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Biomedical subjects

L Sutton

Publications and source records attributed to L Sutton.

At least 73 records · Page 4Linked to original sources
PubMed1996

Liver dysfunction in allogeneic bone marrow transplantation recipients.

Liver dysfunction is common in allogeneic bone marrow graft recipients, but no systematic studies of pre- and posttransplantation liver biopsies have been performed to identify and compare hepatic lesions. This study involved 25 consecutive patients who had undergone serial viral screening tests, liver tests, and pre- and posttransplantation liver biopsy. The aims were to ascertain the origin of liver disorders prior to bone marrow transplantation, to determine the mechanism and severity of liver dysfunction occurring early after transplantation, and to identify a possible relationship between pre-existing liver lesions and the frequency and nature of early liver dysfunction after transplantation. Pretransplantation biochemical liver tests were abnormal in 72% of patients, despite the absence of clinical liver disease. Eleven patients had chronic viral hepatitis B or C. Mild or moderate histological lesions were present in all the patients, with bile duct abnormalities in 48%, central vein abnormalities in 24%, sinusoidal fibrosis in 52%, portal fibrosis in 88%, portal necrosis in 52%, and parenchymal siderosis in 76%. After transplantation, fatal veno-occlusive disease occurred in two patients and biochemical abnormalities occurred in 24. Coded review of needle biopsy specimens failed to provide a single diagnosis. Histological lesions differed between pre- and posttransplantation biopsy specimens only by increased iron overload (96%, P<0.01). We conclude that pretransplant liver lesions contribute to hepatic dysfunction early after bone marrow transplantation, being very similar in nature and degree to lesions observed posttransplantation.

Adolescent↗
PubMed1996

Factors influencing outcome in de novo myelodysplastic syndromes treated by allogeneic bone marrow transplantation: a long-term study of 71 patients Société Française de Greffe de Moelle.

We report on 71 consecutive patients with de novo myelodysplastic syndromes referred to physicians belonging to the Société française de greffe de moelle from 1982 through 1991 and transplanted with marrow from HLA-identical siblings. There were 16 cases of refractory anemia, 27 of refractory anemia with excess of blast cells, and 28 of refractory anemia with excess of blast cells in transformation. Seventeen patients had received cytoreductive chemotherapy before the graft. The disease progressed in 17 patients between diagnosis and grafting. Twenty-three patients are alive with a median follow-up of 6 years, whereas 24 died from relapse and 24 from transplant-related complications. Kaplan-Meier estimates of event-free survival, relapse and transplant-related mortality at 7 years were 32%, 48%, and 39%, respectively. The log-rank test and Cox's model revealed better outcome among young patients, patients in an early stage of the French-American-British (FAB) classification or with a low percentage of marrow blasts before transplantation, patients who did not undergo cytoreductive chemotherapy before transplantation, and patients conditioned with total body irradiation and cyclophosphamide. The high rate of relapse in advanced FAB stages has led us to graft patients earlier in the course of the disease, and we are currently conducting a multicenter, randomized study to determine the value of intensive chemotherapy before grafting in patients with an excess of marrow blasts.

Adult↗
PubMed1996

Treatment of children with newly diagnosed brain stem gliomas with intravenous recombinant beta-interferon and hyperfractionated radiation therapy: a childrens cancer group phase I/II study.

BACKGROUND: Prognosis for the majority of children with brain stem gliomas is dismal. In previous studies, recombinant beta-interferon (r beta IF) has been shown to be effective for children with recurrent brain stem gliomas and may also act synergistically with radiotherapy (RT). METHODS: Thirty-two children with diffuse intrinsic brain stem gliomas were treated with (r beta IF) and 7200 centigray (cGy) of hyperfractionated RT (100 cGy twice-daily fractions) to determine the toxicity of treatment and the tolerance of the brain stem to this regimen, as well as to assess survival. Patients were treated with r beta IF 3 times per week during RT and then for 8 weeks following RT. Initially, a dose escalation trial was performed. RESULTS: Interferon was initially begun at 12.5 x 10(6) IU/m2 and escalated up to 400 x 10(6) IU/m2. The safe starting dose was determined to be 100 x 10 (6) IU/m2. Due to unacceptable toxicity, the maintenance dose was reduced to 200 x 10 (6) IU/m2. Therapy was relatively well tolerated, although 13 of the patients required dose modifications due to hepatic or hematologic toxicity. Four of the patients had to discontinue treatment due to this toxicity. One patient died while receiving maintenance IF of encephalopathy, seizures, and brain stem dysfunction; believed possibly due to the r beta IF. Thirty of the 32 patients have developed progressive disease. The median time to progression from study entry was five months and the median time to death was 9 months. CONCLUSIONS: We conclude that r beta IF plus hyperfractionated therapy can be tolerated by children with newly diagnosed brain stem gliomas, although there is occasional dose-limiting hepatic, blood, and central nervous system toxicity. This therapy did not result in a higher rate of disease control.

Adolescent↗
PubMed1996

Postmortem examinations in a statewide audit of neonatal intensive care unit admissions in Australia in 1992. New South Wales Neonatal Intensive Care Unit Study Group.

The objectives of the investigation were (i) to study infants registered in a statewide audit of tertiary neonatal intensive care units in New South Wales, Australia in 1992 and who died, and (ii) to examine postmortem rates, quality of postmortem reports and compare clinical cause of death with postmortem report. Death rates, data on clinical cause of death and postmortem status were collected prospectively as part of the routine audit. Postmortem reports were examined by LS. Fifteen percent of the cohort died and 43% had a postmortem examination. The postmortem rate was highest in the 28-36 week gestation group and in babies dying of pulmonary haemorrhage, intracranial haemorrhage or sudden infant death syndrome. Fewer than 50% of babies with a major congenital anomaly had a postmortem. The postmortem changed the major diagnosis in 10% of cases and added useful information in 17%. We conclude that postmortem examination should be an essential part of any audit of neonatal intensive care unit outcomes.

Autopsy↗
PubMed1996

Measurement of respiratory parameters by using inspired oxygen sinusoidal forcing signals.

A companion paper (C. E. W. Hahn. J. Appl. Physiol 81: 985-997, 1996) described a continuous-flow gas-exchange mathematical model, which predicted that forced inspired oxygen sinusoids could be used to measure respiratory parameters rapidly, in place of the inert gas argon. We therefore made simultaneous measurements of dead space volume (VD) and alveolar volume (VA) in an animal model, using argon and oxygen inspired gas concentration sinusoid forcing signals, and then compared the results. Our data confirmed the model prediction that the attenuations of the oxygen and argon sinusoid perturbations are identical in the alveolar gas space, even though there is a net uptake of oxygen by the body. Our results show that the calculated values of VD and VA, obtained by using inspired oxygen forcing signals, were independent of both the mean fractional inspired oxygen concentration (FIO2; range 0.18-0.80% vol/vol) and the oxygen forcing signal amplitude (range +/- 2-6% vol/vol). In these studies, oxygen forcing signals, with forcing periods between 1 and 2 min, were able to measure controlled changes in instrument dead space to within 16 ml and also measure positive end-expiratory pressure-induced changes in VA. Under hyperoxic conditions, intravascular oxygen sensors confirmed that the sinusoidal PO2 signal passed into the arterial blood but not into the mixed-venous blood. However, the sinusoid perturbation PO2 signal did pass into the mixed-venous blood when the mean FIO2 was mildly hypoxic (FIO2 = 0.18% vol/vol). These data show that oxygen can be used instead of argon to measure airways dead space and VA.

Animals↗
PubMed1996

A single-center study of 11 patients with intraocular lymphoma treated with conventional chemotherapy followed by high-dose chemotherapy and autologous bone marrow transplantation in 5 cases.

Intraocular lymphoma (IOL) is a rare form of non Hodgkin lymphoma (NHL); it has a poor prognosis and is frequently associated with central nervous system (CNS) infiltration. We report the results of a prospective study of 11 patients with IOL who received conventional chemotherapy (CT), followed by salvage high-dose (HD) CT with autologous bone marrow transplantation (ABMT) in five cases. All 11 patients had abnormal funduscopic findings and six had CNS involvement at diagnosis. The diagnosis was based on vitrectomy in 10 cases and cerebral stereotaxic biopsy in one. Pathologic studies showed large-cell NHL in all cases. These large-cell NHL were of the B-cell type in 8 cases and of the T-cell type in two. First-line therapy consisted of a combination of cisplatin 25 mg/m2 as a 24-hour IV infusion on 4 consecutive days, VP-16 40 mg/m2 for 4 days, aracytine 2 g/m2 IV on day 5, and methylprednisolone 500 mg IV daily for 5 days (ESHAP) in 5 cases; alternating courses of ESHAP and HD methotrexate (MTX) in 4 cases; and HD MTX in 2 cases. Three patients underwent ocular and whole-brain radiation therapy. Five refractory patients subsequently received intensive CT with thiotepa 750 mg/m2, busulfan 10 mg/kg and cyclophosphamide 120 mg/kg, followed by ABMT. First-line treatment failed in 10 evaluable cases. One patient died of CNS progression at 12 months. All the patients who underwent intensive CT and ABMT entered CR; two relapsed at 6 months and three are alive in CR 15, 15 and 14 months after ABMT. Six patients are alive with persistent disease at 8, 13, 14, 15, 18 and 24 months. It seems in conclusion that, high-dose thiotepa, busulfan and cyclophosphamide followed by ABMT is effective in some cases of refractory IOL.

Aged↗
PubMed1996

Transmission of Plasmodium falciparum by allogeneic bone marrow transplantation.

We describe a case of Plasmodium falciparum infection in a Comorian patient undergoing BMT. The patient's last visit to an endemic area was 1 year prior to BMT. The donor left the Comoro Islands 2 months before marrow harvesting. They had both had previous episodes of malaria and were seropositive for Plasmodium falciparum. At the time of BMT, blood smears were negative in both the donor and recipient. On day 12 post-BMT the patient was asymptomatic but a blood smear revealed 12.5% parasitemia. We consider that donors and recipients at risk pre-BMT should routinely be given specific treatment before marrow harvesting and conditioning, independent of the appearance of blood smears.

Adult↗
PubMed1996

Autologous bone marrow transplantation in relapsed HIV-related non-Hodgkin's lymphoma.

There are few reports of salvage chemotherapy for HIV-related non-Hodgkin's lymphoma (NHL). We report a relapsed HIV-related high-grade NHL which was treated successfully with ESHAP chemotherapy followed by high-dose chemotherapy and autologous bone marrow transplantation (ABMT). ABMT may later have triggered opportunistic infections in this patient.

AIDS-Related Opportunistic Infections↗
PubMed1995

No antidepressant effect of biperiden compared with placebo in depression: a double-blind 6-week clinical trial.

Depression may result from an increased ratio of cholinergic to aminergic central neurotransmission. The effect of centrally active anticholinergic agents on depressive ratings in depressed patients, however, has not been well studied. In a previous open label 4-week clinical trial, Kasper et al. (1981) reported that biperiden (Akineton) had antidepressant effects in depressed patients. We compared the effects of placebo and biperiden in a randomized, double-blind, parallel-design 6-week study. All patients received placebo for the first week and then received either biperiden (< or = 12 mg/day) or a peripherally acting anticholinergic agent, glycopyrrolate (Robinul, 1 mg/day) for 4 weeks. All patients received placebo during week 6. Both groups significantly improved, but biperiden did not demonstrate any significant benefit compared with glycopyrrolate. In a subgroup of patients receiving biperiden, the percentage of rapid eye movement sleep was significantly decreased only in the first week of biperiden compared with the initial placebo week, suggesting that tolerance to the central effects of biperiden developed. Further studies would be needed to determine whether anticholinergic agents possess antidepressant properties.

Adult↗
PubMed1995

Exon scanning for mutations of the NF2 gene in pediatric ependymomas, rhabdoid tumors and meningiomas.

Deletions of chromosome 22 have been identified in 3 types of childhood primary brain tumor: meningiomas, rhabdoid or atypical teratoid tumors (ATT) and ependymomas. This implicates the involvement of tumor suppressor genes on chromosome 22 in the genesis of these rare tumors. One such candidate tumor suppressor gene is the recently cloned neurofibromatosis 2 (NF2) locus. The purpose of our study was to determine the frequency of germ-line and somatic NF2 mutations in a selected group of brain tumors in children. Using single-strand conformation polymorphism (SSCP) assays we screened 17 exons of the NF2 gene in 13 pediatric brain tumors and 9 matched normal blood DNA samples. Tumors included 3 meningiomas, 2 rhabdoid or ATTs, 7 ependymomas and 1 malignant tumor of glial lineage. In addition, lymphoblastoid cell lines from 3 patients with rhabdoid/ATT in whom no tumor tissue was available were analyzed for germ-line mutations. Migration shifts were not detected in any of the normal DNA samples analyzed. Of the 13 tumors screened by SSCP, 1 meningioma with monosomy 22 produced a migration shift in exon 13. DNA sequencing of exon 13 revealed a deletion of a single guanine nucleotide (base 1397) in codon 466, causing a frame shift. While not all mutations might have been picked up by this technique, the data suggest that, similar to adult sporadic meningiomas, some pediatric meningiomas may result from somatic mutations in the NF2 gene. For rhabdoid tumors and ependymomas it appears that a locus distinct from NF2 might be responsible for tumorigenesis.

Base Sequence↗
PubMed1995

p53 gene mutations in pediatric brain tumors.

We investigated the frequency of p53 mutations in 47 pediatric brain tumors of various histologic subtypes that were collected over a period of 5 years. The specimens included 15 primitive neuroectodermal tumors (PNETs), 17 low grade astrocytomas, one anaplastic astrocytoma, three glioblastomas (GBMs), one mixed glial tumor, eight ependymomas, one choroid plexus carcinoma, and one gangliocytoma/ganglioneuroma. Mutations were identified by single strand conformation polymorphism analysis of exons 4-8 and verified by sequencing. Mutations were present in 2 of 3 cases of GBM, but not in 17 low grade astrocytomas (P = 0.02, Fisher's exact test). One GBM demonstrated a germline GGC to AGC transition (gly to ser) at codon 245 with loss of the wild-type allele. A second GBM contained a CGG to TGG transition (arg to trp) at codon 248, also with loss of the wild-type allele, but normal tissue was not available for comparison. In addition, one of 15 PNETs retained heterozygosity but demonstrated a somatic CGT to TGT transition (arg to cys) at codon 273. p53 mutations were absent in other histologic subtypes and in two cases with multiple primary cancers. These data are consistent with earlier findings that p53 mutations are rare in PNETs, which are primarily pediatric tumors. In contrast to adult gliomas, p53 mutations in pediatric gliomas appear restricted to the GBMs. The lack of p53 mutations in pediatric low grade astrocytomas suggests not only histological differences, but also a different molecular pathogenesis in adult and pediatric patients.

Adolescent↗
PubMed1995

Lymphoproliferative disorders after organ transplantation: a report of 24 cases observed in a single center.

PURPOSE: Organ recipients are at a high risk of post-transplant lymphoproliferative disorders (PTLDs) as a complication of immunosuppressive therapy. We report the incidence, clinical presentation, pathologic findings, treatment, and outcome for 24 cases of PTLD observed at our institution. PATIENTS AND METHODS: Twenty-four (1.7%) of 1,385 organ transplant recipients developed PTLDs. Dosages of immunosuppressive drugs were reduced in 19 patients. Treatment consisted of anti-B-cell monoclonal antibodies (12 patients), and/or chemotherapy (eight patients), or surgery (two patients). RESULTS: The median time between grafting and the onset of PTLD was 210 days. Tumors were classified as monomorphic and polymorphic in nine and 15 cases, respectively. Three of 24 cases were of T-cell origin. Genotypic studies confirmed the monoclonality of the tumors in 11 cases among 14 PTLDs tested. Epstein-Barr virus (EBV) infection was associated with 70% of B-cell PTLDs tested. The overall survival duration was 5 months. Ten patients are alive and disease-free with a median follow-up time of 37 months; most were treated with anti-B-cell antibodies. Two other patients died in complete remission of unrelated causes at 33 and 38 months. CONCLUSION: Anti-B-cell monoclonal antibody therapy seems to be effective in PTLD, even in monoclonal B-cell forms, but other approaches will be necessary to improve survival further.

Adolescent↗
PubMed1995

Evaluation of renal function in 60 long-term survivors of bone marrow transplantation.

Although the acute nephrotoxicity of bone marrow transplantation is well documented, long-term follow-up studies are scanty. Renal function was evaluated in 60 long-term survivors of allogeneic (24 patients) or autologous (36 patients) bone marrow transplantation (BMT) with a mean follow-up of 2 yr. Renal function tests included serum creatinine, GFR (inulin clearance), effective RPF (p-aminohyppurate clearance), urinary beta 2-microglobulin and N-acetyl-beta-D-glucosaminidase excretion, and renal tomography. The mean serum creatinine level was 83 +/- 3 and 93 +/- 3 mumol/L before and after grafting, respectively (P < 0.05). The mean GFR (93 +/- 3 mL/min) and effective RPF (419 +/- 16 mL/min) were significantly lower than in healthy controls (120 +/- 3 and 500 +/- 1 mL/min; P < 0.05) and than in candidates for BMT matched for age and hematologic diseases (117 +/- 3 and 469 +/- 11 mL/min; P < 0.05). Thirty-four patients had a fall in the GFR of at least 20%. Patients who received total body irradiation had significant lower creatinine clearance (86 +/- 3 mL/min) and GFR (86 +/- 3 mL/min) than the controls and the patients who received high-dose chemotherapy (100 +/- 4 and 104 +/- 5 mL/min; P < 0.05). These results suggest that subclinical renal dysfunction occurs frequently in marrow graft recipients, especially those who undergo total body irradiation.

Adult↗
PubMed1994

The impact of perioperative factors on subsequent intelligence quotient deficits in children treated for medulloblastoma/posterior fossa primitive neuroectodermal tumors.

BACKGROUND: Despite success in treating children with medulloblastoma/posterior fossa primitive neuroectodermal tumor (PF PNET), some children survive with significant neurocognitive sequelae. This study was performed to understand better the significance of perioperative factors on subsequent full scale intelligence quotient (FSIQ) deterioration in these children. METHODS: Twenty-eight children who underwent prospective and serial neurocognitive testing were studied. All children underwent surgery followed by radiotherapy with or without chemotherapy between 1983 and 1987 for medulloblastoma/PF PNET and were disease free when this study was conducted. IQ testing was performed before surgery and after the completion of radiation therapy. The clinical courses of the patients were correlated with changes in the corresponding intelligence quotients of each child. Factors correlating with neurocognitive declines were examined by chi-square or Fisher exact test analysis. Differences in mean IQs were examined by the t test. Factors found to be significant were analyzed by exact logistic regression analysis. RESULTS: The presence of adverse factors such as neurologic deficits, meningitis, or shunt infections, or the need for repeat surgery was correlated significantly with IQ deficits after treatment. Of the subset of children with one or more of these factors, 13 of 16 (81%) sustained decreases in FSIQ; 7 of 16 (43.8%) had decreases of 20 points of more. In contrast, only 3 of 12 (25%) of the children without the factors sustained FSIQ decreases, and no child sustained a decrease of more than 13 points. The mean FSIQ change after treatment in the group with factors was -15.7 (95% confidence interval [CI]: -24.0, -8.4), and the median was -18. The mean FSIQ change in the group without factors was 4.8 (95% CI: -0.5, 10.1), and the median was 5. The difference in mean FSIQ change between the two groups was significant (P < 0.0001). On univariate analysis, both the presence of adverse factors and an age less than six years correlated with neurocognitive deficit. On regression analysis, only the presence of adverse factors was significant (odds ratio 11.53; 95% CI, 1.65-116.58; P = 0.009), whereas age was not (P = 0.27). CONCLUSIONS: Perioperative events or complications may account for some of the neurocognitive deterioration seen in these children after treatment, especially in the very young. The occurrence of these factors is associated with a significantly greater risk of IQ deterioration. Studies of the neurocognitive effects of treatment for children with medulloblastoma/PF PNET should include an analysis of these postoperative factors.

Adolescent↗
PubMed1994

Chicken pox and acute monocytic leukaemia skin lesions in an HIV-seropositive man.

Lymphoid neoplasia is now well known to occur in patients with human immunodeficiency virus (HIV) infection but the first case of acute monocytic leukaemia in an HIV-seropositive man has been only recently described. We report the case of an HIV-infected patient who simultaneously developed skin lesions of acute monocytic leukaemia and chicken pox. We suggest that HIV may produce a malignant transformation of monocytic cells.

AIDS-Related Opportunistic Infections↗
PubMed1994

Detection of Klebsiella pneumoniae and Escherichia coli strains producing extended-spectrum beta-lactamases.

Plasmids encoding extended-spectrum beta-lactamases of the TEM, SHV, and AmpC families were introduced into common Escherichia coli and Klebsiella pneumoniae hosts to create a homogeneous panel for evaluating the abilities of five test systems to detect resistance to eight beta-lactam antibiotics. Although MICs, as determined by agar dilution or E test strips, were increased and disk diffusion zone diameters were diminished, breakpoints for resistance were often not reached, and neither approach was sensitive in detecting resistance to oxyimino-beta-lactams. The MicroScan 18-h microdilution or Vitek rapid automated procedures were similarly insensitive. Ceftazidime was the best single test antibiotic for detecting extended-spectrum beta-lactamase production. beta-Lactamases TEM-7 and TEM-12 were particularly difficult to detect. Because of such difficulties, the prevalence of extended-spectrum beta-lactamases is likely to be greater than is currently appreciated.

Drug Resistance, Microbial↗
PubMed1994

Assessment of cardiorespiratory function using oscillating inert gas forcing signals.

A theoretical model (Hahn et al. J. Appl. Physiol. 75: 1863-1876, 1993) predicts that the amplitudes of the argon and nitrous oxide inspired, end-expired, and mixed expired sinusoids at forcing periods in the range of 2-3 min (frequency 0.3-0.5 min-1) can be used directly to measure airway dead space, lung alveolar volume, and pulmonary blood flow. We tested the ability of this procedure to measure these parameters continuously by feeding monosinusoidal argon and nitrous oxide forcing signals (6 +/- 4% vol/vol) into the inspired airstream of nine anesthetized ventilated dogs. Close agreement was found between single-breath and sinusoid airway dead space measurements (mean difference 15 +/- 6%, 95% confidence limit), N2 washout and sinusoid alveolar volume (mean difference 4 +/- 6%, 95% confidence limit), and thermal dilution and sinusoid pulmonary blood flow (mean difference 12 +/- 11%, 95% confidence limit). The application of 1 kPa positive end-expiratory pressure increased airway dead space by 12% and alveolar volume from 0.8 to 1.1 liters but did not alter pulmonary blood flow, as measured by both the sinusoid and comparator techniques. Our findings show that the noninvasive sinusoid technique can be used to measure cardiorespiratory lung function and allows changes in function to be resolved in 2 min.

Animals↗