Economic Impact of Implementing Malnutrition Screening and Nutritional Management in Older Adults in General Practice.

OBJECTIVES: Malnutrition is a common and significant public health problem, especially for older adults, as the consequences are costly. National guidelines (NICE CG32/QS24) highlight the need to identify and manage malnutrition, the implementation of which was deemed "high impact to produce cost savings". The 'Malnutrition Pathway', endorsed by NICE and other professional bodies, is a practical evidence-based guide to help community healthcare professionals (HCP) to implement guidance on malnutrition management. Published evaluations of its use are needed. DESIGN: This service evaluation in older adults assessed the impact of implementing the 'Malnutrition Pathway' on health care use and costs, as well as the acceptability of the management strategies and effect on malnutrition risk. SETTING: 5 GP surgeries in Gloucestershire. PARTICIPANTS: 163 older adults (80±9 years) with a range of primary diagnoses, living in their own home, were screened using the Malnutrition Universal Screening Tool ('MUST') (n50 low risk (LR); n41 medium risk (MR); n72 high risk (HR)). All patients were managed according to risk (LR: no further management; MR: dietary advice (DA); and HR: DA plus two oral nutritional supplements (ONS) (1 serve 300kcal, 18g protein; 125ml). MEASUREMENTS: At each review (6weeks, 3 and 6 months), 'MUST' score, compliance and satisfaction to their management plan were recorded. Healthcare use was collected from GP records 6 months before and after implementation of the pathway. A simple cost analysis was completed. RESULTS: Implementing appropriate management of malnutrition led to significant reductions in hospital admissions (p=0.028), length of hospital stay (p=0.05), GP visits (p=0.007) and antibiotic prescriptions (p=0.05). Over 6 months, the costs to manage malnutrition (HCP time, ONS) were more than offset by the savings associated with these reductions in health care use (per patient savings of -£395.64 MR+HR; -£997.02 HR). The proportion of individuals at risk of malnutrition reduced over time, and patients reported being satisfied with the DA (97%) and ONS (96%), consuming 90% of their ONS prescription. CONCLUSION: Managing malnutrition significantly reduces healthcare use, with a positive budget impact, in older malnourished patients in primary care. This represents an opportunity to improve patient care with benefit on health care spend.

Freeze-fracture studies of nexuses between smooth muscle cells. Close relationship to sarcoplasmic reticulum.

The freeze-fracture appearance of the nexus was compared in the smooth muscle of guinea pig sphincter pupillac, portal vein, pulmonary artery, taenia coli, uretzr, and vas diferens, mouse vas deferens, chicken gizzard and anterior mesenteric artery, and toad stomach. Nexuses are particularly numerous in the guinea pig sphincter pupillae; they are usually oval and their average area is 0.15 mum2, although some as large as 0.6 mum2 were seen. Small aggregations of particles were observed which would not be recognizable as nexuses in thin section. What constitutes the minimum size of a nexus is discussed. It is estimated that the number of nexuses per cell in this preparation is of the order of tens rather than hundreds. All nexuses examined had 6-9-nm particles in the PF face, with corresponding 3-4-nm pits on the EF face forming a polygonal tending towards a hexagonal lattice. The nexuses are arranged in rows parallel to the main axis of the cell, usually alternating with longitudinal rows of plasmalemmal vesicles. Many nexuses in the guinea pig sphincter pupillae, chicken gizzard, and toad stomach show a close relationship with sarcoplasmic reticulum. The possibility that this may have some role in current flow across this specialized junction is discussed.

Thomy-headed worm infection in north american prehistoric man.

Examination of ova and parasites from coprolites of probable human origin revealed eggs of the phylum Acanthocephala. Specimens were gathered from Danger Cave in Utah, an area heavily populatd with definitive rodent hosts for the Acanthocephala species Moniliformis clarki. It is postulated that prehistoric man developed Acanthocephala infection by ingesting the arthropod intermediate host, or that he was a victim of false parasitism by ingesting the whole rodent.

Enterobius vermicularis: 10,000-year-old human infection.

Eggs of Enterobius vermicularis (human pinworm) were found in hum coprolites from Hopug and Danger Caves, western Utah. The Caves were inhabitated by man from 10,000 B.C. to A.D. 1400. The oldest coprolite containing dated at 7837 B.C. This represents the earliest known association between man abd this exclusively human parasite.

Replication of human endothelial cells in culture.

Investigative studies dealing with the properties and functions of endothelial cells have been hampered because there has been little or no success in the isolation, growth, and passage of individual cells in large numbers. We have developed a system whereby pure cultures of endothelial cells derived from umbilical veins can be subcultured for at least five serial passages. Many facets of endothelial function and interaction can be evaluated with the use of this new adaptive system of isolation and culture.

Effect of aspirin on thrombin-induced adherence of platelets to cultured cells from the blood vessel wall.

An in vitro method was used to detect adherence of (51)Cr-labeled platelets to monolayers of cultured human endothelial, fibroblast, and smooth muscle cells. Washed platelets did not adhere to untreated or aspirin-treated endothelial monolayers in the absence of thrombin. In contrast, thrombin-induced platelet aggregates adhered to all of the monolayers but adherence to endothelium was significantly less than to the other cells. Additional evidence for adherence of platelets to the endothelium was provided by scanning and transmission electron microscopy. Thrombin-induced platelet adherence to endothelium was inhibited by hirudin. Platelet adherence induced by thrombin was enhanced significantly by treatment of the endothelial monolayer with 1-2 mM aspirin. This increase in adherence was seen even when aspirin-treated platelets were used; adherence values approached those seen with fibroblasts and smooth muscle cells. An aspirin concentration of 0.1 mM was sufficient to block thrombin-induced malonaldehyde production in platelets but it did not interfere with the inhibitory effect of the endothelium against platelet adherence. The effect of aspirin on the endothelium was temporary and inhibitory activity of the endothelium was restored 1 h after aspirin had been removed from the incubation system. The ability of thrombin to cause adherence of platelets to undamaged endothelium, and the potential for aspirin to enhance this adherence have implications for mechanisms which operate in platelet interaction with the blood vessel wall.

Utilization of arachidonic and linoleic acids by cultured human endothelial cells.

When cultured human umbilical vein endothelial cells are supplemented with linoleic acid, the arachidonic acid content of the cellular phospholipids is reduced approximately 35%. Most of the fatty acid compositional change occurs during the first 24 h. One factor responsible for this effect is the inability of the endothelial cells to convert appreciable amounts of linoleic to arachidonic acid, due to a fatty acid delta 6-desaturase deficiency. By contrast, these endothelial cultures contain delta 5- and delta 9-desaturase activity and are able to elongate long-chain polyunsaturated fatty acids. The other factor that contributes to the decrease in arachidonic acid is that high concentrations of linoleic acid reduce the incorporation of arachidonate into cellular phospholipids. Stearic acid, a long-chain saturate, does not produce any reduction, whereas eicosatrienoic acid is an even more effective inhibitor than linoleic acid. In spite of the fact that high concentrations of these polyunsaturates produced inhibition, the endothelial cells were found to efficiently incorporate exogenous arachidonic acid into cellular phospholipids and triglycerides. This may serve to compensate for the inability of these cells to synthesize arachidonic acid from linoleic acid. These findings suggest that the endothelium obtains arachidonic acid from an extracellular source, that this cannot be provided in the form of linoleic acid and, in fact, that high concentrations of linoleic acid actually may interfere with the ability of the endothelium to maintain an adequate supply of intracellular arachidonic acid.

Utilization of long-chain free fatty acids by human platelets.

There was a rapid net uptake of free fatty acid (FFA) by human platelets when long-chain FFA, bound to human serum albumin, were incubated with platelet suspensions. Results from experiments in which both palmitate and albumin were labeled indicated that the fatty acid dissociated from the protein during uptake. Much of the FFA taken up by the platelet in short-term incubations remained in unesterified form, i.e., it was recovered as platelet FFA. As the incubation continued, increasing amounts of FFA were oxidized to CO(2) and incorporated into platelet lipid esters, particularly lecithin. Essentially all of the fatty acid that was incorporated into the platelet FFA fraction was released rapidly from the cells when they were exposed to a medium containing FFA-free albumin. The magnitude of uptake into the platelet FFA fraction was similiar at 0 degrees and 37 degrees C. Likewise, the rate and magnitude of FFA release from the platelet were similar at 0 degrees and 37 degrees C. Therefore, it is likely that both FFA uptake and FFA release occur by energy-independent mechanisms. The major effect of increasing the FFA concentration of the incubation medium was increased fatty acid uptake into the platelet FFA fraction. Similar results occurred when platelets were incubated in human plasma containing increasing amounts of added palmitate. At a given extracellular FFA concentration, considerably more of the saturated fatty acids, palmitate and stearate, were taken up as platelet FFA than either oleate or linoleate.

Inhibition of prostacyclin by treatment of endothelium with aspirin. Correlation with platelet adherence.

Aspirin treatment of cultured endothelial cells from the umbilical vein increased the adherence of 51Cr-platelets when thrombin was present. If the cyclooxygenase activity of endothelium was inhibited by aspirin, as it is in the platelet, reduction of endogenous prostacyclin (PGI2) production could have been responsible. By correlating thrombin-induced adherence of platelets to endothelial monolayers with PGI2 release (as measured by radioimmunoassay for 6-keto-prostaglandin FI1 alpha [6-keto-PGF1 alpha]), we have demonstrated an inverse relationship between platelet adherence and PGI2 levels. Untreated endothelial monolayers exposed to thrombin and platelets resulted in 4% platelet adherence and 107 nM 6-keto-PGF1 alpha. With 0.1 mM aspirin treatment, which is known to block platelet cyclooxygenase, adherence was 5% and 6-keto-PGF1 alpha decreased to 45 nM. Increasing the aspirin concentration to 1 mM resulted in 44% adherence and less than 3 nM 6-keto-PGF1 alpha. When 25 nM exogenous PGI2 was added to 1 mM aspirin-treated endothelium, adherence returned to 5%. The increase in thrombin-induced platelet adherence to 1 mM aspirin-treated monolayers was reversed 2 h after removal of the aspirin solution. 6-Keto-PGF1 alpha returned to 37% of the untreated monolayer value. Recovery from the aspirin effect did not occur when cycloheximide, an inhibitor of protein synthesis, was present during the 2-h period.

Effect of fatty acid modification on prostacyclin production by cultured human endothelial cells.

We have investigated whether changes in cellular fatty acid saturation can influence prostacyclin (PGI2) production by cultured human umbilical vein endothelial cells. As compared to control cells, those enriched with linoleic acid released 60--75% less PGI2 in response to thrombin or the calcium ionophore A23187. A similar but considerably smaller effect was observed when the cells were enriched with oleic or linolenic acid, but no reduction occurred with palmitic or linoelaidic acids. Some reduction in PGI2 release was noted as early as 1 h after exposure to linoleic acid. When the culture medium was supplemented with linoleic acid, the cell phospholipids contained four to five times more linoleate and 25--40% less arachidonate. These changes were most marked in the choline and serine plus inositol phosphoglyceride fractions. When the fatty acid composition of the cells enriched with linoleic acid was allowed to revert, there was a progressive increase in the capacity of the cells to release PGI2 in response to thrombin. The increase correlated with a reduction in linoleate content of the cell lipids, but there was no change in arachidonate content. This suggests that linoleic acid may act as an inhibitor of PGI2 production. The cultured endothelial cells were also able to produce PGI2 directly from added arachidonic acid. As the arachidonic acid concentration of the medium was raised, PGI2 formation by the linoleate-enriched cells increased relative to control cells, suggesting that the inhibition produced by linoleic acid may be competitive.

Effects of triiodothyronine-induced hypermetabolism on factor 8 and fibrinogen in man.

Triiodothyronine (liothyronine sodium) (400-500 mug/day for 14 days) was given to six normal subjects. Factor VIII (antihemophilic globulin) activity increased from 109 to 167% (P < 0.05); fibrinogen increased from 344 to 581 mg/100 ml (P < 0.01). To test whether the increases in factor VIII activity and fibrinogen were mediated by beta adrenergic receptors, propranolol (20 mg every 6 hr) was given orally to four other normal subjects in addition to triiodothyronine for 14 days. Factor VIII increased from 100 to 161%; fibrinogen increased from 374 to 564% (P < 0.01). Factor VIII activity did not change in a severe classical hemophiliac made hypermetabolic with triiodothyronine, but it increased from 39 to 82% in a patient with von Willebrand's disease. Triiodothyronine-induced hypermetabolism increased the incorporation of selenomethionine-(75)Se into plasma fibrinogen. These results suggest that the increases in clotting factor activity during triiodothyronine-induced hypermetabolism reflect an effect of increased protein synthesis rather than enhanced stimulation of beta adrenergic receptors.

Impacts of gold mine waste disposal on deepwater fish in a pristine tropical marine system.

Little is known about the impacts of mine waste disposal, including deep-sea tailings, on tropical marine environments and this study presents the first account of this impact on deepwater fish communities. The Lihir gold mine in Papua New Guinea has deposited both excavated overburden and processed tailings slurry into the coastal environment since 1997. The abundances of fish species and trace metal concentrations in their tissues were compared between sites adjacent to and away from the mine. In this study (1999-2002), 975 fish of 98 species were caught. Significantly fewer fish were caught close to the mine than in neighbouring regions; the highest numbers were in regions distant from the mine. The catch rates of nine of the 17 most abundant species were lowest, and in three species were highest, close to the mine. There appears to be limited contamination in fish tissues caused by trace metals disposed as mine waste. Although arsenic (several species) and mercury (one species) were found in concentrations above Australian food standards. However, as in the baseline (pre-mine) sampling, it appears they are accumulating these metals mostly from naturally-occurring sources rather than the mine waste.

Effects of glucocorticoids on the interaction of lymphoblastoid cells with human endothelial cells in vitro.

The adhesive characteristics of cultured acute lymphocytic leukemia cells (CCRF-CEM), lymphoma cells (Raji), and freshly isolated acute lymphocytic leukemia cells to human cultured endothelial cells were studied. An assay system was used whereby these neoplastic cells were allowed to interact with endothelial cells while being continuously agitated on a rocking platform. All cell lines adhered significantly to the endothelium monolayers. This process appeared not to be dependent upon intact microtubular or microfilament function. Likewise, removing surface sialic acid from either cell type did not alter this process. In contrast incubating the endothelial cells for 24 or 48 hr with dexamethasone decreased adhesiveness of either CCRF-CEM or Raji cells to the endothelial cells by approximately 40%. Incubating these cells with hydrocortisone instead of dexamethasone for 48 hr was equally as effective in altering the endothelial cell adhesiveness. The decreased adhesiveness could be blocked by cycloheximide, indicating that this altered adhesiveness of the endothelial cells involves protein synthesis, presumably of a surface protein. We suggest that this assay system may provide a means to evaluate other agents that can alter the surface characteristics of endothelial cells, which may have important implications in various disease states such as inflammation, thrombogenesis, and metastatic disease.

Macrophage-specific expression of human lipoprotein lipase accelerates atherosclerosis in transgenic apolipoprotein e knockout mice but not in C57BL/6 mice.

Transgenic mice with macrophage-specific expression of human (hu) lipoprotein lipase (LPL) were generated to determine the contribution of macrophage LPL to atherogenesis. Macrophage specificity was accomplished with the scavenger receptor A promoter. Complete characterization demonstrated that macrophages from these mice expressed huLPL mRNA and secreted enzymatically active huLPL protein. Expression of huLPL was macrophage specific, because total RNA isolated from heart, thymus, lung, liver, muscle, and adipose tissues was devoid of huLPL mRNA. Macrophage-specific expression of huLPL did not exacerbate lesions in aortas of C57BL/6 mice even after 32 weeks on an atherosclerotic diet. However, when expressed in apolipoprotein E knockout background, the extent of occlusion in the aortic sinus region of male huLPL+ mice increased 51% (n=9 to 11, P<0.002) compared with huLPL- mice after they had been fed a Western diet for 8 weeks. The proatherogenic effect of macrophage LPL was confirmed in serial sections of the aorta obtained after mice had been fed a Western diet for 3 weeks. By immunohistochemical analysis, huLPL protein was detected in the lesions of huLPL+ mice but not in huLPL- mice. Our results establish that macrophage LPL accelerates atherosclerosis in male apolipoprotein E knockout mice.

Epidemiology and clinical features of imported dengue fever in Europe: sentinel surveillance data from TropNetEurop.

Travelers have the potential both to acquire and to spread dengue virus infection. The incidence of dengue fever (DF) among European travelers certainly is underestimated, because few centers use standardized diagnostic procedures for febrile patients. In addition, DF is currently not reported in most European public health systems. Surveillance has commenced within the framework of a European Network on Imported Infectious Disease Surveillance (TropNetEurop) to gain information on the quantity and severity of cases of dengue imported into Europe. Descriptions of 294 patients with DF were analyzed for epidemiological information and clinical features. By far the most infections were imported from Asia, which suggests a high risk of DF for travelers to that region. Dengue hemorrhagic fever occurred in 7 patients (2.4%) all of whom recovered. Data reported by member sites of the TropNetEurop can contribute to understanding the epidemiology and clinical characteristics of imported DF.

Age as a risk factor for severe manifestations and fatal outcome of falciparum malaria in European patients: observations from TropNetEurop and SIMPID Surveillance Data.

Previous studies have indicated that age is a risk factor for severe falciparum malaria in nonimmune patients. The objectives of this study were to reevaluate previous findings with a larger sample and to find out how strongly clinical outcomes for elderly patients differ from those for younger patients. Results of adjusted analyses indicated that the risks of death due to falciparum malaria, of experiencing cerebral or severe disease in general, and of hospitalization increased significantly with each decade of life. The case-fatality rate was almost 6 times greater among elderly patients than among younger patients, and cerebral complications occurred 3 times more often among elderly patients. Antimalarial chemoprophylaxis was significantly associated with a lower case-fatality rate and a lower frequency of cerebral complications. Women were more susceptible to cerebral complications than were men. Our study provides evidence that falciparum malaria is more serious in older patients and demonstrates that clinical surveillance networks are capable of providing quality data for investigation of rare events or diseases.

Imported Falciparum malaria in Europe: sentinel surveillance data from the European network on surveillance of imported infectious diseases.

Malaria continues to have a high morbidity rate associated among European travelers. Thorough recording of epidemiological and clinical aspects of imported malaria has been helpful in the detection of new outbreaks and areas of developing drug resistance. Sentinel surveillance of data collected prospectively since 1999 has begun within TropNetEurop, a European network focusing on imported infectious diseases. TropNetEurop appears to cover approximately 10% of all patients with malaria seen in Europe. Reports of 1659 immigrants and European patients with Plasmodium falciparum malaria were analyzed for epidemiological information and data on clinical features. Regional data were quite diverse, reflecting local patterns of immigration and international travel. By far, the most infections were imported from West Africa. Europeans had more clinical complications; consequently, all deaths occurred in this group. Compared with European standards, the mortality rate was low (0.6% in Europeans). Data from TropNetEurop member sites can contribute to our understanding of the epidemiological and clinical findings regarding imported falciparum malaria.

A new approach to template purification for sequencing applications using paramagnetic particles.

A new method using traditional hybridization methodology, coupled with the new magnetic particle technology, has been developed for DNA purification, specifically for sequencing applications. The method is similar to the reverse hybridization blot system; however, a specific oligonucleotide probe was attached to the paramagnetic particle instead of a sheet membrane. The target DNA containing the complementary sequence of the probe hybridizes to the probe that is attached to the bead and is then magnetically removed from solution, washed and collected. This system eliminates the need of organic extractions and precipitation/concentration steps. The entire hybridization-purification system can be done in a 1.5-ml microcentrifuge tube making the method ideal for automation. M13 phage clones were purified with this method, both by manual means and by using the CATALYST 800 Molecular Biology LabStation fitted with a prototype magnetic station, and then sequenced. DNA sequencing results obtained with this system were reproducible and gave excellent length of read with low background.

Kinetics of HIV infection of human placental syncytiotrophoblast cultures: an ultrastructural and immunocytochemical study.

We previously demonstrated that syncytiotrophoblast (ST) cells from term human placentas could be infected when cocultured with HIV-infected lymphocytic cells. Here, we have used fluorescence microscopy and transmission electron microscopy to examine the kinetics of this infection process. Molt-4 clone 8 cells infected with HIV-1Lai or filtered supernatant from these cultures were incubated with ST cells for different times. In cell-associated infection, immunofluorescence microscopy revealed that some ST colonies were positive for HIV core proteins (p24,p55) after 1 hr. The number of positive colonies and the intensity of the ST-associated fluorescence increased with time. Transmission electron microscopy showed viral particles with HIV morphology associated with the ST cell surface at 1 hr. Immature virions with budding morphology were observed at 2 hr. In cell-free infection, positive p24,p55 staining was first detected in a few ST colonies at 4 hr. The number of positive colonies increased with time. At 24 hr, the fluorescence pattern and intensity resembled that seen with cell-mediated infection at 4 hr. Transmission electron microscopy revealed an increasing number of viral particles associated with the ST cell plasma membrane with respect to time, and budding virions first appeared at 8 hr. These results demonstrate that HIV infection of placental ST cells proceeds very rapidly in culture and that, furthermore, cell-associated infection of ST is much more efficient than the infection with cell-free virus.

Cell-mediated infection of human placental trophoblast with HIV in vitro.

In order to investigate how human immunodeficiency virus (HIV) gains entry to the placenta, we have performed in vitro experiments in which highly purified trophoblast cells isolated from term human placentas were examined for their susceptibility to HIV infection. Trophoblast cells were exposed to cell-free HIV-1 for up to 24 h, after which the cultures were monitored by p24 antigen capture assay, reverse transcriptase assay, and electron microscopy for evidence of virus uptake and replication. None was found. In the second series of experiments, trophoblast cells were cocultured with HIV-infected MOLT-4 cells for 24 h, stained using an anti-HIV antibody, and examined by immunofluorescence microscopy. The MOLT cells were strongly positive, as expected, but many trophoblast colonies also showed a punctate staining pattern. Examination of similar cultures using the electron microscope revealed MOLT cells adherent to trophoblast but no evidence of cell-cell fusion. Virions were observed in coated pits at the trophoblast cell surface and in endosomes or multivesicular bodies in the cytoplasm. These observations are consistent with an endocytosis-mediated mechanism of virus entry. Virions were also observed budding from the trophoblast plasma membrane, indicating that these cells can support HIV replication. To our knowledge, these results show for the first time that HIV can infect placental trophoblast cells in vitro. The results suggest that the placenta could become infected with HIV by the interaction of virus-infected maternal lymphocytes with syncytiotrophoblast bordering the maternal blood in the intervillous space.