Phase II trial of piroxantrone in patients with recurrent and metastatic squamous cell carcinoma of the head and neck

Summary Twenty-two patients with recurrent or metastatic squamous cell carcinoma of the head and neck were treated with piroxantrone 150 mg/m² intravenously every 21 days. There were no objective responses. The 95% upper confidence bound for response is 15%. Primary toxicity was hematologic.     

Keloids

Keloids are benign fibrous growths that result from an abnormal connective tissue response in certain predisposed individuals. Blacks form keloids more often than whites; however, the reason for this racial difference is not known. Trauma, foreign-body reactions, infections, and endocrine dysfunction have all been proposed as precipitating factors. Keloids are found most commonly on the ear lobes, shoulders, upper back, and midchest. They extend past the area of trauma and once present tend to remain stable. Although sometimes pruritic, painful, or tender, they are usually asymptomatic. Histologically, keloids are characterized by thick collagen bundles, abundant mucinous ground substance, few fibroblasts, and few if any foreign-body reactions. Although there have been many therapeutic modalities, most have had limited success. The most commonly used therapeutic approach is a combination of cryotherapy, intralesional steroid injections, surgical excision, and pressure devices.     

Confounders contributing to the reported associations of coffee or caffeine with disease

The role of caffeine or coffee in causing or promoting the incidence of serious disease is equivocal. Two design factors may account for the discrepancies in reported findings on the effects of coffee drinking: (a) imprecision of measurement and (b) confounding variables. A study of 2,714 white U.S. adults disclosed that, of 32 risk factors analyzed by linear and logistic regression, only sex and cigarette smoking were found to be important potential confounders of caffeine and coffee intake. Partial R2 values of the other 30 risk factors were relatively small and were inconsistent for each sex. It is unlikely that any of these factors could explain any of the reported associations between caffeine or coffee consumption and certain diseases. However, certain weak associations with caffeine or coffee intake should be included in the study design when they are known to be risk factors of a disease under investigation. These factors for men are dietary fat intake, vitamin C intake, and body mass index; and for women are vitamin use, alcohol intake, stress, and perceived health status.     

Effect of the amount of body fat on the age-associated increase in serum cholesterol

This study investigates the contribution of body fat stores on the age-associated increase in serum cholesterol and triglyceride levels. Percentage of body fat was measured by hydrostatic weighing, and serum cholesterol, triglyceride, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol levels were determined in a sample of 472 healthy men and women ages 18-50 years. In both sexes, body fat mass was significantly correlated with serum cholesterol (r = 0.21 in men and r = 0.24 in women, P less than 0.01) and triglyceride (r = 0.33 in men and r = 0.24 in women, P less than 0.01) levels. After adjustment for the association between age and serum cholesterol, no correlation was observed between body fat mass and serum cholesterol (r = 0.01 in men and r = 0.09 in women). After correction for age, serum triglyceride levels remained significantly correlated with body fat mass (r = 0.26 and r = 0.17 in men and women, respectively, P less than 0.05). As body fat also increases with age, the possibility that a partial correlation coefficient procedure eliminated a portion of the age effect mediated by an age-related increase in fat, was addressed by performing further analyses. Within each sex subsample two sets of analyses were performed on (a) three groups of subjects individually paired for age but with different levels of body fat stores, and (b) three groups of subjects paired for the amount of body fat but differing in age.(ABSTRACT TRUNCATED AT 250 WORDS)     

Relation between energy expenditure and body composition in man: specific energy expenditure in vivo of fat and fat-free tissue

The relationship between energy expenditure and body composition, in terms of fat and fat-free masses, has previously been described by a variety of predictive regression equations with parameters devoid of physiological content. We present here results obtained by calculating the specific energy expenditure, ie, the energy expenditure per unit of mass, of fat and fat-free tissue on the basis of measurements of the total energy expenditure (EE), the masses of fat (FM), and fat-free (FFM) tissue using the following simple model: EE = k1.FM + k2.FFM where k1 and k2 are the specific energy expenditures of fat and fat-free tissue, respectively. The results of observations on 104 women at rest yielded values for k1 and k2 of 0.31 and 1.35 watts/kg of fat and fat-free mass, respectively, with standard errors of estimate of 0.074 and 0.052 watts/kg, respectively. Analysis of several series of measurements, from other sources and on smaller samples of subjects, yielded similar values at rest but with larger standard errors of estimate. Data from subjects performing varying amounts of work in 24-h measurements showed, as expected, larger values for both tissues. The results explain to a very large extent the well-established relation between resting metabolic rate and body weight, ie, a linear relation with a non-zero intercept. The results also offer a clear-cut explanation for the well known difference in energy expenditure between men and women with the same body weight.     

Reevaluation of procarbazine for the treatment of recurrent malignant central nervous system tumors

Ninety-nine patients with primary recurrent malignant tumors of the central nervous system were treated with procarbazine as a single agent. Procarbazine was not given as a specified protocol, but for patients who were ineligible or refused other protocols. All patients had been treated previously with radiotherapy and 96 patients had also received previous chemotherapy. Twenty-five patients were treated at the first progression of their tumor, 47 were treated at the second progression, and 27 were treated at the third progression of their tumor. For the aggregate, the response plus stabilization rate was 27% for glioblastoma multiforme with median time to tumor progression of 30 weeks, and 28% for other anaplastic gliomas with a median time to tumor progression of 49 weeks. With respect to the percent of patients who responded or stabilized to treatment, these results are inferior to those reported previously for patients treated with procarbazine at recurrence. With respect to duration of response and stabilization, the data are comparable.     

The origin and nature of stromal osteoclast-like multinucleated giant cells in breast carcinoma: implications for tumour osteolysis and macrophage biology

The origin and nature of osteoclast-like multinucleated giant cells (OMGCs), in extraskeletal neoplasms, is uncertain. The ultrastructure, antigenic phenotype and function of OMGCsm in a breast carcinoma were studied in order to clarify the relationship between OMGCs, osteoclasts and other cells of the mononuclear phagocyte system (MPS). OMGCs resorbed cortical bone in a manner similar to osteoclasts. However, unlike osteoclasts, OMGCs did not possess a ruffled border or clear zone, and expressed HLA-DR and Fc receptors and CD14, CD16, CD18 and CD11 (p150,95) antigens. In addition, OMGCs failed to respond morphologically to calcitonin and were directly stimulated by parathyroid hormone (PTH) to increase bone resorption. These findings suggest that OMGCs are a specific type of macrophage polykaryon distinct from both osteoclasts and other types of inflammatory polykaryon. Occasional smaller (20-25 microns) macrophage-like cells were also associated with resorption pits. Bone resorption by OMGCs isolated from the breast indicates that a cell of the MPS can be transplanted to a new tissue location and perform a highly specialised function appropriate to an MPS cell of that tissue (i.e. the osteoclast). PTH stimulation of bone resorption by OMGCs suggests that PTH or a PTH-like protein, may be involved in the bone resorption and consequent hypercalcaemia associated with metastatic breast cancer.