A canine model of hemophilic (factor VIII:C deficiency) bleeding

A model of bleeding due to clotting factor deficiency has been developed in dogs. Normal and hemophilic (factor VIII:C deficient) animals were used. Bleeding was induced in lightly anesthetized animals by severing the apex of the nail cuticle using a guillotine device. In normal animals, bleeding usually ceased spontaneously after 2-8 min. In contrast, in hemophilic animals, bleeding continued for up to 20 min and necessitated either cauterization or the application of topical thrombin to achieve hemostasis. Pretreatment of the hemophilic animals with canine cryoprecipitate corrected the cuticle bleeding time to within the range noted for normal animals. The method is simple and reproducible and has the advantage that a number of observations can be made sequentially on the same animal. Rebleeding of the cauterized cuticle of the hemophilic animals did not usually occur. This model has considerable potential for the preclinical testing of products considered to bypass or replace factor VIII:C in patients with acquired inhibitors of factor VIII:C and may be adapted to the study of other mechanisms involved in normal and abnormal hemostasis.     

Early fluctuations of BFU-E pool size after transfusion or erythropoietin treatment.

The kinetics of erythroid burst-(BFU-E) and colony-forming units (CFU-E) have been evaluated in marrow and spleen of normal or polycythemic mice, respectively, after transfusion or administration or purified erythropoietin (Ep). Ep injection induces an early but temporary rise of BFU-E number, versus a later but more prolonged expansion of the CFU-E pool. Symmetric patterns are observed after transfusion, i.e., an early but transient depletion of the BFU-E population, versus a later but more persistent decrease of the CFU-E number. It is suggested that the size of the BFU-E compartment is Ep-dependent in the "early" phase after erythroid perturbation. Later on, however, compensatory mechanisms allow the BFU-E pool to "escape" from the early Ep influence, thus allowing its size to return to and stabilize in the near normal range. It is further suggested that the BFU-E may represent an early target cell of Ep stimulus.     

Heterogeneous response of antimitochondrial autoantibodies and bile duct apical staining monoclonal antibodies to pyruvate dehydrogenase complex E2: the molecule versus the mimic

The 2-oxo-acid dehydrogenase complexes and, in particular, the E2 component of the pyruvate dehydrogenase complex (PDC) are the target of antimitochondrial antibodies (AMA). More than 95% of primary biliary cirrhosis (PBC) patients have detectable levels of autoantibodies to PDC-E2 and in general these react with a region of the molecule that contains the prosthetic group lipoic acid (LA). LA is vital to the function of the enzyme, although there is conflicting evidence as to whether its presence is required for PDC-E2 recognition by AMA. Some, but not all, monoclonal antibodies (mAbs) to PDC-E2 produce an intense staining pattern at the apical surface of bile duct epithelial cells (BEC) in patients with PBC, and it has been argued that the molecule at the apical surface of PBC bile duct cells is a modified form of PDC-E2 or a cross-reactive molecule, acting as a molecular mimic. Herein, we characterize the epitopes recognized by 4 anti-PDC-E2 mAbs that give apical staining patterns (3 mouse and 1 human). In particular, by using a combination of recombinant antigens, competitive inhibition assays, and a unique peptide-on-bead assay, we determined that these apically staining mAbs recognize 3 or 4 distinct epitopes on PDC-E2. More importantly, this suggests that a portion spanning the entire inner lipoyl domain of PDC-E2 can be found at the BEC apical surface. In addition, competition assays with patient sera and a PDC-E2-specific mAb showed significant epitope overlap with only 1 of the 3 mouse mAbs and showed a differential response to the peptide bound to beads. These findings further highlight the heterogeneous response of patient autoantibodies to the inner lipoyl domain of PDC-E2.     

Microaggregate counts in frozen-preserved erythrocytes: effects of washing in three blood processors and filtration

Since microaggregates have been implicated in posttransfusion pulmonary insufficiency, their elimination has become an active concern in blood transfusion. Various types of filters, as well as frozen-preserved erythrocytes, have been used to provide blood relatively low in microaggregates. We have counted particles in frozen-stored blood before deglycerolization, after washing in each of three cell processing systems, and after filtration through a 40-micrometer filter. Washing frozen erythrocytes reduced the total particle counts by an average of 89%. Slight differences were found among the three blood processors with respect to particle removal. Passing washed blood through a 40-micrometer filter did not result in significant further reduction in particle counts. Hence, the use of such filters in a frozen-preserved blood system is not warranted.     

Use of healthcare a long time after severe burn injury; relation to perceived health and personality characteristics

Purpose.?The aim of the study was to evaluate which factors are associated with the use of healthcare a long time after severe burn injury.

Method.?After a review process based on clinical reasoning, 69 former burn patients out of a consecutive group treated at the Uppsala Burn Unit from 1980?–?1995 were visited in their homes and their use of care and support was assessed in a semi-structured interview. Post-burn health was assessed with the Burn-Specific Health Scale-Brief (BSHS-B) and personality was assessed with the Swedish universities Scales of Personality (SSP).

Results.?The participants were injured on average eight years previously. Thirty-four had current contact with healthcare due to their burn injury and had significantly lower scores on three BSHS-B-domains: Simple Abilities, Work and Hand function, and significantly higher scores for the SSP-domain Neuroticism and the SSP-scales Stress Susceptibility, Lack of Assertiveness, and lower scores for Social Desirability. There was no relation to age, gender, time since injury, length of stay, or to the surface area burned.

Conclusions.?A routine screening of personality traits as a supplement to long-term follow-ups may help in identifying the patient's need for care.     

The Effect of Visual Contrast on Human Vestibulo-Ocular Reflex Adaptation

The vestibulo-ocular reflex (VOR) is the main retinal image stabilising mechanism during rapid head movement. When the VOR does not stabilise the world or target image on the retina, retinal image slip occurs generating an error signal that drives the VOR response to increase or decrease until image slip is minimised, i.e. VOR adaptation occurs. Visual target contrast affects the human smooth pursuit and optokinetic reflex responses. We sought to determine if contrast also affected VOR adaptation. We tested 12 normal subjects, each over 16 separate sessions. For sessions 1–14, the ambient light level (lx) during adaptation training was as follows: dark, 0.1, 0.2, 0.3, 0.5, 0.7, 1, 2, 8, 16, 32, 64, 128 and 255 lx (light level for a typical room). For sessions 15–16, the laser target power (related to brightness) was halved with ambient light at 0 and 0.1 lx. The adaptation training lasted 15 min and consisted of left/right active head impulses. The VOR gain was challenged to increment, starting at unity, by 0.1 every 90 s for rotations to the designated adapting side and fixed at unity towards the non-adapting side. We measured active and passive VOR gains before and after adaptation training. We found that for both the active and passive VOR, there was a significant increase in gain only towards the adapting side due to training at contrast level 1.5 k and above (2 lx and below). At contrast level 261 and below (16 lx and above), adaptation training resulted in no difference between adapting and non-adapting side gains. Our modelling suggests that a contrast threshold of ~ 1000, which is 60 times higher than that provided by typical room lighting, must be surpassed for robust active and passive VOR adaptation. Our findings suggest contrast is an important factor for adaptation, which has implication for rehabilitation programs.     

改良尿道拖入术治疗外伤性后尿道狭窄

自1994年以来,我院采用改良的尿道拖人术治疗外伤性后尿道狭窄22例,取得满意疗效,现报道如下。l临床资料本组病例均为男性,为严重车祸伤或高处跌伤致骨盆骨折所致,年龄则一46岁,平均35岁。临床症状有尿道四溢血、尿摊留、腹胀、肛周青紫肿胀,有休克者2例,合并直肠损伤2例,磅眈破裂6例。术中发现前列腺尖游离者4例。所有病例不能将导尿管插入膀跳,而均行单纯“耻骨上膀胜造疾术”,有膀脱破裂者行“膀脱破裂修补术”,有直肠损伤者,行“乙状结肠造疫术”。患者于术后3－6个月来院行尿道重建术。术前常规尿道造影,显示膜部尿道狭…