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.

Amelioration of bendrofluazide-induced hypokalemia by timolol.

The beta adrenergic blocking drug, timolol, tended to correct the hypokalemia of short-term bendrofluazide treatment in 6 healthy male subjects and although the effect was small it was significant. Timolol also reduced the rise in plasma aldosterone and urine potassium excretion following bendrofluazide and increased the urine sodium/potassium ratio. There was no evidence of a shift of potassium from the intracellular to the extracellular space.

Food iron and lead absorption in humans.

Food iron and lead absorption were measured simultaneously in 28 subjects by extrinsically labeling three consecutive meals with the radioactive tracers, iron 59-sulfate and lead 203-chloride. Absorption was measured directly in all subjects by whole-body counting and indirectly in 15 subjects by assessing subsequent levels of tracer in blood. Iron status of the subjects ranged from iron deficient to replete, thus providing a wide range of iron absorption. Statistically significant positive correlations were obtained between food-iron and lead absorption measured by whole-body counting and also between the tracer levels of iron and lead in the blood. However, the correlation between the absorption of the two elements was not strong, as evidenced by the fact that only 50% of the subjects who hyperabsorbed iron also hyperabsorbed lead.

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.

Red cell magnesium as a function of cell age.

The variation in the magnesium content of human red cells as a function of cell age has been measured by atomic absorption spectrophotometry. The cell population was split into different age fractions using discontinuous density gradient centrifugation, since it is known that cell density increases with age. A mathematical model relating predicted cell age to cell density has been developed which allows the quantification of the observed fall-off in magnesium content with cell age. This model suggests that cells lose magnesium monoexponentially with age, the half-life being approximately 100 days. A previously proposed hypothesis that magnesium could enter the cells only at erythropoiesis and then decay monoexponentially predicted a half-life of 22.4 days and is therefore seen to be an oversimplification of magnesium kinetics in the red cell. The relevance of the present findings to pathologic conditions with abnormal red cell magnesium concentrations is discussed.

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.

Effect of megestrol acetate on weight loss, body composition and blood screen of gastrointestinal cancer patients.

Reduced food intake is probably the major cause of continuing weight loss in cancer patients. Therefore, agents which stimulate food intake may be of significant benefit to such patients. To examine this, a randomized double-blind placebo controlled study of megestrol acetate was carried out. 38 gastrointestinal cancer patients with weight loss (8-43% of pre-illness stable weight) were entered into the study. 26 were evaluable at 6 weeks and 21 at 12 weeks. Clinical details, serum biochemistry and haematology were examined at 6 and 12 weeks and total body water, total body potassium at 12 weeks after the baseline assessment. There was no significant weight change in either group over the 6 or 12 weeks. Furthermore, there was no significant difference in total body water, total body potassium, blood biochemistry or haematology between the groups over the study period. It does not appear that megestrol acetate at a dose of 480 mg/day results in weight gain in advanced gastrointestinal cancer patients with weight loss.

The measurement of radioactivity in people living near the Dounreay Nuclear Establishment, caithness, scotland.

In 1986, a statistically significant excess of leukaemia was reported in young people living near the Dounreay Nuclear Establishment in northern Scotland. The committee on Medical Aspects of Radiation in the Environment (COMARF) confirmed this finding and concluded that, based on conventional dose and risk estimates, the radioactive discharges from the plant could not be held responsible. However, COMARF, recognizing the uncertainties involved in the dose and risk calculations, recommended that levels of radioactivity should be measured in the general population living near the plant. Alpha-emitting contamination has been measured by urinary 239Pu analysis and 241Am in-vivo skull measurements in 66 subjects associated with the Dounreay area and in 42 subjects living remote from reprocessing plants. Whole-body counting was employed to check for gamma ray-emitting contamination. Urinary 90Sr and chromosome abnormality analyses were also carried out on subsets of the study group. No significant inter-group differences for measurements of contamination were demonstrated for groups of leukaemia cases, siblings, parents, matched local controls and controls living remote from reprocessing plants. The findings suggest that it is unlikely that the observed increased incidence in leukaemia is due to the single factor of personal radioactive contamination from the Dounreay Nuclear Establishment.

Kinetics of lead following intravenous administration in man.

Whole body retention of lead (Pb) and lead kinetics in blood, urine and faeces were determined over 2 weeks following i.v. administration of 203Pb-labelled chloride to 2 subjects. Pb was retained with a biological half-life of 73 days (mean). After day 1 Pb excreted in urine and faeces remained fairly constant at 1% and 0.3% of administered dose, respectively. There was a daily loss of 0.5% by other routes. There was a rapid clearance of isotope from plasma with a half-life of 1 min (mean). At 60 min 45% of the administered dose was in erythrocytes; this changed little over the 2 weeks.

Radiological protection guidance for radioactive patients--new data for therapeutic 131I.

Patients leaving hospital after 131I treatment for thyrotoxicosis face restrictions on their contact with other members of the public. These restrictions depend on the level of residual body radioactivity which for practical purposes can be taken to be almost entirely in the thyroid gland. This study provides an appropriate data base from which to draw advice to patients consistent with current radiological protection requirements in terms of the duration of these restrictions. Thyroidal retention of 131I was measured in 77 thyrotoxic patients over a period of 1-50 days after a first therapeutic administration of the radionuclide. Mean 131I activity in the gland (+/- S.D.) at 1 day was 56.1 +/- 11.1% of the administered dose activity and thereafter retention followed a single exponential decay pattern with a mean effective half-life (+/- S.E.M.) of 6.35 +/- 0.14 days. In patients who required further 131I therapy, there was evidence that retention could be markedly reduced if there was virtual ablation of thyroid tissue. It is proposed that these retention data can be used to determine body radioactivity at any interval after the administration of 131I for treatment of thyrotoxicosis, thus obviating the need for serial measurements in every individual patient.

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.

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.

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.

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.

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 effect of acute alcohol withdrawal on the serum potassium and total body potassium in heavy drinkers.

In a group of 20 patients with heavy alcohol intake a relation was found between withdrawal symptoms and fall in serum potassium. Total body potassium (TBK) was measured in all subjects and was lower in the group of subjects who displayed symptoms than in the group who did not. The subgroup of the four most severe reactors had a mean TBK value significantly less than the 'non-reactor' group. The minimum serum potassium levels observed for all subjects in the four day period following alcohol withdrawal correlated with their TBK values. We suggest that the mechanism for the serum potassium fall might be overactivity of the Na-K pump caused by ethanol consumption. There was also an association between withdrawal reaction and abnormal liver function and a transient rise in serum phosphate in the more severely reacting subjects.

The effect of megadose ascorbic acid ingestion on the absorption and retention of vitamin B12 in man.

Radiotracer B12 analogues, hydroxy- and cyano-cobalamin have been used to study the effects of megadose L-ascorbic acid (vitamin C) ingestion on vitamin B12 metabolism in man. By employing whole body counter techniques it has been shown that, while ascorbic acid can partially inactivate both the important dietary analogue, hydroxycobalamin, and the gastric secretion, intrinsic factor which is essential for B12 absorption, the rapid binding of the B12 analogue to intrinsic factor protects the hydroxycobalamin from attack. As a result, the absorption of hydroxcobalamin is unaffected by the simultaneous ingestion of 1 g ascorbic acid. The absorption of cyanocobalamin, the most stable analogue but not found in quantity in the diet, is slightly increased by ascorbic acid. Whole body retention studies on normal subjects ingesting 2 g ascorbic acid per day show no significant evidence of in vivo destruction of body B12 stores.

An evaluation of the 14C-glycocholic acid breath test in the diagnosis of bacterial colonisation of the jejunum.

In order to assess the performance of the 14C-glycocholic acid breath test as an indicator of bacterial colonisation of the jejunum, 145 combined breath tests and jejunal aspirate cultures were carried out on a total of 50 subjects who had an increased probability of being colonised. Ninety-one of the 145 cultures were positive while only 31 of the breath tests were positive. This poor performance of the breath test relative to the aspirate culture can be predicted with reasonable accuracy from known bile deconjugating capabilities of bacteria found in the small intestine.

Endocrine studies in cyanotic congenital heart disease.

Seven male patients with cyanotic congenital heart disease were studied. Serum testosterone, androstenedione, dehydroepiandrosterone, thyroxine and triiodothyronine levels did not differ significantly from control values. Thyroid stimulating hormone and prolactin responses to injected thyrotrophin releasing hormone were normal. Impaired gonadotrophin responses to injected gonadotrophin releasing hormone were noted in two patients. The hypothalmic-pituitary-testicular axis appears to be better preserved in cyanotic congenital heart disease than in chronic obstructive airways disease and restrictive lung disease for a similar degree of hypoxia. Possible explanations are discussed.