Uric acid stones following hepatic transplantation

We report the case of a 52 year old man with a history of insulin-requiring diabetes and hepatitis B with cirrhosis who received an orthotopic liver transplant. One year later he developed renal colic and was found to have a 3 mm stone at the left ureterovesical junction. Numerous other stones formed and infrared spectroscopy analysis demonstrated all to be composed of 100% uric acid. Urine collections demonstrated a low urine pH of 5.1 without hyperuricosuria. His stones were effectively prevented with potassium citrate therapy. Few incidence data are available for uric acid stone occurrence in solid organ recipients. Calcineurin inhibitors are thought to often cause hyperuricemia on the basis of decreased urate excretion. However, this effect would not be expected to cause hyperuricosuria nor uric acid stones. This class of drugs may also be associated with low urine pH, perhaps on the basis of hypoaldosteronism, but the contribution of such a syndrome to uric acid stone formation is not established.     

Hepatotoxic effects of polidocanol in a model of autologously perfused porcine livers

Polidocanol is an effective sclerosing agent that consists of 95% hydroxypolyethoxydodecane and 5% ethyl alcohol and is known to have a low risk of complications. However, since the compound has been proposed for the local treatment of liver diseases, the potential for topical hepatic side effects should be examined. Therefore, the new model of normothermic-hemoperfused isolated porcine slaughterhouse livers was used to examine polidocanol-hepatotoxicity encompassing the advantages of slaughterhouse organs to reduce animal experiments and autologous blood as an optimal perfusate. Polidocanol was administered via the hepatic artery and portal vein and the effects of the sclerosant on organ function parameters were compared with those in an untreated control group. In contrast to the untreated control organs, significant differences were found in the polidocanol group for parameters such as alanine aminotransferase or organ weight after perfusion. The most striking differences were found for hepatic bile flow, which dropped in the polidocanol group to 0.24±0.02 ml/min per 1000 g after administration of the compound compared with 3.80±1.08 ml/min per 1000 g in the control group. In summary, the present observations indicate a risk of hepatotoxic effects of polidocanol. Clinicians should be aware of this problem and the use of polidocanol for intrahepatic sclerosing should be restricted to specialized centers.     

Intrahepatic arterioportal shunting and anomalous venous drainage: understanding the CT features in the liver

The increased use of high-contrast volume, arterial-phase studies of the liver has demonstrated the frequent occurrence of arterioportal shunts within both the cirrhotic and non-cirrhotic liver. This article sets out to explain the underlying microcirculatory mechanisms behind these commonly encountered altered perfusion states. Similarly, well-recognised portal perfusion defects occur around the perifalciform and perihilar liver and are largely caused by anomalous venous drainage via the paraumbilical and parabiliary venous systems. The underlying anatomy will be discussed and illustrated. These vascular anomalies are all caused by or result in diminished portal perfusion and are often manifest in the setting of portal venous thrombosis. The evolving concept of zonal re-perfusion following portal vein thrombosis will be discussed.     

Breast Cancer Survival According to Number of Nodes Removed

BACKGROUND: Results from randomized trials indicate a 5.4% survival advantage associated with axillary dissection. To gain insight on survival outcomes when less than an axillary dissection is performed, we performed a retrospective analysis to determine survival outcome for node-negative and node-positive breast cancer patients when a variable number of nodes were excised. METHODS: The data analyzed in this paper are from the Surveillance, Epidemiology, and End Results (SEER) database, from which 72,102 patients were selected whose breast cancer had been diagnosed in 1988 or later and who were aged 40-79 years at diagnosis, had a single primary lesion, and had 0 to 3 positive lymph nodes. Cases were separated into age groups (40 to 49 and 50 to 79 years), and node-negative cases were separated from those with one to three positive nodes. RESULTS: This analysis indicates that even when all regional lymph nodes are pathologically negative, the number of nodes removed is associated with survival. In the group of breast cancer patients who had one to three pathologically positive nodes, as with the node-negative group, the higher the number of nodes removed, the greater the survival. The hazard rate for death in the node-negative group was roughly 5% less for each additional five nodes removed. For the node-positive group, the hazard rate for death was between 8% and 9% less for each additional five nodes removed. CONCLUSIONS: This retrospective study supports the notion that removal of regional nodes, even when such nodes are interpreted as pathologically negative, is important for the long-term survival of breast cancer patients.     

Bronchopulmonary foregut malformations: embryology,radiology and quandary

Bronchopulmonary foregut malformations (BPFM) are a heterogeneous group of pulmonary developmental anomalies that present at varying ages and with overlapping symptoms, signs and radiology. This article discusses the embryology of these lesions with reference to possible common origins and the link between aetiology and radiological appearance. The radiology of each lesion, both antenatally and postnatally, is described and illustrated. A number of quandaries exist in the prediction of prognosis and subsequent treatment of BPFM. We discuss the radiological features that may help to elucidate an individual prognosis and aid in the planning of treatment. The treatment options available for BPFM are briefly discussed. Finally, the link between BPFM, in particular cystic adenomatoid malformations and malignancy, is discussed. We aim to provide a comprehensive overview of the embryology, radiology, prognosis and treatment highlighting contentious issues of BPFM.     

Some challenges for medical statistics

A broad review is given of some of the issues facing medical statistics organized under the headings of measurement, design, analysis and interpretation.     

Effects of intranucleus accumbens shell administration of dopamine agonists and antagonists on cocaine-taking and cocaine-seeking behaviors in the rat

Rationale Dopamine signaling in the nucleus accumbens (NAc) plays an important role in regulating drug-taking and drug-seeking behaviors, but the role of D₁- and D₂-like receptors in this regulation remains unclear.Objectives Our objective was to study the role of NAc D₁- and D₂-like receptors in the reinstatement of cocaine-seeking behavior and the regulation of stabilized cocaine intake in rats.Methods Using a within-session reinstatement procedure, whereby animals self-administer cocaine (90 min) and extinguish responding (150 min) in a single session, we assessed the ability of NAc microinfusions of the D₁ agonist SKF 81297 and the D₂ agonist 7-OH-DPAT to reinstate extinguished cocaine seeking. The effects of the D₁ antagonist SCH 23390 and the D₂ antagonist eticlopride pretreatment on agonist- and cocaine-primed reinstatement were also measured. Similar agonist and antagonist treatments were tested for their ability to modulate stabilized cocaine and sucrose self-administration.Results Intra-NAc infusions of either SKF 81297 (0.3–3.0 μg) or 7-OH-DPAT (1.0–10.0 μg) dose-dependently reinstated cocaine seeking with greater efficacy in the medial core than in the shell subregion and at doses that also stimulated locomotor behavior. Intra-NAc shell infusions of SCH 23390 (1.0 μg) and eticlopride (3.0–10.0 μg) blocked cocaine-primed reinstatement (2.0 mg/kg, i.v.) and indiscriminately blocked reinstatement induced by either intra-NAc D₁ or D₂ agonists. Doses of agonists that triggered reinstatement failed to alter stabilized cocaine intake, whereas doses of antagonists that blocked reinstatement increased cocaine intake in the shell.Conclusions Both D₁ and D₂ receptors in the NAc play a prominent, and perhaps cooperative, role in regulating cocaine-taking and cocaine-seeking behaviors.     

Prevalence and Persistence of TT Virus DNA in HIV1-Infected Individuals

Background: TT virus (TTV) is a recently discovered virus with a high DNA prevalence in different populations. Its role in pathogenesis is uncertain, particularly in immunocompromised patients.Patients and Methods: Prevalence of TTV-DNA was evaluated in a cohort of HIV-infected patients and in blood donors by nested PCR, using two different primer sets: T primers, derived from the open reading frame ORF1 region N22; B primers, derived from the untranslated region (UTR). Samples positive using T primers were also tested for TTVDNA in peripheral blood mononuclear cells (PBMC) and followed up every 4 months.Results: The overall prevalence of TTV-DNA in HIV-infected patients was 37/376 (9.8%) using T primers and 223/333 (67%) using B primers; prevalence was higher in males (167/237, 70.5% vs 56/96, 58.3%; p = 0.033) and sub- Saharan Africans (22/23, 95.6% vs 201/310, 64.8% in other areas). Discordance was also observed in blood donors: 3.8% prevalence using T primers and 51.4% using B primers (also higher in males: 57% vs 37%, p = 0.056). TTV-DNA was detected in PBMC in 20/23 (87%) TTV-positive sera. Twothirds of the serum samples remained positive over a 2-year follow-up period.Conclusion: TTV-DNA prevalence is higher when detected with primers derived from the UTR region and was highest in male and HIV-infected sub-Saharan Africans. TTV-DNA is frequently isolated in PBMC and chronic infection is common.