Analysis of Deaths Related to Anesthesia in the Period 1996-2004 from Closed Claims Registered by the Danish Patient Insurance Association

Background: Anesthesia is associated with complications, and some of them may be fatal. The authors investigated the circumstances under which deaths were associated with anesthesia. In Denmark, the specialty anesthesiology encompasses emergency medicine, chronic and acute pain medicine, anesthetic procedures, perioperative care medicine, and intensive care medicine.

Methods: The authors retrospectively investigated anesthesia related deaths registered by the Danish Patient Insurance Association.

Results: From 1996 to 2004, 27,971 claims were made by the Danish Patient Insurance Association covering all medical specialties, of which 1,256 files (4.5%) were related to anesthesia. In 24 cases, the patient's death was considered to result from the anesthetic procedure: 4 deaths were related to airway management, 2 to ventilation management, 4 to central venous catheter placement, 4 as a result of medication errors, 4 from infusion pump problems, and 4 after complications from regional blockades. Severe hemorrhage caused 1 death, and in 1 case the cause was uncertain.     

Immature ovarian teratoma: a review of 14 cases

We conducted a clinical and pathologic review of 14 patients with immature ovarian teratoma. In this series of patients, one had monodermal malignant neuroectodermal teratoma and two others had immature ovarian teratoma in association with immature presacral teratoma. Because of the small number of cases of immature ovarian teratoma and the diverse therapeutic modalities used in this study, we cannot recommend a specific treatment for patients with this tumor on the basis of our findings. The histologic grade of the tumor seemed to be a reliable indicator of prognosis. Grade 0 metastatic lesions should be considered benign and are associated with a favorable prognosis.     

Inhibitory and regulatory binding sites on the rat brain serotonin transporter: molecular weight of the [3H]paroxetine and [3H]citalopram binding proteins

Citalopram binds with high affinity to a specific binding site located on the serotonin (5-HT) transporter in 5-HT neurons. The binding affinity of [3H]citalopram was found to increase with increasing concentration of citalopram. This may be a homotropic positive allosteric effect, thus indicating the presence of an allosteric binding site for citalopram. The molecular weight of the proteins containing the high-affinity binding sites for citalopram and paroxetine, as well as the allosteric binding site for citalopram were determined by the irradiation method. The molecular weights of the three binding site proteins were found to be the same, suggesting that all three binding sites are located on the same protein molecule in the 5-HT transporter. The results support a hypothesis that the binding area for [3H]citalopram is located deeper in the transport channel than the [3H]paroxetine binding area. Thus the two high-affinity binding sites probably cover different, but overlapping, parts of the protein molecule. The allosteric binding site may be located elsewhere on the protein where it induces conformational changes of the 5-HT transporter with the result that high-affinity bound ligands get trapped in the transport channel, thereby explaining the increase in affinity.     

Identification of a C → T Mutation in the Reactive-Site Coding Region of the C1-Inhibitor Gene and its Detection by an Improved Mutation-Specific Polymerase Chain Reaction Method

Mutations in the C1-inhibitor (C1-INH) gene, leading to low functional levels of C1-inhibitor protein, cause hereditary angioedema (HAE). The disease is characterized by episodic edema in a number of organs. Typically, swellings occur in extremities and face, often accompanied by crampy abdominal pain. Laryngeal edema may lead to suffocation. Type II HAE patients have low functional C1-INH values stemming from only one normal allele. Antigenic C1-INH values, however, are normal or increased owing to the presence of a dysfunctional protein from the mutated allele. The mutations are usually found in exon 8 coding for the amino acids near the reactive centre (P1). Previously, no mutations in the C1-INH gene had been published from the Scandinavian countries. In this work, exon 8 of the C1-inhibitor gene was sequenced in members of two different kindreds, from western and northern Norway, who were suffering from HAE type II. A common point mutation was found within the bait region encoding the reactive centre. The codon CGC was converted to TGC at position 17 970, corresponding to an Arg → Cys replacement which reportedly is the second most frequent type II HAE mutation. This information was utilized to develop a mutation-specific polymerase chain reaction (PCR) for the identification of affected family members. The antisense 17-mer primer (5'-AAGACCAGCAGGGTGCA-3') was successfully applied and AmpliTaq Gold was used in the PCR.     

Progesterone Receptor Levels Independently Predict Survival in Endometrial Adenocarcinoma

Estrogen receptor (ER) and progesterone receptor (PR) contents were determined by biochemical (dextran charcoal-coated (DCC) assay) and immunohistochemical (ICA) methods in biopsies from 145 primary endometrial adenocarcinomas and those with eligible receptor measurements were analyzed with respect to correlations to cancer-specific survival in a multivariate analysis including histopathological characteristics. Median patient follow-up time was 67 months with 18 cancer deaths. The PR-DCC and ER-DCC values were dichotomized according to levels previously found by us to correspond to the best agreement between receptor status as determined by the DCC and ICA methods (130 fmol/mg cytosol protein for ER, 114 fmol/mg for PR). Using these thresholds, we found by multivariate analysis that “high” PR-DCC levels (>114 fmol/mg) correlated significantly (P= 0.004) with survival, independent of stage risk group (Ia + b vs Ic-IV). Patient age and histologic grade were prognostic factors in a univariate setting, but these parameters were eliminated in the multivariate model. While the PR-ICA scores also correlated significantly and independently with survival, the predictive effect of PR-ICA positivity alone could not be statistically evaluated due to the number of cases with eligible ICA values. However, we suggest that owing to a close correlation between DCC and ICA results, PR-ICA status may provide significant prognostic information when DCC measurements are not available.     

CYP2D6 genotype determination in the Danish population

CYP2D6 genotyping was carried out by XbaI restriction fragment length polymorphism analysis and polymerase chain reaction in 168 healthy Danish volunteers, 77 extensive metabolizers (EM) and 91 poor metabolizers (PM) of sparteine. All EM were genotyped correctly as heterozygous or homozygous for the functional (wild type) gene, D6-wt. However, the D6-wt gene was apparently also present in 11 (12%) of the PM who accordingly were incorrectly genotyped as EM. The specificity of genotyping PM thus was 100% but the sensitivity was only 88%. The most common allele was the D6-wt with an apparent frequency of 0.741 (0.026) in the Danish population and the second most common allele was the D6-B with an apparent frequency of 0.194 (0.024). The median (range) of the sparteine metabolic ratio (MR) in 47 homozygous D6-wt EM was 0.28 (0.11–4.10) and the corresponding value in heterozygous EM was 0.36 (0.11–9.10). The median difference was 0.09 (95% confidence interval: 0.02–0.16). CYP2D6 phenotyping is a promising tool in tailoring the individual dose of tricyclic antidepressants, some neuroleplics and some antiarrhythmics. However if the genotype test could be improved with regard to both sensitivity in PM and the ability to predict CYP2D6 activity in EM then it would be of even greater clinical value in therapeutic drug monitoring.