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Biomedical subjects

J Neglia

Publications and source records attributed to J Neglia.

10 recordsLinked to original sources

Successful treatment of refractory Langerhans cell histiocytosis with unrelated cord blood transplantation.

A 2-month-old girl presented for treatment with a diffuse rash, interstitial pneumonia, otorrhea, and lymphadenopathy. Skin biopsy confirmed Langerhans cell histocytosis by electron microscopy. After receiving multiple courses of chemotherapy, only marginal improvement was achieved, with progressive marrow and liver involvement. The decision was made to pursue a human leukocyte antigen-identical unrelated cord blood transplantation. Two years after transplant, the bone marrow was clear of Langerhans cell histocytosis and 100% donor engraftment. The poor prognosis of patients with an inadequate response to therapy and the presence of organ dysfunction (marrow and liver) substantiated the decision to pursue an unrelated cord blood transplantation.

Bone Marrow↗

Autologous stem cell transplantation for high-risk pediatric solid tumors.

Many solid tumors exhibit a steep dose-response to alkylating agents, and autologous stem cell transplantation (ASCT) allows escalation of the chemotherapy dose for treatment of high risk solid tumors. We have transplanted 24 children and young adults with relapsed or metastatic solid tumors on two consecutive ASCT protocols consisting primarily (protocol MT 8911) or exclusively (MT 9408) of alkylating agents. The median time to neutrophil engraftment was 21 days in protocol MT 8911 (no prophylactic use of growth factors) and 14 days in MT 9408 (G-CSF, 5 microg/kg, started on day 0). Disease-free survival estimated by the Kaplan-Meier method is 39% (95% CI: 19-59%) at 2 years after transplant and 34% (95% CI: 14-54%) at 4 years after transplant. Six of the nine patients with metastatic or relapsed disease that were transplanted while in complete remission (four patients with Ewing's sarcoma family of tumors and two patients with anaplastic Wilms tumor) are alive and disease-free with a median follow-up of 37 months (range 20-74 months). The estimated 4 year survival for patients receiving a transplant while in high risk remission was 78% (95% CI: 51-100%). In contrast, 13/15 patients that were transplanted while in partial remission died because of progressive disease or transplant-related complications. There were three transplant-related deaths (12.5%), including one patient with multiorgan failure, and two patients with complications of hepatic veno-occlusive disease. Our data indicate that autologous stem cell transplantation should be considered for consolidation therapy of high risk and relapsed pediatric patients with solid tumors who have achieved complete remission.

Adolescent↗

Variability of atrial sensing during exercise in a patient with a dual chamber ICD caused inappropriate ICD discharges.

We present the case of a patient with a dual chamber implantable cardioverter defibrillator (ICD) who experienced inappropriate ICD discharges during exercise. Interrogation of the ICD revealed intermittent atrial undersensing during exercise that was responsible for the erroneous classification by the ICD of sinus tachycardia as ventricular tachycardia. Monitoring of the intracardiac electrograms and Marker Channels during an exercise test confirmed a marked decrease in P wave amplitude during exercise. By increasing the atrial sensitivity setting the problem was resolved.

Adult↗

Phase II trial of primary chemotherapy followed by reduced-dose radiation for CNS germ cell tumors.

PURPOSE: A prospective phase II study was initiated to assess the response rate, survival, and late effects of treatment in patients with newly diagnosed CNS germ cell tumors (GCT), using etoposide plus cisplatin followed by radiation therapy prescribed by extent of disease, histology, and response to chemotherapy. PATIENTS AND METHODS: Seventeen patients aged 8 to 24 years with histologically proven CNS GCT received etoposide (100 mg/m2/d) plus cisplatin (20 mg/m2/d) daily for 5 days every 3 weeks for four cycles, followed by radiation therapy. Nine patients had germinomas; eight had mixed GCT. Four patients (three with germinomas and one with mixed GCT) presented with leptomeningeal dissemination. RESULTS: Radiographically, 14 of 17 patients were assessable for response; 11 patients experienced complete regression, and three had major partial regression before radiation. Six of seven assessable patients with elevated CSF levels of alpha-fetoprotein or betahuman chorionic gonadotropin had normalization with chemotherapy alone; all normalized with combined chemotherapy and radiation therapy. All 17 patients are alive without evidence of disease (median follow-up, 51 months). One patient developed a relapse in the spinal leptomeninges and was rendered free of disease with spinal radiation more than 5 years ago. One patient developed carotid stenosis requiring surgery. Thus far, only minimal long-term deterioration in neurocognitive function has been detected as a consequence of protocol treatment. CONCLUSION: Conventional-dose intravenous chemotherapy with etoposide and cisplatin can effect tumor regression in a high proportion of patients with CNS GCT, including those with leptomeningeal metastases. Acute and long-term toxicities are acceptable. Progression-free survival and overall survival are excellent.

Adolescent↗

Interaction between electronic article surveillance systems and implantable defibrillators: insights from a fourth generation ICD.

We present a case report of an inappropriate discharge from a fourth generation implantable cardioverter defibrillator (ICD) as a result of exposure to electromagnetic interference. A 60-year-old man implanted with a Medtronic 7219D defibrillator experienced shocks without preceding symptoms while walking through an electronic surveillance system in a store. Though this has been reported, the mechanism of the interaction remains unexplained. The electrogram storage capabilities of this particular device enabled us to establish that this resulted from inappropriate sensing of the electromagnetic interference.

Defibrillators, Implantable↗

Idiosyncratic pacing with a commercial pacing system analyzer.

An idiosyncratic response of the Medtronic AV Pacing System Analyzers (models 5311 [unipolar] and 5311B [bipolar]) during high output AAI pacing is reported. Using the bipolar analyzer with unipolar cables and a 2734 adaptor, ventricular capture was noted during high output AAI pacing when the ground was displaced from the patient. Using the unipolar analyzer with bipolar cables also resulted in ventricular capture with high output AAI pacing. Implanting physicians should be aware of this phenomenon to avoid false conclusions.

Arrhythmias, Cardiac↗

Autologous peripheral blood cell transplantation in the treatment of advanced neuroblastoma.

PURPOSE: We review the experience with autologous peripheral blood cell transplantation (APBCT) in children with neuroblastoma at the University of Minnesota. PATIENTS AND METHODS: Aspects of peripheral blood cell collection and use in nine patients who had advanced neuroblastoma (eight Evans stage IV, 1 stage III), who were median age 4 years (range 10 months-22 years) and who were treated with high-dose chemotherapy without total body irradiation and APBCT between September 1987 and December 1989 are reviewed. RESULTS: A median of 4.8 x 10(8) (range 3.3-8.9) mononuclear cells per kilogram of body weight were obtained by a median of six (range four-eight) collections. In vitro assay of granulocyte-monocyte colony-forming cells (CFU-GM) demonstrated a median of 3.6 x 10(4) (range 0.7-7.8) CFU-GM/kg of body weight. After APBCT, granulocyte recovery (absolute neutrophil count > 500 x 10(6)/L) occurred at a median of 28 days (range 14-72) and platelet recovery (> 150 x 10(9)/L) occurred at a median of 34 days (range 19-202). All patients but one, who had progressive disease, were transplanted with residual disease. Immunocytological analysis of peripheral blood stem cell harvest showed the presence of circulating neuroblastoma cells in three of nine patients, all of whom had minimal marrow residual disease by biopsy. One patient is still alive with no evidence of disease after 5 years. The others died of recurrent neuroblastoma a median of 14 months (range 3-29) after transplant. CONCLUSION: APBCT is safe and effective for hematopoietic reconstitution after high-dose chemotherapy, and may be useful when a bone marrow harvest cannot be performed because of prior pelvic radiation or minimal residual bone marrow metastasis. Immunocytological methods to ensure that the product is free of tumor contamination should be performed.

Adolescent↗

Donor and host influences in bone marrow transplantation for immunodeficiency disease and leukemia.

Bone marrow transplantation is an effective form of therapy for lethal immunodeficiency diseases and leukemia. Patients who are treated by bone marrow transplantation for these diseases have an improved outcome if treated early after diagnosis, before they have developed secondary complications. Recent advances in transplantation have allowed choices between several donor types. These alternative donor types are the subject of this analysis from the University of Minnesota. In these diseases, matched sibling donor bone marrow transplantation is the standard for comparison. In individuals with lethal immunodeficiencies (severe combined immune deficiency [SCID], Wiskott-Aldrich syndrome [WAS], Chédiak-Higashi syndrome [CHS]) who lack a sibling donor, unrelated transplantation has produced results that are almost equal to those of matched sibling transplants. Patients with high-risk acute lymphoblastic leukemia (ALL) who have received sibling or unrelated transplants have results that are superior to autologous donor transplants. In ALL, there is a need to use new therapies, eg, immunotoxins, to decrease the currently high relapse rate. In patients with acute myelogenous leukemia (AML) in first complete remission, results are excellent and comparable using related and autologous donors. Results in non-first-remission AML are inferior and do not differ if related, unrelated, or autologous transplants are used. In chronic myelogenous leukemia (CML), early survival results are superior using autologous and related transplants as compared with unrelated transplants.

Bone Marrow Transplantation↗

Experience with a third-generation implantable cardioverter-defibrillator.

A Medtronic 7216A pacemaker cardioverter-defibrillator was implanted in 16 patients (mean age 56 years) with sustained ventricular tachycardia (VT) or ventricular fibrillation (VF) and organic heart disease with a mean left ventricular ejection fraction of 33%. Endocardial and epicardial defibrillation shock efficacy was evaluated before or at implant using 1 to 3 shock patterns, i.e., monophasic single, sequential or simultaneous shocks with dual and triple electrode configurations. Endocardial leads used a common right ventricular cathode and dual anodes, whereas epicardial leads used 2 or 3 helical coil patches. VT termination was evaluated using pacing or shock therapy, or both, whereas only shocks were used in VF. Programmable bradycardia pacing, individual zones for VT and VF detection and individualized pacing and shock therapy for VT and VF were used. Monophasic shocks had epicardial defibrillation thresholds ranging from 3 to 18 (mean 10) J and were comparable for sequential and simultaneous shocks (p greater than 0.2). VT detection rates ranged from 340 to 470 ms and VF detection rates from 270 to 330 ms. VT or VF induction, or both, was performed noninvasively in 13 patients after implant and was reproducibly terminated by rapid pacing alone (5 patients), low-energy shocks (2 patients), high-energy shocks (3 patients) and combined therapy (3 patients). Intermediate or high-energy shocks terminated all induced VF episodes. During follow-up (2 to 12 months), there have been 2 noncardiac deaths. Electrical therapy was delivered in 7 patients, for VT (3 patients), VT and VF (3 patients) and indeterminate tachyarrhythmia (1 patient). All VT/VF episodes were successfully terminated, with 78 of 96 (81%) spontaneous VT episodes terminated by pacing. Follow-up reprogramming was required in 5 patients. It is concluded that successful application of individualized electrical therapy prescriptions in patients with VT/VF is feasible. Pacing therapies, which are effective for induced VT, can be reliably used for effective long-term spontaneous VT termination in conjunction with shock therapy and can permit reduced patient exposure to shock therapy. Thus, a programmable hybrid pacemaker cardioverter-defibrillator system provides nonthoracotomy implantation, effective VT/VF termination, demand ventricular pacing and noninvasive modes for arrhythmia induction, event monitoring and clinical trouble-shooting.

Adult↗

Determination of urinary homovanillic and vanillylmandelic acids from dried filter paper samples: assessment of potential methods for neuroblastoma screening.

Urinary homovanillic (HVA) and vanillylmandelic (VMA) acids were analyzed on 200 random urine samples from patients with neuroblastoma and controls, after the samples had been dried onto absorbent filter paper. The acids were determined quantitatively by gas chromatography (GC) and qualitatively by thin layer chromatography (TLC). The results were analyzed for correlation between liquid urine samples and urine dried on filter paper and between TLC and GC methods. A high overall correlation for HVA and VMA (99%) was found between liquid and dried filter samples analyzed by GC. The correlations were more significant for samples with elevated levels of these acids than for those with normal levels. Normalization of the results to the urinary creatinine concentration (UCr) is indicated due to variations in urine concentration. Results from TLC analysis showed a false positive rate of 3.5% and a false negative rate of 0.5% compared to GC analysis. This work suggests that a combination of a sensitive TLC method with a rapid quantitative GC method would be suitable for mass neuroblastoma screening in infants.

Adolescent↗