Changes in bone mineral density over time by body mass index in the health ABC study.

UNLABELLED: Obesity appears protective against osteoporosis in cross-sectional studies. However, results from this longitudinal study found that obesity was associated with bone loss over time. Findings underscore the importance of looking at the longitudinal relationship, particularly given the increasing prevalence and duration of obesity among older adults. INTRODUCTION: Cross-sectional studies have found a positive association between body mass index (BMI) and bone mineral density (BMD), but little is known about the longitudinal relationship in US older adults. METHODS: We examined average annual rate of change in BMD by baseline BMI in the Health, Aging, and Body Composition Study. Repeated measurement of BMD was performed with dual-energy X-ray absorptiometry (DXA) at baseline and years 3, 5, 6, 8, and 10. Multivariate generalized estimating equations were used to predict mean BMD (femoral neck, total hip, and whole body) by baseline BMI (excluding underweight), adjusting for covariates. RESULTS: In the sample (n = 2570), 43 % were overweight and 24 % were obese with a mean baseline femoral neck BMD of 0.743 g/cm(2), hip BMD of 0.888 g/cm(2), and whole-body BMD of 1.09 g/cm(2). Change in total hip or whole-body BMD over time did not vary by BMI groups. However, obese older adults lost 0.003 g/cm(2) of femoral neck BMD per year more compared with normal weight older adults (p < 0.001). Femoral neck BMD change over time did not differ between the overweight and normal weight BMI groups (p = 0.74). In year 10, adjusted femoral neck BMD ranged from 0.696 g/cm(2) among obese, 0.709 g/cm(2) among normal weight, and 0.719 g/cm(2) among overweight older adults. CONCLUSIONS: Findings underscore the importance of looking at the longitudinal relationship between body composition and bone mineral density among older adults, indicating that high body mass may not be protective for bone loss over time.

Caffeine and 3-km cycling performance: Effects of mouth rinsing, genotype, and time of day.

We assessed the efficacy of caffeine mouth rinsing on 3-km cycling performance and determined whether caffeine mouth rinsing affects performance gains influenced by the CYP1A2 polymorphism. Thirty-eight recreational cyclists completed four simulated 3-km time trials (TT). Subjects ingested either 6 mg/kg BW of caffeine or placebo 1 h prior to each TT. Additionally, 25 mL of 1.14% caffeine or placebo solution were mouth rinsed before each TT. The treatments were Placebo, caffeine Ingestion, caffeine Rinse and Ingestion+Rinse. Subjects were genotyped and classified as AA homozygotes or AC heterozygotes for the rs762551 polymorphism of the CYP1A2 gene involved in caffeine metabolism. Magnitude-based inferences were used to evaluate treatment differences in mean power output based on a predetermined meaningful treatment effect of 1.0%. AC heterozygotes (4.1%) and AA homozygotes (3.4%) benefited from Ingestion+Rinse, but only AC performed better with Ingestion (6.0%). Additionally, Rinse and Ingestion+Rinse elicited better performance relative to Placebo among subjects that performed prior to 10:00 h (Early) compared with after 10:00 h (Late). The present study provides additional evidence of genotype and time of day factors that affect the ergogenic value of caffeine intake that may allow for more personalized caffeine intake strategies to maximize performance.

A phase I trial of vertical inhibition of IGF signalling using cixutumumab, an anti-IGF-1R antibody, and selumetinib, an MEK 1/2 inhibitor, in advanced solid tumours.

BACKGROUND: We completed a phase I clinical trial to test the safety and toxicity of combined treatment with cixutumumab (anti-IGF-1R antibody) and selumetinib (MEK 1/2 inhibitor). METHODS: Patients with advanced solid tumours, refractory to standard therapy received selumetinib hydrogen sulphate capsules orally twice daily, and cixutumumab intravenously on days 1 and 15 of each 28-day cycle. The study used a 3+3 design, with a dose-finding cohort followed by an expansion cohort at the maximally tolerated dose that included pharmacokinetic and pharmacodynamic correlative studies. RESULTS: Thirty patients were enrolled, with 16 in the dose-finding cohort and 14 in the expansion cohort. Grade 3 or greater toxicities included nausea and vomiting, anaemia, CVA, hypertension, hyperglycaemia, and ophthalmic symptoms. The maximally tolerated combination dose was 50 mg twice daily of selumetinib and 12 mg kg(-1) every 2 weeks of cixutumumab. Two patients achieved a partial response (one unconfirmed), including a patient with BRAF wild-type thyroid carcinoma, and a patient with squamous cell carcinoma of the tongue, and six patients achieved time to progression of >6 months, including patients with thyroid carcinoma, colorectal carcinoma, and basal cell carcinoma. Comparison of pre- and on-treatment biopsies showed significant suppression of pERK and pS6 activity with treatment. CONCLUSIONS: Our study of anti-IGF-1R antibody cixutumumab and MEK 1/2 inhibitor selumetinib showed that the combination is safe and well-tolerated at these doses, with preliminary evidence of clinical benefit and pharmacodynamic evidence of target inhibition.

The association between vitamin K status and knee osteoarthritis features in older adults: the Health, Aging and Body Composition Study.

BACKGROUND: Vitamin K-dependent (VKD) proteins, including the mineralization inhibitor matrix-gla protein (MGP), are found in joint tissues including cartilage and bone. Previous studies suggest low vitamin K status is associated with higher osteoarthritis (OA) prevalence and incidence. OBJECTIVE: To clarify what joint tissues vitamin K is relevant to in OA, we investigated the cross-sectional and longitudinal association between vitamin K status and knee OA structural features measured using magnetic resonance imaging (MRI). METHODS: Plasma phylloquinone (PK, vitamin K1) and dephosphorylated-uncarboxylated MGP ((dp)ucMGP) were measured in 791 older community-dwelling adults who had bilateral knee MRIs (mean ± SD age = 74 ± 3 y; 67% female). The adjusted odds ratios (and 95% confidence intervals) [OR (95%CI)] for presence and progression of knee OA features according to vitamin K status were calculated using marginal models with generalized estimating equations (GEEs), adjusted for age, sex, body mass index (BMI), triglycerides and other pertinent confounders. RESULTS: Longitudinally, participants with very low plasma PK (<0.2 nM) were more likely to have articular cartilage and meniscus damage progression after 3 years [OR (95% CIs): 1.7(1.0-3.0), 2.6(1.3-5.2) respectively] compared to sufficient PK (≥ 1.0 nM). Higher plasma (dp)ucMGP (reflective of lower vitamin K status) was associated with higher odds of meniscus damage, osteophytes, bone marrow lesions, and subarticular cysts cross-sectionally [ORs (95% CIs) comparing highest to lowest quartile: 1.6(1.1-2.3); 1.7(1.1-2.5); 1.9(1.3-2.8); 1.5(1.0-2.1), respectively]. CONCLUSION: Community-dwelling men and women with very low plasma PK were more likely to have progression of articular cartilage and meniscus damage. Plasma (dp)ucMGP was associated with presence of knee OA features but not progression. Future studies are needed to clarify mechanisms underlying vitamin Ks role in OA.

FGFR2 amplification has prognostic significance in gastric cancer: results from a large international multicentre study.

BACKGROUND: In preclinical gastric cancer (GC) models, FGFR2 amplification was associated with increased tumour cell proliferation and survival, and drugs targeting this pathway are now in clinical trials. METHODS: FGFR2 FISH was performed on 961 GCs from the United Kingdom, China and Korea, and the relationship with clinicopathological data and overlap with HER2 amplification were analysed. RESULTS: The prevalence of FGFR2 amplification was similar between the three cohorts (UK 7.4%, China 4.6% and Korea 4.2%), and intratumoral heterogeneity was observed in 24% of FGFR2 amplified cases. FGFR2 amplification was associated with lymph node metastases (P<0.0001). FGFR2 amplification and polysomy were associated with poor overall survival (OS) in the Korean (OS: 1.83 vs 6.17 years, P=0.0073) and UK (OS: 0.45 vs 1.9 years, P<0.0001) cohorts, and FGFR2 amplification was an independent marker of poor survival in the UK cohort (P=0.0002). Co-amplification of FGFR2 and HER2 was rare, and when high-level amplifications did co-occur these were detected in distinct areas of the tumour. CONCLUSION: A similar incidence of FGFR2 amplification was found in Asian and UK GCs and was associated with lymphatic invasion and poor prognosis. This study also shows that HER2 and FGFR2 amplifications are mostly exclusive.

Radical intermediates in the addition of OH to propene: photolytic precursors and angular momentum effects.

We investigate the photolytic production of two radical intermediates in the reaction of OH with propene, one from addition of the hydroxyl radical to the terminal carbon and the other from addition to the center carbon. In a collision-free environment, we photodissociate a mixture of 1-bromo-2-propanol and 2-bromo-1-propanol at 193 nm to produce these radical intermediates. The data show two primary photolytic processes occur: C-Br photofission and HBr photoelimination. Using a velocity map imaging apparatus, we measured the speed distribution of the recoiling bromine atoms, yielding the distribution of kinetic energies of the nascent C3H6OH radicals + Br. Resolving the velocity distributions of Br((2)P(1/2)) and Br((2)P(3/2)) separately with 2 + 1 REMPI allows us to determine the total (vibrational + rotational) internal energy distribution in the nascent radicals. Using an impulsive model to estimate the rotational energy imparted to the nascent C3H6OH radicals, we predict the percentage of radicals having vibrational energy above and below the lowest dissociation barrier, that to OH + propene; it accurately predicts the measured velocity distribution of the stable C3H6OH radicals. In addition, we use photofragment translational spectroscopy to detect several dissociation products of the unstable C3H6OH radicals: OH + propene, methyl + acetaldehyde, and ethyl + formaldehyde. We also use the angular momenta of the unstable radicals and the tensor of inertia of each to predict the recoil kinetic energy and angular distributions when they dissociate to OH + propene; the prediction gives an excellent fit to the data.

The effect of pulsing movements on the physiological response to common exercises.

AIM: There is a paucity of research on responses to exercises using pulsatile movements (PM) compared to using a full range of motion (FM). The purpose of the present study was to compare the physiological responses to PM vs. FM exercises. METHODS: Eight participants completed two separate exercise sessions, comprised of three sets of 20 repetitions for five different exercises. During the FM trial, all repetitions were performed using a full range of motion. In the PM trial, half of the repetitions were performed using pulsing movements. Average VO2, total VO2, HR and RPE were compared using paired t-tests. Blood lactate [La-] responses were compared using repeated measures analysis of variance. RESULTS: Average VO2 in the PM trial (1.52±0.38 L min-1) was similar to the FM trial (1.57±0.43 L min-1). However, total VO2 (PM=23.1±6.6 L, FM=27.2±6.9 L), average HR (PM=134.4 ± 10.9, FM=146.2±14.6 beats per min) and RPE (PM=12.2±0.9, FM=13.3±0.9) were significantly (P<0.05) lower for the PM trial. There were no significant differences in blood [La-] response (PM pre=1.7±0.8, post=6.1±0.8 mmol L-1; FM pre=1.6±0.4, post=6.8±0.5 mmol L-1). CONCLUSION: FM exercises elicit higher HR and RPE responses compared to PM exercises; without corresponding increases in metabolic rate.

Digital pattern recognition-based image analysis quantifies immune infiltrates in distinct tissue regions of colorectal cancer and identifies a metastatic phenotype.

BACKGROUND: Several studies in colorectal cancer (CRC) indicate a relationship between tumour immune infiltrates and clinical outcome. We tested the utility of a digital pattern recognition-based image analysis (DPRIA) system to segregate tissue regions and facilitate automated quantification of immune infiltrates in CRC. METHODS: Primary CRC with matched hepatic metastatic (n=7), primary CRC alone (n=18) and primary CRC with matched normal (n=40) tissue were analysed immunohistochemically. Genie pattern recognition software was used to segregate distinct tissue regions in combination with image analysis algorithms to quantify immune cells. RESULTS: Immune infiltrates were observed predominately at the invasive margin. Quantitative image analysis revealed a significant increase in the prevalence of Foxp3 (P<0.0001), CD8 (P<0.0001), CD68 (<0.0001) and CD31 (<0.0001) positive cells in the stroma of primary and metastatic CRC, compared with tumour cell mass. A direct comparison between non-metastatic primary CRC (MET-) and primary CRC that resulted in metastasis (MET+) showed an immunosuppressive phenotype, with elevated Foxp3 (P<0.05) and reduced numbers of CD8 (P<0.05) cells in the stroma of MET+ compared with MET- samples. CONCLUSION: By combining immunohistochemistry with DPRIA, we demonstrate a potential metastatic phenotype in CRC. Our study accelerates wider acceptance and use of automated systems as an adjunct to traditional histopathological techniques.

Health-related fitness and academic achievement in middle school students.

AIM: The aim of the present study was to determine the association between health-related fitness (HRF) and academic achievement in middle school youth. METHODS: Subjects were 312 middle school students. HRF was assessed using the FITNESSGRAM test battery. Students were grouped by the number of fitness tests in which they performed within the Healthy Fitness Zone, ranging from <1 test (lowest fitness) to all 5 tests (highest fitness). Academic achievement was assessed using grades (A - F) from four core classes, which were converted to interval data (A=5, F=1) and summed over the academic year and a standardized test (percentile). Maturity offset was calculated to control for the possible effect of maturity status on the association between HRF and academic achievement. Differences in academic achievement among HRF groups were determined using ANOVA. RESULTS: Grades and standardized test percentiles were higher in HRF group 5 (P<0.01) compared to HRF groups <2, 3, and 4. Cardiorespiratory endurance and muscular strength and endurance were the HRF components most strongly associated with academic achievement. CONCLUSION: HRF was related to academic achievement in youth. Students with the highest fitness level performed better on standardized tests and students with the lowest fitness level performed lower in class grades.

Modeling the rovibrationally excited C2H4OH radicals from the photodissociation of 2-bromoethanol at 193 nm.

This study photolytically generates, from 2-bromoethanol photodissociation, the 2-hydroxyethyl radical intermediate of the OH + ethene reaction and measures the velocity distribution of the stable radicals. We introduce an impulsive model to characterize the partitioning of internal energy in the C(2)H(4)OH fragment. It accounts for zero-point and thermal vibrational motion to determine the vibrational energy distribution of the nascent C(2)H(4)OH radicals and the distribution of total angular momentum, J, as a function of the total recoil kinetic energy imparted in the photodissociation. We render this system useful for the study of the subsequent dissociation of the 2-hydroxyethyl radical to the possible asymptotic channels of the OH + ethene reaction. The competition between these channels depends on the internal energy and the J distribution of the radicals. First, we use velocity map imaging to separately resolve the C(2)H(4)OH + Br((2)P(3/2)) and C(2)H(4)OH + Br((2)P(1/2)) photodissociation channels, allowing us to account for the 10.54 kcal/mol partitioned to the Br((2)P(1/2)) cofragment. We determine an improved resonance enhanced multiphoton ionization (REMPI) line strength for the Br transitions at 233.681 nm (5p (4)P(1/2) <-- 4p (2)P(3/2)) and 234.021 nm (5p (2)S(1/2) <-- 4p (2)P(1/2)) and obtain a spin-orbit branching ratio for Br((2)P(1/2)):Br((2)P(3/2)) of 0.26 +/- 0.03:1. Energy and momentum conservation give the distribution of total internal energy, rotational and vibrational, in the C(2)H(4)OH radicals. Then, using 10.5 eV photoionization, we measure the velocity distribution of the radicals that are stable to subsequent dissociation. The onset of dissociation occurs at internal energies much higher than those predicted by theoretical methods and reflects the significant amount of rotational energy imparted to the C(2)H(4)OH photofragment. Instead of estimating the mean rotational energy with an impulsive model from the equilibrium geometry of 2-bromoethanol, our model explicitly includes weighting over geometries across the quantum wave function with zero, one, and two quanta in the harmonic mode that most strongly alters the exit impact parameter. The model gives a nearly perfect prediction of the measured velocity distribution of stable radicals near the dissociation onset using a G4 prediction of the C-Br bond energy and the dissociation barrier for the OH + ethene channel calculated by Senosiain et al. (J. Phys. Chem. A 2006, 110, 6960). The model also indicates that the excited state dissociation proceeds primarily from a conformer of 2-bromoethanol that is trans across the C-C bond. We discuss the possible extensions of our model and the effect of the radical intermediate's J-distribution on the branching between the OH + ethene product channels.

Src inhibitors in early breast cancer: a methodology, feasibility and variability study.

Early clinical trials of anticancer agents may be enriched by robust biomarkers of activity. Surrogate measures used in trials of cytotoxic agents, such as tumor size regression, may not be informative when investigating targeted agents that act principally to inhibit invasion or proliferation. This study aimed to determine the validity of invasion-related biomarkers of activity for AZD0530, a potent Src inhibitor currently in clinical development. Focal adhesion kinase (FAK) and paxillin are downstream phosphorylation substrates of Src and mediate tumor cell adhesion and invasiveness. These were therefore selected as biologically relevant markers of Src inhibition. Early breast cancer was chosen as a model as multiple samples can be collected during standard treatment and there is an intervening period in which experimental intervention can be applied. Tumor tissue was collected from diagnostic core biopsies and subsequent surgical tumor excision samples in 29 women with early breast cancer attending a single center. Protein levels were assessed quantitatively by Luminex and qualitatively by immunohistochemistry. AZD0530 inhibited tumor growth in a manner independent of dose and inhibited phosphorylation of FAK and paxillin in a dose-dependent manner in a Calu-6 xenograft model. In the clinical study, agreement of within-visit and also of between-visit measurements was high and the estimated number of patients required to detect a drug effect would be low enough to allow use of these markers as endpoints in future dose selection studies.

Quantitative multiplexed quantum dot immunohistochemistry.

Quantum dots are photostable fluorescent semiconductor nanocrystals possessing wide excitation and bright narrow, symmetrical, emission spectra. These characteristics have engendered considerable interest in their application in multiplex immunohistochemistry for biomarker quantification and co-localisation in clinical samples. Robust quantitation allows biomarker validation, and there is growing need for multiplex staining due to limited quantity of clinical samples. Most reported multiplexed quantum dot staining used sequential methods that are laborious and impractical in a high-throughput setting. Problems associated with sequential multiplex staining have been investigated and a method developed using QDs conjugated to biotinylated primary antibodies, enabling simultaneous multiplex staining with three antibodies. CD34, Cytokeratin 18 and cleaved Caspase 3 were triplexed in tonsillar tissue using an 8h protocol, each localised to separate cellular compartments. This demonstrates utility of the method for biomarker measurement enabling rapid measurement of multiple co-localised biomarkers on single paraffin tissue sections, of importance for clinical trial studies.

The effects of acute garlic supplementation on the fibrinolytic and vasoreactive response to exercise.

BACKGROUND: The purpose of this project was to examine the effects of acute garlic supplementation on fibrinolysis and vasoreactivity both at rest and following maximal exercise. METHODS: Eighteen healthy trained males (20.9 ± 2.2 years, 178 ± 7.7 cm, 75.5 ± 9.6 kg, VO2max = 59.8 ± 6.7 ml • kg(-1) • min(-1)) performed a graded treadmill test to volitional exhaustion. Blood samples were taken at rest, within two minutes post-exercise, and one hour post-exercise. Eleven of the subjects also had a brachial vasoreactivity test performed immediately after the blood sample to assess flow-mediated dilation (FMD) of the brachial artery. Participants were randomly assigned to ingest either 900 mg of powdered garlic or a placebo three hours before the exercise session. The supplement was distributed in a double-blind, crossover fashion. Participants repeated the protocol with the other treatment after a 14-day washout period. Paired t-tests were used to compare VO2max between the two trials. A two-factor (treatment and time) repeated measures analysis of variance (ANOVA) was used to assess changes in FMD, tPA activity, tPA antigen, and PAI-1 activity. A priori statistical significance was set at P <0.05. RESULTS: VO2max was greater for the garlic treatment trial vs. placebo (Placebo = 59.8 ± 6.7 ml • kg(-1) • min(-1); Garlic = 61.4 ± 6.6 ml • kg(-1) • min(-1)). There was no main effect for treatment and no treatment x time interaction for FMD or any fibrinolytic variables examined. CONCLUSION: Acute garlic supplementation does not alter vasoreactivity, fibrinolytic potential or the fibrinolytic response to exercise in young healthy trained males. Acute garlic supplementation does, however, cause a small but statistically significant increase in VO2max. It remains unclear if this increase in VO2max is of functional importance.

Endothelial reactivity and cardiac risk factors in older patients with peripheral arterial disease.

Peripheral arterial disease (PAD) is a major cause of morbidity and mortality. Endothelium-dependent vasoreactivity, which is advocated as a measure of vascular health, is impaired in persons with cardiac risk factors and coronary artery disease. Few studies have examined the degree of endothelial dysfunction in patients with PAD. Using high-resolution external vascular ultrasound, we measured brachial artery diameter and flow at rest, and in response to reactive hyperemia (flow-mediated dilation) in 50 older patients (age 69 +/- 1 year) with PAD (ankle-to-brachial artery index of 0.67 +/- 0.03), and 50 age-matched non-PAD patients. Coronary artery disease was more prevalent in PAD than in non-PAD patients (40% vs 4%, p <0.001). Systolic blood pressure (153 +/- 4 vs 141 +/- 3 mm Hg, p <0.01), fasting glucose (129 +/- 6 vs 109 +/- 5 mg/dl, p <0.001), and pack-years smoked (54 +/- 7 vs 25 +/- 3, p <0.01) were higher in the PAD than in non-PAD patients. There were no differences in baseline brachial artery diameter, blood velocity, or flow between the 2 groups. However, the 1-minute postocclusion percent change in diameter (6.5 +/- 0.7% vs 9.8 +/- 0.7%, p <0.001) and the change in diameter (0.22 +/- 0.02 vs 0.33 +/- 0.02 mm, p <0.001) were lower in PAD than in non-PAD patients, suggesting impaired endothelium-dependent dilation. The postocclusion hyperemic velocity and blood flow were also lower in PAD than in non-PAD patients. In multiple regression analyses the low-density lipoprotein-to-high-density lipoprotein cholesterol ratio, elevated fasting glucose, and high systolic blood pressure were independent predictors of percent change in brachial artery diameter (r2 = 0.37, p <0.001). Thus, older patients with PAD had impaired endothelial dependent vasodilation compared with controls that was associated with the presence of cardiac risk factors. The effect of cardiac risk factor intervention on endothelial function in patients with PAD remains to be determined.

HIV type 1 envelope sequences from seroconverting patients in Barbados.

PIP: Because of the prevalence of leptospirosis in Barbados, patients who present to the hospital with febrile illnesses are routinely screened for Leptospira infection and their sera are stored for future reference. While the majority of patients are infected with Leptospira, some are not. Since some symptoms of acute HIV-1 illness are similar to those of leptospirosis, patient records were reviewed to identify patients whose clinical symptoms may have been due to HIV-1 infection. 10 HIV-1-positive patients originally hospitalized during 1990-94 were identified whose medical histories suggested the occurrence of acute HIV-1 illness at the time of Leptospira testing. Stored sera from those patients were then tested for the presence of HIV-1 p24 antigen and by Western blotting. Evidence of acute HIV-1 infection was considered to be a positive p24 test or a characteristic Western blot profile occurring at or shortly before the time of seropositivity for HIV-1 antibody. The authors determined the sequence of viral RNA from the 12 remaining sera samples from 8 patients, including paired samples drawn at 3- or 4-day intervals from 4 people. The Barbados patient variants aligned more closely with HIV-1 clade B reference strains than with the other subtypes. 2 variants, however, align separately from the classic B subtype and somewhat closer to variants from clades A and C. The Venezuelan isolate, although different from the patient sequences, is also separate from the other B variants.^ieng

Hydatidiform mole in Nottingham: a 12-year retrospective epidemiological and morphological study.

The results of a 12-year retrospective study on the epidemiology of hydatidiform mole (HM) in Nottingham are presented. We have reviewed the histology of our cases of HM, tried to minimize selection bias, and have used the most reliable data available. Using data from two different sources we have calculated the frequency of HM as 1 in 1400 deliveries. The frequency of HM in this study is one quarter of that reported in an excellent study from Japan. We suggest that, with accurate epidemiological studies, the difference in frequency of HM between 'high risk' and 'low risk' areas is less than previously accepted. The present study also shows a lower incidence of persistent trophoblastic disease than previously generally accepted. We confirm that partial HM is a distinct clinicopathological entity and that two forms are distinguishable histologically. The malignant potential of partial HM is uncertain, and we suggest that the clinical management of partial HM should be no different from that of complete HM until further studies dictate otherwise.

Unusual histological appearances of barium sulphate--a case report with scanning electron microscopy and energy dispersive x ray analysis.

Multiple birefringent rhomboidal crystals seen on histological examination of a resected oesophagus were subsequently found to contain elemental barium and sulphur on energy dispersive x ray ( EDX ) analysis. Scanning electron microscopy and EDX analysis of readily available commercial barium sulphate suspensions suggested that the two forms of barium sulphate previously described in tissue sections may be a result of the method of preparation of the commercial suspension used. With increased use of barium sulphate prepared by crushing the natural compound, birefringent rhomboidal crystals should be found with increasing frequency in endoscopic biopsy samples and resected specimens.

Primary malignant melanoma of the gall bladder.

A case of primary malignant melanoma of the gall bladder is reported, in which a 29 year old man presented with acute cholecystitis which led to perforation of the gall bladder and biliary peritonitis. To help in the differentiation between primary and secondary malignant melanoma in the gall bladder and to overcome some of the difficulties posed by the clinical identification of what is often a small or relatively inaccessible primary tumour, it is suggested that certain criteria should be fulfilled before primary melanoma is diagnosed. (i) Tumours must be solitary and arise from the mucosal surface of the gall bladder; (ii) they must either be papillary or polypoid; (iii) they must either display junctional activity or have any other primary sites excluded by history taking, examination, and investigation. If these criteria are applied to the published case reports of primary malignant melanoma, only six cases, including the present one, can be regarded as true primary tumours.

Isolated arteritis of the epididymis.

The clinical, histological, and immunohistochemical features of two cases of apparently isolated arteritis of the epididymis are presented. The aetiology and pathogenesis of the condition are discussed. Immunoglobulin and complement were shown in the acute arterial lesions, but this is not conclusive evidence that isolated arteritis is either an immune complex disease or a forme fruste of polyarteritis nodosa.

Supplying commercial biomedical companies from a human tissue bank in an NHS hospital--a view from personal experience.

NHS histopathology laboratories are well placed to develop banks of surgically removed surplus human tissues to meet the increasing demands of commercial biomedical companies. The ultimate aim could be national network of non-profit making NHS tissue banks conforming to national minimum ethical, legal, and quality standards which could be monitored by local research ethics committees. The Nuffield report on bioethics provides ethical and legal guidance but we believe that the patient should be fully informed and the consent given explicit. Setting up a tissue bank requires enthusiasm, hard work, and determination as well as coordination between professionals in the NHS trust and in the commercial sector. The rewards are exiting new collaborations with commercial biomedical companies which could help secure our future.