Clinical Assessment of Gestational Age

There is disagreement among authors as to what criteria are most reliable in assessing postnatal fetal age. A comparison–for objectivity, accuracy, and frequency of use– of specific criteria was made using three independent examiners at different educational levels: a second-year medical student, a perinatal nurse practitioner, and a pediatrics resident. It was shown that trained examiners develop favorite criteria which differ among examiners and thus sacrifice accuracy; however, accurate assessment of fetal age can be accomplished by an examiner with minimum clinical knowledge.     

Development of an improved multi-pressure-sensor probe for recording muscle contraction in human intestine

We have developed an improved semiconductor recording probe for monitoring motility of the upper small intestine in humans. The probe consists of six ultraminiature silicon pressure sensors spaced 10 cm apart and encased in a flexible polyurethane sheath. The probe is small [2.67 mm (8F) diameter], is easily passed transnasally, and is tolerated by patients for prolonged recording periods (24–36 hr) with a minimum of discomfort. The initial semiconductor and catheter material were those designed for use in the cardiovascular system, but they proved to be easily damaged by gastric acid and enzymes. After improvement of this probe, we now have recordings from more than 100 patients for an approximate total of 6000 hr of recording time. The improved probe is a durable recording device that facilitates the investigation of motility of the small intestine in humans in health and disease.This study was supported by funds from the Medical Research Service of the Veterans Administration and by National Institutes of Health Clinical Research Center grant RR-82.     

Bioadhesive, non-drug-loaded nanoparticles as modulators of candidal adherence to buccal epithelial cells: a potentially novel prophylaxis for candidosis

Adherence of microorganisms, such as Candida albicans, represents the initial step in the establishment of infection and, accordingly, modification of this step represents a method by which the incidence of infection may be reduced. Therefore, this study uniquely examined the effects of polymeric nanoparticles on the adherence of blastospores of C. albicans to human buccal epithelial cells (BEC) in vitro. Poly(propylcyanoacrylate) nanoparticles were produced by emulsion polymerisation using a range of anionic, cationic and non-ionic surfactants, their particle size and zeta potential characterised and incubated with stationary phase blastospores of C. albicans for a defined period. Following this, the surface properties and size of blastospores with adsorbed nanoparticles were characterised. phosphate buffered saline-treated and nanoparticle-treated blastospores were incubated with human BEC for 2 h, following which the number of adherent blastospores was enumerated by light microscopy. The size and zeta potential of the nanoparticles were dependent on the surfactant employed in the manufacture process. Following nanoparticle adsorption, alteration of the zeta potential and an increase in the diameter of blastospores were observed. However, as this increase in diameter was indirectly related to the size of the nanoparticles, this may indicate a preference for the adsorption of smaller particles. In addition, following nanoparticle adsorption, the cell surface hydrophobicity (CSH) of C. albicans blastospores was increased and, importantly, the subsequent adherence to BEC in vitro was reduced. Most notably, the adherence of blastospores that had been treated with nanoparticles (stabilised with docusate sodium) was circa 73% lower than that of untreated blastospores. A moderate correlation between increased CSH and reduced adherence and a low correlation between blastospore zeta potential and adherence were observed, inferring that other mechanisms, most likely stearic hindrance, are responsible for the antiadherent properties of adsorbed nanoparticles. In light of their ability to reduce candidal adherence to BEC, it is suggested that polymeric nanoparticles may be useful in the prophylaxis of candidosis of the oral cavity.     

Evidence of prostate cancer screening in a UK region

OBJECTIVE: To examine the pattern of use of prostate-specific antigen (PSA) testing in a UK region, where National Health Service policy does not recommend screening for prostate cancer. SUBJECTS AND METHODS: Data were collected on all PSA tests in Northern Ireland between 1990 and 1999. Annual rates of PSA testing were calculated by age, GP Practice and year. RESULTS: In all, 165 862 PSA tests were performed on 84 669 men, and over a third of men aged > or = 50 years had at least one PSA test. Men aged < 50 years accounted for 12.9% of first tests. The proportion of tests from primary care increased from 47.2% in 1993 to 67.0% in 1999. The mean age of men tested once decreased from 65.6 to 61.9 years (P trend < 0.001) and the proportion with an elevated PSA level also declined during the period. Repeat testing increased with PSA level (P < 0.001) but 29.4% of men with a PSA level of < or = 4 ng/mL also had repeat testing. Raised PSA values were more common from hospital than primary care (32.4% vs 20.6%, P < 0.001) and in older men. Test rates varied 100-fold across general practices, a finding not explained by sociodemographic factors, but one which reflects differential adherence to national guidelines, suggesting that general practitioners are key targets for attempting to rationalise the use of the PSA test. CONCLUSION: These findings suggest that PSA screening is taking place against evidence-based advice and has resulted in over 20 000 men being designated as having a raised PSA level, creating a need for further assessment.     

Immunisation of babies of women who screen positive for hepatitis B

Pregnant women from countries with high prevalence rates of hepatitis B virus (HBV) infection may have significant HBV DNA levels despite being hepatitis B e antigen (HBeAg) negative and having antibody to HBeAg (anti-HBe positive). It is suggested that their babies, following delivery, should be given hepatitis B specific immunoglobulin (HBIG) in addition to hepatitis B vaccine in order to ensure their protection against infection.     

Human brain endothelium: coexpression and function of vanilloid and endocannabinoid receptors

The arachidonic acid derivative, 2-arachidonoyl-glycerol (2-AG), was initially isolated from gut and brain; it is also produced and released from blood and vascular cells. Many of the 2-AG-induced cellular responses (i.e., neuromodulation, cytoprotection and vasodilation) are mediated by cannabinoid receptors CB1 and CB2. The findings presented here demonstrate the expression of CB1, CB2 and TRPV1 receptors on cerebromicrovascular endothelial cells (HBEC). The expression of TRPV1, CB1 and CB2 receptor mRNA and proteins were demonstrated by RT-PCR and polyclonal antibodies, respectively. The endocannabinoid 2-AG, and other related compounds [anandamide (ANA), methanandamide (m-ANA), N-(4-hydroxyphenyl-arachidonyl-ethanolamide) (AM404) and capsaicin] dose-dependently stimulated Ca2+ influx in HBEC. The selective TRPV1 receptor antagonist (capsazepine), CB1 receptor antagonist (SR141716A) and CB2 receptor antagonist (SR144528) inhibited these responses. The effects of capsaicin, a specific agonist for TRPV1 receptors, were inhibited by capsazepine, but only weakly by CB1 or CB2 receptor antagonists. 2-AG also induced phosphorylation of vasodilator-stimulated phosphoprotein (VASP); this response was mediated by VR1 receptors. These studies clearly indicate that 2-AG and other related compounds may function as agonists on VR1 receptors, as well as CB1 and CB2 receptors, and implicated these factors in various HBEC functions.     

Akt phosphorylation and kinase activity are down-regulated during hibernation in the 13-lined ground squirrel

Hibernation in mammals is a reversible state of suspended animation associated with tolerance to an otherwise lethal reduction of core body temperature and metabolism. An integral aspect of hibernation is tolerance to a profound decrease of cerebral perfusion. Identification of regulatory mechanisms that control hibernation in ground squirrels can guide efforts to develop improved treatment for stroke and brain trauma. In this study, we show in multiple tissues that S473 phosphorylation of Akt (Protein kinase B), a phosphatidylinositol-3 kinase-regulated serine/threonine kinase, was significantly reduced (P<0.001) as was its kinase activity (P=0.023) in the 13-lined ground squirrel, Spermophilus tridecemlineatus, during hibernation. T308 phosphorylation of Akt was relatively preserved. Brain immunohistochemical staining confirmed these results. In hibernating animals, reduction of immunoreactive phospho (S473)-Akt was noted throughout the brain. Akt is a key molecule in the insulin/insulin-like growth factor signal transduction pathway, which plays a critical role in the balance between survival and apoptosis. The data presented here raise the possibility that down-regulation of Akt phosphorylation plays a regulatory role in hibernation. This would resemble dauer larva formation in Caenorhabditis elegans where Akt inhibition is associated with energy conservation, fat storage, expression of antioxidant enzymes and growth arrest.