Diabetes mellitus and pernicious anemia: interrelated therapeutic triumphs discovered shortly after William Osler's death.

William Osler died on December 29, 1919, at the age of 70. Less than 1 year later, Frederick Grant Banting began a research project at the University of Toronto to find a treatment for diabetes mellitus. John James Rickard Macleod, director of physiology, gave him space, funding, and supplies.

Early stage IgD multiple myeloma in a 50-year-old man.

We present the case of a 50-year-old Hispanic man who presented to the emergency department with an acute right femur fracture after 3 months of intermittent discomfort in the right leg. He was eventually diagnosed with immunoglobulin D (IgD) multiple myeloma, a rare class of myeloma that is often of advanced stage at diagnosis. Fortunately, our patient was stage I at diagnosis and did not have hypercalcemia, anemia, or renal insufficiency, as is common with myeloma.

Recommendations for the diagnosis and initial evaluation of patients with Waldenström Macroglobulinaemia: A Task Force from the 8th International Workshop on Waldenström Macroglobulinaemia.

The diagnosis of Waldenström macroglobulinaemia (WM) can be challenging given the variety of signs and symptoms patients can present. Furthermore, once the diagnosis of WM is established, the initial evaluation should be thorough as well as appropriately directed. During the 8th International Workshop for WM in London, United Kingdom, a multi-institutional task force was formed to develop consensus recommendations for the diagnosis and initial evaluation of patients with WM.

John M. T. Finney: distinguished surgeon and Oslerphile.

John Finney (1863-1942) was born near Natchez, Mississippi. After receiving his medical degree from Harvard, he interned at Massachusetts General Hospital and then went to Baltimore to become one of the first interns at the new Johns Hopkins Hospital. He met William Osler the day the hospital opened and became a lifelong admirer of "the Chief.

Advance care planning knowledge and documentation in a hospitalized cancer population.

To have a better understanding of our patients' knowledge of advance directive planning and execution, as well as communication with their oncologists regarding their wishes, we conducted a survey on our inpatient hematology-oncology services. A total of 68 unique hospitalized patients with a diagnosis of cancer completed surveys. Surveys were given to all oncology patients regardless of their reason for admission.

Role of plasmapheresis in Waldenström's macroglobulinemia.

Despite the absence of randomized trials, plasmapheresis has consistently demonstrated efficacy in treatment of Waldenström's macroglobulinemia (WM) patients with hyperviscosity syndrome (HVS). This procedure can promptly reverse most clinical manifestations of serum HVS. Early diagnosis is crucial and usually can be made from the funduscopic exam.

Results of an educational program to promote the use of pooled instead of single-donor platelet transfusions.

Transfusion of platelets is commonly indicated in the inpatient oncology setting. These platelets are obtained either through apheresis from a single donor or pooled from the whole blood of several donors. The amount of transfused platelets, infection risk, incidence of alloimmunization, and increases in posttransfusion platelet count are similar for these two platelet products.

Response assessment in Waldenström macroglobulinaemia: update from the VIth International Workshop.

This report represents a further update of the consensus panel criteria for the assessment of clinical response in patients with Waldenström macroglobulinaemia (WM). These criteria have been updated in light of further data demonstrating an improvement in categorical responses with new drug regimens as well as acknowledgement of the fact that such responses are predictive of overall outcome. A number of key changes are proposed but challenges do however remain and these include the variability in kinetics of immunoglobulin M (IgM) reduction with different treatment modalities and the apparent discrepancy between IgM and bone marrow/tissue response noted with some regimens.

Long-term follow-up of liver transplantation for Budd-Chiari syndrome with antithrombotic therapy based on the etiology.

Background: Because myeloproliferative disorders (MPDs) are a frequent cause of Budd-Chiari syndrome (BCS), treatment directed toward altering platelet production and function may be more rational and effective than anticoagulation after liver transplantation.

Methods: We reviewed data on 25 patients who received liver transplantation for BCS at our institution from 1987 to 2007. Posttransplant antithrombotic treatment was based on the cause of BCS: 17 patients with MPDs received hydroxyurea/aspirin; 5 received warfarin; and 3 (2 whose hypercoagulable disorder was corrected and 1 with sarcoidosis) received no therapy.

Pathogenesis and morbidity of autoantibody syndromes in Waldenstrom's macroglobulinemia.

A number of autoantibody syndromes have been identified that are mediated by monoclonal macroglobulins. Chronic cold agglutinin disease (CAD), mixed cryoglobulinemia (MC), and various polyneuropathies produce symptoms and signs such as cold sensitivity and sensorimotor neuropathies that bring the patients to attention ("the patients tell you"). Many of these patients would be classified as having monoclonal gammopathy of undetermined significance (MGUS) were it not for the consequences of antigen-antibody interaction.

Biopsy-proven mantle cell lymphoma in brain parenchyma.

Brain parenchymal involvement by mantle cell lymphoma is rare and confers a grim prognosis. More commonly, patients with central nervous system manifestations of mantle cell lymphoma have leptomeningeal involvement on radiographic studies with malignant cells found in the cerebrospinal fluid. Risk factors for central nervous system involvement include a high proliferation index, bone marrow involvement, and blastoid morphology.

Heating up cold agglutinins.

In this issue of Blood, Berentsen and coworkers describe a high response rate which is durable in some patients who receive combination fludarabine and rituximab for chronic cold agglutinin disease (CAD). If confirmed, this is a significant advance in therapy for a frequently difficult clinical problem.

Comparison of serum immunofixation electrophoresis and free light chain assays in the detection of monoclonal gammopathies.

Background: Diagnosis of monoclonal gammopathies (MGs) is determined by demonstration of a monoclonal immunoglobulin molecule or chain in serum and/or urine. Previous results on immunofixation electrophoresis (IFE) and quantitative free light chain (FLC) measurements have been conflicting.

Patients And Methods: The purpose of this study was to compare IFE with serum FLC assays in the detection of MG.

Subcutaneous beta2-microglobulin amyloid shoulder nodulesin a long-term hemodialysis patient.

beta2-Microglobulin accumulation with resultant tumor formation is a known albeit rare complication of long-term hemodialysis. Although these tumors may occur in various locations, subcutaneous shoulder nodules are very infrequent. We report a patient with end-stage kidney failure who had been on hemodialysis for 16 years and noted left shoulder nodules after initiation of hemodialysis; these nodules had slowly grown larger.

Growth inhibition of human multiple myeloma cells by an oncolytic adenovirus carrying the CD40 ligand transgene.

Purpose: The growth-inhibitory activity of recombinant CD40 ligand (CD40L) is well documented in human multiple myeloma (MM). We examined MM-targeted delivery of CD40L by a conditional replicative oncolytic adenovirus, AdEHCD40L.

Experimental Design: The growth-regulatory activity of AdEHCD40L was determined in vitro and in vivo.

Urinary findings in renal light chain-derived amyloidosis and light chain deposition disease.

Background: Early recognition of light chain-derived (AL) amyloidosis and light chain deposition disease (LCDD) is essential for optimal therapy. However, clinical and laboratory manifestations of these unusual conditions often go unrecognized. Renal protein deposits in AL amyloidosis and LCDD can cause both heavy albuminuria and Bence Jones proteinuria.

Waldenström's macroglobulinemia: hyperviscosity syndrome and cryoglobulinemia.

Hyperviscosity syndrome (HVS) is a common manifestation of Waldenström's macroglobulinemia (WM). Patients with HVS have skin and mucosal bleeding, retinopathy with visual disturbances, and a variety of neurologic disorders. HVS can be diagnosed from physical examination by identifying the characteristic retinal venous engorgement ("sausaging") on funduscopic inspection.

Antitumor activity of an oncolytic adenoviral-CD40 ligand (CD154) transgene construct in human breast cancer cells.

Purpose: CD40 ligand (CD40L, CD154) plays a central role in immunoregulation and also directly modulates epithelial cell growth and differentiation. We previously showed that the CD40 receptor is commonly expressed in primary breast cancer tissues. In this proof-of-principle study, we examined the breast cancer growth-regulatory activities of an oncolytic adenoviral construct carrying the CD40L transgene (AdEHCD40L).

Reversibility of pamidronate-associated glomerulosclerosis.

Bisphosphonates such as pamidronate are widely used in the treatment of patients with lytic bony lesions secondary to breast cancer or multiple myeloma, yet they have been associated with deterioration of renal function and histopathological changes in the kidney. There have been recent reports associating the use of pamidronate with the development of the collapsing variant of focal segmental glomerulosclerosis (CFSGS), a rapidly progressive variant of focal segmental glomerulosclerosis that leads to end-stage renal disease. We describe five patients who developed worsening renal function, proteinuria, and nephrotic syndrome while taking pamidronate; three of them had biopsy-proven CFSGS.