Etomidate speech and memory test (eSAM): a new drug and improved intracarotid procedure.

BACKGROUND: The intracarotid amobarbital procedure (IAP) is an important part of comprehensive investigation of patients who are candidates for surgical treatment of epilepsy. Owing to repeated and lengthy shortages of amobarbital, causing delays in elective surgery, attempts have been made to find a suitable alternative anesthetic. The authors report their experience using etomidate, a widely used agent for the induction of anesthesia. METHODS: Sixteen consecutive patients requiring IAP to evaluate memory or to lateralize speech underwent the procedure using etomidate. Prior to the procedure a catheter was placed in the internal carotid artery and an angiogram was performed. EEG was recorded and read online by an electroencephalographer. An anesthetist injected the drug, administered by bolus followed by an infusion, which was maintained until each speech measure had been sampled and new memory items had been introduced. The infusion was then stopped and testing continued as in a standard IAP. RESULTS: In all cases (30 hemispheres) contralateral hemiplegia followed injection. EEG slow waves were observed in every injected hemisphere, with some contralateral slowing anteriorly in 18. Global aphasia with preserved attention and cooperation followed dominant-hemisphere injections. These phenomena remained during infusion, and upon its termination returned gradually to baseline over a period of about 4 minutes. CONCLUSIONS: Etomidate is a viable alternative to amobarbital, and its administration by bolus followed by infusion offers an improvement over the traditional intracarotid amobarbital procedure. Cognitive tests can be performed during an assured hemianesthesia of the injected hemisphere.

Flow modulation of pressure-sensitive tone in rat pial arterioles: role of the endothelium.

BACKGROUND: Cerebral arteriolar tone is modulated in response to changes in transmural pressure and luminal flow. The effect of flow on the relation between pressure and diameter has not been fully evaluated in these vessels. This study was conducted to investigate this interaction and to determine the role of the endothelium in mediating it. METHODS: Rat pial arterioles from the territory of the posterior cerebral artery were mounted in a perfusion myograph. In some arterioles, the endothelium was removed by air perfusion. Diameters were recorded at pressures from 20 to 200 mmHg in the presence and absence of flow (10 microl/min). The response to flow (0-30 microl/min) was recorded at 60 and 120 mmHg. RESULTS: In the absence of flow, endothelium-intact arterioles demonstrated tone at distending pressures between 40 and 140 mmHg. In the presence of flow, tone did not develop until pressure exceeded 100 mmHg, and the vessels remained active at pressures up to 200 mmHg. Endothelium-denuded arterioles developed tone at the same pressure when perfused as when unperfused, but perfused vessels were able to maintain active tone at higher pressures. At 60 mmHg, flow caused dilation if the endothelium was intact and constriction if it had been removed. At 120 mmHg, flow caused constriction. Endothelium-dependent flow-relaxation was inhibited by N(G)-nitro-L-arginine methyl ester (10(-5) M) and abolished by indomethacin (10(-5) M). CONCLUSION: Flow inhibits the development of pial arteriolar tone at low intraluminal pressures through endothelium-dependent mechanisms. Conversely, perfusion extends the upper limit of the myogenically regulated pressure range through endothelium-independent activation of arteriolar smooth muscle contraction.

A new coaxial catheter system with an echodense tip for ultrasonographically guided embryo transfer.

OBJECTIVES: To determine performance of a new coaxial catheter system with an echodense tip for imaging during transabdominal ultrasonographically guided catheter passage. DESIGN: Prospective, descriptive, noncomparative study. SETTING: Fertility center within a tertiary care center. PATIENT(S): Twenty-five patients who were undergoing ET. INTERVENTION(S): The catheter was passed transcervically under transabdominal ultrasonographic guidance. MAIN OUTCOME MEASURE(S): The catheter was assessed for ease of placement and immediacy of identification of the outer and inner sheaths and the degree of catheter movement (if any) needed for identification. RESULTS: The outer sheath of the system was well visualized through the cervix and into the lower uterine segment due to its thickness. Immediate recognition of the echodense tip of the inner sheath was achieved in all patients. With minimal movement of the catheter or ultrasonographic transducer, the tip could be easily tracked during passage through the entire uterine cavity into the fundal region. CONCLUSIONS: In this preliminary study, the echodense tip was immediately identified by transabdominal imaging, reducing the need to move the catheter for identification. Previous investigations have not conclusively shown improved pregnancy rates with ultrasonographic guidance, possibly because of the need for catheter movement for identification of the tip and resultant disruption of the endometrium. The immediate identification of the catheter may provide a method for precise, atraumatic ET.

Effect of platelet-activating factor (PAF) on human spermatozoa-oocyte interactions.

The effect of exogenous platelet-activating factor (PAF) on human spermatozoa was examined by monitoring acrosomal status and hamster oocyte penetration. Induction of the acrosome response by PAF was dose, and time, dependent and required capacitated spermatozoa. Addition of 10(-14) mol PAF l-1 enhanced the acrosome reaction eightfold compared with controls treated with human serum albumin (HSA). Similar concentrations of lyso-PAF failed to induce acrosomal loss and preincubation of spermatozoa with CV3988, an inhibitor of PAF, prevented PAF induction of the acrosome reaction. PAF significantly increased the number of zona-free hamster oocytes penetrated compared with controls (9.8 +/- 0.5 of 25 oocytes were penetrated by control spermatozoa compared with 23.3 +/- 0.8 out of 25 oocytes penetrated after incubation of spermatozoa with 10(-14) mol PAF l-1; 93% of all oocytes were penetrated by at least one spermatozoon following incubation with PAF), and also increased the number of decondensed spermatozoa found per egg during the sperm penetration assay (from 1.7 +/- 0.3 spermatozoa/egg with control spermatozoa to 3.3 +/- 0.5 spermatozoa/egg with PAF-treated spermatozoa). PAF-induced increases in acrosome reaction and sperm penetration assay values were similar to effects obtained with human follicular fluid and were calcium dependent. Induction of the acrosome reaction by physiological concentrations of PAF appeared to be morphologically similar to the response induced by follicular fluid as assessed by electron microscopy.

IUD protocols for international training.

PIP: A review of 9 reference protocols for IUD training in the US and in developing countries revealed conflicting instructions on antibiotic prophylaxis, postpartum insertion of IUDs, management of complications, and sterilization and disinfection procedures. The protocols only agreed on the contraindication status of pregnancy and active gynecological or chlamydial infections (all listed as absolute contraindications) which were just 2 of 32 different contraindications. US physicians considered some conditions to be contraindications to IUD use, but they usually are not applicable to women in developing countries. In developing countries with maternal mortality rates 2 times greater than those in developed countries, 8 contraindications may be inappropriate: prior expulsion of or perforation by an IUD, IUD insertion during the postpartum period, prior pregnancy with and IUD in place, prior ectopic pregnancy, copper allergy, coagulopathy, valvular heart disease, and Wilson's disease. The only inappropriate contraindication addressing infection (1 of 8) was a distant history of pelvic inflammatory disease. This history should not exclude IUD use in a woman not at risk of sexually transmitted diseases. Contraindications referring to cancer of the reproductive tract should be consolidated in a statement warning against hormonal contraceptive and IUD use in women, especially those over 35, who have recent, undiagnosed, irregular vaginal bleeding, until the cause has been determined. The reviewers also discussed justifications for other contraindications, including those related to menstrual blood loss, small uterus, structural abnormality of the uterus, severe vasovagal reactivity or fainting and severe cervical stenosis, no access to services, and future fertility. THis analysis indicated a need to simplify, rationalize, and update current IUD protocols as well as make them consistent. This will improve service quality and reduce unnecessary medical obstacles to contraception.^ieng

Medical barriers to access to family planning.

PIP: Medical barriers to family planning (FP) are identified as contraindications, eligibility, process hurdles, the provider of contraception, provider bias, and regulation. These obstacles to FP are considered practices which may have a medical rationale in some manner but are scientifically unjustified. The denial or interference in obtaining contraception is unacceptable. Examples are given of barriers, i.e., eligibility criteria such as lack of headaches or history of diabetes. Obstacles that deter oral contraception (OC) are a by-product of testing requirements, repeat visits, and long waits. OC provision does not require a physician's prescription; a trained technician can perform similar functions. When a provider such as community-based distributor is limited in provision of methods, women are not given the right to choose from a full menu. Medical barriers occur due to the ignorance about the safety of contraceptives, the benefits of FP, and the role of health professionals in service delivery. Clinics tend to be curative rather than preventive. In place of careful thinking, there are rules in a hierarchical medical system suitable for treatment of complicated life-threatening illness. Barriers are complicated, interrelated, and situational. The solutions suggested are 1) informing the health community and mobilizing medical leadership, 2) defining and treating the FP seeker as a client and not a medical patient, and 3) engaging in more epidemiological research to assess the risk/benefits of contraceptive use and operations research to evaluate ways to reduce medical restrictions. The position that obstacles are an example of quality of care does not support the Bruce-Jain FP quality of care framework. Health and FP services may be integrated but contraceptive usage should not be at the expense of health care. The obstacles are not just in developing countries where it would appear that access to FP far outweighs the risks of maternal mortality from pregnancy. Providers are not the target is creating a win-win-win situation for the client, the provider, and organized public health.^ieng

Effect of tidal volume and PEEP in ethchlorvynol-induced asymmetric lung injury.

We examined the effects of positive end-expiratory pressure (PEEP) and tidal volume on the distribution of ventilation and perfusion in a canine model of asymmetric lung injury. Unilateral right lung edema was established in 10 animals by use of a selective infusion of ethchlorvynol. Five animals were tested in the supine position (horizontal asymmetry) and five in the right decubitus position (vertical asymmetry). Raising PEEP from 5 to 12 cmH2O improved oxygenation despite a redistribution of blood flow toward the damage lung and a consistent decrease in total respiratory system compliance. This improvement paralleled a redistribution of tidal ventilation to the injured lung. This was effected primarily by a fall in the compliance of the noninjured lung due to hyperinflation. The effects of higher tidal volume were additive to those of PEEP. We propose that the major effect of PEEP in inhomogeneous lung injury is to restore tidal ventilation to a population of alveoli recruitable only at high airway pressures.

Platelet-activating factor in sperm from fertile and subfertile men.

STUDY OBJECTIVE: To examine the proposed role of platelet-activating factor (PAF) as a mediator of sperm function first by quantitating the concentration of PAF in sperm and second by incubating sperm with PAF and assessing the change in sperm motion parameters with a computerized motion analysis system. DESIGN: Retrospective, case-control study. SETTING: University hospital urology clinic. PATIENTS: Concentrations of PAF were measured in sperm from 6 randomly chosen normal donors and 8 asthenozoospermic patients. The change in sperm motion parameters was assessed in sperm from 10 randomly chosen normal donors and 7 asthenozoospermic patients. RESULTS: Platelet-activating factor concentrations were significantly higher (P less than 0.05) in spermatozoa from asthenozoospermic patients (149 +/- 18.0 fmol/10(6) sperm) than in sperm from normal donors (91.9 +/- 13.0 fmol/10(6) sperm). Exogenous PAF did not enhance the percent motility of precapacitated or capacitated sperm from either patients or donors, and computerized semen analysis revealed no enhancement of sperm motion parameters in asthenozoospermic patients after addition of PAF to either precapacitated or capacitated sperm. CONCLUSION: Platelet-activating factor does not appear to have therapeutic value as a means of enhancing sperm motility.

Platelet-activating factor induces progesterone secretion and changes in morphological appearance in luteinizing granulosa cells in vitro.

OBJECTIVE: Recent evidence indicates the involvement of platelet-activating factor (PAF) in ovarian periovulatory processes. The objective of this study was to investigate the influence of PAF on ovarian follicular cellular function. DESIGN AND INTERVENTIONS: We examined the effects of PAF on progesterone (P) secretion by cultured human luteinizing granulosa cells obtained from women undergoing in vitro fertilization. Follicular cells were cultured in serum-free conditions for 12 to 36 hours with and without PAF (at dosages of 10(-8) to 10(-14) M). RESULTS: Progesterone secretion was significantly increased at 12 and 36 hours after treatment with 10(-8) M PAF (170% +/- 40% and 210% +/- 40%, respectively) and with 10(-10) M PAF (170% +/- 30% and 180% +/- 10%, respectively). Smaller increases were seen with 10(-12) and 10(-14) M PAF. Maximal increases in P secretion in 10(-10) M PAF-treated wells occurred at 3 to 12 hours. At 36 hours, distinct morphological differences between cells in control wells and those containing PAF were noted. CONCLUSIONS: These results indicate that PAF may influence follicular cell function during ovulation and corpus luteum formation.

Embryo-derived platelet activating factor, a marker of embryo quality and viability following ovarian stimulation for in vitro fertilization.

Embryo-derived platelet-activating factor (PAF) may be an important mediator of early maternal recognition of pregnancy. PAF was higher in media associated with clinical pregnancies when compared to preclinical pregnancies but not higher in pregnant vs nonpregnant groups. The production of PAF by the preimplantation embryo was not related to follicle size or embryo morphology. However, differences in PAF concentrations in the culture media were related to the age of the embryo culture medium and the developmental stage of the embryo.

Pregnancy diagnosis and contraception.

PIP: The benefits of the early diagnosis of pregnancy, such as timely initiation of prenatal care and the avoidance of prescribing hormonal contraceptives to pregnant women--are obvious. In many African settings, however, pregnancy testing reagents are unavailable and the diagnosis is made on the basis of history taking and physical examination. A 1990 survey of maternal child health/family planning service providers in Kenya, Tanzania, and Kenya revealed that only 5.7% of the 70 facilities included in the study provided pregnancy testing with a reagent. When the physical examination produces inconclusive findings, clients are advised to return in 4 weeks for a 2nd examination or--if the client is unwilling to wait this long--given a 6-day course of oral contraceptives containing 50 mcg of estrogen to see if bleeding occurs. Since it is not realistic to expect that reagents will soon become accessible or affordable to clinics in Africa, primary care service supervisors and trainers must ensure that personnel are skilled in non-reagent pregnancy diagnosis procedures. Provider skills can be assessed through 3 methods: role play of history taking and management of suspected pregnancy, use of pelvic model for demonstration of a speculum and bimanual pelvic examination, and actual observation of provider-client interactions.^ieng

Insulin-like growth factor I (IGF-I) levels in follicular fluid from human preovulatory follicles: correlation with serum IGF-I levels.

Insulin-like growth factor I (IGF-I) levels were measured in both serum and fluid of preovulatory follicles (n = 156) in 43 women undergoing in vitro fertilization (IVF). The mean IGF-I level in follicular fluid (FF) was significantly lower than in serum (0.52 +/- 0.02 IU/L versus 0.66 +/- 0.23 IU/L), and FF levels were significantly correlated with individual serum IGF-I levels as well as with follicular size and FF volume but not with oocyte maturity, granulosa cell appearance, or IVF. This suggests that FF IGF-I levels cannot serve as a clinical indicator for the degree of oocyte/granulosa cell differentiation or a predictor for IVF. Serum IGF-I levels were inversely correlated with the number of human menopausal gonadotropin ampules administered during treatment, suggesting that IGF-I might enhance ovarian gonadotropic stimulation.

The cardiopulmonary and renal hemodynamic effects of norepinephrine in canine pulmonary embolism.

Autologous blood clot was injected into six dogs to produce a graduated decrease in cardiac output (CO). The effects of an infusion of norepinephrine, titrated to specific end points, were recorded before embolization and at two levels of pulmonary hypertension. Simultaneous measurements of systemic and renal hemodynamics were made. Sequential blood clot injection increased (p less than .01) pulmonary vascular resistance (PVR) from 1.3 to 13 to 33 mm Hg.L-1.min and reduced CO 45 percent and 75 percent (p less than .01). Norepinephrine increased both stroke volume and CO (p less than .01) in each condition and did not increase PVR. Since the biventricular filling pressures remained constant or fell slightly with norepinephrine, the increase in CO is best explained by an improvement in pump performance. There was no deterioration in renal blood flow or creatinine clearance with norepinephrine. The data suggested that in this model of right ventricular dysfunction, norepinephrine consistently improved myocardial performance without provoking further vasoconstriction in either the pulmonary or renal circulations.

Selective hydrolysis of ether-containing glycerophospholipids by phospholipase A2 in rabbit lung.

The role of phospholipase A2 (PLA2) in the simultaneous generation of lyso-platelet-activating factor and arachidonic acid was investigated by examining the calcium dependency and substrate specificity of PLA2 activities in rabbit lung microsomes. Alkylarachidonoylglycerophosphocholine (alkylarachidonoyl-GPC) was preferentially hydrolyzed as compared to acylarachidonoyl-GPC, and both arachidonate-containing substrates were cleaved to a greater extent as compared to alkyl- and acyl-substrates with oleate at the sn-2 position. Hydrolysis of alkylacyl-GPC substrates was not dependent on calcium in the presence of EGTA (1 mM); however, addition of calcium (2 mM) increased hydrolysis of acylarachidonoyl-GPC 2-fold and hydrolysis of acyloleoyl-GPC 10-fold. Substitution of an alkenyl group in the sn-1 position further enhanced calcium-independent PLA2 hydrolysis, and another substitution of arachidonic acid at the sn-2 position of the plasmalogen substrates substantially increased hydrolysis as compared to hydrolysis of substrates containing oleic acid. Hydrolysis of the choline plasmalogen was 3-fold greater than hydrolysis of the ethanolamine plasmalogen containing arachidonate. Preferential calcium-independent hydrolysis of alkylacyl-GPC substrates was observed in several tissues, including adult and fetal rabbit lung and adult rabbit kidney and human amnion. PLA2 substrate specificity may account for the preferential hydrolysis of arachidonoyl-containing alkyl-GPC in several cell types and explain the simultaneous generation of the precursors of two potent autacoids, platelet-activating factor and eicosanoids.

Platelet-activating factor induces glycogen degradation in fetal rabbit lung in utero.

The role of platelet-activating factor (PAF, 1-alkyl-2-acetyl-sn-glycero-3-phosphocholine) in initiating glycogen breakdown in the fetal rabbit lung was assessed by intraperitoneal administration of this potent ether-linked glycerophospholipid. Forty-five min after in utero injection of PAF (2.5 X 10(-7) mol), fetal pulmonary and hepatic glycogen concentrations were reduced from 326 to 256 and from 9.8 to 6.6 micrograms of glycogen/mg protein, respectively. Glycolytic activity was similarly increased as judged by an elevation of lactate (2-fold) in lung, liver, and plasma upon PAF injection. These actions of PAF were dose- and time-dependent. The glycogenolytic response did not occur when an equimolar dose of the inactive enantiomer, D-PAF was injected. Pretreatment of the fetus with a specific PAF receptor antagonist, SRI-63-441, prevented the PAF response. We have previously demonstrated (Hoffman, D. R., Truong, C. T., and Johnston, J. M. (1986) Biochim. Biophys. Acta 879, 88-96) that PAF biosynthesis and PAF concentrations increase significantly on day 24 of fetal rabbit lung development. A concurrent decrease in pulmonary glycogen concentration at this point of gestation is potentially reflective of the PAF-induced action. Thus, these observations would suggest a role for PAF in the normal physiology of fetal lung maturation.

Platelet-activating factor in the rabbit uterus during early pregnancy.

Platelet-activating factor (PAF) concentrations were low in the non-pregnant, oestrous uterus (mean +/- s.e.m.: 2.2 +/- 1.2 pmol/g, n = 3). However, uterine PAF increased dramatically during pregnancy to a maximum of 37.8 +/- 4.90 pmol/g (n = 7) on Day 5. By Day 7, PAF concentrations in the uteri of pregnant rabbits had returned to levels similar to those found at oestrus. In contrast, uterine PAF in pseudopregnant rabbits peaked at 30.6 +/- 2.8 pmol/g (n = 8) on Day 4, declined to 20.5 +/- 2.4 pmol/g (n = 8) on Day 5 and then remained at that concentration through Day 7. Uterine PAF co-migrated with synthetic PAF (1-O-hexadecyl-2-acetyl-sn-glycero-phosphocholine) in both thin-layer and normal-phase high-performance liquid chromatography. PAF activity in the uterus during pregnancy and pseudopregnancy was found almost exclusively in the endometrium; little or no PAF was found in myometrium, uterine flushings or blastocysts. While no PAF was detected in blastocysts on Days 5 and 6 of pregnancy, the presence of the embryo appears to modulate biosynthesis and/or degradation of PAF by the uterus, since PAF decreased significantly in uterine tissue apposed to the implanting embryo (but not in similar areas between such attachment sites). Increased concentrations of PAF in the preimplantation rabbit uterus followed by a dramatic decrease on the day of blastocyst attachment suggest that this potent inflammatory autacoid may play a vital role in implantation.