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Biomedical subjects

J M Potter

Publications and source records attributed to J M Potter.

At least 19 recordsLinked to original sources

Pharmacoeconomics of therapeutic drug monitoring in transplantation.

Immunosuppressive drugs have contributed significantly to the success of organ transplantation. Therapeutic drug monitoring is an integral part of transplant protocols. However, there is little information concerning its positive contribution to pharmacoeconomics. Before developing studies to demonstrate the potential benefits of TDM, consideration must be given to the type of TDM to be evaluated. It is argued that, given that the lymphocyte in the central compartment is the target for immunosuppressants, Area-Under-the-Curve monitoring may be a better reflection of control and toxicity than traditional trough monitoring.

Area Under Curve↗

The role of urine cytology in the assessment of lower urinary tract symptoms.

OBJECTIVE: To evaluate the role of urine cytology in the investigation of men with lower urinary tract symptoms (LUTS) in the absence of haematuria. PATIENTS AND METHODS: The study comprised 336 men attending a LUTS assessment clinic, who had neither macroscopic nor microscopic haematuria. One sample of urine was collected for cytology. Those with suspicious urine cytology were investigated with intravenous urography and cystoscopy. RESULTS: Five men had abnormal urine cytology results; on further investigation one of them was found to have carcinoma in situ (CIS) and one to have a transitional cell carcinoma. Three had false-positive urine cytology results. CONCLUSION: A bladder tumour or CIS was detected in 0.6% of the population tested. The cost per cancer diagnosed was GB pound 2020. Urine cytology is a simple noninvasive way of assisting accurate diagnosis of men who have LUTS in the absence of haematuria.

Carcinoma in Situ↗

Serological response to influenza vaccination and nutritional and functional status of patients in geriatric medical long-term care.

INTRODUCTION: in the UK the Department of Health recommends influenza vaccination for elderly people resident in institutional care. However, the efficacy of vaccination may be reduced in very frail elderly people with functional impairment, undernutrition and multiple pathologies. Nutritional and functional status is claimed to affect vaccine responses in healthy elderly subjects. We wished to determine if a relationship could be seen between nutritional and functional status and seroconversion in patients receiving long- term care. METHODS: all patients in geriatric medical long-term care were offered vaccine. Consenting patients had pre- and post-vaccine serology measured using single radial haemolysis. Anthropometry was measured to enable body mass index (BMI) to be calculated. Functional independence was assessed using the 20-point Barthel index. RESULTS: of 260 patients who received influenza vaccine, 137 (36 male, 101 female) consented to venesection for serology and thus form the study population. Mean age was 82 years (SD 7.9). The median Barthel score was 3/20 and the mean BMI was 21.6 (SD 4.6, range 13-36.2). Antibodies to influenza A were undetectable both pre- and post-vaccination in 63/137 patients. In 49 patients the antibody titre rose after vaccination and 25 had detectable antibody titres pre-vaccination which failed to rise post-vaccine. There were no significant associations between post-vaccination influenza antibody responses and BMI, Barthel score or age. CONCLUSION: frail elderly patients in geriatric medical long-term care had a poor antibody response to influenza vaccination. Within this group, serological responses could not be predicted by nutritional or functional status.

Aged↗

Functional and structural characterization of isolated perfused stingray liver including effects of ischaemia/reperfusion.

The morphological and functional characteristics of stingray liver were studied, including the effect of ischaemia/reperfusion. With an isolated perfused model, it was shown that the stingray liver was more resistant than the rat liver to ischaemia/reperfusion injury; this was consistent with the differing partial oxygen tensions usually present in the two species. This study confirmed that whereas stingray hepatocytes form tubules with central bile canaliculi as in other fish, the stingray liver has portal triads and a lobular architecture as in mammals. Apoptosis of hepatocytes, demonstrated in the normal liver, was only marginally enhanced by ischaemia/reperfusion. Resulting apoptotic bodies were phagocytized by macrophage-like cells in hepatocyte tubules. In contrast to rat liver, the stingray liver showed no necrosis after ischaemia-reperfusion.

Animals↗

Carbamazepine-10,11-epoxide in therapeutic drug monitoring.

Carbamazepine (CBZ) is widely used in the treatment of epilepsy, frequently in combination with other anticonvulsants. Its metabolite, carbamazepine-10,11-epoxide, is pharmacologically active and is increased with concurrent use of valproate and other anticonvulsants. This pharmacokinetic interaction may be particularly important because CBZ, its epoxide, phenytoin, and lamotrigine all act on fast voltage-dependent sodium channels. Over a 2-month period, routine serum requests for CBZ (n=47) (excluding known cases of overdose) were also analyzed for CBZ epoxide, phenytoin, and lamotrigine using a simultaneous high performance liquid chromatographic (HPLC) method. Valproate was measured using fluorescence polarization immunoassay (FPIA). With concurrent phenytoin and lamotrigine administration, there was a relative increase in CBZ epoxide and a significant decrease in the ratio of CBZ to epoxide (from more than 5 to 3). If valproate was also present, the concentration of parent and metabolite increased significantly, causing potential toxicity. Two patients in this latter group had significant clinical toxicity, with parent CBZ concentrations in the reference range; a third patient suffered from poor control of seizures. This study illustrates the importance of awareness of the contribution of active metabolites in therapeutic drug monitoring and raises questions about the role of the routine monitoring of such metabolites.

Adult↗

Clinical chemistry and post-liver-transplant monitoring.

Liver transplantation is an accepted therapy for end-stage liver disease. After allografting, a variety of clinical problems may require laboratory involvement for accurate and timely diagnosis and intervention. Critical factors in the choice of a laboratory test menu to support a transplant program include turnaround times that support clinical decisionmaking, real diagnostic value, and real value for money. Particular clinical problems, whose early presentation must be anticipated, include graft ischemia, primary nonfunction, and hepatic artery thrombosis. Acute rejection is common at 5-10 days posttransplantation, the principal target being the biliary tree. Longer-term problems are associated with the therapeutic drug measurement of cyclosporin A and, increasingly, tacrolimus (FK506); the side effects of immunosuppressant therapy also require monitoring. A successful liver transplant program can be adequately supported with a simple battery of automated tests that are cheap, fast, and available at all times.

Biomarkers↗

Analysis of responses to angiotensin I and angiotensin I-(3-10) in the mesenteric vascular bed of the cat.

Responses to angiotensin I and antiogensin I-(3-10), the precursors for angiotensin II and IV, were investigated in the mesenteric vascular bed of the cat. Under constant-flow conditions, injections of precursors and the active peptides into the mesenteric arterial perfusion circuit caused dose-related increases in receptor antagonist that were attenuated by the angiotensin AT1 receptor antagonist DuP532 (2-propyl-4-pentafluorethyl-1-[2'-(2H-tetrazol-5-YL)-1,1'-bi phenyl-4-YL methyl]1H-imidazole-5-carboxylic acid), but not by the angiotensin AT2 receptor antagonist PD123,319 ((S)1-[[4-(dimethylamino)-3-methylphenyl]methyl]-5-(diphenylacetyl )-4,5,6,7- tetrahydro-1H-imadazo[4,5-c]pyridine-6-carboxylic acid, ditriflouroacetate]). Responses to angiotensin I and II were similar as were responses to angiotensin I-(3-10) and angiotensin IV, and these responses were not altered by the presence of a time-delay coil in the perfusion circuit. Responses to angiotensin I and angiotensin I-(3-10) were decreased by the angiotensin converting enzyme inhibitor enalaprilat in a dose of the angiotensin converting enzyme inhibitor that had no effect on responses to angiotensin II and IV and that enhanced vasodilator responses to bradykinin. The putative angiotensin AT2 receptor agonist, p-aminophenylalanine6-angiotensin II, produced dose-related increases in mesenteric arterial perfusion pressure that were reduced by DUP532, suggesting that they are mediated by angiotensin AT1 receptors. These results suggest that angiotensin I and angiotensin I-(3-10) are rapidly and efficiently converted by an angiotensin converting enzyme-dependent pathway into active peptides that induce vasoconstriction by activating angiotensin AT1 receptors in the mesenteric vascular bed of the cat.

Angiotensin I↗

The use of lidocaine as a test of liver function in liver transplantation.

The hepatic metabolism of lidocaine to monoethyl-glycinexylidide (MEGX) is the basis of a dynamic test of liver function. To understand its potential value in liver transplantation, the latter has been considered in the following three separate stages: pretransplantation assessment of potential candidates, potential liver donors, and the transplant recipient. In pretransplantation patients, data support its role in assessing risk of morbidity and mortality. In assessment of the liver transplant donor, there are differences concerning apparent usefulness, and these must be resolved. In the liver transplant recipient, serial measurements are useful to measure real-time hepatic metabolic activity. Low MEGX values reflect the clinical condition of the patient, and the importance of entirely assessing the patient, not just noting the test result, is paramount. This review has considered the role of the MEGX test in liver transplantation.

Humans↗

An optimized model for rat liver perfusion studies.

Conditions which influence the viability, integrity, and extraction efficiency of the isolated perfused rat liver were examined to establish optimal conditions for subsequent work in reperfusion injury studies including the choice of buffer, use of oncotic agents, hematocrit, perfusion flow rate, and pressure. Rat livers were perfused with MOPS-buffered Ringer solution with or without erythrocytes. Perfusates were collected and analyzed for blood gases, electrolytes, enzymes, radioactivity in MID studies, and lignocaine in extraction studies. Liver tissue was sampled for histological examinations, and wet:dry weight of the liver was also determined. MOPS-buffered Ringer solution was found to be superior to Krebs bicarbonate buffer, in terms of pH control and buffering capacity, especially during any prolonged period of liver perfusion. A pH of 7. 2 is chosen for perfusion since this is the physiological pH of the portal blood. The presence of albumin was important as an oncotic agent, particularly when erythrocytes were used in the perfusate. Perfusion pressure, resistance, and vascular volume are flow-dependent and the inclusion of erythrocytes in the perfusate substantially altered the flow characteristics for perfusion pressure and resistance but not vascular volume. Lignocaine extraction was relatively flow-independent. Perfusion injury as defined by enzyme release and tissue fine structure was closely related to the supply of O2. The optimal conditions for liver perfusion depend upon an adequate supply of oxygen. This can be achieved by using either erythrocyte-free perfusate at a flow rate greater than 6 ml/min/g liver or a 20% erythrocyte-containing perfusate at 2 ml/min/g.

Animals↗

The use of the lidocaine-monoethylglycinexylidide test in the liver transplant recipient.

The lidocaine-monoethylglycinexylidide (MEGX) test is used to monitor liver function in liver transplant recipients. Serial studies have been undertaken after 155 allografts. The initial MEGX concentration is significantly correlated with the donor MEGX concentration. It is also influenced by the recipient's pretransplant bilirubin concentration, being lowest among patients with very high bilirubin levels. Use of segmental grafts is also accompanied by low MEGX concentrations. The flow-dependent clearance of lidocaine makes it a sensitive indicator of disturbed liver blood flow, with decreased MEGX concentrations occurring in hepatic artery thrombosis and rejection and as a result of cardiac failure and pulmonary effusions. Significant hepatic ischemia resulting in delayed initial function or cholestasis also is associated with low MEGX concentrations. The initial median MEGX concentrations were lowest among patients who required retransplantation or who died within 2 months of allografting.

Adolescent↗

Gait speed and activities of daily living function in geriatric patients.

OBJECTIVE: To establish the relationship between gait speed (GS) and functional independence in elderly people. DESIGN: GS is suggested as being a criterion standard in rehabilitation reflecting muscle strength. This study assessed the relationship between gait speed and functional independence in Activities of Daily Living (ADL). GS was measured by portable accelerometer over 2 meters. The mean of 3 attempts was taken. ADL function was measured by an occupational therapist using the modified Barthel ADL Index. The relationship between these measures was assessed by a statistician. SETTING: A geriatric unit in a hospital in Scotland. PATIENTS: One hundred sixty-one inpatients and outpatients were selected at random from the patients of a geriatric unit over a 3-month period. Patients were eligible if they were mobile with or without a walking aid. INTERVENTIONS: GS was measured by portable ultrasonic accelerometer. Patients were reviewed by an occupational therapist, blinded to their GS, who recorded functional capacity. Case sheet review provided diagnostic details and cognitive function. The type of floor surface was recorded. MAIN OUTCOME MEASURES: GS (m/sec), and Barthel score. RESULTS: Patients with GS of < .25m/sec were more likely to be dependent in one or more ADL function, p < .01. Those with a GS between .35 and .55m/sec were more likely to be independent in all ADL functions, p < .001. Patients whose GS was > .55m/sec did not maintain this independence. There was no relationship between GS and floor surface or cognitive function. CONCLUSIONS: GS is a useful indicator of ADL function in geriatric patients.

Activities of Daily Living↗

Living wills: would sick people change their minds?

Patients admitted acutely to a geriatric medical unit were interviewed on admission about their opinions on cardiopulmonary resuscitation (CPR). They underwent a general examination and their mental health was documented by completing the geriatric depression scale. Those who did not wish CPR in the event of a cardiac arrest were questioned again on recovery. Of 216 patients admitted, only three objected to answering the questions and after the other exclusion criteria were applied, 100 patients were included in the study. A total of 92% of patients wished CPR in the event of a cardiac arrest. The 8% who did not wish CPR contained more people scoring high on the geriatric depression scale. After recovery, three of that eight had changed their minds and wished CPR if required. Patients who are acutely unwell may make decisions that are influenced by their condition at this point in time and it is important to recognize that these decisions may not be maintained. In this study, consultant geriatricians did not reflect their patients' desires in making decisions about who should receive CPR if required.

Acute Disease↗

Basic pharmacology.

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Pharmaceutical Preparations↗

Lignocaine metabolism and liver function testing in primary graft failure following orthotopic liver transplantation.

OBJECTIVE: To report the use of lignocaine and the measurement of its metabolite, monoethylglycinexylidide (MEGX), as a dynamic test of liver function. CLINICAL FEATURES: The conversion of lignocaine to MEGX has been used serially as a test of liver function in a liver transplant recipient for whom retransplantation was necessary because of primary non-function (PNF) of the initial graft. MEGX concentrations were markedly depressed with individual episodes of PNF, cardiac failure and rejection in this patient. CONCLUSION: The test provided useful additional supportive information in assessment of the patient and management of intercurrent problems following liver transplantation.

Female↗

Use of monoethylglycinexylidide as a liver function test in the liver transplant recipient.

The hepatic conversion of lignocaine to monoethylglycinexylidide (MEGX) has been used as a real time monitor of liver function in liver transplant recipients. Data are reported for the first 4 weeks after transplant in 50 consecutive orthotopic liver grafts in 47 adults. The MEGX concentration was significantly depressed by approximately 50% in those patients in whom there was a complicated clinical course (excluding steroid-sensitive rejection) after transplantation, compared with patients in whom major complications did not occur. The MEGX concentration in the recipients after transplant was independent of the donor MEGX concentration, but, in addition to the patient's clinical status, was strongly influenced by the recipients pretransplant biochemical profile, being inversely related to the pretransplant bilirubin concentration. MEGX concentrations < 25 micrograms/L in the first 36 hr after revascularization were predictive of greater morbidity and mortality.

Adolescent↗