MISE AU POINT D'UNE TECHNIQUE D'ADMINISTRATION IN VIVO DES VECTEURS GENETIQUES DANS LEMUSCLE CARDIAQUE

Objective In order to improve the in vivo gene transfer into the heart muscle, we have designed a ECG-synchronized microinjection system that allows sequential gene delivery to the myocardium.Methods A cannula was introduced into the right carotid artery of the Wistar rat under general anesthesia.With the ECG-synchronized injection during diastole, the genetic vector (Ad CMV lacZ ) infusion was performed with various concentrations( l07 ～ l010pfu ) and different frequency ( the ratio of heart beats per injection from 1: 1 to 4: 1 ). The hearts of the rats were removed after 7 days for histological examination. Results Best results were obtained with a total vector amount of l09 pfu and a good ratio 3: 1 between heart frequency and injection frequency. The transfection efficiency was increased by use of vasodilators and by an increase of vascular permeability. No signs of myocardial ischemia or ventricular arrythmia were observed. Conclusion We have established a novel and safe method for in vivo gene transfer into the heart. Transgene expression suggests that this method may be useful technique to study cardiac function of treat cardiac diseases by means of gene theratpy.     

Poor Intraoperative Blood Glucose Control Is Associated with a Worsened Hospital Outcome after Cardiac Surgery in Diabetic Patients

Background: Tight perioperative control of blood glucose improves the outcome of diabetic patients undergoing cardiac surgery. Because stress response and cardiopulmonary bypass can induce profound hyperglycemia, intraoperative glycemic control may become difficult. The authors undertook a prospective cohort study to determine whether poor intraoperative glycemic control is associated with increased intrahospital morbidity.

Methods: Two hundred consecutive diabetic patients undergoing on-pump heart surgery were enrolled. A standard insulin protocol based on subcutaneous intermediary insulin was given the morning of the surgery. Intravenous insulin therapy was initiated intraoperatively from blood glucose concentrations of 180 mg/dl or greater and titrated according to a predefined protocol. Poor intraoperative glycemic control was defined as four consecutive blood glucose concentrations greater than 200 mg/dl without any decrease in despite insulin therapy. Postoperative blood glucose concentrations were maintained below 140 mg/dl by using aggressive insulin therapy. The main endpoints were severe cardiovascular, respiratory, infectious, neurologic, and renal in-hospital morbidity.

Results: Insulin therapy was required intraoperatively in 36% of patients, and poor intraoperative glycemic control was observed in 18% of patients. Poor intraoperative glycemic control was significantly more frequent in patients with severe postoperative morbidity (37% vs. 10%; P < 0.001). The adjusted odds ratio for severe postoperative morbidity among patients with a poor intraoperative glycemic control as compared with patients without was 7.2 (95% confidence interval, 2.7-19.0).     

Surgery and Chemotherapy for Small Cell Lung Cancer in Stages I–II with or without Radiotherapy

PURPOSE: To analyze the effectiveness of surgery and chemotherapy with or without radiotherapy in the management of limited small cell lung cancer (LSCLC) in stages I and II. PATIENTS AND METHODS: 39 patients (median age 62 years) with LSCLC in stages pT1 or pT2 and pN0 or pN1 (stages IA-IIB) who had a tumor resection and systematic lymph node dissection were reviewed retrospectively. The median follow-up period was 29 months. 35 patients (90%) received a median of four cycles of a platinum-containing chemotherapy postoperatively. 16 patients (41%) received an adjuvant thoracic radiotherapy (TRT, median 50 Gy); 21 patients (54%) received a prophylactic cranial irradiation (PCI, median 30 Gy). RESULTS: The median overall survival for all patients was 47 months, resulting in actuarial 1-, 3-, and 5-year survival rates of 97%, 58%, and 49%, respectively. Distant metastases were found in 13 patients (33%) after a median of 16 months. Patients who received an adjuvant TRT showed a trend toward improved thoracic recurrence-free survival (p = 0.06) and improved overall survival (p = 0.07) compared to those treated with surgery and chemotherapy only. Brain metastasis-free survival (p = 0.01) and overall survival (p = 0.01) were improved significantly in patients who received a PCI. CONCLUSION: Surgical tumor resection may be considered for carefully selected patients. Adjuvant chemotherapy and PCI are recommended for all patients. Adjuvant TRT is currently used in patients with positive lymph nodes (pN1), because the probability of a subclinical involvement of the mediastinal lymphatic system appears to be increased in these patients.     

Die Haftung des Ehegatten für Krankenhausbehandlungskosten nach § 1357 BGB

Ohne Zusammenfassung     

Genetic variation in serotonin transporter alters resting brain function in healthy individuals.

BACKGROUND: Perfusion functional magnetic resonance imaging (fMRI) was used to investigate the effect of genetic variation of the human serotonin transporter (5-HTT) gene (5-HTTLPR, SLC6A4) on resting brain function of healthy individuals. METHODS: Twenty-six healthy subjects, half homozygous for the 5-HTTLPR short allele (s/s group) and half homozygous for the long allele (l/l group), underwent perfusion functional and structural magnetic resonance imaging during a resting state. The two genotype groups had no psychiatric illness and were similar in age, gender, and personality scores. RESULTS: Compared with the l/l group, the s/s group showed significantly increased resting cerebral blood flow (CBF) in the amygdala and decreased CBF in the ventromedial prefrontal cortex. The effect of functional modulation in these regions by 5-HTTLPR genotype cannot be accounted for by variations in brain anatomy, personality, or self-reported mood. CONCLUSIONS: The 5-HTTLPR genotype alters resting brain function in emotion-related regions in healthy individuals, including the amygdala and ventromedial prefrontal cortex. Such alterations suggest a broad role of the 5-HTT gene in brain function that may be associated with the genetic susceptibility for mood disorders such as depression.     

Postoperative Analgesic Effects of Continuous Wound Infiltration with Diclofenac after Elective Cesarean Delivery

Background: Postoperative pain mostly results from sensitization of afferent fibers at injury sites driving central sensitization. Recently, peripheral processes have gained attention as mechanisms of hyperalgesia, and prostaglandins are among highly sensitizing agents. To date, perioperative administration of a single local dose of nonsteroidal antiinflammatory drugs has shown inconclusive efficacy. Rather than a single bolus, the current study evaluates the postoperative analgesic effect of diclofenac continuous intrawound infusion after elective cesarean delivery.

Methods: Ninety-two parturients were randomly allocated to receive a 48-h continuous intrawound infusion with 240 ml containing 300 mg diclofenac, 0.2% ropivacaine, or saline. In the ropivacaine and saline groups, patients also received 75 mg intravenous diclofenac every 12 h for 48 h. Postoperative evaluation included intravenous morphine consumption by patient-controlled analgesia and visual analog pain scores. Punctate mechanical hyperalgesia surrounding the wound and presence of residual pain after 1 and 6 months were also assessed.

Results: Continuous diclofenac infusion significantly reduced postoperative morphine consumption (18 mg; 95% confidence interval, 12.7-22.2) in comparison with saline infusion and systemic diclofenac (38 mg; 95% confidence interval, 28.8-43.7) (P = 0.0009) without unique adverse effects. Postoperative analgesia produced by local diclofenac infusion was as effective as local ropivacaine infusion with systemic diclofenac.     

Enhancing laboratory report contents to improve outpatient management of test results

In today''s environment, providers are extremely time-constrained. Assembling relevant contextual data to make decisions on laboratory results can take a significant amount of time from the day. The Regenstrief Institute has created a system which leverages data within Indiana Health Information Exchange''s (IHIE''s) repository, the Indiana Network for Patient Care (INPC), to provide well-organized and contextual information on returning laboratory results to outpatient providers. The system described here uses data extracted from INPC to add historical test results, medication-dispensing events, visit information, and clinical reminders to traditional laboratory result reports. These “Enhanced Laboratory Reports” (ELRs) are seamlessly delivered to outpatient practices connected through IHIE via the DOCS4DOCS clinical messaging service. All practices, including those without electronic medical record systems, can receive ELRs. In this paper, the design and implementation issues in creating this system are discussed, and generally favorable preliminary results of attitudes by providers towards ELRs are reported.