A controlled evaluation of filter paper use during staining of sputum smears for tuberculosis microscopy.

Background: Some sputum smear microscopy protocols recommend placing filter paper over sputum smears during staining for Mycobacterium tuberculosis (TB) . We found no published evidence assessing whether this is beneficial. We aimed to evaluate the effect of filter paper on sputum smear microscopy results. Methods: Sputum samples were collected from 30 patients with confirmed pulmonary TB and 4 healthy control participants. From each sputum sample, six smears (204 smears in total) were prepared for staining with Ziehl-Neelsen (ZN), auramine or viability staining with fluorescein diacetate (FDA). Half of the slides subjected to each staining protocol were randomly selected to have Whatman grade 3 filter paper placed over the dried smears prior to stain application and removed prior to stain washing. The counts of acid-fast bacilli (AFB) and precipitates per 100 high-power microscopy fields of view, and the proportion of smear that appeared to have been washed away were recorded. Statistical analysis used a linear regression model adjusted by staining technique with a random effects term to correct for between-sample variability.   Results: The inclusion of filter paper in the staining protocol significantly decreased microscopy positivity independent of staining with ZN, auramine or FDA (p=0.01). Consistent with this finding, there were lower smear grades in slides stained using filter paper versus without (p=0.04), and filter paper use reduced AFB counts by 0.28 logarithms (95% confidence intervals, CI=0.018, 0.54, p=0.04) independent of staining technique. In all analyses, auramine was consistently more sensitive with higher AFB counts versus ZN (p=0.001), whereas FDA had lower sensitivity and lower AFB counts (p<0.0001). Filter paper use was not associated with the presence of any precipitate (p=0.5) or the probability of any smear washing away (p=0.6) during the staining process. Conclusions: Filter paper reduced the sensitivity of AFB microscopy and had no detectable beneficial effects so is not recommended.

Quality of life, tuberculosis and treatment outcome; a case-control and nested cohort study.

BACKGROUND: Global tuberculosis policy increasingly emphasises broad tuberculosis impacts and highlights the lack of evidence concerning tuberculosis-related quality of life (QOL). METHODS: Participants were recruited in 32 Peruvian communities between July 13, 2016 and February 24, 2018 and followed-up until November 8, 2019. Inclusion criteria were age ≥15 years for "patients" (n=1545) starting treatment for tuberculosis disease in health centres; "contacts" (n=3180) who shared a patient's household for ≥6 h·week-1; and randomly selected "controls" (n=277). The EUROHIS-QOL questionnaire quantified satisfaction with QOL, health, energy, activities of daily living (ADL), self, relationships, money and living place. FINDINGS: Newly diagnosed tuberculosis was most strongly associated with lower QOL scores (p<0.001). Patients initially had lower QOL than controls for all EUROHIS-QOL questions (p≤0.01), especially concerning health, ADL and self. Lower initial QOL in patients predicted adverse treatment outcomes and scores <13 points had 4.2-fold (95% CI 2.3-7.6) increased risk of death versus those with higher QOL scores (both p<0.001). Patient QOL was re-assessed 6 months later, and for patients with successful treatment QOL became similar to participants who had never had tuberculosis, whereas patients who did not complete treatment continued to have low QOL (p<0.001). Multidrug-resistant tuberculosis was associated with lower QOL before and during treatment (both p<0.001). Contacts had lower QOL if they lived with a patient who had low QOL score (p<0.0001) or were a caregiver for the patient (p<0.001). CONCLUSIONS: Tuberculosis was associated with impaired psychosocioeconomic QOL which recovered with successful treatment. Low QOL scores predicted adverse treatment outcome. This brief EUROHIS-QOL eight-item questionnaire quantified the holistic needs of tuberculosis-affected people, potentially guiding patient-centred care.

Optimising fluorescein diacetate sputum smear microscopy for assessing patients with pulmonary tuberculosis.

BACKGROUND: Assessing Mycobacterium tuberculosis (TB) viability by fluorescein diacetate (FDA) microscopy can predict TB culture results, treatment response and infectiousness. However, diverse methods have been published. We aimed to optimise FDA microscopy, minimising sputum processing, biohazard and complexity for use in resource-constrained settings. METHODS AND RESULTS: Optimization: Patients with smear-positive pulmonary TB before treatment and healthy control participants provided sputa. These were divided into equal aliquots that were tested directly or after NaOH centrifuge-decontamination. Each aliquot was cultured and used to prepare slides (n = 80). FDA microscopy used: 1 or 3 drops of sputum; with/out acid-alcohol wash; with/out phenol sterilization; with 0/30/60 seconds KMnO4 quenching. Control samples all had negative culture and microscopy results. FDA microscopy had higher sensitivity when performed directly (without centrifuge-decontamination) on 1 drop of sputum (P<0.001), because 3 drops obscured microscopy. Acid-alcohol wash and KMnO4 quenching made bacilli easier to identity (P = 0.005). Phenol sterilization did not impair microscopy (P>0.1). Validation: The 2 protocols that performed best in the optimization experiments were reassessed operationally by comparing duplicate slides (n = 412) stained with KMnO4 quenching for 30 versus 60 seconds. FDA microscopy results were similar (P = 0.4) and highly reproducible, with 97% of counts agreeing within +/-1 logarithm. Storage: Smear microscopy slides and aliquots of the sputum from which they were made were stored for 4 weeks. Twice-weekly, paired slides (n = 80) were stained with freshly prepared versus stored FDA and read quantitatively. Storing sputum, microscopy slides or FDA solution at 4°C or room temperature had no effect on FDA microscopy results (all P>0.2). Cost: Material costs for each slide tested by FDA microscopy using reagents purchased locally were USD $0.05 and required the same equipment, time and skills as auramine acid-fast microscopy. CONCLUSIONS: We recommend a simple, bio-secure protocol for FDA microscopy that provides sensitive and repeatable results without requiring centrifugation.

Active and passive case-finding in tuberculosis-affected households in Peru: a 10-year prospective cohort study.

BACKGROUND: Active case-finding among contacts of patients with tuberculosis is a global health priority, but the effects of active versus passive case-finding are poorly characterised. We assessed the contribution of active versus passive case-finding to tuberculosis detection among contacts and compared sex and disease characteristics between contacts diagnosed through these strategies. METHODS: In shanty towns in Callao, Peru, we identified index patients with tuberculosis and followed up contacts aged 15 years or older for tuberculosis. All patients and contacts were offered free programmatic active case-finding entailing sputum smear microscopy and clinical assessment. Additionally, all contacts were offered intensified active case-finding with sputum smear and culture testing monthly for 6 months and then once every 4 years. Passive case-finding at local health facilities was ongoing throughout follow-up. FINDINGS: Between Oct 23, 2002, and May 26, 2006, we identified 2666 contacts, who were followed up until March 1, 2016. Median follow-up was 10·0 years (IQR 7·5-11·0). 232 (9%) of 2666 contacts were diagnosed with tuberculosis. The 2-year cumulative risk of tuberculosis was 4·6% (95% CI 3·5-5·5), and overall incidence was 0·98 cases (95% CI 0·86-1·10) per 100 person-years. 53 (23%) of 232 contacts with tuberculosis were diagnosed through active case-finding and 179 (77%) were identified through passive case-finding. During the first 6 months of the study, 23 (45%) of 51 contacts were diagnosed through active case-finding and 28 (55%) were identified through passive case-finding. Contacts diagnosed through active versus passive case-finding were more frequently female (36 [68%] of 53 vs 85 [47%] of 179; p=0·009), had a symptom duration of less than 15 days (nine [25%] of 36 vs ten [8%] of 127; p=0·03), and were more likely to be sputum smear-negative (33 [62%] of 53 vs 62 [35%] of 179; p=0·0003). INTERPRETATION: Although active case-finding made an important contribution to tuberculosis detection among contacts, passive case-finding detected most of the tuberculosis burden. Compared with passive case-finding, active case-finding was equitable, helped to diagnose tuberculosis earlier and usually before a positive result on sputum smear microscopy, and showed a high burden of undetected tuberculosis among women. FUNDING: Wellcome Trust, Department for International Development Civil Society Challenge Fund, Joint Global Health Trials consortium, Bill & Melinda Gates Foundation, Imperial College National Institutes of Health Research Biomedical Research Centre, Foundation for Innovative New Diagnostics, Sir Halley Stewart Trust, WHO, TB REACH, and IFHAD: Innovation for Health and Development.

A score to predict and stratify risk of tuberculosis in adult contacts of tuberculosis index cases: a prospective derivation and external validation cohort study.

BACKGROUND: Contacts of tuberculosis index cases are at increased risk of developing tuberculosis. Screening, preventive therapy, and surveillance for tuberculosis are underused interventions in contacts, particularly adults. We developed a score to predict risk of tuberculosis in adult contacts of tuberculosis index cases. METHODS: In 2002-06, we recruited contacts aged 15 years or older of index cases with pulmonary tuberculosis who lived in desert shanty towns in Ventanilla, Peru. We followed up contacts for tuberculosis until February, 2016. We used a Cox proportional hazards model to identify index case, contact, and household risk factors for tuberculosis from which to derive a score and classify contacts as low, medium, or high risk. We validated the score in an urban community recruited in Callao, Peru, in 2014-15. FINDINGS: In the derivation cohort, we identified 2017 contacts of 715 index cases, and median follow-up was 10·7 years (IQR 9·5-11·8). 178 (9%) of 2017 contacts developed tuberculosis during 19 147 person-years of follow-up (incidence 0·93 per 100 person-years, 95% CI 0·80-1·08). Risk factors for tuberculosis were body-mass index, previous tuberculosis, age, sustained exposure to the index case, the index case being in a male patient, lower community household socioeconomic position, indoor air pollution, previous tuberculosis among household members, and living in a household with a low number of windows per room. The 10-year risks of tuberculosis in the low-risk, medium-risk, and high-risk groups were, respectively, 2·8% (95% CI 1·7-4·4), 6·2% (4·8-8·1), and 20·6% (17·3-24·4). The 535 (27%) contacts classified as high risk accounted for 60% of the tuberculosis identified during follow-up. The score predicted tuberculosis independently of tuberculin skin test and index-case drug sensitivity results. In the external validation cohort, 65 (3%) of 1910 contacts developed tuberculosis during 3771 person-years of follow-up (incidence 1·7 per 100 person-years, 95% CI 1·4-2·2). The 2·5-year risks of tuberculosis in the low-risk, medium-risk, and high-risk groups were, respectively, 1·4% (95% CI 0·7-2·8), 3·9% (2·5-5·9), and 8·6%· (5·9-12·6). INTERPRETATION: Our externally validated risk score could predict and stratify 10-year risk of developing tuberculosis in adult contacts, and could be used to prioritise tuberculosis control interventions for people most likely to benefit. FUNDING: Wellcome Trust, Department for International Development Civil Society Challenge Fund, Joint Global Health Trials consortium, Bill & Melinda Gates Foundation, Imperial College National Institutes of Health Research Biomedical Research Centre, Foundation for Innovative New Diagnostics, Sir Halley Stewart Trust, WHO, TB REACH, and Innovation for Health and Development.

Sputum Microscopy With Fluorescein Diacetate Predicts Tuberculosis Infectiousness.

Background: Sputum from patients with tuberculosis contains subpopulations of metabolically active and inactive Mycobacterium tuberculosis with unknown implications for infectiousness. Methods: We assessed sputum microscopy with fluorescein diacetate (FDA, evaluating M. tuberculosis metabolic activity) for predicting infectiousness. Mycobacterium tuberculosis was quantified in pretreatment sputum of patients with pulmonary tuberculosis using FDA microscopy, culture, and acid-fast microscopy. These 35 patients' 209 household contacts were followed with prevalence surveys for tuberculosis disease for 6 years. Results: FDA microscopy was positive for a median of 119 (interquartile range [IQR], 47-386) bacteria/µL sputum, which was 5.1% (IQR, 2.4%-11%) the concentration of acid-fast microscopy-positive bacteria (2069 [IQR, 1358-3734] bacteria/µL). Tuberculosis was diagnosed during follow-up in 6.4% (13/209) of contacts. For patients with lower than median concentration of FDA microscopy-positive M. tuberculosis, 10% of their contacts developed tuberculosis. This was significantly more than 2.7% of the contacts of patients with higher than median FDA microscopy results (crude hazard ratio [HR], 3.8; P = .03). This association maintained statistical significance after adjusting for disease severity, chemoprophylaxis, drug resistance, and social determinants (adjusted HR, 3.9; P = .02). Conclusions: Mycobacterium tuberculosis that was FDA microscopy negative was paradoxically associated with greater infectiousness. FDA microscopy-negative bacteria in these pretreatment samples may be a nonstaining, slowly metabolizing phenotype better adapted to airborne transmission.

Clinical evaluation of tuberculosis viability microscopy for assessing treatment response.

BACKGROUND: It is difficult to determine whether early tuberculosis treatment is effective in reducing the infectiousness of patients' sputum, because culture takes weeks and conventional acid-fast sputum microscopy and molecular tests cannot differentiate live from dead tuberculosis. METHODS: To assess treatment response, sputum samples (n=124) from unselected patients (n=35) with sputum microscopy-positive tuberculosis were tested pretreatment and after 3, 6, and 9 days of empiric first-line therapy. Tuberculosis quantitative viability microscopy with fluorescein diacetate, quantitative culture, and acid-fast auramine microscopy were all performed in triplicate. RESULTS: Tuberculosis quantitative viability microscopy predicted quantitative culture results such that 76% of results agreed within ±1 logarithm (rS=0.85; P<.0001). In 31 patients with non-multidrug-resistant (MDR) tuberculosis, viability and quantitative culture results approximately halved (both 0.27 log reduction, P<.001) daily. For patients with non-MDR tuberculosis and available data, by treatment day 9 there was a >10-fold reduction in viability in 100% (24/24) of cases and quantitative culture in 95% (19/20) of cases. Four other patients subsequently found to have MDR tuberculosis had no significant changes in viability (P=.4) or quantitative culture (P=.6) results during early treatment. The change in viability and quantitative culture results during early treatment differed significantly between patients with non-MDR tuberculosis and those with MDR tuberculosis (both P<.001). Acid-fast microscopy results changed little during early treatment, and this change was similar for non-MDR tuberculosis vs MDR tuberculosis (P=.6). CONCLUSIONS: Tuberculosis quantitative viability microscopy is a simple test that within 1 hour predicted quantitative culture results that became available weeks later, rapidly indicating whether patients were responding to tuberculosis therapy.

[Music therapy and regional anesthesia in orthopedic surgery]. / Musicoterapia y anestesia locorregional en cirugía ortopédica.

OBJECTIVE: To evaluate the sedative effects, intra-operation, of music therapy in orthopedic surgery patients with locoregional anesthesia in the Hospital Clínic i Provincial of Barcelona. EQUIPMENT AND METHODS: Prospective comparative study on a random sample of 110 patients undergoing or not music therapy. The degree of anxiety was assessed with the Questionnaire STAIC. The application of the music was done with a MP3 player and headphones. The collected data were analyzed with Excel. For the statistical analysis we used the SPSS-18 software and Chi-square test to test the hypothesis of whether there was relationship between the level of peace and music therapy. RESULTS: After the analysis, the results of Chi-square were in the group of no sedation with/without music Chi2 = 2.01, P = 0.35. The statistical significance level was p < 0.05. CONCLUSIONS: No relationship was found between hearing music or not and the patient's comfort level. Most patients recommend listening to music in the operating room despite the sounds around do not bother them.

Musicoterapia y anestesia locorregional en cirugía ortopédica / Therapy and regional anesthesia in orthopedic surgery

Objetivo. Valorar los efectos sedantes, intraoperatorios, de la musicoterapia en pacientes intervenidos de cirugía ortopédica con anestesia locorregional, en el Hospital Clínic i Provincial de Barcelona. Material y métodos. Estudio comparativo prospectivo sobre una muestra aleatoria de 110 pacientes, sometidos o no a musicoterapia. El grado de ansiedad se valoró con el Cuestionario STAIC (State-Trait Anxiety Inventory for Children). La aplicación de la música se hizo con un reproductor de MP3 y auriculares. Los datos recogidos se analizaron con el programa Excel. Para el estudio estadístico se ha utilizado el programa SPSS-18 y la prueba de Chi-cuadrado para verificar la hipótesis de si hay relación entre el nivel de tranquilidad y la musicoterapia. Resultados. Tras el análisis, los resultados de Chi-cuadrado fueron en el grupo de no sedación con/sin música de X2 = 2.01, p = 0.35, siendo el nivel de significación estadística de p < 0.05. Conclusiones. No se ha encontrado relación entre la audición o no de música y el nivel de tranquilidad del paciente. La mayoría de los pacientes recomiendan oír música en el quirófano a pesar de que no les molestan los sonidos del entorno (AU)

Objective. To evaluate the sedative effects, intra-operation, of music therapy in orthopedic surgery patients with locoregional anesthesia in the Hospital Clínic i Provincial of Barcelona. Equipment and methods. Prospective comparative study on a random sample of 110 patients undergoing or not music therapy. The degree of anxiety was assessed with the Questionnaire STAIC. The application of the music was done with a MP3 player and head-phones. The collected data were analyzed with Excel. For the statistical analysis we used the SPSS-18 software and Chi-square test to test the hypothesis of whether there was relationship between the level of peace and music therapy. Results. After the analysis, the results of Chi-square were in the group of no sedation with/without music X2 = 2.01, P = 0.35. The statistical significance level was p < 0.05. Conclusions. No relationship was found between hearing music or not and the patient’s comfort level. Most patients recommend listening to music in the operating room despite the sounds around do not bother them (AU)

Effects of ascent to high altitude on human antimycobacterial immunity.

BACKGROUND: Tuberculosis infection, disease and mortality are all less common at high than low altitude and ascent to high altitude was historically recommended for treatment. The immunological and mycobacterial mechanisms underlying the association between altitude and tuberculosis are unclear. We studied the effects of altitude on mycobacteria and antimycobacterial immunity. METHODS: Antimycobacterial immunity was assayed in 15 healthy adults residing at low altitude before and after they ascended to 3400 meters; and in 47 long-term high-altitude residents. Antimycobacterial immunity was assessed as the extent to which participants' whole blood supported or restricted growth of genetically modified luminescent Bacille Calmette-Guérin (BCG) mycobacteria during 96 hours incubation. We developed a simplified whole blood assay that could be used by a technician in a low-technology setting. We used this to compare mycobacterial growth in participants' whole blood versus positive-control culture broth and versus negative-control plasma. RESULTS: Measurements of mycobacterial luminescence predicted the number of mycobacterial colonies cultured six weeks later. At low altitude, mycobacteria grew in blood at similar rates to positive-control culture broth whereas ascent to high altitude was associated with restriction (p ≤ 0.002) of mycobacterial growth to be 4-times less than in culture broth. At low altitude, mycobacteria grew in blood 25-times more than negative-control plasma whereas ascent to high altitude was associated with restriction (p ≤ 0.01) of mycobacterial growth to be only 6-times more than in plasma. There was no evidence of differences in antimycobacterial immunity at high altitude between people who had recently ascended to high altitude versus long-term high-altitude residents. CONCLUSIONS: An assay of luminescent mycobacterial growth in whole blood was adapted and found to be feasible in low-resource settings. This demonstrated that ascent to or residence at high altitude was associated with decreased mycobacterial growth in whole blood relative to controls, consistent with altitude-related augmentation of antimycobacterial cellular immunity.

Discriminating active from latent tuberculosis in patients presenting to community clinics.

BACKGROUND: Because of the high global prevalence of latent TB infection (LTBI), a key challenge in endemic settings is distinguishing patients with active TB from patients with overlapping clinical symptoms without active TB but with co-existing LTBI. Current methods are insufficiently accurate. Plasma proteomic fingerprinting can resolve this difficulty by providing a molecular snapshot defining disease state that can be used to develop point-of-care diagnostics. METHODS: Plasma and clinical data were obtained prospectively from patients attending community TB clinics in Peru and from household contacts. Plasma was subjected to high-throughput proteomic profiling by mass spectrometry. Statistical pattern recognition methods were used to define mass spectral patterns that distinguished patients with active TB from symptomatic controls with or without LTBI. RESULTS: 156 patients with active TB and 110 symptomatic controls (patients with respiratory symptoms without active TB) were investigated. Active TB patients were distinguishable from undifferentiated symptomatic controls with accuracy of 87% (sensitivity 84%, specificity 90%), from symptomatic controls with LTBI (accuracy of 87%, sensitivity 89%, specificity 82%) and from symptomatic controls without LTBI (accuracy 90%, sensitivity 90%, specificity 92%). CONCLUSIONS: We show that active TB can be distinguished accurately from LTBI in symptomatic clinic attenders using a plasma proteomic fingerprint. Translation of biomarkers derived from this study into a robust and affordable point-of-care format will have significant implications for recognition and control of active TB in high prevalence settings.

Evaluation of bleach-sedimentation for sterilising and concentrating Mycobacterium tuberculosis in sputum specimens.

BACKGROUND: Bleach-sedimentation may improve microscopy for diagnosing tuberculosis by sterilising sputum and concentrating Mycobacterium tuberculosis. We studied gravity bleach-sedimentation effects on safety, sensitivity, speed and reliability of smear-microscopy. METHODS: This blinded, controlled study used sputum specimens (n = 72) from tuberculosis patients. Bleach concentrations and exposure times required to sterilise sputum (n = 31) were determined. In the light of these results, the performance of 5 gravity bleach-sedimentation techniques that sterilise sputum specimens (n = 16) were compared. The best-performing of these bleach-sedimentation techniques involved adding 1 volume of 5% bleach to 1 volume of sputum, shaking for 10-minutes, diluting in 8 volumes distilled water and sedimenting overnight before microscopy. This technique was further evaluated by comparing numbers of visible acid-fast bacilli, slide-reading speed and reliability for triplicate smears before versus after bleach-sedimentation of sputum specimens (n = 25). Triplicate smears were made to increase precision and were stained using the Ziehl-Neelsen method. RESULTS: M. tuberculosis in sputum was successfully sterilised by adding equal volumes of 15% bleach for 1-minute, 6% for 5-minutes or 3% for 20-minutes. Bleach-sedimentation significantly decreased the number of acid-fast bacilli visualised compared with conventional smears (geometric mean of acid-fast bacilli per 100 microscopy fields 166, 95%CI 68-406, versus 346, 95%CI 139-862, respectively; p = 0.02). Bleach-sedimentation diluted paucibacillary specimens less than specimens with higher concentrations of visible acid-fast bacilli (p = 0.02). Smears made from bleach-sedimented sputum were read more rapidly than conventional smears (9.6 versus 11.2 minutes, respectively, p = 0.03). Counting conventional acid-fast bacilli had high reliability (inter-observer agreement, r = 0.991) that was significantly reduced (p = 0.03) by bleach-sedimentation (to r = 0.707) because occasional strongly positive bleach-sedimented smears were misread as negative. CONCLUSIONS: Gravity bleach-sedimentation improved laboratory safety by sterilising sputum but decreased the concentration of acid-fast bacilli visible on microscopy, especially for sputum specimens containing high concentrations of M. tuberculosis. Bleach-sedimentation allowed examination of more of each specimen in the time available but decreased the inter-observer reliability with which slides were read. Thus bleach-sedimentation effects vary depending upon specimen characteristics and whether microscopy was done for a specified time, or until a specified number of microscopy fields had been read. These findings provide an explanation for the contradictory results of previous studies.

Diagnóstico diferencial del temblor: [revisión] / Differential diagnosis of tremor: [review]

Se hace una revisión bibliográfica del temblor con énfasis en la crítica del concepto, los aspectos etiológicos y la semiología, así como la semiotecnia; aspectos estos que conducen, entre otros, a clarificar el diagnóstico diferencial en base a la localización anatómica, las circunstancias conductuales acompañantes, la amplitud del mismo y algunas entidades o factores causales, elementos que derivan en facilitar una propuesta de clasificación con la semiotecnia correspondiente. Finalmente se insiste en las patologías, tóxicos, drogas y aspectos genéticos que pueden originar este síntoma-signo, así como en una entidad nosológica en que el temblor es un síntoma capital y excepcionalmente puede cursar con ausencia total del mismo (Parkinson) y conllevar a dificultades en el diagnóstico. Se evidencia la necesidad de estudiar este tópico por su importancia clínica y neuro- psíquica así como por su escueta bibliografía, sobre todo reciente.

A bibliographical revision of the tremor is made with emphasis in the criticism of the concept, the etiologic aspects and the semiology, as well as the semiotecnia; aspects these that contribute, among other, to clarify the differential diagnosis based on the anatomical localization, the accompanying behavioral circumstances, its extent and some entities or causal factors, elements that derive in facilitating a classification proposal with the corresponding semiotecnia. Finally it is insisted in the pathologies, toxic, drugs and genetic aspects that can originate this symptom-sign, as well as in a nosologic entity that tremor is a capital symptom and exceptionally it can happen with total absence (Parkinson) and to share to difficulties in the diagnosis. The necessity of studying this topic for its clinical and neuro - psychic importance as well as for its concise bibliography, is evidenced mainly recent.

Diagnóstico diferencial del temblor / Differential diagnosis of tremor

Se hace una revisión bibliográfica del temblor con énfasis en la crítica del concepto, los aspectos etiológicos y la semiología, así como la semiotecnia; aspectos estos que conducen, entre otros, a clarificar el diagnóstico diferencial en base a la localización anatómica, las circunstancias conductuales acompañantes, la amplitud del mismo y algunas entidades o factores causales, elementos que derivan en facilitar una propuesta de clasificación con la semiotecnia correspondiente. Finalmente se insiste en las patologías, tóxicos, drogas y aspectos genéticos que pueden originar este síntoma-signo, así como en una entidad nosológica en que el temblor es un síntoma capital y excepcionalmente puede cursar con ausencia total del mismo (Parkinson) y conllevar a dificultades en el diagnóstico. Se evidencia la necesidad de estudiar este tópico por su importancia clínica y neuro- psíquica así como por su escueta bibliografía, sobre todo reciente (AU)

A bibliographical revision of the tremor is made with emphasis in the criticism of the concept, the etiologic aspects and the semiology, as well as the semiotecnia; aspects these that contribute, among other, to clarify the differential diagnosis based on the anatomical localization, the accompanying behavioral circumstances, its extent and some entities or causal factors, elements that derive in facilitating a classification proposal with the corresponding semiotecnia. Finally it is insisted in the pathologies, toxic, drugs and genetic aspects that can originate this symptom-sign, as well as in a nosologic entity that tremor is a capital symptom and exceptionally it can happen with total absence (Parkinson) and to share to difficulties in the diagnosis. The necessity of studying this topic for its clinical and neuro - psychic importance as well as for its concise bibliography, is evidenced mainly recent (AU)

Respuesta completa al tratamiento en un caso de seminoma del mediastino / Complete answer to treatment in a case of seminoma of the mediastinum

Se presenta y discute el caso de un paciente de 46 años con antecedentes de la enfermedad de Hansen y cuadro clínico de dolor torácico, tos seca y derrame pleural de cuatro meses de evolución. Se le diagnosticó por biopsia de las partes blandas a nivel de esternón un seminoma de mediastino avanzado que infiltra la pared torácica y recibió tratamiento con poliquimioterapia basada en cisplatino y radioterapia hace seis años y se mantiene controlado de su enfermedad.

It is present and discusses a case of a 46 year-old patient with antecedents of the Hansen´s disease and clinical picture of thoracic pain, dry cough and pleural effusion of four months of evolution. It was diagnosed by biopsy of the soft parts to sternum level an advanced seminoma of the mediastinum that infiltrates the thoracic wall and he received treatment with polychemotherapy based on cisplatin and radiotherapy six years ago and he stays controlled of his illness.

Respuesta completa al tratamiento en un caso de seminoma del mediastino / Complete answer to treatment in a case of seminoma of the mediastinum

Se presenta y discute el caso de un paciente de 46 años con antecedentes de la enfermedad de Hansen y cuadro clínico de dolor torácico, tos seca y derrame pleural de cuatro meses de evolución. Se le diagnosticó por biopsia de las partes blandas a nivel de esternón un seminoma de mediastino avanzado que infiltra la pared torácica y recibió tratamiento con poliquimioterapia basada en cisplatino y radioterapia hace seis años y se mantiene controlado de su enfermedad(AU)

It is present and discusses a case of a 46 year-old patient with antecedents of the Hansen´s disease and clinical picture of thoracic pain, dry cough and pleural effusion of four months of evolution. It was diagnosed by biopsy of the soft parts to sternum level an advanced seminoma of the mediastinum that infiltrates the thoracic wall and he received treatment with polychemotherapy based on cisplatin and radiotherapy six years ago and he stays controlled of his illness(AU)

Tuberculosis diagnosis and multidrug resistance testing by direct sputum culture in selective broth without decontamination or centrifugation.

Tuberculosis culture usually requires sputum decontamination and centrifugation to prevent cultures from being overgrown by contaminating bacteria and fungi. However, decontamination destroys many tuberculous bacilli, and centrifugation often is not possible in resource-poor settings. We therefore assessed the performance of Mycobacterium tuberculosis culture with unprocessed samples plated directly by using tuberculosis-selective media and compared this procedure to conventional culture using centrifuge decontamination. Quadruplicate aliquots of strain H37RV were cultured in 7H9 broth with and without selective antimicrobials and after centrifuge decontamination. The subsequent comparison was made with 715 sputum samples. Split paired sputum samples were cultured conventionally with centrifuge decontamination and by direct culture in tuberculosis-selective media containing antibiotics. Centrifuge decontamination reduced tuberculosis H37RV colonies by 78% (P < 0.001), whereas direct culture in tuberculosis-selective media had no inhibitory effect. Similarly, in sputum cultures that were not overgrown by contaminants, conventional culture yielded fewer tuberculosis colonies than direct culture (P < 0.001). However, the sensitivity of conventional culture was greater than that of direct culture, because samples were less affected by contamination. Thus, of the 340 sputum samples that were tuberculosis culture positive, conventional culture detected 97%, whereas direct culture detected 81% (P < 0.001). Conventional and direct cultures both took a median of 8.0 days to diagnose tuberculosis (P = 0.8). In those direct cultures that detected drug resistance or susceptibility, there was a 97% agreement with the results of conventional culture (Kappa agreement statistic, 0.84; P < 0.001). Direct culture is a simple, low-technology, and rapid technique for diagnosing tuberculosis and determining drug susceptibility. Compared to that of conventional culture, direct culture has reduced sensitivity because of bacterial overgrowth, but in basic laboratories this deficit may be outweighed by the ease of use.

Improved diagnosis of pleural tuberculosis using the microscopic- observation drug-susceptibility technique.

Tests for pleural tuberculosis are insensitive and expensive. We compared nonproprietary microscopic-observation drug-susceptibility (MODS) culture with Löwenstein-Jensen culture for evaluation of pleural specimens. MODS culture was associated with greatly increased diagnostic sensitivity and shorter time to diagnosis, compared with Löwenstein-Jensen culture (sensitivity of culture of biopsy specimens, 81% vs.51%; time to diagnosis, 11 days vs. 24 days; P < .001). The MODS technique is inexpensive, allows drug-susceptibility testing, and is a considerably improved diagnostic method for pleural tuberculosis.

Evaluation of a PCR-based universal heteroduplex generator assay as a tool for rapid detection of multidrug-resistant Mycobacterium tuberculosis in Peru.

Multidrug-resistant tuberculosis is an increasing health problem worldwide, especially in developing countries. The PCR-UHG-Rif assay, which detects mutations within the rpoB gene associated with rifampin resistance, was evaluated for its ability and reliability to detect and identify drug-resistant Mycobacterium tuberculosis in a developing country where tuberculosis is highly endemic.

[Omeprazole, amoxicillin and clarithromycin in the treatment of helicobacterpylori, in 7 and 10-day regimens]. / Tratamiento del Helicobacter pylori con omeprazol, amoxicilina y claritromicina en esquemas de 7 y 10 días.

AIM: The most accepted treatment for infection by Helicobacter pylori is the proton pump inhibitor based therapy with two antibiotics. However, there is no consensus regarding the duration. The purpose here was to compare eradication percentages in the omeprazole+amoxicillin+clarithromycin regimen administered during 7 days versus 10 days and confront the results with a previous 14-day* experience in Peru. METHOD: Patients from the Central Military Hospital and Peruvian-Japanese Hospital evidencing chronic upper gastrointestinal tract symptoms were recruited. We excluded patients with peptic ulcer. Biopsies were taken for diagnosis, for urease and PCR tests, culture and coloring with silver. Omeprazole+clarithromycin+amoxicillin was used during 7 days versus 10 days. Control endoscopy was performed one month after treatment had been completed and molecular biology techniques were used to differentiate recurrences from new infections. Susceptibility to clarithromycin was assessed. RESULTS: 36 patients were included in each group. Eradication was the same in both groups: 86.1% (31/36). In several patients in whom the bacteria persisted, the same initial nucleus was found. In a previous study* using this same regimen during 14 days, a 93% eradication was obtained. 91.18% of our samples were susceptible to clarithromycin. CONCLUSIONS: In Peru, the omeprazole+clarithromycin+amoxicillin combination gives results higher than 80% in the eradication of infection by Helicobacter pylori. The 7 and 10 days regimens eradicated the bacteria in 86% of our patients.