Elevated high density lipoprotein cholesterol and low grade systemic inflammation is associated with increased gut permeability in normoglycemic men.

BACKGROUND & AIMS: Serum lipids and lipoproteins are established biomarkers of cardiovascular disease risk that could be influenced by impaired gut barrier function via effects on the absorption of dietary and biliary cholesterol. The aim of this study was to examine the potential relationship between gut barrier function (gut permeability) and concentration of serum lipids and lipoproteins, in an ancillary analysis of serum samples taken from a previous study. METHODS AND RESULTS: Serum lipids, lipoproteins and functional gut permeability, as assessed by the percentage of the urinary recovery of 51Cr-labelled EDTA absorbed within 24 h, were measured in a group of 30 healthy men. Serum lipopolysaccharide, high sensitivity C-reactive protein and interleukin-6 were also measured as markers of low-grade inflammation. The group expressed a 5-fold variation in total gut permeability (1.11-5.03%). Gut permeability was unrelated to the concentration of both serum total and low density lipoprotein (LDL)-cholesterol, but was positively associated with serum high density lipoprotein (HDL)-cholesterol (r = 0.434, P = 0.015). Serum HDL-cholesterol was also positively associated with serum endotoxaemia (r = 0.415, P = 0.023). CONCLUSION: The significant association between increased gut permeability and elevated serum HDL-cholesterol is consistent with the role of HDL as an acute phase reactant, and in this situation, potentially dysfunctional lipoprotein. This finding may have negative implications for the putative role of HDL as a cardio-protective lipoprotein.

Adapting clinical gamma cameras for body monitoring in the event of a large-scale radiological incident.

After a release of radionuclides, accidental or otherwise, there will be an urgent need to identify members of the general public who have received a significant intake of radioactive material, sufficient to require medical treatment or further investigation. A large number of people could be contaminated in such an incident. For gamma-ray emitting radionuclides this screening could be carried out using gamma camera medical imaging systems, such as those that are present in many large UK hospital sites. By making a number of simple reversible changes such as removal of collimators, these cameras could be employed as useful additional screening instruments as well as an aid in contamination control. A study was carried out to investigate which systems were present in sufficient number to offer wide scale coverage of UK population centres. Nine gamma cameras (eight dual head and one single head) were assessed using point source and bottle mannequin (BOMAB) phantom measurements so that a mathematical model could be developed for use with the MCNPX Monte Carlo radiation transport code. The gamma camera models were assessed for practical seated and supine geometries to give calibration factors for a list of target radionuclides that could be released in a radiological incident. The minimum detectable activities (MDAs) that were achieved for a five minute measurement demonstrated that these systems are sufficiently sensitive to be used for screening of the general public and are comparable to other body monitoring facilities. While gamma cameras have on-board software that are designed for imaging and provide for a gamma-ray energy range suitable for radionuclides for diagnostic imaging (such as 99mTc), they are not as versatile as custom-built body monitoring systems.

Increased intestinal permeability to oral chromium (51 Cr) -EDTA in human Type 2 diabetes.

OBJECTIVE: In animal models of obesity and Type 2 diabetes, permeability of the intestine is increased because of impairment of tight junction proteins, allowing translocation of bacterial endotoxin and resulting in low-grade systemic inflammation. This has yet to be demonstrated in humans. The objective of this study was the demonstration of increased intestinal permeability in human Type 2 diabetes. METHODS: We examined intestinal permeability using chromium ((51) Cr)-EDTA urinary recovery in twenty well-controlled men with Type 2 diabetes compared with control subjects matched for age, gender and BMI. RESULTS: Intestinal permeability was significantly increased (P = 0.002) in the diabetic group and was correlated to increased levels of systemic inflammatory markers high-sensitivity C-reactive protein (r = 0.694, P = 0.001), interleukin 6 (r = 0.548, P = 0.012) and tumour necrosis factor alpha (r = 0.564, P = 0.010). CONCLUSION: This is the first demonstration that increased intestinal permeability may be a feature of human Type 2 diabetes.

Iodine-131 monitoring in sewage plant outflow.

Three different hospital sites (Oxford, Sutton and Guildford) have performed sampling of their local sewage plant outflow to determine levels of radioactivity resulting from iodine-131 patients undergoing radionuclide therapies. It was found that a maximum of 20% of activity discharged from the hospitals was present in the sewage plant final effluent channel. This is significantly below the level predicted by mathematical models in current use. The results further show that abatement systems to reduce public exposure are unlikely to be warranted at hospital sites.

Radioiodine retention on percutaneous endoscopic gastrostomy tubes.

An 80-year-old male with recurrent thyroid cancer and a percutaneous endoscopic gastrostomy (PEG) tube in situ was referred for radioiodine therapy and was administered 5510 MBq I-131 sodium iodide intravenously. Sequential whole-body images taken over the subsequent 7 days for dosimetric evaluation revealed an area of persistent high uptake in the abdomen. Delayed imaging with single photon emission CT/CT at 15 days post administration revealed this uptake to be at the junction of the PEG tube with the anatomically normal stomach wall. We hypothesise that the PEG tube became contaminated by radioiodine secreted in the gastric mucosa during therapy and this radioactivity subsequently decayed with an increased effective half-life relative to the stomach, leading to the apparent hot spot.

Radiation dose assessment in radioiodine therapy. Dose-response relationships in differentiated thyroid carcinoma using quantitative scanning and PET.

Dose-response charts have been constructed to determine the tumouricidal dose for differentiated thyroid carcinoma metastases and thus enable precise activities of radioiodine to be prescribed in order to maximise tumour kill and minimise morbidity. Tumour and normal residual thyroid absorbed doses from radioiodine-131 have been determined with increased precision using a dual-headed whole-body rectilinear scanner with special high-resolution low-sensitivity collimators. Improved accuracy in the estimation of functioning tumour mass has been achieved using positron emission tomography (PET) with a low-cost large area PET camera. Dose-response data have been obtained for 33 patients. Following near-total thyroidectomy and 3.0 GBq 131I, a mean absorbed dose of 410 Gy achieved complete ablation of thyroid remnants in 75% of patients. Patients who had persistent uptake in the thyroid region on subsequent radioiodine scanning had received a mean dose of only 83 Gy. Cumulative absorbed doses in excess of 100 Gy were found to eradicate cervical node metastases. Patients with bone metastases, who generally have a poor prognosis, were found to have received doses of the order of only 20 Gy to the tumour deposits. The dose-response data explain the spectrum of clinical responses to fixed activities of radioiodine. In future, they will enable precise prescription of radioiodine to achieve tumouricidal doses whilst avoiding the morbidity and expense of ineffective therapy.

Radiation dose assessment in radioiodine therapy. 2. Practical implementation using quantitative scanning and PET, with initial results on thyroid carcinoma.

We have designed special high-resolution, low-sensitivity collimators for a dual-headed whole-body scanner for imaging and quantifying therapy levels of iodine-131. In addition, we have used positron emission tomography (PET) with a low-cost large-area PET camera to achieve improved accuracy in the estimate to tumor mass. The physical performance of these two imaging systems is described. In order to illustrate the practical implementation of these systems for the assessment of radiation dose to normal and tumour tissue during radioiodine therapy, three clinical examples are reported, and a summary of the initial clinical results obtained from 16 patients with carcinoma of the thyroid is presented. The dose to normal thyroid remnants for patients undergoing ablation ranged from 16 to 400 Gy, while the dose to involved neck nodes ranged from 2.5 to 33 Gy for patients undergoing post-ablation radioiodine therapy. In one patient with distant metastasis in the spine, a dose of 100 Gy was achieved. The techniques described in this paper can be used to determine if sufficient activity can be accumulated in tumours to provide a therapeutic effect while minimising irradiation of normal tissues by avoiding administrations which do not provide tumouricidal radiation doses.

White clot syndrome.

Heparin therapy is currently a vital component in the medical management of thromboembolic events. Despite its widespread use, it is associated with relatively few complications, and these are usually minor and quickly reversible. Recently a much more dramatic and serious complication of heparin therapy has been identified. In heparin-induced thrombocytopenia with associated thrombosis or "white clot syndrome," patients have paradoxic thromboembolic events while receiving heparin. These events are of acute onset and of major consequence, often resulting in limb loss or death. This paper describes our own experience with ten patients in whom the white clot syndrome occurred during heparin therapy for thrombotic or embolic events. Both porcine and bovine heparin preparations were being given through various routes. In the three cases in which platelet aggregation testing was completed, results were positive. Our ten patients ultimately had a 20% major limb amputation rate and an overall 50% mortality.

Spontaneous pancreatic duct-colon fistula.

A fistula between the pancreatic duct and the colon is quite rare and usually associated with such manifestations as bleeding and sepsis. We have seen a patient with such a fistula detected almost incidentally at ERCP. We report the course of this fistula and review the literature to suggest a place for conservative surgical management.

Application of different counting systems in measuring localised retention the entero-hepatic circulation.

The use of labelled bile salt retention is likely to be a major new technique in assessing the function of the terminal ileum. Papers to date have described two techniques to measure both the 100% and the seven-day retention values. These use whole body counters or uncollimated gamma cameras. We have compared the use of simple probe systems with an uncollimated gamma camera for the retention measurements. There was no significant difference in the results obtained with any of these systems. It is concluded that simple probe measurements can provide a precise and highly reproducible assessment of bile salt retention which greatly increases the availability of this test.

Preservation of an infected arterial graft with combination systemic-topical antibiotic therapy.

A case is presented which illustrates the unusual ability to retain a bifurcation aortofemoral vascular graft with the graft-to-femoral-artery anastomosis involved in a groin abscess. The drainage of the abscess, debridement of devitalized tissue, and the combined application of topical and systemic antibiotic therapy was successful. Some authors report that should an anastomosis of a bifurcation vascular graft, in the vicinity of the groin, become involved in infection, the threat of anastomotic disruption and continued sepsis may lead to amputation, death, or both. It is not the purpose of this report to advocate conservative management of a vascular graft infection with suture line involvement based on anecdotal experience. However, the case reported here and the experience of other authors mentioned suggest that an attempt to treat an infected graft without its removal may be indicated in selected patients where extra anatomical revascularization would be hazardous.