Manubriotomy versus median sternotomy in thymectomy for myasthenia gravis. Evaluation of the pulmonary status.

OBJECTIVE: In a prospective study, the effect of thymectomy on the pulmonary status of 50 consecutive patients with myasthenia gravis was evaluated over a time range of 4 years in the Chest and Chest surgery departments in the Cairo University Clinics and Thoracic Surgery Department of the Evangelisches Krankenhaus Duisburg-Nord. METHODS: The patients were divided into two groups: Group I included 26 patients who underwent thymectomy through median sternotomy. The mean age of the patients in this group was 24.8+/-10.5 (5-41) years. They were 19 females and seven males. Thirteen of the patients were in Myasthenia Gravis Foundation of America (MGFA) class IIa, and 12 were in class IIb, and one was in class IIIa. Group II included 24 patients who underwent thymectomy through manubriotomy. The mean age of the patients in this group was 25.2+/-9.2 (12-41) years. They were 13 females and 11 males. Eight of the patients were in MGFA class 2a, 14 were in class IIb, and two were in class IIIa. RESULTS: When compared to group I in which postoperative ventilation was required in 15.4% of patients, postoperative ventilation was not necessary in patients of group II with a statistically significant difference (P=0.04). The mean duration of stay in the intensive care unit was 111.4h in group II, and 169.7h in group I (P=0.03). The peak inspiratory flow rate and the forced vital capacity were also statistically significantly better in group II. There was no mortality in both groups, and the morbidity was higher in the median sternotomy group. CONCLUSION: Thymectomy through a manubriotomy, which allows extensive removal of ectopic thymic tissue in addition to the thymus through a less invasive approach than a full median sternotomy, is associated with a significantly smoother postoperative course and less pulmonary complications, when compared with thymectomy through a full median sternotomy.     

Magnetically-labeled sensitized splenocytes to identify glioma by MRI: a preliminary study.

This study investigated the feasibility of imaging the migration and incorporation of magnetically-labeled sensitized splenocytes in an experimental 9L glioma brain tumor model. Splenocytes collected from tumor-bearing (sensitized splenocytes) or control (nonsensitized splenocytes) host rats were analyzed to determine the population of different cells, labeled with ferumoxides-protamine sulfate (FePro) and injected intravenously to recipient rats (N=4, for each group) bearing intracranial 9L tumors. Day 3 postinjection of splenocytes multiecho T2*-weighted and three-dimensional (3D) gradient echo MRI were obtained using a 7 Tesla MR system. R2* (1/T2*) maps were created from the T2*-weighted images. Signal intensities (SIs) and R2* values in the tumors and contralateral brain were determined by hand drawn regions of interest (ROIs). Brain sections were stained for the evidence of administered cells. Both 3D and T2*-weighted MRI showed low signal intensity areas in and around the tumors in rats that received labeled sensitized splenocytes. Prussian blue (PB), CD45- and CD8-positive cells were present in areas at the corresponding sites of low signal intensities seen on MRI. Rats that received labeled nonsensitized splenocytes did not show low signal intensity areas or PB positive cells in or around the implanted tumors. In conclusion, the immunogenic reaction can be exploited to delineate recurrent glioma using MRI following systemically delivered magnetically labeled sensitized splenocytes or T-cells.     

Effects of a toxin from the mucus of the caribbean sea anemone (Bunodosoma granulifera) on the ionic currents of single ventricular mammalian cardiomyocytes

The effects were studied of a toxin (Bainh) isolated from the secretion of the Caribbean sea anemone Bunodosoma granulifera on electrical and mechanical activities of rat ventricular muscle. The effects on the ionic currents of single rat and dog ventricular cardiomyocytes were studied using the whole-cell recording patch-clamp technique. In the concentration range from 1 to 10 mg/ml, Bainh increased the force of contraction and induced an increase in action potential duration of ventricular multicellular preparations. In single cardiomyocytes, at concentrations up to 10 mg/ml Bainh showed no significant effects on the sodium current. However, at 0.5–1 mg/ml it increased the L-type Ca current (I_CaL) by 25–50%. This increase in I_CaL was not voltage dependent and was reversible after washout. The transient outward current was not significantly affected by Bainh (1–10 mg/ml). In this concentration range, Bainh markedly (≈75%) increased the inward-going rectifier current, I_K1. This effect that was not voltage dependent and was fully reversible upon returning to control solution. It is suggested that these effects on ionic currents could explain the positive inotropic action of Bainh on cardiac multicellular preparations.     

Scorpion sting: a management problem.

Admissions for scorpion sting in 1 year and deaths resulting from scorpion sting over 3 years were analysed. Features that indicated the severity of the clinical condition were identified. Pulmonary oedema and shock were the usual causes of death. Poor management of fluid therapy was responsible for the frequently unsatisfactory resolution of envenoming, especially when purified human plasma was used. The role of the scorpion antivenom used is questioned and controversy regarding the most appropriate sedative to use in the management of scorpion sting is still not resolved. An in-depth study of these management issues is urgently required.     

Gallbladder dyskinesia in chronic acalculous cholecystitis

To test the hypothesis that there is an early stage of cholesterol gallstone formation in man characterized by symptoms of chronic cholecystitis, poor gallbladder emptying, and biliary cholesterol crystals, we studied cholecystokinin-stimulated gallbladder emptying by DISIDA scintigraphy and examined bile for cholesterol crystals in symptomatic patients with normal oral cholecystography and gallbladder sonography. Of 36 patients studied, 16 had biliary cholesterol crystals; their mean 30-min gallbladder ejection fraction was 25.9±14.8%. Among the 20 patients without crystals, the mean ejection fraction was 60.3±23.3%. Fifteen patients, 11 with crystals and four without, had cholecystectomy because of persistent symptoms. All with crystals preoperatively and three without had chronic cholecystitis histologically. One patient without crystals had normal histology. We conclude that poor gallbladder contractility, well-established as an etiologic factor in animal models of cholesterol cholelithiasis, is now linked to acalculous cholecystitis, an early stage of human cholesterol cholelithiasis.     

Age and symptom experience at menopause in the Selska Valley, Slovenia

OBJECTIVE: To assess age and symptom experience at menopause in a high-altitude population in the Selska Valley of Slovenia. DESIGN: In four mountain villages, all houses were approached and 80% of eligible residents were interviewed. Additional women were interviewed for comparison in the valley below. Age at interview ranged from 32.7 to 85.5 years, with a mean of 58.2 years. The majority of women (62%) were aged 40 to 65 years. RESULTS: Of the 58 women interviewed, 7 had undergone menopause by hysterectomy (12%). Recalled age at natural menopause ranged from 42 to 54, with a mean of 50.3 (SD 2.9). By probit analysis, median age at natural menopause was 52.03. Fifty-five percent of participants reported ever having experienced a hot flash, although only 24% reported hot flashes during the 2 weeks before being interviewed. When the sample was limited to women aged 40 to 65, frequency of hot flashes in the 2 weeks before the interview was 39%. For all participants, the most frequent complaint was lack of energy (66%), followed by backaches (59%), and joint stiffness (53%). CONCLUSIONS: In contrast to expectations, age at menopause was not earlier and hot flash frequency was not significantly lower at higher elevations.     

miRNPs: a novel class of ribonucleoproteins containing numerous microRNAs

Gemin3 is a DEAD-box RNA helicase that binds to the Survival of Motor Neurons (SMN) protein and is a component of the SMN complex, which also comprises SMN, Gemin2, Gemin4, Gemin5, and Gemin6. Reduction in SMN protein results in Spinal muscular atrophy (SMA), a common neurodegenerative disease. The SMN complex has critical functions in the assembly/restructuring of diverse ribonucleoprotein (RNP) complexes. Here we report that Gemin3 and Gemin4 are also in a separate complex that contains eIF2C2, a member of the Argonaute protein family. This novel complex is a large approximately 15S RNP that contains numerous microRNAs (miRNAs). We describe 40 miRNAs, a few of which are identical to recently described human miRNAs, a class of small endogenous RNAs. The genomic sequences predict that miRNAs are likely to be derived from larger precursors that have the capacity to form stem-loop structures.     

Inhibition of allergic airways inflammation and airway hyperresponsiveness in mice by dexamethasone: role of eosinophils,IL-5, eotaxin,and IL-13

BACKGROUND: Glucocorticoids inhibit allergen-induced airway eosinophilia and airway hyperresponsiveness (AHR). Whether glucocorticoids mediate their effects on AHR by inhibiting eotaxin and IL-5, 2 of the principal mediators of eosinophilia, or through IL-13, an important mediator of AHR, has not been established. OBJECTIVE: We sought to investigate the effects of glucocorticoids on airway eosinophilia and the expression of IL-5, eotaxin, and IL-13 in relation to the induction of AHR in a murine model of allergic asthma. METHODS: Dexamethasone (4 mg/kg) and mAbs against eotaxin (80 micro g/kg) and IL-5 (100 micro g/kg) singly and in combination were administered to immunized mice before antigen challenge. Airway responsiveness to methacholine was measured in anesthetized and mechanically ventilated animals. Eotaxin, IL-5, and IL-13 in bronchoalveolar lavage fluid (BALF), lung homogenates, or both were measured by means of ELISA. RESULTS: A single antigen challenge induced AHR that lasted at least 10 days. Eotaxin protein and mRNA levels increased in lung tissue but not in BALF after challenge. IL-5 protein and mRNA levels increased both in BALF and in lung tissue. Dexamethasone reduced airway eosinophilia, AHR, and protein and mRNA for eotaxin and IL-5. Anti-murine eotaxin and anti-IL-5 antibodies alone and in combination reduced the ovalbumin-induced airway eosinophilia significantly but failed to inhibit AHR. Both dexa-methasone and anti-IL-5/anti-eotaxin inhibited the increases in lung IL-13 levels after ovalbumin challenge to a similar extent. CONCLUSION: These findings suggest that the inhibition of AHR by the glucocorticoid dexamethasone does not appear to be explained by effects on eosinophilia, eotaxin, IL-5, or IL-13.     

Sequence variation in the 3'-untranslated region of the dopamine transporter gene and attention-deficit hyperactivity disorder (ADHD).

The dopamine transporter gene (DAT1) has been reported to be associated with attention-deficit hyperactivity disorder (ADHD) in a number of studies [Cook et al. (1995): Am J Human Genet 56(4):9993-998; Gill et al. (1997): Mol Psychiatry 2(4):311-313; Waldman et al. (1998): Am J Human Genet 63(6):1767-1776; Barr et al. (2001): Biol Psychiatry 49(4):333-339; Curran et al. (2001): Mol Psychiatry 6(4):425-428; Chen et al. (2003): Mol Psychiatry 8(4):393-396]. Specifically, the 10-repeat allele of the 40-bp variable number of tandem repeats (VNTR) polymorphism located in the 3' untranslated region (UTR) of the gene has been found to be associated with ADHD. There is evidence from in vitro studies indicating that variability in the repeat number, and sequence variation in the 3'-UTR of the DAT1 gene may influence the level of the dopamine transporter protein [Fuke et al. (2001): Pharmacogenomics J 1(2):152-156; Miller and Madras (2002): Mol Psychiatry 7(1):44-55]. In this study, we investigated whether DNA variation in the DAT1 3'UTR contributed to ADHD by genotyping DNA variants around the VNTR region in a sample of 178 ADHD families. These included a MspI polymorphism (rs27072), a DraI DNA change (T/C) reported to influence DAT1 expression levels, and a BstUI polymorphism (rs3863145) in addition to the VNTR. We also screened the VNTR region by direct resequencing to determine if there was sequence variation within the repeat units that could account for the association. Our results indicate that DAT1 is associated with ADHD in our sample but not with alleles of the VNTR polymorphism. We did not find any variation in the sequence for either the 10- or 9-repeat alleles in the probands screened nor did we observe the reported DraI (T/C) variation. Our results therefore refute the possibility of the reported DraI variation or alleles of the VNTR as the functional variants contributing to the disorder.