Informant ratings of cognitive decline of elderly people: relationship to longitudinal change on cognitive tests

Formal assessment of cognitive decline with cognitive tests can be difficult, requiring either two measurement points or a comparison of 'hold' with 'don't hold' tests. Informant-based assessment provides an alternative approach because informants can adopt a longitudinal perspective and directly rate cognitive change. A study was carried out to assess the validity of informant ratings collected by means of the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). A community sample of 500 subjects aged 74 or over underwent four cognitive tests on two occasions 3½ years apart. On the second occasion, informants filled out the IQCODE. Subjects rated as having moderate or severe decline were found to have greater change on the cognitive tests. These findings support the validity of informant ratings of cognitive decline.     

The effect of azathioprine (Imuran) on the kinetics of monocytes and macrophages during the normal steady state and an acute inflammatory reaction

The effect of azathioprine on the kinetics of peripheral blood monocytes and peritoneal macrophages was studied in normal mice and in mice in which an inflammatory reaction was provoked. Two dosage levels were used: a high dose of 200mg/kg which is the maximum tolerated daily dose in mice, and low dose of 3 mg/kg which is about equivalent to a nontoxic, immunosuppressive, anti-inflammatory dose in man. The number of peripheral blood monocytes decreases gradually during azathioprine treatment of normal mice, the extent and duration being dependent on the dose and duration of administered over a period of 9 days gives an almost complete reduction, and a low dose (3 mg/kg) given for the same period results in a reduction of about 50%. This effect seems to be reversible, because when treatment is stopped the number of monocytes starts to increase 24-48 hr later. The number of peritoneal macrophages is only affected when a high dose (200 mg/kg) is given over a long period; a low dose has virtually no effect. In mice in which an inflammatory reaction was prevoked in the peritoneal cavity, the normally occurring increase in the numbers of both peripheral blood monocytes and peritoneal macrophages was suppressed, the extent being dependent on the dose of azathioprine administered. Labeling studies with 3H-thymidine indicated that the reduction of peripheral blood monocytes and peritoneal macrophages in the inflammatory exudate is due to a diminished monocyte production.     

Mitral valve surgery in the presence of pulmonary hypertension.

Mitral valve surgery was performed in 59 patients with severe pulmonary hypertension (average systolic pulmonary artery pressure 77.1 +/- 18.6 mmHg; range 50-115 mmHg) between 1983 and 1990. Thirty-eight patients had been subjected to mitral valve replacement, 16 patients both mitral and aortic valve replacement, and 5 patients had open mitral commissurotomy, with an operative (30 day) mortality of 5.0%. These 3 deaths happened during the early postoperative period. Survivors were followed up for a period ranging from 6 months to 7 years with a mean of 36 months. Four late deaths (7.1%) occurred in patients with valve replacement. Actuarial survival was 93 +/- 3% at 5 years, and 90.7 +/- 4.4% at 7 years. Right ventricular catheterization was performed on 14 patients a mean of 38 months following operation. Systolic pulmonary artery pressure had decreased from a mean of 77.1 +/- 18.6 to 39.7 +/- 14.0 mmHg (p less than 0.001) and 90% of the survivors were in New York Heart Association Class 1 or II compared to 23.7% preoperatively. The clinical and hemodynamic findings in this series suggest that severe pulmonary hypertension is not a contraindication, and pulmonary hypertension decreases significantly after mitral valve surgery.     

Melatonin protects against gentamicin-induced nephrotoxicity in rats

Acute renal failure is a major complication of gentamicin (GEN), which is widely used in the treatment of gram-negative infections. A large body of in vitro and in vivo evidence indicates that reactive oxygen metabolites (or free radicals) are important mediators of gentamicin nephrotoxicity. In this study we investigated the role of free radicals in gentamicin-induced nephrotoxicity and whether melatonin, a potent antioxidant could prevent it. For this purpose female Sprague-Dawley rats were given intraperitoneally either gentamicin sulphate (40 mg/kg), melatonin (10 mg/kg), gentamicin plus melatonin or vehicle (control) twice daily for 14 days. The rats were decapitated on the 15th day and kidneys were removed. Blood urea nitrogen (BUN) and creatinine levels were measured in the blood and malondialdehyde (MDA) and glutathione (GSH) levels, protein oxidation (PO) and myeloperoxidase (MPO) activity were determined in the renal tissue. Gentamicin was observed to cause a severe nephrotoxicity which was evidenced by an elevation of BUN and creatinine levels. The significant decrease in GSH and increases in MDA levels, PO and MPO activity indicated that GEN-induced tissue injury was mediated through oxidative reactions. On the other hand simultaneous melatonin administration protected kidney tissue against the oxidative damage and the nephrotoxic effect caused by GEN treatment.     

Fc gamma receptor II (CD32) on malignant B cells influences modulation induced by anti-CD19 monoclonal antibody

Antigenic modulation is one of many factors determining the effectiveness of monoclonal antibody (MoAb)-mediated therapy. To select the isotype of a CD19 MoAb most suitable for radioimmunotherapy of patients with B-cell malignancies, we studied the influence of MoAb isotype on modulation, after binding of the MoAb to different cell-line cells. The CD19-IgG1 MoAb was found to induce modulation of CD19 antigens on Daudi cell line cells more rapidly than did its IgG2a switch variant. We provide evidence that this difference in modulation rate is caused by the expression of Fc gamma receptor II (Fc gamma RII) on these cells. Experiments aimed at elucidating the mechanism of Fc gamma RII involvement in modulation induction by CD19-IgG1 showed that Fc gamma RII did not comodulate with CD19 MoAbs. However, cocrosslinking of CD19 and Fc gamma RII with CD19-IgG1 MoAb resulted in enhanced calcium mobilization in Daudi cells. This increased signal induction accompanies the enhanced capping and subsequent modulation of CD19 antigens. Because Fc gamma RII is expressed in varying densities on malignant B cells in all differentiation stages, our results have implications for the MoAb isotype most suitable for use in MoAb-based therapy of patients with B-cell malignancies.     

The Evaluation of Left Ventricular Functions with Tissue Doppler Echocardiography in Adults with Celiac Disease

Background/Aim:

The aim of this study was to investigate the effects of celiac disease on cardiac functions using tissue Doppler echocardiography (TDE).

Patients and Methods:

The study included 30 patients with celiac disease (CD) and 30 healthy volunteers. Echocardiographic examinations were assessed by conventional echocardiography and tissue Doppler imaging. The peak systolic velocity (S^''m), early diastolic myocardial peak velocity (E^''m), late diastolic myocardial peak velocity (A^''m), E^''m/A^''m ratio, myocardial precontraction time (PCT^''m), myocardial contraction time (CT^''m), and myocardial isovolumetric relaxation time (IVRT^''m), E to E^''m ratio were measured.

Results:

In pulsed wave Doppler echocardiography, mitral late diastolic flow (A) velocity and E to E^''m ratio were significantly higher (P = 0.02 and P = 0,017), E/A ratio was significantly lower (P = 0.008) and IVRT was significantly prolonged (P = 0.014) in patients with CD. In TDE, S^''m, E^''m, and E^''m/A^''m ratio were significantly lower, IVRT^''m was longer (P = 0.009) from septal mitral annulus and S^''m, E^''m, E^''m/A^''m ratio were significantly lower, PCT^''m, PCT/ET ratio, IVRT^''m were longer, and MPI was higher from lateral mitral annulus in celiac group than controls.

Conclusion:

Our study confirms that patients with CD have impaired diastolic function. More importantly, we also demonstrated an impairment of myocardial systolic function in patients with CD by TDE. We recommend using TDE in addition to conventional echocardiography parameters for the cardiovascular risk assessment of patients with CD.     

Levosimendan has an inhibitory effect on platelet function

Levosimendan enhances cardiac contractility by increasing myocyte sensitivity to calcium, and induces vasodilatation. Although studies have evaluated the efficacy of levosimendan in heart failure, it is not clear whether it might produce functional influence on platelet response. In this study, the effect of levosimendan on platelet aggregation was investigated. Platelet function tests were performed in 12 healthy male volunteers. Three concentrations of levosimendan solution were prepared that would result in 10, 25, and 45 ng/ml levosimendan concentrations in the blood similar to that observed after clinical therapeutic intravenous application of 0.05-0.1 microg/kg/min. Each concentration of levosimendan solution and a control diluent without levosimendan were incubated with whole blood at 37 degrees C. After incubation for 15 min, aggregation responses were evaluated with adenosine diphosphate (ADP) (5 and 10 microM) and collagen (2 and 5 microg/ml) in platelet-rich plasma. Preincubation with all dilutions of levosimendan inhibited aggregation of platelets induced by ADP and collagen significantly. Levosimendan also inhibited significantly the secondary wave of platelet aggregation induced by ADP. The results showed that there was a relationship between levosimendan concentration and inhibition of platelet aggregation. In conclusion, this study with an in vitro model showed that levosimendan had a significant inhibitory effect on platelets in clinically relevant doses.     

Impact of Anti-Aggregant,Anti-Coagulant and Non-Steroidal Anti-Inflammatory Drugs on Hospital Outcomes in Patients with Peptic Ulcer Bleeding

Background/Aims:

There are a limited number of studies including the impact of antiplatelet drugs use on hospital outcomes for nonvariceal upper gastrointestinal bleeding. The aim of this study was to determine the effect of anti-aggregant, anti-coagulant and non-steroidal anti-inflammatory drugs upon hospital outcomes in patients with peptic ulcer bleeding.

Materials and Methods:

The patients under treatment with antiaggregant, anticoagulant or non-steroidal anti-inflammatory drugs were categorized as exposed group (n = 118) and the patients who were not taking any of these drugs were categorized as non-exposed group (n = 81). We analyzed the data of drug intake, comorbid disease, blood transfusion, duration of hospital stay, Blatchford/total Rockall score and diagnosis of patients.

Results:

In total, 199 patients were included. Of these 59.3% (exposed group) were taking drugs. The patients in exposed group were significantly older than those in non-exposed group (62.9 ± 17.3 years; 55.5 ± 19.3 years, P = 0.005, respectively). Mean number of red blood cell units transfused (2.21 ± 1.51; 2.05 ± 1.87, P = 0.5), duration of hospital stay (3.46 ± 2.80 days; 3.20 ± 2.30 days, P = 0.532) and gastric ulcer rate (33% vs 23.4%, P = 0.172) were higher in exposed group than in non-exposed group but the differences were not statistically significant. Total Rockall and Blatchford scores of the patients were significantly higher in exposed group than in non-exposed group (3.46 ± 1.72 vs 2.94 ± 1.87, P = 0.045; 10.29 ± 3.15 vs 9.31 ± 3.40, P = 0.038).

Conclusıon:

Our study has shown that anticoagulants, antiaggregants and nonsteroidal anti-inflammatory drugs do not effect duration of hospital stay, red blood cell transfusion requirement and rebleeding for peptic ulcer bleeding.