Malnutrition has been often suggested as contributing to both the high incidence of hip fracture in elderly people and its complications. In a recent prospective controlled randomized study, the clinical outcome of elderly patients with osteoporotic fracture of the proximal femur (hip fracture) improved by giving a simple oral dietary supplement. This study, however, did not prove that protein was responsible for the clinical improvement since the supplement also contained vitamins and minerals. We addressed this question by comparing the clinical outcome and bone mineral density (BMD) changes in elderly patients with hip fracture, receiving two different dietary supplements with different protein contents. Sixty-two patients (mean age 82) admitted into the orthopedic ward for fracture of the proximal femur were randomized into two groups. One group (n = 33) received 250 ml/day of an oral nutritional supplement containing protein (20.4 g), mineral salts (Ca: 0.525 g) and vitamins A = 750 IU; D3 = 25 IU) for a mean of 38 days. A control group (n = 29) received the same supplement dose, but with no protein, for the same period of time. The clinical course was significantly better in the group receiving protein, with 79% having a favorable course as compared to 36% (p less than 0.02) in the control group during the stay in the recovery hospital. The rate of complications and deaths was also significantly lower in the protein-supplemented vs the control group (52 vs 80%, p less than 0.05) 7 months after hip fracture. The median hospital stay was significantly lower in the protein-supplemented group (69 vs 102 days, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Granulocyte colony-stimulating factor (G-CSF) is a glycoprotein that critically regulates the viability, proliferation, and differentiation of granulocytic precursors and the function of neutrophils by si ng through its receptor. Cloning of the human G-CSF receptor (G-CSFR) cDNA has demonstrated sequence homology with other members of the hematopoietic/cytokine receptor superfamily. G-CSF stimulates the appearance of phosphotyrosine proteins in several types of human and murine myeloid cells. Since the receptor does not possess intrinsic tyrosine kinase activity, we hypothesized that G-CSFR interacts with and activates cytosolic protein-tyrosine kinases (PTKs). In vitro protein kinase assay of human G-CSFR immunoprecipitates demonstrated at least two tyrosine phosphoproteins, pp55 and pp7O. We observed that G-CSF activated p53/p56lyn, a Src-related PTK, and p72syk, a non-Src-related PTK. Lyn and Syk were recovered in anti-G-CSFR immunoprecipitates; Lyn was detected in the absence of ligad. In addition, upon G-CSF stimulation, Lyn coimmunoprecipitated with Syk. Analysis of the G-CSFR amino acid sequence revealed a potential receptor activation motif for Syk. On the basis of immunoprecipitation and sequence analysis data, we propose that the human G-CSFR forms a three-component signaling complex with Lyn and Syk. Their sequential recruitment into the G-CSFR saling complex demonstrates the coordinated involvement of two PTKs with a member of the hematopoietic/cytokine receptor superfamily.

An outbreak of Clostridium difficile-associated disease (CDAD) caused by the epidemic North American pulsed-field gel electrophoresis type 1 (NAP1) strain began after a formulary change from levofloxacin to moxifloxacin. Cases of CDAD were associated with moxifloxacin use, but a formulary change back to levofloxacin failed to reduce rates of disease. Substituting use of one fluoroquinolone with use of another without also controlling the overall use of drugs from this class is unlikely to control outbreaks caused by the NAP1 strain of C. difficile.

Legionella pneumophila is an important pathogen that may cause nosocomial and community-acquired pneumonia in patients with normal or altered immunity. The epidemiology of 40 cases of legionella pneumonia in patients hospitalized between 1986 and 1994 was studied. Fourteen patients (35%) were solid organ transplant recipients. The calculated annual incidence of L. pneumophila infection was highest among lung transplant recipients (2.07 cases per 1,000 transplant-years). There was a trend toward reduced mortality rates and less severe disease among transplant patients vs. nontransplant patients: mortality rate, 36% vs. 54%; incidence of intubation, 50% vs. 69%; rate of concurrent infections, 29% vs. 38%; and overall rate of complications, 86% vs. 96%; respectively. In a multivariate analysis, factors independently associated with an increased mortality rate were nosocomial acquisition, need for intubation, formation of lung abscess or cavitation, and presence of pleural effusion. Thus, despite differing host immune responses, the most important prognostic factors affecting the outcome of legionellosis are nosocomial acquisition and the development of pulmonary complications.

Bone mass is an important determinant of resistance to fractures. Whether bone mineral density (BMD) in subjects with a fracture of the proximal femur (hip fracture) is different from that of age-matched controls is still debated. We measured BMD of the femoral neck (FN) on the opposite side to the fracture, as well as femoral shaft (FS) and lumbar spine (LS) BMD by dual-photon absorptiometry in 68 patients (57 women and 11 men, mean age 78.8 +/- 1.0) 12.4 +/- 0.8 days after hip fracture following a moderate trauma. These values were compared with BMD of 93 non-fractured elderly control subjects (82 women and 11 men), measured during the same period. As compared with the controls, FN BMD was significantly lower in fractured women (0.592 +/- 0.013 v. 0.728 +/- 0.014 g/cm2, P less than 0.001) and in fractured men (0.697 +/- 0.029 v. 0.840 +/- 0.052, P less than 0.05). Expressed as standard deviations above or below the mean BMD of age and sex-matched normal subjects (Z-score), the difference in FN BMD between fractured women and controls was highly significant (-0.6 +/- 0.1 v. +0.1 +/- 0.1, P less than 0.001). As compared with mean BMD of young normal subjects, BMD was decreased by 36.9 +/- 1.4 and 22.4 +/- 1.5% (P less than 0.001) in fractured and control women, respectively. There was no significant difference between FN BMD of 33 women with cervical and 24 with trochanteric hip fractures (0.603 +/- 0.017 v. 0.577 +/- 0.020). FN BMD was lower than 0.705 g/cm2 in 90% of fractured women.(ABSTRACT TRUNCATED AT 250 WORDS)

Granulocyte colony-stimulating factor (G-CSF) is produced by several cell types throughout the body and has a variety of effects on neutrophils and their precursors, which are mediated by binding to its receptor. It is not yet known what physiologic factors modulate G-CSF receptor mRNA expression in these cells. We studied the effect of G-CSF on freshly isolated neutrophils and bone marrow cells from normal human subjects and on myeloid leukemic cell lines. We found that G-CSF receptor mRNA levels were maintained by G-CSF in neutrophils but not in bone marrow cells. Of the leukemic cell lines tested, K562 and BV173, both of which contain the bcr-abl translocation, neither expressed G-CSF receptor mRNA. Whereas G-CSF did not affect mRNA levels for its receptor in myeloid leukemic cell lines, exposure of the acute promyelocytic cell line, NB4, to all-trans retinoic acid induced a striking increase in G-CSF receptor mRNA expression and resulted in increased G-CSF receptor surface expression. The effect of retinoic acid on G-CSF receptor mRNA on NB4 cells occurred early, before morphologic evidence of differentiation, and required protein synthesis. All-trans retinoic acid also upregulated G-CSF receptor mRNA in the myeloid leukemia cell line HL-60. Thus, maintenance of G-CSF receptor on neutrophils by G-CSF may extend the duration of ligand responsiveness. Furthermore, the ability of retinoic acid to up-regulate G-CSF receptor may account for the synergistic effect of G-CSF and retinoic acid in differentiation induction of acute promyelocytic leukemia.

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