Biomedical subjects

J M Little

Publications and source records attributed to J M Little.

At least 19 recordsLinked to original sources

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↗

PubMed1992

The effects of partial hepatectomy on serum sex steroids in humans.

In both rats and humans, partial hepatectomy results in a substantial increase in serum estradiol concentrations. Because mammalian liver of both sexes contains estrogen receptor, it has been suggested that this surge in serum estrogen concentration may initiate or facilitate liver regeneration. We have reexamined the potential role of sex steroids in human liver regeneration by measuring serum estradiol and testosterone concentrations in men and postmenopausal women before and after hepatic resection. The results were compared with those obtained in patients subjected to other forms of major surgery. In both men and postmenopausal women, serum estradiol levels increased after partial hepatectomy. However, the magnitude of increase was not related to the amount of liver removed. Moreover, similar increases occurred in patients undergoing other major surgical procedures not involving the liver. Serum testosterone concentrations decreased in men and increased in postmenopausal women undergoing all forms of surgery. It is concluded that effects of partial hepatectomy on serum sex steroid levels are nonspecific and probably related to stress. These observations diminish the likelihood that such changes are an important factor in the control of liver regeneration in humans.

Abdomen↗

PubMed1992

Hepatic metabolism of 3-oxoandrost-4-ene-17 beta-carboxylic acid in the adult rat: formation of carboxyl-linked glucuronides both in vivo and in vitro.

The hepatic metabolism of 3-oxoandrost-4-ene-17 beta-carboxylic acid (etienic acid), a probable acidic catabolite of deoxycorticosterone, was investigated using rats prepared with an external biliary fistula. Metabolic products were identified by GC-MS after hydrolysis with beta-glucuronidase and by proton nuclear magnetic resonance after chromatographic purification of protected glucuronides. About 80% of the injected dose was secreted into bile in 20 hours. Three fully reduced etianic acids (3 alpha-hydroxy-5 alpha-, 3 beta-hydroxy-5 alpha-, 3 alpha-hydroxy-5 beta-androstan-17 beta-carboxylic acids) were identified as were several of their di- and trihydroxylated congeners. Glucuronides of these reduced and/or hydroxylated metabolites constituted over half of the recovered dose, with carboxyl-linked glucuronides predominating over 3-hydroxyl-linked glucuronides. The mode of glucuronidation correlated well with the ability of liver microsomes to form the corresponding compounds in vitro from the set of four 3,5-diastereomeric etianic acids.

Androstenes↗

PubMed1992

Pancreaticojejunostomy for chronic pancreatitis.

The treatment of chronic pancreatitis commonly yields disappointing results. Patients with chronic pancreatitis and a dilated pancreatic duct can be treated by longitudinal pancreaticojejunostomy. In order to evaluate the procedure, 20 patients undergoing pancreaticojejunostomy were followed for a median time of more than 5 years. Their clinical characteristics and outcomes have been compared with a group of 43 patients with chronic pancreatitis and small pancreatic ducts. There were no differences between the two groups in the major epidemiological parameters, except that calcification in the gland was more frequently noted in those with large ducts. The operation of longitudinal pancreaticojejunostomy could be accomplished with an acceptable morbidity. There was one death in the postoperative period. Seventy-six per cent of patients were found to have benefited clinically at five years, compared with 48% of those with small duct disease. This difference was statistically significant. Patients who benefited were defined by four factors; they were carrying out their usual occupation at the time of surgery, they were not narcotic dependent at the time of surgery, they had a pancreatic duct width greater than 7 mm and, they had totally abstained from alcohol from before the operation to the time of follow-up. Longitudinal pancreaticojejunostomy probably remains the best surgical treatment for suitable patients with chronic pancreatitis. The operation should only be performed when the pancreatic duct is greater than 7 mm in width. In such patients the operation produces considerable improvement of pain with minimal metabolic disturbance.

Adolescent↗

PubMed1992

Hepatic cavernous haemangioma: a 10 year review.

Between January 1981 and July 1991, 61 patients with hepatic haemangiomata were examined at Westmead Hospital. There were 14 males (22%) and 47 females (78%). The age range was 26-85 years with a median of 49 years. Forty-one had abdominal symptoms but these could be attributed to a haemangioma in only seven cases. There was at least one subcapsular lesion in 17 (28%). Six of the seven symptomatic lesions were subcapsular and five of these were giant haemangiomata (i.e. more than 4 cm in greatest diameter). One large symptomatic lesion was intrahepatic. No association was observed between hepatic haemangiomata and other hepatic or extrahepatic diseases. Haemangiomata were resected from six patients, four of whom were symptomatic. Symptoms improved in all four but did not resolve completely in any. Follow-up ranged from nil in five patients to 108 months in one. The median follow-up was 12 months after initial diagnosis. Ten patients showed evidence of change in their lesions or symptoms while under observation. Only three had worsening symptoms or suspected change in size of a haemangioma. This study highlights the benign, static nature of most hepatic haemangiomata. When this lesion is suspected, the diagnosis should be confirmed with ultrasound (US) and labelled red blood cell scanning (RBCS). Referral for evaluation by a specialist hepatobiliary surgery unit is necessary when symptoms are intolerable, increasing size is definitely demonstrated or the diagnosis is uncertain and cannot be established without specialized investigations. Bleeding into or from these lesions is rare.

Adult↗

PubMed1992

Iatrogenic injuries to the extrahepatic biliary tract.

Iatrogenic injuries to the extrahepatic biliary tract continue to occur and result in significant morbidity. Over the last 10 years, 26 patients have been referred to Westmead Hospital for management of iatrogenic biliary tract injuries. Of these injuries, 22 occurred during cholecystectomy, three during hepatectomy and one during a pancreaticoduodenectomy. The principles of avoidance and repair are discussed. It is concluded that these injuries, although uncommon, continue to occur and that the best treatment results are achieved in specialized hepatobiliary units.

Adult↗

PubMed1992

The Jepson Lecture 1991. Clinical databases and surgical research.

Modern science is preoccupied with basic mechanisms at the level of the gene, molecule, atom and fundamental particle. This preoccupation has affected attitudes to medical science. Paradoxically, politicians and Departments of Health are largely concerned with clinical epiphenomena--outcomes, interventions, effectiveness, efficiency--that are often disregarded by medical scientists and viewed without favour by granting bodies. In the surgical sciences, there is renewed interest in clinical research. The small computer and the readily available database with its compatible statistical package have added a new dimension to clinical research. Database design and analysis are as much a part of the surgical investigator's skills as are laboratory techniques. There are simple rules that govern database design. The database should be simple and flexible, but provide an adequate patient profile. Entry should be standardized by precise inclusion criteria and precise definitions. Data input should be numerical whenever possible. The database program should convert simply to a comprehensive statistical program. The clinical database is useful for both observational and investigational studies. Case series, case control studies and cohort studies can all be developed from well maintained databases. In the Department of Surgery at Westmead Hospital, databases have been maintained for 10 years. The hepatobiliary and pancreatic group of databases have led to 34 publications. The liver tumour database has produced 12 studies and nearly 20 papers. The process of development of one study is outlined in detail. The chance observation of an excess incidence of gallstones in patients having regular ultrasound examinations after major abdominal surgery has been confirmed in a case control study.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical Protocols↗

PubMed1992

Hepatic focal nodular hyperplasia: a benign incidentaloma or a marker of serious hepatic disease?

Amongst 17 patients with hepatic focal nodular hyperplasia (FNH) encountered at Westmead Hospital between 1981 and 1990, FNH was found in association with hepatocellular carcinoma (HCC) in three (3/17), one male and two females, one of whom also had peliosis and an hepatic adenoma. FNH was also found in association with other conditions which may affect hepatic function, structure or circulation, including chronic obstructive airways disease (2), congestive cardiomyopathy (1), chronic active hepatitis (1), granulomatous hepatitis (1), coeliac artery stenosis (1) and metastatic malignant melanoma (1). This report, derived from our experience with FNH over 10 years draws attention to a possible link between FNH, hepatic malignancy and conditions which may disturb the hepatic circulation. We suggest that patients with FNH should be investigated thoroughly and an aggressive management policy should be adopted.

Adult↗

PubMed1992

A comparison of the gastrointestinal side effects of two forms of erythromycin.

BACKGROUND: The gastrointestinal (GI) side effects of erythromycin frequently limit therapy and compliance. PCE Dispertab, a more expensive brand of erythromycin, has been promoted as a well-tolerated new dosage form; however, no studies compare its GI side effects with those of other forms of erythromycin. We compared erythromycin PCE (particles-in-tablet) with E.E.S. (erythromycin ethylsuccinate) to determine whether there is a difference in the incidence and severity of GI side effects. METHODS: This was a multicenter, prospective, single-blind, randomized trial. Observers, but not participants, were blinded to the brand of erythromycin taken until after data analysis. We enrolled ambulatory patients who were at least 18 years old and weighed at least 90 lb for whom erythromycin had been prescribed at a dosage of 1.0 g/d. Subjects were given either the particles-in-tablet form, 333 mg three times daily, or the ethylsuccinate form, 400 mg four times daily, for 10 days and asked to report efficacy, compliance, and the frequency and severity of four GI symptoms (abdominal pain, nausea, vomiting, and diarrhea) in a daily diary. RESULTS: There were no significant differences between the particles-in-tablet and ethylsuccinate forms in incidence of GI side effects (63% and 61%, respectively), average daily GI symptom severity score (0.62 and 0.68, respectively), and GI-related discontinuations (8.5% and 8.2%, respectively). The incidence of moderate or severe nausea was 5% for the particles-in-tablet form and 25% for the ethylsuccinate form (P < .001). CONCLUSIONS: Although ethylsuccinate caused a higher incidence of moderate to severe nausea, there were no differences in the three main outcome measures: incidence of GI side effects, average daily GI-symptom severity score, and GI-related discontinuations. Therefore, we support prescribing erythromycin ethylsuccinate as a first line of treatment because it costs less.

Adult↗

PubMed1991

Mucolipidosis type IV: clinical manifestations and natural history.

The clinical manifestations and psychomotor development of five patients with mucolipidosis IV (MLIV) from three Ashkenazi-Jewish families are reported. The presenting symptoms were hypotonia, developmental delay, corneal clouding, and puffy eyelids. Four of the patients had convergent strabismus and none progressed beyond a developmental age of 15 months. One patient died of aspiration at 17 years while the oldest patient entered puberty at 20 years, developed a coarse face at 30 years, and is now 32 years old. Histopathological studies in four patients showed storage changes characteristic of MLIV.

Adolescent↗

PubMed1991

Taurine-conjugated bile acids act as Ca2+ ionophores.

The ionophoretic properties of several taurine-conjugated bile acids have been investigated in two experimental systems: in a two-phase bulk partitioning system and in proteoliposomes. In the former, a bile acid/Ca2+ complex was extracted into the bulk organic phase and had an experimental stoichiometry of 1.75. Extraction was specific for Ca2+ over Mg2+; Na+ and K+ did not compete with the extraction of Ca2+. In the second system, bile acids at concentrations as low as 5-100 molecules/vesicle lowered the steady-state Ca2+ gradient maintained by a reconstituted sarcoplasmic reticulum Ca(2+)-ATPase. The effect was not due to nonspecific membrane perturbation. In addition to releasing intravesicular Ca2+ in a transmembraneous process, bile acids caused partition of Ca2+/bile acid complexes into the hydrophobic core of the bilayer. In both experimental systems, the Ca2+ ionophoretic activity correlated well with the concentration and the hydrophobicity of the bile acid. Taurolithocholate was most active, with a significant effect measurable at 10 microM in either system. Since bile acid concentrations equal to those used in our experiments can occur in the blood in certain liver diseases, the results support the notion that bile acids can increase the intracellular Ca2+ concentration bypassing the regulatory systems that maintain cellular Ca2+ homeostasis.

Animals↗

PubMed1991

Gallstone formation after major abdominal surgery.

84 patients underwent multiple abdominal ultrasound examinations over a median of 36 months (range 6-140). 11 had gallstones at their first ultrasound examination, and were excluded from further analysis. Of the remaining 73 patients, 12 of 47 who underwent major abdominal surgery had gallstones within 14-36 months of operation, compared with 0 of 26 who did not undergo such surgery. The cumulative prevalence of new gallstones within 3 years of major surgery was 28%; no new gallstones were seen from 36 to up to 140 months postoperatively. By univariate and logistic regression analysis, age and major abdominal surgery were the only significant clinical determinants for the appearance of gallstones during follow-up. The findings of this retrospective study indicate that major abdominal surgery may accelerate the development of gallstones in some patients. If confirmed in a prospective study, it may be possible to define groups at high risk of gallstones after surgery and to institute prophylactic measures.

Abdomen↗

PubMed1991

Non-operative management of blunt liver injuries.

Over a 10-year period 281 patients with liver injuries following blunt abdominal trauma were seen at Westmead Hospital. A decision to treat the liver injury without an operation was made in 55 (20 per cent) of the 281 patients. Two of these 55 patients required a subsequent laparotomy, one for continued bleeding and one for a bile leak. No patient died from a missed intra-abdominal or retroperitoneal injury or from concealed haemorrhage. These patients were compared with 181 patients with liver injuries who were operated on. The two groups of patients could be distinguished in terms of their clinical status on arrival at the hospital, the magnitude of their injury and the sequelae of the injury. Non-operative management proved a safe alternative to an operation in appropriate patients, but a laparotomy to exclude unsuspected intra-abdominal injuries is associated with little significant morbidity and offers some reassurance in managing patients with multiple injuries.

Adolescent↗

PubMed1991

Urinary excretion of lithocholic acid and its conjugates by the bile duct-ligated rat.

The 3-O-glucuronide of lithocholic acid has been shown to be a potent cholestatic agent in rats. However, even after the onset of lithocholic acid glucuronide-induced cholestasis, little of the administered material was recovered in urine. To determine whether this phenomenon was related to the steroid moiety or the form of conjugation, small doses of radiolabeled lithocholic acid glucuronide, lithocholic acid, taurolithocholic acid and/or lithocholic acid sulfate were administered to rats with ligated bile ducts. Urinary excretion of isotope was followed for 24 hr and urinary metabolites of the administered compounds were identified by thin-layer chromatography. Lithocholic and taurolithocholic acids were slowly but relatively efficiently excreted in urine with 73% and 91% of the dose, respectively, recovered in urine over 24 hr. More than 80% of the label in urine from animals receiving these two compounds was in the form of taurine-conjugated beta-muricholic acid. In contrast, lithocholic acid 3-glucuronide and 3-sulfate were poorly excreted: 9% and 12% of the administered doses, respectively, were recovered in urine in 24 hr. Of the small amount of label in urine from rats given the glucuronide, 90% was identified as lithocholic and taurolithocholic acid glucuronides. When lithocholic acid sulfate was given, thin-layer chromatography of urine showed two peaks, which were tentatively identified as tauromurideoxycholic and taurolithocholic acid sulfates. More definitive identification was not possible because of the small amount of the administered dose excreted in urine in these forms.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1991

Post-traumatic bile fistulae.

Bile leakage after liver injury has been reported to be a complication associated with significant mortality. In a prospective study of 306 patients with liver injuries 13 (4%) developed a bile leak. There appear to be two groups of patients, those with a major bile duct injury (three patients) and those with a more peripheral injury (ten patients). Bile leaks may present either as bile peritonitis (six patients) or as a bile leak through a drain site (seven patients). All but one bile leak closed spontaneously at a median of 33 days (range, 3-110 days). There was no mortality but patients incurred a median of four complications each (range, 1-5). This may reflect the severity of the initial injury rather than the bile leak. Respiratory failure and/or infection and sepsis were the most common complications whilst abnormalities of liver function, although common, were seldom of clinical significance.

Adolescent↗

PubMed1991

Palliation of malignant jaundice.

The great majority--perhaps 90%--of patients with malignant jaundice can only be treated by palliative means. The best method of palliation is yet to be defined. Some groups advocate routine surgical bypass, while others hold that all cases should be managed by the insertion of stents, either endoscopically or percutaneously. Recovery from surgery consumes a significant portion of residual lifespan, while stents produce long-term morbidity from stent blockage and cholangitis. The present study used a convenient and simple method to quantify the quality of life that follows surgical bypass and stent insertion. Six patients were followed for at least 6 months after open bypass, and nine after stent insertion. Four patients in each group were still alive at 12 months. The study suggests that there is no significant difference in the quality of life obtained by either method at 6 months, but that there is a clear-cut advantage in having surgical bypass by 12 months. The study points to the need to evolve better stents, to improve stent management and to define criteria which will identify patients who are likely to survive more than 6 months.

Aged↗

PubMed1991

Impact of the CUSA and operative ultrasound on hepatic resection.

New technologies have been developed for liver surgery, and, like all new technologies, they have a glamour which makes them seem desirable. There is an understanding abroad that they make liver surgery easier and open up the field to those without special training. But there is no proof that the new devices are in any way cost-effective, and certainly no proof that liver surgery has become safer since their advent. Fifty consecutive elective liver resections have been studied, almost half performed with the aid of the ultrasonic dissector and aspirator and diagnostic intraoperative ultrasound. There was no mortality in the whole group, but a 24% morbidity. Operative diagnostic ultrasound was thought to allow more precise planning of surgery. Its use was not associated with any increase in operative time, nor was there any increase in postoperative morbidity. The ultrasonic dissector and aspirator improved technique, reflected in a lower blood loss for each case, in fewer transfusions required, in a shorter postoperative hospital stay and in an ability to achieve these benefits in older patients. Neither device could be said to offer an entree to instant liver surgery. The use of the two devices apparently offered savings measured by a fall in the median postoperative hospital stay of 4.5 days, by a saving of 700 mls in median blood requirement and by a fall in transfusion rate from 64% to 9%.

Adolescent↗

PubMed1991

Hepatic dystychoma: a five year experience.

In 5 years, 64 solid hepatic lesions have been referred for diagnosis and management which have been found unexpectedly on organ imaging in well patients. We have called this lesion a "dystychoma". Patients have undergone a two phase investigation programme which allows a diagnosis without admission to hospital in about 50% of cases. About three quarters of patients (47/64) have had non-neoplastic lesions, and about half (33/64) have had haemangiomas. About one patient in four (17/64) has had a neoplasm, and the neoplasm has been malignant in about one in six (11/64) of all patients. We stress the need to pursue the diagnosis in these patients. There were no reliable clinical, biochemical or imaging characteristics which individually distinguished benign from malignant lesions. Age over 55 years, an enlarged liver or a palpable liver mass and a raised serum alkaline phosphatase were all significantly more frequent with malignant tumours. The risk of malignancy rose with the number of risk factors, and all patients with all three risk factors had malignant tumours. Only 11 of the 64 patients were judged to have benefited by significant increase in quality or quantity of life as a result of what was frequently inappropriate organ imaging. There is no strong argument for replacing history taking and physical examination by CT scanning, ultrasound examination or other organ imaging.

Adolescent↗