Affordable measurement of human total energy expenditure and body composition using one-tenth dose doubly labelled water.

BACKGROUND: The doubly labelled water (DLW) method is the technique of choice for measurement of free-living total energy expenditure (TEE) in humans. A major constraint on the clinical applicability of the method has been the expense of the (18)O isotope. METHOD: We have used a reduced-dose (one-tenth of the currently recommended standard dose) of DLW for the measurement of TEE and body composition in nine healthy adult male volunteers. RESULTS: TEE measured by reduced-dose DLW was positively correlated with resting energy expenditure measured by metabolic cart (r=0.87, P<0.01). Isotope-derived fat mass and body mass index were strongly correlated (r=0.86, P<0.01). In four subjects in whom we performed a complementary evaluation using standard-dose isotope enrichment, the TEE measurements were satisfactorily comparable (mean+/-s.d.: reduced dose 2586+/-155 kcal/day vs standard dose 2843+/-321 kcal/day; mean difference 257+/-265 kcal/day). CONCLUSION: These data indicate that DLW measurements of human energy expenditure and body composition can be performed at a substantially reduced dose (and cost) of isotope enrichment than is currently employed.

Biliary drainage for obstructive jaundice enhances hepatic energy status in humans: a 31-phosphorus magnetic resonance spectroscopy study.

BACKGROUND: Biliary obstruction impairs liver function although the pathophysiological mechanism is incompletely understood. AIMS: The aim of this study was to examine serial changes in liver metabolism in patients with obstructive jaundice using image guided in vivo 31-phosphorus magnetic resonance spectroscopy ((31)P MRS). This technique allows repeated and non-invasive assay of organ energy metabolism and phospholipid biochemistry. PATIENTS: We studied 10 patients presenting with obstructive jaundice secondary to extrahepatic localised malignancy. There were eight men and two women, median age 72 years (range 54-94), six with cholangiocarcinoma (all Bismuth type 1) and four with carcinoma of the head of the pancreas. Ten healthy volunteers (median age 24 years (range 21-26)) were studied for comparison. METHODS: Hepatic metabolism in jaundiced patients was measured by (31)P MRS at presentation and again after a one week period of biliary drainage. Conventional liver function tests were also recorded. RESULTS: Compared with controls, liver spectra from jaundiced patients contained an excess of phosphomonoester (PME) metabolites (PME/total phosphate median 10.3% (interquartile range 8.7-11.5) in controls, 15.4% (13.1-17.7) in jaundiced cases; p<0.01). Biliary decompression was achieved in all patients (five with internal stents and five by external drainage catheters), and plasma biochemistry improved predictably (bilirubin 176 micromol/l (158-351) at presentation, 110 micromol/l (42-241) after drainage for one week; p<0.01). Enhancement of hepatic energy status, measured by the ratio of adenosine triphosphate (ATP) to inorganic phosphate (Pi), was observed in all cases after relief of biliary obstruction (ATP/Pi 1.4 (1.17-1.69) at presentation, 1.97 (1.4-2.48) after drainage; p<0.01) and was independent of the route of bile drainage. Hepatic phosphodiester (PDE) content was decreased after relief of obstruction (PDE/total phosphate 25.2% (20.5-27.4) at presentation, 19.8% (16.6-24.5) after drainage; p<0.01). This change was probably due to a reduction in the contribution from bile contents to this resonance as a strong PDE signal was also detectable in spectra obtained from separate bile specimens. CONCLUSIONS: Obstructive jaundice produces alterations in liver phosphoester biochemistry, most likely reflecting disturbances in phospholipid metabolism. Relief of biliary obstruction is associated with a measurable increase in hepatic energy status. Bile may contribute to the phosphodiester signal of the 31-phosphorus liver spectrum and changes in these resonances must therefore be interpreted with caution and in relation to the clinical situation. Monitoring of liver metabolism by (31)P MRS may allow clinicians to refine the selection and timing of therapeutic options in jaundiced patients.

Human liver regeneration: hepatic energy economy is less efficient when the organ is diseased.

Recovery of liver cell mass following hepatectomy requires a metabolic compromise between differentiated function and organ regrowth. Clinical experience has shown that hepatic failure after resection is more common when the organ is diseased. We have evaluated intracellular hepatic biochemistry in patients with normal and cirrhotic livers undergoing partial hepatectomy, using 31-phosphorus magnetic resonance spectroscopy ((31)P MRS). Eighteen patients were studied, half with normal liver architecture (normal group, n = 9) and half with cirrhotic parenchyma (cirrhosis group, n = 9). Magnetic resonance examinations were performed preoperatively and on postoperative days 2, 4, 6, 14, and 28. Hepatic volume (estimated by magnetic resonance imaging [MRI]) and blood chemistries were measured at the same intervals. Following a comparable reduction in parenchymal volume, the cirrhotic group demonstrated a more sustained fall in adenosine triphosphate (ATP) energy state. Disturbance of membrane phospholipid metabolism and duration of acute-phase reaction were more marked when the liver was diseased. The pattern of derangement of hepatic function, however, was similar in the two groups. Overall, the recovery process was less efficient in the cirrhotic organ, and culminated in a diminished rate and extent of the regenerative response. These outcomes indicate that liver regeneration after partial hepatectomy involves modulation of hepatic energy economy in response to changing work demands. The efficiency of this process is influenced by the histopathologic state of the organ, and in turn governs the physiologic reserve. These findings may explain the mechanism of posthepatectomy liver failure, and offer a rational basis for the assessment of novel hepatic support strategies.

Neutrophil activation and hyperamylasaemia after endoscopic retrograde cholangiopancreatography: potential role for the leukocyte in the pathogenesis of acute pancreatitis.

BACKGROUND AND STUDY AIMS: Hyperamylasaemia occurs in up to 60% of patients following endoscopic retrograde cholangiopancreatography (ERCP), and in a small proportion of patients (1-5%) acute pancreatitis may develop. We evaluated the role of the neutrophil in post-ERCP hyperamylasaemia and acute pancreatitis by measuring circulating CD11b adhesion receptor expression--an indicator of leukocyte activation. PATIENTS AND METHODS: A total of 43 patients undergoing elective ERCP were studied. Peripheral blood measurements of amylase activity and neutrophil CD11b content (by flow cytometry) were made immediately before ERCP (baseline), and at 2 and 24 hours after the procedure. RESULTS: ERCP induced an increase in amylase level above baseline in 41 of 43 patients. The 2-hour and 24-hour post-ERCP amylase levels were directly related (R = 0.9, P < 0.01). Baseline CD11b receptor status was positively correlated with post-ERCP amylase activity (R = 0.4, P < 0.05), and this relationship was stronger when pancreatography had been performed (R = 0.67, P < 0.01). Three patients (7%) developed clinical acute pancreatitis, with post-ERCP amylase levels persistently elevated above 1000 IU/l. Multiple linear regression identified CD11b expression as the most significant explanatory variable for amylase level after ERCP (multiple R = 0.74, P < 0.01). CONCLUSIONS: The findings from this pilot study indicate an association between neutrophil activation and hyperamylasaemia following ERCP, and suggest a role for this leukocyte in the pathogenesis of pancreatitis. Further study of neutrophil characteristics may allow identification of individual susceptibility to ERCP-induced pancreatic injury.

Elevated tumour marker CA19-9: clinical interpretation and influence of obstructive jaundice.

AIMS: The tumour marker CA19-9 has been promoted as a reliable test for the detection of pancreatobiliary malignancy, yet its diagnostic role remains poorly defined. In this study the clinical interpretation of a raised serum CA19-9 level has been evaluated, with particular reference to obstructive jaundice. METHODS: One hundred and sixty-four patients with a CA19-9 level above 33 U/ml were studied. Serum CA19-9 was compared with clinical diagnosis and correlated with serum bilirubin level. In a subgroup of jaundiced patients (16 benign and 15 malignant cases), follow-up CA19-9 levels were determined 2 weeks after biliary drainage. RESULTS: The median CA19-9 level was lower in benign cases (102 (IQR 50-264) U/ml) than those with pancreatobiliary tumours (910 (IQR 263-6170) U/ml; P<0.01), although the overlap was substantial. In benign jaundiced cases, a positive correlation was observed between bilirubin and CA19-9 elevation (R=0.41, P<0.01). Relief of jaundice was associated with a fall in CA19-9 level in all benign cases and in nine of the 15 with malignancy. CONCLUSION: Confident discrimination between benign and malignant disease could not be made on the basis of a solitary elevated CA19-9 measurement. Hyperbilirubinaemia was associated with a further deterioration in specificity and caution is warranted when interpreting the results in jaundiced patients. Overall, only one half of patients with an elevated CA19-9 level ultimately proved to harbour a malignancy.

Late-onset deep prosthetic infection following mesh repair of inguinal hernia.

BACKGROUND: The use of prosthetic biomaterials for the primary repair of inguinal hernias is now commonplace. Late-onset deep-seated prosthetic infection can be an unexpected complication. METHODS: The literature from a Medline search relating to the biology of mesh in the setting of hernia repair is discussed. CONCLUSIONS: The use of a foreign body for hernia repair does not appear to alter the incidence of superficial wound infection. Late-onset deep graft infection has been rarely reported, and the true incidence is yet to be established. With the more widespread use of mesh materials, this complication may become increasingly evident.

Superiority of blood over saline resuscitation from hemorrhagic shock: a 31P magnetic resonance spectroscopy study.

OBJECTIVE: To study the relation between blood and saline administration, postresuscitation hematocrit (Hct) level, and metabolic recovery after hemorrhagic shock. SUMMARY BACKGROUND DATA: It is generally believed that crystalloid can be substituted, in whole or in part, for blood during resuscitation of hemorrhagic shock. This is based on the belief that Hct can be safely reduced but should not fall below a critical level. METHODS: Male rats weighing 200 g were subjected to an isobaric hemorrhagic shock at a mean arterial pressure of 30 mmHg for 14 minutes, after which they were randomized to one of three resuscitation regimens. Control group (n = 36) were resuscitated by return of all shed blood. Mid-Hct (n = 39) and low-Hct (n = 60) groups were depleted of one third and one half of their circulating blood volumes, respectively, and were resuscitated with three times that volume of normal saline. Skeletal muscle intracellular energetics and pH were measured serially using 31P magnetic resonance spectroscopy at baseline, during shock, and after resuscitation. Arterial blood was sampled at the same time points. The number of surviving animals in each group at 24 hours was recorded. RESULTS: After resuscitation, surviving rats in the low-Hct group demonstrated a greater consumption of high-energy phosphocreatine stores than did the other groups (control = 0.479 +/- 0.003, mid-Hct = 0.465 +/- 0.004, low-Hct = 0.457 +/- 0.007, mean +/- standard error of the mean; p < 0.01 low-Hct vs. other groups by analysis of variance). The rats that received saline resuscitation developed a relative intracellular acidosis (control = 7.29 +/- 0.02, mid-Hct = 7.25 +/- 0.02, low-Hct = 7.23 +/- 0.02; p < 0.05 controls vs. other groups by analysis of variance). At 24 hours, the death rates were significantly different among the groups: control = 1 of 36 rats (2.8%), mid-Hct = 6 of 39 (15.4%), and low-Hct = 14 of 60 (23.3%) (p < 0.05 by chi square analysis). CONCLUSION: The oxygen-carrying capacity of resuscitation fluid has an important impact on intracellular metabolism and outcome.

Ultrasound scanning of the acute abdomen by surgeons in training.

Ultrasound is widely used in the investigation of abdominal symptoms. Its increasing popularity may lead to pressure on radiological services, diagnostic delay and prolonged hospital stay. Immediate imaging performed by radiologists can contribute useful information in acute emergencies. This study assessed the accuracy and value of abdominal ultrasonography when carried out by admitting surgeons. Three surgical registrars were first instructed for two half days by a consultant radiologist. Patients with acute symptoms were scanned at the time of initial presentation using an Aloka SSD-620 scanner with 3.5 and 5 MHz probes. A total of 205 scans was performed--124 of the upper and 81 of the lower abdomen. Immediate ultrasound provided information that contributed to the establishment or refutal of a diagnosis in 138 patients (67.3%), predominantly by confirming or excluding hepatobiliary disease, tubo-ovarian pathology or aortic aneurysms and in blunt abdominal trauma. The diagnosis was altered in a small proportion (7.8%). Scanning proved unhelpful in 62 patients and misleading in five. Findings concurred with those of a radiologist in 86% of the 139 patients subsequently scanned. Abdominal ultrasound is a useful tool in the hands of surgeons dealing with emergencies and may occasionally provide vital information. If access to radiological facilities is delayed, ultrasound by the admitting surgeon could lead to improved patient management and cost savings.

Multicentre audit of death from acute pancreatitis.

A prospective audit of acute pancreatitis involving nine hospitals in the North-West Thames Region recruited 631 patients over 54 months. There were 57 deaths (9 per cent); a diagnosis had been reached in 50 patients (88 per cent) before death and in seven (12 per cent) at autopsy. Eighteen patients (32 per cent) died within the first week, usually as a result of multisystem organ failure (15 patients). Thirty-nine patients (68 per cent) died after the first week from complications related to infection (26 patients) co-morbid conditions (nine) or non-infective complications (four). Twenty-one patients (42 per cent) had been inadequately evaluated by Ranson's criteria, and only 22 (44 per cent) of 50 with a premortem diagnosis of pancreatitis had undergone computed tomography (CT). Fifteen of 26 patients who died from infection-related complications had CT and only nine underwent necrosectomy or surgical drainage. These data suggest that improved diagnosis, investigation and management of patients with acute pancreatitis is possible, and may result in improved clinical outcome.

Long-term circulatory access via a peripheral implantable port.

The use of a novel indwelling central venous catheter system is described which combines the safety of peripheral venous catheter placement with a novel electromagnetic locator device for guidance of the catheter tip into the correct position. This locator system obviates the need for radiological screening or chest radiography for checking catheter placement. Fifty-one patients were studied prospectively and all were successfully cannulated. An infection rate of 0.29 per 1000 catheter-days was seen with a mean system life of 220 (range 15-510) days. The new port has a lower infection rate than other commonly used systems and eliminates complications such as pneumothorax and puncture of major arteries.

High-density lipoprotein composition is altered by a common DNA polymorphism adjacent to apoprotein AII gene in man.

25 of a group of 87 White men had Msp 1 restriction site polymorphism within an Alu sequence 3' to the human apo AII gene. Homozygosity for the polymorphism in 8 men was associated with a significant increase in serum apo AII levels (35.4 +/- 1.70 mg/dl, mean +/- SEM) and altered HDL composition, compared with heterozygotes (31.7 +/- 1.29; n = 17) and normal subjects (29.4 +/- 0.64; n = 62). This is the first account of a common variant of an HDL apoprotein gene that affects HDL composition. In view of its association with a high apo AII concentration homozygosity may protect against atherosclerosis.