The effect of tourniquet release timing on perioperative blood loss in simultaneous bilateral cemented total knee arthroplasty: a prospective randomized study.

Today the use of pneumatic tourniquet is commonly accepted in total knee arthroplasty (TKA) to reduce perioperative blood loss. There are a few prospective randomised and nonrandomised studies that compare the effect of tourniquet release timing in cementless or cemented unilateral TKA. However, many of these studies show an inadequate reporting and methodology. This randomized prospective study was designed to investigate the efficiency of tourniquet release timing in preventing perioperative blood loss in a simultaneous bilateral TKA study design. To our knowledge, this is the first study of its kind, in which the effect of tourniquet release timing on perioperative blood loss was investigated in simultaneous bilateral cemented TKA to compare both techniques intraindividually. In 20 patients (40 knees) one knee was operated with tourniquet release and hemostasis before wound closure, and the other knee with tourniquet release after wound closure and pressure dressing. We found no significant difference in total blood loss between both techniques (p=0.930), but a significant difference in operating time (p=0.035). There were no postoperative complications at a follow-up of 6 month. Other studies report an increase the blood loss in early tourniquet release and an increase the risk of early postoperative complications in deflation of tourniquet after wound closure. In this study we found no significant difference in perioperative blood loss and no increase of postoperative complications. Therefore, we recommend a tourniquet release after wound closure to reduce the duration of TKA procedure and to avoid possible risks of extended anaesthesia.     

Neuropsychological functions,sleep, and mental health in adults with Klinefelter syndrome

A few studies have examined neuropsychological functions, sleep, and mental health combined in Klinefelter syndrome (KS; 47,XXY). We investigated neuropsychological functions with standard tests, sleep with actigraphy, and self‐reported mental health in 30 men with KS (Mean age = 36.7 years) compared to 21 controls (Mean age = 36.8 years). Men with KS scored significantly lower on mental speed, attention span, working memory, inhibition, and set‐shifting tests, as well as overall IQ (mean effect size difference Cohen's d = 0.79). Men with KS had significantly longer night wakes, with no differences in other sleep variables (mean d = 0.34). Men with KS reported poorer mental health than controls (mean d = 1.16). Regression analyses showed neuropsychological functions explained variance in some sleep domains for men with KS but not for controls. Neuropsychological functions explained variance in some mental health domains for controls. For men with KS, however, verbal IQ was the only significant predictor of mental health. Altogether, men with KS display problems in neuropsychological functions and mental health but do not appear different from controls on most sleep parameters. Our findings indicate that relations between neuropsychological functions, sleep, and mental health differ between men with KS and controls.     

Modification of rat brain Kv1.4 channel gating by association with accessory Kvβ1.1 and β2.1 subunits

 We have examined the effects of co-expression of Kvβ1.1 and Kvβ2.1 subunits on the gating of rat brain Kv1.4 channels, expressed in Xenopus oocytes. Expression of Kv1.4 subunits alone produced a rapidly inactivating ”A” type current, which activated at potentials beyond –60 mV in a solution containing high levels of rubidium. Current activation curves obtained from tail current measurements were fitted with a Boltzmann function, with V _1/2 = –47 mV and k = 10 mV. Neither the Kvβ1.1 nor Kvβ2.1 subunits altered the voltage dependence of activation. Both subunits accelerated the activation time constant of Kv1.4, without affecting its voltage dependence. Surprisingly, the Kvβ2.1 subunit, which lacks an N-terminal inactivation domain, was almost as effective as the Kvβ1.1 subunit in speeding up Kv1.4. Steady-state inactivation of Kv1.4 was unchanged upon co-expression with either Kvβ1.1 or Kvβ2.1 subunits. Kv1.4 recovered from inactivation with two time constants; apart from an ≈ 50% lengthening of the slow time constant with a high Kvβ2.1 injection ratio, neither time constant was altered by either the Kvβ1.1 or Kvβ2.1 subunits, suggesting little interaction with recovery from C-type inactivation. Clearly, β subunits have the potential to modify the gating of Kv1.4 channels in the brain more subtly than has been suggested previously. Received: 17 March 1997 / Accepted: 30 June 1997     

Presymptomatic diagnosis of SMA III by genotype analysis

Linkage analysis and prenatal prediction in families segregating autosomal recessive spinal muscular atrophy (SMA) has become feasible since the assignment of the locus responsible for type I-III SMA to region 5q12-q13.3. We have performed a segregation study of SMA in Italian families using molecular probes and highly informative PCR-based polymorphic markers. In one family, a 7-year-old boy affected with type III SMA and an 8-year-old apparently healthy brother had identical haplotypes. These findings prompted us to reexamine the apparently unaffected child. His neurological exam was normal. However, the electromyography (EMG) showed a pattern consistent with chronic SMA. To our knowledge this is the first example of presymptomatic diagnosis of SMA based on genotype analysis. © 1993 Wiley-Liss, Inc.     

Lactoferrin gene expression is estrogen responsive in human and rhesus monkey endometrium.

We have previously shown that the estrogen responsiveness of the human lactoferrin gene in a transient transfection system is mediated through an imperfect estrogen response element (ERE) and a steroidogenic factor 1 binding element (SFRE) 26 bp upstream from ERE. Reporter constructs containing SFRE and ERE respond to estrogen stimulation in a dose-dependent manner, whereas mutations at either one of the response elements severely impaired the estrogen responsiveness. In this study, we demonstrated that estrogen receptor (ERalpha) binds to the human lactoferrin gene ERE and forms two complexes in an electrophoresis mobility shift assay (EMSA). These complexes could be supershifted by an antibody to ERalpha. We also showed that in normal cycling women, lactoferrin gene expression in the endometrium increases during the proliferative phase and diminishes during the luteal phase. This in-vivo study thus supported the finding from transient transfection experiments that the human lactoferrin gene expression is elevated in an environment with a high level of estrogen. The estrogen effect on lactoferrin gene expression in the rhesus monkey endometrium was studied by Western blotting and immunohistochemistry. The immunohistochemistry results showed that immunoreactive lactoferrin protein was not detectable in the untreated ovariectomized monkey endometrium, was elevated by estrogen treatment, and was suppressed by sequential, combined estrogen plus progesterone treatment. In conclusion, this study has shown that lactoferrin gene expression is responsive to estrogen in primate endometrium.     

Behavioral Upset in Medical Patients-Revised: Evaluation of a Parent Report Measure of Distress for Pediatric Populations

Examined the utility of a new parent-report measure designedspecifically for pediatric inpatients, the Behavioral Upsetin Medical Patients-Revised (BUMP-R). The BUMP-R was administeredto 151 mothers of hospitalized children ages 4–12 yearsthe day following the child's hospital admission. The BUMP-Rdemonstrated good internal consistency and a factor analysisrevealed four factors identified as negativity/agitation, amiability,dysphoria, and noncom-pliance. Children exhibiting behavioraldistress at home were more likely to experience adjustment problemsupon hospitalization. Demographic and illness-related variableswere not substantial risk factors for hospital adjustment difficulties.     

On the various manifestations of spontaneous autoimmune diabetes in rodent models

Autoimmune (type 1) diabetes mellitus in mouse, rat, and humans shares several features, including T lymphocyte infiltration into pancreatic islets and a dependence on permissive class II major histocompatibility complex (MHC) alleles. We report here on an experimental model involving mice that express influenza hemagglutinin (HA) under the control of the insulin promoter and, at the same time, a transgenic class II MHC-restricted T cell receptor (TcR) specific for an HA peptide. These mice spontaneously develop islet infiltrates resembling those found in NOD mice and most animals become diabetic within 8 weeks of age. Because of the availability of a clonotypic TcR antibody, we can be confident that the Ins-HA transgene does not induce any measurable alterations in the vast majority of T cells with the transgenic TcR in primary and secondary lymphoid organs. Continuous export of large numbers of HA-specific lymphocytes from the thymus was not required for the manifestation of the disease since mice thymectomized at 3 days after birth still developed the disease albeit with smaller infiltrates.     

Peptide-based approaches to treat asthma, arthritis, other autoimmune diseases and pathologies of the central nervous system

In this review we focus on peptide- and peptidomimetic-based approaches that target autoimmune diseases and some pathologies of the central nervous system. Special attention is given to asthma, allergic rhinitis, osteoarthritis, and Alzheimer's disease, but other related pathologies are also reviewed, although to a lesser degree. Among others, drugs like Diacerhein and its active form Rhein, Pralnacasan, Anakinra (Kineret), Omalizumab, an antibody "BION-1", directed against the common beta-chain of cytokine receptors, are described below as well as attempts to target beta-amyloid peptide aggregation. Parts of the review are also dedicated to targeting of pathologic conditions in the brain and in other tissues with peptides as well as methods to deliver larger molecules through the "blood--brain barrier" by exploring receptor-mediated transport, or elsewhere in the body by using peptides as carriers through cellular membranes. In addition to highlighting current developments in the field, we also propose, for future drug targets, the components of the inflammasome protein complex, which is believed to initiate the activation of caspase- 1 dependent signaling events, as well as other pathways that signal inflammation. Thus we discuss the possibility of targeting inflammasome components for negative or positive modulation of an inflammatory response.