Definitive Etiologic Diagnosis Research Articles

Transient Increase in Pressure Gradients After Termination of Dual Antiplatelet Therapy in a Patient After Transfemoral Aortic Valve Implantation

Transcatheter aortic valve implantation (TAVI) is considered a transformational novel technology for the treatment of severe symptomatic aortic valve stenosis. It has been rapidly adopted in the clinical arena and meanwhile evolved to the standard of care for inoperable and an acceptable alternative for high-risk but operable patients.1,2 In analogy to surgical bioprosthetic aortic valve replacement, anticoagulation with vitamin K antagonists is not deemed necessary after TAVI. However, dual antiplatelet therapy with acetylsalicylic acid and clopidogrel is recommended for 6 months2 after the procedure, although this treatment regimen is not supported by any scientific evidence. A 72-year-old man with severe symptomatic aortic valve stenosis (aortic valve area, 0.9 cm2; mean transaortic gradient, 42 mm Hg; New York Heart Association [NYHA] functional class III; chronic kidney disease; logistic EuroSCORE, 19.8%; Society of Thoracic Surgeons score, 5.4%) underwent uncomplicated transfemoral TAVI using the balloon-expandable Edwards-Sapien bioprosthesis (Edwards Lifesciences Inc, Irvine, CA), which resulted in immediate hemodynamic and clinical improvement, especially in view …

Screening of MAMLD1 Mutations in 70 Children with 46,XY DSD: Identification and Functional Analysis of Two New Mutations

More than 50% of children with severe 46,XY disorders of sex development (DSD) do not have a definitive etiological diagnosis. Besides gonadal dysgenesis, defects in androgen biosynthesis, and abnormalities in androgen sensitivity, the Mastermind-like domain containing 1 (MAMLD1) gene, which was identified as critical for the development of male genitalia, may be implicated. The present study investigated whether MAMLD1 is implicated in cases of severe 46,XY DSD and whether routine sequencing of MAMLD1 should be performed in these patients.Seventy children with severe non-syndromic 46,XY DSD of unknown etiology were studied. One hundred and fifty healthy individuals were included as controls. Direct sequencing of the MAMLD1, AR, SRD5A2 and NR5A1 genes was performed. The transactivation function of the variant MAMLD1 proteins was quantified by the luciferase method.Two new mutations were identified: p.S143X (c.428C>A) in a patient with scrotal hypospadias with microphallus and p.P384L (c.1151C>T) in a patient with penile hypospadias with microphallus. The in vitro functional study confirmed no residual transactivating function of the p.S143X mutant and a significantly reduced transactivation function of the p.P384L protein (p = 0.0032). The p.P359S, p.N662S and p.H347Q variants are also reported with particularly high frequency of the p.359T- p.662G haplotype in the DSD patients.Severe undervirilization in XY newborns can reveal mutations of MAMLD1. MAMLD1 should be routinely sequenced in these patients with otherwise normal AR, SRD5A2 and NR5A1genes.

Fabry's Disease: A Prospective Multicenter Cohort Study in Young Adults with Cryptogenic Stroke

Stroke in young adults is etiologically diverse and may represent a diagnostic challenge remaining cryptogenic in one-fourth of cases. Limited information is available on the prevalence of Fabry's disease, a treatable multisystem inherited lysosomal storage disorder, and disability in young patients with cryptogenic stroke. The Canadian Fabry Stroke Screening Initiative (CFSSI) is a prospective multicenter cohort study of young adults (age 18-55) presenting with an ischemic stroke, transient ischemic attack, or intracerebral haemorrhage of unknown etiology to stroke centres across Canada. Diagnosis of Fabry's disease is made by direct DNA analysis of blood samples for α-galactosidase gene mutations or polymorphisms. Demographics, clinical information, and investigations including brain Magnetic Resonance Imaging (MRI) are collected. Functional neurological assessment includes neurological examination, the National Institutes of Health (NIH) stroke scale, modified Rankin scale, and the Barthel index. A follow-up interview is conducted by telephone or in person approximately six-months after the index stroke/transient ischemic attack/intracerebral haemorrhage to determine patient outcomes, quality of life, and patient use of medications. Prevalence of positive DNA mutation or single nucleotide polymorphism screens for Fabry's disease as a proportion of total cryptogenic stroke. Secondary outcomes include incident risk of new or recurrent vascular event at six-months, discharge disposition, disability at six-months as measured by the modified Rankin scale, mean time from symptoms onset to the definite etiological diagnosis, and length of hospital stay. This study constitutes the first initiative to determine the prevalence of a positive screen for Fabry's disease in young adults with stroke in Canada. Moreover, the Canadian Fabry Stroke Screening Initiative will provide information on recurrent vascular events, disability at six-months (modified Rankin scale), and disposition in this understudied population.

Co-infection with Group A <i>Streptococci</i> and <i>Epstein-Barr</i> Virus Presenting with Acute Glomerulonephritis and Acute Left Ventricular Dysfunction

Acute pharyngitis is commonly encountered, but a definite etiological diagnosis is difficult. Although co-infection with Group A Streptococci (GAS) and Epstein-Barr virus (EBV) is uncommon, general physicians should consider the possibility of EBV co-infection in patients with GAS pharyngitis who fail to show prompt remission of symptoms following appropriate antibiotic treatment. In this article, we present a rare case of a 16-year-old girl who had co-infection with GAS and EBV. She developed acute glomerulonephritis and left ventricular dysfunction in an overlapping manner. We were able to follow her until she healed, and herein describe the pathogenesis of her systemic and pulmonary edema.

Neurocysticercosis: relationship between Taenia antigen levels in CSF and MRI

To determine the relationship between Taenia antigen (TA) detection in cerebrospinal fluid (CSF) and magnetic resonance imaging (MRI) findings in patients with definite diagnosis of neurocysticercosis (NC). Sixty-three patients with definite diagnosis of NC were submitted to a MRI of the brain, and to a CSF examination, with a meticulous search for TA by ELISA. TA detection was positive in 36 patients (57.1%). A total of 836 lesions were analyzed, greatly within the cerebral parenchyma (98.7 of the lesions). Intact or non-degenerating cysts were the most common evolutive phase observed (50.4% of all lesions), 22.1% were degenerating cysts and 19.5% calcified cysts. We observed a significant relationship between TA levels detected and the total number of lesions and the number of non-degenerating cysts, but not with calcified lesions. According to our results, we propose at least four important types of contribution: (1) TA detection may allow etiologic diagnosis in transitional phases of NC, with non-characteristic images; (2) in final stages of evolution of cysticercoids in the CNS, lesions may not appear on CT or MRI, and TA detection may contribute to a definite etiologic diagnosis; (3) TA detection may permit diagnosis of NC in some patients with previous negative tests for antibody detection in CSF; (4) TA detection may represent an accurate marker of disease activity in the epileptic form of NC.

Investigations of significance of blood smear results in diagnostics of infectious and parasitic diseases in dogs

The microscopic examination of stained smears of peripheral blood is of vital significance in the speedy diagnostics of infectious and parasitic diseases, in particular during the stage of infection when the cause is present in the blood, or blood cells. It is sometimes possible to make a definitive diagnosis of an infectious or parasitic disease following an examination of a stained smear of the peripheral blood. Since microscopic examinations of a peripheral blood smear are applied increasingly rarely in clinical practice, due to the development of other methods for the diagnostics of infectious and parasitic diseases in dogs, as well as the lack of knowledge of the morphology of the numerous causes that can be present in the blood, we carried out an investigation into the presence and spread of infections whose causes can be present in dog blood. The investigations covered 100 dogs from which peripheral blood smears were taken and then stained with a Giemsa solution according to the standard protocol and examined under a microscope with an immersion lens. The examination of peripheral blood smears stained according to Giemsa resulted in the identification of the presence of an Ehrlichia spp. morula in a neutrophil granulocyte in one dog. The presence of hemotropic mycoplasmas was established in erythrocytes of eleven dogs, while the presence of the protozoa Babesia canis in erythrocytes was identified in five dogs included in the investigations. A microscopic examination of dog peripheral blood smears stained according to Giemsa was shown as a speedy, practical, simple, and inexpensive method for making a definitive etiological diagnosis of these infections, and it should be included regularly in standard protocols for the diagnostics of infectious and parasitic diseases.

Differenzierung von malignen und nichtmalignen, inflammatorischen Perikardergüssen mit Biomarkern

Disorders of the pericardium are commonly associated with pericardial effusion. Its etiology comprises a broad spectrum of diseases including also malignancies. Pericardiocentesis, pericardioscopy and targeted epicardial biopsy with consecutive pericardial fluid and epicardial biopsy analysis by cytology, molecular biology and immunology establish the underlying etiology in the majority of cases. Of particular therapeutic and prognostic importance is the definite differentiation of malignant pericardial effusion from benign pericardial effusion. Biomarkers for cardiovascular diseases can be divided into biochemical, histological, immunologic, serologic and molecular markers as well as imaging biomarkers. Biomarkers have proven to be useful in the diagnosis, differential diagnosis and prognosis of ischemic heart disease and heart failure. With respect to pericardial disorders, a comprehensive approach combining clinical information, imaging biomarkers, biomarkers of pericardial effusion and analysis of epicardial biopsies often leads to the definite etiologic diagnosis of pericardial effusion. Computed tomography and magnetic resonance imaging allow further characterization of the effusion and, of note, also of the surrounding tissue, which is of particular interest in case of malignancies. Biomarkers of pericardial effusion include biochemical markers, autoantibodies, tumor markers, and cytokines. Analysis of pericardial fluid specific gravity, protein level and lactate dehydrogenase (LDH) separates transudates from exsudates. High adenosine deaminase levels (ADA) and low levels of carcinoembryonic antigen (CEA) in the pericardial effusion are observed in tuberculous pericarditis allowing the differentiation from malignant pericardial effusion. Additional markers, such as interferon and lysozyme, have also been suggested for the diagnosis of tuberculous pericarditis. Tumor markers in pericardial fluid have been used to diagnose malignant pericarditis. CEA levels are significantly higher in malignant than benign effusion. By a cutoff level of CEA > 5 ng/ml the diagnostic sensitivity and specificity are 75% and 100%, respectively, in the diagnosis of malignant pericardial effusion. Further analysis of cytokines and mediators, serologic, immunologic and inflammatory markers may help to understand the pathophysiology of the pericardial disease and provide useful diagnostic information.

Developmental regression: Always a worrying signal

An 11-month old girl is presented to you for developmental delay. The child started to roll over at four months of age and sit independently at approximately seven months of age. Afterwards, she gradually regressed and could no longer achieve these motor milestones. In the past few weeks, she lost the ability to hold her head straight or bear weight on her legs. Her babbling and smiling have decreased, and she does not seem to be interested in her surroundings. The pregnancy and delivery were uneventful, and there is no history of neonatal complications, febrile illnesses or head injuries. The family reports that she received her first three pentavalent immunizations. An analysis of family history was negative for developmental delay; however, the parents are distant cousins. On examination, the child was unable to sit, roll or bear weight on her legs. Her eyes fixed poorly on objects and she did not reach for them. Her trunk and limb muscular tone was poor, while the muscle bulk remained normal. Deep tendon reflexes were hard to obtain. In view of the developmental deterioration and abnormal neurological examination, the patient was referred to a paediatric neurologist. LEARNING POINTS Primary health care providers treating children with progressive intellectual and neurological deterioration (PIND) are facing a challenging task, because a myriad of neurodegenerative disorders can present in a similar fashion. Regression of developmental milestones or PIND should alert primary health care providers of the need to conduct a detailed history and physical examination. ○ When clinically indicated, investigations such as magnetic resonance imaging, electroencephalogram, evoked potentials, biochemical studies, genetic investigations (cytogenetic studies and molecular testing) and biochemical evaluations should be considered. ○ A definitive diagnosis may require further investigations and more invasive testing (1,2). The two-year surveillance study (3) on PIND was used to enhance monitoring for the possibility of Creutzfeldt-Jakob disease (CJD) and variant-CJD. While CJD is rare, the occurrence of variant-CJD in Canada would signal an important change in its epidemiology. Canadian Paediatric Surveillance Program participants reported 99 possible PIND cases; 59 of these were confirmed. The three most frequent diagnoses were mitochondrial disorders, ceroid lipofuscinosis and mucopolysaccharidosis. One case of iatrogenic CJD was confirmed; however, no cases of the variant form were reported. Of note, there were no cases with toxic etiologies (4,5). A definitive etiological diagnosis could not be attained in eight cases, even after exhaustive investigations and review by an expert panel consisting of four paediatric neurologists, a medical geneticist and a paediatric neuropathologist. Support for ongoing research and surveillance on PIND disorders is essential to advance knowledge and provide useful public health information about trends occurring in rare neurological disorders.

Surto de pitiose cutânea em bovinos

Setenta e seis bovinos, sem raça definida, jovens, de ambos os sexos, apresentaram lesões cutâneas multifocais nodulares, ulceradas e crostosas nas faces medial e lateral dos membros anteriores e posteriores, região ventral do pescoço, esterno e cauda. A doença ocorreu no verão e as lesões foram observadas nas regiões do corpo que ficavam grande tempo em contato com a água em canais de irrigação. Histologicamente observaram-se múltiplos granulomas e piogranulomas contendo escassas imagens negativas de hifas na área central, as quais foram melhor evidenciadas através da técnica de metenamina nitrato de prata de Grocott. O diagnóstico etiológico definitivo foi baseado na técnica de imuno-histoquímica com anticorpo policlonal anti-Pythium insidiosum. Adicionalmente, foi realizado o teste de ELISA indireto. Surtos de pitiose cutânea bovina são incomuns e, particularmente neste relato, todos os animais afetados tiveram cura espontânea das lesões dentro de duas a três semanas.

Características clínicas y epidemiológicas de las infecciones respiratorias causadas por el metapneumovirus humano en pacientes pediátricos

Human Metapneumovirus (hMPV) was first identified in 2001 in respiratory samples from children and adults with acute respiratory tract infection. The aim of this prospective study was to determine the clinical and epidemiological characteristics of pediatric patients with an acute respiratory tract infection and exclusive isolation of hMPV in respiratory samples (December 2005-January 2007). All respiratory tract samples were submitted to rapid antigen detection against respiratory syncytial virus (RSV) and influenza A and B viruses. To isolate respiratory viruses, samples were inoculated in various cell lines using the shell vial culture assay. To isolate hMPV, the LLC-MK2 cell line was used. Only antigen-negative samples were studied for the presence of hMPV. Over the study period, 32 hMPV were isolated from different patients, accounting for 1.7% of all samples studied for this virus (only RSV-negative samples, 1,791) and 1.5% of all samples studied. Peak incidence was found between December and March of the two years studied. Of the 32 patients in whom hMPV was detected, 17 (53.2%) were female and 15 (46.8%) male. Mean age was 12.5 months (range, 1 month-4 years). The most frequent clinical symptoms were fever (90.6%), cough (87.5%), rhinorrhea and bronchiolitis (46.8%). Three patients (9.4%) were hospitalized. Respiratory infection caused by hMPV is considered an emergent disease in pediatric patients. The clinical manifestations are very similar to those of RSV infection; hence, only virological study can establish the definite etiological diagnosis.

Chronic nasal discharge in cats: 75 cases (1993–2004)

To identify the most common etiologic diagnosis and any historical, physical, or other diagnostic variables associated with a definitive etiologic diagnosis for chronic nasal discharge in cats. Design-Retrospective case series. 75 cats with nasal discharge of >/= 1 month's duration. Medical records of affected cats were reviewed for information on signalment, clinical signs, duration and type of nasal discharge, results of clinical examination, laboratory findings, and advanced imaging findings. A specific etiologic diagnosis for nasal discharge was identified in only 36% of cats. Neoplasia (carcinoma or lymphoma) was the most common etiologic diagnosis. Character and location of nasal discharge did not contribute greatly toward a specific etiologic diagnosis. Sneezing and vomiting were the most common concurrent clinical signs. Routine CBC, serum biochemical panel, and urinalysis did not contribute to a specific etiologic diagnosis. An etiologic diagnosis was more likely in older cats and cats that underwent advanced imaging studies and nasal biopsy. Although advanced diagnostic testing, including imaging studies and biopsy, increases the likelihood of achieving an etiologic diagnosis, the cause of chronic nasal discharge in cats often remains elusive.

Outcomes of clinical examination and genetic testing of 500 individuals with hearing loss evaluated through a genetics of hearing loss clinic

Hearing loss (HL) occurs in approximately 2 out of every 1,000 births and is genetic in origin in approximately 50% of cases. This high incidence coupled with the increasing number of genes implicated in HL and the trend toward universal newborn screening led to the establishment of the Genetics of Hearing Loss Clinic at The Children's Hospital of Philadelphia to manage the diagnosis, genetic screening, and counseling of families with an affected child. To date 500 individuals have been evaluated from 1999 to 2004. To determine the cause of their HL and screen for syndromic forms of HL, individuals were offered a panel of tests. Depending on the type and severity of the HL, recommendations included GJB2 mutation analysis, renal and thyroid function studies, a CT scan of the temporal bones, an ophthalmology evaluation, an EKG, and, at times, additional genetic tests. Of the 500 patients evaluated 70 (14%) had a syndromic etiology for their HL. Twenty-eight different syndromic etiologies were identified. Enlarged vestibular aqueducts (EVAs) and/or Mondini malformations were seen in 18% of individuals with HL who had a CT or MRI of the temporal bones. Genetic testing of the GJB2 gene was completed for 310 of the 377 patients with bilateral sensorineural HL (82.2%). Nineteen different variants were identified in the GJB2 gene. Through GJB2 mutational analysis, clinical examination, and laboratory testing, a definitive etiologic diagnosis was established in 110/500 (22%) of patients.

A role of TNF‐α gene variant on juvenile ischemic stroke: a case–control study

The role of genetic factors in the individual predisposition to develop ischemic stroke has been assessed by previous studies performed both in animal models and in humans. The main goal of the current investigation was to determine the possible contribution of genes encoding procoagulant and inflammatory factors on the occurrence of ischemic stroke in a cohort of young cases and corresponding controls. One hundred and fifteen cases of ischemic stroke were recruited for this study. A detailed clinical assessment, a definite etiologic diagnosis, as well as the presence/absence of known risk factors for ischemic stroke were obtained for each patient. As a control group 180 healthy, unrelated subjects were included. The whole population was screened for polymorphisms belonging to genes encoding FII, FV, alpha-fibrinogen, beta-fibrinogen, GP IIb/IIIa, tumor necrosis factor (TNF)-alpha, interleukin 1-beta. Hypertension was the most important risk factor for ischemic stroke in our cohort [OR = 6.9, confidence interval (CI) 2.9-16.7, P < 0.0001]. Among all genes tested, the TNF-alpha gene variant exerted a significant, independent effect on individual predisposition to ischemic stroke occurrence (OR = 1.8, CI = 1.01-3.3, P < 0.05). Our findings, obtained in a cohort of young Italian patients, may support the existence of a direct contributory role of TNF-alpha, a proinflammatory cytokine protein, in the susceptibility to brain damage.

P0929 NEONATAL DIARRHEA: A MULTICENTER STUDY

Introduction: Many aspects on epidemiology, etiology, treatment and nutrition of newborns with diarrhea are largely undefined. In addition, several chronic diarrheal diseases start in neonatal age and a prompt diagnosis to prevent severe dehydration and poor outcomes is advocated. The aims of the study were to investigate hospital admission rate, etiology, and management strategies in newborns with diarrhea. Methods: Clinical charts of all hospital admissions (from December 1999 to December 2002)of six neonatal care units were reviewed in a multicenter, retrospective study. Results: Diarrhea was the main cause of admission in 34 (24 term, 12 male, median birth weight 2.800 g, 12 breast fed; 10 preterm, 1 male, median birth weight 1.540 g; 2 breast fed) out of 5764 newborns admitted to neonatal units (hospital admission rate: 5.8/1 000/yr, without significant differences during 3 yrs study period). Median duration of hospital stay was 13 days (range 7–22). A definitive etiologic diagnosis was achieved in 24 cases (70.5%): 7 gastrointestinal infections (20.5%) (4 Rotavirus, 1 Salmonella, 1 ETEC, 1 Shigella), 6 cow’s milk allergy (CMA)(17.6%), and 5 antibiotic-associated diarrhea (14.7%), 1 parenteral diarrhea, 1 cystic fibrosis, 1 Hirschsprung’s disease, 1 SCID, 1 urea cycle disorder, 1 glucose-galactose transport defect (2.9%). Diarrhea was acute in 29, protracted in 3, and chronic in 2 patients. Parenteral re-hydration alone or in combination with ORS was adopted in 15 out of 34 newborns(44.1%), remaining cases were re-hydrated by ORS alone (55.9%). Excluding CMA-affected subjects (6/34), breast-feeding was continuated in all cases, and a hydrolysed formula was used in 9 out of the remaining 14 newborns (64%) as re-feeding strategy. Antibiotics were used in all cases of bacterial infections. The clinical outcomes, including diarrhea duration, weight gain and length of hospitalisation were not influenced by different re-hydration and re-feeding approaches. Conclusion: Diarrhea is an infrequent cause of hospital admission in neonatal age. Gastrointestinal infections and CMA are the most common etiologies. Practical guidelines for the optimal management of this condition are needed.

Antigen detection for the diagnosis of pneumonia.

Streptococcus pneumoniae and Haemophilus influenzae type b are the main agents of bacterial community-acquired pneumonia in developing countries, although a definite etiologic diagnosis cannot be established in most cases. This study was carried out to assess the performance of a latex particle agglutination test (LPAT) from a commercial kit (Slidex Méningite Kit trade mark, BioMérieux, France) in diagnosing pneumococcal and H. influenzae type b pneumonia. One hundred and seven children (45 ill subjects and 62 healthy controls) were enrolled. All 45 cases had a presumptive diagnosis of bacterial pneumonia based on clinical (WHO criteria), laboratory (white blood cell count > or = 15.000/mm3, polymorphonuclear leukocytes > or = 70%, bands > or = 500/mm3, and C-reactive protein > or = 40 mg/l), and radiological findings, i.e., two or more positive points in the scoring system described by Khamapirad and Glezen (Semin Respir Infect 1987;2:130-144). Clinical, laboratory, and radiological assessments were performed in a blinded manner. LPAT was performed in urine samples after concentration through an ethanol-acetone solution. Sensitivity, specificity, and positive and negative predictive values were 77.3% (95% CI, 61.8-88.0%), 90.3% (95% CI, 79.5-96.0%), 85.0% (95% CI, 69.5-93.8%), and 84.8% (95% CI, 73.4-92.1%), respectively. Results suggest that LPAT is a useful diagnostic tool for the etiologic diagnosis of S. pneumoniae and H. influenzae type b pneumonia, especially in the developing world.

The Diagnosis of Pneumonia in Renal Transplant Recipients Using Invasive and Noninvasive Procedures

We used invasive and noninvasive procedures to determine the causes of pneumonia in renal transplant recipients. We retrospectively surveyed 565 renal transplant recipients (transplants received March 1984 to August 2001) to find those with pneumonia. Noninvasive diagnostic methods included serologic testing, and blood and sputum cultures with stains. Invasive procedures included fiberoptic bronchoscopy and percutaneous transthoracic procedures. A total of 92 patients were enrolled. Of these, 71 patients had a definite etiologic diagnosis of pneumonia. The major infectious pathogens were bacterial (n = 21) and mixed bacterial infection (n = 10), Mycobacterium tuberculosis (TB) [n = 18], and fungi (n = 8). Noninvasive and invasive procedures led to the diagnosis of pneumonia in 31.5% (n = 29) and 45.6% (n = 42) of patients, respectively. Bronchoscopy was used in 64 patients, with a diagnostic yield of 38 cases (59.3%). Patients were 3.62 times more likely to contract pneumonia within 12 months of renal transplantation than they were > or =12 months thereafter (95% confidence interval, 1.33 to 9.84). Twenty-seven of the 92 patients (29.3%) died. The pneumonia mortality rate has dropped significantly since 1996 (41.8% vs 10.8%, p = 0.002). Both invasive and noninvasive procedures are useful in the diagnosis of pneumonia, with declining mortality, in renal transplant recipients. Bacterial and mixed bacterial infection, TB, and fungal infection are the most common pathogens; cases are most likely to occur within 1 year after renal transplantation.

Etiologic Diagnosis of 204 Pericardial Effusions

The etiologic evaluation of pericardial effusion is frequently unsuccessful when noninvasive methods are used. To determine the cause of the current episode, all patients with echographically identified pericardial effusion from May 1998 to December 2002 underwent noninvasive diagnostic testing of blood, throat, and stool samples. Patients with postpericardiotomy syndrome were excluded. To analyze the value of our tests, we tested randomly selected blood donors as negative controls. Among 204 included patients, 107 (52.4%) had a final etiologic diagnosis: the etiology of 52 was highly suspected at first examination and later confirmed (thyroid deficiency, 5 cases; systemic lupus erythematous, 7; rheumatoid arthritis, 7; scleroderma, 3; cancer, 25; and renal insufficiency, 5). A definite etiologic diagnosis was made in 11 patients from pericardial fluid analysis (cancer, 5 cases; tuberculosis, 3; Streptococcus pneumoniae, Citrobacter freundii, and Actinomyces, 1 case each). Among 141 patients considered to have idiopathic pericarditis, 44 (32.1%) gained an etiologic diagnosis by our systematic testing strategy. This included serologic evaluation of serum (Coxiella burnetii, 10 cases; Bartonella quintana, 1; Legionella pneumophila, 1; Mycoplasma pneumoniae, 4; influenza virus, 1), viral culture of throat swabs (enterovirus, 8 cases; and adenovirus, 1), high-level antinuclear antibodies (>1/400, 3 cases), and thyroid-stimulating hormone (15 abnormal results). Antibodies to Toxoplasma and cytomegalovirus, enterovirus recovered from rectal swabs, and low-level antinuclear antibodies were seen with equal frequency in patients and controls. Using our evaluation strategy, the number of pericardial effusions classified as idiopathic was less than in other series. Systematic testing for Q fever, Mycoplasma pneumoniae, thyroid abnormalities, and antinuclear antibodies, accompanied by viral throat cultures, frequently enabled us to diagnose diseases not initially suspected in patients with pericardial effusion.

Prospective study of etiologic agents of community-acquired pneumonia in patients with HIV infection.

To study prospectively HIV-positive patients admitted to the hospital because of pneumonia by extensive laboratory tests to determine specific microbiologic diagnoses and to establish the best clinical diagnosis after review of all available data by expert clinicians. Patients admitted to one of two hospitals had extensive questionnaires completed and defined diagnostic tests performed on blood, sputum, urine and bronchoalveolar lavage specimens, when available. A total of 230 patients had a diagnosis of pneumonia verified. A definite or probable etiologic diagnosis was made in 155 (67%) of these patients. Pneumocystis carinii caused 35% of all cases of pneumonia. Twenty-seven percent of cases of pneumonia with a single etiology had a definite or probable bacterial etiology. 'Atypical agents' were distinctly uncommon. Few clinical or laboratory parameters could differentiate specific etiologies. P. carinii continues to be a common cause of pneumonia in these patients. The rarity of 'atypical agents' could simplify the empiric approach to therapy. Despite the use of extensive testing we did not find a definite etiology in a large number of cases.

Estudo de casos hospitalizados por pneumonia comunitária no período de um ano

Introdução: Apesar dos avanços obtidos nos métodos propedêuticos, cerca de 50% dos casos de pneumonia adquirida na comunidade não têm sua etiologia esclarecida, inclusive os hospitalizados. Apesar disso, a terapêutica adequada proporciona baixas taxas de mortalidade na maioria dos casos. Objetivos: Descrever a epidemiologia, formas de apresentação, o rendimento dos testes diagnósticos, a permanência hospitalar, a morbidade e mortalidade de 42 pacientes consecutivos, internados para tratamento de PAC. Métodos: Foram incluídos pacientes com quadro clínico compatível com PAC, opacidade radiológica pulmonar recente e com dois itens entre febre, tosse produtiva e leucocitose. A solicitação de exames complementares obedeceu à necessidade de cada caso. Resultados: Dos 42 pacientes, com idade de 64,7 ± 16,8 anos, 27 (64,3%) masculinos, 27 (64%) apresentavam co-morbidades. Dezessete (40,5%) estavam em uso de antibióticos à admissão. Pneumonia grave ocorreu em oito casos (19%); não houve diferença quanto à gravidade (p = 0,57) e permanência hospitalar (p = 0,25) entre os grupos &gt; de 60 ou &lt;= de 60 anos. A permanência hospitalar média foi de 14,3 ± 7,6 dias. Diagnóstico etiológico definitivo foi obtido em três casos: Legionella sp em dois, S. aureus em um caso. Em 31 (74%), manteve-se o antibiótico inicial; em 11 (26%) houve troca, seis (54,5%) devido à má resposta clínica e cinco (45,5%) devido ao resultado microbiológico. Hemoculturas foram feitas em 16 casos (38%), positivas em apenas um (6,3%). Nove amostras de escarro (9/22, 41%) foram validadas. Ocorreu um óbito (2,4%), por pneumonia grave, em um paciente com neoplasia. Conclusões: O diagnóstico etiológico em PAC, mesmo em internados, é obtido em uma minoria de casos, contribuindo para isso o uso concorrente de antibióticos. A terapêutica empírica adequada proporciona baixas taxas de mortalidade. Os testes diagnósticos devem ser empregados de maneira individualizada.

Community-Acquired Pneumonia

We initiated a prospective study with a group of practitioners to assess the etiology, clinical presentation, and outcome of community-acquired pneumonia in patients diagnosed in the outpatient setting. All patients with signs and symptoms suggestive of pneumonia and an infiltrate on chest X-ray underwent an extensive standard workup and were followed over 4 weeks. Over a 4-year period, 184 patients were eligible, of whom 170 (age range, 15-96 yr; median, 43 yr) were included and analyzed. In 78 (46%), no etiologic agent could be demonstrated. In the remaining 92 patients, 107 etiologic agents were implicated: 43 were due to "pyogenic" bacteria (39 Streptococcus pneumoniae, 3 Haemophilus spp., 1 Streptococcus spp.), 39 were due to "atypical" bacteria (24 Mycoplasma pneumoniae, 9 Chlamydia pneumoniae, 4 Coxiella burnetii, 2 Legionella spp.), and 25 were due to viruses (20 influenza viruses and 5 other respiratory viruses). There were only a few statistically significant clinical differences between the different etiologic categories (higher age and comorbidities in viral or in episodes of undetermined etiology, higher neutrophil counts in "pyogenic" episodes, more frequent bilateral and interstitial infiltrates in viral episodes). There were 2 deaths, both in patients with advanced age (83 and 86 years old), and several comorbidities. Only 14 patients (8.2%) required hospitalization. In 6 patients (3.4%), the pneumonia episode uncovered a local neoplasia. This study shows that most cases of community-acquired pneumonia have a favorable outcome and can be successfully managed in an outpatient setting. Moreover, in the absence of rapid and reliable clinical or laboratory tests to establish a definite etiologic diagnosis at presentation, the spectrum of the etiologic agents suggest that initial antibiotic therapy should cover both S. pneumoniae and atypical bacteria, as well as possible influenza viruses during the epidemic season.