Diffuse esophageal leiomyomatosis.

Progressive dysphagia of unknown etiology may still provide a diagnostic challenge despite an increase in the number and quality of investigations available. We describe a 64-year-old man who presented with progressive dysphagia and weight loss. Following a number of investigations, a diagnosis of diffuse esophageal leiomyomatosis was made and the patient was treated appropriately.

Bimolecular DNA triplexes: duplex extensions show implications for H-form DNA stability.

H-form DNA has recently been shown to be biologically relevant by its involvement in the process of homologous recombination [Kohwi, Y. , and Panchenko, Y. (1993) Genes Dev. 7, 1766-1778]. A bimolecular DNA triple-stranded structure (triplex) is central to the formation of H-form DNA. Understanding the formation and factors governing the stability of such bimolecular triplexes is necessary to fully elucidate the structure/function relationship of H-form DNA. In this study, we extend known information on bimolecular triplexes by examining the effect of a variable CNC base triad (where N = A, C, T, or G) on a 10 base triad triplex that mimics the triplex motif in H-form DNA. We also examine the effect that a duplex extension of four base pairs has on triplex stability and selectivity for the base N. Results from thermal denaturation experiments indicate that the fully complementary triplex is more stable than its duplex counterpart (DeltaTm = 13 degrees C) and is resistant to degradation by bovine spleen phosphodiesterase for at least 24 h at 10 degrees C. A single-base mismatch in the purine strand of the triplex structure is destabilizing (DeltaTm = approximately 20 degrees C), and all structures containing a mismatch were readily degraded by bovine spleen phosphodiesterase. An extension of four duplex base pairs onto the triplex structure affects the stability of the DNA complex and may have implications relevant to H-form DNA.

Desmoplastic small round-cell tumor: prolonged progression-free survival with aggressive multimodality therapy.

PURPOSE: To test intensive alkylator-based therapy in desmoplastic small round-cell tumor (DSRCT). PATIENTS AND METHODS: Patients received the P6 protocol, which has seven courses of chemotherapy. Courses 1, 2, 3, and 6 included cyclophosphamide 4,200 mg/m2, doxorubicin 75 mg/m2, and vincristine (HD-CAV). Courses 4, 5, and 7 consisted of ifosfamide 9 g/m2 and etoposide 500 mg/m2 for previously untreated patients, or ifosfamide 12 g/m2 and etoposide 1,000 mg/m2 for previously treated patients. Courses started after neutrophil counts reached 500/microL and platelet counts reached 100,000/microL. Tumor resection was attempted. Post-P6 treatment options included radiotherapy and a myeloablative regimen of thiotepa (900 mg/m2) plus carboplatin (1,500 mg/m2), with stem-cell rescue. RESULTS: Ten previously untreated and two previously treated patients have completed therapy. The male-to-female ratio was 11:1. Ages were 7 to 22 years (median, 14). The largest masses were infradiaphragmatic (n = 11) or intrathoracic (n = 1). Other findings included serosal implants (n = 11), regional lymph node invasion (n = 8), ascites or pleural effusion (n = 7), and metastases to liver (n = 5), lungs (n = 4), distant lymph nodes (n = 3), spleen (n = 2), and skeleton (n = 2). Tumors uniformly responded to HD-CAV, but there were no complete pathologic responses. One patient died at 1 month from tumor-related Budd-Chiari syndrome. Of seven patients who achieved a complete remission (CR), five remain in CR 9, 12, 13, 33, and 38 months from the start of P6, one patient died of infection at 12 months (autopsy-confirmed CR), and one patient relapsed 4 months off therapy. Of four patients who achieved a partial remission (PR), one remains progression-free at 34 months and three developed progressive disease. Five patients received local radiotherapy: three were not assessable for response, but in two patients, antitumor effect was evident. Four patients received thiotepa/carboplatin: two were in CR and remain so, and two patients had measurable disease that did not respond. CONCLUSION: For control of DSRCT, our experience supports intensive use of HD-CAV, aggressive surgery to resect visible disease, radiotherapy to high-risk sites, and myeloablative chemotherapy with stem-cell rescue in selected cases.

Ara-C treatment leads to differentiation and reverses the transformed phenotype in a human rhabdomyosarcoma cell line.

Rhabdomyosarcoma (RMS) is an embryonal tumor of childhood that arises from primitive skeletal muscle-forming cells (rhabdomyoblasts) probably arrested and transformed along the normal myogenic pathway to maturation. Since Ara-C is an antitumor agent known to induce differentiation in human acute myelogenous leukemia, also presumably a disorder of cellular maturation, we treated RD, a human embryonal RMS cell line, with Ara-C and evaluated its effect on growth and differentiation. Ara-C treatment of RD cells in vitro caused a dose-dependent growth inhibition in the absence of cytotoxicity. Interestingly, RD cells treated with 5 x 10(-7) M Ara-C for 4 days were able to recover logarithmic growth after the removal of the drug from the media. A reexposure of these cells to Ara-C led to morphological and biochemical changes related to differentiation, including the appearance of an increased number of multinucleated cells that expressed muscle-specific actin and skeletal muscle myosin heavy chain (MHC) (fast). In vivo studies demonstrated that RD cells pretreated with 5 x 10(-7) M Ara-C lost their ability to form tumors in nude mice. We conclude that treatment of this human embryonal RMS cell line with Ara-C results in marked growth inhibition in vitro, loss of tumorigenicity in vivo, and the expression of biochemical markers present in a more differentiated phenotype. These data suggest a potential role for differentiation therapy as a therapeutic approach in RMS.

Frequency and diversity of p53 mutations in childhood rhabdomyosarcoma.

The p53 gene was examined in primary or metastatic tumors from six patients with rhabdomyosarcoma (RMS) and in five RMS cell lines by screening methods including single-strand conformation polymorphism analysis, the RNase protection assay, sequencing of complementary DNA subclones, and Southern blotting. Six original tumors were of embryonal histology, four alveolar, and one mixed. p53 mutations were identified in four of the six tumors or cell lines derived from tumors with embryonal histology and in one of the four with alveolar histology. Consistent with p53 allele loss, each mutation was found in the homo- or hemizygous state. One tumor showed a G to C transversion at p53 codon 213 (arginine to proline), and another showed deletion of the entire gene. The p53 mutations in cell lines included a codon 248 C to T transition (arginine to tryptophan) in RD and a codon 280 A to T transversion (arginine to serine) in RH30. The cell line CTR contained a 4-base pair deletion at codons 219/220 in exon 6 with resultant frame shift and premature termination in exon 7. These data support the role of diverse types of p53 mutations in the pathogenesis and/or progression of a significant proportion of cases of childhood RMS.

All-trans-retinoic acid inhibits the growth of human rhabdomyosarcoma cell lines.

We have been evaluating the role of all-trans-retinoic acid (RA) in the differentiation and growth of human rhabdomyosarcoma (RMS) cell lines. Treatment of both embryonal (RD) and alveolar (RH30) human RMS cell lines with all-trans-RA resulted in a dose-dependent inhibition of cell growth with a maximal inhibition of 92 and 66%, respectively, at 5 x 10(-6) M. When 13-cis-RA was used under identical experimental conditions, maximal growth inhibition was 41 and 37%, respectively. This stereo-specific growth inhibition was not associated with morphological or biochemical evidence of myogenic differentiation. Furthermore, all-trans-RA demonstrated no evidence of competition with binding of insulin-like growth factor II (IGF-II), an autocrine growth factor in RMS, to its membrane receptor as evaluated by an [125I]IGF-I-receptor-binding assay. Attempts to rescue all-trans-RA growth-inhibited RMS cells with exogenous IGF-II resulted in no increase in growth compared to cells treated with all-trans-RA alone. We conclude that RA inhibits the growth of human RMS cell lines in a dose-dependent, stereo-specific manner, is not associated with differentiation, and does not appear to be directly related to IGF-II.

Physiologic monitoring of combat casualties.

We discuss general concepts and organization of combat casualty care. We identify important issues regarding physiologic monitoring of combat casualties and examine inherent limitations of this monitoring. Effective and practical techniques for monitoring the cardiovascular, pulmonary, central nervous, renal, and coagulation systems are presented in detail.

The treatment of tranquilizer dependence by propranolol.

Forty four subjects were treated for benzodiazepine dependence. The withdrawal programme lasted for 10 weeks and included regular group support sessions. Patients were also treated with either propranolol, placebo or "no pill" under double blind conditions. Twenty three patients complied with the full treatment regimen and completed the trial. The outcome of treatment was moderately successful, with 8 out of the 23 patients stopping their tranquilizers and a further 11 achieving a reduction of 50% or more of their original benzodiazepine dose. Tranquilizer dependence is a difficult condition to treat, but preliminary results suggest that propranolol is helpful in reducing the symptoms of benzodiazepine withdrawal.

Benzodiazepine dependent patients and their psychological treatment.

1. 91 patients were referred to a tranquilizer withdrawal clinic. 44 of these entered a withdrawal programme. The characteristics of the patients are described. 2. 72% of patients accepted for benzodiazepine withdrawal had a history of previous psychiatric contact. They also had significantly higher scores on S.T.A.I. than control groups of non-psychotic psychiatric out-patients indicating a considerable psychiatric morbidity prior to withdrawal. 3. 12 patients were treated with psychological group therapy using anxiety management techniques. The outcome of this pilot study showed that 50% of subjects were able to discontinue their benzodiazepines despite previous failures. 4. Patients found learning to cope with symptoms, sharing problems with others and learning to change thoughts the most useful components of the anxiety management package during withdrawal.

Terpenes of ponderosa pine and feeding preferences by pocket gophers.

Yield and composition of essential oils were compared in foliage, stems, and roots of ponderosa pine seedlings, and preferences for the trees by pocket gophers were determined. Test seedlings represented nine widely separated provenances in the western United States. Seed source of the trees influenced gopher feeding preferences and resulted in varied tree damage. The damage ranged from 0 to 31%, suggesting that some sources might possess sufficient natural resistance to give trees practical protection from gophers in the field. There were no morphological differences among sources to explain differential tree damage. All sources contained essential oils in all tissues examined, but oil yield varied among and within tissue types. Oils were predominantly (76-97%) composed of monoterpene hydrocarbons. Oil composition varied by source, and different tissue types varied greatly in the yield and composition of their oils. Neither yield nor constituents of foliage oils were significantly correlated with gopher damage (or preference). In contrast, some components of stem and root oils were strongly related to preference. Results of correlation and discriminant analyses showed that some oil constituents could serve as indicators of resistance (or susceptibility) to gopher damage. Such important chemical variables, when verified, could be used in selections for ponderosa pine resistant to gophers.