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Biomedical subjects

P D Wright

Publications and source records attributed to P D Wright.

At least 19 recordsLinked to original sources

Cranial magnetic resonance imaging findings in bacterial endocarditis: the neuroimaging spectrum of septic brain embolization demonstrated in twelve patients.

Infective endocarditis (IE) is an elusive systemic disorder that is often associated with neurologic complications. The contribution of brain magnetic resonance imaging (MRI) to the diagnosis of IE and the spectrum of such findings has been only sparsely described previously. The authors report cranial MRI findings in 12 patients with IE. Each of the patients had MRI evidence of cerebral embolization, with multiple brain lesions noted in most patients (n = 10). Cortical branch infarction was the most common lesion (n = 8), which usually involved the distal middle cerebral artery tree. The next most common finding (n = 7) was numerous small embolic lesions which typically lodged in the supratentorial gray-white junction, some of which were clinically silent and many of which enhanced (probable microabscesses). Brain hemorrhages were noted in four patients, most commonly subarachnoid hemorrhage (n = 3). Two patients developed multiple frank parenchymal macroabscesses/cerebritis lesions. A previously unreported finding in septic embolization, a stroke that became infected with abscess formation ("septic infarction"), was noted in two patients. MRI showed orbital cellulitis in two patients. Most patients studied with gadolinium showed enhancement of lesions (n = 5/8). The authors conclude that cranial MRI may be a valuable tool in the evaluation of patients with IE. The presence of characteristic cranial MRI lesions, especially of multiple types, may prompt early diagnosis and treatment.

Adult

Comparison of short term outcomes of open and laparoscopic cholecystectomy.

OBJECTIVE: To compare the three month outcome of open and laparoscopic cholecystectomy. DESIGN: Prospective assessment of outcome for a series of patients encompassing the introduction of the laparoscopic technique. SETTING: One teaching hospital. PATIENTS: 269 patients admitted for open cholecystectomy between January 1989 and March 1992 and 122 admitted for laparoscopic cholecystectomy between January 1991 and March 1992. MAIN MEASURES: Patients' reported symptoms and self assessed scores with the Nottingham health profile before operation and at three month follow up. Incidence of complications and adverse events after discharge. RESULTS: Similar improvements in symptom rates and health scores were seen regardless of surgical technique. A lower rate of postoperative complications was seen in the patients given laparoscopic surgery (6/95(6%) v 45/235(19%)), and their mean length of stay was lower (4.5 v 9.8 days). Similar results were obtained when the analysis was restricted to a subset of fairly uncomplicated cases (patients aged 60 or less without other illnesses on admission who were not undergoing emergency or urgent surgery), which constituted a larger proportion of the group given laparoscopy (35/95(37%) v 40/235(17%)). Between these two groups no significant difference was seen in the frequency of relevant readmissions to hospital or visits to general practitioners or accident and emergency departments. CONCLUSION: Ideally, a new surgical technique would be evaluated in a randomised trial. In the absence of such a trial, this observational study provides some evidence that the switch from open to laparoscopic cholecystectomy has brought benefits, particularly in terms of reduced length of stay in hospital. A range of clinical and patient derived indicators suggests that these gains have not been associated with a reduction in the quality of the outcome at three months.

Cholecystectomy

Evidence for validity of a health status measure in assessing short term outcomes of cholecystectomy.

OBJECTIVE: To assess the validity of the Nottingham health profile (NHP) as an indicator of short term outcome of cholecystectomy. DESIGN: Prospective assessment of outcome. SETTING: One teaching hospital. Patients--161 consecutive patients admitted for cholecystectomy between January 1989 and September 1990. MAIN MEASURES: Patients' reported symptoms and self assessed NHP scores before cholecystectomy and at follow up at three and 12 months (76 patients); assessment before admission (19). RESULTS: Complete data were obtained preoperatively and at three months' follow up from 154 patients; seven did not respond to the follow up questionnaire. 76/84(90%) patients in the study 12 months or more answered the 12 month follow up questionnaire; eight did not respond. Significant changes in score before and at three months after the operation were observed for four of the six dimensions: energy (35.34 v 19.53, p < 0.0001), pain (27.38 v 9.8, p < 0.0001), sleep (26.99 v 17.51, p = 0.0002), and emotional reactions (16.12 v 7.56, p = 0.001). The mean scores for 76 patients followed up at three and 12 months showed little subsequent change. Scores in readmitted patients were all significantly higher, suggesting poor health. Patients with five reported symptoms had significantly worse scores for all dimensions. Scores were similar before cholecystectomy whether the questionnaire was completed before or after admission. CONCLUSION: The NHP is an appropriate tool for monitoring changes in health after cholecystectomy.

Cholecystectomy

Laser recanalization versus endoscopic intubation in the palliation of malignant dysphagia.

Forty patients with widely disseminated or locally advanced malignant obstruction of the middle or lower third of the oesophagus underwent endoscopic treatment by either NdYAG laser recanalization or intubation. Groups were matched on the basis of tumour location and swallowing was graded clinically before and after treatment. Technical success was achieved in 17 of 20 laser treated and 18 of 20 intubated patients. Pretreatment swallowing ability, histology, tumour location and overall length were unrelated to functional outcome in both groups. However, circumferential tumour length identified endoscopically strongly influenced the quality of swallowing after laser recanalization. Patients with excellent swallowing quality (n = 7) had significantly shorter circumferential tumour lengths, 3.1(1.0) cm, than those with poorer quality swallowing (n = 10), 6.3(1.6)cm, (P less than 0.001). Both methods of treatment had low complication rates and there was one death in the series in the laser-treated group. Laser recanalization provides a better functional result than intubation for short (less than 4 cm) circumferential tumour. Intubation at a single session seems more appropriate than repeated laser therapy when tumour length exceeds 4 cm.

Aged

In vitro study of human skeletal muscle strips: effect of nonesterified fatty acid supply on glucose storage.

To examine the effect of increased nonesterified fatty acid concentration on glucose storage in human muscle, an in vitro method for study of glycogen synthesis in this tissue has been established. Muscle strips obtained from rectus abdominus during elective abdominal surgery were clamped at resting length, and adenosine triphosphate/total adenosine nucleotide ratios remained constant for 3 hours ex vivo. Leakage of enzyme markers of muscle damage was minimal, and electron microscopy showed preserved myofibril ultrastructure. Insulin stimulation brought about a dose-dependent increase in rates of glycogen synthesis with a half-maximal effect at 9 x 10(-10) mol/L insulin. In 15 consecutive studies, basal rates of glycogen synthesis were 4.1 +/- 0.5, 3.2 +/- 0.7, and 3.0 +/- 0.3 nmol glucose/25 mg/h in the absence of palmitate, with 1.4 mmol/L and 2.8 mmol/L palmitate, respectively. Insulin-stimulated rates of glycogen synthesis were 8.6 +/- 1.2, 6.0 +/- 1.8, and 5.8 +/- 0.8 nmol glucose/25 mg/h. Thus, increasing fatty acid concentrations decreased rates of glycogen synthesis both basally and with insulin stimulation. The insulin signal itself was not affected as the percentage stimulation over basal rates remained approximately constant in the presence or absence of fatty acid (2.1-, 1.9- and 1.9-fold, respectively). Insulin sensitivity in vivo is usually expressed as absolute rates of glucose uptake during euglycemic hyperinsulinemia, and if plasma fatty acid elevation were to be studied in vivo an erroneous conclusion may be reached of resistance to hormone action per se.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Carnitine acyltransferases and acyl-CoA hydrolases in human and rat liver.

The activities of carnitine acyltransferases and acyl-CoA hydrolases were determined in human and rat liver to establish the validity of extrapolating from studies on rats to human metabolism. In human liver, carnitine acetyltransferase activity was 10-14 times higher and carnitine octanoyltransferase 1.7-2.4 times higher than in rat liver, while carnitine palmitoyltransferase activity was similar in human and rat. Acetyl-CoA hydrolase and octanoyl-CoA hydrolase activities were lower in human (42-57%) than in rat liver, but palmitoyl-CoA hydrolase activity was similar in both species. The activity of citrate synthase was lower (44%) in human than in rat liver. The low citrate synthase activity and the high carnitine acetyltransferase in human liver suggest that in man acetylcarnitine might be more important as a vehicle for export of acetyl units from mitochondria than citrate. The high activity of carnitine acetyltransferase in human liver is consistent with the observation that acetylcarnitine is the predominant acylcarnitine excreted in diabetic ketosis in man. It is concluded that the rat may not be a valid model for carnitine metabolism in man, and that in human liver carnitine may have an important role in transfer of acetyl groups out of mitochondria and possibly also to extra-hepatic tissues.

Acyltransferases

Somatostatin, anaesthesia, and the carcinoid syndrome. Peri-operative administration of a somatostatin analogue to suppress carcinoid tumour activity.

A patient with carcinoid syndrome on long-term antiserotonin therapy with parachlorophenylalanine, experienced a flushing attack with hypotension during the prophylactic administration of aprotonin prior to the induction of anaesthesia. When she was subsequently prepared with a long-acting somatostatin analogue, octreotide (Sandostatin, Sandoz SMS 201-995), plasma levels of tumour-released hormones were reduced and anaesthesia for resection of hepatic metastases was uneventful. The advantages of an anaesthetic approach based on inhibition of carcinoid tumour activity, rather than antagonism of released hormones, are discussed.

Anesthesia, General

Effect of branched chain amino acid infusions on body protein metabolism in cirrhosis of liver.

Thirty seven patients with established cirrhosis of the liver were subjected to measurement of body protein metabolism using L-(1-14C) labelled leucine as a tracer. The effects of disease severity and those of solutions containing 0%, 16%, 35%, 53%, and 100% branched chain amino acids were evaluated. Significant increases in protein synthesis were noted with solutions containing 35%, 53%, and 100% branched chain amino acids, but in patients receiving 100% branched chain amino acids without additional essential amino acid supplement the increase in synthesis was matched by a significant increase in protein breakdown. Protein balance was thus improved only in patients receiving 35% and 53% branched chain amino acids. It was concluded that the high increase in protein breakdown in patients receiving 100% branched chain amino acids was undesirable, and such a solution should not be recommended for clinical use.

Amino Acids, Branched-Chain

Two-year experience of management of bleeding esophageal varices with a coordinated treatment program based on injection sclerotherapy.

The results of 61 consecutive patients treated for bleeding esophageal varices with a coordinated multidisciplinary protocol are described. The primary form of treatment after vigorous resuscitation was fiberoptic endoscopic injection sclerotherapy under general anesthetic. Thirteen patients failed to be controlled by injection, and eight were able to be treated by percutaneous transhepatic embolization. Those patients who were unable to undergo embolization or whose bleeding did not stop after embolization were controlled by surgery. The overall mortality rate with the 2-year limit was 29 patients (47%); however, only 18 deaths (29%) were related to the hospital admission for bleeding. Only one patient died of continued variceal bleeding. All of the other deaths were from later liver failure or unrelated disease. The results of the study confirmed the high mortality rate in patients with severe liver disease (Child's grade C) undergoing surgical control of bleeding, and it was shown that when control was obtained with injection sclerotherapy and embolization, the 1-year survival rate of a similar group of patients may be as high as 32%.

Anesthesia, General

The management of severe brittle diabetes with "Infusaid" implantable pumps.

Two severely brittle diabetic patients were treated with "Infusaid" implantable insulin infusion pumps. Both were young females with recurrent ketoacidosis, prolonged or repeated hospital admissions, and subcutaneous insulin resistance. They also had psychological problems, and had seriously interfered with their treatment to induce glycaemic instability. Delivery of insulin from the pumps was intravenous (i.v.) in one patient, and intraperitoneal (i.p.) in the other. Following implantation, there was a marked improvement in glycosylated haemoglobin level (HbA1), fasting blood glucose (BG), daily insulin dose and hospitalizations. The beneficial effect has continued to date (9 months, and 12 months follow-up) with no major problems.

Adult

The metabolism of 7-ethoxycoumarin in human liver microsomes and the effect of primary biliary cirrhosis: implications for studies of drug metabolism in liver disease.

Using 7-ethoxycoumarin as a probe substrate, microsomal monoxygenase activity has been measured in liver tissue from patients with primary biliary cirrhosis (PBC) of varying histological severity, and in histologically normal control tissue. Interindividual variation in enzyme activity was considerable, and in no histological category was the activity significantly different to control. We conclude that: (a) in PBC, hepatic microsomal monoxygenase activity is determined primarily by factors other than the histological severity of the liver disease, and (b) studies of xenobiotic metabolism in patients with liver disease should specify the nature of the underlying disease process.

Coumarins

Continuous intraperitoneal insulin infusion in the management of severely brittle diabetes--a metabolic and clinical comparison with intravenous infusion.

We report a comparison of continuous intraperitoneal insulin infusion (CIPII) and continuous intravenous insulin infusion (CIVII) in 6 diabetic patients in whom severe hyperglycaemia and ketoacidosis could not be prevented with subcutaneous or intramuscular insulin. In the short term both methods were equally effective in maintaining glycaemic control. Blood glucose, glycerol, and 3-hydroxybutyrate levels were normal but lactate and pyruvate levels remained elevated with both treatments. Insulin requirements were significantly lower on CIPII than CIVII (70 vs 113 U/day, p less than 0.01). Intraperitoneal insulin delivery was associated with near physiological peripheral plasma insulin profiles in 3 patients. In the longer term CIVII was associated with frequent septicaemia and thrombosis, and was successful in preventing hospitalization for 6 months or more in only one patient. Despite technical problems with CIPII complications were less serious and hospital admission due to metabolic decompensation was prevented for 6 months or more in 3 patients. When subcutaneous insulin delivery is unsuccessful in the management of brittle diabetes, CIPII should be considered rather than CIVII because it is more likely to be successful and less likely to cause serious complications.

Adolescent

The effects of nutrition and trauma on whole-body protein metabolism in man.

Whole-body protein metabolism was determined by a primed constant-rate infusion of L-[ 1-14C ]leucine in patients before and after elective surgery, the nutritional intake being carefully controlled and the surgical stress in individuals being assessed. Pre-operatively, whole-body protein flux (P less than 0.05) and synthesis (P less than 0.05), along with amino acid oxidation (P less than 0.01), increased with nutritional intake whereas protein breakdown remained unaltered. Whole-body protein balance also correlated with intake (P = 0.001). Postoperatively, whole-body protein metabolism was determined with patients either fasted (group 1) or fed (group 2) and the change in metabolism in each individual from a pre-operative study, carried out in the fed state, was calculated. Whole-body protein breakdown increased in both groups (group 1, + 0.91 +/- 0.74 g day-1 kg-1; mean +/- SD, n = 7: group 2, + 0.47, + 0.63 and + 1.01 g day-1 kg-1, n = 3), the change being significant in those fasted after surgery (P less than 0.05). However, the pattern of change in whole-body protein synthesis was entirely different in each group, rising in those fed throughout (+ 0.32, + 0.41 and + 0.66 g day-1 kg-1, n = 3) but falling in those fasted after surgery (-0.38, -0.80 and -1.33 g day-1 kg-1, n = 3). The changes in metabolism appeared more marked in those undergoing greatest surgical stress. Some of the factors involved in the calculations are discussed and their effects on the overall conclusions are considered. A concept of whole-body protein metabolism in the metabolic response to trauma is advocated whereby protein breakdown is largely obligatory to the response, whereas synthesis responds to substrate availability.

Aged

Glucose turnover and recycling in colorectal carcinoma.

Glucose metabolism is affected by various pathologic states including tumors. In this project, glucose turnover and recycling rates in 11 patients with colorectal carcinoma were measured using a double-labelled 3-3H and 1-14C glucose injection technique. Fasting blood glucose, lactate, pyruvate, alanine, glycerol, 3-hydroxybutyrate, acetoacetate, plasma cortisol, and plasma insulin concentrations were also measured. No patient in the study had a history of diabetes mellitus or endocrine disorders, nor any abnormal liver function tests. The findings demonstrated a significantly elevated glucose turnover rate in patients with Dukes C and D lesions in comparison to patients with Dukes B lesions. Cori recycling rates were not significantly different between Dukes B vs. Dukes C and D patients. There were no differences between Dukes B and Dukes C and D patients in any of the metabolites measured. Furthermore, there were no significant differences in glucose turnover or recycling rates as a function of pre-illness weight loss. These data suggest that, when colorectal carcinoma extends beyond the limits of the bowel wall, glucose metabolism is significantly altered.

Aged

Increased incorporation of an infused labelled amino acid into plasma proteins as a means of assessing the severity of injury or activity of disease in surgical patients.

Following injury there is increased synthesis of several plasma proteins. During a constant rate infusion of 1-(1-14C) leucine some of the labeled amino acid became incorporated into plasma proteins, the amount being readily determined after precipitation with perchloric acid. This value was correlated with the clinical state of the patient to see if an index of severity of injury could be derived. Before operation 6.7 +/- 0.5% (mean +/- SD, n = 16) of the infused labeled amino acid was incorporated in asymptomatic patients, irrespective of their dietary intakes, while in the presence of symptomatology this value rose, correlating with tumor staging in patients with colorectal neoplasia (r = 0.988, p = 0.001). It returned to normal following tumor resection, but was elevated in the presence of recurrence or residual disease. After operation it also rose, being maximal in the early postoperative period and following the more major surgical procedures, the increase correlating with the change in cortisol level in patients following cholecystectomy (r = 0.84, p less than 0.01; n = 8). The pattern of distribution of the label among the plasma proteins did not change with increased incorporation. The increase in incorporation of 1-(1-14C) leucine into plasma proteins would appear to offer a good index for severity of injury of activity of a disease state.

Blood Proteins

Development of a technique for measuring the oxidation rate of a 14C-labelled substrate from 14CO2 production without the need for collection of expired air.

1. A method is proposed for the determination of the rate of oxidation of 14C-labelled substrates in man from blood sampling only. 2. The method was verified by simulating release of 14C into the bicarbonate pool of patients by using a constant-rate infusion of sodium [14C]bicarbonate, the plasma level of total 14CO2 (d.p.m. ml-1 70 kg-1) correlating well (r = 0.878, P = 0.001) with the infusion rate (microCi/h). 3. Techniques involved in employing this method are discussed, particularly in the light of errors involved.

Bicarbonates