Subungual glomus tumor: combined use of MRI and three-dimensional contrast MR angiography

We describe a case of digital glomus tumor diagnosed by MRI and three-dimensional contrast MR angiography (MRA). Images provided the formal definitive diagnosis and the precise localization of the tumor, guiding the necessary surgical resection. It is possible that noninvasive MRA could replace conventional arteriography for the evaluation of patients with clinical suspicion of glomus tumor.     

Chemical processing in the coma as the source of cometary HNC

The discovery of hydrogen isocyanide (HNC) in comet Hyakutake with an abundance (relative to hydrogen cyanide, HCN) similar to that seen in dense interstellar clouds raised the possibility that these molecules might be surviving interstellar material. The preservation of material from the Sun's parent molecular cloud would provide important constraints on the processes that took place in the protostellar nebula. But another possibility is that HNC is produced by photochemical processes in the coma, which means that its abundance could not be used as a direct constraint on conditions in the early Solar System. Here we show that the HNC/HCN ratio determined for comet Hale-Bopp varied with heliocentric distance in a way that matches the predictions of models of gas-phase chemical production of HNC in the coma, but cannot be explained if the HNC molecules were coming from the comet's nucleus. We conclude that HNC forms mainly by chemical reactions in the coma, and that such reactions need to be considered when attempting to deduce the composition of the nucleus from observations of the coma.     

Endocardial activation mapping of ventricular tachycardia in patients : first application of a 32-site bipolar mapping electrode catheter

BACKGROUND: Localization of early activated endocardial areas during ventricular tachycardia (VT) is mandatory for performance of surgical or radiofrequency catheter interventions. The use of a multielectrode catheter may shorten the procedure time and increase the accuracy of the procedure compared with single-electrode mapping techniques. This study was performed to evaluate the safety and efficacy of a 32-bipolar-electrode mapping catheter in patients. METHODS AND RESULTS: The basket-shaped mapping catheter (BMC), integrated with a computerized mapping system, allowed on-line reconstruction of endocardial activation maps. Twenty patients with VT were studied before surgery (n=4) or radiofrequency catheter ablation (n=16). End-diastolic left ventricular (LV) volume was 280+/-120 mL, with an LV ejection fraction of 33+/-14%. The volume encompassed by the BMC was 164+/-27 mL (130 to 200 mL); the deployment time was 46+/-11 minutes. Endocardial activation time during sinus rhythm was 105+/-34 ms; 14+/-5 electrodes could be used to stimulate the heart. Cycle length of VT was 325+/-83 ms. Earliest endocardial activation was recorded 58+/-42 ms before the onset of the surface ECG. Complications were pericardial effusion (n=2) and transient cerebral disorientation (n=1). CONCLUSIONS: Percutaneous multielectrode endocardial mapping in patients with VT is feasible and relatively safe. The use of this technique shortens the time patients have to endure VT.     

Therapeutic window of serum haloperidol concentration in acute schizophrenia and schizoaffective disorder

Starting from 3-(3-chloro-1H-pyrazol-5-yl)-1H-quinoxalin-2-one (2) a series of substituted [1,2,4]triazolo[4,3-a]quinoxalines (3a-f) was prepared via a multistep reaction sequence. Affinities of the novel derivatives 3a-f for benzodiazepine as well as for adenosine A1- and A2A-receptors of rat brain were determined by radioligand binding assays. 1-Methyl-4-(3-chloro-1H-pyrazol-5-yl) derivative 3a exhibited submicromolar affinity for the benzodiazepine binding site of GABAA receptors (Ki = 340 nM) and was less potent at A1-(Ki = 7.85 microM) and A2A-(Ki = 1.43 microM) adenosine receptors (AR). Derivatives with larger substituents in the 1-position showed reduced binding to benzodiazepine and A2A-AR, but increased A1-AR affinity, the 2-thienylmethyl derivative 3f being the most potent and selective A1-AR ligand of the present series (Ki = 200 nM).     

Constitutional WT1 mutations in Wilms' tumor patients

PURPOSE: Patients with Wilms' tumors (WT) who carry constitutional mutations in the WT1 gene have been described in case reports and small case series. We sought to determine the frequency of constitutional WT1 mutations in a larger cohort, and to identify clinical manifestations associated with the risk for carrying a WT1 mutation. METHODS: We collected clinical data and blood samples from 201 patients with a history of WT. Southern blot analysis, single-strand conformation polymorphism (SSCP) analysis, and direct DNA sequencing were performed on DNA isolated from peripheral-blood lymphocytes from each patient. Odds ratios (ORs) for the carriage of a germline mutation of the WT1 gene were calculated for patients who had specific clinical risk factors compared with those who did not. RESULTS: Of 201 patients with WT in the cohort, eight patients were carriers of mutations in the WT1 gene. Six of the eight mutations were protein-truncating nonsense mutations. None of 56 patients with isolated unilateral WT was a carrier. The OR of carrying a WT1 mutation was elevated for patients with genitourinary anomalies (OR19.3; P < .002). Seven of 28 boys with WT with cryptorchidism carried WT1 mutations. No increased risk was observed for patients with nephrogenic rests, bilateral tumors, history of secondary cancers, or family history of WT. CONCLUSION: Germline WT1 mutations in patients with WT are associated with genitourinary anomalies, especially cryptorchidism and/or hypospadias. Patients with WT and no genitourinary anomalies are at low risk for carrying a WT1 mutation. Constitutional WT1 mutations that encode truncated WT1 proteins may predispose to the development of cryptorchidism, hypospadias, and WTs.     

Increased capacity for interleukin-2 synthesis parallels disease progression in mice infected with Leishmania major

Lymph node cells of BALB/c mice with progressive leishmaniasis produced sixfold more interleukin-2 (IL-2) in culture than those of healing C57BL/6 mice. IL-2 synthesis also increased in C57BL/6 mice made susceptible by IL-12 or gamma interferon deficiency. However, IL-2 mRNA levels in vivo did not reflect IL-2 production in vitro. Because IL-2 contributes to the pathogenesis of progressive leishmaniasis, the functional significance of these findings should be further explored.     

Effects of non-glycated and glycated glucagon-like peptide-1(7-36) amide on glucose metabolism in isolated mouse abdominal muscle

This study investigated the actions of non-glycated and glycated glucagon-like peptide-1(7-36)amide (tGLP-1) on glucose uptake and metabolism in isolated mouse abdominal muscle. Monoglycated tGLP-1 (Mr 3463.8) was prepared under hyperglycemic reducing conditions and purified by HPLC. Non-glycated tGLP-1 (10(-10)-10(-8) mol/l) stimulated both 2-deoxy-D-[1-3H]glucose uptake (1.3-1.5 fold) and 14C-glucose oxidation (1.4-1.7 fold) in muscle compared to controls without tGLP-1. Glycation reduced these stimulatory effects by 27-33% and 25% (at 10(-9) mol/l), respectively. tGLP-1 (10(-10)-10(-8) mol/l) promoted muscle glycogenesis and lactate production, whereas glycated peptide was ineffective below 10(-9) mol/l. This study demonstrates that tGLP-1 has potent glycogenic effects in mouse abdominal muscle in vitro and that glycation impairs its action.     

Amikacin therapy of gram-negative bacteremia

Treatment with amikacin was evaluated in 15 patients with gram-negative bacteremia. The sources of sepsis were urinary tract (in six patients), abdomen (in five) and miscellaneous sites (in four). Sixteen bacterial pathogens were recovered, including three gentamicin-resistant organisms. All isolates were susceptible to amikacin. Eleven of the 14 patients who could be evaluated fulfilled the criteria for cure, including the three patients with gentamicin-resistant organisms. Three patients failed to respond to amikacin therapy. Monitoring untoward effects revealed eighth nerve toxicity in one patient and nephrotoxicity in one patient. These results indicate that amikacin is effective in the treatment of patients with gram-negative bacteremia, even when caused by gentamicin-resistant bacteria.