A comparison of three months of anticoagulation with extended anticoagulation for a first episode of idiopathic venous thromboembolism

BACKGROUND: Patients who have a first episode of venous thromboembolism in the absence of known risk factors for thrombosis (idiopathic thrombosis) are often treated with anticoagulant therapy for three months. Such patients may benefit from longer treatment, however, because they appear to have an increased risk of recurrence after anticoagulant therapy is stopped. METHODS: In this double-blind study, we randomly assigned patients who had completed 3 months of anticoagulant therapy for a first episode of idiopathic venous thromboembolism to continue receiving warfarin, with the dose adjusted to achieve an international normalized ratio of 2.0 to 3.0, or to receive placebo for a further 24 months. Our goal was to determine the effects of extended anticoagulant therapy on rates of recurrent symptomatic venous thromboembolism and bleeding. RESULTS: A prespecified interim analysis of efficacy led to the early termination of the trial after 162 patients had been enrolled and followed for an average of 10 months. Of 83 patients assigned to continue to receive placebo, 17 had a recurrent episode of venous thromboembolism (27.4 percent per patient-year), as compared with 1 of 79 patients assigned to receive warfarin (1.3 percent per patient-year, P<0.001). Warfarin resulted in a 95 percent reduction in the risk of recurrent venous thromboembolism (95 percent confidence interval, 63 to 99 percent). Three patients assigned to the warfarin group had nonfatal major bleeding (two had gastrointestinal bleeding and one genitourinary bleeding), as compared with none of those assigned to the placebo group (3.8 vs. 0 percent per patient-year, P=0.09). CONCLUSIONS: Patients with a first episode of idiopathic venous thromboembolism should be treated with anticoagulant agents for longer than three months.     

Short-term therapy for recurrent abortion using intravenous immunoglobulins: results of a double-blind placebo-controlled Italian study

It is still unclear whether i.v. immunoglobulins (Ig) can facilitate the reproductive prognosis of women who have suffered recurrent pregnancy loss. We report the results of a multicentre placebo- controlled study on the effect of Ig administration on pregnancy outcome in 46 women who had suffered at least three recurrent miscarriages. All were screened to exclude chromosomal or Mullerian abnormalities, the presence of antinuclear antibodies, lupus anticoagulant (LA) or elevated titres of anticardiolipin antibodies which may have revealed an underlying autoimmune problem. To avoid a selection bias towards ongoing pregnancies, i.v. Ig or placebo were administered between weeks 5 and 7 of gestation for 2 consecutive days as soon as each woman knew she was pregnant and before embryonic heart activity could be detected. A further infusion was administered at week 8 when ultrasonography confirmed an ongoing embryonic development. In all, 68% of the women who received Ig went to term versus 79% of those who received a placebo (not significant), with no significant differences in the pregnancy course or the perinatal outcome. These results suggest either that women with recurrent miscarriages who have no recognized cause of pregnancy loss have a good reproductive prognosis without any treatment or that the emotional care associated with the administration of a placebo can indirectly facilitate the progression of pregnancy.      

The ileoanal J pouch: radiographic evaluation

Endorectal ileoanal pull-through offers an attractive alternative to proctocolectomy and ileostomy for patients with ulcerative colitis, Gardner syndrome, and familial polyposis. To our knowledge, a careful radiographic analysis of the ileum, ileal pouch, and ileoanal anastomosis after ileoanal pull-through has not been reported. Thirty-two patients with ulcerative colitis, Gardner syndrome, and familial polyposis underwent colectomy, mucosal proctectomy, and endorectal ileoanal pull-through of a 15-cm ileal "J" pouch and loop ileostomy. Twenty-five (78%) of 32 of all the pouches radiographically demonstrated spiral folds extending from the middle of the pouch to the pectinate line. Other radiographic features included a mesenteric mass effect, pseudopolyps, and a central lucency that indicated intrapouch sutures. Radiographs provide useful information in the postoperative management of the ileal pull-through.     

Black tea and mammary gland carcinogenesis by 7,12- dimethylbenz[a]anthracene in rats fed control or high fat diets

Epidemiological studies suggest that tea may reduce cancer risk, and in laboratory rodents, chemopreventive effects of tea or purified extracts of tea have been demonstrated in lung, gastrointestinal tract and skin. There is some evidence of chemoprevention by tea in the mammary gland, but the data are not conclusive. In order to evaluate more fully the possible influence of black tea on 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary gland tumors in the female S-D (Sprague-Dawley) rat, three large studies were performed: experiment 1, tumorigenesis in rats fed AIN-76A diet and given 25 mg/kg DMBA and 1.25 or 2.5% whole tea extract or water to drink; experiment 2, tumorigenesis in rats given 15 mg/kg DMBA and the same diet and fluids as in experiment 1; experiment 3, tumorigenesis in rats fed control or HF (high fat, corn oil) diet and given 15 mg/kg DMBA and 2% tea or water to drink. Tea was given throughout the experiment; DMBA was given by gastric gavage at 8 weeks of age. There was no consistent effect of tea on tumorigenesis in rats fed AIN-76A diet; there was, however, evidence in experiment 3 of a reduction of tumorigenesis by tea in rats fed the HF diet. In experiment 3, rats fed the HF diet and given water showed the expected increase in tumor burden (number and weight) compared with rats fed control diet. However, rats fed the HF diet and given 2% tea showed no increase in tumor burden; their tumor burden was significantly lower than in rats fed the HF diet and given water (P < 0.01) and was not different from rats fed control diet and given water or tea. In addition, in experiment 3, the number of malignant tumors per tumor- bearing rat was increased by the HF diet in water-drinking rats (P < 0.01) but not in tea-drinking rats. Therefore, it appears that tea partially blocked the promotion of DMBA-induced mammary tumorigenesis by the HF diet.      

Impact of COVID-19 lockdown on sleep quality of pharmacy students in UiTM Puncak Alam

Due to the COVID-19 pandemic, the closure of educational institutions was executed during the period of lockdown. This subsequently led to alterations in daily routines and emotional distress, particularly among university students, affecting their sleep quality resulting in disturbance of immune functioning and mood regulation. Hence, the present study aimed to measure students' sleep quality during the first few months of the lockdown period. This study is a cross-sectional, single-centred survey that was done by distributed electronic questionnaire. The e-questionnaire was divided into 4 sections that assessed socio-demographic characteristics, sleep quality, psychological state and engagement in physical activity. Exactly 248 valid responses were received, 82 % female students. Students with poor sleep quality were three times greater than those with good sleep quality. No association were found between physical activity and sleep quality. However, a significant positive relationship between sleep quality and psychological state was observed (p < 0.01). In conclusion, this study suggests that the majority of pharmacy students in UiTM Puncak Alam are poor sleepers and psychological distress negatively affects sleep quality but, is mainly due to stress. Thus, interventions such as stress management programs and mental health support can be taken by the faculty's management to overcome this problem.     

Coronary patency, infarct size and left ventricular function after thrombolytic therapy for acute myocardial infarction: results from the tissue plasminogen activator: Toronto (TPAT) placebo-controlled trial. TPAT Study Group

Infarct size, left ventricular function and infarct-related coronary artery patency were examined in 108 patients who took part in a previously reported placebo-controlled trial of recombinant tissue-type plasminogen activator (rt-PA) in acute myocardial infarction. Coronary angiography was performed 17 +/- 0.8 h after initiation of treatment in 47 patients (group A) or at 10 days in 61 patients (group B). Both groups underwent radionuclide ventriculography 3.8 +/- 0.8 h and again on day 9 after treatment and quantitative thallium scintigraphy on day 8. In group A, the infarct-related artery was patent in 53%; these patients had a smaller global (15.1 +/- 2.5% vs. 25.7 +/- 4.7%, p = 0.029) and regional (14.7 +/- 2.5% vs. 24.1 +/- 4.7%, p = 0.044) fixed thallium defect than did those with an occluded artery. Infarct regional ejection fraction improved by 10.1 +/- 2.1% between early and late studies when the infarct-related artery was patent and by 4.8 +/- 1.4% if it was occluded (p = 0.048); changes in global and noninfarct regional ejection fraction were similar irrespective of perfusion status. Infarct regional ejection fraction and fixed thallium defect were inversely related only when the infarct-related artery was occluded (r = -0.83, p less than 0.0001). In group B, 10 day patency of the infarct-related artery was 67%; there was no difference in patency by treatment assignment or in left ventricular function or infarct size between patients with and without infarct-related artery patency. There was no evidence of an effect of rt-PA therapy beyond that expressed through coronary patency alone in either group A or group B.     

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.     

Granulocyte colony-stimulating factor administration to healthy volunteers: analysis of the immediate activating effects on circulating neutrophils

In four healthy volunteers, we analyzed in detail the immediate in vivo effects on circulating neutrophils of subcutaneous administration of 300 micrograms of granulocyte colony-stimulating factor (G-CSF). Neutrophil activation was assessed by measurement of degranulation. Mobilization of secretory vesicles was shown by a decrease in leukocyte alkaline phosphatase content of the circulating neutrophils. Furthermore, shortly postinjection, Fc gamma RIII was found to be upregulated from an intracellular pool that we identified by immunoelectron microscopy as secretory vesicles. Intravascular release of specific granules was shown by increased plasma levels of lactoferrin and by upregulation of the expression of CD66b and CD11b on circulating neutrophils. Moreover, measurement of fourfold elevated plasma levels of elastase, bound to its physiologic inhibitor alpha 1- antitrypsin, indicated mobilization of azurophil granules. However, no expression of CD63, a marker of azurophil granules, was observed on circulating neutrophils. G-CSF--induced mobilization of secretory vesicles and specific granules could be mimicked in whole blood cultures in vitro, in contrast to release of azurophil granules. Therefore, we postulate that the most activated neutrophils leave the circulation, as observed shortly postinjection, and undergo subsequent stimulation in the endothelial microenvironment, resulting in mobilization of azurophil granules. Our data demonstrate that G-CSF should be regarded as a potent immediate activator of neutrophils in vivo.