Assessment of gestational age by ultrasonic measurement of the femur length

The effectiveness of ultrasonic femur length measurement from 12 to 40 week's gestation, as a means of assessing fetal age, was tested and compared with that of biparietal cephalometry. The femur length and biparietal diameter (BPD) were obtained from 471 measurements, from pregnant women with confirmed datings, using real-time scanning with a 3,5 mHz transducer frequency. Using a freeze frame and electronic calipers, the mean value of three consecutive measurements of the femur, when visualized with its characteristic appearance, was recorded. Linear regression analysis with the correlation coefficient of the femur growth-curve (r = 0.989, p less than 0.001) and that of the BPD (r = 0.985, p less than 0.001) showed that the former is as good as the latter. The femur growth-curve from 12 to 40 week's gestation with a mean +/- 2 SD was constructed. Estimation of fetal age by femur length measurement was compared with that assessed by the BPD in a further 54 women. A close correlation was found (r = 0.993, p less than 0.001). Measurement of the fetal femur appears to be a reliable method for assessing gestational age, which can compensate for the limitations of the BPD method.     

Subtle abnormalities in follicular development and hormonal profile in women with unexplained infertility

A prospective study of six unselected couples diagnosed as having unexplained infertility was done. In three of six patients, subtle abnormalities in follicular development were detected. In the first case poor follicular growth was observed. There was a premature small rise of luteinizing hormone (LH) with subsequent low levels of estradiol (E2) in the late follicular phase and unusual wide LH peak. This was followed by low progesterone levels in the luteal phase. In the second case follicular growth was abrupted by premature LH surge. This surge was triggered by early rise of E2 level while the follicle was still small in size. In the third case luteinized unruptured follicle syndrome was diagnosed, on ultrasound examination. All of the abnormalities were repetitive.     

Rescue of menotrophin cycles prone to develop ovarian hyperstimulation

In an attempt to prevent the loss of 'overstimulated cycles' associated with human menopausal gonadotrophin (hMG)-induced ovulation, oestradiol levels and ovarian follicular state were monitored in 12 women with 'overstimulated cycles' after withholding hMG for several days. Human chorionic gonadotrophin (hCG) was administered when oestradiol levels were less than or equal to 1700 pg/ml and the leading follicles between 17 and 22 mm in diameter. During the withholding period follicular growth continued in all patients, while oestradiol levels declined in all but three. These three patients conceived. Ovulation was observed in six additional women. Ovarian hyperstimulation did not occur in any of the 12 patients. We conclude that a rescue of 'overstimulated cycles' is sometimes possible. Conception seems to depend on a continuing rise of E2 levels and early detection of 'overstimulation'.     

Mitomycin C and 5-fluorouracil antimetabolite therapy for pediatric glaucoma filtration surgery

PURPOSE: To evaluate the efficacy and safety of augmented trabeculectomy with 5-fluorouracil (5-FU) and mitomycin C (MMC) compared to 5-FU only for the treatment of pediatric glaucoma. PATIENTS AND METHODS: In a prospective randomized clinical trial, 8 children (12 eyes) with pediatric glaucoma, either congenital or secondary to: lens aspiration, Sturge-Weber syndrome, or steroids underwent augmented trabeculectomy. Six patients (8 eyes) underwent augmented trabeculectomy with 5-FU plus MMC and 2 patients (4 eyes) underwent augmented trabeculectomy with 5-FU only. MAIN OUTCOME MEASURES: Between-group comparison of postoperative parameters: change in intraocular pressure (IOP), dependence on antiglaucoma medication, number of 5-FU injections, cup-disc ratio, corneal diameter, drug-induced complications. RESULTS: In the 5-FU/MMC group, 7/8 eyes showed good control of postoperative IOP (9-16 mm Hg), which was independent of antiglaucoma therapy; only 2 injections of 5-FU were needed. By contrast, in the 5-FU group, no control of the postoperative IOP (21-23 mm Hg) was achieved in 4/4 eyes, and these patients remained dependent on antiglaucoma medication; up to 6 injections of 5-FU were used. There was no deterioration in the cup-disc ratio or the corneal diameter in either group. Results were maintained on follow-up (23-27 months). No significant drug-induced complications were noted. CONCLUSION: Augmented trabeculectomy with adjunctive 5-FU/MMC may be an option for the control of pediatric glaucoma in patients with a poor surgical prognosis.     

The SleepStrip: an apnoea screener for the early detection of sleep apnoea syndrome.

Sleep apnoea svndrome (SAS) is a largely undiagnosed and prevalent disorder. It is associated with cardiovascular morbidity as well as excessive daytime sleepiness and poor quality of life. In the present study the SleepStrip, a novel screening device is introduced, which is low cost and easy to use and is aimed for widespread use. The results of three independent validation studies, which compared the SleepStrip score (Sscore) against "gold standard" polysomnographically-determined apnoea/ hypopnoea index (AHI), are reported both separately and combined. Four hundred and two patients suspected of SAS underwent full polysomnography recordings concomitantly with the use of the SleepStrip. For all samples combined, the correlation between AHI and Sscore was r=0.73, sensitivity and specificity values ranged from 80-86% and 57-86% respectively, and the area under the curve derived from receiver-operating characteristic curves ranged from 0.81-0.92 at varying AHI thresholds. Though not intended as a substitute for polysomnography, the SleepStrip may provide initial screening information, which may be useful in both clinical and experimental settings.     

A novel mutation disrupting the cytoplasmic domain of CRB1 in a large consanguineous family of Palestinian origin affected with Leber congenital amaurosis

Leber congenital amaurosis (LCA) is a genetically heterogeneous autosomal recessive condition responsible for congenital blindness or greatly impaired vision since birth. Eight LCA loci have been mapped, but only six out of eight genes have been hitherto identified. A genome-wide screen for homozygosity was conducted in a large consanguineous family originating from Palestine, for which no mutation was found in any of the six known LCA genes and that excluded the LCA3 and LCA5 loci. Evidence for homozygosity, however, was found in all affected patients of the family on chromosome 1q31, a region in which the human homologue of the Drosophila melanogaster crumbs gene (CRB1) has been mapped. Consequently, we proposed a hypothesis that the disease-causing mutation in this family might lie in an unexplored region of this LCA gene. As a matter of fact, while no mutation was found in any of the 11 CRB1 exons originally reported, we identified a 10-bp (del 4121-4130) deletion segregating with the disease in a later reported 12th exon lying in the 3' end of the gene. Interestingly, this deletion disrupts an amino acid sequence that was shown to be crucial for the function of the protein in the Drosophila counterpart (CRB).     

Neurobiology of relapse to heroin and cocaine seeking: a review

The objective of this article is to review data from studies that used a reinstatement model in rats to elucidate the neural mechanisms underlying relapse to heroin and cocaine seeking induced by exposure to the self-administered drug (drug priming), conditioned drug cues, and stressors. These factors were reported to contribute to relapse to drug use in humans following prolonged abstinence periods. In the reinstatement model, the ability of acute exposure to drug or nondrug stimuli to reinstate drug seeking is determined following training for drug self-administration and subsequent extinction of the drug-reinforced behavior. We will review studies in which pharmacological agents were injected systemically or intracranially to block (or mimic) reinstatement by drug priming, drug cues, and stressors. We also will review studies in which brain lesions, in vivo microdialysis and electrochemistry, and gene expression methods were used to map brain sites involved in relapse to drug seeking. Subsequently, we will discuss theoretical issues related to the processes underlying relapse to drugs and address methodological issues in studies on reinstatement of drug seeking. Finally, the implications of the findings from the studies reviewed for addiction theories and treatment will be discussed. The main conclusion of this review is that the neuronal mechanisms involved in relapse to heroin and cocaine seeking induced by drug priming, drug cues, and stressors are to a large degree dissociable. The data reviewed also suggest that the neuronal events mediating drug-induced reinstatement are to some degree dissociable from those mediating drug reinforcement.     

Prospective evaluation of plasma cortisol in recent trauma survivors with posttraumatic stress disorder

Hypothalamic pituitary adrenal axis abnormalities have been described in posttraumatic stress disorder (PTSD), and among the recently traumatized. Plasma cortisol and continuous measures of PTSD symptoms were obtained from 21 survivors, at 1 week and 6 months after traumatic events. Eight survivors met Clinician Administered PTSD Scale criteria for PTSD at 6 months. Cortisol levels at 1 week did not predict subsequent PTSD. Survivors with and without PTSD had similar mean levels of cortisol at both time points. Cortisol levels at 6 months negatively correlated with self-reported PTSD symptoms within PTSD subjects.     

Immune-related mechanisms participating in resistance and susceptibility to glutamate toxicity

Glutamate is an essential neurotransmitter in the CNS. However, at abnormally high concentrations it becomes cytotoxic. Recent studies in our laboratory showed that glutamate evokes T cell-mediated protective mechanisms. The aim of the present study was to examine the nature of the glutamate receptors and signalling pathways that participate in immune protection against glutamate toxicity. We show, using the mouse visual system, that glutamate-induced toxicity is strain dependent, not only with respect to the amount of neuronal loss it causes, but also in the pathways it activates. In strains that are genetically endowed with the ability to manifest a T cell-dependent neuroprotective response to glutamate insult, neuronal losses due to glutamate toxicity were relatively small, and treatment with NMDA-receptor antagonist worsened the outcome of exposure to glutamate. In contrast, in mice devoid of T cell-dependent endogenous protection, NMDA receptor antagonist reduced the glutamate-induced neuronal loss. In all strains, blockage of the AMPA/KA receptor was beneficial. Pharmacological (with alpha2-adrenoceptor agonist) or molecular intervention (using either mice overexpressing Bcl-2, or DAP-kinase knockout mice) protected retinal ganglion cells from glutamate toxicity but not from the toxicity of NMDA. The results suggest that glutamate-induced neuronal toxicity involves multiple glutamate receptors, the types and relative contributions of which, vary among strains. We suggest that a multifactorial protection, based on an immune mechanism independent of the specific pathway through which glutamate exerts its toxicity, is likely to be a safer, more comprehensive, and hence more effective strategy for neuroprotection. It might suggest that, because of individual differences, the pharmacological use of NMDA-antagonist for neuroprotective purposes might have an adverse effect, even if the affinity is low.