Seroepidemiological Survey of Human Visceral Leishmaniasis in Ilam Province,West of Iran In 2013

Background:

Visceral leishmaniasis (VL) as one of the most important human parasitic disease is endemic in some parts of Iran. Several cases of VL have been reported recently in the Ilam Province. The current study aimed to assess the present status of human VL in the region.

Methods:

A random cluster sampling method was used to collect 456 serums samples from the children up to 12 years of age and 10% of adults living in urban and rural areas of the province. All the collected serum samples were tested by direct agglutination test (DAT) to detect anti- Leishmania infantum antibodies.

Results:

Of the examined 456 serum samples with direct agglutination test (DAT), only 21 (0.43%) sera showed anti- Leishmania antibodies at titers 1:400 and higher. Distribution of anti- Leishmania antibodies titers were: 1:400(n=4), 1:800(n=11), 1:1600(n=3), 1:3200(n=1), and 1:6400(n=1). Individuals with titers ≥1:3200 showed clinical signs and symptoms such as fever and splenomegaly. The highest and lowest seropositivity were observed in the age groups of 5–9 and >15 years old, respectively. There were no significant difference between the rate of seropositivity in males and females.

Conclusion:

VL with a low prevalence circulates in some parts of Ilam province, particularly in the southern parts. Complementary studies should be needed to find animal reservoir hosts and vectors. Furthermore, health systems and physicians should pay particular attention to the disease.     

Opposite central cardiovascular effects of nifedipine and BAY k 8644 in anesthetized rats

The central cardiovascular effects of the calcium channel blocker nifedipine and the calcium channel activator BAY k 8644 were studied in anesthetized and ventilated normotensive Wistar-Kyoto (WKY) or spontaneously hypertensive rats (SHR). Both drugs were administered in a 1.5-microliter volume into the lateral ventricle of the brain (i.c.v.) or into the cisterna magna (i.c.). The injection of vehicle alone (i.c. or i.c.v.) did not significantly change mean arterial pressure (MAP) or heart rate. Nifedipine (5 and 50 micrograms/kg) and BAY k 8644 (5 and 50 micrograms/kg) induced opposite effects on MAP when centrally injected. Nifedipine decreased MAP and induced a bradycardia (i.c.v.) or no change in heart rate (i.c.), and BAY k 8644 increased MAP without any significant change in heart rate (i.c. or i.c.v.). These effects were more marked with the highest dose of either drug. These effects seemed to be of central origin, since they were suppressed by ganglionic blockade by hexamethonium (100 mg/kg i.v.), whereas after hexamethonium the hypotensive and the hypertensive responses to intravenously injected nifedipine and BAY k 8644, respectively, were preserved. Bilateral vagotomy suppressed the bradycardia induced by i.c.v. administered nifedipine. Previously i.c.v. administered nifedipine (5 micrograms/kg) antagonized the pressor response to BAY k 8644 (5 micrograms/kg i.c.v.). Changes in MAP and heart rate were significantly more marked in SHR than in WKY. These results indicate that a calcium channel inhibitor and a calcium channel activator can modulate in opposite fashion central mechanisms involved in blood pressure control.     

Long-term fluvastatin reduces the hazardous effect of renal impairment on four-year atherosclerotic outcomes (a LIPS substudy)

Mild renal impairment is an important risk factor for late cardiovascular complications. This substudy of the Lescol Intervention Prevention Study (LIPS) assessed the effect of fluvastatin on outcome of patients who had renal dysfunction and those who did not. Complete data for creatinine clearance calculation (Cockcroft-Gault formula) were available for 1,558 patients (92.9% of the LIPS population). Patients were randomized to fluvastatin or placebo after successful completion of a first percutaneous coronary intervention. Follow-up time was 3 to 4 years. The effect of baseline creatinine clearance on coronary atherosclerotic events (cardiac death, nonfatal myocardial infarction, and coronary reinterventions not related to restenosis) was evaluated. Baseline creatinine clearance (logarithmic transformation) was inversely associated with an incidence of adverse events among patients who received placebo (hazard ratio 0.99, 95% confidence interval 0.982 to 0.998, p = 0.01). However, no association was noted between creatinine clearance and the incidence of adverse events among patients who received fluvastatin (hazard ratio 1.0, 95% confidence interval 0.99 to 1.0, p = 0.63). No further deterioration in creatinine clearance was observed during follow-up, regardless of baseline renal function or allocated treatment. Occurrence of adverse events was not related to changes in renal function during follow-up. Fluvastatin therapy markedly decreased the risk of coronary atherosclerotic events after percutaneous intervention in patients who had lower values of creatinine clearance at baseline. The benefit of fluvastatin was unrelated to any effect on renal function.     

Complementary role of thallium-201 scintigraphy to predischarge exercise electrocardiography for patients stratification after a first myocardial infarction

The value of a predischarge exercise test combined with thallium-201 myocardial scintigraphy in detecting patients with severe multivessel disease (MVD) was studied in 58 consecutive patients discharged after a first acute myocardial infarction. Twelve electrocardiographic, clinical and scintigraphic variables were analysed. Angiography at one month revealed MVD (greater than 70% narrowing in vessels unrelated to infarction) in 26 patients (45%). ST segment depression of 1mm or greater, thallium defects in multiple vascular distributions (MVTL), and reversible thallium defects in a vascular distribution different from the infarct related vessel predicted patients at risk for MVD (predictive value respectively of 68%, 65% and 75%). The other variables were not significantly associated with the presence of MVD. Only ST segment depression and thallium defects in multiple vascular distributions emerged as independent predictors of MVD. Their combination yielded a 77% sensitivity and a 59% specificity for MVD. Combination of thallium imaging with the predischarge exercise ECG significantly improved the stratification provided by the exercise test alone (P less than 0.05). A positive thallium scan (MVTl defects) associated with a positive ECG (ST depression) carried a risk for MVD of 80% in the population studied. When both tests were negative, MVD was infrequent (risk 22%). Because improvement in the stratification of patients is not as clear as expected from studies performed at a later stage, it appears that exercise thallium scintigraphy at a submaximal level one or two weeks after infarction does not provide optimal information. Predischarge exercise thallium-201 scintigraphy, however, is superior to an exercise tolerance test alone in separating patients into those with high and low risk of MVD.     

Combined treatment of liver failure and hepatorenal syndrome with orthotopic liver transplantation.

Hepatorenal syndrome (HRS) is a severe complication of liver failure with high mortality. The pathogenesis of this reversible functional renal failure is not yet clearly understood. Diagnosis is based upon the association of clinical and biological criteria. A patient was admitted to our institution for severe liver failure secondary to an exacerbation of cirrhosis, where he developed a fulminant hepatorenal syndrome. Both, the renal and hepatic failure were successfully treated by orthotopic liver transplantation. Special attention was paid to the immunosuppressive treatment with Cyclosporine whose use, we believe, should be delayed until function has partially recovered.     

Lack of activity of amphotericin B in systemic murine fusarial infection.

Systemic fusarial infections have emerged as a significant cause of mortality in cancer patients. Yet, little is known about the management of these infections. The in vivo antifungal activity of amphotericin B in CF1 mice with disseminated fusarial infections was studied. Two pathogenic strains of Fusarium solani were used. Intraperitoneal administration of amphotericin B in daily doses of 0.5, 1, and 2 mg/kg for less than or equal to 10 days did not prolong survival of treated animals. Clearance of F. solani from kidneys was similar in mice treated with 1 mg/kg per day of amphotericin B and in untreated animals. These results are in agreement with the known in vitro and in vivo resistance of Fusarium species to amphotericin B.     

Aminoglutethimide and glutethimide: effects on 18-hydroxycorticosterone biosynthesis by human and sheep adrenals in vitro.

The conversion of [1,2-3H]corticosterone to 18-hydroxycorticosterone in vitro was studied on human and animal adrenal tissue homogenates. Human adrenals were surgically resected from a patient with Cushing's disease. Sheep adrenal homogenates were prepared from the pooled glands of 20 animals. Incubations supplemented with a NADPH generating system were performed in order to evaluate the effect of aminoglutethimide and its closely related compound glutethimide on corticosterone 18-hydroxylation in vitro. Increasing concentrations of the two drugs were assayed on both human and animal adrenal homogenates. Aminoglutethimide was clearly found to inhibit corticosterone 18-hydroxylation in sheep adrenal homogenates as a 72.6% inhibition occurred in the presence of only 0.2 mumole of the drug. Inhibition reached 91.1% in the presence of 0.5 mumole aminoglutethimide. When added to the human incubated adrenal, a 59.4% inhibition occurred in the presence of 0.5 mumole aminoglutethimide. Glutethimide, a sedative of wide clinical usage, was also found to inhibit corticosterone 18-hydroxylation but the inhibitory effect occurred only in the presence of much higher concentrations. In fact, 5.0 mumoles were necessary to obtain a 43.9% inhibition of 18-hydroxycorticosterone synthesis. This study clearly demonstrates the marked inhibitory effect of aminoglutethimide on corticosterone 18-hydroxylation. Glutethimide, to a lesser extent, also inhibits 18-hydroxycorticosterone synthesis.     

Short- and long-term prognostic importance of complete bundle-branch block complicating acute myocardial infarction

Among 1013 consecutive patients with acute myocardial infarction (AMI), 104 (10%) developed complete bundle-branch block (BBB). The clinical characteristics and the short- and long-term prognosis were similar in the 53 patients with right and the 51 patients with left BBB. Compared to the 909 patients without this conduction disturbance, these 104 patients were older (64 +/- 9 vs. 58 +/- 10 years, p less than 0.001), more frequently women (26 vs. 17%, p less than 0.05), had a larger infarct (peak CK 1672 +/- 1124 vs. 1356 +/- 1089 IU/l, p less than 0.001), more frequently anterior (60 vs. 37%, p less than 0.001). They had a higher incidence of Killip class greater than 1 (63 vs. 38%, p less than 0.001), pericarditis (40 vs. 23%, p less than 0.001), atrial fibrillation or flutter (22 vs. 12%, p less than 0.01), ventricular fibrillation (15 vs. 9%, p less than 0.05), and atrioventricular block (23 vs. 11%, p less than 0.001). Both hospital mortality (32 vs 10%, p less than 0.001) and 3-year posthospital mortality (37 vs. 18%, p less than 0.001) were much higher among patients with complete BBB. Transient BBB had the same deleterious prognosis as BBB persistent at discharge (mortality 33 vs. 39%, NS). The prognostic importance of BBB was more prominent during the first 6 months after infarction (mortality between 6 and 36 months: 18% with BBB vs. 11% without BBB, NS).     

Interaction of a Monoclonal Antibody to Glycoprotein IV (CD36) with Human Platelets and its Effect on Platelet Function

FA6-152, a monoclonal antibody to platelet membrane glycoprotein IV (CP IV), was used to quantify the expression of this glycoprotein on platelets, as well as to evaluate its role in platelet aggregation. On resting platelets, 19 400 ± 7700 molecules of the (125)I-labelled IgC could bind per platelet (n = 20). Binding was not modified following stimulation of the platelets with ADP (10 μmol/l) or thrombin (0.1 U/ml). Fab fragments prepared from the antibody by papain digestion also bound to the platelet surface in a saturable manner. Both the intact IgC and its Fab fragments were found to inhibit platelet aggregation and secretion induced by ADP or collagen in platelet-rich plasma and by thrombin in platelet suspensions. Under nonstirred conditions, whereby the release reaction was only minimally affected, the antibody markedly inhibited thrombin-induced surface expression of α-granule thrombospondin (TSP), whereas it did not alter the concomitant expression of α-granule fibrinogen. In addition, electron microscopy revealed a predominant distribution of TSP and T;P IV on pseudopodia and between adherent cells on thrombin-stimulated platelets. These findings thus support the hypothesis that the interaction of TSP with GP IV on the platelet surface is required for an optimal platelet aggregation/secretion process to occur.     

A defect of platelet aggregation associated with an abnormal distribution of glycoprotein IIb-IIIa complexes within the platelet: the cause of a lifelong bleeding disorder.

A young Italian man (A.P.) has a lifelong history of bleeding from gums and mucocutaneous tissue. Electron microscopy showed a wide diversity of platelet size including giant forms. In citrated platelet-rich plasma (PRP), platelet aggregation induced by adenosine diphosphate (ADP) and other agonists was much reduced. Both secretion and clot retraction were normal. The aggregation of washed platelets with ADP was improved but remained subnormal, as was aggregation with collagen and thrombin. Fibrinogen-binding was analyzed by flow cytometry using platelets in whole blood or PRP and was markedly decreased. Crossed immunoelectrophoresis of Triton X-100 extracts of (A.P.) platelets showed that GP IIb-IIIa levels were 40% to 50% of normal. Glycoprotein (GP) IIb and GP IIIa were of usual migration in sodium dodecyl sulfate-polyacrylamide gel electrophoresis, but their labeling was much reduced during lactoperoxidase-catalyzed iodination. Binding to (A.P.) platelets of four different 125I-labeled monoclonal antibodies to GP IIb-IIIa complexes was reduced to 12% to 20% of normal levels. However, when the patient's platelets were stimulated with alpha-thrombin, monoclonal antibody binding showed the same increase (approximately 20,000 sites) as normal platelets. Both flow cytometry and immunocytochemical studies showed that the distribution of residual surface GP IIb-IIIa within the total (A.P.) platelet population was heterogeneous and not related to platelet size. Staining of ultrathin sections confirmed the presence of an internal pool of GP IIb-IIIa. Monoclonal antibodies to other membrane glycoproteins bound normally to (A.P.) platelets. The patient has a selective deficiency of the surface pool of GP IIb-IIIa complexes that is manifested clinically by a mild Glanzmann's thrombasthenia-like syndrome.