Gene/Protein Disease Symptom Drug Enzyme Compound
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To determine adverse events of ribavirin in the treatment of chronic hepatitis C, 41 patients (18 with cirrhosis), treated with ribavirin at an initial dose of 600-1200mg day(-1), were analysed retrospectively (six patients were treated twice because adverse effects during the first treatment necessitated cessation of ribavirin). Indications for ribavirin included a contraindication (n = 15) an intolerance (n = 11) or a non-response (n = 15) to interferon (IFN). Ribavirin was combined with IFN 3 million units (MU) three times weekly for 15 patients and with azathioprine for six patients (five of whom were transplant patients). No cirrhotics and only one patient treated with ribavirin + IFN received azathioprine. The mean duration of treatment was 5 months (range 1-18 months). Sixteen of 47 treatments (34%) with ribavirin were stopped: four because of vomiting (8.5%), two for psychiatric disorder, one for dry cough, one for an unrelated cause, and eight (at 1-2 months) because of a fall in the level of haemoglobin (Hb) of 4.6 g dl(-1) (range 2.7-5.9 g dl[-1]); however, according to the rules of international protocol, we would have expected only four treatments (two in patients receiving azathioprine) with Hb < 8.5 g dl(-1) to be stopped. The decrease in Hb level occurred more slowly in patients treated with IFN plus ribavirin than in patients treated with ribavirin alone and was of lower clinical significance in patients with cirrhosis than in patients without cirrhosis. After exclusion of patients receiving azathioprine, there was no significant difference in the fall of Hb level between cirrhotic and non-cirrhotic patients and between patients treated with IFN plus ribavirin and patients treated with ribavirin alone. Interestingly, the platelet count of patients treated with IFN plus ribavirin fell less than in patients treated with IFN alone. The most important and expected adverse event associated with ribavirin was haemolysis. Anaemia < 8.5 g dl(-1), requiring cessation of ribavirin therapy, was present in 9% of patients and was worsened by azathioprine. Abdominal discomfort and dry cough were other, potentially important, clinical adverse events found in our study.
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PMID:Effects of cirrhosis, interferon and azathioprine on adverse events in patients with chronic hepatitis C treated with ribavirin. 927 22

The World Health Organization (WHO) in 1993 developed the integrated management of childhood illness (IMCI) draft algorithm which offers guidelines upon the diagnosis and treatment of acute respiratory infections, diarrhea, malaria, measles, ear infections, and malnutrition, as well as immunization status. During a 14-month study period, 1795 children aged 2 months to 5 years were enrolled in the study from the outpatient pediatric clinic of Siaya District Hospital in western Kenya, of whom 52% were male and the median age was 13 months. 51% of the children complained of having fever, 22% of having a cough, and 11% of having diarrhea. 86% of the main complaints were directly addressed by the IMCI algorithm. 1210 children had Plasmodium falciparum infection and 1432 met the WHO definition for anemia. The sensitivities and specificities for classification of illness by a minimally trained health worker using the IMCI algorithm compared to diagnosis by the physician were: pneumonia, 97% sensitivity and 49% specificity; dehydration in children with diarrhea, 51% and 98%, respectively; malaria, 100% and 0%; ear problem, 98% and 2%; nutritional status, 96% and 66%; and need for referral, 42% and 94%. Detection of fever by placing a hand upon the forehead was 91% sensitive and 77% specific. Considerable clinical overlap was observed between pneumonia and malaria, and between malaria and malnutrition. Study findings led to some changes in the IMCI algorithm.
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PMID:Evaluation of an algorithm for integrated management of childhood illness in an area of Kenya with high malaria transmission. 952 16

The differentiation of malaria from other causes of fever in the absence of microscopy is notoriously difficult. Clinical predictors of malaria have been studied in an area of low and unstable transmission on the western border of Thailand. In 1527 children aged 2-15 years who were followed prospectively for 7 months, 82% (1254) had at least one febrile episode. Malaria caused 24% (301) of the first febrile episodes (Plasmodium falciparum 128, P. vivax 151, P. malariae 1, mixed infections with P. falciparum and P. vivax 21). Each malaria case was matched with the next child of similar age presenting to the dispensary with another cause of fever. Clinical symptoms or signs associated with a final diagnosis of malaria were: confirmed fever (> or = 38 degrees C) (odds ratio [OR] 1.6, 95% confidence interval [95% CI] 1.4-1.9), headache (OR 1.5, 95% CI 1.3-1.9), muscle and/or joint pain (OR 2.0, 95% CI 1.6-2.8), nausea (OR 1.7, 95% CI 1.4-2.3), clinical anaemia (OR 1.4, 95% CI 1.3-3.3), palpable spleen (OR 1.3, 95% CI 1.1-1.7), palpable liver (OR 1.4, 95% CI 1.1-2.1), absence of cough (OR 1.6, 95% CI 1.4-2.0), and absence of diarrhoea (OR 1.5, 95% CI 1.2-2.4). None of these signs alone or in combination proved a good predictor of malaria. The best diagnostic algorithms (history of fever and headache without cough, and history of fever with an oral temperature > or = 38 degrees C [sensitivity 51% for both, specificity 72 and 71%, respectively]) would result in prescription of antimalarial drugs in 28-29% of the non-malaria febrile episodes, and only 49% of the true malaria cases. Thus half of the potentially life-threatening P. falciparum infections would not be treated. Although multivariate analysis identified vomiting, confirmed fever, splenomegaly and hepatomegaly as independent risk factors for a diagnosis of falciparum malaria, use of these signs to differentiate falciparum from vivax malaria, and thus to determine antimalarial treatment, was insufficiently sensitive or specific. Malaria diagnosis should be confirmed by microscopical examination of a blood slide or the use of specific dipstick tests in areas of low transmission where highly drug-resistant P. falciparum coexists with P. vivax.
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PMID:Clinical features cannot predict a diagnosis of malaria or differentiate the infecting species in children living in an area of low transmission. 969 50

Idiopathic pulmonary haemosiderosis (IPH) is a disorder characterised by the triad of haemoptysis, diffuse parenchymal infiltrates on chest roentgenogram and iron-deficiency anaemia. It is a diagnosis of exclusion and the prognosis is bleak despite the varied management options. We report a case of IPH occurring in a child who presented at four months of age with cough, wheeze, haemoptysis and pallor and whose symptoms are currently controlled with high-dose inhaled budesonide and low-dose oral prednisolone.
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PMID:Idiopathic pulmonary haemosiderosis--a case report. 971 27

Two imported cases of Penicillium marneffei infection in Belgium are reported. Both patients are Thai women co-infected with HIV. P. marneffei infection should be suspected in immunocompromised patients originating or travelling from South-East Asia with unexplained fever (> 38 degrees C), weight loss, a generalised lymphadenopathy, hepatomegaly, splenomegaly, skin lesions, cough and anaemia. Diagnosis is made by culture and/or histopathological examination. Mild to moderate infections are treated with itraconazole 400 mg/day as first choice. Amphotericin B parenteral therapy may be required for seriously ill patients. Maintenance therapy with itraconazole 200 mg/day is necessary to prevent relapses.
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PMID:Two imported cases of Penicillium marneffei infection in Belgium. 979 45

Copper, zinc, selenium, and molybdenum are involved in many biochemical processes supporting life. The most important of these processes are cellular respiration, cellular utilization of oxygen, DNA and RNA reproduction, maintenance of cell membrane integrity, and sequestration of free radicals. Copper, zinc, and selenium are involved in destruction of free radicals through cascading enzyme systems. Superoxide radicals are reduced to hydrogen peroxide by superoxide dismutases in the presence of copper and zinc cofactors. Hydrogen peroxide is then reduced to water by the selenium-glutathione peroxidase couple. Efficient removal of these superoxide free radicals maintains the integrity of membranes, reduces the risk of cancer, and slows the aging process. On the other hand, excess intake of these trace elements leads to disease and toxicity; therefore, a fine balance is essential for health. Trace element--deficient patients usually present with common symptoms such as malaise, loss of appetite, anemia, infection, skin lesions, and low-grade neuropathy, thus complicating the diagnosis. Symptoms for intoxication by trace elements are general, for example, flu-like and CNS symptoms, fever, coughing, nausea, vomiting, diarrhea, anemia, and neuropathy. A combination of observation, medical and dietary history, and analyses for multiple trace elements is needed to pinpoint the trace element(s) involved. Serum, plasma, and erythrocytes may be used for the evaluation of copper and zinc status, whereas only serum or plasma is recommended for selenium. Whole blood is preferred for molybdenum. When trace element levels are inconsistent with medical evaluations, a test for activity of the suspected enzyme(s) would support the differential diagnosis. Furthermore, it is important to differentiate whether trace element deficiency or toxicity is the primary cause of the disorder, or is secondary to other underlying diseases. Only successful treatment of the primary disorder will lead to complete recovery. In the event of sample contamination during collection or analysis, the physician may be misled by falsely elevated results. Royal blue top evacuated tubes containing negligibly low concentrations of the trace element or acid-washed plastic sterilized syringes should be used for blood, serum, or plasma collection. Powdered gloves must be avoided. When possible, mineral supplements are not to be administered to the patient for a minimum of 3 days prior to sample collection. Serum and plasma specimens are to be transported in acid-washed polypropylene and polyethylene tubes. Analysis is performed in a controlled environment to minimize or eliminate contamination. During analysis, all laboratory wares should be acid-washed for decontamination. A detailed description of these precautions may be found in reviews by Aitio and Jarvisalo and by Chan and Gerson. Copper and zinc analysis on serum and plasma are commonly performed by flame atomic absorption spectrometry, inductively coupled plasma-atomic emission spectrometry, and inductively coupled plasma-mass spectrometry. Serum and plasma selenium levels are determined by graphite furnace atomic absorption with Zeeman background correction and neutron activation analysis. Molybdenum levels are best determined by neutron activation and highly sensitive inductively coupled plasma-mass spectrometry. The reader is referred to reviews by Tsalev and Jarvis.
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PMID:The role of copper, molybdenum, selenium, and zinc in nutrition and health. 989 6

Twenty-three episodes of anticoagulant rodenticide toxicity were found in 21 dogs during a retrospective study conducted at The Ohio State University Veterinary Teaching Hospital. Dyspnea (57%), lethargy (48%), coughing/hemoptysis (30%), and pallor (26%) were the most common presenting complaints. Prolonged activated clotting time (ACT), prolonged one-stage prothrombin time (OSPT), and prolonged activated partial thromboplastin time (APTT) were present in all dogs that had not received any prior therapy. Anemia (83%), thrombocytopenia (61%), hypoproteinemia (57%), positive fibrin degradation products (FDPs) (55%, six of 11 tested), and hyperfibrinogenemia (43%, six of 14 tested) were common hematological findings. Treatment included therapy with vitamin K1, blood products, and supportive care. The survival rate was 83%.
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PMID:Anticoagulant rodenticide toxicity in 21 dogs. 993 27

Amplification of the human epidermal growth factor receptor 2 protein (HER2) in primary breast carcinomas has been shown to correlate with poor clinical prognosis for certain patients. Trastuzumab (Herceptin, Genentech, Inc., South San Francisco, California) is a highly purified recombinant DNA-derived humanized monoclonal immunoglobulin G1 kappa antibody that binds with high affinity and specificity to the extracellular domain of the HER2 receptor. In vitro and in vivo preclinical studies have shown that administration of trastuzumab alone or in combination with paclitaxel or carboplatin significantly inhibits the growth of breast tumor-derived cell lines that overexpress the HER2 gene product. At therapeutic doses in breast cancer patients, the mean half-life of trastuzumab is 5.8 days. Trastuzumab serum concentrations reach steady state with mean trough and peak concentrations of 79 microg/mL and 123 microg/mL, respectively. In a 222-patient, single-arm clinical study, treatment with a loading dose of trastuzumab 4 mg/kg administered IV followed by weekly IV doses of 2 mg/kg produced an overall response rate of 14% (2% complete remission and 12% partial remission). The beneficial effects were greatest in patients with the greatest degree (3+) of HER2 protein overexpression. In another clinical study, 469 women with metastatic breast carcinoma were randomized to a paclitaxel or anthracycline-plus-cyclophosphamide regimen with or without trastuzumab. The overall response rate was significantly greater in the trastuzumab-plus-chemotherapy group than in the chemotherapy-alone cohort. The magnitude of observed effects was greatest with pacli taxel plus trastuzumab. The most common adverse effects attributed to trastuzumab in clinical studies were fever and chills, pain, asthenia, nausea, vomiting, increased cough, diarrhea, headache, dyspnea, infection, rhinitis, and insomnia. Trastuzumab in combination with chemotherapy can lead to cardiotoxicity, leukopenia, anemia, diarrhea, abdominal pain, and infection. Trastuzumab has been approved by the US Food and Drug Administration as a single agent for the treatment of patients who have metastatic breast cancer involving overexpression of the HER2 protein and who have received 1 or more chemotherapy regimens; in combination with paclitaxel, it has been approved for the treatment of such patients who have not received chemotherapy.
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PMID:Trastuzumab, a recombinant DNA-derived humanized monoclonal antibody, a novel agent for the treatment of metastatic breast cancer. 1021 34

Idiopathic pulmonary hemosiderosis (IPH) is a rare disease of unknown etiology characterized by recurrent episodes of pulmonary symptoms such as cough, hemoptysis, and dyspnea. Our study consisted of 23 patients: 12 males and 11 females with IPH. The diagnosis was based on history, presence of anemia, and characteristic chest X-ray, and was confirmed by showing macrophages laden with hemosiderin in gastric washings or bronchoalveolar lavage and/or open lung biopsy. All but one patient were diagnosed in our department between 1979-1994. There was a history of multiple blood transfusions for anemia in 10 patients. Consanguinity between parents was noted in 11 patients. Severe pallor, cough, hemoptysis, and hepatomegaly were the most common findings on physical examination. All but 2 patients had hypochromic microcytic anemia of varying severity. In 12 children, moderate reticulocytosis was noted. Corticosteroids were administered with doses ranging from 5 mg every other day to 2 mg/kg/day depending on the severity of the episodes (duration of disease from 2-14 years). It is our impression that patients with IPH, benefit from long-term steroid treatment which in turn results in a milder course. Long-term low-dose steroid treatment appeared to prevent crises and assured a prolonged survival.
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PMID:Long-term clinical course of patients with idiopathic pulmonary hemosiderosis (1979-1994): prolonged survival with low-dose corticosteroid therapy. 1021 56

A three-year-old weimaraner was presented with lethargy, anorexia, neck pain and a soft fluctuant swelling in the thoracic inlet. A cough had been noted previously. Clinical examination revealed tachycardia, tachypnoea, pallor and a large subcutaneous swelling, with bruising, suggestive of a haematoma in the thoracic inlet. Thoracic radiographs revealed a cranial mediastinal mass which had the ultrasonographic appearance of fluid, and there was also a marked generalised interstitial lung pattern. Routine haematology revealed severe anaemia and thrombocytopenia, although coagulation tests were within normal limits. A diagnosis of immune-mediated thrombocytopenia was however made on the basis of a positive antiplatelet antibody test and a rapid response to prednisolone therapy. Furthermore, a tentative diagnosis of Angiostrongylus vasorum infection was suggested on the basis of clinical and radiographic findings, although no lungworm larvae were identified on faecal analysis. Despite initiating treatment with fenbendazole, the dog died suddenly. Postmortem examination revealed myocarditis, thrombosing arteritis, pneumonia and chronic membranoproliferative glomerulonephritis associated with A vasorum infection.
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PMID:Immune-mediated thrombocytopenia associated with Angiostrongylus vasorum infection in a dog. 1038 68


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