Fetal face: the whole picture.

The fetal face is an essential source of information. Its evaluation makes it possible to diagnose several fetal diseases and syndromes. Three-dimensional ultrasound and four-dimensional ultrasound facilitate the evaluation of superficial anatomical facial structures and have become essential complementary tools to two-dimensional ultrasound, providing additional and more precise information about the presence and severity of facial defects. This article reviews the normal facial development essential to understand the pathogenesis of facial malformations as well as the assessment of a normal and dysmorphic face with two-dimensional, three-dimensional and four-dimensional ultrasound and discusses the clinical implications of detecting facial anomalies in the prenatal period.

Bone parameters are improved with intermittent dosing of vitamin D3 and calcitonin.

Intermittent combination of an anabolic agent to promote bone formation and an antiresorptive agent that would prevent further bone loss is a theoretically attractive approach for restoring bone mass. We tested the potential of intermittently dosed calcitriol and calcitonin (CT) to restore bone properties in ovariectomized (Ovx) rats. Rats had Ovx or sham surgery at 8 weeks old and 4 weeks later were assigned to experimental groups: (1) sham vehicle, (2) Ovx vehicle, (3) Ovx + parathyroid hormone (PTH, 40 microg/kg), and (4) Ovx + calcitriol (2 microg/kg) + CT (2 microg/kg). Group 3 received PTH every week throughout the study, and group 4 received calcitriol at weeks 1, 3, 5, and 7 and CT at weeks 2, 4, 6, and 8. Dosing was carried out for 8 weeks with serum, and micro-computed tomographic analysis was done at 0, 4, and 8 weeks. Femurs and tibias were used for radiological analyses and for mechanical testing. Dosing with PTH improved bone mass and structure of cancellous bone at metaphyses of tibias and femurs as well as properties of cortical bone including geometry and strength. Intermittent dosing with calcitriol and CT was less potent in correcting loss of cancellous bone relative to treatment with PTH and had no effect on cortical bone parameters. However, intermittent dosing with calcitriol and CT was robust enough to improve cancellous bone mass and structure through bone formation without causing deleterious side effects. Our data provide additional evidence that therapies can be devised to ameliorate the skeletal defects associated with established osteoporosis.

Isolation and partial characterisation of a new antiproliferative substance from human leucocytes inhibiting growth of Candida albicans.

AIM: To purify and partially characterise a fraction from human leucocytes containing a substance cytotoxic to Candida albicans. METHODS: Leucocytes were isolated from the buffy coats of healthy blood donors. The cytotoxic factor (CF) was isolated from the soluble fraction of the cells. A cell lysate was passed through a filter with a cut off value of 3 kDa, and the filtrate was processed by anionic exchange chromatography and gel filtration. The purified CF was analysed for its chemical and biological properties. The cytotoxicity of CF was tested on C albicans grown on agar plates. RESULTS: Mass spectrometry showed a molecular mass of 2.148 kDa. CF was found in polymorphonuclear neutrophilic cells only. No amino acids were detected, and a low ultraviolet absorbance at 260 nm and resistance to nuclease indicate the absence of nucleic acids. An anthrone test was positive for carbohydrate. The substance was soluble in water. CF showed a dose related cytotoxicity in the range of 0.1-1 mg/ml. The cytotoxic effect was abrogated by zinc ions. Preliminary testing indicated that CF also had cytotoxic effects against some bacteria. CONCLUSIONS: This report describes a factor from isolated human leucocytes that is cytotoxic to C albicans. The substance contains a carbohydrate moiety, whereas no amino acids were detected. The cytotoxicity can be abrogated by zinc ions in vitro. This substance is probably part of the repertoire by which leucocytes prevent infections.

Pulmonary eosinophilia in a murine model of allergic inflammation is attenuated by small molecule alpha4beta1 antagonists.

Inhibition of alpha4beta1/vascular cell adhesion molecule-1 (VCAM-1) interactions have therapeutic potential in treating allergic airway disease because of the importance of these adhesion molecules in the trafficking of eosinophils, lymphocytes, and monocytes. We examined several small molecule inhibitors of alpha4beta1/VCAM-1 interactions with in vitro potencies (IC(50) values) ranging from 0.52 nM (CP-664511; 3-[3-(1-[2-[3-methoxy-4-(3-O-tolyl-ureido)phenyl]-acetylamino]-3-methyl-butyl)isoxazol-5-yl]-propionic acid) to 38.5 nM (CP-609643; 3-[3-methyl-1-[2-[4-(3-O-tolyl-ureido)-phenyl]-acetylamino]-butyl)-isoxazol-5-yl]-propionic acid). The same compounds were evaluated in vivo using a murine model of ovalbumin-induced pulmonary eosinophilia. In this model, systemic administration of antibodies against alpha4 reduced bronchoalveolar lavage (BAL) eosinophilia approximately 60%. Small molecule alpha4beta1 antagonists were administered by intratracheal instillation and demonstrated dose-dependent inhibition of BAL eosinophil numbers and achieved a maximum inhibition of approximately 60%. In general, the rank order of potency for these compounds in vitro was consistent with that observed in vivo, which confirms that their efficacy is likely via blockade of alpha4beta1/VCAM-1 interactions. The most potent compound, CP-664511, also inhibited BAL eosinophilia following s.c. administration (1-10 mg/kg, s.c.). These data support the utility of small molecule alpha4beta1 antagonists in the treatment of relevant diseases, such as asthma.

Genetic ablation of the src kinase p59fynT exacerbates pulmonary inflammation in an allergic mouse model.

p59fynT is a protein tyrosine kinase in the src family that has been associated with and believed to function in the signaling of many receptors, including the T-cell receptor. A role for the kinase in antigen-driven pulmonary inflammation was examined using mice whose p59fynT gene had been genetically ablated. FynKO mice that were sensitized to ovalbumin exhibited a marked increase in bronchoalveolar lavage eosinophils and cytokines, including interleukin (IL)-4 and IL-5, relative to wild-type mice in response to antigen aerosol exposure. Ovalbumin-stimulated IL-5 production was also increased in cultured splenocytes derived from fynKO mice relative to wild-type mice, whereas interferon-gamma levels were unchanged. Diminished concanavalin A--stimulated IL-4 levels from fynKO splenocytes were consistent with reduced serum immunoglobulin (Ig)E levels observed in sensitized/saline aerosol-challenged animals and may reflect defective natural killer 1.1(+) T cell development. Normalization of IgE levels in sensitized fynKO mice relative to wild-type mice occurred after repeat antigen challenge, which suggests a secondary source of IL-4. Overall, these data demonstrate fyn is a negative regulator of allergic airway inflammation in mice because its absence promotes a shift to a T helper-2 phenotype that may reflect the kinase's role in T-cell receptor signaling.

Characterization of chemokine CCR3 agonist-mediated eosinophil recruitment in the Brown-Norway rat.

1. The ability of various C-C chemokines to elicit tissue eosinophil infiltration following intradermal injection or peripheral blood eosinophilia following intravenous injection were compared in the Brown-Norway rat. 2. Eotaxin (0.1 - 3 microg site-1) of human and murine origin produced equivalent, dose-dependent increases in eosinophil peroxidase activity in rat dermis 4 h post-injection. 3. Human eotaxin-2 was equipotent with human eotaxin in terms of dermal eosinophil recruitment. Other human CCR3 agonists, such as MCP-3, RANTES and MCP-4 failed to increase dermal eosinophil peroxidase activity at doses up to 1 microg site-1 whereas the latter did produce a small effect at 3 microg site-1. 4. Consistent with observations in vivo, human eotaxin displaced [125I]-eotaxin from rat spleen membranes more potently (IC50=2 nM) than did MCP-4 (IC50=500 nM). RANTES did not compete with the radiolabelled chemokine at concentrations up to 1 microM. 5. Human eotaxin (5 microg) administered intravenously increased circulating eosinophils approximately 3 fold whereas MCP-4 (5 microg i.v.) increased circulating monocytes approximately 3 fold without affecting eosinophil numbers. 6. Dexamethasone pretreatment inhibited eotaxin-induced dermal eosinophil influx only at a steroid dose (0.1 mg kg-1, s.c.) which significantly reduced circulating eosinophil numbers. The steroid also reduced eosinophilia in peripheral blood resulting from systemic eotaxin administration (5 microg, i.v.). 7. These data suggest differences in rat CCR3 relative to other species as surmised from a distinctive rank order of chemokine potency. In addition to its chemotactic effects eotaxin, but not MCP-4, promotes eosinophil recruitment into the circulation. One of the mechanisms by which glucocorticoids, such as dexamethasone, acutely inhibits eotaxin-induced dermal eosinophil influx is to diminish the circulating numbers of these cells available for tissue recruitment.

The influence of age on propofol pharmacodynamics.

BACKGROUND: The authors studied the influence of age on the pharmacodynamics of propofol, including characterization of the relation between plasma concentration and the time course of drug effect. METHODS: The authors evaluated healthy volunteers aged 25-81 yr. A bolus dose (2 mg/kg or 1 mg/kg in persons older than 65 yr) and an infusion (25, 50, 100, or 200 microg x kg(-1) x min(-1)) of the older or the new (containing EDTA) formulation of propofol were given on each of two different study days. The propofol concentration was determined in frequent arterial samples. The electroencephalogram (EEG) was used to measure drug effect. A statistical technique called semilinear canonical correlation was used to select components of the EEG power spectrum that correlated optimally with the effect-site concentration. The effect-site concentration was related to drug effect with a biphasic pharmacodynamic model. The plasma effect-site equilibration rate constant was estimated parametrically. Estimates of this rate constant were validated by comparing the predicted time of peak effect with the time of peak EEG effect. The probability of being asleep, as a function of age, was determined from steady state concentrations after 60 min of propofol infusion. RESULTS: Twenty-four volunteers completed the study. Three parameters of the biphasic pharmacodynamic model were correlated linearly with age. The plasma effect-site equilibration rate constant was 0.456 min(-1). The predicted time to peak effect after bolus injection ranging was 1.7 min. The time to peak effect assessed visually was 1.6 min (range, 1-2.4 min). The steady state observations showed increasing sensitivity to propofol in elderly patients, with C50 values for loss of consciousness of 2.35, 1.8, and 1.25 microg/ml in volunteers who were 25, 50, and 75 yr old, respectively. CONCLUSIONS: Semilinear canonical correlation defined a new measure of propofol effect on the EEG, the canonical univariate parameter for propofol. Using this parameter, propofol plasma effect-site equilibration is faster than previously reported. This fast onset was confirmed by inspection of the EEG data. Elderly patients are more sensitive to the hypnotic and EEG effects of propofol than are younger persons.

7-Oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridines as novel inhibitors of human eosinophil phosphodiesterase.

High-throughput file screening against inhibition of human lung PDE4 led to the discovery of 3-ethyl-1-(4-fluorophenyl)-6-phenyl-7-oxo-4, 5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine (11) as a novel PDE4 inhibitor. Subsequent SAR development, using an eosinophil PDE assay, led to analogues up to 50-fold more potent than 11 with IC50 values of 0.03-1.6 microM. One such compound, CP-220,629 (22) (IC50 = 0.44 microM), was efficacious in the guinea pig aerosolized antigen induced airway obstruction assay (ED50 2.0 mg/kg, po) and demonstrated a significant reduction in eosinophil (55%), neutrophil (65%), and IL-1beta (82%) responses to antigen challenge in atopic monkeys (10 mg/kg, po).

The influence of method of administration and covariates on the pharmacokinetics of propofol in adult volunteers.

BACKGROUND: Unresolved issues with propofol include whether the pharmacokinetics are linear with dose, are influenced by method of administration (bolus vs. infusion), or are influenced by age. Recently, a new formulation of propofol emulsion, containing disodium edetate (EDTA), was introduced in the United States. Addition of EDTA was found by the manufacturer to significantly reduce bacterial growth. This study investigated the influences of method of administration, infusion rate, patient covariates, and EDTA on the pharmacokinetics of propofol. METHODS: Twenty-four healthy volunteers aged 26-81 yr were given a bolus dose of propofol, followed 1 h later by a 60-min infusion. Each volunteer was randomly assigned to an infusion rate of 25, 50, 100, or 200 microg x kg(-1) x min(-1). Each volunteer was studied twice under otherwise identical circumstances: once receiving propofol without EDTA and once receiving propofol with EDTA. The influence of the method of administration and of the volunteer covariates was explored by fitting a three-compartment mamillary model to the data. The influence of EDTA was investigated by direct comparison of the measured concentrations in both sessions. RESULTS: The concentrations of propofol with and without EDTA were not significantly different. The concentration measurements after the bolus dose were significantly underpredicted by the parameters obtained just from the infusion data. The kinetics of propofol were linear within the infusion range of 25-200 microg x kg(-1) x min(-1). Age was a significant covariate for Volume2 and Clearance2, as were weight, height, and lean body mass for the metabolic clearance. CONCLUSIONS: These results demonstrate that method of administration (bolus vs. infusion), but not EDTA, influences the pharmacokinetics of propofol. Within the clinically relevant range, the kinetics of propofol during infusions are linear regarding infusion rate.

Characterization of a primate model of asthma using anti-allergy/anti-asthma agents.

The following study was performed to further characterize a primate model of asthma using classes of drugs that target allergy (pyrilamine, cetirizine), are bronchodilators for the treatment of asthma (salbutamol, salmeterol) or are anti-inflammatory (dexamethasone). These drugs were examined for their ability to inhibit acute, antigen-induced bronchoconstriction, the development of airway hyperresponsiveness (AHR) and the infiltration of leukocytes into the lungs of atopic cynomolgus monkeys (Macaca facsicularis) using a 10-day, multiple antigen (Ag) challenge protocol. All compounds except dexamethasone and cetirizine significantly (p < 0.05) reduced acute, Ag-induced bronchoconstriction (salbutamol: 74.2%, salmeterol: 52.6%%, pyrilamine: 62.4% inhibition) compared to vehicle control trials. Only dexamethasone and salmeterol prevented the development of AHR to methacholine challenge by 90.4 +/- 6.81% and 85.7 +/- 5.61% respectively. Dexamethasone significantly reduced the Ag-induced increase in BAL eosinophils by 85.9 +/- 8.53%. Cetirizine reduced the eosinophil response in 5 of 6 monkeys and salmeterol demonstrated a trend towards reduced eosinophil increases after multiple Ag challenge, but neither of these were statistically significant. These results further illustrate the utility of this model in predicting compound effects against several relevant functional endpoints that are consistent with the effects of similar classes of compounds in humans.

In vitro and in vivo effects of leukotriene B4 antagonism in a primate model of asthma.

To test the hypothesis that leukotriene (LT) B4 antagonists may be clinically useful in the treatment of asthma, CP-105,696 was evaluated in vitro, using chemotaxis and flow cytometry assays, and in vivo, using a primate asthma model. CP-105,696 inhibited LTB4-mediated monkey neutrophil chemotaxis (isolated cells, LTB4 = 5 nM) and CD11b upregulation (whole blood, LTB4 = 100 nM) with IC50 values of 20 nM and 16.5 microM, respectively. Using a modification of a previously described in vivo protocol (Turner et al. Am. J. Respir. Crit. Care Med. 1994. 149: 1153-1159), we observed that treatment with CP-105,696 inhibited the acute increase in bronchoalveolar lavage (BAL) levels of IL-6 and IL-8 by 56.9 +/- 13.2% and 46.9 +/- 14.5%, respectively, 4 h after challenge with Ascaris suum antigen (Ag). CP-105,696 tended to reduce the increase in BAL protein levels 0.5 h after Ag challenge by 47.5 +/- 18.3%, but this was not statistically significant. In addition, CP-105,696 prevented the significant 11-fold increase in airway responsiveness to methacholine after multiple Ag challenge. These results suggest that LTB4 partially mediates acute and chronic responses to antigen in an experimental primate asthma model and support the clinical evaluation of LTB4 antagonists in human asthma.

The effect of 5-lipoxygenase inhibition on Ascaris antigen (Ag)-induced responses in atopic monkeys.

The effects of two 5-lipoxygenase (5LO) inhibitors, ZD2138 or Zileuton, on acute, inflammatory responses to aerosolized Ascaris suum (Ag) were determined in atopic Macaca fascicularis monkeys. Monkeys (n = 6 each group) were dosed with vehicle, 3 or 10 mg/kg ZD2138, or 30 mg/kg Zileuton (p.o.). Both ZD2138 or Zileuton significantly inhibited ex vivo LTB4 production in Ca2+ ionophore-stimulated whole blood from these same monkeys (n = 6 each group) by 45.5% (3 mg/kg ZD2138), 82.5% (10 mg/kg ZD2138) and 84.3% (30 mg/kg Zileuton). ZD2138 (10 mg/kg) reduced bronchoalveolar lavage (BAL) LTE4 levels (65.1% inhibition), BAL neutrophils (88.9% inhibition), and IL-6 (54.0% inhibition) 4h post Ag. Zileuton inhibited these responses and also reduced BAL levels of IL-8 (73.4% inhibition). A second study was performed to evaluate the effects of ZD2138 on chronic Ag-induced responses. Treatment with ZD2138 did not prevent pulmonary inflammation or the development of airway hyperresponsiveness (AHR). Based upon these results, 5LO inhibition significantly reduced ex vivo LTB4 and in vivo LTE4 production as well as several acute inflammatory responses to Ag in the lung. However, ZD2138 did not inhibit more chronic responses following multiple Ag exposure.

Calcium binding and concomitant changes in the structure and heat stability of calprotectin (L1 protein).

Aim-To obtain further data on the structure and conformation of calprotectin, a prominent leucocyte protein found in many species.Methods-The binding of Ca(2+) to calprotectin was studied by means of equilibrium dialysis using (45)Ca as tracer. The thermal stability and denaturation kinetics of calprotectin were studied by means of differential scanning calorimetry. Con-comitant alterations in optical activity resulting from different conditions were measured. A computer program calculated the parameters to fit different models of protein structure. Ultraviolet spectroscopy gave absorbtion spectra. Sedimentation velocity studies and molecular weight determinations by the low speed (sedimentation) equilibrium technique were performed.Results-A maximum of six calcium ions were bound per calprotectin molecule at 0.7 mM calcium chloride. The apparent dissociation constants were calculated. Ca(2+) ions increased the denaturation temperature by 26 degrees K. The enthalpy of denaturation was also increased by Ca(2+). Addition of Ca(2+) to the buffers caused a gradual change in the near UV circular dichroism spectrum, while only minor changes were seen at wavelengths of 210-240 nm. A gradual increase in the sedimentation coefficient was observed on addition of calcium chloride. The extinction coefficient at 279nm was determined: E(279)= 2.53.10(4) M(-1) cm(-1).Conclusions-Calprotectin can bind six calcium ions. Upon binding, the protein shows distinct conformational changes and increased thermal stability. The former may be of importance for its function, while the biological significance of the latter is unknown.

Effects of rolipram on responses to acute and chronic antigen exposure in monkeys.

The following study was performed to test the hypothesis that treatment with rolipram, a specific inhibitor of phosphodiesterase (PDE) IV, should inhibit many pulmonary responses to acute and chronic antigen challenge in atopic monkeys by elevating intracellular cAMP and subsequently inhibiting leukocyte function. Monkeys received subcutaneous injections of either vehicle (2% DMSO) or 10 mg/kg of rolipram 1 h before exposure to Ascaris suum antigen (Ag). Acute responses to Ag, including bronchoconstriction, pulmonary leukocyte infiltration, and cytokine production, were monitored before and 4 h after single Ag aerosol administration. To monitor the effects of rolipram on chronic Ag exposure, a 10-d, multiple-Ag protocol, previously demonstrated to induce airway hyperresponsiveness (AHR) to methacholine (MCh), was performed. Ag exposure increased respiratory system resistance (Rrs) 221.7 +/- 31.88% (n = 5). This increase in Rrs was not significantly altered by rolipram. Rolipram significantly (p < 0.002) increased cAMP levels in bronchoalveolar lavage (BAL) leukocytes 1 h after administration (n = 5). Ag-induced increases in BAL IL-8 and TNF were significantly reduced by rolipram, but IL-1 beta and IL-6 increases were unaffected (n = 9). Ag-induced increases in BAL eosinophils and neutrophils were significantly reduced by rolipram (n = 9). In the multiple-Ag protocol (n = 7), rolipram significantly reduced both the number of BAL eosinophils (p < 0.02) and the development of AHR (p < 0.002). Despite its inability to inhibit acute Ag-induced bronchoconstriction, rolipram was protective against acute and chronic inflammatory responses to Ag and prevented the development of AHR, suggesting that selective PDE-IV inhibition is a relevant target for asthma therapy.

Leukotriene D4 receptor antagonism reduces airway hyperresponsiveness in monkeys.

Airway hyperresponsiveness (AHR) and pulmonary inflammation are observations that are consistently associated with asthma and also occur in a well-characterized monkey model of asthma. The following study was performed to determine whether treatment with an LTD4 receptor antagonist, ICI 198,615, could attenuate antigen-induced pulmonary inflammation and AHR in monkeys using the following protocol. On day 0, the PC200 (the concentration of methacholine (MCh) that doubled respiratory system resistance, Rrs) was determined in 6 male, atopic, cynomolgus monkeys, previously characterized in historical control trials (Control #1) as airway hyperresponsive. Bronchoalveolar lavage (BAL) was then performed to determine total and differential leukocyte counts. On days 3, 5 and 7, each monkey received 10 mg/kg ICI 198,615 (im) 30 min prior to Ascaris suum (Ag) aerosol exposures which doubled Rrs. On day 10, the post-Ag PC200 to MCh was determined and BAL was repeated. Five weeks after this trial was complete, a bracketing control trial (Control #2) was performed in which the monkeys were administered vehicle prior to each Ag exposure. In comparison to the response in both control trials, treatment with the LTD4 antagonist significantly (P < 0.05) inhibited the development of AHR and also significantly reduced (P < 0.05) peripheral blood lymphocyte counts after Ag challenge. Treatment with ICI 198,615 reduced the Ag-induced increase in BAL eosinophils, but statistical significance was obtained only when treated animals were compared to Control #1, not Control #2.(ABSTRACT TRUNCATED AT 250 WORDS)

Enzymatic determination of triglyceride, free cholesterol, and total cholesterol in tissue lipid extracts.

Triglyceride, free cholesterol, and total cholesterol were quantified in lipid extracts of liver and thoracic aorta from nonhuman primates using commercially available enzymatic reagents. Lipids were solubilized in water by the addition of Triton X-100. Results of the enzymatic assays compared favorably with chemical assays of lipids separated by thin-layer chromatography. In addition to saving time, the present method has the advantage of measuring each lipid class from a single sample preparation. Furthermore, the procedure has been adapted for use with microtiter plates that conserve both sample and reagent.

Lung function and radiographic signs of pulmonary fibrosis in oil exposed workers in a cable manufacturing company: a follow up study.

Thirty seven workers employed for at least three years in oil impregnation of cables during 1963-83 were followed up in 1990 to study the development of pulmonary fibrosis and consequences for lung function. They had been exposed to concentrations of mineral oil vapours of 50-100 mg/m3, and concentrations of oil mist of 0.5-1.5 mg/m3. All 29 living persons were traced. For each person one control matched for age, height, and smoking habits was selected. Among 25 workers followed up with radiographic studies, 10 cases of pulmonary fibrosis were found, by contrast with one case in the control group (p less than 0.01). Chest radiographs from 1979-80 and 1989-90 were reviewed. The profusion of small opacities increased in seven of 16 persons during 10 years without exposure. Seventeen workers had lung function tests. The bellows function (VC, FEV1, MVV) and lung volumes (TLC, RV) did not differ from those in the matched controls (p greater than 0.05), but the carbon monoxide transfer factor (TLCO) was decreased. The largest reduction of TLCO (1.5 mmol/kPa/min) was found among workers exposed for 10 years or more (p less than 0.05). Arterial blood gases were not affected at rest, but during maximum tread mill exercise, PO2 and HbO2 were reduced in exposed workers compared with controls, particularly among those exposed for at least 10 years (p less than 0.05). Exposure to low viscosity oil mist and vapour is the most plausible cause of the fibrosis. Unaffected bellows function, reduced TLCO, and decreased arterial blood oxygen during exercise is compatible with peribronchiolar fibrosis.

Antimicrobial actions of calcium binding leucocyte L1 protein, calprotectin.

The calcium binding L1 protein was found to inhibit growth of blood culture isolates of Candida spp and cerebrospinal fluid isolates of Cryptococcus neoformans. Minimum inhibitory concentrations (MIC) were 4-128 mg/l, and concentrations 2-4 times the MIC were fungicidal. Blood culture isolates of Escherichia coli, Klebsiella spp, Staphylococcus aureus, and Staphylococcus epidermidis had MIC values of 64-256 mg/l. Antibacterial activity was strongly influenced by the nature of the culture medium. In view of the biological activity of L1, the name calprotectin is proposed to describe this antimicrobial protein with calcium binding properties.

Pulmonary function and gas exchange at rest and exercise in adolescent girls with mild idiopathic scoliosis during treatment with Boston thoracic brace.

Pulmonary function and gas exchange at rest and during and after standard exercise on bicycle ergometer were studied in 49 girls, aged 10 to 16 years (mean, 13.7), with untreated idiopathic scoliosis, before and with Boston thoracic brace, and after treatment for 3 weeks, reducing the thoracic curve angle from a mean of 32.4 degrees (range, 19-60 degrees) to 17.3 degrees (range, 8-33 degrees). The bracing led to marked decrease in lung volumes, below functions, and CO transfer factor, moderate rise in resting O2 intake, CO2 output and ventilation, and marked rise in ventilatory and O2 cost of exercise, probably due to increased dead space ventilation and O2 cost of breathing. However, repeated studies after 1 day without brace, 6 months after onset of bracing, showed no persistent deterioration of pulmonary function or disturbances of gas exchange, as compared with the pre-bracing state.