Bovid ecomorphology and hominin paleoenvironments of the Shungura Formation, lower Omo River Valley, Ethiopia.

The Shungura Formation in the lower Omo River Valley, southern Ethiopia, has yielded an important paleontological and archeological record from the Pliocene and Pleistocene of eastern Africa. Fossils are common throughout the sequence and provide evidence of paleoenvironments and environmental change through time. This study developed discriminant function ecomorphology models that linked astragalus morphology to broadly defined habitat categories (open, light cover, heavy cover, forest, and wetlands) using modern bovids of known ecology. These models used seven variables suitable for use on fragmentary fossils and had overall classification success rates of >82%. Four hundred and one fossils were analyzed from Shungura Formation members B through G (3.4-1.9 million years ago). Analysis by member documented the full range of ecomorph categories, demonstrating that a wide range of habitats existed along the axis of the paleo-Omo River. Heavy cover ecomorphs, reflecting habitats such as woodland and heavy bushland, were the most common in the fossil sample. The trend of increasing open cover habitats from Members C through F suggested by other paleoenvironmental proxies was documented by the increase in open habitat ecomorphs during this interval. However, finer grained analysis demonstrated considerable variability in ecomorph frequencies over time, suggesting that substantial short-term variability is masked when grouping samples by member. The hominin genera Australopithecus, Homo, and Paranthropus are associated with a range of ecomorphs, indicating that all three genera were living in temporally variable and heterogeneous landscapes. Australopithecus finds were predominantly associated with lower frequencies of open habitat ecomorphs, and high frequencies of heavy cover ecomorphs, perhaps indicating a more woodland focus for this genus.

Outbreak investigation and case-control study: penta-resistant Salmonella Typhimurium DT104 associated with biltong in London in 2008.

In August 2008 an outbreak of Salmonella Typhimurium DT104 occurred in South West London. Sixteen cases were identified with a particular multilocus variable number tandem repeat analysis (MLVA) pattern. In a matched case-control study 14 primary cases were included. These were defined as individuals with gastrointestinal symptoms and Salmonella Typhimurium DT104 isolated from a stool specimen, with a characteristic antibiotic resistance profile and MLVA pattern, and diagnosed in a local laboratory. Four controls per case were matched on age, gender and area of residence. Cases were 26 times more likely than controls to have eaten beef biltong, a South African speciality meat product (odds ratio 25·83, 95% confidence interval 4·92­135·59, P < 0·01). Although environmental investigation failed to identify Salmonella in the food product we conclude that beef biltong consumption led to this outbreak. This conclusion has importance in informing the ongoing risk assessment relating to uncontrolled foodstuffs.

Antibiotic administration longer than eight hours after triage and mortality of community-acquired pneumonia in patients with diabetes mellitus.

Studies have established that diabetic patients with community-acquired pneumonia (CAP) may have increased mortality. The primary objective of this study was to investigate if time to first appropriate antibiotic in the emergency department (ED) was associated with in-hospital mortality of CAP in patients with diabetes mellitus (DM). This was a retrospective cohort study of adult diabetic patients who were admitted with CAP. Patients were stratified into two groups: those who received first dose of appropriate antibiotic within 8 hours of triage and those who received it later than 8 hours. A multiple logistic regression analysis was performed. Two hundred six patients were included in the study. Fifty-nine patients (28.6%) had complications of CAP on admission and 31 patients (16%) died. In-hospital mortality was higher in patients who received their initial appropriate antibiotic after 8 hours of triage than those who received it within 8 hours [18 (35.3%), 15 (9.7%), p < 0.0001]. Time to first appropriate antibiotic later than 8 hours of triage was associated with increased in-hospital mortality (OR 4, 95% CI 1.2-13.1, p = 0.02). Antibiotic administration later than 8 hours of triage in the ED was associated with increased in-hospital mortality of CAP among patients with DM.

Prognostic value of the Quick Sepsis-related Organ Failure Assessment (qSOFA) score among critically ill medical and surgical patients with suspected infection in a resource-limited setting.

Background: The Quick Sequential Organ Failure Assessment (qSOFA) score is a simple bedside tool validated outside of the intensive care unit (ICU) to identify patients with suspected infection who are at risk for poor outcomes. Objectives: To assess qSOFA at the time of ICU referral as a mortality prognosticator in adult medical v. surgical patients with suspected infection admitted to an ICU in a resource-limited regional hospital in South Africa (SA). Methods: We conducted a retrospective cohort study on adult medical or surgical patients that were admitted to an ICU in a resource-limited hospital in SA. We performed univariate and multivariable logistic regression and compared nested models using likelihood ratio test, and we calculated the area under the receiver operating characteristic curve (AUROC). Results: We recruited a total of 1 162 (medical n=283 and surgical n=875) participants in the study who were admitted to the ICU with suspected infection. qSOFA at the time of ICU referral was highly associated with but poorly discriminant of in-ICU mortality among medical (odds ratio (OR) 2.60, 95% confidence interval (CI) 1.19 - 5.71; p=0.02; AUROC 0.60; 95% CI 0.53 - 0.67; p=0.02) and surgical (OR 2.74; 95% CI 1.73-4.36; p<0.001; AUROC 0.60; 95% CI 0.55 - 0.65; p=0.04) patients. qSOFA model performance was similar between medical and surgical subgroups (p≥0.26). Addition of qSOFA to a baseline risk factor model including age, sex, and HIV status improved the model discrimination in both subgroups (medical AUROC 0.64; 95% CI 0.56 - 0.71; p=0.049; surgical AUROC 0.69; 95% CI 0.64 - 0.74; p<0.0001). Conclusion: qSOFA was highly associated with, but poorly discriminant for, poor outcomes among medical and surgical patients with suspected infection admitted to the ICU in a resource-limited setting. These findings suggest that qSOFA may be useful as a tool to identify patients at increased risk of mortality in these populations and in this context.

Assessing public health risk in the London polonium-210 incident, 2006.

OBJECTIVES: Mr Alexander Litvinenko died in a London hospital on 23 November 2006, allegedly from poisoning with the radionuclide polonium-210 ((210)Po). Associated circumstances required an integrated response to investigate the potential risk of internal contamination for individuals exposed to contaminated environments. STUDY DESIGN: Descriptive study. METHODS: Contaminated locations presenting a potential risk to health were identified through environmental assessment by radiation protection specialists. Individuals connected with these locations were identified and assessed for internal contamination with (210)Po. RESULTS: In total, 1029 UK residents were identified, associated with the 11 most contaminated locations. Of these, 974 were personally interviewed and 787 were offered urine tests for (210)Po excretion. Overall, 139 individuals (18%) showed evidence of probable internal contamination with (210)Po arising from the incident, but only 53 (7%) had assessed radiation doses of 1mSv or more. The highest assessed radiation dose was approximately 100mSv. CONCLUSIONS: Although internal contamination with (210)Po was relatively frequent and was most extensive among individuals associated with locations judged a priori to pose the greatest risk, a high degree of assurance could be given to UK and international communities that the level of health risk from exposure to the radionuclide in this incident was low.

A Combined Study of Headspace Volatiles using Human Sensory, Mass Spectrometry and Chemometrics.

Smokeless tobacco products (STPs) are widely used in certain parts of the world, yet there is limited understanding of how they are consumed, particularly the impact of chemosensory characteristics on their use. In order to develop an understanding of the drivers of STP use and product acceptability we conducted both human sensory panel testing and chemical analyses on a range of STPs. Free-sorting paired odour testing using sensory panellists identified similarities and clear differences between eleven different STPs. Headspace volatiles, analysed by headspace solid-phase microextraction gas chromatography mass spectrometry (HS-SPME-GC-MS), identified 20 to 70 components depending upon the STP. Key differences in headspace volatiles were found between STPs. For example, the headspace of Skoal Bandits Wintergreen was dominated by methyl salicylate, while Marlboro Spice consists of a more complex profile including pinene, nicotine, eugenol and cymene. Chemometric Target Factor Analysis (TFA) and Hierarchical Cluster Analysis (HCA) of chemistry and sensory data was used to deduce chemical drivers of sensory perceptions. The chemometric strategy used showed that headspace analysis is a complementary screening tool to sensory analysis in classification studies. This study is generic with applications across various product sectors that require routine human sensory panel evaluation.

Measured trends in stratospheric ozone.

Recent findings, based on both ground-based and satellite measurements, have established that there has been an apparent downward trend in the total column amount of ozone over mid-latitude areas of the Northern Hemisphere in all seasons. Measurements of the altitude profile of the change in the ozone concentration have established that decreases are taking place in the lower stratosphere in the region of highest ozone concentration. Analysis of updated ozone records, through March of 1991, including 29 stations in the former Soviet Union, and analysis of independently calibrated satellite data records from the Total Ozone Mapping Spectrometer and Stratospheric Aerosol and Gas Experiment instruments confirm many of the findings originally derived from the Dobson record concerning northern midlatitude changes in ozone. The data from many instruments now provide a fairly consistent picture of the change that has occurred in stratospheric ozone levels.

Prospective comparative study of the scarf and Ludloff osteotomies in the treatment of hallux valgus.

BACKGROUND: This study compares two diaphyseal osteotomies (scarf and Ludloff) which correct moderate to severe metatarsus primus varus. This is a single surgeon, prospective cohort study with clinical and radiological follow~up at 12 months. MATERIALS AND METHODS: There were 57 patients in each group. Both groups were similar in terms of age, gender and preoperative deformity. Clinical assessment included visual analogue scale questionnaires for subjective assessment and functional activities and the American Orthopaedic Foot and Ankle Society (AOFAS) score. Standardized weight bearing radiographs were analyzed. RESULTS: There was no statistically significant difference between the two groups at 6 and 12 months in subjective satisfaction, AOFAS score, improvement in functional activities and range of movements. The improvement in pain (at best) and transfer lesions at 12 months was significantly better in the scarf group (p < 0.05). The radiological results at 6 and 12 months including intermetatrsal angle (p < 0.001), hallux valgus angle (p < 0.01), distal metatarsal articular angle and seasmoid position (p < 0.05) were significantly better in the scarf osteotomy group. There were three cases (5%) of delayed union in the Ludloff group. Two of these healed with dorsiflexion malunion. One patient in the Ludloff osteotomy group developed a complex regional pain syndrome. There were two wound complications in the scarf group. CONCLUSION: Overall the patients who had a scarf osteotomy had a superior outcome at 6 and 12 months.

Partial restoration of impaired interleukin-2 production and Tac antigen (putative interleukin-2 receptor) expression in patients with acquired immune deficiency syndrome by isoprinosine treatment in vitro.

The in vitro effects of isoprinosine (ISO) on interleukin-2 (IL-2) production, the expression of Tac antigen (IL-2 receptor) on lymphocytes, and the ability of Leu 3(+) cells to absorb interleukin-1 (IL-1) were investigated in 10 patients with acquired immune deficiency syndrome (AIDS). In 9 of the 10 patients, production of IL-2 from mononuclear cells and Leu 3(+) cells was depressed; expression of Tac antigen on mononuclear cells and Leu 2(+) cells was found to be depressed in 9 of 10 patients. The ability of the Leu 3(+) lymphocytes to absorb IL-1 was depressed in all (four of four) patients studied. After ISO treatment, IL-2 production, Tac antigen expression and IL-1 absorption were restored to normal or near normal levels in most of the patients. These results suggest that ISO has an immunostimulating capacity in AIDS patients and that the potential of ISO in immune response restoration in AIDS patients deserves critical consideration.

Monoclonal antibodies to human osteosarcoma-associated antigen(s).

Monoclonal antibodies (MoAbs) against human osteosarcoma cells were obtained by the production and cloning of hybrids resulting from the fusion of mouse myeloma cells P3 X 63Ag8.653 with spleen cells from partially purified, osteosarcoma-associated antigen (OSAA)-immunized BALB/c mice. OSAAs were isolated from the spent culture medium of a human osteosarcoma cell line (TE-85). Five hybrid clones were established and designated as OSA1, OSA2, OSA3, OSA4, and OSA5. OSA1 and OSA2 had similar activity. All 5 MoAbs reacted strongly with most osteosarcoma cell lines and with all osteosarcoma tissues tested but not with 10 tumor cell lines and 2 tumor tissues from other cancers. OSA3, OSA4, and OSA5 cross-reacted with a fibrosarcoma cell line, a colon cell line, and fibrosarcoma, respectively, as well as with a melanoma cell line. None of the MoAbs were reactive with activated normal human peripheral blood mononuclear cells (PBMC). Immunoprecipitation of membrane protein isolated from LM cells and TE-85 cells with the MoAbs OSA1 and OSA2 conjugated with Staphylococcus aureus yielded a molecule with molecular weight of approximately 92,000. No detectable membrane protein was precipitated when 125I-labeled membrane protein from pooled activated human PBMC and tumor cells of other histologic types were used in the immunoprecipitation.

Elevated frequency and functional activity of a specific germ-line p53 intron mutation in familial breast cancer.

Previous studies have determined that the frequency of germ-line p53 mutations in familial breast cancer patients is 1% or less, but these reports have not investigated the importance of polymorphic intron base changes in the p53 gene. Therefore, we investigated the frequency of both exon and intron germ-line p53 base changes in 42 breast cancer patients with a strong family history of breast cancer. The mean age of presentation of these patients was 44.0 years (range, 29-69), and 12 of 42 (29%) were of known Ashkenazi ancestry. Purified DNA obtained from the 42 index cases was screened for germ-line p53 mutations in exons 2-11 and surrounding introns using a combination of intron based primers for PCR-single strand conformation polymorphism analysis, direct sequencing, and microarray sequencing using the Affymetrix p53 gene chip methodology. Morphological analysis of apoptosis and cell survival determination were performed on EBV-immortalized lymphoblastoid cell lines from two patients with the p53 intron 6 mutation. A germ-line mutation in the p53 gene at nucleotide 13964 with a G to C base change (13964GC) was identified in 3 of 42 (7.1%) hereditary breast cancer patients. Two patients were heterozygous for this mutation, and one patient had a homozygous mutation. In comparison, 0 of 171 (0%) of sporadic breast cancer patients had the p53 13964GC mutation (P = 0.0003). We found that 0 of 42 (0%) of these hereditary breast cancer patients had other germ-line p53 mutation in exons 2-11. However, pedigree analysis demonstrated that all three patients had strong family histories of multiple types of cancers consistent with Li-Fraumeni syndrome but with late age of onset. Comprehensive BRCA1 and BRCA2 nucleotide analysis from patients with the p53 13964GC mutation revealed no concomitant deleterious BRCA1 or BRCA2 mutations, although they were found in the other hereditary breast cancer patients. Functional analysis of two immortalized lymphoblastoid cell lines derived from patients with the p53 13964GC mutation demonstrated prolonged in vitro survival in response to cisplatinum treatment and showed decreased chemotherapy-induced apoptosis. Immunohistochemical analysis of breast tumors from these patients revealed high levels of mutant p53 protein, suggesting a functional mutation in the p53 gene. In summary, we have identified a single p53 intron mutation in familial breast cancer patients that is present at elevated frequency and has functional activity.

Specific roles for the asparagine-linked carbohydrate residues of recombinant human follicle stimulating hormone in receptor binding and signal transduction.

FSH comprises two distinct subunits, both of which contain asparagine-linked carbohydrate residues, located at positions 52 and 78 on the alpha-subunit and positions 7 and 24 on the beta-subunit. These carbohydrate chains have been shown to regulate the biological activity of FSH, including signal transduction and receptor binding. However, the specific roles of the individual carbohydrate chains have been poorly defined. Using site-directed mutagenesis we disrupted the consensus sequences for glycosylation and expressed the mutated cDNAs in Chinese Hamster Ovary cells. Specifically deglycosylated FSH variants were secreted from all clonal cell lines expressing the mutated FSH cDNAs except for the cell line that lacked all four glycosylation sites. Analysis of the singly or doubly deglycosylated FSH mutants revealed that removal of the carbohydrate residue at position 78 on the alpha-subunit significantly increased the receptor binding affinity of human FSH by 72%. Removal of the other carbohydrate residues had no significant effect on receptor binding. The carbohydrate residue at position 52 on the alpha-subunit was found to play an essential role in signal transduction as its removal resulted in a significant decrease in potency to 26% of wild type levels. The other individual carbohydrate residues appear to play a minor role in signal transduction, although removal of each residue results in reduced maximal response. The removal of both alpha-subunit carbohydrates resulted in a significant decrease in biopotency, to 41% of wild type levels; whereas, the removal of both beta-subunit carbohydrate chains resulted in a significant increase in biopotency, to 216% of wild type levels. These studies have allowed the identification of site-specific roles for the carbohydrate residues of human FSH. Our data suggest that the carbohydrate residues play a greater role in determining the biological activity of FSH than has been suggested in similar studies of other glycoprotein hormones.

Randomized trial of folic acid supplementation and serum homocysteine levels.

BACKGROUND: Lowering serum homocysteine levels with folic acid is expected to reduce mortality from ischemic heart disease. Homocysteine reduction is known to be maximal at a folic acid dosage of 1 mg/d, but the effect of lower doses (relevant to food fortification) is unclear. METHODS: We randomized 151 patients with ischemic heart disease to 1 of 5 dosages of folic acid (0.2, 0.4, 0.6, 0.8, and 1.0 mg/d) or placebo. Fasting blood samples for serum homocysteine and serum folate analysis were taken initially, after 3 months of supplementation, and 3 months after folic acid use was discontinued. RESULTS: Median serum homocysteine level decreased with increasing folic acid dosage, to a maximum at 0.8 mg of folic acid per day, when the homocysteine reduction (placebo adjusted) was 2.7 micromol/L (23%), similar to the known effect of folic acid dosages of 1 mg/d and above. The higher a person's initial serum homocysteine level, the greater was the response to folic acid, but there were statistically significant reductions regardless of the initial level. Serum folate level increased approximately linearly (5.5 nmol/L for every 0.1 mg of folic acid). Within-person fluctuations over time in serum homocysteine levels, measured in the placebo group, were large compared with the effect of folic acid, indicating that monitoring of the reduction in an individual is impractical. CONCLUSIONS: A dosage of folic acid of 0.8 mg/d appears necessary to achieve the maximum reduction in serum homocysteine level across the range of homocysteine levels in the population. Current US food fortification levels will achieve only a small proportion of the achievable homocysteine reduction.

Neurological, visual, and MRI brain scan findings in 87 South African patients with HIV-associated cryptococcal meningoencephalitis.

BACKGROUND: HIV-associated cryptococcal meningoencephalitis (CM) is a leading cause of adult meningitis in sub-Saharan Africa. Neuroradiological data is however limited to case reports and small case series from developed countries and/or immunocompetent patients. METHODS: Eighty seven patients aged ≥18 hospitalized with a first episode of CM had magnetic resonance (MRI) imaging during the first two weeks of admission. A subset of eleven patients had follow-up scans approximately one month from their initial MRI scan. All had prospectively-recorded detailed neurological and visual examinations. RESULTS: An abnormal finding on neurological examination was detected in 33 (39%) patients. 38 (48%) patients experienced some visual loss. Neuroradiological lesions presumed to be cryptococcosis-related, as defined by the presence of dilated Virchow Robin spaces, pseudocysts or cryptococcomas, enhancing nodules, hydrocephalus, meningitis, focal perilesional oedema and infarcts, were detected in 55 (63%) patients. MRI findings suggestive of a second diagnosis were found in 18 (21%) patients. Visual loss was associated with the presence of cryptococcal-related lesions (p = 0.02). Blindness was associated with raised intracranial pressure (ICP) (p = 0.02). Of eleven patients with paired scans, brain swelling was identified on the initial scan in only one patient. CONCLUSION: The majority of patients had MRI brain scan abnormalities presumed secondary to CM. Dilated Virchow Robin spaces were the commonest neuroradiological lesion. Visual loss was associated with the degree of cerebral involvement as reflected by the presence of MRI abnormalities. Blindness was associated with the presence of raised ICP. Initial generalised brain swelling does not appear to be common, but further studies with paired scans are needed.

Both of the beta-subunit carbohydrate residues of follicle-stimulating hormone determine the metabolic clearance rate and in vivo potency.

FSH is a glycoprotein hormone required for the development and maturation of the ovarian follicle and for spermatogenesis. FSH is glycosylated at asparagine residues 52 and 78 on the alpha-subunit and residues 7 and 24 on the beta-subunit. In vitro, the carbohydrate residue at position alpha 52 is required for signal transduction. To define the contribution of the carbohydrate residues to FSH potency in vivo, we assessed the MCR and in vivo bioactivity of site-specifically deglycosylated recombinant human FSH variants. The removal of the beta-subunit carbohydrate residues significantly (P < 0.05) affected the MCR and resulted in significantly (P < 0.05) reduced in vivo bioactivity. For all recombinant human FSH variants, a strong correlation (r = 0.90; P < 0.01) was observed between MCR and in vivo potency, indicating that the circulatory half-life of the hormone appears to be the primary determinant of in vivo bioactivity. Although the beta-subunit carbohydrate residues have the greatest effect in determining FSH potency in vivo; the alpha 52 residue, important in vitro, has no effect on either MCR or in vivo potency. This study highlights the difficulties of translating in vitro results to whole animal physiology.

Isoelectric charge of recombinant human follicle-stimulating hormone isoforms determines receptor affinity and in vitro bioactivity.

Recombinant human FSH (rhFSH) was obtained by expressing the human FSH alpha- and beta-subunit complementary DNAs in the chinese hamster ovary cell line. Isoforms of rhFSH were resolved into specific isoelectric (pI) fractions by chromatofocusing. rhFSH isoforms ranged from pI 3.0-5.5 with a modal value of pI 4.2. Analysis of the biological activity of specific pI isoforms of rhFSH was undertaken using both the rat granulosa cell aromatase (in vitro) bioassay and a RRA. More acidic isoforms (e.g. pI 3.5) showed significantly lower affinity (P < 0.05) for rat testicular FSH receptors than did the less acidic isoforms (e.g. pI 4.8). Consistent with the receptor binding affinity data, the more acidic fractions resulted in significantly less activation (P < 0.05) of rat granulosa cell aromatase activity, as measured by estrogen production, than did the less acidic isoforms. The observed bioactivities and their correlation with the pI values of the rhFSH isoforms are consistent with observations of differing bioactivities seen in both pituitary and urinary FSH isoforms. These results demonstrate that rhFSH, made in the chinese hamster ovary cell line, is both biologically active and has isoform profiles, and presumably carbohydrate structures, that closely resemble those seen in natural hFSH.

Effect of dietary fats and carbohydrate on blood pressure of mildly hypertensive patients.

The effect on blood pressure (BP) of replacing dietary saturated fat with either polyunsaturated fat (linoleic acid) or carbohydrate was studied in 21 untreated mildly hypertensive patients. In a randomized, double-blind, crossover protocol, all subjects received dietary supplements of cream, safflower oil, and carbohydrate in random sequence, each prepared in flavored yogurt or milk. Each supplement was administered for 6 weeks and followed by a 4-week washout period of no supplementation. Dietary linoleic acid increased from 4.6 to 13% of energy intake when the safflower oil replaced cream, while saturated fat decreased from 16 to 10%. Total fat intake was 37 to 38% during the cream and safflower oil periods but was 28% during the carbohydrate period. Compliance with the diets was demonstrated by significant changes in fasting plasma fatty acid measurements. Mean clinic BP was 135 +/- 9/93 +/- 6 mm Hg at baseline. There were no significant differences in BP measured in the clinic or at home among the three dietary periods. The protocol had more than 80% power to detect a mean effect of diet of 3 mm Hg systolic or 2 mm Hg diastolic BP. Therefore, replacing dietary saturated fat with carbohydrate or with linoleic acid does not affect BP in subjects with mild hypertension.

Effects of inherent responsiveness to diet and day-to-day diet variation on plasma lipoprotein concentrations.

We studied the biological variability and responsiveness to dietary fat of plasma lipoprotein cholesterol and triacylglycerol concentrations. Ten normal persons were studied on 3 consecutive days while they were eating their unrestricted usual diets and after 8, 9, and 10 d of eating a constant high-fat and low-fat diet administered in a crossover design. The changes in plasma low-density-lipoprotein (LDL)-cholesterol concentrations from baseline with the high-fat diet were inversely correlated with the changes from baseline with the low-fat diet (r = -0.74, P = 0.01), as well as with the changes from the low-fat to high-fat diet (r = -0.93, P < 0.001). The extent of increases in plasma LDL-cholesterol concentrations from the baseline to the high-fat diet were positively correlated with the increases from the low-fat to the high-fat diet (r = 0.93, P < 0.001). The responses of high-density-lipoprotein (HDL) cholesterol were not consistently correlated. The within-person between-day CV of LDL decreased from 10% with the unrestricted diet to 6% (P < 0.05) with the high-fat diet and to 7% with the low-fat diet (NS). The CV of total triacylglycerol (22%) and very-low-density-lipoprotein (VLDL) triacylglycerol (48%) on the unrestricted diet significantly decreased by 51-59% during both controlled diets (P = 0.03-0.06). The CV of HDL cholesterol was 5.3% during baseline, 4.2% during the high-fat diet, and 3.2% during the low-fat diet (P = 0.4, 0.19, respectively). In summary, individuals have a reproducible plasma LDL-cholesterol response when changing their dietary fat intake. The day-to-day variation in total triacylglycerol, VLDL triacylglycerol, and LDL-cholesterol concentrations decreases when day-to-day dietary variation is eliminated.

Are 18fluorodeoxyglucose positron emission tomography and magnetic resonance imaging useful in the prediction of relapse in lymphoma residual masses?

Treatment of both Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL) frequently results in a residual mass visible radiologically. Such patients may receive radiotherapy unnecessarily because the residual mass may represent benign fibrotic tissue rather than residual active lymphoma. Radiotherapy has been shown to have significant short and more worrying long-term toxicity. Refining the criteria for its use would be a major advance. A number of clinical investigations have been evaluated to more accurately determine the nature of such lesions, including erythrocyte sedimentation rate (ESR), magnetic resonance imaging (MRI) and high-dose gallium-67 scanning (HDGS) but none has proven utility. 18[F]-fluorodeoxyglucose positron emission tomography (FDG-PET) is an imaging technique that has been shown to be useful in distinguishing fibrosis from residual active disease in solid tumours. The aim of this study was to compare FDG PET and MRI in the assessment of residual masses following treatment for lymphoma. Patients with NHL/HD who had a residual mass following chemotherapy were eligible for this study. Patients had a combination of MRI and/or PET. All scans were completed within 5 months of the end of treatment. Patients were followed-up for relapse. 56 patients had an MRI scan, 24 had a PET scan and 22 patients had both investigations. Overall sensitivity and specificity, respectively, were for MRI 45% and 74%, PET 50% and 69%, and PET/MRI concurring 50% and 67%. There was a trend for improved relapse-free survival (RFS) with a negative result of both MRI and PET, but this was not statistically significant. The predictive value for both tests failed to reach statistical significance. Subgroup analysis suggests that PET may be better at predicting relapse in patients with NHL, especially those with masses above the diaphragm. There is no convincing evidence that either MRI or PET or the combination can reliably predict relapse within residual masses after treatment for lymphoma. A negative PET scan however appears to be more informative than a positive result and may well aid clinical decision making. There are a number of factors that may produce false-positive results, including post-treatment inflammatory changes, the sensitivity of the test in the setting of minimal residual disease and the heterogeneity of the histological subtypes studied. A negative PET (or MRI) result in lymphoma residual masses following therapy may negate the necessity for further therapy such as chemotherapy or radiotherapy and their concomitant toxicities.