Changes in maternal middle cerebral artery blood flow velocity associated with general anesthesia in severe preeclampsia

In women with severe preeclampsia, significant increases in mean arterial pressures (MAP) are common after rapid induction of general anesthesia (GA) and tracheal intubation. The objectives of this prospective study were to assess the effects of the rapid induction-intubation technique on middle cerebral artery (MCA) flow velocity in severe preeclampsia and to examine the correlation between mean MCA flow velocity (Vm) and MAP. Eight women with severe preeclampsia (study group) and six normotensive women at term (control group) scheduled to undergo cesarean section under GA were studied. Before induction, patients in the study group received i.v. labetalol in divided doses to lower diastolic pressures to <100 mm Hg. Anesthesia was induced with pentothal 4-5 mg/kg, followed by succinylcholine 1.5 mg/kg to facilitate tracheal intubation. A transcranial Doppler was used to measure Vm. Both Vm and MAP were recorded before induction and every minute for 6 min after intubation. In the study group, after the administration of labetalol, MAP decreased from 129 +/- 9 to 113 +/- 9 mm Hg (P < 0.05), and Vm decreased from 59 +/- 11 to 54 +/- 10 cm/s (P < 0.05). After intubation, MAP increased from 113 +/- 9 to 134 +/- 5 mm Hg (P < 0.001), and Vm increased from 54 +/- 10 to 70 +/- 10 cm/s (P < 0.001). In the control group, while MAP increased significantly from 89 +/- 6 to 96 +/- 4 mm Hg (P < 0.05) after intubation, the concurrent increase in Vm from 49 +/- 5 to 54 +/- 7 cm/s was not significant. There was a significant positive pooled correlation between Vm and MAP (r = 0.5, P < 0.0006) in the study group but not in the control group (r = 0.24). After induction and intubation, both Vm and MAP values were significantly increased in the study group patients at all observation points compared with the control group patients. The findings indicate that Vm increases significantly after rapid-sequence induction of GA and tracheal intubation in women with severe preeclampsia, and there seems to be a direct relationship between MAP and Vm. Implications: In women with severe preeclampsia, rapid-sequence induction of general anesthesia and tracheal intubation can cause severe hypertension. Our results indicate that the increase in blood pressure is associated with a significant increase in maternal cerebral blood flow velocity and that there is a significant correlation between these two variables.     

Seasonal changes in the negative feedback regulation of the secretion of the gonadotrophins by testosterone and inhibin in rams

Three experiments were conducted with castrated Romney Marsh rams (wethers) to investigate the ability of testosterone and inhibin to suppress the secretion of LH and FSH during the breeding and the non-breeding seasons. In Experiment 1, wethers (n=5/group) were treated every 12 h for 7 days with oil or 16 mg testosterone propionate (i.m.) and were then given two i.v. injections either of vehicle or of 0.64 microg/kg human recombinant inhibin A (hr-inhibin) 6 h apart. Blood samples were collected for 4 h before inhibin or vehicle treatment and for 6 h afterwards for the assay of LH and FSH. In Experiments 2 and 3 wethers underwent hypothalamo-pituitary disconnection (HPD) and were given 125 ng GnRH i.v. every 2 h. In Experiment 2, HPD wethers (n=3/group) were injected (i.m.) every 12 h with oil or testosterone and blood samples were collected over 9 h before treatment and 7 days after treatment. In Experiment 3, HPD (n=5/group) wethers were treated with vehicle or hr-inhibin, as in Experiment 1, after treatment with oil, or 4, 8 or 16 mg testosterone twice daily for 7 days. Blood samples were collected over 4 h before treatment with vehicle or hr-inhibin and for 6 h afterwards. Treatment of wethers with testosterone (Experiment 1) resulted in a significant decrease in the plasma concentrations of LH and number of LH pulses per hour but the magnitude of these reductions did not differ between seasons. Testosterone treatment had no effect on LH secretion in GnRH-pulsed HPD wethers in either season and treatment with hr-inhibin did not affect LH secretion in wethers or HPD wethers in any instance. Plasma concentrations of FSH were significantly (P<0.05) reduced following treatment with testosterone alone during the breeding season but not during the non-breeding season. FSH levels were reduced to a greater extent by treatment with hr-inhibin but this effect was not influenced by season. During the non-breeding season, the effect of hr-inhibin to suppress FSH secretion was enhanced in the presence of testosterone. These experiments demonstrate that the negative feedback actions of testosterone on the secretion of LH in this breed of rams occurs at the hypothalamic level and is not influenced by season. In contrast, both testosterone and inhibin act on the pituitary gland to suppress the secretion of FSH and these responses are affected by season. Testosterone and inhibin synergize at the pituitary to regulate FSH secretion during the non-breeding season but not during the breeding season.     

Arterial stenting and balloon angioplasty in ostial atherosclerotic renovascular disease: a randomised trial

BACKGROUND: Percutaneous transluminal angioplasty (PTA) for ostial atherosclerotic renal-artery stenosis has poor results. Angioplasty with stent placement (PTAS) may be more effective. We undertook a randomised prospective study to compare PTA with PTAS in patients with ostial atherosclerotic renal-artery stenosis. METHODS: Patients with ostial atherosclerotic renal-artery stenosis were assigned to receive PTA or PTAS. Secondary PTAS was allowed if PTA failed immediately or during 6 months' follow-up. Analysis was by intention to treat. FINDINGS: 42 patients were assigned PTA and 43 were assigned PTAS, but one patient in the PTAS group was excluded from the study. Primary success rate (<50% residual stenosis) of PTA was 57% (24 patients) compared with 88% (37 patients) for PTAS (difference between groups 31% [95% CI 12-50]). Complications were similar. At 6 months, the primary patency rate was 29% (12 patients) for PTA, and 75% (30 patients) for PTAS (46% [24-68]). Restenosis after a successful primary procedure occurred in 48% of patients for PTA and 14% for PTAS (34% [11-58]). 12 patients underwent secondary stenting for primary or late failure of PTA within the follow-up period: success was similar to that of primary PTAS. Evaluation based on intention to treat showed no difference in clinical results at six months for PTA or PTAS. INTERPRETATION: PTAS is a better technique than PTA to achieve vessel patency in ostial atherosclerotic renal-artery stenosis. Primary PTAS and primary PTA plus PTAS as rescue therapy have similar outcomes. However, the burden of reintervention after PTA outweighs the potential saving in stents, so primary PTAS is a better approach to use.     

Detection of rubella virus-specific immunoglobulin G in saliva by an amplification-based enzyme-linked immunosorbent assay using monoclonal antibody to fluorescein isothiocyanate

An immunoglobulin G (IgG)-capture enzyme-linked immunosorbent assay (ELISA) for rubella virus is described. The assay uses a fluorescein isothiocyanate (FITC)-anti-FITC amplification system. The detection limit of the ELISA was approximately 7 IU of rubella virus-specific IgG per ml of serum sample. For saliva samples the performances of the capture ELISA and previously described radioimmunoassay were assessed, and the results of those two assays were compared to the rubella virus-specific IgG result obtained by a commercial ELISA (Behring Enzygnost) with a panel of paired serum and saliva samples. This comparison showed that the capture ELISA with saliva was more sensitive than the radioimmunoassay and that the results correlated better with the serum IgG result than the results of the radioimmunoassay did, with an overall sensitivity of 82% and a rank correlation of 0.68, whereas the sensitivity and rank correlation for the radioimmunoassay were 74% and 0.45, respectively. For subjects of 10 years of age or younger, the ELISA with saliva had a sensitivity of 94% and a specificity of 100% compared to the results of the ELISA (Behring Enzygnost) for rubella virus-specific IgG with corresponding serum samples. The sensitivity was much lower for subjects ages 17 years or older. The assay may have wider epidemiological use with saliva specimens, particularly those from children.     

Transition metal catalysis in fluorous media: application of a new immobilization principle to rhodium-catalyzed hydrogenation of alkenes

Biphase systems were generated by combining toluene solutions of alkenes (2-cyclohexen-1-one, 1-dodecene, cyclododecene, 4-bromostyrene) and CF₃C₆F₁₁ solutions of the pre-catalyst ClRh[P(CH₂CH₂(CF₂)₅CF₃)₃]₃ ((1); 1.1–0.8 mol%) and placed under 1 atm of H₂. The perfluoroalkyl segments in (1) confer high affinities for fluorocarbons. After 8–26 h at 45°C, the CF₃C₆F₁₁ phases were separated, and extracted with an equal volume of toluene. GLC analyses of the toluene solutions showed 98–87% yields of the hydrogenation products cyclohexanone, dodecane, cyclododecane, and 4-bromoethylbenzene (turnover numbers 120–87). The CF₃C₆F₁₁ phases were charged with new toluene solutions of 2-cyclohexen-1-one or 1-dodecene, and similarly treated with H₂. There was no significant loss of catalyst activity over three cycles. A preparative reaction gave cyclohexanone in 89% yield. Some C=C isomerization could be detected during the course of 1-dodecene hydrogenation, and (1) gave a dihydride complex in the absence of alkene.     

Molecular modelling and site-directed mutagenesis of the active site of endothelin-converting enzyme

Mammalian endothelin-converting enzyme is a membrane-bound metalloprotease; its C-terminal domain contains sequence motifs characteristic of zinc metalloproteases. We examined residues expected from molecular modelling to be important for substrate binding using selectively mutated recombinant rat ECE-1alpha expressed in CHO cells. A conserved N-A-Ar-Ar (Ar = aromatic) motif is likely to be important for substrate binding. Mutating N550 to Gln or Y552 to Phe reduces Vmax/Km by 8- and 18-fold, respectively. The equivalent residue to Y553 in thermolysin binds the inhibitor through its NH group. Removing this putative interaction by mutating Tyr to Pro destroys activity, but mutating it to Ala or Phe also removes most activity. Mutating G583 (in a conserved GGI motif N-terminal of the zinc-binding helix) to Ala has no measurable effect, but mutating G584 to Ala destroys activity. Changing V583 in the zinc-binding helix to Met, to mimic the sequence pattern in bovine ECE-2, increases Vmax/Km to 1.7-fold that of the wild- type. Assays of phosphoramidon binding follow the pattern of those of substrate binding, but the IC50 of the more potent ECE inhibitor CGS 26303 was not significantly altered by any of these mutations, suggesting that this compound may bind to ECE in a different mode from phosphoramidon.      

Increased number of cardiomyocytes in cross-sections from tachycardia-induced cardiomyopathic hearts

Based on positive identification of DNA replication and mitotic division in cardiomyocytes isolated from failing hearts, it has been proposed that adult ventricular cardiomyocytes can gain the capacity to proliferate with progression of heart failure. However, due to the lack of a reliable method to distinctly image individual cardiac cells within the myocardial syntitium, such a concept still remains largely controversial. In the present study, we used laser confocal microscopy, to image cross-sections of intact myocardium stained with fluorescein-conjugated wheat germ agglutinin and propidium iodide. This approach allowed to clearly separate the profile of individual myocytes within cardiac tissue sections. We found that in the left ventricles of dogs, subjected to tachycardia-induced cardiomyopathy, the number of cells was significantly increased in both longitudinal and transversal sections. Treatment with the angiotensin-converting enzyme inhibitor, enalapril, reversed these changes to values similar to those found in controls. Therefore, this study provides evidence, at the in situ level, for cellular hyperplasia in heart failure. This supports the more general notion that adult cardiomyocytes may not be terminally differentiated, and that an increase in cell number could contribute to the increase in left ventricular mass observed with progression of disease.     

The effects of low-frequency ultrasound on Staphylococcus epidermidis

Low frequency ultrasound (LFUS) significantly enhances skin permeability to a variety of drugs; however, its bacterial effects have not been well studied. Staphylococcus epidermidis organisms were grown and standardized to 10(5) cfu/ml 24 h prior to investigation and suspended in normal saline. LFUS was applied with two probes immersed in the bacterial suspensions over a range of suspension volumes, intensities, and exposure times. The suspension temperature was measured, and a sample was removed, streaked onto blood agar plates, and incubated at 37 degrees C for 24 h. Quantitative bacterial counts were then obtained. LFUS resulted in significant reductions in bacterial counts that correlated with fluid temperature. Probe size and ultrasound intensity appeared to affect bacterial counts, but were also correlated with temperature. Bacterial growth was minimal with temperatures exceeding 45 degrees C. While LFUS can reduce bacterial counts, these conditions have the potential to cause burns in humans.