Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0424790 (rigors)
 822 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The efficacy and safety of recombinant human interferon gamma (rIFN-gamma) in the reduction of opportunistic disease in patients with advanced HIV-1 infection are assessed. A 12-month double-blind, placebo-controlled, multicenter, Phase III trial of rIFN-gamma in HIV-positive patients with CD4 < 100 x 10(9)/liter on stable antiretroviral therapy. Eighty-four patients were allocated treatment on a 1:1 basis to rIFN-gamma or placebo. Patients received rIFN-gamma 0.05 mg/m(2) or 0.9% saline subcutaneously three times weekly for 48 weeks (optional extension to 18 months). The primary end point was the incidence of opportunist infections (CDC categories B/C). Secondary end points included mortality, immunological, and virological parameters. Patients on placebo had a mean of 3.45 opportunist infections (OIs) in the first 48 weeks. Patients treated with rIFN-gamma had a mean of 1.71 OIs (p = 0.04). However, the model showed overdispersion and the inclusion of a dispersion factor raised the p value to 0.13. rIFN-gamma appeared to have a particular effect on the incidence of Candida, herpes simplex, and cytomegalovirus infections. Three-year survival in the rIFN-gamma arm was 28% compared to 18% in the placebo group (not significant). rIFN-gamma-associated side-effects of headache, fatigue, rigors, influenza-like symptoms, depression, myalgia, and granulocytopenia were reversible. There was no evidence for HIV activation. Although not significant, the trend towards decreased opportunistic infections and increased survival warrants consideration of further trials of rIFN-gamma. The study gives additional information on the safety profile of this cytokine.
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PMID:A phase III study of recombinant human interferon gamma to prevent opportunistic infections in advanced HIV disease. 1142 20

A review of the published analytical methodology for the tricyclic antiviral (TAV) drugs is presented. While amantadine and rimantadine are the only two approved drugs for the prophylaxis and treatment of the influenza A virus, amantadine has also been approved for the treatment of Parkinson's disease. In addition, a few structurally related compounds are finding important clinical applications in other central nervous system-related disorders. To effectively evaluate the pharmacokinetics, biotransformations, stability, and other critical parameters that are necessary for pre-clinical and clinical studies, analytical methodology that conforms to the rigors of regulatory requirements must be developed and made available. This review discusses the analytical methods used in the determination of amantadine, rimantadine, tromantadine and memantine and the pre-clinical and clinical application of these techniques.
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PMID:Separation methods for tricyclic antiviral drugs. 1181 35

Tick-borne rickettsiae in the genera Ehrlichia and Anaplasma are intracellular bacteria that infect wild and domestic mammals and, more recently, man. The increased desire of humans for recreational activities outdoors has increased the exposure to potential human pathogens that previously cycled almost exclusively within natural, nonhuman enzootic hosts. Anaplasma phagocytophilum causes an acute, nonspecific febrile illness of humans previously known as human granulocytotropic ehrlichiosis (HGE) and now called human granulocytotropic anaplasmosis (HGA). The first patient to have recognized HGA was hospitalized at St Mary's Hospital in Duluth, Minnesota, USA in 1990. However, the clinical and laboratory presentation of this infection remained undefined until 1994, when Bakken and collaborators published their experience with 12 patients who had HGA. By the end of December 2004, at least 2,871 cases of HGA had been reported from 13 U.S. states to the Centers for Disease Control and Prevention (CDC). A limited number of laboratory-confirmed cases have been reported from countries in Europe, including Austria, Italy, Latvia, the Netherlands, Norway, Poland, Slovenia, Spain, and Sweden. Ixodes persulcatus-complex ticks are the arthropod hosts for Borrelia burgdorferi, the agent of Lyme borreliosis, and are also the arthropod hosts for A. phagocytophilum. Most cases of HGA have been contracted in geographic regions that are endemic for Lyme borreliosis. Male patients outnumber female patients by a factor of 3 to 1 and as many as 75% of patients with HGA have had a tick bite prior to their illness. Seroepidemiologic studies have demonstrated that HGA for the most part is a mild or even asymptomatic illness. However, older individuals and patients who are immunocompromised by natural disease processes or medications may develop an acute, influenza-like illness characterized by high fever, rigors, generalized myalgias, and severe headache. Local skin reactions at the site of the tick bite have not been described, and nonspecific skin rashes have been reported only occasionally. Anaplasmosis is associated with variable but suggestive changes in routine laboratory test parameters. Most patients develop transient reductions in total leukocyte and platelet concentrations. Relative granulocytosis accompanied by a left shift and lymphopenia during the first week of illness has been reported frequently. Serum hepatic transaminase concentrations usually increase two- to fourfold, and inflammatory markers, such as C-reactive protein and the erythrocyte sedimentation rate, rise during the acute phase. Abnormal laboratory findings may return toward normal range for patients who have been ill for more than 7 days, which may obfuscate the clinical decision making. Characteristic clusters of bacteria (morulae) are observed in the cytoplasm of peripheral blood granulocytes in 20% to 80% of infected patients during the acute phase of illness. The clinical diagnosis may be confirmed retrospectively by specific laboratory tests, which include positive polymerase chain reaction (PCR), identification of A. phagocytophilum in culture of acute-phase blood, or the detection of specific antibodies to A. phagocytophilum in convalescent serum. Virtually all patients have developed serum antibodies to A. phagocytophilum after completion of antibiotic therapy, and demonstration of seroconversion by indirect immunofluorescent antibody testing of acute-phase and convalescent-phase serum samples is currently the most sensitive and specific tool for laboratory confirmation of HGA. Treatment with doxycycline usually results in rapid improvement and cure. Most patients with HGA have made an uneventful recovery even without specific antibiotic therapy. However, delayed diagnosis in older and immunocompromised patients may place those individuals at risk for an adverse outcome, including death. Thus, prompt institution of antibiotic therapy is advocated for any patient who is suspected to have HGA and for all patients who have confirmed HGA.
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PMID:Clinical diagnosis and treatment of human granulocytotropic anaplasmosis. 1711 14

Transfusion-related acute lung injury (TRALI) is a transfusion reaction that is often under recognized and underreported. Implications for diagnosis not only influence treatment considerations but also extend to donor selection, donor deferral and ultimately the safety of the final blood product. We report a case of a previously well 19-year-old female who presented a one week history of flu-like symptoms and mucosal bleeding. Laboratory results confirmed the diagnosis of thrombotic thrombocytopaenia purpura (TTP) and she was commenced on plasma exchange. During her second day of plasma exchange, she developed dyspnoea and rigors. Examination and investigation findings were consistent with a clinical diagnosis of TRALI. Granulocytes immunofluorescent test (GIFT - flow cytometry) was performed and cross reactivity was demonstrated between the patient's granulocytes and plasma from one of the nine donor fresh frozen plasma (FFP) packs. She made a full recovery. TRALIa accounts for 7% of all adverse events reported in the Serious Hazards of Transfusion (SHOT) database and has a mortality rate between 5-25%. Apheresis patients are a particularly vulnerable group of patients where clinical recognition and rapid laboratory confirmation of TRALI is imperative to minimize the risk of further patient exposure to donor granulocyte or human leukocyte antigen (HLA) antibodies. The provision of plasma from male donors may additionally reduce exposure. On a wider scale, rapid donor identification and deferral maintains the safety of the national blood supply.
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PMID:A case report of transfusion-related acute lung injury during plasma exchange therapy for thrombotic thrombocytopenia purpura. 1825 17

Mifamurtide, also known as liposomal muramyl tripeptide phosphatidyl ethanolamine (L-MTP-PE), has been approved for the treatment of osteosarcoma in Europe. Mifamurtide's rational drug design employs MTP-PE for macrophage activation in a multilamellar liposome drug carrier, containing the synthetic phospholipids 1-palmitoyl-2-oleoyl phosphatidyl choline (POPC) and 1,2-dioleoyl phosphatidyl serine (OOPS). Although the drug is not cytotoxic towards normal or tumor cells in vitro, immune activation against osteosarcoma lung metastases in vivo accounts for mifamurtide's antiosteosarcoma effects. Phosphatidyl serine-containing lipids signal macrophage cells that have "flipped phosphatidyl serine" to the outer membrane after apoptosis (e.g., after damage of tumor cells from chemotherapy); thus, both mifamurtide's active and inactive ingredients target immune cells in the lungs. Mifamurtide administration has resulted in 8% and 13% improvement in 6- and 5-year overall survivals, when added to chemotherapy in nonmetastatic and metastatic patients with osteosarcoma, respectively. The short-term toxicities of mifamurtide (fever, headache, flu-like symptoms and rigors) are reduced or eliminated using ibuprofen (200 mg) as premedication for the first infusion; an algorithm for pre- and postmedication is presented. To date, no long-term side effects of mifamurtide have been reported. Compassionate access programs based in two major cancer centers (MD Anderson and Memorial Sloan-Kettering), have recently provided this potentially life-saving drug in North America. The experience with mifamurtide provides an outstanding example of successful cooperation among regulatory bodies and agencies, the pharmaceutical industry and pediatric oncologists to improve cancer care and outcomes for children and young people with a rare sarcoma.
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PMID:Mifamurtide in osteosarcoma--a practical review. 2051 34

Data about burden of influenza in pregnancy in India are scant. In order to assess the contribution of influenza to acute respiratory illness (ARI) in pregnancy, 266 north Indian pregnant females with febrile ARI were studied from December 2014 to May 2015. Twin nasopharyngeal/oropharyngeal swabs were obtained and tested for influenza viruses by RT-PCR. Fifty (18.8%) patients tested positive for influenza (A/H1N1pdm09 in 41, A/H3N2 in 8, and influenza B Yamagata in 1). Rigors, headache, and a family history of ARI were significantly more frequent in influenza positive patients. Oseltamivir and supportive therapy were administered to all confirmed cases. Nine influenza positive cases needed hospitalization for their respiratory illness, and 5 developed respiratory failure. Of these, 4 (3 in third trimester) succumbed to their illness. We conclude that influenza viruses are a cause of significant morbidity and mortality among pregnant females with ARI in north India. As such, appropriate preventive strategies of influenza vaccination and early initiation of antiviral therapy during illness are stressed.
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PMID:Influenza Illness in Pregnant Indian Women: A Cross-Sectional Study. 2690 62


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