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Biomedical subjects

M Miravitlles

Publications and source records attributed to M Miravitlles.

At least 19 recordsLinked to original sources

[A contagiousness study in 3071 familial contacts of tuberculosis patients].

BACKGROUND: The study of contacts of patients with tuberculosis is an important preventive measure which helps to identify the risk factors for contagion, to detect new cases of the disease early and to break the epidemiological chain of transmission. MATERIAL AND METHOD: Three thousand and seventy-one contacts of 635 patients with tuberculosis were studied in our department over a period of 6 years. With the aid of uni- and multivariate analyses we established the importance of different factors in the appearance of tuberculous disease and infection in contacts. RESULTS: There were 1,341 tuberculin positive contacts (44%). The proportion increased in relation to the degree of the relationship and the bacillary density of the index case. A hundred and seventy-six new cases of tuberculosis were diagnosed among the contacts (5.7%). To study the risk factors for contagion, we analyzed the characteristics of 322 patients with positive sputum smears and their 1,623 contacts; 124 new cases were diagnosed among them (124/176; 70%). The most important factors for contagion in the multivariate analysis were the closer relationship (odds ratio [OR] = 8.32; confidence interval [Cl] 95% = 3.9-17.6), greater TST reaction of contacts (OR = 4.43; Cl 95% = 2.5-7.7), presence of more than 10 bacilli per microscopic field in the sputum samples of the index case (OR = 1.97; Cl 95% = 1.1-3.3), male contacts (OR = 1.86; Cl 95% = 1.2-2.7) and those younger than 15 years (OR = 1.58; Cl 95% = 1.01-2.45). Conversely, the sex of the index case and the history of previous tuberculosis in contacts did not influence the contagion. CONCLUSIONS: The study of contacts offers a high yield in the diagnosis of new tuberculosis cases, because the incidence of the disease is much higher than that of the general population. Moreover, it allows the detection of newly infected subjects in whom the application of chemoprophylaxis prevents the development of the disease, and thus the epidemiologic chain of transmission is broken.

Adolescent

Characterization of specific immunoglobulin G (IgG) and its subclasses (IgG1 and IgG2) against the 23-valent pneumococcal vaccine in a healthy adult population: proposal for response criteria.

The aim of the study was to standardize an enzyme-linked immunosorbent assay (ELISA) method for the quantification of immunoglobulin G (IgG) and its subclasses (IgG1 and IgG2) against the 23-valent pneumococcal vaccine and to establish the criteria for a normal response to the vaccine. Forty healthy individuals (20 women and 20 men; mean age, 29 years) were studied. All were vaccinated with the 23-valent pneumococcal vaccine; blood samples were drawn just prior to and 3 weeks after immunization. Quantification of specific IgG and its subclasses was performed by an ELISA with the vaccine as the antigen. The linearity of the ELISA method was demonstrated by the similar slopes of the linear regression lines generated from the titration of sera with different antibody concentrations. The specificity of the antibodies against the vaccine was demonstrated by (i) an absorption test with pneumococcal vaccine, (ii) a cross-reactivity experiment with Haemophilus influenzae type b polysaccharide, and (iii) affinity chromatography with protein A-Sepharose. Response to the vaccine was defined by using the lower level of the 90% probability interval (one-tailed) for postimmunization-specific IgG, IgG1, and IgG2. By using this cutoff, responders were considered to be those with an absolute increase in antibody titers higher than 395 arbitrary units/ml for IgG, 0.350 A450 units for IgG1, and 0.314 A450 units for IgG2. Overall, 20 (50%) subjects had IgG, IgG1, and IgG2 responses, 9 (22.5%) had IgG and IgG2 responses, 4 (10%) had IgG1 responses, 3 (7.5%) had IgG and IgG1 responses, and 4 (10%) were nonresponders. Ninety percent of our population responded to the 23-valent pneumococcal vaccine. Up to 10% of healthy individuals may respond to an IgG subclass without significant increases in total IgG titers. The ELISA method that is described may be useful for evaluating the specific antibody response against polysaccharides.

Adult

Increased risk of tuberculosis transmission in families with microepidemics.

In the present study, we analysed: 1) prevalence of TB infection and incidence of disease among family contacts of a cohort of patients with TB; 2) differential characteristics of families with microepidemics and families with < or = 1 new case of TB; and 3) efficacy of chemoprophylaxis in this group of contacts. Three thousand and seventy one family contacts of 635 patients with TB were studied. The study consisted of tuberculin skin testing and chest radiography in all cases, and bacteriological studies when active disease was suspected. Contacts were classified as belonging to: families with microepidemics (FME) (those with > or = 2 new cases of TB); families with one new case; and families with with no new cases. Chemoprophylaxis was prescribed in contacts following standard recommendations; all were followed up for 12-18 months. Rates of TB infection and disease among families, as well as the incidence of TB disease between those compliant and noncompliant with chemoprophylaxis were compared. Among the 3,071 contacts, 1,264 (41%) were infected and 176 (6%) had TB. Twenty two families with FME (3%) yielded 55 new cases of TB. The prevalence of infection (excluding the TB cases) was 80% in families with FME, 52% in families with one new case, and 41% in families with no new case (odds ratio (OR) 3.7; 95% confidence interval (95% CI) 2.1-6.5). Sputum smears were positive in 53% of cases in FME and 24% in non-FME families (OR 3.4; 95% CI 1.7-6.5). Bronchial sample cultures were positive in 84% of patients from FME families but in only 40% of those from non-FME families (OR 7.5; 95% CI 3.6-15.8). Chemoprophylaxis was prescribed in 356 contacts, of whom 296 complied and generated only one new case of TB, whilst there were 13 new cases among the 60 who did not comply (OR 81.6; 95% CI 26.7-248.7). This study showed the prevalence of infection and incidence of tuberculosis among family contacts of patients with newly diagnosed tuberculosis to be very high. A small number of families with microepidemics accounted for most new cases of tuberculosis, which were also more infectious. The extremely high risk of transmission in these families, together with the proven efficacy of chemoprophylaxis, justifies prescription of chemoprophylaxis to all their members, regardless of age.

Adult

Empiric treatments impair the diagnostic yield of BAL in HIV-positive patients.

OBJECTIVE: To investigate the influence of empiric treatments prior to fiberoptic bronchoscopy (FOB) on the diagnostic yield of BAL in HIV-positive patients with respiratory symptoms. METHOD: We studied 123 consecutive FOBs with BAL in HIV-positive patients; 101 of these patients (82%) had received previous antimicrobial treatment from 1 to 60 days. Diagnostic yield of BAL for Pneumocystis carinii, Mycobacterium tuberculosis, and bacterial pneumonia was compared between patients with and without previous empiric treatments. RESULTS: A diagnosis was obtained in 85 patients (69%), of whom 17 (20%) had multiple infections. Diagnostic yield was higher in patients without previous treatment, 91% (20/22) compared with 64% (65/101), p < 0.03. Diagnostic yield was also higher for bacterial pneumonia: seven isolations from 22 patients not receiving previous empiric treatment (32%), compared with 11 of those who had (11%; p < 0.02). The duration of empiric treatment against P carinii in patients in whom it was isolated was significantly shorter than in those in whom P carinii was not detected (3.5 +/- 1.8 days compared with 5.2 +/- 2.4 days; p = 0.003). FOB permitted a change in treatment in 62% of patients with a final diagnosis. CONCLUSION: This study demonstrates that empiric treatments prior to FOB significantly impair the diagnostic yield of BAL in detecting common pathogens in HIV-infected patients with respiratory symptoms.

AIDS-Related Opportunistic Infections

[Estimation of initial interobserver variability of forced spirometry in the multicenter epidemiological study IBERPOC. Scientific Committee of the IBERPOC study].

To estimate the interobserver variability and degree of agreement for basic spirometric parameters before beginning field work for the IBERPOC Project. Study of agreement between 7 observers (pneumologists) and a gold standard, using a scheme of incomplete balanced and randomized blocks with an equal number of spirometric measurements (n = 3) per patient and an equal number of measurements (n = 9) per observer performed at the same session. The study population consisted of 14 patients with different degrees of air flow obstruction and 7 normal volunteers. Statistically significant differences attributable to subjects (inter-patient variability) were found for the three variables analyzed. Variability attributable to the observer was found for FVC and FEV1 but not for FEV1/FVC. The greatest interobserver differences were found for FEV1, such that 4 of the 7 observers recorded values that were significantly different from the mean (p < 0.05). The differences were less marked for FVC and for the FEV1/FVC ratio, with only 2 observers recording significantly different values for each variable. The high degree of reproducibility as well as the excellent interobserver agreement found in this standardization session provide an a priori guarantee of validity for spirometric measurements and rule out the existence of differential bias in data recorded at the various geographic areas involved in the study.

Data Interpretation, Statistical

[Study of the frequency of different phenotypes of alpha-1-antitrypsin in a population of Barcelona].

BACKGROUND: Severe alpha-1-antitrypsin (AAT) deficiency is caused by homozygous inheritance of gene Z, and is associated with a high risk of developing pulmonary emphysema. Determination of frequencies of different genes associated with the deficiency (especially S and Z) gives a clue to estimate the number of individuals homozygous PiZZ, carrying a high risk for pulmonary disease, in any given population. PATIENTS AND METHODS: Pi phenotypes of 440 healthy individuals were determined by means of isoelectrofocusing in polyacrylamide gel. Seric values of AAT were determined by immunonephelometry. Mean age of participants was 30 years (range 18-49 yrs.). Results are compared with other published series. RESULTS: Distribution of phenotypes was: PiMM 333 individuals (75%), PiMS 84 (19%), PiMZ 14 (3%), PiSS 4 (0.9%), PiM 3 (0.6%), PiMF 1 (0.2%), PiMP 1 (0.2%). The corresponding gene frequencies were Pi*M 87%, Pi*S 10.4%, and Pi*Z 1.5%. Normal values of AAT (phenotype PiMM) established in our laboratory were 116-232 mg/dl (21-41 micromol/I) (mean +/- 2 SD). According to Hardy-Weinberger equation, expected frequency of PiZZ individuals in our area would be 225 per million. CONCLUSIONS: The frequency of Z gen individuals observed in our study is one of the highest in the Iberian Peninsula, but lower than the frequency in northern Europe. According to these results, AAT deficiency (PiZZ) is not a rare condition in contrast with the small number of patients diagnosed. The gen frequency of the S variant is higher than that of the rest of Europe, and similar to others found in some Spanish populations.

Adolescent

[Pneumology residents trained in Catalonia (1989-1993)].

BACKGROUND: The aim of this study was to analyze the outcome of the latest groups of pneumologists trained in hospitals in Catalonia, Spain, and to compare these results with international estimate rates on the need for pneumologists. METHODS: Information was collected by a self-administered closed response questionnaire which was filled out during the first trimester of 1994 by the pneumologists trained in hospitals in Catalonia from 1989 to 1993. RESULTS: One hundred percent response to the questionnaire was achieved (48 pneumologists). The first job following completion of resident training period consisted in being grant holders in the same department in 27 cases (56%), 15 (31%) received a contract as pneumologists, 2 (4%) as non-pneumologists physicians and 4 (8%) became unemployed. When the periods of 1989-1990 and 1992-1993 were compared, in the latter only 2/26 pneumologists directly obtained a contract on termination of training versus 13/22 from the former period (p < 0.0003). Half of the new pneumologists (24/48) performed other complementary labor activities, the most frequent being the work in medical emergency areas. CONCLUSIONS. Despite the importance of the respiratory diseases in health care, there is an increase in the number of pneumologists with difficulties in working in his specialty. This situation shows the need for searching for secondary professional activities. This fact, together with the scarce of promotion of specialized medical care, may enhance the risk of health care quality in respiratory diseases not improving to the desired level.

Internship and Residency

IgG subclass deficiencies associated with bronchiectasis.

Only a small number of patients with IgG subclass deficiencies (IgGSD) have been observed to have bronchiectasis. Moreover, in the series of patients with bronchiectasis, IgGSD have not been found at any frequency, and the etiology of bronchiectasis remains unclear in 29 to 49% of cases. Serum concentrations of total IgG, IgA, and IgG subclasses as well as pulmonary function were measured in 65 patients (aged: 10 to 74 yr) with bronchiectasis of unknown etiology. An ELISA test was performed to quantify subclasses 1 through 4 using subclass-specific antihuman monoclonal antibodies. IgG subclass estimation in a healthy population with age-stratified normal ranges was derived from 100 adults, 37 children aged between 10 and 12 yr, and 27 adolescents aged between 13 and 16 yr. Serum concentrations of specific IgG antibodies to Haemophilus influenzae type b capsular polysaccharide (Hib-PRP) were also assayed by an ELISA test in 19 of the patients (10 with IgGSD and nine with non-IgGSD) and in 58 healthy individuals before and 3 wk after immunization with Hib-PRP conjugated to meningococcal outer membrane protein complex (OMPC). Thirty-one patients (48%) had low serum concentrations of one or more IgG subclasses (19 IgG2 deficiencies, 2 IgG3 deficiencies, 3 IgG4 deficiencies, and 7 combined subclass deficiencies). All patients showed increased levels of total IgG, IgG1, and IgA, but this rise was significantly higher in patients without IgGSD. Patients with IgGSD showed impaired antibody response to Hib-PRP compared with patients with non-IgGSD and the control group. IgGSD, particularly IgG2 deficiency, are not an unusual cause of bronchiectasis. Therefore, serum levels of IgG subclasses must be assayed whenever other causes of bronchiectasis have been ruled out.

Adolescent

Incidence and significance of acid-fast bacilli in sputum smears at the end of antituberculous treatment.

OBJECTIVE: A group of patients with pulmonary tuberculosis (PT) who received and correctly completed antituberculous therapy were studied to determine the incidence and significance of positive acid-fast bacilli (AFB) in sputum smears at the end of this treatment. DESIGN: Retrospective chart review of persons with bacteriologically proved PT. PATIENTS: Of 1,052 patients diagnosed as having PT between 1988 and 1992, 453 who fulfilled the following criteria were included in the study: (1) diagnosis established by positive AFB and positive culture in sputum smears; (2) no previous antituberculous treatment had been received; (3) HIV serologic test results were negative; (4) treatment was correctly completed; (5) they were followed up throughout the period of treatment; and (6) expectoration was still present at the end of treatment and at least two spontaneous sputum samples could be obtained. RESULTS: Positive AFB of sputum smears were found at the end of treatment in 10 (2.2%) of the 453 patients studied. Five patients had only one positive smear, and the other five had more than one. Of these ten cases, sputum culture was negative in eight, which were considered to be unviable bacilli, and positive for nontuberculous mycobacteria in two. Clinical symptoms or worsening on chest radiograph were observed only in one patient with unviable bacilli, but they were caused by a concomitant nonspecific respiratory tract infection. CONCLUSIONS: Positive AFB smear results at the end of completed treatment regimens analyzed in this study have occurred because of unviable bacilli and nontuberculous mycobacteria colonization. The presence of more than one positive smear seems not to increase the probability of treatment failure and is more frequently due to nontuberculous mycobacteria. Results of culture can thus be awaited without the need to prolong or modify antituberculous therapy.

Humans

[Pulmonary and laryngeal tuberculosis. Study of 26 patients].

A description is reported of tuberculosis cases (TBC) with symptomatic laryngeal involvement diagnosed and treated from 1982 to 1994. Twenty-six out of 2,800 (0.9%) patients diagnosed with TBC had laryngeal symptoms. Twelve patients underwent laryngeal biopsy and the disease was diagnosed in 11; the remaining 15 patients were diagnosed on the basis of the typical lesions at laryngoscopy and resolution with specific therapy; in all of them there was a pulmonary TBC associated. The mean time of clinical laryngeal symptoms was five months and the most common symptom was dysphonia. There were factors which increased the risk for TBC in 16 patients (61.5%), alcoholism being the most common symptom in 10 (38%) patients. X-Ray examination revealed bilateral infiltrates or cavitation in 81% of patients. Sputum examination for acid-fast bacilli was positive in 15 (58%) and culture for Mycobacterium tuberculosis was positive in all of them. All patients adhered correctly to the therapeutic regimen and the clinical course was towards healing: no patient had laryngeal carcinoma after one year of follow-up. The incidence of symptomatic laryngeal TBC in our environment is low and usually presents in patients with risk factors, particularly alcoholism, with a long evolution of the disease and associated with extensive pulmonary TBC. The coexistence with laryngeal carcinoma is exceptional; therefore, when the association of laryngeal symptoms and active pulmonary TBC is present it is reasonable to reserve the laryngeal biopsy for those patients with lymph node enlargement, risk factors, or when symptoms persist after a correct therapeutic regime has been instituted.

Humans

[IgG subclasses in patients with symptomatic IgA deficiency].

BACKGROUND: Patients with IgA deficiency may be asymptomatic or may present recurrent infections mainly respiratory. A possible explanation for this variety of symptoms may be the association with a deficiency of IgG subclasses. METHODS: Twenty-five patients with a symptomatic IgA deficiency with a mean age of 18 +/- 12 years were studied. The quantification of the IgG subclasses was performed by ELISA test with antisubclass specific monoclonal murine antibodies. Serum from 100 healthy adults was collected to determine normal values of the IgG subclasses. RESULTS: Twenty-five (48%) had a deficiency of associated IgG subclasses (6 IgG2 deficiency, 1 IgG3, 3 IgG4 and 2 combined deficiency). The patient with a deficiency of associated IgG subclasses had more recurrent respiratory infections (chi 2, p < 0.03) and pneumonias (chi 2, p < 0.04). This group also had a greater FEV1 alteration (Student-t test, p < 0.04). CONCLUSIONS: Patients with symptomatic IgA deficiency frequently present IgG subclass deficiency and are more likely to have recurrent respiratory infections and greater changes in pulmonary function.

Adolescent

[The use of human gamma globulin in the treatment of common variable immunodeficiency].

BACKGROUND: The indication for treatment with human gammaglobulin in patients with primary hypogammaglobulinemia is well established. Nonetheless, there are no uniform criteria with regard to dose, periodicity and route of administration. METHODS: Twenty-seven patients with common variable immunodeficiency (CVI) who received i.m. or i.v. treatment with gammaglobulin were studied, evaluating the secondary effects, stable levels of IgG achieved, control of symptomatology, clinical evolution and the need for adjuvant therapies. RESULTS: Intravenous administration was more effective than intramuscular administration to achieve higher total IgG serum levels (5.2 +/- 1.2 vs 3.5 +/- 1.6 g/l; p = 0.07) in a shorter period of time (2.1 +/- 1.6 months vs 6.3 +/- 2.8 months; p < 0.01) and with new few secondary effects. The dose and periodicity of the treatment was individualized in each patient on the basis of the needs of consumption and the speed of metabolism of the gammaglobulin, with patients with chronic bronchial suppuration and diarrhea being those requiring the greatest doses (p < 0.0001) and a short interdosis time interval (19.2 +/- 3.1 vs 23.6 +/- 3.6 days; p = 0.01). Treatment with human gammaglobulin allowed the control of recurrent bacterial infection; however, adjuvant treatment with respiratory physical measures and antibiotics were required in patients with chronic bronchial suppuration to avoid progressive alteration of respiratory function. CONCLUSIONS: The administration of human gammaglobulin at adequate doses and frequency is effective to control infection, avoid the development of chronic bronchial disease, alteration of pulmonary function and the appearance of other complications. Intravenous route is safer and produces fewer secondary effects than intramuscular administration with the doses and period of the treatment requiring individualization for each patient.

Adolescent

[Evaluation of replacement therapy in emphysema caused by alpha 1-antitrypsin deficiency].

Assessment of alpha 1-antitrypsin replacement therapy (AAT) for emphysema. Patient characteristics were analyzed along with the possible side effects of the treatment and its efficacy in maintaining appropriate AAT blood levels. Lung function changes were also studied. The treatment protocol began with 4 weekly intravenous doses of 60 mg/kg AAT (Prolastin) and continued with monthly doses of 240 mg/kg. AAT serum levels were measured before each dose. Every 6 months pulmonary function tests (spirometry, plethysmography and CO transfer) were performed. Thirteen patients (mean age 46 yr) have been studied since 1988. Mean initial FEV1 was 0.79 l. Over 250 doses have been infused with no significant side effects reported. AAT levels before treatment in 3 patients were lower than that considered protective (50 mg/dl). Function tests results indicated stabilization of spirometric values in most cases. Diagnosis of AAT deficiency is delayed considerably, meaning that significant functional deterioration takes place before replacement therapy begins. No side effects of treatment have been observed. Until an appropriate interval between doses has been established, each patient's AAT levels must be monitored.

Adult

Scintigraphy, angiography and computed tomography in unilateral hyperlucent lung due to obliterative bronchiolitis.

This study examines the value of different imaging methods in assessing the anatomic structures of unilateral hyperlucent lung due to obliterative bronchiolitis. We studied 9 patients, 5 males and 4 females, suffering from UHL (mean age 49 years). Ventilation-perfusion scan (VPS) and computed tomography (CT) of the chest were performed in all, and conventional angiography or digital substraction angiography (DSA) in 7 patients. The VPS showed the characteristic pattern of a matched ventilation-perfusion defect and considerable air trapping during the washout phase. Conventional angiography and DSA displayed a smaller pulmonary artery on the affected side, with a poor peripheral vasculature. CT displayed a loss of lung volume in all cases, with diminished mean attenuation values, a markedly diminished vasculature and integrity of the main airways. In contrast to other imaging modalities, CT imaged bronchiectasis, which was the cause of the patients' clinical symptoms of bronchorrhea and hemoptysis. We conclude that CT of the chest is the most valuable imaging method for evaluating unilateral hyperlucent lung, particularly in symptomatic patients.

Adult