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.
What's new?
With the rise in obesity and diabetes to epidemic proportions within the USA, people with diabetes are requiring higher doses of insulin (> 100 U) to adequately control their diabetes, resulting in the frequent use of concentrated insulin.
Ours is the first case report of the development of localized insulin amyloidosis due to repeated injections of concentrated insulin at the same site and highlights a potential complication of using concentrated insulin.
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.
Methemoglobinemia is a potentially life threatening medical condition that occurs due to increased methemoglobin production or decreased elimination. Methemoglobin is a derivative of hemoglobin in ...which the normal ferrous (Fe2+) iron state is oxidized to the ferric (Fe3+) state. This oxidized hemoglobin is unable to bind oxygen, hence reducing he oxygen carrying capacity of blood. The clinically presentation is characterized by cyanosis, low pulse oximeter reading and normal arterial PO2. Topical use of benzocaine a local anesthetic widely used in endoscopic procedures is one of the incriminated causes of acquired methemoglobinemia.
We present two cases of patients (pts) who developed methemoglobinemia after benzocaine spray for a transoesophageal echocardiogram. One pt was 50 year old male and other 30 year old female. Both had a methacilline resistant Staphylococcus Aureus bacteremia secondary to septic arthritis, they under went a transesophageal echocardiogram to rule out endocarditis. Topical local anesthesia used was benzocaine 20%. About 10–15 min after local anesthesia they desaturated to the mid 80's and they developed cynosis, they were intubated. On Blood gas analysis methemoglobin. was elevated 38.4% (male pt) and 18.9% (Female pt). They were given methylene blue at the dose of 2mg/kg intravenously over 10 minutes. Cyanosis corrected with in an hour. Methemoglobin level corrected to normal after 3 hours after administration of methylene blue. There were no adverse events with administration. The Glucose 6 Phosphate Dehydrogenase enzyme level was tested and was negative.
In conclusion benzocaine induced methemoglobinemia should be considered in pts under going Transesophageal Echocardiogram when cyanosis develops that is unresponsive to oxygen. Diagnosis can be confirmed by arterial blood gas analysis. If identified early this potentially life threatening condition can be treated with methylene blue with minimal complications and good outcomes.
Background: Idiopathic Thrombocytopenic Purpura (ITP) is a common hematological disorder. We sort to characterize the risk profiles and efficacy of rituximab in relapsed or refractory ITP in a ...largely minority cohort.
Methods: 23 patients (pts) with relapsed or refractory ITP treated with Rituximab were identified and studied as a retrospective cohort. Demographics, presentation, dosage schedule, tolerability and response were analyzed. Continuous data were analyzed via Student's T test, categorical data via Fisher's exact test and time to progression data was analyzed via Kaplan Meier life table analysis and log rank test.
Results: Of the 23 patients, 20 female (87%), 3 male (13%). median age at diagnosis was 45 yr (range 20–66).9 pt were African American (39%), 9 Hispanics (39%), 4 Asian (17.4%), 1 Caucasian(4.3%), 9 (39.6%) had more than one co morbidities, 17 (73.8%) had received 3 or more treatment regimens. All pt received steroids, 18 (78.3%) received IVIg, 13 (56.6%) Anti D immunoglobulin, 5 (21.7%) Vincristine, 3 (13%) Azathioprine, 2(8.7%) Cyclophosamide, 6 (26.1%) underwent a Splenectomy before Rituximab therapy. The median time from diagnosis to rituximab therapy was 15 months (range 1 to 269). Median platelet count before rituximab therapy was 11 (range 3 to 200).
Rituximab was administered at the dose of 375mg/m2 IV once a week for 4 weeks. The response rate was 47.8%. Response was defined as Complete response, platelet count of > 100 × 109/L, Partial response >50 × 109/L. 9 pt (39%) achieved complete response, 2 pt (8.7%) achieved partial response. 12 pt (52.2%) did not respond. Median time to response was 13.5 days (range 1–30). There was no statistically significant difference in the response when compared by gender (p=0.64), race (p= 0.398), prior splenectomy (p=0.64), prior anti D immunoglobulin (p=1.0), prior Vincristine (p=1.0), prior cyclophosamide (p=.45), prior azathioprine (p=1.0). Four pt (17.4%) had a serious adverse reaction to rituximab. One pt had diffuse hives after infusion, three pt developed diffuse pancytopenia, two pts had gram negative sepsis and died. The median follow up after rituximab therapy was 18 months (range 1–60). The median time to relapse was 7 months (range of 1 to 59). There was no statistically significant difference in time to relapse among gender (p=0.19), race (p= 0.45), Prior splenectomy (p=0.86), prior Anti D immunoglobulin (p=0.32), prior vincristine (p=0.75).
Conclusion: In this primarily minority based cohort the response rate to Rituximab (48% vs. 62%) and duration of response (7 months vs. 10.5 months) was lower than other published data but the rate of serious adverse events (17% vs. 7%) was higher. Rituximab must be used cautiously in this sub group of patients. There is need for a randomized controlled clinical trail to assess the efficacy of Rituximab in this population and further studies are warranted in minority populations.
To evaluate high-dose melphalan followed by autologous stem-cell transplantation in patients with refractory multiple myeloma.
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.
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.
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.
Introduction: Imatinib (STI571/ Gleevec) is a tyrosine kinase inhibitor that functions by blocking the binding of ATP to the bcr-abl tyrosine kinase, inhibiting its activity and preventing myeloid ...proliferation, a characteristic of CML. We report our experience with imatinib use in a minority patient population.
Methods: Data from 67 patients (pts) with CML treated at Cook County Hospital, Chicago, Illinois over a 4 year period were collected. Demographics, presentation, dosage schedule, tolerability and response were analyzed. Continuous data were analyzed via Student's T test and categorical data via Fisher's Exact test.
Results: 57 pts with complete data mean age at diagnosis 42.8 yrs, range 19–72 yrs, 46 (80.7%) males and 11 (19.3%) females were identified and analyzed as a retrospective cohort. 41 pts (71.9%) were between 30 and 60 yrs of age and 17 pts (29.8%) had ≥ 1 major comorbidity at presentation. 28 (49.1%) were African American (AA), 4 (7%) Asian, 5 (8.8%) Eastern European, 17 (29.8%) Hispanic, and 3 (5.3%) Middle Eastern. 50 pts (87.7%) were in chronic phase, 5 (8.8%) in accelerated phase, 2 (3.5%) in blast phase, 2 (3.5%) had granulocytic sarcomas and 5 pts (8.8%) had second malignancies at presentation. 54 pts (94.7%) were started on 400mg of imatinib. 19 pts (33.3%) had imatinib-related toxicities including skin rash, cytopenias and nausea. 17 pts (29.8%) were non-compliant with imatinib therapy. AA pts were as old as the non-AA pts 44.8 ± 12.6 yrs vs 40.9 ± 13.8 yrs, p 0.27. Non-AA pts were predominantly male. Following imatinib therapy a hematologic response (HR) was noted in 45.7± 54.6 days (d) in AA vs 31.3 ± 23.9 d in non-AA (p= 0.27), a major cytogenetic response (MCR) in 351 ± 342.6 d in AA pts vs 289±132.7 d in non-AA (p=0.58) and a complete cytogenetic response in 664±265.1 d in AA vs 642±292.5 d in non-AA pts (p=0.87). 11 AA pts failed imatinib therapy vs 8 non-AA pts. These pts were then subjected to imatinib dose escalation (600mg or 800mg) with only 4 pts in the AA group attaining MCR and 1 pt in the non-AA group attaining CCR. 4 AA pts then received Dasatanib and 2 went on to Allogeneic Stem Cell Transplant (ASCT) and 3 pts in the non-AA group received Nillotinib or Dasatanib and 2 went on to ASCT. There were 3 deaths in the AA group vs 1 in the non-AA group.
Conclusion: In this primarily minority-based cohort there appears to be no significant difference in the age or gender distribution of the AA or non-AA pts although there appeared to be a male preponderance amongst the non-AA pts. The ethnic background does not appear to affect the time to significant hematologic response, major cytogenetic response or complete cytogenetic response to imatinib therapy in the AA or non-AA pts. Since the number of patients is small, definitive conclusions in either cohort cannot be made. Further investigation in minority patients is warranted.
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