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L Sutton

Publications and source records attributed to L Sutton.

At least 19 recordsLinked to original sources
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↗
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

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↗
PubMed1994

Late CD8+ lymphocytic alveolitis after allogeneic bone marrow transplantation and chronic graft-versus-host disease.

Late-onset interstitial pneumonitis following allogeneic bone marrow transplantation (BMT) is a rare condition usually caused by a variety of infective agents, although in some cases these are idiopathic. We investigated noninfectious late interstitial pneumonitis with lymphocytic alveolitis in seven allogeneic BMT recipients using bronchoalveolar lavage (BAL), lymphocyte phenotyping analysis, CT lung scans, and pulmonary function tests. The results were compared with those of a control group composed of similar patients with no pulmonary symptoms. Of 65 long-term survivors, seven were included in the study. All had chronic graft-versus-host disease (GVHD) and developed interstitial pneumonitis a median of 210 d (range 120 to 445 d) after BMT. BAL revealed lymphocytosis, with an overall expansion of CD8+ subsets (38 to 90%). Lymphocytic alveolitis was not observed in the control group. Pulmonary function tests revealed a restrictive syndrome, and biopsy samples obtained from 2 patients showed interstitial lymphoid infiltration with fibrosis of the alveolar walls. Of the 7 patients, six were cured by starting immunosuppressive drugs or increasing the dosage with a drastic improvement in respiratory symptoms within 1 mo. These findings suggest that CD8+ alveolitis may be observed in late interstitial pneumonitis in allogeneic BMT recipients and may be a pulmonary manifestation of chronic GVHD.

Adult↗
PubMed1994

Allogeneic bone marrow transplantation in adult acute lymphoblastic leukemia in first complete remission: a comparative study. French Group of Therapy of Adult Acute Lymphoblastic Leukemia.

PURPOSE: Optimal postremission therapy remains controversial in adult patients with acute lymphoblastic leukemia (ALL). In a large multicentric trial (LALA87), we compared allogeneic bone marrow transplantation (BMT) with other postremission therapies (chemotherapy or autologous transplantation) using the result of the human leukocyte antigen (HLA) typing as a random allocation. PATIENTS AND METHODS: Patient eligibility requirements were as follows: (1) inclusion in LALA87 trial, (2) complete response to induction or salvage therapy, (3) age 15 to 40 years, and (4) at least one potential sibling donor. Patients with an HLA-identical sibling were assigned to the BMT group, while patients without a sibling donor constituted the control group. Allogeneic transplantation was scheduled for patients in the BMT group; in the control group, patients were randomly allocated to receive chemotherapy or autologous transplantation. RESULTS: Of 284 eligible points, 257 entered the study: 116 were allocated to the BMT group and 141 to the control group. The 5-year survival rates were not statistically significantly different between the two groups. When only patients with high-risk ALL were considered (those with [1] Philadelphia chromosome [Ph1] ALL, [2] null or undifferentiated ALL, or [3] c-ALL with either age greater than 35 years or WBC count > 30 x 10(9)/L or time to achieve complete remission > 4 weeks), overall survival (P = .03) and disease-free-survival (P = .01) were better for the BMT group compared with the control group (5-year overall survival rates, 44% v 20%; 5-year disease-free survival rates, 39% v 14%). CONCLUSION: Allogeneic transplantation does not improve survival in patients with standard-risk ALL and should be recommended only for patients with adverse prognostic factors.

Adolescent↗
PubMed1993

Sequences of MGH-1, YOU-1, and YOU-2 extended-spectrum beta-lactamase genes.

Genes for MGH-1, YOU-1, and YOU-2 extended-spectrum beta-lactamases have been cloned and sequenced. The gene for MGH-1 has the sequence of blaTEM-10, YOU-2 has that of blaTEM-12, and YOU-1 has that of blaTEM-26. All have evolved from blaTEM-1b but have the strong dual promoter sequence of blaTEM-2.

Amino Acid Sequence↗
PubMed1993

Allogeneic bone marrow transplantation for adult acute lymphoblastic leukemia in first complete remission: factors predictive of transplant-related mortality and influence of total body irradiation modalities.

In a retrospective multicentre study, we analyzed 184 consecutive patients who underwent bone marrow transplantation (BMT) from identical siblings for adult acute lymphoblastic leukemia in first complete remission between March 1980 and May 1989. The main causes of transplant-related mortality were GVHD and interstitial pneumonitis. Univariate and multivariate analyses identified the mode of total body irradiation (TBI) as the only independent predictive factor of transplant-related mortality. Ninety-one patients received single-dose TBI and 93 received fractionated-dose TBI as part of the conditioning regimen prior to BMT. Transplant-related mortality was more frequent in the single dose group (p = 0.017). The incidence of interstitial pneumonitis, acute and chronic GVHD and veno-occlusive disease of the liver was not statistically different between the two irradiation groups. However, fatal interstitial pneumonitis was significantly more frequent in the single dose irradiation group (p = 0.031). These results show that transplant-related mortality is closely associated with the mode of TBI administration. The increased relapse rate in the fractionated group explains why there was no difference between the two groups in terms of overall leukemia-free survival.

Adolescent↗
PubMed1992

Effects of alfentanil on intracranial pressure in children undergoing ventriculoperitoneal shunt revision.

The effects of alfentanil on intracranial pressure in patients with diminished intracranial compliance has not been established. Ten patients with hydrocephalus of varying etiologies, ages 16 months to 20 yr, presenting for ventriculoperitoneal shunt revision were studied. Following induction of anesthesia with thiopental, nitrous oxide/oxygen, and isoflurane, the trachea was intubated and anesthesia was maintained with isoflurane (0.5%), nitrous oxide (70%), and oxygen. After a minimum of 30 min and after the new shunt was placed, alfentanil was administered in increments of 10, 20, and 40 micrograms/kg at 3-min intervals, and intracranial pressure was measured over 12 min via the new shunt. In these unstimulated, normocapnic (PETCO2 32-38 mmHg) patients, heart rate, mean arterial pressure, and cerebral perfusion pressure declined from 110 +/- 26 beats/min, 90 +/- 11 mmHg, and 71 +/- 14 mmHg, to 84 +/- 25 beats/min, 66 +/- 11 mmHg, and 45 +/- 16 mmHg (mean +/- SD), respectively, by 3 min after the third dose (P less than 0.001). Intracranial pressure did not change from baseline (19 +/- 14 mmHg vs. 21 +/- 11) after any dose of alfentanil. Contrary to earlier studies in adult patients with brain tumors, the authors found that alfentanil, in pediatric patients with hydrocephalus anesthetized with oxygen, nitrous oxide, and isoflurane, did not increase intracranial pressure within a 9-min study period. The significant decreases in cerebral perfusion pressure observed merit concern and further study.

Adolescent↗
PubMed1992

Combined therapy with all-trans-retinoic acid and high-dose chemotherapy in patients with hyperleukocytic acute promyelocytic leukemia and severe visceral hemorrhage.

Acute promyelocytic leukemia (APL) is associated with a high incidence of disseminated intravascular coagulation (DIC) and early hemorrhagic death. The risk of early fatal hemorrhage is increased when high peripheral-blood blast count and severe DIC accompanied by visceral hemorrhage are present at diagnosis. Progressive cytolysis induced by daily increased doses of chemotherapy, or differentiation all-trans-retinoic acid (ATRA) therapy have been proposed for initial control of DIC, but both are dangerous in hyperleukocytic APL patients. We report our results obtained in three high-risk APL patients treated with a combination of conventional chemotherapy and ATRA. All patients had documented hyperleukocytic APL [M3 or M3-variant subtype, (15, 17) translocation] with DIC, and all had critical clinical course before treatment. Patient 1 presented with cerebral hemorrhage, patients 2 and 3 had acute respiratory failure probably due to pulmonary leukemic infiltration and pulmonary hemorrhage. In order to minimize the severity of DIC during chemotherapy-induced acute cytolysis, ATRA (45 mg/m2 per day) was started on the first or second day of chemotherapy and withdrawn when complete remission (CR) was achieved. Despite adverse clinical features, CR was obtained in these three high-risk patients. Patient 1 showed no increase of cerebral bleeding during therapy. Patients 2 and 3 required transient intensive care, with mechanical ventilation from day 4 to day 11 for one of them. Differentiating granular cells were present in peripheral blood of all patients from the day 5, 12 and 8 of cytotoxic therapy. For the three patients, the number of days with white blood cell count < 1 x 10(9)/l was only 2, 7 and 11 days respectively. These results suggest that differentiation therapy with ATRA may be useful even in hyperleukocytic APL patients, when ATRA is used in combination with chemotherapy. The mechanisms of this putative beneficial effect are discussed.

Adult↗
PubMed1992

Peripheral blood stem cell collection and autografting in high risk lymphomas.

Peripheral blood stem cells (PBSC) were collected from 29 patients with high risk Hodgkin's disease (n = 3) or non-Hodgkin's lymphoma (n = 26) in partial remission or first sensitive relapse. Patients had either bone marrow involvement or hypoplastic bone marrow. The conditioning regimen prior PBSC collection included amsacrine and cytosine arabinoside (Ara-C) or Ara-C alone. PBSC collection was performed after leukocyte counts reached 1 x 10(9)/1. A good yield was obtained in 23 patients, whereas sufficient numbers of CFU-GM were not obtained in six cases. Twenty-one patients have been transplanted. All patients except one achieved bone marrow engraftment. Eight patients are in complete remission (mean duration 15 months). The estimated 2 years survival rate is 46.4% (CI 25-68%). This procedure would seems a good alternative in poor prognosis lymphomas.

Adult↗
PubMed1991

Dose dependent inhibition of REM sleep in normal volunteers by biperiden, a muscarinic antagonist.

We tested the effect of biperiden (2, 4, and 8 mg per os 30 min before bedtime) on the polygraphically recorded sleep of normal volunteers (n = 8). Biperiden is a cholinergic, muscarinic receptor antagonist that may preferentially block the M1 receptor subtype. Compared with placebo, biperiden significantly prolonged rapid eye movement (REM) latency and suppressed REM sleep time and REM percentage in a dose-dependent manner. These REM suppressing effects of biperiden are similar to those previously reported with scopolamine and other nonselective muscarinic receptor antagonists. Because of uncertainties about the pharmacological specificity of biperiden, further studies are needed to determine the mechanism of action and the role of M1 receptors subtypes in the regulation of REM sleep.

Adult↗
PubMed1991

The effects of scopolamine on sleep and mood in depressed patients with a history of alcoholism and a normal comparison group.

In order to determine the effect of an anticholinergic agent on mood and sleep, scopolamine (0.4 mg IM) was administered before bedtime for three consecutive nights to 10 depressed patients (8 with a history of alcohol abuse) and 10 normal comparison subjects. The patients had a small, statistically significant antidepressant response on the second morning of treatment. Scopolamine inhibited rapid eye movement (REM) sleep and prolonged REM latency equally in depressed patients and the normal comparison group. Partial tolerance to the REM inhibiting effect of scopolamine developed between the first and third night of treatment. A REM rebound occurred during recovery nights. These results are consistent with concepts relating central cholinergic mechanisms to the control of REM sleep. Compared with controls, patients showed a greater increase in Stage 2 and Stage 2% and a lesser and increase in Delta (Stage 3 and 4) sleep % and Stage 4% on the first night of treatment. Further, well-controlled studies are needed to determine whether anticholinergic drugs possess clinically significant antidepressant effects.

Adult↗
PubMed1991

A soluble factor released by CD8+CD57+ lymphocytes from bone marrow transplanted patients inhibits cell-mediated cytolysis.

We report a new inhibitory activity of CD8+CD57+ peripheral blood lymphocytes from allo-bone marrow transplant patients. Positively selected CD8+CD57+ lymphocytes act as potent inhibitors of allospecific cytolytic T lymphocyte and lymphokine activated killer cell cytolytic activities. These suppressor cells are mature T cells expressing the CD2, 5, 7, CD3-TcR alpha beta complex, and lack natural killer cell markers as well as cytolytic function. Their inhibitory activity on both cytolytic processes and T-cell proliferation is mediated by a non-antigen-specific soluble factor released by CD8+CD57+ cells in culture supernatants. Preliminary characterization suggests that the CD8+CD57+ cells' inhibitory activity is mediated by a low molecular weight, glycosylated factor as indicated by its less than 1S coefficient of sedimentation and its binding to concanavalin A lectin.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1991

The cholinergic rapid eye movement induction test with arecoline in depression.

The cholinergic rapid eye movement (REM) induction test using arecoline hydrobromide, a cholinergic muscarinic receptor agonist, was studied in patients with affective disorder and in normal controls to determine whether or not depression is associated with enhanced induction of REM sleep by muscarinic agonists. Arecoline induced REM sleep in a dose-dependent fashion in both patients and controls compared with placebo infusions. Compared with normal controls, patients entered REM sleep significantly more rapidly following intravenous administration of 1.0 mg of arecoline hydrobromide than they did following administration of 0.5 mg of arecoline hydrobromide or placebo. These results, as well as those of previous studies, support the hypothesis that patients with affective disorder show a functional supersensitive induction of REM sleep in response to muscarinic receptor agonists and may be consistent with the hypothesis that functional muscarinic receptor "up regulation" is associated with depression.

Arecoline↗