Current concepts and controversies in meniscal imaging

Analyzing meniscal abnormalities on MR images depends on a thorough understanding of the normal appearance of meniscal structures and on strict adherence to the MR imaging criteria for meniscal tears. When proper MR imaging technique is followed, meniscal tears can be diagnosed more acutely than with clinical examination alone, even in the presence of associated ligament injuries. The value of MR imaging lies in its ability to reveal details of meniscal tears, including location, morphology, length, depth, and possible stability. If this MR imaging information can be synthesized, it will dramatically affect treatment planning by helping to predict meniscal tears that are potentially reparable and tears that might not need surgical intervention.     

Autoantibodies associated with lupus induced by diverse drugs target a similar epitope in the (H2A-H2B)-DNA complex.

IgG reactivity with the (H2A-H2B)-DNA complex, a subunit of the nucleosome, has been detected in many patients with lupus induced by procainamide and quinidine, but the similarity among the epitopes targeted by these antibodies in this heterogeneous patient group as well as the prevalence of this specificity in lupus induced by other drugs is unknown. Studies with histone-DNA complexes formed by sequential addition on a solid phase demonstrated that complexes containing single histones had negligible antigenicity, indicating that DNA stabilizes a protein epitope in the H2A-H2B dimer or that the complete epitope is generated by a surface feature involving H2A-H2B and DNA. F(ab')2 isolated from a patient with procainamide-induced lupus blocked greater than 90% of the anti-[(H2A-H2B)-DNA] reactivity in six of six sera from patients with lupus induced by procainamide, four of four quinidine-induced patients and in sera from patients with lupus induced by acebutolol, penicillamine, and isoniazid, but not methyldopa or auto-antibodies to the component macromolecules. Fab fragments purified from the IgG of two quinidine-induced lupus patients and patients with isoniazid- and procainamide-induced lupus retained 39% +/- 8% of their original IgG reactivity compared to 34 +/- 28% of the original anti-tetanus toxoid activity of Fab fragments in two of the same sera and two normal sera. These results indicate that anti-[(H2A-H2B)-DNA] does not require divalent antigen-antibody complexes for stability, and that the complete epitope is created by the monomeric, trimolecular histone-DNA complex. We conclude that despite their pharmacologic and chemical heterogeneity, many lupus-inducing drugs elicit near identical autoantibodies.     

Time-resolved immunofluorometric dual-label assay for simultaneous detection of autoantibodies to GAD65 and IA-2 in children with type 1 diabetes

BACKGROUND: Autoantibodies to glutamic acid decarboxylase (GADAs), specifically the 65-kDa isoform GAD65, and autoantibodies to the protein tyrosine phosphatase-like molecule IA-2 (IA-2As) predict development of diabetes. Our aim was to develop a time-resolved immunofluorometric (TR-IFMA) dual-label assay method for the simultaneous detection of these autoantibodies and to evaluate the diagnostic sensitivity of the method compared with single-label TR-IFMA and fluid-phase radiobinding assay (RBA) in screening children with type 1 diabetes. METHODS: We incubated combined biotinylated GAD65 and IA-2 proteins, glutathione S-transferase (GST)-IA-2, europium-labeled GAD65, terbium-labeled anti-GST antibody, and serum sample or calibrator and transferred aliquots to a streptavidin-coated 96-well microtiter plate for a second incubation. After washing, we added Delfia Enhancement solution to each well and measured the fluorescence of Eu. We developed the Tb fluorescence signal by use of the Delfia Enhancer solution and measured it. We analyzed serum samples from a cohort of 100 children with newly diagnosed type 1 diabetes. RESULTS: The correlation coefficients between the autoantibody concentrations measured by dual- and single-label TR-IFMA assays were 0.962 for GADA and 0.874 for IA-2A. Among 100 children with newly diagnosed diabetes, 65 of them were GADA positive in the dual-label assay, 64 in the single-label assay, and 66 in the RBA GADA assay. Seventy-four of the children tested positive for IA-2A in both TR-IFMA assay types, and 79 in the RBA IA-2A assay. CONCLUSIONS: The novel dual-label immunofluorometric assay performed comparably to the separate, single-label GADA and IA-2A assays in screening for beta-cell autoimmunity in children with newly diagnosed type 1 diabetes.     

Liver disease and diabetes mellitus

The liver plays an important role in the pathogenesis of NIDDM. More importantly to the clinician is the myriad of situations in which the care of the patient with diabetes is affected by or causes an effect to the liver. Patients with underlying diabetes can present with abnormal liver chemistries, which can represent findings as benign as hepatic steatosis or as severe as cirrhosis of the liver. The medications used to treat diabetes can be potent hepatotoxins. Several primary liver diseases are associated with increased risk of the development of diabetes. Epidemiologically, there seems to be a correlation between diabetes mellitus, the most common endocrinologic disease, and hepatitis C, the leading cause of chronic liver disease in the United States. In the management of end-stage liver disease, both cirrhosis and orthotopic liver transplantation promote glucose intolerance and diabetes in a number of patients through various mechanisms including insulin resistance and impaired insulin secretion. These relationships highlight both the importance of the liver as an endocrine organ and the multisystem aspects of the patient with diabetes mellitus.     

Life skills and subjective well-being of people with disabilities: a canonical correlation analysis

This study examined the canonical relationships between a set of life skill variables and a set of subjective well-being variables among a national sample of vocational rehabilitation clients in the USA. Self-direction, work tolerance, general employability, and self-care were related to physical, family and social, and financial well-being. This analysis also found that communication skill is related to family and social well-being, while psychological well-being is not related to any life skills in the set. The results showed that vocational rehabilitation services aimed to improve life functioning will lead to an improvement in subjective quality of life.     

Phase I-II trial of ONYX-015 in combination with MAP chemotherapy in patients with advanced sarcomas

ONYX-015 is a provisionally replication competent adenovirus with oncolytic activity in cells with malfunctioning p53. Sarcomas represent a rational target for this approach given the high frequency of p53 mutations (40-75%) and MDM-2 amplification (10-30%). We, therefore, undertook a phase I/II study of ONYX-015, days 1-5 every month administered intratumorally under radiographic guidance, in combination with MAP (mitomycin-C, doxorubicin, cisplatin) chemotherapy in patients with advanced sarcoma. Six patients were treated. Injected lesions included liver metastases in four patients and chest wall metastases in two patients. Sarcoma histologies were gastrointestinal stromal tumors (GIST, two patients), leiomyosarcoma (two patients), liposarcoma (one patient), and malignant peripheral nerve sheath tumor (1 patient). Dose escalation was performed from 10(9) plaque forming units (PFU)/dose (total dose of 5 x 10(9) PFU/cycle) to 10(10) PFU/dose (total dose of 5 x 10(10) PFU/cycle) without dose-limiting toxicity being encountered. Immunohistochemistry of the metastatic lesions prior to treatment showed that five out of six patients were positive for p53, while two patients also had mdm-2 overexpression. Adenoviral replication was detected in two out of six patient biopsies on day 5 of the first cycle, by in situ hybridization (ISH). Both patients were treated at the highest dose level. ONYX-015 viral DNA was detected by quantitative PCR in the plasma of 5/6 patients on day 5 of the first cycle, and up to day 12 (7 days after the last viral dose) in one patient who had extended sampling for viral kinetics performed, suggesting viral replication in sarcoma tissue. One patient with p53 mutation and MDM-2 amplification achieved a partial response to treatment that lasted 11 months. In conclusion, intratumoral administration of ONYX-015 in combination with MAP chemotherapy is well tolerated with no significant toxicity due to ONYX-015 being encountered. Detection of viral DNA in post treatment tumor specimens by ISH and detection of the ONYX-015 genome in the peripheral blood by quantitative PCR, up to 7 days after the last viral dose provide evidence for adenoviral replication. There was evidence of antitumor activity in one out of six patients. Further investigation of this approach in patients with recurrent sarcomas is warranted.     

Postmenopausal bleeding: etiology, evaluation, and management

Postmenopausal bleeding can be an alarming symptom for both the patient and the physician because, although in a majority of these cases no pathology is present, the risk of malignancy must be considered. It is important for the physician to fully understand the pathophysiology, differential diagnosis, and the methods of evaluating and treating this disorder in order to ensure the health and comfort of the patient.