Venovenous extracorporeal membrane oxygenation for respiratory failure in inotrope dependent neonates

It is often stated that venovenous extracorporeal membrane oxygenation (VV ECMO) should not be used in inotrope dependent patients. It is our practice to use VV ECMO in most patients with respiratory failure even though many of these patients are receiving significant doses of inotropes. Our objective was to review the mode of ECMO in relation to precannulation doses of inotropes administered to neonates treated with ECMO for respiratory failure. Forty-three consecutive case notes were reviewed. Data were collected for basic demographic and ECMO parameters. Inotropic doses were converted to a single score for ease of comparison, with one point equivalent to 1 microg/kg/min dopamine. Forty-three neonates were studied; 37(86%) were treated with VV ECMO and 6 (14%) were treated with VA ECMO. Significant pre-ECMO inotropic support (score > 10) was present in 30 (70%) of the 43 cases. Of these patients, 26 were treated via VV ECMO with a survival rate of 84%, while 4 were treated with VA ECMO with a survival of 75%. Inotrope scores fell to nonsignificant levels (< 10) within 24 hours, regardless of ECMO mode. Mean arterial blood pressure remained above precannulation levels in both groups. VV ECMO allows safe treatment of neonatal respiratory failure in the presence of significant inotropic support. We recommend VV ECMO for neonatal respiratory failure in all cases except where double lumen cannulation is impossible or when septic shock is refractory to inotropic support (i.e., mean blood pressure < 35 mm Hg despite inotrope score of > 100).     

Prevalence of peanut allergy in primary-school children in Montreal, Canada

BACKGROUND: Peanut allergy is receiving increasing attention. Only one study has estimated the prevalence in North America, but it did not corroborate history with diagnostic testing. OBJECTIVE: We estimated the prevalence of peanut allergy in Montreal by administering questionnaires regarding peanut ingestion to children in kindergarten through grade 3 in randomly selected schools. METHODS: Respondents were stratified as follows: (1). peanut tolerant, (2). never-rarely ingest peanut, (3). convincing history of peanut allergy, and (4). uncertain history of peanut allergy. Groups 2, 3, and 4 underwent peanut skin prick tests (SPTs), and if the responses were positive in groups 2 or 4, measurement of peanut-specific IgE were undertaken. Children in group 3 with a positive SPT response were considered allergic to peanut without further testing. Children in groups 2 and 4 with peanut-specific IgE levels of less than 15 kU/L underwent oral peanut challenges. RESULTS: Of the 7768 children surveyed, 4339 responded, 94.6% in group 1. The prevalence of peanut allergy was 1.50% (95% CI, 1.16%-1.92%). When multiple imputation was used to incorporate data on those responding to the questionnaire but withdrawing before testing, the estimated prevalence increased to 1.76% (95% CI, 1.38%-2.21%). When data regarding the peanut allergy status of nonresponders (as declared to the school before the study) were also incorporated, the estimated prevalence was 1.34% (95% CI, 1.08%-1.64%). CONCLUSION: Our prevalence study is the first in North America to corroborate history with confirmatory testing and the largest worldwide to incorporate these techniques. We have shown that, even with conservative assumptions, prevalence exceeds 1.0%.     

Dynamics of measles virus protein expression are reflected in the MHC class I epitope display

Following measles virus (MV) infection, viral peptides are presented to CTL by MHC class I molecules on infected antigen presenting cells at widely different epitope densities. Whereas three MV epitopes (MV-M(211-219), MV-F(438-446) and MV-H(30-38)) derived from different structural proteins occur at regular densities, one peptide derived from the non-structural C protein (MV-C(84-92)) fully dominates the MV peptide display in HLA class I molecules on end-stage-infected human B cells. Here we demonstrate that this hierarchy in MV epitope density is not a constant, but varies with progression of infection. While MV-M(211-219), MV-F(438-446) and MV-H(30-38) epitopes were already presented by HLA class I molecules early in infection, expression of MV-C(84-92) was restricted to the later phases of infection. These dynamics in epitope densities correlated with features of MV protein expression. Synthesis of C protein mainly focused towards the final stages of infection, while the other MV proteins were more readily synthesised from earlier time points on, in line with the emergence of their respective epitopes. Furthermore, the most abundant MV epitope was derived from the most unstable viral protein and vice versa, suggesting that the stability of viral proteins may be an indicator for the final abundance of their epitopes. Thus, even though many other factors may influence the generation of peptide-MHC class I complexes, we here report that the regulation of viral protein expression seems closely linked to the viral MHC class I epitope display. Finally, the observed dynamics in viral epitope hierarchy may have important implications for the induction of antiviral T cell immunity.     

A paradigm for measuring the olfactory event-related potential in the clinic

Recent research on the olfactory event-related potential (OERP) using inter-stimulus intervals (ISIs) of 90 s and shorter has revealed a marked decrease in component amplitude after the first trial, with a leveling off for the remaining trials. Studies manipulating the ISI in olfactory and other modalities demonstrate an association between higher amplitudes and longer ISIs, suggesting that habituation occurs at short time intervals between each stimulus presentation. The present study attempted to reduce the effects of habituation by using a 10-min ISI and fewer trials. OERPs were recorded monopolarly at the Fz, Cz and Pz electrode sites in ten subjects (five males, five females), for three trials using a 10-min ISI. Results demonstrated no significant reduction in component amplitudes across trials and no significant difference in latencies over trials, indicating no habituation effect at this ISI. These results indicate that with a 10-min ISI and three trial recordings, a complete reduction in habituation can be achieved. These findings may prove to be clinically useful to physicians who can implement this technique to assess olfactory functioning in cognitively impaired individuals or to assess malingering.     

Serotonin receptors 5-HT<Subscript>1A</Subscript> and 5-HT<Subscript>3</Subscript> reduce hyperexcitability of dorsal horn neurons after chronic spinal cord hemisection injury in rat

Spinal cord injury (SCI) results in abnormal pain syndromes in humans. In a rodent model of SCI, T13 spinal hemisection results in allodynia and hyperalgesia due in part to interruption of descending pathways, including serotonergic (5-HT) systems, that leads to hyperexcitability of dorsal horn neurons. To characterize further the role of 5-HT and 5-HT receptor subtypes 5-HT_1A and 5-HT₃ in neuronal activation after hemisection, we have examined the responsiveness of dorsal horn neurons to a variety of innocuous and noxious peripheral stimuli. Male Sprague-Dawley rats, 150–175 g, were spinally hemisected (n=40) at T13 and allowed 4 weeks for development of mechanical allodynia and thermal hyperalgesia. Animals then underwent electrophysiologic recording and the results were compared with those from sham controls (n=15). Evoked responses of convergent dorsal horn neurons (n=224 total) at L3–L5 to innocuous and noxious peripheral stimuli were characterized after administration of vehicle, 5-HT (25, 50, 100, and 200 μg), 5-HT (100 μg) in conjunction with the selective 5-HT_1A antagonist WAY 100135 (100 μg), the 5-HT₃ antagonist MDL 72222 (100 μg), the selective 5-HT_1A agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT, 150 μg), or the 5-HT₃ agonist 2-Me-5HT (75 μg), with or without pretreatment with antagonists; all treatments were delivered topically onto the cord adjacent to the recording electrode. In hemisected animals, increased responsiveness of convergent cells to all peripheral stimuli was observed bilaterally when compared to controls. No changes in ongoing background activity were present. In control animals, only the highest dose of 5-HT (200 μg) was sufficient to reduce evoked activity, whereas in hemisected animals a concentration-dependant decrease in response was observed. In hemisected animals, both 5-HT_1A and 5-HT₃ receptor antagonism reduced the effectiveness of 5-HT, restoring elevated evoked activity by up to 70% at the doses tested. Administration of 5-HT_1A and 5-HT₃ receptor agonists also decreased hyperexcitability, effects prevented by pretreatment with corresponding antagonists. These results demonstrate the development of denervation supersensitivity to 5-HT following SCI, corroborate behavioral studies showing the effectiveness of 5-HT in reducing allodynia and hyperalgesia after SCI, and contribute to a mechanistic understanding of the role of 5-HT receptor subtypes in chronic central pain. Electronic Publication     

Inherited thrombophilias are not increased in "idiopathic" small-for-gestational-age pregnancies

OBJECTIVE: The purpose of this study was to determine (1). whether the inherited thrombophilias (the factor V Leiden and prothrombin gene mutations and the methylenetetrahydrofolate reductase [C677T] polymorphism) are increased in women with "idiopathic" (normotensive) small-for-gestational-age pregnancies and/or in their babies and (2). whether fetal carriage of a thrombophilia is associated with abnormal umbilical Doppler studies. STUDY DESIGN: This was a case-controlled study of normotensive women who were delivered of a singleton small-for-gestational-age baby (birth weight, <10th percentile adjusted for sex) with no clinical evidence of chromosomal or congenital abnormality. Control subjects were healthy women who were delivered of appropriate-for-gestational-age babies. RESULTS: One hundred forty-five women with small-for-gestational-age pregnancies and 290 control subjects were recruited. Small-for-gestational-age babies were born at an earlier gestational age (38 +/- 3.0 weeks) and with a lower birth weight (2373 +/- 521 g) than control babies (39.7 +/- 1.3 weeks and 3606 +/- 423 g, P <.01). There were no differences in the rates of factor V Leiden (2.8% vs 3.8%; relative risk, 0.79; 95% CI, 0.34-1.85), prothrombin gene mutation (2.8% vs 3.1%; relative risk, 0.92; 95% CI, 0.40-2.09), and methylenetetrahydrofolate reductase C677T polymorphism (13% vs 9%; relative risk, 1.27; 95% CI, 0.87-1.84) between mothers with small-for-gestational-age babies and control subjects, respectively. Inherited thrombophilias were not increased in small-for-gestational-age babies compared with control babies. Of small-for-gestational-age babies with abnormal umbilical artery Doppler studies (n = 25), 21% had a thrombophilia compared with 11% with normal umbilical artery Doppler studies (n = 68; relative risk, 1.75; 95% CI, 0.81-3.81). CONCLUSION: The rates of these inherited thrombophilias are not increased in normotensive women with small-for-gestational-age pregnancies. Further studies are required to determine whether thrombophilias are increased in small-for-gestational-age babies with abnormal umbilical Doppler study results.     

Atypical glandular cells of undetermined significance. Histologic findings and proposed management

OBJECTIVE: To increase understanding of the clinical significance of atypical glandular cells of undetermined significance (AGUS) on cervical cytology and to suggest a management plan. STUDY DESIGN: All Pap smears classified as AGUS over a period of five years at the University of Michigan Medical Center were reviewed and the diagnosis confirmed. The charts of these patients were reviewed for demographics, significant previous medical history, symptoms, diagnostic studies performed and final histologic diagnoses. RESULTS: In 1993-1998, a total of 208,041 Pap smears were read. Two hundred seven smears from 189 patients were classified as AGUS, for an incidence of 0.1%. There were 136 patients with follow-up information and 114 patients with histologic diagnoses. In 55 of the 114 patients (48%), significant histologic abnormalities were observed, including 11 endometrial cancers, 1 invasive adenocarcinoma of the cervix, 3 adenocarcinomas in situ of the cervix, 18 CIN 3 lesions and 5 CIN 2 lesions. Among 20 patients with Pap smears subclassified as "atypical glandular cells of undetermined significance, favor benign process," there were two CIN 2, five CIN 3 and one adenocarcinoma in situ of the cervix. CONCLUSION: A diagnosis of AGUS requires an aggressive workup because of the high rate of cancer and precancerous lesions. The evaluation, at the very least, should include colposcopy with directed biopsies and endocervical curettage. Postmenopausal patients, those with irregular bleeding and those with high risk characteristics should also undergo endometrial biopsy.     

Effect of ovarian stimulation with recombinant follicle-stimulating hormone,gonadotropin releasing hormone antagonists,and human chorionic gonadotropin on endometrial maturation on the day of oocyte pick-up

OBJECTIVE: To assess the effect of ovarian stimulation with recombinant FSH, GnRH antagonists, and hCG on endometrial maturation on the day of oocyte pick-up. DESIGN: Prospective study. SETTING: Tertiary referral center. PATIENT(S): Fifty-five women undergoing controlled ovarian hyperstimulation for IVF/intracytoplasmic sperm injection (ICSI). INTERVENTION(S): [1] Ovarian stimulation with recombinant FSH, starting on day 2 of the cycle and GnRH antagonist, starting after a median of 6 days of recombinant FSH stimulation (range, 5-12 days); [2] hCG administration for ovulation induction; and [3] aspirational biopsy of endometrium at oocyte pick-up. MAIN OUTCOME MEASURE(S): Endometrial histology at oocyte pick-up by Noyes criteria. RESULT(S): Advancement of endometrial maturation (2.5 +/- 0.1 days) as compared to the expected chronological date was observed in all antagonist cycles at oocyte retrieval. Endometrial advancement at oocyte pick-up increased in line with values of LH at initiation of stimulation and the duration of recombinant FSH treatment before the antagonist was started. CONCLUSION(S): The higher the values of LH at initiation of stimulation and the longer the duration of recombinant FSH treatment before the antagonist is started, the more advanced the endometrial maturation at oocyte pick-up.