Residual Paralysis in the PACU after a Single Intubating Dose of Nondepolarizing Muscle Relaxant with an Intermediate Duration of Action

Background: Residual neuromuscular blockade remains a problem even after short surgical procedures. The train-of-four (TOF) ratio at the adductor pollicis required to avoid residual paralysis is now considered to be at least 0.9. The incidence of residual paralysis using this new threshold is not known, especially after a single intubating dose of intermediate-duration nondepolarizing relaxant. Therefore, the aim of the study was to determine the incidence of residual paralysis in the postanesthesia care unit after a single intubating dose of twice the ED95 of a nondepolarizing muscle relaxant with an intermediate duration of action.

Methods: Five hundred twenty-six patients were enrolled. They received a single dose of vecuronium, rocuronium, or atracurium to facilitate tracheal intubation and received no more relaxant thereafter. Neuromuscular blockade was not reversed at the end of the procedure. On arrival in the postanesthesia care unit, the TOF ratio was measured at the adductor pollicis, using acceleromyography. Head lift, tongue depressor test, and manual assessment of TOF and DBS fade were also performed. The time delay between the injection of muscle relaxant and quantitative measurement of neuromuscular blockade was calculated from computerized anesthetic records.

Results: The TOF ratios less than 0.7 and 0.9 were observed in 16% and 45% of the patients, respectively. Two hundred thirty-nine patients were tested 2 h or more after the administration of the muscle relaxant. Ten percent of these patients had a TOF ratio less than 0.7, and 37% had a TOF ratio less than 0.9. Clinical tests (head lift and tongue depressor) and manual assessment of fade showed a poor sensitivity (11-14%) to detect residual blockade (TOF < 0.9).     

Suppurative corneal ulceration in Bangladesh

Suppurative keratitis is an important preventable cause of blindness, particularly in the developing world. This study analyses 142 cases of suppurative keratitis referred to Chittagong Eye Infirmary, Bangladesh. Some 53.5% of cases were bacterial and 35.9% were fungal. The five most common pathogens were: Pseudomonas sp. 24%, Streptococcus pneumoniae 17%, Aspergillus sp. 13%, Fusarium sp. 7% and Curvularia sp. 6%. Gram stain and culture results were consistent in 62.6% of cases. Previous antibiotic treatment was a significant factor for failure of culture isolation and less so for Gram stain failure. On Gram stain, 55.9% of pseudomonal cases were missed, but only 2% of fungal cases were missed. Over all, Gram stain had a sensitivity of 62% and positive predictive value of 84% for bacterial cases, and 98% and 94% for fungal cases, respectively. Fungal ulcers were typically filamentous, but an antecedent history of trauma was not common. The most frequent injury was due to rice grains, but the inoculum appeared to be introduced during eye washing with contaminated water. Pseudomonal ulcers occurred most frequently in the monsoon season, and Fusarium cases were seen only in the hot, dry season.     

Nonheme iron in sickle erythrocyte membranes: association with phospholipids and potential role in lipid peroxidation

Previous studies documented the abnormal association of heme and heme proteins with the sickle RBC membrane. We have now examined RBC ghosts and inside-out membranes (IOM) for the presence of nonheme iron as detected by its formation of a colored complex with ferrozine. Sickle ghosts have 33.8 +/- 18.2 nmol nonheme iron/mg membrane protein, and sickle IOM have 4.3 +/- 3.0 nmol/mg. In contrast, normal RBC ghosts and IOM have no detectable nonheme iron. The combination of heme and nonheme iron in sickle IOM averages nine times the amount of membrane- associated iron in normal IOM. Kinetics of the ferrozine reaction show that some of this nonheme iron on IOM reacts slowly and is probably in the form of ferritin, but most (72% +/- 18%) reacts rapidly and is in the form of some other biologic chelate. The latter iron compartment is removed by deferoxamine and by treatment of IOM with phospholipase D, which suggests that it represents an abnormal association of iron with polar head groups of aminophospholipids. The biologic feasibility of such a chelate was demonstrated by using an admixture of iron with model liposomes. Even in the presence of tenfold excess adenosine diphosphate, iron partitions readily into phosphatidylserine liposomes; there is no detectable association with phosphatidylcholine liposomes. To examine the bioavailability of membrane iron, we admixed membranes and t-butylhydroperoxide and found that sickle membranes show a tenfold greater peroxidation response than do normal membranes. This is not due simply to a deficiency of vitamin E, and this is profoundly inhibited by deferoxamine. Thus, while thiol oxidation in sickle membranes previously was shown to correlate with heme iron, the present data suggest that lipid peroxidation is related to nonheme iron. In control studies, we did not find this pathologic association of nonferritin, nonheme iron with IOM prepared from sickle trait, high-reticulocyte, postsplenectomy, or iron-overloaded individuals. These data provide additional support for the concept that iron decompartmentalization is a characteristic of sickle RBCs.     

Audit of general surgical pathology experience of histopathology trainees.

Surgical histopathology is learnt principally by the practical experience of reporting routine cases. This study performed a quantitative audit of the types of specimens reported by trainees at a teaching hospital and a district general hospital. At the teaching hospital all cases are seen by trainees and it was predicted that the distribution of specimens among trainees would be entirely random. Significant variations were found in the number of skin, breast, cervix, prostate, and endometrial cases reported by each trainee. In some cases this related to a trainee having a special interest (skin and breast pathology) or areas requiring special techniques (breast pathology). At the district general hospital the workload was much higher so that juniors did not see all cases and junior trainees were not seeing bronchial, liver, or lymph node biopsy specimens. This type of audit shows that in teaching hospitals specialisation by some trainees (as encouraged by the new MRCPath exam) may be to the detriment of others and that in district general hospitals pressure of work may actually reduce a trainee's exposure to difficult cases. Without systematic audit this would not be recognised and remedied.     

川芎嗪诱导大鼠骨髓间质干细胞分化为神经元样细胞的研究

目的用川芎嗪(ligustrazin hydrochloride)在体外定向诱导SD青年鼠骨髓间质干细胞(mesenchymal stem cells，rMSCs)分化为神经元样细胞。方法用低糖DMEM冲洗骨髓腔，收集骨髓细胞悬液，接种在塑料培养瓶中。经体外扩增、纯化，选用第5代后的骨髓间质干细胞进行诱导分化。用10μg／LbFcF预诱导24h，更换成含川芎嗪的无血清培养基DMEM诱导间质干细胞分化为神经元样细胞。用免疫组织化学SABC法鉴定神经丝蛋白(NF—M)、神经元特异性烯醇化酶(NSE)、巢蛋白(nestin)、微管联合蛋白-2(MAP-2)、生长相关蛋白-43(GAP-43)、胶质纤维酸性蛋白(GFAP)的表达。结果第5代间质干细胞形态达到均一，呈梭形。用川芎嗪诱导15min到3h，间质干细胞胞体逐渐增大，并伸出细长突起形似神经元样细胞。免疫组织化学显示NF-M、NSE、nestin、MAP-2和GAP-43表达阳性，而GFAP阴性。对照组上述染色均为阴性。结论川芎嗪可诱导骨髓间质干细胞分化为神经元样细胞。     

Androgen receptor YAC transgenic mice carrying CAG 45 alleles show trinucleotide repeat instability

X-linked spinal and bulbar muscular atrophy (SBMA) is caused by a CAG repeat expansion in the first exon of the androgen receptor (AR) gene. Disease-associated alleles (37-66 CAGs) change in length when transmitted from parents to offspring, with a significantly greater tendency to shift size when inherited paternally. As transgenic mice carrying human AR cDNAs with 45 and 66 CAG repeats do not display repeat instability, we attempted to model trinucleotide repeat instability by generating transgenic mice with yeast artificial chromosomes (YACs) carrying AR CAG repeat expansions in their genomic context. Studies of independent lines of AR YAC transgenic mice with CAG 45 alleles reveal intergenerational instability at an overall rate of approximately 10%. We also find that the 45 CAG repeat tracts are significantly more unstable with maternal transmission and as the transmitting mother ages. Of all the CAG/CTG repeat transgenic mice produced to date the AR YAC CAG 45 mice are unstable with the smallest trinucleotide repeat mutations, suggesting that the length threshold for repeat instability in the mouse may be lowered by including the appropriate flanking human DNA sequences. By sequence-tagged site content analysis and long range mapping we determined that one unstable transgenic line has integrated an approximately 70 kb segment of the AR locus due to fragmentation of the AR YAC. Identification of the cis - acting elements that permit CAG tract instability and the trans -acting factors that modulate repeat instability in the AR YAC CAG 45 mice may provide insights into the molecular basis of trinucleotide repeat instability in humans.      

Mechanisms underlying variations in excitation–contraction coupling across the mouse left ventricular free wall

Ca²⁺ release during excitation–contraction (EC) coupling varies across the left ventricular free wall. Here, we investigated the mechanisms underlying EC coupling differences between mouse left ventricular epicardial (Epi) and endocardial (Endo) myocytes. We found that diastolic and systolic [Ca²⁺]_i was higher in paced Endo than in Epi myocytes. Our data indicated that differences in action potential (AP) waveform between Epi and Endo cells only partially accounted for differences in [Ca²⁺]_i. Rather, we found that the amplitude of the [Ca²⁺]_i transient, but not its trigger – the Ca²⁺ current – was larger in Endo than in Epi cells. We also found that spontaneous Ca²⁺ spark activity was about 2.8-fold higher in Endo than in Epi cells. Interestingly, ryanodine receptor type 2 (RyR2) protein expression was nearly 2-fold higher in Endo than in Epi myocytes. Finally, we observed less Na⁺–Ca²⁺ exchanger function in Endo than in Epi cells, which was associated with decreased Ca²⁺ efflux during the AP; this contributed to higher diastolic [Ca²⁺]_i and SR Ca²⁺ in Endo than in Epi cells during pacing. We propose that transmural differences in AP waveform, SR Ca²⁺ release, and Na⁺–Ca²⁺ exchanger function underlie differences in [Ca²⁺]_i and EC coupling across the left ventricular free wall.