Flow artifacts in double-contrast esophagography

Artifacts related to barium flow during double-contrast esophagography may obscure mucosal surface details. Double-contrast esophagograms with flow artifacts of 35 patients were evaluated to determine the effect on radiographic interpretation and to assess the method of examination. Initial radiographs obtained during swallowing of barium were compared with those obtained after a slight delay while patients repeatedly dry swallowed. When severe surface flow artifacts were present, the extent of mucosal disease was underestimated in all cases. Mild surface flow artifacts interfered with the demonstration of the reticular pattern of Barrett esophagus, and luminal flow artifacts caused misinterpretation. The demonstration of strictures was unaffected by flow artifacts. This study suggests that the dry swallowing maneuver and some delay improve depiction of esophageal surface details on double-contrast radiographs and obviate interpretive error from barium flow artifacts.     

Identification of monoclonal antibodies that inhibit the function of protein C inhibitor. Evidence for heparin-independent inhibition of activated protein C in plasma

Monoclonal antibodies specific for protein C inhibitor (PCI) partially blocked the inactivation of activated protein C (APC) in plasma, whereas in a purified system, the PCI activity could be completely blocked. The inactivation of APC in normal and in PCI-depleted plasma was similar in the absence of heparin. The addition of heparin did not change the rate of inactivation of APC in PCI-depleted plasma, whereas in normal plasma a rapid phase of inhibition of APC was followed by a slower phase of inhibition. The slower phase was identical to the rate of inhibition of APC in the absence of heparin. After incubation of normal plasma with a monoclonal antibody specific for PCI that blocked its activity, there was no difference in heparin-dependent or heparin- independent inhibition of APC. These results indicate that in the absence of heparin PCI is unable to inactivate APC in a plasma environment.     

The human T-cell V gamma gene locus: cloning of new segments and study of V gamma rearrangements in neoplastic T and B cells

The authors have analyzed the involvement of V gamma and J gamma segments in TRG gamma rearrangement from a series of 40 acute lymphoblastic leukemia (ALL), including 25 T- and 15 B-lineage cases, in which TRG gamma are rearranged. Sixty-five rearranged alleles were studied. The authors first describe the cloning and sequencing of two variable segments, V gamma 11 and psi V gamma 12, which rearrange in T- and B-neoplastic cells. To date three subgroups of translatable V gamma segments have been described. The authors show that V gamma 11 is the unique member of a new fourth V gamma subgroup that also rearranges in normal polyclonal T cells and that psi V gamma 12 is located at 5- kilobase (kb) downstream to V gamma 11. As shown by DNA sequence analysis, V gamma 11 shares a 60% homology with V gamma 10 (third subgroup) and a 50% homology with V gamma 9 (second subgroup) but no appreciable homology with the V gamma segments from the first family. In contrast to psi V gamma 12, V gamma 11 is translatable. In this paper the authors have also attempted to determine which V gamma segments were rearranged in the ALL cases by hybridization with a J gamma probe and genomic probes specific of the four subgroups. In the 54 instances in which the rearrangement was consistent with J gamma 1 or J gamma 2 involvement, the authors have identified the corresponding V gamma segments and have not found any other rearrangements suggestive of the existence of further V regions. The V gamma segments, belonging to the first subgroup, were the most frequently used (41 alleles). V gamma 9, V gamma 10, V gamma 11, and psi V gamma 12 were found rearranged in cases 3, 4, 5, and 1, respectively. No cases using the pseudo psi V gamma 1, psi V gamma 5, and psi V gamma 6 segments were found. Pseudo V gamma segments were not found rearranged in T cells, while V gamma 2 and V gamma 4, segments are frequently used. In contrast to the V gamma I gene rearrangement, the involvement of the V gamma II, V gamma III, and V gamma IV subgroups was most frequently observed in T-ALL with stage II differentiation (CD7+, CD4+, and/or CD8+, CD3-), than in those with stage I (CD7+, CD4-, CD8-, CD3-), than in those with stage I (CD7+, CD4-, CD8-, CD3-) and stage III (CD7+, CD4+/-CD8+/-CD3+).(ABSTRACT TRUNCATED AT 400 WORDS)     

Selective agonists of tachykinin binding sites

Three types of binding sites for the mammalian tachykinins, ie Substance P (SP) Neurokinin A (NKA) and Neurokinin B (NKB), have been found in both the central and peripheral nervous systems. Substance P binds to the NK-1 subclass of binding site while NKA and NKB are less selective endogenous ligands, which preferentially interact with the NK-2 and NK-3 subclasses of binding sites, respectively. Complementary strategies, including 3-dimensional structure analysis by NMR spectroscopy and structure-activity relationship led to the design of selective agonists of these binding sites. [Pro9] SP, [Pro10] SP and the cyclic analogues [Cys3,6, Tyr8, Pro9] SP and [Cys3,6, Tyr8, Pro10] SP are selective NK-1 agonists. [Lys5] NKA(4-10) is a water soluble NK-2 potent agonist. Finally, [Pro7] NKB, which completely discriminates NK-2 and NK-3 binding sites, is a water-soluble NK-3 selective agonist.     

Population pharmacokinetics of amikacin in intensive care unit patients studied by NPEM algorithm

Summary— The population pharmacokinetics of amikacin was studied in 40 intensive care unit patients (212 plasma concentrations) by NPEM algorithm using a one-compartment model. The population was best characterized by the following pharmacokinetic parameters: renal clearance relative to creatinine clearance (C_s = 0.96 ± 0.33), and either the total volume of distribution (V_d = 23.9 ± 7.0 I) or the volume of distribution relative to body weight (V_s = 0.36 ± 0.10 1·kg⁻¹. The volume of distribution was increased with respect to the usual value of 0.25 1·kg⁻¹. The statistical distribution of these pharmacokinetic parameters was approximately gaussian, with no significant correlation between volume of distribution and clearance. The medians and standard deviations of C_s and V_s were used as reference population values to estimate the pharmacokinetics of amikacin in a second group of 29 patients by the bayesian method, with two blood samples per patient. For each patient, the fitted parameters were able to predict the plasma concentrations of amikacin during the next 72 h with no significant bias and good precision (2.9 mg·1⁻¹ for peaks and 0.5 mg·1⁻¹ for troughs). This study confirms the ability of the NPEM algorithm to provide reference population values for use in bayesian monitoring of aminoglycoside therapy.