Colonic delivery of dexamethasone: a pharmacoscintigraphic evaluation

Background: Colonic delivery of corticosteroids may reduce the side-effects commonly associated with their use. Therefore, we tested the ability of the naturally occurring polysaccharide guar gum to deliver a corticosteroid, dexamethasone, to the colon using pharmacoscintigraphy. Guar gum is metabolized in the colon by resident bacterial enzymes to trigger drug release. Materials: Each subject (eight per group, parallel study design) was administered one of four dexamethasone (9 mg) tablet formulations, radiolabelled with ¹⁵³Sm using neutron activation, under fasted conditions. One formulation was designed to release drug rapidly following ingestion while the other three formulations were designed to delay release of dexamethasone to varying degrees. Progression of the formulations down the gastrointestinal tract was followed by gamma scintigraphy. Serum concentrations were measured over time to relate disintegration profiles of the tablets with pharmacokinetic observations. Results: The immediate release formulation disintegrated in the stomach, on average, within 20  min of dosing. One of the three delayed release preparations (CD₁) began to disintegrate in the small intestine 1.7±1.0 h after dosing. The second and third delayed release preparations (CD₂ and CD₃) did not begin to disintegrate until 5.8±2.3 and 3.6±1.6 h after dosing, respectively. All three colonic delivery preparations completely disintegrated in the colon ranging from 7.8±2.7 h (CD₁) to 12.4±3.2 h (CD₂) following oral administration. Pharmacoscintigraphic data indicated that 72–82% of the dexamethasone was delivered into the colon although not all the dexamethasone delivered into the colon was absorbed. Conclusions: Simple guar gum formulations are capable of delivering the corticosteroid dexamethasone to the colon of normal subjects. Locally delivered corticosteroids may be useful in the treatment of ulcerative colitis and Crohn's disease. Pharmacoscintigraphic evaluation is a useful method to discriminate between the in vivo behaviour of colonic delivery systems.     

Twelve-year follow up of a randomized prospective trial comparing bacillus Calmette-Guerin and epirubicin as adjuvant therapy in superficial bladder cancer

AIM: To compare bacillus Calmette-Guerin (BCG) with epirubicin in adjuvant therapy of superficial bladder transitional cell carcinoma, with respect to recurrence, progression and survival. Prognostic factors are also evaluated. METHODS: Between October 1991 and September 1999, all patients harboring superficial bladder cancers (Ta or T1) with any of the relevant criteria (stage>a, grade>1, size>1 cm, multiple or recurrent tumors), after complete transurethral resection were randomized to receive either 81 mg Connaught strain BCG or 50 mg epirubicin. Patients with recurrences were eligible to crossover, even repeatedly, until progression. Recurrence, progression and survival were analyzed in relation to initial treatment, patient characteristics and tumor characteristics. RESULTS: There were 209 patients included in the study, 149 men and 60 women. The mean age was 69.9 years (range, 24-92). The BCG group consisted of 102 patients and the epirubicin group contained 107 patients. Final analysis was made at a median follow up of 23, 47 and 61 months for recurrence, progression and survival, respectively. The 10-year Kaplan-Meier estimates for recurrence-free, progression-free and disease-specific survival were 61%, 78% and 80%, respectively, for the BCG group. The corresponding figures were 32%, 74% and 92%, respectively, for the epirubicin group. Time to recurrence differed significantly between two treatment groups (P=0.0004). Multiplicity increased the risk of recurrence, while grading influenced recurrence, progression and disease specific survival. CONCLUSIONS: Bacillus Calmette-Guerin prolonged time to recurrence when compared with epirubicin. Grading was shown to be a universal prognostic factor for recurrence, progression and disease specific survival.     

Influence of Sulphate Ions on the Structure of AA Amyloid Fibrils

To explore the possible interaction of sulphated GAG with AA amyloid peptides, human AA amyloid fibrils were exposed to buffers containing various salts, and the accessibility of free amino groups on the peptides to reductive methylation was examined. Sodium chloride had little effect except at concentrations of 1 M, where it reduced the accessibility of AA peptides to labelling. In contrast 70 mM Na2SO4 led to a significant increase in peptide accessibility to labelling. The results suggest that, at least in part, GAG interact with AA peptides through their sulphate moieties.     

Dyschromatosis universalis with X-linked ocular albinism

A 10-year-old Chinese boy with the characteristic skin manifestations of dyschromatosis universalis is described. In addition, the patient had congenital nystagmus with poor visual acuity, and ophthalmological examination revealed foveal hypoplasia and albino-like fundi. Histopathology showed giant pigment granules in the skin. Based upon the finding of giant pigment granules in clinically normal skin of the patient's mother, the patient was diagnosed as a case of dyschromatosis universalis with X-linked ocular albinism. To the best of our knowledge, this is the first documented case of this combination.     

After-hours radiology

After-hours radiological procedures are essential but expensive in any major teaching hospital. Using the criteria that radiological procedures performed after-hours should have a reasonable probability of influencing or changing patient management acutely, a study of the justification of after-hours radiological procedures was performed at the Princess Alexandra Hospital. Computer print-outs were used to select the patients based on the dates and times of the procedures. Their charts were then reviewed. The study found that most after-hours radiological procedures were justified. However, it also identified certain procedures that need not be performed or at least could be reduced after-hours. The procedures were: (i) computed tomography (CT) head – epilepsy, meningitis; (ii) CT abdomen – trauma (intubated) – unable to examine abdomen; (iii) CT spine – obvious unstable fractures; (iv) Ultrasound abdomen – biliary colic (afebrile); and (v) Ultrasound kidneys – renal failure (afebrile).     

Use of spiral and non-spiral computed tomography arterial portography in the detection of potentially malignant liver masses

The present study assesses the usefulness of computed tomography (CT) arterial portography (CTAP) in detecting and defining the number and anatomy of potentially malignant liver lesions. One hundred and one adults studied in 1993 and 1994 were retrospectively reviewed, including patients with primary or secondary tumours for possible resection and patients with non-hepatic malignancies in whom the detection of liver metastases would preclude surgery. Twenty-three patients underwent non-spiral CT studies and 78 had studies on a spiral unit, with 22 of these having single phase and 56 having dual phase studies to overcome artefact problems. The relationship between lesion size and detection sensitivity is critical. On non-spiral studies, the overall lesion detection sensitivity and positive predictive value was 69 and 90%, respectively. Detection sensitivity was 100 and 20% for lesions > 1 cm and < 1 cm, respectively. On single phase spiral CTAP the overall detection sensitivity and positive predictive value was 80 and 66%, respectively. Detection sensitivity for lesions > 1 cm and < 1 cm was 100 and 0%, respectively. On dual phase spiral CTAP the overall detection sensitivity and positive predictive value was 76 and 71%, respectively. For lesions > 1 cm and < 1 cm the sensitivity was 81 and 55%, respectively. Eighteen patients with non-hepatic malignancies with unsuspected metastatic spread did not proceed to major surgery because of liver metastases detected on CTAP. Perfusion artefacts occurred in 30 and 64% of non-spiral and of initial portal venous spiral CTAP studies, respectively. By using the double-phase technique, these artefacts were substantially diminished. In conclusion, CTAP is a valuable tool for assessing the presence, site and size of possible liver tumours and confers a benefit even when previous ultrasound and conventional CT have already been used. In addition, CTAP has a lower limit of useful resolution of approximately 1 cm. Perfusion artefacts can be reduced by a dual phase protocol.     

朱震亨从脾胃病探析误诊误治

[目的]通过探析《局方发挥》之脾胃病误诊误治,以期指导与改进现代医家临床治疗。[方法]对《局方发挥》之脾胃病误诊误治进行整理分析,揭示朱震亨从脾胃病探析误诊误治的特色。[结果]朱震亨从脾胃病论误诊误治的特色:1)《和剂局方》具有误导性脾胃病治疗的中医知识,导致当时医者与患者误诊误治脾胃病。2)《和剂局方》引起的脾胃病误诊误治问题,主要可分成两类:辨证失误和治法失误。3)辨证失误所导致的误诊误治包括忽视审证求因、认为"诸寒为病"、误辨寒热虚实等。4)治法失误包括"一方通治诸病"、滥用辛香燥热药组方、利用砒丹巴硇行积垢、修改汤剂为丸剂、用峻剂盲目祛邪及错误滋补等。[结论]朱震亨在《局方发挥》指出当时脾胃病的误诊误治问题,显示出了其独特见解,对现代医家治疗脾胃病,具有一定的指导作用与参考价值。     

吡嗪酰胺耐药性结核分枝杆菌的噬菌体检测技术研究

目的 建立噬菌体生物扩增法（PhaB）快速测定吡嗪酰胺耐药性，并探讨其在结核分枝杆菌吡嗪酰胺耐药性测定中的应用价值。方法 应用建立的PhaB测定108株结核分枝杆菌临床分离株的吡嗪酰胺耐药性，并与绝对浓度法的药敏结果进行比较，对不符合的菌株进行最低抑菌浓度（MIC）测定和序列测定分析。结果 PhaB检测吡嗪酰胺耐药性的最佳测定条件为pH值5．5、药物浓度200μg／ml、37℃作用48h。用绝对浓度法检测108株结核分枝杆菌临床分离株，其中吡嗪酰胺敏感33株、耐药75株；用PhaB检测该108株结核分枝杆菌临床分离株，若以噬菌斑减少95％为判断标准。则吡嗪酰胺敏感32株，耐药76株。2种方法检测均为敏感的为28株，均为耐药的为71株，符合率为91．7％；2种方法检测结果不符的为9株，其中5株的PhaB结果与MIC结果相符，4株的结果不符，测序结果表明9株中有7株的PhaB结果与测序结果相符。如以绝对浓度法药敏结果为判断标准，PhaB检测吡嗪酰胺耐药性的敏感性为94．7％，特异性为84．8％，阳性预测值为93．4％，阴性预测值为87．5％，准确性为91．7％。结论 PhaB测定吡嗪酰胺耐药性简便、快速，3d即可获得药敏结果，可作为吡嗪酰胺耐药性的快速筛选方法。