Risedronate Reduces the Risk of First Vertebral Fracture in Osteoporotic Women

Risedronate treatment reduces the risk of vertebral fracture in women with existing vertebral fractures, but its efficacy in prevention of the first vertebral fracture in women with osteoporosis but without vertebral fractures has not been determined. We examined the risk of first vertebral fracture in postmenopausal women who were enrolled in four placebo-controlled clinical trials of risedronate and who had low lumbar spine bone mineral density (BMD) (mean T-score =–3.3) and no vertebral fractures at baseline. Subjects received risedronate 5 mg (n= 328) or placebo (n= 312) daily for up to 3 years; all subjects were given calcium (1000 mg daily), as well as vitamin D supplementation (up to 500 IU daily) if baseline serum 25-hydroxyvitamin D levels were low. The incidence of first vertebral fracture was 9.4% in the women treated with placebo and 2.6% in those treated with risedronate 5 mg (risk reduction of 75%, 95% confidence interval 37% to 90%; P= 0.002). The number of patients who would need to be treated to prevent one new vertebral fracture is 15. When subjects were stratified by age, similar significant reductions were observed in patients with a mean age of 64 years (risk reduction of 70%, 95% CI 8% to 90%; P= 0.030) and in those with a mean age of 76 years (risk reduction of 80%, 95% CI 7% to 96%; P= 0.024). Risedronate treatment therefore significantly reduces the risk of first vertebral fracture in postmenopausal women with osteoporosis, with a similar magnitude of effect early and late after the menopause. Received: 12 September 2001 / Accepted: 11 December 2001     

Bone mineral density after resumption of menses in amenorrheic athletes

Amenorrheic athletes have been found to have a lower vertebral bone mineral density (BMD) than matched groups of eumenorrheic athletes. This study reports changes in BMD over a 15.5 month period in athletes who regained menses, athletes who remained amenorrheic, and athletes with regular cycles. The BMD was measured at two sites on the radius and at the lumbar vertebrae (L-1 through L-4), using single- and dual-photon densitometry, respectively. Changes in vertebral BMD were significant for the amenorrheic group (+6.3%), but not for cyclic women (-0.3%). A slight increase in radial density at S-1 and S-2 was not significant for either group. Two athletes who remained amenorrheic during this period continued to lose bone (-3.4%). We conclude that resumption of menses was the primary factor for the significant increase in the vertebral BMD of the formerly amenorrheic athletes.     

Radiometric detection of yeasts in blood cultures of cancer patients.

During a 12-month period, 19,457 blood cultures were collected. Yeasts were isolated from 193 cultures derived from 76 cancer patients. Candida albicans or Candida tropicalis accounted for 79% of isolates. Of the three methods compared, the radiometric method required 2.9 days to become positive, "blind" subculture required 2.6 days, and Gram stains required 1 day. However, the radiometric method was clearly superior in detecting positive cultures, since 73% of all cultures were first detected radiometrically, 22% were detected by subculture, and only 5% were detected by Gram stain. Although 93% of the isolates were detected by aerobic culture, five (7%) isolates were obtained only from anaerobic cultures. Seven days of incubation appear to be sufficient for the radiometric detection of yeasts.     

Optimizing vaccine design for cellular processing,MHC binding and TCR recognition

In this review we describe the methods and processes that our group have developed while aiming to test and design multiepitope vaccines for infectious diseases and cancer. Testing the performance of vaccines composed of epitopes restricted by human leukocyte antigen (HLA) molecules is accomplished by in vitro antigenicity assays, as well as in vivo immunogenicity assays in HLA transgenics. The efficiency by which multiepitope vaccines are processed is optimized by spacer residues, which are designed to facilitate generation by natural processing of the various class I- and class II-restricted epitopes. Methods and strategies to test and optimize HLA binding affinity, patient coverage from the vaccine construct, and TCR recognition of HLA/epitope complexes are also discussed.     

Recognition of a novel naturally processed, A2 restricted, HCV-NS4 epitope triggers IFN-gamma release in absence of detectable cytopathicity

Using short term CTL lines derived from HLA A2/K^b transgenic mice and IFN-gamma release assays we demonstrate that the NS4.1769 epitope, is generated from natural processing of the NS4 antigen, and presented in the context of the A2/K^b molecules. Interestingly, T cell recognition of the naturally processed form of the NS4.1769 epitope was associated with significant IFN-gamma release, but no direct cytolytic activity. Epitopes of this phenotype might be of interest, in terms of therapy of chronic HCV infection by associating the benefit of localized lymphokine release with low or absent direct cytopathicity.     

Site of bone density measurement may affect therapy decision

Summary The purpose of this study was to determine whether bone mineral density (BMD) measurements at the lumbar spine and femoral neck provided comparable information to women planning to use that knowledge to help them make a decision about hormone replacement therapy. Eighty-eight healthy Caucasian women, aged 44–59 and within 0 to 5 years of menopause, participated in the study. BMD measurements were performed at the lumbar spine (L1-L4) and the femoral neck by dual energy X-ray absorptiometry (DXA). Criteria suggested by the National Osteoporosis Foundation were used to categorize women as at risk for osteoporosis, bone density more than one standard deviation (SD) below the young adult mean, or as low risk, bone density at or above this level. The re that 46 women would be classified into the low risk category on the basis of spinal BMD alone. However, 28 of these 46 women would fall into the at risk category when the femoral neck BMD was measured. Sixty-one percent of women informed they were at low risk on the basis of spinal BMD would be considered at risk based on femoral neck BMD. When femoral neck BMD was used as the primary risk indicator, 14% of the women classified as low risk would be at risk if spinal BMD were added. These results suggest that both lumbar spine and proximal femur measurements should be made when women are using bone density measurements as an aid in deciding whether or not to use hormone therapy in their postmenopausal years.     

Intracranial Pressure Monitoring: Fundamental Considerations and Rationale for Monitoring

Traumatic brain injury (TBI) is a major cause of death and disability worldwide. In large part critical care for TBI is focused on the identification and management of secondary brain injury. This requires effective neuromonitoring that traditionally has centered on intracranial pressure (ICP). The purpose of this paper is to review the fundamental literature relative to the clinical application of ICP monitoring in TBI critical care and to provide recommendations on how the technique maybe applied to help patient management and enhance outcome. A PubMed search between 1980 and September 2013 identified 2,253 articles; 244 of which were reviewed in detail to prepare this report and the evidentiary tables. Several important concepts emerge from this review. ICP monitoring is safe and is best performed using a parenchymal monitor or ventricular catheter. While the indications for ICP monitoring are well established, there remains great variability in its use. Increased ICP, particularly the pattern of the increase and ICP refractory to treatment is associated with increased mortality. Class I evidence is lacking on how monitoring and management of ICP influences outcome. However, a large body of observational data suggests that ICP management has the potential to influence outcome, particularly when care is targeted and individualized and supplemented with data from other monitors including the clinical examination and imaging.     

Epitope identification and vaccine design for cancer immunotherapy

The development of processes for engineering multi-epitope vaccines based on the identification and selection of epitope packages, along with vaccine design optimization using epitope placements and spacers to optimize processing efficacy, are reviewed. The Epimmune Inc epitope identification process has been applied to numerous cancer types, but also applies to infectious diseases. Epitope-analog efforts in novel vaccine design have also been explored and their uses in prophylactic and therapeutic applications are eagerly anticipated.