Activity-based cost management. Part II: Applied to a respiratory protection program

The ability of IL-12 and IL-15 to enhance natural killer (NK) activity and antibody-dependent cellular cytotoxicity (ADCC) of mononuclear cells (MNCs) from HIV+ children and their mothers was investigated. MNCs from HIV+ patients were deficient in NK and ADCC activity compared to control MNCs against several target cells. Overnight incubation with IL-15 or IL-12 augmented NK activity of MNCs from both patients and controls, and the combination of IL-12 and IL-15 resulted in the greatest enhancement. ADCC in HIV+ patients against gp120-coated CEM.NKR cells or chicken erythrocytes could also be enhanced by IL-2 or IL-15 in overnight cultures. Culturing MNCs with either IL-2 or IL-15 for 1 week increased the NK activity in patients to levels of controls treated with these cytokines. However, the response to the combination of IL-12 and IL-15 was less than that to IL-15 alone in 1-week cultures. Culturing MNCs with IL-2 and IL-15 for 1 week also increased the percentage of CD16+/CD56+ cells in both patients and controls. Thus, IL-15 can restore the deficient NK activity in patients and may be a candidate for immunomodulative therapy in HIV+ patients.     

Intravenous pulse administration of cyclophosphamide versus daily oral treatment in patients with antineutrophil cytoplasmic antibody-associated vasculitis and renal involvement: a prospective, randomized study

OBJECTIVE: There is growing concern about the toxic side effects of daily oral cyclophosphamide (CYC) treatment. Intravenous (i.v.) pulse administration of CYC has been shown to be effective in patients with systemic lupus erythematosus, but contradictory results have been reported in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. METHODS: The efficacy and toxicity of i.v. pulse administration of CYC (0.75 gm/m2) versus daily oral CYC treatment (2 mg/kg body weight) were investigated in a prospective, randomized, multicenter study in patients with ANCA-associated vasculitis and renal involvement. RESULTS: The cumulative CYC dose was reduced by 57% in patients with i.v. pulse treatment (n = 22) compared with patients treated with daily oral therapy (n = 25). Patient survival, remission rate, time of remission, relapse rate, and outcome of renal function were not different between the 2 treatment groups. However, the rate of leukopenia (P < 0.01) and severe infections (P < 0.05 by 1-tailed test) was significantly reduced in the i.v. pulse group compared with the group receiving daily oral treatment. Moreover, gonadal toxicity was reduced in the i.v. pulse group, as indicated by significantly lower levels of follicle-stimulating hormone. CONCLUSION: This randomized study shows that i.v. CYC administration is an effective therapeutic tool with low toxicity in patients with ANCA-associated vasculitis and renal involvement.     

A vaccine consisting of recombinant Borrelia burgdorferi outer-surface protein A to prevent Lyme disease. Recombinant Outer-Surface Protein A Lyme Disease Vaccine Study Consortium

The purpose of this study was to determine whether infrared tympanic membrane thermometry can replace mercury-in-glass temperatures as an assessment tool for detecting fevers earlier and more reliably in a pediatric oncology outpatient setting. A total of 313 patient visits had infrared tympanic temperatures (obtained by using the LighTouch LTX Pedi-Q thermometer (Exergen; Watertown, MA) and axillary temperatures taken simultaneously (obtained by using mercury-in-glass thermometers). Those patients with a normal axillary temperature and an elevated tympanic measurement of 38 degrees C or higher had a follow-up axillary temperature conducted that evening to determine whether an elevated tympanic temperature predicted on coming fever or infection. The mean tympanic temperature was 37.5 degrees C and the mean axillary temperature was 36.8 degrees C, a difference of 0.7 degree C (P = .0001). Sixty-two (20%) patients had discrepant temperatures with a febrile tympanic and normal axillary measurement. Three (5%) of these patients were febrile at their follow-up axillary reading. Tympanic thermometry resulted in a significantly higher temperature reading than the axillary method. Elevated tympanic temperatures were not predictive of oncoming fever or infection. Fevers were not missed when using the tympanic method. To prevent unnecessary medical intervention, it is recommended that mercury-in-glass thermometers verify elevated tympanic temperatures.     

Young inner-city children visiting the emergency room (ER) for asthma: risk factors and chronic care behaviors

A longitudinal growth study with monthly measurements during the 1st year of life was conducted by nine paediatricians working in private practice in Zurich. Of 92 children, none was lost to the study and only 32 of 1104 planned visits were missed; the quality of the measurements was comparable to that of a specialised university clinic. Compared to the Zurich Longitudinal Growth Studies, children of this study were considerably heavier and taller. In 92% of the subjects, growth velocity was at least once outside the reference range (3rd 97th percentile). For weight increments, the corresponding proportion was 87%. CONCLUSIONS: The data indicate that current standards for the 1st year of life for the Zurich area might no longer be appropriate and need to be updated. The currently used velocity percentiles based on 3-monthly measurements are not suitable to assess individual height and weight increments calculated from monthly measurements.     

Optimisation of colour stability of cured ham during packaging and retail display by a multifactorial design

A multifactorial design, including (1) percent residual oxygen, (2) oxygen transmission rate of packaging film (OTR), (3) product to headspace volume ratio, (4) illuminance level and (5) nitrite level during curing, was established to investigate factors affecting light-induced oxidative discoloration of cured ham (packaged in modified atmosphere of 20% carbon dioxide and balanced with nitrogen) during 14 days of chill storage. Univariate statistical analysis found significant effects of all main factors on the redness (tristimulus a-value) of the ham. Subsequently, Response Surface Modelling of the data further proved that the interactions between packaging and storage conditions are important when optimising colour stability. The measured content of oxygen in the headspace was incorporated in the model and the interaction between measured oxygen content in the headspace and the product to headspace volume ratio was found to be crucial. Thus, it is not enough to keep the headspace oxygen level low, if the headspace volume at the same time is large, there will still be sufficient oxygen for colour deteriorating processes to take place.     

The role of prostaglandins in the natriuresis of acutely salt-loaded rats

Mechanisms determining the natriuresis in ECV expansion are not yet completely known. The present study was therefore performed to investigate (1) the extent to which prostaglandins (PG) are involved in the natriuresis of ECV expansion and (2) by which mechanisms PG may affect renal Na absorption. In nonexpanded rats the prostaglandin synthetase inhibitor indomethacin (INDO) had no effect on renal function. In 16 Sprague-Dawley rats EVC expansion with isotonic saline corresponding to an increase in body weight of 10% was induced and maintained for 60 min. Ten animals received an oral dose of 10 mg/kg BW of INDO prior to ECV expansion. Six animals served as controls (C). Blood pressure (INDO: 132 +/- 4 (SE); C: 130 +/- 3 mm Hg), GFR (INDO: 12.5 +/- 1.0; C: 10.5 +/- 0.9 ml/min/kg BW), fractional K excretion (INDO: 32.1 +/- 2.6; C: 43.4 +/- 4.8%), CH2O and Na-k-ATPase activities in renal cortex, medulla and papilla did not significantly differ in either group. Significant differences were observed in urinary flow rate (INDO: 0.82 +/- 0.8; C: 1.82 +/- 0.23 ml/min/kg KG) and fractional Na absorption (INDO: 91.9 +/- 1.1; C: 81.7 +/- 1.2%). The results indicate that PG are involved in the natriuresis following acute expansion of the ECV and suggest that PG may inhibit the intrinsic tubular capacity for Na absorption in the rat.     

Spontaneous aortocaval fistula secondary to ruptured abdominal aortic aneurysm

Twenty-nine patients referred consecutively to a cancer clinic because of recurrent metastatic malignant melanoma were given 5 mg of Connaught Laboratories bacillus Calmette-Guérin (BCG) by multiple cutaneous puncture at weekly and later at monthly intervals. Eight were also treated with autologous tumour vaccine and three with intralesional BCG. This group was compared with a retrospective control group of 54 patients treated with surgery and radiotherapy alone after recurrence. Prognostic features such as site of primary and of first metastasis, disease-free interval, age and sex were similar in the two groups. However, the median survival from the time of first recurrence was 12 months in the control group but 21 months in the BCG-treated group. The major improvement was in patients with disease limited to the regional lymph nodes: the median survival was 16 months in the control group but over 32 months in the BCG-treated group. Autologous tumour vaccine appeared to have no effect on survival. Serial testing of immunocompetence did not offer any prognostic advantage, although the results of some tests correleated well with extent of disease.     

Effect of various sources of phosphorus on the apparent digestibility of crude nutrients, growing and slaughtering performance as well as selected parameters of metabolism in fattening bulls

Polarized IR measurements on single crystals of human hemoglobin, grown under low salt conditions that stabilize the T quaternary structure, allow spectral features to be associated with individual sites within the molecule. Differences between the a- and c-polarized IR spectra in the sulfhydryl stretching region distinguish the contributions of individual Cys residues to the S-H band and lead to an evaluation of possible H-bonding partners for Cys beta-112. Successful modelling of both crystal and solution S-H spectra with component bands having identical frequencies and bandwidths, supports the use of the X-ray structure as a model for the low affinity T-state in solution. Polarization analysis of a crystal partially saturated with CO reveals comparable occupancy of the alpha- and beta-hemes. In the T-state crystal, the C-O bands are broader and lower in frequency than in the R-state solution, and 20% of the CO-ligated beta-subunits adopt an alternate conformation with a 1967 cm(-1) C-O frequency. The latter observation reflects an energetically significant disruption of the distal heme pocket upon CO binding to beta-hemes in the low affinity T-state.     

Paclitaxel reduces anti-dsDNA antibody titer and BUN, prolonging survival in murine lupus

We evaluated the effect of paclitaxel on the severity of autoimmunity in the murine model of systemic lupus erythematosus (SLE), NZB x NZW F1 mice. Fifteen 20 week old (NZB x NZW) F1 female mice were given a dose of 10 mg/kg paclitaxel by the intraperitoneal route on three alternate days followed by 7.5 mg/kg on three additional alternate days. This pattern of treatment was repeated every 4 weeks for a period of 28 weeks. 20 control mice were injected intraperitoneally with an equal volume of the vehicle used. Serum anti-double stranded DNA (dsDNA) antibody titers and the blood urea nitrogen (BUN) were significantly diminished in the paclitaxel treated group compared to the vehicle treated group. While the onset of proteinuria appeared to be delayed in the experimental group, the difference was not significant. Survival rate improved significantly in paclitaxel treated group (p = 0.04 by log-rank test). These results suggest that paclitaxel is beneficial in the suppression of autoimmunity in this strain of mice by reducing the anti-dsDNA antibody titer and the BUN, prolonging survival.     

The Drosophila sanpodo gene controls sibling cell fate and encodes a tropomodulin homolog, an actin/tropomyosin-associated protein

Notch signaling is required in many invertebrate and vertebrate cells to promote proper cell fate determination. Mutations in sanpodo cause many different neuronal peripheral nervous system precursor cells to generate two identical daughter neurons, instead of a neuron and sibling cell. This phenotype is similar to that observed when Notch function is lost late in embryonic development and opposite to the numb loss-of-function phenotype. Genetic interaction studies show that sanpodo is epistatic to numb. sanpodo encodes a homolog of tropomodulin, an actin/tropomyosin-associated protein. Loss of sanpodo leads to an aberrant F-actin distribution and causes differentiation defects of actin-containing sensory structures. Our data suggest that an actin-based process is involved in Notch signaling.