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A novel fiber-packed solid-phase extraction (SPE) tip was designed based on electrospun nanofibers. The tip was used to investigate the extraction of hydrocortisone (HC), cortisone acetate (CA), ethinylestradiol (EE), and estradiol (E2). The effects of diameters, porous figurations, and functional groups of the electrospun fibers on the selectivity and efficiency were studied. The experimental results indicated that the detection limit of cortisol in water sample could be as low as 0.75 ng/mL. When the tip is used for detection of cortisol in human hair the efficiency of biological sample pretreatment is better than the traditional SPE method. Our method could significantly simplify the traditional SPE process and lower the cost. Industrial application of the tip is anticipated.

Objective: Cardiovascular disease has been reported to be more common in patients with endogenous Cushing's syndrome (CS) compared to the normal population. In addition to altered lipid profile, inflammation seems to play an important pathogenic role in atherogenesis, but the role of inflammation in CS-associated cardiovascular disease is still not clear. To further elucidate these issues we measured several markers of inflammation in CS patients at baseline and following operative treatment and potential cure., Subjects: Twenty-eight CS patients (22 women, 6 men) were included in the study and 21 of these patients (15 women, 6 men) were also followed longitudinally for a mean 33 months (range 5-69 months) after operative treatment. For comparison, blood samples were also collected from 24 healthy controls (21 women, 3 men)., Results: We show a distinct cytokine profile in CS patients before and after operative treatment. Thus, while interleukin (IL)-8 and osteoprotegerin (OPG) were significantly increased in CS patients before operation and fell during follow-up, levels of C-reactive protein (CRP) and soluble intracellular adhesion molecule 1 (sICAM) were significantly decreased at baseline, reaching normal levels after operation. While soluble CD40 ligand was within normal limit at baseline, this marker of platelet-mediated inflammation was markedly elevated during follow-up., Conclusions: Our findings suggest a complex interaction between CS and inflammation. In particular, the raised levels of IL-8 and OPG in CS patients, despite glucocorticoid excess, may represent an inflammatory and pro-atherogenic phenotype. However, the clinical relevance of these findings will have to be clarified.

We report on a 19-year-old woman with polyglandular autoimmune syndrome type II (APS II). She was diagnosed with addison's disease and hypothyroidism due to chronic autoimmune thyroiditis. Her mother had celiac disease and her brohter had diabetes mellitus typ 1. Chronic autoimmune thyroiditis was diagnosed in her mother, subsequently. In patients and their relatives, who have autoimmune disorders, a search for autoimmune polyglandular syndrome is crucial. Consequently, it would be appropriate that the patient and all family members are asked for clinical signs and symptoms of autoimmune disorders. Annual measurement of morning cortisol, TSH and fasting plasma glucose may useful. Screening of affected individuals as well as their first-degree relatives for celiac disease is recommended. Therapy of APS II consists of hormone replacement therapy, but thyroxin replacement may induce life-threatening adrenal failure in a patient with untreated Addison's disease. Thus, in case of doubt hydrocortisone should be given before the thyroxine administration is started.

A novel microemulsion based on a mixture of diethyl L-tartrate (DET) and SDS was developed for the microemulsion EKC (MEEKC) determination of structurally related steroids. The system consisted of 0.5% w/w DET, 1.7% w/w SDS, 1.2% w/w 1-butanol, 89.6% w/w phosphate buffer (40 mM, pH 7.0), and 7% w/w ACN. With an applied voltage of +10 kV, a baseline separation of aldosterone (A), cortisone acetate (CA), dexamethasone (D), hydrocortisone (H), hydrocortisone acetate (HA), prednisolone (P), prednisolone acetate (PA), prednisone (Ps), triamcinolone (T), and triamcinolone acetonide (TA) could be achieved. Under the optimized conditions, the reproducibility of the retention time (n = 4) for most of the compounds was less than +/-0.8% with the exception of A, Ps, and T. The average number of theoretical plates was 18 800 plates/m. The results were compared with those achieved by the modified micellar EKC (MEKC). MEEKC showed obvious advantages over MEKC for the separation of highly hydrophobic substances. To further evaluate the system, we tested the MEEKC method by analyzing corticosteroids in a spiked urine sample.

A male presented at age 2.2 years with a 6-week history of intermittent vomiting and hyperpigmentation. Investigations showed salt wasting with hyperkalaemia, a grossly impaired cortisol response to ACTH stimulation, elevated renin and ACTH. Family history revealed that two maternal uncles had died soon after birth. A third uncle failed to thrive during infancy but improved with a course of cortisone, then being untreated until further investigation revealed adrenal insufficiency. A fourth uncle died aged 10 days, with urinary salt loss and hypoplastic adrenal glands at postmortem. Molecular studies on the proband, his mother, maternal grandmother, and surviving uncle showed a novel C to G substitution at nucleotide position 794 (missense mutation T265R) in the DAX1 (NR0B1) gene. The proband has responded well to steroid replacement but has proved sensitive to 9alpha-fludrocortisone treatment, developing hypertension on a dose of 133 microg/m(2)/day. At 8.8 years he was noted to have testicular volumes of 4 ml, despite no other evidence of secondary sexual development and prepubertal gonadotrophin levels. Novel features of this family include a novel DAX1 mutation, marked variability in age of presentation, hypertension on 'standard' doses of 9alpha-fludrocortisone and mild testicular enlargement., (Copyright 2007 S. Karger AG, Basel.)

No ideal parameter is available for assessment of the glucocorticoid replacement therapy in Addison's disease. Serum cortisol day-curves can be used to monitor the therapy, but this technique is cumbersome and expensive. We evaluated the potential for saliva cortisol measurement in this setting. We found excellent correlation between serum and saliva cortisol after oral intake of cortisone acetate (no. 7) or iv administration of hydrocortisone (no. 4) (Pearson's R=0.83-0.98, p<0.002). A morning dose of 12.5 mg cortisone acetate yielded wide interindividual variations in cortisol levels in saliva. Saliva cortisol measurements were successfully adopted to evaluate and adjust doses in outpatients. We conclude that cortisol measurement in saliva is practical and reliable, and is preferable to serum cortisol measurement in the assessment of the glucocorticoid replacement therapy. Our results confirm that only a minority of patients require more than 12.5 mg of cortisone acetate (equivalent to 10 mg hydrocortisone) in the morning to have sufficient cortisol levels during the first part of the day.

Objective: Evaluation of glucocorticoid replacement quality in adrenal insufficiency (AI) relies primarily on clinical judgement and thus largely depends on the physician's expertise. It is a matter of debate whether cortisol day curves are of value in assessing glucocorticoid replacement quality. Here we compared the results of a structured clinical assessment to the outcome of repeated, timed serum cortisol measurements., Design: Cross-sectional study in the outpatient department of a university teaching hospital., Patients: Forty-six patients (19 men, 27 women, age range 16-76 years) with primary (n = 23) and secondary (n = 23) AI on stable replacement with a median dose of 37.5 mg cortisone acetate (range 25-50 mg) since 10 +/- 7 years (range 1-31 years)., Measurements: Clinical performance was scored by structured assessment of signs and symptoms, physical examination and routine biochemical tests. Serum cortisol was measured on two to three separate occasions in three timed samples after the morning glucocorticoid dose. Bone mineral density was measured in 15 patients with long-standing glucocorticoid replacement., Results: Thirty-seven patients were considered well replaced, whereas clinical scores suggested over- or under-replacement in five and four, respectively. There was no correlation of the clinical score with total or body weight-adjusted glucocorticoid dose. The mean z score of serum cortisol differed significantly between under- and over-replaced patients (P < 0.05) but neither group differed significantly from well-replaced patients. Bone mineral density was normal in all patients studied., Conclusions: Our results suggest that serum cortisol day curves are of limited value in the monitoring of glucocorticoid replacement. Bone mineral density in AI is generally normal and does not require routine follow-up.

Introduction: Free fatty acids (FFAs) induce hepatic insulin resistance and enhance hepatic gluconeogenesis. Glucocorticoids (GCs) also stimulate hepatic gluconeogenesis. The aim of this study was to investigate whether the FFA-induced hepatic insulin resistance is mediated by increased activity of hepatic 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1), accompanied by elevated hepatic cortisol levels., Methods: Following a 10-h overnight fast, six healthy male volunteers were investigated. A euglycaemic hyperinsulinaemic clamp was performed during lipid or saline infusion. To assess hepatic 11beta-HSD1 activity, plasma cortisol levels were measured after oral administration of cortisone acetate during lipid or saline infusion. In addition, 11beta-HSD activities were determined in vivo by calculating the urinary ratios of GC metabolites., Results: Lipid infusion increased FFAs (5.41 +/- 1.00 vs. 0.48 +/- 0.20 mmol/l; P < 0.005) and significantly increased insulin resistance [glucose infusion rate (GIR) 6.02 +/- 2.60 vs. 4.08 +/- 2.15 mg/kg/min; P < 0.005]. After lipid and saline infusions no changes in 11beta-HSD1 activity were found, neither by changes in cortisone acetate to cortisol conversion nor by differences in urinary free cortisol (UFF) or cortisone (UFE), 5beta-tetrahydrocortisol (THF), 5alpha-THF, cortisone (THE), UFF/UFE and (5alpha-THF + THF)/THE ratios., Conclusions: We found no change in hepatic and whole-body 11beta-HSD1 activity during acute FFA-induced insulin resistance. Further studies are necessary to clarify whether 11beta-HSD1 in muscle and adipose tissue is influenced by FFAs and whether 11beta-HSD1 is involved in other conditions of insulin resistance.

Isolated ACTH deficiency is a rare disorder often presenting with long-standing aspecific symptoms combined with unusual clinical presentations. We here describe a patient in whom pericardial effusion was part of the dinical presentation and fully resolved on steroid at replacement dosage, highlighting the possibility of hypoadrenalism as an additional cause of pericardial effusion of unknown origin.

The separation of neutral hydrophobic corticosteroids (cortisone, cortisone acetate, hydrocortisone, hydrocortisone acetate, prednisolone and prednisolone acetate) by microemulsion electrokinetic chromatography (MEEKC) was studied. In the preparation of microemulsion, heptane was the solvent, n-butanol the co-surfactant and, as anionic surfactants, sodium dodecyl sulfate (SDS) or taurodeoxycholic acid sodium salt (STDC) were employed. Using an acidic running buffer, (phosphate pH 2.5) a strong suppression of the electroosmotic flow (EOF) was observed; this resulted in a fast anodic migration of the analytes partitioned into the negatively charged microemulsion droplets. Under these conditions, STDC showed better separation of corticosteroids than the conventional SDS; however, the use of a single anionic surfactant did not provide the required selectivity. The addition of the neutral surfactant polyoxyethylene glycol octadecyl ether (Brij 76) significantly altered the migration of each analytes allowing a better tuning of separation; however, in order to obtain adequate resolution between couples of adjacent critical peaks, the addition of neutral cyclodextrins (CDs) was found to be essential. This apparently complex system (CD-MEEKC), was optimized by studying the effect of the most important parameters affecting separation: STDC concentration, Brij 76 concentration, nature and concentration of cyclodextrins. Following a rational step-by-step approach, the optimised conditions providing the complete separation of the analytes were found to be: 4.0% STDC, 2.5% Brij 76, 6.6% n-butanol, 1.36% heptane and 85.54% of a solution 5 mM beta-CD in 50 mM phosphate buffer (pH 2.5). The optimized system was preliminary applied to the detection of corticosteroids related substances at impurity level and it could be considered a useful orthogonal alternative to HPLC methods.

Since the optimal glucocorticoid replacement needs to avoid over and under treatment, the adequacy of different daily cortisone acetate (CA) doses was assessed in 34 patients with primary and central hypoadrenalism. The conventional twice CA 37.5 mg/day dose was administered to all patients (A regimen: 25 mg at 07:00 h, 12.5 mg at 15:00 h), while in 2 subgroups of 12 patients the dose was shifted on 2 thrice daily regimens (B: 25 mg at 07:00, 6.25 mg at 12: 00, 6.25 mg at 17:00; C: 12.5 mg, 12.5 mg, 12.5 mg). In other 12 patients the conventional dose was reduced to a thrice 25 mg/day administration (D regimen: 12.5 mg, 6.25 mg, 6.25 mg). In all patients, urinary free cortisol (UFC) excretion and cortisol day curves were evaluated. During the CA 37.5 mg administration, nadir cortisol levels were significantly higher with the thrice daily regimens (143 +/- 31 on B and 151 +/- 34 nmol/l on C) than with the conventional twice (85 +/- 16 nmol/l). Moreover, UFC, morning cortisol levels and mean cortisol day curves were similar in each group. Finally, during D regimen nadir cortisol levels were higher than in A and similar to B and C regimens. No difference in UFC and in cortisol day curves by reducing the CA dose was found. In conclusion, the thrice daily cortisone regimens, in which more physiological cortisol levels are achieved, perform better as replacement therapy. The administration of 25 mg/day CA confirms that replacement therapy is more adequate with a lower dose, particularly in patients with central hypoadrenalism.

The title compound, C21H28O4, a synthetic glucocorticoid, crystallizes with a single molecule in the asymmetric unit. Ring A is almost in a half-chair conformation, rings B and C are almost in chair conformations, and ring D is between a twist and a 13beta-envelope conformation. The A/B ring junction is quasi-trans, whereas the B/C and C/D ring junctions both approach trans characteristics. The molecule as a whole is slightly convex towards the beta side, with an angle of 9.60 (2) degrees between the C10-C19 and C13-C18 vectors. Molecular-packing and hydrogen-bonding (both intra- and intermolecular) interactions play a major role in the structural association of the compound.

Intestinal maturation can be influenced by intrinsic factors (glucocorticoid hormones) and by extrinsic factors (resident microflora); their relative roles in ontogeny of mouse intestinal trehalase expression, a marker of general gut development, and of beta1,4-galactosyltransferase (beta GT), a marker of glycosyltransferase development, were investigated. In conventional (CONV) mice, beta GT and trehalase gene expression rapidly increased to adult levels by the fourth postnatal week. In germ-free (GF) mice, beta GT expression remained at initial low levels and was rapidly induced on reintroduction of luminal microbes of the adult gut but not of microbes characteristic of the suckling gut. Similar developmental patterns were observed for colonic galactosyl beta1,4-linked glycoconjugates, products of beta GT activity. These results indicate an essential role for microbes in the ontogeny of beta GT. In both CONV and GF mice, cartisone acetate (CA) precociously accelerated the ontogeny of beta GT and trehalase until maturation of the gut occurred (day 22). In the mature gut of CONV mice, both beta GT and trehalase are elevated and insensitive to CA; in GF mature mice, the expression of beta GT remains low, whereas the expression of trehalase was at mature levels, regardless of CA treatment. These changes in enzyme activity were accompanied by parallel changes in mRNA, implying transcriptional regulation. Thus both microbes and cortisone regulate gut ontogeny, but only suckling gut responds to CA, an intrinsic factor, whereas adult gut beta GT expression remains sensitive to microflora, an extrinsic factor. However, induction of the adult pattern of glycosyltransferase expression in mature gut requires colonization by microflora typical of adult gut, suggesting an essential role for intestinal colonization in the ontogeny of normal intestinal mucosal cell surface glycoconjugate receptors.

Objectives: To determine the frequencies of CYP3A4 alleles (CYP3A4*4,*5 and *6) in Chinese hyperlipidemic patients and to observe the impact of CYP3A4*4 (Ile118Val) genetic polymorphism on the lipid-lowering effects of simvastatin and on the activity of CYP3A4., Methods: From hospitalized and non-hospitalized patients, 211 unrelated hyperlipidemic patients were recruited for genotyping. CYP3A4 genotypes were determined by means of polymerase chain reaction and restriction fragment length polymorphism analysis. Of the non-hospitalized hyperlipidemic patients, 8 with CYP3A4*1/*1 and 8 with CYP3A4*1/*4 genotypes were selected to be treated with 20 mg simvastatin daily for 4 weeks. Serum triglycerides (TG), cholesterol (CHO) and low-density lipoprotein (LDL) levels were determined using an automated analyzer (Hitachi 747, Boehringer Mannheim, Mannheim, Germany). CYP3A4 activity was determined by the ratio of 6-hydroxycortisol to free cortisol (6-OHC/FC) in the morning spot urine with a high-throughput liquid chromatography-tandem mass spectrometry method., Results: Of 211 subjects, 14 (allele frequency 3.32%) were heterozygous for CYP3A4*4 (Ile118Val). Nevertheless, no subjects with a CYP3A4*5 or CYP3A4*6 allele or homozygous for CYP3A4*4 were identified. The ratio of 6beta-OHC/FC was 9.9 +/- 13.7 and 56.6 +/- 35.7 in subjects with the Ile118Val variant (n = 8) and in CYP3A4 wild-type subjects (n = 8), respectively (P = 0.0039). After oral intake of simvastatin 20 mg daily for 4 weeks, the change of serum lipids in CYP3A4*1/*1 and CYP3A4*1/*4 groups showed a significant difference, with a mean decrease in triglycerides and total cholesterol of 38.1 +/- 7.6% versus 25.1 +/- 8.3% (P = 0.034) and of 35.8 +/- 9.6% versus 22.0 +/-20.4% (P = 0.0015) (means +/- SD), respectively. We found no statistically significant difference in the reductions of LDL between subjects carrying the *1 and *4 genotypes (29.0 +/- 7.4% versus 36.8 +/- 8.8%, P = 0.0721)., Conclusions: The allele frequency of CYP3A4*4 was 3.32% among the hyperlipidemic patients from the Chinese mainland. CYP3A4*4 was an allelic variant related to a functional decrease of CYP3A4 activity, and *4 expression seemed to increase the lipid-lowering effects of simvastatin.

Necrotizing enterocolitis (NEC) is a major inflammatory disease of the premature human intestine that can be prevented by glucocorticoids if given prenatally before the 34th wk of gestation. This observation suggests that a finite period of steroid responsiveness exists as has been demonstrated in animal models. Human intestinal xenografts were used to determine whether a glucocorticoid responsive period exists in the developing human intestine. Developmental responsiveness was measured by lactase activity and inflammatory responsiveness by IL-8, IL-6, and monocyte chemotactic protein-1 (MCP-1) induction after an endogenous (IL-1 beta) or exogenous (LPS) proinflammatory stimulus, respectively. Functional development of ileal xenografts were monitored for 30 wk posttransplantation, and the lactase activity recapitulated that predicted by in utero development. Cortisone acetate accelerated the ontogeny of lactase at 20 wk (immature) but the effect was lost by 30 wk (mature) posttransplant. Concomitant with accelerated maturation, the IL-8 response to both IL-1 beta and LPS was significantly dampened (from 6- to 3-fold) by glucocorticoid pretreatment in the immature but not mature xenografts. The induction of IL-8 was reflected at the level of IL-8 mRNA, suggesting transcriptional regulation. The excessive activation of IL-8 in the immature gut was mediated by a prolonged activation of ERK and p38 kinases and nuclear translocation of NF-kappa B due to low levels of I kappa B. Steroid pretreatment in immature intestine dampens activation of all three signaling pathways in response to proinflammatory stimuli. Therefore, accelerating intestinal maturation by glucocorticoids within the responsive period by accelerating functional and inflammatory maturation may provide an effective preventive therapy for NEC.

Background: Inflammation and oedema of the facial nerve are implicated in causing Bell's palsy. Corticosteroids have a potent anti-inflammatory action which should minimise nerve damage and thereby improve the outcome of patients suffering from this condition., Objectives: The objective of this review was to assess the effect of steroid therapy in the recovery of patients with Bell's palsy., Search Strategy: We searched the Cochrane Neuromuscular Disease Group register (searched December 2003) for randomised trials, as well as MEDLINE (January 1966 to April 2003), EMBASE (January 1980 to April 2003) and LILACS (January 1982 to April 2003). We contacted known experts in the field to identify additional published or unpublished trials., Selection Criteria: Randomised trials comparing different routes of administration and dosage schemes of corticosteroid or adrenocorticotrophic hormone therapy versus a control group where no therapy considered effective for this condition was administered, unless it was also given in a similar way to the experimental group., Data Collection and Analysis: Two reviewers independently assessed eligibility, trial quality, and extracted the data., Main Results: Four trials with a total of 179 patients were included. One trial compared cortisone acetate with placebo; one compared prednisone plus vitamins, with vitamins alone; one compared high-dose prednisone administered intravenously against saline solution, and one, not-placebo controlled, tested the efficacy of methylprednisolone. Allocation concealment was appropriate in two trials, and the data reported allowed an intention-to-treat analysis. The data included in the meta-analyses were collected from three trials with a total of 117 patients. Overall 13/59 (22%) of the patients allocated to steroid therapy had incomplete recovery of facial motor function six months after randomisation, compared with 15/58 (26%) in the control group. This reduction was not significant (relative risk 0.86, 95% confidence interval 0.47 to 1.59). The reduction in the proportion of patients with cosmetically disabling sequelae six months after randomisation was also not significant (relative risk 0.86, 95% confidence interval 0.38 to 1.98). The trial not included in the meta-analysis showed a non-significant difference in outcomes between the arms., Reviewers' Conclusions: The available evidence from randomised controlled trials does not show significant benefit from treating Bell's palsy with corticosteroids. More randomised controlled trials with a greater number of patients are needed to determine reliably whether there is real benefit (or harm) from the use of corticosteroid therapy in patients with Bell's palsy.

Objective: Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21-OHD) is characterized by high androgen levels, ambiguous genitalia or premature pubarche, increased height velocity and skeletal maturation. Considering the possibility of changes in the IGF system components depending on the state of clinical control, the objective of the present study was to analyse serum IGF-I, IGF-II and IGFBP levels in children with 21-OHD under two states of clinical control., Patients and Design: We studied 12 prepubertal children with 21-OHD CAH aged 4.0 +/- 0.7 years. They were classified as good (GC) or poor control (PC) based on growth rate, signs of adrenal insufficiency or Cushing syndrome, progression of sexual characteristics and serum androgens levels. Blood samples were obtained from each patient in two different states of clinical control (GC and PC) for biochemical measurements., Measurements: IGF-I, IGF-II, IGFBP-1, IGFBP-2 and IGFBP-3 were determined by immunoassays. IGFBPs were also analysed by Western ligand blotting (WLB)., Results: Levels of IGF-I (P = 0.03) and IGFBP-3 (P = 0.01) were higher in GC than in PC while IGFBP-1 (P = 0.004) concentrations were lower in GC patients. A trend towards higher levels of IGF-II (P = 0.08) and lower levels of IGFBP-2 (P = 0.08) was observed in GC children. Increased IGFBP-4 band intensity was observed in GC children (P = 0.03)., Conclusion: Higher levels of IGF-I, IGFBP-3 and IGFBP-4, but lower levels of IGFBP-1, were associated with better control in children with 21-OHD CAH. These findings are different from those observed in children with other causes of increasing androgens levels and are likely to be related to the insufficient glucocorticoid status.

Objective: To assess the usefulness of measuring plasma cortisol profiles in growth hormone-treated hypopituitary adults and to compare these with cortisol levels in healthy controls., Methods: Eleven ACTH-deficient adult patients received 12.5 mg cortisone-acetate orally at 16.00 h and 25 mg at 07.00 h. The patients arrived in the ward at 12.00 h. After tablet intake at 16.00 h, samples for serum cortisol were taken at hourly intervals for the next 24 h, except between 07.00 and 12.00 h when samples were drawn every half hour; 24-h urinary free cortisol (24-h-UFC) excretion was collected simultaneously. For comparison, 8 healthy controls were investigated., Results: The patients had circulating cortisol levels with very low plasma cortisol at 07.00 h before their morning dose of cortisone acetate. At the same time period, controls had their highest plasma cortisol levels. After tablet intake the patients had a rapid initial absorption of cortisol, but a marked variability in the morning peak levels (Cmax), and the Cmax was in general higher and occurred 90 min later than the Cmax in the controls. The 24-h-UFC excretion and 24-h area under the curve (24-h-AUC) did not differ between patients and controls. The female patients had higher 24-h-AUC for plasma cortisol (p=0.032) and tended to have higher plasma cortisol peaks in the morning, but had levels of 24-h-UFC similar to those of the male patients., Conclusions: Conventional cortisone substitution with a twice-daily replacement regimen in hypopituitary adults results in abnormal circulating cortisol profiles with low or non-measurable morning values and variable individual peaks. This suggests that the present dosing schemes have to be improved and that cortisone substitution should be individualized.

A 60-year-old man was hospitalized with complaints of general malaise and weight loss. On admission, ACTH and cortisol levels were low, and thyroid function tests revealed hyperthyroidism. These findings and further examination led to a diagnosis of isolated ACTH deficiency (IAD) with Graves' disease. It is known that IAD is frequently associated with thyroid disease, but its association with Graves' disease is rare. The present case is worth noting, because some reports indicate that aggravation of associated Graves' disease may concomitantly aggravate adrenal insufficiency in patients with IAD.

Purpose: To test the effect of a drug combination therapy on ocular perfusion in human eyes affected by idiopathic intermediate uveitis., Methods: Seven patients (12 eyes) showing active signs of intermediate uveitis, with at least two more similar episodes reported within the previous 12 months, were enrolled in a prospective case series. Two fellow healthy eyes of two of the enrolled patients were studied as internal controls. Color Doppler imaging of the central retinal artery (CRA), the ophthalmic artery (OA), and the posterior ciliary arteries (PCAs) was performed at the time of enrollment, and at 6 and 12 months after starting treatment with oral fluorocortolone, cyclosporine, and parenteral methotrexate. The best-corrected visual acuity was concurrently measured as a second parameter., Results: In the 12 affected eyes, the mean visual acuity (+/-SD) improved from 0.15(+/-0.12) to 0.04(+/-0.18) LogMAR (paired samples Student's t-test: p = 0.015). The resistivity index (RI +/- SD) of the CRA decreased from 0.81(+/-0.13) to 0.71(+/-0.13)(p = 0.0091). Further, the variation of the RI in the PCAs reached a borderline significance (p = 0.062), decreasing from 0.71(+/-0.12) to 0.61(+/-0.12). No significant changes were observed in the OA. Moreover, eyes showing a visual improvement of > or =0.1 (LogMAR) were more likely to show a > or =10% improvement of the RI for the CRA (Fisher's exact test: p = 0.018; power = 90%; alpha probability = 5%; odds ratio = 2,4)., Conclusions: In eyes affected by idiopathic intermediate uveitis, treated with a systemic drug combination therapy, the improvement of the visual acuity seems to correlate with a proportional improvement of the retrobulbar circulation.

Objective: 11 beta-hydroxysteroid dehydrogenase type 1 (11 beta HSD1) converts inactive cortisone to active cortisol. 11 beta HSD1 activity is increased in GH deficiency and inhibited by GH and IGF-I in acromegaly. However it is not known whether these changes in cortisol metabolism exert significant effects during hydrocortisone therapy, and the effect has not been studied in patients taking cortisone acetate. We have studied the effect of GH induced 11 beta HSD1 inhibition in hypopituitary adults with severe GH deficiency to determine whether this inhibition has a different magnitude of effect when patients are taking different forms of glucocorticoid replacement therapy., Design, Patients and Measurements: We have taken the ratio of 11-hydroxy/11-oxo cortisol metabolites (Fm/Em), an established measure of net 11 beta HSD activity to reflect the likely balance of cortisol to cortisone exposure in tissues expressing 11 beta HSD1, principally the liver and adipose tissue. We recruited 10 hypopituitary adults all on established glucocorticoid replacement therapy, but who were not receiving GH. Patients were treated with their standard hydrocortisone therapy for one week and an equivalent dose of cortisone acetate in its place for one week in random order. Serial serum cortisol assessments and urine steroid profiles were performed on each treatment. All patients were then established on GH therapy for at least three months before the two-week cycle was repeated. Fm/Em was also measured in a control population (20F, 20M)., Results: Prior to GH, the ratio Fm/Em was greater with hydrocortisone compared with cortisone acetate replacement (1.17 +/- 0.28 and 0.52 +/- 0.09 respectively, P < 0.001) or with normal subjects (normal males: 0.81 +/- 0.24, females 0.66 +/- 0.14). Following GH replacement Fm/Em fell in patients on hydrocortisone and cortisone acetate (Pre-GH: 0.84 +/- 0.40, Post-GH: 0.70 +/- 0.34, P < 0.05) confirming the inhibition of 11 beta HSD1 by GH/IGF-I. Conversely, the ratio of urinary free cortisol/cortisone did not change indicating unchanged 11 beta HSD2 activity. Mean circulating cortisol also fell in all subjects after GH. This effect was greater during cortisone acetate treatment (-18.7%, P < 0.0001), than during hydrocortisone replacement (-10.9%, P < 0.05)., Conclusions: Our data suggest that tissue exposure to glucocorticoid is supra-physiological in hypopituitary patients with untreated GH deficiency taking hydrocortisone replacement therapy. This situation is ameliorated by GH replacement therapy. However, local and circulating cortisol concentrations are more vulnerable to the inhibitory effect of GH on 11 beta HSD1 in patients taking cortisone acetate, such that serum cortisol assessments should be made in patients taking cortisone acetate after GH therapy to ensure that glucocorticoid replacement remains adequate.

A method is described for the preparation of two types of multi-labeled 6 beta-hydroxycortisol containing either five deuterium atoms at C-19 methyl and C-1 methylene or four 13C atoms at C-1, C-2, C-4, and C-19 in addition to the five deuterium atoms for use as analytical internal standards for gas chromatography-mass spectrometry (GC-MS). BMD derivatives of [1,1,19,19,19-2H(5)]cortisone and [1,2,4,19-13C(4),1,1,19,19,19-2H(5)]cortisone (cortisone-2H(5)-BMD and cortisone-13C(4),2H(5)-BMD) were first synthesized via indan synthon method starting from optical active 11-oxoindanylpropionic acid and labeled isopropenyl anion ([1,1,3,3,3-2H(5)]- or [1,3-13C(2),1,1,3,3,3-2H(5)]isopropenyl anion). The labeled isopropenyl anion was prepared from commercially available [1,1,1,3,3,3-2H(6)]- or [1,3-13C(2),1,1,1,3,3,3-2H(6)]acetone. Ultraviolet (UV) irradiated autoxidation at C-6 position of 3-ethyl-3,5-dienol ether derivatives of the labeled cortisone-BMDs gave 6 beta-hydroxy-[1,1,19,19,19-2H(5)]cortisone-BMD and 6 beta-hydroxy-[1,2,4,19-13C(4),1,1,19,19,19-2H(5)]cortisone-BMD, respectively, as a mixture of 6 beta- and 6 alpha-epimers in a ratio of 4:1. Separation of 6 beta- and 6 alpha-epimers by thin-layer chromatography (TLC) and subsequent hydrolysis of the BMD group at C-17 gave pure labeled 6 beta-hydroxycortisone. After protecting the keto group at C-3 of the labeled 6 beta-hydroxycortisone-BMD as semicarbazone, reduction of 11-keto group with NaBH(4) and subsequent removal of the C-3 and C-17 protecting groups gave 6beta-hydroxy-[1,1,19,19,19-2H(5)]cortisol (6 beta-hydroxycortisol-2H(5)) and 6 beta-hydroxy-[1,2,4,19-13C(4),1,1,19,19,19-2H(5)]cortisol (6 beta-hydroxycortisol-13C(4),2H(5)), respectively, as a mixture of 6 beta- and 6 alpha-epimers (6 beta:6 alpha=4.4:1). The isotopic compositions of 6 beta-hydroxycortisol-2H(5) and 6 beta-hydroxycortisol-13C(4),2H(5) were 90.9 and 92.1 at.%, respectively. Furthermore, 6 beta-hydroxy-[1 alpha,16,16,17 alpha-2H(4)]testosterone was synthesized by the UV irradiated autoxidation at C-6 position of 3-ethyl-3,5-dienol ether derivative of deuterium-labeled testosterone ([1 alpha,16,16,17 alpha-2H(4)]testosterone) obtained by using catalytic deuteration and hydrogen-deuterium exchange reactions.

The aim of this study was to determine whether intestinal xenografts could recapitulate human in utero development by using disaccharidases as markers. Twenty-week-old fetal intestine was transplanted into immunocompromised mice and was followed. At 20-wk of gestation, the fetal human intestine was morphologically developed with high sucrase and trehalase but had low lactase activities. By 9-wk posttransplantation, jejunal xenografts were morphologically and functionally developed and were then monitored for

Production of the proinflammatory cytokines interleukin (IL)-1 alpha and tumor necrosis factor (TNF)-alpha and of the chemotactic chemokine macrophage inflammatory protein (MIP)-1 alpha by bronchoalveolar macrophages (BAMs) from mice in response to Aspergillus conidia was tested after in vivo administration of saline, dexamethasone, cortisone acetate, granulocyte-macrophage colony-stimulating factor (GM-CSF), or a combination. Dexamethasone suppressed production of IL-1 alpha, TNF-alpha, and MIP-1 alpha; GM-CSF reduced secretion slightly but antagonized dexamethasone suppression when the two were given in combination. Cortisone acetate gave results similar to dexamethasone, but cortisone acetate suppression of BAM responses lasted 7 days, > or = 4 days longer than dexamethasone suppression. The effect of GM-CSF on cortisone acetate suppression lasted at least 7 days. GM-CSF could promote resistance to conidia by maintaining proinflammatory responses.

Invasive pulmonary aspergillosis is an emerging devastating infection in the immunocompromised host that is treated with corticosteroids for neoplastic disease or for organ transplantation. By use of a model of invasive pulmonary aspergillosis in corticosteroid-treated CF-1 mice, prior infection and 2 Aspergillus fumigatus vaccine preparations (sonicate and filtrate) administered intranasally and subcutaneously were tested for efficacy in protecting against subsequent lethal A. fumigatus infection. The mortality rates were as follows: control subjects, 100%; prior infection, 12.5%; sonicate administered intranasally, 29%; sonicate given subcutaneously, 0%; filtrate given intranasally, 75%; and filtrate given subcutaneously, 50%. Prior infection and A. fumigatus sonicate vaccine administered by 2 routes protected corticosteroid-treated animals against subsequent lethal invasive pulmonary aspergillosis. The sonicate vaccine was more protective, but the subcutaneous route was more effective.

Problem: Female mice that are injected with estradiol-17beta (E2) and testosterone during the 7-day immune adaptive period are infertile at adulthood. To determine whether the resultant infertility can be caused by steroids other than estrogens/ androgens, this study examined the effect of injecting cortisone, alone, and in combination with E2 and testosterone, on reproductive function., Method of Study: Neonatal (C57BL/6J x A/J)F1 B6A female mice were injected from 3 to 6 days of age with sesame oil:ethanol (9:1; v:v), alone, or containing 20 microgg cortisone acetate, 20 microg E2, or 20 microg testosterone. Two additional groups were given 20 microg cortisone acetate in combination with 20 microg E2 or 20 microg testosterone. At adulthood the animals were killed, the stage of vaginal estrus determined, the ovaries examined for the presence of corpora lutea and follicular cysts, and circulating levels of progesterone, E2, and testosterone were measured by radioimmunoassay (RIA)., Results: It was found that injections of cortisone seriously compromise reproductive development. For example, 11% of cortisone-injected animals had ovaries that lacked corpora lutea. In addition, 39% of cortisone-injected females had ovaries with follicular cysts. Cortisone-injected females also had low levels of circulating progesterone (18 ng/mL versus 30 ng/mL for the sesame oil-injected females)., Conclusion: It is concluded that the deleterious effect of steroids on reproductive function, when administered during the immune adaptive period, is not restricted to estrogens and androgens. It is proposed that injections of cortisone alter T-lymphocyte subsets, which contributes to anovulation and the production of follicular cysts.

Pituitary apoplexy is a sight-threatening syndrome in which a pituitary adenoma undergoes sudden enlargement as a result of haemorrhage, infarction or both. Classic features of the syndrome include sudden severe headaches, reduced consciousness, visual impairment, ophthalmoplegia and/or endocrinological disturbance. Pituitary apoplexy has been reported following cardiac bypass surgery. The case is reported of a 68-year-old man who presented with left external and internal ophthalmoplegia, complete ptosis, mild chemosis, reduced vision, and an orbital bruit following coronary artery bypass grafting. Carotid angiography showed the left internal carotid artery to be bowed anteriorly and narrowed. Magnetic resonance imaging demonstrated features consistent with pituitary apoplexy. It is believed that an orbital bruit has not previously been reported in pituitary apoplexy.

Classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency is characterized by a defect in cortisol and aldosterone secretion and adrenal hyperandrogenism. Current treatment is to provide adequate glucocorticoid and mineralocorticoid substitution to prevent adrenal crises and to suppress excess adrenal androgen secretion. Satisfactory adrenocortical suppression often requires supraphysiological doses of hydrocortisone, which may produce an unacceptable degree of hypercortisolism. A new four-drug treatment regimen of flutamide, testolactone, reduced hydrocortisone dose, and 9alpha-fludrocortisone has been shown to achieve normal growth and development after 2 yr of therapy and may, therefore, represent a potential alternative approach to the treatment of children with classic congenital adrenal hyperplasia. We investigated the effect of flutamide and testolactone, and flutamide alone, on cortisol clearance by performing clearance studies twice in 13 children (6 males and 7 females; age range, 7.0-14.5 yr) with classic 21-hydroxylase deficiency. All studies were conducted at least 3 months after institution of the four-drug treatment regimen. In eight patients (group 1), the first cortisol clearance study was performed on the four-drug regimen, and the second study was performed after a 48-h washout period off flutamide and testolactone. In five patients (group 2), the first study was conducted 1 wk after discontinuation of testolactone and while patients were receiving flutamide, hydrocortisone and 9alpha-fludrocortisone, and the second study was performed after a 48-h washout period off flutamide. Oral hydrocortisone was held on the day of the clearance studies, and all patients received a continuous infusion of hydrocortisone (0.6 mg/m(2).h) from 1800 h to 0200 h, with cortisol concentrations measured once hourly. In addition, an in vitro study was conducted to exclude the possibility of an analytical interference of flutamide, 2-hydroxyflutamide, and testolactone with the serum cortisol immunoassay. Total body cortisol clearance was significantly lower during treatment with the four-drug regimen than during treatment with hydrocortisone and 9alpha-fludrocortisone (153.5 +/- 26.8 vs.355.4 +/- 65.8 ml/min; P = 0.001). Similar results were obtained comparing flutamide, hydrocortisone, and 9alpha-fludrocortisone therapy to hydrocortisone and 9alpha-fludrocortisone therapy (155.8 +/- 26.5 vs. 281.8 +/- 96.2 ml/min; P = 0.037). The in vitro study indicated that an interference with the serum cortisol immunoassay was unlikely. These findings indicate that the addition of flutamide and testolactone to the treatment regimen of hydrocortisone and 9alpha-fludrocortisone decreases cortisol clearance in patients with classic 21-hydroxylase deficiency, and this effect seems to be due to flutamide. Glucocorticoid replacement doses should be reduced when flutamide is added to the treatment regimen of patients receiving hydrocortisone.

Objective: Many patients with Addison's disease have complaints that might be related to the disease or to its treatment. However, only a few studies have addressed the subjective health status of patients with adrenocortical failure. The aim of the present study was to assess the subjective health status with special emphasis on fatigue among patients with Addison's disease. SUBJECTS, DESIGN AND MEASUREMENT: In a postal survey, 79 patients with confirmed primary adrenal failure (Addison's disease) completed the Short Form 36 (SF-36) and the Fatigue questionnaires. The subjective health status in Addison's disease was compared with normative data from the general population., Results: General health and vitality perception were most consistently impaired in the patients with Addison's disease. The scores on physical functioning and role-physical were low in women. Social functioning and role-emotional scores were also lower than normal in the female patients, but this was confined to the patients with autoimmune polyendocrine syndromes. Patients with autoimmune polyendocrine syndromes tended to have lower scores than patients with solitary Addison's disease. The level of fatigue was higher than normal for both men and women. Working disability at ages 18-67 years was 26%, compared with 10% in the corresponding general Norwegian population. The high working disability increased with age and was higher in subgroups with concomitant endocrine diseases. Most subjective health parameters were lower among the disabled compared to the patients in work., Conclusions: Patients with Addison's disease under replacement therapy with cortisone acetate and fludrocortisone have reduced general health perception and vitality, and increased fatigue. Female patients reported reduced physical function, which might be due to adrenal androgen depletion. Mental health seems more influenced by concomitant endocrine diseases, but mental fatigue might be a specific feature in adrenal failure. The patient population is heterogeneous, with normal findings in a substantial proportion but markedly reduced subjective health status and working ability in many others. Thus, there might be potential for further refinement of replacement therapy.

Confusion exists over the species status and host-specificity of the tapeworm Rodentolepis (= Hymenolepis) nana. It has been described as one species, R. nana, found in both humans and rodents. Others have identified a subspecies; R. nana var. fraterna, describing it as morphologically identical to the human form but only found in rodents. The species present in Australian communities has never been identified with certainty. Fifty one human isolates of Rodentolepis (= Hymenolepis) nana were orally inoculated into Swiss Q, BALB/c, A/J, CBA/ CAH and nude (hypothymic) BALB/c mice, Fischer 344 and Wistar rats and specific pathogen free (SPF) hamsters. Twenty four human isolates of R. nana were cross-tested in flour beetles, Tribolium confusum. No adult worms were obtained from mice, rats or hamsters, even when immunosuppressed with cortisone acetate. Only one of the 24 samples developed to the cysticercoid stage in T. confusum; however, when inoculated into laboratory mice the cysticercoids failed to develop into adult worms. The large sample size used in this study, and the range of techniques employed for extraction and preparation of eggs provide a comprehensive test of the hypothesis that the human strain of R. nana is essentially non-infective to rodents.

Background: Inflammation and oedema of the facial nerve are implicated in causing Bell's palsy. Corticosteroids have a potent anti-inflammatory action which should minimise nerve damage and thereby improve the outcome of patients suffering from this condition., Objectives: The objective of this review was to assess the effect of steroid therapy in the recovery of patients with Bell's palsy., Search Strategy: We searched the Cochrane Neuromuscular Disease Group register for randomised trials, as well as MEDLINE, EMBASE and LILACS (to December 2000). We contacted known experts in the field to identify additional published or unpublished trials., Selection Criteria: Randomised trials comparing different routes of administration and dosage schemes of corticosteroid or adrenocorticotrophic hormone therapy versus a control group where no therapy considered effective for this condition was administered, unless it was also given in a similar way to the experimental group., Data Collection and Analysis: Two reviewers independently assessed eligibility, trial quality, and extracted the data., Main Results: Three trials with a total of 117 patients were included. One trial compared cortisone acetate with placebo; one compared prednisone plus vitamins, with vitamins alone; and one, not-placebo controlled, tested the efficacy of methylprednisolone. Allocation concealment was appropriate in two trials, and the data reported allowed an intention-to-treat analysis. Overall 13/59 (22%) of the patients allocated to steroid therapy had incomplete recovery of facial motor function six months after randomisation, compared with 15/58 (26%) in the control group. This reduction was not significant (relative risk 0.86, 95% confidence interval 0.47 to 1.59). The reduction in the proportion of patients with cosmetically disabling sequelae six months after randomisation was also not significant (relative risk 0.86, 95% confidence interval 0.38 to 1.98)., Reviewer's Conclusions: The available evidence from randomised controlled trials does not show significant benefit from treating Bell's palsy with corticosteroids. More randomised controlled trials with a greater number of patients are needed to determine reliably whether there is real benefit (or harm) from the use of steroid therapy in patients with Bell's palsy.

Background: Pediatric endocrinologists initially treat congenital adrenal hyperplasia with either cortisone acetate (CA) or hydrocortisone (HC). Despite high doses of CA, we noted that 17-hydroxyprogesterone (17-OHP) and corticotropin were not fully suppressed in serum from neonates with 21-hydroxylase deficiency (21-OHD) until they were 40- to 80-days-old. In contrast, serum concentrations of 17-OHP were suppressed immediately by oral treatment with HC., Methods: We sought to understand the reason for this discrepancy. Serum cortisol (F), cortisone (E), and 17-OHP were measured by radioimmunoassay or high-performance liquid chromatography in seven neonates with 21-OHD and in 118 normal subjects. From the time of diagnosis, CA was administered to four of the neonates with 21-OHD, while HC was given to the other three., Results: In normal subjects serum E concentrations were greater than F during the first 2 months after birth, whereas F concentrations exceeded E after 2 months of age. Although infants receiving CA initially were given a high dose, serum F concentrations were extremely low, while 17-OHP concentrations were high until about 2 months of age. Then serum F exceeded E, and 17-OHP became fully suppressed even though infants received only a moderate dose of CA. In contrast, HC administration successfully normalized serum 17-OHP in the neonatal period. With temporary switching of neonates from HC to CA, serum F concentrations immediately decreased and 17-OHP concentrations increased., Conclusion: Conversion of E to F may be limited during early infancy, adversely affecting treatment with CA. Cortisone acetate may be inappropriate as a glucocorticoid replacement during early infancy in patients with 21-OHD.

Growth hormone (GH) replacement may inhibit 11beta-hydroxysteroid dehydrogenase type 1 (11betaHSD1) activity, resulting in diminished conversion of cortisone to cortisol. Moreover, GH replacement may lower bioavailability of hydrocortisone tablets. Therefore, substitution therapy with cortisone acetate could be disadvantageous during GH replacement. We conducted a randomized, placebo-controlled GH replacement (1 to 2 U GH/day) study during 6 months, followed by a 6-month open extension study (2U GH/day). Twelve men and 12 women with GH deficiency, of whom 17 received cortisone acetate (25 to 37.5 mg/day), participated. Eight patients were randomized to placebo initially. At baseline, after 6 and 12 months, urinary cortisol and cortisone metabolites were measured. No changes in urinary cortisol metabolites were observed after 6 months placebo (n=8). After 6 months GH the urinary (tetrahydrocortisol+allotetrahydrocortisol)/tetrahydrocortison ratio ((THF+alloTHF)/THE ratio) was unaltered in cortisone acetate treated patients (n = 17) and in patients with intact adrenal function (n = 7), whereas after 12 months GH the (THF + alloTHF)/THE ratio decreased only in cortisone acetate treated patients (1 dropout, n=9). Urinary THF and alloTHF were higher in cortisone acetate treated patients than in patients with intact adrenal function before GH and remained so after 12 months GH (p < 0.05 to p < 0.01). The sum of cortisol + cortisone metabolites did not change after GH in either group. The urinary free cortisol/free cortisone ratio, presumably reflecting renal 11betaHSD2 activity, tended to decrease in cortisone acetate treated patients (p<0.07 and p<0.05 after 6 and 12 months GH, respectively), as well as in patients with intact adrenal function (p<0.05 and a decrease in five/six patients after 6 and 12 months GH, respectively). In conclusion, these results suggest that GH replacement decreases 11betaHSD1 activity, which becomes manifest in patients receiving cortisone acetate substitution therapy. 11betaHSD2 activity is unaltered or may even be increased. It is unlikely that the bioavailability of conventional doses of cortisone acetate is impaired after GH replacement.

Purpose: To examine the intracellular and extracellular expression of myocilin in the human and primate trabecular meshwork (TM) in the presence and absence of glucocorticoids., Methods: Myocilin expression was examined in cultured human TM cells by Northern blot analysis and myocilin antibody-mediated immunoprecipitation. Myocilin expression was quantified using high-resolution two-dimensional polyacrylamide gel electrophoresis of radiolabeled proteins from human TM cells, TM tissue explants, and perfused human anterior segments cultured with and without dexamethasone (DEX) for 14 to 21 days, as well as TM tissue from pigtailed monkeys treated orally for 1 year with cortisone acetate. Immunofluorescence with anti-myocilin antibodies was used to localize cellular and extracellular expression of myocilin in cultured human TM cells., Results: Glucocorticoid treatment caused a significant induction of myocilin mRNA, a tetrad of cell-associated proteins, and 8 to 20 secreted proteins (molecular mass [M(r)] 56 and 59 kDa and isoelectric point [pI] 5.2 and 5.3) in some, but not all the cultured human TM cells and explanted tissues. Western immunoblot analysis using anti-myocilin peptide antibodies identified these proteins as encoded by the MYOC gene. There was significant induction of the myocilin proteins in three perfusion-cultured human eyes, in which DEX-induced elevated intraocular pressure developed. Monkeys treated 1 year with cortisol acetate showed steroid glaucoma-like morphologic changes in the TM that correlated with the induction of myocilin in the TM. Immunofluorescence analysis of cultured TM cells localized myocilin intracellularly in discrete perinuclear and cytoplasmic vesicular deposits as well as extracellularly on the cell surface associated with the extracellular matrix. In several DEX-treated TM cell lines, there were significant levels of myocilin secreted into the media. Enzymatic deglycosylation of proteins in the TM media converted the higher molecular weight isoforms of myocilin (approximately 57 kDa) to the lower molecular weight isoforms ( approximately 55 kDa)., Conclusions: Although the function of myocilin is unknown, induction of these TM proteins was found in eyes in which glucocorticoid-induced ocular hypertension developed. Therefore, myocilin may play an important pathogenic role in ocular hypertension in addition to its role in certain forms of POAG.

Adrenal nodules have been described in patients with 21-hydroxylase deficiency (21OHD). These nodules are usually considered to be ACTH-dependent, as is the commonly seen diffuse cortical hyperplasia. We evaluated the presence and behavior of adrenal nodules in patients with 21OHD. Based upon hormonal status and treatment compliance, the patients were classified into three categories: poor, regular and good control. Out of the 26 patients, eight had the non-classic, four salt-wasting and 14 simple virilizing forms. All patients underwent initial adrenal morphological studies, either by CT or MRI. Those with nodules were reevaluated after 12 months of adequate replacement therapy. Nodules were found in four of eight untreated patients and two of three patients with poor hormonal control, but not in the 15 patients with regular or good control. Adrenal nodules in these six patients demonstrated a considerable size reduction and even disappearance after adequate replacement therapy, showing that these nodules were ACTH-dependent. Thus, six out of 26 patients with 21OHD presented adrenal nodules, which were more frequent in the untreated or poorly-controlled patients, and all regressed in size after adequate therapy.

Objective: To analyze the alterations of pulmonary surfactant in immunocompromised host with Pseudomonas aeruginosa (PA) pneumonia., Methods: 50 rats were randomly divided into two groups, one immunosuppressed with cyclophosphamide and cortisone acetate as ICH group, another as control group (CON), their lung tissue and bronchoalveolar lavage fluid (BALF) were collected before PA challenging and 3 h, 6 h, 9 h, 24 h after PA challenging intratracheally, wet/dry ratio (W/D) of lung tissue were measured, concentrations of total protein (TP), total phospholipids (TPL), disaturated phosphatidylcholine (DSPC) and surfactant protein A (SP-A) in BALF were analyzed., Results: The ratios of DSPC/TPL and DSPC/TP decreased significantly in both ICH and CON groups after PA infection, there were not significant differences between the two groups, no change in the concentrations of TPL and DSPC. Concentration of SP-A and SP-A/TP in ICH group decreased remarkably 6 h after PA pulmonary infection than before [(1.8 +/- 1.1) microgram/ml vs (4.2 +/- 1.5) microgram/ml, (1.4 +/- 0.7) microgram/mg vs (11.7 +/- 8.1) microgram/mg, P < 0.05], meanwhile there were no significant alterations in CON group. W/D and TP concentrations increased in both groups after PA challenging, however the alterations were much greater in ICH group (P < 0.05). Alterations of SP-A appeared a negative correlation with alterations of TP and W/D (r = -0.793, P < 0.01, r = -0.769, P < 0.01). The ratios of SP-A/TPL and SP-A/DSPC decreased significantly 6 h after PA challenging than before, the ratios were much lower in ICH group than in CON group during 6 h-9 h after PA inoculation., Conclusion: After PA pulmonary infection, alterations of phospholipids could initially appear a relative decrement of DSPC during acute phase of infection, much remarkable decrease of SP-A in ICH group could be associated with the more severe lung injury, alterations of SP-A were more obvious than surfactant lipids in ICH.

A reversed-phase HPLC method for the determination of benproperine phosphate tablets is reported. The chromatographic conditions were Hypersil-C18 column(5 microns, 4.6 mm i.d. x 150 mm) at 35 degrees C, mobile phase of methanol-water-glacial acetic acid-triethylamine(60:35:5:0.1, V/V) with a flow rate of 0.9 mL/min and UV detection at 270 nm. Cortisone acetate was selected as the internal standard. The linear relationship of calibration curve was good in the range of 9.96 mg/L-49.8 mg/L(r = 0.9998). The average recovery and RSD were 99.91%(n = 5) and 0.43% respectively. The total time of analysis for a run was within 7 min. The method is simple, sensitive, rapid and accurate.

Purpose: This study was designed to investigate the protective effect of a pedunculated seromuscular flap on intestinal anastomosis after corticosteroid treatment., Methods: Forty male Sprague-Dawley rats were divided into four groups, and all animals underwent intestinal anastomosis. Two groups, with or without seromuscular flap wrapping, received 5 mg cortisone acetate, and two groups received placebo (saline) preoperatively for 16 days. Anastomotic strength was defined as bursting pressure (in millimeters of mercury). The pedunculated seromuscular flap was prepared from a segment of intestine next to the anastomosis. Intestinal bursting strength at the anastomotic site was measured at Postoperative Day 8., Results: The anastomotic bursting strength was significantly lower in the steroid groups at Postoperative Day 8 (P < 0.01). The pedunculated seromuscular flap increased the strength of the anastomosis both in the steroid and control groups (P < 0.05)., Conclusion: The adverse effect of corticosteroids on intestinal anastomoses may be prevented by a pedunculated seromuscular flap.

We report a case of bilateral adrenal incidentaloma caused by the capsulatum variety of Histoplasma capsulatum diagnosed in a 74 years old man born in and a life time resident of Treviso, Italy, with the exception of two years spent in Pakistan (1964-1966) as a well-driller. The patient was hospitalized in 1995 for alcoholic chronic hepatitis, chronic Helicobacter pylori gastritis and post-infarction ischemic cardiomyopathy. Abdominal ultrasound incidentally showed bilateral adrenal masses (the right one 6.3 cm in diameter) confirmed by computed tomography, with adrenal function within normal limits. After three months, the patient was again hospitalized due to evening fever, asthenia, anorexia, weight loss and occasional hyperhidrosis. Abdominal ultrasound showed an increase of the right adrenal lesion with normal adrenal function. Ultrasound-guided fine needle aspiration did not prove useful for diagnosis. Accordingly, a laparotomy with bilateral biopsy was performed; histology showed the presence of numerous tissue form cells of H. capsulatum variety capsulatum. Serum anti-H. capsulatum antibodies were negative. Since March, 1996, the patient was given itraconazole and his symptoms quickly regressed but the computed tomography findings, however, have not changed and the patient has adrenal hypofunction that is being treated with cortisone acetate.

The efficacy of SCH27899, a new everninomicin antibiotic, against replicative Legionella pneumophila lung infections in an immunocompromised host was evaluated using a murine model of Legionnaires' disease. A/J mice were immunocompromised with cortisone acetate and inoculated intratracheally with L. pneumophila serogroup 1 (10(5) CFU per mouse). At 24 h postinoculation, mice were administered either SCH27899 (6 to 60 mg/kg [MPK] intravenously) or a placebo once daily for 5 days, and mortality and intrapulmonary growth of L. pneumophila were assessed. In the absence of SCH27899, there was 100% mortality in L. pneumophila-infected mice, with exponential intrapulmonary growth of the bacteria. In contrast, administration of SCH27899 at a dose of > or =30 MPK resulted in > or =90% survival of infected mice, which was associated with inhibition of intrapulmonary growth of L. pneumophila. In subsequent studies, the efficacy of SCH27899 was compared to ofloxacin (OFX) and azithromycin (AZI). Administration of SCH27899, OFX, or AZI at a dose of > or =30 MPK once daily for 5 days resulted in > or =85% survival of infected mice and inhibition of intrapulmonary growth of the bacteria. However, L. pneumophila CFU were recovered in lung homogenates following cessation of therapy with all three antibiotics. These studies demonstrate that SCH27899 effectively prevents fatal replicative L. pneumophila lung infection in immunocompromised A/J mice by inhibition of intrapulmonary growth of the bacteria. However, in this murine model of pulmonary legionellosis, SCH27899, like OFX and AZI, was bacteriostatic.