Thyrotoxicosis and renal tubular acidosis presenting as hypokalaemic paralysis

We report a case of oesophageal disease as the first manifestation in a patient with CREST syndrome. A 46-year-old man with achalasia-like syndrome developed CREST syndrome 4 years later. A pneumatic dilatation of the cardia was performed. After pneumatic dilatation the dysphagia and regurgitation disappeared but the patient developed reflux oesophagitis. Four years after diagnosis of oesophageal disease he presented with a clinical picture of CREST syndrome. An acute ileus and constipation developed later. After receiving medical therapy with omeprazole and cisapride the patient is free of oesophageal symptoms and bowel movements are normal. Oesophageal disease is common in patients with limited and diffuse scleroderma, but to our knowledge achalasia-like syndrome has not been previously described as the first manifestation of the systemic disease.     

So who was Gerdy... and how did he get his own tubercle?

To elucidate the role of apoptosis in the pathological lesion of hepatitis B virus (HBV) infection, biopsied liver tissue specimens of 38 patients with chronic hepatitis B of varying severity were investigated with in situ immunohistochemistry and TUNEL test. Apoptotic hepatocytes were found to be rare, while the nuclei of many cells were positively stained with TUNEL, suggesting 3'-OH ends generated as the DNA was impaired. Of the 17 cases with mild lesion or without piecemeal necrosis, 14 were negative or weakly positive with both Fas and TUNEL test. Of the 7 cases with piecemeal and bridging necrosis, none was strongly positive. In the 14 cases with active hepatitis and early cirrhosis, strongly positive results with Fas were found in 9 and with TUNEL in 3 respectively. It is suggested that the cytotoxic T lymphocyte (CTL)-Fas-apoptosis mechanism was involved in the hepatocyte death of hepatitis B as well. The Fas expression, DNA damage and apoptotic cells distributed mostly in the piecemeal necrosis region, and the ballooning and the necrotic hepatocytes were also clustering in this region. As both the apoptosis and necrosis are mediated by CTL, they are closely related: while transducted by different ways, they occurred independently.     

Hepatocellular carcinoma presenting as pyogenic liver abscess: characteristics, diagnosis, and management

We performed a 17-year retrospective analysis of 10 cases of hepatocellular carcinoma presenting as pyogenic liver abscess. Spontaneous tumor necrosis and biliary obstruction caused by tumor thrombi, superimposed with bacterial infection, were the two major pathogeneses. Exact diagnosis of the underlying hepatocellular carcinoma was made for five of the 10 patients before management was attempted. Main clinical manifestations included fever, chills, right-upper-quadrant pain, malaise, anorexia, jaundice, and hepatomegaly. Characteristics such as middle age and male sex, seropositivity for hepatitis B and/or hepatitis C, chronic liver disease, unexplained anemia, marked weight loss, and a severely inversed albumin/globulin ratio raise suspicions about the underlying hepatocellular carcinoma. Management strategies included percutaneous drainage (n = 3), surgical drainage (n = 4), and hepatectomy (n = 3) in addition to administration of parenteral antibiotics in all cases. The prognosis was dismal, with a mean survival of 3.5 months (range, 8 days to 6 months).     

Inhibition of vascular smooth muscle cell proliferation by ribozymes that cleave c-myb mRNA

Proliferation of injured smooth muscle cells contributes to the reocclusion or restenosis of coronary arteries that often occurs following angioplasty procedures. We have identified and optimized nuclease-resistant ribozymes that efficiently cleave c-myb RNA. Three ribozymes targeting different sites in the c-myb mRNA were synthesized chemically and delivered to rat aortic smooth muscle cells with cationic lipids; all three inhibited serum-stimulated cell proliferation significantly. RNA molecules with two base substitutions in the catalytic core that render the ribozyme catalytically inactive had little effect on smooth muscle cell proliferation. Ribozymes with scrambled binding arm sequences also failed to affect cell cycle progression of vascular smooth muscle cells. Furthermore, inhibition of rat smooth muscle cell proliferation correlated with a reduction in intact c-myb mRNA. Efficacy of the chemically-modified ribozyme was compared directly to phosphorothioate antisense oligodeoxynucleotides targeting the same site in the c-myb RNA; the ribozyme had superior efficacy and showed greater specificity than the antisense molecules. Exogenously delivered ribozymes also inhibited porcine and human smooth muscle cell proliferation effectively. Ribozymes targeting c-myb or other regulators of smooth muscle cell proliferation may represent novel therapeutics for the treatment of restenosis after coronary angioplasty.     

Hyaluronan in human cerebrospinal fluid

We studied the concentration of hyaluronan in cerebrospinal fluid (CSF) in various diseases and attempted to define its reference interval. A radioassay utilizing cartilage proteins with affinity for hyaluronan was used in determining the concentration of 200 lumbar and 27 ventricular CSF specimens and 11 brain cyst fluids. Molecular weight distributions were determined by gel chromatography and localization in brain tissue by histochemistry. The hyaluronan level of lumbar CSF showed an increase with age; comparatively healthy children had (mean +/- SD) 50 +/- 41 micrograms/L (n = 40) and adults 166 +/- 77 micrograms/L (n = 9); i.e. significantly different values. The highest level was recorded in a patient with meningitis (> 8000 micrograms/L). More than 4000 micrograms/ L was noted in a patient with tumour metastasis in the cerebellum. Significantly elevated levels were especially found with spinal stenosis, head injury and cerebral infarction, but also in inflammatory medical disorders, hydrocephalus and encephalitis. We found no significant increase in multiple sclerosis and some other neurological diseases. Ventricular CSF of adults contained significantly less hyaluronan (53 +/- 73 micrograms/L; n = 16) than lumbar CSF. Hyaluronan in cyst fluids varied from 31 to 25,000 micrograms/L. Weight average molecular weight of hyaluronan in CSF was 2.9-3.0 x 10(5) and in brain tumour cyst fluid 2.4 x 10(6). In search for the origin of hyaluronan in CSF it was found that its concentration in the choroid plexus and leptomeninges was low, but that hyaluronan was accumulated in the superficial layer of the cerebral cortex. Continued screening for hyaluronan in CSF may be valuable in cases of inflammatory diseases, tumours and obstruction to CSF flow.     

Experimental vaccine strategies for cancer immunotherapy

Recently, cancer immunotherapy has emerged as a therapeutic option for the management of cancer patients. This is based on the fact that our immune system, once activated, is capable of developing specific immunity against neoplastic but not normal cells. Increasing evidence suggests that cell-mediated immunity, particularly T-cell-mediated immunity, is important for the control of tumor cells. Several experimental vaccine strategies have been developed to enhance cell-mediated immunity against tumors. Some of these tumor vaccines have generated promising results in murine tumor systems. In addition, several phase I/II clinical trials using these vaccine strategies have shown extremely encouraging results in patients. In this review, we will discuss many of these promising cancer vaccine strategies. We will pay particular attention to the strategies employing dendritic cells, the central player for tumor vaccine development.     

Optimizing three-dimensional gadolinium-enhanced magnetic resonance angiography. Original investigation

RATIONALE AND OBJECTIVES: This primarily theoretical work examines three-dimensional gadolinium-enhanced magnetic resonance angiography f8p4Gd-MRA) with the goal of understanding how to achieve the best possible images with respect to signal to noise ratio (SNR) and k-space induced artifacts. Patient variables, contrast injection schemes, and pulse sequence parameters are considered for this purpose. METHODS: A theoretical analysis, including computer simulation, describes how contrast material injection profiles influence 3D Gd-MRA images, both in terms of intravascular signal and resultant artifacts. Further theoretical analysis of the spoiled gradient refocused pulse sequence describes how to maximize SNR. Clinical imaging complements computer modeling. RESULTS: Equations were derived relating contrast injection parameters and pulse sequence variables to SNR and artifacts. For present imaging equipment, administering contrast material over a duration of 60% to 80% of the total imaging time and using fractional echo techniques gives the best SNR without significantly sacrificing image quality. CONCLUSIONS: Three-dimensional Gd-MRA can be tailored to a specific clinical situation and imaging system through the use of proper breath-holding, bolus timing, Gd administration, and pulse sequence design.     

Neutralizing antibodies from the sera of human immunodeficiency virus type 1-infected individuals bind to monomeric gp120 and oligomeric gp140

Antibodies that neutralize primary isolates of human immunodeficiency virus type 1 (HIV-1) appear during HIV-1 infection but are difficult to elicit by immunization with current vaccine products comprised of monomeric forms of HIV-1 envelope glycoprotein gp120. The limited neutralizing antibody response generated by gp120 vaccine products could be due to the absence or inaccessibility of the relevant epitopes. To determine whether neutralizing antibodies from HIV-1-infected patients bind to epitopes accessible on monomeric gp120 and/or oligomeric gp140 (ogp140), purified total immunoglobulin from the sera of two HIV-1-infected patients as well as pooled HIV immune globulin were selectively depleted of antibodies which bound to immobilized gp120 or ogp140. After passage of each immunoglobulin preparation through the respective columns, antibody titers against gp120 and ogp140 were specifically reduced at least 128-fold. The gp120- and gp140-depleted antibody fraction from each serum displayed reduced neutralization activity against three primary and two T-cell line-adapted (TCLA) HIV-1 isolates. Significant residual neutralizing activity, however, persisted in the depleted sera, indicating additional neutralizing antibody specificities. gp120- and ogp140-specific antibodies eluted from each column neutralized both primary and TCLA viruses. These data demonstrate the presence and accessibility of epitopes on both monomeric gp120 and ogp140 that are specific for antibodies that are capable of neutralizing primary isolates of HIV-1. Thus, the difficulties associated with eliciting neutralizing antibodies by using current monomeric gp120 subunit vaccines may be related less to improper protein structure and more to ineffective immunogen formulation and/or presentation.     

Female sex hormones and the immune system

Generally, females have a more active immune response and a concomitantly higher incidence of autoimmune diseases as compared to males. Growing evidence has shown that female sex hormones play a major role in this heightened immune response. However, despite extensive studies, the mechanisms of female sex hormones are not precisely understood. Earlier evidence suggest that female sex hormones acted via the thymus gland. In recent years it has become apparent that female sex hormones have distinct effects on the function of T cells, B cells, or mononuclear phagocytes. The presence of sex hormone receptors on the immune cells indicates the effects of female sex hormones on these cells are mediated by these receptors. The effects of female sex hormones on the immune system and the possible mechanisms are discussed in this review. Female sex hormone modulation of immune responses provides a basis for understanding gender-related differences in certain autoimmune and neoplastic disorders.     

Anatomy and histology of the A5 pulley

Sustained iontophoresis of NMDA potentiated visual responses for minutes after the application in 16 of 38 cells (42%), peaking 3 min after the end of the application and declining to control levels within 12 min. Potentiation was also seen after application of ACPD (36%, n = 14) and AMPA (29%, n = 14), but not after application of ACh (n = 20). ACh also excites dLGN cells, but does not interact with amino acid receptors, and ACh receptors are not directly involved in the transmission of visual information. We suggest that this modulation is a form of visually induced potentiation which permits dynamic modification of the strength of visual information to be relayed to the cortex depending upon the history of previous activity levels.