Maintenance chlorambucil after CVP in the management of advanced stage, low-grade histologic type non-Hodgkin's lymphoma. A randomized prospective study with an assessment of prognostic factors

One hundred sixty-two patients with Stages III and IV non-Hodgkin's lymphoma of low-grade histologic type were treated with combination chemotherapy using cyclophosphamide, vincristine, and prednisolone (CVP) followed by radiotherapy to sites of previous bulk disease. The patients were randomized to receive either follow-up alone or "maintenance" chemotherapy with 2 years of intermittent chlorambucil. A complete remission was obtained in 56% of patients and the median survival was 64 months (median follow-up, 74 months). Multivariate analysis revealed stage (P less than 0.0001) and Karnofsky performance status (P = 0.021) to predict complete response (CR) and the achievement of a CR (P less than 0.0001), female sex (P = 0.008), the absence of bulk disease (P = 0.038) and low serum alkaline phosphatase (P = 0.002) to predict prolonged survival. The median relapse-free survival (RFS) of the complete responders was 41 months. A prolonged RFS was predicted by low stage (P = 0.014), low serum lactic dehydrogenase (LDH) (P = 0.045) levels, and by the administration of maintenance chlorambucil (P = 0.045). A prolonged survival of the complete responders was predicted by a low number of nodal sites of involvement with lymphoma at presentation (P = 0.022) and lack of liver involvement (P = 0.011). The administration of oral maintenance therapy with chlorambucil for a full 2 years was only possible in 38% of patients, mainly because of progression of disease and the induction of thrombocytopaenia, but despite this it prolonged the median RFS by 38 months and its use could be considered when future studies are being designed.     

Physical characteristics related to coronary heart disease risk factors: comparison of hispanics and navajo, acoma and laguna indians in new Mexico

Abstract The Checkerboard Cardiovascular Curriculum (CCC) project was designed to develop a culturally-oriented educational program for reducing coronary heart disease (CHD) risk factors in rural American Indians and Hispanics in the state of New Mexico. Because so little information is available on children from these ethnic groups, the purposes of this paper are: 1) to describe and compare some physical characteristics of Hispanics and Navajo, Laguna and Acoma Indians which are associated with CHD risk factors; and 2) to assess the short-term effectiveness of the CCC in altering these CHD risk factors. Body weight, height, blood pressure, one mile walk/run data, and triceps, subscapula, and calf skinfold thicknesses were collected for 97 boys and 79 girls from the four ethnic groups. Results of analyses of covariance (ANCOVA), controlling for age, indicated ethnic differences for all dependent variables. The average body mass index of all Indian children exceeded the median values reported in the second National Health and Nutrition Examination Survey (NHANES-II). The average sum of the triceps and subscapula skinfolds of the children from all ethnic groups failed to meet acceptable standards established by The National Children and Youth Fitness Study (NCYFS). The results of the CCC project suggest that these children are in need of health promotion and physical fitness programs that emphasize obesity and cardiovascular fitness and provide for ethnic and cultural differences.     

The Total Life Concept Transplanted from AT&T to Sandia National Laboratories

Abstract This study illustrates how the Total Life Concept (TLC) program originated by AT&T was successfully transplanted to another work site, Sandia National Laboratories. Demographics of the participants at A T&T and Sandia differ and make comparisons difficult, but it is possible to assess program impact in terms of participation rates for each program. The original AT&T TLC pilot study had three major components: orientation, testing, and risk interpretation; lifestyle-improvement courses; and activities to promote health. Sandia kept the three major components of the AT&T TLC concept and made some modifications to meet Sandia's needs. Sandia's experience of adopting a model program and tailoring it to local needs worked well, demonstrating that an existing model can be successfully altered to meet the needs of different companies in varied settings.     

Phosphodiesterase isozyme inhibition, activation of the cAMP system, and positive inotropy mediated by milrinone in isolated guinea pig cardiac muscle

The purpose of the present study was to examine the interrelationships among phosphodiesterase (PDE) isozyme inhibition, cAMP formation, activation of cAMP-dependent protein kinase (cAPK), and positive inotropy in isolated guinea pig cardiac muscle mediated by the cardiotonic/vasodilator agent, milrinone. Milrinone was a potent and selective inhibitor of the "low Km" cAMP PDE isozyme (peak III) isolated by diethylaminoethyl ether cellulose chromatography, with IC50 values of 0.7 microM for peak III PDE and 100 microM for peak I PDE. In isolated papillary muscles frozen at peak inotropic responses, positive and significant correlations were evident between isometric force development as a function of cAMP content (r = 0.72, p less than 0.05) or cAPK activity ratio, an index of activation of cAPK (r = 0.79, p less than 0.001), for concentrations of milrinone from 0.1-1000 microM. Similar correlations were evident in muscles frozen at peak inotropic responses for the beta-adrenoreceptor agonist isoproterenol (r = 0.96, p less than 0.001; r = 0.98, p less than 0.001, respectively), but not for ouabain or Bay K-8644. The temporal sequence of these events was also quantitated for concentrations of milrinone (100 microM) and isoproterenol (3 nM) that produced approximately a 100% increase in isometric force. Whereas early time interval of force development (30 s, 1 min, isoproterenol; 30 s milrinone) were not accompanied by significant increases in either cAMP content or cAPK activity ratio, peak increases in force development for both isoproterenol (2 min) and milrinone (1 min) were related to peak increases in cAPK activity ratios. In summary, these results show that significant increases in cAMP content or cAPK activation are correlated with positive inotropy in isolated guinea pig papillary muscles with milrinone. These correlations occur at concentrations of milrinone that inhibit cardiac PDE isozymes and are similar to the known cAMP-dependent cardiostimulant isoproterenol. These data support the hypothesis that selective PDE isozyme inhibition is a mechanism by which milrinone effects positive inotropy.     

Initial results of a phase I trial of continuous infusion SR 2508 (etanidazole): a radiation therapy oncology group study

To exploit both the oxygen-mimetic and "pre-incubation" or continuous exposure effects of the 2-nitroimidazole radiosensitizers, we are conducting a Phase I trial of continuous infusion SR 2508 for patients receiving brachytherapy. Following the administration of a loading dose of 2 g/m2, SR 2508 is administered by continuous infusion for 48 hr. Twenty-one patients have completed treatment. The initial total dose was 8 g/m2 with patients currently receiving 15 g/m2. No toxicity has been observed. At the higher doses the steady-state plasma concentrations have been between 50 and 70 micrograms/ml. It is not yet known whether or not hypoxic sensitizers will be of benefit clinically, and if so, when during a course of treatment is the optimal time to use them. Given the lack of toxicity and plasma concentrations achievable with continuous infusion, future studies will be conducted using SR 2508 during both the external beam and brachytherapy aspects of treatment.     

Mosaic ring 12p and total anomalous pulmonary venous return

An infant born with total anomalous pulmonary venous return (TAPVR) was found to have an extra chromosome present as a small ring. Spectral karyotyping and FISH analysis identified the material as a duplication involving the short arm of chromosome 12. Previous cases describing a variety of cytogenetic abnormalities that have been associated with TAPVR are reviewed along with prior cases of duplication 12p with their associated findings. We believe ours is the first case to report the occurrence of mosaic ring 12p and its association with TAPVR.     

Propionyl coenzyme A carboxylase deficiency presenting as non-ketotic hyperglycinaemia.

A 4-month-old girl presented with myoclonic seizures and an electroencephalogram showing hypsarrhythmia. Hyperglycinuria and a cerebrospinal fluid to plasma glycine ratio of 0.2 suggested the diagnosis of non-ketotic hyperglycinaemia. Propionic acid and methyl citric acid were present in the urine, and propionyl coenzyme A carboxylase was deficient in leucocytes and fibroblasts. The ketotic and non-ketotic hyperglycinaemias cannot be differentiated by CSF: plasma glycine ratios.     

Molecular approach to the epidemiology of swine vesicular disease: correlation of variation in the virus structural polypeptides with serological properties.

Variation has been observed in the structural polypeptides of swine vesicular disease viruses isolated from the United Kingdom and Hong Kong. Despite the limited number of isolates examined, several distinct polypeptide patterns were obtained when the virus structural proteins were examined by polyacrylamide gel electrophoresis. Isolates from outbreaks in the United Kingdom which were known to be connected gave the same polypeptide pattern, whereas viruses with different polypeptide patterns could not be traced to a common source. The different polypeptide patterns were obtained consistently and were not altered by passage of the virus in tissue culture. In general, isolates with identical polypeptide patterns could not be distinguished by neutralization or antibody blocking tests or by competition radioimmunoassays. However, isolates with different polypeptide patterns could be differentiated by antibody blocking tests or radioimmunoassay. The correlation between the serological tests and the polyacrylamide gel electrophoresis analyses illustrates the value of analyzing structural polypeptides in the epidemiological study of swine vesicular disease.