Partial protein S gene deletion in a family with hereditary thrombophilia

Familial thrombophilia, the hereditary predisposition to venous thromboembolic disease, is associated with a protein S deficiency in approximately 8% of the cases. Laboratory measurements of total protein S antigen in affected families have indicated that heterozygotes, ie, individuals carrying both a normal and a defective protein S gene, are severely at risk of developing venous thrombosis at a young age. The recent isolation of protein S cDNA has enabled us to start a search for genetic defects in the protein S gene of heterozygotes. Using Southern blotting on probands of six unrelated families with hereditary protein S deficiency, one proband was found to have a grossly abnormal gene pattern. The abnormality appears to involve at least the deletion of the middle portion of the protein S coding sequence. Family analysis showed that the defect cosegregates with the protein S deficiency. These data agree with the notion that hereditary thrombophilia associated with protein S deficiency is indeed directly the result of a defect in the protein S gene.     

Influence of low and high frequency inputs on spike timing in visual cortical neurons

Cortical neurons in vivo respond to sensory stimuli with the generation of action potentials that can show a high degree of variability in both their number and timing with repeated presentations as wells as, on occasion, a high degree of synchronization with other cortical neurons, including in the gamma frequency range of 30-70 Hz. Here we examined whether or not this variability may arise from the intrinsic mechanisms of action potential generation in cortical regular spiking, fast spiking and intrinsic burst-generating neurons maintained in vitro. For this purpose, we performed intracellular recordings in slices of ferret visual cortex and activated these cells with the intracellular injection of various current waveforms. Some of these waveforms were derived from barrages of postsynaptic potentials evoked by visual stimulation recorded in vivo; others were artificially created and contained various amounts of gamma range fluctuations; finally, others consisted of swept-sinewave current (ZAP current) functions. Using such stimuli, we found that, as expected given the resistive and capacitive properties of cortical neurons, low frequencies have a larger effect on the membrane potential of cortical neurons than do higher frequencies. However, increasing the amount of gamma range fluctuations in a stimulus leads to more precise timing of action potentials. This suggests that different frequencies play different roles, low frequencies being efficient for depolarizing cells with high frequencies increasing the precision of action potential timing. In parallel to increases in temporal precision, the addition of higher frequency components increases the range of interspike intervals present in the action potential discharge. These results suggest that higher frequency components such as gamma range fluctuations may facilitate the generation of action potentials with a high temporal precision while at the same time exhibiting a high degree of variability in interspike intervals on single trials. This temporal precision may facilitate the use of temporal codes or the generation of precise synchronization for the transmission and analysis of information within cortical networks.      

经腹腔镜开窗减压术治疗巨大非寄生虫性脾囊肿是有效的保脾术式

原发性脾囊肿是一种罕见的疾病,目前尚缺乏对该疾病的理想治疗方法的相关研究.大多数原发性脾囊肿是上皮性囊肿.近几年,腹腔镜脾脏外科手术普及率不断提高.该研究报告了关于经腹腔镜保脾手术治疗脾囊肿的相关经验.1996年至2006年间,作者治疗了11例有症状的非寄生虫性脾脏巨大囊肿病人.病人均诉左上腹涨满症状,触诊可扪及腹部包块.术前腹部超声及CT均已明确诊断.病人接受经腹腔镜脾脏囊肿部分切除术或脾脏囊肿开窗减压术.结果发现,7例病人为脾脏间皮囊肿,2例为脾脏表皮样囊肿,2例为脾脏假性囊肿,没有发现囊肿癌变.手术操作时间为62～85 min,无中转开腹.     

AIDS retrovirus antibodies in hemophiliacs treated with factor VIII or factor IX concentrates, cryoprecipitate, or fresh frozen plasma: prevalence, seroconversion rate, and clinical correlations

Antibodies to the AIDS retrovirus, specifically to human T cell lymphotropic virus, type III, and AIDS-associated retrovirus, were detected with increasing prevalence in a population of 190 hemophiliacs from western Pennsylvania between 1981 and 1984: 7.7% in 1981, 20.0% in 1982, 45.5% in 1983, and 62.5% in 1984. The seropositive included approximately three fourths of those receiving factor VIII concentrate, nearly one third of those receiving factor IX concentrate, nearly one fifth of those receiving cryoprecipitate, and none of those receiving fresh frozen plasma. The seroconversion rate, determined on 43 seropositive hemophiliacs from this group who were serially sampled, was 0% in 1977, 4.7% in 1978, 4.9% in 1979, 2.6% in 1980, 10.5% in 1981, 52.9% in 1982, 87.5% in 1983, and 100% in 1984. Of 27 seropositive for three or more years (since 1982 or before), four (15%) have developed AIDS and seven (26%), diffuse lymphadenopathy (ARC); of 16 seropositive for less than three years, none has developed AIDS and three (19%) have developed ARC. The mean time from seroconversion to onset of ARC, 0.8 +/- 0.2 years (SEM), was shorter (P less than .001) than the time to onset of AIDS, 4.1 +/- 0.6 years. These findings confirm the widespread presence of AIDS retrovirus and support the association of these retroviruses with the acquired immunodeficiency syndrome and related conditions.     

Ultrasonographic evidence of Gatekeeper™ prosthesis migration in patients treated for faecal incontinence: a case series

Background

Faecal incontinence (FI) is both a medical and social problem, with an underestimated incidence. For patients with internal anal sphincter damage, implantation of biomaterial in the anal canal is a recognised treatment option. One such material, Gatekeeper?, has previously shown promising short- and medium-term results without any major complications, including displacement. The main aim of the present study is to assess the degree to which displacement of Gatekeeper prostheses may occur and to determine whether this is associated with patient outcomes.

Methods

Seven patients (six females) with a mean age of 55.6 years [50.5–57.2] and a mean FI duration of 6 ± 2 years were prospectively enrolled in the study. Each subject was anaesthetised and underwent implantation of six prostheses in the intersphincteric region, guided by endoanal 3D ultrasound (3D-EAU). Follow-up was performed at post-interventional months 1, 3, and 12 (median 12 ± 4 months), during which data were obtained from a defaecation diary, Wexner scale assessment, anorectal manometry (ARM), 3D-EAU, and a health status and quality of life questionnaire (FIQL).

Results

At 3-month follow-up, 3D-EAU revealed displacement of 24/42 prostheses in 5/7 patients. Of these, 15 had migrated to the lower portion and 9 to the upper portion of the anal canal and rectum. Despite this migration, treatment was considered successful in 3/7 patients. In one patient, it was necessary to remove a prosthesis due to spontaneous extrusion.

Conclusions

We have shown that displacement of the Gatekeeper? prosthesis occurs, but is not associated with poorer clinical outcomes.

     

Randomized study of didanosine monotherapy and combination therapy with zidovudine in hemophilic and nonhemophilic subjects with asymptomatic human immunodeficiency virus-1 infection. AIDS Clinical Trial Groups

To evaluate the safety and efficacy of didanosine (ddl) monotherapy and three different combinations of zidovudine (ZDV) and ddl in asymptomatic human immunodeficiency virus-1 (HIV-1) infection, we conducted an open-label, phase I/II study in 126 asymptomatic HIV-1- infected hemophilic and nonhemophilic subjects with a CD4 count of 200 to 500/mm3 stratified for prior zidovudine treatment and baseline CD4 count. Study arms included arm A, low-dose combination (ZDV 150 mg and ddl 134 mg, daily); arm B, moderate-dose combination (ZDV 300 mg and ddI 334 mg, daily); arm C, high-dose combination (ZDV 600 mg and ddl 500 mg, daily), and arm D, ddl monotherapy (ddl 500 mg, daily). Earlier, more frequent hepatotoxicity was experienced by hemophilic subjects (P = .008), but there were no differences in toxicity between treatment arms (P = .51), nor were there any differences in the rate of development of clinical endpoints by treatment (P = .41). Smaller median CD4 increases occurred over the first 12 weeks for arms A and D, 44/mm3 and 42/mm3, than arms B and C, 105/mm3 and 114/mm3, respectively, (P = .015). Hemophilia status (P = .0004) and prior ZDV experience (P = .044) independently predicted weaker CD4 responses during the first 12 weeks of treatment. Using a regression model and adjusting for hemophilia status, prior ZDV treatment, and baseline CD4, there was a significant reduction in quantitative viral load from baseline by week 12 for all treatment arms combined (P = .0001), with significantly lower median percent reduction for arm A (56.3%) than arms B, C, and D (94.6%, 98.5%, and 91.9%, respectively, P = .015). Although greater hepatoxicity and weaker CD4 responses occur in hemophilic subjects, didanosine monotherapy and combination therapy with zidovudine are safe and effective in asymptomatic HIV-1-infected patients.     

Efficacy and safety of rizatriptan wafer for the acute treatment of migraine

Rizatriptan is a potent, highly selective 5HT1B/1D agonist with rapid onset of action for acute treatment of migraine. Rizatriptan wafer is a novel, freeze-dried dosage formulation of rizatriptan which rapidly disintegrates on the tongue, is swallowed with saliva, and may be taken without liquids. The efficacy and tolerability of rizatriptan wafer were examined in a placebo-controlled, double-blind, outpatient study in 555 migraineurs. The primary efficacy endpoint was pain relief at 2 h. From 30 min onwards, significantly more patients experienced pain relief and became pain-free after rizatriptan 10-mg wafer compared to placebo. At 2 h, the percentage of patients with pain relief was significantly higher after rizatriptan 10-mg wafer (74%), 5-mg wafer (59%) compared with placebo (28%). Rizatriptan 10-mg wafer was superior to rizatriptan 5-mg wafer on pain relief at 1.5 and 2 h (p < 0.05). Significantly more patients were pain-free at 2 h after rizatriptan 10-mg wafer (42%), 5-mg wafer (35%) compared with placebo (10%). Both doses of rizatriptan wafer were well tolerated. Rizatriptan wafer is a convenient, highly effective new formulation for acute treatment of migraine.