Cytokines and acute-phase serum proteins as markers of inflammatory regression during pulmonary tuberculosis treatment

Tuberculosis is still increasing and was declared a worldwide sanitary emergency by the World Health Organization (WHO) in 1995. Its control is difficult due to long treatment duration and lack of markers of treatment success or failure. Cytokines such as IFN-gamma and TNF-alpha, a central factor in immune response against Mycobacterium tuberculosis, are responsible for the interaction between T lymphocytes and the infected macrophage and are also produced during this interaction. As proinflammatory cytokines have a close relationship with mycobacteria clearance, in fact even preceding it, they could be used as markers for inflammatory activity and response to treatment. Proinflammatory cytokines act in the liver and stimulate a strong local and systemic acute-phase response as a result of homeostatic and physiological responses also induced by them. Acute-phase proteins produced by cytokine activity are useful diagnostic markers that could also be used to monitor treatment response as they can be serially quantified. The objective of this study was to evaluate IFN-gamma, TNF-alpha, IL-10 and TGF-beta production in supernatant of peripheral blood mononuclear cell (PBMC) and monocyte (MO) cultures, as well as serum acute-phase response through total protein, albumin, globulin, C-reactive protein (CRP), alpha-1-acid glycoprotein (AGP), and erythrocyte sedimentation rate (ESR) as regression markers of inflammatory response during pulmonary tuberculosis treatment. Twenty blood donors (G1) from the Blood Bank at Botucatu School of Medicine's University Hospital (BSM-UH) were evaluated once and 28 pulmonary tuberculosis patients (G2): 13 from BSM-UH and 15 from the Bauru State Health Secretariat. Patients were evaluated at three moments of treatment: before (M1), at three months (M2), and at the end (M3). Cytokines were determined in 20ml of peripheral blood (ELISA), with or without activation: lipopolysaccharide (LPS) for MO culture and phytohemagglutinin (PHA) for PBMC culture. Acute-phase protein behavior in G2 throughout treatment was: Globulins: M1> M2, M1> M3 (rho < 0.001); CRP: M1> M2> M3 (.< 0.001); AGP for men: M1> M2, M1> M3 (rho < 0.001); ESR for men: M1> M2, M1> M3 (rho < 0.0016) and for women: M1> M2 (.< 0.025). Comparison between cytokine levels found in supernatant of MO and PBMC cultures, with and without stimulus, in G1 and G2 during treatment showed: TNF-alpha (with/ without LPS) at M1: G2> G1; at M2: G2> G1 (rho < 0.001); (without LPS) at M3: G2> G1 (rho < 0.001), (with LPS) at M3: G2> G1 (rho < 0.028); IFN-. (with and without PHA) at M1: G2> G1; at M2: G2> G1 (rho < 0.001); IL-10 (with and without LPS) at M1: G2> G1; at M2: G2> G1; at M3: G2> G1 (rho < 0.001); TGF-beta (with and without LPS) at M1: G2> G1; at M2: G2> G1 (rho < 0.001), (without LPS) at M3: G2> G1 (rho < 0.001). In G2, all cytokines in supernatant of MO and PBMC cultures, with and without stimulus, showed: M1> M2> M3 (rho < 0.01). Levels of globulins, CRP, AGP, and ESR in patients with pulmonary tuberculosis before treatment (M1) were significantly higher than reference values, suggesting their use as diagnostic markers and indicators of treatment. The CRP decreasing values along treatment could be taken as a marker of the regression of inflammatory process and of response to treatment in patients with pulmonary tuberculosis.Regarding cytokines, there was significant increase in TNF-alpha, IFN-gamma, IL-10, and TGF-alpha levels before and at three months treatment, with and without stimulus; in TNF-a and IL-10 lvels, with and without stimulus, as well as in TGF-alpha levels without stimulus at six months. Patients had higher levels of all studied cytokines than controls before treatment, and these values decreased along treatment. In this study, pulmonary tuberculosis patients showed a Th0 cytokine profile before treatment, with the production of both Th1 (IFN-gamma) and Th2 (IL-10) cytokines, in addition to TNF-alpha inflammatory and TGF-alpha regulatory and fibrosis-inducer cytokines. At the end of treatment, all had evolved to Th2 profile, probably in an attempt to reduce the harmful effects of the proinflammatory activity of the Th1 cytokine profile and of the still above-normal levels of TNF-alpha. The high levels of TGF-alpha, also found in these patients, are related to its important role in the extracellular matrix deposition and fibrosis induction that characterize tuberculosis healing process. IFN-gamma was the only cytokine reaching normal levels at the end of treatment, which suggests its use as a marker of response to treatment.

Scintigraphy of the hepatobiliar system in patients with pulmonary tuberculosis

The objective of this paper was to evaluate the hepatobiliary function of patients with pulmonary tuberculosis under triple treatment, using the technetium-99m-DISIDA (99mTc-DISIDA) hepatobiliary scintigraphy. Ten men and three women with pulmonary tuberculosis were subjected to hepatobiliary scintigraphy at the beginning of triple treatment (M1) and two months after it (M2). Patients were from the urban area, of low socioeconomic level, malnourished, and chronic alcohol and/or tobacco users. Ten normal individuals were evaluated as controls. Radiotracer images were acquired on a computerized gamma camera (Orbiter-Siemens) and T1/2 uptake and excretion values were calculated. Nutritional status and serum hepatic enzyme levels for each patient were evaluated at M1 and M2. None presented clinical or laboratory antecedent of hepatobiliary disease. At M1, there were no hepatic serum or kinetic alterations of the 99mTc-DISIDA. At M2, patients presented better nutritional conditions than at M1; there was increased serum aspartate aminotransferase (AST) and reduced excretion time for 99mTc-DISIDA, which was interpreted as a more adaptive than toxic phenomenon, yet not all alterations were significant and none manifested clinically. Apparently, triple treatment acted on the liver inducing the P450 cytochrome enzymatic system, accelerating radiotracer excretion, which follows the same path as the bilirubins.

Primary Pulmonary Choriocarcinoma After Human Chorionic Gonadotropin Normalization Following Hydatidiform Mole A Report of Two Cases

BACKGROUND: Primary pulmonary choriocarcinoma (PPC) is rare and frequently leads to death.CASES: Two young patients presented with previous molar pregnancy and spontaneous serum human chorionic gonadotropin (hCG) normalization. Patient 1 was referred to our center after partial response to chemotherapy. Pulmonary lobectomy was performed, and hCG rapidly declined. During further chemotherapy, liver metastasis was detected by positron emission tomography. Right hepatectomy was performed, and hCG declined for 28 days, but increased again despite chemotherapy. This patient died from hepatic failure 3 years after diagnosis. Patient 2 presented with persistently high hCG, though the affected organ was not identified. Chemotherapy was unsuccessful. Patient reevaluation showed an isolated pulmonary mass. Pulmonary lobectomy was performed; 2 weeks later, hCG was normal and consolidation with 2 cycles of chemotherapy was administered. The patient has been in remission for 24 months. PPC was confirmed by histo pathology and immunohistochemistry in both cases. Gestational origin of the tumor was confirmed by molecular genetic analysis (polymorphic microsatellite markers).CONCLUSION: The possibility of choriocarcinoma cannot be overlooked in young women with an isolated pulmonary mass. Early diagnosis, prompt chemotherapy, and surgical resection in a specialized center improves the prognosis. (J Reprod Med 2010;55:311-316)

Obsessive-compulsive disorder and personality disorder - Evidence from the British National Survey of Psychiatric Morbidity 2000

Background Previous studies indicate that most individuals with obsessive-compulsive disorder (OCD) have comorbid personality disorders (PDs), particularly from the anxious cluster. However, the nature and strength of this association remains unclear, as the majority of previous studies have relied heavily on clinical populations. We analysed the prevalence of screen positive personality disorder in a representative sample of adults with OCD living in private households in the UK. Methods A secondary analysis of data from the 2000 British National Survey of Psychiatric Morbidity. The prevalence of PD, as determined by the SCID-II questionnaire, was compared in participants with OCD, with other neuroses and non-neurotic controls. Within the OCD group we also analysed possible differences relating to sex and subtypes of the disorder. Results the prevalence of any screen positive PD in the OCD group (N = 108) was 74%, significantly greater than in both control groups. The most common screen positive categories were paranoid, obsessive-compulsive, avoidant, schizoid and schizotypal. Compared to participants with other neuroses, OCD cases were more likely to screen positively for paranoid, avoidant, schizotypal, dependent and narcissistic PDs. Men with OCD were more likely to screen positively for PDs in general, cluster A PDs, antisocial, obsessive-compulsive and narcissistic categories. The presence of comorbid neuroses in people with OCD had no significant effect on the prevalence of PD. Conclusions Personality pathology is highly prevalent among people with OCD who are living in the community and should be routinely assessed, as it may affect help-seeking behaviour and response to treatment.

Treatment seeking by individuals with obsessive-compulsive disorder from the British Psychiatric Morbidity Survey of 2000

Objective: For several reasons, many individuals with obsessive-compulsive disorder (OCD) do not seek treatment. However, data on treatment seeking from community samples are scant. This study analyzed service use by adults with OCD living in private households in Great Britain. Methods: Data from the British Survey of Psychiatric Morbidity of 2000, in which 8,580 individuals were surveyed, were analyzed. Service use was compared for those with OCD, with other neuroses, with different subtypes of OCD (only obsessions, only compulsions, or both), and with OCD and comorbid neuroses. Results: Persons with OCD (N=114) were more likely than persons with other neuroses (N=1,395) to be receiving treatment (40% compared with 23%, p<.001). However, those with OCD alone (N=38) were much less likely than those with OCD and a comorbid disorder to be in treatment (14% compared with 56%, p<.001). In the previous year, 9.4% of persons with OCD had seen a psychiatrist and 4.6% had seen a psychologist. Five percent were receiving cognitive-behavioral therapy, 2% were taking selective serotonin reuptake inhibitors, and 10% were taking tricyclics. Conclusions: Most persons with OCD were not in contact with a mental health professional, and apparently very few were receiving appropriate treatments. Very few persons with noncomorbid OCD were receiving treatment. Individuals with OCD who are in treatment may not be disclosing their obsessions and compulsions and may be discussing other emotional symptoms, leading to inappropriate treatment strategies. Public awareness of OCD symptoms should be raised, and primary care professionals should inquire about them with all patients who have depressive or anxiety disorders.

Obsessive-compulsive disorder: Prevalence, comorbidity, impact, and help-seeking in the British National Psychiatric Morbidity Survey of 2000

Objective: There is little information about obsessive-compulsive disorder in large representative community samples. The authors aimed to establish obsessive-compulsive disorder prevalence and its clinical typology among adults in private households in Great Britain and to obtain generalizable estimates of impairment and help-seeking.Method: Data from the British National Psychiatric Morbidity Survey of 2000, comprising 8,580 individuals, were analyzed using appropriate measurements. The study compared individuals with obsessive-compulsive disorder, individuals with other neurotic disorders, and a nonneurotic comparison group. ICD-10 diagnoses were derived from the Clinical Interview Schedule-Revised.Results: the authors identified 114 individuals (74 women, 40 men) with obsessive-compulsive disorder, with a weighted 1-month prevalence of 1.1%. Most individuals (55%) in the obsessive-compulsive group had obsessions only. Comorbidity occurred in 62% of these individuals, which was significantly greater than the group with other neuroses (10%). Co-occurring neuroses were depressive episode (37%), generalized anxiety disorder (31%), agoraphobia or panic disorder (22%), social phobia (17%), and specific phobia (15%). Alcohol dependence was present in 20% of participants, mainly men, and drug dependence was present in 13%. Obsessive-compulsive disorder, compared with other neurotic disorders, was associated with more marked social and occupational impairment. One-quarter of obsessive-compulsive disorder participants had previously attempted suicide. Individuals with pure and comorbid obsessive-compulsive disorder did not differ according to most indices of impairment, including suicidal behavior, but pure individuals were significantly less likely to have sought help (14% versus 56%).Conclusions: A rare yet severe mental disorder, obsessive-compulsive disorder is an atypical neurosis, of which the public health significance has been underestimated. Unmet need among individuals with pure obsessive-compulsive disorder is a cause for concern, requiring further investigation of barriers to care and interventions to encourage help-seeking.

Idiopathic pulmonary hemosiderosis with cystic lesions: A rare presentation

This report describes a case of a 49-year-old man with cough, recurrent hemoptysis, and dyspnea during 18 months, presenting with radiological findings of alveolar infiltrate and cystic lesions in left upper lobe. Laboratory studies revealed normocytic hypochromic anemia and normal coagulation tests. C-reactive protein and mucoproteins were negative. Serum protein electrophoresis and complement, urinalysis, serum creatinine, creatinine clearance, and 24-hour urine protein were normal. Tests for antineutrophil cytoplasmic antibodies and anti-glomerular-basement membrane antibodies were negative. Tests for connective tissue diseases were all negative. Histological findings were consistent with those of idiopathic pulmonary hemosiderosis. Radiological findings are discussed.

Resting energy expenditure and carbohydrate oxidation are higher in elderly patients with COPD: a case control study

Background: Elderly patients with chronic obstructive pulmonary disease (COPD) usually have a compromised nutritional status which is an independent predictor of morbidity and mortality. To know the Resting Energy Expenditure (REE) and the substrate oxidation measurement is essential to prevent these complications. This study aimed to compare the REE, respiratory quotient (RQ) and body composition between patients with and without COPD.Methods: This case-control study assessed 20 patients with chronic obstructive pulmonary disease attending a pulmonary rehabilitation program. The group of subjects without COPD (control group) consisted of 20 elderly patients attending a university gym, patients of a private service and a public healthy care. Consumption of oxygen (O-2) and carbon dioxide (CO2) was determined by indirect calorimetry and used for calculating the resting energy expenditure and respiratory quotient. Body mass index (BMI) and waist circumference (WC) were also measured. Percentage of body fat (%BF), lean mass (kg) and muscle mass (kg) were determined by bioimpedance. The fat free mass index (FFMI) and muscle mass index (MMI) were then calculated.Results: The COPD group had lower BMI than control (p = 0.02). However, WC, % BF, FFMI and MM-I did not differ between the groups. The COPD group had greater RQ (p = 0.01), REE (p = 0.009) and carbohydrate oxidation (p = 0.002).Conclusions: Elderly patients with COPD had higher REE, RQ and carbohydrate oxidation than controls.

Aspectos epidemiológicos da tuberculose pulmonar nos municípios de Botucatu, Conchas, São Manuel e Avaré, Estado de São Paulo, Brasil, de 1963 a 1972

O diagnóstico da situação da tuberculose pulmonar nos Municípios de Botucatu, Conchas, São Manuel e Avaré, SP, Brasil, baseou-se na prevalência e risco de infecção em escolares de lª série, em 1972, e em dados de morbidade e mortalidade específica, de 1963 a 1972. Realizou-se inquérito tuberculínico em 2.913 escolares, com PPD 23 RT-2UT; foram analisados os prontuários de 718 casos inscritos no CSI de Botucatu e os atestados de óbito de residentes, incluindo-se os ocorridos em hospitais especializados. As taxas de prevalência de infecção para os quatro Municípios foram respectivamente 2,4%; 6,8%; 1,9% e 4,5%. Para a idade de 7,5 anos, os riscos de infecção foram: 0,27%; 0,32; 0,20% e 0,34%. O nível de infecção apurado caracterizou o conjunto como área de média prevalência da tuberculose pulmonar. Os índices de prevalência de infecção relacionaram-se diretamente à incidência de casos bacilíferos de cada Município. em 530 casos com baciloscopia, houve 62,0% de positividade. As formas radiológicas moderada e avançada predominaram principalmente em adultos jovens do sexo masculino. Foram registradas alta taxa de abandono (39,5%}, baixo percentual de cura (17,9%) e 3,4% de óbitos; ao redor de 32,0% estava em tratamento. Não houve diferenças estatisticamente significativas das proporções de abandono, segundo procedência por Município ou formas da doença. Invocaram-se razões técnico-administrativas do sistema vigente para explicar esses achados. A incidência média de casos confirmados, no período, foi de 35,4 em Conchas, 33,1 em Avaré, 23,7 em Botucatu e 18,5 em São Manuel (por 100.000). Com casos confirmados e suspeitos os índices foram: 57,6; 48,8; 43,8 e 35,3. Os índices médio-anuais de mortalidade, foram: 7,6 em Botucatu, 12,14 em Conchas, 5,0 em São Manuel e 18,7 em Avaré (por 100.000). Apenas em Botucatu registrou-se declínio das taxas de mortalidade de 1963 a 1972. A mortalidade específica em adultos jovens ainda era elevada, predominando no sexo masculino, principalmente em Conchas. Sublinhou-se a necessidade de descentralizar as atividades antituberculose para atingir um controle eficiente.

Morbidity-mortality and performance evaluation of Brahman calves from in vitro embryo production

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Vacinação contra influenza em idosos por área de residência: prevalência e fatores associados

A vacinação contra influenza é a principal forma de prevenir e reduzir a morbidade e mortalidade associadas à doença entre os idosos e grupos de risco. O objetivo deste estudo é determinar fatores demográficos, socioeconômicos, comportamentais e de saúde associados à vacinação, entre idosos residentes em diferentes áreas do Estado de São Paulo, no período de 2001 a 2002. Trata-se de um delineamento transversal de base populacional que considerou os idosos residentes em duas áreas do Estado: uma composta pelo município de Campinas e distrito do Butantã, na cidade de São Paulo, e outra pelos municípios de Taboão da Serra, Embu e Itapecerica da Serra (região metropolitana do município de São Paulo). A amostra foi composta por 849 e 641 indivíduos com 60 anos ou mais, residentes em tais localidades, respectivamente. Na análise bruta foram utilizadas razões de prevalência e intervalos de confiança de 95% e a análise multivariada foi realizada pela regressão de Poisson. A prevalência de vacinação auto-referida foi de 66,9% entre os residentes em Campinas e no distrito do Butantã e 67,6% naqueles das demais localidades. Após análise ajustada, para os idosos de Campinas e Butantã, apenas menor escolaridade (RP = 1,25; IC 95%: 1,02-1,54) esteve associada à vacinação. Já na área composta pelos municípios menos populosos, idade mais avançada (RP = 1,15; IC 95%: 1,02-1,31), hipertensão arterial (RP = 1,21; IC 95%: 1,02-1,45), diabetes (RP = 1,16; IC 95%: 1,01-1,33) e doença crônica de pulmão (RP = 1,30; IC 95%: 1,03-1,64) referidas, estiveram também associadas. Apesar de a prevalência de vacinação contra influenza entre os idosos das diversas localidades ser praticamente a mesma, pôde-se observar diferenças no perfil do idoso quanto à referência desse procedimento preventivo.

Effects of chronic acetazolamide administration on gas exchange and acid-base control in pulmonary circulation in exercising horses

P>Reasons for performing study:Carbonic anhydrase (CA) catalyses the hydration/dehydration reaction of CO(2) and increases the rate of Cl- and HCO(3)- exchange between the erythrocytes and plasma. Therefore, chronic inhibition of CA has a potential to attenuate CO(2) output and induce greater metabolic and respiratory acidosis in exercising horses.Objectives:To determine the effects of Carbonic anhydrase inhibition on CO(2) output and ionic exchange between erythrocytes and plasma and their influence on acid-base balance in the pulmonary circulation (across the lung) in exercising horses with and without CA inhibition.Methods:Six horses were exercised to exhaustion on a treadmill without (Con) and with CA inhibition (AczTr). CA inhibition was achieved with administration of acetazolamide (10 mg/kg bwt t.i.d. for 3 days and 30 mg/kg bwt before exercise). Arterial, mixed venous blood and CO(2) output were sampled at rest and during exercise. An integrated physicochemical systems approach was used to describe acid base changes.Results:AczTr decreased the duration of exercise by 45% (P < 0.0001). During the transition from rest to exercise CO(2) output was lower in AczTr (P < 0.0001). Arterial PCO(2) (P < 0.0001; mean +/- s.e. 71 +/- 2 mmHg AczTr, 46 +/- 2 mmHg Con) was higher, whereas hydrogen ion (P = 0.01; 12.8 +/- 0.6 nEq/l AczTr, 15.5 +/- 0.6 nEq/l Con) and bicarbonate (P = 0.007; 5.5 +/- 0.7 mEq/l AczTr, 10.1 +/- 1.3 mEq/l Con) differences across the lung were lower in AczTr compared to Con. No difference was observed in weak electrolytes across the lung. Strong ion difference across the lung was lower in AczTr (P = 0.0003; 4.9 +/- 0.8 mEq AczTr, 7.5 +/- 1.2 mEq Con), which was affected by strong ion changes across the lung with exception of lactate.Conclusions:CO(2) and chloride changes in erythrocytes across the lung seem to be the major contributors to acid-base and ions balance in pulmonary circulation in exercising horses.