Enhanced susceptibility of blood monocytes from patients with pulmonary tuberculosis to productive infection with human immunodeficiency virus type 1.

Blood monocytes from patients with active pulmonary tuberculosis and age-matched healthy purified protein derivative-reactive donors were infected with human immunodeficiency virus type 1 (HIV-1)JR-FL in vitro to assess their susceptibility to productive infection by HIV-1. HIV-1 p24 levels (enzyme-linked immunosorbent assay) in supernatants of infected cells from patients with tuberculosis, albeit variable, were significantly higher at days 10-20 of culture; the maximum levels of p24 antigen were greater in supernatants of HIV-1-infected monocytes from patients than maximum levels for controls (p < 0.05). The maximum increment in p24 levels for patients also exceeded that for controls (p < 0.05). Entry of HIV-1 and/or initiation of reverse transcription, measured by polymerase chain reaction using HIV-1 R/U5 primer pairs, was variable and low in infected monocytes from both patients and controls, and did not correlate with HIV-1 p24 levels. The frequency of infected cells as assessed by endpoint dilution viral cultures was similar for both groups. Therefore, blood monocytes from patients with active tuberculosis can develop a highly productive infection with HIV-1 that does not appear to be due to enhanced HIV entry or higher frequency of infected cells. The enhanced susceptibility may result directly from activation of monocytes by exposure to Mycobacterium tuberculosis and its products in situ.

'Punch' actinomycosis causing osteomyelitis of the hand.

Osseous actinomycosis usually results from direct invasion of bone from adjacent soft-tissue infection. Involvement of the jaw and vertebral column has been frequently reported, but involvement of the bones of the wrist or hand is rare. A patient with osteomyelitis of the distal right first metacarpal bone due to Actinomyces israelii following a punch injury during fisticuffs is described. Review of similar cases revealed a striking association of this type of infection with punch injuries; hence the term, punch actinomycosis. Analysis of the pus in these infections typically reveals sulfur granules; strict anaerobic conditions must be employed to culture the etiologic agent, A israelii. Management of individual cases should include surgical débridement combined with high-dose parenteral penicillin, followed by long-term penicillin therapy, orally.

Invasive cavitary pulmonary aspergillosis in patients with cancer: a clinicopathologic study.

We studied the histopathology and clinicopathologic correlates of invasive cavitary pulmonary aspergillosis in 11 immunosuppressed patients with disseminated malignancy. In most patients cavities were produced by separation of necrotic from viable lung, resulting in an intracavitary sequestrum ("lung ball"). Central dissolution of large necrotic areas and suppurative granulomatous aspergillary pneumonia were additional causes of cavities in three patients. In four patients with chronic cavities sequestra had been replaced by intracavitary mycetomas ("fungus balls"). Neutrophils usually were numerous at the interface of the sequestrum and adjacent lung, but were minimally present in three patients with prolonged severe neutropenia. The lack of neutrophils in some patients suggests that factors other than neutrophil-derived proteases may be important in cavity formation. A prominent giant cell reaction was seen in three patients with chronic cavities. Hemoptysis occurred in five patients and massive hemoptysis due to a bronchoarterial fistula caused the death of one patient. The "air-crescent" sign was not observed radiographically in any patient and is therefore considered to be an insensitive marker for lung cavitation in invasive aspergillosis. Persistent intracavitary fungal growth may serve as a reservoir for recurrent fungal invasion in patients with prolonged or repeated episodes of severe neutropenia.

Anterior segment upper lobe tuberculosis in the adult. Occurrence in primary and reactivation disease.

Nine patients with pulmonary tuberculosis involving predominantly or exclusively the anterior segment of one or both upper lobes were seen over a five-year period. The incidence of anterior segment upper lobe tuberculosis was 6.3 percent of 142 patients presenting with pulmonary tuberculosis during the same time period. Five of the nine patients with anterior segment upper lobe involvement had reactivation disease. An increased incidence of advanced age, diabetes, associated malignant neoplasms, alcoholism, and steroid use were noted in those patients with anterior segment involvement, although only the occurrence of diabetes was statistically significant. We suggest vigilance with regard to the diagnosis of tuberculosis in patients who are elderly, diabetic, or alcohol abusers, particularly where the roentgenographic appearance of anterior segment upper lobe involvement would tend to favor an alternative diagnosis.

Primary intravascular lymphomatosis associated with Mycobacterium marinum.

Intravascular lymphomatosis (i.v.l.) is a rare condition in which neoplastic cells preferentially infiltrate blood vessels of the central nervous system. Nonspecific symptoms associated with i.v.l. include dementia, seizures, and multifocal cerebrovascular events. i.v.l. was discovered at autopsy of a patient whose neurological deficits were predated by a particularly aggressive form of Mycobacterium marinum soft-tissue infection. It is speculated that i.v.l. may have had an occult effect on the patient's cell-mediated immunity that predisposed him to this normally innocuous mycobacteria.

Hindsight bias: an impediment to accurate probability estimation in clinicopathologic conferences.

Although clinicopathologic conferences (CPCs) have been valued for teaching differential diagnosis, their instructional value may be compromised by hindsight bias. This bias occurs when those who know the actual diagnosis overestimate the likelihood that they would have been able to predict the correct diagnosis had they been asked to do so beforehand. Evidence for the presence of the hindsight bias was sought among 160 physicians and trainees attending four CPCs. Before the correct diagnosis was announced, half of the conference audience estimated the probability that each of five possible diagnoses was correct (foresight subjects). After the correct diagnosis was announced the remaining (hindsight) subjects estimated the probability they would have assigned to each of the five possible diagnoses had they been making the initial differential diagnosis. Only 30% of the foresight subjects ranked the correct diagnosis as first, versus 50% of the hindsight subjects (p less than 0.02). Although less experienced physicians consistently demonstrated the hindsight bias, more experienced physicians succumbed only on easier cases.

Effectiveness of high-frequency jet ventilation in management of an experimental bronchopleural fistula.

An animal model was prepared to compare the effectiveness of high-frequency jet ventilation (HFJV) with that of conventional intermittent positive pressure ventilation (IPPV) in managing bronchopleural fistula. In ten adult beagles, the left upper pulmonary lobe was resected and the left upper lobe bronchus was cannulated to establish a permanent bronchopleural fistula. Apposition of the middle lobe to the chest wall was examined via an open thoracotomy. Fistula leakage was measured with the thoracotomy closed, and chest tube drainage was set at 20 cm H2O. With HFJV, lung apposition was attained at lower peak (8.9 cm H2O) and expiratory (5.7 cm H2O) pressures than with IPPV (21.2 cm H2O Peak pressure and 10.7 cm H2O expiratory pressure). With equivalent arterial blood gases, fistula leakage was 47 per cent higher with IPPV than with HFJV (P less than .001). Each 5 cm of positive end expiratory pressure (PEEP) added increased fistula leakage similarly to both systems. Varying the frequency of HFJV did not alter leakage significantly, but increasing the driving pressure markedly increased leakage. Thus, experimentally, HFJV proved superior to IPPV in the management of bronchopleural fistula. When HFJV is used clinically to manage a bronchopleural fistula, the driving pressure should be kept as low as possible and PEEP should be limited. The ventilatory rate may be varied to achieve the desired PaCO2 without significantly affecting leakage through the fistula.

Postpericardiotomy syndrome: its diagnosis and treatment after muscle flap closure of an infected sternal wound.

After nearly any form of cardiac surgery, an acute febrile illness characterized by leukocytosis, pericarditis with pericardial effusion, and pleural effusion may occur. In some instances, this postpericardiotomy syndrome may suggest the presence of mediastinal infection. Treatment of postpericardiotomy syndrome is conservative, and symptoms typically resolve with nonsteroidal antiinflammatory medication. We report a case of postpericardiotomy syndrome that mimicked recurrent mediastinal infection and developed after muscle flap closure of an infected sternal wound. Pericardial, pleural, and periflap fluid accumulated postmuscle flap closure and was sterile on culture. A diagnosis of postpericardiotomy syndrome was made, and the patient improved while receiving oral indomethacin. She has remained free of infection as of the 2-year follow-up.

Vancomycin-dependent enterococcal strains: case report and review.

We report, to our knowledge, the first isolation of VDE from a burn unit. Our experience was similar to earlier reports, in that continuous administration of vancomycin and previous VRE isolation preceded the recovery of VDE. Given the increasing prevalence of VRE as a nosocomial pathogen, intensive care units must now be attuned to the emergence of VDE as serious pathogen.

Emergence of a new opportunistic pathogen, Candida lusitaniae.

Candida lusitaniae has been an infrequently reported opportunistic pathogen. Most previously reported cases of serious infection caused by this organism have proven fatal and were associated with amphotericin resistance of the organism. We report two patients with hematologic malignancies undergoing cytotoxic chemotherapy who developed fungemia with this organism while they were granulocytopenic. The organisms isolated from each patient were fully susceptible and were treated successfully with amphotericin B. When isolated from an immunocompromised host, C. lusitaniae should be considered an opportunistic pathogen and undergo antifungal susceptibility testing. Amphotericin B should be considered the drug of choice, but a poor clinical response may be indicative of a resistant isolate.

In vitro restoration of T cell responses in tuberculosis and augmentation of monocyte effector function against Mycobacterium tuberculosis by natural inhibitors of transforming growth factor beta.

We examined the capacity of the naturally occurring inhibitors of transforming growth factor beta (TGF-beta), decorin and latency associated peptide (LAP), to reverse depressed T cell functions in peripheral blood mononuclear cells (PBMCs) from patients with pulmonary tuberculosis (TB) in vitro and to counteract the suppressive properties of TGF-beta on mycobacterial replication in blood monocytes (MN) in vitro. T cell blastogenesis in response to purified protein derivative (PPD) in PBMCs of TB patients that were cocultured with decorin or LAP reached levels comparable to those observed in healthy tuberculin-responsive control subjects. Decorin and LAP were as effective as neutralizing antibody to TGF-beta in correcting depressed T cell proliferation. Coculture of PBMCs from healthy PPD reactive individuals with neutralizing antibody to TGF-beta, decorin, or LAP did not affect T cell blastogenesis. Levels of interferon-gamma in cultures of PPD-stimulated PBMCs from patients with TB increased by more than 2-fold in the presence of maximal concentrations of either of the inhibitors of TGF-beta, whereas TGF-beta immunoreactivity declined to background levels. Coculture with optimal concentrations of decorin or LAP also led to reductions in mycobacterial growth in MN infected with Mycobacterium tuberculosis (MTB) in vitro by 51% and 62%, respectively, when compared with cells left untreated. In parallel, levels of immunoreactive TGF-beta in MTB-infected MN cultures containing decorin or LAP decreased to background levels. These data indicate that the naturally occurring inhibitors of TGF-beta, decorin and LAP, efficiently abrogate the suppressive effects of TGF-beta in PBMCs of TB patients and in MN infected with MTB in vitro. Therefore, these agents may be considered as adjuncts to antituberculous chemotherapy, and may be particularly useful in treatment of TB that is unresponsive to conventional chemotherapy.

Cutaneous manifestations of toxoplasmosis.

Toxoplasmosis is a common, largely asymptomatic infection. Early reports of acquired disease noted frequent dermatologic manifestations, whereas recent reviews of toxoplasmosis stress the lymphadenopathic presentation of the disease. We report the case of a patient with acute toxoplasmosis associated with a prominent macular and papular rash involving the palms and soles. We have reviewed the literature on dermatologic manifestations of acute acquired toxoplasmosis to underscore the importance of considering toxoplasmosis in the differential diagnosis of febrile illnesses with varied dermatologic presentations.

Probable neutropenic enterocolitis in patients with AIDS.

Neutropenic enterocolitis is well documented in patients with leukemia or lymphoma who are recovering from the adverse effects of chemotherapy. We report two cases of probable neutropenic enterocolitis in two patients with AIDS who developed the syndrome during an episode of moderate neutropenia. To the best of our knowledge, this syndrome has not been reported previously in a patient with AIDS. Both of our patients manifested a mild form of enterocolitis that was characterized by fever, abdominal pain, and evidence of colonic edema easily recognized by computed tomography of the abdomen. Both patients were managed successfully with use of conservative measures including discontinuation of use of marrow-suppressive drugs and therapy with broad-spectrum antimicrobial agents. Neutropenic enterocolitis should be considered as a treatable cause of fever and abdominal pain in patients with AIDS.

Successful treatment of disseminated Mycobacterium chelonae infection with linezolid.

We describe a 57-year-old man with steroid-dependent myasthenia gravis and progressive ulcerating leg nodules due to clarithromycin-resistant Mycobacterium chelonae. The patient was successfully treated with linezolid.

Pulmonary disease due to infection by Mycobacterium avium complex in patients with AIDS.

We reviewed the clinical, radiographic, and histologic features of nine patients with AIDS and pulmonary disease due to Mycobacterium avium complex (MAC). Pulmonary MAC disease was defined by (1) the isolation of MAC from two or more lower respiratory tract specimens or from a single lung biopsy sample, (2) an infiltrate revealed by chest radiography, and (3) the absence of other identified pulmonary pathogens or malignancies. Pulmonary MAC disease was present in five (2.5%) of 200 patients with disseminated MAC infection and in four additional patients without evidence of dissemination, as assessed by blood culture. The median CD4 cell count at the time of presentation was 90/microL. Pulmonary MAC disease was the initial AIDS-defining infection in five patients and presented within a median of 5 months after the initial infection in four patients. Radiographic patterns for these nine patients included consolidating or nodular infiltrates and cavitation. The histopathology of pulmonary MAC disease was characterized by granulomatous inflammation, often associated with necrosis and few evident organisms. The conditions of all patients treated with multidrug regimens clinically improved.

Spread of strain W, a highly drug-resistant strain of Mycobacterium tuberculosis, across the United States.

Strain W, a highly drug-resistant strain of Mycobacterium tuberculosis, was responsible for large nosocomial outbreaks in New York in the early 1990s. To describe the spread of strain W outside New York, we reviewed data from epidemiologic investigations, national tuberculosis surveillance, regional DNA fingerprint laboratories, and the Centers for Disease Control and Prevention Mycobacteriology Laboratory to identify potential cases of tuberculosis due to strain W. From January 1992 through February 1997, 23 cases were diagnosed in nine states and Puerto Rico; 8 were exposed to strain W in New York before their diagnosis; 4 of the 23 transmitted disease to 10 others. Eighty-six contacts of the 23 cases are presumed to be infected with strain W; 11 completed alternative preventive therapy. Strain W tuberculosis cases will occur throughout the United States as persons infected in New York move elsewhere. To help track and contain this strain, health departments should notify the Centers for Disease Control and Prevention of cases of tuberculosis resistant to isoniazid, rifampin, streptomycin, and kanamycin.