Biomedical subjects

L Sutton

Publications and source records attributed to L Sutton.

At least 19 recordsLinked to original sources

PubMed1998

Emergent/urgent therapeutic irradiation in pediatric oncology: patterns of presentation, treatment, and outcome.

PURPOSE: We reviewed all pediatric cases referred for emergent/urgent therapy (requiring treatment within 48 hours) to identify frequency, patterns of presentation, and efficacy of therapy. We defined five categories of emergent/urgent therapy based on irradiated site and/or signs: Group I, spinal cord compression; Group II, respiratory compromise; Group III, infradiaphagmatic distress; Group IV, intracranial signs; Group V, pain. MATERIALS AND METHODS: From 2/1/88-3/1/ 94, 104 children with 115 problems were referred by specialists at the Children's Hospital of Philadelphia. Diagnosis, nature of the emergency, and response were examined. Responses were categorized as complete resolution, improvement or stabilization, and progression. RESULTS: The 104 children represented 12% of referrals during the study period. The most common tumors were CNS PNET and gliomas (20%); and neuroblastoma (20%). Forty-five problems occurred with newly diagnosed tumors and 70 after progression. Ninety-one episodes were managed with radiation therapy and 24 with other modalities. Patients with spinal cord/cauda equina (n = 33) compression improved (55%) or stabilized (30%). Patients with respiratory compromise from thoracic (n = 14) or abdominal (n = 5) disease had a response rate of 72%. Eight patients in group III had a 66% response. In Group IV (n = 16), 63% had complete responses and 19% had stabilization. Group V (n = 15) patients had a complete or partial response of 93%. CONCLUSION: Approximately 10% of children referred for radiation therapy required emergent/urgent treatment. Eighty percent of patients achieved stabilization or showed improvement in signs and symptoms, indicating that radiotherapy is a valuable and reliable component of multimodal care in such situations.

Adolescent↗

PubMed1997

Expansion of CD4+CD7- T cells, a memory subset with preferential interleukin-4 production, after bone marrow transplantation.

BACKGROUND: Inadequate reconstitution of CD4+ lymphocyte and interleukin (IL)-2 production defect are observed after bone marrow or peripheral blood stem cell transplantation (SCT). METHODS: We studied immune reconstitution after SCT in 33 consecutive patients who received allogeneic SCT (17 patients) or autologous SCT (16 patients). The aims were to assess the regeneration of the CD4+ T-cell subset with regard to helper cell differentiation. CD4+ T-cell subset regeneration and expansion of the CD4+CD7- subset were studied by immunofluorescence analysis. CD4+CD7- cell cytokine secretion was analyzed after cell sorting and costimulation of the CD3 and CD28 pathways, in enzyme-linked immunosorbent assay and reverse transcription-polymerase chain reaction assays. RESULTS: We report a relative expansion of the CD4+CD7- subset within CD4+ T cells, detected as early as 1 month after bone marrow transplantation and decreasing after day 60. CD4+CD7- T cells preferentially expressed CD45RO and activation markers such as CD57, CD25, and HLA-DR. No relationship was observed between the CD4+CD7- expansion and transplant-related complications. We observed no significant IL-2 production in supernatants from sorted CD4+CD7- T cells, whereas IL-4 levels were comparable to those produced by cells from normal individuals. Autologous CD4+CD7+ cells showed little, if any, IL-4 production, and IL-2 production was lower than that by normal CD4+CD7+ T cells. Reverse transcription-polymerase chain reaction assays showed similar amounts of interferon-gamma transcripts in the two subsets; tumor necrosis factor-alpha, IL-4, and IL-10 transcripts were detected in CD4+CD7- T cells but not in their CD4+CD7+ counterparts. CONCLUSIONS: These data confirm the IL-2 production defect after bone marrow transplantation and suggest that the CD4+CD7- T-cell subset might be preferentially involved in the enhanced production of IL-4 and low production of IL-2. These data show that the early immune reconstitution in CD4+ T cells after SCT preferentially involves memory T cells with a Th0/Th2 differentiation that might participate in the T-helper cell defect.

Adult↗

PubMed1997

Early onset of immunoglobulin heavy chain gene rearrangements in normal human bone marrow CD34+ cells.

To characterize early B-cell precursors in humans, we correlated immunoglobulin heavy chain (IgH) gene rearrangement status with the CD34, CD19, and CD10 cell surface markers. Highly purified adult bone marrow (BM) cell fractions were obtained by two successive rounds of flow cytometric cell sorting, and IgH rearrangements were analyzed by polymerase chain reaction (PCR) amplification. Complete VDJH rearrangements were observed in the CD34+ CD19+ fraction, but not in the more immature CD34+ CD19- fraction. About one quarter of these rearrangements had an open reading frame, thus potentially permitting the synthesis of a mu chain. Partial DJH rearrangements were detected in both CD34+ CD19+ and CD34+ CD19- subsets, although they were less abundant in the latter. When triple labeling was used to better characterize the CD34+ CD19- population, DJH rearrangements were found to be present in the CD34(+) CD10+ CD19- fraction, but not in the more primitive CD34+ CD10- CD19-. These results indicate that IgH gene rearrangements occur in CD34+ BM cells and that they initiate in immature progenitors expressing the CD10, but not yet the CD19 surface antigen. Finally, the presence of IgH gene rearrangements in CD34+ BM cells provides a useful marker of clonality to evaluate the possible involvement of these cells in various B-cell lymphoid malignancies.

Adult↗

PubMed1997

Adjuvant chemotherapy for the treatment of intracranial ependymoma of childhood.

BACKGROUND: Current treatment for childhood intracranial ependymomas with surgery and radiation therapy (RT) yields 5-year survival rates ranging from 50-70% after complete resection to 0-30% after incomplete surgical resection. The role of chemotherapy in the treatment of ependymoma has not been established. In this pilot study, children with newly diagnosed intracranial ependymoma were treated with RT and chemotherapy using agents comparable to those found to be active in the treatment of intracranial ependymoma in infants. METHODS: Nineteen children age 3-14 years (median, 7.5 years) were treated with postoperative RT and chemotherapy. Chemotherapy was comprised of carboplatin, 560 mg/m2, with vincristine, 1.5 mg/m2, weekly for 3 weeks, alternating at 4-week intervals with ifosfamide, 1.8 g/m2, and etoposide, 100 mg/m2, for 5 consecutive days for a total of 4 cycles. RESULTS: The 5-year progression free survival (PFS) estimate was 74%. The extent of surgical resection was not a significant prognostic factor in this study. By contrast, ependymomas located in the posterior fossa were associated with a higher rate of progression (P = 0.036). Toxicity, limited predominantly to myelosuppression, was manageable. CONCLUSIONS: The PFS for children with postoperative residual ependymoma treated with RT and chemotherapy in this study was higher than published survival results for RT alone. These results suggest a role for multialkylator chemotherapy in incompletely resected intracranial ependymoma and provide the rationale for a randomized trial comparing this strategy with conventional postoperative RT.

Adolescent↗

PubMed1997

Phase II study of daily oral etoposide in children with recurrent brain tumors and other solid tumors.

Pre-clinical data and adult experience suggests that topoisomerase targeted anti-cancer agents may be highly schedule dependent, and efficacy may improve with prolonged exposure. To investigate this hypothesis, 28 children with recurrent brain and solid tumors were enrolled in a phase II study of oral etoposide (ETP). Patients were prescribed ETP at 50 mg/m2/ day for 21 consecutive days. Courses were repeated every 28 days pending bone marrow recovery. Evaluation of response was initially performed after 8 weeks and then every 12 weeks either by CT or MRI. Three of 4 patients with PNET (primitive neuroectodermal tumor)/medulloblastora achieved a partial response (PR). Two of 5 with ependymoma responded, one with a complete response and one with a PR. Toxicity was manageable with only 1 admission for fever and neutropenia in 120 cycles of therapy. Five patients had grade 3 or 4 neutropenia. One had grade 4 thrombocytopenia and one grade 2 mucositis and withdrew as a result. One patient had grade 2 diarrhea. Two patients who achieved a PR had received ETP as part of prior combination chemotherapy regimens. Daily oral etoposide is active in recurrent PNET/medulloblastoma and ependymoma. Toxicity is manageable and rarely requires intervention. Daily oral etoposide in combination with crosslinking agents should be considered in future phase III trials. Determination of activity in glioma and solid tumors is not complete.

Administration, Oral↗

PubMed1997

Oxygen transport with oscillations of inspired oxygen concentration.

A theoretical model predicts that forced inspiratory oxygen concentration oscillations can be used to recover cardiorespiratory data and elicit information about the oxygen transport system (Hahn, 1996). The effects of hypoxia on the penetration of these generated oxygen oscillations into arterial and venous blood were explored in dogs exposed to a graded severity of hypoxia. Continuously recorded sinusoidal oxygen oscillations in the respired partial pressure, blood tension and mixed-venous saturation show that the transmission of forced oxygen oscillations from the lungs to the arterial blood depends on the mean arterial saturation. When mean inspired oxygen is high enough to fully saturate arterial haemoglobin, an inspired oscillation can only be transmitted in the blood as an oscillation in oxygen tension. However, in the presence of arterial hypoxaemia, oscillations in both the oxygen saturation and partial pressure of arterial blood are observed. Under these conditions, the oxygen saturation and partial pressure oscillations are also transmitted to mixed-venous blood. Our data illustrates that the link between the arterial and mixed-venous oscillations is non-linear and dependent on the sigmoidal binding relationship between oxygen and haemoglobin.

Animals↗

PubMed1997

Allogeneic bone marrow transplantation for agnogenic myeloid metaplasia. French Society of Bone Marrow Transplantation.

Agnogenic myeloid metaplasia is a rare indication for allogeneic bone marrow transplantation (BMT). We have retrospectively studied 12 patients allografted for this disease within the French BMT group. Prior to BMT, the mean age was 40 years (range 14-49). Diagnosis was based on the Polycythaemia Vera Study Group criteria. Before BMT, 10 patients had been splenectomized, eight required transfusions, and four had received at least two lines of chemotherapy. Cyclophosphamide and total body irradiation was the main conditioning regimen used (n=8). The donor was an HLA-identical sibling except in one case where there was one HLA-DR mismatch. Acute graft-versus-host disease (GVHD) prophylaxis consisted of methotrexate and cyclosporine A. 11 patients engrafted with median times to achieve absolute neutrophil count > 0.5 x 10(9)/l and platelet count > 50 x 10(9)/l of 17 (range 12-44) and 29 (range 12-196) days respectively. One primary graft failure occurred. 10 patients developed grade II-IV acute GVHD, four developed extensive chronic GVHD. One patient relapsed 16 months post-BMT and was untreated and well 14 months later. Three patients died from the BMT procedure. In May 1996 the median follow-up was 25 months and the 4-year overall and event-free survivals were 71% and 59%, respectively. Thus, we conclude that extensive myelofibrosis is not associated with delayed engraftment, and that HLA-identical sibling allogeneic BMT can be considered in a small proportion of patients with agnogenic myeloid metaplasia.

Adolescent↗

PubMed1997

Endocrine outcome in long-term survivors of low-grade hypothalamic/chiasmatic glioma.

OBJECTIVE: We have evaluated the frequency of endocrine abnormalities in a large group of patients with hypothalamic/chiasmatic glioma (H/CG) and its correlation with the different forms of therapy. DESIGN: Descriptive retrospective study using case note review analysis. PATIENTS: The records of 68 children who survived H/CG were analysed. One third had neurofibromatosis. The mean age at tumour presentation was 5 years. The median time of follow-up was 3.6 years. Thirty-eight children received cranial radiation, of whom 17 also had surgery. Surgery was performed in a total of 24 patients. Fifteen patients received only chemotherapy. Eight children, all with neurofibromatosis, received no specific tumour treatment. MEASUREMENTS: Endocrine dysfunction was determined by clinical manifestations and biochemical evaluation of hypothalamic-pituitary function. RESULTS: Endocrine dysfunction occurred in 42% of the children. The most common disorder was GH deficiency (GHD). Of 50 children evaluated, 15 of the 19 with GHD received cranial irradiation (P < 0.05). HOwever, 15 children treated with more than 15 Gy grew normally. Precocious puberty was diagnosed in 11 patients. Nine patients, all treated with cranial irradiation, developed hypogonadotrophic hypogonadism. Of the 14 patients with hypothyroidism, 10 had surgery (P < 0.005). Hypoadrenalism and diabetes insipidus each occurred in eight patients, and were associated with multiple endocrine deficiencies and surgery. Endocrine deficiencies occurred in children with neurofibromatosis as frequently as children without neurofibromatosis but only when comparing those treated with cranial irradiation or surgery. CONCLUSIONS: Nearly all studies assessing the patients with different tumour therapy evaluate patients wit different tumour types. This study investigates a specific and large population of patients with H/CG and correlates the different form of treatment with the endocrine outcome. Precocious puberty, in children with this tumour, is probably due to tumour location rather than oncological therapy. Conversely, although endocrine deficiencies can be a result of tumour location, the major causes of endocrine abnormalities were field irradiation and tumour surgery. A notable finding not previously reported is that endocrine dysfunction occurs less often in neurofibromatosis patients treated conservatively. Furthermore, this study documents that a significant number of young children grew normally despite receiving brain irradiation of greater than 45 Gy.

Adolescent↗

PubMed1997

Sequential versus simultaneous combination antiretroviral regimens for the treatment of human immunodeficiency virus type 1 infection in vitro.

Two-, three-, and four-drug antiretroviral combinations in either simultaneous or sequential regimens were evaluated for their ability to suppress human immunodeficiency virus (HIV) type 1 replication in vitro. Zidovudine, lamivudine, saquinavir, and nevirapine were used at IC(90)s, IC(99)s, or IC(> or = 99)s in a CD4-positive human lymphoblastoid cell line (H9 cells) acutely infected with HIV-1. In sequential regimens, drugs were added at weekly intervals. In simultaneous regimens, all drugs were added on day 0. Increasing the number of drugs in a combination regimen both increased the degree of viral inhibition and delayed the time of breakthrough viral replication. Simultaneous regimens provided more profound and earlier viral inhibition than did sequential regimens. However, sequential addition provided relatively more durable viral inhibition than did simultaneous regimens when drug concentrations were low. The relative effectiveness of different HIV-1 therapeutic strategies depends on both the numbers and concentrations of the drugs used.

Anti-HIV Agents↗

PubMed1997

Alveolar and dead space volume measured by oscillations of inspired oxygen in awake adults.

Forced sinusoidal oscillations in the inspired concentration of a low-solubility inert gas can be used to measure airways dead space and alveolar volume. When inspired oxygen is oscillated about its mean value in the same way, the ratio between the amplitudes of the resulting end-expired and inspired oxygen oscillations is the same as that of an inert gas such as argon. Thus, oxygen forcing oscillations can be used to measure lung volume. In nine healthy spontaneously breathing adults, the FIO2 (mean FIO2 = 0.26, mean minute volume = 8.5 L/min) was forced to sinusoidally oscillate with an amplitude of +/- 0.04. The mean airways dead space measured using FIO2 oscillations with a forcing period of 3 min was 0.17 +/- 0.04 L, and the airways dead space measured by a single-breath C02 technique was no different at 0.19 +/- 0.03 L. An oxygen oscillation of the same period measured the mean end-expired alveolar volume at 3.1 +/- 0.7 L. Adding together the airways dead space and end-expired alveolar volume, obtained by the oxygen oscillation technique, provided a measure of FRC that at 3.3 +/- 0.7 L matched the FRC of 3.3 +/- 0.8 L measured by whole-body plethysmography. A third measure of FRC using a multiple-breath nitrogen washout technique gave a smaller volume of 3.00 +/- 0.85 L. The advantage of using FIO2 oscillations is that accurate FRC measurements can be made continuously, without interfering with the subject's natural breathing rhythm.

Adult↗

PubMed1997

Indications and timing of allogeneic bone marrow transplantation in myelodysplastic syndromes.

Allogeneic bone marrow transplantation is an effective treatment for myelodysplastic syndromes, providing a probable cure in about one-third of cases overall. It is generally reserved for patients under 50 years who have an HLA-compatible donor. Post-transplant disease-free survival rates vary according to several prognostic factors, which often overlap with those predicting the spontaneous outcome of the disease. Consequently, it is sometimes difficult to choose the indications and timing of bone marrow transplantation in this setting. Here we review the literature in an attempt to draw up relevant guidelines.

Antigenic Variation↗

PubMed1996

Total body irradiation prior to bone marrow transplantation: efficacy and safety of granisetron in the prophylaxis and control of radiation-induced emesis.

PURPOSE: Radiation-induced emesis is one of the most disturbing side effects of total body irradiation (TBI). To evaluate the efficacy and to determine the best schedule of granisetron (a selective 5-hydroxytryptamine3 serotonin receptor antagonist) administration in the prevention of radiation-induced nausea and vomiting, we conducted a trial involving patients receiving single-dose TBI before bone marrow transplantation (BMT). METHODS AND MATERIALS: Thirty-six patients with non-Hodgkin's lymphoma (n = 12), multiple myeloma (n = 8), acute lymphoblastic leukemia (n = 7), acute nonlymphoblastic leukemia (n = 6), and chronic myeloid leukemia (n = 3) referred to our department between March 1992 and February 1994 were enrolled in this study to assess the efficacy of granisetron during single-dose TBI before autologous BMT (n = 26), allogeneic BMT (n = 8), or syngeneic BMT (n = 2). The male-to-female ratio was 22:14 (1.57), and the mean age was 41 +/- 11 years (range 16-58). Before TBI, conditioning chemotherapy consisted of cyclophosphamide (CY) alone (60 mg/kg per day on 2 successive days) in 24 patients, CY combined with other drugs in 6, and combinations without CY in 6. All patients received single-dose TBI (10 Gy administered to the midplane at L4, and 8 Gy to the lungs). The mean instantaneous and average dose rates were 0.039 +/- 0.012 Gy/min (range 0.031-0.058), and 0.025-0.006 Gy/min (range 2.08-3.96), respectively. Granisetron was administered 30-45 min before TBI according to two different modalities: a total dose of 3 mg as a 5-min intravenous (i.v.) infusion (Treatment A, n = 15; 42%) or the same treatment plus 3 mg of granisetron as a 24-h continuous i.v. infusion (total dose: 6 mg, Treatment B, n = 21; 58%). Depending on the BMT teams, hyperdiuresis was continued (n = 19, 53%) or suspended (n = 17, 47%) during TBI. Nausea and vomiting were assessed during the TBI session and the following 12 h, and were scored as follows: S1 = no nausea or vomiting; S2 = moderate nausea; S3 = severe nausea and/or single episode of vomiting; and S4 = multiple episodes of vomiting. RESULTS: During TBI, 18 (50%) patients were scored as complete responders (S1), 1 (3%) as a major responder (S2), 9 (25%) as minor responders (S3), and 8 (22%) as nonresponders (S4). During the following 12 h, 28 (78%) patients were free of severe nausea and vomiting (S1 or S2), whereas 8 (22%) vomited (S3 or S4). In univariate analyses, the 12-h probability of emesis was significantly higher in patients undergoing hyperdiuresis (63% vs. 30%; p = 0.05), and in patients older than 45 years (65% for age > 45 vs. 33% for age < or = 45; p = 0.05). The probability of S3 or S4 emesis was 50% with Treatment A and 47% with Treatment B (p = 0.86). Sex, body weight, and type of conditioning chemotherapy did not influence the 12-h probability of emesis. Multivariate analysis revealed that hyperdiuresis (p = 0.02) and Treatment A (p = 0.04) were independently associated with radiation-induced emesis, whereas sex (p = 0.85), body weight (p = 0.13), age (p = 0.12), and type of conditioning chemotherapy (p = 0.92) were not. No early toxicity related to granisetron was observed. CONCLUSION: Granisetron is a well-tolerated and effective antiemetic agent that can be used as monotherapy during single-dose TBI. Good control of nausea and vomiting is obtained with this antiemetic drug, and its effect is increased when hyperdiuresis is suspended during TBI.

Adolescent↗

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↗