New estimates of influenza-related pneumonia and influenza hospitalizations among the elderly.

OBJECTIVES: The aim of this study is to present a method to provide accurate estimates of influenza-associated pneumonia and influenza (P&I) hospitalizations and costs for use in tracking the continuing burden of influenza. METHODS: We estimated influenza-associated P&I hospitalizations among the U.S. elderly population for six influenza seasons, 1990-91 through 1995-96, by applying a Poisson regression model to national influenza virus surveillance information and Medicare administrative data. This model is similar to that recently published by the U.S. National Centers for Disease Control and Prevention (CDC) to estimate influenza-related mortality. RESULTS: During the six years of the study, 318,666 (9.8%) of P&I hospitalizations were estimated to be associated with influenza: range = 25,819 to 70,068 per year; average annual cost = $372.3 million. Influenza A(H3N2) was associated with 73.9% of influenza-related P&I hospitalizations; influenza B with 21.3% and influenza A(H1N1) with 4.8%. CONCLUSIONS: Our estimates were consistent with the estimates of influenza-associated P&I mortality reported by CDC. Thus, we suggest that estimates of influenza-associated morbidity and costs based on virus surveillance and administrative data may be used for monitoring the impact of influenza and of intervention strategies.     

Presentation of growth velocities of rural Haitian children using smoothing spline techniques

The examination of monthly (or quarterly) increments in weight or length is important for assessing the nutritional and health status of children. Growth velocities are widely thought to be more important than actual weight or length measurements per se. However, there are no standards by which clinicians, researchers, or parents can gauge a child's growth. This paper describes a method for computing growth velocities (monthly increments) for physical growth measurements with substantial measurement error and irregular spacing over time. These features are characteristic of data collected in the field where conditions are less than ideal. The technique of smoothing by splines provides a powerful tool to deal with the variability and irregularity of the measurements. The technique consists of approximating the observed data by a smooth curve as a clinician might have drawn on the child's growth chart. Spline functions are particularly appropriate to describe bio-physical processes such as growth, for which no model can be postulated a priori. This paper describes how the technique was used for the analysis of a large data base collected on pre-school aged children in rural Haiti. The sex-specific length and weight velocities derived from the spline-smoothed data are presented as reference data for researchers and others interested in longitudinal growth of children in the Third World.     

Differences in dietary intake associated with smoking status

This study was designed to identify and describe smoking-related differences in dietary and nutritional factors that are potential independent predictors of cancer risk or effect modifiers or confounders of tobacco-cancer relationships. Data were obtained from a large hospital-based case-control study which was designed to estimate the cancer risk from various tobacco products and consisted of 465 male and 300 female incident lung cancer cases and 870 male and 556 female hospitalized patient controls matched on sex and age (+/- 5 years). Nutritional data were analysed as log-transformed frequencies of thirty food items, nine factor scores generated to describe overall patterns of dietary intake, and estimated daily nutrient scores for fat, vitamin A, fibre, and cholesterol. In general, the dietary habits of ex-smokers more closely resembled those of never-smokers than those of current smokers. We found that after controlling for case-control status, education, alcohol consumption, and age, there were many more significant differences in nutritional exposures by smoking status than could be explained merely by chance. For both sexes we observed significantly increased consumption of fruits and higher vitamin A and fibre scores in non-smokers compared to current smokers (for any smoking vs non-smoking comparison the P-value was always less than 0.002, 0.01, and 0.007, respectively). A similar but weaker relationship was observed for high-fat, sweet foods such as ice cream. An inverse association, also of smaller magnitude, was found for other high-fat foods items. Implications for further study and strengths and weaknesses of the current study are discussed.     

The validity and reliability of hand-held dynamometry in assessing isometric external rotator performance

The validity and reliability of hand-held dynamometry and Cybex dynamometry were investigated using maximal isometric contractions of the external rotators of the shoulder in 14 healthy male subjects. Three maximum voluntary contractions were recorded from each subject by a hand-held dynamometer and a Cybex isokinetic dynamometer at two testing sessions approximately 1 week apart. Analysis of variance did not reveal any significant differences between the mean peak torques obtained with either instrument or between days. The intrarater reliability was clearly established for both the hand-held dynamometer (r = 0.986) and Cybex dynamometer (r = 0.993). Within-day correlations between the two instruments accounted for 27% (day 1) and 60% (day 2) of the explainable variance. This suggests that although both techniques produced identical peak torque values and measured the same element of performance-strength, they did so in a slightly different manner. The possible nature of these differences is discussed.J Orthop Sports Phys Ther 1988;10(6):213-217.     

Pathways of destruction in metacarpal and metatarsal joints of patients with rheumatoid arthritis.

219 metatarsal (MTP) and 69 metacarpal (MCP) capitulae obtained during surgery from patients with definite rheumatoid arthritis (RA) were histologically evaluated. This evaluation, focussing on primary pathways of joint destruction by tumor-like proliferated synovial cell masses revealed 3 pathways of aggression: Pathway A: In 15% aggression onto the articular cartilage only. Pathway B: In 49% direct invasion exclusively into the cortical bone. Pathway C: In 36% a "forceps-like" aggression, a combination of A and B in which the joint is attacked from both sides. In contrast to the hitherto conventional concepts, the findings of this study reveal a clear preference of the synovial aggression for the cortical bone rather than for the articular cartilage. The different concepts of joint destruction in RA are being discussed in the light of our findings. Thus, future pathogenetic considerations with regard to joint destruction in RA should take this fact into consideration.     

Mg(2+)-dependent inward rectification of ROMK1 potassium channels expressed in Xenopus oocytes.

1. ROMK1 potassium channel currents were examined in Xenopus oocytes by two-microelectrode voltage-clamp and patch-clamp techniques following injection of oocytes with in vitro transcribed ROMK1 cRNA. Macroscopic currents recorded from intact cells rectified inwardly at positive potentials. 2. In inside-out membrane patches rectification is manifested as an apparent reduction of single channel current (at 500 Hz) in the presence of 0.1-10 mM Mg2+, without a decrease in the channel open probability. No inward rectification is observed when membrane patches are isolated into solutions containing potassium as the only internal inorganic cation. 3. Mg2+ block can be described by a simple one-site model for Mg2+ binding with K0 ([Mg2+] causing half-maximal block at 0 mV) of 16.7 mM and delta (the fraction of the membrane field sensed by the blocking Mg2+) of 0.35. 4. The voltage dependence of channel block by cytoplasmic Mg2+ was shifted approximately -50 mV by a reduction in extracellular [K+] from 140 to 0 mM, corresponding to a decrease of K0 to 4.4 mM. 5. At negative membrane potentials, ROMK1 channels exhibit a single subconducting state that is approximately 4/10 of the full conductance. The incidence of subconductance states is not appreciably enhanced in the presence of Mg2+.     

Inhibition of cysteine proteinases by autolytic digestion is mediated by CBP2/Hsp47

CBP2/Hsp47 is a glycoprotein normally limited to the ER-Golgi where it is first associated with procollagen chains at a very early point during translation of nascent chains and later with properly folded procollagen. Although CBP2/Hsp47 is regarded as a molecular chaperone belonging to the serpin superfamily, this protein does not appear to inhibit serine proteinases. Here we demonstrate that CBP2/Hsp47 functions in a manner similar to other serpin superfamily members by cross class inhibiting cysteine proteinases. A CBP2/Hsp47 to cathepsin L inactivation stoichiometery of approximately 1.5 revealed concurrent cleavage of CBP2/Hsp47 with proteinase inactivation. Cleavage of the CBP2/Hsp47 was shown to occur outside the P1-P1' at the P16-P15 and P2'-P3' bonds. In addition, the proteinase bands in SDS/PAGE diminished on reaction of the enzyme with CBP2/Hsp47. These results sustain a mechanism advocated by Bjork et al. (1998), in which cysteine proteinases assault a peptide bond in the reactive site loop of serpins, (CBP2/Hsp47) adjacent to the P1-P1' bonds involved in serine proteinase inhibition. The reaction proceeds with the substrate pathway dominating in the cysteine proteinase reaction. In these complexes the cysteine proteinases, papain and cathepsin L, are rendered more susceptible to proteolysis and are degraded by active enzyme. These properties help explain the mechanism by which CBP2/Hsp47 increases the fidelity of collagen production. Moreover, if CBP2/Hsp47 is shown to involve the multiplexin subclass of collagens, it may further provide a mechanism by which the motogen and angiogenic properties during development and/or neoplasia are regulated.