Color-doppler velocimetry of uterine arteries in pregnant and nonpregnant patients during multiovulation induction for IVF

Objectives To evaluate uterine artery resistance during multiovulation induction in relation to the implantation rate in patients attendingin vitro fertilization (IVF) cycles.Patients Multiovulation induction for IVF was monitored by daily determination of the pulsatility index (PI) of the uterine arteries, obtained by a transvaginal probe (6.5 MHz) implemented with color-flow imaging. Doppler data were obtained from 5 days before hCG administration to the day of follicular aspiration. One IVF cycle was monitored in 70 patients. In 17 patients, 41 IVF cycles were monitored until a successful attempt occurred.Results In the 70 patients studied during one IVF attempt, the PI of the uterine arteries significantly varied (P < 0.001) in the different phases of the cycle. In the 24 patients who conceived, a significantly lower PI (P < 0.03) was found throughout the cycle. This result was mainly due to a highly significant difference of PI values observed the day after hCG administration (P < 0.005). In the 17 patients who conceived after 1 to 4 negativein vitro fertilizations, no significant difference in PI was observed in the uterine artery resistance in cycles in which implantation was or was not successful.Conclusions Uterine artery resistance varies significantly during phases of the induction therapy. Uterine artery resistance is lower throughout the course of multiovulation induction in patients with higher pregnancy rates. The PI on the day after hCG administration was the best index of pregnancy rate. Low uterine artery resistance was present even in negative attempts in patients who eventually achieved a successful implantation. PI values 3 can be considered a favorable prognostic factor for future IVF cycles.Presented at the 49th Annual Meeting of the American Fertility Society, Montreal, 1993 and the 50th Annual Meeting of the American Fertility Society, November 5–10, 1994, San Antonio, Texas.     

Cardiac output measurement by the thermodilution method: An in vitro test of accuracy of three commercially available automatic cardiac output computers

Objective To describe the accuracy and the reproducibility of the thermodilution flow measurements obtained using 3 commercially available cardiac output computers commonly used in intensive care units.Design An experimental in vitro study. Twelve different values of control flow (Qctr) were measured (Qmsr) using 3 different cardiac output computers (Abbott Critical Care System, Oximetrix 3 SvO₂/CO Computer, Baxter Oximeter/Cardiac Output Computer SAT-1^TM; American Edwards Laboratories, 9520 A Cardiac Output Computer). Standard equipment and techniques were employed, taking account of the specific weight and heat of warm water relative to blood. In addition, separate sets of measurements were performed in order to investigate the effect on Qmsr of some variables which may influence the indicator loss (time for injection, depth of immersion of the catheter, temperature of the injected fluid).Setting Our laboratory, inside the intensive care unit.Measurements and results The analysis of the linear regression of Qmsr versus Qctr (r values between 0.992 and 0.984; residual standard deviation values comprised between 0.24 and 0.49 l/min; intercepts and slopes not significantly different from identity line), the values of the percentage errors (PE=[Qctr–Qmsr]·100/Qctr; PE mean values 7.9, 5.0 and 13.1), and those of the coefficients of variability (CV=standard deviation mean value, %; CV mean values 5.4, 5.8 and 4.6), show a good level of accuracy and reproducibility of the measurements. Our data confirm previously reported results. Furthermore, the cumulative effect of variables capable of influencing the indicator loss, even if corrected according to the calculation constant the manufacturers provide, was found to result in statistically significant changes of Qmsr.Conclusion The accuracy and reproducibility of the automatic cardiac computers tested is sufficient for practical clinical purpose. It may also depend on the modality of injection of the cooling bolus, which may significantly influence the effective indicator losses.     

The effect of accident mechanisms and initial findings on the long-term course of whiplash injury

The aim of this study was to assess the relationships between accident mechanisms as well as initial findings and the long-term course of whiplash injury. A representative sample of 117 consecutive patients referred by primary care physicians was followed-up over 12 months. Fractures or dislocations of the cervical spine, head trauma and pre-existing neurological disorders were exclusion criteria. The interval between the accident and the baseline examination was 7.4 days (SD 4.2 days). Assessment included accident features (e.g. passenger position in the car, head restraint, head position, type of collision), initial symptoms (e.g. intensity and onset of pain, symptoms of neurological dysfunction, multiple symptom score), and signs (restricted neck movement, neurological deficits). At the 1-year examination, patients were divided into an asymptomatic and a symptomatic group and were compared with respect to accident features and baseline findings. Twenty-four percent of patients were still symptomatic after 1 year. Analysing accident mechanisms separately, rotated or inclined head position was the primary feature related to symptom persistence (P=0.005). The symptomatic group scored higher at baseline on the multiple symptom rating (P=0.004) and had a higher incidence of initial headache (P=0.004) and neurological symptoms (P=0.008) together with a higher intensity of headache (P=0.0002) and neck pain (P=0.0009). The following set of initial variables predicted persistence of symptoms at 1 year (logistic regression): intensity of neck pain (P=0.001) and headache (P=0.009), rotated or inclined head position (P=0.02), unpreparedness at the time of impact (P=0.01) and car stationary when hit (P=0.01). In conclusion, accident mechanisms and initial findings suggestive of more severe injury were significantly related to long-term persistence of symptoms after whiplash injury.This study was supported by the Swiss National Science Foundation (project number: 3.883-0.88) and the Swiss Accident Insurance Company (Schweizerische Unfallversicherungsanstalt), Berne     

Effects of coexisting neurochemicals on the release of serotonin from the intermediate area of rat thoracic spinal cord

Serotonin (5-HT), substance P (SP), neurokinin A (NKA), and thyrotropin-releasing hormone (TRH) coexist in the nerve terminals of the intermediolateral cell column (IML) of the thoracic spinal cord. The Ca2⁺-dependent release of 5-HT from the microdissected intermediate area (including the IML) of the rat thoracic spinal cord, and the 5-HT_1B autoreceptor regulator of 5-HT release, were previously demonstrated. In this paper, the effects of SP, NKA, TRH, and/or their analogs on the release of [³H]5-HT from the intermediate area were investigated using an in vitro superfusion system. Both SP (the endogenous ligand for neurokinin-1 (NK₁) receptor) and an NK₁, agonist (GR 73632) significantly increased the basal release of [³3H]5-HT. SP and GR 73632 did not change the K⁺-stimulated release of [³H]5-HT. The effect of the NK₁ agonist on the basal release of [³H]5-HT was dose-dependent, was reduced by an NK₁ antagonist (GR 82334), and was not dependent on extracellular Ca²⁺. Neither NKA, an NK₂, agonist (GR 64349), nor a TRH analog (MK-771) altered the basal or stimulated release of [³H]5-HT. These data suggest that basal release of 5-HT from the intermediate area of the rat thoracic spinal cord is regulated by SP (acting through an NK₁ receptor), but not by NKA or TRH. These results provide evidence for the role of SP as a modulator of serotoninergic neurons in the intermediate area of the thoracic spinal cord, and may help to clarify the role of coexisting neurochemicals in the spinal regulation of the sympathetic nervous system. © 1995 Wiley-Liss, Inc.

1 This article is a US Government work and, as such, is in the public domain in the United States of America.

     

Shiva-1: in vitro and in vivo tests of the effects of a novel,synthetic, lytic peptide on ocular cells

An investigation was undertaken to determine the toxicity of an intravitreal injection of a novel peptide drug, Shiva-1, in rabbits. The drug, a synthetic peptide modeled after lytic peptides secreted by certain insects, has antiproliferative and antibacterial properties. Initial in vitro experiments showed that the drug, at a concentration of 100 M, was toxic to both Y-79 retinoblastoma cells and human retinal pigment epithelial cells. A wide range of doses (6–1200 g) was injected into the rabbit vitreous in an attempt to determine the maximum tolerated dose. Retinal toxicity was evaluated clinically, by electroretinography, and by light microscopy. Some localized toxicity was evident at 200 g; all doses of 240 g and above were toxic. While the drug appears to exhibit a narrow range between effective and toxic doses, the results suggest that this and other peptides of similar design merit further investigation for the treatment of proliferative and infectious diseases of the eye.Supported in part by U.S. Public Health Service grants EY07541 and EY02377 from the National Eye Institute, the National Institutes of Health Services, Bethesda, MD, USA     

Selective blockade of muscarinic M2 receptors in vivo by the new antagonist tripitramine

The antimuscarinic effects of tripitramine (1, 1, 24--tris [[5, 11-dihydro-6-oxo-6H-pyrido [2, 3-b][1, 4]-benzodiazepin-11-yl)(carbonyl] methyl]-8, 17-dimethyl-1, 8, 17, 24-tetraazatetracosane tetraoxalate), a member of a series of polymethylene tetraamines with in vitro cardioselectivity, were assessed in two in vivo preparations: anaesthetized and pithed rats. The well-known M₂ selective antagonist methoctramine was used in a comparative study. Tripitramine (0.0202 mol/kg i.v.) proved to be a potent antagonist at cardiac M₂ receptors that mediate the decrease in heart rate in the pithed rat; the same dose of this antagonist in the anaesthetized rat did not significantly affect the depressor action of methacholine mediated by vascular M₃ receptors. In the pithed rat, this dose did not affect the ganglionic M₁ receptor-mediated tachycardia and pressor response to muscarme or McN-A-343. These in vivo data are consistent with the in vitro findings and confirm that tripitramine is a more potent and selective muscarinic M₂ receptor antagonist than methoctramine.     

Use of Drug Kinetics in Dermis to Predict in VivoBlood Concentration After Topical Application

Purpose. To use the drug kinetics in dermis to predict the in vivo blood concentration after topical administration. Methods. A two-step pharmacokinetic model was established. The first step was to calculate the drug input rate or flux from the skin to the systemic circulation using the drug kinetic parameters in dermis. These parameters include (a) distance over which the drug concentration declines by 50%, (b) drug concentration at the epidermal-dermal junction, and (c) minimal plateauing drug concentration in the muscle layer. These parameters were experimentally determined from the drug concentration-tissue depth profiles in the dermis, after the application of a topical dose of ddI (200 mg/kg) to rats. The second step was to use the drug input rate together with the systemic disposition pharmacokinetics of ddI in rats to predict the plasma concentration-time profiles. The model-predicted plasma concentration-time profiles were compared with the observed profiles, to determine the validity of the proposed pharmacokinetic model. Results. The observed steady state concentration (C_ss) in individual animals (n = 6) deviated from the predicted values by 3 to 55% with 3 of 6 rats showing a <15% deviation. The mean observed C_ss of all animals deviated from the mean predicted values by less than 15%. Conclusions. The close agreement between the observed and the model-predicted drug concentrations indicates that the systemic drug input can be calculated from the drug kinetics in the dermis.     

Amelanotic melanoma in situ

Amelanotic lentigo malignant melanoma is a very rare skin tumor, and no similar case of the in situ stage has been found in the literature. Clinically, the lesion presents itself as a localized ill defined macular erythema, but the diagnosis can only be made histologically. The treatment consists of surgical excision and years of careful follow-up.Presented at the Spring Meeting of the Belgian Society of Plastic Surgery, 1993     

Compression or distraction of the anterior cruciate injured knee

100 consecutive patients with a recent anterior cruciate ligament injury were examined with respect to type of sports activity that caused the injury, mechanism of injury and the occurrence of collateral ligament and meniscal lesions. There were 53 medial collateral ligament injuries, 12 medial, 35 lateral and 11 bicompartmental meniscal lesions. 59 patients were injured during contact sports, 30 in downhill skiing and 11 in other recreational activities, traffic accidents or at work. An associated medial collateral, ligament tear was more common in skiing (22/30) than during contact sports (23/59), whereas a bicompartmental meniscal lesion was found more frequently in contact sports (9/59) than in skiing (0/30). Weightbearing was reported by 56/59 of the patients with contact sports injuries and by 8/30 of those with skiing injuries. Non-weightbearing in the injury situation led to the same rate of MCL tears (18/28) as those reporting weightbearing (35/72) but significantly more intact menisci (19/28 vs 23/72). Thus, contact sports injuries were more often sustained during weightbearing, with a resultant joint compression of both femuro-tibial compartments as shown by the higher incidence of bicompartmental meniscal lesions. This might be an important prognostic factor for future joint disease and arthrosis. The classic unhappy triad was a rare finding (8/100) and we suggest that this entity should be replaced by the unhappy compression injury.