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Biomedical subjects

K D Waters

Publications and source records attributed to K D Waters.

At least 19 recordsLinked to original sources

The role of Epstein-Barr virus in Hodgkin's disease from different geographical areas.

Recent studies have suggested that Epstein-Barr virus (EBV) may play a role in the aetiology of Hodgkin's disease. To determine the role of EBV in childhood Hodgkin's disease in different geographical areas, immunohistochemical staining and in situ hybridisation were used to analyse latent membrane protein 1 (LMP 1) and small nuclear non-transcribed RNAs (EBER-1) respectively. Testing for EBV within the Reed-Sternberg and Hodgkin's cells was carried out in childhood Hodgkin's disease from 10 different countries. The proportion of LMP 1 positive cases varied significantly, being 50% of cases from the United Kingdom (38/75), South Africa (9/18), Egypt (7/14), and Jordan (8/16), 60% from the United Arab Emirates (6/10), 70% from Australia (11/16), 81% from Costa Rica (34/42), 88% from Iran (7/8), 90% from Greece (20/22), and 100% of the 56 cases from Kenya. A sensitive polymerase chain reaction based EBV strain typing technique was established using archival tissues. EBV strain type 1 was shown to be predominant in childhood Hodgkin's disease from the United Kingdom, South Africa, Australia, and Greece. Type 2 was predominant in Egypt. EBV strain types 1 and 2 were both detected in some cases of childhood Hodgkin's disease in the United Kingdom, Costa Rica, and Kenya. The high incidence of EBV and the presence especially in developing countries of dual infection with both strain types 1 and 2 may reflect socioeconomic conditions leading to malnutrition induced immunological impairment. The possibility of HIV infection also needs to be explored.

Adolescent↗

Wilms' tumor: a rational use of preoperative imaging.

OBJECTIVE: To determine whether a preoperative imaging protocol relying predominantly on a chest X-ray film (CXR) and ultrasound in patients with Wilms' tumor is adequate for patient management and to determine the frequency more sophisticated imaging, in particular, computed tomography (CT), is required. DESIGN AND SETTING: Historical cohort study at a tertiary pediatric hospital. SUBJECTS: 60 consecutive patients with Wilms' tumor treated at our institution between 1980 and 1990. MAIN OUTCOME MEASURE: The preoperative imaging was recorded and 2- and 4-year survival were compared with the National Wilms' Tumor Study. RESULTS: 100% of patients had a preoperative CXR, 95% abdominal ultrasound, 5% abdominal CT, 13% chest CT, 47% abdominal X-ray, 2% aortography, 5% cavography, and 35% intravenous urography. The overall 2- and 4-year survivals of 92% and 90%, respectively, did not statistically differ from the National Wilms' Tumor Study 2- and 4-year survivals of 94% and 91%. CONCLUSIONS: A preoperative imaging protocol relying predominantly on a CXR and abdominal ultrasound does not reduce survival. Other more sophisticated imaging, in particular, CT, is not required in the majority of cases and is warranted only when a CXR or ultrasound is unable to resolve relevant management problems.

Abdomen↗

Invasive central nervous system aspergillosis: cure with liposomal amphotericin B, itraconazole, and radical surgery--case report and review of the literature.

Invasive aspergillosis of the central nervous system is a rare but well-described disease. There have been only a few reported survivors, and mortality exceeds 95% in the immunosuppressed host. We present a 2-year-old boy with acute lymphatic leukemia and multiple Aspergillus brain abscesses who was successfully treated with liposomal amphotericin B, itraconazole, and surgical excision of the abscesses. Liposomal amphotericin B is a new preparation that safely allows the attainment of significantly higher tissue levels with less toxicity than standard amphotericin B. The treatment of patients with invasive central nervous system aspergillosis is reviewed.

Amphotericin B↗

Results of intensive therapy in childhood acute myeloid leukemia, incorporating high-dose melphalan and autologous bone marrow transplantation in first complete remission.

Childhood acute myeloid leukemia (AML) has a poor prognosis with standard chemotherapy. Allogeneic bone marrow transplantation (BMT) in remission improves the outlook only for the one third of patients with sibling donors. Autologous BMT with a lower morbidity and mortality is available to all. In this study, maximum cytoreduction was achieved by intensive early chemotherapy. Final intensification, with autologous BMT was offered to all those remaining in first complete remission (CR). Patients received two induction and two consolidation courses of intensively scheduled chemotherapy. Cytoreduction was assessed on day 14 and remission was assessed after courses 2 and 4. Bone marrow was harvested after recovery from the second consolidation course or after the first maintenance course and separated on a discontinuous percoll gradient before cryopreservation. Twenty-eight of 31 consecutively enrolled patients achieved CR. Three relapsed early and, of the 25 eligible, 24 underwent autologous BMT. Twenty-three patients received high-dose melphalan and 1 received busulphan and cyclophosphamide before autologous BMT at a median of 113 days (range, 86 to 301) after initial CR. Trilineage engraftment occurred in all. Neutrophil recovery to greater than 0.5 x 10(9)/L occurred at a median of 46 days (range, 13 to 92) after autologous BMT. Platelet recovery was delayed, with a median time to achieve greater than 20 x 10(9)/L of 42 days (range, 18 to 215). With a minimum follow up of 25 months following autologous BMT only 3 children have relapsed. The 5-year event-free survival rate (EFS) from diagnosis is 68% (95% confidence interval, 46% to 90%). Five-year EFS following autologous BMT is 87% (95% confidence interval, 67% to 100%). Autologous BMT with high-dose melphalan administration after intensive chemotherapy has produced EFS equivalent to allogeneic BMT and is associated with a strikingly low relapse rate. High-dose melphalan appears to be a valuable agent for conditioning therapy in AML.

Acute Disease↗

Prevention of cyclophosphamide/cytarabine-induced emesis with ondansetron in children with leukemia.

Ondansetron, a 5HT3 antagonist, was given to 20 children aged 4 to 18 years who were undergoing treatment with the Australian and New Zealand Childhood Cancer Study Group Acute Lymphocytic Leukaemia (ALL) Study V Protocol. The study was open, dose ranging, and noncomparative, and designed to evaluate safety and efficacy of ondansetron in preventing nausea and vomiting caused by cyclophosphamide intravenous (IV) 1,000 mg/m2 day 1, and cytarabine IV subcutaneously (SC) 75 mg/m2 on days 2 to 5. Ten patients were given ondansetron 5 mg/m2 IV (group A) and subsequently another 10 patients were given ondansetron 3 mg/m2 IV (group B). Oral ondansetron was given for 14 doses, at the same dosage for both groups, commencing simultaneously with the IV infusion and continuing at 8 hourly intervals, ie, until day 5. The oral dose was based on surface area with the following schedule: 0.3 to 0.6 m2, 2 mg; 0.6 to 1 m2, 3 mg; and greater than 1 m2, 4 mg. Vomiting on the first day of chemotherapy was reported in group A by one patient and by one patient in group B. Vomiting during days 2 to 5 was reported by two group-A patients and by three group-B patients. Nausea was recorded on day 1 by one patient in group A, and two in group B, and on days 2 to 5 by three patients in group A, and by seven in group B. All patients were alert during treatment with ondansetron and there was no dystonia. There were no changes in renal function or hematology values that could be ascribed to the study drug. Transient elevations in bilirubin and liver enzymes were observed. We conclude that our results indicate that ondansetron is a safe and extremely effective single-agent antiemetic with minimal side effects, when administered both IV and orally.

Administration, Oral↗

Enhanced cis-platinum ototoxicity in children with brain tumours who have received simultaneous or prior cranial irradiation.

We report on four children who received cis-platinum simultaneously with, or in one case 10 months after, cranial irradiation and experienced exaggerated ototoxicity affecting all audible frequencies. The hearing loss was severe, affecting the critical areas for speech perception, and necessitated the provision of bilateral hearing aids. The audiograms of these patients are shown and compared to those of four children who had received cis-platinum as part of their treatment for neuroblastoma but without cranial irradiation. The precipitation of the exaggerated hearing loss with the administration of cis-platinum in one patient 10 months after finishing cranial irradiation suggests that care should be taken in the timing of cis-platinum administration in relation to concurrent or previous cranial irradiation.

Adolescent↗

Treatment with MOPP or ChlVPP chemotherapy only for all stages of childhood Hodgkin's disease.

Fifty-three children with Hodgkin's disease were clinically staged and treated with chemotherapy alone. Forty-six received mechlorethamine (Mustargen; Merk Sharpe & Dohme, West Point, PA), vincristine (Oncovin; Eli Lilly and Company, Indianapolis), procarbazine, and prednisolone (MOPP) and 7 chlorambucil, vinblastine, prednisolone, and procarbazine (ChlVPP). There were four events in the 38 children with stage I and II disease. One patient with massive mediastinal disease failed to remit and subsequently failed mantle irradiation and changes of chemotherapy. Another relapsed at the site of local disease and was salvaged with involved field irradiation and further courses of MOPP. Two other children died as a result of acute graft-v-host disease (GVHD) following transfusion. At autopsy there was no evidence of Hodgkin's disease. Fifteen children had stage III and IV disease and 14 achieved complete remission (CR) and none have relapsed. The child who failed to achieve remission died of virus infections. A mediastinal mass greater than 1/3 the thoracic width was present in 19 children of whom 18 achieved remission and none relapsed. An infradiaphragmatic presentation occurred in eight, all achieved remission and none relapsed. Overall at a median follow-up time of 45 months survival was 94%; the percent of patients without treatment failure was 92; and the percent without relapse was 98.

Adolescent↗

Malignant lymphoma of bone in children.

From 1960 to 1985 at the Royal Children's Hospital, Melbourne, seven cases of malignant lymphoma of bone (MLB) were identified in children younger than 16 years of age. Over the same period there were 88 cases of Ewing's sarcoma (ES), which illustrates the rarity of MLB. All cases were staged and treated according to protocols current at the time, namely, systemic chemotherapy with radiotherapy to the primary lesions. One child received radiotherapy alone as chemotherapy was not then available (1963). The disease-free five-year survival rate in our small series is 57%, which compares favorably with the 62% that we have calculated from survival data available from 26 previously reported cases of MLB in children and better than the 35% to 50% quoted in adult series of MLB. The main problem in differential diagnosis is distinguishing MLB from ES. A positive diagnosis of MLB rather than ES can be made, however, by observation of the characteristic reticulin staining pattern, the absence of cytoplasmic glycogen, and the ultrastructure.

Adolescent↗

Function after partial pelvic resection for Ewing's sarcoma.

Seven patients with Ewing's sarcoma of the pelvis were treated by chemotherapy followed by wide resection of the primary tumour. Although good function after operation is possible, survival in this series reflects the poor prognosis associated with the disease; two patients died, two are alive with local recurrence and metastases and three patients are alive with no evidence of disease.

Adolescent↗

Bilateral metachronous periosteal osteosarcoma.

The first case of bilateral metachronous periosteal osteosarcoma (OS) is reported. A 14-year-old white boy presented with a 1-month history of pain and swelling in his right thigh. Periosteal OS was diagnosed on a basis of the radiologic and pathologic findings. Treatment was with local resection and total hip replacement after a short course of high-dose methotrexate; multi-agent chemotherapy was continued postoperatively for 3 months. He remained well for 3 years. He then represented with a mass in the left femur that had been slowly growing for about 1 year. Radiologic and biopsy studies showed periosteal OS. Full investigations showed no evidence of metastatic disease. Treatment consisted of local resection without chemotherapy. He remained well for 6 months after the second excision until developing multiple pulmonary metastases. All further therapy was refused. The question as to whether the second tumor was a new primary lesion or a metastasis is discussed, together with possible differential diagnoses.

Adolescent↗

Marrow function reconstitution by fraction 3 of Percoll-density-gradient-separated cells.

Eight children with advanced tumors or acute myeloid leukemia were treated either with very-high-dose multi-agent chemotherapy (4) or marrow ablative high-dose melphalan (4) followed by autologous marrow rescue, using only fraction 3 from a Percoll-discontinuous density gradient separation of bone marrow buffy coats. Each patient received less than 20% of the number of cells usually reinfused from the buffy coat. The yield of CFU-c in Percoll gradient 3 was similar to the yield obtained from whole buffy coats of bone marrow. Reconstitution of marrow function with a neutrophil count greater than 0.5 X 10(9)/L and platelet count greater than 50 X 10(9)/L occurred in 7 patients in a medium time of 15 and 16 days, respectively--a time comparable to that following infusion of whole buffy coat in 20 other patients. In one patient, hemopoietic recovery was considerably delayed, suggesting that fraction 3 from the Percoll gradient had been relatively ineffective in marrow reconstitution. We conclude that fraction 3 from marrow separated on Percoll gradients has the advantages of small volume and good recovery of marrow stem cells and can promptly reconstitute marrow function in the majority of children treated with very-high-dose chemotherapy or marrow ablative doses of melphalan.

Adolescent↗

Primitive neuroectodermal tumour of the central nervous system associated with malignant rhabdoid tumour of the kidney: report of a case.

Malignant rhabdoid tumour of the kidney is a recently reported tumour presenting in young children. Irrespective of stage and despite intensive chemotherapy these tumours have a poor prognosis, with death usually occurring within a matter of months. A recent report has shown the association of second embryonal tumours of the central nervous system occurring in patients with the renal tumour; most of these second tumours have occurred in the posterior fossa. We report here an infant who presented with a mass in the right groin, showing features of a poorly differentiated sarcoma, possibly rhabdomyosarcoma. Further investigations revealed a tumour in the lower pole of the right kidney which was subsequently shown to be a malignant rhabdoid tumour. The child was given chemotherapy but re-presented at 10 months of age with hydrocephalus, irritability and spasms leading to death. At autopsy a large tumour was found filling the right lateral and third ventricles; histology showed a primitive neuroectodermal tumour with focal astrocytic differentiation. Residual rhabdoid tumour was restricted to a few para-aortic lymph nodes and focal lymphatic micrometastases in lungs. The association of two embryonal neoplasms of possible similar histogenesis is discussed.

Brain Neoplasms↗

Testicular neuroblastoma.

We describe, in a young boy, a case of neuroblastoma presenting only as a painless unilateral testicular mass. Clinical and laboratory evidence of disseminated neuroblastoma was first apparent nine months after high orchiectomy. As far as we are aware this is the only reported instance of testicular neuroblastoma in the absence of disseminated disease. Discussion is directed to the possible explanations for this rare testicular lesion, and in addition, underlines the potential difficulties in the diagnosis of certain small cell tumors.

Antineoplastic Combined Chemotherapy Protocols↗

Experience with high dose multiagent chemotherapy and autologous bone marrow rescue in the treatment of twenty-two children with advanced tumours.

Intensive chemotherapy followed by infusion of cryopreserved autologous bone marrow (ABMR) was used in the treatment of 22 children with advanced tumours. In nine this was their initial therapy; in eight it was used after partial or complete remission had been achieved with standard therapy; and in five, after relapse had occurred. Recovery of marrow function occurred in 20 patients with a mean time of 13.2 and 18.2 days to recovery of neutrophils (greater than 0.5 X 10(9)/l) in newly diagnosed and previously treated patients respectively. Platelet count recovery to greater than 50 X 10(9)/l occurred in a mean time of 13.4 days in newly diagnosed and 20.4 days in previously treated patients. Control of extensive local tumour was obtained in three of three evaluable patients with abdominal non-Hodgkin's lymphoma (NHL). Metastatic bony and marrow disease was controlled in two of two patients with retinoblastoma. In Ewing's sarcoma, temporary control of widespread metastatic disease occurred in one patient. In the other, eradication of extensive local mass disease at the primary site had been achieved. Poor response to treatment has been seen in seven of eight patients with Stage III or IV rhabdomyosarcoma, three patients with neuroblastoma and four of five patients with recurrent disease. Apart from the anticipated bone marrow toxicity, the major complications were severe mucositis, anaphylaxis following bone marrow infusion and haemorrhagic cystitis. The presence of herpes simplex infection appeared to aggravate mucosal complication.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Extradural chloroma with spinal compression--an unusual presentation of acute myelogenous leukemia.

Chloromas are solid tumours resulting from the localised proliferation of myelogenous leukemia cells, and are frequently responsible for the initial manifestations of acute myelocytic leukemia. We report a patient with a thoracic extradural chloroma whose presentation with acute paraplegia led to the diagnosis of an unsuspected myelocytic leukemia. Early recognition of the etiology of the paraplegia and the underlying systemic involvement with leukemia resulted in an excellent neurological and hematological outcome. The previously described association of the 8:21 chromosomal translocation with a good prognosis is noted in our patient.

Child↗

Results of treatment of 18 children with Hodgkin disease with MOPP chemotherapy as the only treatment modality.

Eighteen children with Hodgkin disease (16 previously untreated; two relapsed) were treated with MOPP chemotherapy (nitrogen mustard, vincristine, prednisone, procarbazine) only. Ten had clinical stage I and II disease, four had stage III, and four had stage IV. In ten patients, the clinical stage was confirmed by staging laparotomy. Six courses of MOPP were given to eight stage I and II patients and two stage IV patients. Between 7 and 12 courses were given to two stage I and II, and six stage III and IV patients. Dose reduction of 75-50% was required in 13% and delay of treatment in 22% of the first six courses of MOPP. Hematologic toxicity, minor and major viral infections, and nausea and vomiting were the major complications. Complete remission (CR) was obtained in 17 patients. Of these 17, there has been one death in CR, and one relapse. Sixteen patients have discontinued treatment and have been observed off treatment for 8 months to 7.5 years. The actuarial disease-free survival with a median follow-up of 28 months is 80% and overall survival is 92%.

Adolescent↗

The treatment of Wilms' tumor: results from Royal Children's Hospital, Melbourne, 1967-1977.

A retrospective review of the treatment of Wilms' tumor from 1967 to 1977 at the Royal Children's Hospital, Melbourne, was undertaken, allowing a minimum 2-yr followup. Fifty-four (77%) of the 70 patients in the study are alive, with 23/25 (92%) in Stage I, 12/16 (75%) in Stage II, 12/19 (63%) in Stage III, and 7/9 (78%) in Stage IV. Survival was significantly better in Stage I disease, and those patients less than 5-yr-old at presentation. Recurrence of disease was significantly lower after the introduction of multiple courses of chemotherapy in 1971. Sixteen deaths occurred during the period: three infants from drug toxicity, four patients with "unfavorable" sarcomatous histology, and four patients with recurrent local disease, where irradiation had been confined to the tumor bed after tumor spill with recurrence beyond the irradiated field.

Abnormalities, Multiple↗