A prospective study of positive/negative ex vivo B-cell depletion in patients with chronic lymphocytic leukemia.

OBJECTIVE: Autologous peripheral blood stem cell (PBSC) transplantation is increasingly being used in patients with chronic lymphocytic leukemia (CLL). As the autografts are frequently contaminated with large numbers of tumor cells, we have prospectively investigated the feasibility and efficacy of ex vivo double purging of PBSC grafts in an open, nonrandomized, single-center phase I/II clinical study. MATERIALS AND METHODS: Twenty consecutive patients with poor-risk CLL underwent uniform stem cell mobilization with chemotherapy and granulocyte colony-stimulating factor (G-CSF). Double B-cell depletion of the harvested PBSC products was performed using immunomagnetic CD34(+) cell selection (Isolex300i Nexell, Irvine, CA) followed by a negative step with anti-CD19/20/23/37-labeled immunomagnetic beads. The purified PBSC were reinfused after myeloablative treatment with TBI/CY. RESULTS: A total of 25 separation runs was accomplished using collection products containing 3.4% (1.1-8.1) CD34(+) cells and 1.2% (0.1-42) CD19(+)CD5(+) CLL cells. After double selection, 33% (15-67) CD34(+) cells were recovered with a purity of 98.8% (89.1-99. 8). CLL cells were undetectable by high-resolution flow cytometry in 15 of 25 final products; median purging efficacy was 5 (4.1-6) log. The CD34(+) content of the 20 final grafts was 4.6 (2.2-6.5) x 10(6)/kg. Rapid and durable engraftment developed in all cases. With a median follow-up of 20 (6-29) months, 17 patients live in complete clinical remission, two have recurrent disease, and one patient died due to pulmonary embolism five months after transplant. Persistence of the leukemic clone on the molecular level was demonstrated by dot blotting with clone-specific CDR3 probes in an additional five patients. Serious or unexpected infectious complications did not occur. CONCLUSIONS: Positive/negative purging with the Isolex system allows preparation of highly purified CD34(+) fractions and up to six log of tumor cell depletion in patients with B-CLL and can be safety reinfused after myeloablative therapy without affecting hematopoietic engraftment.

Evaluation of complications during and after conscious sedation for endoscopy using pulse oximetry.

All events prolonging an endoscopic procedure or recovery, or requiring a medication or an intervention, were analyzed from a consecutive sample of 508 patients receiving conscious sedation. Although 102 events were identified (20%), 33 of these (7%) were major. These included four episodes of apnea and four patients with a prompt and sustained fall in oxygenation during the procedure; 19 additional patients had a decrease to less than 89% in oxygen saturation in the 30 minutes after the completion of the procedure. The patients with observed events had significantly more major illnesses, a higher fraction older than 70 years, and a higher fraction of endoscopic retrograde cholangiopancreatography than those without events (p < 0.05) but had a similar dose of sedative medications, mean age, and fraction of colonoscopies.

Computer programs in gastrointestinal endoscopy: issues, problems, and solutions.

For 10 years, a computerized gastrointestinal endoscopy database was promoted as necessary and desirable. At least 2 endoscopy societies, the American Society for Gastrointestinal Endoscopy (ASGE) and the World Society for Gastrointestinal Endoscopy (OMED), devoted considerable effort to develop appropriate terminology and structure. Numerous vendors and individuals developed software conforming, to various degrees, with the ASGE and OMED recommendations, and hundreds of institutions in the United States and an equal number worldwide have computerized their endoscopy paperwork. Dozens of articles and several large multicenter research efforts signal the usefulness of the database concept. Although desired, and apparently needed, endoscopy databases have not, however, caught the attention of a majority of physicians who could benefit from them--probably because of perceived difficulty with user interface. Whereas the keyboard has succeeded in virtually every other discipline, it is an enigma why there is so much anathema to this ubiquitous device among the majority of the medical community. Attempts at alternate input modalities, such as voice, resulted in several commercially available report-writers; however, the original database concept is insignificant in these current products. The international experience with this subject is reviewed with an optimistic prediction that a satisfactory doctor-computer interface will be developed, perhaps with totally new technology, and that continued interest, use, and development of an endoscopy database is justified.

Intraluminal fungal colonization of gastrostomy tubes.

Percutaneous endoscopic gastrostomy tubes are frequently colonized with fungal and bacterial organisms. This has not been previously reported. In our sample of 10 patients, nine percutaneous endoscopic gastrostomy tubes were colonized with fungi. This occurred as early as 1 week after placement. Candida tropicalis was isolated in five patients. It is hypothesized that a variety of fungi use components of the gastrostomy tube polymer, such as polymer additives, which contribute to the structural deterioration of the tube.

Apnea and cardiopulmonary arrest during and after endoscopy.

Ten patients developed apnea or cardiopulmonary arrest during or following endoscopy in more than 10,000 consecutive endoscopies. These complications occurred in patients over the age of 60 years with many associated diseases. Four of the reactions occurred close to the time of giving intravenous medication, the majority after the stimulation of the procedure had ended, usually more than 30 min after the last dose of medication. The initial 7,500 procedures were conducted without automated monitoring, but the most recent 2,500 procedures employed finger pulse oximetry. Monitoring has not prevented apnea and cardiopulmonary arrest, but it provides earlier recognition.

Colon polyps in the elderly: appropriate primary care follow-up.

The presence of adenomatous polyps in the colon identifies patients at increased risk of colon cancer. Removal of such polyps and undertaking repeated future examinations is proven to diminish subsequent development of the disease. Discussing with the patient, at the time of index colonoscopy, the need for repeat examination and including a note in the patient's medical record are not by themselves adequate measures of obtaining follow-up. A reminder letter mailed directly to the patient shortly before the desired appointment is a highly effective method of obtaining follow-up, when accompanied by information on the importance of repeat colonoscopy.

Therapeutic options for biliary tract disease in advanced cirrhosis.

Between 1979 and 1984, 21 male cirrhotic patients with advanced liver disease, cholecystitis, and jaundice were seen. Eight patients had persistent symptoms of acute cholecystitis despite intense symptoms of acute cholecystitis despite intense medical management. Of these patients, five underwent cholecystostomy and survived. The other three patients had cholecystectomy and one died. Thirteen patients presented with jaundice. Twelve patients underwent endoscopic retrograde cholangiography which revealed gallbladder stones in four but no stones in the common bile duct. They did not undergo further surgical procedures. One patient presented with jaundice, cholangitis, and pancreatitis was found to have stones in the common bile duct and underwent endoscopic sphincterotomy with removal of multiple small, pigmented stones. This patient died from sepsis and renal failure 37 days after sphincterotomy. Endoscopic retrograde cholangiography was unsuccessful in four patients who later underwent percutaneous transhepatic cholangiography which revealed stones in one and cirrhotic ductal changes in three. The remaining jaundiced patient underwent cholecystectomy and common bile duct exploration which revealed no ductal stones. This patient died 21 days after operation from sepsis and multiple organ system failure. Three of five patients with gallstones on endoscopic retrograde cholangiography or percutaneous transhepatic cholangiography died, but none of the deaths were due to biliary tract disease. At last follow-up the two surviving patients were asymptomatic. The overall mortality rate was 14 percent (3 of 21 patients). Cholecystostomy in cirrhotic patients with advanced liver disease and acute cholecystitis is associated with minimal mortality and morbidity. Cirrhotic patients with jaundice are probably best evaluated initially by endoscopic retrograde cholangiopancreatography which is safe, diagnostic, and sometimes therapeutic.

Healing of benign gastric ulcer. A placebo-controlled comparison of two dosage regimens of misoprostol, a synthetic analog of prostaglandin E1.

Misoprostol, a synthetic prostaglandin E1 methyl ester analog with gastric antisecretory and cytoprotective properties, prevents the development of acute experimental gastric and duodenal ulcers in various animal models. This study was designed as a multicenter randomized double-blind parallel-group comparison of the effects of two dosage strengths (25 and 100 micrograms q.i.d.) of orally-administered misoprostol and placebo on the healing of endoscopically-proven benign gastric ulcer in 299 out-patients. Safety was evaluated by comparison of pre- and post-treatment physical examinations, clinical laboratory tests, gastric antral biopsies and monitoring of adverse experiences. A statistically significant difference in gastric ulcer healing rate was seen at eight weeks among the treatment groups in the Intent-to-Treat Cohort: misoprostol 100 micrograms (62.0%), misoprostol 25 micrograms (50.0%), placebo (44.7%). The proportion of subjects healed in up to eight weeks of treatment was greatest in the misoprostol 100 micrograms group in all cohorts. Ulcer pain decreased in all treatment groups in successive weeks and there were no statistical differences among any of the three treatment groups. Diarrhea was the most frequently reported adverse experience: misoprostol 100 micrograms (9.8%), misoprostol 25 micrograms (7.7%), placebo (1.9%). The diarrhea was mild and self-limiting despite continued use of misoprostol. Overall evaluation of gastric antral biopsies showed no adverse changes in the morphology of the antral mucosa. We conclude that misoprostol 100 micrograms q.i.d. for up to eight weeks is safe and effective in the treatment of benign gastric ulcer.

Explosion-safe, enema-free, nutritious colonoscopy preparation using a prepackaged formula diet.

Breath hydrogen and methane concentrations were normal before morning colonoscopy in 72 ambulatory patients randomly assigned to Ensure or clear liquid diet preparation for 48 hours. Mechanical bowel preparation was equal with each diet using an evening-laxative and morning-enema regimen and with Ensure using two consecutive evenings of laxatives without enemas. Ensure is an explosion-safe, mechanically acceptable, nutritionally adequate method of colonoscopy preparation. With a suitable laxative, Ensure eliminates the need for enemas in colonoscopy preparation.

common duct obstruction in patients with intractable pain of chronic pancreatitis.

Fibrosis of chronic pancreatitis can cause obstructive jaundice by compressing the intrapancreatic portion of the common bile duct. The frequency and clinical manifestations of common bile duct stricture from symptomatic chronic pancreatitis have been evaluated in 26 patients undergoing lateral pancreaticojejunostomy for intractable pain between 1974 and 1980. Four patients (15%) had a stricture with partial obstruction of the common duct in addition to pancreatic duct obstruction. Three of the four strictures were identified prior to operation by ERCP. The fourth developed biliary obstruction six months after pancreaticojejunostomy. Slight elevation of alkaline phosphatase was common and occurred in 12 of 22 patients with chronic pancreatitis without biliary obstruction. Alkaline phosphatase was elevated greater than four times normal in three of the four patients with a biliary stricture. Elevation of total and direct serum bilirubin occurred only in patients with stricture of the distal common duct. A waxing and waning picture of jaundice was seen in these four patients. When a fixed smooth stricture of the common duct is demonstrated in a patient with symptomatic chronic pancreatitis, drainage of the biliary tree should be combined with pancreatic duct drainage in order to prevent cholangitis, biliary cirrhosis, diagnostic confusion with pancreatic carcinoma, and persistence of pain.

Evaluation of therapeutic options for pancreatic pseudocysts.

A review of 81 patients with pancreatic pseudocyst was conducted to assess the value of different treatment modalities. Resection was associated with 18% mortality (two of 11 patients) and 36% morbidity. In three of nine patients undergoing external drainage a recurrent pseudocyst developed, and in one additional patient, a pancreatic fistula persisted. Internal drainage by cystogastrostomy (21 patients) resulted in 9.5% mortality and 9.5% morbidity, whereas cystojejunostomy (33 patients) was associated with a 6% mortality and 6% morbidity. Endoscopic drainage through the posterior wall of the stomach was unsuccessful in the two patients in which it was used. Internal drainage into the stomach, duodenum, or jejunum is a safe and effective approach for most pseudocysts. Persistent symptoms following surgical treatment were primarily related to failure to recognize multiple cysts and/or pancreatic duct obstruction and dilation characteristic or chronic pancreatitis.

Cimetidine, antacid, and hospitalization in the treatment of benign gastric ulcer: a multicenter double blind study.

Two hundred forty patients with benign gastric ulcer were treated in a controlled clinical trial to assess the effect on healing of cimetidine, antacids, and hospitalization. Inpatients and and outpatients were randomly assigned to one of three treatments: cimetidine plus antacid, cimetidine plus dummy antacid, or placebo tablet plus antacid. In 206 patients who met criteria for analysis, ulcer healing as shown by endoscopy occurred by 12 days in 11 to 26 percent and by 42 days in 58 to 76 percent. There were no significant differences in healing between hospitalized and nonhospitalized patients or between treatment subgroups. Symptomatic response was equivalent in all groups. The median antacid consumption was 328 mEq of in vitro buffering capacity per day. Patients taking antacids experienced significant diarrhea compared with those taking no antacid. This investigation suggests that the effect of cimetidine is equivalent to that of large amounts of antacid, but because a true placebo group was not studied it is not possible to conclude from this study alone whether either agent influenced healing. In contrast to widespread belief, initiation of treatment in the hospital did not enhance healing, but because patients were not randomly assigned to inpatient and outpatient status no final conclusion about the effect of hospitalization on healing can be drawn.

Safety of cimetidine.

Our review of published material, manufacturer's files, and submissions to the United States Food and Drug Administration indicates that cimetidine is safe for short term use (up to 8 weeks). This judgment is based on a total experience with over 3000 patients. Clinically insignificant elevations of serum creatinine occur in a high percentage of patients, persisting until the end of therapy, then disappearing. Gynecomastia occurred in some patients on long term therapy.