Relationship of early changes in bone resorption to the reduction in fracture risk with risedronate.

Changes in the level of biochemical markers of bone resorption with risedronate treatment for osteoporosis were examined as a surrogate for the decrease in fracture risk. Greater decreases in bone resorption markers were associated with greater decreases in vertebral (and nonvertebral) fractures. Antifracture efficacy of antiresorptive therapies is only partially explained by increases in bone mineral density. Early decreases in bone resorption may also play a role. We tested this hypothesis by measuring two bone resorption markers, the C-telopeptide of type I collagen (CTX) and the N-telopeptide of type I collagen (NTX), in osteoporotic patients in risedronate vertebral fracture trials. We studied 693 women with at least one vertebral deformity (mean age, 69 +/- 7 years) who received calcium (and vitamin D if required) and placebo or risedronate 5 mg daily for 3 years. The reductions in urinary CTX (median, 60%) and NTX (51%) at 3-6 months with risedronate therapy were significantly associated (p < 0.05) with the reduction in vertebral fracture risk (75% over 1 year and 50% over 3 years). The changes in both CTX and NTX accounted for approximately one-half (CTX, 55%; NTX, 49%) of risedronate's effect in reducing the risk of vertebral fractures in the first year and approximately two-thirds (CTX, 67%; NTX, 66%) over 3 years compared with placebo. The changes in CTX and NTX accounted for 77% and 54%, respectively, of risedronate's effect in reducing the risk of nonvertebral fractures over 3 years compared with placebo. The relationships between vertebral fracture risk and changes from baseline in CTX and NTX were not linear (p < 0.05). There was little further improvement in fracture benefit below a decrease of 55-60% for CTX and 35-40% for NTX. The decrease in bone resorption in patients taking risedronate accounts for a large proportion of the reduction in fracture risk. There may be a level of bone resorption reduction below which there is no further fracture benefit.

Effects of long-term risedronate on bone quality and bone turnover in women with postmenopausal osteoporosis.

The effects of 3 years of oral risedronate treatment on bone quality and remodeling were assessed in women with postmenopausal osteoporosis. Transiliac bone biopsies were obtained at baseline and after treatment with placebo or risedronate 5 mg/day in 55 women (placebo, n = 27; risedronate 5 mg, n = 28); these pairs of samples allowed comparison of treatment effects vs. both baseline values and between treatment groups. A further 15 women (placebo, n = 6; risedronate 5 mg, n = 9) had measurements from a posttreatment biopsy, but not from a baseline biopsy. Samples were examined for qualitative changes (e.g., osteomalacia, peritrabecular fibrosis, and woven bone); no histological abnormalities were found to be associated with treatment. Among women with both baseline and posttreatment biopsies, risedronate-treated women experienced a moderate and expected reduction from baseline in bone turnover, which was reflected in mean decreases in mineralizing surface of 58% and in activation frequency of 47%. Histomorphometrical parameters indicated that bone formation rate decreased significantly from baseline with risedronate treatment, reflecting a decrease in bone turnover; bone mineralization was normal following treatment. Basic multicellular unit (BMU) balance tended to improve in the risedronate-treated women, whereas it tended to worsen in the placebo-treated women, although these changes were not statistically significant. There were no significant changes in structural parameters with treatment. The effects of 3 years of risedronate treatment on bone histology and histomorphometry reflect the antiresorptive mechanism of action, and are consistent with the antifracture efficacy and favorable bone safety profile demonstrated in large clinical trials.

Dual-wavelength operation diffractive phase elements for pattern formation.

We report on the design and fabrication of novel diffractive phase elements that reconstruct distinct intensity patterns in the far-field on illumination with two specific wavelengths. The elements contain deep surface-relief structures that represent phase-delays of greater than 2p radians. The design process incorporates a modified version of the iterative Fourier transform algorithm. A 16 phase-level element for dual wavelength (blue and red) operation, with high diffraction efficiency, is demonstrated experimentally.

Recurrences after first episodes of genital herpes in patients treated with topical acyclovir cream.

The effect of topical acyclovir treatment of first episode genital herpes on the time to first recurrence in a group of 42 patients receiving either acyclovir or placebo was investigated. Topical acyclovir treatment had no effect on time to first recurrence in patients with either first episode HSV-1 or HSV-2 infections. There was no significant difference in the time to first recurrence in patients with either true primary or initial genital infections. However, the time to first recurrence in patients with first episode HSV-2 was significantly shorter than in patients with first episode HSV-1. Acyclovir treatment appeared to have no effect on the development of neutralising antibody in patients with either virus type.

Efficacy of topical acyclovir cream in first and recurrent episodes of genital herpes.

Fifty-three patients with first episodes and 60 patients with prior culture proven recurrent genital herpes were enrolled in a single centre, double-blind, placebo-controlled trial of 5% acyclovir in an aqueous cream base versus matching placebo. For first episodes treated with topical acyclovir the median duration of pain (4 vs. 8 days, P less than 0.05), time to healing of all lesions (8 vs. 14 days, P less than 0.001), duration of viral shedding (4 vs. 11 days, P = 0.001) and duration of new lesion formation (0 vs. 2.5 days, P less than 0.001) were reduced compared with placebo recipients. In patients with recurrent episodes who completed the study topical acyclovir significantly reduced the median duration of all symptoms (3 vs. 6 days, P less than 0.001), the time to healing of all lesions (4 vs. 6 days, P less than 0.01), and the formation of new lesions (5 vs. 29%, P less than 0.01) compared with the controls. Greater clinical benefits were demonstrated in females than in males, particularly for first episodes, but the number of males was small. Topical acyclovir cream is well tolerated and an effective treatment for first and recurrent episodes of genital herpes.

Isolation and characterisation of two strains of Herpesvirus hominis type 1 from fallopian tubes.

Herpesvirus hominis type 1 (HSV-1) was isolated from fallopian-tube biopsies of two women who were using an intra-uterine contraceptive device; the strains were isolated on different dates and at different hospitals. Both the isolates were shown to be HSV-1 by restriction-enzyme analysis, polypeptide profiles and indirect immuno fluorescence; the two isolates could not be distinguished by these tests, but the tests distinguished them from HSV-1 strain 71-15 and HSV-2 strain 333. The viruses were again isolated from samples of fallopian-tube tissue stored in liquid nitrogen, and their polypeptide and restriction-enzyme profiles were the same as those in the initial isolates. Virus was not isolated from fallopian-tube samples obtained from other IUD patients undergoing surgery at the same two hospitals at the same time.

Progression and treatment of chronic adult periodontitis.

BACKGROUND: The periodontal status of 41 medically healthy adults with untreated chronic periodontitis was monitored before and after scaling and root planing (SRP). METHODS: During a 6-month pretreatment phase, clinical measurements, digital subtraction radiography (DSR) analysis of alveolar bone, and measurement of gingival crevicular fluid (GCF) prostaglandin E2 (PGE2) levels were undertaken. SRP was provided during a 1-month treatment phase. Clinical, radiographic, and biochemical analyses were repeated in a 6-month post-treatment healing period. RESULTS: Pretreatment: no clinically significant changes in mean plaque indices (PI), probing depths (PD), bleeding on probing (BOP), or relative clinical attachment levels (CAL) were detected (P>0.05). DSR revealed small but statistically significant bone height (0.04 mm) and mass (0.97 mg) loss (P<0.001). GCF PGE2 levels gradually increased from 38.8 ng/ml at month 1 to 79.4 ng/ml at month 6. Post-treatment: statistically and clinically significant reductions were observed in mean PI, BOP, and PD (P<0.05). A statistically significant reduction in CAL was noted (P<0.05). The trend towards progressive bone loss was halted and reversed, and a statistically significant decrease in GCF PGE2 concentrations was detected (P<0.001). Smokers, non-smokers, and ex-smokers did not differ significantly in PI, BOP, CAL, radiographic, or biochemical parameters at any time. Mean PD was significantly greater in current smokers than in non- and ex-smokers (P<0.005). PD reduced comparably in all 3 smoking subgroups following treatment (P<0.01). CONCLUSIONS: Conventional clinical measurements failed to identify disease progression over a 6-month period. Significant improvements were observed in clinical parameters after SRP, and a trend towards progressive bone loss was halted and reversed. Regular and frequent maintenance visits are important following treatment to maintain improvements in clinical parameters. Smokers had deeper probing depths than non- and ex-smokers, but pockets were reduced significantly and comparably in all 3 smoking subgroups following efficacious treatment.

Positive effect of etidronate therapy is maintained after drug is terminated in patients using corticosteroids.

Following a 52-wk randomized controlled trial of intermittent cyclic etidronate therapy in patients using corticosteroids, we performed a 52-wk open-label trial of calcium alone in 114 corticosteroid-treated patients to determine whether the beneficial effect of etidronate is maintained after the drug is discontinued. All patients were given 500 mg/d of elemental calcium. Sixty-one and 53 patients made up the former placebo and etidronate groups, respectively. A total of 89 (98%) of patients in the former placebo and etidronate groups remained on corticosteroids throughout the second year. The mean (SE) percentage change in bone mineral density of the lumbar spine, femoral neck, and trochanter were compared between groups. The difference between groups in mean percentage change from baseline (wk 0, initiation of etidronate or placebo therapy) in the bone density of the lumbar spine, femoral neck, and trochanter, following 104 wk, was 3.8 (0.9), 3.0 (1.1), and 4.3 (1.1), respectively (p < 0.05, all sites), in favor of the former etidronate group. While not significant, the former placebo group demonstrated a slightly larger rate of decline in bone density over the second year than the former etidronate group at all three sites. Following the discontinuation of etidronate therapy, there was no accelerated bone loss and there was evidence of a residual protective effect in both the lumbar spine and femoral neck for up to 1 yr posttreatment.

Infectious bovine keratoconjunctivitis: seasonal variation in cultural, biochemical and immunoreactive properties of Moraxella bovis isolated from the eyes of cattle.

The eyes of 20 young cattle were examined over an 18 month period in which 12 members of the group contracted infectious bovine keratoconjunctivitis (IBK). On each of 23 occasions cultural, biochemical and immunoreactive properties of up to 6 isolates of Moraxella bovis derived from each eye were determined. Relationships between the clinical response of eyes, phenotypic properties of M. bovis and annual variations in the level of solar ultraviolet radiation of 280 to 320 nm wavelength were examined. M. bovis was isolated from all IBK-affected and some unaffected eyes less than one month after the maximum annual level of the mean weekly UV radiation (2,840 mWh.m-2 X nm-1) was recorded. A high proportion of M. bovis from IBK lesions were simultaneously active in haemolysis, agar corrosion, gelatin liquefaction and litmus milk peptonisation. Some of these characteristics showed marked dissociation despite consistent reactivity in the fluorescent antibody test, which had a sensitivity and specificity of 95%. Fall in the mean weekly level of UV radiation below 1,438 mWh X m-2 X nm-1 in autumn was accompanied by healing of ulcers, persistent scar formation and a decline in the number of M. bovis isolated from affected eyes. A slower decline in the number of M. bovis isolated from apparently healthy eyes occurred in the winter and occasional fresh IBK lesions occurred.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of risedronate on fracture risk in postmenopausal women with osteopenia.

UNLABELLED: This posthoc analysis of four trials studied the efficacy of risedronate to reduce fragility fractures in postmenopausal women with osteopenia (i.e., T-scores between -1 and -2.5). Risedronate reduced the fracture risk by 73% (p = 0.023) in this population of women with low femoral neck bone mass and no prevalent vertebral fractures. INTRODUCTION: Low bone mass represents an increasing health risk and burden. Half of fragility fractures occur in osteopenic women underscoring the need for treatments reducing fracture risk. This analysis reports the effect of risedronate to reduce fragility fracture risk in osteopenic women without prevalent vertebral fractures. METHODS: Postmenopausal women with osteopenia, defined as femoral neck T-score between -1 and -2.5 by DXA and no prevalent vertebral fractures, were identified from four controlled randomized trials (BMD Multinational, BMD North America, VERT Multinational and VERT North America). The risk reduction for fragility fractures in patients receiving 5 mg risedronate daily for 1.5 to 3 years compared to placebo was assessed. An additional sensitivity analysis excluded patients who were osteopenic at the femoral neck but had a BMD lower than -2.5 SD at the lumbar spine. RESULTS: Six hundred and twenty postmenopausal women with osteopenia were included, receiving either placebo (n = 309) or risedronate 5 mg (n = 311). Risedronate reduced the risk of fragility fractures by 73% over 3 years versus placebo (p = 0.023); cumulative fragility fracture incidence was 6.9% in placebo-treated versus 2.2% in risedronate-treated patients. The magnitude of the effect was similar in the sensitivity analysis subset. CONCLUSION: Risedronate significantly reduced the risk of fragility fractures in postmenopausal women with osteopenia (femoral neck T-score between -1 and -2.5 SD) and no prevalent vertebral fractures.

Risedronate decreases fracture risk in patients selected solely on the basis of prior vertebral fracture.

The aim of this study was to examine the effects of risedronate (5 mg/daily) in patients identified solely on the basis of a prior fragility fracture, without BMD as an inclusion criterion. A total of 1,802 patients were examined from the VERT-NA and VERT-MN clinical trials. Lateral radiographs (T4 to L4) were obtained at baseline and annually; incident fractures were evaluated using quantitative and semiquantitative methods at the central facility. BMD was measured at the lumbar spine and femoral neck by dual-energy X-ray absorptiometry. Secondary analyses evaluated vertebral fracture efficacy in patient subgroups categorized according to the presence of risk factors for osteoporosis at baseline (age, femoral neck BMD, lumbar spine BMD, more severe BMD, height, weight, body mass index, prevalent nonvertebral fracture status, smoking, and bone turnover marker levels). Over 3 years, risedronate reduced the risk of new vertebral fractures by 44% (95% CI, 28% to 56%) compared with placebo. In patients subgrouped according to the presence or absence of putative risk factors, the efficacy of risedronate was comparable across all groups (all treatment-by-non BMD subgroup interactions p > or =0.210). Adjustment for age, baseline BMD, and prevalent vertebral fractures on fracture risk gave results similar to the unadjusted analysis. In patients taking placebo, the incidence of new vertebral fracture was higher in several of the high-risk categories (elderly, T-score < or = -2.5 SD). In conclusion, the findings of this study suggest that risedronate is effective in patients identified solely on the basis of a prior fragility fracture and that the efficacy of risedronate in the reduction of vertebral fractures is largely independent of the presence of clinical risk factors for osteoporotic fracture.

Infrared continuum water vapor absorption coefficients derived from satellite data.

In a recent paper W. B. Grant ["Water Vapor Absorption Coefficients in the 8-13-microm Spectral Region: a Critical Review," Appl. Opt. 29, 451-462 (1990)] reviewed experimental measurements of the water vapor continuum absorption coefficients in the 8-13-microm spectral region. In comparing three different groundbased techniques he concluded that the absorption coefficients used in the HITRAN and LOWTRAN-7 codes are in reasonable agreement with the measurements. These coefficients are approximately 20% lower than those used in the LOWTRAN-6 code. A fourth method of experimentally determining the water vapor absorption coefficients is described which suggests an opposite result. A comparison between sets of satellite measured infrared radiances and ship measurements of sea surface temperature using a model of infrared transmission through the atmosphere gives coefficients that are 20-40% larger than those used in LOWTRAN-6. Agreement between the four different measurement techniques is only posible if a much stronger negative temperature dependence of the continuum absorption coefficients is adopted. This results in significant increases in the coefficients at temperatures below 270 K.

Fluid and electrolyte disorders. Sodium.

Because water is freely exchangeable across most cell membranes, its distribution is largely determined by physical factors and by the relative osmolal concentrations of the extracellular and intracellular fluids. As the major extracellular cation, sodium is a principal determinant of the extracellular fluid volume.

Application of optimization algorithms to the design of diffractive optical elements for custom laser resonators.

We report what we believe to be the first applications of numerical optimization algorithms to the design of diffractive elements that customize the fundamental mode profile of a laser system. Standard design techniques treat these elements as specific phase-conjugation devices, which leads to performance loss when they are quantized to permit fabrication. Numerical optimization can account for quantization of the element to increase the effective performance. Also, it is shown that allowing a slight increase in the intrinsic loss of the cavity can substantially increase the fidelity of the fundamental mode of the customized cavity. The good discrimination qualities of the mode-selection elements are shown to be unaffected by this process.

Differential-absorption lidar measurements in the oxygen A band using a ruby lidar and stimulated Raman scattering.

Stimulated Raman scattering has been used to convert the output wavelength of a ruby-laser radar (lambda = 6943 A) into the oxygen A band near 7660 A. The system has been used to measure the energy backscattered from the lower atmosphere at both 6943 and 7658 A. Smith and Platt [NOAA Technical Memorandum, NESS 89 (1977)] have shown that such differential-absorption lidar measurements can be used to give both pressure height profiles and vertical temperature profiles. Some correlation between pressure height and oxygen absorption has been found, but greater transmitted energies and better frequency stability at the converted wavelength are required before an operational system can be implemented.

Instrumentation for remote sensing solar radiation from light aircraft.

The paper outlines the instrumentation needed to study, from a light aircraft, the solar radiation reflected by ground surfaces and the incoming solar radiation. A global shortwave radiometer was mounted on the roof of the aircraft and a specially designed mount was used to support a downward pointing 70-mm aerial camera, a downward pointing narrow-beam pyranometer, and, sometimes, a downward pointing global shortwave pyranometer. Calibration factors were determined for the three pyranometers by comparison with a standard Angstrom compensation pyrheliometer. Results have indicated trends in the albedos of major plant communities and have shown that the calculated albedo values vary according to whether the downward pointing instrument is narrow-beam or global. Comparisons were also made with albedos measured on the ground.