Clinical trial of DADDS in lepromatous leprosy

Trypanosome circadian rhythms in rats infected with Trypanosoma lewisi and mice infected with T. duttoni (equals T. musculi) were observed. Peak numbers of trypanosomes were recorded at nightfall and fewest organisms seen at daybreak. Reversal of the photoperiod resulted in a comparable reversal of the trypanosome parasitaemia. Periodicities of blood glucose levels and circulating leucocytes were relatively similar in T. lewisi-infected rats to rhythms previously defined in normal aimals. In trypanosome-infected mice, circulating leucocytes had a peak at 1800 hours and were minimal at midnight. Immune serum and epinephrine apparently had opposite effects on numbers of circulating rat trypanosomes; antisera reduced and epinephrine increased the numbers. Increased motor activity appeared to induce increased parasitaemia. Results of these and other studies suggest that in diurnally active hosts, trypanosome periodicities are characterized by increasing numbers in the circulation throughout the day and reach a peak just before darkness. In nocturnally active animals a similar rhythm was observed with only a slight phase change; circulating trypanosomes increased throughout the day and were maximal soon after nocturnal onset.     

Fate of the excluded abdominal aortic aneurysm sac: long-term follow-up of 831 patients

PURPOSE: Nonresective treatment of the infrarenal abdominal aortic aneurysm by proximal and distal ligation of the aneurysm sac (exclusion) combined with aortic bypass has been previously reported. A 10-year experience with 831 patients undergoing this procedure was reviewed. METHODS: From 1984 to 1994, 831 (761 elective, 70 urgent) of 1103 patients being treated for abdominal aortic aneurysm underwent repair with the retroperitoneal exclusion technique. Perioperative morbidity and mortality, estimated blood loss, transfusion requirements, natural history of the excluded aneurysm sac, and long-term survival were all assessed. RESULTS: The operative mortality rate for patients undergoing exclusion and bypass was 3.4%. The incidence of nonfatal perioperative complications was 5.2%. Colon ischemia requiring resection occurred in 2 (0.2%) of the 831 patients. Estimated blood loss was 638 +/- 557 cc (50 to 330 cc). On follow-up 17 (2%) patients were found to have patent aneurysm sacs as detected by duplex examination. Fourteen patients required surgical intervention. No cases of graft infection or aortoenteric fistula have been noted. CONCLUSION: Retroperitoneal exclusion and bypass is a viable alternative to traditional open endoaneurysmorraphy in surgery for abdominal aortic aneurysm. Most excluded aneurysm sacs have thrombosis without any long- or short-term complications; however, in a small number of patients delayed rupture of patent aneurysm occurs, thus emphasizing the need for diligent follow-up and appropriate intervention.     

Bioavailability of selenium accumulated by selenite-reducing bacteria

The bioavailability of selenium (Se) was determined in bacterial strains that reduce selenite to red elemental Se (SeO). A laboratory strain of Bacillus subtilis and a bacterial rod isolated from soil in the vicinity of the Kesterson Reservoir, San Joaquin Valley, CA, (Microbacterium arborescens) were cultured in the presence of 1 mM sodium selenite (Na2SeO3). After harvest, the washed, lyophilized B. Subtilis and M. arborescens samples contained 2.62 and 4.23% total Se, respectively, which was shown to consist, within error, entirely of SeO. These preparations were fed to chicks as supplements to a low-Se, vitamin E-free diet. Three experiments showed that the Se in both bacteria had bioavailabilities of approx 2% that of selenite. A fourth experiment revealed that gray SeO had a bioavailability of 2% of selenite, but that the bioavailability of red SeO depended on the way it was prepared (by reduction of selenite). When glutathione was the reductant, bioavailability resembled that of gray SeO and bacterial Se; when ascorbate was the reductant, bioavailability was twice that level (3-4%). These findings suggest that aerobic bacteria such as B. subtilis and M. arborescens may be useful for the bioremediation of Se-contaminated sites, i.e., by converting selenite to a form of Se with very low bioavailability.     

Validity of DSM-IV attention-deficit/hyperactivity disorder for younger children

OBJECTIVE: Little is known about the validity of the diagnosis of attention-deficit/hyperactivity disorder (ADHD) in young children. Moreover, the results of the DSM-IV field trials raised concerns that inclusion of the new predominantly hyperactive-impulsive type of ADHD in DSM-IV might increase the likelihood of the diagnosis being given to active but unimpaired preschool and primary school children. METHOD: The validity of DSM-IV criteria for each subtype of ADHD was evaluated in 126 children, aged 4 through 6 years, and 126 matched comparison children. Probands and controls were classified by using structured diagnostic interviews of the parent and a DSM-IV checklist completed by the teacher. RESULTS: Children who met DSM-IV criteria for each subtype of ADHD according to parent and teacher reports differed consistently from controls on a wide range of measures of social and academic impairment, even when other types of psychopathology and other potential confounds were controlled. CONCLUSIONS: When diagnosed by means of a structured diagnostic protocol, all three DSM-IV subtypes of ADHD are valid for 4- through 6-year-old children in the sense of identifying children with lower mean scores on measures of adaptive functioning that are independently associated with ADHD.     

Short recurrence-free survival associated with high oestrogen receptor levels in the natural history of postmenopausal, primary breast cancer

The ability of oestrogen and progesterone receptor (ER and PgR, respectively) status to discriminate recurrence-free survival (RFS) among a cohort of consecutively accrued 952 postmenopausal patients has been studied. None of the cohort members investigated were treated with adjuvant therapy. Using a graduated scale of receptor status [low, intermediate and high receptor levels (< 10 vs. 10-107 vs. > or = 108 fmol/mg cytosol protein, respectively)] instead of the more commonly used dichotomous subdivision (positive vs. negative), ER level significantly discriminated between groups of patients with long vs. short RFS. Contrary to our expectations, patients with highest ER levels have as poor a prognosis as ER-negative patients, while patients with intermediate ER levels have longest RFS. The group of patients with ER levels > or = 108 fmol/mg cytosol protein comprises 47% of the cohort. The independent significance of overexpression of ER as a prognostic factor among this patient group is demonstrated in multivariate analysis where ER level is more significant than either grade of anaplasia or tumour size. PgR status did not significantly predict RFS among these patients. While the highest ER levels predispose for poorer prognosis among postmenopausal patients, it is precisely this group that experiences greatest benefit from adjuvant treatment with tamoxifen. Thus, patients who might otherwise go untreated due to their node-negative status can be readily identified and offered adjuvant treatment.     

cAMP signaling mechanisms with aging in rats

This work focuses on the maize root as a one-membrane osmo-diffusive converter of free energy. Energy expenditures of the root on water transport by radial route as well as on xylem water uptake, occurring according to the principle of osmotic root pressure, are analyzed. The so-called practical method of osmo-diffusive energy conversion (Kargol 1990, 1993) and experimental data taken from the work by Steudle et al. (1987) were employed, including coefficients of filtration (Lpr), reflection (sigma) and permeation (omega) of the maize root treated as a one-membrane model system. It is shown a.o. that the energy efficiency of the root does not depend (within a certain concentration interval) on the concentration of a given solute in solution into which the root is placed. This suggests a certain independence of environmental conditions. The efficiency is different for different dissolved substances contained in the solution.     

Abomasal infusion of cis or trans fatty acid isomers and energy metabolism of lactating dairy cows

Diets for dairy cows that provide or induce formation of trans isomers of polyunsaturated fatty acids result in reduced percentages of milk fat. The effect of abomasal infusion of trans-C18:1 fatty acid isomers on energy utilization by mature cows was determined. Six multiparous Holstein cows in midlactation had ad libitum access to a basal diet containing 50% forage and 50% concentrate. Treatments were 1) no infusion, 2) infusion of 630 g/d of a fat mixture high in cis-C18:1 isomers (64% cis-C18:1; 68% high oleic sunflower oil and 32% cocoa butter), and 3) infusion of 623 g/d of a fat mixture high in trans-C18:1 isomers (42% trans-C18:1; 90% partially hydrogenated soybean oil and 10% high linoleic safflower oil). The experiment was a replicated 3 x 3 Latin square design with 4-wk periods. Measurements of energy balance were made in open circuit respiration chambers during wk 4 of each period. Fat infusion increased milk production by 2.5 kg/d; apparent digestibility of DM, OM, energy, ADF, and ash by 1 to 4 percentage units; metabolizable energy by 11%; and NEL of the diet by 15%. Milk fat percentage and yield were higher when cows were infused with cis-C18:1 than when they were infused with trans-C18:1 (4.12% and 1.41 kg/d vs. 3.15% and 1.06 kg/d, respectively). Infusion of fat increased milk production, but trans-C18:1 reduced milk fat and energy output.     

Hydrophobic core substitutions in calbindin D9k: effects on Ca2+ binding and dissociation

Hydrophobic core residues have a marked influence on the Ca2+-binding properties of calbindin D9k, even though there are no direct contacts between these residues and the bound Ca2+ ions. Eleven different mutants with substitutions in the hydrophobic core were produced, and their equilibrium Ca2+-binding constants measured from Ca2+ titrations in the presence of chromophoric chelators. The Ca2+-dissociation rate constants were estimated from Ca2+ titrations followed by 1H NMR1 and were measured more accurately using stopped-flow fluorescence. The parameters were measured at four KCl concentrations to assess the salt dependence of the perturbations. The high similarity between the NMR spectra of mutants and wild-type calbindin D9k suggests that the structure is largely unperturbed by the substitutions. More detailed NMR investigations of the mutant in which Val61 is substituted by Ala showed that the mutation causes only very minimal perturbations in the immediate vicinity of residue 61. Substitutions of alanines or glycines for bulky residues in the center of the core were found to have significant effects on both Ca2+ affinity and dissociation rates. These substitutions caused a reduction in affinity and an increase in off-rate. Small effects, both increases and decreases, were observed for substitutions involving residues far from the Ca2+ sites and toward the outer part of the hydrophobic core. The mutant with the substitution Phe66 --> Trp behaved differently from all other mutants, and displayed a 25-fold increase in overall affinity of binding two Ca2+ ions and a 6-fold reduction in calcium dissociation rate. A strong correlation (R = 0.94) was found between the observed Ca2+-dissociation rates and affinities, as well as between the salt dependence of the off-rate and the distance to the nearest Ca2+-coordinating atom. There was also a strong correlation (R = 0.95) between the Ca2+ affinity and stability of the Ca2+ state and a correlation (R = 0. 69) between the Ca2+ affinity and stability of the apo state, as calculated from the results in the present and preceding paper in this issue [Julenius, K., Thulin, E., Linse, S., and Finn, B. E. (1998) Biochemistry 37, 8915-8925]. The change in salt dependencies of koff and cooperativity were most pronounced for residues completely buried in the core of the protein (solvent accessible surface area approximately 0). Altogether, the results suggest that the hydrophobic core residues promote Ca2+ binding both by contributing to the preformation of the Ca2+ sites in the apo state and by preferentially stabilizing the Ca2+-bound state.