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Biomedical subjects

K B Miller

Publications and source records attributed to K B Miller.

At least 55 records · Page 3Linked to original sources

A novel approach to providing educationally based low vision services and outreach clinical and vision support services to the visually impaired.

BACKGROUND: The Perkins Low Vision Service is affiliated with the New England Eye Institute, the primary teaching clinic of the New England College of Optometry. Low Vision Services for patients of all ages as well as vision services for the multi-impaired are provided on site at the Perkins School for the Blind in Watertown, Massachusetts. RESULTS: Evaluations are provided by the low vision team comprised of specialists with expertise in pediatric and rehabilitative optometry, special education, orientation and mobility training, rehabilitation teaching and the interns at the New England College of Optometry. The full scope of services offered as well as alternative modes of practice employed will be discussed.

Adolescent↗

Bone marrow necrosis in two patients with acute promyelocytic leukemia during treatment with all-trans retinoic acid.

All-trans retinoic acid has been used for the treatment of acute promyelocytic leukemia (APL) with encouraging results. However, it has recently been associated with a number of potentially serious complications including the retinoic acid syndrome. We describe two patients with APL who were begun on all-trans retinoic acid therapy (45 mg/m2), but who developed leukocytosis which was treated with hydroxyurea. Both patients demonstrated clinical and laboratory findings of disseminated intravascular coagulation, massive cell lysis manifested by marked increases in serum lactic dehydrogenase, and rapid clinical deterioration. Both patients developed bone marrow necrosis within viable, noninfarcted bone trabeculae. We postulate that the development of bone marrow necrosis in these two patients was not a chance occurrence. Rather, the specific combination of cytotoxic and differentiating agents used in these patients (hydroxyurea with all-trans retinoic acid) caused massive cell lysis and death. The absence of bone marrow necrosis in the setting of induction therapy for APL both with and without all-trans retinoic acid therapy suggests that the addition of hydroxyurea was critical to the development of marrow necrosis. We, therefore, recommend caution in the use of hydroxyurea and all-trans retinoic acid in the treatment of APL.

Adult↗

Adjusted-dose continuous-infusion cyclosporin A to prevent graft-versus-host disease following allogeneic bone marrow transplantation.

Graft-versus-host disease (GVHD) remains a major obstacle to allogeneic bone marrow transplantation. We administered cyclosporin A (CsA) by continuous intravenous infusion for prophylaxis against GVHD and adjusted the dose to maintain a constant whole blood level. Forty-five patients, ranging in age from 16 to 56, mean 39.5 years, undergoing allogeneic transplantation for various hematological malignancies received CsA as a continuous intravenous infusion. CsA was started on day -1 and continued until day +22 when oral CsA was initiated. The whole blood level of CsA was determined and the dose adjusted to maintain a fixed level. Methotrexate 15 mg/m2 i.v. was given on day +1, followed by 10 mg/m2 on days +3 and +6. CsA administered as a continuous infusion was well tolerated. All patients required multiple adjustments of the infused dose of CsA to maintain the targeted whole blood level. The mean rise in creatinine was 0.89 mg/dl. There was an association between the concomitant administration of amphotericin B and CsA and the development of nephrotoxicity. Hypertension developed in 30/45 patients, and all responded to oral nifedipine. Tremors were noted in 16/45 patients. None of the patients developed serious neurological side effects. Greater than grade-I acute GVHD developed in only 13% of the patients. We conclude that administering CsA as an adjusted dose by continuous intravenous infusion is well tolerated and effective in preventing acute GVHD in patients undergoing allogeneic bone marrow transplantation.

Adolescent↗

Waldenström's macroglobulinemia with an IgM paraprotein that is both a cold agglutinin and a cryoglobulin and has a suppressive effect on progenitor cell growth.

BACKGROUND: A patient with Waldenström's macroglobulinemia was admitted to the hospital with fever, leg pain, and dyspnea. The patient had gas gangrene of the left leg that required above-the-knee amputation. Plasmapheresis was instituted to treat hyperviscosity. STUDY DESIGN AND METHODS: The patient's serum contained an IgM-kappa paraprotein, a cryoglobulin, and a cold agglutinin. The serum was studied. RESULTS: The patient's red cells typed as A1, Rh-positive. The direct antiglobulin test was negative. The serum contained a cold agglutinin with anti-Pr cold agglutinin specificity (titer 4096). Maximal thermal range was 30 degrees C. Following dithiothreitol treatment, the cold agglutinin activity disappeared. The serum IgM concentration in the tested sample was 62.3 g per L. The cold agglutinin titer in the supernatant after removal of the cryoglobulin was 256, and the IgM level was 0.31 g per L. Redissolving the cryoglobulin in a equivalent volume of saline resulted in a cold agglutinin titer of 4096 and an IgM level of 68.4 g per L. These results indicate that the cryoglobulin and the cold agglutinin are the same paraprotein. Serum protein electrophoresis using agarose gel and immunofixation of the serum revealed an IgM-kappa monoclonal band. Progenitor cell assays were performed by adding the patient's serum at final concentrations of 0, 1, 5 and 10 percent (vol/vol) to patient's and normal donor's peripheral blood mononuclear cells. Inhibition of burst-forming units-erythroid and colony-forming units-granulocyte/macrophage by the patient's serum was demonstrated. Appropriate controls and the use of the serum of another patient with Waldenström's macroglobulinemia did not suppress progenitor cell growth. The patient's serum inhibited colony formation in a dose-response fashion. CONCLUSION: Reports of cryoprecipitable cold agglutinins are rare. This case is unusual because the IgM-kappa paraprotein was also a cold agglutinin with anti-Pr specificity and erythroid and granulocyte-macrophage progenitor cell-suppressive properties.

Agglutinins↗

Vascular responsiveness to nitric oxide synthesis inhibition in hypertensive rats.

We contrasted in normotensive and hypertensive rats the effect of inhibition of nitric oxide synthesis on isometric tension development by aortic rings bathed in Krebs' bicarbonate buffer. NG-Nitro-L-arginine methyl ester (L-NAME) (3 x 10(-4) mol/L) increased tension (82 +/- 11% of the response to 120 mmol/L potassium chloride) in rings of thoracic aorta taken from hypertensive rats 7 to 14 days after aortic coarctation, whereas rings of abdominal aorta from below the coarctation were unresponsive, as were rings of thoracic aorta from rats with deoxycorticosterone-salt-induced hypertension and from the corresponding normotensive controls of either model of hypertension. The contractile response to L-NAME in aortic rings of rats with aortic coarctation was reversed by L-arginine (1 mmol/L), attenuated by removal of the endothelium, and blunted by the protein kinase C inhibitor staurosporine but was unaffected by inhibition of cyclooxygenase, scavengers of superoxide anion, or blockade of receptors for angiotensin, norepinephrine, serotonin, or endothelin. In additional experiments we contrasted the effect of L-NAME (10 mg/kg IV) on the blood pressure of sham-operated rats and rats with aortic coarctation after pretreatment of animals in both groups with DuP 753 (30 mg/kg IV) to achieve blood pressure equalization. The pressor response to L-NAME was twofold greater in rats with aortic coarctation than in sham-operated controls. That pressor and aortic constrictor responsiveness to L-NAME are increased after aortic coarctation suggests that a mechanism of vasodilation, mediated by nitric oxide, is preferentially manifested in rats with aortic coarctation-induced hypertension.

Animals↗

Phase I/II study of cyclophosphamide, carboplatin, and etoposide and autologous hematopoietic stem-cell transplantation with posttransplant interferon alfa-2b for patients with lymphoma and Hodgkin's disease.

PURPOSE: To evaluate the safety and toxicity of interferon alfa-2b (IFN) following an intensive preparative transplantation regimen in patients with relapsed Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS: Thirty-two patients with NHL or HD underwent autologous transplantation following cyclophosphamide 7,200 mg/m2, carboplatin 1,600 mg/m2, and etoposide 1,600 mg/m2 (CCV). Fourteen patients received an escalating dose of IFN. IFN was started at 1 x 10(6) U/m2 subcutaneously (SC) three times per week with a monthly dose escalation to a maximum of 3 x 10(6) U/m2 SC three times per week. IFN was continued for a total of 6 months. RESULTS: The preparative regiment was well tolerated. Renal dysfunction was noted more frequently in patients with a history of pretransplant cisplatin treatment, and cardiac dysfunction was responsible for the single transplant-related death (3%). IFN was well tolerated with no serious complications. Transient neutropenia and thrombocytopenia were noted in several patients. The mean maximal-dose IFN achieved was 2 x 10(6) IU/m2. The median duration of treatment with IFN was 5.2 months. The overall probability of survival (OS) and event-free survival (EFS) at 36 months, with a median follow-up duration of 18 months, was 42% OS and 14% EFS in HD and 70% OS and 56% EFS in NHL. The EFS at 36 months was 73% for all NHL patients who received IFN and 50% for patients who refused IFN treatment (P = .12), with OS estimates of 100% in the IFN group and 35% in the untreated group (P = .0002). CONCLUSION: CCV is a safe, effective conditioning regimen in patients with NHL or HD. Posttransplant IFN can be safely administered at 2.0 x 10(6) U/m2 three times per week for 6 months and may have a meaningful antitumor effect.

Adolescent↗

Hematology.

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Hematologic Diseases↗

Pseudocoarctation of the aorta presenting as a mediastinal mass with dysphagia.

Pseudocoarctation is an uncommon anomaly thought to be caused by congenital elongation and kinking of the aorta. We report a case of pseudocoarctation of the aorta presenting as a superior mediastinal mass causing dysphagia. Aortography and echocardiography revealed dilatation of the aorta and an aneurysm below the level of the pseudocoarctation. The patient underwent operative repair of the pseudocoarctation and associated aneurysm with good symptomatic relief. Review of the literature and experience with this case demonstrate that pseudocoarctation of the aorta cannot necessarily be regarded as a benign condition. Surgical treatment is recommended for all symptomatic patients and for those with associated aneurysm formation.

Aorta, Thoracic↗

Combined hamartoma of the retina and retinal pigment epithelium.

Combined hamartoma of the retina and retinal pigment epithelium is a rare, congenital fundus lesion which typically presents with a history of reduced acuity and/or the onset of strabismus. Clinically, the lesion is elevated, with a variably pigmented outer portion and a lighter central core of dilated tortuous vessels and gliosis. This benign lesion may be confused with more threatening conditions such as malignant melanoma or retinoblastoma. An appropriate diagnosis through clinical appearance and fluorescein angiography is imperative to prevent unnecessary enucleation. The authors report one case of combined hamartoma of the retina and retinal pigment epithelium in a patient presenting with a complaint of decreased vision.

Adult↗

Demyelinating neuropathy and acute lymphocytic leukemia.

We report a 67-year-old man with acute lymphocytic leukemia (ALL) who developed a rapidly progressive areflexic quadriparesis following chemotherapy. Electrophysiologic studies demonstrated an acute demyelinating polyneuropathy. Although peripheral nervous system dysfunction in ALL is often attributed to leukemic infiltration or chemotherapy, a diligent search with electrophysiologic evaluation should be considered and may suggest alternative diagnoses.

Action Potentials↗

Treatment of acute myeloid leukemia in the elderly with low-dose cytarabine, hydroxyurea, and calcitriol.

Twenty-nine patients aged 62-82 years with acute myeloid leukemia (AML) were treated with a 21-day course of continuous infusion cytarabine, oral hydroxyurea, and 1,25-dihydroxyvitamin D3 (calcitriol). Ten patients had an antecedent myelodysplastic syndrome. Calcitriol was continued as the only postremission therapy. Thirteen patients (45%) obtained a complete remission, and 10 patients (34%) had a partial response for an overall 79% response rate. There were three early deaths. The median remission duration was 9.8 months. Overall median survival was 12 months for all patients and 14 months for responding patients. All responding patients had marked bone marrow hypoplasia. Twenty patients received part or all of their chemotherapy as outpatients. This regimen has acceptable toxicity and can result in prolonged remissions in elderly, high-risk patients with AML. The favorable results may be related to the synergistic effect of hydroxyurea, cytarabine, and calcitriol.

Acute Disease↗

The evaluation of low-dose cytarabine in the treatment of myelodysplastic syndromes: a phase-III intergroup study.

One hundred and forty one patients were treated in a combined Eastern Cooperative Oncology Group and Southwest Oncology Group phase-III study evaluating low-dose cytarabine (LDAC) versus supportive therapy for the treatment of myelodysplastic syndrome (MDS). Patients were randomized to either cytarabine 10 mg/m2 subcutaneously BID or supportive therapy. Central pathology review was required. All patients were classified according to the FAB criteria for MDS. The overall concordance rate for the MDS subtype was 52%, and 25 patients were pathology exclusions, including 20 with AML. The overall response rate to a single cycle of LDAC was 32%, with 11% complete and 21% partial responses. The median duration of response was 5.9 months, with a range of 1.4-33.5 months. Responses were seen in all subtypes. Infections were more common in the LDAC arm. There was no difference in the time to progression or the overall survival for patients treated with LDAC or supportive therapy. The incidence of leukemic transformation was similar in both arms at 15%, but it differed according to the MDS subtype. Patients receiving LDAC had a decreased transfusion requirement after 3 months. There was a significant correlation between the degree of cytoreduction after receiving a single cycle of LDAC and survival. This survival difference was most marked in patients with the RAEB and RAEB-T subtypes. Although LDAC produced responses in all subtypes of the MDS, there was no effect on overall survival or transformation to AML. However, selected patients benefited from a single cycle of LDAC with durable responses. A cytoreductive effect appears to be required for a durable response. Future studies should include pathology review and must address the clinical and biological heterogeneity of MDS.

Adult↗

Engraftment with peripheral blood stem cells collected by large-volume leukapheresis for patients with lymphoma.

Seven patients with refractory lymphomas underwent marrow reconstitution with peripheral blood stem cells (PBSCs) harvested by large-volume leukapheresis (LVL). PBSCs were collected from all patients more than 1 month after the last cycle of chemotherapy, and no patient received growth factors. The median number of LVL procedures performed per patient was 4.5, with a mean volume of 24.5 L of blood processed per procedure to obtain 7 x 10(8) mononuclear cells per kg. Autologous PBSCs and platelets were frozen at a controlled rate in plasma and 10-percent dimethyl sulfoxide and stored in the vapor phase of liquid nitrogen. This group of patients was compared to a control group (n = 18) who received medullary marrow (MM) transplants for the same diagnoses under the same protocols during the same period. Posttransplant days to white cell engraftment (PBSC = 17, MM = 15.5) were no different. Days to platelet independence were significantly longer in the LVL PBSC group (PBSC = 33, MM = 16; p < 0.05). This pattern of engraftment is typical of patients treated in this manner. Although Day 0 platelet counts (PBSC = 75.5 x 10(9)/L, MM = 85 x 10(9)/L) and total single-donor unit platelet use (PBSC = 8, MM = 9) were no different, Day 1 platelet counts (PBSC = 128 x 10(9)/L, MM = 61.5 x 10(9)/L; p < 0.05) and Day 14 platelet use (PBSC = 5, MM = 8; p < 0.05) were significantly different, because of the transfusion of cryopreserved autologous platelets with PBSCs on Day 0.

Adolescent↗

latrogenic pseudoaneurysm of the innominate artery.

Central venous cannulation by the subclavian approach is a commonly performed procedure with an overall complication rate of up to 11%. In the English literature, however, there has been no previous documentation of pseudoaneurysm of the innominate artery as a complication of right subclavian vein catheterization. We report a case of a 55-year-old woman on chronic hemodialysis admitted to the hospital with pneumonia and sepsis who underwent multiple attempts at placement of a right subclavian vein catheter. These were unsuccessful and resulted in arterial puncture. The patient was discharged, but returned to the hospital 2 weeks later with shortness of breath and stridor. Evaluation revealed a pseudoaneurysm of the innominate artery with compression of the airway, which was successfully repaired.

Journal Article↗

Hematology.

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Hematology↗