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Biomedical subjects

J Korpela

Publications and source records attributed to J Korpela.

At least 19 recordsLinked to original sources

Docetaxel with epirubicin--investigations on cardiac safety.

The aim was to evaluate clinical and subclinical cardiac toxicity of epirubicin-docetaxel (ET) combination. Breast cancer patients were given epirubicin (75 mg/m2 for 15 min), followed 1 h later by a 1-h infusion of docetaxel (75 mg/m2) q3w as first-line treatment. Cardiac function was monitored using a 24-h ambulatory electrocardiogram (ECG), left ventricular ejection fraction (LVEF), physical examination and chest radiography. The median LVEF did not decrease during the course of the treatment: median LVEF was 64% prior to treatment and 68% after cycle 8. The 24-h ECG did not reveal any significant changes in heart rate variability. The number of extrasystoles or cardiac arrhythmia did not increase with the ET treatment. No patient experienced congestive heart failure during treatment or the mean follow-up of 34 months. We conclude that first-line ET caused no major cardiac changes during 6 months of treatment (8 cycles) or during follow-up. Twenty-four-hour ECG, combined with echocardiography to measure LVEF, was a feasible method for the close monitoring of the cardiac effects during chemotherapy.

Adult↗

Epirubicin/docetaxel regimen in progressive breast cancer-a phase II study.

The purpose of this investigation was to evaluate the efficacy and toxicity of 6 months' treatment with the combination of epirubicin and docetaxel in metastatic breast cancer. Thirty-eight women (mean age 51 years, range 35-72) with metastatic breast cancer were treated with a regimen of epirubicin 75 mg/m and docetaxel 75 mg/m every 3 weeks, given 4 times if progression was seen upon evaluation after 4 courses or 8 times in responding/stable patients. The patients received 285 cycles of combination treatment and two treatments with docetaxel or epirubicin alone. When neutropenia with fever was observed, further cycles were given with dose reduction. The median cumulative docetaxel dose was 462 mg/m (range 199-600) and that of epirubicin 476 mg/m (range 199-740). The overall response rate was 54% (95% CI 37-71), with a median duration of response of 14.8 months (95% CI 8.8-27.8). Median time to progression was 12 months, median survival 26 months. Neutropenia below 0.5 x 10 /l occurred following 113 (39%) of the total of 285 cycles given; 21 patients (55%) were hospitalized for febrile neutropenia. We conclude that dose tailoring is required in treatment with an epirubicin and docetaxel regimen to avoid grade 3/4 adverse effects in a significant number of patients treated for metastatic breast cancer.

Adult↗

Antimicrobial susceptibilities and biotypes of Arcanobacterium haemolyticum blood isolates.

Isolates obtained from the blood of ten patients with Arcanobacterium haemolyticum septicaemia were biotyped as smooth or rough using morphological and biochemical criteria, and their susceptibilities to 18 antibacterial agents were determined. Nine of the clinical cases included here have not been reported previously and are discussed in brief. One of the strains was highly resistant to macrolides and clindamycin. With one exception, the strains belonged to the smooth biotype. The data presented here indicates that the treatment of systemic Arcanobacterium haemolyticum infections should be based on the antibacterial susceptibility profiles of individual strains and on the site of the infection.

Adolescent↗

Subtyping of Shigella sonnei for tracing nosocomial transmission.

Nosocomial transfer of Shigella spp. occurred between two patients sharing the patient room and toilet in a ward for internal medicine. Both patients had travelled abroad shortly before the onset of illness. Based on the epidemiology of Shigella sonnei strains imported into Finland, nosocomial infection was strongly suspected. The isolates of S. sonnei were subtyped using ribotyping, plasmid analysis and antibiotic resistance patterns. The greatest discrimination between the strains was achieved by ribotyping. The results of the typing scheme confirmed the nosocomial transmission of S. sonnei. The outbreak did not spread further within the ward. The importance of isolation of a patient with diarrhoea in a hospital setting is emphasized.

Adult↗

[Aromatarii, pharmacopolae, thurarii et ceteri. On the social history of Rome].

This paper contains a collection of data concerning different holders of medical, especially pharmacological functions in ancient Rome and a discussion of their social status. There were no clear official distinctions between the several kinds of drugsellers in Rome, and all of them belonged to the class of ordinary shopkeepers. Drugselling especially flourished in the first two centuries AD because of economical welfare and intensive foreign commercial contacts.

Complementary Therapies↗

Fidelity of DNA synthesis by the Thermococcus litoralis DNA polymerase--an extremely heat stable enzyme with proofreading activity.

We demonstrate that the DNA polymerase isolated from Thermococcus litoralis (VentTM DNA polymerase) is the first thermostable DNA polymerase reported having a 3'----5' proofreading exonuclease activity. This facilitates a highly accurate DNA synthesis in vitro by the polymerase. Mutational frequencies observed in the base substitution fidelity assays were in the range of 30 x 10(-6). These values were 5-10 times lower compared to other thermostable DNA polymerases lacking the proofreading activity. All classes of DNA polymerase errors (transitions, transversions, frameshift mutations) were assayed using the forward mutational assay (1). The mutation frequencies of Thermococcus litoralis DNA polymerase varied between 15-35 x 10(-4) being 2-4 times lower than the respective values obtained using enzymes without proofreading activity. We also noticed that the fidelity of the DNA polymerase from Thermococcus litoralis responds to changes in dNTP concentration, units of enzyme used per one reaction and the concentration of MgSO4 relative to the total concentration of dNTPs present in the reaction. The high fidelity DNA synthesis in vitro by Thermococcus litoralis DNA polymerase provides good possibilities for maintaining the genetic information of original target DNA sequences intact in the DNA amplification applications.

Archaea↗

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History of Medicine↗

[Not Available].

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History of Medicine↗

Synthetic env gp41 peptide as a sensitive and specific diagnostic reagent in different stages of human immunodeficiency virus type 1 infection.

An enzyme immunoassay (EIA) for serum antibodies to human immunodeficiency virus type 1 (HIV-1), based on the synthetic pentadecapeptide SGKLICT-TAVPWNAS, a segment of the transmembrane glycoprotein (gp41) of the virus, was developed and tested for sensitivity and specificity. Sera of 152 individuals at various stages of HIV-1 infection, including two prospectively and six retrospectively studied patients exposed to HIV-1 but seronegative on initial testing in whole-virus EIA and immunoblotting, were screened with the gp41 peptide antibody EIA. The reference population consisted of 1,000 healthy HIV-1 antibody-negative blood donors. In addition, five individuals with antibodies to HIV-2 were studied. Antibodies to the synthetic peptide were detected in 100% of those with asymptomatic infection. Only one patient with LAS failed to react in the peptide EIA. Patients with HIV-2 infection did not react in this test. The peptide antibodies appeared rapidly after infection, were detectable at the time when seroconversion was observed by immunoblotting, and preceded reactivity in whole-virus EIA. Sera of seven patients with verified HIV-1 infection did not react with gp41 in immunoblotting, although antibodies were readily detectable in the gp41 peptide EIA.

AIDS-Related Complex↗

Inactivation of human immunodeficiency virus in serum specimens as a safety measure for diagnostic immunoassays.

Since the human immunodeficiency virus (HIV) may be transmitted accidentally to laboratory personnel analyzing patient sera, the efficiency of a non-ionic detergent, Triton X-100, in inactivation of HIV in human serum as a safety measure was studied. Semliki Forest virus, an enveloped toga virus, was used as a model virus to create optimal treatment conditions. In the presence of 50% serum, complete inactivation (i.e. no residual virus detected, greater than 7 log reduction of virus titre) was achieved by incubation with 0.2% Triton X-100 for 1 h at 37 degrees C. Under these conditions HIV was also completely inactivated (i.e. no residual infectious virus detected, greater than or equal to 5 log reduction of virus titre). Both treated and untreated serum specimens were also tested with several enzyme immunoassays used in virological laboratories to determine whether the inactivation treatment interfered with the assays. The treated specimens, further diluted as recommended for each assay, were subjected to 15 enzyme immunoassays for microbial antibodies and antigens (HIV IgG, hepatitis A IgG and IgM, hepatitis B s, c, and e antigens and antibodies, cytomegalovirus IgG, mumps virus IgG, poliovirus IgG, rubellavirus IgM, toxoplasma IgG, and chlamydia IgG). Clearly decreased sensitivity was found only with two hepatitis B tests (e antigen and antibody to the surface antigen). It is concluded that safe inactivation of HIV in serum is achieved by 0.2% Triton X-100, but the treatment may decrease the sensitivity of some tests in which low specimen dilution is used.

Acquired Immunodeficiency Syndrome↗

No antibodies to HTLV-I and HIV in patients with dementia in Finland.

Patients with human immunodeficiency virus (HIV) have often progressive dementia. Human T cell lymphotropic virus Type I (HTLV-I) infection has not been reported to cause dementia. We tested antibodies to HTLV-I and HIV in serum and cerebrospinal fluid in 69 Finnish patients referred because of dementia to an outpatient department of neurology. No antibodies to HTLV-I and HIV were detected in patients with the clinical diagnosis of Alzheimer's disease, vascular dementia, secondary dementia due to a specific cause, or in cases of atypical dementia.

Acquired Immunodeficiency Syndrome↗

[Not Available].

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History of Medicine↗

The occurrence and production of avidin: a new conception of the high-affinity biotin-binding protein.

The production of avidin, a high-affinity biotin-binding egg-white protein, is not restricted to the avian, amphibian and reptilian oviducts. In the acute phase of inflammation, avidin is synthesized and secreted by various injured tissues in the domestic fowl, both male and female. Also in other avian species and a lizard, injured tissues produce an avidin-like biotin-binding factor. The non-oviductal production of avidin in domestic fowl has a great variety of inducers, for example acute inflammation caused by mechanical or thermal tissue injury, septic bacterial infection and (toxic) drugs, and even retrovirus-induced cell transformation. In culture, chicken embryo fibroblasts and yolk sac macrophages synthesize and secrete avidin. Besides the albumen, avidin may act as an antibacterial protein also in the tissues.

Animals↗

[Not Available].

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History of Medicine↗

Localization of avidin in virus-transformed and damaged chicken embryo fibroblasts by immunofluorescence and the avidin-biotin-peroxidase complex (ABC) technique.

Avidin, a high-affinity biotin-binding protein of chicken oviduct, was recently found to be synthesized and secreted by damaged or virus-transformed chicken embryo fibroblasts and by chicken macrophages. We have now localized avidin in fibroblasts that were transformed by Rous sarcoma virus. The cells released to the culture medium up to 12 micrograms avidin per 10(6) cells, as judged by the [14C] biotin-binding method. In immunofluorescence microscopy, avidin was localized to the cytoplasm of transformed and of untransformed damaged cells. Treatment with the ionophore monensin was used to determine whether avidin is processed through the Golgi region, which was localized using rhodamine-labeled wheat germ agglutinin. Under these conditions avidin was largely confined to the Golgi region. At the electron microscopic level avidin could be localized to the endoplasmic reticulum of transformed cells, using anti-avidin antibodies and the avidin-biotin-peroxidase complex (ABC) technique. Biotinyl peroxidase did not stain the endogenous avidin in cell layers processed for light or electron microscopy indicating that its biotin-binding sites were either saturated or denaturated. The possibility that endogenous avidin in tissues or cell cultures may bind biotinylated reagents should be controlled for in techniques involving the avidin-biotin interaction.

Animals↗

Chicken macrophages synthesize and secrete avidin in culture.

It was previously shown that avidin, a glycoprotein secreted in vivo by chicken oviduct, is produced by cultured transformed or damaged chicken embryo fibroblasts [27]. This report demonstrates synthesis and secretion of large amounts of avidin by macrophages isolated from chicken yolk sac. Avidin was secreted to the culture medium as shown by immunoprecipitation of metabolically labeled proteins. In the culture medium of macrophages the avidin concentration (up to 47.5 +/- 0.5 microgram/mg cellular protein) exceeded, in agreement with previous findings, that of fibroblasts (up to 7.3 +/- 0.7 microgram/mg) infected with transforming retroviruses (Rous sarcoma virus, its mutants temperature sensitive for transformation and OK 10 virus). No difference between the macrophage avidin and the egg white avidin was detected by both the heat-induced [14C] biotin exchange assay and immunoblotting (subunit Mr = 15600). By immunofluorescence 10 to 20% of the cells were positive for avidin, independent of the time in culture (1-30 days). The staining pattern varied between dense or granular perinuclear and strong reticulo-granular fluorescence throughout the cytoplasm. Double staining for avidin and the Golgi region by wheat germ agglutinin showed that avidin is concentrated, and might be processed, in the Golgi complex. The production of avidin by macrophages supports a role for avidin in host defence mechanisms.

Animals↗