From commodity to money: The rise of silver coinage around the Ancient Mediterranean (sixth-first centuries bce).

The reasons why the Western Mediterranean, especially Carthage and Rome, resisted monetization relative to the Eastern Mediterranean are still unclear. We address this question by combining lead (Pb) and silver (Ag) isotope abundances in silver coinage from the Aegean, Magna Graecia, Carthage and Roman Republic. The clear relationships observed between 109Ag/107Ag and 208Pb/206Pb reflect the mixing of silver ores or silver objects with Pb metal used for cupellation. The combined analysis of Ag and Pb isotopes reveals important information about the technology of smelting. The Greek world extracted Ag and Pb from associated ores, whereas, on the Iberian Peninsula, Carthaginians and Republican-era Romans applied Phoenician cupellation techniques and added exotic Pb to Pb-poor Ag ores. Massive Ag recupellation is observed in Rome during the Second Punic War. After defeating the Carthaginians and the Macedonians in the late second century bce, the Romans brought together the efficient, millennium-old techniques of silver extraction of the Phoenicians, who considered this metal a simple commodity, with the monetization of the economy introduced by the Greeks.

Tiotropium improves walking endurance in COPD.

The primary objective of this study was to evaluate the effects of a 3-week treatment with tiotropium on walking capacity in chronic obstructive pulmonary disease (COPD). After familiarisation with study procedures, 36 patients were randomised to receive tiotropium 18 µg once daily or a matching placebo in a double-blind, parallel-group study. Pre- (trough) and 2-h post-dose pulmonary function was measured. An endurance shuttle walk was then completed. The same procedures were repeated after 3 weeks of treatment. Ventilatory parameters were monitored during exercise. At 3 weeks, tiotropium significantly improved walking endurance time in comparison with placebo, with a mean±sd between-group difference of 128±141 s (p=0.017). At 3 weeks, trough values for forced expiratory volume in 1 s (FEV(1)) and forced vital capacity (FVC) were significantly improved with tiotropium in comparison with placebo. The post-dose response to tiotropium was statistically superior to placebo after the first dose and after 3 weeks of treatment for FEV(1), FVC and inspiratory capacity. Ventilation and tidal volume at the end of walking were significantly improved with tiotropium. 3 weeks of tiotropium resulted in a greater walking endurance in patients with COPD. Improvements in FEV(1), maximal ventilation and tidal volume may contribute to this enhanced exercise capacity.

Regulation of epithelial cell proliferation by bronchial fibroblasts obtained from mild asthmatic subjects.

BACKGROUND: Bronchial epithelium is considered a key player in coordinating airway wall remodelling. The function of epithelial cells can be modulated by the underlying fibroblasts through autocrine and paracrine mechanisms. OBJECTIVE: To investigate the effect of phenotypic changes in bronchial fibroblasts from asthmatic subjects on epithelial cell proliferation. METHODS: Epithelial cells and fibroblasts derived from bronchial biopsies of asthmatic and healthy controls were cultured in an engineered model. Proliferation was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium-bromid (MTT). Epidermal growth factor receptor (EGFR), cyclin-dependent kinase inhibitors p21 and p27 were measured by western blots. Total and active forms of transforming growth factor (TGF)-ß1 were measured using ELISA and bioassay. TGF-ß was inhibited using a recombinant TGF-ß soluble receptor II protein. RESULTS: Proliferation of epithelial cells from asthmatics (AE) is increased when cells were cultured with fibroblasts from normal controls (NF). Fibroblasts from asthmatics (AF) significantly decreased the proliferation of epithelial cells from healthy subjects (NE). Activation of p21, p27, EGFR and TGF-ß1 reflects the proliferation data by decreasing in AE cultured with NF and increasing in NE cultured with AF. Neutralization of TGF-ß increased proliferation of epithelial cells cultured in the asthmatic model. CONCLUSION: Fibroblasts from asthmatic subjects regulate epithelial cell prolifearation, and TGF-ß signalling may represent one of the pathway involved in these interactions.

Monitoring sputum eosinophils in mucosal inflammation and remodelling: a pilot study.

Normalisation of eosinophil counts in sputum of asthmatic patients reduces eosinophilic exacerbations. However, the effect of this strategy on airway remodelling remains to be determined. We compared bronchial inflammation and collagen deposition after 2 yrs of treatment guided by either sputum eosinophils (sputum strategy, SS) or by clinical criteria (clinical strategy, CS). As a pilot study, 20 mild asthmatic patients were randomly assigned to CS or SS strategies. Bronchial biopsies were obtained when minimum treatment needed to maintain control was identified and this was continued for 2 yrs. Biopsies were immunostained for inflammatory cells, mucin 5A (MUC5A) and collagen. The mean dose of inhaled corticosteroids at the start and end of the study was similar in both SS and CS groups. Forced expiratory volume in 1 s increased in both groups at the study end. In SS, mucosal lymphocyte and eosinophil counts, but not neutrophils, were reduced at the end of the study. In CS, only activated eosinophil and neutrophil counts decreased. MUC5A staining decreased in SS but not CS. No change in collagen deposition underneath the basement membrane was observed in either strategy. Treatment strategies that normalise sputum eosinophils also reduce mucosal inflammatory cells and MUC5A expression, but do not change subepithelial collagen deposition in mild to moderate asthma.

The effect of IVX-0142, a heparin-derived hypersulfated disaccharide, on the allergic airway responses in asthma.

BACKGROUND: IVX-0142 is a heparin-derived hypersulfated disaccharide devoid of anticoagulant activity while possessing anti-allergic and anti-inflammatory activity in preclinical studies. In a proof-of-concept study, the allergen inhalation challenge model was used to investigate the effect of IVX-0142 in mild atopic asthma. METHODS: Nineteen subjects, not on controller medications, were randomized to an evaluator-blind, placebo-controlled, cross-over study. The effect of a single nebulized dose of IVX-0142 (80 mg) or placebo administered 30 min prior to allergen inhalation was evaluated on the allergic airway responses, airway responsiveness, and airway inflammation. RESULTS: When compared with placebo, 14 and 13 subjects experienced a relatively smaller maximum fall in forced expiratory volume in 1 s (maxFEV(1)%) for the early airway response (EAR) and late airway response (LAR) with IVX-0142, respectively (P < 0.01). The degree of attenuation in the EAR [maxFEV(1)% (mean +/- SE) 26.5 +/- 2.8%vs placebo 31.0 +/- 2.8%, P = 0.059] and LAR (15.6 +/- 2.9%vs placebo 19.0 +/- 2.9%, P = 0.24) with IVX-0142, however, was small and did not reach statistical significance compared with placebo. Similarly, a trend in the attenuation of allergen-induced increase in the absolute sputum cell counts was also observed. No difference in the allergen-induced increase in airway hyper-responsiveness and exhaled nitric oxide was noticed. CONCLUSIONS: The majority of mild atopic asthmatics demonstrated a reduction in the EAR and LAR to IVX-0142. However, the treatment effect observed with a single prechallenge dose of IVX-0142 was small and heterogeneous. The potential anti-allergic and anti-inflammatory effects using multiple higher doses need to be evaluated.

Endurance shuttle walking test: responsiveness to salmeterol in COPD.

Few studies have shown that the endurance shuttle walking test (ESWT) is responsive to treatment in patients with chronic obstructive pulmonary disease (COPD). This exercise test needs to be further investigated because of its relevance for activity of daily living. The aim of the present study was to evaluate, in patients with COPD, the responsiveness of the ESWT in detecting improvement in walking performance after a single dose of salmeterol. In a randomised, double-blind, placebo-controlled crossover trial, 20 patients with COPD performed two ESWT at 80% of peak capacity 2.5 h after inhaling either a placebo or 50 microg of salmeterol. Cardiorespiratory parameters were monitored during each walking test. Inspiratory capacities and Borg ratings for dyspnoea were obtained every other minute throughout the tests. Compared with placebo, salmeterol produced a significant change in lung function and a significant improvement in walking performance (mean+/-sd difference in time: 117+/-20 s; difference in distance: 160+/-277 m). At isotime (the latest exercise time that was reached on both ESWT), a significant reduction in dyspnoea was observed after bronchodilation. Bronchodilation with salmeterol reduced dyspnoea during walking and improved walking capacity in patients with chronic obstructive pulmonary disease. These findings provide further support for the use of the endurance shuttle walking test as an evaluative tool in chronic obstructive pulmonary disease.

Effect of salmeterol on allergen-induced airway inflammation in mild allergic asthma.

A previous study suggested that the long-acting beta2-adrenergic agonist salmeterol (SM) had inhibitory effects on bronchial mucosal inflammation 6 hours after allergen exposure. To further evaluate the influence of SM on allergen-induced airway inflammation. We studied, in a randomized, double-blind, cross-over trial, 16 mild asthmatic patients who had a dual asthmatic response to allergen inhalation. Subjects received 50 microg of SM or placebo (P), twice daily for 1 week each, separated by a 2-week wash-out period. At the end of each treatment period, after withholding SM for 24 h, they had a methacholine inhalation test (medication was resumed after the test), followed 24 h later by an AC with the concentration of allergen that had induced a LAR at baseline. Airway inflammation was assessed 24 h after the AC by bronchoalveolar lavage (BAL) (n = 16) and bronchial biopsies (n = 13). As expected, SM improved baseline FEV1 and PC20 (P < or = 0.009) and decreased the allergen-induced early bronchoconstrictive response. There were no significant differences in BAL cell counts after the two treatments. On bronchial biopsies, numbers (median, mm2) of submucosal CD45 (P: 43 +/- 23; SM: 161 +/- 43, P = 0.031), CD45Ro (P: 37 +/- 19; SM: 126 +/- 41, P = 0.047) and AA1 positive cells (P: 38 +/- 6, SM: 65 +/- 17, P = 0.006) were significantly higher after SM than P treatment. The numbers of CD4 (P: 11 +/- 10; SM: 32 +/- 7, P = 0.085), HLA-DR (P: 65 +/- 30; SM: 116 +/- 36, P = 0.079) and EG2 positive cells (P: 25 +/- 15; SM: 38 +/- 26, P = 0.09) tended to increase with SM treatment. In summary, compared to placebo, 1 week of regular use of SM is associated with an increase in bronchial inflammatory cells 24 h after AC. This is in keeping with the recommendation that salmeterol should only be used with an anti-inflammatory agent, particularly in the context of significant allergen exposure.

Incidence and predictors of ARDS after cardiac surgery.

BACKGROUND: Severe pulmonary injury with the development of ARDS is a potential complication of cardiac surgery and cardiopulmonary bypass (CPB). STUDY OBJECTIVES: This retrospective, case-control study was designed to determine the incidence and mortality of ARDS after cardiac surgery and CPB, as well as to identify preoperative and perioperative predisposing factors of this complication. METHODS: Of 3,278 patients who underwent cardiac surgery and CPB between January 1995 and December 1998, 13 patients developed ARDS during the postoperative period. Each patient was matched with four or five control subjects who had the same type of surgery on the same day but did not develop postoperative respiratory complications. RESULTS: The incidence of ARDS was 0.4%, with an ARDS mortality of 15%. In the ARDS group, 38% had previous cardiac surgery, as compared to 3.5% in the control group (p < 0.002). During the postoperative period, ARDS patients received more blood products (4 +/- 5 vs 2 +/- 3; p < 0.01) and developed shock more frequently (31% vs 5%; p < 0.02) than patients in the control group. Multivariate regression analysis identified previous cardiac surgery, shock, and the number of transfused blood products as significant independent predictors for ARDS, with odds ratios of 31.5 (p = 0.015), 10.8 (p = 0.03), and 1.6 (p = 0.03), respectively. CONCLUSIONS: ARDS following cardiac surgery and CPB was a rare complication that carried a 15% mortality rate. Previous cardiac surgery, shock, and number of blood products received are important predicting factors for this complication.

Long-term influence of inhaled corticosteroids on bone metabolism and density. Are biological markers predictors of bone loss?

Long-term effects of high doses of inhaled corticosteroids (ICS) on bone density and metabolism are still uncertain. Fifty-one patients (37 male, 14 female) using beclomethasone or budesonide at a daily dose > 800 microgram/d (high-dose group [Group HD] mean: 983 microgram/d [prescribed dose x estimated compliance]) or no or < 500 microgram/d (control group [Group C] mean: 309 microgram/d) for more than 5 yr were enrolled in this study. Each had, 3 yr ago and at this last evaluation, a clinical evaluation and measurements of expiratory flows and of bone density and bone metabolism markers. Lumbar spine bone density (last visit) was similar in the two groups with respective values of 0.94 +/- 0.03 (HD) and 0.96 +/- 0.03 g/cm2 (C) (p > 0.05). T and Z scores were -1.21 +/- 0.19 and -0.70 +/- 0.18 (HD), -0.95 +/- 0.25 and -0.47 +/- 0.21 (C) respectively (p > 0.05). A correlation was found between the decrease in bone density and the mean daily dose of corticosteroid in Group HD although these changes were quite small, mean bone density being unchanged over the 3-yr period. Serum and urinary parameters were similar in the two groups. Furthermore, neither initial bone density nor any of the biological parameters could predict changes in bone density over a period of 3 yr. In conclusion, bone density was similar in both study groups and not significantly different over a 3-yr period. Neither initial bone density nor biological markers of bone metabolism helped to predict changes in bone mass.

Persistent hyperplastic primary vitreous with retinal tumor in tuberous sclerosis: report of a case including tumoral immunohistochemistry and cytogenetic analyses.

OBJECTIVE: The authors describe an ocular lesion combining the characteristics of persistent hyperplastic primary vitreous (PHPV) and a retinal tumor in an infant with tuberous sclerosis complex (TSC). STUDY DESIGN: Case report. METHODS: Immunohistochemistry and cytogenetic studies were performed on TSC cells from an intraocular tumor in a 6-week-old infant. RESULTS: Histopathologic examination showed a thick fibrovascular membrane between the aspect of the lens and the astrocytic component of the mass. Glial fibrillary acidic protein (GFAP) showed a variable intracytoplasmic reaction in the astrocytic proliferation, involving approximately 50% of the cells. Tissue culture studies showed a fairly rapid proliferation of fusiform cells, consistent with bipolar astrocytic cells. Cytogenetic studies showed one abnormal clone consisting of three hyperdiploid cells with a loss of chromosome 9 and a gain of chromosomes 6 and 12. CONCLUSION: The atypical localization of the retinal tumor could be explained by the fact that it was trapped during its proliferation by the retinal detachment associated with the PHPV.

Influence of beclomethasone and salmeterol on the perception of methacholine-induced bronchoconstriction.

BACKGROUND: Patient evaluation of asthma severity and medication needs is mostly based on respiratory symptoms and may be influenced by changes in perception of bronchoconstriction-induced sensations. However, the influence of asthma medication on the ability to perceive symptoms is still to be documented. This study evaluated the effects of short-term and regular use of salmeterol on the perception of methacholine-induced bronchoconstriction (MIB) in subjects with mild asthma, using inhaled salbutamol on an "as required" basis (n=15), and in subjects with moderate asthma, using daily inhaled beclomethasone (mean daily dose, 640 microg; n=15) in addition to salbutamol to control their asthma. METHODS: Methacholine challenges (MC) were performed at entry into the study, and then before, 1, and 12 h following inhalation of 50 microg of salmeterol or a placebo, after a 15-day baseline period; and after 4 weeks of twice daily use of those treatments. The measurements were then repeated with the alternate treatment after a 15-day washout period. Finally, a last MC was performed after another 15-day washout period. For each MC, the perception score of bronchoconstriction-associated breathlessness at 20% fall in FEV1 (PS20) was evaluated on a modified Borg scale from 0 to 10. RESULTS: Subjects using regular beclomethasone had a higher baseline PS20 than those using only salbutamol (means: 3.06 0.06 and 2.01+/-0.07, p=0.0001). Short- and long-term use of salmeterol did not change significantly the PS20 compared with placebo (p>0.05) in either group (with or without corticosteroid). Although there were some intraindividual variations, mean PS20 did not vary significantly throughout the study. CONCLUSION: These observations show that the perception of bronchoconstriction-associated breathlessness is not influenced by regular use of salmeterol. Patients using inhaled corticosteroids show a greater perception of MIB.

Tolerance to the protective effects of salmeterol on methacholine-induced bronchoconstriction: influence of inhaled corticosteroids.

Long-acting beta2-adrenoceptor agonists such as salmeterol reduce airway responsiveness for at least 12 h, but this effect seems to decrease with regular use. We evaluated the time-course of the protective effects of salmeterol on methacholine-induced bronchoconstriction, its modulation by inhaled corticosteroids (ICS) and its influence on asthma control. Thirty two subjects (13 males and 19 females) with mild to moderate stable asthma were divided into two groups according to their medication needs: bronchodilators (BD) alone (n=16) or with ICS (n=16). After a 2 week run-in period, a double-blind crossover study was conducted. Subjects from both groups received salmeterol 50 microg b.i.d. or a placebo for 4 weeks each in random order, separated by a 2 week washout period. The provocative concentration of methacholine causing a 20% fall in forced expiratory volume in one second (PC20) was measured before and after each treatment period, 1 h prior to inhalation of salmeterol or placebo and 1 and 12 h after. Baseline forced expiratory volume in one second (FEV1) increased significantly after salmeterol, both after the first dose and at 4 weeks (BD group: 19 and 17%; ICS: 22 and 13%). On the first day of administration, salmeterol provided significant protection in both groups up to 12 h with a PC20 before and 1 and 12 h postdose of 2.2, 21.7 and 12.4, mg x mL(-1), respectively, in the BD group and 2.1, 11.6 and 55 mg x mL(-1), respectively, in the ICS group. After 4 weeks, this effect was significantly attenuated in both groups with a PC20 before, 1 and 12 h postdose of 3.3, 10.9 and 7.1 mg x mL(-1), respectively, in the BD group and 2.1, 5.0 and 2.3 mg x mL(-1), respectively, in the ICS group. This loss of protective effect was of similar magnitude in both groups. Respiratory symptoms, rescue beta2-agonist use and baseline FEV1 did not change significantly throughout the study in both groups. In conclusion, the bronchoprotective effect of salmeterol decreased with regular use both 1 and 12 h postdose; inhaled corticosteroids did not prevent this reduction. However, the development of tolerance was not associated with loss of asthma control.

Recombinant interferon alfa-2b in the treatment of vision-threatening capillary hemangiomas in childhood.

INTRODUCTION: Hemangiomas of the orbit and eyelids may cause serious ocular problems usually related to amblyopia and astigmatism. Steroids have become the accepted treatment. However, some hemangiomas are resistant to steroids or require prolonged use,with unacceptable side effects. Interferon alfa-2b, an antiangiogenic protein, was used in this prospective study to treat visually threatening hemangiomas that were unresponsive to oral or intralesional steroid treatment. METHODS: Forty patients aged 2 to 36 months with life- or organ-threatening hemangiomas were prospectively enrolled to evaluate the efficacy and safety of interferon alfa treatment for hemangiomas. Sixteen of these 40 patients had hemangiomas causing serious ocular dysfunction. The patients were treated with 3 x 10(6) U/m2 interferon alfa-2b subcutaneously daily for 3 months; treatment was then tapered or retreated according to response and protocol. Therapeutic responses were documented. RESULTS: Fifteen patients with ocular hemangiomas have finished treatment. The pretreatment volume measured by computed axial tomographywas an average of 22.3 cm3. Clinical response with eye opening was observed at an average of 6 weeks. There was a significant regression of the hemangioma in all patients, with an average 82% reduction in volume. Patients were treated with glasses and occlusion therapy as appropriate. Final visual acuities with a follow-up averaging 14 months after cessation of interferon treatment were normal, except that five of 15 patients had amblyopia; one of these patients had 20/40, two had 20/60, and two had 20/70. There were no major illnesses or serious adverse side effects. CONCLUSION: Interferon alfa-2b treatment resulted in good to excellent regression of all the hemangiomas. This regression was clinically significant,with patients able to open the affected eye an average of 6 weeks into treatment. Visual results were good, with moderate amblyopia occurring only in patients treated at a later age. Interferon alfa-2b was well tolerated by these young patients, and no significant illness or side effect has occurred.

Influence of inhaled steroids on recovery from occupational asthma after cessation of exposure: an 18-month double-blind crossover study.

Occupational asthma (OA) is a useful model for the study of asthma in humans. The possibility that inhaled corticosteroids, in addition to withdrawal from the workplace, could improve clinical and functional recovery from OA can be hypothesized. We assessed clinical, functional, and behavioral characteristics of 32 subjects (22 male, 10 female), in all but one of whom OA was confirmed by specific inhalation challenges induced by either high- (n=13) or low-molecular-weight (n=19) agents within 3 mo after cessation of exposure. In this randomized, crossover, double-blind study, subjects (paired for baseline PC20 and duration of symptoms after exposure) received either placebo or 1,000 micrograms of inhaled beclomethasone daily for 1 yr, followed by the alternate medication for 6 mo. Various clinical, functional, and behavioral parameters were examined at each 3-mo visit. Significant improvement in clinical (nocturnal symptoms, cough), functional (morning and evening peak expiratory flow rates), and behavioral (quality of life) parameters were detected in the active-treatment period, although the magnitude of the improvement was relatively small. Side effects (oropharyngeal, reduced cortisol) were similar in the placebo and treatment groups. Distinguishing subjects who started with the active preparation from those who were given placebo first showed that most clinical and behavioral parameters improved in the former instance, whereas there was no significant difference in the latter. We conclude that inhaled corticosteroids induce a small but significant overall improvement of the asthmatic condition in subjects with occupational asthma caused by high- and low-molecular-weight agents after withdrawal from exposure. The beneficial effect is, however, more pronounced if inhaled steroids are given early after diagnosis.

On- and off-responses in the photopic electroretinogram in complete-type congenital stationary night blindness.

We examined the on- and off-responses of the photopic electroretinogram in patients with complete congenital stationary night blindness. Standard flash electroretinograms as well as those produced in a ganzfeld modified for long-duration light stimuli (500 msec) permitted the separation of on- and off-responses in four patients and four normal subjects. The amplitude and latency of the elctroretinogram on-response (a- and b-waves) and off-response (d-wave) in addition to the oscillatory potentials of the off-response in normal subjects and patients were compared. The abnormal on-response was demonstrated in all the patients, and the off-response with its oscillatory potentials were preserved. We showed that the second portion of the off-response (of inner retinal origin) is normal. If congenital stationary night blindness is a defect of depolarizing bipolar cells, these results preclude input of the depolarizing bipolar cells and support the hyperpolarizing bipolar cells as the cellular origin of the off-response electroretinogram.

Clinical evaluation of aminocaproic acid for managing traumatic hyphema in children.

PURPOSE: The purpose of this study is to determine the incidence of secondary hemorrhage after traumatic hyphema in children and to evaluate the efficacy of epsilon aminocaproic acid in reducing this incidence. METHODS: In a prospective, randomized, double-blind study performed between November 1987 and February 1994, 94 children admitted for traumatic hyphema were assigned to receive either aminocaproic acid (n = 48) (100 mg/kg every 4 hours; maximum, 30 g daily) or placebo (n = 46) for 5 days. Patients who had ingested aspirin in the week preceding admission were excluded from the study. RESULTS: Mean age of the patients was 9.4 years. Black patients comprised 4% of the study population. Secondary hemorrhage occurred in only three patients (3.2%), two from the placebo group and one from the aminocaproic acid group, none of whom had any complications. The duration of hospital stay and the clot resorption times were increased significantly in the aminocaproic acid group (P < 0.001). CONCLUSIONS: The authors report a very low incidence of secondary hemorrhage compared with most previous studies. This difference is likely related to the small proportion of black patients in our study and to the exclusion of patients having ingested aspirin, two factors that seem to be associated with higher rates of rebleeding. The efficacy of aminocaproic acid could not be determined due to the low incidence of hemorrhage. The results of this study, however, suggest that the incidence of secondary hemorrhage in white patients without prior ingestion of aspirin is insufficient to justify routine use of aminocaproic acid in managing traumatic hyphema. Rather, an individualized decision based on the risk factors of each patient would seem more appropriate to avoid a slower clot resorption time and possible side effects of this medication.

Putative effects of nerve extract on carbonic anhydrase III expression in rat muscles.

Carbonic anhydrase III (CA III), the predominant CA isoform in skeletal muscle is very sensitive to neuronal influences. We aimed to determine whether CA III expression could be influenced by neurotrophic factor(s) present in sciatic nerve extract (SNE). Intact muscles were thus compared with denervated soleus (SOL), extensor digitorum longus (EDL), and tibialis anterior (TA) muscles injected daily for 7 days with saline solution (SS) or with SNE. CA III activity was significantly increased in SS-treated EDL and TA muscles compared to control (CTR), while SNE injections partially prevented this increase. There was no significant difference for CA III activity in the SOL between CTR, SS, and SNE groups. The CA III mRNA increase observed in response to denervation was reduced by 40% in SNE-treated EDL and TA muscles. While SOL CA III mRNA level was not affected by denervation, a 52% decrease was observed with SNE. We concluded that neuronal modulation of CA III expression in type II fibers may involve a neurotrophic component.

Anterior transposition of the inferior oblique for dissociated vertical deviation with inferior oblique overaction.

We reviewed the charts of 17 children (27 eyes) who underwent anterior transposition of the inferior oblique muscle for dissociated vertical deviation coexistent with inferior oblique overaction. All the eyes showed an improvement in the inferior oblique overaction. Twenty-one eyes had reduction in the dissociated vertical deviation, five eyes showed no change in the degree of dissociated vertical deviation, and in one case the hyperdeviation increased after surgery. No intraoperative or late postoperative complications were noted. Anterior transposition is an effective procedure for weakening inferior oblique overaction coexistent with dissociated vertical deviation.

Effects of long-term use of high-dose inhaled steroids on bone density and calcium metabolism.

BACKGROUND: Inhaled steroids are the mainstay in the antiinflammatory treatment of asthma. In the last few years, these agents have been used in increasing doses. Because high doses of inhaled steroids can reduce serum osteocalcin levels, there are concerns regarding their long-term effects on bone metabolism. METHODS: We examined the effects of doses of 800 micrograms/day or greater of beclomethasone or budesonide for more than 18 months in 37 asthmatic subjects (group A), matched to a control group of 37 asthmatic subjects using little or no inhaled steroids (< 500 micrograms, group B). All had a clinical evaluation, measurements of expiratory flows, and determination of serum creatinine, calcium, phosphate, gamma-glutamyl transpeptidase, alkaline phosphatase, cortisol, and osteocalcin levels. A 2-hour urinary sample was obtained for creatinine, calcium, phosphate, hydroxyproline, and cortisol measurements. Bone density was assessed at the lumbar spine level and at the hip with a Hologic-QDR-2000 osteodensitometer (Hologic, Boston, Mass.). RESULTS: The mean (+/- SD) daily dose of inhaled steroids over the last 2 years was 1140 +/- 353 micrograms in group A (mean duration of use of > 800 micrograms/day, 34.2 +/- 13.0 months) and 89 +/- 98 micrograms for group B (mean duration of use of < 500 micrograms/day, 15.7 +/- 18.8 months). The number of oral steroid treatments (< 15 days) during the last 2 years was small in the two groups, 0.92 +/- 1.27 in group A and 0.05 +/- 0.23 in group B (p > 0.05). The only differences between our two groups in terms of serum or urinary parameters were for mean osteocalcin level, which was lower in group A (2.16 +/- 1.09 ng/ml) than in group B (2.70 +/- 0.98 ng/ml) (p = 0.029), and in mean urinary phosphorous level, which was higher in group A (1.44 +/- 0.76 mmol/2 hr) than in group B (1.26 +/- 0.89 mmol/2 hr (p = 0.034). Mean urinary hydroxyproline levels were 15.51 +/- 6.98 mumol/2 hr in group A and 13.53 +/- 7.13 mumol/2 hr in group B (p > 0.05). Mean mineral bone densities of the lumbar spine and hip were similar in the two groups with values of 0.923 +/- 0.136 gm/cm2 and 0.719 +/- 0.147 gm/cm2 in group A and 0.933 +/- 0.154 gm/cm2 and 0.694 +/- 0.095 gm/cm2 in group B (p > 0.05). The T and Z scores for lumbar spine were -1.32 +/- 1.22 and -0.85 +/- 1.02 in group A and -1.19 +/- 1.33 and -0.72 +/- 1.08 in group B (p > 0.05). There was no correlation between the duration or dose of steroid use and bone density or osteocalcin. Although the serum osteocalcin level was lower in the group of subjects using high-dose inhaled steroids, suggesting an osteoblastic depression, bone density was not significantly different compared with the control group. CONCLUSIONS: This study shows that although the serum osteocalcin level was lower and the urinary phosphorus level was higher in subjects using high-dose inhaled steroids for a mean of 34 months, compared with a control group, no significant difference in bone density or other markers of bone metabolism was found between the two groups.

Five-year changes in airflow obstruction and airway responsiveness in mild to moderate asthma.

We documented changes in airflow obstruction and airway responsiveness to histamine after a period of 5 +/- 1 y in 40 subjects with mild to moderate asthma, 14 men and 26 women, aged 20-68 y (mean: 43.6 y). Asthma had to be stable at both evaluations. Each subject answered a respiratory questionnaire and expiratory flows and airway responsiveness to histamine were measured. No significant difference was found between the sub-groups based on atopic status and medication use for mean 5-y changes in FEV1 or PC20. However, although severity of asthma was similar in both groups, the number of subjects who significantly increased their FEV1 or PC20 at 5 y tended to be higher in the group using corticosteroids regularly (> 9 months/y): FEV1: 35.7%, PC20: 42.9% compared to those using them intermittently (< 3 months/y): FEV1: 23.3%, PC20: 35.3% (p > 0.05). This difference was related to recent (< 6 months) use of inhaled corticosteroids. On the other hand, the number of subjects with a significant reduction in FEV1 or PC20 after 5 y was lower when inhaled corticosteroids were used regularly: FEV1: 14.3%; PC20: 28.6%, compared to intermittently: FEV1: 41.2%; PC20: 41.2%, although this difference was not statistically significant. Changes in FEV1 or PC20 at 5 y were not correlated with the duration of asthma, the number of months on inhaled corticosteroids, or age at the time of diagnosis. Airway responsiveness was most often improved in atopics compared to non-atopics. In conclusion, overall 5-y changes in FEV1 or PC20 in our group of subjects were minimally influenced by the duration of the asthma and age at the time of diagnosis. The number of subjects with improved airway responsiveness was higher among atopics and after regular use of inhaled corticosteroids. Further prospective studies should be done on the long-term influence of regular vs. intermittent use of inhaled corticosteroids on the natural history of asthma.