Role of collagen and immunostaining for TGF-ß in the clinical and microscopic findings of pyogenic granuloma and peripheral ossifying fibroma.

BACKGROUND: Collagen is a component of Pyogenic Granuloma (PG) and Peripheral Ossifying Fibroma (POF) and performs different functions in these lesions. The objective of this study is to evaluate the role of collagen and immunostaining for Transforming Growth Factor beta (TGF-ß) in the clinical and microscopic findings of PG and POF. MATERIAL AND METHODS: PG (n=20) and POF (n=20) were selected for clinical evaluation (sex, age, localization, size and evolution time) and microscopic analysis (picrosirius red staining for collagen analysis and immunohistochemistry for TGF-ß) performed in the superficial and deep areas of the two lesions. ANOVA/Bonferroni and t-test, Pearson correlation and χ2 were used to compare the sites and parameters analyzed (p<0.05, GraphPad Prism 5.0). RESULTS: The depth of PG presented the highest amount of collagen (p<0.001), and its surface showed the lowest amount of type 1 collagen (yellow-red strong birefringence). Type 1 collagen gradually increased in depth of PG, surface and depth of POF (p<0.001). The number of TGF-ß+ cells was lower on the surface of PG compared with the depth of PG and the two areas of POF (p<0.001). Sex and localization did not affect these parameters, but the profile of collagen and immunostaining for TGF-ß suffered from modifications by the time of evolution and the size of the lesion. CONCLUSIONS: Although PG and POF are reactive gingival lesions, the expression of TGF-ß and its role in collagen showed different biological behaviors in these lesions, suggesting different biological origins for its components.

Epidemiologic analysis of salivary gland tumors over a 10-years period diagnosed in a northeast Brazilian population.

BACKGROUND: Salivary gland tumors (SGT) correspond to a heterogeneous group of lesions with variable biological behavior. The present study aimed to determine the distribution and demographic findings of salivary gland neoplasms in a northeast Brazilian population. MATERIAL AND METHODS: A retrospective descriptive cross-sectional study was performed. A total of 588 cases of SGT were diagnosed between 2006 and 2016 of 4 pathology services in the state of Sergipe, Brazil. All cases were reviewed, and data such as sex, age, anatomical location, and histopathological diagnosis were collected. RESULTS: A total of 470 (79.9%) tumors were benign and 118 (20.1%) were malignant. The majority of the patients were females (n=328, 55.8%) with an overall female:male ratio of 1.2:1. The major salivary glands were affected more than the minor glands (69.5% vs. 30.5%). Pleomorphic adenoma (n=419, 71.3%) and mucoepidermoid carcinoma (n=29, 4.9%) were the most frequent benign and malignant tumors, respectively. In addition, both benign and malignant tumors occurred more frequently in the parotid gland (n=300, 51%, p<0.05). CONCLUSIONS: The epidemiologic profile and clinical characteristics of SGT were similar to those described in other countries and other regions of Brazil. Epidemiological studies of SGT help to understand their clinical and pathological features and are essential to establish the proper management and prognosis.

Purinergic system in psychiatric diseases.

Psychiatric disorders are debilitating diseases, affecting >80 million people worldwide. There are no causal cures for psychiatric disorders and available therapies only treat the symptoms. The etiology of psychiatric disorders is unknown, although it has been speculated to be a combination of environmental, stress and genetic factors. One of the neurotransmitter systems implicated in the biology of psychiatric disorders is the purinergic system. In this review, we performed a comprehensive search of the literature about the role and function of the purinergic system in the development and predisposition to psychiatric disorders, with a focus on depression, schizophrenia, bipolar disorder, autism, anxiety and attention deficit/hyperactivity disorder. We also describe how therapeutics used for psychiatric disorders act on the purinergic system.

Factors associated with first thrombosis in patients presenting with obstetric antiphospholipid syndrome (APS) in the APS Alliance for Clinical Trials and International Networking Clinical Database and Repository: a retrospective study.

OBJECTIVE: To evaluate the subsequent rate of thrombosis among women with obstetric antiphospholipid syndrome (Ob-APS) in a multicentre database of antiphospholipid antibody (aPL)-positive patients, and the clinical utility of the adjusted Global Antiphospholipid Syndrome Score (aGAPSS), a validated tool to assess the likelihood of developing new thrombosis, in this group of patients. DESIGN: Retrospective study. SETTING: The Antiphospholipid Syndrome Alliance for Clinical Trials and International Networking Clinical Database and Repository. POPULATION: Women with Ob-APS. METHODS: Comparison of clinical and laboratory characteristics and measurement of aGAPSS in women with Ob-APS, with or without thrombosis, after initial pregnancy morbidity (PM). MAIN OUTCOME MEASURES: Risk factors for thrombosis and aGAPSS. RESULTS: Of 550 patients, 126 had Ob-APS; 74/126 (59%) presented with thrombosis, and 47 (63%) of these women developed thrombosis after initial PM, in a mean time of 7.6 ± 8.2 years (4.9/100 patient years). Younger age at diagnosis of Ob-APS, additional cardiovascular risk factors, superficial vein thrombosis, heart valve disease, and multiple aPL positivity increased the risk of first thrombosis after PM. Women with thrombosis after PM had a higher aGAPSS compared with women with Ob-APS alone [median 11.5 (4-16) versus 9 (4-13); P = 0.0089]. CONCLUSION: Based on a retrospective analysis of our multicentre aPL database, 63% of women with Ob-APS developed thrombosis after initial obstetric morbidity; additional thrombosis risk factors, selected clinical manifestations, and high-risk aPL profile increased the risk. Women with subsequent thrombosis after Ob-APS had a higher aGAPSS at entry to the registry. We believe that aGAPSS is a valid tool to improve risk stratification in aPL-positive women. TWEETABLE ABSTRACT: More than 60% of women with obstetric antiphospholipid syndrome had thrombosis after initial pregnancy morbidity.

The dental pulp stem cell niche based on aldehyde dehydrogenase 1 expression.

AIM: To detect cells expressing the stem cell marker ALDH1 (aldehyde dehydrogenase1) in the pulp of human permanent teeth and to investigate the expression of ALDH1 in isolated dental pulp cells. METHODOLOGY: Pulp tissue was collected and processed for immunohistochemistry to detect ALDH1-, STRO-1- and CD90-positive cells. In addition, cells were isolated and analysed by flow cytometry for ALDH1 activity and for the cell surface markers CD44, CD73, CD90, STRO-1 and CD45. Cells were also examined for multidifferentiation capacity. Within these cells, an ALDH1(+) cell subpopulation was selected and evaluated for multidifferentiation capacity. RESULTS: The immunohistochemistry analyses showed that ALDH1-, CD90- and STRO-1-positive cells were located mainly in the perivascular areas and nerve fibres of dental pulps. Cells on the fifth passage had high expression for CD44, CD73 and CD90, whereas moderate labelling was observed for STRO-1 and ALDH1 in flow cytometry analysis. On the same passages, cells were able to differentiate into osteogenic, adipogenic and chondrogenic lineages. The ALDH1(+) cell subpopulation also demonstrated multilineage differentiation ability. CONCLUSIONS: Dental pulp stem cells reside in the vicinity of blood vessels and nerve fibres, indicating the possible existence of more than one stem cell niche in dental pulps. Furthermore, ALDH1 was expressed by isolated dental pulp cells, which had mesenchymal stem cell characteristics. Thus, it can be suggested that ALDH1 may be used as a DPSC marker.

Efficiency and economic feasibility of pest control systems in watermelon cropping.

The aim of this work was to determine the efficiency and feasibility of two different watermelon pest control systems on pest infestations, natural enemies, and on the productivity and sustainability of watermelon cropping. Two independent experiments were carried out during the dry season of 2011. Both experiments were carried out using a randomized block experimental design, with three treatments; weekly application of pesticide (WAP), integrated pest management (IPM), and nonpesticide application (control); and four replicates. Arthropods sampling was performed every 2 d by direct counting at five randomly selected points in each plot. Samples were taken by beating the leaves from the apical portion of the plant against a white plastic tray. Arthropods that moved along the soil surface were sampled weekly using pitfall traps. Both WAP and IPM treatments negatively affected the arthropod population. We conclude that IPM is an attractive strategy for watermelon cropping both economically and environmentally because it provides the grower with an option to lower production cost, achieves the same production, and there is less need for pesticide application when compared with the prophylactic control treatment when pesticides are applied on a weekly basis. This has not been reported for watermelon before.

Nitrogen and potassium synergism influences the yield and quality of Dioscorea cayennensis.

This study aimed to evaluate yield, quality, nematode incidence, chlorophyll content, and primary foliar macronutrients of yam in response to nitrogen and potassium fertilization. A complete randomized block design was used in a factorial scheme (5 x 5), with five nitrogen (0; 60; 120; 180 and 240 kg ha-1 of N) and five potassium doses (0; 60; 120; 180 and 240 kg ha-1 of K2O), with four replicates. The mass, total and commercial productivity of tubers, starch content, ash, leaf N, P, and K content, chlorophyll, and nematode incidence were evaluated. The average mass of tubers obtained was 1.935 kg with doses of 133 kg ha-1 of N and 105 kg ha-1 of K2O. The dose of 178 kg ha-1 of N promoted maximum total tuber productivity (22.56 t ha-1). The doses of 132 kg ha-1 of N and 118 kg ha-1 of K2O resulted in maximum productivity of commercial tubers with 20.35 t ha-1. Leaf N and K, starch, and ash contents were within the standards for yam. The incidence of Meloidogyne, Scutellonema, and Pratylenchus reduced with the increasing simple effect doses of N and K2O. The maximum chlorophyll content was obtained at the dose of 240 kg ha-1 of N. The nitrogen and potassium interaction, despite the antagonistic effects on the accumulation of foliar P and starch, increased the productivity and average mass of commercial tubers, consequently ensuring the profitability of yam cultivation.

Clinical characteristics and outcomes of patients hospitalized with COVID-19 in Brazil: Results from the Brazilian COVID-19 registry.

OBJECTIVES: To describe the clinical characteristics, laboratory results, imaging findings, and in-hospital outcomes of COVID-19 patients admitted to Brazilian hospitals. METHODS: A cohort study of laboratory-confirmed COVID-19 patients who were hospitalized from March 2020 to September 2020 in 25 hospitals. Data were collected from medical records using Research Electronic Data Capture (REDCap) tools. A multivariate Poisson regression model was used to assess the risk factors for in-hospital mortality. RESULTS: For a total of 2,054 patients (52.6% male; median age of 58 years), the in-hospital mortality was 22.0%; this rose to 47.6% for those treated in the intensive care unit (ICU). Hypertension (52.9%), diabetes (29.2%), and obesity (17.2%) were the most prevalent comorbidities. Overall, 32.5% required invasive mechanical ventilation, and 12.1% required kidney replacement therapy. Septic shock was observed in 15.0%, nosocomial infection in 13.1%, thromboembolism in 4.1%, and acute heart failure in 3.6%. Age >= 65 years, chronic kidney disease, hypertension, C-reactive protein ≥ 100mg/dL, platelet count < 100×109/L, oxygen saturation < 90%, the need for supplemental oxygen, and invasive mechanical ventilation at admission were independently associated with a higher risk of in-hospital mortality. The overall use of antimicrobials was 87.9%. CONCLUSIONS: This study reveals the characteristics and in-hospital outcomes of hospitalized patients with confirmed COVID-19 in Brazil. Certain easily assessed parameters at hospital admission were independently associated with a higher risk of death. The high frequency of antibiotic use points to an over-use of antimicrobials in COVID-19 patients.

Evaluation of the humoral and cellular immune response to different antigens of Corynebacterium pseudotuberculosis in Canindé goats and their potential protection against caseous lymphadenitis.

Corynebacterium pseudotuberculosis is the etiologic agent of caseous lymphadenitis, a disease that affects goats and sheep, and can cause severe economic losses. In this study, four different antigenic extracts were obtained from the attenuated strain T1, which was isolated in the state of Bahia (Brazil). Forty-four Canindé breed goats were divided in five groups, each receiving a different antigen solution and saline buffer as a control. The humoral response was monitored through the identification of specific IgG by indirect ELISA and Western Blotting, and the production of IFN-gamma was followed in order to observe the activation of cellular response. After twelve weeks of antigen inoculation, the animals were challenged with 2 x 10(5)CFU of a wild strain, also isolated in Bahia, and necropsy was performed on all animals twelve weeks afterwards. It was observed that the attenuated bacteria gave a protection of 33.3%, in addition to the weak humoral response elicited. Animals inoculated with secreted antigen associated with Freund's incomplete adjuvant and oligodeoxynucleotide containing unmethylated CpG dinucleotides (CpG ODN) showed a strong humoral response, but this inoculation could not prevent the spread of challenge bacteria in the majority of animals. These results demonstrate the immunogenic potential of the attenuated T1 strain in the development of a vaccine against caseous lymphadenitis in goats.

Estimation of the critical effect level for pollution prevention based on oyster embryonic development toxicity test: the search for reliability.

In spite of the consideration that toxicity testing is a reduced approach to measure the effects of pollutants on ecosystems, the early-life-stage (ELS) tests have evident ecological relevance because they reflect the possible reproductive impairment of the natural populations. The procedure and validation of Crassostrea rhizophorae embryonic development test have shown that it meets the same precision as other U.S. EPA tests, where EC(50) is generally used as a toxicological endpoint. However, the recognition that EC(50) is not the best endpoint to assess contaminant effects led U.S. EPA to recently suggest EC(25) as an alternative to estimate xenobiotic effects for pollution prevention. To provide reliability to the toxicological test results on C. rhizophorae embryos, the present work aimed to establish the critical effect level for this test organism, based on its reaction to reference toxicants, by using the statistical method proposed by Norberg-King (Inhibition Concentration, version 2.0). Oyster embryos were exposed to graded series of reference toxicants (ZnSO(4) x 7H(2)O; AgNO(3); KCl; CdCl(2)H(2)O; phenol, 4-chlorophenol and dodecyl sodium sulphate). Based on the obtained results, the critical value for C. rhizophorae embryonic development test was estimated as EC(15). The present research enhances the emerging consensus that ELS tests data would be adequate for estimating the chronic safe concentrations of pollutants in the receiving waters. Based on recommended criteria and on the results of the present research, zinc sulphate and 4-chlorophenol have been pointed out, among the inorganic and organic compounds tested, as the best reference toxicants for C. rhizophorae ELS-test.

Plasma rotation measurement in small tokamaks using an optical spectrometer and a single photomultiplier as detector.

The method for plasma rotation measurement in the tokamak TCABR is reported in this article. During a discharge, an optical spectrometer is used to scan sequentially spectral lines of plasma impurities and spectral lines of a calibration lamp. Knowing the scanning velocity of the diffraction grating of the spectrometer with adequate precision, the Doppler shifts of impurity lines are determined. The photomultiplier output voltage signals are recorded with adequate sampling rate. With this method the residual poloidal and toroidal plasma rotation velocities were determined, assuming that they are the same as those of the impurity ions. The results show reasonable agreement with the neoclassical theory and with results from similar tokamaks.

Colony membership is reflected by variations in cuticular hydrocarbon profile in a Neotropical paper wasp, Polistes satan (Hymenoptera, Vespidae).

Nestmate recognition is one the most important features in social insect colonies. Although epicuticular lipids or cuticular hydrocarbons have both structural and defensive functions in insects, they also seem to be involved in several aspects of communication in wasps, bees and ants. We analyzed and described for the first time the cuticular hydrocarbons of a Neotropical paper wasp, Polistes satan, and found that variation in hydrocarbon profile was sufficiently strong to discriminate individuals according to their colony membership. Therefore, it seems that small differences in the proportion of these compounds can be detected and used as a chemical-based cue by nestmates to detect invaders and avoid usurpation.

In vitro IFN-gamma production by goat blood cells after stimulation with somatic and secreted Corynebacterium pseudotuberculosis antigens.

Corynebacterium pseudotuberculosis is the causal agent of caseous lymphadenitis, a chronic illness that attacks goats and sheep characterized by pyogranulomas formation in lymph nodes and organs. Regarding the current knowledge of the pathogenesis of the caseous lymphadenitis, there is evidence that besides the humoral response the induction of a durable cellular response is fundamental for its control. In this sense, research on antigens of C. pseudotuberculosis that are capable to inducing cellular immunity is an important step for the development of diagnosis tests and more efficient vaccines. In the present study, the interferon-gamma production in cultures of whole blood from infected goats stimulated with secreted bacterial antigen or somatic antigen were used to evaluate the cellular response. The results demonstrated a significant difference in the ability of the two antigens to induce a cellular response. That is, IFN-gamma production was high with cells from infected animals in response to the secreted antigen while IFN-gamma production was low when somatic antigen was used. The concomitant use of these antigens with PWM also showed differences. That is, the secreted antigen increased the IFN-gamma production induced by PWM, while the somatic antigen seems not to have altered the response to PWM.

Serologic immunoreactivity to Neospora caninum antigens in dogs determined by indirect immunofluorescence, western blotting and dot-ELISA.

Neospora caninum, is a coccidian protozoan known as a major cause of bovine abortion and canine neuropathies. The aim of the present study was to develop a reliable and quick test to detect antibodies to N. caninum in dog sera. Sixty-five serum samples from dogs, including 35 positive and 30 negative for N. caninum antibodies were used for standardization of the test. In parallel, immunoreactivity of the sera to Toxoplasma gondii antigens was investigated using a passive agglutination test. A dot-ELISA test, using soluble extract of N. caninum tachyzoites on nitrocellulose ester membranes, was developed and standardized. SDS-PAGE and complementary analysis of reactivity by Western blotting were used for the characterization of the immunoreactive fractions of all tested sera. The sensitivity and specificity of the dot-ELISA were 94 and 73%, respectively, compared to IFAT at a cut-off of 1:50, and 87 and 100% compared to IFAT at a cut-off of 1:25. Among the sera that tested positively for both IFAT and dot-ELISA, only 8.6% were reactive to T. gondii. The most immunoreactive fractions in Western blots were the 14-, 33-, 42- and 55 kDa bands, with percentages of 42, 60, 42 and 37%, respectively. The 60 kDa band showed a non-specific reaction in 43% of neosporosis-negative animals by both dot-ELISA and IFAT. These results indicate that the dot-ELISA using N. caninum antigen present good sensitivity and specificity, and might be used as a screening test to detect antibodies to N. caninum in dogs.

Postnatal expression of the plasticity-related nerve growth factor-induced gene A (NGFI-A) protein in the superficial layers of the rat superior colliculus: relation to N-methyl-D-aspartate receptor function.

Immediate early gene expression in the CNS is induced by sensory stimulation and seems to be involved in long-term synaptic plasticity. We have used an immunohistochemical method to detect the nerve growth factor-induced gene A (NGFI-A) protein expression in the superficial layers of the rat superior colliculus during postnatal development. Our goal was to correlate the expression of this candidate plasticity protein with developmental events, especially the activity-dependent refinement of the retinocollicular and corticocollicular pathways. We have also investigated the N-methyl-D-aspartate (NMDA)-receptor dependence of the NGFI-A expression. Animals of various postnatal ages were used. Postnatal day (P) 12 and older animals were submitted to a protocol of dark adaptation followed by light stimulation. NGFI-A expression was never observed during the first 2 postnatal weeks. The first stained cells were observed at P15, 2 days after eye opening (P13). The highest number of stained cells was observed at the end of the third postnatal week (P22). Adult-like level of expression was reached at P30, since at this age, the number of stained cells was comparable to that found in adult rats (P90). Both P22 animals submitted to an acute treatment with MK-801 (i.p. injection) and adult animals submitted to chronic intracranial infusion of a MK-801 presented a clear decrease in the NGFI-A expression in response to light stimulation. These results suggest that the NGFI-A expression is dependent on the NMDA receptor activation, and the observed pattern of expression is in close agreement with previous descriptions of the changes in the NMDA receptor-mediated visual activity in the developing rat superior colliculus (SC). Our results suggest that the plasticity-related NGFI-A protein might play a role in the developmental plasticity of the superficial layers of the rat SC after eye opening.

Vascular endothelial growth factor (VEGF) levels as a tool to discriminate between malignant and nonmalignant ascites.

Ascites formation is commonly associated with cancer, although it is also present in other diseases. The aim of this study was to evaluate the usefulness of vascular endothelial growth factor as a malignancy marker in ascites of different etiologies. The levels of VEGF in 32 malignant and in 31 non-malignant ascites were determined by enzyme immunoassay (ELISA). VEGF levels were significantly higher in malignant than in non-malignant ascites (median=1265.9 pg/ml x 114.6 pg/ml; p<0.0001). We observed 72% sensitivity and 90% specificity, using 662 pg/ml as a cut-off value. Therefore, this approach can be used as a marker for a first screening to discriminate between malignant and nonmalignant ascites.

Hyperventilation challenge test in panic disorder and depression with panic attacks.

Our aim was to determine whether panic disorder (PD) patients, major depressive patients without panic attacks (MD) and major depressive patients with panic attacks (MDP) respond similarly to hyperventilation challenge tests. We randomly selected 35 PD patients, 33 MDP patients, 27 MD patients and 30 normal volunteers with no family history of anxiety or mood disorder. The patients had not been treated with psychotropic drugs for at least 1 week. They were induced to hyperventilate (30 breaths/min) for 4 min, and anxiety was assessed before and after the test. A total of 16 (45.7%) PD patients, 12 (36.4%) MDP patients, four (11.1%) MD patients, and two (6.7%) normal volunteers had a panic attack after hyperventilating. The PD and MDP patients were significantly more responsive to hyperventilation than the MD patients and the normal volunteers. The MD patients had a significantly lower heart-rate response to the test than all the other groups. There is growing evidence that PD patients are more sensitive to the vasoconstrictive effects on basilar arterial blood flow caused by hyperventilation-induced hypocapnia than are comparison subjects. Our data suggest that there is an association between panic attacks and hyperreactivity to an acute hyperventilation challenge test.

Double-blind acute clonazepam vs. placebo in carbon dioxide-induced panic attacks.

The inhalation of 35% carbon dioxide has consistently been shown to provoke panic attacks in panic disorder patients. We aim to determine if an acute dose of clonazepam (2 mg) attenuates the panic attacks induced by an inhalation of 35% carbon dioxide in panic disorder. Twenty-two panic disorder patients who had been drug-free for 1 week participated in a carbon dioxide challenge test 1 h after a dose of either 2 mg of clonazepam or placebo with a randomized double-blind method. Also in a double-blind design during the tests the patients inhaled either atmospheric compressed air ('placebo control') or the carbon dioxide mixture. All patients participated in both tests which were done with a 20-min interval. Immediately before and after the inhalation, the anxiety levels and the symptoms of panic were always assessed. In the clonazepam group (n=11) two patients (18.2%) had a mild panic attack and in the placebo group (n=11) nine patients (81.8%) had a moderate to severe panic attack in the CO(2) challenge test. No patient had panic attacks during inhalation of atmospheric compressed air although anticipatory anxiety levels tended to be higher than in the CO(2) tests. After the CO(2) test anxiety levels were significantly greater in the CO(2) group (three-way ANOVA with Geisser-Greenhouse adjustments, F(31.92,1.86)=17.15, d.f.=7, P=0.013). Although a small sample was studied, the findings suggest the efficacy of an acute dose of clonazepam in attenuating panic attacks induced by carbon dioxide inhalation.

Experimental Corynebacterium pseudotuberculosis primary infection in goats: kinetics of IgG and interferon-gamma production, IgG avidity and antigen recognition by Western blotting.

Corynebacterium pseudotuberculosis is the cause of caseous lymphadenitis (CLA) in small ruminants, a chronic granulomatous disease that provokes significant zootechnics losses to ovine and goat breeders in northern Brazil. The present work was conducted to analyse aspects of humoral and cellular immune responses after experimental infection. Eight goats were infected intradermally with a single dose of virulent C. pseudotuberculosis strain and specific IgG, interferon-gamma (IFN-gamma) production as well as IgG avidity and antigens pattern recognition dynamics against an excreted-secreted antigen were recorded during 20 weeks. At the end of the follow-up, animals were slaughtered and necropsied. Although no animals showed apparent clinical signs of infection at the end of the trial, IFN-gamma response, even more so than the humoral response, differentiated animals into two groups of high or medium/low response. The time-course of IFN-gamma production presented a short-lived primary response on day 5 after infection of animals of both groups, and a strong and long lasting secondary response starting on day 16 after infection in the high response group. The indirect ELISA used was able to detect a positive antibody titre between 6 and 11 days after infection in the two groups. IgG avidity index oscillated initially between 15 and 45%, and showed approximately 5% units increment during the 20 follow-up weeks. With only one individual exception, the qualitative antigens pattern recognition showed on day 11 after infection remained constant through the experiment. IgG avidity is highly correlated with IgG production, but could not be related with specific immunodominant bands. Both humoral and cellular responses kinetics presented a similar pattern of activation/deactivation but necropsy results suggested that the IFN-gamma test would be a very specific marker of CLA status.

Respiratory panic disorder subtype and sensitivity to the carbon dioxide challenge test.

The aim of the present study was to verify the sensitivity to the carbon dioxide (CO2) challenge test of panic disorder (PD) patients with respiratory and nonrespiratory subtypes of the disorder. Our hypothesis is that the respiratory subtype is more sensitive to 35% CO2. Twenty-seven PD subjects with or without agoraphobia were classified into respiratory and nonrespiratory subtypes on the basis of the presence of respiratory symptoms during their panic attacks. The tests were carried out in a double-blind manner using two mixtures: 1) 35% CO2 and 65% O2, and 2) 100% atmospheric compressed air, 20 min apart. The tests were repeated after 2 weeks during which the participants in the study did not receive any psychotropic drugs. At least 15 of 16 (93.7%) respiratory PD subtype patients and 5 of 11 (43.4%) nonrespiratory PD patients had a panic attack during one of two CO2 challenges (P = 0.009, Fisher exact test). Respiratory PD subtype patients were more sensitive to the CO2 challenge test. There was agreement between the severity of PD measured by the Clinical Global Impression (CGI) Scale and the subtype of PD. Higher CGI scores in the respiratory PD subtype could reflect a greater sensitivity to the CO2 challenge due to a greater severity of PD. Carbon dioxide challenges in PD may define PD subtypes and their underlying mechanisms.