aged 36.3 +/- 5.3 years, 15 cirrhotic patients with sterile ascitic fluid aged 37.1 +/- 4.1 years and 15 age- matched healthy control subjects. Serum bilirubin, serum albumin, serum creatinine, CBC, ascitic fluid polymorphonuclear leucocytes [PMNL], plasma and ascitic fluid levels of TNF-alpha, IL-6 and sICAM-1, abdominal X-ray and ultrasonography were assessed. It was concluded that cirrhotic patients with SBP have an abnormal inflammatory and immune responses in terms of increased ascitic fluid and plasma levels of TNF-alpha, IL-6 and sICAM-1. SICAM-1 implies a favorable condition for PMNL migration towards the peritoneum accentuating the inflammatory and immune responses which may be an important mechanism of SBP that induced renal impairment and death

Plasma soluble tumor necrosis factor-alpha recepector 2 in lean normoglycemic subjects with a strong family history of type 2 diabetes

Twenty lean normoglycemic subjects with strong family history of type 2 diabetes [aged 38.2 +/- 8.61 years, with BMI 22.35 +/- 1.57 kg/m 2] and 15 age, sex and BMI matched subjects with no family history of type 2 diabetes [control group] were included in this study. Fasting plasma glucose [FPG], oral glucose tolerance test, fasting plasma insulin [FPI], homeostasis model assessment for insulin resistance [HOMA-IR], plasma lipids, plasma TNF-alpha and soluble tumor necrosis factor alpha receptor 2 [sTNFR2] were assessed. The study concluded that lean subjects with strong family history of type 2 diabetes are insulin resistant. The insulin resistance in this group is not due to an increase in plasma TNF-alpha and may be due to the up-regulation of TNF-alpha system manifested by the increased plasma sTNFR2 levels. Therefore, sTNFR2 is a better marker of TNF- alpha action in these subjects than the circulating cytokine itself

Diurnal variability of blood pressure, autonomic function tests, QT measurements and hemostasis in diabetic patients with hepatosplenic schistosomiasis

In our locality, hepatosplenic schistosomiasis [HSS]: is frequently encountered in association with diabetes mellitus. Diurnal variability of autonomic nervous system and hemostasis had been previously suggested in diabetic patients but not proved in HSS. The impact HSS on diurnal variability of heart rate, blood pressure, QT interval. QT. dispersion autonomic nervous system and hemostasis had not been previously studied in diabetic patients. Therefore, we studied ninety-five female patients: 30 patients with type 2 diabetes [diabetic group.], 30 patients with hepatosplenic schistosomtasis [HSS group], and 35 patients with combined diabetes mellitus and HSS [combined group] and thirty age-matched healthy women [control group]. The coexistence of diabetes mellitus and HSS affect many of the studied parameters. The combined group had more significant deterioration of deep breathing test: valsalva test and blood pressure response to sustained handgrip together with reduced plasma fibrinogen and euglobulin lysis time in comparison to the diabetic group. Altered diurnal variability of deep breathing test. Mean blood pressure and hemostasis were found in the combined group in comparison to the diabetic group. Loss of diurnal variability of Corrected QT interval [QTc] was also found in the three studied groups of patients in comparison to the control group. QTc and QT dispersion [QTD] were significant increased and correlated with autonomic function tests in the three studied groups of patients. it is concluded that, diurnal variability of autonomic nervous system, blood pressure and hemostasis should be considered during assessment of these variable Day-night difference in autonomic nervous system and arterial blood pressure together with hemostatic changes observed in the combined group in comparison to the diabetic group could be a possible explanation for the reduced occurrence and altered timing of cardiac events in the combined group. QTc and QTD are sensitive, noninvasive, simple predictors of cardiac autonomic dysfunction and could be used routinely to identify patients with autonomic dysfunction and increased cardiovascular risk

Insulin resistance and hyperinsulinemia: independent relation to left ventricular mass in humans

Hyperinsulinemia and insulin resistance may contribute to the development of cardiac hypertrophy which is a major cardiovascular risk factor. In humans, however, the evidence is inconclusive. Antihypertensive drugs have different effects on insulin metabolism, sensitivity, and on left ventricular mass [LVM]. To study the association between LVM and insulin resistance as well as some other cardiovascular risk factors. Also, to compare the effects of two drugs [Atenolol, lisinopril], which have different effects on insulin sensitivity on LVM. The study included four groups: Group [I] control group included 10 healthy lean females aged 35.7+3.4 years. Group [II] included 28 obese normotensive female patients aged 35.39+3.9 1 years, body mass index [BMI] 36.18+3.93 Kg/m2. Group [III] included 28 newly diagnosed obese hypertensive female patients aged 35.85+ 7.8 years, BMI 39.34+4.12 Kg/m2. Group [IV] included 28 newly diagnosed lean hypertensive female patients aged 34.36+4.45 years, BMI 22.98+1.60 Kg/m2. Patients in groups III and IV were randomized to treatment with atenolol or lisinopril [14 patients in each group]. The following parameters were assessed BMI, WHR, systolic and diastolic blood pressure, fasting plasma glucose and insulin, fasting insulin resistance index [FIRI], LVM and left ventricular mass index [LVMI]. Obese and hypertensive patients had significant increase in insulin resistance, LVM and LVMI compared to controls [P<0.05]. Abdominal obesity as repesented by WHR, was directly associated with insulin resistance, LVM, and LVMI [r = 0.749, P<0.001; r = 0.523,P<0.O01; r = 0.656, P<0.001 respectively]. LVM was positively correlated with systolic and diastolic blood pressure, BMI. WHR, and insulin resistance [r = 0.749, P<0.001; r = 0.639, P<0.001; r = 0.224, P = 0.041, r = 0.523, P<0.001; r = 0.509, P<0.001 respectively]. After adjustment for systemic blood pressure and obesity, LVM was independently associated with insulin resistance [P<0.001]; Lisinopril, but not atenolol was associated with favorable effect on insulin resistance and led to more significant regression of LVM in lean [P<0.001] and obese [p = 0:004] hypertesnive patients. LVM has a positive independent correlation with hyperinsulinemia and insulin resistance. Hyperinsulinemia has independent role in promoting left ventricular hypertrophy. Agents and maneuvers which improve insulin sensitivity might be beneficial in management of left ventricular hypertrnphy and other deleterious effects of hyperinsulinemia

Longevity life expectancy, mortality rates, and causes of deaths of elderly rural population, Egypt, 1996

It is a descriptive analytical study utilizing death records of aged ones after 60 years and its causes, together with using available data from national vital statistics. The results showed that the age of deaths is increasing from [65-70] years reaching the age groups 85 + years in the last [3-5]years [1989-l 996]. The death causes are statistically different from combined to rural health units, which uncontrolled and not guided by WHO's international classification of diseases and causes of death. It was done on 521 cases and the age of death reached 85+ years mostly due to heart failure