Drug management in emergent liver transplantation of mitochondrial disorder carriers: review of the literature

Vater Y, Dembo G, Martay K, Klein Y, Vitin A, Weinbroum AA. Drug management in emergent liver transplantation of mitochondrial disorder carriers: review of the literature.
Clin Transplant 2010 DOI: 10.1111/j.1399‐0012.2009.01203.x
© 2010 John Wiley & Sons A/S. Abstract: Background: Mitochondrial respiratory‐chain disorders (MRCD) lead to progressive disabling of neurological and cellular conditions that involve muscles, brain, kidney, and liver dysfunction. Affected individuals may need surgery, including orthotopic liver transplantation (OLT). Surgery poses anesthesia challenges because of the prolonged use of anesthetic drugs and sedatives, which may inhibit oxidative phosphorylation, mimic mitochondrial cytopathic disorders, or unveil them ex novo. Materials and methods: We conducted a multilingual PubMed search of surgical and non‐surgical anesthesia reports between the years 1992 and 2008, where anesthetic drugs were used in MRCD patients, especially for those undergoing urgent OLTs. Results: There were 51 case reports of 210 anesthesia and critical care interventions in patients with MRCD, a large part of them were children. Data pertaining to the safe usage of anesthesia and perioperative drugs were limited and conflicting. We found no article that addressed the issue of perioperative handling of urgent OLT in MRCD patients. We therefore suggest our own – although limited – experience for such occasions. Conclusion: There are no randomized, controlled, trial‐based indications regarding safe anesthetic drugs to be used perioperatively in MRCD carriers. Consultation among geneticists, anesthesiologists, intensivists, and surgeons is essential in patients with known/suspected metabolic syndrome for planning appropriate perioperative care.     

Bestandsverminderung bei verwilderten Haustauben Teil 1 Bilanz mitteleurop?ischer Stadtverwaltungen Bilanz mitteleurop?ischer Stadtverwaltungen

Der zweiteilige Bericht fa?t die Ergebnisse einer Umfrage zusammen, bei der sich die Verwaltungen von 52 mitteleurop?ischen St?dten zum Stra?entaubenproblem ge?u?ert haben. überwiegend versucht man mehr oder minder erfolglos, eine Bestandsverminderung durch Taubenfütterungsverbot zu erreichen. H?ufig wird auch von Bürgerbelehrungen und Informationskampagnen berichtet. Ferner spielen Fangaktionen, Taubenh?user, Hormonpr?parate und Chemosterilantien, Abschu? und Absperrma?nahmen an Geb?uden eine meist ambivalente Rolle. Bei der Verminderung der Brutplatzangebote sind nur schwache Bemühungen erkennbar. Natürliche Feinde (Greifv?gel) scheinen in den wenigsten St?dten eine Rolle bei der Reduzierung von Stra?entauben zu spielen. Vergiftungen werden offenbar nicht mehr vorgenommen.     

Preoperative fasting after soft drink intake: 2 hours may be enough

Sufficient preoperative fasting time is essential for safe induction of anesthesia to prevent aspiration of gastric contents. However, the time recommended for sufficient preoperative fasting varies greatly, depending on the nature of the oral intake, from 2 h for clear liquids to 6 h for solid foods. We report the case of a 30-year-old man who drank about 600 ml of the carbonated, glucose-rich soft drink, 7-UP, 2 h before surgery and absorbed nearly all of it within these 2 preoperative hours. Received: September 10, 2001 / Accepted: January 8, 2002     

Generation and characterization of human monoclonal scFv antibodies against Helicobacter pylori antigens

Infection with Helicobacter pylori is chronic despite a vigorous cellular and humoral immune response and causes severe pathology in some patients. In this study, phage display was used as a new approach in order to investigate the role of the host's humoral immune response in the pathogenesis of H. pylori gastritis. Human monoclonal single-chain Fv (scFv) antibody fragments against H. pylori cell lysate and the H. pylori urease were isolated from an immune phage display library, constructed from peripheral blood lymphocytes of an H. pylori-infected patient. After affinity selection, 23% of the clones tested showed binding activity against a lysate of the H. pylori Sydney strain in enzyme-linked immunosorbent assay (ELISA) and 9% bound the H. pylori urease. Further characterization by PCR-fingerprint analysis and sequencing revealed that two closely related H. pylori binders and one antiurease scFv could be isolated. The selected scFvs were highly specific as analyzed by ELISA and immunoblots using various bacterial lysates and recombinant proteins. Analysis of the humoral immune response following H. pylori infection using human monoclonal antibodies might contribute to a better understanding of the pathogenesis of the disease. Moreover, using immune phage display libraries, it might be possible for relevant epitopes of H. pylori antigens to be determined, which might be of use for vaccine development.     

When grandiosity and vulnerability collide: Implicit and explicit self-esteem in patients with narcissistic personality disorder

BACKGROUND AND OBJECTIVES: Narcissistic personality disorder (NPD) is characterized by reports of grandiosity including exaggerated illusions of superiority and entitlement (DSM-IV-TR, APA, 2000). Based on clinical theories (e.g., Kernberg, 1975), many researchers argue that high explicit self-esteem in narcissists masks underlying implicit vulnerability (low implicit self-esteem). Conversely, based on social learning theories (i.e., Millon, 1981), people with NPD are characterized by implicit grandiosity (high implicit self-esteem). We test these competing hypotheses in patients diagnosed with NPD. METHODS: The present study examined implicit self-esteem (using an Implicit Association Test) and explicit self-esteem (using a self-report questionnaire) in patients with NPD in comparison to non-clinical and clinical, non-NPD (Borderline Personality Disorder, BPD) control groups. RESULTS: Patients with NPD scored lower on explicit self-esteem than non-clinical controls. In comparison to patients with BPD, NPD patients scored higher on explicit and implicit self-esteem. Moreover, within the group of NPD patients, damaged self-esteem (i.e., low explicit, high implicit) was associated with higher narcissistic psychopathology. LIMITATIONS: In both clinical groups we included participants seeking psychiatric treatment, which might influence explicit self-esteem. Longitudinal studies are needed to further assess self-esteem stability in NPD patients in comparison to the control groups. CONCLUSIONS: Our findings are indicative of vulnerable facets in patients with NPD (i.e., low explicit self-esteem). Furthermore, damaged self-esteem is connected to specific psychopathology within the NPD group. Implications for research on NPD are discussed.     

Recurrent mutation of JAK3 in T‐cell prolymphocytic leukemia

T‐cell prolymphocytic leukemia (T‐PLL) is an aggressive post‐thymic T‐cell malignancy characterized by the recurrent inv(14)(q11q32)/t(14;14)(q11;q32) or t(X;14)(q28;q11) leading to activation of either the TCL1 or MTCP1 gene, respectively. However, these primary genetic events are insufficient to drive leukemogenesis. Recently, activating mutations in JAK3 have been identified in other T‐cell malignancies. Since JAK3 is essential for T‐cell maturation, we analyzed a cohort of 32 T‐PLL patients for mutational hot spots in the JAK3 gene using a step‐wise screening approach. We identified 14 mutations in 11 of 32 patients (34%). The most frequently detected mutation in our cohort was M511I (seen in 57% of cases) previously described as an activating change in other T‐cell malignancies. Three patients carried two mutations in JAK3. In two patients M511I and R657Q were simultaneously detected and in another patient V674F and V678L. In the latter case we could demonstrate that the mutations were on the same allele in cis. Protein modeling and homology analyses of mutations present in other members of the JAK family suggested that these mutations likely activate JAK3, possibly by disrupting the activation loop and the interface between N and C lobes, increasing the accessibility of the catalytic loop. In addition, four of the 21 patients lacking a JAK3 point mutation presented an aberrant karyotype involving the chromosomal band 19p13 harboring the JAK3 locus. The finding of recurrent activating JAK3 mutations in patients with T‐PLL could enable the use of JAK3 inhibitors to treat patients with this unfavorable malignancy who otherwise have a very poor prognosis. © 2014 Wiley Periodicals, Inc.     

Biological Considerations for Combining Carcinogenicity Data for Quantitative Risk Assessment

Quantitative risk assessments for carcinogens conducted by the U.S. EPA have most frequently been based on results of a bioassay from a single sex/strain/species of animal. In some cases, more than one data set derived from different sexes, strains, or species of animals is suitable for quantitative risk assessment. When there is no apparent difference among the data sets in sensitivity to the carcinogen, use of more of the available data should result in a higher level of confidence in the risk estimate. Several biological factors must be considered before combining data from different animal sexes, strains, species, or tumor sites. The relevance of the animal models, study design and execution, dose selection, and route of administration are factors which influence whether data from separate studies should be combined. The decision to combine data sets is also based on what is known of the mechanism of action of the agent, its pharmacokinetics, any species/sex specificity of the effect, and considerations regarding tumor site specificity. Statistical analysis also indicates whether the data sets may be described by the same multistage model. The evaluation of these factors in the decision to combine or not combine data sets is discussed.     

Binaural properties of single units in the superior olivary complex of the mustached bat.

1. Previous studies of the superior olive of echolocating bats suggest that the lateral superior olive (LSO) retains the same structure and function as in other mammals but that the medial superior olive (MSO) is different in structure and possibly also in function. The present study is an examination of this idea in Pteronotus parnellii, a bat that has a large and well-defined MSO. 2. Using pure tones presented via earphones, we obtained data on frequency tuning for 60 single units and 96 multiunits in LSO and 94 single units and 154 multiunits in MSO. Of these we also obtained binaural response characteristics from 55 single units in LSO and 72 single units in MSO. 3. LSO and MSO each have a complete tonotopic representation, arranged in a sequence similar to that of other mammals studied. However, in both LSO and MSO there is an expanded representation of the frequencies around 60 kHz, the main frequency component of the bat's echolocation call; there is another expanded representation of the range around 90 kHz, the third harmonic of the call. The expansion of these frequency ranges suggests that the functions of LSO and MSO in Pteronotus are related to echolocation behavior. 4. The binaural characteristics of cells in LSO were essentially the same as those seen in other mammals. Most LSO units (93%) were excited by the ipsilateral ear and inhibited by the contralateral ear. The responses of nearly all LSO units were completely suppressed when the sound level at the two ears was equal. 5. The binaural characteristics of cells in MSO were different from those in nonecholocating mammals. Most MSO units (72%) were excited by the contralateral ear but were neither excited nor inhibited by the ipsilateral ear. Of the remaining units, 21% were excited by the contralateral ear and inhibited by the ipsilateral ear, and only 6% were excited by both ears. 6. The temporal discharge patterns of units in MSO differed from the tonic response pattern seen in LSO. Most MSO units had phasic response patterns, with a few spikes at the onset or offset of the stimulus; the response often changed from ON to OFF depending on stimulus frequency. 7. The results support the idea that in evolution LSO has remained unchanged, whereas MSO has undergone adaptation. The function of LSO in Pteronotus seems to be identical to that in other mammals, i.e., analysis of interaural sound level differences to derive azimuthal location. The function of MSO in Pteronotus must be different from that in nonecholocating mammals.(ABSTRACT TRUNCATED AT 400 WORDS)