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Biomedical subjects

J M Little

Publications and source records attributed to J M Little.

At least 91 records · Page 5Linked to original sources

Hepatic venous injury after blunt abdominal trauma.

Data on 306 liver injuries were collected prospectively during a 10-year period. Of the 306 injuries, 281 were the result of blunt trauma. Major hepatic venous injuries were encountered in 41 of 306 patients (13%). Blunt trauma was responsible for 39 of the 41 venous injuries. Twenty-five (61%) of these patients died compared with an overall mortality rate of 31% (chi 2; p less than 0.001). Twenty-two of the 25 deaths were caused by blood loss. Two patterns of hepatic venous injury appeared to predominate: avulsion of the trunk of the right hepatic vein from the inferior vena cava and avulsion of the upper branch of the right hepatic vein. The trunk injury was seen in 15 patients, 12 of whom died. The branch injury was seen in 13 patients, only 4 of whom died (Fisher's exact test; p = 0.006). In what appears to be the largest series of blunt hepatic venous injuries published, the injuries have been classified according to the anatomic site of the injury. Such a classification correlates with prognosis. Differences between blunt and penetrating hepatic venous trauma have been discussed.

Abdominal Injuries↗

Metabolism of lithocholic acid in the rat: formation of lithocholic acid 3-O-glucuronide in vivo.

Milligram amounts of [3 beta-3H]lithocholic (3 alpha-hydroxy-5 beta-cholanoic) acid were administered by intravenous infusion to rats prepared with a biliary fistula. Analysis of sequential bile samples by thin-layer chromatography (TLC) demonstrated that lithocholic acid glucuronide was present in bile throughout the course of the experiments and that its secretion rate paralleled that of total isotope secretion. Initial confirmation of the identity of this metabolite was obtained by the recovery of labeled lithocholic acid after beta-glucuronidase hydrolysis of bile samples. For detailed analysis of biliary metabolites of [3H]lithocholic acid, pooled bile samples from infused rats were subjected to reversed-phase chromatography and four major labeled peaks were isolated. After complete deconjugation, the two major compounds in the combined first two peaks were identified as murideoxycholic (3 alpha, 6 beta-dihydroxy-5 beta-cholanoic) and beta-muricholic (3 alpha, 6 beta, 7 beta-trihydroxy-5 beta-cholanoic) acids and the third peak was identified as taurolithocholic acid. The major component of the fourth peak, after isolation, derivatization (to the methyl ester acetate), and purification by high pressure liquid chromatography (HPLC), was positively identified by proton nuclear magnetic resonance as lithocholic acid 3 alpha-O-(beta-D-glucuronide). These studies have shown, for the first time, that lithocholic acid glucuronide is a product of in vivo hepatic metabolism of lithocholic acid in the rat.

Animals↗

The diagnostic use of the second oscillatory potential in clinical electroretinography.

Of all the electroretinogram (ERG) components (a-wave, b-wave, and oscillatory potentials) only one oscillatory potential, OP2, was found to be significantly correlated with the absolute intensity of the flash stimulus (i.e., the intensity of the stimulus irrespective of the state of retinal adaptation). Our finding was further confirmed in single cell recordings of lateral geniculate unit activity in rabbits in which peak time of OP2 was found to correlate better with the geniculate activity. For these reasons we have identified OP2 as the "intensity coding" oscillatory potential of the ERG. In order to investigate if this new feature could have some clinical significance, we examined photopic ERGs recorded from patients affected with various retinopathies. In most instances the peak time of OP2 paralleled that of the b-wave, that is, in the ERG with delayed b-wave the peak time of OP2 was also delayed, while in ERGs with normal b-wave peak time the peak time of OP2 was also normal. However, in some conditions (especially in cone-rod diseases) a delayed OP2 was found in ERGs with normal b-wave peak times.

Adult↗

The electroretinogram in Stargardt's disease and fundus flavimaculatus.

A retrospective study was performed comparing the ERG results of 15 patients with Stargardt's disease and fundus flavimaculatus. Patients with fundus flavimaculatus had "fish-tail" lesions with or without macular changes, while the Stargardt's group had macular atrophy without fish-tail flecks. The mean visual acuity was 20/200 for the Stargardt's patients compared with a mean of 20/80 for the fundus flavimaculatus patients. The Stargardt's photopic and scotopic amplitudes were respectively 33% and 34% of normal, while the fundus flavimaculatus values were less impaired at 58% and 64% of normal.

Adolescent↗

Percutaneous fine needle aspiration biopsy of canine pancreas allograft provides diagnosis of treatable rejection.

Despite improved pancreas transplant graft survival, early diagnosis of rejection remains a clinical challenge. Using a canine model of whole pancreas transplantation with bladder exocrine drainage we have shown fine needle aspiration biopsy (FNAB) to provide an earlier diagnosis of rejection than fall in urinary amylase (UA). The aim of this study was to assess the ability of anti-rejection therapy to reverse rejection when the diagnosis was based on either FNAB findings or a fall of UA. Sixteen dogs received a total pancreas allograft with an inadequate dose of oral cyclosporine (5 mg/kg/day). Fasting UA levels were measured daily and percutaneous FNAB with ultrasound guidance was performed three times weekly on all dogs. The diagnosis of rejection was made in alternate dogs with either a fall of UA to a level of less than 5000 IU/liter (median 7 days) or when the total corrected increment (TCI) of aspirated infiltrating cells was greater than 2.6 (median 5 days). Anti-rejection therapy consisted of methylprednisolone 10 mg/kg/day iv for 5 days and an increase of oral cyclosporine dosage to 25 mg/kg/day. Early vascular thrombosis (Day 2) occurred in three allografts. Diagnosis of rejection based on a low level of UA permitted the successful reversal of rejection in only one of six grafts, whereas five of seven grafts were successfully treated when rejection diagnosis was based on FNAB. Median allograft survivals were 9 days (range 8-19) and 32 days (range 11-63), respectively (P less than 0.01). The earlier diagnosis of allograft rejection made by FNAB improved the ability of conventional anti-rejection therapy to reverse pancreas allograft rejection and significantly improved allograft survival.

Amylases↗

Perihepatic packing: its role in the management of liver trauma.

Perihepatic packing was used in 25 of 197 (12.7%) patients presenting with liver trauma to Westmead Hospital over an 8 year period. Packing was used either to provide temporary haemostasis prior to transfer or as part of a definitive treatment plan at this hospital. Thirteen patients were packed prior to transfer. Only two were unstable on arrival, one of whom died. They were compared with 18 'comparison' patients with liver injuries of similar severity. In this group 10 were unstable on arrival (P = 0.027), nine of whom died (P = 0.015). Packing was used as part of a definitive treatment plan at Westmead on 17 occasions. Four patients were coagulopathic and five had also been packed prior to arrival. Eight of this group died. Packing is a convenient and safe way of controlling major hepatic haemorrhage prior to transfer to a tertiary referral centre. It may also be part of a definitive treatment plan to control hepatic bleeding especially as many patients arrive with a coagulopathy or develop a coagulopathy during the course of surgery to control bleeding. Packing will control haemorrhage until the coagulopathy has been corrected.

Adolescent↗

Canine whole pancreatic transplantation with exocrine drainage into the bladder.

A canine model of whole pancreas transplantation with pancreaticocystostomy was studied for reproducibility and long-term graft function with oral cyclosporine. The feasibility of the operative technique was established in three dogs and the graft histology at 5 days was studied. Seven pancreatectomized dogs were transplanted without immunosuppression; acute rejection was evident at a median of 10 days (range: 7-12 days). Another 14 non-pancreatectomized dogs were given oral cyclosporine (25 mg/kg per day) resulting in prolonged graft survival (P less than 0.01) with a median (actuarial) survival of 91 days (range: 8-159 days); five dogs had vascular thrombosis or graft rejection and eight dogs died with functioning grafts. Early technical loss in two dogs (8.3%) was due to arterial thrombosis. It is concluded that the model of whole pancreas transplantation was reproducible in dogs, that long-term graft function can be achieved on oral cyclosporine, and that duct patency can be maintained. Graft infarction, either primary or due to rejection, continues to complicate this model of pancreas transplantation.

Animals↗

Albendazole treatment of recurrent hydatid disease: serial evaluation with ultrasound.

Four patients with complex abdominal hydatid cysts, one of whom also had pulmonary and pelvic involvement, were treated with up to six 28-day courses of albendazole 400 mg per oral twice daily. As part of a prospective study, serial ultrasound scanning was performed after each 28-day course of albendazole and showed evidence of remission of disease in all four patients. Transient minor abnormalities of liver function were noted during treatment. Ultrasound scanning showed the disappearance of daughter cysts and cystic septation, increase in echogenicity and marked reduction in cyst size. Consolidation of these changes and, in some cases, disappearance of the cysts, were noted with continued therapy. Albendazole seems to be a safe and effective agent in the treatment of recurrent hydatid disease, exerting most of its cysticidal activity within the first 2-3 months of therapy.

Adult↗

Hilar biliary cancer--are we getting it right?

Recent reviews of the management of hilar biliary cancer suggest that radical resection is the preferred treatment option. It seems true that most of the long term survivors are treated this way, but it is equally true that most patients receive palliative rather than curative treatment. Before we go too far in our advocacy of radical treatment, we need to develop methods for quantifying palliation because that is in truth what we usually achieve. A method of quantifying palliation is described. Surgeons are encouraged to use methods of this kind in order to allow valid comparison of the results of different methods of treatment.

Bile Duct Neoplasms↗

Obstructive jaundice in chronic pancreatitis.

Significant obstructive jaundice in chronic pancreatitis is generally considered to be rare. Eleven of 57 consecutive patients with proven chronic pancreatitis have developed significant obstructive jaundice of more than transient duration. Eight presented as jaundice complicating known pancreatitis and three as jaundice of unknown cause. Life table analysis showed a steady rise in the risk of developing jaundice up to the end of 10 years from the onset of chronic pancreatitis. Jaundice was found to occur in the presence of more "destructive" disease, and jaundiced patients had a higher incidence of pancreatic calcification, diabetes and malabsorption at the time of presentation with jaundice. Obstructive jaundice caused by chronic pancreatitis was found to carry a good prognosis for jaundice, for pain and for life. Only one of the 11 patients died in hospital. It is important to distinguish chronic pancreatitis from cancer in these patients. Pre-operative and intra-operative cytology have been helpful. Stent insertion is not an appropriate method of treatment for these patients because of the benign nature of the disease and the possibility of exacerbating the pancreatitis. It is important to be aware of another form of "malignant masquerade" causing obstructive jaundice.

Adolescent↗

Improvement of canine pancreas-allograft survival with diagnosis of rejection by fine-needle aspiration biopsy.

Early diagnosis of rejection in pancreas-allograft transplantation remains a clinical challenge. The aim of this study was to assess the ability of antirejection therapy to reverse rejection when the diagnosis was based on either fine-needle aspiration biopsy (FNAB) or urinary amylase (UA). Sixteen dogs received a total-pancreas allograft with exocrine drainage into the bladder. Initially, a deliberately low dose of cyclosporin was given. Monitoring included percutaneous FNAB with ultrasound guidance and fasting spot measurements of UA. The diagnosis of rejection was made in alternate dogs when UA fell to less than 5000 IU/L (group A) or when the total corrected increment (TCI) of aspirated infiltrating cells was greater than 2.6 (group B). Antirejection therapy consisted of 10 mg.kg-1.day-1 i.v. methylprednisolone for 5 days and an increased dose of cyclosporin (25 mg.kg-1.day-1). The median allograft survival was 9 days (range 8-19) in group A and 32 days (range 10-63) in group B (P = .01). A fall in UA permitted the successful reversal of rejection in only one of six grafts, whereas five of seven grafts were successfully treated when rejection diagnosis was based on FNAB. In conclusion, early diagnosis of rejection was achieved by FNAB, improving the ability of antirejection therapy to reverse pancreas-allograft rejection and prolong survival.

Animals↗

Effect of bile acids on calcium efflux from isolated rat hepatocytes and perfused rat livers.

The changes in intracellular Ca2+ concentration [( Ca2+]i) of hepatocytes induced by certain bile acids are biphasic: an initial increase is followed by a more gradual decrease. This latter decline in [Ca2+]i may be due to an efflux of Ca2+ across the plasma membrane. This hypothesis was tested by studying the effect of different bile acids on the efflux of 45Ca from preloaded rat hepatocytes and isolated perfused rat livers. The following bile acids were studied: cholic (C), ursodeoxycholic (UDC), chenodeoxycholic (CDC), and deoxycholic (DC) acids; their taurine (T) conjugates (TC, TUDC, TCDC, and TDC); and the taurine, sulfate (S), and glucuronide (Glu) derivatives of lithocholic acid (TLC, LS, TLS, and LGlu, respectively). At 0.3 mM, all bile acids except C, TC, TCDC, UDC, and TUDC significantly increased 45Ca efflux from preloaded hepatocytes without affecting cell viability. Dose-response studies revealed that the minimum effective concentration needed to induce 45Ca efflux was 0.06 mM for LS, 0.8 mM for TCDC, and 10 mM for TC. Efflux of 86Rb from preloaded hepatocytes was not significantly altered by 0.1 mM LS, indicating relative specificity for calcium. TDC and DC, but not TC, increased 45Ca efflux from preloaded perfused rat livers. These results showed that bile acids known to increase [Ca2+]i (CDC, DC, TDC, and TLC) also increased 45Ca efflux from hepatocytes and perfused livers and that efflux was also stimulated by LS, TLS, and LGlu. The extent of this efflux was related to the hydrophobicity of the steroid nucleus of the bile acid. It is speculated that bile acid-induced increases in [Ca2+]i activate the plasma membrane Ca2+ pump resulting in increased Ca2+ efflux.

Animals↗

Defective biliary secretion of bile acid 3-O-glucuronides in rats with hereditary conjugated hyperbilirubinemia.

Biliary secretion of bile acid glucuronides was studied in control rats and in rats with a congenital defect in hepatobiliary transport of organic anions (GY rats). In control animals, hepatobiliary transport of [3H]lithocholic acid 3-O-glucuronide and [3H]cholic acid 3-O-glucuronide was efficient (greater than 95% in 1 h) and comparable to that of [14C]taurocholic acid. Secretion of both glucuronides was impaired in GY rats (24% and 71% at 1 h), whereas that of taurocholate was similar to control values. However, recovery of the glucuronides in bile was nearly complete within 24 h; virtually no radioactivity was found in urine. In control rats, biliary secretion of lithocholic acid 3-O-glucuronide, but not that of cholic acid 3-O-glucuronide or taurocholate, could be delayed by simultaneous infusion of dibromosulphthalein. In mutant rats, dibromosulphthalein infusion was also able to inhibit secretion of cholic acid 3-O-glucuronide. [3H]Hydroxyetianic acid, a C20 short-chain bile acid, was secreted by control rats as a mixture of 20% carboxyl-linked and 80% hydroxyl-linked (3-O-)glucuronide; secretion was very efficient (99% in 1 h). In GY rats, secretion was drastically impaired (16% at 1 h and 74% over a 24-h period). Initially, the mutant secreted more carboxyl- than hydroxyl-linked glucuronide, but the ratio reached that of control animals after 24 h. The rates of formation of both types of hydroxyetianic acid glucuronide by hepatic microsomes from mutant rats were similar or even slightly higher than those of control microsomes. These findings indicate that bile acid 3-O-glucuronides, but probably not carboxyl-linked glucuronides, are secreted into bile by a transport system shared with organic anions such as conjugated bilirubin and dibromosulphthalein, but different from that for amino acid-conjugated bile acids.

Androstanols↗