Arthropathy,hypouricemia and normal serum iron studies in hereditary hemochromatosis

A patient manifesting the arthropathy of hemochromatosis without abnormal serum iron studies is described. Hemochromatosis was confirmed by liver biopsy. This case serves to emphasize the diagnostic value of the characteristic arthropathy of hemochromatosis. Our observations in this patient support the hypothesis that the pathogenesis of hereditary hemochromatosis differs from that of acquired iron overload states. The concurrent presence of hypouricemia is explored in this patient and in 18 other patients with hereditary hemochromatosis. Men with hereditary hemochromatosis were found to have lower serum uric acid levels than expected. In our patient, a renal defect in tubular reabsorption of uric acid appears responsible for hypouricemia.The apparent association of hemochromatosis and hypouricemia deserves further investigation.     

Transjugular intrahepatic portal-systemic shunts (TIPS) – initial experience and clinical outcome

Background: The clinical role of the transjugular intrahepatic portal-systemic shunt (TIPS) has not been fully defined.
Aims: To determine the technical results of TIPS and the clinical outcome of patients undergoing the procedure.
Methods: Retrospective audit of the results of the first 31 procedures performed in Melbourne.
Results: Thirty procedures were performed for variceal haemorrhage, one procedure was for ascites. The aetiology of the liver disease was cirrhosis due to alcohol in 20, cryptogenic in five, chronic viral infection in four, and autoimmune chronic active hepatitis in one. Nodular regenerative hyperplasia was present in one patient. Seventy-seven per cent of procedures were considered successful based on the angiographic demonstration of shunt patency at the end of the procedure. The in-hospital mortality in all patients undergoing TIPS was 45% and was 42% in patients undergoing technically successful TIPS. Only age could be identified as predictive of death in hospital. In patients leaving hospital, we found a rebleeding rate of 57% with one patient dying of bleeding, one requiring balloon tamponade and two requiring variceal sclerotherapy. Hepatic trauma was documented in six cases, shunt thrombosis in four cases, stent displacement in two cases and severe hepatic encephalopathy in one case.
Conclusions: TIPS has the potential to decompress the portal venous system, but the procedure is technically complex and should be performed in the knowledge that mortality and morbidity can be relatively high, particularly in patients whose condition is poor.     

Hepatocellular carcinoma and chemoembolization

Abstract
Background : Chemoembolization is often used in the treatment of hepatocellular carcinoma; however, there are limited data on its efficacy in an Australian setting.
Aims : To review retrospectively the experience of 21 patients with hepatocellular carcinoma who collectively had 36 chemoembolizations performed between October 1995 and February 1999 in a teaching hospital and liver transplant centre in Victoria.
Methods : Selective catheterization of the right or left hepatic arteries was performed. A mixture of cis-platin 50 mg, epirubicin 50 mg, mitomycin C 10 mg, Lipiodol and gelfoam was injected. Computed tomography (CT) scans were performed at baseline and at 1–3 months after chemoembolization. Outcome measures included response rates, toxicity, progression-free and overall survival.
Results : CT response rates: partial response 19% ( n = 7), median duration 11 months (range 2+ to 37+); minor response 17% ( n = 6), median duration 7 months (1+ to 12+); stable disease 42% ( n = 15), median duration 3 months (1+ to 15 months); and progressive disease 22% ( n = 8). Major toxicities included one case each of acute renal failure, contrast encephalopathy, gastric ulceration and hepatorenal failure. Median progression-free survival was 3 months (range 0–37+). Median overall survival was 15 months (range 6–50+).
Conclusion : Chemoembolization has a role in the palliative treatment of hepatocellular carcinoma. Our response rates and toxicity data are consistent with those in the published literature. However, new treatments are needed and prevention of disease by reduction in the prevalence of chronic hepatitis B and C will be required to significantly reduce mortality from this tumour. (Intern Med J 2001; 31: 517–522.     

Continuity and Change in the Genetic and Environmental Etiology of Youth Antisocial Behavior

Behavior Genetics - Trajectories of youth antisocial behavior (ASB) are characterized by both continuity and change. Twin studies have further indicated that genetic factors underlie continuity,...     

Precompensation of 3D field distortions in remote focus two-photon microscopy

Remote focusing is widely used in 3D two-photon microscopy and 3D photostimulation because it enables fast axial scanning without moving the objective lens or specimen. However, due to the design constraints of microscope optics, remote focus units are often located in non-telecentric positions in the optical path, leading to significant depth-dependent 3D field distortions in the imaging volume. To address this limitation, we characterized 3D field distortions arising from non-telecentric remote focusing and present a method for distortion precompensation. We demonstrate its applicability for a 3D two-photon microscope that uses an acousto-optic lens (AOL) for remote focusing and scanning. We show that the distortion precompensation method improves the pointing precision of the AOL microscope to < 0.5 µm throughout the 400 × 400 × 400 µm imaging volume.     

Association of granulocyte-macrophage colony-stimulating factor with the crystalloid granules of human eosinophils

We have previously shown that normal-density human peripheral blood eosinophils transcribe and translate mRNA for granulocyte-macrophage colony-stimulating factor (GM-CSF) and that the intracellular distribution was granular as assessed by light microscopy immunocytochemistry. The present study was conducted to confirm this apparent association between GM-CSF and the crystalloid granule using a subcellular fractionation method for human eosinophils and immunogold electron microscopy (EM). Highly purified (> 99%, by negative selection using anti-CD16 immunomagnetic microbeads) human peripheral blood eosinophils were obtained from four asthmatic subjects (not taking systemic medication), homogenized and density fractionated (5 x 10(7) cells/subject) on linear Nycodenz gradients. Twenty-four fractions were collected from each cell preparation and analyzed for marker enzyme activities as well as total protein. Dot blot analysis with specific monoclonal antibodies (MoAbs) was used to detect the eosinophil granule proteins major basic protein (MBP) and eosinophil cationic protein (ECP). An anti-CD9 MoAb was used as an eosinophil plasma membrane marker. Lactate dehydrogenase (LDH) was used as a cytosolic marker. Immunoreactivity for GM-CSF was detected by a specific enzyme-linked immunosorbent assay using a polyclonal antihuman GM-CSF antibody and confirmed by dot blot. GM-CSF coeluted with the cellular fractions containing granule markers (MBP, ECP, eosinophil peroxidase, hexosaminidase, and arylsulphatase), but not those containing cytoplasm (LDH+) or membrane (CD9+) markers. EM examination of pooled fractions associated with the peak of GM-CSF immunoreactivity confirmed that they contained crystalloid and small granules, but not plasma membrane. In addition, quantification, using immunogold labeling with an anti/GM-CSF MoAb, indicated preferential localization of gold particles over the eosinophil granule cores of intact cells. Thus, our results indicate that GM-CSF resides as a granule-associated, stored mediator in unstimulated human eosinophils.