Rectal cancer masquerading as an amoeboma: case report and review of the literature

Despite the prevalence of amoebiasis in many parts of the world, amoebomas are relatively uncommon. Amoebomas within the colorectum are indistinguishable from carcinomas either macroscopically or by barium enema examination and the presence of both conditions is much rarer still. Herein, we describe such a case and review the possible reasons for their coexistence.     

Safety, tolerability, pharmacokinetics, and pharmacodynamics of an orally active novel camptothecin analog, DRF-1042, in refractory cancer patients in a phase I dose escalation study

The objective of this study was to characterize the maximum tolerated dose (MTD), dose-limiting toxicities (DLT), pharmacokinetics, and antitumor effects of DRF-1042, a novel camptothecin analog, in refractory solid tumor patients. DRF-1042 was given for 5 consecutive days for 2 weeks, repeated every 3 weeks at 1.5 to 270 mg/m(2). Adverse events were monitored following NCI-CTC. Pharmacokinetics of lactone and total forms were determined using validated high-performance liquid chromatography (HPLC) and noncompartmental methods. Efficacy was evaluated applying World Health Organization (WHO) criteria. The 1st course was used to determine DLT and MTD. Twenty-five patients received 73 courses of therapy. Myelosuppression and diarrhea were DLTs. MTD was 120 mg/m(2)/day. AUC increased approximately linearly with dose. The t(1/2) for lactone and total forms was 9.9 and 29 hours, respectively. AUCs correlated significantly with nadir leucopenia and grade 4 diarrhea. Two complete responses (CRs) and 2 partial responses (PRs) were observed. In addition, 4 stable diseases were observed. The recommended phase II dose is 80 mg/m(2)/day.     

Right atrial aneurysm in adults--report of three cases and review of literature

Right atrial aneurysm (RAA) or RA diverticula are described as saccular structures originating from the RA free wall. This must be differentiated from aneurysmal dilation of the entire right atrium. We diagnosed three cases of RAA since 2000. The first patient presented with effort intolerance, the second with recurrent palpitations, and the third was totally asymptomatic. In all the cases transthoracic echocardiography was definitive with little additional information obtained from catheterization. We report our experience and review the literature pertaining to adult presentation of this interesting pathology, of which only 20 cases have thus far been reported.     

Identification and characterization of a novel allosteric modulator (SoRI-6238) of the serotonin transporter

In the present study we describe a novel agent, SoRI-6238 (ethyl 5-amino-3-(3,4-dichlorophenyl)-1,2-dihydropyrido[3,4-b]pyrazin-7-ylcarbamate) that partially inhibits 5-HT transporter (SERT) binding and allosterically modulates SERT function. Membranes were prepared from rat brain. SoRI-6238 partially inhibited SERT binding to brain membranes with a plateau at about 40% of control. SoRI-6238 fully inhibited norepinephrine transporter (NET) and dopamine transporter (DAT) binding with IC(50) values of 12.1 microM and 5.8 microM, respectively. The apparent K(d) of [(125)I]RTI-55 binding to SERT increased, then reached a plateau with increasing concentrations of SoRI-6238. SoRI-6238 fully inhibited [(3)H]5-HT uptake, acting to decrease the V(max) (noncompetitive inhibition). In kinetic experiments, SoRI-6238 slowed the dissociation of [(125)I]RTI-55 from SERT and slowed the initial association rate. We conclude that SoRI-6238 partially inhibits SERT binding and function, most likely via an allosteric mechanism.     

Neodymium:yttrium-aluminum-garnet capsulotomy and intraocular pressure in pseudophakic patients with glaucoma

OBJECTIVE: To determine the 1- and 3-hour changes in intraocular pressure after neodymium:yttrium-aluminum-garnet (Nd:YAG) capsulotomy in pseudophakic patients with glaucoma and to determine the effect of acetazolamide and apraclonidine on these changes. DESIGN: Randomized controlled trial. PARTICIPANTS: Pseudophakic patients with glaucoma requiring Nd:YAG posterior capsulotomy (n = 76). INTERVENTION: Patients undergoing Nd:YAG posterior capsulotomy were randomly allocated to receive no therapy, oral acetazolamide (250 mg), or topical apraclonidine 1% within 1 hour before capsulotomy. MAIN OUTCOME MEASURES: Intraocular pressures 1 and 3 hours after laser therapy were recorded. RESULTS: Data were available for 76 eyes in 76 patients. Twenty-nine patients received no therapy; 24, oral acetazolamide; and 23, apraclonidine. One fifth (6/29) of patients with glaucoma developed a pressure rise of > or =5 mmHg if untreated, and 3% (1/29) developed a pressure rise of >10 mmHg. In comparison, no patients in the acetazolamide group developed a pressure rise of > or =5 mmHg (P = 0.02), and 1 of 24 in the apraclonidine group (P = 0.08) developed such a pressure rise, with none developing a pressure rise of >10 mmHg. When comparing all treated with nontreated, a reduction in the proportion with pressure rise was found (P = 0.01). All of the patients who developed a pressure rise of > or =5 mmHg did so within the first hour. CONCLUSIONS: In the absence of therapy, clinically significant post-Nd:YAG pressure rises occur in one fifth of patients with glaucoma undergoing capsulotomy. Oral acetazolamide and topical apraclonidine reduce the frequency and magnitude of pressure rises and are of comparable effectiveness. In this study, all clinically important pressure rises developed within the first hour.     

Ocular presentation of sphenoid mucocele

A sphenoid mucocele often presents late due to its deep-seated anatomical site. It has a varied presentation, due to its close relationship to the cavernous sinus and the base of the skull. It can present initially to the ophthalmologist with ocular complaints. In the present paper, the authors present two cases of sphenoid mucocele, one with an isolated third and one with an isolated sixth cranial nerve palsy.     

Genotype-phenotype correlations for EPM2A mutations in Lafora's progressive myoclonus epilepsy: exon 1 mutations associate with an early-onset cognitive deficit subphenotype

Mutations in the EPM2A gene encoding a dual-specificity phosphatase (laforin) cause an autosomal recessive fatal disorder called Lafora's disease (LD) classically described as an adolescent-onset stimulus-sensitive myoclonus, epilepsy and neurologic deterioration. Here we related mutations in EPM2A with phenotypes of 22 patients (14 families) and identified two subsyndromes: (i) classical LD with adolescent-onset stimulus-sensitive grand mal, absence and myoclonic seizures followed by dementia and neurologic deterioration, and associated mainly with mutations in exon 4 (P = 0.0007); (ii) atypical LD with childhood-onset dyslexia and learning disorder followed by epilepsy and neurologic deterioration, and associated mainly with mutations in exon 1 (P = 0.0015). To understand the two subsyndromes better, we investigated the effect of five missense mutations in the carbohydrate-binding domain (CBD-4; coded by exon 1) and three missense mutations in the dual phosphatase domain (DSPD; coded by exons 3 and 4) on laforin's intracellular localization in HeLa cells. Expression of three mutant proteins (T194I, G279S and Y294N) in DSPD formed ubiquitin-positive cytoplasmic aggregates, suggesting that they were folding mutants set for degradation. In contrast, none of the three CBD-4 mutants showed cytoplasmic clumping. However, CBD-4 mutants W32G and R108C targeted both cytoplasm and nucleus, suggesting that laforin had diminished its usual affinity for polysomes. Our data, thus, represent the first report of a novel childhood syndrome for LD. Our results also provide clues for distinct roles for the CBD-4 and DSP domains of laforin in the etiology of two subsyndromes of LD.