Cutaneous sarcoidosis in a patient with ulcerative colitis on infliximab.

The advance of anti-tumour necrosis factor (TNF) therapy had dramatically changed the treatment algorithm of inflammatory bowel disease (IBD). This had significantly improved the quality of life for patients with Crohn's disease (CD) and ulcerative colitis (UC).(1) However, side-effects of anti-TNF treatment were unavoidable with paradoxical inflammation (for example leucocytoclastic vasculitis and psoriasis) being well-known phenomena of anti-TNF therapy.(2) We report a case of infliximab induced cutaneous sarcoidosis in a patient with ulcerative colitis and review the literature.

A randomised study of peri-prosthetic bone density after cemented versus trabecular fixation of a polyethylene acetabular component.

The ideal acetabular component is characterised by reliable, long-term fixation with physiological loading of bone and a low rate of wear. Trabecular metal is a porous construct of tantalum which promotes bony ingrowth, has a modulus of elasticity similar to that of cancellous bone, and should be an excellent material for fixation. Between 2004 and 2006, 55 patients were randomised to receive either a cemented polyethylene or a monobloc trabecular metal acetabular component with a polyethylene articular surface. We measured the peri-prosthetic bone density around the acetabular components for up to two years using dual-energy x-ray absorptiometry. We found evidence that the cemented acetabular component loaded the acetabular bone centromedially whereas the trabecular metal monobloc loaded the lateral rim and behaved like a hemispherical rigid metal component with regard to loading of the acetabular bone. We suspect that this was due to the peripheral titanium rim used for the mechanism of insertion.

Peri-prosthetic bone mineral density after total knee arthroplasty. Cemented versus cementless fixation.

We compared peri-prosthetic bone mineral density between identical cemented and cementless LCS rotating platform total knee arthroplasties. Two matched cohorts had dual energy x-ray absorptiometry scans two years post-operatively using a modified validated densitometric analysis protocol, to assess peri-prosthetic bone mineral density. The knee that was not operated on was also scanned to enable the calculation of a relative bone mineral density difference. Oxford Knee and American Knee Society scores were comparable in the two cohorts. Statistical analysis revealed no significant difference in absolute, or relative peri-prosthetic bone mineral density with respect to the method of fixation. However, the femoral peri-prosthetic bone mineral density and relative bone mineral density difference were significantly decreased, irrespective of the method of fixation, particularly in the anterior distal portion of the femur, with a mean reduction in relative bone mineral density difference of 27%. There was no difference in clinical outcome between the cemented and cementless LCS total knee arthroplasty. However, both produce stress-shielding around the femoral implants. This leads us to question the use of more expensive cementless total knee components.

Longitudinal study of resting energy expenditure, body cell mass and the inflammatory response in male patients with non-small cell lung cancer.

The aim of this study was to examine the inter-relationship between the inflammatory response and resting energy expenditure in patients with non-small cell lung cancer (NSCLC) before and after the onset of weight loss. Healthy subjects (n=7) and patients with NSCLC without weight loss (n=12) were studied. Resting energy expenditure adjusted for metabolically active tissue, as measured by total body potassium, was approximately 15% higher in the NSCLC group (P<0.01). Moreover, the resting energy expenditure, correlated with the magnitude of the inflammatory response (r=0.753, P<0.01). Six cancer patients subsequently lost weight and the relationship between resting energy expenditure and the inflammatory response was maintained. These results highlight the impact of the inflammatory response on the increase in the resting energy expenditure which precedes the onset of weight loss in patients with NSCLC.

Albumin concentrations are primarily determined by the body cell mass and the systemic inflammatory response in cancer patients with weight loss.

The association between hypoalbuminemia and poor prognosis in patients with cancer is well recognized. However, the factors that contribute to the fall in albumin concentrations are not well understood. In the present study, we examined the relationship between circulating albumin concentrations, weight loss, the body cell mass (measured using total body potassium), and the presence of an inflammatory response (measured using C-reactive protein) in male patients (n = 40) with advanced lung or gastrointestinal cancer. Albumin concentrations were significantly correlated with the percent ideal body weight (r = 0.390, p < 0.05), extent of reported weight loss (r = -0.492, p < 0.01), percent predicted total body potassium (adjusted for age, height, and weight, r = 0.686, p < 0.001), and log10 C-reactive protein concentrations (r = -0.545, p < 0.001). On multiple regression analysis, the percent predicted total body potassium and log10 C-reactive protein concentrations accounted for 63% of the variation in albumin concentrations (r2 = 0.626, p < 0.001). The interrelationship between albumin, body cell mass, and the inflammatory response is consistent with the concept that the presence of an ongoing inflammatory response contributes to the progressive loss of these vital protein components of the body and the subsequent death of patients with advanced cancer.

DXA body composition studies are not affected by extracellular water measurements using stable sodium bromide dilution.

Body composition studies using dual energy x-ray absorptiometry (DXA) are being increasingly reported in the literature. When DXA body composition measurements are combined with body water studies, stable bromide is often administered to measure extracellular water. Bromine attenuates x-rays significantly more than soft tissue and so could affect DXA body composition analysis. DXA scans were performed on 26 adults (12 F, 14 M) before and after the intravenous injection of 3 g sodium bromide (NaBr). No significant differences were noted pre- and post-NaBr infusion for whole-body fat mass, fat-free soft tissue mass and bone mineral content. These findings were supported by a simple mathematical analysis of the likely effect of the sodium bromide infusion. This showed that when 3 g NaBr was introduced into the body, the effect on fat mass estimates was expected to be marginally less than the precision of the DXA technique.

The symptoms of chronic fatigue syndrome are related to abnormal ion channel function.

The pathogenesis of chronic fatigue syndrome (CFS) is unknown but one of the most characteristic features of the illness is fluctuation in symptoms which can be induced by physical and/or mental stress. Other conditions in which fluctuating fatigue occurs are caused by abnormal ion channels in the cell membrane. These include genetically determined channelopathies, e.g. hypokalemic periodic paralysis, episodic ataxia type 2 and acquired conditions such as neuromyotonia, myasthenic syndromes, multiple sclerosis and inflammatory demyelinating polyneuropathies. Our hypothesis is that abnormal ion channel function underlies the symptoms of CFS and this is supported also by the finding of abnormal cardiac-thallium201 SPECT scans in CFS, similar to that found in syndrome X, another disorder of ion channels. CFS and syndrome X can have identical clinical symptoms. CFS may begin after exposure to specific toxins which are known to produce abnormal sodium ion channels. Finally, in CFS, increased resting energy expenditure (REE) occurs, a state influenced by transmembrane ion transport. The hypothesis that ion channels are abnormal in CFS may help to explain the fluctuating fatigue and other symptoms.

99Tcm-MAG3: problems with radiochemical purity testing.

The radiochemical purity (RCP) of 99Tcm-MAG3 was determined using solid-phase extraction (SPE), high-performance liquid chromatography (HPLC) and thin-layer chromatography (TLC). The difference between the HPLC and SPE methods was highly significant (P < 0.001), yielding values for RCP of 94.4 +/- 1.4% and 86.0 +/- 5.1% [corrected] respectively (mean +/- s). Further qualitative analysis of the SPE fractions obtained, was carried out using HPLC and TLC. The unexpected presence of 99Tcm-MAG3 in one of the fractions was observed together with the appearance of hydrophilic impurities in the hydrophobic extract. This lack of specificity may be the reason for the discrepancy between the SPE and HPLC methods. Use of the SPE method leads to an underestimation of the RCP of 99Tcm-MAG3 and, indeed, had we been relied solely on this method of analysis, we would have had to reject most kits we prepared. In a separate study, we compared a TLC method with HPLC. Differences were found to be highly significant (P < 0.001), yielding values of 98.3 +/- 0.6% and 95.8 +/- 0.9% respectively. Comparison of the data points showed that TLC gave consistently higher RCP yield than HPLC. This elevated value was found to be due to the inability of the TLC method to separate 99Tcm-lipophilic impurity, seen on HPLC, from the 99Tcm-MAG3. Therefore, use of this TLC method leads to an overestimation of the RCP of 99Tcm-MAG3.

Lean body mass changes in cancer patients with weight loss.

BACKGROUND AND AIMS: Metabolic measurements (e.g. resting energy expenditure) are adjusted to lean body mass to account for body composition differences. Usually lean body mass is estimated from total body water. However, this may be compromised in weight-losing cancer patients owing to alterations in the degree of hydration of the lean body mass. This study examined the relationship between two independent estimates of lean body mass in healthy subjects and cancer patients with weight loss. METHODS AND RESULTS: Height, weight, total body water and total body potassium were measured in healthy subjects (n=9) and weight losing cancer patients (n=13). They were similar in terms of age and gender. However, the cancer group had a significantly lower percentage ideal body weight (P<0.001). The measured total body water values in both groups were similar to those predicted. In contrast, measured total body potassium values in the cancer group were significantly lower than predicted (P<0.001). There was a correlation between the ratio of measured lean body mass (water/lean bodymass (potassium) and the percentage weight loss (r=0.698, P<0.001). CONCLUSIONS: These results suggest that total body water significantly overestimates metabolically active tissue in weight-losing cancer patients and therefore its use as the basis for metabolic requirements in this group of patients is questionable.

A two-compartment model for zinc in humans.

The oral absorption of zinc, from a test meal of minced beef, mashed potatoes and peas, have been measured in 19 healthy adults using the radiotracer 65Zn. The oral absorption, expressed as a percentage of the administered dose, was 20 +/- 5% (mean +/- 1 SD) in good agreement with previous results. In a subset of 9 subjects, tracer retention in whole body and whole blood was followed out to one year. The data were fitted to a simple two compartment model yielding total body zinc (TBZn), the zinc content in each of the 2 compartments and zinc turnover. The TBZn values ranged from 15.5 to 35.9 mmol while zinc turnover ranged from 0.043 to 0.073 mmol/d in keeping with results reported for significantly more complicated compartmental models applied to more comprehensive 65Zn tracer data sets. Additionally, TBZn correlated well with total body potassium, a measure of lean body mass, measured by whole body counting of the naturally-occurring potassium radioisotope, 40K. The zinc content of the more rapidly turning over compartment ranged from 3.2 to 5.6 mmol in reasonable agreement with exchangeable zinc pool estimations reported for short term studies using stable zinc isotopes. Therefore, the simple dataset and model employed in the present study yielded information on the short- and long-term behaviour of zinc compatible with both more complex radiotracer studies and analytically more demanding stable isotope studies.

Radionuclides in seals and porpoises in the coastal waters around the UK.

It has been suggested that marine predators be assessed for biologically relevant contamination levels because of their trophic position. Accordingly, in studying radioactive contamination in the marine environment around the UK, tissues from seals and porpoises have been chosen. Liver and muscle tissue from dead seals and porpoises found stranded around the UK coast have been analysed for the following radionuclides: 134Cs, 137Cs, 238Pu, 239Pu + 240Pu. Multifactor analysis of variance indicated that, for radiocaesium, there was no significant difference for harbour seals, grey seals or porpoises in terms of species or gender; however, the tissue activity concentration increased with body weight and decreased with distance from Sellafield, the major nuclear reprocessing plant in the UK. The levels of radiocaesium in muscle were higher than those in liver, while there appeared to be a concentration factor of approximately 3-4 for muscle radiocaesium when compared to radiocaesium levels reported for fish, the main food source of the marine mammals under study. Approximate radiation dose calculations indicated that the average dose from radiocaesium was less than 10% of the dose from the naturally occurring radioisotope of potassium, 40K. The highest tissue activity concentration for plutonium of 0.037 Bq/kg (239Pu + 240Pu) was detected in a grey seal stranded at Rathlin Island in Northern Ireland. Calculation of approximate radiation doses from plutonium contamination showed that, as with radiocaesium, the average dose was small compared with that from 40K. In summary, the radiocaesium contamination in seals and porpoises decreased with distance from Sellafield indicating that the BNF plc processing plant was the major source of the contamination. The marine mammals concentrated radiocaesium from their environment by a factor of 300 relative to the concentration in seawater indicating the value of using marine mammal tissue to measure radiocaesium contamination in the marine environment. The maximum radiation dose to the marine mammals from radiocaesium was higher than doses previously assessed for critical groups of humans living near Sellafield, while the maximum dose from plutonium was comparable to the doses for humans.

Longitudinal study of body cell mass depletion and the inflammatory response in cancer patients.

There is recent evidence that the inflammatory response may be important in the disproportionate loss of body cell mass in cancer patients. To examine this further, 18 male patients with lung or gastrointestinal cancer were studied over a 12-week period. In addition to weight, anthropometry, C-reactive protein (marker of the inflammatory response), albumin, and total body potassium were measured at baseline and 12 weeks. When those patients who lost total body potassium were compared with those who had not, there was a significant increase in the baseline and 12-week C-reactive protein concentrations (p < 0.05). The reduction in total body potassium was also associated with a reduction in triceps skinfold thickness (p < 0.05). There were significant correlations between the mean C-reactive protein concentration and the relative (r = -0.846, p < 0.001) and absolute (r = -0.806, p < 0.001) change in total body potassium over the follow-up period. This study demonstrates the association of a chronic inflammatory response with the rate of loss of body cell mass observed in cancer patients.