MIP-1 alpha and MIP-1 beta induction by dengue virus.

Dengue virus (DV) infection can result in either a mild febrile illness known as dengue fever (DF) or a life-threatening disease called dengue hemorrhagic fever (DHF). DHF is more prevalent in patients undergoing secondary DV infection. This observation has led to the hypothesis that DHF may be the result of immune reactions to the secondary DV infection; an event termed immunopathology. Two cellular factors, MIP-1 alpha and MIP-1 beta, have been found to be induced by infection with DV. MIP-1 induction by DV infection was observed in a myelomonocytic cell line, as well as in peripheral blood mononuclear cells isolated from a dengue naive donor. MIP-1 induction was not due to factors secreted by infected cells. In fact, replication-competent virus was required to induce MIP-1. Evidence is also provided that MIP-1 genes are expressed in patients with dengue disease. It is hypothesized that these chemokines may have roles in the immunopathology of dengue infections and may contribute to fever and bone marrow suppression observed in patients with DV infections.

Intrathoracic granulocytic sarcomas.

Recent trends in the treatment of intrathoracic granulocytic sarcoma (IGS) call for an overview of its radiographic manifestations. Nine patients from our institution and a review of 41 from the literature provide the basis of our conclusions on the typical and atypical appearance of IGS. Of the nine patients with IGS, all had chest radiographs, five had computed tomographic (CT) scans, and one had magnetic resonance (MR) scans. Radiographic studies and medical records were examined to establish the site and appearance of IGS. Three cases were histologically proved; in the others, the diagnosis was based on clinical presentation and response to chemotherapy. The mediastinum was the most common site of involvement (six of nine cases). A focal mass or mediastinal widening was visible on chest radiographs, and a focal mass or diffuse infiltration or replacement of fat was visible on chest CT. Less common sites of involvement were the lungs (two cases), the pleura (two), the pericardium (two), and the hilar (two). Mediastinal or hilar mass or mediastinal widening is the characteristic finding in IGS. Less common manifestations such as pleural and pericardial effusions and lung opacities should be confirmed histologically, since fluid or tissue is readily accessible.

Pulmonary lymphangitic carcinomatosis: chronicity of radiographic findings in long-term survivors.

OBJECTIVE: Long-term survival after development of pulmonary lymphangitic carcinomatosis is considered unusual. However, modern chemotherapy can result in surprising stability or only gradual progression of lymphangitic carcinomatosis. We evaluated the course of radiographic findings in 10 patients with chronic lymphangitic carcinomatosis. MATERIALS AND METHODS: Ten patients met our criterion of having lymphangitic carcinomatosis for at least 6 months. The primary tumor was a carcinoma of the breast in six cases, the ovary in two, the pancreas in one, and the skin in one. Serial radiographs (all cases) and CT scans (eight cases) were analyzed retrospectively. RESULTS: Survival with lymphangitic carcinomatosis ranged from 11 to 30 months (median, 13 months). With chemotherapy, the radiographic abnormalities and pulmonary symptoms initially regressed in six patients, progressed in two, and remained unchanged in two; the radiographic findings of lymphangitic carcinomatosis were progressing at the time of death in four patients. All patients had periods of at least 4 months of relative stability or slow progression of pulmonary radiographic abnormalities. Serial transbronchial biopsies in one case confirmed persistent lymphangitic carcinomatosis despite therapy, and autopsy disclosed persistent lymphangitic tumor in two others. CONCLUSION: Stability or slow progression of radiographic findings can occur in some patients with lymphangitic carcinomatosis. Therefore, chronicity of radiographic findings should not be taken as evidence against lymphangitic carcinomatosis as the cause of an interstitial abnormality in a patient with cancer.

Opioidergic, serotonergic, and dopaminergic manipulations and rats' intake of a sweetened alcoholic beverage.

Groups of rats were maintained on a daily regimen of 22 h of water deprivation followed by a 2-h opportunity to take either water or a sweetened ethanol solution (ES). In one experiment, it was shown that previous morphine (M) dependence had no effect on initial daily intakes of fluids. After stable ES intakes were achieved, a variety of pharmacological manipulations were assessed for their effects on intake of the ES. Nalmefene, an opioid antagonist, dose-relatedly decreased intakes of ES, and was effective across days of injections. Fluoxetine (FX), a serotonergic reuptake inhibitor, also reduced ES intakes dose relatedly, and across days of injections, but the reduction was not as great as that seen with opioid antagonists. A small dose of M increased ES intakes when given in combination with an ineffective dose of FX, just as it does by itself. However, M had no effect on ES intakes in combination with an effective dose of FX. Pimozide (PIM), a dopaminergic antagonist, dose-relatedly decreased intakes of ES and water, and responding for positively reinforcing intracranial stimulation (ICS). When given in combination, M blunted PIM's reduction of ES intake, but had no effect on PIM's ability to decrease either intake of water or responding for ICS. Amphetamine did not reliably affect rats' intakes of ES across a range of doses. The data, in addition to previous work, lead to the idea that endogenous opioid systems are more salient, with respect to intake of alcoholic beverages, than the other tested neurotransmitter systems. Furthermore, the collective data suggest that a long-lasting opioid antagonist may be an effective pharmacological adjunct to other treatments for alcohol abuse and alcoholism.

Using antagonists to assess neurochemical coding of a drug's ability to establish a conditioned place preference.

Rats were given morphine as an agent of putative conditioning to establish a place preference. Doses of 4 and 8 mg/kg of morphine did establish reliable conditioned place preferences (CPP's). Other rats were given one of the doses of morphine and one of a number of antagonists in procedures designed to assess which antagonists would specifically block morphine's ability to establish a CPP indicative of positivity. Doses of naloxone and larger doses of naltrexone but not smaller ones did antagonize morphine's effects. A dose of the benzodiazepine antagonist Ro 15-1788 did not attenuate morphine's effects. It was concluded that morphine's positivity is dependent upon actions by way of receptors sensitive to naloxone and naltrexone, but that morphine's positivity is less sensitive to naltrexone's effects than morphine's analgesia.

Diagnostic imaging in the initial staging of mycosis fungoides and Sézary syndrome.

Four imaging examinations-gallium citrate Ga 67 scintigraphy, liver-spleen scans, lymphangiography, and computed tomography-were used in the initial staging of mycosis fungoides and Sézary syndrome in 62 patients (85% with stage I or II disease). None of the imaging modalities added significantly to the information already available from physical examinations and routinely performed lymph node biopsies. The results of this investigation did not support routine performance of imaging studies in patients with early stages of cutaneous T-cell lymphoma.

Preliminary experience with portable digital imaging for intensive care radiography.

A digital radiography system based on reusable, photostimulable phosphor technology was evaluated in approximately 3,500 portable chest radiographs of patients in an intensive care unit. The system functioned well in this application. No major problems were encountered in the visualization of tubes or catheters or in the detection of pneumothoraces. Assessment of fluid volume status or the presence of small pleural effusions, especially when these were bilateral, was initially somewhat difficult but became easier as investigators became familiar with the system. Radiologists were quicker than nonradiologists to accept the minimized two-on-one display format. Critical evaluation of the overall performance of digital systems such as this one is needed for a better definition of the system's strengths and weaknesses. Specifically, statistical analyses of the ability to detect disease states such as pneumothoraces, interstitial lung disease, lung nodules, and pleural abnormalities need to be performed.

Measuring morphine's capacity to establish a place preference.

A series of experiments are described providing an assessment of the procedures of conditioned place preference (CPP) testing involving an automated system having 12 separate chambers. Experiment 1 provides data to demonstrate (a) that in these chambers no initial preferences for one side over the other exists among rats, (b) that this neutrality of sides is not affected by session lengths between 15 and 60 min, and (c) that the optimal session length for tests in these chambers is on the order of 30 min. Experiment 2 demonstrates the stability of control groups' scores across a number of conditioning and testing sessions. Experiments 3 and 4 provide data to demonstrate (a) that a positive CPP can be established in our chambers using injections of morphine, (b) that a regimen of dosing with unequal numbers of days of putative and alternate conditioning is a reliable and conservative test of the opioid's ability to establish a CPP, and (c) that although the activity of rats decreases across a session, the general activity of rats before and after conditioning procedures is the same. Experiment 5 replicates the procedures employed by Scoles and Siegel (25) and demonstrates that the tendency for rats to explore novel environments is strong, and care must be taken to provide an opportunity for rats to pair different experiences with each side of the chamber in order for a CPP to emerge.

PCP and conditioned place preferences.

Phencyclidine (PCP), in doses of 0.25, 0.35, and 0.45 mg/kg, was administered systemically to male Sprague-Dawley rats in order to determine if a positive conditioned place preference (CPP) could be achieved. Other subjects received systemic injections of morphine, 4.0 mg/kg, as a standard for comparison. At testing, rats receiving 0.45 mg/kg PCP showed a positive CPP compared to controls, as did rats receiving morphine. Previous research had shown that larger doses of PCP and prolonged times after PCP administration produced aversion as indexed by CPP testing. The narrow dose range and short time span in which PCP's positively reinforcing properties are apt to emerge may be related to PCP's psychotomimetic potential and to its ability to sustain its own intake even though aversive effects are often manifest.

Ethanol with small doses of morphine establishes a conditioned place preference.

Conditioned place preference (CPP) testing is a way of indexing the reinforcing efficacy of drugs among rats. CPP testing involves using an alley with two distinctive sides. Typically, rats have drug experiences on one side and placebo experiences on the other. At testing, without drugs, their preference for side is tabulated. Rats' (6 groups of 12 each) place preferences were assessed before and after they were placed, once a day for 9 days, in the putative side of conditioning, and on 3 interspersed days, in the other side. During putative conditioning, one group received saline prior to being placed in both sides (a control group). Two groups had either morphine (2.0 mg/kg) or ethanol (0.5 g/kg) with the putative side of conditioning and saline with the other side. Three groups received morphine plus ethanol before being placed in the putative side of conditioning and either saline, morphine, or ethanol in the other side. At testing, rats that received morphine plus ethanol on side of putative conditioning showed a strong CPP whereas others did not. Results are compatible with the idea that ethanol's reinforcing effect is enhanced when there is a surfeit of opioidergic activity.

A small dose of morphine increases intake of and preference for isotonic saline among rats.

Water-deprived rats were given hourly opportunities to ingest physiological saline and water for a number of days until they were taking substantial amounts of both solutions. Prior to some opportunities to ingest, they were injected with either morphine (2.0 mg/kg) or a placebo. Across a variety of procedures, morphine increased intake of and, in 1-hr tests, increased preference for 0.9% NaCl. Intake of 1.5% NaCl also increased after administration of morphine. These data suggest that endogenous opioids are involved in sodium intake. These data also provide further support for the idea that one or more of the endogenous opioid systems are involved in the regulation of ingestion.

Radiologic investigation of thoracic metastases from unknown primary sites.

When a patient presents with thoracic metastases from a tumor whose site of origin is not apparent from the initial history, physical examination, and routine laboratory studies, there is a considerable likelihood that the individual will be subjected to an extensive and frequently unrewarding series of radiologic examinations. An analysis of the "behavior" of so-called tumors of unknown origin suggests that these tumors metastasize to distant sites with a frequency that is different from the more common tumors, that is to say, those whose primary site is readily apparent. While compulsive testing should unquestionably be eschewed, certain radiologic tests are still appropriate. These studies should be supplemented, when necessary, by newer pathologic studies, primarily those that involve the rapidly developing field of immunocytochemistry.

Preservation of normal lung regions in the adult respiratory distress syndrome. Analysis by computed tomography.

In this report, we challenge the commonly held assumption that the adult respiratory distress syndrome (ARDS) is a homogeneous process associated with generalized and relatively uniform damage to the alveolar capillary membrane. We studied 13 patients with ARDS, comparing the pulmonary parenchymal changes seen by standard bedside chest roentgenograms with those seen by computed tomography of the chest. Three patients demonstrated generalized lung involvement by both radiologic techniques. In another eight patients, despite the appearance of generalized involvement on the standard chest x-ray film, the computed tomographic scans showed patchy infiltrates interspersed with areas of normal-appearing lung. Two patients showed patchy involvement by both techniques. The fact that ARDS spares some regions of lung parenchyma is useful knowledge in understanding the gas-exchange abnormalities of ARDS, the variable responsiveness to positive end-expiratory pressure, and the occurrence of oxygen toxicity. The problem of regional inhomogeneity should also be kept in mind when interpreting lung biopsy specimens or bronchoalveolar lavage fluid in patients with ARDS.

Radiologic assessment of head trauma.

We have endeavored through the use of an actual clinical scenario to emphasize that reliance on skull radiographs for assessing the acutely traumatized patient is both unwarranted and unwise. Not only are these films fundamentally useless, but they have the potential to lull us into a false sense of security. A negative skull examination cannot and does not imply that the brain substance is normal. If there is a legitimate indication for any examination, that examination should be computed tomography. To reinforce this notion, we offer for your consideration the following algorithm for the management of head trauma (Table 1: see text).