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Biomedical subjects

A Shulkes

Publications and source records attributed to A Shulkes.

At least 55 records · Page 3Linked to original sources
PubMed1996

Conjugation of para-nitrophenol by isolated perfused fetal sheep liver.

Using our recently described, isolated perfused fetal sheep liver model, we have studied the metabolism and disposition of para-nitrophenol (PNP) in intact fetal liver. Fetal sheep (mean gestational age, 137 +/- 7 days; range, 127-145 days; n = 8) were delivered under anesthesia near term, and the livers were isolated and perfused in situ, via the umbilical vein, in an oxygenated 1-liter recirculating system, at pH 7.40 at 37 degrees C. The perfusate delivery rate was 4.39 +/- 1.46 ml/g liver/min. Either a 14-micromol (n = 4), 72-micromol (n = 3), or 144-micromol (n = 5) bolus dose of PNP was added to the reservoir. Samples were taken from the reservoir every 5-10 min, and all bile was collected at 15-30-min intervals. Elimination of PNP from perfusate demonstrated Michaelis-Menten kinetics, and the calculated pharmacokinetic parameters for PNP elimination were KM = 13.0 +/- 9.66 microM, Vmax = 32.1 +/- 22.4 nmol/min/g liver, and intrinsic clearance = 3.39 +/- 2.54 ml/min/g liver. At the end of the 120-min perfusion period, PNP could be accounted for entirely as PNP-sulfate (PNP-S) and PNP-glucuronide (PNP-G). The perfusate ratio of PNP-S to PNP-G at 120 min was 2.21 +/- 0.88 at the 14-micromol dose, 0.86 +/- 0.56 at the 72-micromol dose, and 0.31 +/- 0.17 at the 144-micromol dose, because of saturation of sulfate production with increasing dose. PNP-S and PNP-G were eliminated into bile in small amounts (<3% of dose), and the PNP-S/PNP-G ratio in bile was 1. We conclude that near-term fetal sheep liver can metabolize PNP to PNP-G and PNP-S with efficiencies that may be comparable to those of adults, that, as in adults, sulfation is of low capacity, relative to glucuronidation, and that, unlike adults, fetuses have little capacity to transport the PNP-G formed in the hepatocytes into bile.

Animals↗
PubMed1995

Comparison of continuous versus intermittent ischaemia-reperfusion during liver resection in an experimental model.

It has been proposed that regular restoration of blood flow is beneficial during liver surgery with vascular isolation. The aim of this study was to compare intermittent versus continuous occlusion of blood flow to the resected liver, as measured by survival, liver function tests and histological examination. Male Wistar rats were allocated to have either sham operation, 80 per cent liver resection with 30 min continuous occlusion, or resection with intermittent occlusion (two 15-min periods of ischaemia separated by 5 min reperfusion). There was no significant difference in the survival rate, with 17 of 20 animals surviving in both ischaemia groups. There was a significantly higher serum alanine aminotransferase concentration on day 1 in animals receiving continuous occlusion, and significantly higher concentrations of bilirubin on days 8 and 23 and of serum alkaline phosphatase on day 23 in those having intermittent ischaemia (P < 0.001). There was a significantly greater loss and slower regaining of weight when occlusion was intermittent. Histological changes were significantly more pronounced at day 23 in animals undergoing intermittent ischaemia (P < 0.05), although these were in only one grading. Continuous and intermittent occlusion affected the components of liver function tests differently, with no advantage for one technique. These findings suggest that periodic release of inflow occlusion during liver surgery is not necessary.

Animals↗
PubMed1995

Hepatic ischemia-reperfusion injury modification during liver surgery in rats: pretreatment with nifedipine or misoprostol.

The aim of the study was to determine if pretreatment with misoprostol (a prostaglandin analogue) or nifedipine (a calcium antagonist), know protectants of the whole liver, would ameliorate the ischemia-reperfusion injury (IRI) of resected liver associated with vascular occlusion. Male Wistar rats were allocated to 5 groups (n = 20 each group): sham-operated, liver resection only, liver resection plus pretreatment with 0.1 mg/kg misoprostol, 10 mg/kg, or 2 mg/kg nifedipine during the 3 days before IRI with liver resection. Fifteen percent of the liver was made ischemic by 30-minute continuous vascular occlusion, and the remaining 85% nonischemic liver was resected. The model was designed to have survival of the rats so that liver function could be studied over 3 weeks. Seventeen of 20 control resection rats survived indicating a suitable model for study. The bilirubin level was reduced by 25% on postoperative days 3 through 23 with misoprostol. The serum alanine aminotransferase (ALT) peak was significantly lower on day 1 with misoprostol and high-dose nifedipine (both reduced to half the control resection value). There was a modest but significant reduction of serum alkaline phosphatase (SAP) for low-dose nifedipine on days 1, 2, and 23. Prothrombin had a lower peak and lower values on days 1 through 4 with misoprostol. Liver histological changes were minor, being cytoplasmic vacuolization only, and was slightly more marked in the nifedipine groups. Preoperative misoprostol 0.1 mg/kg and nifedipine 10 mg/kg each ameliorate the IRI associated with liver resection, as measured by liver function tests. Different aspects of liver function were altered by the different agents. These results justify initiating a trial for human liver resections.

Animals↗
PubMed1995

Expression, processing, and secretion of gastrin in patients with colorectal carcinoma.

BACKGROUND & AIMS: The relationship between gastrin and the development of colorectal carcinoma (CRC) remains controversial. Problems with previous studies include failure to measure all forms of gastrin, lack of comparison between stored and secreted gastrin, and not controlling for Helicobacter pylori infection (a known cause of hypergastrinemia). The aim of this study was to quantify progastrin and progastrin-derived peptides in the resected tumor and plasma of patients with CRC and in the antrum and plasma of normal subjects. METHODS: Four region-specific gastrin antisera were used to measure progastrin, glycine-extended gastrin, amidated gastrin, and total gastrin. RESULTS: Progastrin, amidated gastrin, total gastrin, and glycine-extended gastrin were detected in 100%, 69%, 56%, and 44% of tumors, respectively (n = 32). When allowing for H. pylori infection, circulating amidated gastrin levels were not significantly elevated in patients with CRC. However, compared with control H. pylori-positive and H. pylori-negative subjects, fasting plasma total gastrin levels were increased in H. pylori-positive (5.2-fold) and H. pylori-negative (2.3-fold) patients with CRC. CONCLUSIONS: Gastrin or its processing intermediates are present in a high proportion of CRCs. Nonamidated gastrin levels are elevated in the circulation of patients with CRC regardless of H. pylori status. We conclude that gastrin should continue to be assessed as a circulating or autocrine growth factor in the development of CRC.

Aged↗
PubMed1995

Peptide amidating activity and gastrin processing in the developing sheep pancreas.

Gastrin is a regulator of both gastric acidity and gastrointestinal growth and is expressed transiently in the neonatal ovine and human pancreas. C-terminal amidation of glycine extended gastrin (G-gly) to gastrin amide (G-amide) by peptidylglycine alpha-amidating mono-oxygenase (PAM) is the final processing step. To investigate the relationship between PAM and gastrin synthesis in the developing pancreas, we measured PAM activity and the concentrations of gastrins in ovine pancreatic extracts from 95 days of gestation onwards. Pancreatic PAM activity was highest in the 95-day-old fetus (138 +/- 29 pmol/h/mg protein, mean +/- S.E.M.) and decreased to 9.5 +/- 3.7 pmol/h/mg protein in the adult. The circulating enzyme was also highest in the youngest fetus (1840 +/- 165 pmol/h/ml plasma) decreasing to approximately 50% in the 135-day-old fetus, with no further significant changes. The concentration of bioactive G-amide in the pancreas was 2.0 +/- 0.6 pmol/g at 95 days of gestation, 3.4 +/- 0.9 pmol/g at 135 days and decreased to 0.7 +/- 0.1 pmol/g in the adult. The precursor G-gly followed a similar pattern but its concentration was less than 10% of G-amide. These results show that: (a) there are high levels of PAM activity in the ovine fetal pancreas and in the fetal circulation, (b) PAM activity is apparently not rate-limiting in the bioactivation of pancreatic gastrin and (c) the dual expression of both PAM and gastrin in the fetal pancreas is similar to that observed in peptide-secreting tumours of the adult.

Animals↗
PubMed1995

Fetal hepatic propranolol metabolism. Studies in the isolated perfused fetal sheep liver.

We have used an isolated perfused fetal sheep liver preparation to study the fetal hepatic metabolism of propranolol in vitro in the intact organ. Eight livers were perfused in situ via the umbilical vein in an oxygenated recirculating system at 300 ml/min. Radiolabeled 15-microns microspheres were used to quantify the hepatic ductus venosus shunt. Propranolol (4 mg) was dosed into the reservoir as a single bolus and perfusate and bile sampled over 150 min. Propranolol, 4-hydroxy propranolol (4OHP), 5-hydroxy propranolol (5OHP), desisopropylpropranolol (DIP), naphthoxylactic acid (NLA), and alpha-naphthoxyacetic acid (NAA) were assayed by HPLC, before and after deconjugation by enzyme hydrolysis. Mean age was 125 +/- 10 days, and mean liver weight was 66.1 +/- 18.8 g. Oxygen consumption (1.10 +/- 1.03 mumol/g/min), bile flow (0.51 +/- 0.18 microliters/g/min), and perfusion pressure (8.7 +/- 3.3 mm Hg) were stable. Ductus venosus shunt was 41.6 +/- 17.4% of umbilical vein flow. Propranolol clearance was 26.2 +/- 13.4 ml/min, and shunt-corrected extraction of propranolol was 0.26 +/- 0.13. The relative amounts of metabolites in perfusate after 150 min were: 4OHP (25.1%), 5OHP (5.08%) (ring-oxidation products), DIP (6.57%), and NLA (4.33%) (side-chain oxidation products). No alpha NAA (a product of N-dealkylation of NLA) was detected. Except for NLA, metabolites were present predominantly as conjugates. Biliary excretion of unchanged drug and metabolites accounted for a further 1.33% of the propranolol dose. These data indicate that, although the hepatic clearance and extraction of propranolol are low, the fetal sheep liver can metabolize propranolol by both ring- and side-chain oxidation reactions and can conjugate these metabolites.

Animals↗
PubMed1994

Hepatic uptake and excretion of [14C]sodium taurocholate by the isolated perfused fetal sheep liver.

We have developed an in situ isolated perfused fetal sheep liver preparation to study fetal hepatic function free from the confounding influences of the mother and other fetal organs, and we have used the preparation to study the fetal hepatic clearance and biliary excretion of sodium taurocholate (TC). The viability and stability of this model were established by monitoring perfusion pressure, oxygen consumption, perfusate enzymes and electrolytes, the perfusate concentration ratio of lactate to pyruvate, bile flow, and liver histology. Perfusate delivery was 300 mL/min with a mean value of 3.94 mL/min/g liver (range: 2.46-6.72 mL/min/g liver). Gadolinium radiolabeled 15 microns microspheres were used to quantify the ductus venosus shunt through the liver and to determine relative flow rates between right and left hepatic lobes. TC was added to the reservoir either as a [14C]TC tracer bolus dose (2 microCi, N = 5) followed by a constant infusion of unlabeled TC, or as an initial bolus of [14]TC (54 mumol) followed by a [14C]TC constant infusion (30 mumol/hr, specific activity 30 microCi/mmol; N = 3). Perfusate samples were taken from the reservoir every 15 min and bile was collected in 30 min aliquots. Perfusion pressure (7.9 +/ 0.30 mmHg), perfusate potassium and oxygen consumption (0.9 +/- 0.07 mumol/min/g liver) were constant throughout, and the perfusate lactate/pyruvate concentration ratio was low (< 20). Liver histology showed no hypoxic changes. Bile flow fell slightly over the 150 min experiment time from 0.6 to 0.5 muL/min/g liver. These data indicate preparation viability and stability. The extent of the ductus venosus shunt was 16-66% (mean 35 +/- 6%) of umbilical vein flow, which correlated inversely with fetal gestational age (r = 0.94, P < 0.001). Relative flow to right and left lobes of liver was 1:1.4. In bolus dose experiments, TC t1/2 was 81.6 +/- 26 min, clearance (Cl) was 35.0 +/- 22.6 mL/min, shunt corrected extraction (E*) was 0.29 +/- 0.17 and biliary clearance (ClB) was 35.5 +/- 19.5 mL/min. In constant infusion experiments the corresponding results were Cl: 34.7 +/- 18.2, E*: 0.23 +/- 0.16, and ClB 32.7 +/- 17.7. The cumulative biliary excretion of [14C]TC in bolus dose experiments was 86.5 +/- 8.7% of the dose, and in constant infusion experiments, concentration of TC in bile was on average over 800 times that in plasma.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1994

An evaluation of laparoscopic versus open cholecystectomy.

OBJECTIVE: To compare open cholecystectomy (OC) with laparoscopic cholecystectomy (LC) in terms of clinical aspects and a limited review of costs. SETTING: The Austin Hospital, Melbourne, a university teaching hospital. DESIGN: Prospective LC patients were compared with a retrospective group of OC patients whose surgery had been performed by the same surgeons. METHODS: Consecutive patients undergoing LC were interviewed, their medical records were analysed and the cost of their hospitalisation was assessed. Similar data, collected previously from patients undergoing OC, were used for comparison. RESULTS: There were 108 patients in each group, 93.5% treated electively. All had gallstones. No deaths or common bile duct injury occurred. The mean operating room time was 131 +/- 3.7 minutes for OC and 164 +/- 4.7 minutes for LC. Operative cholangiography was attempted in 80% in each group, being successful when attempted in all OCs and in 95% of LCs. The conversion rate of LCs to OCs was 4.5%. Minor complications were more frequent with OCs. The mean duration of hospital stay was 6.5 +/- 0.3 days for OCs and 2.0 +/- 0.2 days for LCs. The amount and period of analgesia were significantly less in the LC group. Patients recovered significantly faster after LC (P < 0.01) during the first eight weeks after surgery. There was no difference by 12 weeks. The overall cost for each LC was $838 less than OC for the entire hospital stay. CONCLUSION: These results support the view that LC is a safe and justified replacement for OC in the elective situation, with benefits to the patient, hospital and general community. The hospital cost for LC was less than for OC.

Adolescent↗
PubMed1994

Somatostatin: physiology and clinical applications.

Somatostatin (SOM) was originally isolated as the hypothalamic inhibitor of growth hormone release but was subsequently shown to have a widespread distribution including the gastrointestinal tract. In fact the gastrointestinal tract contains about 70% of the total body SOM. SOM has inhibitory actions on gastrointestinal exocrine and endocrine secretions, motility and blood flow. Within the gut it functions as an endocrine, paracrine, autocrine and neurocrine factor. SOM is released by a meal, and a number of neurotransmitters and regulatory peptides also influence SOM release. SOM is a key component of the gastrin-acid feedback loop as luminal acid releases SOM, which in turn has inhibitory effects on both gastrin and gastric acid. Consistent with the diverse functions of SOM, a number of different although related SOM receptors with distinct distribution patterns and intracellular mediators have been cloned and sequenced. SOM is the first of the gut regulatory peptides to have a significant therapeutic use. By inhibiting both the target cell (e.g. parietal cell) and the release of the active agent (e.g. gastrin) the therapeutic potential of SOM is magnified. To date most of the clinical experience has been with the one analogue, octreotide. This analogue has a longer half-life than SOM (hours versus minutes) but has only minimal oral activity, therefore requiring subcutaneous injections several times a day. The definite gastrointestinal applications include treatment of gastroenteropancreatic tumours. It is also becoming a favoured treatment for gastrointestinal fistulae, variceal bleeding and diarrhoea. However, octreotide has no consistent effect on tumour growth. The high density of SOM receptors on tumours has allowed localization of tumours using in vivo scintography with labelled octreotide. The sequencing of a variety of SOM receptors with different distributions and differing cellular effector systems raises the likelihood of developing SOM analogues for specific clinical applications.

Amino Acid Sequence↗
PubMed1994

The role of the kidney in the clearance of calcitonin gene related peptide (CGRP).

Calcitonin gene-related peptide (CGRP) is a 37 amino-acid peptide, undetectable in the plasma in health but elevated in certain disease states such as medullary thyroid cancer, and potentially causes symptoms. The kidney is a major site of and influence on the clearance of exogenously infused CGRP. As CGRP might cause symptoms in renal dysfunction, this study was performed to determine the clearance of CGRP in humans and animals with altered renal function. In chronic renal failure patients, CGRP was not detected in plasma either before or after haemodialysis. In sheep, before and after bilateral nephrectomy, there was an approximate halving of plasma clearance and doubling of the circulating half-life of infused CGRP. This reduction in clearance was greater than that which could be accounted for by the reduction in degradation by renal substance alone. This renal influence on extra-renal CGRP metabolism was not due to the renal production of a circulating peptidase as evidenced by the absence of such peptidase in the plasma of normal and anephric sheep. Further, severity of uraemia had no influence on the extra-renal metabolism. The mechanism by which the kidney influences the extra-renal metabolism of CGRP remains obscure.

Animals↗
PubMed1994

Measurement of surgical costs: a clinical analysis.

Because of reduced health care funding it is becoming necessary for surgeons to take a greater interest in the costs of individual operations. This study reports costs directly measurable to the patient, and also the indirect costs of hospital overheads, an operating suite and teaching, which were 37, 10 and 15%, respectively (62%), of hospital budget. A scheme has been developed which could give surgeons a standard to report direct costs. Pre-admission, ward, operating room, recovery, intensive care and post-admission are defined as cost periods and the modalities of staff, equipment (capital, maintenance and replacement), imaging, laboratory and consumables apply to each. This strategy was applied to assess open cholecystectomy (OC) and laparoscopic cholecystectomy (LC) as an example. The direct costs for OC were $3706 and LC $2868, a difference of $838; the indirect and direct costs were OC $6004 and LC $4646, a difference of $1358. Thus indirect cost magnified the difference between the operations. Bed stay, density of nursing and use of disposable instruments were the major influence on direct costs. The individual cost advantage of a shorter bed stay may be countervailed by an increased hospital activity. The main patient benefit of new operations may be improved quality of life and more rapid return to work with prevention of salary losses. A method has been developed to define costs of a particular surgical operation with the purpose of stimulating surgeons' interest in this topic and developing a common style of reporting.(ABSTRACT TRUNCATED AT 250 WORDS)

Cholecystectomy↗
PubMed1994

A peptide related to gastrin releasing peptide is synthesised and secreted by the ovine endometrium in early pregnancy.

We have previously shown that the peptide immunoreactivity related closely to the mitogen GRP is expressed by the pregnant ovine endometrium during the final third of pregnancy. In this study we have established that GRP is also expressed early in ovine pregnancy and have quantified the temporal changes in synthesis, storage and secretion of GRP in the peri- and post-attachment period. Secreted GRP peptide levels rise 10 fold just prior to implantation, while endometrial peptide and mRNA concentrations increase 4 and 13 fold respectively between day 17 and 20, immediately following attachment and corresponding to the onset of placentome development. The main molecular form of endometrial GRP has similar binding characteristics on RP-HPLC to GRP 18-27, but is larger. We conclude that a GRP-like peptide is expressed by the pregnant ovine endometrium from early in pregnancy until term, and that it is likely to play an important role in fetal or uterine maturation.

Animals↗
PubMed1993

Pharmacokinetics and biological activity of kinetensin in conscious sheep.

Kinetensin is a nonapeptide, originally isolated from pepsin-treated plasma, that shares some sequence homology with the C-terminal end of neurotensin. The present study was designed to determine, by infusing kinetensin to conscious sheep, the pharmacokinetics and a neurotensin-like biological activity (pancreatic polypeptide response) of kinetensin. Kinetensin was rapidly metabolized, approximately 200-fold more rapidly than neurotensin. The majority of the metabolism occurred in the circulation as demonstrated both in vivo and in vitro. The lung and gut cleared kinetensin also. Inhibition of converting enzyme, present in highest concentration in the lung, abolished lung clearance but was without effect on kinetensin metabolism by the gut or in the general circulation. Arterial infusion of kinetensin which achieved high blood kinetensin levels at the pancreas did not increase plasma pancreatic polypeptide. We conclude that the extremely rapid degradation of exogenous kinetensin, together with the lack of biological activity, makes it unlikely that kinetensin plays a role as a circulating regulatory peptide. Nevertheless, since the putative kinetensin substrate circulates at microM concentrations, it is feasible that kinetensin is generated and metabolized at the target organ.

Animals↗
PubMed1993

Developmental expression of pancreatic gastrin and somatostatin in the sheep.

The nature and developmental profile of pancreatic gastrin and somatostatin were determined in the ovine fetus, a model considered relevant to human development. Gastrin and somatostatin peptide and mRNA were examined in the pancreas of fetal sheep at 80, 105, 125 and 140 days gestation (term: 145 days), 15-day-old lambs and adult sheep. Highest concentrations of gastrin (both amidated and the glycine-extended precursor) were observed in the lamb pancreas with gastrin mRNA levels highest at 140 days gestation. Amidated gastrin was present almost entirely as sulphated gastrin-17 while glycine-extended gastrin was mostly present as a high molecular weight form. Only glycine-extended gastrin was detected in the adult pancreas, indicating attenuated processing in mature adult pancreas. Up to 140 days gestation, gastrin mRNA correlated better with glycine-extended gastrin than with the amidated form, suggesting that amidation was a rate-limiting factor in the production of bioactive gastrin. Somatostatin mRNA and peptide reached a higher concentration and peaked before that of gastrin. Gastrin is a normal product of the fetal and adult pancreas although, when compared to the antrum, the levels are low and the processing to amidated forms is substantially reduced. Unlike in the stomach, the developmental profile of pancreatic gastrin and somatostatin does not appear to be linked.

Amino Acid Sequence↗
PubMed1993

Peptide alpha-amidation activity in human plasma: relationship to gastrin processing.

OBJECTIVE AND DESIGN: C-terminal amidation is an essential processing step towards bioactivation of many peptides including gastrin. This reaction is catalysed by peptidylglycine alpha-amidating mono-oxygenase (PAM, EC 1.14.17.3) which converts the glycine extended precursors on their carboxyl termini to the des-glycine amidated peptide products. In the case of gastrin, most of the amidation is thought to occur in the antrum. However substantial quantities of glycine extended gastrin and PAM are present in plasma. It is unclear whether circulating PAM reflects the secretory activity of the gastrin secreting cell or whether PAM is involved in the postsecretory processing of gastrin. The aim of the present study was to relate the circulating amidation activity to the plasma concentrations of glycine extended and amidated gastrins. PATIENTS AND MEASUREMENTS: Plasma PAM, gastrin-amide and gastrin-gly were measured in subjects with different gastrin secretory status: healthy subjects basally and following a meal, members of families with multiple endocrine neoplasia type 1 (MEN-1) with normal and high plasma gastrin, and patients with hypergastrinaemic atrophic gastritis. RESULTS: Patients with MEN-1 and hypergastrinaemia tended to have a higher plasma PAM activity than MEN-1 subjects with normal circulating G-NH2 indicating a cosecretion of hormone and PAM. However in contradistinction to patients with medullary thyroid carcinoma, PAM activity does not appear to be a useful tumour marker of gastrinoma. Hypergastrinaemia from a non-tumour source (hypergastrinaemic non-atrophic gastritis) was associated with a lower plasma PAM activity than in normal subjects and may reflect the secretion of a greater proportion of already amidated gastrin. In general, there was no relationship between plasma PAM activity and the ratio of amidated to non-amidated gastrin suggesting that circulating PAM was not involved in the amidation of gastrin. Feeding increased circulating gastrin but had no effect on plasma PAM activity. CONCLUSION: The results support the view that gastrin is amidated at the site of its synthesis and that hypergastrinaemia is associated with elevated plasma amidating enzyme activity only when the gastrin originates from tumour sources.

Anemia, Pernicious↗
PubMed1993

Attitudes towards liver transplantation in Victoria, Australia.

Liver transplantation commenced on a regular basis in Australia in 1985. This followed the first successful orthotopic transplant in Brisbane in 1985 and the setting up of a National Centre for Liver Transplantation in Sydney in 1985 with clinical transplantation beginning there in 1986. A centre was subsequently developed in Melbourne in 1988. As this procedure was perceived to be expensive, and because of discussion on rationing of medical services, the authors were prompted to test the Victorian community awareness and attitude to government funding of transplantation. One year after the establishment of the Victorian Liver Transplantation Programme, a random survey of the Victorian population and of general practitioners in Melbourne was conducted with the assistance of a professional polling company. Sixty-five per cent of the Victorian population knew liver transplantation was available in Victoria, 12% said it was not available and 23% did not know. Among general practitioners, 79% knew liver transplantation was available 14% said it was not available and 7% did not know. Eighty-eight per cent of Victorians and a similar proportion of general practitioners said the State Government should provide funding. Forty-seven per cent of the Victorian population said government should provide total funding and a further 39% funding of more than 50%. Among general practitioners, 33% said total funding should be provided and a further 46% thought that more than 50% of funding should be provided. This survey has revealed convincingly that Victorians have decided that their health care should include the expense of liver transplantation paid for by government. Awareness of the availability of the operation of liver transplantation is developing rapidly.

Attitude to Health↗
PubMed1993

Mammalian bombesin as a hormone in ovine pregnancy: ontogeny, origin, and molecular forms.

Mammalian gastrin-releasing peptides (GRP) are present in female reproductive tissues and stimulate uterine contraction and DNA synthesis in the endometrium. We set out to establish whether the GRP were likely to play a role in fetal development by measuring the fetal and maternal plasma concentrations in chronically cannulated fetal sheep from 115 days gestation to term (145 days) and for 18 days after parturition. Placental fluids and fetal urine were also obtained. In a separate series of animals, uterine, placental, and fetal gut and lung tissues were collected. Samples were extracted in acid and assayed by radioimmunoassay, and molecular forms were characterized by high-performance liquid chromatography. GRP were present in the decidua (> 10 pmol/g), as well as placental, uterine, lung, and gastrointestinal tissues (all < 6 pmol/g). Fetal and maternal plasma GRP were elevated compared with nonpregnant ewes, falling sharply after parturition. Placental fluids and urine also contained GRP (80-410 fmol/ml). The main molecular form in all tissues and fluids examined coeluted with porcine GRP-(18-27). GRP immunoreactivity was primarily localized to epithelial cells of the decidua. These data suggest that plasma GRP is probably derived from the decidua and may play a role as a circulating hormone in ovine fetal and uterine development.

Animals↗