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.     

Tariquidar-induced P-glycoprotein inhibition at the rat blood-brain barrier studied with (R)-11C-verapamil and PET.

The multidrug efflux transporter P-glycoprotein (P-gp) is expressed in high concentrations at the blood-brain barrier (BBB) and is believed to be implicated in resistance to central nervous system drugs. We used small-animal PET and (R)-11C-verapamil together with tariquidar, a new-generation P-gp modulator, to study the functional activity of P-gp at the BBB of rats. To enable a comparison with human PET data, we performed kinetic modeling to estimate the rate constants of radiotracer transport across the rat BBB. METHODS: A group of 7 Wistar Unilever rats underwent paired (R)-11C-verapamil PET scans at an interval of 3 h: 1 baseline scan and 1 scan after intravenous injection of tariquidar (15 mg/kg, n = 5) or vehicle (n = 2). RESULTS: After tariquidar administration, the distribution volume (DV) of (R)-11C-verapamil was 12-fold higher than baseline (3.68 +/- 0.81 vs. 0.30 +/- 0.08; P = 0.0007, paired t test), whereas the DVs were essentially the same when only vehicle was administered. The increase in DV could be attributed mainly to an increased influx rate constant (K1) of (R)-11C-verapamil into the brain, which was about 8-fold higher after tariquidar. A dose-response assessment with tariquidar provided an estimated half-maximum effect dose of 8.4 +/- 9.5 mg/kg. CONCLUSION: Our data demonstrate that (R)-11C-verapamil PET combined with tariquidar administration is a promising approach to measure P-gp function at the BBB.     

De novo esophageal neoplasia after liver transplantation.

The purpose of the study was to determine the incidence, risk factors, treatment, and influence on survival of patients with de novo esophageal cancer after liver transplantation (LT). From 1988 to 2006, 1,926 patients underwent LT in our institution. A total of 9 patients (0.5%) developed a de novo esophageal cancer and 1 patient a cancer of the cardia (0.05%). A retrospective analysis was performed to reveal underlying diseases, timeframes between LT and appearance of cancer, predisposing factors, cancer therapy, complications, immunosuppressive regimens, and survival. Of our 10 patients, 7 (70%) suffered from esophageal squamous cell carcinoma (SCC) and 3 patients (30%) developed an adenocarcinoma, including the patient with cancer of the cardia. A total of 9 patients were transplanted due to alcoholic cirrhosis; 1 patient suffered from hepatocellular carcinoma in nonA-nonB hepatitis-related cirrhosis. Median time to tumor diagnosis was 51 months after transplantation. A total of 5 patients were treated conservatively with combined radiochemotherapy and 5 underwent surgical resection. Patients with radiochemotherapy showed a mean survival of 14.8 months vs. 24.8 months for the patients of the surgery group. No major postoperative complication has been observed. A total of 2 patients of the surgery group are still alive after a follow-up of 15 and 89 months. In conclusion, de novo esophageal and cancer of the cardia after LT is a rare event. In spite of immunosuppression, no increased complication rate has been observed. Patients may have a survival benefit from surgical resection.     

Serum 25-hydroxyvitamin D concentrations of free-living subjects consuming olestra

The effect of olestra on vitamin D status was assessed in a 6-wk, double-blind, placebo-controlled study involving 202 free-living adults. Subjects consumed a total of 20 g/d of olestra or triglycerides in cookies eaten at each meal. A 20-micrograms ergocalciferol capsule was taken with each morning meal. Serum 25-hydroxyergocalciferol (25-OHD2) concentrations rose from approximately 5.7 to 39.0 and 31.7 nmol/L in the placebo and olestra groups, respectively, at week 6. At week 6, 25-OHD2 contributed 46-54% to total serum 25-OHD concentration compared with 11% at baseline. The 19% decrease in serum 25-OHD2 concentrations produced by olestra in this study is equivalent to a decrease of approximately 1.2 nmol/L under nonsupplemented dietary conditions. Ingesting 20 g olestra/d in the diet is thus not expected to affect vitamin D nutritional status.     

Human immunodeficiency virus infection in disadvantaged adolescents. Findings from the US Job Corps

OBJECTIVE--To describe the human immunodeficiency virus (HIV) epidemic among socially and educationally disadvantaged young persons in the United States. DESIGN.-We analyzed demographic and geographic findings from the screening of Job Corps students for antibody to HIV. SETTING--The Job Corps is a federal training program for disadvantaged, out-of-school youth. POPULATION SCREENED--Residential students aged 16 to 21 years who entered the Job Corps from October 1987 through February 1990. MAIN OUTCOME MEASURE--Rates of observed HIV infection in entering students, stratified by demographic and geographic features. RESULTS--Of 137,209 Job Corps students screened, 488 were HIV seropositive (3.6 per 1000), a seroprevalence rate higher than that among military applicants of the same age. Overall seroprevalence was slightly higher in male (3.7 per 1000) than in female (3.2 per 1000) Job Corps students, but among those students aged 16 and 17 years, seroprevalence was higher among females (2.3 per 1000) than among males (1.5 per 1000) (P less than .05). For students aged 16 to 21 years, seroprevalence increased with year of age: 1.8 per 1000 per year for males and 0.7 per 1000 per year for females. Among those aged 21 years, HIV prevalence was 8.9 per 1000. For black and Hispanic students from large Northeastern cities, seroprevalence increased by 4.3 per 1000 per year of age and reached 24.8 per 1000 (one of 40) in students aged 21 years. However, among students from rural areas and small towns, HIV seroprevalence was disproportionately high in the Southeast. Compared with recently described US patients with the acquired immunodeficiency syndrome, HIV-infected students who entered the Job Corps were much more likely to be female. CONCLUSIONS--These findings show that disadvantaged, out-of-school adolescents are at high risk for HIV infection. The screening results identified surprisingly high seroprevalence in the southeastern United States and demonstrated a marked shift in the HIV epidemic to young women. Controlling the HIV epidemic among teenagers must include interventions that will reach adolescents early and outside of the formal educational system.     

Chronic orchialgia: Consider gabapentin or nortriptyline before considering surgery

OBJECTIVE: To establish if there is a role for gabapentin or nortriptyline in the treatment of chronic orchialgia. METHODS: Twenty-six consecutive patients with chronic orchialgia were seen in the chronic pain clinic by a multidisciplinary team. A pain questionnaire was completed prior to commencing either gabapentin or nortriptyline. They were reviewed at 3 months and a repeat questionnaire completed. A 50% improvement in pain was considered successful. RESULTS: Complete data was available for 19 patients. Overall, 61.5% of patients commenced on gabapentin and 66.6% of patients commenced on nortriptyline had a greater than 50% improvement in pain. Patients with post-vasectomy testicular pain were considered as a subgroup. None of these patients had a greater than 50% improvement in pain. However, 80% of patients in the subgroup with idiopathic chronic orchialgia had a greater than 50% improvement in pain. CONCLUSION: Although this is a small study, it appears that gabapentin and nortriptyline are effective in the treatment of idiopathic chronic orchialgia but not post-vasectomy pain.     

Interaction of permanently charged chlorpromazine and dopamine analogs with the striatal D-1 dopaminergic receptor

Although a structural feature common to all dopaminergic agonists and antagonists is a side-chain basic amino group, it is unclear whether this moiety binds to the D-1 dopamine (DA) receptor in the charged or uncharged form. To obtain information on this point, we synthesized permanently charged dimethylsulfonium and quaternary ammonium analogs of chlorpromazine and DA and determined whether these compounds can bind to the D-1 receptor by measuring their abilities to inhibit the binding of SCH 23390, a D-1 receptor antagonist. Chlorpromazine and the dimethylsulfonium and trimethylammonium analogs of chlorpromazine were found to inhibit the binding of [3H]SCH 22390, which was maximally inhibited to the same extent by all three compounds. In addition, inhibition curves for the compounds fit a one-site binding model, indicating binding to a single class of sites. However, while the permanently charged chlorpromazine analogs were able to inhibit [3H]SCH-23390 binding, they were considerably less potent than chlorpromazine. DA and dimethyl DA were also able to inhibit [3H]SCH 23390 binding. However, the permanently charged dimethylsulfonium and trimethylammonium analogs of DA were ineffective in inhibiting [3H]SCH 23390 binding. In addition, the permanently uncharged methylsulfide analog did not inhibit binding. These studies show that permanently charged analogs of chlorpromazine can bind to the striatal D-1 receptor, which is consistent with an anionic recognition site on the D-1 receptor that interacts with antagonists in the cationic form. In addition, it appears that a nitrogen atom is not required for binding to the D-1 receptor, since the sulfonium analog of chlorpromazine bound to the receptor to the same extent as chlorpromazine. However, since the permanently charged or uncharged analogs of DA did not bind to the D-1 receptor, it is still unclear as to whether the charged form of a dopaminergic agonist can bind. The lower potency or ineffectiveness of the permanently charged analogs compared to the parent amines (chlorpromazine, DA, dimethyl DA) in binding to the D-1 receptor may reflect the inability of the permanently charged analogs to undergo hydrogen binding with the anionic site of the receptor.