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Biomedical subjects

R Hickman

Publications and source records attributed to R Hickman.

At least 19 recordsLinked to original sources

Invited critique

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Journal Article↗

New ultrasound approaches to dialysis access monitoring.

The failure of dialysis access is a frequent source of morbidity and hospitalization. Traditional methods of graft surveillance include: (1) clinical examination, (2) venous line pressure measurements during dialysis, (3) urea or tracer recirculation measurement, (4) continuous wave (CW) Doppler methods, (5) duplex ultrasonography, and (6) radiograph angiography. All these methods require special training and/or laboratory tests. The purpose of this study was to test a simple continuous-wave Doppler method that could be applied to measure the flow rate in dialysis access every time the patient undergoes dialysis. Twenty dialysis patients, 15 with polytetrafluoroethylene grafts and 5 with arteriovenous fistulae, were studied. Two hundred fifty-three examinations were performed over an 8-month period. Doppler waveforms of the access flow were obtained with the pump on, with the pump off, and with the pump on again. Systolic and diastolic Doppler frequency measurements were made, and the pump-on and pump-off measurements were compared. In an access functioning normally, the Doppler frequencies are higher with the pump off than with the pump on. In 22% of the cases, there were abnormal findings in which the Doppler frequencies were lower with the pump off than with the pump on. This occurs if the needles are incorrectly placed, suggesting that recirculation is occurring. Recirculation also occurs if there is stenosis of the access. Examining the hemodialysis access during each dialysis session with an inexpensive directional Doppler may identify a significant stenosis and improve the efficiency of dialysis by detecting those patients in whom the arterial and venous needles are reversed.

Adult↗

A five way crossover human volunteer study to compare the pharmacokinetics of paracetamol following oral administration of two commercially available paracetamol tablets and three development tablets containing paracetamol in combination with sodium bicarbonate or calcium carbonate.

This report concerns a single dose randomized five way crossover study to compare the pharmacokinetics of paracetamol from two commercially available paracetamol (500 mg) tablets and three different development paracetamol (500 mg) tablet formulations containing either sodium bicarbonate (400 mg), sodium bicarbonate (630 mg) or calcium carbonate (375 mg). The results demonstrated that addition of sodium bicarbonate (630 mg) to paracetamol tablets, increased the rate of absorption of paracetamol relative to conventional paracetamol tablets and soluble paracetamol tablets. Addition of sodium bicarbonate (400 mg) to paracetamol tablets increased the absorption rate of paracetamol relative to conventional paracetamol tablets, but there was no difference in the rate of absorption compared to soluble paracetamol tablets. Inclusion of calcium carbonate (375 mg) to paracetamol tablets had no effect on absorption kinetics compared to the conventional paracetamol tablet. The faster absorption observed for the sodium bicarbonate formulations may be as a result of an increase in gastric emptying rate leading to faster transport of paracetamol to the small intestine where absorption takes place.

Acetaminophen↗

Tumour necrosis factor levels during acute rejection and acute tubular necrosis in renal transplant recipients.

Plasma tumour necrosis factor levels were measured serially in 16 patients following renal transplantation, and in 10 patients on haemodialysis and in 12 patients on peritoneal dialysis. The patients on peritoneal dialysis had lower plasma TNF levels than the patients on haemodialysis. There was a decrease in TNF levels immediately following renal transplantation; this is probably related to the bolus doses of methylprednisolone administered intra-operatively. Patients with acute rejection had higher levels of TNF than non-rejecting patients. The increase in TNF levels in rejecting patients was observed 2 days before the clinical manifestation of acute rejection. There was a marked decrease in TNF levels in rejecting patients in response to treatment with steroids. Patients with delayed graft function had higher levels of TNF on the first post-operative day compared to patients with immediate function. These changes in plasma TNF levels following renal transplantation have important clinical and therapeutic implications.

Acute Disease↗

One-stage total hepatectomy in the rat using microvascular anastomoses.

A method is described for one-stage total hepatectomy in the rat using microvascular techniques. The operation consists of creation of a side-to-side mesocaval shunt performed just distal to the renal veins, total removal of the liver with ligation of the portal vein, hepatic arteries, and the bile duct. The vena cava is reconstructed with a segment of vena cava taken from a donor animal. The procedure takes 32 +/- 5 min to complete. Blood glucose concentration was maintained by infusions of balanced salt solution containing from 0.625% to 2.5% dextrose. Mean survival time was 10.5 hr (range, 5.5 to 21.5 hr).

Anastomosis, Surgical↗

Effect of alcohol intoxication on hemodynamic physiology and outcome in patients with traumatic cardiac tamponade.

BACKGROUND: Alcohol intoxication has a detrimental effect on hypovolemic shock. Our aim, was to study its effects on "pure" cardiac tamponade (i.e., without hypovolemia) in patients with penetrating chest injuries. METHODS: Thirty-five intoxicated and 15 nonintoxicated patients (blood alcohol > and < 17 mmol/L) were studied. Initial vital signs (trauma scores), special investigations (hematologic profiles, blood gases, glucose, lactate, and catecholamines), clinical progress (24- and 72-hour acute physiology and chronic health evaluation II scores) and outcome were compared. RESULTS: Intoxicated patients were older (p = 0.02) and more tachypneic on admission (p = 0.006), but no other differences were noted. Mortality was proportional to the degree of shock and was greater in patients who had "front-room" thoracotomies (p < 0.001). Despite the higher percentage of intoxicated patients who were "lifeless" or "in extremis" on admission, they fared no worse than nonintoxicated patients. CONCLUSION: Alcohol intoxication does not have an adverse affect on traumatic cardiac tamponade.

APACHE↗

Fragmentation pattern of mucins in normal and diseased gastric mucosae: a glycoprotein fractionates with gastric mucins purified from mucosal scrapings of cancer and peptic ulcer patients.

BACKGROUND/AIMS: Gastric cancer, a fatal malignancy, is prevalent in the Western Cape region of South Africa. The aim of this study was a biochemical characterisation of gastric mucins in this disease, compared with gastric ulceration and controls from transplant donors. METHODS: Mucins were extracted in a denaturing medium (to prevent endogenous proteolysis) and purified by caesium chloride density gradient ultracentrifugation. Analysis of mucin was by gel filtration, SDS-PAGE and Western blotting methods. RESULTS: All samples of mucin when analysed by gel filtration were found to contain polymeric glycoprotein together with varying amounts of lower-molecular-weight glycoprotein. SDS-PAGE and Western blot analysis showed that diseased stomachs had glycopeptides of a wider range in size and antigenicity with a greater number of smaller fragments immunoreactive to monoclonal antibodies 2-12M1 and 9-13M1. We identified by SDS-PAGE a glycoprotein which co-fractionates in a caesium chloride density gradient with mucins isolated from gastrectomy specimens resected for carcinoma and peptic ulceration and which was absent from mucins of the transplant donor control group. This neuraminidase-sensitive glycoprotein resisted dissociation from mucin during purification in a 3.5 M CsCl density gradient but was partially separable by Sepharose 2B gel chromatography and heat treatment (100 degrees C, 2.0 min) in SDS. Chemical analysis of the glycoprotein by HPLC favours it being an N-linked glycoprotein. Its non-ideal electrophoretic properties make its exact size estimation difficult and we ascribe to it a broad size range of Mr approximately 55-65 kD. CONCLUSION: We conclude that mucins from diseased stomachs were more degraded than those from donors and that the diseased mucosa reproducibly secretes a Mr approximately 55-65 kD glycoprotein, the role of which needs to be established.

Adenocarcinoma↗

The changes in circulating hepatocyte growth factor after partial hepatectomy in the baboon.

There is no established model of regenerative liver resection in the baboon, and no study comparing the circulating hepatocyte growth factor (HGF) response with the DNA synthetic response after liver resection. A mean 20% partial hepatectomy (PH) was performed in 19 baboons and a sham operation comprising liver mobilisation only was performed in 20 baboons. Blood HGF levels were measured up to 5 days after either procedure, using the human HGF enzyme-linked immunosorbent assay (ELISA) kit (Otsuka, Japan). The white cell count (WCC), aspartate transaminase (AST) and bilirubin were also measured. Liver regeneration, reflected by an increase in DNA synthesis, was determined from serial liver biopsies in 23 baboons, using a tritiated thymidine assay of liver thymidine kinase (TK). Liver resection and WCC had a significant influence on circulating HGF levels. There was a linear relationship between WCC and circulating HGF levels, which was independent of PH. For a constant value of WCC, resection produced a peaking of HGF over time, with the maximal levels occurring between 2 and 3 days, compared with the linear response in HGF in sham-operated baboons. Liver damage, as reflected by AST levels, was found to have no significant influence on circulating HGF levels. The 20% PH produced a significant increase in liver TK, with maximum levels evident between 2 and 4 days. Accordingly in this baboon model of PH the increase in biologically active, circulating HGF preceded the increase in liver DNA synthesis over 5 days. This observation supports the role of HGF in hepatocyte proliferation and as an initiator of liver regeneration, and suggests that further investigation into the potential endocrine action of HGF could be studied in this established liver regenerative primate model.

Animals↗

Blood supply of the right and left hepatic ducts.

BACKGROUND: Increasing precision of liver resection and use of reduced liver grafts stimulated this study of the blood supply of the intrahepatic bile ducts. METHOD: Corrosion casts of human liver were dissected to study the blood supply of the right and left hepatic ducts. RESULTS: The dissected casts showed that the ducts are surrounded by a vascular plexus supplied from the main right and left hepatic arteries, segmental arteries, gastroduodenal artery and accessory hepatic arteries. This plexus is closely associated with the arteries supplying the caudate lobe. They arise from both right and left in two general patterns. This plexus links the arterial supplies of the right and left livers. Segment i.v. and the central portion of the left hepatic duct are often supplied by the right arterial system. CONCLUSION: This study provides further insights into bile duct blood supply. The caudate lobe and biliary plexus provide collateral connections between the right and left livers.

Adolescent↗

A modified method of continuous venous anastomosis in microsurgery.

The continuous suture technique for end-to-end vascular anastomosis is cautioned against because of the risk of vessel constriction. A modified method of continuous suture for end-to-end venous microanastomosis is presented in which vessel constriction does not occur. This technique was compared with the conventional interrupted suture technique in the rat femoral vein, with each rat serving as its own control. Forty-eight Long-Evans rats were used. The mean time taken to complete the anastomosis was 9.8 minutes (range, 8-14 minutes) for the modified continuous technique and 17.7 minutes (range, 14-24 minutes) for the conventional interrupted technique (p < 0.05, independent t-test). In addition, the veins were examined under the microscope for patency and the milk test was performed on each anastomosis 30 minutes postanastomosis, and 1 week and 1 month postoperatively. Two groups of rats were sacrificed, one at 1 week and one at 1 month, and the two different anastomoses were compared using vessel morphometry in 40 rats and corrosion casts in 8 rats. All veins were patent postoperatively, as well as at 1 week and 1 month postoperatively. Vessel morphometry confirmed a similar luminal surface area in all veins examined at 1 week and 1 month. A two-way analysis of variance of vessel morphometry indicated no significant interaction between the methods used and the postoperative time (p = 0.60). The modified continuous technique is twice as quick as the conventional interrupted technique for end-to-end microvenous anastomosis and does not lead to vessel constriction.

Analysis of Variance↗

Hepatic energy charge and adenine nucleotide status in rats anesthetized with halothane, isoflurane or enflurane.

BACKGROUND: Volatile anesthetics are known to have varying effects on hepatic oxygen supply in vivo and have been shown to depress hepatic mitochondrial respiration and so energy charge in vitro. However, the effect of halothane, isoflurane and enflurane on hepatic adenine nucleotide status in vivo has not been evaluated. METHODS: Ninety male rats were exposed to 40% oxygen (n = 22) or 40% oxygen in equipotent (1 MAC) concentrations of halothane (1%) (n = 23), isoflurane (1.4%) (n = 22) or enflurane (2%) (n = 23) for 2 hours. All animals were then administered intraperitoneal pentobarbital and anesthesia continued and laparotomy was performed. A liver biopsy was taken for determination of hepatocellular adenosine-5-triphosphate (ATP), adenosine-5-diphosphate (ADP) and adenosine-5-monophosphate (AMP) and computation of energy charge (EC) from ¿(ATP + 1/2ADP)+(ATP + ADP + AMP)¿ and total adenine nucleotides (TAN) from (ATP + ADP + AMP). After the biopsy the aorta was cannulated for blood sampling. RESULTS: Rats in each group were similar in weight, as well as acid base and blood gas status just after liver biopsy. Hepatic energy charge, ATP, ADP, AMP, and TAN levels were not different in animals receiving either halothane, isoflurane or enflurane when compared with those receiving only oxygen. CONCLUSION: One MAC of anesthesia for a period of 2 hours with the described volatile anesthetic agents did not affect adenine nucleotide status in vivo in rats.

Adenine Nucleotides↗

Alterations in porcine gastric mucin during the development of experimental ulceration.

Bile duct ligation in the pig results in ulceration of the pars oesophagea (oesophagogastric junction) within 48 h with 100% reproducibility. This work describes novel observations made during development of such ulcers using an endoscope introduced at intervals postoperatively via a Thomas gastric cannula. Macroscopic and histological changes were recorded and compared with quantitative and qualitative changes in crude mucus scrapings and purified mucins. Crude mucus scrapings of the cardiac gland region had a higher protein content in the ulcerated states than in the normals. After bile duct ligation, the (degraded) mucin glycopeptide/total protein ratio was higher in partially purified mucus from pre-ulcerated and ulcerated stomachs as compared with normal samples. The quantity of purified mucin was less in samples from ulcerated stomachs, and the N-acetylgalactosamine and fucose contents were also decreased. It is possible that these changes resulted in the failure of the mucus barrier and the development of oesophagogastric junction ulceration.

Animals↗