Interaction of Propofol and Sevoflurane on Loss of Consciousness and Movement to Skin Incision during General Anesthesia

Background: Loss of consciousness (LOC) and immobility to surgical incision seem to be mediated at different levels of the central nervous system. Pharmacologic studies of hypnotic agents have previously focused on combinations of either volatile or intravenous anesthetics. This study examined the combination of inhaled sevoflurane and intravenous propofol at these two clinically relevant anesthetic end points.

Methods: Thirty-six elective surgical patients were initially enrolled. Conditions approximating steady state were obtained for sevoflurane and target-controlled propofol infusions. Patients were sequentially evaluated for LOC (loud voice plus mild prodding) and immobility to surgical incision. The study was designed using the Dixon up-down method.

Results: The observed propofol effect target with 50% response plus sevoflurane (0.46% end-tidal concentration) was 1.2 [mu]g/ml (95% confidence interval, 1.1-1.3 [mu]g/ml). It was not significantly different from that predicted (1.5 [mu]g/ml; 95% confidence interval, 1.2-1.7 [mu]g/ml) by simple additivity. The effective plasma concentration of propofol that suppressed movement to skin incision in 50% of patients was 5.4 [mu]g/ml (95% confidence interval, 4.8-6.0 [mu]g/ml) plus sevoflurane (0.86%) and was not significantly different from that predicted by additivity (5.4 [mu]g/ml; 95% confidence interval, 4.8-5.9 [mu]g/ml). Both analyses had adequate power (90%) to detect a significant change (+/-19 to 25%) from predicted value. Repeated-measures analysis of variance identified a Bispectral Index value of 70 as the break point between those who responded at LOC or did not.     

Molecular determinants of cetuximab efficacy.

PURPOSE: To investigate whether mRNA expression levels of cyclin D1 (CCND1), cyclooxygenase 2 (Cox-2), epidermal growth factor receptor (EGFR), interleukin 8 (IL-8), and vascular endothelial growth factor (VEGF), all members of the EGFR signaling pathway, are associated with clinical outcome in patients with EGFR-expressing metastatic colorectal cancer (CRC) treated with cetuximab. PATIENTS AND METHODS: Thirty-nine patients with metastatic CRC, refractory to both irinotecan and oxaliplatin, were enrolled on IMCL-0144 and treated with single-agent cetuximab. The intratumoral mRNA levels of CCND1, Cox-2, EGFR, IL-8, and VEGF were assessed from paraffin-embedded tissue samples using laser-capture microdissection and quantitative real-time polymerase chain reaction. RESULTS: There were 21 women and 18 men with a median age of 64 years (range, 35 to 83 years). Higher gene expression levels of VEGF were associated with resistance to cetuximab (P = .038; Kruskal-Wallis test). The combination of low gene expression levels of Cox-2, EGFR, and IL-8 was significantly associated with overall survival (13.5 v 2.3 months; P = .028; log-rank test). Both findings were independent of skin toxicity that was itself significantly correlated to survival. Patients with a lower mRNA amount of EGFR had a longer overall survival compared with patients that had a higher mRNA amount (7.3 v 2.2 months; P = .09; log-rank test). Patients with lower expression of Cox-2 had a significantly higher rate of grade 2 to 3 skin reactions under cetuximab treatment. CONCLUSION: This pilot study suggests that gene expression levels of Cox-2, EGFR, IL-8, and VEGF in patients with metastatic CRC may be useful markers of clinical outcome in single-agent cetuximab treatment.     

Voltammetric Quality Control of Bioactive Additives: Determination of B<Subscript>1</Subscript>, B<Subscript>2</Subscript>, C,E Vitamins and Quercetin

Rapid voltammetric procedures for the determination of water-soluble vitamins C, B₁, and B₂, fat-soluble vitamin E (α-tocopherol acetate), and quercetin in bioactive food additives have been developed. The systematic error (i.e., correctness) of the proposed procedures was evaluated using certified reference materials and the additive recovery tests, which gave the following limiting metrological characteristics: relative error, 25 %; reproducibility, 28 %; convergence, 22 %. The full analysis time (with sample preparation) did not exceed 2 hours. Voltammetric determinations under optimum conditions can be performed in the automated regime controlled by a computer according to the specially developed software.__________Translated from Khimiko-Farmatsevticheskii Zhurnal, Vol. 39, No. 3, pp. 54 – 56, March, 2005.     

Alkaline Hydrolysis Kinetics and No-Donor Activity of Tenonitrozole

The kinetics of alkaline hydrolysis of N-(5-nitro-2-thiazolyl)-2-thiophenylcarboxamide (tenonitrozole or atrican) has been studied by photometric and polarographic techniques, and the thermodynamic parameters in the intermediate state of this process were determined. A mechanism explaining the nitric oxide (NO) production during the hydrolytic decomposition of tenonitrozole is proposed. It is suggested that the antiprotozoal and antimicrobial activity of this drug under anaerobic conditions is related to the formation of nitro radical anions and NO. Under aerobic and microaerophilic conditions, the hydrolysis of tenonitrozole may lead to the formation of a peroxynitrite anion, which is a strong cytotoxic agent. __________ Translated from Khimiko-Farmatsevticheskii Zhurnal, Vol. 39, No. 6, pp. 15 – 18, June, 2005.     

Susceptibility of upper-genital tract isolates from women with pelvic inflammatory disease to ampicillin, cefpodoxime, metronidazole, and doxycycline

The antibiotics that are recommended for treatment of pelvic inflammatory disease (PID) in the outpatient setting are efficacious against Neisseria gonorrhoeae and Chlamydia trachomatis. The susceptibility of non-sexually transmitted pathogens to these agents has not been well studied. The mean inhibitory concentrations of ampicillin, cefpodoxime, metronidazole, and doxycycline were determined for 137 upper-genital tract isolates from 84 women with confirmed PID. Antibiotic resistance was noted in 16%, 9%, 93%, and 72% of the facultative and 0%, 11%, 10%, and 56% of the anaerobic bacteria when tested against ampicillin, cefpodoxime, metronidazole, and doxycycline, respectively. The authors conclude that doxycycline is limited to coverage of Chlamydia and that a single dose of another antibiotic may not be adequate to eradicate the non-sexually transmitted disease pathogens from the upper-genital tract. Additional clinical and microbiologic studies are needed to determine whether the current outpatient antibiotic regimens provide optimal coverage for the non-sexually transmitted pathogens that are associated with PID.     

Misdiagnosis of hysteria

The diagnosis of hysteria is often incorrect and must be made with great caution. A retrospective study demonstrates that an erroneous diagnosis of hysteria is most likely to be given to females, the psychiatrically ill, patients who embellish and patients who present plausible psychogenic explanations for their illness. Movement disorders and paralysis are the neurologic disorders most frequently mislabeled as hysteria.     

Uncemented two-component femoral prosthesis for the hip joint. A 50-month follow-up study

The Monk Duopleet femoral interlocking uncemented two-component endoprosthesis consists of a polyethylene cup covered by a metal cap and an Austin-Moore type stem. Seventy-two patients (average age, 71 years) were treated by this arthroplasty: 27 for subcapital femoral neck fracture, 36 for osteoarthritis, and nine as an exchange operation. Three patients died following operation. After a mean follow-up time of 50 months, 47 patients were reexamined clinically and radiographically. Because of loosening, four patients had the prosthesis removed. Twenty-six patients were classified as excellent, 12 as good, six as fair, and three as poor. There were no cases of acetabular intrusion. The Monk Duopleet prosthesis may solve the problem of the loosening that had been associated with femoral component alone. The long-term results are promising and appear to be better than the results of the standard Moore prosthesis. The Monk Duopleet prosthesis is an alternative to other two-component endoprostheses for the treatment of subcapital hip fractures and in the group of patients suffering from osteoarthritis, where an arthroplasty with a cemented prosthesis may be considered hazardous because of age or general disease.     

Patient survival and local recurrence rate following radical prostatectomy for prostatic carcinoma

From 1970 to 1980, 153 patients with stages A2, B1 and B2 prostatic cancer and proved negative pelvic lymph nodes underwent radical prostatectomy (84 underwent radical perineal and 69 underwent radical retropubic prostatectomy). Seventeen patients were lost to followup. Of 136 patients who were followed for 5 years or until death 128 (94 per cent) were alive at 5 years, including 118 (87 per cent) who were without evidence of recurrence. Patients with microscopic invasion of the prostatic capsule have a better outcome at 5 years than those with microscopic involvement of the seminal vesicles. Only 46 of the patients could be assessed at 10 years or had died 6 to 10 years postoperatively. Results at 10 years are considered preliminary, since many more patients will reach the 10-year milestone within the next few years.     

Total lymphoid irradiation in chronic polyarthritis--a new therapeutic concept

Eleven patients with refractory rheumatoid arthritis were submitted to a total lymphoid irradiation up to a dose of 20 Gy. A constant improvement of clinical symptoms was observed in four out of the eleven patients already during the treatment and in the other patients not later than two months after. The frequency of attacks decreased and the number of joints involved in the attack was reduced. Morning rigidity and joint swellings decreased. One patient developed joint empyemas 4 and 26 months after the treatment. Four patients died in the meantime. In two patients the cause of death were renal insufficiency and a postoperative cardiogenic shock associated with generalized amyloidosis. The third patient died because of a toxically induced left cardiac decompensation with sepsis that could not be controlled by antibiotic drugs and multiple joint empyemas. The fourth patient developed an abscess after surgical treatment of a Kaposi syndrome. She died three months later from acute left cardiac decompensation. The therapy induced a lymphocytopenia with decrease of T helper lymphocytes and unchanged number of T suppressor lymphocytes. The constant therapy results of total lymphoid irradiation in primary chronic polyarthritis is probably due to this modification in the immune regulation.