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Biomedical subjects

C J Peine

Publications and source records attributed to C J Peine.

6 recordsLinked to original sources

Gallstone-dissolving agents.

It can be anticipated that most new therapies will generate considerable excitement and optimism when introduced. This is usually tempered with time as additional clinical experience is gained and therapeutic limitations and adverse effects are realized. All areas in the nonsurgical management of gallstones have experienced this course--some, such as ESWL, rather meteorically. Perspective, however, is important and may allow the appropriate use of each of these modalities in the correct clinical setting. For example, ursodiol when given in sufficient dose to nonobese patients with small radiolucent stones, could be expected to effect partial or complete dissolution in as many as 75% of patients, with minimal or no adverse effects and in a cost-effective manner. Contact dissolution using MTBE has been shown to be safe and generally effective but requires diligent characterization of stones to avoid those that are pigmented or heavily calcified. Similarly, ESWL combined with oral bile acids may be consistently effective if treatment is restricted to patients with acceptable cholesterol stone burdens and if treatment can be safely continued until fragments are substantially reduced. Continued experience with each of these treatment options, along with advances in research providing new solvents and technologies or in preventing recurrence, is likely to establish this field in an appropriately optimistic light.

Bile Acids and Salts

Safety of same-day sequential extracorporeal shock wave lithotripsy and dissolution of gallstones by methyl tert-butyl ether in dogs.

Passage of stone fragments after extracorporeal shock wave lithotripsy (ESWL) of gallstones has resulted in biliary colic, duct obstruction, and pancreatitis in some patients. Rapid dissolution of these fragments with methyl tert-butyl ether (MTBE) may prevent such side effects and achieve complete clearance of gallstones within hours rather than several months to a year or longer. This study examines the safety of same-day ESWL fragmentation and MTBE dissolution of surgically implanted human gallstones in 15 dogs. The animals were randomly assigned to one of four treatment groups to assess MTBE absorption from the gallbladder and to observe hematology and chemistry profiles after 0, 400, and 1,200 shock waves from a lithotriptor followed by MTBE dissolution therapy. They were sacrificed either immediately after treatment (12 dogs) or 2 weeks later (3 dogs). The results demonstrated that although ESWL causes moderate trauma to the gallbladder, this did not result in increased MTBE absorption or histologic evidence of mucosal disruption. Blood profiles demonstrated an increase in only the level of aspartate aminotransferase. The three dogs that were sacrificed 2 weeks after the combined treatment had no residual evidence of gallbladder injury or remaining stone material. In all animals, severe injury occurred where shock waves passed through lung or air-filled colon. This study suggests that same-day sequential fragmentation of gallstones by ESWL followed by dissolution of stone fragments with use of MTBE may be associated with only mild to moderate and reversible gallbladder trauma and can rapidly achieve clearance of gallstones.

Animals

Dissolution of cholesterol gallbladder stones by methyl tert-butyl ether administered by percutaneous transhepatic catheter.

We treated 75 patients with symptomatic cholesterol gallstones by dissolving the stones with methyl tert-butyl ether (MTBE) instilled into the gallbladder through a percutaneous transhepatic catheter. The MTBE was continuously infused and aspirated manually four to six times a minute, for an average of five hours per day for one to three days; the treatment was monitored by fluoroscopy. The placement of the catheter and the administration of MTBE caused few side effects or complications, and treatment did not have to be stopped in any patient for this reason. In 72 patients there was complete dissolution of stones or more than 95 percent dissolution. Among 21 patients who were completely free of stones after treatment, 4 had recurrence of stone formation 6 to 16 months later. The other 51 patients had residual debris, which spontaneously cleared completely in 15 patients within 6 to 35 months; only 7 with persisting debris have had symptoms. Five of the initial 6 patients treated, but only 1 of the next 69 patients, have required surgery during follow-up periods of 6 to 42 months. We conclude that the dissolution of gallstones by MTBE delivered through a percutaneous transhepatic catheter is a useful alternative to surgery in selected patients with symptomatic cholesterol stones. Further study will be necessary to establish the long-term effectiveness of this treatment and its appropriate role in the management of the various types of gallstones.

Adult

Extracorporeal shock-wave lithotripsy and methyl tert-butyl ether for partially calcified gallstones.

To explore the possibility that gallbladder stone fragments might be able to be safely dissolved using methyl tert-butyl ether immediately after extracorporeal shock-wave lithotripsy (ESWL), a feasibility study in 8 patients with one to four partially calcified gallbladder stones was performed. The gallstones averaged 2.2 cm in diameter (range 1.3-3 cm) and contained layered or diffuse calcium detectable by computed tomography scan only (7 patients) or plain film (1 patient). After a 5F (1.7 mm) pigtail catheter was placed percutaneously into the gallbladder, ESWL fragmentation was performed using a renal stone lithotriptor. The patients were under general anesthesia and in the prone position on a support gantry designed for gallbladder stone ESWL. Following ESWL, methyl tert-butyl ether was infused and aspirated via the gallbladder catheter until no further stone material was radiologically detectable or could be dissolved. After 8-26 h (mean = 13 h) of methyl tert-butyl ether therapy, no radiologically detectable gallstones remained in 6 of 8 patients. Shell fragments of three peripherally calcified stones in 1 patient and the densely calcified, predominantly pigment stone in a second patient were refractory to combined therapy. Both ESWL and treatment with methyl tert-butyl ether were well tolerated in all patients, although bile leakage after catheter removal occurred in 3 patients, one of whom was treated by cholecystectomy. Additional measures to prevent bile leakage may be advisable if these two modalities are to be used in tandem. We found no evidence, however, that predissolution stone fragmentation with ESWL predisposed the gallbladder to either mucosal damage by methyl tert-butyl ether or increased absorption of it.

Aged

Scanning electron microscopy of cardiac endothelium of the dog.

Tissue obtained from young dogs was fixed in buffered aldehydes by vascular perfusion or direct immersion. Selected hearts were maintained in modified mammalian Ringer's solution for three to five minutes prior to fixation. The chambers of the heart and related valves were exposed by dissection and prepared by routine techniques for observation by scanning electron microscopy (SEM). Subsequent to SEM studies, selected specimens were embedded in Epon 812 and sectioned for transmission electron microscopy (TEM). The cardiac endothelium, when fixed immediately in buffered aldehydes, presents an essentially invariable surface throughout the interior of the heart. The predominant nuclear bulges and attenuated peripheral plasmatemma are consistently smooth, with occasional marginal ruffles, scattered microvilli and small blebs. Apart from the higher population of nuclear bulges on valvular surfaces, local variations in SEM of endocardium occur in response to the various stages of systole and diastole encountered. These physiological changes do not produce microappendages. Immersion for three to five minutes in (Chenoweth's) Ringer's solution, prior to fixation, produces a substantial population of microappendages. The cellular surface acquires a swirled appearance erupting in microvilli, blebs and ruffles. These exhibit considerable pleomorphism. There is great lability of the endocardial surface in response to a classic "holding solution" widely used in preparatory techniques. In preparing soft tissues for SEM caution must be used if physiological "holding solutions" are used prior to fixation.

Animals