Nitrous oxide anxiolysis for elective cesarean section

STUDY OBJECTIVE: To determine if inhaled 40% nitrous oxide (N(2)O) via facemask is an effective anxiolytic in women undergoing elective cesarean section under spinal anesthesia. STUDY DESIGN: Prospective, randomized, double-blinded study. SETTING: Tertiary-care women's hospital. PATIENTS: Sixty American Society of Anesthesiologists physical status I and II patients scheduled for elective cesarean section under spinal anesthesia. INTERVENTIONS: Patients were randomized to 2 groups to receive either 100% O2 via facemask or 40% N2O in O2 via facemask. MEASUREMENTS: Vital signs (blood pressure, heart rate, and oxygen saturation) and measured variables (visual analog scale [VAS] anxiety, VAS pain, and sedation scores) were obtained at specific periods during the procedure (preoperatively, entering the operating room, spinal injection, skin incision, uterine incision, delivery, and at the conclusion of the surgical procedure). In addition, surgical time and delivery time, mean dose and percentage of patients requiring ephedrine or phenylephrine boluses, the emesis rate, and Apgar scores were measured. MAIN RESULTS: No differences were noted with respect to maternal mean blood pressure, heart rate, pulse-oximeter oxygen saturation, and sedation or VAS pain scores during the measured periods. No differences were noted in surgical and delivery times, mean dose, or percentage of patients who required ephedrine or phenylephrine to maintain maternal blood pressure, the emesis rate, or 1- and 5-minute Apgar scores. Mean anxiety scores for the N2O group were significantly lower at the time of spinal injection, skin incision, and uterine incision. Multivariate analysis of variance for high-anxiety patients (> or =50 VAS) revealed significantly lower VAS scores in the N2O group, compared with the O2 group again at spinal injection, skin incision, and uterine incision. CONCLUSIONS: Inhaled 40% N2O via facemask provides effective anxiolysis in women undergoing elective cesarean section under spinal anesthesia in patients with high anxiety (> or =50 VAS) at the time of spinal injection, skin incision, and uterine incision.     

Update on community-acquired pneumonia. New pathogens and new concepts in treatment

Recent years have witnessed the emergence of new pathogens linked to community-acquired pneumonia (CAP) along with new antibiotics designed to combat them. In this article, Dr Mandell presents an expert's view on these developments in the context of treatment guidelines for CAP. He also explores monotherapy versus combination therapy, the efficacy of rapid initiation of treatment, and short-course therapy as a hedge against antimicrobial resistance.     

Disk susceptibility of ofloxacin, a new carboxyquinolone.

Ofloxacin, a fluorinated carboxyquinolone, was tested against 485 clinical isolates, and the MICs and disk inhibitory zones were correlated. A critical zone of greater than or equal to 19 mm and an MIC of less than or equal to 2 micrograms/ml indicate susceptibility. An MIC of 4 micrograms/ml and a zone size of 16 to 18 mm is intermediate, and an MIC of greater than or equal to 8 micrograms/ml with a zone size of less than 15 mm indicates resistance. Alternatively, organisms inhibited by an MIC of less than or equal to 4 micrograms/ml with a critical zone diameter of greater than or equal to 15 mm could be considered susceptible. By either of these criteria, major errors in judging susceptibility or resistance are less than 1%.     

Aromatic alkylamine N-acetyltransferase in regional tissues of developing rat brain

The specific activities of N-acetyltransferase (EC 2.3.1.5) were examined in several regions of rat brain of both sexes at various times after birth. The enzyme activity increased with development in whole brain, hippocampus, midbrain, cerebellum and the remainder of brain, peaking around 36 days of age. Lineweaver-Burk plots indicated linear kinetics for N-acetyltransferase in dialyzed supernatant and ammonium sulfate precipitates from the newborn rat brain, whereas enzyme preparation further purified by Bio Gel yielded biphasic kinetics. These data remain consistent with the possibility that there are two forms of N-acetyltransferase in rat brain even from birth.     

Functional and genomic approaches reveal an ancient CHEK2 allele associated with breast cancer in the Ashkenazi Jewish population

Functional and genomic approaches can be integrated to screen efficiently for pathogenic alleles in founder populations. We applied such approaches to analysis of the cancer-associated cell cycle regulator CHEK2 in the Ashkenazi Jewish population. We first identified two extended haplotypes at CHEK2 that co-segregated with breast cancer in high-risk families. We sequenced CHEK2 in a case representing each haplotype and discovered two novel amino acid substitutions, CHEK2.S428F in the kinase domain and CHEK2.P85L in the N-terminal region. To assay these alleles for loss of CHEK2 function, we tested their capacity to complement Rad53 deletion in Saccharomyces cerevisiae. CHEK2.S428F failed to complement Rad53 and thus largely abrogates normal CHEK2 function, whereas CHEK2.P85L complemented Rad53 as well as did wild-type CHEK2. Epidemiologic analyses were concordant with the functional tests. Frequencies of CHEK2.S428F heterozygotes were 2.88% (47/1632) among female breast cancer patients not selected for family history or age at diagnosis and 1.37% (23/1673) among controls (OR=2.13, 95% CI [1.26, 3.69], P=0.004), whereas frequencies of CHEK2.P85L were 0.92% among cases and 0.83% among controls. On the basis of the experience of mothers, sisters and daughters of probands, breast cancer risk due to CHEK2.S428F was estimated as 0.17 (+/-0.08) by age 60. We conclude that CHEK2.S428F increases breast cancer risk approximately 2-fold among Ashkenazi Jewish women, whereas CHEK2.P85L is a neutral allele. In general, these results suggest that selecting probands with extended haplotypes that co-segregate with disease can improve the efficiency of resequencing efforts and that quantitative complementation tests in yeast can be used to evaluate variants in genes with highly conserved function.     

Endoscopic KTP laser excision of severe tracheotomy-associated suprastomal collapse

OBJECTIVE: The purpose of this study was to investigate the feasibility, safety, and clinical utility of potassium-titanium-phosphate (KTP) laser bronchoscopy for excision of severe, obstructing tracheotomy-associated suprastomal collapse. METHODS: A retrospective review was performed of six children at a tertiary care children's hospital with severe tracheotomy-associated collapse of the suprastomal anterior tracheal wall cartilage, precluding decannulation. All subjects had undergone KTP laser endoscopic excision of the collapsed segment of suprastomal tracheal cartilage. Medical records were assessed for: (1) endoscopic demonstration of relief of suprastomal collapse, and (2) successful tracheotomy decannulation. RESULTS: All six patients had endoscopic evidence of relief of suprastomal airway obstruction after KTP laser therapy. Five of six (83%) subsequently underwent successful decannulation. There was one case of minimal thermal airway injury associated with a laser fire during use of the KTP laser, the effects of which were fortunately transient. CONCLUSIONS: KTP laser bronchoscopic excision of severe tracheotomy-associated suprastomal collapse: (1) is a feasible technique; (2) results in relief of suprastomal obstruction with subsequent successful decannulation in selected patients; and (3) avoids the need for more extensive open neck procedures. However, risks of KTP laser therapy are not negligible and strategies must be in place to minimize the occurrence of complications.     

Use of complementary and alternative medicine among children recently diagnosed with autistic spectrum disorder

This study examined the prevalence and correlates of use of different types of complementary and alternative medicine (CAM) among a sample of children with suspected or recently diagnosed autism. The authors' review of 284 charts of children seen at the Regional Autism Center of The Children's Hospital of Philadelphia, Pennsylvania, found that more than 30% of children were using some CAM, and that 9% were using potentially harmful CAM. Having an additional diagnosis was protective against CAM use and being Latino was associated with CAM use. Having seen a prior provider regarding the child's health condition was predictive of potentially harmful CAM use. Further research is required on cultural differences in treatment decisions about CAM, as well as the reasons for the association between the use of prior providers and CAM. The high prevalence of CAM use among a recently diagnosed sample indicates that clinicians should discuss CAM early in the assessment process.     

Phosphorylation state-specific antibodies: applications in investigative and diagnostic pathology

Until recently, the investigation of protein phosphorylation was limited to biochemical studies of enzyme activities in homogenized tissues. The availability of hundreds of phosphorylation state-specific antibodies (PSSAs) now makes possible the study of protein phosphorylation in situ, and is opening many exciting opportunities in investigative and diagnostic pathology. This review illustrates the power of PSSAs, especially in immunohistochemical applications to human disease and animal models. Technical considerations, including antibody specificity and lability of phosphoepitopes, are covered, along with potential pitfalls, illustrated by a case study. In the arena of oncology, PSSAs may prove especially valuable in directly demonstrating the efficacy of chemotherapies targeted at protein kinase cascades. Novel applications of PSSAs are also beginning to reveal molecular mechanisms of inflammatory, degenerative, and toxin-induced diseases.