In vivo characterization of the novel ebolavirus Bombali virus suggests a low pathogenic potential for humans.

Ebolaviruses cause outbreaks of haemorrhagic fever in Central and West Africa. Some members of this genus such as Ebola virus (EBOV) are highly pathogenic, with case fatality rates of up to 90%, whereas others such as Reston virus (RESTV) are apathogenic for humans. Bombali virus (BOMV) is a novel ebolavirus for which complete genome sequences were recently found in free-tailed bats, although no infectious virus could be isolated. Its pathogenic potential for humans is unknown. To address this question, we first determined whether proteins encoded by the available BOMV sequence found in Chaerephon pumilus were functional in in vitro assays. The correction of an apparent sequencing error in the glycoprotein based on these data then allowed us to generate infectious BOMV using reverse genetics and characterize its infection of human cells. Furthermore, we used HLA-A2-transgenic, NOD-scid-IL-2γ receptor-knockout (NSG-A2) mice reconstituted with human haematopoiesis as a model to evaluate the pathogenicity of BOMV in vivo in a human-like immune environment. These data demonstrate that not only does BOMV show a slower growth rate than EBOV in vitro, but it also shows low pathogenicity in humanized mice, comparable to previous studies using RESTV. Taken together, these findings suggest a low pathogenic potential of BOMV for humans.

Antiviral activity of the natural alkaloid anisomycin against dengue and Zika viruses.

Flaviviruses constitute a public health concern because of their global burden and the lack of specific antiviral treatment. Here we investigated the antiviral activity of the alkaloid anisomycin against dengue (DENV) and Zika (ZIKV) viruses. At non-cytotoxic concentrations, anisomycin strongly inhibited the replication of reference strains and clinical isolates of all DENV serotypes and Asian and African strains of ZIKV in Vero cells. Anisomycin also prevented DENV and ZIKV multiplication in human cell lines. While initial steps of DENV and ZIKV replicative cycle were unaffected, a high inhibition of viral protein expression was demonstrated after treatment with anisomycin. DENV RNA synthesis was strongly reduced in anisomycin treated cultures, but the compound did not exert a direct inhibitory effect on 2' O-methyltransferase or RNA polymerase activities of DENV NS5 protein. Furthermore, anisomycin-mediated activation of p38 signaling was not related to the antiviral action of the compound. The evaluation of anisomycin efficacy in a mouse model of ZIKV morbidity and mortality revealed that animals treated with a low dose of anisomycin exhibited a significant reduction in viremia levels and died significantly later than the control group. This protective effect was lost at higher doses, though. In conclusion, anisomycin is a potent and selective in vitro inhibitor of DENV and ZIKV that impairs a post-entry step of viral replication; and a low-dose anisomycin treatment may provide some minimal benefit in a mouse model.

Modular branched neurotensin peptides for tumor target tracing and receptor-mediated therapy: a proof-of-concept.

The aim of this study was to demonstrate that oligo-branched peptides can be effective either for spotlighting tumor cells that overexpress peptide receptors, or for killing them, simply by exchanging the functional moiety coupled to the conserved receptor-targeting core. Tetra-branched peptides containing neurotensin (NT) sequence are described here as selective targeting agents for human colon, pancreas and prostate cancer. Fluorophore-conjugated peptides were used to measure tumor versus healthy tissue binding in human surgical samples, resulting in validation of neurotensin receptors as highly promising tumor-biomarkers. Drug-armed branched peptides were synthesized with different conjugation methods, resulting in uncleavable adducts or drug-releasing molecules. Cytotoxicity on human cell lines from colon (HT-29), pancreas (PANC-1) or prostate (PC-3) carcinoma indicated branched NT conjugated with MTX and 5-FdU as the most active agents on PANC-1 (EC(50) 4.4e-007 M) and HT-29 (1.1e-007 M), respectively. Tetra-branched NT armed with 5-FdU was used for in vivo experiments in HT-29-xenografted mice and produced a 50% reduction in tumor growth with respect to animals treated with the free drug. An unrelated branched peptide carrying the same drug was completely ineffective. In vitro and in vivo results indicated that branched peptides are valuable tools for tumor selective targeting.

Response of small cell carcinoma of pancreas to a small cell lung cancer regimen: a case report.

Small cell carcinoma of the pancreas is a very rare malignancy with 18 cases reported in the literature, of which only 3 were treated with chemotherapy. A 52-year-old man was diagnosed with small cell carcinoma originating in the head of the pancreas and invading the duodenum. He was treated with a similar approach as for localized small cell lung cancer, with six cycles of combination chemotherapy and local radiotherapy, and went into complete remission. After 3 months, he developed liver metastases along with an enlarged left supraclavicular lymph node. He was treated with two cycles of CVA, but developed lung metastases and was treated with ifosfamide/mesna. However, his overall condition deteriorated and hospice care was instituted until the patient's demise. The patient survived 14 months following diagnosis, significantly longer than the 15 reported patients with small cell pancreatic carcinomas not treated with chemotherapy. Combination chemotherapy and radiation therapy as it is utilized for small cell lung cancer appear to be beneficial for small cell carcinoma of the pancreas.

The incidence of multifocal renal cell carcinoma in patients who are candidates for partial nephrectomy.

PURPOSE: A prospective study was performed to determine the incidence of multifocal renal cell carcinoma in patients who are candidates for partial nephrectomy. MATERIALS AND METHODS: Preoperative imaging studies and surgical specimens in 44 patients suitable for partial nephrectomy but undergoing radical nephrectomy were prospectively reviewed. RESULTS: Of 44 renal cell cancers 11 (25%) demonstrated pathological multifocality, while 10 of 11 multifocal tumors (91%) occurred in the face of a primary tumor 5 cm. or smaller. Tumor multifocality was independent of the size of the primary renal tumor but occurred with a slightly higher frequency in tumors of stage T3A or greater even if the primary tumor was small. CONCLUSIONS: Partial nephrectomy in patients with unilateral renal cancer should be approached with caution and should not be performed simply because it is technically feasible.

Image-directed percutaneous biopsy with large-core needles. Comparison of cytologic and histologic findings.

Large biopsy needles (18 and 19 gauge) have been reported to yield high-quality tissue cores for reliable histologic diagnosis. In our institution, image-directed percutaneous biopsy specimens obtained with these needles are processed routinely for simultaneous cytologic and histologic analysis. For the present study, we reviewed our experience with 82 such biopsies of the thoracoabdominal region. We examined the value of cytologic analysis as a supplement to histologic analysis of such biopsies in terms of diagnostic yield and sensitivity for detecting malignancy. Among the 82 specimens, material was adequate for histologic diagnoses in 70 (85%) and for cytologic diagnosis in 63 (77%). Combining the histologic and cytologic results increased the diagnostic yield to 93% (76 of 82 specimens). Forty-eight lesions were diagnosed as malignant by either one or both means of analysis. While histologic analysis produced 44 of the 48 positive results (92%), cytologic analysis produced 33 (66%) (P < .05, McNemar's test). Because tissue fragments were selected preferentially for histologic processing, histologic evaluation was more valuable than cytologic evaluation in achieving definitive diagnoses of malignancy. In spite of this bias in preparation technique, malignancy was diagnosed by cytologic analysis alone in 4 of the 48 positive cases (8%). We conclude that the combined approach of histologic and cytologic examination of large-gauge core needle biopsy specimens maximizes the diagnostic yield and sensitivity for detecting malignancy.

Abdominal manifestations of sarcoidosis. CT appearances.

Sarcoidosis frequently involves the abdomen, although imaging studies often fail to demonstrate disease. The most common computed tomography (CT) findings in abdominal sarcoidosis are hepatosplenomegaly and retroperitoneal adenopathy, followed by focal low-attenuation lesions of the liver and spleen. Other abdominal viscera are involved infrequently. We present four cases of abdominal sarcoidosis demonstrating a range of CT findings.

AIDS-related cholangiopancreatographic changes.

The cholangiographic and pancreatographic appearances of the acquired immunodeficiency syndrome (AIDS) associated cholangitis were evaluated in 26 patients. Twenty-four patients were diagnosed by retrograde cholangiography or endoscopic cholangiopancreatography (ERC or ERCP). One patient was diagnosed by T-tube cholangiography and another patient by transhepatic cholangiography. The radiographic findings ranged from intrahepatic ductal abnormalities with or without involvement of the extrahepatic biliary tree (eight patients) to irregularities and strictures involving the ampulla of Vater or the intrapancreatic portion of the common bile duct (CBD) with proximal dilatation (18 patients). Significant strictures involving the juxta-ampullary pancreatic duct were identified in six of 12 patients. Twenty-one of the 26 patients had associated infections which included: Cryptosporidium (CS), Mycobacterium avium intracellulare (MAI), cytomegalovirus (CMV), Microsporidium (MSP), and Isospora (ISP). Three patients were operated upon for acute acalculous cholecystitis. In each instance, organisms were identified in both the bile duct and the inflamed gallbladder.

A comparison of iopromide with iopamidol and iohexol for contrast-enhanced computed tomography.

RATIONALE AND OBJECTIVES: Iopromide is a new monomeric, nonionic contrast agent that exhibits low osmolality and low viscosity in high concentration in aqueous solutions. Double-blind, randomized clinical trials have established the efficacy, safety, and tolerance of iopromide for excretory urography, coronary angiography, routine and digital subtraction angiography, and phlebography. However, iopromide had not previously been evaluated in blinded clinical trials for contrast-enhanced computed tomography (CECT). Thus, a double-blind, prospective randomized trial was performed to compare the efficacy, safety, adverse experience profile, and tolerance of iopromide to that of iopamidol and iohexol in patients requiring CECT of the head or body. METHODS: Of 190 patients entered into the study, 95 received iopromide and 95 received a comparator (iopamidol, n = 55; and iohexol, n = 40) at 300 mg I/mL. Efficacy, adverse experiences (AEs), and tolerance were measured, and a safety profile was obtained that monitored changes at 24 hours in physical examination, vital signs, hematologic profile, and blood chemistries. RESULTS: Efficacy was similar for all drugs with excellent/good visualization in 98.4% of studies. The total number of patients reporting AEs was equivalent (iopromide 13.8%, comparators 12.6%; P > .10). However, although 2.5% of patients in the iopromide and iopamidol groups had possibly related mild AEs, 15% receiving iohexol had related AEs, one of which was severe. Excellent tolerance was noted, with no patients reporting localized pain; there were low rates of mild to moderate warmth on injection (8.5% for iopromide versus 9.5% for comparators; P > .10). Safety profiles were comparable. Postprocedure, there were no significant changes or significant differences between groups, except for a significantly increased incidence of systolic blood pressure decrease by greater than 20 mm Hg at 24 hours in the comparator group. CONCLUSIONS: Iopromide has an efficacy, safety, and tolerance profile comparable to that of iopamidol and iohexol at 300 mg I/mL for head and body CECT. It may have a superior adverse experience profile to iohexol, but is similar to iopamidol. Thus, iopromide is a reasonable choice of nonionic contrast medium for all CECT procedures.

Tc-99m DISIDA hepatobiliary scintigraphy in AIDS cholangitis.

Sixteen patients with documented AIDS cholangitis who underwent Tc-99m DISIDA hepatobiliary scintigraphy were retrospectively reviewed to assess the spectrum of changes observed in this disease. AIDS cholangitis was documented by either ERCP with aspiration/biopsy or the presence of typical sonographic/CT abnormalities with positive stool culture and a minimum of 6 months follow-up. Images were graded as regards parenchymal function (blood pool clearance, peak parenchymal activity, and degree of parenchymal retention), gallbladder visualization, presence of ductal dilatation, and time of intestinal activity. Three patterns were identified: 1) focal ductal dilatation with focal narrowing and focal or diffuse parenchymal retention; 2) ductal dilatation, without narrowing, and diffuse parenchymal retention; and 3) severe diffuse parenchymal retention with or without ductal abnormality. All 16 studies revealed abnormal parenchymal retention. Gallbladder nonvisualization was demonstrated in nine studies and delayed in two. The hepatobiliary scan is a very sensitive technique for evaluating AIDS cholangitis. Although a spectrum of findings may be observed, parenchymal retention with some degree of ductal abnormality is the most commonly observed pattern.

Hepatic SPECT imaging in the detection and clinical assessment of hepatocellular disease.

A total of 95 patients, including 45 people with no evidence of liver disease and 50 documented hepatocellular disease patients, were studied to assess the value of planar and SPECT scintigraphy in the evaluation of hepatocellular disease. The accuracy and concordance between techniques was assessed using two criteria. Criterion 1, heterogeneity of the tracer in liver, yielded a concordance of 64%, whereas with criterion 2, liver and spleen tracer pattern, concordance was 78%. SPECT was significantly more accurate than planar imaging (P < 0.01), using both criteria. The clinical severity of the hepatocellular disease was further assessed in 72 of the patients and correlated with a liver scan severity rating scale. The SPECT technique showed a good correlation (r = 0.89) with the composite clinical severity score; however, no significant relationship with planar imaging was noted. The results of this study suggest that liver SPECT is a reliable technique for the assessment of hepatocellular disease.

The value of SPECT imaging in the diagnosis of hepatic hemangioma.

Radionuclide flow studies, planar, and SPECT hepatic blood pool imaging were performed in 23 patients with 39 hepatic hemangiomas, 23 patients with primary and secondary liver tumors, 12 patients with hepatocellular disease, two patients with hepatic cysts, and 10 patients with no evidence of liver disease. The hepatic SPECT imaging identified all 39 hemangiomas as having a sequestration pattern compared with a yield of 69% (27 of 39 cases) for the planar imaging. None of the 47 other patients demonstrated this pattern. The SPECT approach is considered superior to planar blood pool imaging because of improved diagnostic yield, reduced patient imaging time, and greater ease of correlation with other cross-sectional imaging modalities.

Single photon emission computed tomography and transmission computed tomography in the evaluation of liver disease.

To assess the relative strengths of hepatic SPECT and transmission computed tomography (TCT), a comparison of these methods was made in 88 patients during a 20-month period. The scans were classified into four categories: normal, solitary focal, multifocal, or diffuse hepatocellular patterns. The final disease category was determined by histologic evaluation-biopsy/autopsy, surgery, or a combination of ultrasound, laboratory, and clinical follow-up for a minimum of 6 months. Both SPECT and TCT were normal in the 47 patients classified as normal. Of the 16 patients with diffuse hepatocellular disease, SPECT correctly identified 16 and TCT identified two patients. Eleven patients had solitary focal disease; 11 were detected by SPECT and 10 by TCT. Fourteen patients were in the multifocal disease group; 13 were detected by SPECT and 10 by TCT. Overall, SPECT and TCT findings were in agreement in 68 (77%) of the cases. This study demonstrates that SPECT is equal to TCT in the assessment of the liver parenchyma in normal and focal disease states and that SPECT is superior in the assessment of diffuse disease.

Abdominal SPECT imaging.

Over the past several years, abdominal single photon emission computed tomography (SPECT) imaging has evolved from a research tool to an important clinical imaging modality that is helpful in the diagnostic assessment of a wide variety of disorders involving the abdominal viscera. Although liver-spleen imaging is the most popular of the abdominal SPECT procedures, blood pool imaging is becoming much more widely utilized for the evaluation of cavernous hemangiomas of the liver as well as other vascular abnormalities in the abdomen. Adjunctive indium leukocyte and gallium SPECT studies are also proving to be of value in the assessment of a variety of infectious and neoplastic diseases. As more experience is acquired in this area, SPECT should become the primary imaging modality for both gallium and indium white blood cells in many institutions. Renal SPECT, on the other hand, has only recently been used as a clinical imaging modality for the assessment of such parameters as renal depth and volume. The exact role of renal SPECT as a clinical tool is, therefore, yet to be determined.

Preoperative detection of gallbladder perforation.

Tc-99m-hepatobiliary imaging is an excellent tool for noninvasive investigation of biliary tract perforation. This article documents a case in which this imaging method was employed to establish a preoperative diagnosis of gallbladder perforation.

Delayed intracerebral hemorrhage as demonstrated by CT scanning.

Three patients are presented who developed delayed intracerebral hematomas after head injury. Two patients had essentially negative CT scans on admission and developed intracerbral hematomas within 24 h after injury. They required surgical treatment and had fatal outcomes. The third patient presented with an epidural hematoma on CT scan, developed an intracerebral hematoma 48 h after evacuation of the epidural hematoma, and did well with conservative management.