The molecular genetic basis of Glanzmann's thrombasthenia in a gypsy population in France: identification of a new mutation on the alpha IIb gene

Glanzmann's thrombasthenia is a rare inherited bleeding disorder caused by a qualitative or quantitative defect of platelet alpha IIb beta 3. We describe here a new mutation that is the molecular genetic basis of Glanzmann's thrombasthenia in two gypsy families. Our investigation was focused on the alpha IIb gene as a result of biochemical and immunologic analysis of patients' platelets showing undetectable alpha IIb but residual beta 3 levels. The entire alpha IIb cDNA was polymerase chain reaction (PCR) amplified using patients platelet RNA. Sequence analysis showed an 8-bp deletion located at the 3' end of exon 15. This deletion causes a reading-frame shift leading to a premature stop codon and the synthesis of a severely truncated form of alpha IIb. Genomic DNA study showed a G-->A substitution, the Gypsy mutation, at the splice donor site of intron 15. This mutation results in an abnormal splicing occurring at an alternative donor site located 8 bp upstream from the mutation. Based on those results, an allele-specific PCR analysis was developed to allow a rapid identification of the mutation in patients and potential carriers of the gypsy community. This PCR analysis can also be used for genetic counseling and antenatal diagnosis.     

Intimal fibromuscular dysplasia and Takayasu arteritis: delayed response to percutaneous transluminal renal angioplasty

Percutaneous transluminal renal angioplasty has been shown to be an effective technique to dilate renal artery lesions, particularly those due to fibromuscular dysplasia. However, four of 70 patients in this study experienced atypical responses to angioplasty. Their lesions initially resisted dilation and had incomplete dilatation immediately after angioplasty. Long-term follow-up (1 week to 2 years) angiograms, however, demonstrated fully dilated arteries. In cases of focal nonatherosclerotic lesions from intimal or adventitial fibroplasia, initial incomplete dilatation may be satisfactory in the long term whereas repeated inflations may result in undesirable complications.     

石斛类叶鞘的显微鉴定研究

商品石斛的植物来源复杂,规格繁多,外形鉴定较困难。为了准确鉴定石斛的品种,对常作为药用的16种石斛属(Dendrobium Sw)植物的叶鞘进行了显微观察,发现其表皮细胞的形状,大小,所含草酸钙结晶的形状、大小、分布等种间区别较明显,可作为鉴别石斛种类的科学依据之一。本文对金钗石斛D.nobile Lindl。等16种石斛的叶鞘表面特征加以描述,并附主要特征图和检索表。     

动物组织膜L-维生素C电极的研究

本文以猪肝组织切片偶合氧电极制成了维生素C生物电极。测试了电极的响应特性,当Cu²⁺)离子存在下,在21.14～352.3μg/ml的维生素C浓度范围,电极的动力学响应与维生素C浓度的对数呈线性关系。研究了激活剂的浓度、缓冲介质、温度等因素对电极性能的影响。测得该条件下酶促反应的米氏常数8.0×10^-4mol/L。将电极用于药物中Vc含量分析,结果令人满意。     

Small bowel function in acute lymphoblastic leukaemia

Small bowel function before, during, and after treatment for acute lymphoblastic leukaemia was studied in 26 children. A significant impairment of D-xylose absorption was found during treatment. Permeability studies showed a significant decrease in mannitol and a significant increase in lactulose concentrations; five of 20 children tested had evidence of lactose malabsorption, three of whom were symptomatic. Intestinal function abnormalities were greater in children whose methotrexate treatments were separated by 7 day than by 16 day intervals. Only five (19%) children had no abnormal tests. Abnormalities of small bowel function may be treatment induced and this has implications for morbidity from gastrointestinal symptoms, impairment of the mucosal barrier, and malabsorption of both nutrients and drugs leading to malnutrition and suboptimal drug concentrations.     

A phase I dose-escalation and pharmacokinetic study of brostallicin (PNU-166196A), a novel DNA minor groove binder, in adult patients with advanced solid tumors.

PURPOSE: This study was performed to determine the maximum tolerated dose, dose-limiting toxicities, and pharmacokinetics of brostallicin, a nonalkylating DNA minor groove binder and a synthetic derivative of distamycin A, given as a weekly i.v. infusion. EXPERIMENTAL DESIGN: Using an accelerated dose escalation design, patients with advanced solid tumor malignancies were treated with brostallicin administered as a 10-min i.v. infusion on days 1, 8, and 15 of a 28-day cycle. The starting dose of brostallicin was 0.3 mg/m(2)/week. To study the pharmacokinetic behavior of brostallicin, serial blood samples were obtained before and after the first and last infusions during cycle 1, and in cycles 2 and 4 in a limited number of patients. RESULTS: Fourteen patients received 32 complete cycles of brostallicin. Dose-limiting toxicity was febrile neutropenia and was observed in 3 of 5 patients treated at 4.8 mg/m(2)/week. The maximum tolerated dose and recommended Phase II dose was 2.4 mg/m(2)/week. The mean +/- SD terminal half-life at the maximum tolerated dose was 4.6 +/- 4.1 h. There was moderate distribution of brostallicin into tissues, and the clearance was approximately 20% of the hepatic blood flow. The area under the concentration time curve(0- infinity ) of brostallicin increased in a dose-linear fashion. No significant relationship was observed between any plasma pharmacokinetic parameter and clinical toxicities. There were no objective responses during the trial, but 5 patients had stable disease after two cycles of treatment. CONCLUSIONS: The dose-limiting toxicity of weekly brostallicin was neutropenia. Systemic exposure increases linearly with dose. The recommended dose for Phase II studies is 2.4 mg/m(2) on days 1, 8, and 15 of a 28-day cycle.     

Hiding in the Bunker: Challenges for a radiation oncology department operating in the Severe Acute Respiratory Syndrome outbreak

In February 2003, one woman returned from Hong Kong to Singapore with a previously undescribed atypical pneumonia. Two months later, Singapore is facing its greatest ever threat to its population's health and the country's economy. The government has taken strong action to break the chain of infection of Severe Acute Respiratory Syndrome (SARS). As a radiation oncology department in Singapore, we have faced challenges in keeping staff and patients safe while continuing to provide a service to our patients. In this article, we outline the measures taken to curb SARS in Singapore and discuss the implications for Australasian radiation oncology departments.