Role of beta-lactamase in expression of resistance by methicillin-resistant Staphylococcus aureus.

Of 27 unique clinical isolates of methicillin-resistant Staphylococcus aureus, only 4 were homogeneously resistant, and all 4 produced little or no beta-lactamase. Among heterogeneously resistant strains, those most resistant to beta-lactam antibiotics produced the most beta-lactamase. Similar genes may regulate production of the low-affinity penicillin-binding protein and beta-lactamase.     

Absence of tumorigenicity in athymic mice by normal human epidermal keratinocytes after culture in serum-free medium.

The very rapid growth rate (1 population doubling/day) of normal human epidermal keratinocytes (HK) cultured in serum-free medium can be utilized for wound closure in burn treatment. However, rapid growth in vitro may present the possibility of neoplastic transformation. To investigate this possibility, HK were cultured from primary isolation to large populations in MCDB 153 medium supplemented with epidermal growth factor (EGF, 10 ng/ml), insulin (5 micrograms/ml), hydrocortisone (0.5 micrograms/ml), and Bovine Pituitary Extract (BPE, 70 micrograms/ml). HK were studied for their ability to form tumors in athymic mice after subcutaneous inoculation. Sixteen separate HK strains were inoculated from primary cultures, or from secondary cultures either before or after storage in liquid nitrogen. Transformed cell lines, SCC 13 and FL, derived from human epithelial carcinomata were used as controls for tumor formation. HK formed no tumors (0/79) after 26 weeks incubation, SCC 13 formed nodular tumors (3/5) after 20 weeks incubation, and FL formed tumors (5/5) after 4 weeks incubation. HK cells were not found by histological examination of inoculation sites of keratinocyte cultures derived from primary culture from skin. In contrast, palpable tumors from both SCC 13 and FL were returned to tissue culture and continued to proliferate. These results support the conclusion that the rapid growth rate of human epidermal keratinocytes in vitro can be attributed to permissive culture conditions, and not to neoplastic transformation.     

Transnasal jet ventilation is a useful adjunct to teach fibreoptic intubation: a preliminary report

PURPOSE: Fibreoptic intubation (FOI) has become an essential technique in the anesthetic management of patients with difficult airways. Unfortunately, residents may graduate from anesthesiology training programs with insufficient skills in FOI. To enhance resident proficiency at FOI without compromising patient comfort or safety, the technique of transnasal jet ventilation-assisted FOI was developed. This report describes our initial experience with this technique. METHODS: Sixty-four patients scheduled for oromaxillofacial surgery under nasal endotracheal anesthesia were recruited. Twenty-eight residents at all levels of training performed FOI through the patient's right nostril after the induction of general anesthesia and neuromuscular blockade. Oxygenation and ventilation were maintained by a faculty anesthesiologist using a Sanders device to deliver a jet of oxygen through a nasal trumpet placed in the patient's left nostril. The time from induction until completion of the FOI was recorded. Residents were subsequently queried about the educational benefit of the technique using a standardized questionnaire. RESULTS: All residents were able to successfully intubate all patients in this study. Thirteen residents successfully performed intubations on three or more occasions with 70% performing the technique faster on the third trial than on the first. No evidence of hypoxemia, gastric distension, pneumothorax, hemodynamic instability or recall was observed. All respondents to the questionnaire reported that the technique was useful as an educational tool and recommended its use with other residents. CONCLUSION: Transnasal jet ventilation-assisted FOI is a useful method to train residents in FOI while maximizing patient comfort and safety.     

Do chronic changes in nasal airflow have any physiological or pathological effect on the nose and paranasal sinuses? A systematic review

? A reduction in nasal airflow associated with anatomical defects of the nose such as nasal septal deviation has been proposed to cause nasal pathology. ? The majority of animal experiments where one nasal passage is surgically closed over several months report only minor changes in the histology of the nasal epithelium and no rhinitis or sinusitis. ? Complete abolition of nasal airflow associated with laryngectomy or the treatment of atrophic rhinitis is not associated with the development of rhinitis or sinusitis. ? Radiological studies have shown a lack of association between the degree of nasal septal deviation and evidence of rhinosinusitis. ? Such studies provide evidence that reduced nasal airflow causes no significant nasal disease. ? There is no convincing evidence that a reduction in nasal airflow is a causative factor for rhinitis or sinusitis.     

Pharmacokinetics of xamoterol after intravenous and oral administration to volunteers

Summary The pharmacokinetics of xamoterol, a -adrenoceptor partial agonist under clinical evaluation for the treatment of mild to moderate heart failure, have been studied in 12 healthy male subjects. They received 14 mg i.v. and oral doses of 50 and 200 mg as a tablet and 200 mg as a solution in a 4 way cross-over design.After i.v. dosing the elimination half-life was 7.7 h, the total body clearance was 224 ml·min^–1 and the volume of distribution at steady-state (V_ss) was 48 l. Sixty-two percent of the dose was recovered unchanged in urine. After oral doses, the absolute bioavailability of xamoterol was shown to be 5% irrespective of whether the dose was administered as a tablet or solution. Peak plasma concentrations occurred at about 2 h for the tablet dose and slightly earlier (1.4 h) for the solution. Peak plasma concentration, AUC and urinary recovery of unchanged drug increased in proportion to dose. The apparent elimination half-life after oral doses (16 h) was significantly longer than that observed after an intravenous dose.Despite the low bioavailability, the degree of inter-subject variability of oral bioavailability was small probably indicating that the controlling factor is the hydrophilic nature of the molecule rather than extensive first pass metabolism or poor dissolution of xamoterol from the tablet formulation.     

Linkage and association of adrenergic and dopamine receptor genes in the distal portion of the long arm of chromosome 5 with systolic blood pressure variation

Elevated blood pressure is an important risk factor for renal-, cerebro- and cardiovascular diseases. We used an efficient discordant sib-pair ascertainment scheme to investigate the impact of the distal end of the long arm of human chromosome 5 (chromosomal region 5q31.1-qter) containing genes for the alpha1B and beta2 adrenergic receptors and the dopamine receptor type 1A on variation of systolic blood pressure in young Caucasians. We measured eight highly polymorphic markers spanning this positional candidate gene-rich region in 427 individuals from 55 three-generation pedigrees containing 69 discordant sibling pairs, and calculated multipoint identity by descent (MIBD) probabilities. The results of genetic linkage and association tests indicate that the region between markers D5S2093 and D5S462 is significantly linked to one or more polymorphic genes influencing interindividual variation in systolic blood pressure levels. Since the alpha1B adrenergic receptor and dopamine receptor type 1A genes are located close to these markers, these data suggest that genetic variation in one or both of these G protein-coupled receptors, which participate in the control of vascular tone, plays an important role in influencing interindividual variation in systolic blood pressure levels.      

Nosocomial pneumonia caused by a glucose-metabolizing strain of Neisseria cinerea.

We describe what appears to be the first reported case of nosocomial pneumonia caused by Neisseria cinerea. The isolate metabolized glucose when tested in BACTEC Neisseria Differentiation Kits (Johnston Laboratories), but did not produce detectable acid in cystine-Trypticase (BBL Microbiology Systems) agar medium or in modified oxidation-fermentation medium. Clinical laboratories that rely on the BACTEC method for differentiation of pathogenic neisseriae should be aware of the fact that N. cinerea may mimic N. gonorrhoeae when tested in BACTEC Neisseria Differentiation kits. The ability of N. cinerea to grow well on tryptic soy and Mueller-Hinton agars and its inability to grow on modified Thayer-Martin medium are characteristics which help to distinguish N. cinerea from N. gonorrhoeae.