Avoidance of Nitrous Oxide for Patients Undergoing Major Surgery: A Randomized Controlled Trial

Background: Nitrous oxide is widely used in anesthesia, often administered at an inspired concentration around 70%. Although nitrous oxide interferes with vitamin B12, folate metabolism, and deoxyribonucleic acid synthesis and prevents the use of high inspired oxygen concentrations, the consequences of these effects are unclear.

Methods: Patients having major surgery expected to last at least 2 h were randomly assigned to nitrous oxide-free (80% oxygen, 20% nitrogen) or nitrous oxide-based (70% N2O, 30% oxygen) anesthesia. Patients and observers were blind to group identity. The primary endpoint was duration of hospital stay. Secondary endpoints included duration of intensive care stay and postoperative complications; the latter included severe nausea and vomiting, and the following major complications: pneumonia, pneumothorax, pulmonary embolism, wound infection, myocardial infarction, venous thromboembolism, stroke, awareness, and death within 30 days of surgery.

Results: Of 3,187 eligible patients, 2,050 consenting patients were recruited. Patients in the nitrous oxide-free group had significantly lower rates of major complications (odds ratio, 0.71; 95% confidence interval, 0.56-0.89; P = 0.003) and severe nausea and vomiting (odds ratio, 0.40; 95% confidence interval, 0.31-0.51; P < 0.001), but median duration of hospital stay did not differ substantially between groups (7.0 vs. 7.1 days; P = 0.06). Among patients admitted to the intensive care unit postoperatively, those in the nitrous oxide-free group were more likely to be discharged from the unit on any given day than those in the nitrous oxide group (hazard ratio, 1.35; 95% confidence interval, 1.05-1.73; P = 0.02).     

Interaction of epidermal growth factor, Ca2+, and matrix metalloproteinase-9 in primary keratinocyte migration

Elevations of epidermal growth factor (EGF) and Ca²⁺ concentrations in the wound site are associated with reepithelialization during wound healing. In addition, Ca²⁺ and EGF can both induce increases in matrix metalloproteinase‐9 (MMP‐9) synthesis. However, little is known about the interplay of these events in regulating the migration properties of primary keratinocytes on collagen I, the most abundant extracellular matrix component in the skin. We found that EGF stimulated both chemokinetic and chemotactic migration of primary keratinocytes on collagen I; however, MMP‐9 was required for EGF‐stimulated chemotaxis but not EGF‐stimulated chemokinesis. Calcium at 0.5 mM stimulated chemokinetic migration of keratinocytes. Together, Ca²⁺ and EGF stimulated higher levels of chemokinesis than either stimulus alone. Furthermore, Ca²⁺ could restore the ability of keratinocytes from MMP‐9 null mice to undergo EGF‐stimulated chemotaxis. The phosphatidylinositol‐3 kinase inhibitor LY294002 inhibited both EGF‐ and Ca²⁺‐stimulated chemokinetic migration. In contrast, the MEK inhibitor PD98059 blocked Ca²⁺‐ but not EGF‐stimulated chemokinetic migration of keratinocytes. A combination of PD98059 and LY294002 was required to inhibit Ca²⁺ enhancement of EGF‐stimulated migration completely. Calcium‐stimulated chemokinesis was completely blocked by either the protein kinase C‐α inhibitor Gö6976 or the src/fyn inhibitor PP2. Using primary keratinocytes, our results showed how the combined action of Ca²⁺, EGF, and MMP‐9 regulated the contributions of extracellular‐regulated kinase and phosphatidylinositol‐3 kinase toward chemokinetic and chemotactic migration of keratinocytes.     

Variation of multifocal electroretinogram with axial length

INTRODUCTION: The first-order kernel response of multifocal electroretinogram (mfERG) decreases in myopia. A recent study indicates that the flash ERG is also reduced with increased axial length. The aim of this study was to investigate the variations in the first-order response (K1) and the first slice of second-order response (K2.1) across the retina for different axial lengths. METHODS: Thirty healthy subjects with axial length from 23.72 to 28.13 mm (spherical equivalent refractive errors from plano to -10.50 D) were recruited for mfERG measurement using VERIS 4.0. All subjects were fully corrected after cycloplegic refraction and pupils were dilated prior to mfERG recording. There is one trough, n1, and one peak, p1, in the K1 response and three troughs, n1, n2, n3, and three peaks, p1, p2, p3, in the K2.1 response. The amplitudes and implicit times of K1 and K2.1 responses were analysed to determine the characteristic of the responses across retina and the correlation to axial length. RESULTS: The amplitudes of p1 (in the first-order kernel-K1) decreased in the central region and the paracentral region (ring 3) as the axial length increased. The central retinal region showed high rates of reduction in both n1 and p1 (in K1). The amplitudes of n1p1 and n2p2 (in the first slice of the second-order kernel-K2.1) were reduced in the paracentral region (from ring 2 to ring 5) as axial length increased. The average n1 and p1 in K1, and n1p1 and n2p2 in K2.1 mfERG responses are decreased in amplitude by 6-10% per millimetre elongation of axial length. CONCLUSION: Eyes with longer axial lengths, usually with high myopia, have a weaker mfERG response and this attenuation is across the measured retina (from central to paracentral regions) but different kernel responses show a different pattern of attenuation at different retinal eccentricities. The weaker mfERG responses may be related to the morphological changes associated with increased axial length.     

Laparoscopic repair of recurrent childhood inguinal hernias after open herniotomy

Background Open repair of recurrent paediatric inguinal hernias (IH) is difficult and there is definite risk of damaging the vas deferens and testicular vessels during dissection of the previous open herniotomy field. Laparoscopic repair (LR) has the benefit of avoiding the previous operative site. Method Records of patients with recurrent IH that had LR after open repair were reviewed and evaluated retrospectively. The results were compared with data from cases in which the LR method was used in the initial IH repair. Results From September 2002 to October 2005, four boys and one girl (mean age 58.8 months) were treated in our institution for recurrent IH after open repair. Operative time, success rate and complications did not show any statistically significant difference when compared with our previous prospectively collected data for primary repairs. Conclusion Laparoscopic repair is the preferred operation for recurrent childhood IH after open repair.     

Thymidine labeling index in breast tumors

The relationship between primary tumor proliferative activity and clinical and pathologic characteristics was analyzed in relation to menopausal status in 32 patients with malignant or benign breast disease. The thymidine labeling index (TLI) showed significantly higher median values in the cancer patients (3.48 per cent) than in the patients with benign diseases (1.02 per cent). TLI was not significantly affected by delayed incubation at room temperature for about 1 hour. In the breast cancer patients, TLI did not significantly correlate to tumor size, the presence of axillary lymph node metastasis or pathologic nuclear grading. The only significant difference was limited to the breast cancer patients without axillary lymph node metastasis in relation to menopausal status; the TLI in the premenopausal patients (5.10 per cent) was significantly higher (p<0.05) than that in the postmenopausal patients (2.28 per cent). These data thus suggest that among premenopausal patients without axillary lymph node metastasis, those with a high TLI could be potential candidates for adjuvant chemotherapy.     

Pentasomy 8q in Myelodysplasia

Trisomy 8 and, less commonly tetrasomy 8, are karyotypic aberrations found in myeloid malignancies. We describe a unique case of acute myeloid leukemia with partial pentasomy 8 resulting from duplication of isochromosome 8q, and discuss its possible roles in leukemogenesis.     

Phase I trial of piroxicam in 62 dogs bearing naturally occurring tumors

Summary Piroxicam, a nonsteroidal antiinflammatory drug, was given to 62 dogs bearing naturally occurring tumors in a phase I clinical trial. Dose escalation was performed, with oral doses ranging from 0.5 mg/kg every 48 h (q48h) to 1.5 mg/kg q48h being tested. Dose-limiting gastromestinal irritation/ulceration occurred in all four animals that received 1.5 mg/kg q48h. The maximum tolerated dose was 1 mg/kg q48h. Subclinical renal papillary necrosis occurred in two dogs (initial dosages, 1 and 1.5 mg/kg q48h, respectively). Following dose escalation, an additional group of dogs was treated with 0.3 mg/kg piroxicam q24h per os, the accepted canine dosage prior to this trial. Inclusion of this treatment group enabled evaluation of the toxicity of and tumor response to a daily dosage regimen. No complete remissions occurred in this trial. Partial remission was documented in three of ten dogs exhibiting transitional-cell carcinoma, in three of five animals bearing squamous-cell carcinoma, in one of three dogs displaying mammary adenocarcinoma, and in the one dog that exhibited a transmissible venereal tumor. The results of this study support the additional evaluation of piroxicam in a phase II clinical trial in dogs bearing naturally occurring tumors.This investigation was supported by Pfizer Inc.