Effect of melatonin administration on subjective sleep quality in chronic obstructive pulmonary disease

Disturbed sleep is common in chronic obstructive pulmonary disease (COPD). Conventional hypnotics worsen nocturnal hypoxemia and, in severe cases, can lead to respiratory failure. Exogenous melatonin has somnogenic properties in normal subjects and can improve sleep in several clinical conditions. This randomized, double-blind, placebo-controlled study was carried out to determine the effects of melatonin on sleep in COPD. Thirty consecutive patients with moderate to very severe COPD were initially recruited for the study. None of the participants had a history of disease exacerbation 4 weeks prior to the study, obstructive sleep apnea, mental disorders, current use of oral steroids, methylxanthines or hypnotic-sedative medication, nocturnal oxygen therapy, and shift work. Patients received 3 mg melatonin (N = 12) or placebo (N = 13), orally in a single dose, 1 h before bedtime for 21 consecutive days. Sleep quality was assessed by the Pittsburgh Sleep Quality Index (PSQI) and daytime sleepiness was measured by the Epworth Sleepiness Scale. Pulmonary function and functional exercise level were assessed by spirometry and the 6-min walk test, respectively. Twenty-five patients completed the study protocol and were included in the final analysis. Melatonin treatment significantly improved global PSQI scores (P = 0.012), particularly sleep latency (P = 0.008) and sleep duration (P = 0.046). No differences in daytime sleepiness, lung function and functional exercise level were observed. We conclude that melatonin can improve sleep in COPD. Further long-term studies involving larger number of patients are needed before melatonin can be safely recommended for the management of sleep disturbances in these patients.

Studies in search of a suitable experimental insect model for xenodiagnosis of hosts with Chagas' disease: 4 - The reflection of parasite stock in the responsiveness of different vector species to chronic infection with different Trypanosoma cruzi stocks

Previous studies (1982,1987) have emphasized the superiority of sylvatic vector species over domestic species as xenodiagnostic agents in testing hosts with acute or chronic infections by T. cruzi "Y" stock. The present study, which is unique in that it contains data on both infectivity rates produced by the same stock in 11 different vector species and also the reaction of the same vector species to seven different parasite stocks, establishes the general validity of linking efficiency of xenodiagnosis to the biotope of its agent. For example, infectivity rates produced by "São Felipe" stock varied from 82.5% to 98.3% in sylvatic vectors but decreased to 42.5% to 71.3% in domestic species. "Colombiana" stock produced in the same sylvatic vectors infectivity rates ranging from 12.5% to 45%. These shrank to 5%-22.5% in domestic bugs. The functional role of the biotope in the vector-parasite interaction has not been eluddated. But since this phenomenon has been observed to be stable and easy to reproduce, it leads us to believe that the results obtained are valid. Data presented also provide increasing evidence that the infectivity rates exhibited by bugs from xenodiagnosis in chronic hosts, are parasite stock specific. For example, infectivity rates produced by "Berenice", "Y", "FL" and "CL" varied in R. neglectus from 26.3% to 75%; in P. megistus from 56.3% to 83.8%; in T. sordida from 28.8% to 58.8% in T. pseudomaculata from 41.3% to 66.3% and in T. rubrovaria from 48.8% to 85%. Data from xenodiagnosis in the same hosts, carrying acute infections by the same parasite stocks, gave the five sylvatic vectors a positive rating of approximately 100%, thus suggesting that the heavy loads of parasites circulating in the acute hosts obscured the characteristic interspecific differences for the parasite stock. Nonetheless these latter were revealed in the same hosts with chronic infections stimulated by very low numbers of the same parasite stocks. Certain observations here described lead us to speculate as to the possibility of further results from other parasite stocks, allowing the association of the infectivity rates produced in bugs by different parasite stocks with the isoenzymic patterns revealed by these stocks.

Effect of eliminating chronic diseases among elderly individuals

OBJECTIVE: To determine whether the elimination of certain chronic diseases is capable of leading to the compression of morbidity among elderly individuals.METHODS: A population-based, cross-sectional study was carried out with official data for the city of Sao Paulo, Southeastern Brazil in 2000 and data from the SABE (Health, Wellbeing and Ageing) study. Sullivan's method was used to calculate disability-free life expectancy. Cause-deleted life tables were used to calculate the probabilities of death and disabilities with the elimination of health conditions.RESULTS: The largest gains in disability-free life expectancy, with the elimination of chronic illness, occurred in the female gender. Among individuals of a more advanced age, gains in disability-free life expectancy occurred as result of a relative compression of morbidity. Among men aged 75 years, all conditions studied, except heart disease and systemic arterial pressure, led to an absolute expansion of morbidity and, at the same time, to a relative compression of morbidity upon being eliminated.CONCLUSIONS: The elimination of chronic diseases in the elderly could lead to the compression of morbidity in elderly men and women.

Chronic use of benzodiazepines among older adults

OBJECTIVE To analyze the perception of and motivation for the chronic use of benzodiazepine among older adults. METHODS A qualitative study was conducted on 22 older adults living in Bambuí, MG, Southeastern Brazil, who were taking benzodiazepines and had the clinical and cognitive ability to respond to interview questions. The collected data were analyzed on the basis of the “signs, meanings, and actions” model. RESULTS The main reasons pointed out for the use of benzodiazepines were “nervousness”, “sleep problems”, and “worry” due to family and financial problems, everyday problems, and existential difficulties. None of the interviewees said that they used benzodiazepines in a dose higher than that recommended or had been warned by health professionals about any risks of their continuous use. Different strategies were used to obtain the prescription for the medication, and any physician would prescribe it, indicating that a bond was established with the drug and not with the health professional or healthcare service. Obtaining and consuming the medication turned into a crucial issue because benzodiazepine assumes the status of an essential food, which leads users to not think but sleep. It causes a feeling of relief from their problems such as awareness of human finitude and fragility, existential difficulties, and family problems. CONCLUSIONS Benzodiazepine assumes the characteristics of polyvalence among older adults, which extrapolate specific clinical indications, and of essentiality to deal with life’s problems in old age. Although it relieves the “nerves”, the chronic use of benzodiazepines buffers suffering and prevents older adults from going through the suffering. This shows important difficulties in the organization and planning of strategies that are necessary for minimizing the chronic use in this population.

Burden of physical inactivity and hospitalization costs due to chronic diseases

OBJECTIVE To evaluate the physical inactivity-related inpatient costs of chronic non-communicable diseases. METHODS This study used data from 2013, from Brazilian Unified Health System, regarding inpatient numbers and costs due to malignant colon and breast neoplasms, cerebrovascular diseases, ischemic heart diseases, hypertension, diabetes, and osteoporosis. In order to calculate the share physical inactivity represents in that, the physical inactivity-related risks, which apply to each disease, were considered, and physical inactivity prevalence during leisure activities was obtained from Pesquisa Nacional por Amostra de Domicílio (Brazil's National Household Sample Survey). The analysis was stratified by genders and residing country regions of subjects who were 40 years or older. The physical inactivity-related hospitalization cost regarding each cause was multiplied by the respective share it regarded to. RESULTS In 2013, 974,641 patients were admitted due to seven different causes in Brazil, which represented a high cost. South region was found to have the highest patient admission rate in most studied causes. The highest prevalences for physical inactivity were observed in North and Northeast regions. The highest inactivity-related share in men was found for osteoporosis in all regions (≈ 35.0%), whereas diabetes was found to have a higher share regarding inactivity in women (33.0% to 37.0% variation in the regions). Ischemic heart diseases accounted for the highest total costs that could be linked to physical inactivity in all regions and for both genders, being followed by cerebrovascular diseases. Approximately 15.0% of inpatient costs from Brazilian Unified Health System were connected to physical inactivity. CONCLUSIONS Physical inactivity significantly impacts the number of patient admissions due to the evaluated causes and through their resulting costs, with different genders and country regions representing different shares.

Prevalence of chronic low back pain: systematic review

OBJECTIVE To estimate worldwide prevalence of chronic low back pain according to age and sex. METHODS We consulted Medline (PubMed), LILACS and EMBASE electronic databases. The search strategy used the following descriptors and combinations: back pain, prevalence, musculoskeletal diseases, chronic musculoskeletal pain, rheumatic, low back pain, musculoskeletal disorders and chronic low back pain. We selected cross-sectional population-based or cohort studies that assessed chronic low back pain as an outcome. We also assessed the quality of the selected studies as well as the chronic low back pain prevalence according to age and sex. RESULTS The review included 28 studies. Based on our qualitative evaluation, around one third of the studies had low scores, mainly due to high non-response rates. Chronic low back pain prevalence was 4.2% in individuals aged between 24 and 39 years old and 19.6% in those aged between 20 and 59. Of nine studies with individuals aged 18 and above, six reported chronic low back pain between 3.9% and 10.2% and three, prevalence between 13.1% and 20.3%. In the Brazilian older population, chronic low back pain prevalence was 25.4%. CONCLUSIONS Chronic low back pain prevalence increases linearly from the third decade of life on, until the 60 years of age, being more prevalent in women. Methodological approaches aiming to reduce high heterogeneity in case definitions of chronic low back pain are essential to consistency and comparative analysis between studies. A standard chronic low back pain definition should include the precise description of the anatomical area, pain duration and limitation level.

Treatment of relapsing chronic infections of the respiratory tract: a comparative study of the effectiveness of non specific immunotherapy with the immunoadjuvant p40 and of vaccinotherapy

The treatment of relapsing chronic infections (RCI) encounters many difficulties. In the present study, the use of the immuno adjuvant P40 either alone or in association with vaccinotherapy for the treatment of RCI turned out to be very effective, whereas vaccinotherapy alone was not. It is hypothesized that cell-mediated immunity may play a major role in controlling RCI, since the clinical improvement of the patients kept up with the positivation of previously negative skin tests carried out with either the specific infecting agent or with recall-anti gens.

Acute myocardial infarction in chronic Chagas' cardiomyopathy: report of two cases with no obstructive coronary artery lesions

This report describes two patients with chronic Chagas' Heart Disease who developed clinical and laboratorial signs of myocardial infarction. Both patients presented sudden oppressive chest pain, without precipitating factor. In the first case, the highest MB-CK value was 65 IU, 22 hours after the beginning of the pain. On the second case, it was 77 IU at 18 hours after the beginning of the pain. In both cases ECG changes suggesting non-transmural infarction were present. The 99mTc PYP myocardial scintigram of the first case was positive. Coronary angiograms performed on the 18th and 9th day, respectively, after the acute infarction did not display obstructive lesions. Possible mechanisms causing myocardial infarction with normal coronary arteries in Chagas' Disease may include: embolic event's, particularly when there is associated congestive heart failure; coronary thrombosis and coronary spasms.

Immunoperoxidase technique in experimental chronic chagasic myocarditis

Chagas'disease has been described as the commonest form of chronic myocarditis. An immunologic pathogenesis has been discribed for this form of the disease. So far, no immunoperoxidase technique has been used for the detection of immunological deposits in chronic experimental Chagas'myocardiopathy. Forty-one Swiss mice, three months old were inoculated intraperitoneally with doses between 10 and 10(5) Tulahuen trypomastigotes. Mice were reinoculated one month after with doses between 10² and 10(5) and sacrificed at 6 (n=21) and 9 months (n=9) after the first inoculation. ECGs were recorded before sacrifice. Immunoperoxidase technique (peroxidase-antiperoxidase method), immunofluorescence (direct and indirect) as well as histological studies were performed in myocardiums and skeletal muscles of the surviving animals. The most sensitive methods for detecting chronic chagasic infection were the routine histologic studies (73%) and the ECGs 83% and 89% on 6 and 9 mo. post-infected mice, respectively. Myocardial involvement varied from interstitial mild focal lymphocyte infiltrates up to replacement of myocytes by loose connective tissue. Atrial myocardiums (21/23, 91%) were more affected than ventricles (9/23, 39%). Typical chagasic nests were rarely found. Skeletal muscle involvement (11/18 and 7/9) varied from mild to extensive lymphocyte and plasmacell infiltrates, and necrotic fibers. The involved antigen were shown in skeletal muscles by the immunoperoxidase technique as diffusely arranged granular intracytoplasmatic deposit for both IgC and total immunoglobulins. The coincidence between this technique and histologic muscle lesions was 11/18 (61(%) in 6 mo. and 6/8 (75%) at 9 mo. post-infection. In heart, delicate granular deposits of total immunoglobulins were seen diffusely arranged within the ventricular myocytes; coincidence between immunoperoxidase technique anl histologic involvement increased from 36 to 66% in animals sacrifeced 6 and 9 mo. post-infection. This strongly stressed the increase of immunologic phenomena with the chronification of infection. Concerning sensitivity, immunoperoxidase and direct immunofluorescence were highly sensitive in skeletal muscle (100%, p < 0.01). Conversely, direct immunofluorescence technique showed poor results in heart while immunoperoxidase increased its sensitivity from 21.4% (at 6 mo.) to 66.6% (at 9 mo.) post-infection (p < 0.001). Considering the necessity of obtaining an adequate vaccine in order to prevent this disease an experimental model like this, rendering immunological reactions as revealed by the immunoperoxidase technique, would be useful.

Tuberculosis in patients with chronic renal failure

Nine cases of tuberculosis (TB) were diagnosed among 800 uremic patients, followed-up during 11 years, a prevalence of 1125%, 2.5 times higher than that in the general population. Six patients (66.7%) had lymph node involvement (4 cervical and 2 mediastinal). Three patients (33.3%) had pulmonary involvement (2 pleuro-pulmonary and 1 bilateral apical pulmonary). Eight patients were undergoing dialysis and 1 was pre-dialytic. The duration of dialysis ranged from 1 to 60 months. Three patients had previously received immunosuppressive drugs for unsuccessful renal transplantation. Daily fever was present in all but one patient; he was asymptomatic and TB was suspected after routine chest radiography. Biopsy was the diagnostic procedure in 7 patients (77.8%), four by direct cervical lymph node biopsy, 2 by mediastinal, performed by mediastinoscopy and 1 by pleural biopsy. In 2 other patients TB was confirmed by the presence of tubercle bacilli; in sputum (1 patient) and in a bronchial flushing specimen (the other patient). Triple therapy was used in all patients (isoniazid and ethambutol in all), plus rifampicin in 8 and streptomycin in 1. One patient had jaundice and another had optical neuritis. Five patients were cured. The other four died during treatment of causes unrelated to TB or its treatment.

Chronic glomerulonephritis associated with hepatosplenic schistosomiasis mansoni

In a series of 36 cases of renal disease associated with hepatosplenic schistosomiasis the following morphologic types of glomerulonephritis were found: mesangio-capillary (33.2%), mesangial proliferative (25.0%), focal glomerular sclerosis (16.7%) and sclerosing glomerulonephritis (8.3%). No significant statistical differences were found when these results were compared with those from 36 cases of glomerulonephritis not associated with hepatosplenic disease. On the other hand, endocapillary glomerulonephritis was found to be predominant in the latter group of cases. These results did not substantiate the assumption that mesangio-capillary glomerulonephritis is specifically related to hepatosplenic schistosomiais. However, if the types of glomerulonephritis that predominantly involve the me-sangium are considered together, they are significantly associated with hepatosplenic schistosomiasis. Mesangial involvement is known to occur in other parasitic diseases and that may be related to a common immunopathogenesis.

Comparison of serum hepatitis B virus replication markers in patients with chronic hepatitis B: studies on HBeAg/Anti-HBe system, viral dna polymerase and HBV-DNA

The detection of HBV-DNA in serum by molecular hybridization is the most sensitive and specific marker of replication and infectivity of hepatitis B virus and currently is proposed as a routine diagnostic technique in the follow-up of HBV - related diseases. Comparing different techniques already described, we found that direct spotting of serum samples on nitrocellulose membranes under vacuum filtration, followed by denaturing and neutralizing washes is more practical, simple, sensible and reproducible. DNA polymerase assay using phosphonoformic acid as specific viral inhibitor has shown 86.8% of concordance with HBV-DNA detection, and so, it is an useful alternative in the follow-up of hepatitis B chronic patients. We found 19.2% HBeAg positive samples with no other markers of viral replication and no anti-HBe positive sample had detectable HBV-DNA. Discordance between the 2 systems have been extensively described, and we confirm this for the first time in our country. Molecular biological techniques are essential to determine the replication status of chronic hepatitis B patients.

Chronic myocardial damage in experimental T. cruzi infection of a new world primate, Cebus sp. monkey

Eighteen Cebus apella monkeys, (juvenile and adult of both sexes) were inoculated five years ago, with three Trypanosoma cruzi strains (CA1, n = 10; Colombian, n=4 and Tulahuen, n=4), either by conjunctival or intraperitoneal route, once or repeatedly. Parasitological, hematological, serological, enzymatic, radiographic, electro and echocardiographic findings have been peviously published15 and they are similar to those observed in human pathology. The most frequent electrocardiographic alteration was right branch bundle block. Six animals, chosen at random, were sacrificed. Those sacrificed 20 to 25 months post-first inoculation showed focal accumuli of leukocytes with myocytolysis. Foci of diffuse interstitial fibrosis with mild infiltrate of leukocytes among fibers were observed in the animals sacrificed 36 to 47 months post-inoculation. No parasites were seen. The lesions were more prominent in the ventricular walls and the septum. The fact that the infiltrates were predominant in the animals sacrificed at a shorter time after first inoculation and that fibrosis was more severe in those sacrificed at a longer time suggests that there is a progression of the infiltrative lesions to fibrosis, with a leukocytic activity indicative of a chronic phase. These lesions are similar to those described in human chronic Chagas' disease. This would demonstrate that this model is useful in evaluating a progress in the knowledge of the pathogenesis which is still a controversial issue, immunology, immunogenesis and chemotherapeutic agents of the chronic and indeterminate phases of this disease.

Chagas' disease: IgA, IgM and IgG antibodies to T. cruzi amastigote, trypomastigote and epimastigote antigens in acute and in different chronic forms of the disease

In an attempt to find a better T. cruzi antigen and possible immunological markers for the diagnosis of different clinical forms of Chagas' disease, amastigote and trypomastigote antigens obtained from immunosuppressed mice infected with T. cruzi (Y strain) were assessed in comparison with conventional epimastigote antigens. A total of 506 serum samples from patients with acute and with chronic (indeterminate, cardiac and digestive) forms, from nonchagasic infections, and from healthy individuals were assayed in immunofluorescence (IF) tests, to search for IgG, IgM and IgA antibodies. Amastigote proved to be the most convenient antigen for our purposes, providing higher relative efficiency indexes of 0.946, 0.871 and 0.914 for IgG, IgM and IgA IF tests, respectively. Anti-amastigote antibodies presented higher geometric mean titers (GMT) than anti-trypomastigote and anti-epimastigote. Anti-amastigote IgG antibodies were found in all forms of Chagas' disease, and predominantly IgA antibodies, in chronic digestive and in acute forms, as well as IgM antibodies, in latter forms. Thus, tests with amastigote antigen could be helpful for screening chagasic infections in blood banks. Practical and economical aspects in obtaining amastigotes as here described speak in favour of its use in developing countries, since those from other sources require more complex system of substruction, specialized personnel or equipment.

Lymphocyte subpopulations and neutrophil function in chronic human Chagas' disease

The absolute numbers of total leukocytes, lymphocytes, T cells, helper/inducer, suppressor/cytotoxic and B cells were decreased in the peripheral blood of patients with chronic Chagas' disease. Since antilymphocyte antibodies were present only in a minority of patients they probably cannot account for the abnormalities in lymphocyte subsets. Patient neutrophils stimulated with endotoxin-treated autologous plasma showed depressed chemotactic activity and this seems to be an intrinsic cellular defect rather than plasma inhibition. Random migration of neutrophils was normal. Reduction of nitroblue tetrazolium by endotoxin- stimulated neutrophils was also decreased. These findings further document the presence of immunosuppression in human Chagas' disease. They may be relevant to autoimmunity, defense against microorganisms and against tumor cells at least in a subset of patients with more severe abnormalities.