Adrenal hypofunction from histoplasmosis: a literature review from 1971 to 2012.

PURPOSE: While histoplasmosis has been reported from most continents, the disease is most often recognized in the midwestern United States. The recent diagnosis of adrenal hypofunction in two patients with progressive disseminated histoplasmosis (PDH) in our hospital led us to review the literature. METHODS: We reviewed PubMed using the search term "adrenal histoplasmosis" for the years 1971 to 2012. RESULTS: The results included 242 patients with adrenal histoplasmosis from either case reports or case series. Most of the reported patients were from countries not previously considered to be heavily endemic for histoplasmosis. In addition, 41.3 % of patients with adrenal involvement developed adrenal hypofunction. CONCLUSION: As modern technology elucidates more cases of adrenal histoplasmosis, the global boundaries of endemicity are being redefined.

Fungal meningitis manifesting as hydrocephalus.

Four patients with fungal meningitis and hydrocephalus were treated by placement of intraventricular shunts prior to the diagnosis of infection. As a consequence, they were subjected to the risks of surgery as well as to shunt suprainfection. We suggest that chronic meningitis be ruled out in all patients prior to placement of shunts. Preoperative evaluation should include the examination of cisternal or ventricular CSF when a lumbar CSF specimen is nondiagnositc. When fungal meningitis is present, a course of amphotericin B should be initiated and the CSF sterilized prior to the placement of the permanent extracranial shunt. Where acute hydrocephalus supervenes, temporary ventricular drainage may be employed. In some cases of fungal meningitis, the symptoms of hydrocephalus will be resolved with antifungal therapy alone, obviating the need for ventricular decompression.

Outbreak of parasitic gastroenteritis among travelers returning from Africa.

Eosinophilia and intestinal infections with a trematode parasite developed in 18 of the 20 American tourists who traveled to Kenya and Tanzania; the fact that the two other tourists also had eosinophilia suggested that they too had been infested. Because no adult flukes were recovered, a specific identification could not be made, but the eggs we observed resembled those of an Echinostoma. Several tour members had mild, nonspecific abdominal complaints, but ten had moderately severe abdominal cramps and loose or watery stools. Treatment with praziquantel was associated with rapid symptomatic improvement, and after treatment no parasitic eggs were recovered from patients' stools.

Erythema nodosum and blastomycosis.

Two patients with blastomycosis and erythema nodosum are described. In one patient, the underlying blastomycosis resolved after wedge resection of the pulmonary infiltrate, but without chemotherapy. In the second patient, the underlying disseminated blastomycosis required amphotericin B therapy. Blastomycosis should be included in the differential diagnosis of erythema nodosum.

Azithromycin vs cefuroxime plus erythromycin for empirical treatment of community-acquired pneumonia in hospitalized patients: a prospective, randomized, multicenter trial.

OBJECTIVE: To compare the efficacy and safety of azithromycin dihydrate monotherapy with those of a combination of cefuroxime axetil plus erythromycin as empirical therapy for community-acquired pneumonia in hospitalized patients. METHODS: Patients were enrolled in a prospective, randomized, multicenter study. The standard therapy of cefuroxime plus erythromycin was consistent with the American Thoracic Society, Canadian Community-Acquired Pneumonia Consensus Group, and Infectious Disease Society of America consensus guidelines. The doses were intravenous azithromycin (500 mg once daily) followed by oral azithromycin (500 mg once daily), intravenous cefuroxime (750 mg every 8 hours), followed by oral cefuroxime axetil (500 mg twice daily), and erythromycin (500-1000 mg) intravenously or orally every 6 hours. Randomization was stratified by severity of illness and age. Patients who were immunosuppressed or residing in nursing homes were excluded. RESULTS: Data from 145 patients (67 received azithromycin and 78 received cefuroxime plus erythromycin) were evaluable. Streptococcus pneumoniae and Haemophilus influenzae were isolated in 19% (28/145) and 13% (19/145), respectively. The atypical pathogens accounted for 33% (48/145) of the etiologic diagnoses; Legionella pneumophila, Chlamydia pneumoniae, and Mycoplasma pneumoniae were identified in 14% (20/ 145), 10% (15/145), and 9% (13/145), respectively. Clinical cure was achieved in 91% (61/67) of the patients in the azithromycin group and 91% (71/78) in the cefuroxime plus erythromycin group. Adverse events (intravenous catheter site reactions, gastrointestinal tract disturbances) were significantly more common in patients who received cefuroxime plus erythromycin (49% [30/78]) than in patients who received azithromycin (12% [8/67]) (P<.001). CONCLUSIONS: Treatment with azithromycin was as effective as cefuroxime plus erythromycin in the empirical management of community-acquired pneumonia in immunocompetent patients who were hospitalized. Azithromycin was well tolerated.

Trephine biopsy of the bone marrow in disseminated histoplasmosis.

Twenty-two patients had bone marrow aspirates for culture and marrow trephine biopsies for histologic examination during the evaluation of an illness eventually proved to be disseminated histoplasmosis. These procedures provided evidence of involvement of the bone marrow with Histoplasma capsulatum in 19 cases. Fungi were demonstrated in trephine biopsy sections in 15 of the patients, permitting a rapid specific diagnosis. Three patterns of bone marrow morphology were observed; each reflected a variation of macrophage proliferation. In two of the patterns, diffuse macrophage proliferation and loose aggregates of macrophages, typical 2 to 4 microns intracellular hisoplasma organisms were numerous and obvious in hematoxylin and eosin-stained sections, were infrequent and were often relatively large (6 to 12 microns). There were four patients from whom H. capsulatum was cultured when organisms could not be demonstrated in either hematoxylin and eosin- or silver-stained sections. The patients with diffuse proliferation of macrophages in the marrow comprised a distinct clinical group associated with immunosuppression, a fulminant course and a fatal outcome despite therapy. Patients in the other two morphologic groups responded well to therapy even though the immune responses on many were also suppressed. Bone marrow examination is an excellent diagnostic procedure in disseminated histoplasmosis. Trephine biopsies permit a rapid diagnosis in most cases and may be of prognostic significance.

Central nervous system histoplasmosis. An unappreciated complication of the acquired immunodeficiency syndrome.

Involvement of the central nervous system (CNS) by Histoplasma capsulatum is a rare event. It is usually not included in the differential diagnosis of CNS lesions in patients with acquired immunodeficiency syndrome (AIDS). Herein are described four patients with AIDS and progressive disseminated histoplasmosis who had CNS involvement. Histoplasmosis in the CNS may produce meningitis, single or multiple brain abscesses, and may present with either a clinical picture of obtundation or a deteriorating space-occupying CNS lesion. Three of the four patients were treated with amphotericin B and had initial clinical response, but ultimately, all experienced a relapse and died from their infection.

Progressive disseminated histoplasmosis in patients with acquired immunodeficiency syndrome.

PURPOSE: Progressive disseminated histoplasmosis is now diagnosed frequently in patients with the acquired immunodeficiency syndrome (AIDS) living in the central United States. Previous review articles of AIDS have failed to mention this infection. Herein, we describe 48 AIDS patients with progressive disseminated histoplasmosis in an effort to better understand the clinical presentation and diagnosis of the condition in this setting and to assess the efficacy of antifungal chemotherapy. PATIENTS AND METHODS: In the Houston metropolitan area, there were 66 cases of progressive disseminated histoplasmosis among 1,300 confirmed cases of AIDS from January 1983 to July 1987. Of AIDS patients in East Texas with histoplasmosis, 16 patients were available for follow-up by one of us, and the histories of 32 were obtained by examination of hospital charts and physician records. RESULTS: Fever, weight loss, and splenomegaly were the most common presenting signs and symptoms, occurring in 81, 52, and 31 percent, respectively. One-third of the patients had hematologic abnormalities. Infiltrates on chest roentgenograms were observed in 52 percent. Progressive disseminated histoplasmosis was the initial manifestation of AIDS in almost three-fourths of our patients. Biopsy and culture of the bone marrow established the diagnosis of progressive disseminated histoplasmosis in 69 percent. Clinical or autopsy proof of relapse occurred in three patients despite an initial course of more than 2 g of amphotericin B chemotherapy followed by ketoconazole suppression. CONCLUSION: Progressive disseminated histoplasmosis is often the first sign of immunodeficiency in patients with AIDS, and the diagnosis of this condition is most often established by bone marrow biopsy and culture. Because of the permanence of the immunodeficient state in these patients, progressive disseminated histoplasmosis is resistant to treatment.

Chronic blastomycotic meningitis.

Three cases of blastomycosis which presented as chronic meningitis are reported. Blastomycotic meningitis is an uncommon form of chronic fungal meningitis and is difficult to diagnose during life unless the patient has obvious systemic blastomycosis elsewhere. Evaluation of cerebrospinal fluid obtained by lumbar tap is usually not diagnostic. Obstructive hydrocephalus developed in all three patients during the course of their fungal meningitis. Culture of ventricular fluid yielded the fungus in all three patients (although only after death in one case). One patient received only minimal therapy before death whereas the third patient received a full course of amphotericin B with restoration to his premorbid state. Blastomycosis should be included in the differential diagnosis of chronic meningitis and, when suspected, the cisternal or ventricular fluid should be sampled.

Blastomycosis in children.

Four cases of blastomycosis in children selected from a larger series of cases seen over 36 months are presented. This infection in the pediatric age group is not often considered in the setting of a slowly resolving pneumonic illness. The morbidity and mortality of this disease in the adult warrant careful consideration of this entity in the pediatric age group, since effective therapy is available.

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.

Nocardia asteroides pericarditis: report of a case and review of the literature.

In this report, we describe a patient who had purulent Nocardia asteroides pericarditis. In addition, we identified 13 previously suspected and reported cases of Nocardia pericarditis, but only 5 of these studies reported isolation of Nocardia from cultures of pericardial fluid or pericardium. Analysis of the clinical course of these five patients and our patient revealed the importance of long-term sulfonamide antibiotic therapy in combination with surgical pericardial drainage procedures. In our review, only patients who received antibiotics and underwent pericardiectomy survived. Our case substantiates the excellent penetration of sulfisoxazole into the pericardial fluid, even with oral administration of the drug, and provides evidence in support of aggressive management of Nocardia pericarditis.

Acute cavitary histoplasmosis.

A case of acute cavitary histoplasmosis in the upper lobes is documented. The relationship of this entity to chronic cavitary histoplasmosis is discussed.

Evaluation of the Winthrop-University Hospital criteria to identify Legionella pneumonia.

STUDY OBJECTIVE: To measure the ability of a set of clinical parameters, the Winthrop-University Hospital (WUH) criteria, to identify Legionella pneumonia while discriminating against bacteremic pneumococcal pneumonia at the time of hospitalization for community-acquired pneumonia (CAP). DESIGN: Retrospective case-control study. SETTING: An urban county hospital and a tertiary-care Veterans Affairs hospital. PATIENTS: Thirty-seven patients with Legionella pneumonia (diagnosed by a positive result of a urinary Legionella antigen test) and 31 patients with bacteremic pneumococcal pneumonia. A subgroup of patients with all required laboratory criteria were studied further. RESULTS: The WUH criteria correctly identified 29 of 37 patients with Legionella pneumonia (sensitivity, 78%; 95% confidence interval [CI], 61 to 90%), while successfully excluding legionellosis in 20 of 31 patients with bacteremic pneumococcal pneumonia (specificity, 65%; 95% CI, 45 to 80%). The positive and negative predictive values, adjusted for a relative prevalence of 1:3 between Legionella and Streptococcus pneumoniae bacteremia, were 42% (95% CI, 25 to 61%) and 90% (95% CI, 74 to 97%), respectively. In the subgroup analysis, the WUH criteria were successful in identifying 20 of 23 patients with Legionella pneumonia (sensitivity, 87%; 95% CI, 65 to 97%), while excluding legionellosis in 9 of 18 patients with bacteremic pneumococcal pneumonia (specificity, 50%; 95% CI, 27 to 73%). The adjusted positive and negative predictive values for a 1:3 relative prevalence were 37% (95% CI, 20 to 59%) and 92% (95% CI, 62 to 98%), respectively. The predictive values were changed in the directions expected for an increased relative prevalence of 1:1. The areas under the receiver operating characteristic curves were 0.72 +/- 0.06 for the entire study group and 0.68 +/- 0.09 for the subgroup. CONCLUSIONS: Although the WUH criteria discriminated fairly well between cases (mean +/- SE) and control subjects, the sensitivity is not high enough to exclude legionellosis confidently. These results suggest that empiric therapy for Legionella pneumonia should be included in the initial antibiotic regimen for hospitalized patients with CAP.

Exfoliative cytology in the rapid diagnosis of pulmonary blastomycosis.

Four patients with pulmonary blastomycosis are reported. Their bronchial washings, submitted for cytologic evaluation and stained by the standard Papanicolau technique, yielded the diagnosis, subsequently confirmed by cultural identification of the fungus. In three additional cases, retrospective evaluation of cytologic material also revealed the organism, even though the diagnostic significance was not appreciated originally. Since cytologic techniques are simple, readily available, and rapid, they can be helpful in differentiating pulmonary neoplasms from pulmonary blastomycosis, thus reducing the need for diagnostic thoracotomies.

Chronic cavitary histoplasmosis. Failure of oral treatment with ketoconazole.

Ketoconazole appears to be a safe drug in the treatment of chronic cavitary histoplasmosis. Primary failure and relapse have been described, requiring amphotericin B, even after long therapy with ketoconazole. Four typical cases are presented. We caution about such potential failures and stress the importance of close observation of patients begun on therapy with ketoconazole for chronic cavitary histoplasmosis.

PACAP-38 causes phospholipase C-dependent calcium signaling in rat acinar cell line.

BACKGROUND: Pituitary adenylate cyclase activating peptide (PACAP-38), a neuropeptide of the vasoactive intestinal peptide/secretin family, localizes to intrapancreatic neurons and stimulates exocrine secretion from the pancreas. PACAP-38 stimulates calcium signaling in the rat pancreatic cell line AR42J. The purpose of this study was to elucidate the mechanisms of PACAP-evoked calcium signaling in these cells. METHODS: Continuous measurements of intracellular calcium were taken by fluorescent digital microscopy with the dye fura-2. Mechanisms of PACAP-38-evoked calcium signals were determined by a panel of inhibitors. Inositol phosphates production in response to PACAP-38 was measured. The ability of PACAP-38 to stimulate amylase release was used to determine a relevant dose range for these studies. RESULTS: We have shown that (1) AR42J cells respond to PACAP-38 with biphasic increases in [Ca2+]i in a dose-dependent fashion; (2) PACAP-38 acts through phospholipase C to release inositol triphosphate (IP3)-sensitive Ca2+ stores with (3) a subsequent influx of extracellular Ca2+. CONCLUSIONS: PACAP-38 activates calcium signaling through phospholipase C at concentrations that stimulate amylase release in AR42J cells.

Tachykinin neuropeptide-evoked intracellular calcium transients in cultured guinea pig myenteric neurons.

Substance P and related tachykinins are present in the mammalian gut and act as neurotransmitters. Microfluorimetric measurement of intracellular calcium ([Ca2+]i) was used to study tachykinin-sensitive myenteric neurons. Substance P (0.001-10 microM) evoked concentration-dependent increases in percentage of neurons responding (6-75%) and delta [Ca2+]i (88 +/- 24 to 212 +/- 16 nM). Neurokinin A (0.001-1 microM) produced similar responses. Removal of extracellular Ca2+ abolished substance P-induced Ca2+ signals, as did the addition of the Ca2+ channel blockers lanthanum chloride (5 mM) and nickel chloride (2.5 mM). Both nifedipine (1-50 microM) and diltiazem (1-50 microM) inhibited substance P-evoked Ca2+ responses in a dose-dependent manner. Substance P and related tachykinins evoke Ca2+ signaling in cultured myenteric neurons by the influx of extracellular Ca2+ through L and N-type plasma membrane Ca2+ channels.

Calcium signaling induced by angiotensin II in the pancreatic acinar cell line AR42J.

The purpose of this study was to characterize the nature and mechanisms of angiotensin II-evoked calcium signaling in AR42J cells. Cytosolic calcium concentrations were determined using fura-2-based microfluorimetry. Angiotensin II causes elevations in free cytosolic calcium ([Ca2+]i) in the rat pancreatic acinar cell line AR42J. The mechanisms of angiotensin II-evoked calcium signaling were examined using fura-2-based fluorescent digital microscopy. Angiotensin II caused dose-dependent increments in [Ca2+]i over a concentration range of 0.1-1,000 nM, with an average increment of 243 +/- 16 nM at an angiotensin II concentration of 1,000 nM. Dup753, an AT1-specific antagonist, inhibited angiotensin II-evoked signaling, whereas the AT2 antagonist PD123,319 had no effect. Preincubation with the phospholipase C inhibitor U73122 reduced the response in [Ca2+]i to 25% of that of the control. Thapsigargin abolished angiotensin II-evoked calcium signaling. The inositol 1,4,5-trisphosphate receptor antagonist heparin introduced by radiofrequency electroporation inhibited responses to 46 +/- 6% of controls. Angiotensin II-evoked signals were reduced in magnitude and duration by elimination of Ca2+ from the extracellular buffer. Preincubation with pertussis toxin (100 ng/ml) had no effect. Angiotensin II did not stimulate cyclic AMP or suppress vasoactive intestinal peptide stimulated cyclic AMP production over the concentration range that caused Ca2+ signaling.