Potentially modifiable determinants of malnutrition in older adults: A systematic review.

BACKGROUND & AIMS: Malnutrition in older adults results in significant personal, social, and economic burden. To combat this complex, multifactorial issue, evidence-based knowledge is needed on the modifiable determinants of malnutrition. Systematic reviews of prospective studies are lacking in this area; therefore, the aim of this systematic review was to investigate the modifiable determinants of malnutrition in older adults. METHODS: A systematic approach was taken to conduct this review. Eight databases were searched. Prospective cohort studies with participants of a mean age of 65 years or over were included. Studies were required to measure at least one determinant at baseline and malnutrition as outcome at follow-up. Study quality was assessed using a modified version of the Quality in Prognosis Studies (QUIPS) tool. Pooling of data in a meta-analysis was not possible therefore the findings of each study were synthesized narratively. A descriptive synthesis of studies was used to present results due the heterogeneity of population source and setting, definitions of determinants and outcomes. Consistency of findings was assessed using the schema: strong evidence, moderate evidence, low evidence, and conflicting evidence. RESULTS: Twenty-three studies were included in the final review. Thirty potentially modifiable determinants across seven domains (oral, psychosocial, medication and care, health, physical function, lifestyle, eating) were included. The majority of studies had a high risk of bias and were of a low quality. There is moderate evidence that hospitalisation, eating dependency, poor self-perceived health, poor physical function and poor appetite are determinants of malnutrition. Moderate evidence suggests that chewing difficulties, mouth pain, gum issues co-morbidity, visual and hearing impairments, smoking status, alcohol consumption and physical activity levels, complaints about taste of food and specific nutrient intake are not determinants of malnutrition. There is low evidence that loss of interest in life, access to meals and wheels, and modified texture diets are determinants of malnutrition. Furthermore, there is low evidence that psychological distress, anxiety, loneliness, access to transport and wellbeing, hunger and thirst are not determinants of malnutrition. There appears to be conflicting evidence that dental status, swallowing, cognitive function, depression, residential status, medication intake and/or polypharmacy, constipation, periodontal disease are determinants of malnutrition. CONCLUSION: There are multiple potentially modifiable determinants of malnutrition however strong robust evidence is lacking for the majority of determinants. Better prospective cohort studies are required. With an increasingly ageing population, targeting modifiable factors will be crucial to the effective treatment and prevention of malnutrition.

Informed consent in refractive eye surgery: learning from patients and the courts.

Refractive eye laser surgery involves ablation of the cornea using excimer laser to correct short or long sightedness and thus negate the need for glasses and/or contact lenses. With the doctrine of informed consent often central to claims of medical negligence in this area, we examine the attitudes, understanding and recall of patients to consent for refractive surgery and outline the relevant law. 102 patients undergoing first time refractive surgery were analysed to examine their understanding and recall of the consenting process. Only 2 patients remembered all 5 risks outlined preoperatively, while 11 remembered no risks at all. 65% of patients consulted the internet to learn more about the operation. Our study demonstrates that patient understanding and recall remains poor. A signed consent form is not, of itself a full defence to allegations of uninformed consent, and the consent process must be comprehensive.

Tag rugby: a safe alternative? A review of hand injuries sustained playing tag rugby (2007 season).

INTRODUCTION: Tag rugby is a non-contact, seven-a-side, team sport in which each player wears specially designed shorts with velcro 'tags' attached to them. While tag rugby is a relatively new sport it has grown rapidly in popularity. As a result of its increasing popularity an increased frequency of attendances at plastic surgery clinics was observed and it was decided a review of all hand injuries associated with this new sport was required. MATERIALS AND METHODS: A retrospective case note review of all hand injuries occurring during the tag rugby season for 2007 (March-August) was conducted, with any tag rugby-related hand injuries being selected for further examination. RESULTS: Tag rugby, while being a non-contact sport, is certainly not without a definite injury risk with 12 patients having single digit injuries, ranging from tendon avulsions to phalangeal fractures. The mean age of the injured patients was 26.8 years. DISCUSSION: All of the hand injuries were sustained while 'tackling' during regular play, the hand injuries sustained were all treated using well-described methods and all the patients are recovering well. While the risk of a severe, life-threatening injury is unlikely while playing tag rugby, there is a real risk of sustaining a potentially debilitating hand injury.

Five year follow up of laser in situ keratomileusis for all levels of myopia.

AIMS: To assess the long term refractive and visual outcome of patients who have laser in situ keratomileusis (LASIK) surgery. METHODS: This was a retrospective study of visual and refractive outcome of patients who had LASIK surgery performed in 1998 and 1999. All levels of myopia were included in the study. 49 patients attended for follow up. The main outcome measures were safety, predictability, efficacy, and stability. Postoperative complications and aberrations were also recorded. The mean preoperative spherical equivalent was -4.85. RESULTS: At 2 months postoperatively 67% of eyes were within plus or minus 0.5D of attempted correction with 81% within plus or minus 1.0D. At 5 years postoperatively 60% of eyes were within plus or minus 0.5D of attempted correction with 83% within plus or minus 1.0D. 88% of eyes had a vision of 6/12 or better at 2 months compared to 89% of eyes at 5 years. Best spectacle corrected visual acuity (BSCVA) was unchanged or improved in 51%. No eye lost more than one line of BSCVA. Overall, there was regression towards myopia with a mean change in refraction of -0.5D over the 5 years. As expected, severely myopic patients regressed more with a mean change of -1.06D. However, there was a high level of patient satisfaction with the surgery. CONCLUSION: LASIK surgery offers predictable results in terms of refractive and visual outcome with mild regression in refraction over time.

Cystoid macular oedema in paediatric aphakia and pseudophakia.

AIM: To assess the incidence of cystoid macular oedema (CMO), following lensectomy, anterior vitrectomy (limbal and pars plicata), and primary posterior capsulorhexis following surgery for congenital and developmental cataract. METHODS: A prospective study was carried out involving 30 eyes (20 children) with cataract. Lensectomy, primary posterior capsulorhexis, and anterior vitrectomy were performed on all eyes. Vitrectomy was performed using either a limbal or pars plicata approach. Fluorescein angiography was carried out 4-7 weeks after surgery. Fluorescein was administered intravenously and visualised using the Retcam. RESULTS: Anterior vitrectomy was carried out via the limbal approach in 12 eyes and, of these, six were implanted with an intraocular lens. The pars plicata approach was carried out in 18 eyes and 10 received an implant. CMO was not detected in any eye. CONCLUSION: CMO was not detected in the early postoperative period irrespective of approach to anterior vitrectomy or presence of an intraocular lens. Intravenous fluorescein angiography was performed without complication.

Non-anaemic iron deficiency identified by ZPP test in extremely premature infants: prevalence, dietary risk factors, and association with neurodevelopmental problems.

INTRODUCTION: The aims of this study were to determine, in a cohort of extremely premature infants, the prevalence of iron deficiency identified by zinc protoporphyrin/heme ratio (ZPP) testing, and its association with neurodevelopmental problems and dietary risk factors for iron deficiency. METHODS: Infants of less than 29 weeks' gestation or less than 1000 g birth weight were studied prospectively at a multidisciplinary follow-up clinic. Assessments were made at a corrected age of either 12 months (n=72) or 2 years (n=69). Physical examination, Griffiths Developmental Scale, and neurosensory-motor assessment were administered, information on diet and behaviour was obtained by questionnaire, and a fingerprick ZPP ratio was performed to identify iron deficiency. RESULTS: 18.4% of infants had positive ZPP tests. There was no significant association between a positive ZPP test result and dietary risk factors, or symptoms of lethargy, irritability or poor attention. In children without cerebral palsy, there was no difference on Griffiths scores or neurosensory-motor assessment between ZPP-positive and ZPP-negative groups. The diagnosis of cerebral palsy (n=12) was significantly associated with both a positive ZPP test and a lower Griffiths general quotient (GQ) score. CONCLUSIONS: Iron deficiency occurs commonly in extremely low birth weight (ELBW) children in early childhood, and is not predicted by dietary risk factors. The prevalence of iron deficiency is increased in ELBW children with cerebral palsy. Non-anaemic iron deficiency (NAID) does not impair development or significantly affect behaviour of ELBW subjects who do not have cerebral palsy.

Tumour cell radiosensitization using constitutive (CMV) and radiation inducible (WAF1) promoters to drive the iNOS gene: a novel suicide gene therapy.

Nitric oxide (NO(*)) has many characteristics including cytotoxicity, radiosensitization and anti-angiogenesis, which make it an attractive molecule for use in cancer therapy. We have investigated the use of iNOS gene transfer, driven by both a constitutive (CMV) and X-ray inducible (WAF1) promoter, for generating high concentrations of NO(*) within tumour cells. We have combined this treatment with radiation to exploit the radiosensitizing properties of this molecule. Transfection of murine RIF-1 tumour cells in vitro with the iNOS constructs resulted in increased iNOS protein levels. Under hypoxic conditions cells were radiosensitized by delivery of both constructs so that these treatments effectively eliminated the radioresistance observed under hypoxic conditions. In vivo transfer of the CMV/iNOS construct by direct tumour injection resulted in a delay (4.2 days) in tumour growth compared with untreated controls. This was equivalent to the effect of 20 Gy X-rays alone. Combination of CMV/iNOS gene transfer with 20 Gy X-rays resulted in a dramatic 19.8 day growth delay compared with controls. Tumours treated with the CMV/iNOS showed large areas of necrosis and abundant apoptosis. We believe that iNOS gene transfer has the potential to be a highly effective treatment in combination with radiotherapy.

Development of thymic and splenic dendritic cell populations from different hemopoietic precursors.

The antigen-presenting dendritic cells (DCs) found in mouse lymphoid tissues are heterogeneous. Several types of DCs have been identified on the basis of the expression of different surface molecules, including CD4, CD8alpha, and DEC-205. Previous studies by the authors showed that the mouse intrathymic lymphoid-restricted precursors (lin(-)c-kit(+)Thy-1(low)CD4(low)) can produce DCs in the thymus and spleen upon intravenous transfer, suggesting a lymphoid origin of these DCs. In the current study, the potential for DC production by the newly identified bone marrow (BM) common lymphoid precursors (CLPs), common myeloid precursors (CMPs), and committed granulocyte and macrophage precursors was examined. It was found that both the lymphoid and the myeloid precursors had the potential to produce DCs. All the different DC populations identified in mouse thymus and spleen could be produced by all these precursor populations. However, CLPs produced predominantly the CD4(-)CD8alpha(+) DCs, whereas CMPs produced similar numbers of CD4(-)CD8alpha(+) and CD4(+)CD8alpha(-) DCs, although at different peak times. On a per cell basis, the CLPs were more potent than the CMPs at DC production, but this may have been compensated for by an excess of CMPs over CLPs in BM. Overall, this study shows that the expression of CD8alpha does not delineate the hemopoietic precursor origin of DCs, and the nature of the early precursors may bias but does not dictate the phenotype of the DC product.

c-Rel regulates interleukin 12 p70 expression in CD8(+) dendritic cells by specifically inducing p35 gene transcription.

Interleukin 12 (IL-12) is a 70-kD proinflammatory cytokine produced by antigen presenting cells that is essential for the induction of T helper type 1 development. It comprises 35-kD (p35) and 40-kD (p40) polypeptides encoded by separate genes that are induced by a range of stimuli that include lipopolysaccharide (LPS), DNA, and CD40 ligand. To date, the regulation of IL-12 expression at the transcriptional level has mainly been examined in macrophages and restricted almost exclusively to the p40 gene. Here we show that in CD8(+) dendritic cells, major producers of IL-12 p70, the Rel/nuclear factor (NF)-kappaB signaling pathway is necessary for the induction of IL-12 in response to microbial stimuli. In contrast to macrophages which require c-Rel for p40 transcription, in CD8(+) dendritic cells, the induced expression of p35 rather than p40 by inactivated Staphylococcus aureus, DNA, or LPS is c-Rel dependent and regulated directly by c-Rel complexes binding to the p35 promoter. This data establishes the IL-12 p35 gene as a new target of c-Rel and shows that the regulation of IL-12 p70 expression at the transcriptional level by Rel/NF-kappaB is controlled through both the p35 and p40 genes in a cell type-specific fashion.

Molecular cloning of F4/80-like-receptor, a seven-span membrane protein expressed differentially by dendritic cell and monocyte-macrophage subpopulations.

A novel dendritic cell (DC) surface molecule termed F4/80-like-receptor (FIRE) has been selected based on its differential expression between DC subsets. The gene encoding FIRE has been cloned and sequenced, and mAbs specific for FIRE have been produced. FIRE is a seven-transmembrane-spanning molecule with two epidermal growth factor-like domains in the extracellular region. It is a novel member of the epidermal growth factor/transmembrane-7 protein subfamily and shows similarity to the macrophage marker F4/80. FIRE is expressed by CD8- DC, but not by CD8+ DC, and it is down-regulated on DC activation. It is expressed by blood monocytes and by some tissue macrophages, but not by most macrophage cell lines or by lymphoid cells. FIRE is a useful marker of myeloid cells with a DC developmental potential.

The development, maturation, and turnover rate of mouse spleen dendritic cell populations.

Three distinct subtypes of dendritic cells (DC) are present in mouse spleen, separable as CD4(-)8alpha(-), CD4(+)8alpha(-), and CD4(-)8alpha(+) DC. We have tested whether these represent stages of development or activation within one DC lineage, or whether they represent separate DC lineages. All three DC subtypes appear relatively mature by many criteria, but all retain a capacity to phagocytose particulate material in vivo. Although further maturation or activation could be induced by bacterially derived stimuli, phagocytic capacity was retained, and no DC subtype was converted to the other. Continuous elimination of CD4(+)8(-) DC by Ab depletion had no effect on the levels of the other DC subtypes. Bromodeoxyuridine labeling experiments indicated that all three DC subtypes have a rapid turnover (half-life, 1.5-2.9 days) in the spleen, with none being the precursor of another. The three DC subtypes showed different kinetics of development from bone marrow precursors. The CD8alpha(+) spleen DC, apparently the most mature, displayed an extremely rapid turnover based on bromodeoxyuridine uptake and the fastest generation from bone marrow precursors. In conclusion, the three splenic DC subtypes behave as rapidly turning over products of three independent developmental streams.

Interleukin (IL)-4 is a major regulatory cytokine governing bioactive IL-12 production by mouse and human dendritic cells.

Interleukin (IL)-12 may be secreted as a bioactive T helper type 1 (Th1) cell-inducing heterodimer, as a monomer, or as an antagonistic homodimer. We analyzed the IL-12 produced by mouse splenic dendritic cells (DCs), human thymic DCs, and cultured human monocyte-derived DCs. IL-12 production required both a microbial or T cell-derived stimulus and an appropriate cytokine milieu. The different IL-12 forms were differentially regulated by the cytokines present rather than the stimulus used. IL-4 alone or together with granulocyte/macrophage colony-stimulating factor or interferon gamma effectively enhanced the production of the bioactive heterodimer and selectively reduced the antagonistic homodimer of IL-12. Therefore, IL-4, the major Th2-driving cytokine, provides a negative feedback causing DCs to produce the major Th1-inducing cytokine, bioactive IL-12.

Effect of granulocyte-macrophage colony-stimulating factor on the generation of epidermal Langerhans cells.

The role of granulocyte-macrophage colony-stimulating factor (GM-CSF) and Flt3 ligand in the in vivo development of Langerhans cells (LC) was assessed, considering both the steady-state levels of LC in the epidermis and the rate of LC recovery after depletion following lipopolysaccharide (LPS) treatment. The density of LC was determined by counting following IA-specific immunofluorescent staining of epidermal sections from mouse ears. LC levels were compared in beta common chain receptor null (beta c(-/-)) mice that fail to respond to GM-CSF interleukin-5 (IL-5), in GM-CSF transgenic mice with elevated GM-CSF levels, and in mice given daily injections of Flt3 ligand. In the steady state, LC levels were increased in GM-CSF transgenic mice and present at reduced levels in beta c(-/-) mice but unchanged in Flt3 ligand-injected mice. Application of LPS to the ears of control BL/6 mice led to an approximately 70% reduction in LC 4 days later, with recovery beginning by day 8 and a return to normal levels by 2 weeks. This recovery was significantly delayed in beta c(-/-) mice and unchanged in Flt3 ligand-injected mice. These results suggest that GM-CSF (but not Flt3 ligand) enhances recruitment/maturation of LC even though GM-CSF is not essential for their formation.

Sheep CD4(+) alphabeta T cells express novel members of the T19 multigene family.

The sheep T19 multigene family contains at least 50 genes which are thought to be expressed exclusively on gammadelta T cells. The archetypal T19 molecule (represented by a full-length cattle cDNA clone termed WC1) is thought to have a relative molecular mass of about 220 000 and to contain 11 scavenger receptor cysteine rich (SRCR) repeats and a long cytoplasmic tail. In this study, purified CD4(+) and gammadeltaTCR+ sheep lymphocytes were examined by reverse transcriptase-polymerase chain reaction for the expression of T19 molecules. As expected, gammadelta T cells were found to express T19 molecules which closely resembled the archetypal form. However, CD4(+) alphabeta T cells were found to express at least two different types of T19 molecules; one resembled the previously described T19 molecules of gammadelta T cells which possessed the archetypal WC1-like structure, but a novel type of T19 variant which lacked SRCR domains 10 and 11 was also found in CD4(+) T cells but not gammadelta T cells. This novel molecule exhibited an unusual, incomplete SRCR repeat 9 joined directly to a hinge region. The transmembrane and cytoplasmic domains of this unusual T19 variant resembled the cattle T19 clone WC1, except that a complete exon within the cytoplasmic region was missing. These results, in contradistinction to existing serological data, suggest that expression of the T19 gene family is not confined to gammadelta T cells. Selected T19 genes are apparently expressed within CD4(+) T cells and possibly other lymphocytes as well.

Studies on the determination of chlorotestosterone and its metabolites in bovine urine.

Chlorotestosterone and its metabolites were determined in urine samples from bovine animals treated with chlorotestosterone acetate by oral and intramuscular routes. Sample preparation, involving enzymatic deconjugation and solid-phase extraction, was optimised. The effect of different enzyme preparations, pH, and time of incubation were studied. An extraction/clean-up procedure based on solid-phase extraction (C18 cartridge) and liquid-liquid clean-up was developed. Determination of chlorotestosterone and its metabolites was by enzyme immunoassay and GC-MS. Metabolites were converted into their TMS-enol-TMS-ether and TMS-oxime-TMS-ether forms before GC-MS (EI) analysis.

A novel multi-gene family of sheep gamma delta T cells.

The WC1 protein is a cell surface constituent of bovine gamma delta T cells and is absent from most or all CD4+, CD8+ T cells and from B cells. It is a single polypeptide chain of 1413 amino acids consisting of 11 non-identical repeats of a 110 amino acid consensus sequence, homologous to the macrophage scavenger receptor cysteine rich (SRCR) domain. A 1059 nucleotide segment of the bovine WC1 cDNA sequence was used as a probe to molecularly clone homologous DNA segments from a sheep genomic library in which the presence of numerous positive plaques was documented. The high representation of such recombinants (1-2/1000 clones) within the library suggested the existence of multiple genes for WC1 (called T19 in sheep) and supported Southern blotting data which revealed an unexpectedly high number of WC1/T19 restriction fragments in sheep genomic DNA. Restriction digests of 27 samples of T19 genomic recombinants were examined by electrophoresis and Southern blotting. All but two pairs of recombinants exhibited non-overlapping restriction digest patterns. Four recombinant DNA samples were partially sequenced and in all cases putative exons were identified and exhibited high homology to appropriate segments of the WC1 cDNA at the levels of both nucleotide and amino acid sequence. Furthermore, multiple nucleotide and amino acid differences occurred between all sequences compared, establishing the existence of a repertoire of non-identical T19 genes, each with the potential to encode a different protein.

Congenital absence of extraocular muscles: MR demonstration.

We describe a case of an infant with complete congenital absence of the extraocular muscles, noted at surgery and confirmed by multiplane MR, which found no evidence of extraocular muscle tissue. This almost certainly represents an extreme form of bilateral congenital fibrosis syndrome.

A controlled study of the ocular effects of tamoxifen in conventional dosage in the treatment of breast carcinoma.

The use of tamoxifen is expanding in its application in the treatment of breast carcinoma, and proposed prophylactic use. Tamoxifen in high dosage and in some reports at conventional dosage is associated with ocular toxicity. This study in a single blind fashion examined 79 patients receiving tamoxifen for varying treatment durations at conventional dosage and 115 patients not receiving tamoxifen. No ocular toxicity was found. Further follow up studies are required to ensure no toxicity develops in patients receiving high cumulative dosage on conventional therapy.

Nicotine gum: dose-related effects on cigarette smoking and subjective ratings.

The effects of nicotine-containing chewing gum on cigarette smoking and subjective and physiological response were evaluated in eight normal volunteers. Isolated subjects smoked their regular brand of cigarettes freely in a naturalistic laboratory environment while watching television or reading. Before 90-min smoking sessions subjects chewed two pieces of placebo or nicotine-containing gum (0, 2, 4, or 8 mg) under double-blind conditions. Each subject received each treatment four times in a mixed order across days. Analysis of the chewed gum for remaining nicotine revealed that the mean delivered nicotine doses were 0, 1.02, 2.39, and 5.20 mg nicotine. Nicotine preloading produced dose-related increases in plasma nicotine, while producing dose-related decreases in various measures of cigarette smoking including number of cigarettes smoked, number of puffs taken, expired air carbon monoxide level, and ratings of smoking satisfaction. Nicotine preloading produced dose-related increases in ratings of gum dose-strength, while producing decreases in ratings of gum dose acceptability and liking. Heart rate and blood pressure were not significantly affected by nicotine gum. Taken together, the present results confirm that responses to nicotine in the gum preparation are orderly and related to dose, and the results suggest that the efficacy of treating tobacco dependence with nicotine gum may be enhanced by increasing the administered dose.

Effects of marijuana smoking on subjective ratings and tobacco smoking.

Multiple measures of tobacco cigarette smoking and subjective and physiological effect were collected during 90 minute test sessions in volunteer cigarette smokers who also had histories of recreational marijuana use. Before sessions, subjects smoked one marijuana cigarette (placebo or 1.29%, 2.84%, 4.00%) using a standardized puffing procedure. Each dose and placebo was given four times to each subject in a randomized block sequence. Marijuana smoking produced dose-related increases in heart rate, ratings of dose strength and drug liking. However, marijuana produced no significant alterations in tobacco cigarette smoking. Puff duration within each marijuana cigarette varied in a fashion similar to that observed in previous studies of tobacco cigarette smoking: puff duration progressively decreased as the cigarette was smoked. This effect is probably due to progressive decreases in resistance to draw as the cigarette is smoked. Expired air carbon monoxide (CO) levels following marijuana smoking were inversely related to marijuana dose, suggesting the occurrence of some compensatory changes in marijuana smoking in response to dose manipulations. It is concluded that, although marijuana produces dose-related effects on physiological and subjective effects and on marijuana smoking behavior, marijuana differs from a variety of other psychoactive drugs previously studied in this paradigm in that no reliable changes in tobacco smoking were produced.