A prospective, cohort evaluation of major and minor airway management complications during routine anaesthetic care at an academic medical centre.

The aim of this study was to develop an audit tool to identify prospectively all peri-operative adverse events during airway management in a cost-effective and reproducible way. All patients at VU University Medical Center who required general anaesthesia for elective and emergency surgical procedures were included during a period of 8 weeks. Daily questionnaires and interviews were taken from anaesthesia trainees and anaesthetic department staff members. A total of 2803 patients underwent general anaesthesia, 1384 men and 1419 women, including 2232 elective patients and 571 emergency procedures, 697 paediatric and 2106 adult surgical procedures. A total of 168 airway-related events were reported. The incidence of severe airway management-related events was 24/2803 (0.86%). There were 12 (0.42%) unanticipated ICU admissions, two patients (0.07%) required a surgical airway. There was one (0.04%) death, one cannot intubate cannot oxygenate (0.04%), one aspiration (0.04%) and eight (0.29%) severe desaturations < Sp O2 50%. We suggest that our method to determine and investigate airway management-related adverse events could be adopted by other hospitals.

Metabolic parameters and their relationship to energy balance in multiparous Simmental, Brown Swiss and Holstein cows in the periparturient period as influenced by energy supply pre- and post-calving.

A study was conducted to evaluate the effects of three energy supply (E) levels [low (L), medium (M), high (H)], both pre-partum (PRE) and post-partum (POST), and their interactions on metabolic parameters and energy balance (EB) in dairy cows of three breeds. In both phases, E levels applied to a total of 81 multiparous cows of breeds Simmental (SI), Brown Swiss (BS) and Holstein-Friesian (HF; n = 27 for each breed) were 75%, 100% and 125% of recommendations of the German Society of Nutrition Physiology, using a 3 × 3 factorial arrangement of treatments. During the pre-calving period, serum concentrations of non-esterified fatty acids (NEFA) were higher for L(PRE) cows, and glucose concentrations were elevated for H(PRE) cows. During the lactation period, NEFA concentrations were greatest for treatment L(POST). Mean concentrations of ß-hydroxybutyrate (BHB) were highest for cows of the L(POST) treatment, intermediate for M(POST) and lowest for H(POST). Glucose concentrations were lower for L(POST) cows. SI cows had lower BHB concentrations both pre- and post-calving and higher glucose concentrations during early lactation than the other breeds. BHB concentration POST was highest for BS cows. Restricted feeding PRE resulted in a better energy status of cows fed above energy requirements POST (E(PRE) × E(POST) interaction). HF cows had a higher EB pre-calving, whereas SI cows had a less negative EB during early lactation, compared with the other breeds respectively. Correlations of serum NEFA, BHB and glucose concentrations with EB were strongest during the transition period. Results suggest that controlling energy intake during the dry period might be advantageous for the energy status of dairy cows after calving, whereas energy restriction in early lactation leads to metabolic stress. Evidence is provided of a clear relationship between EB and the blood metabolites NEFA and BHB, especially in the transition period.

Tracheal intubation with a camera embedded in the tube tip (Vivasight(™) ).

We studied tracheal intubation in manikins and patients with a camera embedded in the tip of the tracheal tube (Vivasight(™) ). Four people in two teams and two individuals attempted intubation of a manikin through an i-gel(™) 10 times each. The tracheas of 12 patients with a Mallampati grade of 1 were intubated with a Vivasight tracheal tube through a Berman airway, passed over a Frova(™) introducer. All 60 manikin intubations were successful, taking a mean (SD) time of 1.4 (0.5) s. The fastest intubation was performed in 0.5 s. All 12 participants' tracheas were successfully intubated in a median (IQR [range]) time of 90 (70-120 [50-210]) s. Seven participants complained of a sore throat, comparable with earlier findings for standard laryngoscopy and intubation: five mild; one moderate; and one severe. Tracheal intubation with the Vivasight through the i-gel or Berman airway is an alternative to existing techniques, against which it should be compared in randomised controlled trials in human participants. It has potential as a fast airway rescue technique.

Visualizing gene expression in time and space in the filamentous bacterium Streptomyces coelicolor.

Streptomycetes are prokaryotic microorganisms that exhibit a complex, mycelial fungus-like cycle of morphological differentiation. Development involves at least two spatially separated types of cells: the branching hyphae of the substrate mycelium, which penetrate the stratum upon which the colony feeds, and the upwardly protruding hyphae of the aerial mycelium, which undergo metamorphosis into spores. The luciferase-encoding luxA and luxB operon of the luminescent marine bacterium Vibrio harveyi was used as a promoter probe to visualize gene expression in differentiating colonies of Streptomyces coelicolor. Promoters for developmental genes of several kinds gave distinctive temporal and spatial patterns of light emission.

Lipoprotein apheresis influences monocyte subpopulations.

BACKGROUND: Monocytes can be differentiated into subpopulations depending on their expression profile of CD14 and CD16. CD16-positive monocytes are associated with coronary artery disease. Up to now, no data exist about the effect of lipoprotein apheresis (LA) on the distribution of monocyte subpopulations. METHODS: 80 patients who underwent LA at the University Hospital Dresden were included in the study. 8 out of the 80 LA patients received LA for the first time at the time point of blood analysis. Six different methods of LA were used (H.E.L.P. n = 8; Liposorber D n = 10; LF n = 14; DALI n = 17; MONET n = 11; Therasorb® LDL n = 12). Blood samples were taken immediately before and after LA and analyzed for CD14 and CD16 expression on monocytes. A total of 42 patients with cardiovascular risk factors but no indication for LA served as control group. RESULTS: The composition of monocyte-population was analyzed in regard to the 3 subpopulations. After LA, an increase in classical monocytes (CD14++CD16-) (93.3% vs. 93.9%, p < 0.01) and a decrease in non-classical monocytes (CD14+CD16+) (1.5% vs 1.0%; p < 0.001) were observed. LA did not change the amount of intermediate monocytes (CD14++CD16+) (5.3% vs. 5.1%). Two methods (MONET and Therasorb® LDL) did not influence the distribution of monocyte subpopulations. Interestingly, patients with LDL-C above 2.5 mmol/l prior LA showed increased amounts of intermediate monocytes. CONCLUSION: The distribution of monocyte populations is influenced by LA but depends on the distinct method of LA. Influences of LA were mainly observed in the content of classical and non-classical monocytes, whereas the intermediate monocyte population remained unaltered by LA.

The effect of administration rate on cisplatin-induced emesis.

In an attempt to determine the influence of administration time on cisplatin-induced emesis, 20 adults previously untreated with cisplatin were enrolled into this double-blind study. Twenty patients were randomly assigned to receive high-dose cisplatin (greater than 100 mg/m2) either by a one-hour infusion or by an eight-hour infusion. All patients received antiemetic therapy with metoclopramide 2 mg/kg intravenously one-half hour before cisplatin administration, and 1 1/2, 3 1/2, 5 1/2, and 8 1/2 hours after cisplatin administration. Patients in the eight-hour infusion group experienced significantly fewer emesis episodes than did patients in the one-hour infusion group. The median of emesis episodes in the eight-hour group was one (range, 0 to 2) and in the one-hour group was three (range, 0 to 8). In patients receiving high-dose cisplatin plus metoclopramide, increasing the administration time from one hour to eight hours resulted in a small but significant decrease in emesis episodes. The cisplatin infusion rate should be considered as a variable in cisplatin-antiemetic trials.

lambda N antitermination system: functional analysis of phage interactions with the host NusA protein.

Coliphage lambda gene expression is regulated temporally by systems of termination and antitermination of transcription. The lambda-encoded N protein (pN) acting with host factors (Nus) at sites (nut) located downstream from early promoters is the first of these systems to operate during phage development. We report observations on some of the components of this complex system that, in part, address the way in which these elements interact to render RNA polymerase termination-resistant. (1) The isolation of a conditionally lethal cold-sensitive nusA mutation demonstrates that NusA is essential for bacterial growth. (2) The effect on lambda growth in a host in which the Salmonella NusA protein is overproduced suggests that NusA is essential for N-mediated antitermination in phage lambda. (3) A truncated NusA product, representing only the amino two-thirds of the native protein, is active for both bacterial growth and pN action, indicating that the carboxy end of the molecule may not be a functionally important region. (4) lambda pN can function with the heterologous nut region from Salmonella typhimurium phage P22 when lambda pN is overproduced, demonstrating that lambda pN can function with the nut regions of other lambdoid phages. (5) A single base-pair change in the lambda nutR boxA sequence that was selected to permit a lambda derivative to utilize the Salmonella NusA protein restores lambda growth in the Escherichia coli nusA1 host.

HORSE SPECIES SYMPOSIUM: The aging horse: Effects of inflammation on muscle satellite cells.

With improvements in care, the equine population is living longer, remaining active, and competing at increasingly older ages. Both advancing age and exercise result in increased concentrations of circulating and local cytokines, including IL-1ß, IL-6, and tumor necrosis factor-α. Athletic endeavors in the aged horse may further increase the proinflammatory environment in muscle, decreasing the ability to react appropriately to exercise. Poor response to exercise limits the athletic ability of geriatric horses, thus reducing their useful life span and potentially increasing the risk of injury. Satellite cells are muscle stem cells that reside adjacent to muscle fibers in skeletal muscle and are at least partially responsible for maintenance of muscle mass and muscle hypertrophy. In the adult animal, these cells normally exist in a quiescent state, becoming active, proliferating, and differentiating in response to specific stimuli. Growth factors and cytokines present during hypertrophy and following exercise affect satellite cell activity. Whereas the specific effects of cytokines on equine satellite cells are not well established, cytokines can influence satellite cell and myoblast proliferation and differentiation both positively and negatively. Understanding the effects of cytokines on equine satellite cell function will provide insight into the mechanisms responsible for the poor response to exercise in the aged horse. The proinflammatory environment in aged horses may inhibit exercise induced satellite cell activity, thereby diminishing exercise-induced hypertrophy. As more horses are surviving and competing into their 20s, more research is required to understand the response of these animals to exercise during normal aging.

Muscle growth in young horses: Effects of age, cytokines, and growth factors.

Success as equine athletes requires proper muscle growth in young horses. Muscle hypertrophy occurs through protein synthesis and the contribution of muscle satellite cells, which can be stimulated or inhibited by cytokines and growth factors present during exercise and growth. The hypotheses of this study were that 1) the LM area in young horses would increase over 1 yr, and 2) specific cytokines and growth factors (IL-1ß, IL-6, tumor necrosis factor [TNF]-α, IGF-I, and fibroblast growth factor [FGF]-2) would alter proliferation and differentiation of satellite cells isolated from young horses. Fourteen horses were divided into 3 age groups: weanlings ( = 5), yearlings to 2 yr olds ( = 4), and 3 to 4 yr olds ( = 5). The area, height, and subcutaneous fat depth of the LM were measured using ultrasonography, and BW and BCS were taken in October (Fall1), April (Spring), and October of the following year (Fall2). Satellite cells obtained from 10-d-old foals ( = 4) were cultured in the presence of IL-6, IL-1ß, TNF-α, IGF-I, or FGF-2 before evaluation of proliferation and differentiation. Data were analyzed using PROC MIXED in SAS. Body weight increased from Fall1 to Spring in weanlings ( < 0.001) and increased in all horses from Spring to Fall2 ( ≤ 0.02). Area and height of the LM increased over time ( < 0.001) and with increasing age group of horse ( ≤ 0.03), although there was no interaction of time and age ( > 0.61). There was a significant increase in LM area in all animals from Spring to Fall2 ( < 0.001) but not from Fall1 to Spring. Interleukin-6 and TNF-α decreased satellite cell proliferation by 14.9 and 11.5%, respectively ( ≤ 0.01). Interleukin-6 increased fusion 6.2%, whereas TNF-α decreased fusion 8.7% compared with control cells ( ≤ 0.001). Interleukin-1ß had no effect on proliferation ( = 0.32) but tended to decrease fusion ( = 0.06). Satellite cell proliferation was increased 28.8 and 73.0% by IGF-I and FGF-2, respectively ( < 0.0001). Differentiation was decreased 13.1% in the presence of FGF-2 but increased 3.5% in the presence of IGF-I ( ≤ 0.01). In summary, the LM area increases over the course of a year in young horses with the most growth occurring in summer. By stimulating or inhibiting proliferation and differentiation of satellite cells, IL-6, TNF-α, IL-1ß, IGF-I, and FGF-2 may alter muscle growth in young horses, thereby impacting athletic potential.

Tn4556 and luciferase: synergistic tools for visualizing transcription in Streptomyces.

Progress in understanding genetic regulatory controls in the Actinomycetes has been rate limited by the properties of in vivo transcriptional probes. We have developed a set of plasmid- and transposon-based promoter-probe vectors that employ the Vibrio harveyi luciferase-encoding luxAB cassette as a reporter of transcription. The primary advantages of luciferase (Lux) over other reporter gene products are: (i) unsurpassed sensitivity; (ii) utility during stationary-phase gene expression; and (iii) the ability to localize promoter activity spatially within developing colonies. We have used these vectors to screen for Streptomyces coelicolor promoters that exhibit developmental phenotypes or that are induced by various environmental stimuli. The plasmid-based probes have proved invaluable for identifying cis- and trans-acting elements that are required for stationary-phase expression of the S. coelicolor sapA gene. A collection of novel bld and whi insertion mutants has been obtained by use of the Lux-encoding transposon, Tn5353.

Eight-year results of a prospective non-randomised study on therapy of small breast cancer. The German Breast Cancer Study Group (GBSG).

In this report, the results of the first controlled clinical trial on breast cancer in Germany, begun in 1983, are presented after a median follow-up of 8 years. Four-year results have been previously published. In pT1 N0 M0 breast cancer, mastectomy as the standard treatment was to be compared with tumorectomy plus radiotherapy to the remaining breast tissue. The study design, originally planned as a comprehensive cohort study including randomised and non-randomised patients, had to be changed into a prospective observation study due to the low randomisation rate. 1036 out of 1119 recruited patients were evaluable. After a median follow-up of 97 months, 237 events (local recurrence, regional recurrence, distant metastases, contralateral breast cancer or death of the patient without previous recurrence) occurred. With the exception of death without recurrence, the events were evenly distributed among the two treatment groups. The 8-year local recurrence rate of the whole patient population is 8.8%. Out of all prognostic factors examined, only tumour size and grade had a significant influence on recurrent disease. Event-free survival decreased in cases with 'uncertain' tumour margins, whereas the width of the margin has no influence on disease recurrence. Based on 151 deaths observed so far, there was no significant difference in overall survival between the two treatment groups. The 8-year results of this study are in accordance with the 4-year results reported previously and with those of other breast-conserving treatment trials. There was no significant difference between the two treatment groups with regard to event-free and overall survival. Incomplete tumorectomy had a negative influence on recurrence.

Heterogeneity of tumour necrosis factor production in renal cell carcinoma.

Endogenous tumour necrosis factor (TNF) production was investigated by in situ hybridisation and immunohistochemistry in 8 renal cell carcinoma (RCC) patients at different stages of disease. Analysis of frozen sections of tumour biopsy specimens revealed variable degrees of macrophage infiltration and great heterogeneity in TNF gene expression. Two metastatic tumours investigated showed abundant TNF protein production and marked macrophage infiltration. Based on morphological criteria, these TNF-positive cells most likely belong to the macrophage lineage. Two years after nephrectomy the individual survival time was recorded; however, the small numbers did not yet allow any correlation of TNF production to the clinical course of disease. Further studies will be required to eventually reveal the role of TNF in renal cell carcinoma development.

Expression of the p53 tumour suppressor gene as a prognostic marker in platinum-treated patients with ovarian cancer.

Drug resistance is one of the most important clinical problems in the treatment of ovarian cancer. This study was designed to determine whether expression of p53 could be used as a marker for predicting the response to chemotherapy of ovarian cancer. Tissue blocks were obtained from 187 patients with diagnosed untreated ovarian cancer. Paraffin sections from the primaries were immunohistochemically analysed for p53 expression. All patients underwent platinum-based chemotherapy after surgery. We analysed whether the number of chemotherapy cycles was related to survival in women with p53 positive and p53 negative ovarian cancer. 27/187 cases were p53 positive. Expression of p53 was associated with other factors of unfavourable prognosis. Patients with p53 positive tumours had a significantly worse prognosis compared with patients with p53 negative tumours (P = 0.037). There was a statistically significant dose-response effect of platinum-based chemotherapy in patients with p53 negative tumours, which could not be seen in patients with p53 positive tumours (P = 0.01 versus P = 0.553). This could also be observed in patients with residual tumour after surgery (P = 0.0001 versus P = 0.8866). Expression of p53 may be an additional useful marker in predicting response to chemotherapy. Thus, it is possible to identify a subgroup of patients who may benefit from alternative therapy regimens.

Therapy of small breast cancer: a prospective study on 1036 patients with special emphasis on prognostic factors.

In 1983, The German Breast Cancer Study Group, sponsored by the Federal Ministry of Research and Technology, started a prospective multicenter trial on the treatment of early breast cancer pT1 pN0 M0. Treatment consisted of initial tumorectomy with microscopically free margins and lower axillary dissection. After conformation of a pT1 pN0-stage, additional treatment was either mastectomy or adjuvant radiotherapy (50 Gy in 25 fractions to the entire breast plus 12 Gy electron boost). In medially located tumors, the parasternal and supraclavicular area was also irradiated with 50 Gy. A randomization between both treatment modalities was initially planned but was not feasible and abandoned. Nearly all patients were treated according to their own choice. From November 1983 through December 1989, 1119 patients were recruited. Eighty-three were excluded from the protocol. Out of the remaining 1036 patients, 733 (71%) underwent breast preservation and 303 (29%) mastectomy. A detailed pathohistological examination of all tumorectomy specimens was performed in a pathologic reference center. Oncogen overexpression was evaluated by immunohistological detection of the transmembrane protein p-185 (corresponding to c-erb-B2) in 425 cases. After a median follow-up of 48 months, the frequency of local recurrences (4.7%), regional recurrences (1%), and distant metastases (5.4%) was the same in the breast preservation group and the mastectomy group. The 3-year disease-free survival was 90% after breast preservation and 88% after mastectomy (p = 0.21). In the breast preserving group, 24 patients with microscopically involved margins had a poorer disease-free survival than the study group (75% vs 90% after 3 years). The width of the margins had no impact on prognosis. Other prognostic factors in an univariate and multivariate analysis were tumor size and tumor grade. Age, menopausal status, hormone receptor status, histological tumor type, and treatment (mastectomy vs breast preservation) were not significant. P-185-expression was dependent on tumor grade and was the strongest prognostic factor in an univariate and multivariate analysis (p less than 0.001). The results emphasize the central role of tumor grade for prognosis and suggest the independent prognostic significance of the c-erb-B2 oncogen (corresponding to p-185) in pN0-patients.

Differences of ploidy status in progression of head and neck melanomas.

Thirty-three common naevi, 26 dysplastic naevi, 58 primary melanomas of facial skin, 24 oral melanomas, 32 lymph nodes and 12 distant melanoma metastases were stained using Feulgen method to evaluate the ploidy status by image analysis GAS-200 system. Eight percent of common naevi, 22% of dysplastic naevi, 43% of facial melanomas, 65% of oral melanomas, 40% of lymph nodes with melanoma metastases and 66% of distant melanoma metastases were classified as aneuploid. In facial melanomas the percentage of aneuploid cases increased with Clark level. Survival time of patients was significantly shorter for aneuploid cases as compared to euploid ones (p <0.01).

neu overexpression correlates with extent of disease in large cell ductal carcinoma in situ of the breast.

In a retrospective study of ductal carcinoma in situ (DCIS) of the breast, the expression of the neu oncogene was determined immunohistochemically in 76 women treated by local excision or mastectomy. The histopathological features, including the extent of the lesion, histological subtype, cell type, and number of mitoses, were related to neu overexpression. Immunopositivity was found only in DCIS of large cell type, where it correlated with extent of disease but not with mitotic rate. Our findings, together with previous experimental evidence, suggest that this relationship is a consequence of the effect of the neu protein on cell motility.

An unusual case of adamantinoma of long bones.

Adamantinoma of the tibia is a rare bone lesion, in which it is impossible to predict the biological behaviour. A case of extremely late local recurrence and lung metastasis is presented. Additionally, the patient developed pneumothorax on the right side months before intrapulmonary metastasis could be detected by X ray. Finally 1 week before her death the young woman suffered from paraneoplastic severe hypercalcemia leading to hypercalcemic coma and pancreatitis.