A novel mutation in the last exon of ATRX in a patient with α-thalassemia myelodysplastic syndrome

Abstract:  We describe a patient with acquired alpha-thalassemia myelodysplastic syndrome (ATMDS). A previously healthy 66-year-old man presented with hemoglobin of 9.3 g/dL, mean corpuscular volume 59 fL, and a bone marrow aspirate with increased erythroid precursors and hypolobulated megakaryocytes. Hemoglobin H inclusions were seen in most red cells after 1% brilliant cresyl blue supravital stain of the peripheral blood. At the molecular level, we identified of a novel mutation in the most 3' exon of the ATRX gene ( C GA→ T GA substitution in codon 2407) resulting in a premature termination codon (p.R2407X). This case provides further evidence for a link between ATRX mutations and ATMDS, and suggests a possible role for the conserved Q-box element in ATRX function.     

Severe hemorrhagic radiation proctitis advancing to gradual cessation with hyperbaric oxygen

Summary We report a case of a male patient suffering from a severe hemorrhagic radiation proctitis which gradually ceased with hyperbaric oxygen. We discuss the mechanisms of chronic radiation injury and the effect of the hyperbaric oxygen. This therapy is proposed as an alternative to surgical intervention for this abnormality.     

Diffusion-weighted imaging study of patients with essential tremor.

The pathophysiology of essential tremor (ET) is unknown. PET and fMRI studies have revealed bilateral activation and (1)H-MRS studies metabolic abnormalities in the cerebellum and other functionally related brain structures in ET. Diffusion-weighted imaging (DWI) was used to search for evidence of tissue integrity abnormalities in these areas in ET patients and 10 matched controls by calculating water apparent diffusion coefficients (ADCs). Regions of interest included the left and right cerebellum, red nucleus, thalamus, caudate, putamen, pallidum, and frontal white matter. Histograms of ADCs were generated for all pixels in the infratentorial compartment and manually segmented areas corresponding to brainstem, vermis, and cerebellar hemispheres. ADC values were similar in all brain areas in patients and controls. Our study did not detect changes affecting the investigated brain regions in ET patients. These findings argue against major structural damage in the ET brain, although more subtle neurodegenerative changes cannot be ruled out.     

Treatment of hepatitis B and C after liver transplantation. Part 1, hepatitis B

Abstract The outcome of OLT for HBV-related liver disease is dependent on the prevention of allograft re-infection. Over the past decade, major advances have been made in the management of HBV transplant candidates. The advent of long-term hepatitis B immune globulin (HBIG) administration as a prophylaxis against HBV recurrence, and the introduction of new antiviral agents against HBV infection, such as lamivudine (LAM), were a major breakthrough in the management of these patients. Results of OLT for HBV infection are similar to those achieved with other indications. Pre-OLT antiviral treatment such as LAM can suppress HBV replication before OLT and thus decrease the risk of re-infection of the graft. Combination prophylaxis with LAM and HBIG after transplantation highly effectively reduces the rate of HBV re-infection, even in HBV replicative cirrhotic, patients. The optimal HBIG protocol in the LAM era is yet to be defined: dosing of HBIG, routes of administration, and possibility of stopping HBIG. Several antiviral drugs have been developed for the management of HBV infection on the graft, so outcome is currently good.     

Rupture of a submitral ventricular aneurysm into the left atrium diagnosed by transesophageal echocardiography.

Submitral ventricular aneurysm is a thoroughly studied pathology but is not well known due to its rarity. Clinically, it is manifested by symptoms and signs of heart failure, mitral regurgitation and/or ventricular arrhythmias, and may be associated with thromboembolic phenomena and myocardial ischemia due to compression of the coronary arteries by the aneurysm. A rare complication of this type of aneurysm is rupture into the left atrium. Transthoracic echocardiography plays an important role in the definitive diagnosis of this pathology, although the role of transesophageal echocardiography in the evaluation of these patients is less known. We report a case of a submitral ventricular aneurysm complicated by rupture into the left atrium, which was diagnosed by transesophageal echocardiography.     

Effects of rufloxacin in Salmonella typhimurium infection in mice.

This study was undertaken to investigate the efficacy of rufloxacin, a new quinolone which is interesting due to its pharmacokinetics characterized by a long plasma half-life, in the treatment of systemic salmonella infections in the mouse typhoid model. Innately susceptible BALB/c and resistant CBA mice were used to investigate the efficacy of rufloxacin in controlling systemic salmonella infections when given for brief or prolonged periods. The present study shows that rufloxacin is not only very effective on both mouse strains, but can completely eradicate the salmonellae from livers and spleens when given early in the infection of CBA resistant mice.     

Autoinduction of Androgen Receptor mRNA in Primary Cultures of Hamster (Mesocricetus auratus) Harderian Gland Cells

The Harderian gland (hg) is a gland which occupies a large portion of the orbital cavity. In many species, a sexual dimorphism occurs, which suggests a gonadal steroid control of the hg. The present study examines, in primary cultures of hamster hg cells, the regulation of the androgen receptor mRNA (AR mRNA) expression. In dose–response experiments measuring the expression of AR mRNA, testosterone (T) (10⁻¹²M) induced a 1-fold increase of AR mRNA compared with unexposed cells, and this effect reached its zenith (6.2-fold) when cells were exposed to 10⁻⁸MT. In other experiments, cells were exposed or not to different drugs [T, T + flutamide (F), F, T + cycloheximide (Cy), Cy] for different times (up to 96 hr). These experiments showed a time-dependent increase of AR mRNA in the cells exposed to T, while in the cells exposed to F, T+F, T+Cy, Cy, and control (unexposed), a time-dependent decrease of AR mRNA was observed. The size of the hamster AR mRNA in thesein vitroexperiments was similar to that observed in other mammals (9.5 kb). It is concluded that primary cultures of hamster hg cells are a valuable model for studying hg cell activity and that in this system T autoinduces its own receptor.     

Arecoline, but not haloperidol, induces changes in the permeability of the blood-brain barrier in the rat

The aim of the present study was to investigate the existence of alterations of the blood-brain barrier (BBB) permeability in rats injected with centrally acting drugs, by calculating a unidirectional blood-to-brain transfer constant (Ki) for the circulating tracer [14C]-alpha-aminoisobutyric acid. The intraperitoneal (i.p.) injection of the dopaminergic antagonist haloperidol (1 mg kg-1) did not modify the regional BBB permeability. When the cholinomimetic agent arecoline hydrobromide (6.25 mg kg-1) was injected i.p. into methylatropine-pretreated rats, it induced a significant decrease of Ki values within the frontal cortex, parietal cortex, striatum and brain-stem. Our findings emphasize two concepts: (1) centrally acting drugs, such as arecoline, can induce changes in the BBB permeability, through several mechanisms; (2) there is no predictable correlation of drug stimulation of specific brain neuronal pathways and changes in the permeability of the BBB.