The risk of myocardial ischemia in patients receiving desflurane versus sufentanil anesthesia for coronary artery bypass graft surgery. The S.P.I. Research Group.

Desflurane, a coronary vasodilator, may induce myocardial ischemia in patients with coronary artery disease. To determine whether desflurane is safe to administer to the at-risk patient population (with known coronary artery disease), we compared the incidence and characteristics of perioperative myocardial ischemia in 200 patients undergoing coronary artery bypass graft (CABG) surgery randomly assigned to receive desflurane (thiopental adjuvant) versus sufentanil anesthesia. Under conditions of hemodynamic control, perioperative ischemia was assessed using continuous echocardiography (precordial: during induction; transesophageal: during surgery) and Holter electrocardiography (ECG); hemodynamics (including pulmonary artery pressure) were measured continuously. Hemodynamic results: During induction, no significant changes in hemodynamics occurred in the sufentanil group, while in the desflurane group, heart rate, systemic and pulmonary arterial pressure increased and stroke volume decreased significantly. During the intraoperative period, the incidence of hemodynamic variations was low in both anesthetic groups; however, the prebypass incidence of tachycardia (greater than 120% of preoperative baseline heart rate) was greater in the desflurane group (4 +/- 7% of total time monitored) than in the sufentanil group (1 +/- 6%) (P = 0.0003). Similarly, the incidence of prebypass hypotension (less than 80% of preoperative baseline systolic arterial blood pressure) was greater in the desflurane group (21 +/- 14%) than in the sufentanil group (15 +/- 16%) (P = 0.01). ECG results: Preoperatively, 15% (28/191) of patients developed ECG ischemia, with no difference between patients who received desflurane, 13% (12/96) or sufentanil, 16% (16/95) (P = 0.6). During anesthetic induction, 9% (9/99) of patients who received desflurane developed ECG ischemia, compared with 0% (0/98) who received sufentanil (P = 0.007). During the prebypass period, 5% (10/197) of patients developed ECG ischemia, with no difference between patients who received desflurane, 7% (7/99) or sufentanil, 3% (3/98) (P = 0.3). Postbypass, 12% (24/194) of patients developed ECG ischemic changes, with no difference between patients who received desflurane, 13% (13/97) or sufentanil, 11% (11/96) (P = 0.9). Echocardiographic results: The incidence of precordial echocardiographic ischemia during anesthetic induction was 13% (5/39) in the desflurane group versus 0% (0/29) in the sufentanil group (P = 0.1). Moderate to severe transesophageal echocardiographic (TEE) ischemic episodes occurred in 12% (21/175) of patients during prebypass, with no significant difference between the desflurane group, 16% (15/91) and the sufentanil group, 7% (6/84) (P = 0.09). TEE ischemic episodes occurred in 27% (49/178) of patients during the postbypass period, with no difference between the desflurane, 29% (27/92) and sufentanil, 25% (22/86) groups (P = 0.7).(ABSTRACT TRUNCATED AT 400 WORDS)     

Selective modification at the N-terminal region of human growth hormone that shows antagonistic activity

A new analogue of recombinant human growth hormone (hGH), hGH des(1–6,14) was expressed in Escherichia coli, refolded and purified to homogeneity. The mutation decreased the hormone's ability to bind lactogenic and somatogenic receptors through its site 1, and almost completely abolished its ability to bind these receptors through site 2, as evidenced by both binding and gel-filtration experiments. More specifically, the binding to prolactin receptors (PRLRs) from various species or their soluble recombinant extracellular domains (ECDs) was decreased 1.5–4-fold, whereas the binding to hGH receptor (hGHR) was decreased 10–85-fold. These changes caused an almost total loss of hormone agonistic activity in several in vitro bioassays and subsequently, the hGH des(1–6,14) analogue acquired antagonistic properties. This antagonistic activity was dependent upon modification of site 1. In those cases in which the binding was reduced only slightly, e.g. binding to rabbit PRLRs, hGH des(1–6,14) acted as a strong antagonist, whereas in others in which the binding of site 1 was reduced to a higher degree, such as other PRLRs and, in particular, hGHR, the antagonistic activity was correspondingly weaker. Circular dichroism spectra of the analogue suggested that these changes do not result from a decrease in overall -helix content, but rather from minor local structural modifications at the N-terminus.     

The yeast VPS genes affect telomere length regulation

Eukaryotic cells invest a large proportion of their genome in maintaining telomere length homeostasis. Among the 173 non-essential yeast genes found to affect telomere length, a large proportion is involved in vacuolar traffic. When mutated, these vacuolar protein-sorting (VPS) genes lead to telomeres shorter than those observed in the wild type. Using genetic analysis, we characterized the pathway by which VPS15, VPS34, VPS22, VPS23 and VPS28 affect the telomeres. Our results indicate that these VPS genes affect telomere length through a single pathway and that this effect requires the activity of telomerase and the Ku heterodimer, but not the activity of Tel1p or Rif2p. We present models to explain the link between vacuolar traffic and telomere length homeostasis.     

Estimating the relative frequency of leukodystrophies and recommendations for carrier screening in the era of next‐generation sequencing

Leukodystrophies are a heterogeneous group of heritable disorders characterized by abnormal brain white matter signal on magnetic resonance imaging (MRI) and primary involvement of the cellular components of myelin. Previous estimates suggest the incidence of leukodystrophies as a whole to be 1 in 7,000 individuals, however the frequency of specific diagnoses relative to others has not been described. Next generation sequencing approaches offer the opportunity to redefine our understanding of the relative frequency of different leukodystrophies. We assessed the relative frequency of all 30 leukodystrophies (associated with 55 genes) in more than 49,000 exomes. We identified a relatively high frequency of disorders previously thought of as very rare, including Aicardi Goutières Syndrome, TUBB4A‐related leukodystrophy, Peroxisomal biogenesis disorders, POLR3‐related Leukodystrophy, Vanishing White Matter, and Pelizaeus‐Merzbacher Disease. Despite the relative frequency of these conditions, carrier‐screening laboratories regularly test only 20 of the 55 leukodystrophy‐related genes, and do not test at all, or test only one or a few, genes for some of the higher frequency disorders. Relative frequency of leukodystrophies previously considered very rare suggests these disorders may benefit from expanded carrier screening.     

Biofluid Aspects of Embryo Transfer

Embryo transfer (ET) is the last stage of extracorporal fertilization during which the embryo is placed in the uterine cavity with a medium-filled catheter 2–3 days after in vitro fertilization. While fertilization in the laboratory occurs at very high rates (>:90%), the overall success of the procedure (i.e., take home baby) is still very low (<25%) and assumed to be mainly due to implantation failure. A computational model was developed to simulate ET within the uterine cavity by a fluid-filled catheter inserted into a two-dimensional channel with oscillating walls. The results showed that the speed at which the embryos are injected from the catheter dominates the procedure and controls the velocity of their transport within the uterine cavity. ET at excessively high injection speeds may lead to ectopic pregnancies, while uterine peristalsis affects transverse dispersion only during injection at low injection speeds. The presence of the catheter within the uterus does not affect flow patterns downstream of its tip. The potential risks to implantation failure due to mechanical factors involved in the ET processes are discussed. © 2003 Biomedical Engineering Society. PAC2003: 8719-j, 8710+e     

Enlarging skull fractures in children

Large skull fractures are conventionally followed radiographically until healing occurs. Fractures which enlarge or remain unhealed are commonly termed leptomeningeal cysts or growing skull fractures. This study of ten children with this injury and a review of the literature shows that a true leptomeningeal cyst is seldom present and that skull fractures do not grow. Moreover, careful history-taking and physical examination will correctly identify all enlarging or unhealed skull fractures of childhood without the need for plain radiographs or computed tomography of the skull.     

A comparison of spinal, epidural, and general anesthesia for outpatient knee arthroscopy

We compared general, epidural, and spinal anesthesia for outpatient knee arthroscopy (excluding anterior cruciate ligament repairs). Forty-eight patients (ASA physical status I-III) were randomized to receive either propofol-nitrous oxide general anesthesia with a laryngeal mask airway with anesthetic depth titrated to a bispectral index level of 40-60, 15-20 mL of 3% 2-chloroprocaine epidural, or 75 mg of subarachnoid procaine with 20 microg fentanyl. All patients were premedicated with <0.035 mg/kg midazolam and <1 microg/kg fentanyl and received intraarticular bupivacaine and 15-30 mg of IV ketorolac during the procedure. Recovery times, operating room turnover times, and patient satisfaction were recorded by an observer using an objective scale for recovery assessment and a verbal rating scale for satisfaction. Statistical analysis was performed with analysis of variance and chi(2). Postanesthesia care unit discharge times for the general and epidural groups were similar (general = 104+/-31 min, epidural = 92+/-18 min), whereas the spinal group had a longer recovery time (146+/-52 min) (P = 0.0003). Patient satisfaction was equally good in all three groups (P = 0.34). Room turnover times did not differ among groups (P = 0.16). There were no anesthetic failures or serious adverse events in any group. Pruritus was more frequent in the spinal group (7 of 16 required treatment) than in the general or epidural groups (no pruritus) (P<0.001). We conclude that epidural anesthesia with 2-chloroprocaine provides comparable recovery and discharge times to general anesthesia provided with propofol and nitrous oxide. Spinal anesthesia with procaine and fentanyl is an effective alternative and is associated with a longer discharge time and increased side effects. Implications: For outpatient knee arthroscopy, anesthesia can be provided adequately with regional or general anesthesia. Epidural and general anesthesia provide equal recovery times and patient satisfaction, whereas spinal anesthesia may prolong recovery and have increased side effects. The choice of anesthesia may depend primarily on the patient's interest in being alert or asleep during the procedure.