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.     

Physical therapy and cognitive-behavioral treatment for complex regional pain syndromes

Complex regional pain syndromes (CRPS; type 1, reflex sympathetic dystrophy, and type 2, causalgia) involve persistent pain, allodynia, and vasomotor signs. We conducted a prospective, randomized, single-blind trial of physical therapy (PT) and cognitive-behavioral treatment for children and adolescents with CRPS. Children 8 to 17 years of age (n = 28) were randomly assigned to either group A (PT once per week for 6 weeks) or group B (PT 3 times per week for 6 weeks). Both groups received 6 sessions of cognitive-behavioral treatment. Assessments of pain and function were repeated at two follow-up time periods. Outcomes were compared at the three time points through the use of parametric or nonparametric analysis of variance and post hoc tests. All five measures of pain and function improved significantly in both groups after treatment, with sustained benefit evident in the majority of patients at long-term follow-up. Recurrent episodes were reported in 50% of patients, and 10 patients eventually received sympathetic blockade. Most children with CRPS showed reduced pain and improved function with a noninvasive rehabilitative treatment approach. Long-term functional outcomes were also very good.