Excipient effects on gastrointestinal transit and drug absorption in beagle dogs

Previous work has shown that polyethylene glycol 400 (PEG 400) has an accelerating effect on gastrointestinal transit and a modulating influence on drug absorption in humans. The aim of this study was to assess the impact of various excipients, PEG 400, propylene glycol, d--tocopheryl-polyethylene glycol-1000 succinate (TPGS) and Labrasol on gastrointestinal transit and drug absorption in four beagle dogs using scintigraphy. Each dog received, on five separate occasions, water (control) or a dose of excipient equivalent to 1 g PEG 400, 2 g propylene glycol, 1 g TPGS or 2 g Labrasol dissolved in water and administered in the form of two capsules. The model drugs ampicillin (200 mg) and antipyrine (100 mg) were co-administered in the capsules. The capsule solutions were radiolabelled with technetium-99m to follow their transit using a dual-headed gamma camera, and blood samples were collected to determine drug pharmacokinetics. On a separate occasion, the drugs were dissolved in saline and given intravenously. The capsules rapidly disintegrated in the stomach liberating their liquid contents. The mean small intestinal transit times for the different treatments (control, PEG 400, propylene glycol, TPGS and Labarasol) were 183, 179, 195, 168 and 154 min, respectively. The corresponding mean absolute oral bioavailability figures were 36, 32, 39, 42 and 32% for ampicillin and 76, 74, 85, 73 and 74% for antipyrine, respectively. The transit and bioavailability data for the excipient treatments were not significantly different from the control. In summary, these excipients, at the doses administered, have limited influence on gastrointestinal transit and drug absorption in beagle dogs.     

Effect of image uncertainty on the dosimetry of trigeminal neuralgia irradiation

OBJECTIVE: Our objective was to quantify the uncertainty in localization of the trigeminal nerve (TGN) with magnetic resonance imaging (MRI) and computed tomography (CT) and to determine the effect of this uncertainty on gamma-knife dose delivery. METHODS: An MR/CT test phantom with 9, 0.6-mm diameter, copper rings was devised. The absolute ring positions in stereotactic space were determined by the angiographic module of the LGP software. The standard deviation, sigma, in the difference between the absolute and MR-measured or CT-measured coordinates of the rings was determined. The trigeminal nerve in 52 previously treated patients was contoured and expanded by 1sigma and 2sigma margins to model the uncertainty in the location of the nerve. For gamma-knife treatment, a single isocenter was used and was located at the distal cisternal portion of the trigeminal nerve root. Irradiation methods included a 4-mm collimator, 90 Gy to isocenter and a 4&8-mm collimator, 70 Gy to isocenter. A patient outcome survey that sampled pain relief and morbidity was done. RESULTS: The MR coordinate sigma was 0.7 mm left-right, 0.8 mm anterior-posterior, and 0.6 mm superior-inferior, and the CT coordinate sigma was 0.4 mm left-right, 0.2 mm anterior-posterior, and 0.2 mm superior-inferior. A 45% higher dose line covered the TGN with the 4&8-mm method. No significant increase in pain reduction or morbidity occurred. CONCLUSIONS: The uncertainty of target location by MRI is more than twice that found in CT imaging. The 4&8-mm collimator method covers the trigeminal root cross section with a higher isodose line than does the 4-mm method. This higher dose did not significantly reduce pain or increase morbidity.     

Postmenopausal levels of sex hormones and risk of breast carcinoma in situ: results of a prospective study

We report on a prospective study to assess the association of postmenopausal serum levels of sex hormones with subsequent risk of breast carcinoma in situ. We conducted a case-control study nested within the cohort of the New York University Women's Health Study, a large prospective study documenting a positive association of circulating levels of estrogens and androgens with invasive breast cancer. The study included 69 cases of incident in situ carcinoma and 134 individually matched controls. No statistically significant trend of increasing risk with increasing level of any of the hormones was observed. Odds ratios (95% CIs) for the highest tertile relative to the lowest were 1.10 (0.51-2.39) for estradiol, 0.95 (0.41-2.19) for estrone, 1.63 (0.69-3.88) for testosterone, 0.99 (0.44-2.24) for androstenedione, 0.99 (0.45-2.20) for dehydroepiandrosterone sulfate and 0.81 (0.38-1.74) for sex hormone-binding globulin. Adjusting for potential confounders did not materially affect the results, nor did limiting the analysis to the 59 cases of ductal carcinoma in situ, the lesion thought to be the direct precursor of most invasive breast cancers. Our results are at variance with the positive associations observed in this same cohort with risk of invasive breast cancer. Possible explanations for our results include lack of power, an effect of sex hormones limited to the progression from in situ to invasive tumors, overrepresentation of indolent tumors or an effect of sex hormones on the induction of only a subset of in situ tumors, those that would develop into invasive tumors.     

HBV感染肝癌患者血清中Ig和CIC的检测与研究

目的了解HBV感染肝癌患者血清中Ig和CIC含量。方法用速率散射比浊法对正常组与HBV感染肝癌组以及HBV阴性肝癌组进行对比。结果肝癌患者与对照组相比前者血清中Ig和CIC含量明显升高(P<0.05),HBV感染肝癌患者与阴性肝癌患者相比前者血清中Ig和CIC含量明显升高(P<0.05)。结论肝癌患者由于HBV的感染,病毒复制时伴有血清Ig、CIC升高,是病情危险的信号,要紧密观察患者,采取必要的救治措施。     

γ谱测量中非长期平衡的识别

目的确定含天然放射性物质的物料是否处于非长期平衡，以及衰变链中那些长寿命核素被分离或减少。方法γ能谱测量中，长期平衡时天然放射系中各子体的活度浓度与母体相同，在非长期平衡时，各子体及母体的活度浓度各不相同。结果处于长期平衡和非长期平衡的物料，在判断它们是否“放射性物质”时，所依据的核素种类及其豁免活度浓度是不一样的；它们的辐射剂量计算也是不一样的。结论γ能谱测量中对非长期平衡的识别非常重要。     

大剂量人血丙种球蛋白治疗儿童ITP的疗效观察及护理

目的:观察大剂量人血丙种球蛋白治疗血小板减少性紫癜(ITP)的疗效及护理方法。方法:将172例住院病人随机分成两组,观察组在应用肾上腺糖皮质激素同时加用大剂量人血丙种球蛋白(IV IG)治疗,对照组按传统方法应用肾上腺糖皮质激素等药物治疗。结果:观察组于治疗第3天血小板均明显升高,皮肤无新鲜的出血点。结论:大剂量人血丙种球蛋白治疗特发性血小板减少性紫癜疗效确切,疗程较短,与对照组比较差异有显著性意义(P<0.05)。全面细致的护理与病情观察有利于特发性血小板减少性紫癜患儿的治疗和康复,减少并发症。     

Stereotactic Radiosurgery for Hemangioblastomas of the Brain

Summary  Objective. To assess the effectiveness of stereotactic radiosurgery in achieving tumor control and improving survival in patients with hemangioblastoma, we evaluated results from patients who were managed at the University of Pittsburgh and the Mayo Clinic.  Patients and Methods. Twenty-seven patients with 29 hemangioblastomas had stereotactic radiosurgery over a 10 year interval. The mean patient age was 32 years (range, 14–75 years). The tumor volumes varied from 0.36 to 27 ml (mean, 3.2 ml), and the mean tumor margin dose was 16 Gy (range, 11.7–20). Clinical and neuroimaging follow-up was obtained for all patients between 0.5 and 9 years (mean, 4 years) after radiosurgery.  Results. At this assessment, 21 patients (79%) were alive and six (21%) had died. The median survival after radiosurgery was 6.5 years (actuarial 5 year survival=75.1±11.5%). The median survival from the initial diagnosis was 15 years. Twenty two of 29 evaluable tumors were controlled locally. The two-year actuarial control rate was 84.5±7.1% and at five years, 75.2±8.9%. Multivariate testing of factors affecting good outcome indicated that smaller tumor volume and higher radiosurgical dose (>18 Gy) were significant.  Conclusion. For small to moderate size hemangioblastomas, multiple or recurrent tumors, and for patients who are not surgical candidates, radiosurgery is a safe and effective option to control disease and improve survival.     

分娩方式对乙型肝炎母婴传播阻断效果的影响

目的探讨乙型肝炎(乙肝)病毒携带孕妇不同的分娩方式对乙肝母婴传播的影响。方法51例HBV感染但无临床症状的孕妇分成2组,实验组(联合免疫组):孕妇产前及新生儿均注射乙肝免疫球蛋白(HBIG);对照组(单用乙肝疫苗组):孕妇产前及新生儿均不注射HBIG;上述所有新生儿均注射乙肝疫苗。随访3 a,每年检测新生儿HBsAg和抗-HBs,同时询问所观察婴儿的生产方式。结果3 a中剖宫产和经阴道分娩的两组婴儿HBsAg携带率和抗-HBs阳性率差异均无显著性(P>0.05)。结论不同分娩方式对乙肝母乳传播的阻断效果影响不大。     

Glutamate-induced gamma oscillations in the dentate gyrus of rat hippocampal slices

In this paper we show that gamma oscillations can be elicited by brief (< or = 200 ms) local applications of glutamate in the dentate gyrus of rat hippocampal slices. Dentate gamma oscillations show an initial peak frequency of approximately 70 Hz and last for up to 4 min. The network activity involves functional GABA(A) receptors as it is drastically reduced by GABA(A) receptor antagonists. The oscillations can be observed in the whole dentate gyrus-CA3-network and are coherent between the dentate gyrus and area CA3 for variable periods. Thus, long-lasting gamma oscillations can be experimentally induced in the dentate gyrus and are propagated into the hippocampus proper.     

Feto-maternal alloimmune thrombocytopenia due to HPA-5b incompatibility: a case report

Feto-maternal alloimmune thrombocytopenia (FMAIT) results from the maternal production of antibodies against fetal platelets with incompatible antigens inherited from the father. We present a case where this condition was diagnosed prenatally without previously affected siblings. The severe fetal thrombocytopenia was due to anti-HLA-5b maternal alloantibodies. This was treated successfully by intravenous immunoglobulins. Our case reflects that FMAIT due to anti-HPA-5b may be severe and may be corrected successfully with intravenous immunoglogulins.