Citations

We have examined the relief from pain and the functional outcome in 18 patients who underwent resection arthroplasty of the shoulder as a salvage operation between 1988 and 2002. The indications included failed shoulder replacement in 17, with infection in 13, and chronic septic arthritis in one. The mean follow-up was 8.3 years (2.5 to 16.6). Two intra-operative fractures of the humerus occurred, both of which healed. The level of pain was significantly decreased (t-test, p < 0.001) but five patients continued to have moderate to severe pain. The mean active elevation was 70° (0° to 150°) postoperatively and represented an improvement from 39° (0° to 140°) (t-test, p = 0.003), but internal and external rotation were hardly changed. The mean number of positive answers on the 12-question Simple Shoulder Test was 3.1 (0 to 12) but the shoulder was generally comfortable when the arm was positioned at rest by the side. The mean post-operative American Shoulder and Elbow Surgeon’s score was 36 (8 to 73). Despite applying this procedure principally to failed shoulder replacements, the results were similar to those reported in the literature for patients after severe fracture-dislocation. Reduction of pain is possible in one half to two-thirds of patients. The outcome of this operation in providing relief from pain cannot be guaranteed, but the shoulder is usually comfortable at rest, albeit with profound functional limitations.

Coronary artery disease (CAD) accounts for a large fraction of the morbidity, mortality, and cost of diabetes. Recognizing this, nearly 10 years ago the American Diabetes Association published a consensus recommendation that clinicians consider a risk factor–guided screening approach to early diagnosis of CAD in both symptomatic and asymptomatic patients. Subsequent clinical trial results have not supported those recommendations. Since the prior consensus statement, newer imaging methods, such as coronary artery calcium scoring and noninvasive angiography with computed tomography (CT) techniques, have come into use. These technologies, which allow quantitation of atherosclerotic burden and can predict risk of cardiac events, might provide an approach to more widespread coronary atherosclerosis screening. However, over this same time interval, there has been recognition of diabetes as a cardiovascular disease (CVD) equivalent, clear demonstration that medical interventions should provide primary and secondary CVD risk reduction in diabetic populations, and suggestive evidence that percutaneous coronary revascularization may not provide additive survival benefit to intensive medical management in patients with stable CAD. This additional evidence raises the question of whether documenting asymptomatic atherosclerosis or ischemia in people with diabetes is warranted. More data addressing this issue will be forthcoming from the BARI 2-D (Bypass Angioplasty Revascularization Investigation 2 Diabetes) trial. Until then, for patients with type 2 diabetes who are asymptomatic for CAD, we recommend that testing for atherosclerosis or ischemia, perhaps with cardiac CT as the initial test, be reserved for those in whom medical treatment goals cannot be met and for selected individuals in whom there is strong clinical suspicion of very-high-risk CAD. Better approaches to identify such individuals based on readily obtained clinical variables are sorely needed.

Lenalidomide is approved for red blood cell (RBC) transfusion-dependent anemia due to low or intermediate-1 (int-1) risk myelodysplastic syndromes (MDSs) associated with a chromosome 5q deletion with or without additional cytogenetic abnormalities. We report results of a multicenter, phase 2 trial evaluating lenalidomide therapy for transfusion-dependent patients with low- or int-1–risk MDS without deletion 5q. Eligible patients had 50 000/mm3 or more platelets and required 2 U or more RBCs within the previous 8 weeks; 214 patients received 10 mg oral lenalidomide daily or 10 mg on days 1 to 21 of a 28-day cycle. The most common grade 3/4 adverse events were neutropenia (30%) and thrombocytopenia (25%). Using an intention-to-treat analysis, 56 (26%) patients achieved transfusion independence (TI) after a median of 4.8 weeks of treatment with a median duration of TI of 41.0 weeks. In patients who achieved TI, the median rise in hemoglobin was 32 g/L (3.2 g/dL; range, 10-98 g/L [1.0-9.8 g/dL]) from baseline. A 50% or greater reduction in transfusion requirement occurred in 37 additional patients, yielding a 43% overall rate of hematologic improvement (TI response +‖≥ 50% reduction in transfusion requirement). Lenalidomide has clinically meaningful activity in transfusion-dependent patients with low- or int-1–risk MDS who lack the deletion 5q karyotypic abnormality. This study is registered at www.clinicaltrials.gov as no. NCT00064974.

OBJECTIVE—Triglyceride-rich lipoproteins, primarily chylomicrons, can contribute to plasma free fatty acid (FFA) concentrations via spillover of fatty acids during intravascular hydrolysis into the venous effluent of some tissues. The present study was undertaken to determine whether spillover occurs in the splanchnic bed of humans. RESEARCH DESIGN AND METHODS—Arterial and hepatic venous blood was sampled in postabsorptive (n = 6; study A) and postprandial (n = 5; study B) obese humans during infusion of carbon-labeled (14C or 13C) oleate and 3H triolein, the latter incorporated into a lipid emulsion as a surrogate for chylomicrons. Spillover was determined by measuring production of 3H oleate. RESULTS—Splanchnic spillover was higher than nonsplanchnic systemic spillover in both study A (60 ± 7 vs. 24 ± 6%; P &lt; 0.01) and study B (54 ± 3 vs. 16 ± 5%; P &lt; 0.005). Because portal vein sampling is not feasible in humans, assumptions regarding actual spillover in nonhepatic splanchnic tissues were required for the spillover calculation. A mathematical model was developed and demonstrated that nonhepatic splanchnic spillover rates in study A and study B of 69 and 80%, respectively, provided the best fit with the data. There was preferential splanchnic uptake of triglyceride fatty acids compared with FFAs in study B (fractional extraction 61 ± 3 vs. 33 ± 2%; P &lt; 0.005). CONCLUSIONS—These data confirm previous studies indicating that the transport of FFAs and triglyceride fatty acids are partitioned in tissues and indicate that splanchnic spillover from triglyceride-rich lipoproteins may be a significant source of both portal venous and systemic FFAs.

Abstract The c-jun-NH2-kinases (JNK) play a critical role in tumor promoter–induced cell transformation and apoptosis. Here, we showed that the nuclear factor of activated T3 (NFAT3) is phosphorylated by JNK1 or JNK2 at Ser213 and Ser217, which are located in the conserved SP motif. The transactivation domain of NFAT3 is found between amino acids (aa) 113 and 260 and includes the phosphorylation targets of JNK1 and JNK2. NFAT3 transactivation activity was suppressed in JNK1−/− or JNK2−/− mouse embryonic fibroblast (MEF) cells compared with wild-type MEF cells. Moreover, a 3xNFAT-luc reporter gene assay indicated that NFAT3 transcriptional activity was increased in a dose-dependent manner by JNK1 or JNK2. Double mutations at Ser213 and Ser217 suppressed NFAT3 transactivation activity; and SP600125, a JNK inhibitor, suppressed NFAT3-induced 3xNFAT-luciferase activity. Knockdown of JNK1 or JNK2 suppressed foci formation in NIH3T3 cells. Importantly, ectopic expression of NFAT3 inhibited AP-1 activity and suppressed foci formation. Furthermore, knockdown of NFAT3 enhanced Ras-JNK1 or JNK2-induced foci formation in NIH3T3 cells. Taken together, these results provided direct evidence for the anti-oncogenic potential of the NFAT3 transcription factor. [Cancer Res 2007;67(18):8725–35]

Abstract Introduction: Colorectal adenomas and other types of polyps are commonly used as end points or risk factors in epidemiologic studies. However, it is not known how accurately patients are able to self-report the presence or absence of adenomas following colonoscopy. Methods: Participants in the Colon Cancer Family Registry provided self-reports of recent colorectal cancer (CRC) screening activity, and whether or not they had ever been told they had a polyp. Positive and negative predictive values for polyp self-report were calculated by comparing medical records with self-reports from 488 participants. Results: The positive predictive value for self-reported polyp was 80.9%, and the negative predictive value was 85.8%. The predictive values did not differ by age group or sex, but participants with a previous diagnosis of CRC had a lower negative predictive value (76.2%) than participants with no personal history of CRC (89.0%; P = 0.04). Conclusions: Predictive values for self-reports of polyps are fairly high, but researchers needing accurate polyp data should obtain medical record confirmation. Pursuing medical records on only those participants self-reporting a polyp could result in an underestimation of the polyp prevalence in a study population. (Cancer Epidemiol Biomarkers Prev 2007;16(9):1898–901)

AbstractEvidence for familial aggregation of glioma has been documented in both case-control and cohort studies and occurs apart from the well-described rare inherited genetic syndromes involving glioma: neurofibromatosis type 1 and 2, tuberous sclerosis, Turcot's syndrome, and Li-Fraumeni syndrome. Nonsyndromic glioma families have been studied but no genes have been identified in the two published linkage studies of familial glioma probably due to the small number of families. Because glioma is a rare but devastating cancer, and a family history of glioma has been observed in ∼5% of the cases, we initiated an international consortium to identify glioma families not affected by syndromes to better understand the inherited factors related to this disease. The international consortium GLIOGENE is an acronym for “glioma gene” and includes 15 research groups in North America, Europe, and Israel to study familial glioma. The overarching goal is to characterize genes in glioma families using a genome-wide single-nucleotide polymorphism approach and conducting linkage analysis to identify new genomic regions or loci that could harbor genes important for gliomagenesis. Here, we review the rationale for studying familial glioma and our proposed strategy for the GLIOGENE study. (Cancer Epidemiol Biomarkers Prev 2007;16(9):1730–4)

AbstractPurpose: Passive immunotherapy with antitumor antibodies has the potential to induce active tumor immunity via the opsonic enhancement of immunogenicity of tumor antigen. We have assessed whether immune sensitization to the HER-2/neu tumor antigen occurs during treatment with the anti-HER-2/neu monoclonal antibody trastuzumab.Experimental Design: Twenty-seven patients treated with trastuzumab and chemotherapy were assessed for the induction of HER-2/neu–specific immunity. Sera and peripheral blood mononuclear cells obtained before and after trastuzumab therapy were compared for the presence of anti-HER-2/neu endogenous Igλ antibodies and HER-2/neu–specific CD4 responses by ELISA and enzyme-linked immunospot, respectively.Results: Anti-HER-2/neu antibodies were detectable in 8 of 27 (29%) patients before trastuzumab treatment and in 15 of 27 (56%) patients during trastuzumab treatment. In the overall study population, anti-HER-2/neu humoral responses significantly increased during therapy (P &lt; 0.001) and were not associated with development of an anti-idiotypic response. In 10 evaluable individuals, 6 showed augmented HER-2/neu–specific CD4 T-cell responses during therapy. Of the 22 individuals treated for metastatic disease, those patients showing objective clinical responses exhibited more frequent (P = 0.004) and larger (P = 0.006) treatment-associated anti-HER-2/neu humoral responses.Conclusion: Humoral immune sensitization occurs during treatment with chemotherapy and trastuzumab. Further studies are warranted to investigate whether augmented anti-HER-2/neu humoral and cellular immunity contributes mechanistically to clinical outcome.