Larger tidal volume increases sevoflurane uptake in blood: a randomized clinical study

Background: The rate of uptake of volatile anesthetics is dependent on alveolar concentration and ventilation, blood solubility and cardiac output. We wanted to determine whether increased tidal volume (V_T), with unchanged end‐tidal carbon dioxide partial pressure (P_ETCO₂), could affect the arterial concentration of sevoflurane. Methods: Prospective, randomized, clinical study. ASA physical status ² and II patients scheduled for elective surgery of the lower abdomen were randomly assigned to one of the two groups with 10 patients in each: one group with normal V_T (NV_T) and one group with increased V_T (IV_T) achieved by increasing the inspired plateau pressure 0.04 cmH₂O/kg above the initial plateau pressure. A corrugated tube added extra apparatus dead space to maintain P_ETCO₂ at 4.5 kPa. The respiratory rate was set at 15 min^?1, and sevoflurane was delivered to the fresh gas by a vaporizer set at 3%. Arterial sevoflurane tensions (P_asevo), F_isevo, P_ETsevo, P_ETCO₂, P_aCO₂, V_T and airway pressure were measured. Results: The two groups of patients were similar with regard to gender, age, weight, height and body mass index. The mean P_ETsevo did not differ between the groups. Throughout the observation time, arterial sevoflurane tension (mean±SE) was significantly higher in the IV_T group compared with the NV_T group, e.g. 1.9±0.23 vs. 1.6±0.25 kPa after 60 min of anesthesia (P<0.05). Conclusion: Ventilation with larger tidal volumes with isocapnia maintained with added dead‐space volume increases the tension of sevoflurane in arterial blood.     

De novo 16p13.11 microdeletion identified by high-resolution array CGH in a fetus with increased nuchal translucency

Objective  We investigated the application of high-resolution microarray-based comparative genomic hybridisation (array CGH) on a fetus showing increased nuchal translucency (NT).
Design  Case study.
Setting  Tertiary referral obstetrics unit.
Sample  Pregnant woman attended the antenatal clinic.
Methods  Conventional karyotyping and genetic test was carried out for the alpha-globin gene. High-resolution array CGH using the high-density 244K Agilent microarray was performed on fetal blood sample by cordocentesis to investigate the possibility of any genomic imbalance.
Main outcome measures  Detection of chromosomal abnormality.
Results  Karyotyping analysis showed 46,XY. Molecular genetic diagnosis confirms the fetus has Hb-H constant spring disease but cannot explain the increased NT to 3.2 mm. Array CGH analysis discovered a 1.32-Mb microdeletion on chromosome 16p13.11. Deletion at 16p13.11 has been implicated to predispose to autism and/or mental retardation. Baby was delivered at 40 weeks of gestation, and follow up was carried out at 3 months of age without sign of mental retardation/developmental delay.
Conclusions  This case study demonstrated that array CGH can accurately calibrate the size and identify de novo interstitial chromosome imbalances. However, the presence of chromosome copy variants with unknown clinical significance currently limits its wider scale application in prenatal diagnosis and needs further investigations.     

Accidental Cs-137 contamination

Widespread use of radionuclides in medicine and industry poses the possibility of radiation accidents. We describe such an occurrence involving three industrial workers. The accident resulted from careless handling of a Cs-137 source. Evaluation of the Cs-137 whole body burden was carried out using stationary and scanning whole body counters. In addition, regional and whole body activity from contamination was assessed using an uncollimated gamma camera. This report emphasizes the value of the gamma camera for detection of radionuclide contamination in radiation accidents.     

Clinical and experimental vasogenic edema: in vivo sodium MR imaging. Work in progress

To investigate the sodium magnetic resonance (MR) imaging characteristics of acute vasogenic edema, an experimental canine model was developed. Vasogenic edema was produced in the hemisphere of the dogs by the intraarterial infusion of hypertonic mannitol (25%). This solution opens the blood-brain barrier, allowing the influx of water, electrolytes, and proteins into the brain. The main advantage of this model over the established "cold injury" model is the lack of associated brain necrosis. Two patients with chronic vasogenic edema secondary to well-circumscribed meningiomas also underwent MR imaging. The sodium signal was markedly elevated in both clinical and experimental studies of vasogenic edema fluid compared with signal in healthy brain tissue. Extracellular sodium associated with vasogenic edema displayed MR imaging characteristics similar to that of sodium in serum. There was a trend toward a shortened T2 in edema fluid secondary to the presence of serum macromolecules.     

Value of CT in the preoperative assessment of lung cancer: a survey of thoracic surgeons

Practicing thoracic surgeons were randomly surveyed to evaluate how computed tomography (CT) has influenced the preoperative evaluation of bronchogenic carcinoma. Thirty-six percent of the 529 respondents routinely requested CT and 62% did so selectively. Approximately 40% indicated that CT provided useful information in most cases. Nearly all surgeons (98.7%) do not rely on the identification of enlarged lymph nodes with CT to spare the patient surgical staging; however, 77.5% are influenced by CT results in their staging procedures. Fifty-seven percent reported that a negative CT study eliminates surgical staging entirely unless the patient has a "coin lesion," in which case 75% are willing to proceed directly to thoracotomy. For surgeons who use CT selectively, an abnormal mediastinal contour on the radiograph was the most frequent radiologic abnormality to prompt CT (85%). Thirty-seven percent are influenced by tumor histology in their decision to request CT. There was little difference in the pattern of CT use between university and community hospital surgeons.     

The factor VIII complex: structure and function

Normal human plasma contains a complex of two proteins that are important in hemostasis and coagulation. The factor VIII procoagulant protein (antihemophilic factor) and the factor VIII-related protein (von Willebrand factor) are under separate genetic control, have distinct biochemical and immunologic properties, and have unique and essential physiologic functions. While the nature of their interaction and the details of the biochemical structures remain to be determined, the information now available permits a preliminary understanding of the molecular defects in hemophilia and von Willebrand's diseases.     

Evidence for a multipotential stem cell disease in some childhood Philadelphia chromosome-positive acute lymphoblastic leukemia

Children with Philadelphia chromosome (Ph+) acute lymphoblastic leukemia (ALL) have a poorer prognosis than do most pediatric patients with ALL. Because of this poor prognosis and the presence of the Ph chromosome, we have asked whether or not Ph + ALL involves a multipotential stem cell. We cultured hematopoietic progenitors from two children with Ph+ ALL and examined individual BFU-E and CFU-GM colonies for the Ph chromosome. We studied cells from two patients after 18 to 34 months of first complete clinical remission; direct cytogenetic analyses showed 26% and 13% Ph+ metaphases in these patients' marrow cells. BFU-E colonies were obtained from light density marrow cells cultured in methylcellulose supplemented with erythropoietin and CFU-GM colonies from agar or methylcellulose cultures stimulated with leukocyte feeder layers. Fifty-seven G-banded metaphases were recovered from 33 colonies. Ten metaphases from seven colonies were Ph+. Ph+ metaphases were found in three of 12 and three of five BFU-E colonies from the two patients. One of 16 CFU-GM colonies from one patient had the Ph+ chromosome; analyzable metaphases were not obtained from CFU-GM of the other patient. No colonies contained both Ph+ and Ph- cells. These results indicate that Ph+ ALL with persistence of Ph+ cells in remission involves a multipotential stem cell for erythroid and granulocyte/macrophage as well as lymphoid lineages. Multipotential stem cell involvement in the pathogenesis of some childhood Ph+ ALL suggests similarities to Ph+ chronic myelocytic leukemia and may contribute to the poor prognosis of these patients.     

Comparative biochemical and cytogenetic studies of childhood acute lymphoblastic leukemia with the Philadelphia chromosome and other 22q 11 variants

We studied the relationship of direct karyotypes, determined at diagnosis and remission, to Abelson-related tyrosine kinase activity and the cytogenetic features of erythroid and myeloid colonies derived from remission marrow of six children with acute lymphoblastic leukemia (ALL). These patients had either the characteristic Philadelphia chromosome (Ph1) [t(9;22)(q34;q11)] or cytogenetically similar variants with a 22q11 breakpoint but no detectable cytogenetic involvement of 9q34. The findings suggested two distinct subtypes of ALL: one defined by t(9;22)(q34;q11) and expression of P185BCR-ABL tyrosine kinase and one with variant karyotypes and no P185BCR-ABL expression. The former comprises cases with Ph1 + marrow cells and Ph1 + erythroid and (or) myeloid colonies in remission marrow and others in which the t(9;22) is undetectable in remission marrow cells. In the latter subgroup, the disease may reflect more extreme mosaicism with a similar stem cell that is cytogenetically undetectable. Variant karyotypes included a del(22)(q11) in one patient and a t(6;22;15;9) (q21;q11;q?22;q21) in another; in both instances, the malignant blast cells lacked P185BCR- ABL expression. Thus ALL with t(9;22)(q34;q11) should be distinguished from ALL with other involvement of the 22q11 breakpoint by molecular studies including protein expression. The diversity of karyotypic findings in cases with involvement of 22q11 suggests at least two mechanisms of leukemogenesis in patients with ALL defined by this breakpoint.     

Some factor VIII inhibitor antibodies recognize a common epitope corresponding to C2 domain amino acids 2248 through 2312, which overlap a phospholipid-binding site

The finding that human factor VIII (fVIII) inhibitor antibodies with C2 domain epitopes interfere with the binding of fVIII to phosphatidylserine (PS) suggested that this is the mechanism by which they inactivate fVIII. We constructed a recombinant C2 domain polypeptide and demonstrated that it bound to all six human inhibitors with fVIII light chain specificity. Thus, some antibodies within the polyclonal anti-light chain population require only amino acids within C2 for binding. Recombinant C2 also partially or completely neutralized the inhibitor titer of these plasmas, demonstrating that anti-C2 antibodies inhibit fVIII activity. Immunoblotting of a series of C2 deletion polypeptides, expressed in Escherichia coli, with inhibitor plasmas showed that the epitopes for human inhibitors consist of a common core of amino acid residues 2248 through 2312 with differing extensions for individual inhibitors. The epitope of inhibitory monoclonal antibody (MoAb) ESH8 was localized to residues 2248 through 2285. Three human antibodies and anti-C2 MoAb NMC-VIII/5 bound to a synthetic peptide consisting of amino acids 2303 through 2332, a PS- binding site, but MoAb ESH8 did not. These antibodies also inhibited the binding of fVIII to synthetic phospholipid membranes of PS and phosphatidylcholine, confirming that the blocked epitopes contribute to membrane binding as well as binding to PS. In contrast, MoAb ESH8 did not inhibit binding. As the maximal function of activated fVIII in the intrinsic factor Xase complex requires its binding to a phospholipid membrane, we propose that fVIII inhibition by anti-C2 antibodies is related to the overlap of their epitopes with the PS-binding site. MoAb ESH8 did not inhibit fVIII binding to PS-containing membranes, suggesting the existence of a second mechanism of fVIII inhibition by anti-C2 antibodies.