Autonomic circulatory and cerebrocortical responses during increasing depth of propofol sedation/hypnosis in humans

PURPOSE: To describe the relative effects of graded central nervous system (CNS) depression, using increasing propofol infusion rates, on neurovegetative brainstem-mediated circulatory control mechanisms and higher cortical activity in healthy humans. METHODS: Propofol was administered using an infusion scheme designed to achieve three target blood concentrations in ten healthy volunteers. Blood propofol concentrations and sedation scores were determined at baseline, during the three propofol infusion levels, and 30 min into the recovery period. Electroencephalographic (EEG) power was measured in three frequency bands to quantify cortical activity, and autonomic heart rate control was quantified using spontaneous baroreflex assessment and power spectral analysis of pulse interval. RESULTS: Sedation scores closely paralleled propofol blood concentrations (0, 0.53 +/- 0.34, 1.24 +/- 0.21, 3.11 +/- 0.80, and 0.96 +/- 0.42 microg x mL(-1) at baseline, three infusion levels and recovery respectively), and all subjects were unconscious at the deepest level. Indices of autonomic heart rate control were decreased only at the deepest levels of CNS depression, while EEG effects were apparent at all propofol infusion rates. These EEG effects were frequency specific, with power in the beta band being affected at light levels of sedation, and alpha and delta power altered at deeper levels. CONCLUSIONS: The results of this study support a relative preservation of neurovegetative circulatory control mechanisms during the early stages of CNS depression using gradually increasing rates of infusion of propofol. Indices of circulatory control did not reliably reflect depth of sedation.     

Thyroid-specific ablation of the Carney complex gene, PRKAR1A, results in hyperthyroidism and follicular thyroid cancer

Thyroid cancer is the most common endocrine malignancy in the population, and the incidence of this cancer is increasing at a rapid rate. Although genetic analysis of papillary thyroid cancer (PTC) has identified mutations in a large percentage of patients, the genetic basis of follicular thyroid cancer (FTC) is less certain. Thyroid cancer, including both PTC and FTC, has been observed in patients with the inherited tumor predisposition Carney complex, caused by mutations in PRKAR1A. In order to investigate the role of loss of PRKAR1A in thyroid cancer, we generated a tissue-specific knockout of Prkar1a in the thyroid. We report that the resulting mice are hyperthyroid and developed follicular thyroid neoplasms by 1 year of age, including FTC in over 40% of animals. These thyroid tumors showed a signature of pathway activation different from that observed in other models of thyroid cancer. In vitro cultures of the tumor cells indicated that Prkar1a-null thyrocytes exhibited growth factor independence and suggested possible new therapeutic targets. Overall, this work represents the first report of a genetic mutation known to cause human FTC that exhibits a similar phenotype when modeled in the mouse. In addition to our knowledge of the mechanisms of human follicular thyroid tumorigenesis, this model is highly reproducible and may provide a viable mechanism for the further clinical development of therapies aimed at FTC.     

55-kd tumor necrosis factor receptor is expressed by human keratinocytes and plays a pivotal role in regulation of human keratinocyte ICAM-1 expression.

Tumor necrosis factor alpha (TNF alpha) is a potent modulator of human keratinocyte intercellular adhesion molecule-1 (ICAM-1) expression. TNF alpha is known to exert its biologic effects by binding to specific cell-surface receptors. Two distinct TNF binding molecules, the 55-kd and the 75-kd TNF receptor (TNFR) recently have been found to be expressed by human cells. These two receptor types are independently regulated and differ markedly in their intracellular regions, indicating functional dichotomy. In order to gain further insight into the mechanisms underlying ICAM-1 regulation in human keratinocytes, in the present study, the receptor molecules mediating TNF alpha induced ICAM-1 upregulation in human keratinocytes was defined. Human keratinocyte TNFR expression was assessed using monoclonal antibodies that specifically recognize the 55-kd or the 75-kd TNFR. Using FACS analysis, normal (HNK) as well as transformed (KB) human keratinocytes were found to react with anti-55-kd TNFR, but not anti-75-kd TNFR antibodies. These immunofluorescence data were confirmed by Northern blot analysis revealing clearly detectable amounts of mRNA specific for the 55-kd TNFR in KB cells. Incubation of human keratinocytes with anti-55-kd TNFR antibodies at 37 degrees C for 24 h increased ICAM-1 expression in a TNF alpha-like fashion. Moreover, the well known synergistic effect of IFN gamma plus TNF alpha on keratinocyte ICAM-1 induction could be mimicked by stimulation of cells with IFN gamma plus anti-55-kd TNFR antibodies. Synergistic ICAM-1 induction was not associated with increased expression of the 55-kd TNFR in IFN gamma-stimulated human keratinocytes. These studies indicate that human keratinocytes express the 55-kd TNF receptor and that this surface molecule may play an important role in regulation of human keratinocyte ICAM-1 expression.     

Compatibility of ringer’s lactate with AS-3 packed red blood cells

Canadian Journal of Anesthesia/Journal canadien d'anesthésie -     

Limitations of preoperative dobutamine stress echocardiography in identifying severe left main coronary artery stenosis: a report of two cases and a brief review

PURPOSE: Using case illustrations, to elucidate factors which increase the likelihood of false negative preoperative dobutamine stress echocardiography (DSE) studies in patients with severe left main coronary artery stenosis, and to provide criteria which must be met in order to ensure the accurate interpretation of these tests. CLINICAL FEATURES AND SOURCE: Two patients presented for elective abdominal aortic aneurysm repair within a one-month period of time. Both patients had DSE as part of their preoperative assessment, which were interpreted as normal. Nevertheless, both suffered major coronary events in the perioperative period, and both proved to have severe left main coronary artery stenosis on postoperative angiography. A narrative review is presented based on a selection of the current literature, and local experience with the technique. Some pitfalls in the interpretation of these tests are presented, along with modalities to increase their sensitivity and specificity. CONCLUSION: DSE is an important and useful modality in the preoperative cardiac evaluation of patients who are unable to exercise. However the reliable interpretation of the test depends on an understanding of the limitations of the procedure.     

Tetanus in developing countries: a case series and review

Purpose

Few anesthesiologists have expertise in the diagnosis and treatment of tetanus, a disease that remains prevalent in developing countries. We report on a series of four cases of tetanus cases recently encountered in Rwanda. We review the clinical epidemiology, pathophysiology, diagnosis and the treatment of tetanus, and provide implications for anesthesiologists and critical care physicians.

Clinical features

We report four cases, two involving adults who were inadequately vaccinated and experienced injuries, and two involving neonates, both of whom underwent umbilical cord transection using unsterilized equipment. All patients required tracheal intubation, and were mechanically ventilated when equipment was available. One adult and one neonate succumbed to the disease. These cases highlight the difficulties of diagnosis and management of complicated diseases in the resource-challenged health care setting of developing countries.

Conclusions

The differential diagnosis of tetanus may be confusing, and survival depends on the rapidity of treatment with antitoxin, as well as adequate supportive care. High doses of sedatives and muscle relaxants, as well as prolonged mechanical ventilation, are usually necessary. Mortality remains high, usually resulting from late respiratory failure and cardiovascular collapse, associated with autonomic instability. Anesthesiologists and critical care physicians have an important role to play in the management of these patients. Increased involvement in humanitarian health organizations, immigration from developing countries, and emergence of high risk groups in developed countries will likely result in more exposure of anesthesiologists to the complexities of this disease.     

Contraception by means of a silastic vaginal ring impregnated with medroxyprogesterone acetate

Cylindrical rings, made of silicone rubber impregnated with medroxyprogesterone acetate were placed in the vaginas of 3 regularly menstruating women on the first cycle day. Silastic rings without medication were used in 3 controls. During the 28 days that the rings were in place, there was continuous systemic absorption of the progestogen as evidenced by elevation of the basal body temperature, shift in maturation index, abolition of the midcycle LH peak, and change in the endometrial histology. In the 3 controls, no significant alterations occurred in any of the parameters measured (BBT, vaginal cytology, endometrial biopsies and gonadotrophins) as compared with the cycles before and after insertion of the ring. After removal of the rings in the test group, the advent of withdrawal bleeding and a fall in the basal body temperature indicated a prompt termination of drug activity. Presumptive evidence of ovulation followed shortly thereafter. It is hoped that this method of administering a progestogen may be developed for family planning.