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Biomedical subjects

R E Harris

Publications and source records attributed to R E Harris.

At least 37 records · Page 2Linked to original sources
PubMed1997

Bone marrow transplantation versus chemotherapy for maintenance of second remission of childhood acute lymphoblastic leukemia: a study of the Children's Cancer Group (CCG-1884).

BACKGROUND: Maintenance of second remission of childhood acute lymphoblastic leukemia (ALL) with intensive chemotherapy is often unsuccessful. The major cause of treatment failure is relapse. MATERIALS AND METHODS: Of 96 children with ALL who relapsed in the marrow while on or within 1 year of completing initial therapy, 62 achieved a second remission. Nineteen patients underwent bone marrow transplantation in second remission, 11 from a human leukocyte antigen (HLA)-matched related donor, seven using autologous marrow, and one from a matched unrelated donor. The event-free survival (EFS) of transplanted patients was compared to that of patients treated with intensive chemotherapy using high-dose cytarabine, vincristine, escalating dose methotrexate, L-asparaginase, and an anthracycline (daunorubicin or idarubicin). Only those patients treated with chemotherapy who survived in second remission up to the mean time that patients were transplanted (135 days) were included in the control group (33 of 43 patients who achieved second remission). RESULTS: The actuarial 2-year event-free survival of transplanted patients is 37+/-22% (95% C.I.) compared to 18+/-13% for chemotherapy-treated patients (P=0.017). EFS for allo-transplant recipients was similar to that for auto-transplant recipients. Duration of initial remission was a strong predictor of the outcome of retrieval therapy. Patients whose initial remission was greater than 3 years had better EFS after achieving second remission (five of 11 still in remission, compared to four of 41 patients whose initial remission was less than 3 years). Adjustment in the multivariate analysis for duration of initial remission did not diminish the benefit of transplant over chemotherapy. CONCLUSIONS: While there remains considerable possibility for further improvement in EFS after achieving second remission of childhood ALL, bone marrow transplant is superior to chemotherapy in maintaining second remission.

Adolescent↗
PubMed1997

Antithrombin-III for the treatment of chemotherapy-induced organ dysfunction following bone marrow transplantation.

A hypercoaguable state has been shown to follow high-dose chemotherapy for bone marrow transplantation (BMT). Deficiency of the natural anticoagulants, antithrombin III (AT-III), protein C and protein S correlate with organ dysfunction following BMT. We treated 10 patients with severe post-BMT organ dysfunction with AT-III concentrate. Indications for treatment included AT-III anticoagulant level less than 88% and life-threatening single or multiorgan dysfunction. All patients were loaded with 50 units/kg AT-III every 8 h for three doses followed by 50 units/kg/day each day for 3-12 days. Clinical improvement was seen within 1-5 days of start of therapy in all patients. Patients with veno-occlusive disease (VOD) showed a decrease in platelet consumption in nine of nine patients, resolution of hepatic tenderness in six of eight patients, and reduction of severe ascites and weight gain in four of five patients. The probability of death due to VOD and life-threatening organ dysfunction was significantly less in the AT-III-treated group when compared to a historical control group receiving the same preparative regimen (P = 0.047 and P = 0.034, respectively). Significant improvements in organ dysfunction following AT-III treatment in this small study supports a causal relationship between AT-III deficiency and post-BMT chemotherapy-induced organ dysfunction.

Adolescent↗
PubMed1997

Longevity in obese and lean male and female rats of the Zucker strain: prevention of hyperphagia.

Zucker obese (fa/fa) and lean (Fa/Fa) rats were fed a soy protein diet ad libitum under barrier conditions from 4 wk of age until death. Obese rats were also pair fed with lean controls to prevent hyperphagia. Time of death was determined and tissues collected at necropsy for histologic examination. Lean rats had longer 10th percentile survivorship (males 966 compared with 667 d, females 983 compared with 620 d) and maximum life spans (males 1067 compared with 803 d, females 1163 compared with 744 d) than did obese rats. Preventing hyperphagia increased maximum life span in both males (1010 d) and females (975 d). Pathologies in lean rats were similar to those reported for other rodent strains. For obese rats fed ad libitum, end-stage renal disease (ESRD) was the major cause of mortality (males: 91.1%, females: 93.3%). Prevention of hyperphagia decreased deaths attributable to ESRD (males: 64.4%, females: 51.1%). A smaller restriction in energy intake (8-18%) required to prevent hyperphagia compared with the 35-40% in most other studies produced similar increases in longevity, suggesting that obese Zucker rats are particularly sensitive to energy restriction. Amelioration of early onset of renal disease is a likely explanation. Percentage body fat in food-restricted obese rats did not differ from that of animals fed ad libitum; thus, reduced longevity is not the result of obesity per se, but rather is influenced by other metabolic pathologies occurring in this strain of rats homozygous for the fa gene. Because microalbuminuria with progression to ESRD is a complication in human obesity, the Zucker strain offers the opportunity to investigate initiating mechanisms of this pathology.

Aging↗
PubMed1997

The need to know versus the right to know: privacy of patient medical data in an information-based society.

"Whatever, in connection with my professional practice, or not in connection with it, I see or hear, in the life of men, which ought not to be spoken of abroad, I will not divulge, as reckoning that all such should be kept secret."(1) "Safeguards to privacy in individual health care information are imperative to preserve the health care delivery relationship and the integrity of the patient record."(2) As early as the fourth and fifth centuries B.C., Hippocrates contemplated the importance of medical information to the care and treatment of patients. His oath suggests that privacy of a patient's medical information creates the foundation upon which a patient reposes trust in his or her physician. While defining the earliest version of the physician-patient privilege, the oath does not envision the extent of modern day access to healthcare information. A patient's relationship with the modern healthcare delivery system often includes a team of physicians, nurses, and other clinical support personnel. This relationship extends beyond direct caregivers and may include healthcare administrators, payor organizations, and persons unfamiliar with a patient's identity, such as researchers and public health officials. Accessing a patient's medical information links these participants to the patient's healthcare delivery relationship. The Hippocratic Oath does not contemplate such broad access, nor does it contemplate the emerging privacy crisis resulting from the application of computer technology to medical record storage and retrieval. The combination of broad access, individual privacy rights, and computer technology requires a rethinking of measures designed to protect the realities of the modern medical information society.

Computer Security↗
PubMed1996

Prolonged administration of granulocyte colony-stimulating factor (filgrastim) to patients with Fanconi anemia: a pilot study.

This report examines the effect of filgrastim (granulocyte colony-stimulating factor, [G-CSF] in 12 patients with neutropenia [absolute neutrophil count [ANC] < 1,000/mm3]) caused by Fanconi anemia (FA). Two of 14 patients who were evaluated for study entry were ineligible because of unsuspected cytogenetic abnormalities in their bone marrow (BM). G-CSF was started at 5 micrograms/kg/d. All patients had an increase in their ANC at week 8 (mean increase = 15,664/mm3). The median ANC during therapy was 5,030/mm3. Eight of 10 patients who completed 40 weeks on study maintained an ANC > 1,500/mm3 on G-CSF given every-otherday. Four patients had an increase in their platelet count by week 8 without transfusion (maximum increase = 23,000 to 45,000/mm3); however, platelet counts fell toward baseline levels as the G-CSF dose was reduced. BM CFU-MK were increased at week 8 in three of four evaluable patients. Four patients who did not receive red blood cell transfusions had an increase in their hemoglobin level of at least 2.0 g/dL. A fifth patient had a red blood cell transfusion in week 2 and then had a similar increase in hemoglobin level without subsequent transfusion. Eight of 10 patients who completed 40 weeks of treatment showed increases in the percentage of BM CD34+ cells measured by flow cytometry. The same proportion showed increases in peripheral blood CD34+ cells. Increased BM cellularity and myeloid hyperplasia were constant findings and were associated with increased expression of the proliferating cell nuclear antigen. Adverse experiences were mild fever (1 patient) and a new BM cytogenetic abnormality at week 40 (1 patient). This study shows that prolonged administration of G-CSF exerts a stimulatory effect on the BM of FA patients and may be used to maintain a clinically adequate ANC in these patients. G-CSF has beneficial effects on multiple hematopoietic lineages in some patients and may be a good candidate for use in combination cytokine protocols for FA patients with progressive aplastic anemia. G-CSF use results in an increase in circulating CD34+ cells, a finding with important implications for future gene transfer protocols.

Adolescent↗
PubMed1996

Comparison of idarubicin to daunomycin in a randomized multidrug treatment of childhood acute lymphoblastic leukemia at first bone marrow relapse: a report from the Children's Cancer Group.

The outcome of children with acute lymphoblastic leukemia (ALL) and bone marrow relapse has been unsatisfactory largely because of failure to prevent subsequent leukemia relapses. Ninety-six patients were enrolled and received vincristine, prednisone, L-asparaginase, and an anthracycline as reinduction therapy. Ninety-two patients were randomized to receive either daunomycin (DNR) or idarubicin (IDR). After achievement of second complete remission (CR2), maintenance chemotherapy included the same anthracycline, IDR or DNR, high-dose cytarabine, and escalating-dose methotrexate. Compared to DNR (45 mg/m2/week x 3), IDR (12.5 mg/m2/week x 3) was associated with prolonged myelosuppression and more frequent serious infections. Halfway through the study, the dose of IDR was reduced to 10 mg/m2. Overall, second remission was achieved in 71% of patients. Reinduction rate was similar for IDR and DNR. Reasons for induction failure differed; none of 15, 1 of 5, and 5 of 7 reinduction failures were due to infection for DNR, IDR (10 mg/m2), and IDR (12.5 mg/m2), respectively. Two-year event-free survival (EFS) was better among patients who received IDR (12.5 mg/m2) (27 +/- 18%) compared to DNR (10 +/- 8%, P = 0.05) and IDR (10 mg/m2) (6 +/- 12%, P = 0.02). However, after 3 years of follow-up, late events in the high-dose IDR group result in a similar EFS to the lower-dose IDR and DNR groups. In conclusion, IDR is an effective agent in childhood ALL. When used weekly at 12.5 mg/m2 during induction, the EFS outcome during the first 2 years of treatment appears better than lower-dose IDR or DNR (45 mg/m2), although this difference was not sustained at longer periods of follow-up. Increased hematopoietic toxicity seen at this dose might be reduced through the use of supportive measures, such as hematopoietins and intestinal decontamination.

Antibiotics, Antineoplastic↗
PubMed1996

Hydrophobic mutations alter the movement of Mg2+ in the pore of voltage-gated potassium channels.

The permeation pathways of the voltage-gated K+ channels Kv3.1 and ShakerB delta 6-46 (ShB delta) were studied using Mg2+ block. Internal Mg2+ blocked both channels in a voltage-dependent manner, and block was partially relieved by external K+, consistent with Mg2+ binding within the pore. The kinetics of Mg2+ block was much faster for Kv3.1 than for ShB delta. Fast block of Kv3.1 was transferred to ShB delta with transplantation of the P-region, but not of S6. The difference in the P-region, causing the change in Mg2+ binding kinetics, was attributed to ShB delta (V443) and its analog Kv3.1(L401), because in both channels leucine at this position gave fast block, whereas valine gave slow block. For Kv3.1 the major determinant of the voltage dependence of Mg2+ binding resided primarily in the off rate, whereas for Kv3.1(L401V) the voltage dependence resided primarily in the on rate, consistent with a change in the rate-limiting barrier for Mg2+ binding. Our data suggest that hydrophobic residues at positions 401 of Kv3.1 and 443 of ShB delta act as barriers to the movement of Mg2+ in the pore.

Amino Acid Sequence↗
PubMed1996

Nonsteroidal antiinflammatory drugs and breast cancer.

We examined the association of nonsteroidal antiinflammatory drugs and breast cancer risk in a case-control study of 511 breast cancer patients and 1,534 population control subjects. The relative risk of breast cancer was reduced in women using these compounds at least 3 times per week for > or = 1 year [odds ratio (OR) = 0.66; 95% confidence interval (CI) = 0.52-0.83]. Odds ratios were similar for use of ibuprofen (0.57) or aspirin per se (0.69). Breast cancer risk declined with increasing exposure, and the greatest risk reduction (40%; odds ratio = 0.60; 95% CI = 0.40-0.91) occurred at the highest level of use (daily intake for > or = 5 years). These results indicate that nonsteroidal antiinflammatory drugs may have chemopreventive potential against the development of breast cancer.

Adult↗
PubMed1996

Pilot study of high-dose thiotepa and etoposide with autologous bone marrow rescue in children and young adults with recurrent CNS tumors. The Children's Cancer Group.

PURPOSE: This study was designed to determine the toxicity, radiographic response rate, and outcome following high-dose thiotepa, etoposide, and autologous bone marrow rescue (ABMR) for young patients with recurrent malignant brain tumors. METHODS: Eligibility criteria required adequate renal, hepatic, and pulmonary function, and no bone marrow infiltration. Thiotepa 300 mg/m2 and etoposide 500 mg/ m2 were infused on 3 consecutive days, and autologous bone marrow was infused 72 hours following chemotherapy. RESULTS: Forty-five patients with recurrent high-grade brain tumors, aged 8 months to 36 years (median, 8 years), were treated. Seven patients (16%) died of treatment-related toxicities within 56 days of marrow reinfusion. Delayed platelet engraftment occurred in 44% of patients who survived beyond day 56. Of 35 patients with radiographically measurable disease who survived at least 28 days following ABMR, there were two complete responses (CRs) and six partial responses (PRs), for an overall response (CRs plus PRs) rate of 23% (SE = 7%). Objective responses were observed in four of 14 assessable patients with high-grade glioma and in two of six with primitive neuroectodermal tumors (PNETs)/ medulloblastoma. Survival was significantly improved in patients treated with minimal residual disease (P < .0005). Five of 18 patients (28%) with high-grade gliomas remain free of disease at 39+, 44+, 49+, 52+, and 59+ months post-ABMR. CONCLUSION: The combination of high-dose thiotepa and etoposide has activity against a variety of recurrent childhood brain tumors. These results merit further evaluation in children and young adults with both recurrent and newly diagnosed high-grade brain tumors.

Adolescent↗
PubMed1996

Metabolites of a tobacco-specific nitrosamine, 4-(methylnitrosamino)- 1-(3-pyridyl)-1-butanone (NNK), in the urine of smokeless tobacco users: relationship between urinary biomarkers and oral leukoplakia.

Two metabolites of the carcinogenic tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone were quantified in the urine of smokeless tobacco users. The metabolites are 4-(methylnitrosamino) -1-(3-pyridyl)-1-butanol (NNAL) and [4-(methylnitrosamino)-1-(3-pyridyl) but-1-yl]-beta-O-D-glucosiduronic acid (NNAL-Gluc). The study population consisted of 47 male nonsmokers, of whom 23 were snuff dippers, 13 were tobacco chewers, 3 were users of both products, and 8 were nonusers. The levels of NNAL-Gluc in urine ranged from 0.14-30.3 pmol/mg creatinine with a mean +/- SD of 3.47 +/- 5.86, whereas the levels of NNAL ranged from 0.02-8.73 pmol/mg creatinine with a mean +/- SD of 0.92 +/- 1.59. The mean levels of NNAL-Gluc and NNAL were not significantly different from those measured in a previous study of smokers. The levels of NNAL-Gluc were significantly higher in snuff dippers than in tobacco chewers. The ratio of NNAL-Gluc:NNAL was higher in snuff dippers than in tobacco chewers or smokers. There was no indication of two phenotypes of the NNAL-Gluc:NNAL ratio in smokeless tobacco users, in contrast to previous observations in smokers. Of the 39 smokeless tobacco users in this study, 16 presented with oral leukoplakia. When the total levels of NNAL-Gluc, NNAL, or NNAL-Gluc + NNAL were divided into tertiles, there was a significant association between the presence of leukoplakia and increasing levels of these metabolites; a similar relationship was found between urinary cotinine and leukoplakia. The results of this study demonstrate that there is significant uptake of carcinogenic nitrosamines in smokeless tobacco users, and that such products are not harmless alternatives to cigarettes. Moreover, the urinary biomarkers NNAL-Gluc, NNAL, and cotinine were associated with the presence of leukoplakia, which provides biochemical support for the role of smokeless tobacco products as a cause of oral leukoplakia.

Adult↗
PubMed1995

Bone marrow transplantation for Fanconi anemia.

Fanconi anemia is a genetic disorder associated with diverse congenital abnormalities, progressive bone marrow failure, and increased risk of leukemia and other cancers. Affected persons often die before 30 years of age. Bone marrow transplantation is an effective treatment, but there are few data regarding factors associated with transplant outcome. We analyzed outcomes of HLA-identical sibling (N = 151) or alternative related or unrelated donor (N = 48) bone marrow transplants for Fanconi anemia performed between 1978 and 1994 and reported to the International Bone Marrow Transplant Registry. Fanconi anemia was documented by cytogenetic studies in all cases. Patient, disease, and treatment factors associated with survival were determined using Cox proportional hazards regression. Two-year probabilities (95% confidence interval) of survival were 66% (58% to 73%) after HLA-identical siblings transplants and 29% (18% to 43%) after alternative donor transplants. Younger patient age (P .0001), higher pretransplant platelet counts (P = .04), use of antithymocyte globulin (P = .005), and use of low-dose (15 to 25 mg/kg) cyclophosphamide plus limited field irradiation (P = .009) for pretransplant conditioning and cyclosporine for graft-versus-host disease prophylaxis (P = .002) were associated with increased survival. Bone marrow transplants are effective therapy for Fanconi anemia. The adverse impact of increasing age and lower pretransplant platelet count on transplant outcome favors earlier intervention, especially when there is an HLA-identical sibling donor.

Adolescent↗
PubMed1994

Neural crest tumors: I-123 MIBG imaging in children.

PURPOSE: To determine 24- and 48-hour distribution of iodine-123 metaiodobenzylguanidine (MIBG) and to establish an optimized pediatric imaging protocol. MATERIALS AND METHODS: Seventy-seven I-123 MIBG scans obtained in 33 children undergoing evaluation for neural crest tumor were reviewed. RESULTS: Activity in the salivary glands, myocardium, liver, gut, and bladder was demonstrated on almost all scans. Activity was noted in the neck muscles, thyroid gland, and uninvolved adrenal gland in fewer studies. In 20 studies, abnormal uptake was present in the chest or abdomen at 24 and 48 hours, and lesion identification was improved at 48 hours in 12 studies. Detection of skeletal lesions on 14 scans was similar at 24 and 48 hours. Foci of tumor were first detected at I-123 MIBG imaging in nine studies, and in only two patients was tumor involvement initially missed on I-123 MIBG studies. CONCLUSION: Distribution of I-123 MIBG on images in children differs from that in earlier descriptions in adults. Images of the torso at 48 hours after injection are a useful adjunct in detection of lesions.

3-Iodobenzylguanidine↗
PubMed1994

Familial erythrophagocytic lymphohistiocytosis: neuroradiologic evaluation with pathologic correlation.

PURPOSE: To report neuroradiologic findings in eight patients with familial erythrophagocytic lymphohistiocytosis (FEL), a rare, fatal autosomal recessive disease of infancy. MATERIALS AND METHODS: All patients underwent neuroradiologic magnetic resonance (MR) imaging and computed tomography before and after treatment. MR imaging-guided proton MR spectroscopy was performed in four. RESULTS: Seizures, focal neurologic deficits, and gait abnormalities were the most common neurologic manifestations. Brain involvement on MR images was progressive and consisted of parenchymal atrophy, diffuse abnormal signal intensity in the white matter on T2-weighted images, focal hyperintense lesions in both the white and gray matter, delayed myelination, and parenchymal calcifications. MR spectroscopy showed lower ratios of N-acetyl aspartate to total creatine and higher ratios of choline-containing compounds to total creatine, suggestive of decreased neuronal density and gliosis. CONCLUSION: Brain MR imaging and MR spectroscopy allow assessment of the severity of FEL and may aid in monitoring the response to treatment.

Brain↗
PubMed1994

Allogeneic versus autologous purged bone marrow transplantation for neuroblastoma: a report from the Childrens Cancer Group.

PURPOSE: We have compared the toxicity, relapse rate, and progression-free survival (PFS) of high-risk neuroblastoma patients receiving identical induction therapy and myeloablative chemotherapy plus total-body irradiation (TBI) followed by allogeneic or autologous purged bone marrow transplantation (BMT). PATIENTS AND METHODS: Fifty-six patients with high-risk neuroblastoma underwent BMT at investigator and parent option if they did not have progressive disease after induction chemotherapy with cisplatin, cyclophosphamide, doxorubicin, and etoposide. After surgery and local radiation to residual tumor, myeloablative therapy consisting of etoposide, melphalan, cisplatin, and TBI was given followed by BMT. Patients with human leukocyte antigen (HLA)-compatible siblings received allogeneic bone marrow (n = 20). The remaining patients (n = 36) received autologous bone marrow that had undergone multimodality purging and had no remaining detectable tumor cells by immunocytology. RESULTS: Four of 20 allogeneic patients had a treatment-related death, compared with three of 36 autologous patients (P = .21). The relapse rate among allogeneic BMT patients was 69%, compared with 46% for autologous BMT patients (P = .14). The estimated PFS rates 4 years after BMT were 25% for allogeneic BMT patients and 49% for autologous BMT patients (P = .051). CONCLUSION: Overall outcome for patients with neuroblastoma given this same induction therapy followed by autologous purged marrow was similar to that with allogeneic marrow, although bias in patients selection cannot be excluded in a nonrandomized comparison.

Adolescent↗