Serum TRACP 5b and ICTP as markers of bone metastases in breast cancer.

BACKGROUND: The purpose of this cross-sectional study was to evaluate the value of serum tartrate-resistant acid phosphatase 5b (TRACP 5b) and carboxyterminal telopeptide of type I collagen (ICTP) separately and in combination as markers of bone metastases compared to total alkaline phosphatase (tALP) in breast cancer. MATERIALS AND METHODS: Two groups of patients were studied, one with verfied bone metastases (N=46) and one without bone metastases (N=141). Bone marker levels were correlated with the presence or absence of bone metastases. RESULTS: Serum TRACP 5b concentrations exhibited the largest area under the receiver-operating characteristics (ROC) curve (AUC=0.845), followed by ICTP (0.818) and tALP (0.814) when all patients were included in the analysis. With the combination of TRACP 5b and ICTP, the AUC increased to 0.881. In multivariate regression analysis, all three markers were significant predictors of bone metastases. CONCLUSION: Serum TRACP 5b, ICTP and tALP exhibited equal performances in the detection of bone metastases. The combination of TRACP with ICTP did not significantly improve the detection of bone metastases over tALP.

Serum tartrate-resistant acid phosphatase 5b (TRACP 5b) as a marker of skeletal changes in prostate cancer.

Skeletal metastases are a significant problem in prostate cancer (PC). The patients are also exposed to treatment-related skeletal changes. This cross-sectional study evaluated a marker of bone resorption, TRACP 5b in relation to the standard analyte total alkaline phosphatase (tALP) as a marker of skeletal changes. Serum levels of TRACP 5b, tALP and PSA were measured in 130 prostate cancer patients. Comparison was made between patients with (BM+, n = 25) and without (BM-, n = 105) skeletal metastases, and between those treated with (n = 64) or without (n = 66) androgen deprivation (AD). Sensitivities and specificities were calculated for each marker and diagnostic accuracy was evaluated by ROC curve analysis. ROC curves indicated the superior accuracy of tALP, whereas TRACP 5b and PSA were comparable. With tALP the best combination of sensitivity (96%) and specificity of (91%) was reached at a cut-off point 224 U/L, the corresponding values were for TRACP 5b sensitivity (76%), specificity (89%) with a cut-off point 4.89 U/L, and for PSA sensitivity (65%), specificity (81%) at 23 ng/L for skeletal metastases. Patients treated with AD showed with increasing duration an increase in TRACP 5b values. TRACP 5b was less specific than tALP as a marker of skeletal metastases. TRACP 5b may have a role in the diagnostics of skeletal changes in PC with a focus on treatment-related skeletal changes.

Androgen deprivation and cognition in prostate cancer.

Androgen deprivation (AD) is commonly used in neoadjuvant and adjuvant setting with prostate cancer (PC) radiotherapy. This prospective study assessed whether cognitive functioning is impaired during 12 months of AD therapy. Longitudinal testing of 25 patients treated with AD and curative radiotherapy was undertaken at baseline, and at 6 and 12 months. CogniSpeed software was used for measuring attentional performances. Other cognitive performances were evaluated using verbal, visuomotor and memory tests. The Beck depression inventory was employed to evaluate depressive mood and EORTC QLQ-C30 for quality of life (QoL). During longitudinal testing of the AD group, no impairment in cognitive performances was found. Instead, improvement was observed in object recall (immediate, P=0.035; delayed, P<0.001), and in semantic memory (P=0.037). In QoL, impairment in physical function was observed. Androgen deprivation of 12 months appears to be associated with preserved cognitive functioning, although physical impairment occurs. These results have implications for counseling and psychosocial support of patients in the context of treatment options in PC.

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.

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.

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.

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.

[Aromatarii, pharmacopolae, thurarii et ceteri. On the social history of Rome]. / Aromatarii, pharmacopolae, thurarii et ceteri. Zur Sozialgeschichte Roms.

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.

Fecal bile acid metabolic pattern after administration of different types of bread.

Increased concentrations of fecal bile acids have been suggested to be associated with increased risk of colorectal cancer. Fecal bile acid profiles were determined in 12 healthy Finnish women who included in their normal diets for 2-week periods in turn three different types of bread, 200-300 g/day. The breads contained either low-fiber wheat, whole-meal wheat, or whole-grain rye. During consumption of rye bread, the total mean concentration of fecal free bile acids was 4.77 +/- 0.90 mumol/g of dry feces (mean +/- SEM), which was much lower than with the normal omnivorous diet (8.05 +/- 1.56 mumol/g) or during administration of the low-fiber wheat bread (8.83 +/- 1.56 mumol/g) or the whole-meal wheat bread (7.88 +/- 1.34 mumol/g) (P less than 0.05). This decrease was mainly caused by increased proportions of saponifiable bile acids (P less than 0.01). During intake of the whole-grain rye bread, 46% +/- 3% of the fecal bile acids were in their saponifiable forms; this percentage was 30% +/- 3% during the control period, 30% +/- 4% during the low-fiber wheat bread period, and 27% +/- 4% during the whole-meal wheat bread period. It is concluded that the type of bread significantly effects concentrations of cocarcinogenic and comutagenic free lithocholic and deoxycholic acids by changing modes of conjugation in the gut.

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.

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.

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.

Fecal free and conjugated bile acids and neutral sterols in vegetarians, omnivores, and patients with colorectal cancer.

Increased excretion and intestinal bacterial metabolism of bile acids and neutral sterols have been suggested to be associated with an increased risk of colorectal cancer. We determined fecal neutral sterol and bile acid profiles by new capillary column gas-liquid chromatographic methods in 18 patients with colorectal cancer, 10 omnivores, and 10 vegetarians. The methods also determine concentrations of esterified neutral sterols and saponifiable bile acids formed by intestinal bacterial action. Patients with colorectal cancer had the highest concentrations of neutral animal sterols, the lowest degree of esterification of neutral sterols, the lowest relative amount of saponifiable bile acids, and the highest concentrations of unconjugated primary bile acids. These differences were statistically significant (p less than 0.05) and more profound when the patients were compared with vegetarians than with omnivores. Since epidemiologic studies suggest that vegetarians have a lower risk of colorectal cancer than omnivores, these differences are discussed as possible risk factors for colorectal cancer.

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.

Effect of oxytetracycline administration on intestinal metabolism of oestrogens and on plasma sex hormones in healthy men.

The effect of oxytetracycline (1 g/day for five days) on the enterohepatic recycling of oestrogens and on plasma sex hormone concentrations was assessed in healthy men. Plasma oestrone (E1), oestradiol-17 beta (E2), 4-androstenedione (A), 5 alpha-dihydrotestosterone (5 alpha-DHT), total and free testosterone (T and free T), binding capacity of sex hormone binding globulin, luteinizing hormone, dehydroepiandrosterone-sulphate, urinary total E1, E2, and oestriol (E3), and oestriol-3-glucuronide (E3-3G) and faecal unconjugated and conjugated E1, E2, and E3 were measured by radioimmunoassay (RIA). Treatment with the antibiotic significantly increased the excretion of faecal conjugated oestrogens, which parallelled a decrease in urinary oestrogen excretion, especially of E3. The effect on urinary E3 could be explained almost entirely by the simultaneous decrease of urinary E3-3G concentrations. In urine and faeces the E2/E3 and E1 + E2/E3 ratios increased, probably because of the diminished reductive metabolism of oestrogens in the gut. No significant effects on plasma unconjugated oestrogen concentrations were observed. Moreover, in the present study oxytetracycline had no remarkable effect on plasma total, or free T concentrations, nor on other plasma hormones measured. Our results suggest that enterohepatic recycling and intestinal metabolism of oestrogens may be significant in men. The mechanism of action of antibiotics on oestrogen metabolism probably involves decreased hydrolysis by beta-glucuronidase of oestrogen conjugates by the intestinal contents, diminishing the reabsorption of aglycones of oestrogen conjugates and resulting in faecal loss of the steroids.

Multicomponent analysis of bile acids in faeces by anion exchange and capillary column gas-liquid chromatography: application in oxytetracycline treated subjects.

A method is described for the multicomponent analysis of bile acids in faeces. Following homogenization and extraction, bile acids are separated into several groups according to their mode of conjugation by anion exchange chromatography on DEAE-Sephadex A-25 in the acetate form. The different conjugate groups are then processed separately and quantified using capillary column gas-liquid chromatography (GC), the identity of the individual bile acid components being established by gas chromatography-mass spectrometry (GC-MS). The method permits the quantitative determination, with good precision, of unconjugated bile acids, their saponifiable derivatives, and their glycine-, taurine- and sulfated conjugates. In five healthy men the mean daily excretion of bile acids was 472 +/- 21.8 mumol (SEM) and the mean faecal concentration 7.74 +/- 1.07 mumol (SEM)/g dry weight. Free bile acids constituted 74.8% +/- 5.8% (SEM), saponifiable conjugates 23.5% +/- 5.8% (SEM) glycine-conjugates 0.7% +/- 0.2% (SEM), taurine-conjugates 0.2% +/- 0.07% (SEM), and their sulfated conjugates 0.8% +/- 0.1% (SEM) of total faecal bile acids. In addition to a detailed description of the methodology the effect of antibiotics on faecal bile acid profiles is presented. Oxytetracycline consistently decreased faecal concentrations of saponifiable derivatives of bile acids while increasing the taurine- and sulfated conjugates. The concentrations of the primary bile acids, cholic- and chenodeoxycholic acid, were higher during the course of oxytetracycline.