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Biomedical subjects

J S Dooley

Publications and source records attributed to J S Dooley.

At least 37 records · Page 2Linked to original sources

Endoscopic retrograde cholangiography in the diagnosis and endoscopic management of biliary complications after liver transplantation.

OBJECTIVE: Biliary reconstruction in orthotopic liver transplantation is increasingly being performed without T tube drainage. This increases the difficulty of diagnosing subsequent biliary tract problems, with a greater reliance placed on endoscopic retrograde cholangiopancreatography (ERCP) for the diagnosis of biliary tract complications. The usefulness of ERCP was evaluated in patients who underwent liver transplant where biliary reconstruction was not done with T tube drainage. DESIGN AND PARTICIPANTS: A retrospective study of the case notes of 90 patients who underwent liver transplantation, and in whom the biliary reconstruction was by end to end choledochocholedochostomy without T tube splintage. RESULTS: ERCP was performed as the primary procedure to investigate a suspected biliary complication in 30 patients (33%). The procedure was successful in 26 patients (87%), and showed a biliary stricture in 12 patients and a bile leak in six patients. ERCP was normal in seven patients and demonstrated dilated ducts alone in one patient. Six of the biliary strictures were successfully dilated endoscopically (50%), but none of the bile leaks resolved with endoscopic drainage. CONCLUSION: This study confirms the diagnostic role of ERCP post liver transplant. The therapeutic role requires clearer evaluation with a controlled trial.

Adolescent↗

Temperature-dependent protein and lipopolysaccharide expression in clinical Aeromonas isolates.

Clinical isolates of Aeromonas were grown at eight different temperatures from 10 degrees C to 40 degrees C. Whole cell lysates were examined by SDS-PAGE and major temperature-dependent changes to both protein and lipopolysaccharide (LPS) profiles were identified. Cells grown at the higher temperatures (37 degrees C and 40 degrees C) produced abundantly a protein of c. 60 kDa which was not detected at the lower temperatures. Temperature-dependent expressions of other proteins were also noted but these were more variable among the isolates. An effect of temperature on expression of lipopolysaccharides was also noted in that some strains produced significantly less O-polysaccharides at the higher temperatures. After fractionation of cells, major differences in the expression of cell envelope and outer-membrane proteins between cells grown at low and high temperatures were noted although no unifying patterns could be discerned. Such growth temperature-induced changes in the cell envelope constituents have not been described previously for Aeromonas isolates from man.

Aeromonas↗

Assessment of pancreatic duct damage following trauma: is endoscopic retrograde cholangiopancreatography the gold standard?

A 12-year-old girl was admitted as an emergency with blunt pancreatic trauma. Computed tomography (CT) showed an intact pancreas. She failed conservative treatment. Endoscopic retrograde cholangiopancreatography (ERCP) demonstrated division of the pancreatic duct at the neck of pancreas. At laparotomy, however, there was complete necrosis of the pancreatic head. She recovered well following enteric drainage of the body of pancreas. CT and ERCP are considered the optimal imaging for pancreatic trauma but the findings may be misleading.

Child↗

Longterm follow-up of biliary stents for retained common bile duct stones in elderly patients.

Common bile duct (CBD) stones in elderly patients are best treated by endoscopic sphincterotomy (ES). If CBD clearance cannot be achieved endoscopically a biliary stent may be inserted. Although satisfactory short-term results have been reported, few reports on their longterm outcome are available. Over a 3-year period, January 1987 to December 1989, 100 patients with CBD stones were referred for endoscopic stone removal. In 14 of these patients (3 men, 11 women; median age 83 years, range 79-97 years) the CBD could not be cleared endoscopically and a stent was inserted. Twelve of the 14 patients were jaundiced and 5 had acute cholangitis (AC). The maximum diameter of the retained stones ranged from 10-42 mm with a median of 17 mm. Stent insertion resolved jaundice and sepsis in all cases and all patients were discharged from hospital. In-patient stay ranged from 1-82 days (median 12 days) and was significantly increased by the presence of acute cholangitis (P = 0.03, Mann-Whitney U-test). Longterm follow-up was obtained in 13 of the 14 patients (93%) by referral to their general practitioner and out-patient notes. Seven patients are alive and well (median follow-up 43 months, range 34-60 months). One of these 7 developed further jaundice owing to stent migration and had further ES and stone removal. Six patients died at 1, 3, 12, 32, 36 and 42 months following stent insertion from unrelated causes. One patient developed further AC requiring antibiotic treatment and another patient required stent replacement.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

Chromosome allele loss in colorectal liver metastases and its association with clinical features.

Molecular genetic changes are better characterized in colorectal carcinoma than in other common adult tumours. Consistent allele losses, or loss of heterozygosity (LOH), on chromosomes 5q, 17p and 18q have been well established. These changes are associated with the prognosis of the disease. Little is known of such changes in liver metastases of colorectal origin. The extent of allelic loss and its association with clinical features were investigated in 19 patients with colorectal liver metastases by using 24 probes to detect restriction fragment length polymorphism. A high frequency of LOH on chromosomes 5q, 17p and 18q was found in these secondary tumours. No consistent loss has so far been shown in any other chromosome. The frequency of allele loss correlated significantly with prognostic features such as the number and size of liver secondaries (P < 0.005), metastasis to the lymph nodes (P < 0.01) and curative or palliative operation (P < 0.02).

Alleles↗

Nucleic acid probes for the food industry.

Recombinant DNA technology has revolutionised microbiological analysis by providing rapid and sensitive methods for the direct detection and identification of organisms. These advances have been most successfully applied to basic research and to clinical microbiology. Continued improvements in the techniques and in assay formats have now brought them to the stage where they could be useful on an industrial scale. The use of nucleic acid techniques for the identification of bacteria of importance to the food industry is discussed with emphasis on developments in practical applications.

Journal Article↗

Coordinate transcriptional control of murine endogenous retrovirus and Ig genes during B cell differentiation.

Proliferation and differentiation of B lymphocytes are usually concurrent but independently regulated events. Anti-mu treatment of murine B lymphocytes stimulated with LPS provides a model system in which proliferation and differentiation may be independently studied. This treatment causes enhanced proliferation but with coordinate suppression of transcription of a family of unrelated genes including those for Ig heavy and light chains, J chain, and endogenous murine leukemia virus (MuLV) sequences. We show that in comparison to B lymphocytes stimulated with LPS alone cells stimulated with a combination of anti-mu and LPS exhibit relatively increased amounts of a nuclear binding factor(s), NF mu E1, which interacts with the B (mu E1) site of the IgH enhancer; binding is strongly inhibited by a synthetic probe of the B sequence. A negative regulatory sequence contained within the upstream conserved region (UCR) of the MuLV long terminal repeat (LTR) is identical to the complement of mu E1 in eight of nine bases and inhibits binding of NF mu E1 to the IgH enhancer probe. The mu E1 site is also present 3' to the kappa-light chain gene; binding of this sequence to a repressor protein may coordinately suppress the transcription of mu, kappa, and MuLV genes. Others have reported that the cDNA encoding NF mu E1, also known as mu EBP-B, CF-1, and YY-1, predicts a protein with structural features consistent with variable function as either a transcriptional activator or repressor.

Animals↗

A cosmid library specific for human chromosome regions 6p21.3 and 6q27.

We have explored the potential of irradiation-fusion gene transfer (IFGT) hybrids as a source of well-defined human chromosome fragments from which probes can be derived. Extensive characterization of the IFGT hybrid 4J4 with a full panel of markers from Chromosome (Chr) 6 showed that the human DNA content derives largely from 6p21.3 and 6q27. A cosmid library has been constructed from 4J4 DNA, and 370 recombinants containing human DNA have been isolated and overlapping clones ordered into 20 contigs. Regional localization of representative clones from each contig, determined by fluorescent in situ hybridization (FISH), places 13 contigs in 6q27 and 6 in 6p21.3. Preliminary screening of cDNA libraries with selected cosmids has identified two expressed sequences. Since there are a number of medically important genes in both these regions of human Chr 6 with several disease loci linked to the HLA-A region in 6p21.3 and various tumor suppressor genes to 6q27, this library will provide a valuable resource to aid the isolation of candidate genes for these diseases. In addition, unique markers for detailed physical and genetic mapping of these regions of human Chr 6 can be easily obtained.

Base Sequence↗

Loss of constitutional heterozygosity on chromosomes 5 and 17 in cholangiocarcinoma.

It has been established that loss of tumour suppressor genes is crucial in carcinogenesis. There has been no reported study on searching for tumour suppressor genes in cholangiocarcinomas as yet. In order to investigate the loss of heterozygosity (LOH), which may represent such gene loss, in cholangiocarcinoma, we studied 14 patients with this tumour using restriction fragment length polymorphism analysis. Twenty-two probes assigned to chromosomes 1, 5, 7, 9, 11, 12, 13, 14, 16, 17 and 18 were used. Allelic losses were found in chromosomal regions 5q35-qter and 17p13. Loss of genetic material in these regions in cholangiocarcinoma was shared with hepatocellular carcinoma. Probes for other chromosomes have as yet shown no consistent LOH. In conclusion, this study for the first time showed LOH on chromosomes 5 and 17 in cholangiocarcinoma.

Adenoma, Bile Duct↗

Infrequent chromosome allele loss in fibrolamellar carcinoma.

As yet, there is no reported study of chromosome allele loss in fibrolamellar carcinoma (FLC), a distinct, rare variant of hepatocellular carcinoma (HCC). We searched for evidence of allele loss in FLC using 18 DNA probes for 10 chromosomes and compared the pattern of loss with our series of HCC. Two of the probes, lambda MS32 (1q42-43) and cMS621 (5p) showed allele losses in one tumour, while other probes showed no loss. The frequency of allele loss in FLC was much lower than in HCC, which may be associated with their different prognoses.

Adult↗

Pellagra secondary to 5-fluorouracil.

The development of pellagra in a patient treated with 5-fluorouracil for malignant disease is reported. The aetiology of pellagra in this patient is discussed, and the reasons for possible under-diagnosis of pellagra in association with malignant disease considered. We report a patient who presented with the typical skin changes of pellagra. The rash, and an associated acute deterioration in cerebral function, were exacerbated by treatment with 5-fluorouracil. The importance of considering nicotinic-acid deficiency in patients with malignant disease has not been emphasized in the literature.

Aged↗

Endoscopic extraction of bile duct stones: management related to stone size.

Endoscopic sphincterotomy has become the first line treatment for patients with common bile duct (CBD) stones. This technique may fail, however, due to difficult anatomy, previous surgery, periampullary diverticula or the presence of a large stone. The importance of stone size to the success of endoscopic sphincterotomy has not been fully assessed. A prospective study was carried out over the period January 1987 to December 1989 on 100 patients (45 male, 55 female, median age 69 years, range 19-97) with CBD stones in which a policy of early duct clearance was followed. Endoscopic retrograde cholangiopancreatography (ERCP) was performed and the stone size and number recorded from the cholangiograms and corrected for magnification. Sphincterotomy was performed using a diathermy unit with a cutting current and stones were extracted using a balloon catheter or a Dormia basket. Of the 100 patients with CBD stones receiving ERCP, successful clearance of the biliary tree was possible in seven without endoscopic sphincterotomy and five were felt to be unsuitable for endoscopic sphincterotomy. Of the remaining 88 patients endoscopic sphincterotomy was successful in 75 (85%). Of the 75 patients having endoscopic sphincterotomy stone clearance was successful in 44 (59%). There were no deaths and only four complications, which rapidly resolved on conservative treatment (two acute pancreatitis, two bleeding). The number of CBD stones present was similar in those patients with successful endoscopic sphincterotomy and duct clearance (median 1, range 1-10, n = 44) as in those in whom it failed (median 2, range 1-6, n = 31). In contrast there was a highly significant difference when stone size was analysed (successful clearance median stone size 10 mm, range 3-27 mm; unsuccessful: median 18 mm, range 10-42, p<0.001). Stones less than 10 mm in diameter (n=21) were all removed successfully whereas in patients with stones over 15 mm (n=25) only three were removed endoscopically (12%). All patients with evidence of residual stones had additional treatment. Of these 31 patients, 10 had surgery, 11 had insertion of an endoprosthesis, and 10 had dissolution treatment with methyl-tert-butyl ether through a nasobiliary catheter. This study shows the importance of stone size to the success rate of endoscopic removal of bile duct stones.

Adult↗

Benign familial hyperphosphatasaemia as a cause of unexplained increase in plasma alkaline phosphatase activity.

AIMS: To consider a possible genetic origin for the persistent unexplained increase in plasma alkaline phosphatase (ALP) in five non-related patients referred over an 18 month period. METHODS: Plasma ALP isoenzyme activities were measured in patients and their first degree relatives. RESULTS: In each patient there was a noticeable increase in intestinal plasma ALP, either alone or accompanied by an increase in bone or liver ALP. Family studies showed an unexpected increase in plasma ALP and similar isoenzyme changes in first degree relatives. The findings were consistent with autosomal dominant inheritance. CONCLUSION: Inherited raised plasma ALP activity is a reasonably common cause of persistent unexplained hyperphosphatasaemia which deserves wider recognition.

Adult↗

A prospective study of biliary cytology in 100 patients with bile duct strictures.

In patients with obstructive jaundice due to biliary tract stricture a tissue diagnosis is essential because of the varied treatment options available. Radiological imaging of a biliary stricture may suggest that it is malignant, but only a tissue diagnosis can be conclusive. The difficulty of obtaining biopsy tissue has encouraged the use of cytology in this field. This study prospectively analyzed the diagnostic value of exfoliative bile and brush cytology methods. One hundred consecutive patients with biliary strictures diagnosed at endoscopic retrograde cholangiopancreatography or percutaneous transhepatic cholangiography (60 men and 40 women; median age = 71 yr, range = 31 to 91 yr) underwent biliary cytology and were divided into two groups. Group 1 comprised the first 47 patients, who were studied by means of bile cytology alone; and group 2 comprised the subsequent 46 patients, who were studied by means of bile and brush cytology techniques. Seven patients were excluded from analysis because of inadequate follow-up information. A single experienced cytologist examined all samples to determine whether they were neoplastic. Eighty-one patients had malignant strictures and 12 had benign strictures. Combined bile and brush cytology (group 2) was more sensitive than bile cytology alone (group 1) (69% [27 of 39] vs. 33% [16 of 42], p < 0.01). In the patients studied by means of bile and brush cytology methods (group 2), cytologic study of brushings was more sensitive (69% vs. 26%, p < 0.01). No false-positive results were reported in either group (specificity = 100%).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

The putative tumor suppressor gene on chromosome 5q for hepatocellular carcinoma is distinct from the MCC and APC genes.

We have previously shown that the tumor suppressor gene for hepatocellular carcinoma (HCC) without cirrhosis may be located on chromosome 5q35-qter. In this study, we analyzed nine cases of primary HCC without cirrhosis using probes from the MCC and APC genes, which are in the region 5q21-22. None of the informative cases had allele loss detected by these probes, whereas the probe lambda MS8 for the region 5q35-qter showed allele loss in six out of six informative cases. The results confirm that the putative tumor suppressor gene for HCC without cirrhosis on chromosome 5q is distinct from the MCC and APC genes.

Alleles↗

Loss of heterozygosity on chromosomes 1 and 11 in carcinoma of the pancreas.

Little is known of the molecular-genetic changes in carcinoma of the pancreas (CaP). In order to investigate the allele loss, or loss of heterozygosity (LOH), in CaP, we studied 13 patients with exocrine CaP and two with endocrine CaP using restriction fragment length polymorphism analysis. Twenty probes assigned to chromosomes 1, 5, 7, 9, 11, 12, 13, 14, 16, 17 and 18 were used. The frequency of LOH, or fractional allele loss (FAL), was found in two endocrine tumours to be 0.333 and 0.455 respectively; and FAL in 13 oxocrine tumours ranged from 0 to 0.25. Allele loss was shown in both exocrine and endocrine tumours by the probes Lambda MS1 at 1p33-35, and pMS51 at 11q13. Probes for other chromosomes have as yet shown no consistent LOH. In conclusion, the study showed LOH on chromosomes 1 and 11 in both exocrine and endocrine CaP.

Carcinoma↗