Common bile duct calculi: updated experience with dissolution with methyl tertiary butyl ether

The authors describe their experience with methyl tertiary butyl ether (MTBE) in a larger series of patients than previously reported in order to acquaint physicians with both its effectiveness for dissolution of common bile duct calculi and the limitations of its use. Ten patients with 13 biliary calculi underwent percutaneous stone dissolution treatment with the experimental cholesterol solvent, MTBE. Three stones completely dissolved within 30 minutes, seven were reduced in size, and three were visibly unaffected. All stones not completely dissolved were easily extracted by means of a stone basket except for one in a patient taken to surgery. Although MTBE perfusion is an effective technique for management of biliary calculi, practitioners should be aware that its use is quite time consuming and its odor difficult to control.     

Segmental intestinal muscular thinning: a possible cause of intestinal obstruction in the newborn

Intestinal obstruction proximal to a transition zone without an interposed physical barrier usually indicates Hirschsprung disease. The authors report one case of focal small bowel muscular thinning just distal to a transition zone that produced clinical and radiographic findings that simulated long-segment Hirschsprung disease in a 2-day-old infant.     

Image-directed percutaneous biopsies with a biopsy gun

Core tissue for histologic study is believed by many pathologists to be more diagnostic than material from needle aspiration. Recently, a biopsy "gun" has been introduced, which simplifies core biopsies. With this device, 182 biopsies of multiple anatomic sites were performed with ultrasonic, computed tomographic, and fluoroscopic guidance and 18-gauge needles. High-quality histopathologic specimens were obtained in 177 of the biopsies, and diagnostic target tissue was obtained in 167. Only three significant complications occurred: one bleeding complication that required transfusion and two cases of pneumothorax that necessitated placement of chest tubes. The biopsy gun eliminated the disjointed movements of conventional "skinny" needle biopsies, and none of the samples demonstrated significant "crush" artifact or obscuring blood, problems that are commonly associated with manual biopsy techniques. Patient discomfort was decreased with this system compared with that of manual biopsies, and the total procedure time was reduced. Because of these distinct advantages, the authors now use the biopsy gun exclusively for all percutaneous biopsies and recommend that other institutions consider the use of this biopsy method.     

颅内蛛网膜囊肿34例

1　临床资料1.1　一般资料　 1986 / 1997收治颅内蛛网膜囊肿 34(男 2 8,女 6 )例 .年龄 3～ 6 8岁 ,其中 16岁以下 17例 .有头部外伤史者 15例 ,无明显诱因者 19例 .病程 :2 m o～ 14a.头部外伤至发病时间 :7d～ 2 a. 34例中幕上 30例 ,幕下 4例 ,其中侧裂池 15例 .1.2　临床症状　表现头疼、头昏或伴呕吐、视力下降、视乳头水肿等颅内压增高的症状 18例 ,癫痫发作 7例 ,偏瘫 6例 ,行走不稳 2例 ,失语 1例 .1.3　辅助检查　本组 2 8例作 CT检查 ,6例行 MRI检查证实 .头颅 CT扫描特征 :脑实质外有一边界清楚的低密度病灶 ,CT值与脑脊液…     

The Binding of Cyclosporin A to Human Plasma: An in Vitro Microdialysis Study

Purpose. The human plasma binding of cyclosporin A was studied in vitro using the technique of microdialysis. The effect of temperature on the overall binding interaction between cyclosporin A and human plasma was also investigated. Methods. Flow-through loop-type microdialysis probes were constructed from fused silica tubing and regenerated cellulose tubing with a MWCO of 13000 daltons. Probes were perfused with phosphate buffer (0.5 µl/min) and the concentration of ³H-cyclosporin A in the well-mixed medium (plasma or buffer) was 1200 ng/ml. Relative recoveries of cyclosporin A from plasma or buffer were determined for each probe by separate experiments to measure the solute gain or loss with reference to the perfusate. Results. Recoveries determined by loss were significantly greater than those determined by gain and in each case temperature dependent, with higher recoveries at higher temperatures. The plasma free fraction of cyclosporin A calculated from the recovery data and the perfusate to plasma concentration ratios was dependent on temperature in a log-linear fashion. Mean ± s.d. plasma free fractions expressed in percent were 33.5 ± 4.6, 17.9 ± 3.6, 6.2 ± 0.8, 3.0 ± 0.6, and 1.5 ± 0.2 at temperatures of 4, 10, 20, 30, and 37°C, respectively. Assuming that the enthalpy of binding is constant over the temperature range studied and pseudo-first order conditions exist, the binding reaction at these temperatures was spontaneous, endothermic (H = 74.0 kJ/mole), and entropically driven (S = 0.274 kJ/mole/deg). Conclusions. These results show that the free fraction of cyclosporin A in human plasma is dependent on temperature with the fraction unbound decreasing with temperature in the range of 4 to 37°C. The thermodynamic parameters for the binding of cyclosporin A to plasma components indicate that the reaction is a spontaneous endothermic reaction that is mainly entropy driven, similar to the partitioning of lipophilic molecules from an aqueous to a hydrophobic phase. Moreover, these results show that microdialysis is a feasible method to determine the binding interactions between plasma and cyclosporin A, which indicates the method may be suitable for other difficult binding studies where the solutes have nonspecific binding to separation devices.     

Efficacy of Zoladex LA (goserelin) in the treatment of girls with central precocious or early puberty

OBJECTIVE: To assess the efficacy of a longer acting preparation of the gonadotrophin releasing hormone (GnRH) analogue goserelin (Zoladex LA, 10.8 mg) in 12 girls with central precocious or early puberty. METHODS: Two girls started treatment de novo; the remainder had been on suppressive treatment for a median duration of 1.5 (range, 0.2-5.6) years. Assessment comprising auxology, pubertal staging, and pelvic ultrasound examination was carried out at weeks 0, 4, 8, 10, and 12 (first cycle) and weeks 8, 10, and 12 (second cycle) to evaluate the required injection frequency. Thereafter, assessment was performed on the day of injection. Zoladex LA was given every 12 weeks unless pubertal progression occurred. RESULTS: Satisfactory control was achieved in eight patients using this regimen, and three patients required more frequent injections. One girl was removed from the study because of clinical progression and extreme mood swings. No serious adverse effects occurred. Mean height velocity during the study period was 4.5 cm/year (range, 3.1-6.6) compared with 6.5 cm/year (range, 3.8-9.6) before treatment in nine patients for whom data were available. CONCLUSIONS: Zoladex LA was effective in controlling precocious puberty in girls when given at intervals of 9-12 weeks and it is recommended that an initial assessment is made eight weeks after beginning treatment.     

Expression of various multidrug resistance-associated protein (MRP) homologues in brain microvessel endothelial cells

Multidrug resistance-associated protein (MRP) actively transports a broad range of anionic compounds out of the cell. To date, six different homologues of MRP (i.e. MRP1-MRP6) have been identified. The current study examines the expression of the various MRP homologues in both primary cultured bovine brain microvessel endothelial cells (BBMEC) and the capillary-enriched fraction from bovine brain homogenates. RT-PCR analysis demonstrated the presence of MRP1, MRP4, MRP5 and MRP6 in both BBMEC and the capillary-enriched fractions of brain homogenates. While low levels of MRP3 were detected in the BBMEC, it was not observed in the capillary-enriched fraction. In addition, RT-PCR and Western blot studies indicated an absence of MRP2 expression in both blood-brain barrier preparations. The presence of several different MRP homologues in the brain microvessel endothelial cells may be important in controlling the permeability of the blood-brain barrier to organic anions.     

Barriers to Effective Drug Treatment for Brain Metastases: A Multifactorial Problem in the Delivery of Precision Medicine

The treatment of metastatic lesions in the brain represents a serious unmet medical need in the field of neuro-oncology. Even though many effective compounds have demonstrated success in treating peripheral (non-CNS) tumors with targeted agents, one aspect of this lack of success in the brain may be related to poor delivery of otherwise effective compounds. Many factors can influence the brain delivery of these agents, but one key barrier is a heterogeneously “leaky” BBB that expresses efflux transporters that limit the BBB permeability for many targeted agents. Future success in therapeutics for brain metastases must take into account the adequate delivery of “active, free drug” to the target, and may include combinations of targeted drugs that are appropriate to address each individual patient’s tumor type. This review discusses some issues that are pertinent to precision medicine for brain metastases, using specific examples of tumor types that have a high incidence of brain metastases.     

"Early-peak" carbon monoxide production in certain erythropoietic disorders

The "early-labeled" peak (ELP) of 14CO excretion following injection of glycine-2-14C was used to study erythropoiesis in a patient with sideroblastic anemia and in four subjects with myeloproliferative disorders. The ELP was greatly enlarged in all patients, as compared with a normal volunteer. The contour of the peaks from the hematologically abnormal subjects suggested the presence of increased erythroid heme degradation. In the patient with sideroblastic anemia, all hours of the early peak were significantly reduced after transfusion. This was interpreted to mean that even the earliest or "nonerythroid" phase of the peak is influenced by erythropoietic activity, at least under conditions of erythropoietic stress.