Endoscopic ultrasound-guided fine-needle aspiration for the diagnosis of extra-pulmonary tuberculosis.

SETTING: The incidence of extra-pulmonary tuberculosis (EPTB) is surprisingly high among certain subgroups of patients in industrialized countries. Diagnosis is often difficult and can require costly invasive workup. Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is a safe, minimally invasive, accurate, out-patient diagnostic modality for assessing mediastinal and abdominal lymphadenopathy and masses. OBJECTIVE: To evaluate the usefulness of EUS-FNA for diagnosing EPTB. DESIGN: Retrospective 6-year review, including all patients who had evidence of lymphadenopathy or mass on computed tomography scan accessible by EUS and consideration of tuberculosis (TB) in the differential diagnosis. RESULTS: Of 81 potential patients, a total of 20 cases with EPTB diagnosed by EUS-FNA were identified. Necrotizing granulomas had a 58% likelihood of TB vs. 14% for other cytologic findings (P < 0.0001); necrosis was also predictive, with a 44% likelihood of TB vs. 19% (P < 0.0225). EUS-FNA cytology was diagnostic for TB when an African-born patient had necrotizing granulomas (P < 0.0001), and was highly suggestive with necrosis alone (P < 0.0514). Non-necrotizing granulomas were not predictive of TB and an alternative diagnosis was more likely, including sarcoidosis and cancer. CONCLUSION: EUS-FNA is a useful diagnostic modality that should be used early in the diagnostic workup of suspected EPTB.

Surface modification and electrostatic charge of polystyrene particles.

Particle surface modification by poloxamer adsorption can significantly alter the electrostatic charge, adhesion behaviour and consequently handling properties of a material. The charge reduction on polystyrene spheres achieved by this modification technique is dependent on the concentration, molecular weight and conformation of poloxamer at the particle surface. Adsorption isotherms of poloxamers on polystyrene particles follow a Langmuir profile and there is an apparent correlation between the extent of adsorption and ability of poloxamer to reduce electrostatic charge. Surface analysis techniques, X-ray photoelectron spectroscopy and Time of Flight Secondary Ion Mass Spectrometry have generated data on the thickness of the adsorbed poloxamer layer and provided evidence to suggest that the polypropylene oxide component of the poloxamer adsorbs to the polystyrene surface and there is a polyethylene oxide rich outer surface which may influence the charge alteration.

Epidemiological and clinical features of pulmonary blastomycosis.

The epidemiological and clinical aspects of Blastomycosis are reviewed. The central United States is the most heavily endemic area in the world, although the extent of the endemic zone has been mapped only by individual case finding, rather than by large skin test surveys (as was done for histoplasmosis). The difficulties in developing a sensitive and specific skin test antigen are reviewed, and the sequence of antigens from Blastomycin to antigen A to the ASWS (alkali and water soluble) antigen to the WI (Wisconsin) antigen are discussed. The absence of good immunological markers of remote subclinical disease means that the size of the iceberg of subclinical cases relative to clinically apparent and diagnosed pulmonary and extrapulmonary cases remains uncertain. Clinical presentations of blastomycosis range from (1) asymptomatic, currently discovered only in outbreak situation, (2) flulike illness of brief duration resembling other upper respiratory infections, (3) illness resembling bacterial pneumonia with acute onset, high fever, lobar infiltrates, and productive cough, (4) subacute or chronic respiratory illness with symptom complex resembling tuberculosis or lung cancer and radiographic presentation of fibronodular infiltrates or mass-like lesions, and (5) fulminant infectious adult respiratory distress syndrome (ARDS) with high fever, diffuse infiltrates, and progressive respiratory failure. Radiographic presentations are highly variable and even more confusing because of lack of standard terminology to describe these abnormalities. Examples of some of the radiographic presentations of blastomycosis are shown. Available information concerning computed tomographic studies is also reviewed. Special mention is made of blastomycosis in AIDS, which is uncommon but tends to be fulminant, systemic, and rapidly progressive. An overview of current diagnostic strategies and treatment options is also presented.

Fungal pulmonary complications.

With AIDS has come a new level of T-cell immunosuppression, beyond that previously seen. The impact of the HIV pandemic on the field of fungal infections includes a major increase in the number of serious fungal infections, an increase in the severity of those infections, and even some entirely new manifestations of fungal illness. In this article fungal pulmonary complications of AIDS are discussed. T-cell opportunists including Cryptococcus neoformans and the endemic mycoses are the most important pathogens. Phagocyte opportunists, including Aspergillus species and agents of mucormycosis, are less important.

Muscle weakness in mechanically ventilated patients with severe asthma.

Patients who undergo mechanical ventilation for severe asthma are at risk of developing diffuse muscle weakness because of acute myopathy. The relative importance of corticosteroids and neuromuscular paralysis in causing the myopathy is controversial, and it is uncertain whether the chemical structure of the drug used to induce paralysis influences the risk of myopathy. Using a retrospective cohort study design, we evaluated 107 consecutive episodes of mechanical ventilation for severe asthma to assess (1) the incidence of clinically significant weakness in patients treated with corticosteroids alone versus corticosteroids with neuromuscular paralysis, (2) the influence of the duration of paralysis on the incidence of muscle weakness, and (3) the relative risk of weakness in patients paralyzed with the nonsteroidal drug atracurium versus an aminosteroid paralytic agent (pancuronium, vecuronium). The use of corticosteroids and a neuromuscular blocking agent was associated with a much higher incidence of muscle weakness as compared with the use of corticosteroids alone (20 of 69 versus O of 38, p < 0.001). The 20 weak patients were paralyzed significantly longer than the 49 patients who received a neuromuscular blocking agent without subsequent weakness (3.4 +/- 2.4 versus 0.6 +/- 0.7 d, p < 0.001). Eighteen of the 20 weak patients had been paralyzed for more than 24 h. The incidence of weakness was not reduced when paralysis was achieved with atracurium as opposed to an aminosteroid neuromuscular blocking agent. In conclusion, corticosteroid-treated patients with severe asthma who undergo prolonged neuromuscular paralysis are at significant risk for the development of muscle weakness, and the risk of weakness is not reduced by use of atracurium.

Transmission of invasive aspergillosis from a subclinically infected donor to three different organ transplant recipients.

OBJECTIVE: To describe a cluster of donor-transmitted cases of invasive aspergillosis. DESIGN: Case series of epidemiologically linked cases of invasive aspergillosis. SETTING: Two tertiary care centers with solid-organ transplant programs. PATIENTS: Two kidney recipients, one heart recipient, and the single donor. MEASUREMENTS: Routine clinical, microbiological, and pathologic investigation as dictated for patient care. Epidemiologic analysis to establish linkage among cases. RESULTS: Three allografts (two kidneys and a heart) from a single donor transmitted invasive aspergillosis to the recipients. Three weeks after transplantation, the two kidney recipients had fever and urine cultures positive for Aspergillus fumigatus. The infected kidneys had multiple Aspergillus abscesses and had to be removed to cure the patients. The heart recipient had a negative workup when a diagnosis of aspergillosis was made for the kidney recipients but presented three months later with aspergillus endocarditis with hematogenous spread to the eyes and to the skin. Treatment included eye surgery, aortic valve replacement, and antifungal therapy; control of infection ensued. The donor was intensely immunosuppressed (17 days post-liver transplantation with death from intracerebral bleeding) but had no clinical or autopsy evidence of aspergillosis. Donor tracheal secretions obtained at the time of organ harvest later grew A fumigatus. CONCLUSION: Expanded criteria for organ donation have to be balanced against infectious risk to organ recipients. A fumigatus can be transmitted from a subclinically infected donor to solid-organ transplant recipients.

Endemic mycosis complicating human immunodeficiency virus infection.

Persons infected with the human immunodeficiency virus are prone to the development of many fungal diseases. Normal hosts with intact immunity usually recover from infection by these less-invasive fungi. In persons with compromised T-cell-mediated immunity, however, widespread dissemination from a pulmonary focus occurs. In this review, we discuss the epidemiology, clinical manifestations, diagnosis, and treatment of the three major North American mycoses, histoplasmosis, blastomycosis, and coccidioidomycosis. In most cases, amphotericin B is the initial drug of choice, followed by one of the azoles for lifelong maintenance therapy.

Outbreak of tuberculosis among regular patrons of a neighborhood bar.

BACKGROUND: Outbreaks of tuberculosis have been reported in prisons, nursing homes, urban homeless shelters, and other crowded settings. We report a nonresidential outbreak of tuberculosis that originated in a neighborhood bar. METHODS: A homeless patient with highly infectious pulmonary tuberculosis was a regular patron of a neighborhood bar during a long symptomatic interval before diagnosis. We investigated 97 other regular customers and employees of the bar through interviews, tuberculin skin testing, and chest roentgenography. We performed DNA fingerprinting on isolates from the index patient and 11 other patients. RESULTS: The index patient apparently infected 41 of 97 contacts (42 percent), resulting in 14 cases of active tuberculosis and 27 cases of infection but no disease (indicated by positive tuberculin skin tests). Four other cases of active tuberculosis occurred among regular customers of the bar who were missed by the contact investigation. There were also two secondary cases. Radiographic findings in active cases included upper-lobe disease in seven cases (three cavitary) and negative chest films at the time of diagnosis in four cases. All 12 culture isolates we tested had the same chromosomal-DNA restriction pattern. CONCLUSIONS: The spread of tuberculosis in a neighborhood bar can be a major public health problem. The high rate of infection and disease among the contacts was unexpected and was not due to coinfection with the human immunodeficiency virus. Possible explanations include heavy alcohol use among the contacts, high infectivity of the index case, or both. Sputum cultures must be performed in tuberculin-positive contacts who have symptoms, even if the chest films are normal.

Unilateral phrenic nerve paralysis from cutting down a Christmas tree.

Stretch injury to the phrenic nerve is an unusual cause of unilateral diaphragmatic paralysis. In this case the injury occurred while the patient was lying on the ground and cutting down a Christmas tree with a hand saw.

Therapy for fungal infections.

In the past, few pharmacologic agents were available for management of fungal disease. After the early introduction of amphotericin B and miconazole, the more recent advent of several new antifungal agents, including ketoconazole, fluconazole, and itraconazole has expanded the options for treatment of fungal infections. The dramatic increase in number of immunocompromised patients--both those with acquired immunodeficiency syndrome (AIDS) and those with immunosuppression for other reasons, such as organ transplantation--emphasizes the importance of therapeutic strategies for combating systemic mycoses. In this article, we review our personal recommendations for treating histoplasmosis, blastomycosis, coccidioidomycosis, and cryptococcosis, along with other less common fungal infections, and discuss the efficacy and toxic effects of the various antifungal drugs.

Fungal pneumonia.

Fungal pneumonias are rare but important. Sometimes the clinical presentation is identical to more common bacterial or atypical pneumonias. In such cases, the diagnosis is either not made or is made accidentally from diagnostic specimens obtained to determine the likely bacterial pathogen. Other cases look like routine bacterial or atypical pneumonia at presentation but do not improve or even progress as they are being treated with appropriate antibacterial agents. In such cases, it is important not to give a series of treatment courses with different antibacterial antibiotics that all cover essentially the same range of pathogens. Rather the diagnostic efforts must be escalated, progressing to more aggressive measures (fiberoptic bronchoscopy, fine needle aspiration, and rarely thoracoscopic or traditional open lung biopsy) until a specific diagnosis is reached. In some cases, there are clinical clues that point to a fungal cause. Attention to these clues can lead to early initiation of appropriate diagnostic sequences, faster diagnosis, and earlier initiation of specific therapy. A review of some of these clinical clues is provided in Table 1.

Profound sleep hypoxia in morbidly obese hypercapnic patients with obstructive sleep apnea.

Profound periodic sleep hypoxemia (as low as 9-10% saturation) was observed in 41 morbidly obese patients with obstructive sleep apnea (OSA). Group 1 consisted of 14 patients with awake hypercapnia (mean PaCO2 54 +/- 8 torr, s.d.) and group 2 were 27 with eucapnia (PaCO2 38.6 +/- 2.9). Group 1 OSA patients were more obese (BMI 48.7 +/- 8.5 vs 38.3 +/- 6.8 kg/m2, had lower FEV1 (61 +/- 17% vs 86 +/- 15% pred.) and lower FVC (62 +/- 16% vs 77 +/- 13% pred.), all the differences insufficient per se to account for hypercapnia. Group I remained apneic longer in REM (100 +/- 50 s vs 65 +/- 32 s), and tolerated lower mean SpO2 (pulse oximeter SaO2) in NREM (71 +/- 16% vs 81 +/- 7%) and lower minimum SpO2 values in NREM (54 +/- 12% vs 69 +/- 11%) (all the differences were significant, p < 0.05). We conclude that daytime hypercapnia predicts more severe sleep desaturation in NREM in obese patients with OSA. The combination of morbid obesity and hypercapnia with OSA is associated with the most profound and repeated hypoxemia ever reported as occurring without evident brain damage or death.

Aerosol pentamidine prophylaxis following Pneumocystis carinii pneumonia in AIDS patients: results of a blinded dose-comparison study using an ultrasonic nebulizer.

PURPOSE: To compare the efficacy and safety of three different doses of prophylactic aerosol pentamidine in patients with one prior episode of Pneumocystis carinii pneumonia (PCP) and the acquired immunodeficiency syndrome. PATIENTS AND METHODS: The design of the study was a double-blind, randomized, dose-comparison clinical trial conducted at 13 medical centers within the United States. In stage I of the trial, patients were randomized to receive either 5 mg, 60 mg, or 120 mg of aerosol pentamidine delivered biweekly with the Fisoneb (Fisons, Inc., Rochester, New York) ultrasonic nebulizer. After 24 weeks of therapy, patients entered stage II of the trial, where the 5-mg group was re-randomized to either the 60-mg or 120-mg group. RESULTS: One hundred seventy-five patients entered stage I of the trial and received prophylaxis for a mean of 123.6 days. Seven assigned to the 5-mg biweekly dosing schedule had a confirmed recurrence of PCP, compared with none in the 60-mg group (p = 0.007) and three in the 120-mg group (p = 0.304). During stage II of the trial, eight patients in the 60-mg group and one additional patient in the 120-mg group had recurrent PCP. After 52 weeks of observation, the likelihood of being PCP-free was 88.0% in the 60-mg group and 93% in the 120-mg group (p = 0.712). Minor adverse events related to aerosol pentamidine administration included cough, taste perversion, chest pain, bronchospasm, and dyspnea. These side effects were more common in the 60-mg and 120-mg treatment groups and resulted in withdrawal from the study by one patient. Serious events were more common after 24 weeks of therapy and included asymptomatic hypoglycemia (five), pancreatitis (two), pneumothorax (one), and extrapulmonary pneumocystosis (one). CONCLUSIONS: These results demonstrate that biweekly administration of 60 mg or 120 mg of aerosol pentamidine significantly decreases PCP recurrence when compared with a 5-mg regimen or findings in historic controls and is generally well tolerated. There is no significant difference in effect or safety between these two dosing regimens in patients followed for at least 52 weeks of therapy.

Evidence of subclinical blastomycosis in forestry workers in northern Minnesota and northern Wisconsin.

PURPOSE: To investigate the incidence of remote subclinical blastomycosis in a high-risk population of forestry workers. PATIENTS AND METHODS: The study consisted of 39 male forestry workers from northern Minnesota and northern Wisconsin, areas endemic for blastomycosis but not for histoplasmosis. All subjects were histoplasmin skin test-negative, and none had ever been diagnosed with blastomycosis or pneumonia. An antigen-specific lymphocyte stimulation assay was performed to determine the presence of blastomycosis. RESULTS: Peripheral blood lymphocytes from 12 of 39 subjects demonstrated specific antigen-induced proliferation when stimulated with a purified alkali- and water-soluble antigen derived from the cell wall of Blastomyces dermatitidis. CONCLUSION: The finding that 30% of these men had evidence of previous blastomycosis suggests that subclinical cases do occur sporadically, and are probably more common than diagnosed symptomatic cases. This is similar to histoplasmosis, in which the majority of infections are subclinical. However, the reservoir of persons with previous undiagnosed blastomycosis is probably small compared to the huge number of persons (perhaps 30 million) with prior histoplasmosis.

Influence of acid-base status on plasma catecholamines during exercise in normal humans.

The influence of acid-base status on plasma catecholamines during exercise was investigated in six healthy volunteers. Incremental exercise to 175 W was performed on a bicycle ergometer under four conditions: 1) control, 2) during forced hyperventilation (HV), 3) after pretreatment with acetazolamide (AZE), and 4) while breathing 4% CO2. Resting plasma norepinephrine (PNE) and epinephrine (PE) were not different among the four protocols despite higher resting pH during HV and lower resting pH after AZE [control, 7.4 +/- 0.02; HV, 7.48 +/- 0.03 (P less than 0.005); AZE, 7.36 +/- 0.01 (P less than 0.005) (P values indicate significant differences from the control protocol)]. Resting pH was not different from control during the 4% CO2 study (7.4 +/- 0.01). At the 175-W exercise load, there were significant differences in both pH and PNE. During the control test, pH was 7.38 +/- 0.02, PNE was 951 +/- 164 pg/ml, and PE was 264 +/- 132 pg/ml. During HV, pH was 7.46 +/- 0.5 (P less than 0.001), PNE was 976 +/- 67 pg/ml, and PE was 210 +/- 27 pg/ml. After AZE, pH was 7.31 +/- 0.2 (P less than 0.001), PNE was 1,866 +/- 561 pg/ml (P less than 0.005), and PE was 382 +/- 264 pg/ml. While subjects breathed 4% CO2, pH was 7.29 +/- 0.02 (P less than 0.001), PNE was 1.842 +/- 617 pg/ml (P less than 0.01), and PE was 467 +/- 275 pg/ml.(ABSTRACT TRUNCATED AT 250 WORDS)

Histoplasmosis: update 1989.

Histoplasmosis is a relatively mature disease that was first described 85 years ago. Histoplasmosis was long thought to be a rare and uniformly fatal illness. However, widespread use of skin testing in the 1940s proved that it was a common infection, especially in the central United States, and almost invariably benign. Primary histoplasmosis often presents as a self-limited, nonspecific respiratory infection, and thus, it was realized that a huge iceberg of subclinical and mildly symptomatic cases had been missed for years, since only the highly symptomatic and progressive infections had been diagnosed. Once the disease was recognized as a common one, many new clinical forms of the illness were recognized, including diffuse infiltrates due to heavy exposure, chronic cavitary disease resembling tuberculosis, and complications of primary infection, including mediastinal granuloma and the superior vena caval syndrome. Despite the mature state of histoplasmosis, it is still a disease capable of producing surprises. In this article, the history of histoplasmosis is reviewed, as well as current major concepts about the epidemiology, pathogenesis, clinical features, diagnosis, and treatment of this infection. Newer developments are then highlighted using the same outline.

Nocturnal rocking bed therapy: improvement in sleep fragmentation in patients with respiratory muscle weakness.

Three patients with respiratory muscle weakness developed sleep fragmentation due to nonobstructive apnea and hypopnea. In two patients in whom inspiratory muscle electromyogram was recorded, the apneas and hypopneas were terminated only by arousal and excessive recruitment of accessory muscles. Nocturnal rocking bed ventilatory support resulted in immediate improvement in sleep fragmentation and inhibited arousal-associated phasic accessory muscle activation, resulting in improvement in daytime hypercapnia and subjective sleepiness. Sleep fragmentation may occur more commonly than generally appreciated in neuromuscular disease patients who are independent of daytime ventilatory support. The use of nocturnal rocking bed is an effective noninvasive method of reversing sleep fragmentation and daytime sequelae when obstructive apnea is absent.