Mesenchymal hamartoma and undifferentiated embryonal sarcoma: diagnostic keys that radiologists need to know. / Hamartoma mesenquimatoso y sarcoma embrionario indiferenciado: claves diagnósticas que el radiólogo debe conocer.

OBJECTIVE: Hepatic tumors are uncommon in pediatric patients. Among the most common of these uncommon tumors are mesenchymal hamartoma and undifferentiated embryonal sarcoma, which have different origins but similar appearance on imaging studies. This paper reviews the characteristic findings and differential diagnosis of these entities. Ultrasonography is the first-line imaging test to study these tumors. Magnetic resonance imaging and computed tomography are useful for further characterizing the tumors and planning surgery. CONCLUSION: Radiologists need to be familiar with the imaging findings of the different disease entities and to evaluate them together with the patient's age, personal history, and bloodwork.

GD3 ganglioside antibody augments tumoricidal capacity of canine blood mononuclear cells by induction of interleukin 12.

Monoclonal antibody R24 recognizes ganglioside GD3 expressed on the cell surfaces of some tumor cells and on a subset of human T lymphocytes. Binding of R24 to these lymphocytes induces proliferation, cytokine production, and activation of intracellular signaling pathways. In the current report, we investigated expression of gangliosides by canine mononuclear immune cells and studied the ability of antiganglioside antibody to activate these cells using tumor cell killing as a measure of activation. A subset of canine monocytes, but not lymphocytes, was found to express gangliosides GD3 and GD2 as determined by the binding of monoclonal antibodies R24 and 14.G2a, respectively. Only R24 augmented the tumoricidal potential of fresh canine peripheral blood mononuclear cells (PBMCs) against tumor cell lines that did not express surface gangliosides GD3 or GD2. The augmenting effect of R24 on PBMC-mediated tumor cytotoxicity required cooperation between monocytes and lymphocytes because there was no enhancement of cytotoxicity mediated by R24 combined with either monocytes or lymphocytes individually. The enhancing effect of R24 on canine PBMC-mediated tumor cytotoxicity was blocked by anti-interleukin (IL)-12 neutralizing antibody, suggesting that R24 binding to monocytes triggered IL-12 release, contributing to the observed tumor killing effects. Reverse transcription-PCR confirmed that the binding of R24 to canine monocytes induced transcription of mRNA for canine IL-12. These data indicate that monocytes can be activated for tumoricidal responses through a membrane structure associated with ganglioside GD3 triggered by the binding of R24 and that the mechanism for enhanced cytotoxicity is due to the production and secretion of IL-12.

Diffuse pulmonary uptake of indium-111-labeled leukocytes in drug-induced pneumonitis.

Indium-111-labeled-leukocyte scintigraphy was performed on three febrile patients, two of whom had no signs or symptoms referable to the respiratory tract. The third patient had dyspnea on exertion, unchanged over two months. Their past histories were remarkable in that all three had recently undergone chemotherapy for malignancy (2 lymphoma, 1 malignant thymoma). Diffuse pulmonary uptake of labeled leukocytes was observed in all three individuals. As a direct result of leukocyte imaging, all three underwent fiberoptic bronchoscopy and transbronchial biopsy. The final diagnosis in each of these patients was drug-induced pneumonitis, which responded to treatment with corticosteroids. This entity should be added to the group of conditions, both infectious and noninfectious, that cause diffuse pulmonary uptake on labeled leukocyte images. Moreover, in the appropriate clinical setting, even in the absence of pulmonary signs or symptoms, diffuse pulmonary uptake of labeled leukocytes should alert the physician to the possibility of drug-induced pneumonitis.

Effect of interferon on a primary conjunctival epithelial cell model of trachoma.

An in vitro human primary conjunctival epithelial system was adapted to determine if the effects of interferon-gamma (IFN-gamma), as described in cultured cell lines, were applicable to human ocular infection with Chlamydia trachomatis, Primary human epithelial cell cultures were exposed to varying concentrations of IFN-gamma. The treatment resulted in the induction of the tryptophan decyclizing enzyme indolamine 2,3-deoxygenase (IDO) in a dose-dependent manner as determined by assaying the conversion of tryptophan to its metabolites using reversed-phase high-performance liquid chromatography. Little IDO induction occurred in the presence of IFN-alpha or IFN-beta. Catabolism of up to 38% of available tryptophan occurred in IFN-gamma-treated cells in contrast to controls that showed only baseline activity. Cells cultured with IFN-gamma and then infected with an ocular isolate of C. trachomatis (TW-5), had a reduction in the percentage of inclusion-containing cells by over 80% in a dose-dependent manner. Reversal by the addition of exogenous tryptophan substantiated that IFN-gamma-mediated induction of IDO and catabolism of tryptophan were responsible for inhibition of intracellular growth of C. trachomatis.

Normoprolactinaemia in spontaneously hypertensive rats: absence of a close relationship between plasma concentrations of prolactin and systolic blood pressure.

Prolactin has been involved in different types of hypertension both in man and in rats. In an attempt to substantiate this hypothesis, we have analysed the correlation between plasma concentrations of prolactin and systolic blood pressure (SBP) in female and male rats from spontaneously hypertensive (SH) and normotensive Wistar-Kyoto strains (30, 60 and 90 days old), as well as in adult female Wistar rats rendered hyperprolactinaemic by the administration of 100 micrograms testosterone propionate on day 1 of life, or adult males with low plasma concentrations of prolactin after administration of bromocriptine (4 mg/kg per day) over 15 days. Our results indicate a lack of correlation between plasma concentrations of prolactin and SBP since plasma concentrations of prolactin were normal in male and female SH rats and hyper- and hypoprolactinaemia did not affect SBP. In spite of these normal plasma concentrations of prolactin, SH rats showed subtle changes in the secretion of this hormone in vitro and in vivo in response to exogenous serotonin administration and to immobilization.

Pulmonary complications in cardiac transplant recipients.

BACKGROUND: The incidence of pulmonary complications in heart transplant recipients has not been extensively studied. We report pulmonary complications in 159 consecutive adult orthotopic heart transplantations (OHTs) performed in 157 patients. MATERIALS AND METHODS: Retrospective review of medical records. RESULTS: Forty-seven of 159 recipients (29.9%) had 81 pulmonary complications. Pneumonia was the most common (n = 27), followed by bronchitis (n = 15), pleural effusion (n = 10), pneumothorax (n = 7), prolonged respiratory failure requiring tracheotomy (n = 7), and obstructive sleep apnea syndrome (n = 6). All patients with late-onset (> 6 months after transplantation) community-acquired bacterial pneumonia presented with fever, cough, and a new lobar consolidation on the chest radiograph, and responded promptly to empiric antibiotics without undergoing an invasive diagnostic procedure. In contrast, early-onset nosocomial bacterial pneumonias carried a 33.3% mortality rate. A positive tuberculin skin test result was associated with a significantly higher rate of pulmonary complications (62.5% vs 26.8%, p = 0.007). Lung cancer and posttransplant lymphoproliferative disorder (PTLD) developed exclusively in 6 of the 61 patients (8.1%) who received induction immunosuppression with murine monoclonal antibody (OKT3). CONCLUSION: Pulmonary complications are common following heart transplantation, occurring in 29.9% of recipients, and are attributed to pneumonia of primarily bacterial origin in one half of cases. Late-onset community-acquired pneumonia carried an excellent prognosis following empiric antibiotic therapy, suggesting that in the appropriate clinical setting invasive diagnostic procedures are unnecessary. Analogous to reports in other solid-organ transplant recipients, induction therapy with OKT3 was associated with an increased incidence of lung cancer and PTLD. Overall, the development of pulmonary complications after OHT has prognostic significance given the higher mortality in this subset of patients.

Dobutamine thallium 201 perfusion imaging in candidates for lung transplantation.

BACKGROUND: Thallium-201 stress imaging is the most often used noninvasive test for detection of coronary artery disease. Its utility in patients with end-stage lung disease has not been defined. METHODS: Feasibility, safety, and reliability of thallium 201 perfusion imaging was evaluated in 23 consecutive candidates for lung transplantation. All underwent graded dobutamine thallium 201 single photon emission computed tomography imaging. The perfusion imaging results were correlated with results of coronary angiography, radionuclide angiography, and right heart catheterization. RESULTS: The testing was completed without complications in all patients. No perfusion abnormality was detected in five patients, and none had evidence of coronary artery disease on coronary angiography. In 18 patients with abnormal thallium 201 imaging, coronary artery disease was detected in four patients only, and no angiographic data was available in three patients. Thus, in at least 11 of 23 patients, thallium 201 imaging was falsely positive. There was a trend toward lower left ventricular ejection fraction in patients with abnormal thallium 201 imaging. No correlation was found between thallium 201 results, pulmonary artery and right atrial pressures at rest. Possible noncoronary origin of the perfusion defects include the following (1) presence of sarcoid in the myocardium, (2) left ventricular attenuation by hypertrophied right ventricle, and (3) altered left ventricular anatomy, function, and coronary perfusion as a result of right ventricular pressure overload. CONCLUSIONS: Dobutamine thallium 201 stress test can be safely performed in lung transplant candidates. However, its specificity for detection of coronary artery disease is low. Selective use of coronary angiography in patients with multiple risk factors is likely a more cost-effective approach.

Conversion of non-iodine-concentrating differentiated thyroid carcinoma metastases into iodine-concentrating foci after anticancer chemotherapy.

We present the unusual case of a 29-year-old man diagnosed in 1975 with papillary carcinoma of the thyroid metastatic to regional lymph nodes. The patient underwent surgical resection, postoperative iodine-131 (131I) radioablation and levothyroxine suppression. He was subsequently lost to follow-up. In 1991, he presented with extensive metastatic disease that was not demonstrable on whole-body 131I imaging, but was seen on computerized tomography and whole-body thallium chloride scanning. The patient was treated with cisplatin (Platinol) and doxorubicin (Adriamycin). Repeat 131I imaging after three cycles of chemotherapy showed significant 131I uptake in previously non-iodine-concentrating lesions. The patient was subsequently treated with 200 mCi 131I. We postulate this patient's non-iodine-concentrating thyroid cancer may have become functional by either a differentiating effect of chemotherapy on the tumor cells, or perhaps a selective cytotoxicity against nonfunctional, less differentiated papillary thyroid cancer cells, or both. This would allow more functional differentiated cells to overgrow and become the predominant cell type in the lesions. Chemotherapy may be beneficial in patients with advanced non-iodine-concentrating differentiated thyroid carcinoma by inducing radioiodine uptake and allowing subsequent radioiodine therapy. The possible mechanisms of induction of iodine uptake by chemotherapy are discussed.

Sarcoidosis and transplantation.

BACKGROUND AND AIM OF WORK: Organ transplantation is an accepted treatment for patients with end-stage organ failure. There is limited information about transplantation in patients with sarcoidosis. While there has been no systematic study of transplantation in sarcoidosis, there have been several reports of patients with sarcoidosis undergoing organ transplantation. The purpose of this review is to analyze the available literature. METHODS: We reviewed the literature regarding transplantation of kidney, liver, heart, heart-lung and lung in patients with sarcoidosis with attention to survival, complications and the incidence of recurrence of sarcoidosis in the transplanted organ and at distant sites. RESULTS: Survival and complication rates are similar to those of patients undergoing transplantation for other indications. Recurrence of pulmonary sarcoidosis has been estimated to be 47% following lung transplantation. The published cases represent a fraction of the patients reported to the International Registry maintained by the United Network of Organ Sharing (UNOS). CONCLUSIONS: Transplantation can be carried out safely in patients with sarcoidosis. Recurrence is frequent, often asymptomatic, and does not compromise graft function or patient survival. Radiographic abnormalities or symptoms associated with recurrence are responsive to increased adrenocorticosteroid therapy. Exacerbation of sarcoidosis in transplant recipients occurs in the setting of intense immunosuppression.

Mechanism of reproductive deficiency in spontaneously hypertensive rats.

Spontaneously hypertensive rats (SHR) show multiple endocrine disorders. In the present work, specific reproductive modifications were analysed using normotensive Wistar-Kyoto rats (WKY) as controls. SHR showed delayed vaginal opening and first estrus presentation, regular vaginal cycles and released a normal number of ova each cycle. When compared with controls, SHR showed a decrease in the percentage of successful pregnancies (69% vs. 86% in WKY) and in the litter size (7.83 +/- 0.5 vs. 10.41 +/- 0.5). In SHR, progesterone plasma levels were significantly increased during the days 1-14 of pregnancy, and on the 5th day of pregnancy the plasma concentrations of LH but not of FSH were enhanced. Mortality during the first month of life was higher in SH (50%) than in control (24%) strain. When the SH females were mated with Wistar or WKY males, the percentage of pregnancies rose up to 95%. On the contrary, Wistar or WKY females mated with SH males showed a decrease in the percentage of pregnancies (62.5% and 50%, respectively). Besides, the litter sizes were significantly reduced in Wistar females mated with SH males. Newborn SH suckled immediately after birth from a WKY mother showed a significant reduction in the mortality during the first month of life (8% vs. 50%). In conclusion, our results suggest that changes in fertilization and/or implantation processes of SH rats were responsible for the reduced pregnancy rate, whereas the increased neonatal mortality could be due to lactation activity of SH mothers.

Immunostimulatory effects of human recombinant interleukin-12 on peripheral blood mononuclear cells from normal dogs.

Interleukin-12 (IL-12) plays a pivotal role in regulating cellular immune responses involving autoimmunity, infectious disease, and cancer. Human recombinant (hr) IL-12 is being evaluated for therapy of human cancer. We investigated the potential of hrIL-12 to activate canine peripheral blood mononuclear cells (PBMC) using proliferation and cytotoxicity as readouts. Human rIL-12 caused increased proliferation of PBMC, and enhanced lysis of allogeneic canine tumor targets mediated by PBMC from normal dogs in vitro. In addition, antibody-dependent cellular cytotoxicity (ADCC) mediated by canine PBMC was enhanced by hrIL-12. These results indicate that hrIL-12 is recognized by canine immune cells, triggering a number of immune responses in canine PBMC, that may be important for immunotherapy of canine cancer. Information from this investigation provides impetus for evaluation of the effects of hrIL-12 on PBMC from tumor-bearing dogs and should be helpful in the development of hrIL-12 as an immune cell activator in vivo in the dog.

Sarcoidosis mythology.

BACKGROUND: Sarcoidosis continues to be shrouded by anecdotal misinformation which has gained credence by repetition. These myths have been developing for the past 50 years and continue to accumulate, despite remedial data. Among the most egregious myths are that sarcoidosis is a disease of Blacks, that the chest radiography is diagnostic of sarcoidosis, and has chronologic significance, that serum angiotensin converting enzyme and bronchoalveolar lavage are diagnostic of sarcoidosis and serve as guides to therapy, that the Kveim-Siltzbach test is not a reliable diagnostic test for sarcoidosis, that sarcoidosis is difficult to diagnose, and that sarcoidosis is tuberculosis. METHODS AND RESULTS: The literature regarding these myths has been reviewed and supported by the experience with more than 10,000 patients with sarcoidosis who have been treated at Mount Sinai Medical Center, New York. CONCLUSIONS: Sarcoidosis occurs with varying frequency among all races. The chest radiograph typical of sarcoidosis can be mimicked by other granulomatous and neoplastic diseases. The classic radiographic stages, from 0 to 111, do not reflect the time course of sarcoidosis can be made relatively easily in most patients, but its etiology is still unknown.

Latchkey children: a review of the literature.

Professional interest in the latchkey phenomenon has increased in the past 20 years. This article gives background information and reviews empirical research.

Dissociation of preparatory attention and response monitoring maturation during adolescence.

OBJECTIVE: Substantial brain development occurs during adolescence providing the foundation for functional advancement from stimulus-bound "bottom-up" to more mature executive-driven "top-down" processing strategies. The objective was to assess development of EEG markers of these strategies and their role in both preparatory attention (contingent negative variation, CNV) and response monitoring (Error Related Negativity, ERN, and Correct Related Negativity, CRN). METHODS: CNV, ERN and CRN were assessed in 38 adolescents (18 girls), age 11-18 years, using a variation of a letter discrimination task. RESULTS: Accuracy increased with age and developmental stage. Younger adolescents used a posterior attention network involved in inhibiting irrelevant information. Activity in this juvenile network, as indexed by a posteriorly-biased CNV and CRN decreased with age and advancing pubertal development. Although enhanced frontal CNV, known to be predictive of accuracy in adults, was not detected even in the older adolescents, top-down medial frontal response monitoring processes (ERN) showed evidence of development within the age-range studied. CONCLUSIONS: The data revealed a dissociation of developmental progress, marked by relatively delayed onset of frontal preparatory attention relative to error monitoring. SIGNIFICANCE: This dissociation may render adolescents vulnerable to excessive risk-taking and disinhibited behavior imposed by asynchronous development of component cognitive control processes.

Aberrant p53 expression in feline vaccine-associated sarcomas and correlation with prognosis.

Eighty spontaneously occurring feline vaccine-associated sarcomas (VAS) were evaluated to determine the immunohistochemical expression of the tumor suppressor gene p53. Sixty-five of 80 VAS (81%) exhibited positive immunoreactivity with Mab240, a murine monoclonal antibody that specifically recognizes mutated p53. Only 44 of 81 tumors (55%) were positive with rabbit polyclonal antibody CM-1. CM-1 often yielded nonspecific staining of nonneoplastic tissues. Nonspecific staining was greatly reduced or absent with Mab240. Cytoplasmic staining for p53 was a consistent pattern of VAS, occurring in 44% of tumors evaluated. Cats with tumors that exhibited cytoplasmic p53 had significantly shorter time to tumor recurrence compared to those cats with tumors that exhibited nuclear p53 staining (P = 0.0284), but no significant difference in survival outcome was observed. Immunohistochemical detection of p53 offers a prognostic tool for VAS, and, because abnormal p53 expression appears to be a common feature of feline VAS, molecular targeting of mutant p53, may offer a promising new therapeutic opportunity for this cancer.

Induction of emphysema in hamsters by intratracheal instillation of cathepsin B.

Current theories of pathogenesis suggest that pulmonary emphysema develops in humans because of progressive loss or derangement of lung elastin through a process mediated by elastolytic enzymes released by inflammatory cells. Neutrophils are considered primary etiologic factors because these cells produce and release two potent serine proteinases that cause emphysema when instilled into the lungs of animals. It has been suggested that alveolar macrophages also contribute to the development of emphysema through production of several enzymes with elastolytic activity, including the lysosomal cysteine proteinases cathepsin B and cathepsin L, but this has not been verified experimentally. In the current study, we instilled 115 micrograms of active cathepsin B into the lungs of hamsters three times at 48-h intervals. After 6 wk microscopic evaluation revealed that lung sections of five of seven animals given cathepsin B contained focal areas of enlarged and distorted alveoli, in the absence of fibrosis, which were similar to changes seen in the lungs of animals given papain intratracheally. Morphometrically, mean linear intercept (micron) values were significantly higher (p less than 0.025) in animals given cathepsin B (204.4 +/- 20.8) as compared with control animals (173.2 +/- 7.8), and internal surface area (sqcm) values were significantly lower (935 +/- 120 versus 1,083 +/- 56 in control animals), thereby confirming that airspace enlargement had developed after instillation of the enzyme. Lung volumes (ml) and compliance (ml/cm H2O) were not significantly higher in animals given cathepsin B.(ABSTRACT TRUNCATED AT 250 WORDS)

Lung transplantation in interstitial lung disease.

Interstitial lung disease is a heterogeneous group of illnesses, some of which may progress to a fibrosing stage and cause respiratory failure. For selected candidates, lung transplantation is the ultimate therapeutic option. We review data on lung transplantation for various interstitial lung diseases. We address indications, procedures, and outcomes for patients undergoing transplantation. Unique issues affecting morbidity, mortality, and recurrence of disease are discussed. We review the literature of transplantation for specific interstitial lung diseases and the outcomes of transplantation for interstitial lung diseases. Candidates with idiopathic pulmonary fibrosis experience high mortality on the waiting list, but derive significant survival benefit from lung transplantation. Recurrence is reported for several interstitial lung diseases after lung transplantation. Survival with lung transplantation for interstitial lung diseases is comparable with that attained in recipients with other indications. Lung transplantation is a well-tolerated, effective therapy for respiratory failure in interstitial lung disease.

Flexible fiberoptic bronchoscopy in metastatic cancer to the lungs.

Seventy-eight patients with metastatic cancer to the lungs underwent flexible fiberoptic bronchoscopy for diagnosis. The patients were divided into two groups by presenting radiographic pattern as: (I) diffuse linear interstitial infiltrations (55 patients); and (II) localized or multiple nodular opacities (23 patients). The diagnosis of cancer was established by bronchoscopy in both groups of patients with approximately equal frequency. In Group I, bronchoscopic biopsy results were positive in 34 patients (62%), cytology results were positive in 30 patients (55%), and 42 patients (76%) had a positive biopsy and/or cytology result. In group II, biopsy results were positive in 14 patients (61%), cytology results were positive in 8 patients (35%), and 15 (65%) patients had a positive biopsy and/or cytology result. Patients whose chest radiograph showed atelectasis, suggesting the presence of endobronchial metastases, were excluded from the study. However, endobronchial examination unexpectedly revealed metastatic endobronchial carcinoma in 9 patients, 4 in Group I and 5 in Group II. Fiberoptic bronchoscopy is a relatively simple and direct technique for the histologic diagnosis of metastatic cancer to the lungs. Endobronchial metastases are common, even when not suspected by radiographic examination.

High cathepsin B activity in alveolar macrophages occurs with elastase-induced emphysema but not with bleomycin-induced pulmonary fibrosis in hamsters.

Cathepsin B activity was quantitated in alveolar macrophages obtained from hamsters 10, 21, and 105 days after the intratracheal instillation of porcine pancreatic elastase, bleomycin, or normal saline. Alveolar macrophages lavaged from animals receiving elastase contained significantly higher enzyme levels at 21 and 105 days (16,200 and 17,000 U/mg protein/hr, respectively) as compared with saline-treated animals (12,300 units). In contrast, cells from animals receiving bleomycin showed a decrease in activity at 21 and 105 days (9700 and 9900 units, respectively). At 10 days enzyme levels did not differ significantly. The results suggest that cathepsin B levels in alveolar macrophages reflect differences in lung destruction and connective tissue repair in vivo. In addition, the finding of high cathepsin B activity in animals with emphysema suggests the possibility that cysteine proteases contribute to progressive lung destruction initiated by the intratracheal instillation of elastase.