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Biomedical subjects

L Lockwood

Publications and source records attributed to L Lockwood.

18 recordsLinked to original sources
PubMed2005

Nutritional status and energy expenditure in children pre-bone-marrow-transplant.

The aims of this study were to establish the nutritional status of children pre-BMT and to determine whether predictive methods of assessing nutritional status and resting energy expenditure (REE) are accurate in this population. We analysed the body cell mass (BCM) (n=26) and REE (n=24) in children undergoing BMT. BCM was adjusted for height (BCM/HT(p)) and expressed as a Z score to represent nutritional status. To determine whether body mass index (BMI) was indicative of nutritional status in children undergoing BMT, BMI Z scores were compared to the reference method of BCM/HT(p) Z scores. Schofield predictive equations of basal metabolic rate (BMR) were compared to measured REE to evaluate the accuracy of the predictive equations. The mean BCM/HT(p) Z score for the subject population was -1.09+/-1.28. There was no significant relationship between BCM/HT(p) Z score and BMI Z score (r=0.34; P>0.05); however there was minimal difference between measured REE and predicted BMR (bias=-11+/-149 kcal/day). The results of this study demonstrate that children undergoing BMT may have suboptimal nutritional status and that BMI is not an accurate indication of nutritional status in this population. However, Schofield equations were found to be suitable for representing REE in children pre-BMT.

Adolescent↗
PubMed2001

Single institution outcomes of treatment of severe aplastic anaemia.

BACKGROUND: In severe aplastic anaemia, the treatment of choice for young patients with a human leucocyte antigen-matched sibling is now established as allogeneic bone marrow transplantation (BMT). In older patients and in those without a matched sibling donor, immunosuppressive therapy is the usual first option. 'Alternative' marrow donors are emerging as an option for those without a matched sibling donor. AIMS: To review 10 years of local experience in treating severe aplastic anaemia with BMT and immunosuppressive therapy with emphasis on long-term outcomes. METHODS: A retrospective analysis was performed of all patients with severe aplastic anaemia presenting to the Royal Brisbane and Royal Children's Hospitals between 1989 and 1999. Data were abstracted regarding patient demographics, pretreatment characteristics and outcome measures, including response rates, overall survival and long-term complications. RESULTS: Twenty-seven consecutive patients were identified, 12 treated with immunosuppression alone and 15 with BMT. In these two groups, transfusion independence was attained in 25% and 100%, respectively, with overall survival being 36% and 100%, respectively. Those treated with immunosuppression were significantly older (median 41.5 versus 22 years, P = 0.008). Long-term survivors of either treatment had extremely low morbidity. Three patients carried pregnancies to term post-transplant. Three patients received alternative donor BMT with correspondingly excellent survival. CONCLUSIONS: Patients treated with allogeneic BMT for severe aplastic anaemia enjoyed extremely good long-term survival and minimal morbidity. Patients treated with immunosuppressive therapy had a poorer outcome reflecting their older age and different usage of therapies over the past decade. Optimal treatment strategies for severe aplastic anaemia remain to be determined.

Adolescent↗
PubMed1997

A dose-intensive, cyclophosphamide-based regimen for the treatment of recurrent/progressive or advanced solid tumors of childhood: a report from the Australia and New Zealand Children's Cancer Study Group.

BACKGROUND: Children with solid tumors that progress or recur after conventional multimodality therapies have a very poor prognosis. In a pilot study, vincristine, etoposide, and dose-escalated cyclophosphamide (VETOPEC) was shown to be a promising salvage regimen. Continued accrual of patients and increased duration of follow-up has resulted in substantial experience with VETOPEC. METHODS: Between May 1991 and March 1994, 56 pediatric patients from 6 centers were enrolled in this study; 44 had recurrent or progressive tumors (Group A) and 12 had newly diagnosed, advanced tumors with a very poor prognosis (Group B). The VETOPEC regimen was comprised of vincristine, 0.05 mg/kg, on Days 1 and 14; etoposide, 2.5 mg/kg, on Days 1, 2, and 3; and fractionated, dose-escalated cyclophosphamide on Days 1, 2, and 3. The initial cyclophosphamide dose was 90 mg/kg (2.7 g/m2)/cycle with an escalation of 15 mg/kg/cycle in each subsequent cycle, to a maximum (over 6 cycles) of 165 mg/kg (5.0 g/m2)/cycle. Tumor response was evaluated every two to three cycles and included central review of imaging. RESULTS: The combined and partial response rates for Groups A and B were 66% (25 of 38 patients) and 91% (10 of 11 patients), respectively. In Group A, best evaluable responses and event free (EF) survivors were observed with: brain tumors (7 of 9 patients; 2 EF at 39 and 45 months [mos], respectively), Wilms' tumor (6 of 7 patients; 3 EF at 37-49 mos), and lymphoma (4 of 4 patients; 2 EF at 52 and 59 mos, respectively); in Group B best evaluable responses and EF were observed with: neuroblastoma (5 of 6 patients; 1 disease free at 57 mos) and rhabdomyosarcoma (4 of 4 patients; no survivors). Hematologic toxicity was limiting despite support with myeloid growth factors in 33 patients. Four deaths in Group A and one in Group B were directly associated with this toxicity. Specifically, no cases of drug-related myocardial toxicity or pneumonitis were observed. CONCLUSIONS: This chemotherapy regimen with its intense scheduling produced a high response rate and appreciable survival in patients with a variety of recurrent, progressive, or advanced solid tumors of childhood.

Adolescent↗
PubMed1997

Granulocyte-macrophage colony-stimulating factor in association with high-dose chemotherapy (VETOPEC) for childhood solid tumors: a report from the Australia and New Zealand Children's Cancer Study Group.

PURPOSE: Combination chemotherapy with vincristine, etoposide, and high-dose, escalating cyclophosphamide (VETOPEC) is an effective regimen in pediatric patients with high-risk solid tumors. The toxicity of the regimen is predominantly haematologic. This study addressed the role of recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) following each cycle of chemotherapy in decreasing neutropaenia, incidence of fever/ hospitalization, and/or increasing chemotherapy dose-intensity. PATIENTS AND METHODS: Twenty-nine children with recurrent solid tumors were treated with the VETOPEC regimen. Sequential cohorts of patients received no GM-CSF (Group I), or GM-CSF in a dosage of 5 micrograms/kg/day (Group II) or 10 micrograms/kg/day (Group III) on days 4-18 of each chemotherapy cycle. Up to four cycles of chemotherapy were analysed with respect to haematopoietic recovery, clinical parameters, and dose intensity. RESULTS: Neutrophil recovery was significantly more rapid in patients treated with GM-CSF. Time to achieving an absolute neutrophil count (ANC) over 0.5 x 10(9)/L in Groups I, II, and III were 21, 18, and 16 days, respectively (P < 0.0001). Time to achieving an absolute neutrophil count (ANC) over 1.0 x 10(9)/L in Groups I, II, and III were 24, 19, and 17 days, respectively (P < 0.0001). There was no significant difference in the incidence of febrile neutropaenia between the three groups. Febrile neutropaenia occurred following 42, 68, and 62% of chemotherapy cycles in Groups I, II, and III, respectively (P = 0.27). Chemotherapy dose intensity was not different between the three groups. GM-CSF was associated with pericarditis and myalgias in one patient, and transient hypoxia/hypotension in another. CONCLUSION: GM-CSF led to significantly more rapid neutrophil recovery following VETOPEC chemotherapy, but did not lead to any demonstrable clinical benefit, either in reducing febrile events, or in increasing chemotherapy dose intensity.

Adolescent↗
PubMed1997

Vertebral osteomyelitis due to Pseudallescheria boydii.

A case of primary vertebral osteomyelitis due to an opportunistic fungus, Pseudallescheria boydii, in a child with acute myeloid leukemia, is reported. To our knowledge this is the first such case in a child, and only the second reported case in the international literature of primary spinal osteomyelitis due to this organism. We discuss the problems presented by this case both in terms of diagnosis and management. We also discuss the role of surgery and systemic antifungal chemotherapy in the treatment of deep infections due to Pseudallescheria boydii.

Child, Preschool↗
PubMed1996

Inhibition of gap junctional intercellular communication in heptachlor- and heptachlor epoxide-treated normal human breast epithelial cells.

Based on the concern of organochlorides in the environment and in human tissue, this study was designed to determine whether various noncytotoxic levels of heptachlor and heptachlor epoxide could inhibit, reversibly, gap junctional intercellular communication in human breast epithelial cells (HBEC). Cytotoxicity and gap junctional intercellular communication (GJIC) were evaluated by lactate dehydrogenase assay and fluorescence redistribution after photobleaching analysis, respectively. Both heptachlor and heptachlor epoxide were noncytotoxic up to 10 microg/ml. At this concentration, heptachlor and heptachlor epoxide inhibited GJIC of normal human breast epithelial cells after 1 h treatment. Within a 24 h treatment with heptachlor and heptachlor epoxide at 10 microg/ml, recovery of GJIC had not returned. GJIC completely recovered after a 12 h treatment of 1 microg/ml heptachlor epoxide, but it did not recover after a 24 h treatment of 1 microg/ml heptachlor. RT-PCR and Western blots were analyzed to determine whether the heptachlor or heptachlor epoxide might have altered the steady-state levels of gap junction mRNA and/or connexin protein levels or phosphorylation state. No significant difference in the level of connexin 43 (Cx43) message between control and heptachlor-treated cells was observed. Western blot analyses showed hypophosphorylation patterns in cells treated with 10 microg/ml heptachlor and heptachlor epoxide for 1 h with no recovery within 24 h. Immunostaining of Cx43 protein in normal HBEC indicated that heptachlor and heptachlor epoxide caused a loss of Cx43 from the cell membranes at noncytotoxic dose levels. Taken together, these results suggest that heptachlor and heptachlor epoxide can alter GJIC at the post-translational level, and that, under the conditions of exceeding a threshold concentration in the breast tissue containing 'initiated' cells for a long time and not being counteracted by anti-tumor-promoting chemicals, they could act as breast tumor promoters.

Base Sequence↗
PubMed1996

Successful bone marrow transplantation in a child with X-linked chronic granulomatous disease.

A 16-month-old Aboriginal boy was diagnosed with chronic granulomatous disease (CGD) when he presented with frequent significant infections from the age of 12 months. BMT was performed from a HLA-matched sibling after conditioning with busulphan, cyclophosphamide, etoposide and antithymocyte globulin. A small bowel obstruction developed in the first week and settled with conservative treatment. VOD occurred in the third week, resolving after treatment with tissue plasminogen activator. Sustained engraftment has occurred, as indicated by return of the nitroblue tetrazolium (NBT) test to normal when performed at 11 weeks and 7 months post-BMT. No further infections have occurred. BMT can be successfully performed for CGD. Complications occurring post-BMT may be related to the underlying disease (CGD). BMT remains an attractive option for CGD in children who have a matched sibling donor.

Bone Marrow Transplantation↗
PubMed1995

Inhibition of gap junctional intercellular communication and malignant transformation of rat liver epithelial cells by neu oncogene.

A retrovirus containing a neu oncogene was introduced into a Fischer F344 rat liver epithelial cell line (WB-F344) to study the effect of the expression of neu oncoprotein on gap junctional intercellular communication (GJIC), the ability to form colonies in soft agar and the ability to form tumors in rat liver by these cells. After viral infection, five different neu-transduced epithelial clones were randomly selected for further analysis. Southern blot analysis of HindIII-digested genomic DNA hybridized with a neu-specific probe indicated that the neu oncogene carried by the retrovirus was integrated into different chromosomal locations in the five different neu-transduced WB cell lines. Using the fluorescence recovery after photobleaching (FRAP) assay, we found that GJIC was significantly reduced in neu-transduced WB clones, compared with control virus-infected and parental WB cells. Western blot analysis of connexin 43 in the neu-transduced cell lines showed altered phosphorylation patterns compared with the normal WB-rat liver cell line. Confocal image analysis of the neu-transduced cells showed that the connexin 43 protein, as detected by fluorescent immunostaining, was localized in the cell nucleus. The neu-transduced WB cell lines also acquired the ability to grow in soft agar. Furthermore, cells from three of the five neu-transduced cell lines, when injected into the liver of Fischer F344 rats through the portal vein, were highly tumorigenic (multiple focal hepatic tumors developed within 2 weeks). Cells derived from the tumor were shown to be G-418 resistant, demonstrating that the tumor was derived from the injected WB-neu cells. The results of this study demonstrate that the expression of the neu oncogene is able to block GJIC and to induce tumorigenicity in the rat liver WB-F344 cell line.

Animals↗
PubMed1995

Autologous bone marrow transplantation for advanced neuroblastoma using teniposide, doxorubicin, melphalan, cisplatin, and total-body irradiation.

BACKGROUND: Disseminated neuroblastoma after infancy has a dismal prognosis; long-term survival with conventional therapy occurs in approximately 10% of cases. PATIENTS AND METHODS: Between 1985 and 1992, we followed a strategy aimed to achieve remission with an induction combination of intensive chemotherapy, primary resection, and tumor-bed radiotherapy (TBRT). Patients who achieved remission proceeded to myeloablative chemoradiotherapy and unpurged autologous bone marrow transplant (ABMT). Twenty-eight patients older than 1 year presented with stage IV disease during the study period; six died of progressive disease and three died of complications of therapy. Nineteen patients achieved remission, two of whom did not receive ABMT. Seventeen patients proceeded to ABMT. Conditioning was with teniposide 130 mg/m2, doxorubicin 30 mg/m2, melphalan 120 mg/m2, cisplatin 80 mg/m2, and total-body irradiation 12 Gy in six fractions (modified VAMP-TBI). RESULTS: Principal nonhematologic toxicities were mucositis and diarrhea. There were no ABMT-related deaths. Two patients relapsed at 8 and 26 months post-ABMT, respectively. Fifteen patients remain in complete remission (CR) at 24 to 102 months (median, 71) from ABMT and 30 to 114 months (median, 78) from diagnosis. Survival rates of all 28 patients are 61% and 50% at 2 and 5 years, respectively, and the disease-free survival (DFS) of the ABMT group is 94% and 87% at 2 and 5 years, respectively. CONCLUSION: Modified VAMP-TBI appears to be an effective conditioning regimen, with 15 of 17 patients remaining disease-free, with no toxic deaths. This result compares favorably with that of other groups. Larger numbers of patients need to be treated to confirm the efficacy of this therapy.

Adrenal Gland Neoplasms↗
PubMed1994

Dose-intensive cyclophosphamide with etoposide and vincristine for pediatric solid tumors: a phase I/II pilot study by the Australia and New Zealand Childhood Cancer Study Group.

PURPOSE: This pilot study of the Australia and New Zealand Childhood Cancer Study Group investigated the effectiveness and toxicity of a regimen incorporating vincristine (VCR), etoposide, and divided-dose, escalating cyclophosphamide (CPA) (VETOPEC) in 23 patients aged 1 to 20 years with solid tumors. PATIENTS AND METHODS: Seventeen patients (group A) had recurrent or refractory tumors after prior multiagent therapy, and six patients (group B) with adverse prognostic indicators were treated at initial presentation. Treatment cycles were 21 to 28 days and consisted of vincristine (0.05 mg/kg) on days 1 and 14, with etoposide (2.5 mg/kg/d) plus escalating CPA on days 1, 2, and 3. The CPA dosage was escalated from 30 mg/kg/d in cycle no. 1 by 5 mg/kg/d in each cycle to a maximum of 55 mg/kg/d in cycle no. 6. RESULTS: Of 20 patients assessable for tumor response, 19 (95%) responded after two to six cycles of VETOPEC: seven complete responses (CRs); eight very good partial responses (VGPRs); and four partial responses (PRs). In group A, 13 of 14 (93%) assessable patients responded (five CRs, four VGPRs, four PRs), and in group B, five stage IV and one stage III patient achieved two CRs and four VGPRs. The principal toxicity was myelosuppression. Grade IV neutropenia occurred after 98% of cycles, and the incidence of grade IV thrombocytopenia increased from 37% after cycle no. 1 to 91% after cycle no. 6 (P = .002). A total of 115 cycles delivered were followed by 62 febrile admissions (54%), and showed a significant rise with increasing cycles (P = .001). One patient died of septicemia. CONCLUSION: This combination and scheduling produced a high response rate in patients with recurrent, refractory, or advanced solid tumors of childhood. Further studies of this regimen and of strategies to reduce hematologic toxicity are warranted.

Adolescent↗
PubMed1993

Cisplatin-resistant metastatic hepatoblastoma: complete response to carboplatin, etoposide, and liver transplantation.

A child with stage 4 hepatoblastoma failed to respond to treatment with cisplatin and adriamycin. She then showed a response to carboplatin with complete clearing of pulmonary metastases. Bilobar liver disease persisted, although significantly reduced in size. A liver transplant was subsequently performed and she remains in complete remission 36 months later. After the first course of carboplatin, there was a dramatic rise in alpha-feto protein which then fell exponentially. Carboplatin warrants further study in hepatoblastoma.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

Childhood B cell lymphomas arising in the mediastinum.

AIMS: To report the clinical features and pathology of four childhood cases of primary mediastinal non-Hodgkin's lymphoma of non-lymphoblastic pathology. METHODS: Biopsy material was fixed in formol-saline and routinely processed and stained. Immunohistochemical staining was performed on paraffin wax embedded sections using the alkaline phosphatase anti-alkaline phosphatase method. RESULTS: The four patients presented with a large mediastinal mass and symptoms consistent with superior vena cava syndrome secondary to lymphoma. None of the patients had any clinically important disease outside the mediastinum. The four tumours had a histological appearance similar to diffuse large cell non-Hodgkin's lymphoma with sclerosis. Immunohistochemical staining showed that these tumours were of B cell origin. One patient died from infection during treatment and two patients died with progressive disease. The remaining patient remained well 43 months off all treatment. CONCLUSIONS: These four cases further illustrate the heterogeneity of paediatric large cell lymphomas. Clinically, they seem to be equivalent to the B cell lymphoma of the mediastinum, sclerosing type, that is seen in young (predominantly female) adults. The clinical and biological features of this type of tumour in childhood are largely unknown. Using standard treatment protocols, this tumour seems to have a poor prognosis and its optimal treatment therefore requires further clarification.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

The intensive care unit in paediatric oncology.

There were 70 admissions from a regional paediatric oncology centre to the intensive care unit over a six and a half year period. Patients were divided into those with systemic infections (n = 19), respiratory infections (n = 15), metabolic effects (n = 9), tumour mass effects (n = 10), neurological complications (n = 8), and others (n = 9). The overall survival was 51%. Patients admitted with metabolic or tumour mass related effects had the best prognosis with a survival of 84%. If dialysis is required in this group of patients then continuous arteriovenous haemofiltration is recommended. Patients with systemic or respiratory infections comprised the main poor prognosis group with a survival of 26%. For patients with a systemic infection who required ventilation, the mortality was 100%. The outlook for patients with a generalised encephalopathy was also poor, with no neurologically intact survivors. The median APACHE-II (acute physiology and chronic health evaluation) score for patients who died was 27 and for survivors was 16. There is a need for close cooperation between staff of intensive care and paediatric oncology units. Alternative treatments should be considered for patients with systemic infections who require ventilation.

Adolescent↗
PubMed1984

Cognitive determinants of the perception of mental health status.

This paper suggests that an individual's perception of his health and mental health status may be largely determined by his concept or definitions of health and mental health and that how one defines these terms are a function of one's level of awareness of higher needs. A conceptual model is presented that locates these cognitive variables within the causal framework relative to help-seeking behavior and provides the theoretical basis for a methodology of determining the mental health needs of a population, especially in a developing country, based on self-assessment of health status.

Cognition↗
PubMedDate not supplied

Postoperative chemotherapy in children less than 4 years of age with malignant brain tumors: promising initial response to a VETOPEC-based regimen. A Study of the Australian and New Zealand Children's Cancer Study Group (ANZCCSG).

PURPOSE: Postoperative chemotherapy with indefinite postponement of radiation therapy in children < 4 years old with brain tumors was investigated in a multi-institutional study. PATIENTS AND METHODS: From 1991 to 1995, 42 patients aged 3 to 47 months (median 20) with brain tumors were enrolled in a 2-phase chemotherapy protocol: 16 patients had medulloblastoma (MB); 8 had supratentorial primitive neuroectodermal tumor (PNET); 14 had ependymoma; and 4 had other tumors. The initial phase was comprised of 4 courses of the 3-drug regimen: vincristine (VCR), etoposide (VP-16), and intensive cyclophosphamide (CPA) in a previously reported schedule (VETOPEC). The continuation phase was comprised of 2-drug courses: A, CPA + VCR; B, cisplatin + VP-16; and C, carboplatin + VP-16, for a total duration of 64 weeks. RESULTS: Response to VETOPEC was evaluable in 28 patients with postresection residual (25) and/or metastatic (1 M2, 6 M3) tumor. There were 9 complete responses (CR) and 9 partial responses (PR) with a combined CR + PR of 64% (95% confidence interval [CI] 44 to 81). In 12 evaluable patients with MB, CR + PR was 82% (48 to 98); in 6 patients with PNET, 50% (12 to 88); and, in 8 patients with ependymoma, 86% (42 to 99). Of 40 patients eligible for further analysis, 6 remain progression-free at a median of 30 months, 14 are alive at a median of 38 months, 29 have progressed at a median of 7 months (range, 2 to 37 months), and 26 have died. The progression-free and overall survival rates at 36 months are estimated to be 11% (95% CI 1 to 22) and 34% (18 to 50), respectively. CONCLUSIONS: The initial response to the VETOPEC regimen is encouraging and warrants study of further dose escalation. Survival remains poor with current strategies in this high-risk population.

Antineoplastic Combined Chemotherapy Protocols↗