Biomedical subjects

G S Hebbard

Publications and source records attributed to G S Hebbard.

29 records · Page 2Linked to original sources

PubMed1996

Hyperglycemia affects proximal gastric motor and sensory function during small intestinal triglyceride infusion.

Hyperglycemia slows gastric emptying in normal individuals and patients with diabetes mellitus and may affect both somatic and visceral sensation. The effects of hyperglycemia on proximal gastric motility and sensation during intraduodenal infusion of a triglyceride emulsion were evaluated using a barostat in six normal subjects during euglycemia and hyperglycemia (approximately 15 mmol/l). Isobaric distension induced greater bag volumes during hyperglycemia compared with euglycemia at 3 (452 +/- 26 vs. 343 +/- 12 ml, P < 0.05) and 4 mmHg (600 +/- 55 vs. 497 +/- 50 ml, P < 0.05) above basal pressure. During isovolumetric distension, intrabag pressure was less during hyperglycemia at 500 (2.5 +/- 0.3 vs. 3.5 +/- 0.5 mmHg above basal pressure, P < 0.05) and 600 ml (3.0 +/- 0.4 vs. 4.5 +/- 0.5 mmHg above basal pressure, P < 0.05). Perception of nausea (P < 0.05) and fullness (P < 0.05) was increased during hyperglycemia compared with euglycemia. We conclude that hyperglycemia 1) reduces proximal gastric tone during intraduodenal triglyceride infusion, an effect that may contribute to delayed gastric emptying, and 2) increases the intensity of nausea and fullness during intraduodenal triglyceride infusion and proximal gastric distension, indicative of an effect on visceral sensation.

Adult↗

PubMed1996

Gastric emptying in diabetes: an overview.

Gastric emptying is delayed in 30%-50% of patients with longstanding diabetes mellitus. The prevalence of disordered gastric emptying in patients with "early" Type 2 diabetes is controversial, but it has been suggested that gastric emptying is often accelerated. The pathogenesis of delayed gastric emptying in diabetes is poorly understood. It is, however, clear that acute changes in the blood glucose concentration have a major effect on gastric motor function and gastric emptying. There is an inverse relationship between the rate of gastric emptying and the blood glucose concentration, so that emptying is slower during hyperglycaemia and faster during hypoglycaemia. The motor dysfunctions responsible for delayed gastric emptying in patients with diabetes are heterogeneous. There is a high prevalence of upper gastrointestinal symptoms in diabetes. However, the correlation between symptoms and delay in gastric emptying is poor. Recent studies indicate that the blood glucose concentration modulates the perception of some sensations arising from the gastrointestinal tract. In both normal subjects and patients with diabetes the blood glucose response to oral carbohydrate and gastric emptying are related and there is evidence that modulation of the rate of gastric emptying, by dietary or pharmacological means, could be used to optimise glycaemic control. The use of prokinetic drugs, particularly cisapride, is currently the most effective approach to the treatment of symptomatic patients with gastroparesis. An improved understanding of the pathophysiology of both symptoms and delayed gastric emptying is fundamental to the development of more effective treatments.

Appetite↗

PubMed1995

Postural changes in proximal gastric volume and pressure measured using a gastric barostat.

A barostat was used to examine the effect of changes in posture on the volume and pressure in a bag positioned in the proximal stomach of 14 normal volunteers. Volumes in the supine position were compared with those in the standing, left lateral and right lateral positions at a constant pressure 2 mmHg above basal intragastric pressure. A separate series of measurements was then used to evaluate the effects of the same postural changes on pressure within the bag whilst its volume was kept constant. Changing from the supine to the left lateral position decreased bag volume by 62% when pressure was controlled; pressure increased by 60% when volume was controlled. In contrast, movement from the supine to the right lateral position resulted in a 68% increase in bag volume and a 31% fall in pressure. Moving from supine to standing had inconsistent effects on bag volume and pressure. There was a negative correlation between the magnitudes of the changes in pressure and volume (r2 = 0.557). The observed effects of posture probably result from changes in the compression of the stomach by abdominal viscera and indicate that subject position must be specified and maintained constant in studies of proximal gastric motor function using a barostat.

Adult↗

PubMed1995

Pharmacokinetic considerations in gastrointestinal motor disorders.

Although it has been recognised that alterations in gastrointestinal motility, whether induced by physiological or pathological processes, have significant effects on the pharmacokinetics of orally administered drugs, this subject has received inappropriately little attention. Studies relating to this topic have focused on healthy volunteers and animals and have largely been confined to the effects of single drug doses. There is limited information about the effects of disease on pharmacokinetics under steady-state conditions. Changes in gastrointestinal motility may affect the pharmacokinetics of orally administered drugs by altering the rate of delivery, bioavailability or mucosal absorption of the drug. In general the rate of absorption and time taken to achieve maximal plasma concentrations for well absorbed drugs may be modified by changes in gastrointestinal motility, but overall bioavailability is not usually affected. In these cases the therapeutic and clinical effects of the alteration in pharmacokinetics will, therefore, depend on which parameters are important for the action of the drug. For poorly absorbed drugs both the rate of absorption and bioavailability are likely to be altered by changes in gastrointestinal motility. However, the complex effects of food and disease, as well as the properties and formulation of any drug (solubility, ease of dispersion, delayed release formulation) often make the prediction of the magnitude, or even the direction, of any effect difficult to predict. Drugs with direct effects on gastrointestinal motility may influence their own patterns of absorption. In patients with gastrointestinal motility disorders, drugs administered in a controlled release formulation, or those with poor bioavailability, are most likely to have a poorly predictable therapeutic effect. Care should be taken to ensure that the formulation of the drug, its timing of administration in relation to meals and the use of coadministered drugs optimise, or at least ensure consistent absorption.

Administration, Oral↗

PubMed1994

Oxygen supplementation during upper gastrointestinal endoscopy: a comparison of two methods.

The optimal method of oxygen supplementation during upper gastrointestinal endoscopy has not been clearly defined. The aim of this study was to compare oxygen supplementation via nasal prongs with that via a catheter passed into the low oropharynx to eliminate the effect of mouth breathing. Patients were stratified according to the American Society of Anesthesiologists (ASA) classification of physical status into lower-risk (ASA 1 and 2) and higher-risk (ASA 3) groups. The lower-risk group received intranasal, intrapharyngeal, or no oxygen supplementation, and higher-risk patients received either intranasal or intrapharyngeal oxygen. Continuous arterial oxygen saturation (SpO2) was recorded, using a pulse oximeter, before and during endoscopy. Critical desaturations (SpO2 < or = 90%), minimum SpO2 during endoscopy, and maximum desaturation from the baseline oxygen on air, were evaluated. There was no significant difference in the number of patients desaturating, minimum SpO2, or in the maximum desaturation from the baseline between the groups receiving intranasal or intrapharyngeal oxygen supplementation. In lower-risk patients receiving no supplementary oxygen (n = 27), ten patients (37%) desaturated, compared with one of 52 patients (2%) receiving supplementary oxygen (p < 0.001). There was also a significant difference between these groups in the minimum SpO2 (91% vs 97%, p < 0.001) and the maximum desaturation from the baseline (-5.2% vs +0.7%, p < 0.001) during endoscopy. We conclude that the intranasal and intrapharyngeal methods of oxygen supplementation are of similar efficacy, and that supplementary oxygen significantly decreases the incidence of critical arterial oxygen desaturation that occurs even in healthy patients undergoing upper gastrointestinal endoscopy.

Administration, Intranasal↗

PubMed1994

Transjugular intrahepatic portal-systemic shunts (TIPS)--initial experience and clinical outcome.

BACKGROUND: The clinical role of the transjugular intrahepatic portal-systemic shunt (TIPS) has not been fully defined. AIMS: To determine the technical results of TIPS and the clinical outcome of patients undergoing the procedure. METHODS: Retrospective audit of the results of the first 31 procedures performed in Melbourne. RESULTS: Thirty procedures were performed for variceal haemorrhage, one procedure was for ascites. The aetiology of the liver disease was cirrhosis due to alcohol in 20, cryptogenic in five, chronic viral infection in four, and autoimmune chronic active hepatitis in one. Nodular regenerative hyperplasia was present in one patient. Seventy-seven per cent of procedures were considered successful based on the angiographic demonstration of shunt patency at the end of the procedure. The in-hospital mortality in all patients undergoing TIPS was 45% and was 42% in patients undergoing technically successful TIPS. Only age could be identified as predictive of death in hospital. In patients leaving hospital, we found a rebleeding rate of 57% with one patient dying of bleeding, one requiring balloon tamponade and two requiring variceal sclerotherapy. Hepatic trauma was documented in six cases, shunt thrombosis in four cases, stent displacement in two cases and severe hepatic encephalopathy in one case. CONCLUSIONS: TIPS has the potential to decompress the portal venous system, but the procedure is technically complex and should be performed in the knowledge that mortality and morbidity can be relatively high, particularly in patients whose condition is poor.

Adult↗

PubMed1993

Chronic hepatic encephalopathy following portacaval shunt: management by loop ileostomy.

A 69 year old woman developed intractable episodic hepatic encephalopathy 12 years after an end-to-side portacaval shunt for variceal haemorrhage. Medical management was ineffective in preventing repeated episodes of encephalopathy and caused incapacitating faecal incontinence. A loop ileostomy was created with minimal morbidity and was effective in preventing further episodes of encephalopathy over a follow-up period of 33 months. The patient returned to a normal diet and was able to be discharged home from institutional care. Loop ileostomy is an alternative in the management of patients with hepatic encephalopathy who are poorly responsive to, and/or intolerant of, medical therapy following portasystemic shunt surgery.

Aged↗

PubMed1993

Percutaneous transhepatic measurement of the pressure gradient between the portal and hepatic veins.

BACKGROUND: Knowledge of the portal pressure may be of value in the assessment of patients with chronic liver disease but its measurement is problematic. AIMS: To evaluate the ease and safety of percutaneous transhepatic measurement of the pressure gradient between the portal and hepatic veins and to determine directly the need for an internal zero. METHODS: Sixty-one patients undergoing liver biopsy for suspected liver disease had pressures in branches of portal and hepatic veins measured using a flexible 22G (Chiba) needle. RESULTS: The procedure was successful in all patients, took less than ten minutes in most, and was associated with minimal discomfort. Post-procedure morbidity was similar to that of liver biopsy. Portal pressure using an external zero (either puncture site or sternal angle) was inaccurate compared with pressures obtained using the generally accepted gold standard internal zero, hepatic venous pressure, and led to incorrect classification of the presence or absence of portal hypertension in at least 10% of patients. Variations in hepatic venous pressure were not predictable on clinical grounds. The only histopathological feature predictive of portal hypertension was cirrhosis, 20 of 25 patients with and four of 36 patients without cirrhosis having portal hypertension. Of routine biochemical and haematological tests, only plasma albumin and platelet count jointly (and negatively) predicted hepatic venous pressure gradient on multiple regression analysis (R2 = 0.40). CONCLUSIONS: The use of an internal zero is essential for accurate measurement of portal pressure and this can be achieved safely using the percutaneous, transhepatic route in patients with well compensated liver disease.

Adolescent↗

PubMed1992

Augmentin-induced jaundice with a fatal outcome.

OBJECTIVE: To report a case of death due to Augmentin-induced cholestatic hepatitis and discuss a possible drug interaction between Augmentin and oestrogenic steroids. CLINICAL FEATURES, INTERVENTION AND OUTCOME: An 81-year-old man, on oestrogen therapy for prostatic malignancy, presented with obstructive jaundice one week after completing a four-week course of Augmentin for recurrent urinary tract infection. Liver biopsy showed features of a drug-induced cholestatic hepatitis with bile duct injury. His clinical course was marked by progressive deterioration with increasing jaundice and the development of hepatic encephalopathy. A course of prednisolone did not result in any improvement and he died nine weeks after the onset of jaundice. CONCLUSIONS: The cholestatic hepatitis induced by Augmentin is usually reversible but may be progressive, leading to death. The concurrent administration of ethinyloestradiol, a potentially cholestatic agent, may have altered the susceptibility and/or course of the reaction in this patient.

Aged↗

PubMed1992

99Tcm-labelled IgG scanning does not predict the distribution of intestinal inflammation in patients with inflammatory bowel disease.

In order to assess the value of 99Tcm-labelled-immunoglobulin G(99Tcm-IgG) in the assessment of the activity and distribution of intestinal inflammation in patients with inflammatory bowel disease (IBD), 99Tcm-IgG scans were performed in 18 patients. Patients were divided clinically into two groups, those with (ten patients) and those without (eight patients), intestinal inflammation. Disease activity and distribution were assessed by 111In-oxine granulocyte scanning and/or histological extent of inflammation at endoscopy or surgery in all patients with IBD and most of those without intestinal inflammation. In the assessment of the presence or absence of inflammation, a sensitivity of 80% and specificity of 87% were achieved. However, when the localization of intestinal inflammation was evaluated, only five of eight true positive scans were concordant with the distribution of intestinal inflammation as determined by other methods. Thus, significant areas of inflammation were missed in five of ten patients with IBD (two false negative, three incorrect localization of inflammation). Although 99Tcm-IgG scanning appears to have moderate sensitivity and acceptable specificity in the detection of intestinal inflammation, it performs poorly in assessing the distribution of inflammation and is, therefore, of little value in the assessment of patients with suspected or proven IBD.

Australia↗

PubMed1984

Single-cell studies on hapten-specific B cells: response to T-cell-dependent antigens.

The effectiveness of the hapten-gelatin antigen-affinity fractionation technique for selection of hapten-specific B cells activatable by "T-cell-dependent" (TD) stimuli was assessed. Normal adult murine spleen cells were fractionated on fluorescein (Flu)-gelatin layers and the adherent cells were cultured singly or in small numbers with various sources of syngeneic keyhole limpet hemocyanin (KLH)-primed T lymphocytes. Conditions were defined under which the addition of Flu-KLH caused optimal clonal proliferation and differentiation of B cells into anti-Flu directly hemolytic plaque-forming cells (pfc). It was found that 3-5% of the Flu-specific B cells could be activated, versus 1 in 5000 unfractionated spleen cells. The mean enrichment factor for fractionation was 179, almost identical to that seen when the stimulus is "T-cell-independent" (TI), showing that the method is capable of isolating B cells responsive to antigenic stimuli requiring specific T-cell help. Efforts were made to determine whether TD B cells constituted a separate population from TI B cells by determining clone frequencies using Flu-KLH, the TI antigen Flu-polymerized flagellin (Flu-POL), or a mixture of both for stimulation. With Flu-POL alone and with the mixed stimulus 2-3 times more pfc clones were produced than with Flu-KLH, yet evidence for separate B-cell subsets was not obtained because of strong "bystander" stimulation due to the presence of the carrier-primed T cells in a confined volume of 10 microliters.

Animals↗