Prognostic factors in osteosarcomas. A regression analysis

A multivariate regression analysis of survival data, using the Cox proportional hazards model (PHM), was performed on the retrospective material of 184 osteosarcoma patients treated at the Aarhus and Copenhagen oncology centers, Denmark, from 1963 to 1984. All patients were previously untreated. Radical surgery, in general ablative when possible, was the primary treatment goal throughout this period. A number of clinical and pathologic variables were tested in the model to elucidate their prognostic importance. Tumors localized to the trunk, pelvis, or femur, and symptom duration of less than 6 months were poor prognostic signs. Tumors dominated by fibroblastic cells and a patient age of approximately 25 to 30 years were associated with an especially good prognosis. The prognosis worsened with advancing age. Children, adolescents, and adults ages 5 to 25 years had significantly poorer prognosis than young adults 25 to 30 years of age. Sex, radiologic appearance, and year of referral had no significant prognostic value in this series. Based on the regression model, a prognostic index is derived and survival is calculated for a good and a poor prognostic case. The overall 10-year survival with one standard deviation was 28.6 +/- 3.5%. Cancer deaths continue to occur 10 years after initial treatment, and the estimated hazard rate is still four times greater than that of a sex- and age-matched group of healthy individuals.     

Correlation of levels of volatile versus carcinogenic particulate polycyclic aromatic hydrocarbons in air samples from smokehouses

Summary In the present study, data on the concentration of polycyclic aromatic hydrocarbons (PAH) in air samples from fish smokehouses (Nordholm et al. 1986) and meat smokehouses (Hansen et al. submitted for publication) were used to analyze the extent to which six different volatile PAH compounds could function as markers for the total concentration of six different carcinogenic particulate PAH compounds. Although a significant positive correlation was observed between the concentration of each of six volatile compounds and the total concentration of carcinogenic PAH compounds, a particularly good correlation was observed for phenanthrene, anthracene, fluoranthene and pyrene. Calculations of the sensitivity, specificity, positive predictive value and negative predictive value of these potential markers revealed that naphthalene and phenanthrene exhibited the highest sensitivity as markers for total carcinogenic PAH compounds in air samples from smoke-houses, whereas fluoranthene and pyrene displayed the highest specificity. However, when the applicability of the six markers was tested on air samples from iron foundries, only naphthalene and pyrene were useful as markers for the carcinogenic compounds. The present study indicates that naphthalene and pyrene might function as markers for carcinogenic PAH compounds, that are present at low concentrations and are therefore difficult and time-consuming to measure directly.This study was supported by the Danish National Institute of Occupational Health and the Danish Academy of Science     

Erectile dysfunction in multiple sclerosis

In a sample of 29 impotent men with multiple sclerosis and erectile problems, penile arterial inflow and venous outflow were within normal limits. In 26 patients, the pudendal evoked potential (PEP) was abnormal, and eight of these also had abnormal bulbocavernous reflex (BCR). Three patients had abnormal PEP and normal BCR, and of these, two had normal and one had abnormal nocturnal erectile activity. The validity of PEP/BCR testing was supported by normal findings in six patients with MS and without erectile problems. Nocturnal erectile activity was normal in 11 patients, of whom nine had abnormal PEP and/or BCR. A high disability score corresponded poorly with both reduced sexual function, insufficient nocturnal erectile activity, and abnormal PEP and/or BCR. Intracavernous injection of papaverine gave erection in 27 patients, the dose needed to create an erection being inversely related to the level of disablement. PEP and BCR testing may be more sensitive in defining neurogenic erectile dysfunction (ED) than nocturnal erectile activity. We considered 26 of the cases to have a neurogenic cause of ED and three to have mainly a psychogenic cause.     

Pneumococcal IgA1 Protease Activity Interferes with Opsonophagocytosis of Streptococcus Pneumoniae Mediated by Serotype-Specific Human Monoclonal IgA1 Antibodies

Immunity against tuberculosis (TB), caused by Mycobacterium tuberculosis , depends largely on activation and maintenance of strong cell-mediated immune responses involving both CD4⁺ and CD8⁺ T cells and the ability to respond with Th1-type cytokines, particularly IFN-γ. Recent studies suggested that BCG, the only licensed vaccine against M. tuberculosis , may fail to induce T-cell responses in the lung mucosa and may therefore not protect against pulmonary TB. A decrease in TB mortality may be achieved by enhancing immunity in the lung. The present study evaluated the induction of antigen-specific immunity in the lung by intranasal (i.n.) delivery of the lipoprotein I (OprI) from Pseudomonas aeruginosa . OprI has shown to be a Toll-like receptor 2/4 agonist that, when given subcutaneously, induces Type-1 immune responses against heterologous antigens. Here, a fusion of OprI to Ag85A of Mtb (OprI-Ag85A) was used as a subunit vaccine in homologous prime-boost immunizations. In addition, OprI-Ag85A was combined with an Ag85A-encoding DNA vaccine (Ag85A DNA) or with BCG in heterologous prime-boost vaccinations. Intranasal and parenteral delivery with OprI-Ag85A elicited comparable T-cell responses in the spleen; in addition, i.n. delivery elicited specific T-cell responses in the lung lymph nodes (LLNs). Intramuscular delivery of Ag85A DNA induced significant systemic Th1 immune responses. Intranasal boosting with OprI-Ag85A enhanced this response and in addition induced an antigen-specific IFN-γ response in LLN. OprI may therefore be an efficient adjuvant for mucosal boosting. We continue to evaluate the protection induced by OprI-based prime-boost vaccinations against pulmonary TB. Results on the immunogenicity and protection against intravenous Mtb H37Rv infection will be presented.     

Buspirone pharmacokinetics in patients with cirrhosis.

The pharmacokinetics of a single oral dose of buspirone (20 mg) were determined in 12 patients with cirrhosis and 12 normal subjects. The mean AUC of buspirone was 55 +/- 38 s.d. ng ml-1 h in cirrhotics and 3.5 +/- 2.4 s.d. ng ml-1 h in normals. The time until maximum concentration (tmax) attained was similar in the two groups (0.6 vs 0.7 h), but mean maximum concentration Cmax was higher in patients (18.8 +/- 16.3 s.d. ng ml-1) than in normals (1.2 +/- 0.8 s.d. ng ml-1). Mean elimination half-life of buspirone was greater in cirrhotics, but this difference was marginally significant statistically (cirrhotics, 6.1 +/- 3.5 s.d. h, normals 3.2 +/- 1.5 s.d. h, P = 0.05). Eight of 12 patients and seven of 12 normal subjects had a second peak in the plasma concentrations of buspirone. In patients this occurred at 10.8 +/- 7.4 s.d. h after the dose, and its mean concentration was 3.1 +/- 6.6 ng ml-1. In normal subjects the second peak occurred at 4.3 +/- 2.1 h after the dose and its mean concentration was 0.5 +/- 0.3 ng ml-1. On the kinetic evidence buspirone should be used with caution in liver disease.     

Relation between mammographic findings and hormonal receptor content in breast cancer

A comparative investigation of 85 patients with unilateral primary breast cancer was performed to elucidate a possible correlation between the mammographic appearance of the cancer and the content of hormonal receptors (estrogen and progesterone). The mammographic appearance was divided into five types: (1) spiculated; (2) structural changes in the parenchyma (density); (3) calcifications; (4) circumscribed; and (5) not visible on mammogram. The hormonal content was found to be high in types 1 and 2, low in 3 and 4, and intermediate in 5. Statistically significant difference in the estrogen receptor content was found between 1 and 3; 1 and 3 + 4; 1 and 3 + 4 + 5. In progesterone receptor content, a statistically significant difference was found between 1 and 3 + 4. The results concerning estrogen receptor content within each cancer type, except type 2, are comparable to those of a Swedish study. No correlation was found between Wolfe's parenchymal patterns and hormonal receptor content, which contradicts a recent English study. Reasons for this discrepancy are discussed.     

Influence of dose and route of administration on disposition of metronidazole and its major metabolites

Summary The influence of dose and route of administration on the kinetics of metronidazole and its major metabolites has been investigated in 8 healthy volunteers given 0.5 and 2.0 g i.v. and p.o. Metronidazole elimination kinetics from plasma could be described by an open two-compartment model. The systemic oral bioavailability of both doses was approximately 1. The total systemic clearance of the intravenous 2.0 g dose was 9% lower than that of the 0.5 g dose (p<0.05). There were no significant dose-related differences in volume or rate of distribution. The elimination half-life was similar after the four treatments with metronidazole. The major elimination pathways, renal excretion and hepatic oxidation and glucuronidation, accounted for more than 2/3 of the total systemic clearance. Clearance both by hepatic oxidative metabolism and renal excretion was significantly lower after 2.0 than after 0.5 g i.v., whereas there was no significant difference after the oral doses. The results indicate that a high therapeutic dose of metronidazole may be eliminated at a reduced rate, but this is probably not of clinical importance. No single saturable elimination pathway was identified.