Stephen H. Robinson

Assessing Clinical Skills of Residents with Standardized Patients

Current techniques do not provide a reproducible, reliable, or valid basis for assessing clinical skills. The need for large-scale direct observation and standardized assessment procedures has precluded development of better techniques. A project using standardized patients presenting with common clinical problems evaluated the skills of 336 internal medicine residents at 14 New England residency programs in 1289 standardized patient and resident encounters. Results indicated that reproducible assessment of the clinical skills could be achieved in approximately 1 day of testing time using standardized patients. Resident performance improved with years of training, and senior residents and those from programs with stronger reputations performed better and were more homogeneous in ability. Low correlations between standardized-patient-based measures of clinical skills and other evaluation techniques suggested that standardized patients provided unique information. Reactions of residents and faculty to standardized-patient-based evaluations were favorable.

Efficacy of platelet transfusions in immune thrombocytopenia

Records of 11 patients with immune thrombocytopenia (idiopathic and quinidine-induced) were evaluated retrospectively for response to platelet transfusion. Good post-transfusion platelet count increments occurred on one or more occasions in seven of the 11 patients, with 13 of 31 platelet transfusions (42 percent) resulting in immediate post-transfusion increments of 20,000/mm3 or more. Next-day platelet counts remained elevated in association with five of these 13 transfusions. This study demonstrates that, contrary to common opinion, platelet transfusions can raise the platelet count in many patients with immune thrombocytopenia, and therefore may be beneficial in actively bleeding or high-risk patients with this disorder.

Transferrin receptors in developing murine erythroid cells.

Summary. Techniques of cell separation were used to isolate murine erythroid cells at different stages of maturation. The number of transferrin receptors in these cell populations was assayed by measuring binding of 125I‐labelled transferrin. Nearly 23 times as many receptors were found in the least mature cells, chiefly pronormoblasts, as in reticulocytes. Iron transport, determined by measurement of the rate of 59Fe uptake from 59Fe‐labelled transferrin, was proportional to the number of receptors at all stages of differentiation. Electron microscope radioautographic studies of the interaction of 125I‐labelled transferrin with erythroid precursor cells demonstrated that 15–35% of cell associated transferrin was intracellular in erythroid precursors.

Mobilization of iron from the plasma membrane of the murine reticulocyte. The role of ferritin

1. Plasma membranes prepared by pre-incumbation of mouse reticulocytes with 125I, 59Fe-labeled murine transferrin were able to release 59Fe in preference to 125I when incubated in the presence of murine reticulocyte cytosol, demonstrating that the latter mobilized iron which had been dissociated from transferrin. 2. 59Fe in cytosol was associated with at least two components in addition to hemoglobin, a high molecular weight component, identified as ferritin by specific immunoprecipitation, and an as yet unidentified, low molecular weight component of approx 17 00. 3. Ferritin itself, in the absence of added cytosol, was abloe to mobilize 59Fe from s9Fe-labeled reticulocyte plasma membranes. 4. Lysates of reticulocytes synthesized 59Fe-labeled heme when incubated with 59Fe-labeled ferritin. 5. These findings reflect a pathway of iron uptake and incorporation into heme in which ferritin plays an active role.

Transferrin receptors, iron transport and ferritin metabolism in Friend erythroleukemia cells.

Abstract Four aspects of iron metabolism were studied in cultured Friend erythroleukemia cells before and after induction of erythroid differentiation by dimethyl sulfoxide. (1) The binding of 125I-labeled transferrin was determined over a range of transferrin concentrations from 0.5 to 15 μM. Scatchard analysis of the binding curves demonstrated equivalent numbers of transferrin binding sites per cell: 7.78 ± 2.41 · 105 in non-induced cells and 9.28 ± 1.57 · 105 after 4 days of exposure to dimethyl sulfoxide. (2) The rate of iron transport was determined by measuring iron uptake from 59Fe-labeled transferrin. Iron uptake in non-induced cells was approx. 17 000 molecules of iron/cell per min; 24 h after addition of dimethyl sulfoxide it increased to 38 000, and it rose to maximal levels of approx. 130 000 at 72 h. (3) Heme synthesis, assayed qualitatively by benzidine staining and measured quantitatively by incorporation of 59Fe or [2-14C]glycine into cyclohexanone-extracted or crystallized heme, was not detected until 3 days after addition of dimethyl sulfoxide, when 12% of the cells were stained by benzidine and 6 pmol 59Fe and 32 pmol [2-14C]glycine were incorporated into heme per 108 cells/h. After 4 days, 60% of the cells were benzidine positive and 34 pmol 59Fe and 90 pmol [2-14C]glycine were incorporated into heme per 108 cells/h. (4) The rate of incorporation of 59Fe into ferritin, measured by immunoprecipitation of ferritin by specific antimouse ferritin immunoglobulin G, rose from 4.4 ± 0.6 cells to 18.4 ± 1.3 pmol 59Fe/h per 108 cells 3 days after addition of dimethyl sulfoxide, and then fell to 11.6 ± 3.1 pmol 4 days after dimethyl sulfoxide when heme synthesis was maximal. These studies indicate that one or more steps in cellular iron transport distal to transferrin binding is induced early by dimethyl sulfoxide and that ferritin may play an active role in iron delivery for heme synthesis.

Lymphoma with Autoimmune Neutropenia and Hepatic Sinusoidal Infiltration: A Syndrome

A relation between lymphoma and autoimmune neutropenia, unlike autoimmune hemolytic anemia and idiopathic thrombocytopenic purpura, has not previously been well documented. We report a patient with a disorder presenting as autoimmune agranulocytosis, splenomegaly, and infiltration of the hepatic sinusoids by lymphocytes. Antineutrophil antibodies were present. Over a 2 1/2-year period, the illness progressed to an aggressive, poorly differentiated lymphocytic lymphoma with terminal liver failure and fibrosis. Peripheral blood lymphocyte markers identified the tumor as a proliferation of T-cells of the helper class. A review of previous literature disclosed other reports of similar patients who had neutropenia, a lymphoproliferative illness, and hepatic disease. Our case is representative of a previously unrecognized syndrome characterized by autoimmune neutropenia in the setting of a lymphoproliferative disorder of T cells, with a predilection for liver involvement.

Does the mean corpuscular volume help physicians evaluate hospitalized patients with anemia

The authors analyzed the value of using mean corpuscular volume (MCV) as a guide for selecting tests for further evaluation of anemia in hospitalized patients. Of the 2,082 patients with anemia admitted to the medical service of a teaching hospital over one year, 655 (31%) had further diagnostic tests to evaluate the cause of the anemia. Within this group of 655 patients, 399 (61%) had normal MCVs. Over half the patients with abnormal serum vitamin B12, folate, or ferritin levels, or with low serum iron (Fe) levels with elevated total iron-binding capacity (TIBC), did not have the MCVs expected according to the classification of anemia proposed by Wintrobe. Furthermore, 5% of patients with evidence of iron deficiency had high MCVs, and about 12% of patients with decreased vitamin B12 levels had low MCVs. The MCV was quite specific in identifying patients who had low ferritin levels: specificity was 83%; however, sensitivity was only 48%. The MCV was also specific (88%) for identifying patients who had low Fe with elevated TIBC; however, sensitivity was only 43%. The MCV was poor in identifying patients with abnormalities of serum vitamin B12 and folate levels. In this study the MCV did not provide sufficient diagnostic accuracy to be a useful criterion for the selection of more definitive tests in the evaluation of anemia in hospitalized patients.

Iron transport from sepharose-bound transferrin

Abstract To ascertain whether transferrin need enter the reticulocyte to deliver its iron after the association of transferrin with the cell membrane, { 125 I, 59 Fe-}labeled transferrin was covalently bound to Sepharose beads. Iron uptake from Sepharose-bound transferrin into rabbit reticulocytes was about 9% that from free transferrin while heme synthesis was more efficient at nearly 19%. Similar results were obtained with murine transferrin and murine reticulocytes. These results indicate that the entrance of transferrin inside the cell is not an obligatory step in the process of iron uptake in rabbit and murine reticulocytes.

Atypical lymphoma with prolonged systemic remission after splenectomy. Description of three cases.

Abstract Three patients with an unusual clinicopathologic picture and a striking response to splenectomy are described. All three presented with fever and severe systemic symptoms, pancytopenia and splenomegaly. Two of the patients had hypogammaglobulinemia and absent delayed hypersensitivity. Atypical lymphohistiocytic proliferation consistent with lymphoma was present in the spleen in all three patients, and also in the bone marrow and abdominal lymph nodes in two. Splenectomy led to prompt and prolonged clinical remissions in all three patients, possibly of a permanent nature in one.

Chronic granulomatous disease. Expression of the metabolic defect by in vitro culture of bone marrow progenitors.

Chronic granulomatous disease (CGD), an often fatal syndrome of recurrent infections results from the inability of patients peripheral blood phagocytic leukocytes to generate superoxide despite otherwise normal phagocytic functions such as ingestion and degranulation. Circulating granulocytes and monocytes are the progeny of bone marrow progenitor cells, colony-forming units in culture. We compared the function of cells grown in two different in vitro cuture systems from the bone marrow of a CGD patient with those from normal subjects. The cells of normal colony-forming unit in culture colonies grown in semisolid medium reduced nitroblue tetrazolium dye when stimulated by phorbol myristate acetate; none of the cells from colonies derived from CGD marrow did so. Cells grown in liquid suspension culture from normal marrow generated superoxide nearly as well as normal peripheral blood granulocytes; those from CGD marrow produced no superoxide, similarly cultured cells from both normal and CGD marrow ingested opsonized bacteria at rates equal to peripheral blood granulocytes. CGD marrow-derived cells showed increased exocytic degranulation relative to both normal marrow-derived cells and normal peripheral blood granulocytes. These studies demonstrate that the basic functional characteristics of CGD are embedded in the genetic program of granulocyte progenitors.