Gene/Protein Disease Symptom Drug Enzyme Compound
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During the last 40 years vaccines have been developed that have greatly reduced the incidence of infectious diseases of dogs. In general, modified live products have been superior to inactivated vaccines for dogs. It can be expected that recombinant and/or DNA vaccines may dominate the market in the future. Although most vaccines on the market are safe and efficacious, there have been exceptions where disease was induced by vaccination or dogs were not protected. The failure of protection may in part be due to variations in individual vaccine batches. Only potency tests but not efficacy tests are required, which may not be sufficient. For example, a virus titer in a vaccine may be meaningless if the minimum protective dose is not known. Overattenuated virus (e.g., CDV-Ond or parvovirus in cat cells) may have a high titer in tissue culture but is not immunogenic. The question of frequency of vaccination of dogs should be addressed. Annual revaccinations for CDV, CPV, and CAV are probably not needed. However, it would be desirable to collect more data to support less frequent vaccinations. Annual immunization for bacterial diseases such as kennel cough, Lyme disease, and leptospirosis should continue. It also would be desirable to develop more oro/nasal vaccines, perhaps combined with newly developed vectors that are less likely to induce undesirable side effects that may be seen after parenteral vaccination. Finally a word of warning against homeopathic "nosodes" to replace tested canine vaccines. They will appear highly effective as long as the majority of dogs remain vaccinated. As soon as a nonvaccinated dog population is large enough to allow virulent agents to spread, disease outbreaks will occur and we will be back where we began 40 years ago.
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PMID:Forty years of canine vaccination. 989 24

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

Cystic fibrosis (CF) is a fatal hereditary disease; patients with CF have an average lifespan of 30 years. By cleaving neutrophil-derived DNA, dornase alfa (recombinant human deoxyribonuclease I) decreases the adhesiveness and visco-elasticity of sputum in the infected lungs of patients with CF. As a result, respiratory function is improved in patients with all degrees of disease severity, and the relative risk of pulmonary exacerbations is reduced in patients with mild to moderate disease. Resource utilisation (days spent in hospital or receiving parenteral antibiotics) in patients with mild to moderate disease is also reduced by dornase alfa, as evidenced by a placebo-controlled trial in > 900 patients. Cost savings generated by these reductions in resource use during 24 weeks of dornase alfa therapy offset about 17 to 37.5% of the acquisition cost of the drug, depending on local cost data for various countries. Reductions in resource utilisation with dornase alfa have not been observed in patients with severe disease. Available cost-effectiveness and cost-utility analyses are not fully published. One analysis estimated that the incremental cost of avoiding one hospitalisation was about $Can 15,000 relative to standard therapy after 1 year of treatment. Informal analysis in the UK suggests a cost per quality-adjusted life-year of 25,000 Pounds for dornase alfa. Some quality-of-life (QOL) domains (mainly cough frequency and chest congestion) have shown modest improvement in patients treated with dornase alfa, mainly those with mild CF. Persuasive evidence of QOL benefit is lacking in those with more severe disease. Identifying patients most likely to benefit from dornase alfa therapy is essential to maximise clinical and cost benefits. The lack of a demonstrated reduction in resource utilisation in patients with severe CF makes its use more difficult to justify economically in this group than in those with less severe disease. However, in the absence of other treatments for this group, economic considerations must be weighed against clinical benefits. In conclusion, the acquisition cost of dornase alfa is partially offset by savings gained by reducing resource utilisation in patients with mild to moderate CF, and the drug appears to improve quality of life in some patients, mostly those with less severe disease. However, in the absence of guidance from definitive cost-effectiveness analyses, individual healthcare providers must make their own decisions about how best to provide dornase alfa to patients with CF in a rational and cost-justifiable manner.
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PMID:Dornase alfa. A review of pharmacoeconomic and quality-of-life aspects of its use in cystic fibrosis. 1017 Apr 64

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

A case of concurrent canine systemic lupus erythematosus (SLE) and generalized bacterial infection in a six-year-old female Beauceron is reported. The dog presented with purulent nasal and ocular discharges, skin lesions (including seborrhea, hyperkeratotic areas, and papules as well as ecchymoses around the eyes, on both sides of the pinnae, and on the vulva), generalized lymph node enlargement, a mitral murmur, and lameness. Later, facial swelling, a retrobulbar abscess, and a cough also developed. Occurrence of a generalized bacterial infection was established by culture of group-C, beta-hemolytic Streptococcus from the throat, the mouth, a biopsy site (popliteal lymph node area), the retrobulbar abscess, and the lung. The diagnosis of SLE was based on the clinical signs and particularly on the occurrence of antinuclear antibody (ANA) and antidoublestranded-desoxyribonucleic acid (ds-DNA) antibody. Interestingly, the latter type of antibodies were also detected in two young female puppies whelped by this dog. Salient histological findings included an extreme cell depletion of the lymph nodes and spleen and severe pneumonitis and peribronchiolitis. The results of this case indicate that a definite diagnosis of canine SLE can, at times, be made on the basis of the presence of serum ANA and ds-DNA antibodies.
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PMID:Nonresponsive generalized bacterial infection associated with systemic lupus erythematosus in a Beauceron. 1033 60

The porcine respiratory disease complex (PRDC) is an increasingly important cause of decreased swine productivity and is characterized by slow growth, decreased feed efficiency, anorexia, cough, and dyspnea. Mycoplasma hyopneumoniae is among the most prevalent and important infectious agents associated with PRDC. Understanding of mycoplasmal pneumonia has been hindered by inadequate diagnostic methods. Many of the currently available tests are relatively insensitive or nonspecific when used in a diagnostic laboratory setting or are too costly or difficult for routine diagnostic use. Several polymerase chain reaction (PCR) assays have been described, but they are not sensitive enough to detect the microorganisms in live pigs, from either nasal or tracheal swabs. A nested PCR using 2 species-specific sets of primers from the 16S ribosomal DNA gave positive results with as little as 80 microorganisms and did not cross-react with other mycoplasma species or with other microorganisms commonly found in the respiratory tract of pigs. This assay was better suited for detection of M. hyopneumoniae from nasal swabs than was conventional PCR. Nasal swab samples were taken at different time periods following experimental challenge of 10 susceptible pigs. Only 2 of the 55 swabs examined gave a positive result with conventional PCR, whereas 30 of the 55 swabs gave a positive result using the nested PCR. Twenty of 40 (50%) nasal swabs from pigs experiencing a respiratory disease outbreak where M. hyopneumoniae had been diagnosed also gave a positive result with the nested PCR. To confirm that the amplified product was specific, 4 nested PCR products were purified, sequences were determined and aligned, and they were confirmed to be from M. hyopneumoniae.
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PMID:Application of a nested polymerase chain reaction assay to detect Mycoplasma hyopneumoniae from nasal swabs. 1035 56

A 32-year old male was admitted to our hospital complaining of cough, fever, and skin eruptions. He was coctacted with a child who had chickenpox 3 weeks before the onset. He showed the elevating of antibody to varicella-zoster virus. Despite of the administration of Acyclovir for four days, cough was not relieved and a chest X-ray film showed infiltrative shadow in right middle lobe of the lung. Bronchoscopic examination revealed vasicle and edema, and the varicella-zoster virus (VZV) DNA was detected in the bronchoalveolar lavage by the polymerase chain reaction. The patient in first case confirmed by the virus DNA in the bronchial washing by the PCR.
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PMID:[Case of varicella-zoster pneumonia with bronchioalveolar lavage confirmed by the detection of VZV DNA in the bronchial washing by the polymerase chain reaction]. 1035 93

We report on a primary mediastinal large B-cell lymphoma with aberrant expression of beta-human chorionic gonadotropin (beta-hCG). The patient, a 33-year-old man, had cough, dyspnea, fever, superior vena cava syndrome, and a mediastinal bulky tumor. A biopsy showed that the latter was characterized by large cells, sclerosis, and compartmentalization. The neoplastic elements expressed CD45, CD20, CD79a and, partially, CD30, whereas they were negative for CD3, epithelial membrane antigen and cytokeratins. Surprisingly, they displayed a clear-cut positivity for beta-hCG. The remaining oncofetal markers applied (PLAP and alpha1-fetoprotein) were negative. Electron microscopy demonstrated the presence of numerous nuclear pockets and the lack of intercellular junctions. DNA analysis by polymerase chain reaction showed clonal rearrangement of Ig heavy-chain genes. The patient responded promptly to the administration of MACOP-B. To the best of our knowledge, this is the first example of B-cell lymphoma showing positivity for beta-hCG; a similar aberrant expression was previously observed only in three Japanese patients with human T-cell lymphotropic virus type I+ adult T-cell lymphoma/leukemia. Because primary mediastinal large B-cell lymphoma has in the past been frequently confused with germ cell tumors, pathologists should be aware of possible beta-hCG expression by lymphomatous cells to avoid the risk of misdiagnosis.
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PMID:Beta-HCG aberrant expression in primary mediastinal large B-cell lymphoma. 1036 55

The use of zinc in metal alloys and medicinal lotions dates back before the time of Christ. Currently, most of the commercial production of zinc involves the galvanizing of iron and the manufacture of brass. Some studies support the use of zinc gluconate lozenges to treat the common cold, but there are insufficient data at this time to recommend the routine use of these lozenges. Zinc is an essential co-factor in a variety of cellular processes including DNA synthesis, behavioral responses, reproduction, bone formation, growth, and wound healing. Zinc is a relatively common metal with an average concentration of 50 mg/kg soil and a range of 10-300 mg/kg soil. Meat, seafood, dairy products, nuts, legumes, and whole grains contain relatively high concentrations of zinc. The mobility of zinc in anaerobic environments is poor and therefore severe zinc contamination occurs primarily near points sources of zinc release. The recommended daily allowance for adults is 15 mg zinc. The ingestion of 1-2 g zinc sulfate produces emesis. Zinc compounds can produce irritation and corrosion of the gastrointestinal tract, along with acute renal tubular necrosis and interstitial nephritis. Inhalation of high concentrations of zinc chloride from smoke bombs detonated in closed spaces may cause chemical pneumonitis and adult respiratory distress syndrome. In the occupational setting inhalation of fumes from zinc oxide is the most common cause of metal fume fever (fatigue, chills, fever, myalgias, cough, dyspnea, leukocytosis, thirst, metallic taste, salivation). Zinc compounds are not suspected carcinogens. Treatment of zinc toxicity is supportive. Calcium disodium ethylenediaminetetraacetate (CaNa2EDTA) is the chelator of choice based on case reports that demonstrate normalization of zinc concentrations, but there are few clinical data to confirm the efficacy of this agent.
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PMID:Zinc. 1038 62

A 57-year-old woman who had been operated on for colon cancer and given chemotherapy, presented in September 1995 with worsening cough and abnormalities on her chest X-ray film. Acid-fast bacilli were isolated from the sputum. The organism was classified as M. gordonae by biochemical tests and DNA/DNA hybridization. The patient was treated with rifampicin and clarithromycin. Subsequently, sputum cultures became negative and the chest x-ray film showed a decrease infiltration. The findings in the present case suggest that M. gordonae may cause pulmonary infection and should be considered as an opportunistic pathogen.
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PMID:[Pulmonary infection caused by Mycobacterium gordonae]. 1038 30


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