Comparison of neuromuscular effects, efficacy and safety of rocuronium and atracurium in ambulatory anaesthesia

PURPOSE: To compare the neuromuscular effects, efficacy, and safety of equi-effective doses of rocuronium and atracurium in ambulatory female patients undergoing surgery. METHODS: Forty-one patients undergoing laparoscopic gynaecological surgery were randomized to receive 2 X ED90 rocuronium (0.6 mg.kg-1; n = 20) or atracurium (0.5 mg.kg-1; n = 21) during intravenous propofol/alfentanil anaesthesia with N2O/O2 ventilation. Neuromuscular block was measured with a mechanomyogram eliciting a train-of-four (TOF) response at the wrist. Intubation conditions 60 sec after administration of muscle relaxant and immediate cardiovascular disturbances or adverse events during the hospital stay were noted by blinded observers. RESULTS: Compared with atracurium, rocuronium was associated with a shorter onset time (59.0 +/- 22.2 vs 98.6 +/- 41.4 sec; P < 0.001) and clinical duration of action (33.3 +/- 7.1 vs 44.7 +/- 7.2 min; P < 0.001), but longer spontaneous recovery index (9.6 +/- 2.41 vs 6.9 +/- 1.89 min; P = 0.023) and a similar time to spontaneous recovery to TOF 70%; 53 +/- 6.31 vs 59.2 +/- 7.59 min; P = 0.139). Tracheal intubation was accomplished in < 90 sec in all patients receiving rocuronium but in only 14 of 21 patients receiving atracurium. The incidence of adverse events and the cardiovascular profiles for the two drugs were similar, although one patient receiving atracurium experienced transient flushing of the head and neck. CONCLUSION: Rocuronium has minimal side effects, provides conditions more suitable for rapid tracheal intubation, and is associated with a shorter clinical duration than atracurium. Once begun, the spontaneous recovery profile of rocuronium is slightly slower than that of atracurium.     

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The study of intrarenal and upper urinary tracts urodynamics in the presence of the ureteropelvic obstruction and of the function of the lower urinary tract shows that congenital hydronephrosis was in 42.8% of cases associated with bladder dysfunction presenting with hyperreflex-type dysfunction. Maladapted hyperreflex bladder was diagnosed in 29.4%, adapted--in 13.5% of cases. The hyporeflex dysfunction occurred in 15.9% of cases. The urinary bladder dysfunction in children with congenital hydronephrosis accounts for 58.7%. These aggravate the same defects of the upper urinary tracts and deteriorate the course of chronic obstructive pyelonephritis.     

Synthesis and analgesic properties of new 5-thioaryl pyrazole derivatives

A new series 5-thio aryl pyrazole derivatives were proposed aiming analgesic activity. In this work, 8 new compounds of this class were synthesized using usual synthetic methodology, having as key intermediate the 3-methyl-4-nitro-5-chloropyrazole-1-phenyl derivative and subsequent reaction with several nucleophiles sulfides. Pharmacological evaluation of this series showed analgesic activity in the some extent in especially for 5-(4-bromophenyl)-thio-3-methyl-4-nitro-1-phenylpyrazole which was the most potent in this series, presenting an analgesic action comparable to that show by dipyrone.     

Variability in blood flow and pO2 in tumors in response to carbogen breathing

PURPOSE: There is speculation that the CO2 in carbogen (95% O2, 5% CO2) can block the vasoconstrictive effects of oxygen. However, it has recently been shown that blood flow in human tumors is variable while patients breathe carbogen. Furthermore, we have shown a consistent decrease in tumor blood flow (TBF) with carbogen breathing in the rat window chamber model. Also, we have previously shown that there is no significant difference in tumor growth time after radiation with air vs. carbogen breathing. This study was designed to investigate the effects of carbogen breathing on blood flow and oxygen levels in a solid tumor. METHODS: Measurements were made in Fischer-344 rats with 8-10 mm diameter R3230Ac tumors transplanted either within the quadriceps muscle (n = 16) or subcutis (n = 14). Nontumor-bearing quadriceps muscle was studied in six other rats. After a 20-minute air-breathing baseline, rats breathed carbogen for an additional 40 minutes. Partial pressure of oxygen (pO2) was continuously monitored at one position for 60 minutes using 9-12 microm diameter oxygen microelectrodes. Blood flow was simultaneously monitored in all animals using laser Doppler flowmetry (1-2 probes/tumor). RESULTS: Blood flow changes during carbogen breathing were variable in all tissues and intratumoral heterogeneity was observed. Despite variability in blood flow, pO2 consistently increased in normal muscle but varied in both tumor sites. During carbogen breathing, the percent pO2 measurements greater than the baseline average were 99.5% +/- 0.4% (mean +/- SEM), 42.7% +/- 13.8%, and 79.8% +/- 11.0% in normal muscle, subcutaneous tumor, and muscle tumor, respectively. To show the magnitude of change, average pO2 values during air and carbogen breathing were calculated for each site. Normal muscle increased from 14.9 +/- 2.3 to 39.0 +/- 6.4 mm Hg (paired t-test; p = 0.009). Muscle tumors showed a rise from 14.6 +/- 3.2 to 34.5 +/- 8.2 mm Hg (p = 0.019). However, pO2 in subcutaneous tumors remained unchanged, with a pO2 of 7.3 +/- 2.0 mm Hg on air and 7.3 +/- 4.1 mm Hg (p = 0.995) during carbogen breathing. CONCLUSIONS: Carbogen had no consistent effect on blood flow and was ineffective at increasing tumor pO2. These results may partially explain why carbogen breathing failed to improve the efficacy of radiation in this tumor model when transplanted subcutaneously.     

Pharmacology and subcellular distribution of [3H]rilmenidine binding sites in rat brain

We have previously reported that in rat brain membranes, [3H]rilmenidine, in addition to labelling alpha2-adrenoceptors and the I2B-subtype of imidazoline receptor binding site (I2B-RBS), may label an additional I-RBS population, distinct from previously classified I1-RBS and I2-RBS. In this study, using crude or fractionated rat brain membranes we examined the possible association of [3H]rilmenidine-labelled I-RBS with the A- and B-isoforms of monoamine oxidase (MAO) by studying the inhibition of [3H]rilmenidine binding by a number of MAO inhibitors; and comparing the maximal binding density (Bmax) and subcellular distribution of [3H]rilmenidine binding sites with that of MAO-A and MAO-B catalytic sites labelled by [3H]RO41-1049 and [3H]RO19-6327 and 12-RBS labelled by [3H]2-BFI. Inhibition of [3H]rilmenidine binding by all MAO inhibitors tested produced very shallow curves (slope 0.29-0.56). Clorgyline and moclobemide (selective MAO-A inhibitors) displayed moderate affinities (60-140 nM), while pargyline (non-selective MAO-inhibitor), RO41-1049 (selective MAO-A inhibitor) and RO19-6327 (selective MAO-B inhibitor) exhibited very low affinities (> 2 microM) for 50-75% of [3H]rilmenidine-labelled I-RBS in crude brain membranes and even lower affinity for the remaining binding. Under identical buffer conditions, the Bmax of [3H]rilmenidine-labelled I-RBS (1.45+/-0.14 pmol/mg protein) was considerably lower than those of MAO-A (13.10+/-0.15 pmol/mg) and MAO-B (10.35+/-0.50 pmol/mg) sites. These results suggest that [3H]rilmenidine does not interact directly with the active catalytic site of either MAO enzyme and could at best only associate with a subpopulation of MAO molecules. Binding studies on five fractions of rat cortex homogenates-nuclear (N), heavy (M) and light (L) mitochondrial, microsomal non-mitochondrial (P), and soluble cytosolic (S) fractions-revealed that 45% of total [3H]rilmenidine binding was present in the P fraction cf. 20 and 23% in the M and L fractions, in contrast to [3H]RO19-6327 and [3H]2-BFI which bound 11-13% in the P fraction and 36-38% and 35-44% in the M and L fractions, respectively. Binding of all ligands in the N fraction was 6-15% of total. These studies reveal that [3H]rilmenidine-labelled I-RBS, unlike the I2-RBS, are not predominantly associated with mitochondrial fractions containing the MAO enzymes (and cytochrome oxidase activity), but appear to be distributed in both the mitochondrial and plasma membrane fractions in rat cerebral cortex.     

Acute erythroleukemia: evaluation of 48 cases with reference to classification, cell proliferation, cytogenetics, and prognosis

We evaluated 48 archival cases of acute erythroleukemia and divided them into 3 groups: M6a, corresponding to the traditional French-American-British M6 category; M6b, which is pure erythroleukemia; and M6c, in which myeloblasts and pronormoblasts each account for more than 30% of cells by the French-American-British exclusion criteria. No significant differences were noted among the subtypes for ratio of males to females; age; or exposure to toxins, alcohol, or both. However, compared with the patients in the M6a group, patients in the M6b and M6c groups demonstrated a statistically significant increase in cytogenetic aberrations, proliferation markers (proliferating cell nuclear antigen and Ki67), and ringed (type III) sideroblasts. Marked survival differences were noted between the M6a (30.1 +/- 29.5 months) and M6b (3.15 +/- 4.2 months) groups, with patients in the M6c group demonstrating an intermediate prognosis (10.5 +/- 12.7 months). Chemotherapeutic regimens induced remission in all treated patients in the M6a and M6c groups but did not appear to affect the M6b group. However, the patients in the M6c group remained in remission for a significantly shorter period of time than did patients in the M6a group. Overall, survival appeared to depend on the ratio of pronormoblasts to myeloblasts at diagnosis and demonstrated a rapid decline with increasing pronormoblast and decreasing myeloblast counts. We must, therefore, devise chemotherapeutic regimens that target both blastic components of this disease.     

Leukocytes in the cervix: a quantitative evaluation of cervicitis

OBJECTIVE: To quantify the numbers of leukocytes in the normal cervix and relate these numbers to the diagnosis of cervicitis. METHODS: Isolated cell suspensions were prepared from cervical tissue recovered at hysterectomy from 37 women who had no obvious cervical disease. The percentages of CD45+ cells (leukocytes) in these preparations were determined using immunofluorescence-based flow cytometric analysis. These percentages were compared with the pathologist's assessment of cervicitis. RESULTS: Leukocytes were present in all cervical samples tested. For endocervical samples, the mean (+/- standard error of the mean [SEM]) percentage of CD45+ cells was 12.4 +/- 1.9% of cells in patients with a diagnosis of cervicitis (n = 16) and 9.1 +/- 1.1% in patients without cervicitis (n = 17). For ectocervical samples, the mean (+/- SEM) percentage was 14.8 +/- 3.0% in those with cervicitis (n = 16) and 9.5 +/- 1.6% in those without cervicitis (n = 19). The differences between samples from patients with cervicitis and those without cervicitis were not statistically significant at the .05 level. Intra- and interassay variabilities were 5.7 +/- 1.2% and 7.3 +/- 1.6%, respectively. CONCLUSION: Our study demonstrates there is a resident population of leukocytes in the cervix. Leukocyte number did not relate clearly and consistently to the diagnosis of cervicitis made by the pathologist. We suggest that the resident population of leukocytes, in the absence of other indicators of infection, may confuse determinations of cervicitis.     

Menin, the product of the MEN1 gene, is a nuclear protein

The MEN1 gene, mutations in which are responsible for multiple endocrine neoplasia type 1 (MEN1), encodes a 610-amino acid protein, denoted menin. The amino acid sequence of this putative tumor suppressor offers no clue to the function or subcellular location of the protein. We report herein, based on immunofluorescence, Western blotting of subcellular fractions, and epitope tagging with enhanced green fluorescent protein, that menin is located primarily in the nucleus. Enhanced green fluorescent protein-tagged menin deletion constructs identify at least two independent nuclear localization signals (NLS), both located in the C-terminal fourth of the protein. Among the 68 known independent disease-associated mutations, none of the 22 missense and 3 in-frame deletions affect either of the putative NLS sequences. However, if expressed, none of the truncated menin proteins resulting from the 43 known frameshift/nonsense mutations would retain both the NLSs. The precise role(s) of menin in the nucleus remain to be understood.     

EMS1 gene expression in primary breast cancer: relationship to cyclin D1 and oestrogen receptor expression and patient survival

The EMS1 and CCND1 genes at chromosome 11q13 are amplified in about 15% of primary breast cancers but appear to confer different phenotypes in ER positive and ER negative tumours. Since there are no published data on EMS1 expression in large series of breast cancers we examined the relationship of EMS1 expression with EMS1 gene copy number and expression of mRNAs for cyclin D1 and ER. In a subset of 129 patients, where matched tumour RNA and DNA was available, EMS1 mRNA overexpression was associated predominantly with gene amplification (P = 0.0061), whereas cyclin D1 mRNA overexpression was not (P = 0.3142). In a more extensive series of 351 breast cancers, there was no correlation between cyclin D1 and EMS1 expression in the EMS1 and cyclin D1 overexpressors (P = 0.3503). Although an association between EMS1 mRNA expression and ER positivity was evident (P = 0.0232), when the samples were divided into quartiles of EMS1 or cyclin D1 mRNA expression, the increase in the proportion of ER positive tumours in the ascending EMS1 mRNA quartiles was not statistically significant (P = 0.0951). In marked contrast there was a significant stepwise increase in ER positivity in ascending quartiles of cyclin D1 mRNA (P = 0.030). A potential explanation for this difference was provided by the observation that in ER positive breast cancer cells oestradiol treatment resulted in increased cyclin D1 gene expression but was without effect on EMS1. The relationship between EMS1 expression and clinical outcome was examined in a subset of 234 patients with median follow-up of 74 months. High EMS1 expression was associated with age > 50 years (P = 0.0001), postmenopausal status (P = 0.0008), lymph node negativity (P = 0.019) and an apparent trend for worse prognosis in the ER negative subgroup. These data demonstrate that overexpression of EMS1 mRNA is largely due to EMS1 gene amplification, is independent of cyclin D1 and ER expression and, in contrast to cyclin D1, is not regulated by oestrogen. Independent overexpression of these genes may confer different phenotypes and disease outcomes in breast cancer as has been inferred from recent studies of EMS1 and CCND1 gene amplification.     

Effect of evaluator and resident gender on the American Board of Internal Medicine evaluation scores

OBJECTIVE: To examine the effects of resident and attending physician gender on the evaluation of residents in an internal medicine training program. DESIGN: Cross-sectional study. SETTING: Large urban academic internal medicine residency program. PARTICIPANTS: During their first 2 years of training, 132 residents (85 men, 47 women) received a total of 974 evaluations from 255 attending physicians (203 men, 52 women) from 1989 to 1995. MEASUREMENTS: The primary measurements were the numerical portions of the American Board of Internal Medicine evaluation form. Separate analyses were performed for each of the nine evaluation dimensions graded on a scale of 1 to 9. The primary outcome was the difference in the average scores received by each resident from male versus female attending physicians. RESULTS: Compared with female trainees, male residents received significantly higher scores from male attending physicians than from female attending physicians in six of the nine dimensions: clinical judgment, history, procedures, relationships, medical care, and overall. Similar trends, not reaching conventional levels of statistical significance, were observed in the other three categories: medical knowledge, physical exam, and attitude. These differences ranged from 0.24 to 0.60 points, and were primarily due to higher grading of male residents by male attending physicians than by female attending physicians. CONCLUSIONS: In one academic training program, we found a significant interaction in the grading process between the gender of internal medicine residents and the gender of their attending evaluators. This study raises the possibility that subtle aspects of gender bias may exist in medical training programs.