Metastatic tumors of the mandibular condyle. Review of the literature and report of a case

A metastatic tumor involving the mandibular condyle presented symptoms of temporomandibular joint (TMJ) dysfunction. Positive identification of the primary malignant lesion as prostatic adenocarcinoma was accomplished through the use of immunohistochemical stains for prostate-specific antigen and subsequent prostate biopsy. A review of the literature revealed fifteen additional cases of metastatic lesions of the mandibular condyle, seven of which also demonstrated TMJ-related symptoms as the initial manifestation of malignant disease. Such cases represent a diagnostic challenge, both clinically and microscopically. Symptoms of TMJ dysfunction coupled with radiographic evidence of a destructive lesion or pathologic fracture should suggest a possible malignant process indicating the need for biopsy. Subsequent examination of routine sections in combination with the use of selected stains, including immunohistochemistry may be helpful in identification of the primary tumor site.     

Signalling Pathways Mediating Secretory and Mitogenic Responses to Galanin and Pituitary Adenylate Cyclase-Activating Polypeptide in the 235-1 Clonal Rat Lactotroph Cell Line

The neuropeptides galanin and pituitary adenylate cyclase-activating peptide (PACAP) have been implicated in the physiological regulation of lactotroph function. Using the 235-1 clonal lactotroph rat cell line we have studied the signalling pathways mediating the secretory and mitogenic responses to galanin and PACAP. Both peptides stimulated prolactin release to a similar maximal extent. PACAP (100  nM) stimulated an increase in the proliferation rate of 235-1 cells, but was significantly less effective than 100  nM galanin (161.8±2.3% vs 296.1±9.1% of control). PACAP stimulated cAMP accumulation with an ED₅₀ of 3.2  nM, and a maximal effect of almost two-fold at a concentration of 100  nM. Galanin depleted cAMP, by 30% at a concentration of 100  nM. The aminosteroid phospholipase C (PLC) inhibitor U-73122 virtually abolished maximal peptide stimulated prolactin release. Depletion of inositol phosphates or downregulation of protein kinase C reduced maximal peptide stimulated prolactin release from about 260% to about 160% of unstimulated release. Both peptides at a concentration of 100  nM caused a sustained increase in intracellular calcium when incubated with cells for 30  min. These results demonstrate that both peptides stimulate prolactin release and the proliferation rate of 235-1 cells. The most important signalling pathway for prolactin release activated by both peptides is via PLC, although they also regulate cAMP levels, which are increased by PACAP and decreased by galanin. Despite maximal peptide stimulated prolactin release being equal, galanin has a greater mitogenic effect on 235-1 cells than PACAP, raising the possibility that it activates an additional mitogenic signalling pathway.     

Lung cancer in women. Lahey Clinic experience, 1957-1980

The incidence of lung cancer is increasing dramatically worldwide. Cancer of the lung, the number one cause of death from cancer in men in the United States, will soon surpass breast cancer to become the most frequent cause of cancer death in women. To detail the changing pattern of lung cancer, we reviewed the clinical features of all 1752 patients whose lung cancer was diagnosed at the Lahey Clinic from 1957 through 1980. Women comprised a constant proportion of the total number of clinic patients during this 24-year period. Lung cancer in women increased markedly from 13% of all patients (1 to 6.8 ratio of women to men) in 1957 through 1960 to 35% (1 to 1.8 ratio) in 1977 through 1980. The authors reviewed pathologic specimens of 394 women with lung cancer. No significant change occurred in cell type distribution over the years: adenocarcinoma, 38%; epidermoid carcinoma, 20%; large cell carcinoma, 15%; small cell undifferentiated tumor, 13%; and other cell types, 14%. The incidence of all lung cancer cell types (Kreyberg Group 1 and Group 2) increased in women who smoked. Our study suggests that smoking is a major causal factor in the rising occurrence of all lung cancer cell types in women as contrasted to the preponderance of Kreyberg Group 1 tumors in men who smoke.     

Autologous bone marrow transplantation following high-dose busulfan and VP-16 for advanced non-Hodgkin's lymphoma and Hodgkin's disease

Ten patients with non-Hodgkin's lymphoma (NHL) and nine with Hodgkin's Disease (HD) received high-dose busulfan and etoposide (VP-16) prior to autologous bone marrow transplantation (ABMT). All patients with NHL and eight with HD had poor prognostic factors. Marrows from patients with NHL were purged with 4-hydroperoxy-cyclophosphamide. Busulfan (16 mg/kg body weight) was given orally over 4 days; VP-16 was administered as a single 4-h infusion. VP-16 was initiated at a dose of 60 mg/kg but reduced to 50 mg/kg after three of the first seven patients developed fatal toxicity. The 100-day regimen-related mortality was 21% (95% confidence interval 14%-46%). An absolute neutrophil count of 500/microliters was achieved at a median of 18 days in NHL and 23 days in HD. The median time to achieve a platelet count of 50,000/microliters was slower in HD (100 days) than in NHL (31 days) (p less than 0.05). Complete remissions were documented in four of nine evaluable patients with NHL and two of eight evaluable patients with HD. Actuarial survival at 18 months was 21% (95% confidence interval 3%-39%). The combination of high-dose VP-16 and busulfan as used in this study, although comparable to other regimens in efficacy, is associated with several toxicities.     

The motor effect of neuromedin U on rat stomach in vitro

A series of neuromedin U (NmU)-like peptides were found to evoke concentration-response contraction of rat fundic circular muscle in vitro. Isometric contraction of this tissue was induced by rat NmU, porcine NmU-8 and NmU-25, and frog NmU. Rat NmU was significantly more potent than frog NmU. The contractile action of rat NmU upon rat fundic strips was not affected by either atropine or tetrodotoxin indicating a direct effect. Maximal NmU-induced contractions were 10% of the maximal contraction induced by carbachol and ranged between those of the bradykinin and angiotensin II. None of the NmU peptides were active on the circular smooth muscle of the frog stomach or on the small and large intestinal longitudinal smooth muscle of either rat or frog. The results of this study demonstrate that members of the NmU peptide family all induce in vitro contraction of rat gastric circular smooth muscle independent of cholinergic or other neuronal mechanisms. Their activity, however, appears to be both tissue and species specific.     

Enteroglucagon and experimental intestinal carcinogenesis in the rat.

To assess the association between the putative intestinal trophic hormone enteroglucagon and the development of intestinal tumours, four groups of 20 rats underwent either jejunal transection or 20%, 50%, or 80% proximal small bowel resection. Tumours were induced with azoxymethane 10 mg/kg weekly for 12 weeks. At 26 weeks there was a promotion of colonic neoplasia from a median of 0.5 (range 0-3) per rat in the transection group to 1.0 (0-3) in the 50% resected group (p less than 0.01) but no significant promotion in the 80% resection group. In the small bowel, increasing resection resulted in a progressive promotion of tumours from a median of 1.0 (range 0-3) per rat in the transection group to 2.0 (0-5) in the 50% resection group (p less than 0.001) and 3.0 (0-11) in the 80% group (p less than 0.01). Plasma enteroglucagon was measured at 2, 16, and 26 weeks and was raised seven-fold in the 80% resected group (p less than 0.001). There was a significant correlation between enteroglucagon concentrations and number of duodenal tumours but not colonic tumours. Crypt cell production rate in the duodenum increased from 11.5 +/- 1.9 to 29.2 +/- 1.4 cells/crypt/h in the 80% resected group (p less than 0.001) and showed a close correlation with both enteroglucagon levels and tumour promotion in the small bowel. There were no changes in crypt cell production rate in the colon with resection. This study shows a close association between enteroglucagon concentrations, promotion of tumours and crypt cell production rate in the duodenum but not in the colon.     

Toward a technology in primary prevention: Educational strategies and tactics

The coming major task of primary prevention is to inform people about what works, what will prevent problems and promote desired potentials. This will be the task of educational technology, converying those tested packages of effective methods for achieving specified social ends. This paper explores the nature of this preventive/promotive technology. Examples of primary prevention programs illustrating the various issues in such a technology are given. A model for educational technology is provided: the application of systematic procedures that can be employed in concert to affect factors which prevent predictable problems, protect current healthy functioning, and/or promote desired potentials.     

Low grade glioma of the cerebral hemispheres in adults: a retrospective analysis of 88 cases

Eighty-eight adult patients with histologically verified cerebral low grade gliomas (grades 1 and 2) treated with post-operative radiotherapy at the Royal Marsden Hospital between 1960 and 1985 were reviewed. Survival of oligodendroglioma patients was greater than those with astrocytoma (64% vs 36% at 5 years) but the difference was less marked in the long term (35% vs 26% at 10 years). Previous studies have identified prognostic factors important in these tumors: age, extent of surgery, grade, performance status, and duration of symptoms. In this study of low grade astrocytomas and oligodendrogliomas, age (highly significant in the former and significant in the latter), extent of surgery (oligodendrogliomas), and performance status have been demonstrated as factors influencing outcome. The precise role of radiotherapy including the optimal radiation dose and timing of treatment remains unclear. The information, given by a retrospective analysis such as this, helps in the design of prospective, randomized studies looking at radiation dose and time of surgical and radiotherapeutic interventions, always with careful assessment needed of quality of life and treatment morbidity.     

Recombinant BCG as a candidate oral vaccine vector

Bacille Calmette-Guerin (BCG), currently the most widely used vaccine in the world, was originally administered for many years as an oral vaccine. The low frequency of serious complications, inexpensive production, and adjuvanticity make BCG an ideal candidate for a recombinant vaccine vehicle. Although mycobacteria are slow growing and not yet well characterized genetically, we have recently developed technology for the genetic manipulation of BCG and other mycobacteria. Phage and plasmid systems based on a shuttle strategy to manipulate DNA in Escherichia coli and transfer it to mycobacteria have been developed. We have established that the aminoglycoside phosphotransferase gene can be used as an effective selectable marker in the mycobacteria and that a foreign antigen from Mycobacterium leprae can be expressed in BCG. Furthermore, a thorough analysis of mycobacterial expression sequences has been undertaken to optimize the expression of foreign antigens in BCG. We constructed an expression probe shuttle plasmid with beta-galactosidase as reporter gene, and have used it successfully to identify multiple mycobacteriophage DNA sequences with varying levels of constitutive or regulable promoter activity. Further genetic advances required for development of recombinant BCG into an effective recombinant vaccine vehicle, including possibilities for oral administration, are adumbrated.