Preoperative pregabalin prevents succinylcholine-induced fasciculation and myalgia: A meta-analysis of randomized trials.

Succinylcholine is the gold standard neuromuscular blocker for rapid sequence induction; however, its use is associated with fasciculation and myalgia. We performed a systematic review and meta-analysis of randomized controlled clinical trials comparing gabapentinoids versus placebo for the prevention of fasciculations and succinylcholine-induced myalgias. Six randomized clinical studies were included with a total of 481 patients - 241 in the intervention group and 240 in the placebo group. Gabapentinoids reduced the incidence of succinylcholine-induced myalgia (RR = 0.69, 95% CI 0.56-0.84, P < .001), which remained statistically significant for pregabalin (RR = 0.71, 95% CI 0.54-0.93, P = .013) and gabapentin (RR = 0.61, 95% CI 0.45-0.82, P = .001) separately. There was no difference in fasciculations between the groups (RR = 0.92, 95% CI 0.82-1.03, P = .148). Preoperative use of gabapentinoids is associated with lower incidence of succinylcholine-induced myalgias within the first 24 h of surgery.

Factores asociados al consumo de sustancias psicoactivas de un grupo de pacientes con diagnóstico de esquizofrenia de una institución de salud mental de Medellín, Antioquia / Factors associated with the consumption of psychoactive substances in a group of patients diagnosed with schizophrenia from a mental health institution in Medellín, Antioquia / Fatores associados ao consumo de substâncias psicoativas em um grupo de pacientes com diagnóstico de esquizofrenia de uma instituição de saúde mental de Medellín, Colômbia

Objetivo: establecer la relación entre factores sociodemográficos y clínicos con el con­sumo de sustancias psicoactivas (SPA) en un grupo de pacientes con diagnóstico de esquizofrenia, atendidos en una institución de salud mental de la ciudad de Medellín, Colombia. Metodología: estudio observacional, retrospectivo de intención analítica, de un grupo de 268 pacientes atendidos en una institución de salud mental de Medellín, en los últi­mos seis meses del año 2021. Se identificaron factores sociodemográficos, de consumo de SPA y clínicos como tipo de medicamentos, reingresos hospitalarios y adherencia al tratamiento farmacológico. Se consideraron valores de Odds Ratio con intervalo de confianza (IC95%) y se identificaron factores asociados al consumo por medio de un modelo de regresión logística. Resultados: se identificó que el 34.7% de la muestra reporta consumo de SPA; variables clínicas asociadas, tipo de medicamentos, número de ingresos hospitalarios y adherencia al tratamiento. Se encontraron diferencias significativas en la edad entre el grupo de consumidores y no consumidores, con una mediana de edad menor para el grupo de consumidores. Se determinó que ser hombre, tener una mediana de edad de 27 años y estar desempleado representa un riesgo mayor para el consumo de SPA. Finalmente se establece que la edad, el sexo, la ocupación y la adherencia al tratamiento, podrían predecir el consumo en un 34%. Conclusiones: los pacientes jóvenes, en su mayoría hombres, con diagnóstico de es­quizofrenia, tienen mayor riesgo de consumo de SPA, lo que implica mayor riesgo de recaídas y menor adherencia al tratamiento farmacológico.

Objective: to establish the relationship between sociodemographic and clinical factors with the consumption of psychoactive substances (PAS) in a group of patients diagnosed with schizophrenia, treated at a mental health institution in the city of Medellín, Colombia. Methodology: observational, retrospective study with analytical intent, of a group of 268 patients treated at a mental health institution in Medellín, in the last six months of 2021. Sociodemographic, SPA consumption, and clinical factors such as the type of medication, hospital readmissions and adherence to drug treatment were identified. Odds Ratio values with confidence interval (95% CI) were considered and factors associated with consumption were identified by means of a logistic regression model. Results: it was shown that 34.7% of the sample reports PAS consumption, associated clinical variables, type of medication, number of hospital admissions, and adherence to treatment. Significant differences in age were found between the group of users and non-users, with a lower median age for the group of users. It was determined that being a man, having a median age of 27 years and being unemployed represent a greater risk for the consumption of PAS. Finally, it is established that age, sex, occupation, and adherence to treatment could predict consumption by 34%. Conclusions: young patients, mostly men, with a diagnosis of schizophrenia, have a higher risk of PAS consumption, which implies a higher risk of relapse and lower adherence to drug treatment.

Objetivo: estabelecer a relação entre fatores sociodemográficos e clínicos com o consumo de substâncias psicoativas (SPA) em um grupo de pacientes diagnosticados com esquizofrenia, atendidos em uma instituição de saúde mental na cidade de Medellín, Colômbia. Metodologia:estudo observacional, retrospectivo com intenção analítica, de um grupo de 268 pacientes atendidos em uma instituição de saúde mental em Medellín, nos últimos seis meses de 2021. Foram identificados fatores sociodemográficos, consumo de SPA e clínicos quanto ao tipo de medicamento, readmissões hospitalares e adesão ao tratamento medicamentoso. Valores de Odds Ratio com intervalo de confiança (IC95%) foram considerados e fatores associados ao consumo foram identificados por meio de um modelo de regressão logística. Resultados: identificou-se que 34,7% da amostra relata consumo de SPA; variáveis clínicas associadas, tipo de medicamento, número de internações e adesão ao tratamento. Foram encontradas diferenças significativas de idade entre o grupo de usuários e não usuários, com menor mediana de idade para o grupo de usuários. Foi determinado que ser homem, ter idade mediana de 27 anos e estar desempregado representa maior risco para o consumo de SPA. Por fim, estabelece-se que idade, sexo, ocupação e adesão ao tratamento poderiam predizer o consumo em 34%. Conclusões: pacientes jovens, em sua maioria homens, com diagnóstico de esquizofrenia, apresentam maior risco de consumo de SPA, o que implica maior risco de recaída e menor adesão ao tratamento medicamentoso

Real-life analysis on safety and efficacy of asciminib for ponatinib pretreated patients with chronic myeloid leukemia.

Failure of second-generation tyrosine kinase inhibitors (2GTKI) is a challenging situation in patients with chronic myeloid leukemia (CML). Asciminib, recently approved by the US Federal Drug Administration, has demonstrated in clinical trials a good efficacy and safety profile after failure of 2GTKI. However, no study has specifically addressed response rates to asciminib in ponatinib pretreated patients (PPT). Here, we present data on responses to asciminib from 52 patients in clinical practice, 20 of them (38%) with prior ponatinib exposure. We analyzed retrospectively responses and toxicities under asciminib and compared results between PPT and non-PPT patients.After a median follow-up of 30 months, 34 patients (65%) switched to asciminib due to intolerance and 18 (35%) due to resistance to prior TKIs. Forty-six patients (88%) had received at least 3 prior TKIs. Regarding responses, complete cytogenetic response was achieved or maintained in 74% and 53% for non-PPT and PPT patients, respectively. Deeper responses such as major molecular response and molecular response 4.5 were achieved in 65% and 19% in non-PPT versus 32% and 11% in PPT, respectively. Two patients (4%) harbored the T315I mutation, both PPT.In terms of toxicities, non-PPT displayed 22% grade 3-4 TEAE versus 20% in PPT. Four patients (20% of PPT) suffered from cross-intolerance with asciminib as they did under ponatinib.Our data supports asciminib as a promising alternative in resistant and intolerant non-PPT patients, as well as in intolerant PPT patients; the resistant PPT subset remains as a challenging group in need of further therapeutic options.

miR-146a rs2431697 identifies myeloproliferative neoplasm patients with higher secondary myelofibrosis progression risk.

Myelofibrosis (MF) occurs as part of the natural history of polycythemia vera (PV) and essential thrombocythemia (ET), and remarkably shortens survival. Although JAK2V617F and CALR allele burden are the main transformation risk factors, inflammation plays a critical role by driving clonal expansion toward end-stage disease. NF-κB is a key mediator of inflammation-induced carcinogenesis. Here, we explored the involvement of miR-146a, a brake in NF-κB signaling, in MPN susceptibility and progression. rs2910164 and rs2431697, that affect miR-146a expression, were analyzed in 967 MPN (320 PV/333 ET/314 MF) patients and 600 controls. We found that rs2431697 TT genotype was associated with MF, particularly with post-PV/ET MF (HR = 1.5; p < 0.05). Among 232 PV/ET patients (follow-up time=8.5 years), 18 (7.8%) progressed to MF, being MF-free-survival shorter for rs2431697 TT than CC + CT patients (p = 0.01). Multivariate analysis identified TT genotype as independent predictor of MF progression. In addition, TT (vs. CC + CT) patients showed increased plasma inflammatory cytokines. Finally, miR-146a-/- mice showed significantly higher Stat3 activity with aging, parallel to the development of the MF-like phenotype. In conclusion, we demonstrated that rs2431697 TT genotype is an early predictor of MF progression independent of the JAK2V617F allele burden. Low levels of miR-146a contribute to the MF phenotype by increasing Stat3 signaling.

Ab initio studies of the electronic structure of L-cysteine adsorbed on Ag(111).

We have performed ab initio calculations for the adsorption of L-cysteine on Ag(111) using density functional theory. We have focused on two possible adsorbed species: the L-cysteine radical (•S-CH(2)-CH-NH(2)-COOH) adsorbed almost flat at a bridge site, slightly displaced toward an fcc location, and the zwitterionic radical Z-cysteine (•S-CH(2)-CH-NH(3)(+)-COO(-)) adsorbed at a bridge site, shifted to a hcp site forming a (4 × 4) unit cell (θ = 0.06) and a (√3 × âˆš3) R 30° unit cell (θ = 0.33), respectively. Special attention has been paid to the electronic structure of the system. The adsorbate-silver bond formation has been exhaustively investigated by analyzing the density of states projected onto the different atoms of the molecule, and by charge density difference calculations. A complicated interplay between sp and d states of silver in the formation of bonds between the adsorbates and the surface has been found. The role of the carboxyl group in the interaction with the surface has been also analyzed.

Optimization of the crossflow microfiltration of arazá juice (Eugenia stipitata) under different operation modes / Optimización del proceso de microfiltración tangencial de jugo dearazá (Eugenia stipitata) a diferentes modos de operación

This study analyzed the effects of temperature and transmembrane pressure on the crossflow microfiltration process of arazá (Eugenia stipitata) juice treated with a commercial pectic enzyme preparation, thus finding the appropriate operation values of the process. Clarified arazá juice was obtained with a crossflow microfiltration pilot plant equipped with ceramic membranes with a 0.48 m2 total effective filtration area and mean pore diameter of 0.2 µm. The juice was evaluated at transmembrane pressures 1.5,3.0 and 4.5 bar, and at temperatures of 30, 35 and 40ºC at different volumetric reduction factors. The tests were carried out using three systems (total recirculation, concentration, and continuous mode). In total recirculation, it was found that the most influential variable was the transmembrane pressures, and that the partial enzymatic liquefaction of the arazá juice, prior to microfiltration, produced an unusual pattern of permeate flux, characterized by an increase following an abrupt decrease at 4.5 bar and 6.5 m/s. In this case, the highest values of the flux were obtained when compared with those obtained during the crossflow microfiltration in concentration mode. After reaching the value of volumetric reduction factor (3.2), during the crossflow microfiltration in continuous mode, it was not necessary to stop the process as the volumetric reduction factor remained constant for the continuous removal of retained, achieving a high permeate fluxin a short period of time 319 L/(h m2), thus adding to the economic viability of the process.

En este trabajo se analizaron los efectos de la temperatura y la presión transmembrana sobre el proceso de microfiltración tangencial de jugo de arazá (Eugenia stipitata) tratado con una preparación comercial de enzimas pectolíticas, encontrando los valores adecuados de operación. Se obtuvo un jugo clarificado de arazá con un equipo piloto de microfiltración tangencial provisto de membranas cerámicas de 0,48 m2 de área total efectiva de filtración, diámetro promedio de poro de 0,2 µm, evaluado a diferentes presionestransmembrana de 1,5; 3,0 y 4,5 bar y temperaturas de 30, 35 y 40ºC, a diferentes factores de reducciónvolumétrica. Las pruebas fueron llevadas a cabo utilizando tres modos de operación: recirculación total,concentración y continuo. En recirculación total, se encontró que la variable más influyente sobre el proceso fue la presión transmembrana y que la licuefacción enzimática parcial realizada al jugo de arazá, previo a la microfiltración, produjo un patrón inusual del flux de permeado, caracterizado por un incremento después de una disminución abrupta cuando se trabajó a 4,5 bar y 6,5 m/s. En este caso se encontraron los valores más altos del flux al compararse con los obtenidos durante la microfiltración tangencial en modo de concentración. Una vez alcanzado el valor de factor de reducción volumétrica (3,2) durantela microfiltración tangencial en modo continuo no fue necesario detener el proceso, ya que el factor de reducción volumétrica se mantuvo constante durante la eliminación continua de retenido, lográndose altos flujos de permeado en corto tiempo (319 L/(h m2)), facilitando la viabilidad económica del proceso.

Valores de referencia para el control de calidad de plantas medicinales como materia prima para fines terapéuticos en Colombia / Reference values for quality control of medicinal plants as raw materials for therapeutic purposes in Colombia

Se presentan los valores obtenidos, en el proceso de evaluación y desarrollo de métodos, para el control de calidad de 11 de las plantas medicinales aprobadas en Colombia: Semillas de anís (Pimpinella anisum), bulbos de ajo (Allium sativum), corteza de canela (Cinnamomum zeylanicum.), semillas de cardamomo (Elettaria cardamomum), flores de caléndula (Calendula officinalis), raíces de genciana (Gentiana lutea), hojas de hamamelis (Hammamelis virginiana), semillas de lino (Linum usitatissimum), semillas entera de trigo (Triticum aestivum), rizomas y raíces de valeriana (Valeriana officinalis) y flores de manzanilla (Matricaria chamomilla). Los análisis realizados a cada planta medicinal comprenden: La descripción morfológica macro- y microscópica, la cuantificación de cenizas totales, el contenido de sustancias extraíbles, la pérdida de peso por secado, el contenido de aceites esenciales y la identificación por cromatografía de capa fina de marcadores taxonómicos

Breast cancer and human immunodeficiency virus: a report of 20 cases.

Carcinoma of the breast is the most common malignancy in women in the United States. More than 40% of patients with human immunodeficiency virus (HIV) infection develop cancer during their illness, but breast cancer has seldom been reported. Twenty patients with breast cancer and HIV infection seen at the University of Miami/Jackson Memorial Hospital between January 1988 and August 2000 were retrospectively analyzed. Seventeen patients had a previous or concurrent diagnosis of HIV at the time of the breast cancer diagnosis. Their CD4 count ranged from 13-1126/microL (median, 309/microL). Most patients were premenopausal (16 of 20), with ages ranging from 31-61 years (median, 44 years). All stages of breast cancer were seen: ductal carcinoma in situ (2 patients), stage I (1 patient), stage II (9 patients), stage III (6 patients), and stage IV (2 patients). Ten tumors had estrogen receptors. Four of the 13 patients who underwent axillary lymph node dissection had abnormal lymph node findings, including 2 with follicular hyperplasia and 2 with caseating granulomas. Seven patients received chemotherapy with very poor tolerance. Estrogen receptor-positive patients were treated with tamoxifen. Of the 18 patients who presented with local disease, 7 have died: 2 of breast cancer, 4 of acquired immunodeficiency syndrome, and 1 of cardiac arrest. Nine patients remain free of disease (5 of them > 5 years) and 2 patients are alive with metastatic disease. Breast cancer in the HIV-positive population is similar to that seen in seronegative women. Most of the patients that are long-term survivors were treated with surgery and tamoxifen. The benefits of adjuvant chemotherapy are not clear.

Atheroemboli to the brain: size threshold for causing acute neuronal cell death.

OBJECTIVE: The objective of this study was to investigate the dilemma posed by the observations that carotid angioplasty dislodges significant numbers of plaque fragments but is reported to have a low rate of neurologic consequences. We examined the fragments released by ex vivo carotid angioplasty. The smaller and most numerous were separated by size and injected into rats to determine the tolerance of the brain to microemboli. METHODS: Ex vivo angioplasty was performed on a total of 20 human carotid plaques removed en bloc. Plaques were placed within polytetrafluoroethylene grafts, and three manipulations were performed: guide wire insertion, 3.5- or 4.0-mm balloon angioplasty, and 5-mm angioplasty with or without a Palmaz stent. After each manipulation, the lumen was flushed, effluent was collected, and fragments were counted under 100x magnification. Using 200-microm and 500-microm micropore mesh, we separated fragments by size into two groups: (1) less than 200 microm and (2) 200 to 500 microm. We then injected rats with saline alone (Group A), with 100 fragments less than 200 microm (Group B), or with 100 fragments 200 to 500 microm (Group C). Animals were euthanized at 1, 3, and 7 days, and brain sections were examined for cell viability and expression of HSP- 72. RESULTS: The total number of fragments dislodged from the plaques varied from 30 to 553. The mean number of fragments released with each manipulation was as follows: guide wire passage, 24; initial balloon angioplasty, 97; second balloon angioplasty, 68; and second angioplasty plus stent, 172. Sixteen of the 20 plaques dislodged fragments that were 1 mm or more in greatest dimension. There was no evidence of brain ischemia in Group A at any time. Group B also showed no injury at 1 or 3 days. However, injection of 200- to 500-microm fragments (Group C) caused a scattered pattern of neuronal cell death. At 7 days, brain sections from both Group B and Group C animals had a scattered pattern of ischemic neurons. There were no classic wedge-shaped infarctions. DISCUSSION: The brain appears to have a surprising tolerance for microembolization in the acute setting. Thus, carotid angioplasty may dislodge plaque fragments, but there may still be a low incidence of stroke. However, even small plaque fragments, less than 200 microm, may cause neuronal ischemia at later time points. Periprocedural microemboli could cause subtle neurologic dysfunction in late follow-up.

Novel structural determinants of mu-conotoxin (GIIIB) block in rat skeletal muscle (mu1) Na+ channels.

mu-Conotoxin (mu-CTX) specifically occludes the pore of voltage-dependent Na(+) channels. In the rat skeletal muscle Na(+) channel (mu1), we examined the contribution of charged residues between the P loops and S6 in all four domains to mu-CTX block. Conversion of the negatively charged domain II (DII) residues Asp-762 and Glu-765 to cysteine increased the IC(50) for mu-CTX block by approximately 100-fold (wild-type = 22.3 +/- 7.0 nm; D762C = 2558 +/- 250 nm; E765C = 2020 +/- 379 nm). Restoration or reversal of charge by external modification of the cysteine-substituted channels with methanethiosulfonate reagents (methanethiosulfonate ethylsulfonate (MTSES) and methanethiosulfonate ethylammonium (MTSEA)) did not affect mu-CTX block (D762C: IC(50, MTSEA+) = 2165.1 +/- 250 nm; IC(50, MTSES-) = 2753.5 +/- 456.9 nm; E765C: IC(50, MTSEA+) = 2200.1 +/- 550.3 nm; IC(50, MTSES-) = 3248.1 +/- 2011.9 nm) compared with their unmodified counterparts. In contrast, the charge-conserving mutations D762E (IC(50) = 21.9 +/- 4.3 nm) and E765D (IC(50) = 22.0 +/- 7.0 nm) preserved wild-type blocking behavior, whereas the charge reversal mutants D762K (IC(50) = 4139.9 +/- 687.9 nm) and E765K (IC(50) = 4202.7 +/- 1088.0 nm) destabilized mu-CTX block even further, suggesting a prominent electrostatic component of the interactions between these DII residues and mu-CTX. Kinetic analysis of mu-CTX block reveals that the changes in toxin sensitivity are largely due to accelerated toxin dissociation (k(off)) rates with little changes in association (k(on)) rates. We conclude that the acidic residues at positions 762 and 765 are key determinants of mu-CTX block, primarily by virtue of their negative charge. The inability of the bulky MTSES or MTSEA side chain to modify mu-CTX sensitivity places steric constraints on the sites of toxin interaction.

Charged residues between the selectivity filter and S6 segments contribute to the permeation phenotype of the sodium channel.

The deep regions of the Na(+) channel pore around the selectivity filter have been studied extensively; however, little is known about the adjacent linkers between the P loops and S6. The presence of conserved charged residues, including five in a row in domain III (D-III), hints that these linkers may play a role in permeation. To characterize the structural topology and function of these linkers, we neutralized the charged residues (from position 411 in D-I and its homologues in D-II, -III, and -IV to the putative start sites of S6) individually by cysteine substitution. Several cysteine mutants displayed enhanced sensitivities to Cd(2+) block relative to wild-type and/or were modifiable by external sulfhydryl-specific methanethiosulfonate reagents when expressed in TSA-201 cells, indicating that these amino acids reside in the permeation pathway. While neutralization of positive charges did not alter single-channel conductance, negative charge neutralizations generally reduced conductance, suggesting that such charges facilitate ion permeation. The electrical distances for Cd(2+) binding to these residues reveal a secondary "dip" into the membrane field of the linkers in domains II and IV. Our findings demonstrate significant functional roles and surprising structural features of these previously unexplored external charged residues.

Bcl-x(L) forms an ion channel in synthetic lipid membranes.

Bcl-2-related proteins are critical regulators of cell survival that are localized to the outer mitochondrial, outer nuclear and endoplasmic reticulum membranes. Despite their physiological importance, the biochemical function of Bcl-2-related proteins has remained elusive. The three-dimensional structure of Bcl-xL, an inhibitor of apoptosis, was recently shown to be similar to the structures of the pore-forming domains of bacterial toxins. A key feature of these pore-forming domains is the ability to form ion channels in biological membranes. Here we demonstrate that Bcl-xL shares this functional feature. Like the bacterial toxins, Bcl-xL can insert into either synthetic lipid vesicles or planar lipid bilayers and form an ion-conducting channel. This channel is pH-sensitive and becomes cation-selective at physiological pH. The ion-conducting channel(s) formed by Bcl-xL display multiple conductance states that have identical ion selectivity. Together, these data suggest that Bcl-xL may maintain cell survival by regulating the permeability of the intracellular membranes to which it is distributed.

Cyclic ADP-ribose does not affect cardiac or skeletal muscle ryanodine receptors.

The cardiac muscle isoform of the ryanodine receptor/Ca2+ release channel (RYR) has been proposed to be an important target of cyclic ADP-ribose (cADPR) action in mammalian cells. However, we now demonstrate that neither cADPR (0.1-5 microM), nor the related metabolites beta-NAD+ (0.1-30 mM) and ADP-ribose (0.1-5 microM), affected cardiac RYR activity as determined by [3H]ryanodine binding to cardiac sarcoplasmic reticulum (SR) vesicles. Similarly, cADPR (1 microM) failed to activate single cardiac RYR channels in planar lipid bilayers. Skeletal muscle SR [3H]ryanodine binding was also unaffected by cADPR (up to 30 microM). These results argue against a direct role for the well-characterized RYRs of cardiac or skeletal muscle in mediating cADPR-activated Ca2+ release.

A method for training surgeons in laparoscopic ultrasound.

With the increased use of laparoscopic surgery and the obligatory loss of palpation of solid organs, laparoscopic ultrasound will be an invaluable tool for the location and evaluation of solid or fluid-filled masses and retroperitoneal organs. Surgeons have heretofore had limited experience with ultrasound but are increasingly using other minimally invasive techniques to perform major operations. A graduated learning experience has been developed for surgeons, including a didactic introduction to ultrasound, inanimate and ex vivo training models, and finally, a live large animal model. Hepatic metastases were simulated and surgeons trained to locate and biopsy these lesions within the liver parenchyma under laparoscopic ultrasound guidance. The devised training session has allowed the participating surgeons to feel confident that they could identify and then biopsy intrahepatic lesions using minimally invasive techniques.

Laparoscopic colonic and rectal resection.

The technology that has permitted the rapid advance of minimal access surgery has now made it feasible to perform laparoscopically assisted colon resections safely. As the instrumentation improves, specimen removal problems are solved, surgeons' sewing skills improve, and other anastomotic methods are devised, an increasing amount of colonic surgery will be done using laparoscopy. It is clear that the techniques now in use are evolving, and will be substantially different a few years hence. Previously accepted surgical principles may continue to be challenged by new techniques, which must be evaluated under strict protocol before being widely accepted. These operations should be performed by surgeons who are able to achieve the same level of radical operation that they would achieve through a laparotomy. Special training in advanced laparoscopic techniques including microsurgical suturing is a distinct advantage in performing these operations successfully. It may be best for surgeons to start with palliative procedures or operations for benign diseases of the colon, to avoid the risk of jeopardizing an operation for cancer.

Adrenal function in paracoccidioidomycosis: a prospective study in patients before and after ketoconazole therapy.

The adrenal gland functional reserve was studied in a group of 22 patients with active paracoccidioidomycosis before therapy and in 18 of the same patients after termination of six months of ketoconazole treatment. 22 control subjects were also tested. Serum cortisol was measured before and after i.v. infusion of 250 micrograms of corticotropin given over a period of two hours. Basal cortisol levels were subnormal in only one patients before treatment and in four of 18 patients after therapy. Overt Addison's disease was found in 14% of the patients before treatment. However, corticotropin stimulation revealed diminished adrenal reserve in 23% of patients before, and in 44% of the patients after treatment. Although decreased adrenal cortex function after therapy may be influenced by ketoconazole, more studies are needed to determine the role of this agent after prolonged use. The high frequency of subclinical adrenal failure in paracoccidioidomycosis should alert clinicians in charge of such patients, should they face physiological stress.