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Biomedical subjects

J M Little

Publications and source records attributed to J M Little.

At least 19 recordsLinked to original sources
PubMed1995

Frantz's tumour: papillary and cystic carcinoma of the pancreas.

Frantz's tumour (papillary and cystic tumour) of the pancreas is a rare neoplasm usually seen in young women. It is of low grade malignancy and deserves special note among pancreatic malignancies as it is frequently amenable to local resection and has a good long-term survival rate after excision. Three such cases have been treated at Westmead Hospital, one young male and two females. In two the disease was confined to the pancreas. In one, local invasion outside the pancreas and trans-coelomic spread to the ovaries was present at the time of diagnosis. Complete surgical removal of macroscopic disease was achieved in all three and all remain disease free between 2 and 4 years post-surgery. All have good exocrine and endocrine pancreatic function. These cases are discussed in detail. The need to be aware of this uncommon variant of pancreatic cancer is stressed. Investigation and treatment options are reviewed. The role of cytology studies in diagnosis and the potential for long-term surgical control of this tumour are highlighted on the basis of our limited experience and that presented in recent surgical literature.

Adolescent↗
PubMed1995

Including smoking status as a new vital sign: it works!

BACKGROUND: Despite the adverse health consequences of smoking, many physicians still neglect to counsel smokers to quit. This study evaluated the effect of including smoking status as a vital sign on the frequency of physician discussions with patients about smoking and physician advice to quit smoking. METHODS: A consecutive sample of adult ambulatory patients in our metropolitan family practice residency program completed exit surveys on physician and nurse counseling about smoking. Control group data were collected for 1 month before the change was made to include smoking status as a vital sign on patient charts. Charts were then marked with a stamp as a chart prompt in the vital signs section. Data were collected for 2 months after smoking status was added to the stamp. RESULTS: There were 637 individuals surveyed, of whom 179 were current smokers; 95 in the "prestamp" group and 84 in the "poststamp" group. The percentage of patient-physician encounters during which smoking was discussed increased from 47% to 86% (P < .001). Physician advice to quit increased from 50% to 80% (P < .001). Physician discussion of smoking with patients increased across all of the five stages of change but most dramatically (53% to 95%) in the "preparation" stage. Physicians were much less likely to counsel patients in the "precontemplation" stage to quit smoking. CONCLUSIONS: Including smoking as a new vital sign significantly increased the likelihood of smoking-related discussions between patients and their physicians. The stamp is inexpensive and easy to use, and because it is a one-time office system change, it is more likely to be implemented and maintained in busy practices.

Adult↗
PubMed1995

Characterization of human liver microsomal UDP-glycosyltransferases using photoaffinity analogs.

The photoaffinity analogs [beta-32P]5-azido-UDP-glucuronic acid ([32P]5N3UDP-GlcUA) and [beta-32P]5-azido-UDP-glucose ([32P]5N3UDP-Glc) were used to characterize UDP-glycosyltransferases of microsomes prepared from human liver. Photoincorporation of both probes into proteins in the 50- to 56-kdalton range, known to contain UDP-glucuronosyl transferases (UGTs), was concentration dependent, and photolabeled proteins were susceptible to trypsin digestion only in the presence of detergent. The latter was demonstrated by the appearance on Western blots of the trypsin-treated, detergent-disrupted microsomes of a protein band of slightly lower molecular mass than, and presumably derived from, the UGTs. However, a labeled cleavage product was found only in samples photolabeled with [32P]5N3UDP-GlcUA and not in those labeled with [32P]5N3UDP-Glc. In detergent-treated microsomes, all of the nucleotide sugars that were tested protected better against photoinsertion of [32P]5N3UDP-GlcUA than of [32P]5N3UDP-Glc, with UDP-glucose being the most effective, followed by UDP-GlcUA and UDP-galactose. The pattern of inhibition of a series of uridinyl analogs toward photolabeling by the two probes was quite different: one inhibitor that was ineffective in blocking photoincorporation of [32P]5N3UDP-GlcUA (L-DPASiU) was one of the most potent inhibitors of photolabeling with [32P]5N3UDP-Glc. A similar dichotomy was seen with several inhibitors in enzymatic assays measuring hyodeoxycholic acid 6-O glucuronidation and glucosidation activities; the most potent inhibitors of HDCA glucosidation were not as effective against glucuronidation. The results indicate a lumenal orientation for human microsomal UGTs and provide substantial evidence that two distinct enzyme systems are involved in 6-O glucuronidation and 6-O glucosidation of HDCA.

Affinity Labels↗
PubMed1994

Characterization of UDP-glucuronic acid transport in rat liver microsomal vesicles with photoaffinity analogs.

The endoplasmic reticulum (ER) of rat liver contains several well characterized UDP-glucuronosyltransferases (UGTs), membrane-bound proteins of 50-54 kDa, and also less well identified UDP-glucosyltransferases, with nucleotide binding sites located on the lumenal surface. There is evidence that the substrates for these enzymes, UDP-glucuronic acid (UDP-GlcUA) and UDP-glucose (UDP-Glc), biosynthesized in the cytosol, are transported into the lumen of the ER via unknown mechanisms, the characteristics of which are poorly defined. A new approach for the study of the transport process has been devised using two active-site directed photoaffinity analogs, [beta-32P]5-azido-UDP-GlcUA and [beta-32P]5-azido-UDP-Glc. Photoincorporation of these probes into the lumenally oriented UGTs of intact rat liver microsomal vesicles was used as an indicator of transport. In intact vesicles, [32P]5N3UDP-GlcUA was efficiently incorporated into UGTs in a time, temperature and concentration dependent manner. In contrast, [32P]5N3UDP-Glc apparently was not transported effectively; maximal photolabeling of the 50-54 kDa proteins by this probe was dependent on detergent disruption of the vesicles. Vesicular uptake of and subsequent photolabeling of the 50-54 kDa proteins by [32P]5N3UDP-GlcUA were inhibited by UDP-GlcUA and 5N3UDP-GlcUA while UDP-Glc, 5N3UDP-Glc, UDP-xylose and UDP-N-acetylglucosamine were less inhibitory, suggesting a high degree of specificity for the uptake/photolabeling process. The anionic transport inhibitors DIDS and SITS inhibited [32P]5N3UDP-GlcUA photoincorporation into UGTs in intact vesicles, but also inhibited photolabeling of these and other enzymes in detergent disrupted vesicles. These data suggest the presence in rat liver microsomal vesicles of a specific, carrier-mediated transport process for UDP-GlcUA which is distinct from the mechanism of UDP-Glc transport.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1994

Hepatocellular carcinoma in western Sydney. Aetiology, changes in incidence, and opportunities for better outcomes.

OBJECTIVES: To examine the incidence of hepatocellular carcinoma (HCC) in western Sydney over the last 14 years, to assess risk factors for the disease among ethnic groups of Australian residents, and to consider the opportunities for improving its usually poor outcome. DESIGN AND SUBJECTS: Retrospective case-record review of clinical features in all (122) patients discharged from a 900-bed tertiary-referral teaching hospital with a diagnosis of HCC from January 1979 to March 1993. MAIN OUTCOME MEASURES: Annual number of new cases; risk factors according to birthplace; surgical resectability of tumours. RESULTS: New cases admitted each year at least doubled between 1979-1985 and 1986-1992. This apparent increase involved individuals born in Australia (50% of all patients) as well as immigrants. Cirrhosis was found in 93% at liver biopsy or autopsy. Excessive alcohol intake was an associated risk factor for 46% of Australian-born patients and for 13% of those born overseas. Among the latter, HCC was associated with markers of hepatitis B virus infection in 64%. Since hepatitis C virus (HCV) tests became available in 1990, five of nine patients tested were anti-HCV positive. Surveillance screening of patients known to have cirrhosis detected eight cases of early HCC. Seven of these had surgical resection and all are alive. CONCLUSIONS: New diagnoses of HCC have increased recently, irrespective of country of birth. In Australian-born patients alcoholic liver disease remains a major aetiological factor but the role of HCV requires further evaluation. Among immigrants, cirrhosis from chronic viral hepatitis accounts for most cases. We propose that prevention of cirrhosis caused by chronic viral hepatitis should have the greatest long-term impact on prevention of HCC in Australia. The role of surveillance of people with cirrhosis to detect small and potentially resectable tumours should be explored.

Adult↗
PubMed1994

Bile acid glucuronidation by rat liver microsomes and cDNA-expressed UDP-glucuronosyltransferases.

Four rat UDP-glucuronosyltransferases (UGTs), UGT2B1, UGT2B2, UGT2B3 and UGT2B6, synthesized in COS-7 cells from appropriate cDNA clones were screened for activity towards a range of bile acids, neutral steroids and retinoic acid. For comparison, as well as optimization of enzymatic assays and product identification, rat liver microsomal preparations from Sprague-Dawley, Fischer 344 and phenobarbital-induced Fischer 344 male rats were also used as enzyme sources. Only two of the expressed proteins, UGT2B1 and UGT2B2, were active in bile acid glucuronidation. UGT2B1 exhibited a high substrate specificity for the carboxyl function of bile acids, whereas UGT2B2 demonstrated less specificity, accepting both hydroxyl and carboxyl functions of bile acids. The preferred substrates for both cloned enzymes were mono-hydroxylated bile acids, followed by di-hydroxylated 6-OH compounds. The levels of UGT activity were sufficient to allow for the identification of the biosynthesized products. The data presented here demonstrate that bile acid glucuronidation is carried out, at least in part, by members of the UGT2B subfamily. Similar results have been obtained previously for neutral steroid glucuronidation. UGT2B3 and UGT2B6 was not involved in BA glucuronidation; none of the cloned enzymes was active toward retinoic acid.

Affinity Labels↗
PubMed1993

Recording the oscillatory potentials of the electroretinogram with the DTL electrode.

Suprathreshold photopic oscillatory potentials recorded with a DTL electrode were compared to those obtained with a Lovac corneal electrode. The overall oscillatory potential response (sum of oscillatory potentials) recorded with the DTL electrode was half of that obtained with the Lovac electrode. However, there was no evidence of a selective attenuation (or amplification) of any given oscillatory potential with the DTL electrode. Similarly, the oscillatory potential relative amplitude ratios and the peak times of the oscillatory potentials were identical for both electrodes. Our findings clearly indicate that the DTL electrode is adequate to record the high-frequency oscillatory potentials. Given the low cost and ease of use, as well as the disposable nature of the DTL electrode, we believe that electroretinographic specialists should seriously consider a wider utilization.

Adolescent↗
PubMed1993

Communication and the humanities: the nature of the nexus.

Humanism and the humanities open the way to communication, to a better professional and political performance, and to a better image of the profession in the eyes of its "real" public. They also offer to individual physicians a richer life, a greater understanding of their own achievements, a protection against isolation, a sense of place, and another sense of purpose. They help to augment the practical wisdom required for and generated by the one-to-one relationship that is the basis of medical practice. Of most importance, they allow a person, in the words of author John Fowles, "to learn one's particular powers, and then with them to humanize the whole: that is the best for the situation."

Communication↗
PubMed1993

Injuries to the bile duct resulting from laparoscopic cholecystectomy.

Laparoscopic cholecystectomy has now become the treatment of choice for symptomatic gall stones. There does, however, appear to be an increased incidence of bile duct injuries. In this article, experience with eight patients who sustained a bile duct injury and were referred to the Hepatobiliary Service at Westmead Hospital, between 1990 and 1992, is reported.

Adult↗
PubMed1993

Non-iatrogenic trauma to the extrahepatic biliary tract.

Between 1980 and 1991, 15 cases of non-iatrogenic extrahepatic biliary tract trauma have been managed at Westmead and the Royal Canberra Hospitals. There were seven cases of gall-bladder injury and eight bile duct injuries. Four cases resulted from penetrating trauma whereas 11 resulted from blunt trauma. Associated injuries were common. Cholecystectomy was the preferred method of management for gall-bladder injuries whereas the bile duct injuries were managed by a variety of techniques. There were three deaths in the series, mostly related to associated injuries. Bile duct injuries were associated with longer hospitalization than gallbladder injuries.

Adolescent↗
PubMed1993

A case of metastatic malignancy masquerading as a hepatic hemangioma on labeled red blood cell scintigraphy.

A 36-yr-old woman with a past history of gastric neuro-endocrine carcinoma (carcinoid tumor) underwent 99mTc-red blood cell (RBC) scintigraphy for evaluation of a 2-cm echogenic liver mass demonstrated on ultrasound. Scan findings were typical of a cavernous hemangioma. On follow-up, however, there was progressive lesion enlargement; histopathology of the resected mass revealed neuro-endocrine carcinoma. This case report, one of the few examples of a false-positive 99mTc-RBC scan, highlights the need for cautious evaluation of focal liver masses, even when there are typical scintigraphic features of cavernous hemangioma.

Adult↗
PubMed1992

Chronic pancreatitis beginning in childhood and adolescence.

We identified 10 patients with symptoms beginning before the age of 20 years in a group of 69 patients with proven chronic pancreatitis. Six of the 10 patients were women. There was a family history of pancreatitis in three patients and alcohol exposure in seven patients. Three patients were dependent on narcotics at the time of presentation. Six of the 10 patients had pancreatic duct dilatation to 10 mm or more in diameter during observation. These six patients underwent pancreaticojejunostomy, with clinical improvement in five patients. The median time of follow-up was 19 years from presentation. No patient developed diabetes and one developed malabsorption. Only three patients were free of pain, but four other patients had only mild episodes that rarely required hospital admission. One patient died of metastatic abdominal carcinoma of unknown origin 51 years after developing familial pancreatitis. Chronic pancreatitis beginning at a young age is sufficiently common to merit special awareness. It is compatible with prolonged survival, and pancreaticojejunostomy may help if the pancreatic duct reaches sufficient size. The disease does not seem to burn out with time.

Adolescent↗