Localized insulin amyloidosis with use of concentrated insulin: a potential complication.

BACKGROUND: Insulin-derived amyloidosis is a rare form of amyloidosis composed of insulin fibrils. The pH and concentration of insulin are known to influence the conformational state of the insulin hormone, with an increasing concentration favouring a more complex conformation. Concentrated insulin delivers a large amount of insulin to a localized area, raising the possibility of inducing conformational changes, forming insulin fibrils and leading to localized insulin amyloidosis. CASE REPORT: A middle-aged woman with long history of Type 2 diabetes mellitus, treated with concentrated human insulin (U-500 insulin) presented with nodular lesions at the site of her daily insulin injections. A punch biopsy of the nodules showed skin with dermal amyloidosis staining favourably with Congo Red stain. The amyloid tumours were resected and areas positive for Congo Red stain were sent for liquid chromatography tandem mass spectrometry, which showed a peptide profile consistent with amyloid insulin. CONCLUSION: Concentrated insulin was first introduced in 1952, however, it is only over the last two decades that it has been used increasingly, in congruence with the increasing incidence of obesity and diabetes mellitus seen in the USA. Only a few cases of insulin amyloidosis at the site of injection have been described in literature. With the increase in the use of insulin, this complication seems to be occurring more frequently. This is the first case report of a person with diabetes mellitus who developed localized insulin amyloidosis with the use of concentrated insulin, and points towards a potential complication of developing insulin amyloidosis with the use of concentrated insulin.

Racial differences in primary cytogenetic abnormalities in multiple myeloma: a multi-center study.

We examined four clinically assessed cytogenetic subtypes (t(11;14), t(4;14), monosomy 13/del13q and monosomy 17/del17p in 292 black patients with newly diagnosed multiple myeloma (MM) from four medical centers, who had fluorescent in situ hybridization testing results available in their medical records. We then compared the prevalence of these abnormalities with a previously characterized Mayo Clinic cohort of 471 patients with MM. We found a significant difference in the prevalence of the t(11;14) immunoglobulin heavy chain (IgH) translocation between blacks and whites, 6.5% versus 17.6%, respectively, P<0.0001. Blacks also had lower rates of the t(4;14) IgH translocation, (5.5% versus 10%); monosomy 13/del13q (29.1 versus 49.3%); and monosomy 17/del17p (7.9% versus 13%). Consequently, 63.4% of blacks versus 34.6% of whites did not have any of the four abnormalities that we studied, P<0.001. As almost all MM is associated with either an IgH translocation or trisomies, we hypothesize that MM in blacks is associated with either excess prevalence of either the trisomic (hyperdiploid) form of MM or an IgH translocation besides t(11;14) or t(4;14). We conclude that there are significant differences in the cytogenetic subtypes of MM that occur in blacks and whites.

High-dose melphalan with autotransplantation for refractory multiple myeloma: results of a Southwest Oncology Group phase II trial.

PURPOSE: To evaluate high-dose melphalan followed by autologous stem-cell transplantation in patients with refractory multiple myeloma. PATIENTS AND METHODS: Multiple myeloma patients with alkylating agent or vincristine/doxorubicin/dexamethasone-refractory disease were eligible for the phase II multi-institutional Southwest Oncology Group trial S8993. Patients up to age 70 years were enrolled between April 15, 1991, and May 1, 1996. Patients without prior stem-cell collection were primed with high-dose cyclophosphamide (HD-CTX; 6 g/m(2)) and granulocyte-macrophage colony-stimulating factor. After stem-cell procurement, patients received melphalan 200 mg/m(2) with autologous transplantation. Upon recovery from melphalan, patients were to receive interferon alfa-2b until relapse. RESULTS: Seventy-two patients were enrolled onto S8993; five were ineligible and one received no therapy. Of the 66 assessable patients, 56 patients underwent the transplant procedure; 54 were assessable for response and 56 for toxicity. The response to HD-CTX (n = 37) included three complete remissions (CRs; 8%) and five partial remissions (PR; 14%); response to melphalan (n = 54) included 16 CRs (30%) and 19 PRs (35%), for an overall CR and >/= PR (n = 66; intent-to-treat) of 27% and 58%, respectively. Toxicities included six treatment-related deaths: two during HD-CTX and four during transplantation. The median progression-free survival (PFS) and overall survival (OS) durations on an intent-to-treat basis from transplant registration was 11 months and 19 months (95% confidence interval, 14 to 29 months), respectively. The 3-year actuarial PFS and OS rates were 25% and 31%, respectively. CONCLUSION: High-dose therapy with melphalan 200 mg/m(2) is feasible with high response rates (58% overall) and an OS of 19 months in patients with refractory multiple myeloma.

Social factors affecting interest in participating in a prostate cancer chemoprevention trial.

PURPOSE: A sample survey was conducted to assess the feasibility of recruiting participants, specifically African Americans, and to determine social factors influencing participation in a prostate cancer chemoprevention trial. METHODS: A convenience sample of adults visiting a hospital was identified and asked to participate in the survey. The survey included brief background information about prostate cancer and questions concerning four independent (age, marital status, race, insurance status) and three dependent (willingness to join a trial, involvement in long-term drug intake, interest in receiving more information) variables. RESULTS: The study analyzed 165 responses. Of the 165 respondents, 67% were African American. Marital status was a significant predictor of general willingness to participate (p = 0.047) for male respondents. No significant predictor was found for female respondents. Furthermore, for men, ethnicity/race showed a significant difference (30% white men vs 70% of minority men) for willingness to take the pills. CONCLUSION: The results suggest that African Americans are receptive to participating in chemopreventive trials. Thus, future studies exploring chemoprevention trials as an effective tool for reaching African Americans are warranted.

Peripheral blood stem cell collection with reduced platelet loss to the patient/donor.

Apheresis procedures that optimize peripheral blood stem cell (PBSC) harvesting also result in a significant loss of platelets to the patient/donor because of their similar densities. We compared the percent drop in platelet count and hemoglobin concentration in the patients before and after PBSC collection using two different collection chambers with the CS-3000. A modified plateletpheresis procedure was utilized. Seven patients underwent 38 PBSC collections during steady state hematopoiesis using the standard A-35 collection chamber. At the end of the procedure, a second low-speed centrifugation of the PBSC concentrate was performed in the manual mode, with siphoning out and return of the PRP to the patient through a transfer pack. For 14 patients who underwent 113 PBSC collections, a small volume collection chamber (SVCC) was substituted for the A-35 chamber and the second centrifugation step was omitted. These patients were also primed with 4 g/m2 of cyclophosphamide. The percent drop in platelet count in the patients after the collection procedures was significantly less in the SVCC group (20.4 +/- 9.1 vs. 36.0 +/- 12.3, P = 0.000), even after correction for the difference in the volume of blood processed between the two groups (3.2 +/- 1.4 vs. 3.9 +/- 1.3, P = 0.006). The percent drop in hemoglobin concentration was also less with the SVCC both before (5.4 +/- 3.8 vs. 11.7 +/- 3.0, P = 0.000) and after (0.8 +/- 0.6 vs. 1.3 +/- 0.3, P = 0.000) correction for the difference in the volume of blood processed.(ABSTRACT TRUNCATED AT 250 WORDS)

Toxic epidermal necrolysis following bone marrow transplantation.

Toxic epidermal necrolysis (TEN) has been reported following bone marrow transplantation. This rare and unfortunate complication may portend fatal outcome. We report on a patient with an allogeneic bone marrow transplant and graft-versus-host disease (GVHD) in whom TEN subsequently developed. In contrast to a previously reported case, our patient survived and is well two years after bone marrow engraftment.

Disseminated histoplasmosis complicating bone marrow transplantation.

A patient receiving allogeneic bone marrow transplant for treatment of acute myelomonocytic leukemia died on the 78th post-transplant day with clinically unrecognized disseminated histoplasmosis. Granulomas and Histoplasma organisms were found in the histologic sections of the marrow aspirate. Patients from endemic areas referred to transplant centers may be at high risk for disseminated histoplasmosis when treated with long-term prednisone for graft-versus-host disease. Aspiration of bone marrow with use of clot sections is a minimally invasive, sensitive, and rapid means of detecting granulomatous infection in such febrile immunosuppressed hosts. Disseminated histoplasmosis has not been described previously as a complication of bone marrow transplantation.

Bone fragment emboli in the lungs of patients undergoing bone marrow transplantation.

In a study of biopsy and autopsy specimens from the lungs of patients undergoing bone marrow transplantation, we noted the presence of hematoxyphilic material within pulmonary vessels. This material, which consisted of calcium, was observed in arteries, arterioles, and capillaries. There were 12 specimens (two from open lung biopsies and 10 from autopsies) and all showed these emboli of calcified fragments. These bony spicules are derived from bone fragments in the grafted marrow and not from degenerative changes in the fatty marrow. The emboli are not associated with any significant pathologic change.

Angiotensin-converting enzyme in serum and in bronchoalveolar lavage in sarcoidosis.

Angiotensin-converting enzyme (ACE) determinations were made in serum and in bronchoalveolar lavage fluid in 20 controls and in 28 patients with sarcoidosis. Serum ACE was significantly higher in patients with active sarcoidosis (54.3 +/- 19.0 SD nmol/ml/ min; n = 24) compared to controls (25.7 +/- 8.2; n = 20) or to patients with inactive sarcoidosis (23.6 +/- 7.3; n = 4). In contrast, ACE in bronchoalveolar lavage fluid was similar in nonsmoking controls (16.4 +/- 7.3 nmol/ml/min/macrophage; n = 8), smoking controls (10.4 +/- 11.9; n = 7); nonsmoking active sarcoidosis patients (16.7 +/- 14.6; n = 10), smoking sarcoidosis patients (17.9 +/- 8.4; n = 6) and inactive sarcoidosis patients (14.5 +/- 8.2; n = 3). Since ACE has been demonstrated by immunofluorescence in mononuclear phagocytes in granulomas, the authors speculate that macrophages recovered by alveolar lavage are not activated and do not reflect sarcoid alveolitis at the tissue level.

Coexistence of IgA myeloma and Gaucher's disease.

An elderly woman of Ashkenazic Jewish descent, who had had adult Gaucher's disease diagnosed seven years previously, was found to have IgA myeloma. The diagnosis of IgA myeloma was confirmed by the presence of lytic lesions in the skull and long bones, atypical plasma cells in bone marrow, and monoclonal elevation of IgA, kappa-type. In addition, the marrow contained Gaucher's cells. A causal relationship between these two pathologic entities remains speculative.

Effect of short-term protein deprivation on hemopoietic functions of healthy volunteers.

To ascertain the effects of protein deprivation on hemopoietic parameters in otherwise healthy subjects, three volunteers were placed on diets containing 0.15 g protein/kg body weight for 8 days followed in 2 mo by another 8-day study period during which they ingested their usual diets containing more than 0.9 g protein/kg body weight. Complete blood counts, serum protein determinations, and tests of in vitro and in vivo leukocyte chemotaxis were performed prior to and at the conclusion of each study period. Subjects were phlebotomized of 500 ml on day 7 of each study period. Twenty-four-hour urinary erythropoietin excretion rates were assayed just prior to and again postphlebotomy. Reticulocyte counts were performed at intervals up to 1 wk postphlebotomy. Some of these determinations were replicated during a subsequent study. The hemoglobin and hematocrits decrased slightly but significantly after 8 days on low protein diets. Erythropoietin excretion rates and reticulocyte responses to phlebotomy were also less marked while subjects were on protein depleted diets. Leukocyte chemotaxis, measured both in vitro and in vivo, was also markedly reduced while subjects were on protein-depleted diets. We conclude that 8 days of moderately severe protein deprivation significantly impairs erythropoiesis and leukocyte function in otherwise healthy individuals.

Intralesional Bacillus Calmette-Guérin immunotherapy of canine venereal tumors.

Canine transmissible venereal tumors were studied for response to intralesional Bacillus Calmette-Guérin (BCG) therapy. Six pairs of littermates, identical for the major histocompatibility complex, were evaluated. One member of each pair received intralesional BCG to one of two growing tumors. Lesions of control animals received 0.9% NaCl solution. Both injected and noninjected lesions of BCG-treated animals underwent regression within 63 days, as compared to an extended period of tumor growth (beyond 100 days) for controls (p less than 0.05). Serial in vitro assays during therapy included; (a) mixed lymphocyte-tumor culture, (b) phytohemagglutinin stimulation, and (c) assessment of lymphocyte surface markers. Lymphocytes from BCG-treated dogs were significantly more responsive to tumor cells in mixed lymphocyte-tumor culture assay than were those from controls (p less than 0.05). Maximal responses occurred during tumor regression. T- and B-lymphocyte levels as assayed by rosette formation and surface marker immunoglobulins were not influenced by BCG therapy. It was concluded that intralesional BCG therapy of canine venereal tumors was highly effective in causing regression of injected and noninjected lesions. This tumor model system may be useful for the evaluation of the effectiveness of new immunotherapeutic approaches on established neoplasms in large, randomly bred animals.

Hemopoietic colony forming units in fresh and cryopreserved peripheral blood cells of canines and man.

Colony forming units (CFUa) were assayed in the peripheral blood and separated mononuclear cells of canines and man. Fresh and cryopreserved samples were studied. By plating 3 x 10-5 canine buffy coat cells or 3 x 10-6 human buffy coat cells between 33 plus or minus 6.6 and 38 plus or minus 1.0 colonies were observed. A high degree of reproducibility was shown for duplicate plates and on repeated testing. Cryopreservation for a one-month period resulted in a minimal recovery of 80 per cent CFUa for canine cells and 96 per cent for human cells. In vivo correlation between peripheral blood CFUa and marrow repopulation was assessed indogs following supralethal whole body irradiation. Prompt repopulation of the marrow was observed and this correlated well with the CFUa assay following infusion of stored buffy coat cells. It was concluded that the peripheral blood of both man and dog have significant numbers of cells with CFUa capabilities that may be potentially useful for marrow grafting purposes.