Turbulent stress measurements downstream of three bileaflet heart valve designs in pigs

Objective: Mechanical heart valves can cause thromboembolic complications, possibly due to abnormal flow patterns that produce turbulence downstream of the valve. The objective of this study was to investigate whether three different bileaflet valve designs would exhibit clinically relevant differences in downstream turbulent stresses. Methods: Three bileaflet mechanical heart valves (Medtronic Advantage^®, CarboMedics© Orbis™ Universal and St. Jude Medical^® Standard) were implanted into 19 female 90 kg pigs. Blood velocity was measured during open chest conditions in the cross sectional area downstream of the valves with 10 MHz ultrasonic probes connected to a modified Alfred^® Pulsed Doppler equipment. As a measure of turbulence, Reynolds normal stress (RNS) was calculated at three different cardiac output ranges (3–4, 4.5–5.5, 6–7 L/min). Results: Data from 12 animals were obtained. RNS correlated with increasing cardiac outputs. The highest instantaneous RNS observed in these experiments was 47 N/m², and the mean RNS taken spatially over the cross sectional area of the aorta during systole was between 3 N/m² and 15 N/m². In none of the cardiac output ranges RNS values exceeded the lower critical limit for erythrocyte or thrombocyte damage for any of the valve designs. Conclusions: Reynolds normal stress values were below 100 N/m² for all three valve designs and the difference in design was not reflected in generation of turbulence. Hence, it is unlikely that any of the valve designs causes flow induced damage to platelets or erythrocytes.     

Effects of the antimigraine compound zolmitriptan ('Zomig') on psychomotor performance alone and in combination with diazepam in healthy volunteers

Zolmitriptan (Zomig^TM) is a 5HT_1B/1D agonist which has the ability to cross the intact blood-brain barrier to access central as well as peripheral receptors. Because of the potential for central nervous system side effects, this randomized, double-blind, placebo-controlled, 6-period crossover study evaluated the effects of 2.5 and 5 mg doses of zolmitriptan on psychomotor performance and investigated any pharmacodynamic or pharmacokinetic interaction with diazepam. Twelve healthy volunteers received the following "treatments" as single doses: zolmitriptan 2.5 mg, zolmitriptan 5 mg, diazepam 10 mg, zolmitriptan 2.5 mg+diazepam 10 mg, zolmitriptan 5 mg+diazepam 10 mg and placebo. Pre-dose and at 1, 4, 8, and 24 h post-dose, the following validated battery of psychomotor tests was performed: Bond-Lader visual analogue scales (calmness, contentedness, and alertness factors), critical flicker fusion test, choice reaction time (recognition, motor, and total reaction times), finger-tapping test, number cancellation test and digit symbol substitution test. Plasma concentrations of zolmitriptan, its active metabolite, and diazepam and its active metabolites were measured at the same timepoints. Zolmitriptan 2.5 and 5 mg had no effect on psychomotor function when given alone. In contrast, diazepam 10 mg had profound effects, consistent with its sedative properties, but there was no synergism on concomitant administration of either dose of zolmitriptan. Plasma concentrations of zolmitriptan, diazepam, and their respective active metabolites were similar when the two drugs were given alone or in combination.     

Indapamide inhibits endothelium-dependent contractions in the aorta of the spontaneously hypertensive rat

Summary— Experiments were designed to determine whether or not indapamide, an antihypertensive agent with vasodilator properties, inhibits endothelium-dependent contractions. Rings of aortae with and without endothelium from spontaneously hypertensive rats (SHR) were suspended in conventional organ chambers for the measurement of isometric force. Acetylcholine and adenosine diphosphate-β-S in the presence of a nitric oxide synthase inhibitor, caused endothelium-dependent contractions, which were inhibited by indapamide. The compound (10⁻⁴M) also slightly reduced the contractions of rings without endothelium evoked by U-46,619, which activates thromboxane-endoperoxide receptors. These results demonstrate that indapamide inhibits endothelium-dependent contractions in the SHR aorta, and suggest that the inhibition is due, at least in part, to the action of the drug on the hypertensive vascular smooth muscle.     

Needle biopsy of renal allografts: comparison of two techniques

Two techniques for renal allograft biopsy were retrospectively evaluated to compare relative safety and efficacy. After ultrasound (US) localization of the kidney and biopsy with a hand-held 14-gauge cutting needle, an adequate specimen was obtained in 74 of 77 cases (96%). Major complications occurred in six of these 77 cases (8%). One hundred four biopsies were performed by using a smaller 18-gauge cutting needle with a spring-loaded biopsy "gun" and real-time US guidance. With this newer technique, specimens adequate for diagnosis were obtained in 99 biopsies (95%). There was a single major complication with this technique (1%). The 18-gauge needle with real-time US guidance yields comparably adequate specimens with a lower frequency of complications.     

Genetic mapping of "Lubag" (X-linked dystonia-parkinsonism) in a Filipino kindred to the pericentromeric region of the X chromosome.

"Lubag" is an X-linked disorder causing dystonia and parkinsonism that has only been described in families from the Philippines, principally from the island of Panay. We have established linkage between the disease phenotype "lubag" and DNA markers which span the Xp11.22-Xq21.3 region by using a large Filipino family with 8 affected men in three generations. These DNA markers define an interval of about 20 centimorgans in the pericentromeric region of the X chromosome as the most likely site of the disease locus XDPD (X-linked dystonia-parkinsonism). XDPD has a maximum multipoint log likelihood ratio score (Zmax) of about 4.6 over the interval from Xq12 to Xq21.31 (DXS159-DXYS1X). The co-occurrence of dystonia and parkinsonism in lubag and in other known disorders suggests there may be a common pathogenetic mechanism. Identification of the genetic defect in this family may provide an important clue toward understanding the pathogenesis and pathophysiology of both dystonia and parkinsonism.     

Large-bowel carcinomas with different ploidy, related to secretory component, IgA, and CEA in epithelium and plasma.

Immunofluorescence staining for carcinoembryonic antigen (CEA), secretory component (SC), and epithelial IgA was evaluated semiquantitatively in 85 large-bowel carcinomas in relation to degree of tumour differentiation, Dukes'' stage, and plasma CEA level. The tumours were divided into a near-diploid (ND, 28) and an aneuploid group (AN, 57) by means of flow-cytometric DNA measurements. Expression of SC and IgA in neoplastic epithelium was positively related to differentiation in both groups. The AN tumours scored significantly higher for CEA than the ND ones, but the staining was apparently unrelated to differentiation or Dukes'' stage. CEA expression in the transitional mucosa adjacent to ND tumours was negatively correlated with tumour differentiation, whereas epithelial IgA and SC in this zone showed a substantially higher positive correlation with tumour differentiation, and a somewhat stronger negative correlation with Dukes'' stage in the ND than in the AN group. Plasma CEA levels were significantly related to Dukes'' stage, only in patients with AN tumours, and only in this group were positively correlated with estimates of total tumour CEA for Dukes'' stages A and B. For Dukes'' stages C and D (disseminated tumours), moreover, the plasma CEA levels were found to be significantly higher in the AN group. These findings indicate that the DNA profile of large-bowel carcinomas is related both to the way neoplastic cells influence the activity of the transitional mucosa and their capacity for expression and release of epithelial products. AN tumours thus seem to be more active as "secretors" of CEA than ND ones.     

Recovery of function in adjacent nerve roots after surgery for lumbar disc herniation: use of quantitative sensory testing in the exploration of different populations of nerve fibers

Results from experimental and clinical studies indicate that adjacent nerve roots may be affected in sciatica because of lumbar disc hemiation. This may be caused by proinflammatory mediators in the epidural space being transported into nerve roots at the same or neighboring lumbar segments. The aim of the present study was to investigate the recovery of function of sensory nerve fibers in the adjacent noncompressed nerve roots. Thirty-nine patients undergoing microdiscectomy for monoradiculopathy were investigated with quantitative sensory testing immediately before surgery, and at 6 weeks, 4 months, and 12 months after the operation. Twenty-one healthy volunteers were used as controls. The patients were classified as having a good or a poor result at the 1-year follow-up according to a clinical score. Significant improvement of function in the noncompressed nerve roots were only observed in the 31 patients with a good result. The improvement in small myelinated nerve fibers came within 12 months in the adjacent nerve roots in both the symptomatic as well as the asymptomatic leg. The improvement of function in small unmyelinated fibers also came within 12 months after surgery; however, significant improvement was only observed in the ipsilateral neighboring nerve root. The function in large myelinated fibers did not improve in any of the adjacent nerve roots during the observation period. The observed recovery of function in adjacent noncompressed nerve roots after successful surgical decompression in monoradiculopathy may be because of less production of proinflammatory mediators when the disc herniation is removed.