Single-energy non-contrast hepatic steatosis criteria applied to virtual non-contrast images: is it still highly specific and positively predictive?

AIM: To determine the sensitivity, specificity, and predictive values of single-energy non-contrast hepatic steatosis criteria on dual-energy virtual non-contrast (VNC) images. MATERIALS AND METHODS: Forty-eight computed tomography (CT) examinations, which included single-energy non-contrast (TNC) and contrast-enhanced dual-energy CT angiography (CTA) of the abdomen, were enrolled. VNC images were reconstructed from the CTA. Region of interest (ROI) attenuations were measured in the right and left hepatic lobes, spleen, and aorta on TNC and VNC images. The right and left hepatic lobes were treated as separate samples. Steatosis was diagnosed based on TNC liver attenuation of ≤40 HU or liver attenuation index (LAI) of ≤-10 HU, which are extremely specific and predictive for moderate to severe steatosis. The sensitivity, specificity, and predictive values of VNC images for steatosis were calculated. VNC-TNC deviations were correlated with aortic enhancement and patient water equivalent diameter (PWED). RESULTS: Thirty-two liver ROIs met steatosis criteria based on TNC attenuation; VNC attenuation had sensitivity, specificity, and a positive predictive value of 66.7%, 100%, and 100%, respectively. Twenty-one liver ROIs met steatosis criteria based on TNC LAI. VNC LAI had sensitivity, specificity, and positive predictive values of 61.9%, 90.7%, and 65%, respectively. Hepatic and splenic VNC-TNC deviations did not correlate with one another (R2=0.08), aortic enhancement (R2<0.06) or PWED (R2 <0.09). CONCLUSIONS: Non-contrast hepatic attenuation criteria is extremely specific and positively predictive for moderate to severe steatosis on VNC reconstructions from the arterial phase. Hepatic attenuation performs better than LAI criteria. VNC deviations are independent of aortic enhancement and PWED.

Cannabidiol reduces lesion volume and restores vestibulomotor and cognitive function following moderately severe traumatic brain injury.

Despite the high incidence of traumatic brain injury (TBI), there is no universal treatment to safely treat patients. Blunt brain injuries destroy primary neural tissue that results in impaired perfusion, excessive release of glutamate, inflammation, excitotoxicity, and progressive secondary neuronal cell death. We hypothesized that administration of cannabidiol (CBD) directly to a brain contusion site, will optimize delivery to the injured tissue which will reduce local neural excitation and inflammation to spare neural tissue and improve neurological outcome following TBI. CBD was infused into a gelfoam matrix forming an implant (CBDi), then applied over the dura at the contusion site as well as delivered systemically by injection (CBD.IP). Post-injury administration of CBDi+IP greatly reduced defecation scores, lesion volume, the loss of neurons in the ipsilateral hippocampus, the number of injured neurons of the contralateral hippocampus, and reversed TBI-induced glial fibrillary acidic protein (GFAP) upregulation which was superior to either CBD.IP or CBDi treatment alone. Vestibulomotor performance on the beam-balance test was restored by 12 days post-TBI and sustained through 28 days. CBDi+IP treated rats exhibited preinjury levels of spontaneous alternation on the spontaneous alternation T-maze. In the object recognition test, they had greater mobility and exploration of novel objects compared to contusion or implant alone consistent with reduced anxiety and restored cognitive function. These results suggest that dual therapy by targeting the site of injury internally with a CBD-infused medical carrier followed by systemic supplementation may offer a more effective countermeasure than systemic or implant treatment alone for the deleterious effects of penetrating head wounds.

Isolation and characterization of an immortal neoplastic cell line (KS Y-1) from AIDS-associated Kaposi's sarcoma.

BACKGROUND: Acquired immunodeficiency syndrome (AIDS) is associated with the occurrence of tumors such as Kaposi's sarcoma (KS) and B-cell lymphoma. However, no evidence exists yet that human immunodeficiency virus type 1, the causative agent of AIDS, is directly responsible for cell transformation. It is also not clear whether KS lesions, which are of complex cellularity, contain tumor cells derived from a true monoclonal malignancy (originating from a single malignant cell) or whether the lesions are just polyclonally hyperplastic in nature (containing increased numbers of normal cells). In fact, the presence of malignant KS cells has never been unequivocally shown in AIDS-associated KS, and previously isolated KS cell cultures were not immortal or malignant. PURPOSE: Our purpose was to (a) utilize technology that could facilitate isolation and enrichment of tumor cells from AIDS-associated KS lesions, (b) establish and characterize an immortalized KS cell line, and (c) test the malignant potential of such a cell line in animal models. METHODS: Mononuclear cells were isolated from 2.5 L of pleural effusion from an AIDS-associated KS patient. T-lymphocytes, B-lymphocytes, monocytes/macrophages, and fibroblasts were removed by a cytotoxicity method, using monoclonal antibodies specific for cell surface markers and baby rabbit complement. KS cells were cultured in the absence of exogenous growth factors in an effort to select for transformed cells capable of self-sustained growth. The karyotype abnormalities were detected by G-banded marker studies, and phenotypic markers were determined by indirect immunofluorescence and immunocytochemical methods. Beige nude XID and severe combined immunodeficient mice were used to evaluate the tumorigenic, angiogenic, and metastatic potentials of cells. RESULTS: An immortalized cell line, named KS Y-1, was isolated. Its phenotype is similar to that of endothelial cells with positive CD34 and CD31 markers. Tetraploid chromosomal abnormalities were found in primary fresh KS tissue and in vitro passages of KS Y-1 cells. These cells promoted tumorigenesis, angiogenesis, and metastasis in immunodeficient mice. Tumors produced at the site of injection as well as metastases in the lung, spleen, pancreas, gastrointestinal tract, and skin showed a human tetraploid karyotype. KS Y-1 cells show high plating efficiency. CONCLUSION: The KS Y-1 cell line could be the first evidence of AIDS-associated KS cells that may develop clones with an indisputable malignant cell phenotype. IMPLICATIONS: KS Y-1 cells in the in vivo mouse model can be used to study the effects of therapeutic compounds in advanced KS.

Renal mass imaging: the internist's role.

The busy internist will encounter numerous renal masses when ordering nonurologic imaging. Concise and quick delineation of cystic from solid masses is necessary. Cystic masses constitute the majority of these masses and once their nature is diagnosed, they require no further work-up or referral. Often, a single imaging technique is unable to confidently establish the cystic nature of a renal mass. Proper selection of an additional imaging modality will often be successful in establishing the cystic characteristics of a benign mass. Referral to a urologist is not necessary in this setting, since the internist can coordinate the imaging evaluation with proper radiologic consultation. Alternatively, when a mass is determined to be solid, urologic consultation and surgical evaluation are necessary. Minimization of the imaging sequence and hospitalization are critical in the diagnostic-related group era. Aimless wandering in the quagmire of imaging techniques is very expensive and nonproductive. Proper selection of one or two imaging tools and occasionally needle puncture should produce clarification of the cystic or solid nature of renal mass. On the basis of our experience, we have designed an imaging algorithm that provides a simple and concise approach to the diagnosis of a renal mass. It differs in design from that previously suggested by us and others because of decreased emphasis on nuclear medicine and greater emphasis on computed tomography. The more pivotal position assumed by computed tomography is based on improved scanner design and several large series attesting to the accuracy and cost-effectiveness of this imaging technique. It behooves internists to appreciate the role of various imaging tools in evaluating a renal mass. With radiologic consultation, internists should strive to confidently establish the cystic nature of a renal mass and to refer to a urologist solid masses or those whose nature remains persistently equivocal.

The value of bowel preparation in Ga-67 citrate scanning: concise communication.

In order to assess the value of bowel preparation in Ga-67 citrate scanning, we retrospectively analyzed 156 randomly selected 72-hr Ga-67 scans and compared the extent of bowel activity in two groups of patients: those receiving a vigorous 3-day bowel preparation and those receiving no preparation. The populations were studied with regard to age, sex, and bowel preparation. A three-way analysis of variance (prep X sex X age) revealed no influence of these parameters on the degree of colonic gallium activity. We conclude that bowel preparation as used at our institution did not seem to reduce colonic gallium content significantly (p greater than 0.10).

Tc-99m HIDA cholescintigraphy: the distended photon-deficient gallbladder.

Four patients with distended, photon-deficient gallbladders are presented. Markedly delayed apearance of Tc-99m HIDA in a distended gallbladder may represent chronic cholecystitis, partial obstruction of the common bile duct, or physiologic gallbladder distention. Obtaining delayed images is important in this group of patients to avoid premature diagnosis of cystic-duct obstruction. If the distended gallbladder fails to visualize within 24 hr, hydrops with cystic-duct obstruction is suggested.

Tc-99m HIDA scintigraphy in segmental biliary obstruction.

Segmental biliary obstruction as a result of primary or secondary hepatic malignancy has been reported with increasing frequency. For two representative patients, the clinical and Tc-99m HIDA scintigraphic findings in segmental biliary obstruction are described. The presence of photon-deficient dilated bile ducts in one segment of the biliary tree is highly suggestive of localized biliary obstruction and should be considered in the patient with suspected or proven hepatic malignancy despite the absence of jaundice.

Improved detection of small cavernous hemangiomas of the liver with high-resolution three-headed SPECT.

The purpose of this study was to review our experience with 99mTc-red blood cell scintigraphy for diagnosis of cavernous hemangiomas of the liver using a new three-headed, high-resolution dedicated SPECT system. Of 19 patients referred with a total of 38 lesions seen on CT, US, or MRI, 14 patients had 24 lesions that were hemangioma-positive with SPECT (all true-positives). Six of these 14 patients also had 9 hemangioma-negative lesions; all were less than or equal to 1.3 cm in size and false-negative. The remaining five patients had hemangioma-negative lesions only (1 false-negative, 4 true-negatives). Two hemangiomas were seen by SPECT that were not detected by CT, US, or MR. The sensitivity for hemangiomas greater than or equal to 1.4 cm. was 100% (20/20). The sensitivity was 33% for lesions 0.9-1.3 cm, and 20% for lesions less than or equal to 0.8 cm. The smallest hemangioma detected was 0.5 cm. These results show a definite improvement in sensitivity with high-resolution triple-headed SPECT over previously reported results using single-headed SPECT. High-resolution SPECT has improved our ability to detect small cavernous hemangiomas of the liver.

Antisense phosphorothioate oligodeoxynucleotides alter HIV type 1 replication in cultured human macrophages and peripheral blood mononuclear cells.

The use of antisense oligodeoxynucleotides as antiviral drugs to combat HIV-1 infection may offer an alternative to traditional pharmacological therapies. We compared the effects of two 28-mer antisense phosphorothioate oligodeoxynucleotides [PS-oligo(dN)] with non-sequence-specific controls on HIV-1 replication in long-term human monocyte/macrophage and PBMC cultures. The anti-rev PS-oligo(dN) was complementary to the messenger RNA (mRNA) sequences derived from the overlapping region of the HIV-1 regulatory genes tat and rev, while anti-gag targeted the translational initiation site of the gag mRNA. In vitro cytotoxicity of the PS-oligo(dN) was evaluated at concentrations ranging from 0.1 to 10.0 microM for a period of 20 days. Cell survival was 100% at 0.1 microM, but decreased to 5% at 10.0 microM in relation to the untreated control cultures. Our data demonstrate that replication of both the T cell-tropic and macrophage-tropic HIV-1 strains in primary cells can be inhibited by PS-oligo(dN) in a sequence-specific and dose-dependent manner at concentrations achievable in vivo. However, the sequence-dependent antiviral activity of the utilized PS-oligo(dN) was limited to a window of specificity at concentrations between 0.25 and 1.0 microM.

Promoter elements and second messenger pathways involved in transcriptional activation of tyrosine hydroxylase by ionomycin.

Membrane depolarization, or agents which increase intracellular calcium, elicit transcriptional activation of tyrosine hydroxylase (TH). In this study we analyze the factors involved in the regulation of the TH promoter by a calcium ionophore. PC12 cells were transiently transfected with plasmids containing wild type or mutated 5' flanking sequences of the rat TH gene, fused to bacterial chloramphenicol acetyl transferase (CAT). Point mutations introduced into the consensus cAMP-regulatory element (CRE) abolished the induction of CAT by ionomycin indicating that it is essential for mediating the calcium response. An intact and functional AP1 site did not confer calcium inducibility when the CRE/CaRE sequence was mutated. The extent and kinetics of the increase in intracellular calcium as well as the induction of CAT activity under the control of TH promoter by ionomycin were similar in PC12 cells and in the A123.7, protein kinase A (PKA) deficient cell line. In both cell lines addition of ionomycin rapidly increased the phosphorylation of transcription factor CREB at Ser-133. These results suggest that the activation of TH transcription by ionomycin does not require PKA. However, KN62 an inhibitor of Ca2+/calmodulin dependent (CaM) kinases prevented the induction indicating possible involvement of CAM kinases in the calcium response.

Computed tomography appearance of a right cervical aortic arch.

The clinical diagnosis of cervical aortic arch rests on the detection of a pulsatile mass in the supraclavicular fossa. Unfortunately, clinical differentiation of a cervical arch from an aneurysm of the great vessels can be difficult. Dynamic computed tomography (CT) can aid in this differentiation and avert the need for angiography.

Computed tomographic cholangiography in a canine model of biliary obstruction.

The CT scanner was used to generate the time-density relationship for hepatic parenchyma following Iodipamide (Cholografin, E.R. Squibb Co., New York, N.Y.) infusion. The curves which resulted from the normal, acutely obstructed, and chronically obstructed biliary system are shown. The peak enhancement of parenchyma is seen to be blunted in acute obstruction prior to anatomic evidence of dilated ducts. This finding may be of value in the early diagnosis of obstructive jaundice.

Enhanced pancreatic CT imaging utilizing a geometric magnification technique.

Computed tomography (CT) using a geometric magnification technique was found to improve spatial resolution in phantom studies when compared with conventional third-generation geometry images. The clinical feasibility of using geometric magnification, small focal spot size, and dynamic contrast enhancement was studied in 143 patients referred to CT for clinically suspected pancreatic disease. This population included 46 patients with a normal pancreas and 36 patients subsequently proven to have primary pancreatic carcinoma. Using this new technique in conjunction with dynamic contrast enhancement resulted in high quality pancreatic images. Despite the limitations in tube current associated with a small focal spot size and low total heat capacity of the system, clinical imaging was not adversely affected. Use of the geometric magnification technique is recommended in departments where it is technically feasible.

Quantitative ultrasonic detection of parenchymal structural change in diffuse renal disease.

OBJECTIVE: The authors determined whether quantitative ultrasound could be useful in the evaluation of diffuse renal disease. METHODS: Digitized radiofrequency ultrasound data were acquired from the kidneys of patients with biopsy-proven diffuse renal disease and transplant rejection (37 patients plus 18 normal volunteers). The results of the quantitative analysis were compared with histology results to determine if microscopic renal structure could be correlated with quantitative features such as scatterer size and scatterer spacing. The results also were analyzed using receiver operating characteristic analysis to determine if diffuse disease could be detected reliably using quantitative methods. RESULTS: The three most useful features in the native kidneys were mean scatterer spacing (MSS), sigma's, and average scatterer size (D). Using these features, it was possible to detect diffuse renal disease causing a decrease in renal function with an area under the ROC curve (Az) of 0.93. The feature D corresponded closely to histologically measured average glomerular diameters. For normals, D = 216 microns and glomerular diameter = 211 microns. No histologic correlate was found for scatterer spacing. In transplants, MSS and integrated backscatter were most useful for detecting rejection (Az = 0.87), and D in rejection was similar to the values for normal kidney and normally functioning transplants. CONCLUSIONS: The D value corresponds to glomerular diameter, and glomerular enlargement can be detected readily using quantitative ultrasound. Combinations of two to four quantitative features can detect diffuse renal disease and transplant rejection reliably.

Oat cell carcinoma metastatic to ureter.

A rare and perhaps unique case of oat cell carcinoma metastatic to the ureter is presented.

Rhabdomyolysis: need for high index of suspicion.

Rhabdomyolysis, both traumatic and nontraumatic, may be defined as a triad of skeletal muscle injury, pigmented urine, and acute renal failure. Nontraumatic rhabdomyolysis may be more of a subtle diagnosis and requires a high index of suspicion. Pertinent findings in the history as well as clinical evidence of muscle injury with a marked elevation of creatinine kinase will suggest the diagnosis. A disproportionate elevation of serum creatinine to blood urea nitrogen may also occur. Treatment consists of adequate hydration to help prevent oliguric or anuric renal failure without additional calcium or bicarbonate supplementation in most cases. Radiologic studies involving intravenous contrast media as well as urologic instrumentation should be avoided in the acute setting. With early diagnosis and prompt treatment the prognosis for recovery is excellent.

Protein phosphatase inhibitors prolong Ca(2+)-transients and divalent cation-dependent action potentials in leech Retzius cells.

Elevation of [K+]o for 30 s from 4 to 120 mM produced a fast and reversible depolarization and transient increase in [Ca2+]i in fura-2 loaded Retzius cells of the leech. The protein phosphatase inhibitor, okadaic acid, significantly slowed the return of [Ca2+]i toward baseline without affecting the amplitude of depolarization or rate of repolarization. Furthermore, okadaic acid and another phosphatase inhibitor, calyculin A, prolonged Ba(2+)-dependent action potentials. These results suggest that the kinetics of Ca2+ influx may be regulated by the activity of phosphatases PP-1 and/or PP-2A.

Magnetic resonance. Principles and applications.

Magnetic resonance is a unique, noninvasive imaging modality which allows direct, multiplanar imaging and the possibility of obtaining biochemical information in vivo. Presently, MR appears most applicable to the evaluation of central nervous system abnormalities. The high sensitivity of MR in the evaluation of intracranial pathology suggests that it may eventually replace CT for many suspected diseases, if future investigations are able to improve its specificity. As previously noted, MR may be more diagnostic than other radiologic studies in the evaluation of suspected Chiari malformation, syringomyelia, congenital abnormalities, tumors of the spinal axis, and disc space infection. In the chest, MR appears to be more accurate than CT in the determination of the extent of mediastinal tumor, but at present cannot replace CT because of the lack of experience in imaging parenchymal nodules and benign diseases. MR of the breast is promising, but the size of the lesion may prove to be a limiting factor with magnetic field strengths commonly being utilized. There are inherent difficulties in the evaluation of cardiac disease with MR, but it offers a noninvasive method of investigating congenital heart disease and may provide valuable information in suspected myocardial ischemia and altered cardiac function. MR provides a new method of evaluating the vascular system, both in terms of providing anatomic information on large and medium-sized vessels and flow analysis. In the abdomen, MR appears to be most sensitive in the evaluation of suspected hepatic masses, but as with the brain, greater specificity will be needed to replace CT. At the present time, MR offers no distinct advantage over conventional imaging modalities in the evaluation of pancreatic disease, it maybe more accurate than CT in the staging of renal cell carcinoma. Larger studies are needed to determine the role of MR in the investigation of retroperitoneal adenopathy and adrenal abnormalities. In the pelvis, MR offers the hope of earlier diagnosis of prostatic carcinoma and may replace CT for staging of prostatic carcinoma and transitional cell carcinoma of the bladder. Limited MR experience with benign disease of the female pelvis suggests that it is currently more accurately evaluated with ultrasound. MR appears to be highly sensitive and specific for the diagnosis of avascular necrosis and may provide an early clue in suspected osteomyelitis. Finally, in vivo MR spectroscopy may provide unique metabolic information that was unobtainable prior to the advent of magnetic resonance, if this proves to be technically feasible.

Noninvasive imaging of the gastrointestinal tract.

Numerous radiographic and scintigraphic imaging modalities are now available for evaluating the gastrointestinal system. With a well-formulated plan based on patient history, physical examination, and laboratory values, together with knowledge of patient preparation techniques and consultation, an efficient customized approach to gastrointestinal disease can be accomplished.

Imaging of the liver, biliary tract, and pancreas.

The interaction between the various noninvasive and invasive imaging modalities used to evaluate the liver, biliary tract, and pancreas is demonstrated in this article. By understanding this interaction and correlating noninvasive studies, the clinician will avoid diagnostic redundancy and the need for invasive testing may be reduced.