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Biomedical subjects

J Coleman

Publications and source records attributed to J Coleman.

At least 91 records · Page 5Linked to original sources

Intrahepatic stones. The transhepatic team approach.

OBJECTIVE: The authors reviewed the combined interventional radiologic and surgical management of 54 patients with intrahepatic stones at the Johns Hopkins Hospital. The team approach used large-bore transhepatic stents to access the intrahepatic ducts until they were stone free. SUMMARY BACKGROUND DATA: Intrahepatic stones are uncommon in western countries. As a result, few American institutions have had much experience, and multiple management algorithms have been suggested. Nonoperative, operative, and combination surgical and nonoperative approaches have been advocated. At Johns Hopkins, combined surgical and percutaneous management has been used for 18 years. METHODS: This team approach includes (1) percutaneous placement of transhepatic access catheters, (2) surgery for underlying biliary disease and stone removal, and, when necessary (3) postoperative percutaneous choledochoscopy and stone removal through the transhepatic stents. RESULTS: The median age of the 54 patients was 50 years, and 32 were men. Biliary disease included 27 benign strictures, 7 sclerosing cholangitis, 5 choledochal cysts, 5 parasitic infections, 5 choledocholithiasis, and 5 biliary tumors. Fourteen patients (26%) were treated exclusively with percutaneous techniques. Forty patients (74%) had surgery, including 36 Roux-en-Y hepatico- or choledochojejunostomies with large-bore transhepatic stents. Eighteen of these 40 patients (45%) with multiple intrahepatic stones, strictures, or both required additional procedures after operation. No hospital deaths occurred after any of the percutaneous or surgical procedures. With a mean follow-up of 60 months, 94% of patients were stone free, 87% of patients were symptom free, and 73% have had their transhepatic stents removed. CONCLUSIONS: A combined radiologic and surgical approach with transhepatic stents is a safe and effective method for managing intrahepatic stones.

Adult↗

Mutations in firA, encoding the second acyltransferase in lipopolysaccharide biosynthesis, affect multiple steps in lipopolysaccharide biosynthesis.

The product of the firA (ssc) gene is essential for growth and for the integrity of the outer membrane of Escherichia coli and Salmonella typhimurium. Recently, Kelly and coworkers (T. M. Kelly, S. A. Stachula, C. R. H. Raetz, and M. S. Anderson, J. Biol. Chem., 268:19866-19874, 1993) identified firA as the gene encoding UDP-3-O-(R-3-hydroxymyristoyl)-glucosamine N-acyltransferase, the third step in lipid A biosynthesis. We studied the effects of six different mutations in firA on lipopolysaccharide synthesis. All of the firA mutants of both E. coli and S. typhimurium examined had a decreased lipopolysaccharide synthesis rate. E. coli and S. typhimurium strains defective in firA produced a lipid A that contains a seventh fatty acid, a hexadecanoic acid, when grown at the nonpermissive temperature. Analysis of the enzymatic activity of other enzymes involved in lipid A biosynthesis revealed that the firA mutations pleiotropically affect lipopolysaccharide biosynthesis. In addition to that of UDP-3-O-(R-3-hydroxymyristoyl)-glucosamine N-acyltransferase, the enzymatic activity of the lipid A 4' kinase (the sixth step of lipid A biosynthesis) was decreased in strains with each of the firA mutations examined. However, overproduction of FirA was not accompanied by overexpression of the lipid A 4' kinase.

Acyltransferases↗

Unresectable hilar cholangiocarcinoma: percutaneous versus operative palliation.

BACKGROUND: Several nonoperative and operative options are available for palliation of patients with unresectable hilar cholangiocarcinoma. This retrospective analysis compares the results of nonoperative percutaneous stenting and operative palliation in 65 patients. METHODS: Twenty-one patients were managed with percutaneous biliary stents (group A), and 44 patients underwent laparotomy (group B) with placement of large-bore silicone rubber transhepatic stents in 33. The two groups were similar with respect to age, gender, mean laboratory data, and cholangiographic extent of tumor. RESULTS: Group A and group B patients were comparable in hospital morbidity (67% vs 61%), hospital mortality (14% vs 7%), and mean initial hospital stay (27 vs 31 days). Survival was greater in group B laparotomy patients at 1, 3, and 6 months (p < 0.01), and median survival was 5 months for group A compared with 8 months for group B patients (p = 0.06). Group A patients who were managed with percutaneous stents required more stent changes per month of survival (0.5 vs 0.3, p = 0.06). However, group B patients who underwent operative palliation were more likely to undergo a second operation (0% vs 21%, p = 0.05), most often for duodenal or small-bowel obstruction. CONCLUSIONS: Operative placement of large-bore transhepatic stents may reduce cholangitis, delay hepatic failure, and prolong survival. We conclude that patients with unresectable hilar cholangiocarcinoma who are fit for surgery may benefit from operative palliation.

Adult↗

Experience with ambulatory preoperative bowel preparation at the Johns Hopkins Hospital.

A transition to ambulatory preoperative antibiotic bowel preparation was carried out. The protocol included a liquid diet for 40 hours preceding surgery and coordination of purging with buffered oral saline laxative, 45 mL containing 8 g sodium phosphate and 22 g sodium biphosphate (Fleet Phospho-Soda, C.B. Fleet Co, Lynchburg, Va) and bisacodyl preparation with an oral erythromycin base-neomycin routine. Enemas were omitted. Personnel in the preoperative evaluation center had the responsibility of instructing patients, distributing directions and drugs, and reviewing for compliance and possible problems during the preoperative period. All patients scheduled for any of a variety of gastrointestinal procedures, as well as some other complex operations, were included in this study. Follow-up data were obtained. Surgeons' comments regarding efficacy were highly favorable. In only five cases was there comment regarding liquid stool, and this was no impediment to surgery. This incidence was comparable with that of the inpatient experience, as was the spectrum of postoperative complications. Transfer of responsibility to the department proceeded with ease. Results were entirely comparable with those of the former inpatient experience.

Adult↗

One hundred and forty-five consecutive pancreaticoduodenectomies without mortality.

OBJECTIVE: A review of mortality and morbidity for pancreaticoduodenectomy was performed for 145 consecutive patients who underwent the operative procedure between 1988 and 1991. SUMMARY BACKGROUND DATA: In the past, pancreaticoduodenectomy has carried a high hospital morbidity and mortality. During the 1970s, many considered that the operation should be abandoned. Recent data, however, suggest that a marked drop in both morbidity and mortality have occurred for this operative procedure. METHODS: Among the 145 consecutive patients who underwent pancreaticoduodenectomy, 108 patients were 69 years of age or younger, and 37 were 70 years of age or older. Four patients were 80 years of age or older. One hundred and seven patients had a malignant neoplasm, whereas 38 patients had benign disease. There were no significant differences in preoperative risk factors when the younger and older, and benign disease and malignant disease groups were compared. RESULTS: Mean operative time was 7.3 hours. Median blood loss was 0, indicating that more than one-half of the patients underwent pancreaticoduodenectomies without blood transfusions. There were no significant differences in postoperative complications when the younger and older, and benign disease and malignant disease groups were compared. There was no hospital or 30-day mortality. CONCLUSIONS: With appropriate preoperative selection, virtually any patient in any age group, with benign or malignant disease, can undergo pancreaticoduodenectomy with minimal risk of hospital mortality.

Adult↗

Cardiac precautions for non-acute inpatient settings.

Activity progression of persons with physical disabilities and accompanying cardiovascular disease in medical rehabilitation centers is traditionally based on cardiac precautions derived from acute care settings. Concern that these guidelines were too conservative and restrictive led to exercise testing and evaluation of 64 physically disabled male patients with a history of coronary artery disease. The sample had a mean age of 62.4 years. The exercise test was an adaptation of the Schwade Arm Ergometer Protocol with blood pressure measured at baseline, immediately after each 2 minutes of exercise, peak exercise and each minute for 6 minutes after peak exercise. Heart rate was monitored continuously. Patients achieved a mean peak heart rate of 115 beats per minute, mean peak systolic pressure of 169 mm Hg and mean peak diastolic pressure of 89 mm Hg. Ischemic electrocardiographic changes occurred in four of the 64 patients. Based on the achieved ranges of values of heart rate, systolic and diastolic pressures and comparison of these results with baseline (pre-exercise) values, more liberal guidelines for prescribing activity in the non-acute inpatient setting are provided.

Adult↗

Pancreaticoduodenectomy for selected pancreatic endocrine tumors.

Endocrine tumors are distributed throughout the pancreas and can usually be removed by local excision or distal pancreatectomy. Those tumors arising in the pancreatic head and uncinate process may be difficult to enucleate because of size, location or malignant extension. In the past, surgeons have been reluctant to perform a pancreaticoduodenectomy (Whipple procedure) for these lesions because of the high morbidity and mortality rates. In recent years, we and others have reported a marked reduction in the morbidity and mortality rates after the Whipple procedure and, since 1981, have used pancreaticoduodenectomy to resect pancreatic endocrine neoplasms successfully in 12 patients. Tumors were resected from six men and six women who ranged in age from 28 to 61 years (median of 49 years). Six of the tumors were benign and included three insulinomas, one glucagonoma, one gastrinoma and one nonfunctioning islet cell tumor. The six malignant tumors included two insulinomas, one VIPoma and three nonfunctioning islet cell tumors. In all instances, enucleation could not be performed safely or would have resulted in an inadequate excision. Pylorus preservation was used in seven of the patients, including the last six. The average operative time was 6.8 hours, and six of the patients did not require perioperative blood transfusions. There was no hospital mortality. Hospital morbidity included three self-limited pancreatic fistulas, one gastrocutaneous fistula, one hepatic abscess and one postoperative myocardial infarction. One patient with a malignant VIPoma died three years postoperatively of metastatic tumor. The remaining 11 patients are alive and well with a median follow-up period of three and one-half years (range of zero to 9.7 years). These data indicate that pancreaticoduodenectomy is an appropriate procedure for properly selected patients with pancreatic endocrine neoplasms and can be performed with acceptable morbidity and mortality rates.

Adenoma, Islet Cell↗

Retroviral integrase functions as a multimer and can turn over catalytically.

A number of studies have demonstrated that the retroviral protein integrase (IN) alone is sufficient to carry out two discrete steps required for retroviral integration: the endonucleolytic processing of viral DNA ends and the cleavage and joining of host DNA to the processed viral DNA termini. Little is known about the biochemical and biophysical mechanisms involved in these reactions. Here, we employ in vitro assays of Rous sarcoma virus IN to demonstrate for the first time that IN is capable of multiple turnover in both the processing and joining reactions. The turnover number calculated for the processing reaction is 0.26 cleavages/min/mol of IN. Our steady state kinetic studies indicate that both the processing and joining activities require a multimeric form of IN. Ultracentrifugation analyses reveal a substrate-independent reversible equilibrium among the monomeric, dimeric, and tetrameric forms of this protein. From these results we conclude that the minimal functional unit for both the processing and joining of each viral DNA end is an IN dimer.

Animals↗

Novel antagonists of the 5-HT3 receptor. Synthesis and structure-activity relationships of (2-alkoxybenzoyl)ureas.

A series of benzoylureas derived from bicycle amines were prepared and evaluated for 5-HT3 antagonist activity on the rat isolated vagus nerve. From among these compounds, those analogues which were ortho substituted by an alkoxy group on the benzoyl function were shown to be potent 5-HT3 antagonists with similar or greater potency than the standard agent ondansetron. NMR and X-ray crystallography studies showed these o-alkoxy compounds to exist as a planar, hydrogen-bonded, tricyclic ring system. In molecular modeling studies on endo-N-[[(8-methyl-8-azabicyclo[3.2.1]octan-3-yl-amino] carbonyl]-2-(cyclopropylmethoxy)benzamide (30) the central hydrogen-bonded ring was able to mimic an aromatic ring present in previously reported 5-HT3 antagonists.

Animals↗

A component of 5-HT-evoked depolarization of the rat isolated vagus nerve is mediated by a putative 5-HT4 receptor.

This study describes a component of 5-HT-evoked depolarization of the rat isolated vagus nerve which was unaffected by the 5-HT3 receptor antagonist ondansetron. A grease-gap extracellular recording technique was used. Ondansetron (10-100 nmol/l) displaced the 5-HT concentration-response curve to the right yielding a pA2 value of 8.6 (8.5-8.8), consistent with 5-HT3 receptor antagonism, and revealing a component of the 5-HT response which was resistant to ondansetron blockade. In the presence of ondansetron (100 nmol/l) the maximum depolarization in the resistant phase was 15.5 (12.6-19.2)% of the initial maximum response to 5-HT and the pEC50 value was 7.0 (6.7-7.3). The mechanism of the ondansetron-resistant component of the 5-HT response resembled a 5-HT4-receptor-effect in being absent in preparations equilibrated with 5-methoxytryptamine (10 mumol/l) and antagonised by ICS 205930 (tropisetron, pA2 6.4). 5-Methoxytryptamine alone was an agonist in the vagus nerve with a maximum response similar to that of the ondansetron resistant phase of the 5-HT response. Similarly renzapride alone evoked small depolarizations of this preparation but antagonized the ondansetron resistant phase of the 5-HT response (pA2 7.3-7.4). These effects of 5-methoxytryptamine and renzapride are also consistent with a 5-HT4 receptor mechanism. Ketanserin (1 mumol/l) and methysergide (1 mumol/l) had little effect on responses to 5-HT. The depolarization evoked by this putative 5-HT4 receptor mechanism was small but prolonged and appears to mask and after-hyperpolarizing phase of the 5-HT response in this tissue.

5-Methoxytryptamine↗

Characterization of the Escherichia coli gene for 1-acyl-sn-glycerol-3-phosphate acyltransferase (plsC).

An Escherichia coli strain deficient in 1-acyl-sn-glycerol-3-phosphate acyltransferase activity has previously been isolated, and the gene (plsC) has been shown to map near min 65 on the chromosome. I precisely mapped the location of plsC on the chromosome, and determined its DNA sequence. plsC is located between parC and sufI, and is separated from sufI by 74 bp. Upstream of plsC is parC, separated by 233 bp, which includes an active promoter. parC, plsC, and sufI are all transcribed in the counterclockwise direction on the chromosome, possibly in an operon with multiple promoters. The amino-terminal sequence of the partially purified protein, combined with the DNA sequence, reveal 1-acyl-sn-glycerol-3-phosphate acyltransferase to be a 27.5 kDa highly basic protein. The plsC gene product, 1-acyl-sn-glycerol-3-phosphate acyltransferase, is localized to the cytoplasmic membrane of the cell. The amino-terminal sequence of the purified protein reveals the first amino acid to be a blocked methionine residue, most probably a formyl-methionine. The amino acid sequence of 1-acyl-sn-glycerol-3-phosphate acyltransferase has a short region of homology to two other E. coli acyltransferases that utilize acyl-acyl carrier protein as the acyl donor, sn-glycerol-3-phosphate acyltransferase and UDP-N-acetyl-glucosamine acyltransferase (involved in lipid A biosynthesis).

1-Acylglycerol-3-Phosphate O-Acyltransferase↗

Spectrum of cystic tumors of the pancreas.

The pathologic and clinical classification, as well as the behavior, of cystic tumors of the pancreas has been the subject of controversy. We retrospectively reviewed 50 patients with a diagnosis of cystic tumor of the pancreas observed at The Johns Hopkins Hospital from 1984 to 1991. These tumors were classified into three broad groups: I, cystadenoma; II, cystadenocarcinoma; and III, adenocarcinoma with mucin production or an associated cyst. The three groups did not differ with respect to age or sex. The most common clinical presentation was abdominal pain. Symptoms and signs among the three groups were similar except that patients with cystadenomas were less likely (p less than 0.05) to be jaundiced and more likely (p less than 0.05) to be asymptomatic. Radiologic findings on computerized tomography, cholangiography, and arteriography also overlapped, making precise preoperative determination of tumor type difficult. Operative classification was also often not possible. The resectability rate (Group I, 91%; Group II, 67%; Group III, 53%) and 5-year survival rate (Group I, 90%; Group II, 72%; Group III, 14%) correlated with careful pathologic determination. Cystic tumors of the pancreas represent a spectrum of disease ranging from benign cystadenoma to adenocarcinoma masquerading as cystadenocarcinoma. We recommend resection whenever possible, even when preoperative evaluation suggests benign disease.

Actuarial Analysis↗

Patterns of ileal recurrence in Crohn's disease. A prospective randomized study.

To gain information on the pathogenesis of ileal recurrence, 86 patients with Crohn's disease undergoing their first ileocolic resection were randomized to receive either an end-to-end (n = 47) or side-to-end (n = 39) anastomosis. The demographic and clinical characteristics of both groups were similar. There were no statistically significant differences between the two groups in postoperative complications or in the subsequent development of symptomatic or documented recurrences. Among the 43 patients with follow-up in the end-to-end anastomosis group, there were 10 documented ileal recurrences (23%), and all involved distal ileum in the characteristic preanastomotic location. Among the 35 patients with follow-up in the side-to-end anastomosis group, there were 11 documented recurrences (31%, not significant). The ileal recurrence pattern could be determined accurately in five of these 11 patients and involved the ileum adjacent to the colon, but spared the distal ileum in the blind pouch. This study suggests that the fecal stream and reflux of colonic contents are important factors in determining the pattern of ileal recurrence after ileocolectomy for Crohn's disease.

Adult↗

Gastric and duodenal obstruction in patients with cholangiocarcinoma in the porta hepatis: increased prevalence after radiation therapy.

OBJECTIVE: Our objective was to study the imaging findings in patients who had gastric and duodenal obstruction as a long-term complication of cholangiocarcinoma and to determine if the obstruction was associated with radiation therapy. MATERIALS AND METHODS: Between 1973 and 1989, 96 patients had either curative resection or palliative stenting for cholangiocarcinoma involving the hepatic duct bifurcation. Sixty-three (66%) also received adjuvant radiation therapy ranging from 4960 to 7220 rad (cGy). Gastric outlet or duodenal obstruction or both developed subsequently in seven of the 63 patients treated with radiation therapy. Radiographic studies, including upper gastrointestinal series and CT, and medical and surgical records for these seven patients were retrospectively reviewed. RESULTS: Upper gastrointestinal series in the seven patients with obstruction showed narrowing of the lumen, deformity and enlargement of gastric and duodenal mucosal folds, and delayed gastric emptying. CT performed in five of the seven patients showed thickening of the wall of the gastric antrum and small bowel and retained food and fluid within the stomach. All seven patients required gastrojejunostomy; at surgery, dense adhesions and fibrosis were found, and it was not evident whether the obstruction was due to the tumor or to radiation fibrosis. However, because this complication was seen only after radiotherapy, it was presumed to be radiation fibrosis. CONCLUSION: Our experience suggests that radiation therapy increases the risk of postoperative gastric and duodenal obstruction in patients undergoing surgery for cholangiocarcinoma.

Adenoma, Bile Duct↗

Reduced postoperative hospitalization after laparoscopic cholecystectomy.

An initial experience of laparoscopic cholecystectomy in 50 consecutive patients was reviewed and the results compared with those of a group of 25 patients who underwent laparotomy cholecystectomy during the 3 months before the introduction of laparoscopic cholecystectomy. Laparoscopic cholecystectomy was successfully performed in 44 of 50 consecutive patients in whom it was attempted. When compared with laparotomy, laparoscopy cholecystectomy was associated with longer mean (s.d.) anaesthesia, 155 (61) min versus 102 (31) min (P less than 0.001), shorter mean postoperative hospital stay, 3.5 (1.5) versus 8.8 (3.2) days (P less than 0.001), and reduced mean cost, pounds 895 (376) versus pounds 2210 (822) (P less than 0.001). Perioperative morbidity was also reduced following laparoscopy cholecystectomy (9 per cent versus 16 per cent) but not significantly so. Laparoscopic cholecystectomy is a safe, effective procedure which completely removes the gallbladder. It significantly reduces hospital stay, is cosmetically satisfactory and has financial benefits. We suggest that this technique be considered for all patients having cholecystectomy.

Adolescent↗

Factors influencing survival after pancreaticoduodenectomy for pancreatic cancer.

Eighty-nine patients with carcinoma of the head of the pancreas underwent pancreaticoduodenectomies. The actuarial 5-year survival for all 89 patients was 19%, with a median survival of 11.9 months. The 81 hospital survivors were analyzed in an effort to determine factors influencing long-term survival. Negative lymph nodes and the absence of blood vessel invasion both favored long-term survival. The strongest predictive factor was negative lymph node status with a median survival of 55.8 months, compared with 11 months with lymph nodes involved with tumor (p less than 0.05). Blood transfusions were also predictive, with patients receiving two or fewer units having a median survival of 24.7 months, compared with 10.2 months for those receiving three or more units (p less than 0.05). The most important determinant of long-term survival after pancreaticoduodenectomy for pancreatic cancer is biology of the tumor (lymph node status, blood vessel invasion). However, performance of the resection (units of blood transfused) also appears to be an important factor influencing survival.

Adult↗