Primary thyroid disorders in endogenous Cushing's syndrome

OBJECTIVE: To study the prevalence of primary thyroid disorders in patients who underwent endogenous hypercortisolism. DESIGN: Retrospective evaluation of 59 patients with Cushing's syndrome (CS) who had, at least, a record of thyroid palpation by expert endocrinologists and basal measurements of TSH by second generation assays. When available, tri-iodothyronine and thyroxine serum levels, TRH-TSH tests and anti-thyroid antibodies were also analyzed. There were two age- and gender-matched control groups. The 'goiter control group' comprised 118 healthy subjects who underwent thyroid palpation. The 'antibody control group' was composed of 40 individuals who attended the blood bank of our hospital. Antibodies against thyroperoxidase and measurements of TSH were analyzed in their blood samples. METHODS: Available files of 83 CS patients admitted to our endocrine unit from 1985 to 1998 were examined. Fifty-nine patients (52 women and 7 men) with a mean age of 36.2 years (range 14-61 years) met the above requirements. Diagnosis of hypercortisolism had been established by a standard 1-mg overnight dexamethasone suppression test and urinary free cortisol (UFC). Etiological diagnosis involved dynamic testing, measurements of ACTH levels and imaging techniques. After treatment, all but one of the patients were cured or controlled of their hypercortisolism. This was established by the finding of subnormal serum cortisol concentrations and/or subnormal 24-h UFC levels. Primary thyroid disorders were defined by the presence of one or more of the following diagnostic criteria: (i) goiter, (ii) positive anti-thyroid antibodies and/or (iii) primary thyroid function abnormalities. RESULTS: Eighteen (30.5%) patients had goiter (diffuse in 78% and nodular in 22%), 14 (23.7%) had primary subclinical hypothyroidism and 5 (8.4%) had hyperthyroidism. In 41 patients evaluated for antithyroid antibodies, it was found that 23 (56.1%) had positive titers. In a group of patients in which thyroid autoantibodies were measured both before and after resolution of hypercortisolism, prevalences of positive titers were 26.7% and 86.7% respectively (P=0.001). The overall frequency of primary thyroid abnormalities in our patients with Cushing's syndrome was 55.9%. CONCLUSIONS: Patients with endogenous Cushing's syndrome exhibit a remarkably high prevalence of primary thyroid disease. Resolution of hypercortisolism seems to trigger the development of autoimmune thyroid disorders in presumably predisposed subjects.     

Characterizing immune reconstitution after long-term highly active antiretroviral therapy in pediatric AIDS

In this study, we sought to characterize the T lymphocyte recovery in vertically HIV-1-infected children who respond to long-term highly active antiretroviral therapy (HAART). A 3-year longitudinal retrospective study was used to perform a cross-sectional study of 32 children rated according to the time course of CD4(+) T cell percentages in response to antiretroviral therapy and CDC clinical classification: (1) long-term asymptomatic (LTA group): 8 children in A1 during the whole follow-up period; (2) responsive to HAART (Rec group): 13 children in C3 before HAART who achieved CD4(+) T cell counts of > 500 cells/mm(3) after 3 years of HAART; and (3) nonresponsive to HAART (Non-Rec group): 11 children in C3 during the whole follow-up period despite 3 years of HAART. We also studied 17 healthy age-matched uninfected children as controls. Lymphoproliferative responses (LPRs) were evaluated by incorporation of [(3)H]thymidine, identification of T cell subsets by three-color flow cytometry, and determination of thymic production of T cells by quantification of T cell receptor rearrangement excision circles (TRECs). Interestingly, the Rec group showed an increase in percentage of CD4(+) T cells and a decrease in viral load, and recovered LPRs to mitogens and recall antigens, with values similar to those of the LTA group. Moreover, the Rec group produced similar percentages and absolute counts of naive (CD45RA(+)CD62L(+)) CD4(+) and CD8(+) T cells, and TRECs similar to those of the LTA group. In particular, the Rec group produced similar percentages of CD8(+)CD28(-)CD57(+) and CD8(+)CD28(-)CD57(-) T cell subsets compared with controls. Our data indicate that among children who have already progressed to AIDS and severe immunodeficiency but who respond to HAART, the immune system can recover and resemble those of nonprogressors or even uninfected children, in quantitative as well as in functional terms.     

The role of the vitreous in retinal detachment surgery with external buckling

PURPOSE: To prove the role of the vitreous in retinal detachment surgery with scleral buckling procedures, we retrospectively investigated the charts of patients who were operated on for retinal detachment by scleral buckling between January 1995 and June 1997. METHODS: Out of a total of 718 cases, 41 retinal detachments occurred in previously vitrectomized eyes. The buckling procedure consisted of silicone sponge explants in 513 cases (254 radial, 259 circumferential) and of encircling elements in 202 cases. Three eyes received a temporary balloon. The minimal follow-up was 3 months. RESULTS: After primary surgery in the 677 nonvitrectomized eyes, the retina was attached in 482 eyes (71.2%), after reoperation in 627 eyes (92.6%). With up to 3 reoperations (including vitrectomy with gas or silicone oil tamponade in 79 eyes), the final success rate was 98.7%. The corresponding reattachment rates in the 41 vitrectomized eyes were 82.9% after primary surgery and 97.6% after reoperation. Repeated surgery in 6 eyes consisted of successful internal tamponade by silicone oil. The reattachment rates after primary buckle procedure are of most interest to the role of the vitreous: the highest success rate (82.9%) was achieved in the vitrectomized eyes versus 71.2% in the nonvitrectomized eyes. The difference is statistically not significant. CONCLUSIONS: We therefore conclude that the absence of the vitreous has no adverse effect on the results of buckling procedures for retinal detachment. The choice of the surgical technique in treating retinal detachments in vitrectomized eyes should only determined by retinal findings such as the number and extent of breaks or the presence and stage of proliferative vitreoretinopathy.     

Methyl psilalate: a new antimicrobial metabolite from Psila boliviensis

Psila boliviensis (Wedd.) Cabr. yielded a new phenylpropanoid, named methyl psilalate. The structure was established by means of standard spectroscopic techniques. The microbiological evaluation of the compound revealed antibacterial activity against Gram-positive and Gram-negative bacteria.     

Early benefits of pravastatin to experimentally induced atherosclerosis

There is little information regarding the time of hypolipidemic treatment of changes in atherosclerotic plaque, tissue cholesterol content, and also for the recovery of endothelial function. To assess the early effects of lipid-lowering treatment on these parameters, six groups of New Zealand male rabbits were studied. Animals in groups I and II were fed regular chow; groups III and IV received a 12-week 0.5% cholesterol diet followed by 12 weeks of 0.05% cholesterol diet. Finally, groups V and VI were fed a 12-week 0.5% cholesterol diet and were then shifted to a regular diet for 12 weeks. During the last four weeks, the rabbits in groups I, III, and V received low-dose pravastatin (2 mg/day), added to the diet. Group IV animals had the highest cholesterol plasma levels (vs. groups I, II, III, and V, p < 0.01) and presented atherosclerotic plaques in a more advanced stage. Nonatherogenic diet was insufficient to restore endothelial function in animals previously fed cholesterol-enriched diets (groups IV and VI). Conversely, pravastatin treatment promoted significant improvement in endothelial function and reduced the progression of atherosclerosis. Marked increase in cholesterol content was seen in aorta and liver in response to the atherogenic diet. However, neither treatment with pravastatin nor nonatherogenic diet was capable of modifying the tissue cholesterol content. Our study supports the hypothesis that the early use of statins can attenuate the progression of atherosclerosis and ameliorate endothelial function. In addition, significant changes in the tissue cholesterol pool probably need a longer period of treatment.     

Novel high energy intermediate analogues with triazasterol-related structures as inhibitors of ergosterol biosynthesis. Part I: synthesis and antifungal activity of N-alkyl-N'-(phenethyl- and cyclohexenylethyl)guanidines and N2-substituted 2-imidazolinamines

A series of N-alkyl-N'-(phenethyl- and cyclohexenylethyl) guanidines and N(2)- and N(2), 4-substituted imidazolin-2-amine hydrochlorides with triazasterol-related structures was designed and synthesized as stable analogues to mimic high energy intermediates of ergosterol biosynthesis. The in vitro antifungal susceptibility tests with a standard panel of pathogenic fungi revealed moderate to strong antimycotic effects of the sixteen prepared compounds, in some cases comparable with the activity observed for itraconazole.     

Synthesis and evaluation of new oxamniquine derivatives

Oxamniquine derivatives were synthesized and evaluated as novel schistosomicide agents. Oxamniquine (1,2,3,4-tetrahydro-2-[[(1-methylethyl)amino]methyl]-7-nitro-6-quinolinemethanol) was submitted to the Mannich reaction, using formaldehyde, paraformaldehyde and acetaldehyde as reagents, and gave three unexpected products: two of them were cyclized on the alkylamine side chain and another etherified on the aminequinolinemethanol group. The three compounds were biologically evaluated using mice infected with Schistosoma mansoni and showed promising activities, but had higher toxicities. For studies on structure-activity relationships, results demonstrate that the side alkylamine group can be modified with preserved activity, but that this modification is associated with increased toxicity.     

A telemedicine system to support a new model for care of chronically ill patients

We have developed a new model for the care of chronically ill patients, based on home care supported by remote monitoring technology and telemedicine. The variables monitored included non-invasive blood pressure, blood oxygen saturation, threelead electrocardiogram, spirometry (including flow-volume curve) and respiratory rate. The telemedicine system consisted of a home-based patient unit and a management centre that received information from the home units. The chronic care management centre was installed in two hospitals, in Spain (Barcelona) and Belgium (Leuven). We expect this to result in significant cost-savings and a better quality of care.     

Direct and indirect inhibition by nociceptin/orphanin FQ on noradrenaline release from rodent cerebral cortex in vitro

1 The modulation exerted by nociceptin/orphanin FQ (NC) on noradrenaline (NE) release in rodent cerebral cortex slices and synaptosomes was studied. 2 Rat, mouse and guinea-pig cortical slices and synaptosomes were preincubated with 0.1 micro M [(3)H]-NE and superfused. NE release was evoked by 2 min of electrical (3 Hz) stimulation in slices and by 1 min pulse of 10 mM KCl in synaptosomes. 3 In rat cortical slices, 0.01-3 micro M NC reduced the evoked [(3)H]-NE efflux (E(max)-54%), with a bell-shaped concentration-response curve, which regained its monotonic nature in the presence of either 0.1 micro M naloxone (NX) or 30 micro M bicuculline. In synaptosomes, the NC effect curve was sygmoidal in shape and reached a plateau at 1 micro M concentration. 4 In the rat, both 1 micro M [Phe(1)psi(CH(2)-NH)Gly(2)]NC(1-13)NH(2) and 10 micro M [Nphe(1)]NC(1-13)NH(2) (NPhe) antagonised NC-induced inhibition, without per se modifying [(3)H]-NE efflux. The effects of 0.3-1 micro M NC concentrations were partially prevented by 1 micro M NX; 1 micro M D-Phe-Cys-Thr-D-Trp-Orn-Thr-Pen-Thr-NH(2) (CTOP) was also an effective antagonist, but 0.1 micro M norbinaltorphimine was not. 5 In the mouse cerebral cortex, NC-induced inhibition of NE release (pEC(50) 6.87, E(max)-61%, in the slices) was prevented by Nphe but was NX-insensitive. In guinea-pig cortical slices, NC effect (pEC(50) 6.22, E(max)-38%) was prevented by Nphe, but was NX-insensitive. 6 These findings demonstrate that NC inhibits NE release from rodent cerebral cortex via presynaptically located ORL(1) receptors. In the rat, micro opioid and GABA(A) receptors are involved as well.