Intramuscular Injection of Sevoflurane Detects Malignant Hyperthermia Predisposition in Susceptible Pigs

Background: The authors hypothesized that intramuscular sevoflurane injection allows diagnostic differentiation between malignant hyperthermia-susceptible (MHS) and -nonsusceptible (MHN) pigs by measurement of intramuscular lactate and carbon dioxide partial pressure (Pco2), and that dantrolene reduces the sevoflurane-induced Pco2 increase.

Methods: With approval of the local animal care committee, microdialysis probes with attached microtubing for sevoflurane injection were placed in the adductor muscles of nine MHS and six MHN pigs, and Pco2 probes with microtubing were positioned in the triceps muscle of eight MHS and six MHN pigs. After equilibration, sevoflurane boluses at different concentrations and a sevoflurane-dantrolene bolus were injected synchronously. Lactate, pyruvate, and glucose as well as Pco2 were measured spectrophotometrically, and the rate of Pco2 increase was calculated.

Results: Intramuscular sevoflurane injection increased local lactate and Pco2 dose dependently, and significantly higher in MHS than in MHN pigs. Measurement of the rate of Pco2 increase allowed a distinct differentiation between single MHS and MHN pigs. No significant increase in Pco2 was found with sevoflurane and dantrolene.     

Implantation of a colorectal stent as a therapeutic approach in the treatment of esophageal leakage

Background  

While the mortality of esophageal surgery has decreased due to technological advancements, there is still a complication rate of about 30%. One of the main complications is the anastomotic leakage associated with a significant rate of morbidity and mortality. To close the leakage the efficacy of self-expanding stents (SES) has been shown in different studies. However, the high rate of stent migration limits the use of commercial available stents. In our case we were faced with the problem that the diameter of all available stents was too small to attach tightly to the mucosal wall of the esophagogastric anastomosis.     

Effects of Lovastatin Alone or Combined with Irradiation on Tumor Cells in Vitro and in Vivo

PURPOSE: To evaluate the effect of lovastatin alone or combined with radiation on U87MG and FaDu cells in vitro and U87MG tumors in vivo. MATERIAL AND METHODS: Cell number, p21(WAF1) expression, apoptosis, reproductive cell death, and cell-cycle distribution were investigated after incubation of U87MG and FaDu cells in vitro. The effect of lovastatin (50 mg/kg/day) on tumor growth and on tumor growth delay after single-dose irradiation with 20 Gy was investigated using U87MG tumors in nude mice. RESULTS: Lovastatin dose dependently decreased cell number and proliferation of U87MG and FaDu cells. The proportion of cells in G0/G1 phase, apoptosis and p21 protein expression increased after lovastatin alone or combined with 4-Gy irradiation in both cell lines. Effects of lovastatin on cell cycle and cell number were more pronounced in U87MG compared to FaDu. No radiosensitization of clonogenic cells by lovastatin could be demonstrated in both cells lines, but the colony-forming ability after lovastatin alone was decreased in FaDu cells. In vivo, lovastatin decreased tumor volume over time but did not increase growth delay after irradiation of U87MG tumors with 20 Gy. CONCLUSION: The data support effects of lovastatin on proliferation, apoptosis and colony-forming ability in vitro and tumor volume in vivo. At the drug concentration achievable, lovastatin did not improve the effects of radiation on U87MG tumors in vivo.     

Molecular and cytogenetic characterization of a non-mosaic isodicentric Y chromosome in a patient with Klinefelter syndrome

We report on an adult male with Klinefelter phenotype and an isodicentric Y chromosome (47,XX,+idic(Y)(q12)), a combination which has to the best of our knowledge not been reported before. The patient was hospitalized in forensic psychiatry because of repeated delinquency, aggressive, aberrant and inappropriate behavior, and borderline intelligence. Molecular cytogenetic studies (FISH) showed that the SRY gene was present on both ends of the idicY, while there was only one signal for the Yq subtelomere probe. Molecular investigations by multiplex PCR, using STS markers covering the short and long arm of the Y chromosome did not indicate a deletion of Y chromosomal material. Molecular investigations of STR markers located on Xp22.3 and Xq28 indicated paternal origin of the additional X chromosome and an error in paternal meiosis I. Results of FISH analysis and molecular investigations are compatible with a phenotype as described for individuals with a 48,XXYY karyotype and support the findings that isodicentric Y chromosomes are frequently accompanied by other sex chromosomal abnormalities.     

Two independent mutations in a family with neurofibromatosis type 1 (NF1)

We report on two independent alterations of the NF1 gene in a three-generation kindred with neurofibromatosis type 1 (NF1). Using temperature gradient gel electrophoresis (TGGE) in a mutation analysis of exon 31 of the NF1 gene we detected the previously reported nonsense mutation R1947X. This C-to-T transition at codon 1947 in exon 31 is considered to represent a mutation "hot spot" of the NF1 gene due to 5mCpG deamination. All living family members together with their genomic DNA were included in this investigation. However, the mutation R1947X was absent from two undoubtedly affected siblings of the propositus. Another NF1 mutation (889-2A-->G) was identified in the two sibs by the protein truncation test (PTT). The novel splice site mutation 889-2A-->G results in a skip of NF1 exon 7 during splicing and protein truncation due to frameshift. The two NF1 alterations are linked to different paternal haplotypes. In our study of a three-generation kindred, R1947X represents a de novo mutation whereas 889-2A-->G is an inherited splice mutation. Implications for phenotype variation are discussed.     

An overview of Canadian physician work force databases

Physician-resource planning activities have increased dramatically in Canada since the release of the Barer-Stoddart report, "Toward Integrated Medical Resource Policies for Canada" in 1991. One of the key concepts of the Barer-Stoddart report is the "medical career life cycle," beginning with entry to medical school and ending with exit from practice. To apply this concept in a planning context, it is essential to have a current information base that will contain data on numbers of physicians, where they are, what they do, and how active they are. In addition, a longitudinal capability is important for understanding issues such as retention and attrition. The objective of this article is to review and assess recent initiatives in the establishment of physician-resource databases in Canada by medical associations, governments, licensing bodies, certifying colleges, and other groups with a respect to comprehensiveness and comparability of key data elements and their ability to address key policy questions in physician-resource planning and to identify opportunities for collaboration and links.     

Factors influencing the emigration of physicians from Canada to the United States.

OBJECTIVE: To determine whether location of postgraduate medical training and other factors are associated with the emigration of physicians from Canada to the United States. DESIGN: Case-control study, physicians were surveyed with the use of a questionnaire mailed in May 1994 (with a reminder sent in September 1994), responses to which were accepted until Dec. 31, 1994. PARTICIPANTS: Physicians randomly selected from the CMA database, 4000 with addresses in Canada and 4000 with current addresses in the United States and previous addresses in Canada. OUTCOME MEASURES: Sex, age, location of undergraduate and postgraduate medical training, qualifications, practice location, opinions concerning residence decisions, current satisfaction and plans. RESULTS: The overall response rate was 49.6% (50.0% among physicians in the United States and 49.2% among those in Canada). Age and sex distributions were similar among the 8000 questionnaire recipients and the nearly 4000 respondents. Physicians living in the United States were more likely to be older (mean 53.2 v. 49.6 years of age), male (87% v. 75%) and specialists (79% v. 52%) than those practising in Canada. Postgraduate training in the United States was associated with subsequent emigration (odds ratio 9.2, 95% confidence interval 7.8 to 10.7). However, in rating the importance of nine factors in the decision to emigrate or remain in Canada, there was no significant difference between the two groups in the rating assigned to location of postgraduate training. Professional factors rated most important by most physicians in both groups were professional/clinical autonomy, availability of medical facilities and job availability. Remuneration was considered an equally important factor by those in Canada and in the United States. Six of seven personal/family factors were rated as more important to their choice of practice location by respondents in Canada than by those in the United States. Current satisfaction was significantly higher among respondents in the United States. Most physicians in each group planned to continue practising at their current location. Of Canadian respondents, 22% indicated that they were more likely to move to the United States than they were a year beforehand, whereas 4% of US respondents indicated that they were more likely to return to Canada. CONCLUSIONS: Factors affecting the decision to move to the United States or remain in Canada can be categorized as "push" factors (e.g., government involvement) and "pull" factors (e.g., better geographic climate in the US). Factors can also be categorized by whether they are amenable to change (e.g., availability of medical facilities) or cannot be managed (e.g., proximity of relatives). An understanding of the reasons why physicians immigrate to the United States or remain in Canada is essential to planning physician resources nationally.     

Antecedents of respiratory pauses in extremely low birth weight infants supported by proportional assist ventilation.

OBJECTIVE: To determine characteristics of breathing patterns prior to respiratory pauses in extremely low birth weight (ELBW) infants breathing spontaneously under proportional assist ventilation (PAV). METHODS: Thirteen infants (mean +/- SD: gestational age 25 +/- 1 weeks; birth weight 753 +/- 149 g; age 4 +/- 3 days) were studied. Recordings were obtained under PAV over two-hour periods on two consecutive days. The last 10 breaths preceding respiratory pauses were analyzed. RESULTS: Tidal volume, inspiratory and expiratory peak flow, and mean inspiratory flow decreased in the last breaths prior to respiratory pauses compared to all other breaths (p < 0.001). Of all apneas 89% were preceded by a decrease in tidal volume of at least 33% (435/487; p < 0.001). The positive predictive value of a decrease in tidal volume to predict an apnea was 26% (435/1640; p < 0.001). CONCLUSIONS: Decreases in tidal volume of at least 33% and in airflow are the predominant changes in the breathing pattern prior to respiratory pauses in ELBW infants, preceding 89% of all respiratory pauses. Their low positive predictive value of 26% however, indicates that further variables of breathing need to be implemented to predict cessation of breathing with higher precision.