Use of unconventional therapies by children with cancer at an urban medical center

PURPOSE: The aim of this study was to determine the prevalence, modalities, and determinants of use of unconventional therapies among children with cancer receiving conventional treatment at an urban academic medical center in the United States. PATIENTS AND METHODS: We interviewed the parents of patients and/or patients who were receiving or had received conventional therapy for treatment of childhood cancer. Of 78 patients/ parents asked, 75 consented to the interview, which included demographic factors, life events, and use of unconventional therapies. All participants also consented to the abstraction of chart data for this study. RESULTS: Overall, 84% of respondents reported the use of one or more unconventional therapies. The most commonly used modalities were changes in diet, nutritional and herbal agents, and mind/body treatments. Most users had tried more than one unconventional modality. No difference in use was seen by cancer diagnosis, race/ethnicity, socio-economic status, or educational attainment of the respondent. Of the therapies used, 50% were not reported to the physicians. Of patients reporting use of an unconventional approach, 85% were concurrently enrolled on clinical trials for primary treatment of their cancer. CONCLUSIONS: The use of unconventional therapies is highly prevalent among children with cancer and is not associated with demographic or clinical factors or participation in clinical trials. The possibility that an unconventional treatment may interact with a protocol treatment underscores the need for more information about the use of such therapies among all patients.     

Dissolution behaviour of nalidixic acid solid dispersions using water soluble dispersion carriers

The oral bioavailability of nalidixic acid (NA) is low due to its poor solubility and slow dissolution. Solid dispersions of NA containing varying concentrations of polyvinylpyrrolidone (PVP), beta-cyclodextrin (BCD) and sodium starch glycolate (SSG) were prepared by solvent evaporation technique in an attempt to improve dissolution rate of NA. Physical characterization of NA, physical mixtures (PM) and solid dispersions were investigated by a variety of analytical methods including scanning electron microscopy (SEM), infrared (IR) spectroscopy and powder X-ray diffraction (XRD). SEM was useful in the verification of possible nalidixic acid inclusion in the dispersion system by studying its surface and shape characteristics of different samples. IR analysis demonstrated no strong interaction between the drug and the carrier exists in the solid dispersions. The degree of crystallinity of nalidixic acid decreased and also differed with the dispersion systems of different carriers. Disolution studies indicated that the dissolution rate and percent dissolution efficiency (DE) were significantly increased in the solid dispersions compared with drug alone. The relative potency of the carriers to enhance the dissolution rate of nalidixic acid was in the order: BCD > PVP > SSG. The dissolution rate of the drug in the solid dispersions was faster when the ration of the drug to carrier was smaller. F-test suggests that first order model may be used for explaining the kinetics of drug release from all the solid dispersion systems.     

Formation of physically stable amorphous phase of ibuprofen by solid state milling with kaolin.

Ibuprofen was milled in the solid state with kaolin (hydrated aluminium silicate) in different ratio to examine the extent of transformation from crystalline to amorphous state. The physical stability of the resultant drug was also investigated. X-ray powder diffractometry (XRD) and birefringence by Scanning Electron Microscopy (SEM) studies indicated almost complete amorphization of the drug on ball milling with kaolin at 1:2 ratio. Fourier transform infrared spectroscopy (FTIR) data showed a reduction in the absorbance of the free and the hydrogen-bonded acid carbonyl peak of carboxylic acid group accompanied by a corresponding increase in the absorbance of the carboxylate peak, indicating an acid-base reaction between the carboxylic acid containing ibuprofen and kaolin on milling. The extent of amorphization and reduction in the carbonyl peak and increase in carboxylate peak was a function of kaolin concentration in the milled powder. On storage of milled powder (at 40 degrees C and 75% RH for 10 weeks), XRD and birefringence of SEM study showed the absence of reversion to the crystalline state and FTIR data revealed continued reduction of carbonyl peak, whereas, ibuprofen converted from its crystalline acid form to amorphous salt form on milling with kaolin. Kaolin-bound state of ibuprofen was physically stable during storage. In-vitro dissolution studies revealed that percent release of ibuprofen from the kaolin co-milled powder is in the order: 1:2>1:1>1:0.5>1:0.1>milled alone ibuprofen>crystalline ibuprofen.     

Effect of pentoxifylline on the pharmacokinetics of rosiglitazone in Wistar rats

The aim of this study was to investigate the effect of pentoxifylline (PTX), an antiplatelet agent, on the pharmacokinetics of rosiglitazone (RSG) in rats. Pharmacokinetic parameters of RSG were determined in rats after oral administration (3 mg/kg/day) in the presence and absence of PTX (10 mg/kg) 3 times daily. Compared to control animals, rats pretreated with PTX for 7 days had a decrease in RSG peak plasma concentration (Cmax) of 19% with no change in the values of the area under the concentration-time curve (AUC). Alternatively, rats coadministered single-dose PTX did not show any differences from control with regard to RSG Cmax and AUC parameters. The time to peak concentration (tmax) of RSG was significantly increased in rats pretreated with PTX under both single- and multiple-dose conditions, whereas the elimination half-life (t1/2) of RSG was increased only with multiple-dose PTX pretreatment. In conclusion, the presence of PTX was found to cause a slight decrease in the oral exposure of RSG in rats. Concurrent use of PTX with RSG therefore needs to be appropriately evaluated for proper dose adjustments in humans.     

Role of the lateral septal noradrenergic system in the elaboration of male sexual behavior in rats

The study was aimed at investigating the possible involvement of noradrenergic mechanisms in the lateral septum (LS) for elaboration of male sexual behavior in rats. In this study, norepinephrine (NE), yohimbine (YOH), isoproterenol (ISOP), propranolol (PROP), saline (SAL) and dimethyl sulfoxide (DMSO) were injected bilaterally in the LS in six different groups of sexually active male rats, and various components of sex behavior were recorded. The application of NE (3 microg) and alpha(2)-antagonist YOH (1 microg) produced a stimulation of most of the components of male sexual behavior, and there was increase in sexual arousal as well as performance. The microinfusion of nonspecific beta-agonist ISOP (2 microg) also produced a stimulation of copulatory behavior whereas beta-antagonist PROP (2 microg) produced an inhibition. The stimulation of male sexual behavior by YOH application at the LS could be due to an increased release of NE by its blocking effect on presynaptic alpha(2)-receptors. These results suggest that the noradrenergic system in the LS has stimulatory effect upon male sexual behavior, probably acting through beta-receptors.     

Use of chlorophyll fluorescence in metal-stress research: a case study with the green microalga Scenedesmus

Metal toxicity on the photosystem II (PS II) photochemistry of the green microalga Scenedesmus obliquus was investigated in vivo using a pulse-amplitude-modulated fluorometer. The results demonstrated that the test metals (copper, chromium, nickel, cadmium, and zinc) inhibited PS II photochemistry substantially, which was clearly evident for F0, Fv/Fm, qN, and qP following 12h of metal exposure, whereas Fm, Fv/2, and F0/Fv depicted significant alteration after only 1h of treatment. Thus, metals are not only found to affect the initial and maximal fluorescence, maximum quantum yield, photochemical and nonphotochemical quenching, and plastoquionone pool but the water-splitting apparatus was also significantly altered under metal stress. Among all these fluorescence characteristics, the F0/Fv registered the highest sensitivity to all the five test metals, thus indicating that the water-splitting apparatus of the oxidizing side of PS II is the primary site of action of toxic metals. This study therefore, concludes that F0/Fv ratio can be used as a powerful tool in metal-stress research.     

Sequential study of the IgA system in relapsing IgA nephropathy

Cellular and immunochemical parameters of the IgA system were studied in 15 subjects with IgA nephropathy (IgAN) and 15 agematched controls. In IgAN remission no abnormalities of the IgA system were detectable by the methods used. In IgAN relapse, [macroscopic hematuria associated with upper respiratory tract infection (URTI) (N = 6)] there were rises in IgA-bearing B-lymphocytes (three of six), T helper/suppressor cell ratio (six of six) and pokeweed mitogen-induced IgA production (four of six). Total serum and salivary IgA were unchanged. Serum IgA profile (HPLC-ELISA) showed increases in polymer IgA (three of six). No such changes were found during URTI in controls. These findings support the view that an exaggerated IgA response to mucosal antigen challenge initiates glomerular damage and hematuria in IgAN.