Immunology: High fecundity rates following in- vitro fertilization and embryo transfer in antiphospholipid antibody seropositive women treated with heparin and aspirin

This study was undertaken to explore whether intervention withheparin and aspirin (H/A) in selected patients undergoing in-vitrofertilization (TVF) and embryo transfer could improve fecundityrates. Specifically, it explored the possibility that womendiagnosed with organic pelvic disease who demonstrated antiphospholipidantibodies (APA) could benefit from H/A administration in asimilar manner to that used in patients with recurrent pregnancyloss. We used an enzyme–linked immunosorbent assay forsix different phospholipids to identify patients who expressedAPA before they underwent IVF/embryo transfer. This study wasconfined to the first IVF/embryo transfer cycle that followedassessment of APA status and accordingly, the number of IVF/embryotransfer cycles corresponds with the number of patients treated.APA seropositive patients were treated with aspirin, 81 mg orallyq.d., and heparin 5000 IU s.c. b.i.d., beginning on day 1 ofcontrolled ovarian stimulation. The endpoint for success wasa live birth or an ultrasound confirming fetal cardiac activity(a viable pregnancy). The prevalence of APA in patients diagnosedwith organic pelvic disease (53%) was much higher than in thosewithout female pathology (14%). The administration of H/A toAPA seropositive patients significantly (P < 0.05) improvedthe viable pregnancy rate (49%) compared to the untreated APAseropositive group (16%). The viable pregnancy rate for APAseropositive women treated with H/A was also significantly (P< 0.001) higher than for untreated APA seronegative patients(27%). We conclude that all women undergoing IVF/embryo transfershould be tested for APA prior to initiating ovarian stimulation,and those with APA seropositivity should be treated with H/A.     

Decrement of the skin conductance response to repeated volitional inspiration.

OBJECTIVE: To examine response decrement of the recently reported inspiratory skin conductance response (SCR) [Lim CL, Seto-Poon M, Clouston PD, Morris JG. Sudomotor nerve conduction velocity and central processing time of the skin conductance response. Clin Neurophysiol 2003;114:2172-80]. METHODS: Twelve healthy adult volunteers performed 3 tasks (A) a control task of maintaining tidal breathing and then two randomized tasks, (B) a deep inspiration to a target oral pressure and (C) tapping with a finger. Each task was performed 30 times on cue every 20s in 3 runs with 5 min of rest between runs. The SCR, oral pressure, airflow, inspired volume and cue signal were recorded continuously and analysed offline. SCR amplitude was logarithmically transformed and then statistically analysed, using a linear mixed effects model, as a function of run number, trial number and absolute error between target and actual oral pressures. RESULTS: Inspiratory efforts elicited exponentially decreasing SCR amplitude with increasing trial number during each run (P < 0.0001). After adjusting for trial number, the mean SCR amplitude of the second and the third run were, respectively, 24.2 (95% CI (0.175, 0.336), P < 0.001) and 14.4% (95% CI (0.104, 0.200), P < 0.001) of the first run amplitude. CONCLUSIONS: Volitional deep inspiration reliably activates an SCR that exhibits response decrement with repetition, which may be habituation. SIGNIFICANCE: The volitional inspiratory SCR may assist in the assessment of sympathetic autonomic status in patients with peripheral afferent neuropathy.     

Statins—Treatment Option for Central Nervous System Autoimmune Disease?

Statins, inhibitors of the enzyme 3-hydroxy-3-methylglutaryl coenzyme A reductase, are well-established agents to lower cholesterol levels and prevent cardiovascular morbidity. Independent of their lipid-lowering properties, statins have been shown to exert pleiotropic immunomodulatory effects in various animal models of human autoimmune disease. In experimental autoimmune encephalomyelitis, a murine model for multiple sclerosis, statins prevented disease onset and even reversed paralysis when treatment was initiated after experimental autoimmune encephalomyelitis was fully established. Furthermore, well-tolerated oral statins were recently shown to exert synergistic benefit in experimental autoimmune encephalomyelitis in combination with existing agents for multiple sclerosis therapy. Based primarily on these encouraging results, statins are now being tested in clinical trials as a mono-therapy for multiple sclerosis, as well as in combination with approved disease-modifying therapies.     

Sensitivity-encoded (SENSE) proton echo-planar spectroscopic imaging (PEPSI) in the human brain.

Magnetic resonance spectroscopic imaging (MRSI) provides spatially resolved metabolite information that is invaluable for both neuroscience studies and clinical applications. However, lengthy data acquisition times, which are a result of time-consuming phase encoding, represent a major challenge for MRSI. Fast MRSI pulse sequences that use echo-planar readout gradients, such as proton echo-planar spectroscopic imaging (PEPSI), are capable of fast spectral-spatial encoding and thus enable acceleration of image acquisition times. Combining PEPSI with recent advances in parallel MRI utilizing RF coil arrays can further accelerate MRSI data acquisition. Here we investigate the feasibility of ultrafast spectroscopic imaging at high field (3T and 4T) by combining PEPSI with sensitivity-encoded (SENSE) MRI using eight-channel head coil arrays. We show that the acquisition of single-average SENSE-PEPSI data at a short TE (15 ms) can be accelerated to 32 s or less, depending on the field strength, to obtain metabolic images of choline (Cho), creatine (Cre), N-acetyl-aspartate (NAA), and J-coupled metabolites (e.g., glutamate (Glu) and inositol (Ino)) with acceptable spectral quality and localization. The experimentally measured reductions in signal-to-noise ratio (SNR) and Cramer-Rao lower bounds (CRLBs) of metabolite resonances were well explained by both the g-factor and reduced measurement times. Thus, this technology is a promising means of reducing the scan times of 3D acquisitions and time-resolved 2D measurements.     

Predictors of punding in Parkinson's disease: results from a questionnaire survey.

Dopamine replacement therapy (DRT) for Parkinson's disease (PD) has recently been linked to the development of a number of nonmotor behavioral control problems. Punding, one of these nonmotor problems, is a term used to describe complex, purposeless stereotyped behaviors such as the repetitive handling or sorting of objects. A self-report questionnaire was adapted to assess punding in the context of dysfunctional hobby-related activities. We report the results of a survey of PD outpatients from a PD research clinic (n = 141) and non-PD controls (n = 103); conducted to identify clinical and psychological factors predictive of punding behaviors. The PD group reported hobbies and activities, which scored significantly higher on the Punding Scale than controls. Higher impulsivity, poorer disease-related quality of life, younger age of disease onset, and concomitant daily medication dosage from dopamine receptor agonists were independently predictive of higher Punding Scale scores in the PD group. These findings are similar to those seen in dopamine dysregulation syndrome, and provide further evidence for the role of impulsivity and age at disease onset in DRT-related nonmotor behavioral problems in PD.     

Hypogonadotropic hypogonadism.

Gonadotropin-releasing hormone (GnRH) and olfactory neurons migrate together from the olfactory placode, and GnRH neurons eventually reside in the hypothalamus. Hypogonadism in male infants may be diagnosed in the first 6 months of life but cannot be diagnosed during childhood until puberty occurs. Patients with low serum testosterone and low serum gonadotropin levels have idiopathic hypogonadotropic hypogonadism (IHH). Mutations in three genes (KAL1, FGFR1, and GNRHR) comprise most of the known genetic causes of IHH. Treatment with testosterone is indicated if fertility is not desired, whereas GnRH or gonadotropin treatment induces spermatogenesis and fertility.     

D2-40 immunohistochemistry in the differential diagnosis of seminoma and embryonal carcinoma: a comparative immunohistochemical study with KIT (CD117) and CD30.

The distinction between seminoma and embryonal carcinoma based on morphology alone can sometimes be problematic, requiring the use of immunohistochemistry to facilitate diagnosis. D2-40 is a monoclonal antibody that reacts with an oncofetal antigen expressed by fetal germ cells and testicular germ cell tumors. The diagnostic value of D2-40 immunohistochemistry in distinguishing seminoma from embryonal carcinoma has not been determined. D2-40 immunoreactivity was evaluated in a series of testicular germ cell tumors and compared with that of KIT (CD117) and CD30, to assess the relative utility of this marker in discriminating between seminoma and embryonal carcinoma. Forty testicular germ cell neoplasms were examined, which included 19 seminomas, three embryonal carcinomas, three teratomas, one yolk sac tumor, and 14 mixed germ cell tumors. The 14 cases of mixed germ cell tumors contained components of seminoma (n=7), embryonal carcinoma (n=11), teratoma (n=10), yolk sac tumor (n=2), and choriocarcinoma (n=1). All cases of pure seminoma and the seminomatous components of mixed germ cell tumors exhibited positive immunoreactivity for D2-40. Focal positivity for D2-40 was also observed in 29% of the embryonal carcinoma samples. D2-40 immunoreactivity in seminomas was characterized by diffuse membrane staining, whereas for embryonal carcinomas, staining was focal and distributed along the apical surfaces of the neoplastic cells. Immunohistochemical staining for KIT was observed in 92% of the seminoma samples and in none of the embryonal carcinomas. Conversely, CD30 expression was identified in 93% of the embryonal carcinoma samples and in none of the seminomas. Other germ cell components showed no immunoreactivity for D2-40, KIT, or CD30. KIT and CD30 are effective immunohistochemical markers in separating seminoma from embryonal carcinoma. Although a highly sensitive marker for seminomas, D2-40 positivity was also observed in a subset of embryonal carcinomas, thus limiting the utility of this antibody for discriminating between these two malignancies.