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Apoenzyme samples of aspartate aminotransferase (AspAT) purified from the cytosolic fraction of pig heart were reconstituted with [4'-13C]pyridoxal 5'-phosphate (pyridoxal-P). The 13C NMR spectra of AspAT samples thus generated established the chemical shift of 165.3 ppm for C4' of the coenzyme bound as an internal aldimine with lysine 258 of the enzyme at pH 5. In the absence of ligands the chemical shift of C4' was shown to be pH dependent, shifting 5 ppm upfield to a constant value of 160.2 ppm above pH 8, the resulting pKa of 6.3 in agreement with spectrophotometric titrations. The addition of the competitive inhibitor succinate to the internal aldimine raises the pKa of the imine to 7.8, consistent with the theory of charge neutralization in the active site. In the presence of saturating concentrations of 2-methylaspartic acid the C4' signal of the coenzyme was shown to be invariant with pH and located at 162.7 ppm, midway between the observed chemical shifts of the protonated and unprotonated forms of the internal aldimine. The intermediate chemical shift of the external aldimine complex is thought to reflect the observation of an equilibrium mixture composed of roughly equal populations of the protonated ketoenamine and a dipolar anion species, corresponding to their respective spectral bands at 430 and 360-370 nm. Conversion to the pyridoxamine form was accomplished via reaction of the internal aldimine with L-cysteinesulfinate or by reduction with sodium borohydride, and the resulting C4' chemical shifts were identified by difference spectroscopy. Finally, the line widths of the C4' resonance under the various conditions were measured and qualitatively compared. The results are discussed in terms of the current mechanism and molecular models of the active site of AspAT.

Symptomatic cholelithiasis affects a large segment of the population. Several nonoperative therapeutic alternatives for treatment of these gallstones have recently been developed. We present here the technical aspects and results of gallstone dissolution in 75 patients with the use of methyl tert-butyl ether (MTBE) administered via a small percutaneously placed cholecystostomy catheter. Successful stone dissolution was achieved in 69 patients. The average time required for stone dissolution was 12.4 h over an average of 2.4 days, with the success and rate of dissolution being very dependent on technique. Six patients have developed recurrent gallstones. Future efforts will focus on decreasing the labor intensity of the procedure, dealing with the noncholesterol components of gallstones, and preventing gallstone recurrence.

Suppression of rheumatoid factor (RF) production in rheumatoid arthritis (RA) has been variably attributed to the use of remittive agents per se or to clinical improvement associated with their use. There have been conflicting reports with regard to the influence of methotrexate (MTX) on serum RF levels in RA. We determined IgM-RF and IgA-RF levels in paired serum samples (obtained at study entry and completion) from RA patients enrolled in multicenter trials with the Cooperative Systematic Studies of Rheumatic Diseases program. After exclusion of the 14 IgM-RF-negative sera, there were samples from 30 MTX-treated patients and 52 placebo-treated patients. Changes in IgM-RF and IgA-RF levels were weakly associated with each other. Significant decreases in IgM-RF levels were observed in the MTX-treated patients, but not in the placebo group. These changes were most significant in the MTX-treated patients who improved clinically. There were significant decreases in IgA-RF levels at study completion among MTX-treated patients who had improved clinically and those who had not improved clinically, but not in the placebo group. The contributions of clinical improvement and MTX treatment to changes in serum IgM-RF and IgA-RF levels were examined using a logistic regression model. Changes in IgM-RF were strongly related to MTX treatment and, to a lesser extent, to clinical improvement; changes in IgA-RF were related only to MTX treatment. These results indicate that MTX treatment per se decreases both IgM-RF and IgA-RF levels, whereas clinical improvement correlates with decreased IgM-RF levels only.(ABSTRACT TRUNCATED AT 250 WORDS)

Males ofXylocopa micans employ two mating systems in south-central Texas. They defend territories around flowering wisteria and redbud in March and April, and they maintain nonresource-based or landmark territories in July and August. Mandibular and mesosomal gland contents (analyzed by GC-MS) are different in bees employing the two mating systems. Mandibular glands contain only straight-chain hydrocarbons in bees defending floral resources, but include ethyl oleate in bees defending landmark territories. Mesosomal glands contain saturated, mono- and diunsaturated straight-chain hydrocarbons and methyl and ethyl esters of long-chain fatty acids. The major ethyl ester, ethyl oleate, comprises only 1.1% of mesosomal gland contents in bees defending floral resources but comprises 39.7% of gland content of bees defending landmark territories. These findings are discussed relative to the proposed sex pheromone function ofXylocopa gland secretions.

Aspirin is recommended for initial therapy of RA. If aspirin is not tolerated, an NSAID is recommended. The choice of NSAID should be based on cost, convenience, safety, and the personal experience of the physician. An adequate trial of at least 2 weeks should be completed before changing to another NSAID. Therapy should be closely monitored for adverse reactions, particularly renal and gastrointestinal effects.

A composite index for estimating improvement in individual rheumatoid arthritis (RA) patients during trials of slow-acting, disease-modifying antirheumatic drugs (DMARDs) was developed by analyzing the responses of 130 placebo-treated participants in Cooperative Systematic Studies of Rheumatic Diseases studies. If responses in 4 of 6 selected measures were required for improvement (by greater than or equal to 20% for morning stiffness, Westergren erythrocyte sedimentation rate, joint pain/tenderness score, and joint swelling score, and by greater than or equal to 2 grades on a 5-grade scale, or from grade 2 to grade 1 for patient's and physician's overall assessments of current disease severity), few placebo-treated patients qualified as improved, whereas significantly more DMARD-treated patients demonstrated improvement. The proposed index appears to be useful in estimating the probability that an RA patient will improve if taking a placebo during a DMARD trial, and may be a useful tool for analysis of DMARD studies.

In a double-blind, randomized trial of methotrexate vs placebo in rheumatoid arthritis, the effect of treatment on physical, social, and emotional function was measured in two different ways: the same, standard measurements in all patients, and individualized measurements selected by the patients at the start of the trial as representing the functions they most wanted to have improved by treatment. On the standard measurements, methotrexate-treated patients fared better than placebo-treated patients in their physical, social, and emotional function by 11%, 5%, and 6%, respectively, results that, although statistically significant, were small. However, methotrexate-treated patients were 29% better in the individualized measures, a result that was both highly statistically significant and greater than the differences in the standard measurements or in joint counts, grip strength, proximal interphalangeal joint circumference, morning stiffness, or walking time. Because the individualized measurements were as efficient as the best direct joint examination measures, yet reflected functional outcomes of greatest importance to individual patients, they constitute useful measures for such trials.

This study assessed the relative efficacy and toxicity of second-line antirheumatic drugs in patients 65 years of age or older compared to younger counterparts. The results of three prospective, double-blind, parallel, randomized, multicenter trials were reanalyzed, stratifying outcomes by intervention and patient age. Efficacy was assessed by categorizing patient responses as follows: important improvement, no meaningful change, or progressive disease. Toxicity was analyzed by comparing withdrawal rates due to adverse effects. The three trials compared the following treatments: (1) D-penicillamine 10-12 mg/day versus azathioprine 1.25-1.5 mg/kg/day; (2) gold sodium thiomalate 50 mg intramuscularly weekly versus auranofin 6 mg/day versus placebo; and (3) pulse oral methotrexate 7.5-15.0 mg weekly versus placebo. At baseline, 103 patients age 65 or older were similar to 485 patients less than 65 years of age, with the exception of disease duration in all studies and erythrocyte sedimentation rate in one study. For patients completing each study, efficacy outcomes based on age were not significantly different. Withdrawal rates due to adverse drug reactions were also not significantly different.

A comparison of placebo, auranofin, and parenteral gold sodium thiomalate therapy in 209 patients with active rheumatoid arthritis was performed in a 21-week prospective, controlled, double-blind multicenter trial. When the 161 patients who completed at least 20 weeks of treatment were analyzed for different degrees of response, no remissions were identified. When 50 percent or greater improvement of pain/tenderness scores were compared for end of trial versus entry values, 9 percent of placebo-treated patients, 34 percent of auranofin-treated patients, and 48 percent of gold sodium thiomalate-treated patients showed important improvement that was statistically significant for both gold treatments. When 50 percent improvement for joint swelling was analyzed, 12 percent of the placebo-treated group, 28 percent in the auranofin-treated group, and 37 percent in the gold sodium thiomalate-treated group showed this degree of improvement. Auranofin almost achieved statistical significance for improvement in joint swelling when compared with placebo (p = 0.07), but gold sodium thiomalate was much better than placebo (p = 0.009). There was no statistically significant difference between the two gold treatments. Thus it appears that a subset of patients had an important response to gold therapy that would not be evident by the usual analyses of mean or median changes. Analysis for predictors of response did not discriminate between responders and nonresponders. Because the trial was limited to 21 weeks of therapy, no prediction of the longer-term-effects, especially for auranofin, should be inferred.

Two hundred twenty-five patients with active severe rheumatoid arthritis were admitted to a multiclinic, controlled, double-blind trial comparing the use of 500 mg D-penicillamine per day, 125 mg D-penicillamine per day, and placebo. One hundred seventy-one patients completed at least 30 weeks of therapy. The 500 mg D-penicillamine group demonstrated statistically significant improvement over the placebo group in grip strength, average circumference of swollen proximal interphalangeal joints, and patient assessment. While the trend was for greater improvement with the larger dose of D-penicillamine, there was no statistically significant difference among the 3 groups in duration of morning stiffness, walking time, physician's assessment, number of swollen joints, or scores for tender and swollen joints. The slight increase in efficacy of higher dose D-penicillamine was associated with increased toxicity.

Articular complications are now frequently recognized with jejunoileal-bypass surgery for morbid obesity. We have evaluated 6 referred patients with these problems and 50 consecutive patients who had this procedure. The arthritis is variable but usually affects multiple joints. Four patients were seen during acute attacks of arthritis and all had cryoprecipitable material in their sera and plasma. Three of these 4 patients had evidence of Group D streptococcal antigen present while their joint disease was active, suggesting a possible role for bacterial antigens in the pathogenesis of the arthritis of jejunoileal bypass.

Combined gas chromatography-electroantennogram (GC-EAG) recording ofCampoletis sonorensis (Cameron) responses to cotton plant volatile chemicals was performed.C. sonorensis antennal olfactory receptors respond differentially to green leaf, mono-, and sesquiterpene chemicals that have been identified previously in cotton. EAG depolarizations to green leaf chemicals were greater than to terpenes.

Gas chromatographic analysis revealed that chemicals attractive toCampoletis sonorensis (Cameron), previously identified in cotton, were not present in wheat germ diet-rearedHeliothis virescens (F.) larvae. Diet-reared larvae fed cotton obtained the chemicals from cotton, with the consequence of enhanced kairomonal activity of the larvae and their frass toC. sonorensis. Parasitoids, presented a choice between cotton, cotton plus hosts, hosts alone, and control in an olfactometer, responded non-randomly, with the greatest number of responses to cotton plus hosts, and three times as many responses to cotton alone as to larvae alone. The role of the plant in the parasitoid-host relationship is discussed.

Two hundred eight patients were studied in a prospective, controlled, double-blind multicenter trial comparing auranofin (AUR), gold sodium thiomalate (GST), and placebo. One hundred sixty-one patients completed at least 20 weeks of therapy. Response to a variety of measures of efficacy was generally modest for both gold treatment groups although improvement was continuing in both groups at the end of the study. There was statistically significant improvement with both gold preparations compared to placebo for the number of tender joints, the joint tenderness score, and physician assessment of disease severity. GST was also significantly better than placebo for the joint swelling score. GST demonstrated more improvement in patients with anemia and thrombocytosis compared to the other treatment groups and both gold preparations were superior to placebo in improvement of an elevated erythrocyte sedimentation rate. Twenty-seven percent of patients on GST were withdrawn from the study for adverse drug reaction with rash and stomatitis being the predominant cause. Only 6% of patients on AUR were withdrawn for untoward drug effect. The time of onset of the adverse reactions is discussed. The two gold preparations were similar in efficacy although AUR was better tolerated.

A 32-year-old woman underwent jejunoileal bypass surgery for morbid obesity. Her postoperative course was marked with many of the complications of this type of surgery. In addition, tender, erythematous nodules developed on her legs and abdomen that were grossly and microscopically consistent with nodular nonsuppurative panniculitis. She did not have any condition or disease previously reported to be associated with nodular nonsuppurative inflammation. The nodular panniculitis in this patient appears to be a new complication of small-bowel bypass surgery.

Thirty-seven patients with psoriatic arthritis were entered into a 12-week prospective, controlled, double-blind multicenter trial comparing placebo and oral pulse methotrexate therapy. Methotrexate was given in a dose of 2.5-5.0 mg every 12 hours in 3 consecutive doses per week. A stable background medication program with nonsteroidal antiinflammatory drugs was allowed. Methotrexate was superior to placebo only in physician assessment of arthritis activity and in improvement of the amount of skin surface area with psoriasis. A small but statistically significant rise of serum total bilirubin occurred in the methotrexate-treated patients. No patients were withdrawn from the study for adverse drug effects.

This report describes clinical experience with a radiopaque silicone elastomere (Silastic) umbilical artery catheter. Twenty infants, ten with polyvinyl chloride (PVC) umbilical artery catheters and ten with Silastic umbilical artery catheters, all positioned at the aortic bifurcation, had aortograms performed at the time of catheter removal. Catheter-associated thrombus formation was observed in nine of the ten infants (90%) with PVC umbilical artery catheters and in one of the ten infants(10%) with Silastic catheters. The incidence of lower extremity vasospasm associated with the two catheters was not significantly different. Aortic pressure tracing recorded through Silastic catheters were accurate, but slightly damped. Autopsies were performed on five additional infants who died with indwelling Silastic umbilical artery catheters. None of the catheters, nor their surrounding tissues, showed evidence of thrombus formation on either gross or microscopic examination. It is our experience that radiopaque silicone elastomere tubing can be used as an umbilical artery catheter and appears to have the advantage of being less thrombogenic than the standard PVC tubing currently in general use.

Two hundred six patients were entered into a prospective controlled, double-blind, multicenter trial comparing azathioprine (AZA) 1.25-1.5 mg/kg/day with D-penicillamine (DP) 10-12 mg/kg/day. One hundred thirty-four patients completed 24 weeks of therapy. Improvement in nearly all efficacy variables was seen in both groups. Patients taking DP demonstrated a greater rise in hemoglobin concentration and greater fall in erythrocyte sedimentation rate than patients receiving AZA; these were the only efficacy variables with a significant difference between the treatment groups. Fewer withdrawals for adverse reactions occurred among the patients receiving AZA, but the difference was not significant. Patients receiving AZA were withdrawn from the drug mainly for abnormal liver function test results, nausea and gastrointestinal upset, and leukopenia. The main reasons for withdrawal of patients receiving DP were nausea, rash and pruritus, thrombocytopenia, dysgeusia, and proteinuria.

A prospective controlled, double-blind multicenter trial compared placebo, auranofin (an orally administered gold complex), and parenteral gold sodium thiomalate (GST) in patients with active rheumatoid arthritis (RA). Of 193 patients who received any treatment, the only important improvement identified for either auranofin or GST was for pain/tenderness scores. When 161 patients who completed 20 weeks of treatment were examined, both auranofin and GST treatments were superior to placebo as measured by improvement in number of painful and/or tender joints, joint pain/tenderness scores, physician's assessment of disease activity, and decrease in erythrocyte sedimentation rate when elevated at entry. GST was superior to placebo in improvement of joint swelling scores, anemia, thrombocytosis, and rheumatoid factor. No drug-related remissions were observed. The only statistically significant advantages of GST over auranofin for efficacy were an increase in hemoglobin concentration and decrease of thrombocytosis with GST. Withdrawals for adverse effects were 5 times more frequent with GST treatment. Thrombocytopenia, proteinuria, elevated liver enzymes, "nitritoid" reactions, and "gold pneumonitis" were observed only in the GST treatment group. These results confirm that both parenteral and oral gold may be effective for the treatment of RA, that GST tends to show greater efficacy than auranofin, and that auranofin has fewer significant adverse effects than GST. However, long-term benefits, tolerability, and safety cannot be inferred from this study.

Percutaneous renal and ureteral stone removal procedures are widely practiced. A new technique is described for removal of small symptomatic ureteral calculi using small (less than or equal to 14 French) tearable sheaths and standard stone retrieval baskets placed through acute percutaneous nephrostomy tracks. This fluoroscopically-guided technique was successful in 60 of 64 patients, who ranged from 16 to 88 years old. Subsequent endoscopic percutaneous calculus removal was successful in the four failures. The use of these small sheaths over previously described large tracks has produced no major complications, short hospital stays, and minimal patient disability.

Gallstone formation complicating cardiac valve replacement has been amply documented in adults. Two children who developed gallstones shortly after cardiac valve surgery are reported.

Gynecomastia was found in a patient taking 12 mg of auranofin (AF) daily. The gynecomastia was noticed after AF was increased to this dose and resolved after the drug was discontinued. The patient refused rechallenge.

Males of the solitary Central American beeCentris adani Cockerell possess enlarged mandibular glands filled with a fragrant fluid that was shown by gas chromatographic and mass spectral analysis to consist of nerol, geraniol, neral, ethyl laurate, and geranyl acetate. Male bees set up territories by marking a semicircular array of grass stems with these compounds. Grass stems marked by the bees showed the presence of the same chemicals.

One hundred eighty-nine patients with rheumatoid arthritis were entered into a prospective, controlled, double-blind multicenter trial comparing placebo and methotrexate (MTX). One hundred ten patients completed 18 weeks of therapy. No remissions were seen, but patients able to tolerate low-dose pulse MTX therapy were significantly improved, compared with patients receiving placebo therapy, for all clinical variables measured, including joint pain/tenderness and swelling counts, rheumatoid nodules, and patient and physician assessment of disease activity. MTX treatment demonstrated statistically significant improvement over placebo in patients with anemia, elevated erythrocyte sedimentation rate, and rheumatoid factor. However, nearly one-third of the patients receiving MTX were withdrawn for adverse drug reactions, of which elevated levels of liver enzymes was the most common. Pancytopenia occurred in 2 patients taking MTX. All adverse drug effects resolved without sequelae. MTX appears to be effective in the treatment of active rheumatoid arthritis but requires close monitoring for toxicity.

Our experience in 1,024 computed tomography examinations of the head in 954 infants and children performed in a private office is reported. Immobilization in infants was achieved using relatively large dosages of chloral hydrate (as high as 75 mg/kg) supplemented, when necessary, by I.M. Benadryl. The usual dose of chloral hydrate recommended for children is 25 mg/kg as a sedative and 50 mg/kg as a hypnotic. Satisfactory immobilization was accomplished in 350 of the 360 children under 6 years of age. Thus, routine general anesthesia was avoided. The wide spectrum of conditions demonstrated has been tabulated and selectively illustrated.

Three chemicals isolated from ovipositor rinses of virgin femaleEoreuma loftini Dyar (Mexican rice borer) moths were identified as (Z)-13-octadecenyl acetate (I), (Z)-11-hexadecenyl acetate (II), and (Z)-13-octadecenal (III) in the approximate ratio 8∶1∶1.3, respectively. Preliminary tests indicate that in laboratory bioassays, these chemicals in the above ratio induce the same activity response as heptane extracts of rice borer ovipositors. Only one combination of two chemicals (I and III, 6.2∶1 ratio) elicited a similar response. Individual chemicals elicited no response. In field tests, the average number of male rice borer moths caught per night over a five-night period was the same in traps baited with 200-600-μg quantities of the 8∶1∶1.3 ratio of chemicals dispensed from strips of filter paper as with traps baited with virgin females. The two-component mixture (I and III, 6.2∶1 ratio) was not active in the field.

Measurement of improvement in clinical trials in chronic diseases commonly compares baseline data to endpoint values by performing t-tests or analysis of variance (ANOVA) on raw gains or percentage changes. This procedure can be misleading and the use of an analysis of covariance (ANCOVA) should be considered. Properly used, ANCOVA increases statistical power in a clinical trial. However, its advantage over t-tests can be nullified by small numbers of patients, violations of assumptions, and incorrect application of the techniques. An evaluation of ANCOVA in chronic disease studies is given, with examples of its strengths and weaknesses as seen in several drug trials in the rheumatic diseases. Recommendations on its use and a decision tree for the nonstatistician are provided.

Solvent partitioning and column chromatography of MeOH root extracts of Jatropha dioica yielded four pure compounds, beta-sitosterol, jatropholone B, a previously unknown diterpene epoxytrione given the trivial name citlalitrione, and riolozatrione. Structures were determined using physical and spectral techniques and X-ray crystallography.

In laboratory bioassays, the parasitoidCampoletis sonorensis was attracted to the following sesquiterpenes isolated from cotton essential oil: α-humulene, γ-bisabolene, β-caryophyllene oxide, spathulenol, β-bisabolol, and a new, naturally occurring bisabolene-related alcohol, (2-p-tolyl-6-methylhept-5-en-2-ol) which we name gossonorol. This is the first report of spathulenol in cotton. β-Caryophyllene, a major component of cotton, was not attractive to the parasitoids. The response of the parasitoids to these compounds and the possibility of augmenting parasitoid activity in the field by manipulating plant secondary metabolites is discussed.

Double-contrast examination and proctosigmoidoscopy were performed in 240 patients with ulcerative colitis and 60 patients with granulomatous colitis. Both examinations were evaluated for accuracy of detection of disease, accuracy of classification of disease, and the ability of one examination to add information not gained by the other. Endoscopy was more sensitive than double-contrast examination in detection of disease of the distal colon and rectum in 18% of cases of ulcerative colitis and 17% of cases of granulomatous colitis. Double-contrast examination was more specific than proctosigmoidoscopy in differentiation of disease in cases of ulcerative colitis; endoscopy incorrectly classified 11% of cases as granulomatous colitis, and double-contrast examination misclassified only one case (less than 1%). Neither examination misclassified a case of granulomatous colitis as ulcerative colitis. Finally, double-contrast examination demonstrated disease proximal to the range of the proctosigmoidoscope of a greater severity than that seen endoscopically in 24% of patients with ulcerative colitis and 70% of patients with granulomatous colitis. Radiographic variations in disease presentation occasionally caused difficulty in classification. Double-contrast examination and proctosigmoidoscopy are complementary, and both should be used in evaluating patients with inflammatory disease of the colon.

Percutaneous nephrostomy placement was performed in 700 patients as the initial procedure in renal or ureteral calculus removal. The ease or complexity of the subsequent calculus removal procedure is directly dependent on precise nephrostomy placement. The most important technical factors in nephrostomy placement for calculus removal are selection of the nephrostomy track course, the track entry site into the renal collecting systems, intrarenal catheter and guidewire manipulations, and the final catheter positioning across the ureteropelvic junction and down the ureter.

A newborn infant with the respiratory distress syndrome in whom pulmonary venous air embolism (PVAE) developed as a complication of positive pressure therapy is reported. The underlying pathophysiology in this disorder is probably the development of alveolar-capillary fistulae secondary to unduly high intrabronchial pressures. An increased awareness by radiologists and clinicians of PVAE as a potential complication of aggressive respiratory therapy will result in more frequent recognition of this uncommon but lethal disorder.

The majority of patients with rheumatologic problems are seen and followed by nonrheumatologists. Of concern is the perception that a significant number of United States medical schools do not have adequate teaching programs in the rheumatic diseases. Two thousand two hundred and seventy practicing physicians, trainees, and medical students were surveyed in the Intermountain West to determine what they think undergraduate medical students should learn about rheumatology. Most respondents felt that common diseases and problems should be emphasized and that basic skills in history taking and physical examination are more important than disease related information.

Two patients had colonic perforation as a result of percutaneous nephrostomy placement followed by track dilatation and renal calculus removal. We present the technical aspects of nephrostomy placement and stone removal, as well as the clinical diagnosis and management of these cases. Both patients recovered well with conservative therapy and required no surgical intervention. This report reviews the anatomic considerations for percutaneous nephrostomy in patients undergoing renal stone removal.

Our clinical experience in 28 patients receiving chlorambucil for rheumatoid arthritis (RA) and the reports on chlorambucil therapy are reviewed. Our study population and other reports generally represent patients with severe RA who had either failed to improve or developed significant toxicity during previous treatment with conventional slow acting anti-rheumatic drugs (SAARDs). Seventy-two percent of patients had a significant clinical improvement during chlorambucil therapy and reports of complete remission are given, although the incidence of remission is unknown. Hematologic complications are often reported, but appeared more frequently in our experience than previously reported. Hematologic toxicity required that chlorambucil be discontinued in the majority of our cases. Two deaths from suspected drug induced malignancies are reported. Although chlorambucil appears to be effective in the control of active RA, the potential for drug induced toxicity and malignancies may outweigh the benefit of continued use of this experimental therapy in RA.

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.

A prospective, randomized, double-blind trial compared topical therapy with 0.85% normal saline, 2% dimethyl sulfoxide (DMSO), and 70% DMSO for treatment of digital ulcers in 84 patients with systemic sclerosis. There were no statistically significant differences among the 3 treatment groups in the improvement in the total number of open ulcers, total surface area of open ulcers, average surface area per open ulcer, number of infected ulcers, number of inflamed ulcers, or patient pain assessment. While some patients improved during the study, improvement could not be attributed to a specific treatment. Over one-quarter of the patients treated with 70% DMSO were withdrawn for significant skin toxicity.

Clinical trials with slow-acting or disease-modifying drugs in rheumatoid arthritis are difficult to design and execute. Such trials are expensive and require long periods of observation. However, there is no acceptable alternative to the properly designed and completed controlled clinical trial. Broad principles for the design of such trials and the basic elements of the study design are outlined and discussed.

1. CT and sonography are helpful in distinguishing between an obstructing lesion and hepatocellular disease as the cause of jaundice. 2. CT and sonography can demonstrate the level and extent of an obstructing lesion, and can define its nature if a mass more than 1-2 cm is present; sonography is usually the preferred screening study because of its availability, relatively low cost and lack of radiation hazard. 3. PTC or ERCP is useful in the evaluation of jaundice when sonography and CT are equivocal, fail to provide information necessary to establish proper therapy, or are at variance with the clinical impression of obstructive jaundice; in addition to defining obstructions these techniques can detect atrophy, sequestra, stones, abscesses, fistulas, primary sclerosing cholangitis, etc. 4. PBD offers an expedient alternative to surgical decompression in patients with obstructive jaundice, since most cancers that cause biliary obstruction are not resectable for cure at the time of diagnosis.