Citations

There are theoretical and practical advantages to modular rather than monoblock designs of prostheses for shoulder arthroplasty, but there are no reported studies which specifically compare the clinical and radiological results of their use. We have compared the results of unconstrained total shoulder arthroplasty for osteoarthritis using both types of implant. The monoblock design was used between 1992 and 1995 and the modular design after 1995. Both had cemented all-polyethylene glenoids, the monoblock with matched and the modular with mismatched radii of curvature. There were 34 consecutive shoulders in each group with a mean follow-up of 6.1 years in the first and 5.2 years in the second. There were no significant differences in improvement of pain scores, active elevation, external rotation, internal rotation, patient satisfaction, or the Neer ratings between the two groups. Two of 28 glenoid components in the first group and six of 30 in the second met the criteria for being radiologically at risk for loosening (p = 0.25). There were no significant differences in clinical outcome or radiological changes between the first- and second-generation designs of implant for shoulder arthroplasty.

Abstract Background: The quantitative assay for free light chains (FLCs) is a recently introduced commercial test reported to be sensitive and specific for detecting FLC diseases such as primary systemic amyloidosis (AL), light chain deposition disease (LCDD), nonsecretory multiple myeloma (NSMM), and light chain multiple myeloma. We evaluated its diagnostic performance in clinical practice. Methods: All FLC clinical test results generated in 2003 were abstracted from the Laboratory Information System. Diagnoses were obtained from the Dysproteinemia database and the patient medical history. Results: In 2003, we received samples for FLC assays from 1020 Mayo Clinic patients. The majority of these patients (88%) had bone marrow-derived monoclonal plasma cell disorders (PCDs). The 121 patients who did not have monoclonal gammopathy all had FLC κ/λ ratios within the range of values obtained for a reference population in our laboratory. Among the patients with monoclonal gammopathies were patients with multiple myeloma (330), AL (269), monoclonal gammopathy of undetermined significance (114), smoldering multiple myeloma (72), plasmacytoma (22), NSMM (20), macroglobulinemia (9), LCDD (7), and a variety of other PCDs. Among the 110 AL patients who had not been previously treated and who had a FLC assay performed within 120 days of diagnosis, the FLC κ/λ ratio was positive in 91% compared with 69% for serum immunofixation electrophoresis (IFE) and 83% for urine IFE. The combination of serum IFE and serum FLC assay detected an abnormal result in 99% (109 of 110) of patients with AL. Conclusion: The performance of the FLC assay in this analysis of clinical laboratory data is consistent with results from published retrospective validation studies.

Two oncogenic pathways have been hypothesized for multiple myeloma (MM) and premalignant monoclonal gammopathy of undetermined significance (MGUS) tumors: a nonhyperdiploid pathway associated with a high prevalence of IgH translocations and a hyperdiploid pathway associated with multiple trisomies of 8 chromosomes. Cyclin D1, D2, or D3 expression appears to be increased and/or dysregulated in virtually all MM tumors despite their low proliferative capacity. Translocations can directly dysregulate CCND1 (11q13) or CCND3 (6p21), or MAF (16q23) or MAFB (20q11) transcription factors that target CCND2. Biallelic dysregulation of CCND1 occurs in nearly 40% of tumors, most of which are hyperdiploid. Other tumors express increased CCND2, either with or without a t(4;14) translocation. Using gene expression profiling to identify 5 recurrent translocations, specific trisomies, and expression of cyclin D genes, MM tumors can be divided into 8 TC (translocation/cyclin D) groups (11q13, 6p21, 4p16, maf, D1, D1+D2, D2, and none) that appear to be defined by early, and perhaps initiating, oncogenic events. However, despite subsequent progression events, these groups have differing gene expression profiles and also significant differences in the prevalence of bone disease, frequency at relapse, and progression to extramedullary tumor.

Background— Heart failure (HF) with normal ejection fraction (diastolic HF [DHF]) usually occurs in elderly patients with hypertension. The presence and significance of altered systolic and diastolic ventricular function in DHF is increasingly controversial. Our objective was to develop a clinically relevant large-animal model to better understand the pathophysiology of DHF. Methods and Results— Ventricular structure and function were characterized in young control (YC group; n=6), old control (OC group; n=7), and old dogs made hypertensive by renal wrapping (experimental DHF [ExDHF] group; n=8). The ExDHF group was associated with normal left ventricular (LV) volume, increased LV mass, and myocardial fibrosis. LV relaxation was impaired in ExDHF (τ=53±6 ms) compared with OC (τ=35±3 ms; P <0.05) and YC (τ=33±6 ms; P <0.05) dogs. The percent diastole at which relaxation is complete was increased in ExDHF (116±30%) compared with OC (69±8%; P <0.05) and YC (35±5%; P <0.05) dogs. The coefficient of LV diastolic stiffness was similar in OC, YC, and ExDHF dogs. Diastolic pressures increased dramatically in response to increases in blood pressure. End-systolic LV stiffness was enhanced in ExDHF dogs and after load enhancement of myocardial performance was maintained. Arterial stiffness was increased in ExDHF dogs. Conclusions— Aged dogs with chronic hypertension exhibit LV hypertrophy and fibrosis with impaired LV relaxation but no increase in the coefficient of LV diastolic stiffness. LV systolic and arterial stiffness are increased, which may exacerbate load-dependent impairment of relaxation and contribute to increased filling pressures with hypertensive episodes. This model mimics many of the structural and functional characteristics described in the limited studies of human DHF and provides insight into the pathogenesis of DHF.

Previous studies in native tissues have produced conflicting data on the localization and metabolic fate of WT and ΔF508 cystic fibrosis transmembrane regulator (CFTR) in the lung. Combining immunocytochemical and biochemical studies utilizing new high-affinity CFTR mAbs with ion transport assays, we examined both 1) the cell type and region specific expression of CFTR in normal airways and 2) the metabolic fate of ΔF508 CFTR and associated ERM proteins in the cystic fibrosis lung. Studies of lungs from a large number of normal subjects revealed that WT CFTR protein localized to the apical membrane of ciliated cells within the superficial epithelium and gland ducts. In contrast, other cell types in the superficial, gland acinar, and alveolar epithelia expressed little WT CFTR protein. No ΔF508 CFTR mature protein or function could be detected in airway specimens freshly excised from a large number of ΔF508 homozygous subjects, despite an intact ERM complex. In sum, our data demonstrate that WT CFTR is predominantly expressed in ciliated cells, and ΔF508 CFTR pathogenesis in native tissues, like heterologous cells, reflects loss of normal protein processing.