Two-year randomized controlled trial of vitamin K1 (phylloquinone) and vitamin D3 plus calcium on the bone health of older women.

Dietary supplementation with vitamin K(1), with vitamin D(3) and calcium or their combination, was examined in healthy older women during a 2-year, double-blind, placebo-controlled trial. Combined vitamin K with vitamin D plus calcium was associated with a modest but significant increase in BMC at the ultradistal radius but not at other sites in the hip or radius. INTRODUCTION: The putative beneficial role of high dietary vitamin K(1) (phylloquinone) on BMD and the possibility of interactive benefits with vitamin D were studied in a 2-year double-blind, placebo-controlled trial in healthy Scottish women > or =60 years of age. MATERIALS AND METHODS: Healthy, nonosteoporotic women (n = 244) were randomized to receive either (1) placebo, (2) 200 microg/day vitamin K(1), (3) 10 microg (400 IU) vitamin D(3) plus 1000 mg calcium/day, or (4) combined vitamins K(1) and D(3) plus calcium. Baseline and 6-month measurements included DXA bone mineral scans of the hip and wrist, markers of bone turnover, and vitamin status. Supplementation effects were tested using multivariate general linear modeling, with full adjustment for baseline and potential confounding variables. RESULTS: Significant bone mineral loss was seen only at the mid-distal radius but with no significant difference between groups. However, women who took combined vitamin K and vitamin D plus calcium showed a significant and sustained increase in both BMD and BMC at the site of the ultradistal radius. Serum status indicators responded significantly to respective supplementation with vitamins K and D. Over 2 years, serum vitamin K(1) increased by 157% (p < 0.001), the percentage of undercarboxylated osteocalcin (%GluOC) decreased by 51% (p < 0.001), serum 25-hydroxyvitamin D [25(OH)D] increased by 17% (p < 0.001), and PTH decreased by 11% (p = 0.049). CONCLUSIONS: These results provide evidence of a modest synergy in healthy older women from nutritionally relevant intakes of vitamin K(1) together with supplements of calcium plus moderate vitamin D(3) to enhance BMC at the ultradistal radius, a site consisting of principally trabecular bone. The substantial increase in gamma-carboxylation of osteocalcin by vitamin K may have long-term benefits and is potentially achievable by increased dietary intakes of vitamin K rather than by supplementation.     

The diagnostic usefulness of tumour markers CEA and CA-125 in pleural effusion

Pleural effusion is a common diagnostic problem. The analysis of serum and pleural fluid for tumour markers is widely used as a diagnostic aid in clinical practice. The aim of the present study was to determine the usefulness of simultaneous quantification of carcinoembryonic antigen (CEA) and carbohydrate antigen (CA-125) in distinction of malignant from benign effusion. Data from a total of 78 patients including 53 patients with benign and 25 patients with malignant effusion was evaluated. The cut-off values for differentiating benign from malignant effusions were determined using results obtained from patients with known benign effusions (mean + 2 SD, 95% confidence interval). The cut-off for CEA and CA-125 were 5.1 ng/ml and 1707 IU/ml respectively. CEA assay in pleural fluid had an acceptable sensitivity and good specificity of 64% and 98% respectively. CA-125 had a sensitivity of 36% and specificity of 94%. The combination of the two tumour markers gave a sensitivity of 72% and specificity of 92.4%. We suggest a good clinical strategy may be to begin with CEA measurement (assay specificity 98%); if CEA is below the cut-off value (negative), CA-125 could then be measured to improve the sensitivity of detection of malignant effusions. However, measurement of these tumour markers is not cost effective from the point of view that it does not give information on the type of malignancy present. The latter has to be determined either by histological or cytological study.     

Neurotoxicity of Clostridium perfringens Epsilon-Toxin for the Rat Hippocampus via the Glutamatergic System

The neurotoxicity of epsilon-toxin, one of the major lethal toxins produced by Clostridium perfringens type B, was studied by histological examination of the rat brain. When the toxin was injected intravenously at a lethal dose (100 ng/kg), neuronal damage was observed in many areas of the brain. Injection of the toxin at a sublethal dose (50 ng/kg) caused neuronal damage predominantly in the hippocampus: pyramidal cells in the hippocampus showed marked shrinkage and karyopyknosis, or so-called dark cells. The dark cells lost the immunoreactivity to microtubule-associated protein-2, a postsynaptic somal and dendric marker, while acetylcholinesterase-positive fibers were not affected. Timm’s zinc staining revealed that zinc ions were depleted in the mossy layers of the CA3 subfield containing glutamate as a synaptic transmitter. The cerebral blood flow in the hippocampus was not altered significantly before or after administration of the toxin, as measured by laser-Doppler flowmetry, excluding the possibility that the observed histological change was due to a secondary effect of ischemia in the hippocampus. Prior injection of either a glutamate release inhibitor or a glutamate receptor antagonist protected the hippocampus from the neuronal damage caused by epsilon-toxin. These results suggest that epsilon-toxin acts on the glutamatergic system and evokes excessive release of glutamate, leading to neuronal damage.     

Diagnosis of visceral leishmaniasis: comparative potential of amastigote antigen,recombinant antigen and PCR

Development of simple, economical and non-invasive tests for the early diagnosis of visceral leishmaniasis (VL) or kala-azar (KA) remains a challenge, and serological studies based on antigen prepared from the amastigote stage of Leishmania donovani, the stage that causes infection, are lacking. In the present study, circulating antibodies to total antigen isolated from the promastigote and amastigote stages of the parasite, as well as to recombinant K39 (rK39) antigen, are measured by enzyme-linked immunosorbent assay (ELISA) and the results compared with a polymerase chain reaction (PCR) test for KA diagnosis. In 116 samples of KA examined, the amastigote antigen gave significantly higher mean absorbance values in ELISA than did the promastigote antigen. The sensitivity for KA detection was significantly higher using the amastigote antigen (94%) than the promastigote antigen (90.5%). Analysis in 91 controls showed that specificity was higher with amastigote antigen (92.3%) than with promastigote antigen (86.8-89.0%). Reliability of ELISA diagnosis with amastigote antigen was only marginally lower than that with rK39 ELISA or with the PCR test. Easy availability and low cost of indigenous amastigote antigen, together with the simplicity of ELISA compared with PCR, make ELISA based on amastigote antigen a promising choice for the diagnosis of KA.     

Microbicides 2006 conference

Current HIV/AIDS statistics show that women account for almost 60% of HIV infections in Sub-Saharan Africa. HIV prevention tools such as male and female condoms, abstinence and monogamy are not always feasible options for women due to various socio-economic and cultural factors. Microbicides are products designed to be inserted in the vagina or rectum prior to sex to prevent HIV acquisition.     

Fine-needle aspiration cytology of phyllodes tumors

Breast lesions with a significant spindle cell or mesenchymal component are not commonly encountered in fine-needle aspiration (FNA) cytologic material and include a heterologous variety of benign and malignant conditions, with phyllodes tumors (PTs) being the foremost differential diagnostic consideration. This study comprises 28 tumors diagnosed histologically as PT in which FNAC material was available for review. Histological sections and cytological smears from these cases were retrieved and subjected to detailed morphological review. Cytological parameters assessed included ratio of stroma to epithelium, pattern characteristics and cytological characteristics of the stromal, and epithelial components and the background cells. Large and hypercellular stroma fragments, dissociated spindle and plump stromal cells, often accompanied by large, folded sheets of epithelium were cytological features that characterized PT. Smears from malignant PT showed predominantly or solely mesenchymal components. FNAC was a highly reliable procedure for the diagnosis of PT, giving an accuracy rate of 92.8%.     

Papillary cystic type of acinic cell carcinoma of parotid: fine needle aspiration cytological features of a high grade variant with oncocytic metaplasia

A 60-year-old female developed a right parotid swelling six months after surgery for intra-oral squamous cell carcinoma. Fine needle aspiration (FNA) cytological smears showed dissociated large and small pleomorphic tumour cells with abundant mitoses and oncocytic features. A cytological diagnosis of parotid acinic cell carcinoma (ACC) was made. Histological study of the subtotal parotidectomy specimen showed a papillary cystic variety of acinic cell carcinoma (ACC-PCV). FNA cytological features in this case of ACC-PCV differs from the two previously reported cases in that it showed prominent oncocytic and high grade features and absence of papillary pattern in the cytological smears. ACC-PCV is an uncommon tumour and knowledge of its varied FNA cytological features is important for the diagnosis of this neoplasm.     

Demographics of the UK cystic fibrosis population: implications for neonatal screening

The objective was to determine the composition of the Cystic Fibrosis (CF) Population attending specialist UK CF centres in terms of age, gender, age at diagnosis, genotype and ethnicity. With the planned introduction of the national CF screening programme in the UK, cystic fibrosis transmembrane regulator (CFTR) mutations were compared between different ethnic groups enabling a UK-specific frequency of mutations to be defined. Data were analysed from the patient biographies held in the UK CF Database (see www.cystic-fibrosis.org.uk). The currently registered population of 5,274 CF patients is 96.3% Caucasian with a male preponderance that significantly increases with age. The majority of the 196 non-Caucasian CF patients are from the Indian Subcontinent (ISC), of which one in 84 UK CF patients are of Pakistani origin. The commonest CFTR mutation, deltaF508, is found in 74.1% of all CF chromosomes. In the Caucasian CF population, 57.5% are deltaF508 homozygotes but the UK ISC CF population with only 24.7%, has significantly fewer deltaF508 homozygotes patients (95% confidence interval (CI) 0.2-0.4). The distribution of Caucasian patients with deltaF508/deltaF508, deltaF508/Other and Other/Other does not fit the expected distribution with a Hardy-Weinberg model unless those patients without a detected mutation are excluded (P<0.001). The UK CF Database has shown the UK CF population to have distinct characteristics separate from the North American and European CF Registries. The ISC group contains many mutations not recognised by current genetic analysis, and one in four ISC patients have no CFTR mutations identified. The CFTR analysis proposed for the screening programme would detect 96% of patients registered in the database, but is unlikely to achieve the desired >80% detection rates in the ethnic minority groups. Screen-positive, non-Caucasian infants without an identifiable CFTR mutation should be referred for a sweat test and genetic counselling when serum trypsinogen concentrations remain elevated after birth.