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.

Review of minimally invasive esophagectomy and current controversies.

Esophagectomy is a complex operation with significant morbidity and mortality. Minimally invasive esophagectomy (MIE) was described in the 1990s in an effort to reduce operative morbidity. Since then many institutions have adopted and described their series with this technique. This paper reviews the literature on the variety of MIE techniques, clinical and quality of life outcomes with open versus MIE, and controversies surrounding MIE-such as prone positioning, stapling techniques, size of the gastric conduit, and robotic techniques.

Characterization of telomerase-immortalized, non-neoplastic, human Barrett's cell line (BAR-T).

Barrett's esophagus, a metaplasia predisposed to malignant transformation, has been studied in vitro using esophageal adenocarcinoma cell lines. However, findings in such transformed cells may not be applicable to the non-neoplastic cells of benign Barrett's esophagus. Therefore, we have developed and characterized a Barrett's cell line derived from a patient without malignancy or dysplasia. Human Barrett's epithelial cells were immortalized with the insertion of hTERT (human telomerase reverse transcriptase) using a Cre-lox recombination system. We then examined properties of this continuous cell line, such as in vitro tumorigenicity, growth patterns, histological differentiation characteristics, karyotype, and checkpoint arrest mechanisms (e.g., p16, p21, and p53). Non-neoplastic Barrett's epithelial cells infected with hTERT (BAR-T cells) have been sustained in culture beyond 200 population doublings. BAR-T cells maintain a diploid chromosome number and exhibit non-neoplastic properties, such as contact inhibition and anchorage-dependent growth. BAR-T cells express differentiation Barrett's epithelial markers, such as villin and cytokeratins 4, 8 and 18, and stain positive for Alcian blue, indicating the presence of mucin-producing cells. Expression of checkpoint arrest proteins p21 and p53 are intact, while p16 expression is lost. Thus, we have created a human Barrett's cell line that is not malignantly transformed, and yet can be maintained indefinitely in culture. BAR-T cells are diploid, have histological differentiation markers characteristic of benign Barrett's epithelium, and also maintain appropriate expression of p21 and p53. This cell line should be a useful model for the study of the early events in carcinogenesis in Barrett's esophagus.

Rapid diagnostic evaluation of bronchial washings in patients with suspected coccidioidomycosis.

Coccidioidomycosis is a regionally common fungal infection, primarily affecting the lung. While in the majority of cases the tempo of the disease allows for a more leisurely diagnostic plan, including multiple serologic tests and culture of respiratory secretions, occasionally, patients will present with rapidly progressive, life-threatening pulmonary illness, in whom there is an urgent need for rapid diagnosis. Evaluation of respiratory secretions including expectorated sputum as well as bronchial washings are frequently available or obtained for diagnosing pulmonary infiltrates. We compared the sensitivity of the Papanicolaou stain with 10% potassium hydroxide digestion (10% KOH) and with calcofluor white (cw). The Papanicolaou test performed the best and should be used in the evaluation of suspected patients with coccidioidomycosis.

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.

The role of atypical pathogens in community-acquired pneumonia.

The atypical pathogens in community-acquired pneumonia traditionally have included Mycoplasma pneumoniae, Chlamydia pneumoniae, and Legionella spp. Recent studies documenting their epidemiology and clinical characteristics have shown that these organisms are indistinguishable from the pneumococcus. Furthermore, therapy no longer depends on the specific bacterial cause of community-acquired pneumonia. Etiologic diagnosis is still difficult, although new methods are becoming available. This article focuses on these issues and on why the term atypical is no longer meaningful.

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.

Pyomyositis in the acquired immunodeficiency syndrome.

Pyomyositis, a purulent infection of skeletal muscle, is usually caused by Staphylococcus aureus. Many cases of pyomyositis in human immunodeficiency virus (HIV) seronegative patients have been reported in North America and have been reviewed extensively. Moreover, pyomyositis has been reported in association with HIV infection in patients with or without the acquired immunodeficiency syndrome (AIDS). We describe two patients with pyomyositis and HIV and review the available English language literature. Leukocytosis and bacteremia tend to occur less frequently in those with HIV infection and pyomyositis. However, fever, S aureus infection, and bilateral involvement occur more frequently in HIV-positive patients. Antibiotic therapy together with surgical drainage or aspiration is usually sufficient.

Fungal pneumonias. The endemic mycoses.

Each year, a vast number of individuals are infected with the endemic fungi. An expanding population, along with further land development in endemic areas, will likely continue to place individuals at risk for exposure to these organisms. A high index of suspicion may be required to diagnose histoplasmosis, blastomycosis, or coccidioidomycosis, particularly for patients who do not reside in endemic areas. Although the majority of patients with histoplasmosis, blastomycosis, and coccidioidomycosis experience self-limited infections, treatment is necessary for patients with severe pneumonitis as well as various forms of chronic pulmonary and disseminated infections. The newer azole agents--itraconazole and fluconazole--are useful in the treatment of these infections and have provided alternatives to long-term therapy with amphotericin B for many patients.

'Atypical pneumonia'. Why this term may be better left unsaid.

I have attempted to mount an argument to rid the medical literature of the term "atypical pneumonia." It really adds nothing to diagnostic and therapeutic decisions in patients with respiratory infections caused by various organisms.

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.

Capacitative Ca2+ entry in enteric glia induced by thapsigargin and extracellular ATP.

Mobilization of intracellular Ca2+ stores is coupled to Ca2+ influx across the plasma membrane, a process termed capacitative Ca2+ entry. Capacitative Ca2+ entry was examined in cultured guinea pig enteric glia exposed to 100 microM ATP, an inositol trisphosphate-mediated Ca2+-mobilizing agonist, and to 1 microM thapsigargin, an inhibitor of microsomal Ca2+ ATPase. Both agents caused mobilization of intracellular Ca2+ stores followed by influx of extracellular Ca2+. This capacitative Ca2+ influx was inhibited by Ni2+ (88 +/- 1%) and by La3+ (87 +/- 1%) but was not affected by L- or N-type Ca2+ channel blockers. Pretreatment of glia with 100 nM phorbol 12-myristate 13-acetate for 24 h decreased capacitative Ca2+ entry by 48 +/- 2%. Chelerythrine (0.1-10 microM), a specific antagonist of protein kinase C (PKC), dose dependently inhibited capacitative Ca2+ entry. The nitric oxide synthase inhibitor NG-nitro-L-arginine (1 mM) decreased Ca2+ influx by 42 +/- 1%. Capacitative Ca2+ entry was inhibited to a similar degree by the guanylate cyclase inhibitor (1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one). Capacitative Ca2+ entry occurs in enteric glial cells via lanthanum-inhibitable channels through a process regulated by PKC and nitric oxide.

Endothelin-stimulated capacitative calcium entry in enteric glial cells: synergistic effects of protein kinase C activity and nitric oxide.

Depletion of intracellular calcium stores by agonist stimulation is coupled to calcium influx across the plasma membrane, a process termed capacitative calcium entry. Capacitative calcium entry was examined in cultured guinea pig enteric glial cells exposed to endothelin 3. Endothelin 3 (10 nM) caused mobilization of intracellular calcium stores followed by influx of extracellular calcium. This capacitative calcium influx was inhibited by Ni2+ (89 +/- 2%) and by La3+ (78 +/- 2%) but was not affected by L-, N-, or P-type calcium channel blockers. Chelerythrine, a specific antagonist of protein kinase C, dose-dependently inhibited capacitative calcium entry. The nitric oxide synthase inhibitor NG-nitro-L-arginine decreased calcium influx in a dose-dependent manner. The combination of chelerythrine and NG-nitro-L-arginine produced synergistic inhibitory effects. Capacitative calcium entry occurs in enteric glial cells via lanthanum-inhibitable channels through a process regulated by protein kinase C and nitric oxide.

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.

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.

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.