Antineuroblastoma activity of desferoxamine in human cell lines

That ferritin, an iron storage protein, can be produced by neuroblastoma cells raises the possibility that iron may have some role in promoting tumor cell growth. To explore this possibility, we studied the effects of desferoxamine, a compound which chelates iron, on viability of CHP 126 and CHP 100, two human neuroblastoma cell lines. Cells (5 X 10(4)) were incubated with graded amounts of desferoxamine or ferrioxamine, an iron-saturated analogue of desferoxamine. Within 5 days of exposure to 60 microM desferoxamine, approximately 90% of cells from each of these cell lines were dead. This effect was dose dependent, was not seen with ferrioxamine, and could be prevented by coincubation with greater than stoichiometric amounts of ferric citrate. As determined by binding of OK-T9, desferoxamine also resulted in increased expression of receptors for transferrin, an iron transport protein. Desferoxamine had only minimal effects on viability of several non-neuroblastoma cell lines. These results suggest that iron is required for growth of neuroblastoma and that desferoxamine has potent, specific, antineuroblastoma activity in vitro.     

Effect of different levels of oral pyridoxine supplementation on plasma pyridoxal-5'-phosphate and pyridoxal levels and urinary vitamin B-6 excretion

Plasma pyridoxal-5'-phosphate and pyridoxal levels increased significantly (p less than 0.05) when single, oral bolus doses of pyridoxine were increased from 10 to 25 and from 25 to 50 mg in nine female volunteers. However, when the dose was increased to 100 mg, plasma pyridoxal-5'-phosphate levels did not differ significantly from those recorded after the 50 mg dose. Within 3 h plasma pyridoxal levels rose with a factor of 3.85 compared with the 50 mg dose but high pyridoxal levels were eliminated from the circulation. Renal clearance of pyridoxal remained a constant, low percentage (less than 2.0%) of each pyridoxine supplement in spite of the observed very high circulating pyridoxal levels. Pyridoxine supplementation is discussed in relation to circulating pyridoxal-5'-phosphate and pyridoxal availability for cellular metabolism.     

Therapeutic potential of choline magnesium trisalicylate as an alternative to aspirin for patients with bleeding tendencies

We have compared the effects of acetyl salicylic acid (ASA, aspirin) and choline magnesium trisalicylate (CMT), a non-acetylated salicylate product, on platelet aggregation in human whole blood ex-vivo. Using a whole blood platelet counter, platelet aggregation was quantified by measuring the fall in the number of single platelets at peak aggregation in response to collagen, arachidonic acid (AA), as well as spontaneous aggregation. In double blind and random order, 12 healthy volunteers received, on two separate occasions 10 days apart, a single oral dose of 652 mg ASA or 655 mg CMT. Despite a comparable absorption of salicylic acid from the two drugs, ingestion of ASA resulted in a marked inhibition of platelet aggregation induced by collagen (p less than 0.005), AA (p less than 0.01) and spontaneous aggregation (p less than 0.01), whereas such effects were not observed after CMT ingestion. We suggest that CMT may have therapeutic potential as an alternative to aspirin when inhibition of platelet aggregation can induce bleeding complications.     

Ileoanal reservoir for ulcerative colitis and familial polyposis

Although total proctocolectomy with permanent ileostomy is regarded as the definitive therapy for ulcerative colitis and familial polyposis, psychologic and physical complications with this operation have stimulated the development of the operation of total abdominal colectomy, mucosal proctectomy, ileal reservoir, and ileoanal anastomosis as an alternative surgical procedure. Since 1980, 104 of these operative procedures have been completed with no operative mortality; experience has been gained with both the J- and S-type reservoirs. Despite an appreciable number of postoperative complications, satisfactory function of the reservoir has been achieved in 86 of 91 patients followed up for at least three months after closure of the ileostomy. The remaining five patients have required reinstitution of fecal diversion. Functional results have not differed between two-limbed and three-limbed reservoirs. This operation must be considered a viable alternative in patients with ulcerative colitis and familial polyposis.     

Maintaining family planning acceptance levels through development incentives in Northeastern Thailand

The results of a two-year longitudinal study of the effect that development program incentives have upon family planning in Northeastern Thailand are presented. These incentives, implemented by the Population and Community Development Association, Thailand, included animal raising and agricultural, home industry, and environmental activities. An experimental design including baseline and follow-up surveys supplemented by a continuous monitoring system was utilized to test hypotheses on the family planning impacts of the incentives. Findings indicate that the incentives contributed significantly to the maintenance of high levels of family planning practice through the program period 1982-1984.     

The simultaneous determination of chloroformates and phosgene at low concentrations in air using a solid sorbent sampling--gas chromatographic procedure

A method was developed for the simultaneous determination of a number of reactive chloroformates and phosgene in air at low concentration levels. The procedure utilized the collection of air containing these contaminants on a di-n-butylamine-coated solid adsorbent. After samples were taken, the carbamate and urea derivatives were desorbed with hexane, washed with 1N HCl and analyzed by gas chromatography with flame ionization detection. The procedure provided an accurate exposure level for each of the desired compounds on a time-weighted average basis. Average recovery efficiencies ranged from 98% to 106%, with an average detection limit of 0.7 micrograms or 0.08 ppm v/v in 1.5 L of air. More recent tests have extended the use of the technique to include carboxylic acid chlorides--specifically, pivalic acid chloride and 3-chloropivalic acid chloride. The average recovery efficiency for these compounds was 69%.     

Design of clinical trials for chronic diseases: implications for periodontal disease

In order to make effective use of the statistical theory of design of clinical trials for chronic diseases such as periodontal disease, certain issues must be considered. Any clinical trial requires that the disease definition be well-specified; that patient eligibility be explicit; that the observation times be explicit; that the duration and endpoint of therapy be specified; that the duration of subsequent followup observation be specified; and that the unit of observation (e.g., tooth, set of teeth, patient) be defined. In a chronic disease, the potential biases that can readily be introduced by self-selection of patients who enter the trial and/or who return for subsequent observation become more important, because subjects are required to remain on treatment and/or observation for prolonged periods. Further, the cyclical nature of some chronic diseases may require special attention to baseline definitions of active disease and disease outcome. These issues are illustrated with examples from clinical trials of hypertension, breast cancer screening, and Polycythemia Vera. Implications for periodontal disease are discussed.