Malnutrition in Hospitalised Older Adults: A Multicentre Observational Study of Prevalence, Associations and Outcomes.

BACKGROUND: Malnutrition is common in older adults and is associated with high costs and adverse outcomes. The prevalence, predictors and outcomes of malnutrition on admission to hospital are not clear for this population. DESIGN: Prospective Cohort Study. SETTING: Six hospital sites (five public, one private). PARTICIPANTS: In total, 606 older adults aged 70+ were included. All elective and acute admissions to any speciality were eligible. Day-case admissions and those moribund on admission were excluded. MEASUREMENTS: Socio-demographic and clinical data, including nutritional status (Mini-Nutritional Assessment - short form), was collected within 36 hours of admission. Outcome data was collected prospectively on length of stay, in-hospital mortality and new institutionalisation. RESULTS: The mean age was 79.7; 51% were female; 29% were elective admissions; 67% were admitted to a medical specialty. Nutrition scores were available for 602/606; 37% had a 'normal' status, 45% were 'at-risk', and 18% were 'malnourished'. Malnutrition was more common in females, acute admissions, older patients and those who were widowed/ separated. Dementia, functional dependency, comorbidity and frailty independently predicted a) malnutrition and b) being at-risk of malnutrition, compared to normal status (p < .001). Malnutrition was associated with outcomes including an increased length of stay (p < .001), new institutionalisation (p =<0.001) and in-hospital mortality (p < .001). CONCLUSIONS: These findings support the prioritisation of nutritional screening in clinical practice and public health policy, for all patients ≥70 on admission to hospital, and in particular for people with dementia, increased functional dependency and/or multi-morbidity, and those who are frail.

Serum cytokine levels in infectious mononucleosis at diagnosis and convalescence.

Infection with the Epstein-Barr virus (EBV) is common worldwide. A significant number of infected individuals develop infectious mononucleosis (IM). IM is manifested in most patients as a benign disease with mild symptoms. However, serious complications may develop in a subset of patients. Because EBV-infected B lymphocytes produce various cytokines that may provide the cells with a proliferative advantage, cytokine concentrations in serum samples taken from IM patients were measured in order to identify the cytokines responsible for the clinical manifestations of the disease. The concentrations of interleukin-1beta (IL-1beta), IL-2, IL-6, IL-8, IL-10, tumor necrosis factor-alpha (TNF-alpha), and lymphotoxin (LT) were measured using an enzyme-linked immunosorbent assay (ELISA) in serum obtained from 14 IM patients during the acute phase of the disease and during convalescence, 5 patients with identical clinical manifestations who did not have IM (sick controls), and 11 healthy volunteers. It was found that the serum levels of TNF-alpha and IL-6 were significantly high in patients with acute IM compared with the serum levels in healthy individuals (P = 0.008 and P < 0.001, respectively) but returned to normal at convalescence (P = 0.009 and P = 0.005 respectively). However, whereas TNF-alpha concentrations were significantly higher (P = 0.04) in patients with acute IM than in the sick controls, no significant difference in IL-6 concentrations was found between the two groups of patients. Changes in IL-10 concentration were not statistically significant, and IL-1beta, IL-2, IL-8, and LT were detected only sporadically. The data in this study suggest that TNF-alpha may have a specific role in causing the clinical manifestations of IM. Further studies should determine the clinical significance of TNF-alpha inhibition in IM.

Oxygen dose-response curve of cardiac papillary muscle from fetal and nonpregnant adult sheep exposed to long-term, high-altitude hypoxemia.

OBJECTIVE: We tested the hypothesis that hearts of fetal and nonpregnant adult sheep exposed to long-term hypoxemia would be able to sustain higher contractile function during exposure to acute hypoxia than hearts from normoxic animals. METHODS: Pregnant and nonpregnant sheep were exposed to high altitude (3820 m) for 100 days. Right and left ventricular papillary muscle strips were obtained from fetuses and nonpregnant adults, mounted in an isolated bath system, stimulated electrically and subjected to acute hypoxia in a dose response manner. Measurements were made of maximum tension production (Tmax), maximum rate of tension development (+dT/dtmax), maximum rate of relaxation (-dT/dtmax), time to peak tension, and duration of contraction. Results were compared to papillary muscle from a normoxic group of animals. RESULTS: Baseline values (95% O2 + 5% CO2 bubbled in the bath) of Tmax and +/- dt/dtmax for each ventricle were greater in adults than fetuses in both normoxic and long-term hypoxemic groups. During hypoxia (at 40 and 20% O2) Tmax and +/- dT/dtmax, were all maintained at significantly higher values in papillary muscle from long-term hypoxemic fetuses than in papillary muscle from normoxic fetuses. Duration of contraction and time to peak tension did not differ between the normoxic and hypoxemic groups. In both ventricles of the long-term hypoxemic adult, Tmax and +/- dT/dtmax, as well as duration and time to peak tension, were significantly higher than in normoxic adults, but only at the lowest level of hypoxia (20% O2). CONCLUSIONS: Contrary to the original hypothesis, heart muscle from both fetal and adult sheep that had been exposed to long-term hypoxemia could maintain contractile function better during acute hypoxia. The responsible mechanisms are not clearly understood.

Physiology and pathophysiology of dendritic cells.

Dendritic cells are antigen-presenting cells derived from the hematopoietic stem cell. The dendritic cell family includes Langerhans' cells (CD1a-positive dendritic cells of the skin), and antigen-presenting cells that are found in the lymphoreticular system and throughout the organ parenchyme. Dendritic cells play a key role in both the primary and secondary immune responses. Several studies indicate that these cells participate in antitumor immunity, tumor surveillance, graft-versus-host disease, and in the pathogenesis of clinical syndromes of unknown origin or those induced by viruses, such as the human immunodeficiency virus. Different disorders are characterized by an abnormal proliferation and accumulation of dendritic cells; for example, the Langerhans' histiocytes, which accumulate in Langerhans' cell histiocytosis. In this review the immunophenotypic, morphological, and functional characteristics of the dendritic cell family is described. The clinical and laboratory studies suggesting a unique role for these cells in various syndromes and diseases are reviewed. The Langerhans' cell histiocytoses and the malignant disorders associated with transformation of cells belonging to the dendritic cell family, are discussed.

Phase I pharmacokinetic study of multicycle high-dose carboplatin followed by peripheral-blood stem-cell infusion in patients with cancer.

PURPOSE: To examine the feasibility of escalating carboplatin area under the concentration-time curve (AUC), using dose predictions based on individual estimates of drug clearance, in a phase I trial of multicycle carboplatin, paclitaxel, and cyclophosphamide chemotherapy with peripheral-blood stem-cell (PBSC) replacement. PATIENTS AND METHODS: Forty-four patients (37 breast, seven ovarian) received 165 courses. Initial target carboplatin AUC was 10 mg/ml x min, with interpatient escalation in increments of 25%. Initial carboplatin dose estimates used creatinine clearance (CrCl) to estimate carboplatin clearance. Subsequent clearance and dose estimates were determined using a model incorporating Bayesian estimation and two measured carboplatin plasma ultrafiltrate concentrations. RESULTS: Median clearance was 80.5 mL/min/m2 (range, 41.6 to 131.8). Carboplatin doses up to 2,440 mg/m2 per course were administered without major extramedullary toxicity. Doses varied 2.6-fold at each exposure level. Using the Bayesian model, AUC was predicted with a mean accuracy of 101.2% (83% using CrCl). Ninety-six of 117 courses were within 25% of the target AUC. This model was less biased (0.15 v -2.35 mg/mL x min) and more precise (2.76 v 3.52) in predicting AUC compared with one using CrCl. Hematologic recovery was not prolonged with increasing exposure. The carboplatin maximum-tolerated systemic exposure (MTSE) was 13.3 mg/mL x min (level five). The dose-limiting toxicity was cardiac toxicity, which occurred at dose levels six and seven. CONCLUSION: Results demonstrate that (1) CrCl is a poor estimator of carboplatin clearance in this population, and (2) the use of a model incorporating limited sampling and Bayesian estimation improves the precision of carboplatin clearance estimation and is suitable for targeting carboplatin exposure in an ambulatory setting.

Activator calcium and myocardial contractility in fetal sheep exposed to long-term high-altitude hypoxia.

We studied myocardial contractility in fetal sheep from ewes exposed to approximately 112 days of hypoxia at high altitude (3,820 m). We measured the inotropic response to extracellular Ca2+ concentration ([Ca2+]o, 0.2-10 mM) and ryanodine (10(-10) to 10(-4) M) in isometrically contracting papillary muscles and quantified dihydropyridine (DHPR) and ryanodine (RyR) receptors. In hypoxic fetuses, curves describing the force-[Ca2+]o relationship were shifted left, and the top plateaus were decreased by approximately 35% in both left and right ventricles. In normoxic and hypoxic fetuses, ryanodine (10(-4) M) reduced maximum active tension (Tmax) to approximately 25-40% of baseline values, indicating that the sarcoplasmic reticulum was the chief source of activator Ca2+ and that Ca2+ influx alone was not sufficient to activate a contraction of normal amplitude. Hypoxia resulted in a lower Tmax in the right ventricle and a lower maximum rate of rise in the left ventricle after treatment with ryanodine. DHPR number did not change, but RyR number and the RyR/DHPR in both ventricles were higher in hypoxic fetuses. We conclude that hypoxia decreases contractility, possibly by reducing the availability of activator Ca2+. Further studies are needed to directly measure the Ca2+ current and intracellular Ca2+ transient and to examine myofilament protein and adenosinetriphosphatase activity.

Cardiac beta-adrenergic receptor function in fetal sheep exposed to long-term high-altitude hypoxemia.

In this study, we hypothesized that a reduction in beta-adrenergic receptor number or a decrease in functional coupling of the receptor to the adenylate cyclase system may be responsible for the blunted inotropic response to isoproterenol observed in fetal sheep exposed to high altitude (3,820 m) from 30 to 138-142 days gestation. We measured the contractile response to increasing doses of isoproterenol and forskolin in papillary muscles from both ventricles, estimated beta-adrenergic receptor density (Bmax) and ligand affinity (Kd) using [125I]iodocyanopindolol, and measured adenosine 3',5'-cyclic monophosphate (cAMP) levels before and after maximally stimulating doses of isoproterenol and forskolin. Left ventricular wet weight was unchanged, but right ventricular weight was 20% lower than controls. At the highest concentration of isoproterenol (10 microM), maximum active tension was 32 and 20% lower than controls in hypoxemic left and right ventricles, respectively. The contractile response to forskolin was severely attenuated in both hypoxemic ventricles. Bmax was unchanged in the left ventricle, but increased by 55% in the hypoxemic right ventricle. Kd was not different from controls in either ventricle. Basal cAMP levels were not different from controls, but isoproterenol-stimulated and forskolin-stimulated cAMP levels were 1.4- to 2-fold higher than controls in both hypoxemic ventricles. The results suggest mechanisms downstream from cAMP in the beta-adrenergic receptor pathway are responsible for the attenuated contractile responses to isoproterenol.

Plasmapheresis in a case of eosinophilia-myalgia syndrome with ascending polyneuropathy.

Eosinophilia-myalgia syndrome complicated by ascending polyneuropathy in a 40-year-old woman is described. High-dose intravenous steroids had no beneficial effect on the clinical course. Dramatic and rapid clinical improvement occurred with the use of plasmapheresis. The use of this therapeutic modality should be considered in patients with a similar clinical presentation.

Faculty and house staff members as role models.

In the fall of 1986 approximately 100 faculty members, community physicians, house staff members, and students associated with Indiana University School of Medicine participated in a conference on "Teachers as Role Models: The Impact on the Learning Process." Small-group discussions allowed the participants to define and discuss the impact of role-modeling in medical education. It was anticipated by the organizers that after the conference the participants would be more cognizant of their influence as role models and would be motivated to become better role models and support good role-modeling. A synopsis of the conference indicates that the participants identified both the positive and negative impact of role-modeling and concluded that medical educational programs should use positive role-modeling as a teaching tool to instill within students the desire to gain new knowledge and to apply that knowledge as medical professionals.