Fibrinolysis in left-sided mechanical prosthetic valve thrombosis with high INR.

BACKGROUND: A significant number of patients with prosthetic valve thrombosis have a prothrombin time international normalised ratio in the therapeutic range at presentation. Surgery may not be possible in many patients and traditionally a high international normalised ratio is considered a relative contraindication for fibrinolysis. METHODS: We conducted an observational study in patients with left-sided obstructive prosthetic valve thrombosis with international normalised ratio at or above the therapeutic range at presentation who received fibrinolysis. The fibrinolytic regimens, timing of initiation, success of fibrinolysis, risk of major and minor bleeding and ischaemic stroke were evaluated in the study. RESULTS: Of 30 patients included in the study 70% received immediate fibrinolysis and in 30% it was delayed. The majority of patients (90%) presented with New York Heart Association class III/IV symptoms. The mean international normalised ratio at fibrinolysis was 3.04 ± 0.70 in the immediate group and 2.42 ± 0.89 in the delayed group. Haemodynamically stable patients who had delayed initiation of fibrinolysis had a trend towards less bleeding without an increase in mortality. The rates of intracranial haemorrhage (0% vs. 7.7%), minor bleeding (12.5% vs. 25.1%) and ischaemic stroke (0% vs. 30.7%) were lower in patients who received low dose infusion compared to a conventional dose. CONCLUSIONS: Fibrinolysis can be considered in patients with prosthetic valve thrombosis with high international normalised ratio at presentation. For haemodynamically stable patients, delayed initiation of fibrinolysis is associated with a marginally lower bleeding risk without an increase in mortality. Low dose infusion may be considered over a conventional dose as it is associated with a lower incidence of ischaemic stroke and a good rate of valve function restoration with a trend towards less bleeding.

Thrombolysis with reteplase in acute pulmonary embolism.

OBJECTIVE: Reteplase (recombinant plasminogen activator) is a mutant of alteplase. It has a longer half-life than its parent molecule and has shown better vessel patency rates in acute myocardial infarction. In this study, we analyzed the efficacy and safety of reteplase in acute pulmonary embolism (PE). METHODS: This observational study included patients with high- and intermediate-risk acute PE, presenting within 14 days of symptom onset. The patients were treated with reteplase, which was given in two bolus doses of 10 U each, 30 min apart, along with intravenous heparin. Patients with hemodynamic compromise (high-risk or massive PE) and normotensive patients with evidence of right ventricular (RV) dysfunction (intermediate-risk or submassive PE) on echocardiography or computed tomography were included in the study. The efficacy outcomes assessed were in-hospital death and improvement of RV function by echocardiography. The safety outcomes were major bleeding, minor bleeding, and ischemic or hemorrhagic stroke during hospitalization. RESULTS: Of the 40 patients included, 25% were classified as high risk with hemodynamic compromise and 75% were classified as intermediate risk. RV dysfunction was present in all the patients (100%). Concomitant lower extremity deep vein thrombosis was present in 55% of the patients. The mortality rate was 5%. There was significant improvement in RV function and reduction in pulmonary artery systolic pressure and tricuspid regurgitation severity. There was no major bleeding event or stroke, and 7.5% patients had minor extracranial bleeding. CONCLUSIONS: Double-bolus reteplase given with heparin is effective in the treatment of high- and intermediate-risk PE, with minimal risk of bleeding.

Trihexyphenidyl Misuse in Delusional Disorder.

Trihexyphenidyl is an anticholinergic medication that is routinely used for the management of extrapyramidal symptoms in patients who receive antipsychotic medications. Trihexyphenidyl has been reported to be abused by some patients, who start to take it in increasing doses and tend to report a sensation of relaxation or pleasure with this medication. Hence, whether trihexyphenidyl should be considered a psychoactive substance and whether nonprescription misuse of this medication should be considered under the purview of substance use disorders need further clarity. We present here two cases of trihexyphenidyl misuse which developed in the context of persistent delusional disorders and highlight the challenges in diagnosis in such a situation.

Physical comorbidity in schizophrenia & its correlates.

The presence of common physical comorbidities, their demographic and clinical correlates and impact on functioning was assessed in 100 patients with schizophrenia. The patients had a mean age of 35.12±10.7 yr with mean duration of illness of 8.3±0.58 years. Seventy per cent were detected to have a comorbid physical condition. Common conditions included hypertension (21%), diabetes mellitus (15%) and anaemia (12%). Increasing age, being female, being married, longer duration of illness and longer duration of treatment were associated with higher risk of having a comorbid physical illness. Further studies need to be done with a large sample to confirm these findings.

Isolated pulmonary valve endocarditis in a patient with aplastic anaemia.

A 42-year-old female patient of aplastic anaemia on maintenance blood transfusion presented with a 3-week history of fever, cough, dyspnoea and pedal oedema. Upon examination she  was found to have severe pallor, temperature of 101°F, tachycardia, bilateral pitting pedal oedema, raised jugular venous pressure, ejection systolic murmur (grade 2/6) in pulmonary area and petechiae over extensor aspect of both lower limbs. Blood investigations revealed low haemoglobin, thrombocytopaenia and mild increase in serum creatine. Chest x-ray was normal. Initial 2D trans thoracic echocardiography performed after hospital admission was normal. Antibiotics were started empirically to treat a possible underlying infection. Subsequently, three sets of blood cultures grew Enterococcus faecalis. Upon searching for the source, repeat echocardiograph done showed 2×0.5 cm vegetation on both pulmonary leaflets with severe pulmonary regurgitation, all other valves were free of vegetations. She was treated with intravenous antibiotics for the endocarditis and improved.

Alcohol-induced deterioration in primary antioxidant and glutathione family enzymes reversed by exercise training in the liver of old rats.

Chronic alcohol consumption causes severe hepatic oxidative damage, particularly to old subjects by decreasing various antioxidant enzymes. In this study, we test the hypothesis that exercise training can protect the aging liver against alcohol-induced oxidative damage. Two different age groups of Wistar albino rats (3 months young, n=24; 18 months old, n=24) were evenly divided into four groups: control (Con), exercise trained (Tr, 23 m/min 30 min/day, 5 days/week for 2 months), ethanol drinking/treated (Et, 2.0 g/kg b.w. orally), and exercise training plus ethanol drinking/treated (Tr+Et). We found significantly (P<.001) lowered hepatic antioxidant enzymes including superoxide dismutase, catalase, selenium (Se)-dependent glutathione peroxidase (Se-GSH-Px), Se-non-dependent glutathione peroxidase (non-Se-GSH-Px), glutathione reductase, and glutathione S-transferase activities in aged rats compared with young. Age-related decrease in antioxidant enzyme status was further exacerbated with ethanol drinking, which indicates liver in aged rats is more susceptible to oxidative damage because of decreased free radical scavenging system in aged/old ethanol-drinking rats. However, the decrease in liver antioxidant enzymes status with ethanol consumption was ameliorated by 2 months exercise training in old and young rats. These results demonstrate that age-associated decrease in hepatic free radical scavenging system exacerbated by ethanol drinking. For the first time, we found that this deterioration was significantly reversed by exercise training in aging liver, thus protects against alcohol-induced oxidative damage.

Effect of exercise training on ethanol-induced oxidative damage in aged rats.

It is well known that lipid peroxidation increases with age, and alcohol drinking further exacerbates this damage. The present study determined the effect of regular exercise training on alcohol-induced oxidative damage and antioxidant status in the liver of aged animals. The age-matched Wistar albino rats (3 months young, n=24; 18 months old, n=24) were evenly divided into four groups: control (C), exercise trained (Ex), ethanol drinking (Et), and exercise plus ethanol drinking (Ex+Et). With ethanol drinking, hepatic malondialdehyde (MDA) level was significantly elevated above control (P<.001), whereas glutathione (GSH) and ascorbic acid (vitamin C) contents were significantly decreased below control. These changes were found to be greater in the aged rats than those of the young rats. For both age groups, exercise training significantly reversed the increase in MDA and decreases in GSH and ascorbic acid induced by ethanol drinking. The present study showed that ethanol-induced deterioration in lipid peroxidation and reduction in antioxidant status in the liver were exacerbated with age. Here, we found that exercise training significantly reversed the adverse conditions that were caused by ethanol in aged rats.

Myocardial antioxidant status and oxidative stress after combined action of exercise training and ethanol in two different age groups of male albino rats.

The interaction of exercise training and ethanol on the myocardial antioxidant enzymes and the oxidative stress markers was investigated in the Wistar strain male albino rats. We also tested the interactive effects of exercise training and ethanol on the age-associated free radical production and antioxidant defense system. We found a significant decrease (p<0.05) in the activity levels of superoxide dismutase (SOD) and catalase (CAT) in the myocardium of old rats when compared to young rats by 26% and 58%, respectively, suggesting the onset of age-dependent decrease in the myocardial antioxidant enzyme system. In contrast to the decreased antioxidant enzyme activity, xanthine oxidase (XOD) and lipid peroxidation (LPO) levels were elevated, suggesting the age-induced oxidative stress. Exercise training significantly (p < 0.05) elevated the activities of SOD, CAT, XOD and LPO levels in both the age groups of animals. Ethanol consumption significantly lowered the SOD and CAT activities in both the age groups, whereas a significant increase was observed in the XOD and LPO levels. In contrast, the combination of exercise training plus ethanol lowered XOD and LPO levels in both the age groups of rats compared to ethanol treated rats. A significant (p < 0.05) increase in the activities of SOD and CAT was reported in the rats treated with the combination of exercise training plus ethanol. This increase was more pronounced in the younger rats than the older rats. The findings of the present investigation on the potential role of antioxidant enzymes to counter the ethanol-induced pro-oxidants showed an increase with the interaction of exercise training. With age, a decrease in the antioxidant enzyme capacity was observed. This reveals that the old age rats were more affected to the pro-oxidants when compared to the young age rats. In conclusion it is demonstrated that two months treadmill endurance exercise training is beneficial to both young and old rats in improving antioxidant defense to challenge the oxidative stress in the myocardial tissue and thereby successfully countering the free radical production due to ethanol intoxication.

Hepatic glutathione mediated antioxidant system in ethanol treated rats: Decline with age.

Alcoholism is a pervasive problem. The aim of the present study was to clarify the effect of ethanol on the hepatic glutathione antioxidant system in young and elderly rats. Male albino Wistar rats of two age groups (3 months and 18 months old) were divided into two experimental groups. The first group of untreated rats served as controls (C; young n=6 and old n=6) and second group received ethanol (Et; young n=6 and old n=6) 2g of ethanol/kg b.w. for 2 months. After the completion of last treatment glutathione (GSH) and antioxidant enzymes glutathione peroxidase (GSH-Px), glutathione reductase (GR) and glutathione-S-transferase (GST) were determined. All these parameters including GST were remarkably decreased in the liver with advancing of age. The ethanol treatment decreased GSH, GSH-Px and GR, whereas, GST was increased in both age groups. The decrease of hepatic antioxidant status with ethanol and aging may be due to over production of free radicals. The changes of parameters studied were greater in the older than in the young rats. In conclusion, ethanol stress exhibited age dependent response on glutathione mediated antioxidant system in the liver.