Rosa Segura

Interleukin-6, nitric oxide, and the clinical and hemodynamic alterations of patients with liver cirrhosis

Objective: Nitric oxide has been proposed as a mediator of hyperdynamic circulation in cirrhosis. Endotoxin and cytokines induce the synthesis of nitric oxide. The aim of this study was to investigate the relationship between endotoxemia, cytokines, and nitric oxide in patients with cirrhosis, and to correlate these findings with clinical, biochemical, and hemodynamic parameters. Methods: Clinical, biochemical, and hemodynamic parameters were assessed in 66 patients with cirrhosis and 15 controls. Levels of antidiuretic hormone, plasma renin activity, aldosterone, interferon γ, interleukin-1, interleukin-6, tumor necrosis factor α, endotoxin, and nitrates-nitrites were determined. Results: Mean arterial pressure was lower and interleukin-6, tumor necrosis factor α, nitrites-nitrates levels, and endotoxin positivity rates were higher in cirrhotics than in controls (p < 0.005). Mean arterial pressure decreased and interleukin-6 levels increased with worsening of Child score (p < 0.005). Patients with ascites had higher levels of interleukin-6, tumor necrosis factor α, and nitrates-nitrites than patients without ascites (p < 0.01). Elevated levels of interleukin-6 were found in patients with encephalopathy grade I, compared with patients without (p < 0.001); this association was independent of the severity of liver disease. In patients with low mean arterial pressure, interleukin-6 levels were higher than in patients with high mean arterial pressure (p= 0.001), whereas tumor necrosis factor α and nitrates-nitrites levels were not different. By multivariate analysis, high interleukin-6 levels showed independent associations with the presence of ascites, encephalopathy, and low mean arterial pressure. Only interleukin-6 levels had significant correlations with Child score, plasma renin activity, serum and urinary sodium, and mean arterial pressure (r ≥ 0.4, p < 0.005). Conclusions: Although the activity of the nitric oxide pathway is increased in patients with cirrhosis and might contribute to the hemodynamic alteration, other factors are involved. Interleukin-6, possibly through nitric oxide-independent mechanisms, also might play a role in the vasodilatation of cirrhosis and the pathogenesis of hepatic encephalopathy.

Free insulin growth factor-I and vascular endothelial growth factor in the vitreous fluid of patients with proliferative diabetic retinopathy

PURPOSE To investigate the relationship between insulin-like growth factor-I (IGF-I) and vascular endothelial growth factor (VEGF) in the vitreous fluid of diabetic patients with proliferative diabetic retinopathy (PDR). DESIGN Observational case-control study. METHODS In a prospective study, 37 consecutive diabetic patients with PDR (14 type I and 23 type II diabetes mellitus) in whom a vitrectomy was performed were compared with 21 nondiabetic patients with other conditions requiring vitrectomy (control group). Free IGF-I and VEGF were measured by ELISA. RESULTS Vitreal levels of both free IGF-1 and VEGF were higher in diabetic patients with PDR than in control subjects (P <.01, and P <.0001, respectively). After adjusting for total intravitreous protein concentration, VEGF (ng/mg of proteins) remained significantly higher in diabetic patients with PDR than in the control group (P <.0001), whereas free IGF-I (ng/mg of proteins) was lower in diabetic patients than in control subjects (P <.0001). The vitreous concentrations of VEGF were higher in patients with active PDR than in patients with quiescent PDR (P <.005), whereas vitreous free IGF-I was not related to PDR activity. Finally, we did not observe a correlation between the vitreal levels of free IGF-I and VEGF. CONCLUSIONS We conclude that free IGF-I and VEGF are both increased, but not related, within the vitreous fluid of diabetic patients with PDR. In addition, our results support the current concept that VEGF is directly involved in the pathogenesis of PDR, whereas the precise role of free IGF-I remains to be established.

Time course and rate dependence of Q-T interval changes during noncomplicated acute transmural myocardial infarction in human beings

Abstract The sequential changes and the rate dependence of the Q-T interval were studied in 21 patients 6 hours to 5 days after an anterior (11 cases) or an inferior (10 cases) acute transmural myocardial infarction. The Q-T interval was analyzed at fixed atrial-paced heart rates in leads aVF and V3 recorded at 100 mm/s and at twice the standard amplitude. Values were compared with those of a group of normal subjects matched by age and sex. Severe ventricular arrhythmias, electrolyte or conduction disturbances and pericarditis were excluded in all patients. Sequential changes in the Q-T interval were apparent only in the leads showing the ischemic changes (lead V3 in anterior and lead aVF in inferior myocardial infarction) in 19 of 21 patients. After an initial shortening (first 12 hours), there was a remarkable lengthening of the Q-T interval coinciding with T wave inversion (12 to 24 hours after the myocardial infarction). By the 4th to the 6th day, there was a return to normal values. The lengthening of the Q-T interval was greater in anterior than in inferior myocardial infarction. The rate-dependent shortening of the Q-T interval at increasing rates was more prominent at the beginning of T wave inversion. It is concluded that lengthening of the Q-T interval is common 12 to 24 hours after the onset of an acute myocardial infarction and that prolongation of up to 20 percent over the initial values may occur in cases not complicated by severe ventricular arrhythmias.

Hepatocyte growth factor in vitreous and serum from patients with proliferative diabetic retinopathy

BACKGROUND Hepatocyte growth factor (HGF) is an endothelium specific growth factor that has been implicated in angiogenesis, a crucial event for the development of proliferative diabetic retinopathy (PDR). The aim of the study is to determine the intravitreous concentrations of HGF in diabetic patients with PDR, and to investigate whether its serum levels could contribute to its intravitreous concentration. METHODS 17 diabetic patients and seven non-diabetic patients in whom a vitrectomy was performed were studied. Both groups were matched by serum levels of HGF. Venous blood and vitreous samples were collected simultaneously at the time of vitreoretinal surgery. Vitreous and serum HGF were determined by ELISA. RESULTS Intravitreous concentrations of HGF (median and range) were higher in diabetic patients (17.04 ng/ml (9.98–80)) in comparison with non-diabetic patients (5.88 ng/ml (2.57–14.20); p=0.003). Intravitreous HGF concentrations were strikingly higher than serum HGF concentrations both in diabetic patients (17.04 ng/ml (9.98–80) v0.66 ng/ml (0.26–1.26); p<0.001) and in the control group (5.88 ng/ml (2.57–14.20) v 0.68 ng/ml (0.49–0.96); p=0.003). No correlation was found between serum and vitreous levels of HGF in both groups (diabetic patients,r= −0.31; p=0.5 and control subjectsr= −0.15; p=0.5). CONCLUSION The high vitreous levels of HGF observed in diabetic patients with PDR cannot be attributed to serum diffusion across the blood-retinal barrier. Therefore, intraocular synthesis appears to be the main contributing factor for the high vitreous HGF concentrations in diabetic patients, a cytokine that seems to be directly involved in the pathogenesis of PDR.

Adenosine deaminase activity in the diagnosis of lymphocytic pleural effusions of tuberculous, neoplastic and lymphomatous origin

We studied the activity of adenosine deaminase in 74 lymphocytic pleural effusions which were divided into four groups according to the aetiology: tuberculous (38 cases), neoplastic (17), lymphomatous (7) and miscellaneous (12). The mean enzyme value was significantly higher in the tuberculous cases (93.81 +/- 29.56 U/I) than for the other three groups and significantly higher in pleural effusions of lymphomatous origin than in the neoplastic and miscellaneous groups. Based on the lowest value of enzyme activity found in the tuberculous group (50 U/I), the test had a sensitivity of 1 and a specificity of 0.97.

Adrenomedullin, a vasodilator peptide implicated in hemodynamic alterations of liver cirrhosis: relationship to nitric oxide.

This prospective cohort study was aimed atinvestigating the role of adrenomedullin, a potentvasodilator peptide, in liver cirrhosis and itsrelationship with nitric oxide and cytokines. Overall,66 consecutive patients with liver cirrhosis and 15 controlsmatched for age and sex distribution were included.Adrenomedullin levels in patients with cirrhosis werehigher than in controls [28.1 (23.5-34.8) vs 21.9 (21.1-26.4) pmol/liter, P = 0.002]. Child classA patients had adrenomedullin levels similar to those ofcontrols, but lower than patients in class B and C,respectively (P = 0.01). Patients with ascites showed more elevated adrenomedullin levels thanpatients without (P = 0.001). Adrenomedullin levels hadsignificant correlations with aldosterone (r = 0.55; P< 0.001), plasma renin activity (r = 0.49; P < 0.001) and nitrates-nitrites levels (r= 0.52; P < 0.001). Weak correlations were found withtumor necrosis factor-alpha and interleukin-6. Thisstudy shows that high levels of adrenomedullin in liver cirrhosis correlate with featuresassociated with plasma volume expansion, and suggeststhat, in late stages of cirrhosis, adrenomedullin mightcontribute to vasodilatation by increasing thegeneration of nitric oxide.

Diagnostic value of ascites gamma interferon levels in tuberculous peritonitis. Comparison with adenosine deaminase activity

The value of ascites gamma interferon concentration and ascites adenosine deaminase activity in distinguishing tuberculosis from other causes of ascites was examined in a prospective study of 86 patients with ascites, including 16 with tuberculous peritonitis. Gamma interferon concentration was higher in tuberculous peritonitis than in the other causes of ascites (p less than 0.0001), and a cut-off between 3 and 9 u/ml reached a sensitivity and a specificity of 100%. The mean (+/- SD) gamma interferon level in tuberculous ascites was 39.3 +/- 18.3 u/ml in patients seronegative for HIV and 14.2 +/- 4.7 u/ml in patients with AIDS (p = 0.01). Adenosine deaminase activity in tuberculous ascites was also higher than in the other causes of ascites (p less than 0.0001), and a cut-off of 40 u/l reached a sensitivity of 100% and a specificity of 97%. The two false positives for adenosine deaminase test were true negatives for the gamma interferon test. There was no significant correlation between gamma interferon concentration and adenosine deaminase activity either in tuberculous ascitis or in any other group. This study suggests that ascites gamma interferon determination may be very useful in the screening of tuberculous peritonitis, but its cost makes it advisable to use adenosine deaminase activity as a routine test, at least in areas where tuberculosis is endemic.

Polymorphonuclear Elastase in the Early Diagnosis of Complicated Pyogenic Pleural Effusions

Background: Polymorphonuclear elastase (PMN-E) is a neutrophilic marker that has been implicated in acute inflammatory responses. Objectives: To evaluate the accuracy of PMN-E in the diagnosis of complicated pyogenic effusions. Patients and Method: We studied 536 patients with pleural effusion of various etiologies. There were 125 pyogenic bacterial effusions (42 typical parapneumonic, 17 borderline complicated parapneumonic and 66 complicated parapneumonic or empyema), 83 tuberculous, 91 malignant, 42 paramalignant, 95 transudates, 28 miscellaneous and 72 effusions of unknown origin. Classic markers (pH, glucose, proteins, adenosine deaminase, LDH, leukocytes and differential count) and the PMN-E level were quantified in pleural fluid. The accuracy of PMN-E as an early marker in the diagnosis of complicated pyogenic infectious effusions was evaluated among pleural effusions that were not diagnosed with classic biochemical markers, radiological findings or Gram stain. Since results of pleural fluid culture and cytological examination are generally available after a 48-hour delay, they were not included as early markers in the initial diagnosis of pleural effusions. Results: Early diagnosis of complicated pyogenic bacterial effusions was achieved in only 48 of 66 cases with classic markers. Among those that were not diagnosed with these parameters, a pleural PMN-E value >3,500 µg/l discriminated between complicated and noncomplicated pyogenic bacterial effusions with a sensitivity of 67% and a specificity of 97%. Conclusions: PMN-E is useful in the early diagnosis and management of complicated pyogenic infectious effusions, which may be delayed with classic markers.

Free insulin-like growth factor 1 in the vitreous fluid of diabetic patients with proliferative diabetic retinopathy: a case-control study

The aim of the study was to evaluate the vitreous levels of free insulin-like growth factor 1 (IGF-1) in patients with proliferative diabetic retinopathy (PDR). For this, a total of 36 diabetic patients with PDR (group A) and 28 non-diabetic patients (group B) in whom a vitrectomy was performed were compared. Both groups were matched by age, sex and serum-free IGF-1. In a subgroup of diabetic patients (n =21) and non-diabetic patients (n =13), vitreous and serum total IGF-1, IGF-binding protein 1 (IGFBP-1) and IGFBP-3 were also determined. Serum and vitreous levels of free IGF-1, total IGF-1, IGFBP-1 and IGFBP-3 were measured by immunological methods. Vitreal proteins were assessed by a turbidimetric method and adjusted for vitreous haemoglobin. Vitreous levels of free IGF-1 were elevated in group A (median, 0.16 ng/ml; range 0.06-0.57 ng/ml) in comparison with group B (median, 0.12 ng/ml; range 0.06-0.22 ng/ml; P <0.001); however, after adjusting for vitreal proteins, free IGF-1 levels were significantly lower in group A in comparison with group B [0.05 ng/mg (0.01-0.45 ng/mg) versus 0.15 ng/mg (0.07-0.66 ng/mg); P <0.001]. The relatively lower free IGF-1 level observed in group A could not be attributed to differences in the distribution of intravitreous IGFBP-1 and IGFBP-3 in relation to total IGF-1. Notably, the contribution of free IGF-1 to total IGF-1 in vitreous fluid was 10% in group A and 42% in group B; these percentages largely exceed that obtained in serum (<1%). Our results suggest that although there is an enhancement of intravitreous free IGF-1 in diabetic patients due to serum diffusion, a deficit in its intraocular production also exists. In addition, these findings support the concept that intraocular-produced free IGF-1 plays a relevant role in retinal homoeostasis.

Validation of Automated Blood Cell Counters for the Diagnosis of Spontaneous Bacterial Peritonitis

Validation of Automated Blood Cell Counters for the Diagnosis of Spontaneous Bacterial Peritonitis