Analysis of absorption and spreading of moisturizer on the microscopic region of the skin surface with near-infrared imaging.

BACKGROUND/PURPOSE: Near-infrared (NIR) light with high water absorption enables us to visualize the water content distribution appeared in the superficial skin layer. The light penetration depth with the wavelength of 1920 nm is almost 100 µm from the skin surface. Thus, the water distribution in the stratum corneum can be effectively imaged by detecting the wavelength band around 1920 nm. The aim of this article was to measure the time-lapse behavior of the tiny droplet of the moisturizer spreading on the skin surface by imaging in 1920 nm wavelength band for investigating the correlation with the traditional index of the skin condition such as the water content and transepidermal water loss (TEWL). METHODS: Experiment is performed with three moisturizer products and seven volunteer subjects. The NIR image is acquired by an originally designed imaging scope equipped with the white light of the strong brightness [super continuum (SC) light], the bandpass filter with the center wavelength of 1920 nm, and the NIR image sensor. A tiny droplet of the moisturizer is put on the surface of the skin and the time-lapse images are saved. Each acquired image is analyzed from a view point of the droplet area and elapsed time for absorption into the skin. The water content and TEWL of all subjects are measured by the conventional electrical method for investigating the relationship with the measured droplet dynamics parameters. RESULTS: Elapsed time for moisturizer droplet to be absorbed into the skin, the droplet area just before absorption for three moisturizer products, skin water contents, and TEWL for seven subjects were measured and correlation coefficients for each parameters were calculated. It was found that the skin with higher water contents or lower TEWL absorbed the moisturizer faster and spreads moisturizer wider. Also absorption and spreading speed depend on moisturizer property (moisturizing or fresh) which is originated from the moisturizer constituents. CONCLUSION: The correlation values between the moisturizer dynamics on the skin surface and the traditional index of the skin property were clarified. It was found that the skin with the high water content or low TEWL absorbs the moisturizer droplet fast. The spreading area depends not only on the skin property but on the constituents of the moisturizers.

Long-term outcome in Japanese patients with lupus nephritis.

The objective of this study was to clarify the long-term outcome in patients with lupus nephritis (LN) according to the International Society of Nephrology and Renal Pathology Society classification. This retrospective analysis comprised 186 Japanese patients given a diagnosis of LN by renal specimen with a mean observation period of 12 years. Primary end point was defined as death or end-stage renal disease, and standardized mortality ratios were calculated. Five patients presented with histopathological class I, 62 with II, 21 with III or III+V, 73 with IV or IV+V and 25 with V. Fourteen deaths occurred, corresponding to an overall standardized mortality ratio of 3.59 (95% confidence interval 2.02-5.81, p < 0.0001). Kaplan-Meier analysis revealed a 10-year overall survival of 95.7%. Nephrotic proteinuria (≥3.5 g/day) at baseline was identified as an independent poor prognostic factor for overall survival in Cox regression analysis. Kaplan-Meier analysis revealed a 10-year renal survival as 94.3%. Male gender and nephrotic proteinuria at baseline were identified as independent poor prognostic factors for renal survival in Cox regression analysis. In conclusion, LN was associated with a 3.59-fold increase in mortality compared with the general population. Male gender and nephrotic proteinuria were predictive for poor renal outcome.

Background values for evaluation of heavy metal contamination in sediments.

The contamination of sediments can be evaluated from comparison of the current concentration with the estimated background value. Although it is known that grain size affects background concentrations, there have been difficulties in evaluating this effect. The specific surface area of sediments, which can be calculated from the grain size distribution, is introduced as a property index for correlation of background values. The results show that for sandy-to-sandy silt sediments, the background values of metals are expressed in terms of fines content, which can be correlated with the corresponding specific surface area. However, for silty clay or clayey silt sediments, which would have a high metal retention capacity, the level of the background may be constrained by the relatively low concentrations of metals in seawater. Finally, background levels of Zn, Cu and Pb are presented.

Effects of magnesium and sodium ions on the outer membrane permeability of cephalosporins in Escherichia coli.

Both Mg2+ and Na+ stimulated the outer membrane permeation of negatively charged cephalosporins in Escherichia coli without any significant alteration of the permeation of a zwitterionic cephalosporin. Such stimulation was not observed in an E. coli mutant lacking porins. The stimulation was caused by the direct interaction between the cations and the porin pores, which resulted in a decrease in cation selectivity of both the Omp F and Omp C porin pores.

Erythromycin and common cold in COPD.

STUDY OBJECTIVES: To investigate whether erythromycin therapy lowers the frequency of the common cold and subsequent exacerbation in patients with COPD. DESIGN: Prospective, randomized, controlled, but not blinded, trial. PATIENTS: One hundred nine patients with COPD were enrolled into the study. Patients were randomly assigned to erythromycin therapy or to no active treatment in September 1997. Patients then were observed for 12 months, starting in October, during which time the risk and frequency of catching common colds and COPD exacerbations were investigated. Fifty-five patients received erythromycin at study entry (erythromycin group). The remaining 54 patients received no active treatment (control group). MEASUREMENTS AND RESULTS: The mean (+/- SE) number of common colds for 12 months was significantly lower in the erythromycin group than in the control group (1.24 +/- 0.07 vs 4.54 +/- 0.02, respectively, per person; p = 0.0002). Forty-one patients (76%) in the control group experienced common colds more than once, compared to 7 patients (13%) in the erythromycin group. The relative risk of developing two or more common colds in the control group compared with that in the erythromycin group was 9.26 (95% confidence interval [CI], 3.92 to 31.74; p = 0.0001). Thirty patients (56%) in the control group and 6 patients (11%) in the erythromycin group had one or more exacerbations. The relative risk of experiencing an exacerbation in the control group compared with that in the erythromycin group was 4.71 (95% CI, 1.53 to 14.5; p = 0.007). Significantly more patients were hospitalized due to exacerbations in the control group than in the erythromycin group (p = 0.0007). CONCLUSION: Erythromycin therapy has beneficial effects on the prevention of exacerbations in COPD patients.

Interventions to prevent pneumonia among older adults.

Pneumonia is a common cause of death in older people. Antimicrobial drugs do not prevent pneumonia and, because of increasingly resistant organisms, their value in curing infection will become more limited. Establishing new strategies to prevent pneumonia through consideration of the mechanisms of this devastating illness is essential. The purpose of this review is to discuss how pneumonia develops in older people and to suggest preventive strategies that may reduce the incidence of pneumonia among older adults. Aspiration of oropharyngeal bacterial pathogens to the lower respiratory tract is one of the most important risk factors for pneumonia; impairments in swallowing and cough reflexes among older adults, e.g., related to cerebrovascular disease, increase the risk for the development of pneumonia. Thus, strategies to reduce the volumes and pathogenicity of aspirated material should be pursued. For example, since both swallowing and cough reflexes are mediated by endogenous substance P, pharmacologic therapy using angiotensin-converting enzyme inhibitors, which decrease substance P catabolism, may improve both reflexes and result in the lowering of the risk of pneumonia. Similarly, since the production of substance P is regulated by dopaminergic neurons in the cerebral basal ganglia, treatment with dopamine analogs or potentiating drugs such as amantadine (and, of course, prevention of cerebral vascular disease, which can result in basal ganglia strokes) should affect the incidence of pneumonia. The purpose of this review is to consider promising pharmacologic treatments as methods of preventing pneumonia in older adults and to review other proven strategies, e.g., infection control and cerebrovascular disease prevention that will lessen the incidence of pneumonia.

Endopeptidase activity of cathepsin C, dipeptidyl aminopeptidase I, from bovine spleen.

By employing various synthetic substrates, as well as soluble denatured protein substrate (TAP-lysozyme) and its derivatives, endopeptidase activity of cathepsin C, dipeptidyl aminopeptidase I [EC 3.4.14.1], from bovine spleen was investigated. Cathepsin C efficiently degraded Z-Phe-Arg-MCA, Pro-Phe-Arg-MCA, and Suc-Leu-Leu-Val-Tyr-MCA. This endopeptidase activity required sulfhydryl reagents and halide ions, as in the case of the dipeptidyl aminopeptidase (DAP) activity. We confirmed that this endopeptidase activity is due to cathepsin C itself based on the results on gel-filtration and anion-exchange chromatographies, comparative studies of the inhibitory effects of leupeptin and E-64 on this activity and those of cathepsins B and L, and further the competitive inhibitions by mutual substrates for the DAP and endopeptidase activities of cathepsin C. We also found that cathepsin C endopeptidase activity towards TAP-lysozyme and its N-alpha-acetylated tryptic peptides showed marked dependence on sulfhydryl reagents and chloride ion. Thus, we concluded that cathepsin C has endopeptidase activity as well as DAP activity. The binding energy between the enzyme and the amino acid side chains of the substrate may be as important for the endopeptidase activity as is the electrostatic interaction between the enzyme and the free alpha-amino group of the substrate for the DAP activity.

Control of larynx during loaded breathing in normal subjects.

We examined laryngeal resistance (Rla) in six normal subjects in control and four kinds of loaded breathing: hypercapnia, chest strapping, added external resistance, and inhaled methacholine. Rla was measured with a low-frequency sound methed (Sekizawa et al., J. Appl. Physiol. 55: 591-597, 1983). In control and the four kinds of loaded breathing, changes in Rla were tightly coupled with ventilation and Rla decreased during inspiration and increased during expiration. Hypercapnia and chest strapping significantly decreased Rla in both inspiration and expiration in all subjects. Added external resistance decreased inspiratory Rla in all subjects, but decreased expiratory Rla in three subjects, did not change it in two subjects, and increased it in one subject. Inhaled methacholine increased Rla in both inspiration and expiration in all subjects. The present study suggests that although laryngeal movement is tightly coupled with ventilation, laryngeal aperture may be determined by the complex competition of dilating and constricting mechanisms associated with the activity of the respiratory center and neural reflexes from the airway.

Effect of a previous voluntary deep breath on laryngeal resistance in normal and asthmatic subjects.

We studied changes in both laryngeal resistance (Rla) and respiratory resistance (Rrs) after a voluntary deep breath in 7 normal and 20 asthmatic subjects. Rla was measured using a low-frequency sound method (Sekizawa et al. J. Appl. Physiol. 55: 591-597, 1983) and Rrs by forced oscillation at 3 Hz. In normal subjects, both Rla and Rrs significantly decreased after a voluntary deep breath (0.05 less than P less than 0.01). During methacholine provocation in the normal subjects, a voluntary deep breath significantly decreased Rrs (0.05 less than P less than 0.01, but Rla was significantly increased (0.05 less than P less than 0.01). In 10 asthmatic subjects in remission, a voluntary deep breath significantly increased Rrs (0.05 less than P less than 0.01) but significantly decreased Rla (0.05 less than P less than 0.01). In another 10 asthmatic subjects during spontaneous mild attacks, a voluntary deep breath significantly increased both Rrs and Rla (0.05 less than P less than 0.01). The present study showed that without obvious bronchoconstriction, Rla decreased after a voluntary deep breath in both normal and asthmatic subjects but, with bronchoconstriction, Rla increased in both groups. Subtraction of the change in Rla from Rrs gives the change in Rrs below the larynx (Rlow). Rlow changed little or decreased in normal subjects and increased in asthmatic subjects, irrespective of base-line bronchomotor tone. These results suggest that airway response below the larynx after a voluntary deep breath differentiates patients with bronchial asthma from normal subjects.

Site of airway obstruction in pulmonary disease: direct measurement of intrabronchial pressure.

To partition the central and peripheral airway resistance in awake humans, a catheter-tipped micromanometer sensing lateral pressure of the airway was wedged into the right lower lobe of a 3-mm-ID bronchus in 5 normal subjects, 7 patients with chronic bronchitis, 8 patients with emphysema, and 20 patients with bronchial asthma. We simultaneously measured mouth flow, transpulmonary pressure, and intra-airway lateral pressure during quiet tidal breathing. Total pulmonary resistance (RL) was calculated from transpulmonary pressure and mouth flow and central airway resistance (Rc) from intra-airway lateral pressure and mouth flow. Peripheral airway resistance (Rp) was obtained by the subtraction of Rc from RL. The technique permitted identification of the site of airway resistance changes. In normal subjects, RL was 3.2 +/- 0.2 (SE) cmH2O.l-1.s and the ratio of Rp to RL was 0.24 during inspiration. Patients with bronchial asthma without airflow obstruction showed values of Rc and Rp similar to those of normal subjects. Although Rc showed a tendency to increase, only Rp significantly increased in those patients with bronchial asthma with airflow obstruction and patients with chronic bronchitis and emphysema. The ratio of Rp to RL significantly increased in three groups of patients with airflow obstruction (P less than 0.01). These observations suggest that peripheral airways are the predominant site of airflow obstruction, irrespective of the different pathogenesis of chronic airflow obstruction.

Ozone increases susceptibility to antigen inhalation in allergic dogs.

To determine whether O3 exposure increased airway responsiveness to antigen inhalation, we studied airway responsiveness to acetylcholine (ACh) and Ascaris suum antigen (AA) before and after O3 in dogs both sensitive and insensitive to AA. Airway responsiveness was assessed by determining the provocative concentration of ACh and AA aerosols that increased respiratory resistance (Rrs) to twice the base-line value. O3 (3 parts per million) increased airway responsiveness to ACh in dogs both sensitive and insensitive to AA, and it significantly decreased the ACh provocation concentration from 0.541 +/- 0.095 to 0.102 +/- 0.047 (SE) mg/ml (P less than 0.01; n = 10). AA aerosols, even at the highest concentration in combination with O3, did not increase Rrs in dogs insensitive to AA. However, O3 increased airway responsiveness to AA in AA-sensitive dogs and significantly decreased log AA provocation concentration from 2.34 +/- 0.22 to 0.50 +/- 0.17 (SE) log protein nitrogen units/ml (P less than 0.01; n = 7). O3-induced hyperresponsiveness to ACh returned to the base-line level within 2 wk, but hyperresponsiveness to AA continued for greater than 2 wk. The plasma histamine concentration after AA challenge was significantly higher after than before O3 (P less than 0.01). Intravenous infusion of OKY-046 (100 micrograms.kg-1.min-1), an inhibitor of thromboxane synthesis, inhibited the O3-induced increase in responsiveness to ACh, but it had no effects on the O3-induced increase in responsiveness to AA and the increase in the plasma histamine concentration. These results suggest that O3 increases susceptibility to the antigen in sensitized dogs via a different mechanism from that of O3-induced muscarinic hyperresponsiveness.

Responsiveness of and interactions between airways and tissue in guinea pigs during induced constriction.

Mechanical interdependence between airways and tissues can modify the magnitude of induced bronchoconstriction. We questioned whether the guinea pig, an animal with abundant airway smooth muscle, would differ from other species in the relative responsiveness of and interactions between airways and tissues. Therefore we induced constriction with aerosolized methacholine (MCh) and partitioned responses into airway and tissue components. We measured tracheal and alveolar pressures using alveolar capsules in open-chest guinea pigs (n = 9) during mechanical ventilation [frequency = 1 Hz, tidal volume = 6 ml/kg, positive end-expiratory pressure (PEEP) = 5 cmH2O] and calculated the resistance of lung (RL), tissue (Rti), and airway (Raw) before and after administration of aerosols of MCh in progressively doubling concentrations (0.063-16 mg/ml). In separate animals (n = 10), measurements were made at 3-13 cmH2O PEEP. After aerosols of saline and MCh (0.125-32 mg/ml), measurements were repeated at 3, 7, and 11 cmH2O PEEP. At submaximal levels of constriction, the airways and lung tissues demonstrated similar responsiveness. Increasing PEEP increased RL and Rti and decreased Raw under baseline conditions. At low concentrations of MCh, increasing PEEP increased RL but decreased RL at the highest concentration. Increases in PEEP significantly increased Rti at all concentrations of MCh but decreased Raw only at 8 mg/ml of MCh. These observations demonstrate that, in guinea pigs, during submaximal constriction, airways and tissues behave similarly; moreover, airway-parenchymal interdependence is important in determining the level of bronchoconstriction.

Kinetics of technetium-labeled heparin in hemodialyzed patients.

Technetium-labeled heparin kinetics studies were undertaken in 12 hemodialyzed patients, where heparin was used over a long term (1 to 10 years) for anticoagulation of the extracorporeal circuit. The 99mTc-heparin (99mTc VECTOSCINT, Solabco Nuclear, Coutras, France) used has a 10 mCi activity and a labeling efficiency of more than 95%. Two healthy subjects served as control. After an i.v. bolus of 2 ml 99mTc-heparin, corresponding to 170 +/- 10 IU, radioactivity of kidney, liver, knee and shoulder was recorded with a gamma camera at t1-h, t3-h and t6-h during 120, 152 and 215 s, respectively. Radioactivity recorded was computerized, giving quantitative data for comparison. In hemodialyzed patients, accumulation of radioactivity (mean +/- SEM 10(6) x activity count) was significantly higher at the knee (11.3 +/- 1.1 vs. 4.9 +/- 0.4; p < 0.05; 13.4 +/- 1.1 vs. 5.7 +/- 0.7; < 0.02; and 14.7 +/- 0.8 vs. 5.3 +/- 0.6; < 0.001), and on the shoulder (17.3 +/- 1.1 vs. 10.7 +/- 1.4; p < 0.05; 19.9 +/- 1.0 vs. 10.9 +/- 1.7; < 0.01; 20.8 +/- 1.1 vs. 10.1 +/- 0.9; < 0.01) at t1-h, t3-h and t6-h, respectively, than in control subjects at the same areas. Although direct evidence is not in hand, accumulation of heparin in bone tissue due to renal excretion failure could play a role in mineral metabolism resulting in osteopenia in hemodialyzed patients.

Urea rebound and residual renal function in the calculation of Kt/V and protein catabolic rate.

Kt/V-urea and protein catabolic rate (PCR) are used for dialysis prescription and evaluation of protein intake of patients on regular dialysis treatment. The study was undertaken to determine the implication of urea rebound and residual renal function (RRF) on the calculation of Kt/V-urea and PCR for 61 patients. Kt/V-urea and PCR were calculated, implementing or not urea rebound at one hour after the end of dialysis session. Urea and creatinine rebound rate in patients without RRF was significantly higher than in patients with RRF (P < 0.05). In patients without RRF, creatinine generation rate and Kt/V-urea calculated without rebound were significantly higher than calculated with rebound (P < 0.001). On the contrary, calculation of urea generation and PCR is not affected by these parameters. It is concluded that: (1) Rebound rate magnitude of urea and creatinine is dependent on solute molecular weight, RRF and probably on dialysis duration, whereas rebound rate magnitude of phosphorus is not affected, and (2) Rebound should be taken into account in the calculation of Kt/V-urea and creatinine generation rate in patients without RRF, otherwise, they would be overestimated.

Production and secretion of adrenomedullin in cultured human alveolar macrophages.

To explore the role of adrenomedullin (ADM) in macrophages, we investigated the secretion of ADM by alveolar macrophages. Human alveolar macrophages obtained from bronchoalveolar lavage were cultured for 24 h. Northern blot analysis revealed ADM mRNA expression in alveolar macrophages. The levels of immunoreactive ADM in the media were 0.89+/-0.12 fmol/10(5) cells/24 h (n = 10). Reverse-phase high-performance liquid chromatography of the extract of culture media showed one major peak eluting in the position of the human ADM standard. The present study shows that alveolar macrophages produce and secrete ADM.

Treatment outcome and prognostic factors in childhood acute myeloblastic leukemia: a report from the Japanese Children's Cancer and Leukemia Study Group (CCLSG)

Treatment outcome and prognostic factors were evaluated in 152 children with acute myeloblastic leukemia (AML) treated on three consecutive protocols (ANLL 861, 8912, 9205) of the Children's Cancer Leukemia Study Group (CCLSG, Japan). In the ANLL 9205 protocol, anthracycline was used with a continuous infusion of cytosine arabinoside, followed by an intensive sequential post remission chemotherapy of short duration. Forty-two of these 46 patients (91.3%) achieved complete remission, and 58.8% of these patients projected a 3-year disease-free survival. These results were apparently superior to those obtained with the ANLL 861 and 8912 protocols, which used conventional doses of multiple drugs followed by a moderate post remission chemotherapy of long duration. This favorable response with the ANLL 9205 protocol was attributed mainly to the high induction rate of patients with the M4 and M5 FAB subtypes, as compared to those in the previous two protocols (93.3% in ANLL 9205 vs. 57.9% in ANLL 861 + 8912; P < 0.05). The ANLL 861 and 8912 protocols, an older age (> or = 8 years), higher WBC counts (> or = 10 x 10(9)/1) and all predicted an increased risk of relapse and decreased the survival following univariate analysis (P < 0.05). An older age and high WBC count continued to predict an increased risk of relapse in multivariate analyses: patients with an age > 8 years and WBC counts > 10 x 10(9)/1 had a 4.5 times higher risk of relapse than patients without these adverse features.

Occasional infection of hepatitis C virus occurring in haemodialysis units identified by serial monitoring of the virus infection.

To examine whether hepatitis C virus (HCV) infection still occurs in haemodialysis units even after a decrease in the number of blood transfusions and in those contaminated with HCV, we tested anti-HCV antibodies and HCV RNA in 142 patients from Japanese haemodialysis units, and examined the serial prevalence of anti-HCV antibodies in 86 patients from 1992 to 1997. A high prevalence of HCV infection was observed: 34 (23.9%) and 38 (26.8%) of the 142 patients were positive for serum anti-HCV antibodies and HCV RNA, respectively. These positive rates were related to the duration of haemodialysis. We found that five patients treated in the same unit seroconverted from 1993 to 1995. Four of the five patients had been treated at the same shift and were affected at the same time. Phylogenetic analysis of the hypervariable region 1 (HVR1) sequence of HCV from serum of these patients showed that three of the four patients' sequences were phylogenetically clustered and that two of the three were closely related. Thus, an occasional transmission of HCV occurred in the haemodialysis unit. The universal precautions by staff such as carefully changing gloves may be important in inhibiting spread of HCV because no instances of infection have been seen since the instigation of educational measures for unit staff.