Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030193 (pain)
 261,466 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A retrospective analysis of 7 patients with streptococcal toxic shock revealed isolated prolongation of the activated partial thromboplastin time, which returned to normal during recovery. Levels of factor XII were reduced in 2 patients who had single factor assays performed, consistent with activation of the kallikrein-kinin system. We speculate that bradykinin release following activation of the kallikrein-kinin system in streptococcal toxic shock may underlie the features of pain, capillary leaking, and severe hypotension characteristic of this syndrome.
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PMID:Kallikrein-kinin system activation in streptococcal toxic shock syndrome. 1088 Mar 16

In 1967 we reported for the first time five cases of an acquired bleeding disorder in humans which developed after contact with saturnidae caterpillars. Since that time, other cases have been reported in Brazil, French Guyana, Peru, Paraguay and Argentina. The caterpillars have been identified as Lonomia achelous (LA) in Venezuela and northern Brazil and as Lonomia obliqua (LO) in southern Brazil. All patients present pain and a burning sensation at the site of contact. Within a few hours hematomas and hematuria are seen in combination with intracerebral and intraperitoneal hemorrhage (in some cases also renal failure). Hematological tests show: mild anemia with leucocytosis; prolonged PT, PTT and ThT; decreased fibrinogen, factor V, factor XIII, plasminogen and alpha2-antiplasmin levels; increased factor VIII:c, von Willebrand factor, and FDPs/D-dimers levels with normal ATIII and platelets. Factor VII, factor II and PC levels varied. Several activities similar to or directed against blood clotting factors have been identified in LA: fibrinolytic enzymes, which degrade fibrinogen producing abnormal FDPs; prothrombin activators: one direct and one factor Xa-like; a thermostable factor V activator; a thermolabile factor V inhibitor; a factor XIII proteolytic/urokinase-like activity; and a kallikrein-like activitiy. In LO three activities have been described: a prothrombin activator called 'Lonomia obliqua prothrombin activator protease' (LOPAP); a factor X activator; and a phospholipase A(2)-like activity called Lonomiatoxin. No fibrinolytic activity has been described in LO. Subcutaneous injection of crude hemolymph and some chromatographic fractions of LA induce a decrease in fibrinogen, plasminogen and factor XIII. Intravenous injection of factor XIII proteolytic/urokinase-like activity induce a dose-dependent thrombolysis with a decrease in plasmatic factor XIII without hemorrhagic manifestations. Intradermal injection of LO bristle extracts in rats and rabbits produce incoagulability whereas intravenous injection of LOPAP induced DIC in mice.
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PMID:Lonomia genus caterpillar toxins: biochemical aspects. 1108 23

Given daily, low molecular weight (LMW) heparins are established for prophylaxis against deep vein thrombosis (DVT). We describe delivery by a novel, needle-less device that is virtually painless in action. Its use could provide benefits for patients in terms of comfort both psychologically and physically, and for healthcare workers in terms of safety from needle-stick injury. Patients undergoing elective surgery received LMW heparin delivered subcutaneously by either a standard needle and syringe or by the needle-less injection device, J-Tip. Pain was scored at the time of injection and plasma anti-factor Xa levels compared between the two methods of drug delivery 4 h later: 29 patients received LMW heparin delivered by the J-Tip and 31 patients by standard needle and syringe. The J-Tip was significantly more comfortable for the patient as the method of drug delivery (P < 0.001). When delivered by the J-Tip, LMW heparin was equally as efficacious, as plasma anti-factor Xa levels were similar for both methods of delivery (P < 0.42). In summary, delivery of LMW heparin by the J-Tip device was both comfortable and effective. These findings, taken in conjunction with its ease of use and complete freedom from risk of needle-stick injury might encourage further examination and use of this type of product.
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PMID:Delivery of low molecular weight heparin for prophylaxis against deep vein thrombosis using a novel, needle-less injection device (J-Tip). 1110 65

The present study was designed to determine the maximum tolerated dose (MTD), toxicity profile, pharmacokinetics (PKs), and antitumor activity of the protein kinase C-alpha antisense oligonucleotide ISIS 3521 (ISIS Pharmaceuticals, Inc., Carlsbad, CA) when administered in combination with 5-fluorouracil (5-FU) and leucovorin (LV). Patients with refractory solid tumors received ISIS 3521 as a 21-day continuous infusion administered simultaneously with 5-FU and LV given daily for 5 days repeated every 4-5 weeks (one cycle). 5-FU and ISIS 3521 PK analysis were performed on samples taken during the first cycle in all patients. Fifteen patients received ISIS 3521 at one of three dose levels: (a) 1.0 (n = 3 patients); (b) 1.5 (n = 3 patients); and (c) 2.0 (n = 9 patients) mg/kg/day. All patients simultaneously received 5-FU (425 mg/m(2)/day) and LV (20 mg/m(2)/day) for 5 consecutive days. Grade 1-2 toxicities included alopecia, fatigue, mucositis, diarrhea, anorexia, nausea/vomiting, and tumor pain. One patient had grade 3 chest pain considered to be related to 5-FU therapy, another patient had dose-limiting grade 3 mucositis resolving in <7 days, and one patient with a history of gastritis had an acute upper gastrointestinal bleed thought to be 5-FU-induced toxicity. Five patients developed cycle 1 grade 4 neutropenia, which resolved without colony-stimulating factors before the next treatment cycle. There were no effects on prothrombin time and activated partial thromboplastin time. A clinically defined MTD was not reached. The character and severity of these toxicities do not seem to be dose related, and, as such, there was no classical dose-limiting toxicity defining the MTD. ISIS 3521 PKs in the presence of 5-FU was consistent with those reported previously. 5-FU PK parameters were also similar in the presence or absence of ISIS 3521. Six of 14 patients ( approximately 43%) across all dose cohorts had an improvement in measurable tumor response ranging from minor reduction in tumor size (4 patients) to objective partial response (>50% reduction in tumor size, 2 patients). ISIS 3521 is tolerable at its recommended single-agent dose when given with 5-FU and LV. There is no apparent PK interaction between ISIS 3521 and 5-FU and LV. Antitumor activity was observed with the combination; however, it is uncertain whether clinical activity is a result of enhanced drug interaction. Our study warrants further exploration of efficacy in a Phase II and/or Phase III clinical trial setting.
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PMID:Phase I clinical and pharmacokinetic study of protein kinase C-alpha antisense oligonucleotide ISIS 3521 administered in combination with 5-fluorouracil and leucovorin in patients with advanced cancer. 1194 11

Management of bleeding in haemophiliacs with a history of inhibitor remains problematic. With infusion of factor VIII (FVIII), development of an anamnestic response and possible appearance of high-titre inhibitor remains a valid concern. We report a case of a haemophiliac with a history of moderately high-titre FVIII inhibitor that had become undetectable. He had not received FVIII since 1997, when he became inhibitor negative. He had been managed during his bleeding episodes with prothrombin complex factor concentrates, which became less effective in controlling his bleeding. The patient had a history of recurrent, spontaneous shoulder joint dislocations with bleeding, pain and significant disability. Shoulder joint replacement surgery was suggested. Replacement therapy was discussed with the patient, who refused treatment with human FVIII because of his concern for possible anamnestic response and inhibitor rebound. Porcine FVIII was not acceptable due to his poor response when used once in the past, and his history of moderate allergic reaction. Therefore, recombinant factor VIIa (NovoSeven, Novo Nordisk, Princeton, NJ) was considered to be an acceptable option for the contemplated shoulder surgery. The patient underwent 2.5 h of surgery with NovoSeven infusion. The surgeons were impressed with the lack of bleeding in this traumatic surgery. Despite the continuously prolonged activated partial thromboplastin time and low FVIII levels, the patient maintained a remarkably dry surgical field. Effective haemostasis was achieved during and after this procedure. This case illustrates the usage of NovoSeven as an effective treatment modality in a haemophilia A patient with past history of inhibitor undergoing joint surgery.
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PMID:Efficacy of NovoSeven during surgery on a haemophiliac with previous history of inhibitors. 1255 92

A 60-year-old woman with multiple psychosocial issues presented with a history of spontaneous painful bruising on her left upper arm. Extensive investigations did not reveal any abnormality apart from an elevated activated partial thromboplastin time as a result of factor XII deficiency. An autoerythrocyte sensitization test reproduced the tender bruises on her back. Our patient reported relief of pain with promethazine injections. She was subsequently referred to the psychiatric team for ongoing assessment and management. Having an awareness of this rare condition will assist in the prevention of unnecessary investigation of such cases and will allow the early referral of patients for appropriate psychological counselling.
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PMID:Periodic painful purpura: fact or factitious? 1496 12

The risks and benefits of adult-to-adult living donor liver transplantation need to be carefully evaluated. Anesthetic management includes postoperative epidural pain relief; however, even patients with a normal preoperative coagulation profile may suffer transient postoperative coagulation derangement. This study explores the possible causes of postoperative coagulation derangement after donor hepatectomy and the possible implications on epidural analgesia. Thirty donors, American Society of Anesthesiology I, with no history of liver disease were considered suitable for the study. A thoracic epidural catheter was inserted before induction and removed when laboratory values were as follows: prothrombin time (PT) > 60%, activated partial thromboplastin time < 1.24 (sec), and platelet count > 100,000 mmf pound sterling (mm3). Standard blood tests were evaluated before surgery, on admission to the recovery room, and daily until postoperative day (POD) 5. The volumes of blood loss and of intraoperative fluids administered were recorded. Coagulation abnormalities observed immediately after surgery may be related mostly to blood loss and to the diluting effect of the intraoperative infused fluids, although the extent of the resection appears to be the most important factor in the extension of the PT observed from POD 1. In conclusion, significant alterations in PT and platelet values were observed in our patients who underwent uncomplicated major liver resection for living donor liver transplantation. Because the potential benefits of epidural analgesia for liver resection are undefined according to available data, additional prospective randomized studies comparing the effectiveness and safety of intravenous versus epidural analgesia in this patient population should be performed.
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PMID:Increased prothrombin time and platelet counts in living donor right hepatectomy: implications for epidural anesthesia. 1535 5

Circulating platelets play a pivotal role in hemostasis. The platelet hemostatic function involves the direct interaction with damaged vessel walls, and circulating coagulation factors, primarily thrombin resulting in platelet activation, aggregation and formation of hemostatic plug. Flow cytometry is a useful technique for the study of platelet activation in circulating blood. Platelet activation markers for ex vivo analysis may include a) activation-dependent epitopes of the membrane glycoprotein (GP) IIb/IIIa (CD41a) receptor, as demonstrated by the binding of activation-specific monoclonal antibodies (MoAbs) PAC1, anti-LIBS1 and anti-RIBS); b) the expression of P-selectin (CD62p), the alpha-granule GP translocated to the platelet surface following release reaction; and c) platelet procoagulant activity, as demonstrated by the binding of i) annexin V protein to the prothrombinase-complex (prothrombin, activated factor X (Xa) and V (Va)) binding sites on the surface of activated platelets, and of ii) MoAbs against activated coagulation factors V and X bound to the surface of activated platelets. Using this method, platelet activation as a marker for in vivo prothrombotic activity can be demonstrated in various clinical conditions including coronary angioplasty, orthostatic challenge in primary depression, sickle cell disease in clinical remission and during pain episode, and in pregnancy-related hypertension with marked increase during preeclampsia. The finding of platelet procoagulant activity is corroborated by increased levels of plasma markers for thrombin generation and fibrinolytic activity.
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PMID:Platelet activation as a marker for in vivo prothrombotic activity: detection by flow cytometry. 1547 Dec 23

We report the case of a 41-year-old woman, affected by Vaquez syndrome, admitted to our hospital for a severe pain in the right hypochondrium, suddenly followed by hepatomegaly and ascites. The clinical and laboratory data were suggestive of hepatic insufficiency and abdominal ultrasonography, integrated by color Doppler and computed tomography, revealed an interrupted hepatic venous outflow. In addition a spontaneous prolonged partial thromboplastin time was present and the patient was found to be positive for lupus anticoagulant. A transient clinical improvement, with a partial reperfusion of suprahepatic veins, was achieved with medical treatment by using anticoagulants, diuretics and paracentesis. However, the patient showed a subsequence of suprahepatic venous thrombosis, although two transjugular intrahepatic portosystemic shunts with stent placement and local thrombolysis were performed. The polycythemia vera is a disease mainly associated with Budd-Chiari syndrome but, in our patient, the thrombotic event occurred in spite of normal values of hematocrit and platelet count. Certainly in this case the lupus anticoagulant positivity represents an additional thrombogenic factor. Nowadays the antiphospholipid antibody syndrome is a recognized and not unusual cause of Budd-Chiari syndrome but, to our knowledge, this is the first case characterized by the presence of polycythemia vera and antiphospholipid antibody syndrome to be reported.
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PMID:[Budd-Chiari syndrome with fatal outcome in a patient with polycythemia vera and antiphospholipid antibody syndrome]. 1552 39

Parecoxib (Dynastat) is a parenteral cyclooxygenase-2 inhibitor available in Europe. Clinical trials have reported a benefit in reducing pain following oral, orthopedic, gynecologic and cardiac surgeries. The overall efficacy was dose-related and similar to ketorolac (Toradol). Several trials reported an opioid-sparing effect with parecoxib. No trials have reported significantly fewer opioid-related gastrointestinal side effects (e.g., nausea, vomiting, constipation and intestinal ileus) when opioids were administered with parecoxib versus placebo. Gastroduodenal ulcers, gastric ulcers and duodenal ulcers or erosions were less common with parecoxib than ketorolac. Parecoxib does not affect platelet aggregation, interfere with the antiplatelet affect of aspirin, affect prothrombin and partial thromboplastin time or platelet counts when administered with heparin.
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PMID:Parecoxib: a shift in pain management? 1585 57


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