Gene/Protein Disease Symptom Drug Enzyme Compound
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 23,468 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fifteen Thai children, diagnosed with dengue hemorrhagic fever and admitted to the Children's Hospital in Bangkok, were studied. All cases were serologically proved to be secondary dengue infections. The clinical signs and symptoms in the first few days of the acute febrile phase were similar to those observed in cases with classical dengue fever, and included continuously high fever, headache, muscle pain, nausea, vomiting and abdominal pain, etc. In the laboratory findings we noted hypoalbuminemia and mild elevation of the GOT and GPT. The hemogram showed an increasing atypical lymphocyte count during the acute febrile period. Prolongations of the partial thromboplastin time and thrombin time were also found, especially in the severe shock cases. All patients had varying degrees of hepatomegaly and pleural effusion from their chest x-rays accompanied by a rapid increase in the hematocrit of more than 20% and a fall in the platelet count to less than 100000/microliters. During the plasma leakage period the patients easily developed shock, even leading to death, unless adequate fluid supplies were given. This is also the major pathophysiological difference between dengue hemorrhagic fever and classical dengue fever. Although some studies concerning the pathogenesis of dengue hemorrhagic fever have been reported, but the exact mechanisms need further investigation.
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PMID:[Clinical observation of 15 Thai children with dengue hemorrhagic fever]. 234 55

Carbetimer (carboxyimamidate) is a low molecular weight derivative of ethylene/maleic anhydride polymer. This compound has demonstrated antitumor activity against several animal models with a daily x 5 schedule appearing most effective. A phase I clinical study of the daily x 5 schedule repeated every 28 days was therefore performed. Forty-one evaluable patients received 66 evaluable cycles of Carbetimer at daily doses ranging from 100-11,000 mg/m2. Hypercalcemia was the dose limiting toxicity with both patients at the 11,000 mg/m2 daily dose level and one patient who received 6 cycles of drug at the 4200 mg/m2 dose level developing severe hypercalcemia not explained by the underlying malignancy. Mild nausea, concentration and rate dependent arm pain at the site of infusion, proteinuria, and coagulopathy were also seen. Calcium balance studies revealed hypercalciuria, suggesting increased mobilization of calcium rather than renal retention. In vitro coagulation studies revealed concentration dependent prolongation of the partial thromboplastin time and thrombin time. No complete or partial responses were seen. However mixed response or biochemical response (reduction in serum lactic dehydrogenase) were seen in 5 patients with melanoma or renal cancer. Due to unacceptable toxicity at the 11,000 mg/m2 daily dose level, Carbetimer 8500 mg/m2 is the recommended dose for a 5-day treatment schedule every 28 days. Special attention should be directed toward possible activity against melanoma and renal cancer.
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PMID:Phase I trial of a 5-day course of carbetimer. 238 16

Observations were made of 15 fatal and 35 nonfatal Crimean-Congo hemorrhagic fever (CCHF) infections diagnosed from February 1981 to March 1987 in Kimberly and Sandringham, Republic of South Africa. Following an incubation period of 2-9 days after exposure to infection, patients had a sudden onset of disease with fever, nausea, severe headache, and myalgia. Petechial rash and hemorrhagic signs such as epistaxis, hematemesis, and melena supervened on days 3-6 of illness. Deaths occurred on days 5-14 of illness. Patients with fatal infections had thrombocytopenia and markedly elevated levels of serum aspartate and alanine aminotransaminases, gamma-glutamyltransferase, lactic dehydrogenase, creatine kinase, bilirubin, creatinine, and urea. Total protein, albumin, fibrinogen, and hemoglobin levels were depressed. Values for prothrombin ratio, activated partial thromboplastin time, thrombin time, and fibrin degradation products were grossly elevated, findings that indicate the occurrence of disseminated intravascular coagulopathy. Many of the clinical pathologic changes were evident at an early stage of the disease and had a highly predictive value for fatal outcome of infection. Changes were present but less marked in nonfatal infections.
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PMID:The clinical pathology of Crimean-Congo hemorrhagic fever. 274 11

The effects of 9 beta-methyl carbacyclin, a chemically stable analogue of epoprostenol (prostacyclin, PGI2) were studied, in comparison with epoprostenol, both in vitro and in vivo in man. In vitro 9 beta-methyl carbacyclin and epoprostenol inhibited platelet aggregation induced by ADP, collagen, the endoperoxide analogue U46619 and arachidonic acid. The potency of 9 beta-methyl carbacyclin relative to epoprostenol was comparable in ADP and collagen-aggregated platelet rich plasma (PRP), 9 beta-methyl carbacyclin being 0.01 times as active as epoprostenol. The anti-aggregatory potencies of the two compounds were comparable in PRP and whole blood. The phosphodiesterase inhibitor isobutyl methyl xanthine enhanced the anti-aggregatory activity of both compounds in vitro. 9 beta-methyl carbacyclin and epoprostenol elevated platelet cyclic AMP, 9 beta-methyl carbacyclin being 0.04 times as active as epoprostenol. In a placebo controlled trial both drugs produces significant headache and facial flushing when compared with placebo. Nasal stuffiness, abdominal discomfort and nausea were reported on all three treatments. Both drugs caused significant and comparable increase in heart rate and decrease in pre-ejection (PEP) and PEP/left ventricular ejection time (LVET) ratio compared with placebo. Systolic and diastolic blood pressure, LVET and QS2 index were unchanged. Platelet aggregation responses to ADP were significantly inhibited by all three doses of both drugs compared with placebo. Bleeding time was significantly longer during epoprostenol infusion than either placebo or 9 beta-methyl carbacyclin infusion. Neither drug had significant effect, compared with placebo, on kaolin activated clotting time in PPP, PRP or in PRP in the presence of heparin, prothrombin time, partial thromboplastin time, thrombin clotting time, fibrinogen, fibrinogen degradation products or euglobulin clot lysis time. The pharmacodynamic effects and duration of action of 9 beta-methyl carbacyclin and of epoprostenol are similar; 9 beta-methyl carbacyclin is approximately 100 times less potent than epoprostenol in man.
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PMID:A chemically stable analogue, 9 beta-methyl carbacyclin, with similar effects to epoprostenol (prostacyclin, PGI2) in man. 608 4

We report the successful treatment of envenoming by the Gaboon viper (Bitis gabonica) and include results of in vitro investigations of the haemostatic properties of the whole venom. The patient was admitted to casualty soon after the bite with chest tightness, dizziness, nausea and swelling at the site of the bite and was treated immediately with polyspecific antivenom, hydrocortisone, chlorpheniramine and antibiotics. Results of haemostatic investigations were essentially normal on admission but on day 3 the thrombin time became prolonged and was associated with significant hypofibrinogenaemia and elevated D-dimers. Factors V and VIII, antithrombin III and protein C levels and platelet number were not significantly reduced. The haemostatic disturbances persisted for more than 24 h despite treatment with blood products (16 units of cryoprecipitate, 2 units of fresh frozen plasma and 6 units of platelet concentrate). Resolution of the abnormalities occurred only after administration of a further dose of antivenom. The period of hypofibrinogenaemia occurred at a time when venom antigen was undetectable in plasma by enzyme-linked immunosorbent assay. Studies in vitro with whole venom and a panel of amidolytic substrates commonly employed for measurement of haemostatic proteins revealed significant activity of venom with substrates sensitive to kallikrein and plasmin. The venom inhibited washed platelet aggregation induced by collagen, thrombin, arachidonic acid and the calcium ionophore A23187 in a dose-dependent manner.
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PMID:Accidental envenoming by a Gaboon viper (Bitis gabonica): the haemostatic disturbances observed and investigation of in vitro haemostatic properties of whole venom. 846

Pentoxifylline (POF) may suppress overproduction of tumor necrosis factor alpha (TNF alpha), which is thought to contribute to complications of human falciparum malaria. However, POF is believed to improve impaired capillary blood flow, which can be impaired in falciparum malaria. To test whether POF affects TNF alpha serum levels or other variables in this disease, we administered POF (20 mg/kg/day intravenously in 150 ml of saline for five days) randomized versus placebo (150 ml of saline without POF) in addition to standard antimalarial therapy. After recruitment of 51 patients with Plasmodium falciparum malaria, those receiving POF had more nausea and abdominal discomfort than the placebo group, as expected. Eleven of 27 patients receiving POF and three of 24 patients receiving placebo requested termination of the study medication (P < 0.05). Pentoxifylline did not change the decrease of TNF alpha levels or affect the clinical course in a significant way. Since POF failed to improve the clinical situation or to impact numerous laboratory parameters (including TNF alpha, thrombin-antithrombin III, thrombomodulin, and human neutrophil elastase), the study was terminated earlier than planned. While this study does not specifically address cerebral complications of malaria, the results suggest that POF is not useful as a routine adjunct to the standard therapy of falciparum malaria.
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PMID:Supportive pentoxifylline in falciparum malaria: no effect on tumor necrosis factor alpha levels or clinical outcome: a prospective, randomized, placebo-controlled study. 915 47

Enoxaparin (enoxaparin sodium) is a low-molecular-weight heparin that binds to and increases the activity of antithrombin III. The resulting complex inhibits prothrombinase-mediated thrombin generation and direct thrombin generation by binding to factor Xa and thrombin factor IIa. Enoxaparin, used as prophylaxis in medically ill patients at increased risk for thromboembolism, has shown significantly increased efficacy compared with placebo in reducing the incidence of deep vein thrombosis and pulmonary embolism. Indeed, 291 patients receiving subcutaneous enoxaparin 40 mg/day had a frequency of venous thromboembolism of 5.5% during 14 days of treatment, whereas 14.9% of the 288 placebo recipients experienced thromboemboli (p < 0.001). There was no reduction in the incidence of thromboembolism in the 287 recipients of enoxaparin 20 mg/day (15%). In other studies, prophylactic treatment for 7 days with subcutaneous enoxaparin 40 mg/day was at least as effective as unfractionated heparin in reducing the frequency of venous thromboembolism in 959 nonsurgical patients at increased risk for deep vein thrombosis and pulmonary embolism (total incidence = 0.2 and 1.4%, respectively). Moreover, enoxaparin recipients experienced fewer adverse events than did heparin recipients. The most frequent adverse events reported in medically ill and surgical patients receiving enoxaparin 40 mg/day were hemorrhage (17.4 vs 14.3% for placebo), hematoma at injection site, anemia, fever, peripheral edema, nausea, ecchymosis and edema (unspecified site).
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PMID:Enoxaparin: in the prevention of venous thromboembolism in medical patients. 1472 9

Various hematological abnormalities including fall in serial values of hemoglobin or hematocrit, coagulation factor abnormalities, leukocytosis, acute hemolytic anemia, thrombocytopenia, and thrombotic thrombocytopenic purpura or hemolytic uremic syndrome have been reported in patients with acute pancreatitis. Similarly, abnormalities of blood coagulation factors consistent with disseminated intravascular coagulopathy (DIC) have also been noticed in patients with pancreatitis. We report a case of a 33-year-old female with acute pancreatitis who presented with one episode of epistaxis and abnormal prothrombin time and partial prothrombin time. Coagulation work-up revealed thrombin time 24.3 s fibrinogen 110 mg/dl, D-dimers >1 and < 2, and fibrin degradation products >22. Pancultures did not show any evidence of infection. The patient maintained a normal renal and mental status during her illness. Her D-dimers continued to decrease with resolution of acute pancreatitis as evidenced by decreased abdominal pain, relief of nausea, control of vomiting, and decrease in serum amylase and lipase levels. This case report suggests that coagulation abnormalities are encountered in patients with acute pancreatitis. It is hypothesized that such hemostatic abnormalities may be related to early intravascular consumption of coagulation factors secondary to circulating pancreatic enzymes, particularly trypsin, or secondary to vascular injury. Recognition of these hematological complications including DIC is paramount. Physicians caring for these patients should be aware of such a complication of acute pancreatitis.
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PMID:DIC secondary to acute pancreatitis. 1604 98

A 37-year-old woman with congenital afibrinogenemia presented with chronic subdural hematoma (CSDH) manifesting as severe headache, nausea, and somnolence after a minor head trauma. Brain computed tomography scans showed a right subdural hematoma associated with midline shift. Laboratory studies showed prolongation of prothrombin time, activated partial thromboplastin time, and undetectably low level of fibrinogen. Until the present episode, she had received plasma-derived fibrinogen concentrate around menstruation and pregnancy. She had also suffered from spinal cord infarction due to vertebral artery occlusion. Burr-hole evacuation and drainage of CSDH was successfully performed using fibrinogen concentrate. The development of CSDH with afibrinogenemia is very rare. Although the past repeated administrations of fibrinogen concentrate were suspected to generate CSDH, paradoxical thrombotic complications caused by upregulation of prothrombin activation, thrombin generation, and growth factors released from platelets might be related to the development of CSDH with congenital afibrinogenemia.
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PMID:Chronic subdural hematoma in a patient with congenital afibrinogenemia successfully treated with fibrinogen replacement. 2212 82

We report a challenging case of cerebral venous sinus thrombosis (multiple etiologic factors) that was complicated by heparin resistance secondary to suspected antithrombin III (ATIII) deficiency. A 20-year-old female previously healthy and currently 8 weeks pregnant presented with worsening headaches, nausea, and decreasing Glasgow Coma Scale/Score (GCS), necessitating mechanical ventilatory support. Imaging showed extensive clots in multiple cerebral venous sinuses including the superior sagittal sinus, transverse, sigmoid, jugular veins, and the straight sinus. She was started on systemic anticoagulation and underwent mechanical clot removal and catheter-directed endovascular thrombolysis with limited success. Complicating the intensive care unit care was the development of heparin resistance, with an inability to reach the target partial thomboplastin time (PTT) of 60 to 80 seconds. At her peak heparin dose, she was receiving >35 000 units/24 h, and her PTT was subtherapeutic at <50 seconds. Deficiency of ATIII was suspected as a possible etiology of her heparin resistance. Fresh frozen plasma was administered for ATIII level repletion. Given her high thrombogenic risk and challenges with conventional anticoagulation regimens, we transitioned to argatroban for systemic anticoagulation. Heparin produces its major anticoagulant effect by inactivating thrombin and factor X through an AT-dependent mechanism. For inhibition of thrombin, heparin must bind to both the coagulation enzyme and the AT. A deficiency of AT leads to a hypercoagulable state and decreased efficacy of heparin that places patients at high risk of thromboembolism. Heparin resistance, especially in the setting of critical illness, should raise the index of suspicion for AT deficiency. Argatroban is an alternate agent for systemic anticoagulation in the setting of heparin resistance.
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PMID:Heparin Resistance and Anticoagulation Failure in a Challenging Case of Cerebral Venous Sinus Thrombosis. 2768 23


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