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Biomedical subjects

R K Woodruff

Publications and source records attributed to R K Woodruff.

At least 19 recordsLinked to original sources

Assessment of proliferative responses to granulocyte-macrophage colony-stimulating factor (GM-CSF) in acute myeloid leukaemia using a fluorescent ligand for the nucleoside transporter.

Nucleoside transporter expression has been linked to proliferation in a variety of haemopoietic cell types. Granulocyte-macrophage colony-stimulating factor (GM-CSF) was given for 72 h before commencing chemotherapy in 15 patients with relapsed or refractory acute myeloid leukaemia (AML) and in 11 patients serial bone marrows were taken for measurement of [3H]thymidine labelling index, Ki-67 positivity and maximal binding of 5-(SAENTA-x8)-fluorescein, a flow cytometry ligand which enumerates nucleoside transporter sites. GM-CSF caused proliferation of marrow myeloblasts in eight of 11 patients, while in three patients there was no change in proliferative indices. The expression of nucleoside transporters increased up to 4-fold in the myeloblasts from the patients showing a proliferative response to GM-CSF but there was no increase in transporters on the myeloblasts from the three non-responding patients. A close correlation was found between the fold increase in nucleoside transporter expression and the fold increase in labelling index of marrow myeloblasts (r = 0.86, n = 9, p < 0.01). In one patient with acute megakaryoblastic leukemia, GM-CSF caused parallel increases in labelling index, Ki-67 positivity and numbers of nucleoside transporters on peripheral blood blast cells. Thus induction of proliferation by cytokine increases the expression of nucleoside transporters on leukaemic myeloblasts studied in serial samples from the same source (bone marrow or blood). The suitability of 5-(SAENTA-x8)-fluorescein for two colour flow cytometric analysis allows the rapid enumeration of nucleoside transporters in the myeloblast compartment of heterogeneous marrow samples.

Acute Disease

Intestinal obstruction in patients with widespread intraabdominal malignancy.

The clinical course of 28 patients with surgically documented widespread intraabdominal malignancy who developed intestinal obstruction was reviewed. Of 26 patients, 13 responded to initial conservative management. In the ten patients treated surgically, there was significant morbidity in 80% and a postoperative mortality of 40%. Reobstruction occurred in 11 patients, responded poorly to therapy, and was associated with a short life expectancy. These results support the use of conservative therapy in the management of intestinal obstruction due to widespread intraabdominal malignancy, with emphasis on the palliation of symptoms and maintenance of quality of life.

Abdominal Neoplasms

Complications and failure of anticoagulation therapy in the treatment of venous thromboembolism in patients with disseminated malignancy.

Thirty-one patients with malignancy, anticoagulated for the treatment of venous thromboembolism (VTE) are reported. Complications of treatment included major bleeding (35%), redevelopment of VTE whilst on therapeutic levels of anticoagulants (13%) and recurrent VTE following cessation of anticoagulant (42%). Forty-two per cent of patients died within three months of initiating anticoagulant therapy. The cause of death was progressive malignancy, except in one patient who died of anticoagulant-related bleeding. The high incidence of bleeding is frequently associated with over-anticoagulation and indicates the need for improved monitoring. The frequent recurrence of VTE is associated with chronic disseminated intravascular coagulation, for which warfarin is ineffective and heparin is indicated.

Adult

Palliative care in a general teaching hospital. 2. Establishment of a service.

OBJECTIVE: To assess the first year of operation of a palliative care service in a general teaching hospital. DESIGN, SETTING, PATIENTS: A retrospective analysis of 241 terminally ill patients referred to the Austin Hospital Palliative Care Service during its first year of operation. MAIN OUTCOME MEASURES: The occurrence and relief of pain, the occurrence and management of social and psychological problems, involvement of allied health services and the place of death. MAIN RESULTS: Unrelieved pain was the most frequent medical problem but, with appropriate medical management as well as input from other members of the multidisciplinary team, all patients achieved satisfactory pain control. The occurrence and severity of social and psychological problems was greater than expected. Most of the patients were discharged home and referred to domiciliary palliative care services; one-quarter of patients were able to die at home, one-third died in an inpatient hospice, and the remainder died in hospital. CONCLUSIONS: The Service was able to achieve most of its stated aims and has generated a much improved appreciation of the palliative care needs of patients with terminal illness and their families within the Hospital. A multidisciplinary approach to the management of terminally ill patients is crucial, and this Service has been successful despite limited staffing because of the willing involvement of other Units and Services in the Hospital. The difficulties inherent in the evaluation of a palliative care program (quality of life, cost-effectiveness) are discussed.

Hospital Departments

Palliative care in a general teaching hospital. 1. Assessment of needs.

OBJECTIVE: To assess the palliative care needs and the results of treatment of patients with terminal cancer admitted to a general teaching hospital. DESIGN, SETTING, PATIENTS: A retrospective analysis of 110 consecutive patients with terminal cancer admitted to the Austin Hospital. MAIN OUTCOME MEASURES: The occurrence and relief of pain, the use of allied health services and the place of death. MAIN RESULTS: Pain was the most common symptom and was satisfactorily improved in only two-thirds of the patients. Allied health services were used sporadically and appeared to be underused. Psychological problems were documented in very few patients. Only seven patients died at home, the remainder dying in hospital (82) or in a hospice (21). CONCLUSIONS: One-third of patients with terminal cancer in a general teaching hospital received inadequate pain relief; the reasons for this included lack of medical expertise in the use of analgesics for chronic cancer pain and the frequent use of analgesia given only "as required". The underuse of allied health services, the infrequent documentation of psychological issues and the observation that only a small proportion of patients were able to die outside hospital all underline the need for a coordinated multidisciplinary approach to the management of patients with terminal cancer.

Adult

Subxiphoid partial pericardiectomy with or without sclerosant instillation in the treatment of symptomatic pericardial effusions in patients with malignancy.

Twenty-two patients with malignant pericardial effusions were treated with subxiphoid partial pericardiectomy between 1984 and 1989. Thirteen patients also had a sclerosing agent instilled intrapericardially. Tamponade was relieved by pericardiocentesis before administration of general anesthesia. In 18 patients (82%), the effusions were controlled for longer than 30 days, and two patients died before 30 days without effusion. There were two recurrences at 1.5 and 7 months. There was one death due to hemorrhage from a laceration in a heavily infiltrated pericardium, and one patient had persistent dyspnea after the procedure. Complications included transient atrial arrhythmias (two patients), chest pain after sclerosant instillation (three patients), and fever greater than 37.5 degrees C after sclerosant (five patients). The survival range was 0.1 to 18 months (median, 5 months). Subxiphoid partial pericardiectomy with or without intrapericardial sclerosant is a safe and efficacious treatment for malignant pericardial effusions.

Adult

Demonstration of monoclonal IgE by isoelectric focusing: first reported case of IgE myeloma in Australia.

A 56-year-old man who presented with back pain was diagnosed with multiple myeloma. Serum protein analysis by isoelectric focusing identified a monoclonal IgE lambda of unique spectrotype compared with other monoclonal immunoglobulins. The similarity of the spectrotype of this monoclonal IgE to that of two purified monoclonal IgEs suggests that these proteins have a characteristic spectrotype, sufficiently different from those of other immunoglobulin classes to allow its recognition.

Antibodies, Monoclonal

Cytosine arabinoside in the treatment of T-cell acute lymphoblastic leukemia.

The place of cytosine arabinoside (araC) in the treatment of T-cell acute lymphoblastic leukemia was studied by measuring nucleoside transport sites and the conversion of araC to its triphosphate (araCTP) in lymphoblasts from the peripheral blood of two patients, who were then treated with araC. Equilibrium binding of 3H-nitrobenzylmercaptopurine riboside (3H-NBMPR), a specific ligand of the nucleoside transporter, gave 16,510 to 29,400 sites/cell for T-lymphoblasts on presentation or early in relapse compared with 2730 +/- 1570 sites/cell for non-T-lymphoblasts. Accumulation of araCTP from 1 microM araC was four times greater in T-cell than non-T-cell lymphoblasts. One patient was treated with araC (100 mg/m2 daily x 7 days, continuous intravenously) at the time of her first leukemic relapse and complete remission was achieved with this single agent. When this patient relapsed and developed advanced disease the T lymphoblasts showed a 75% reduction in their ability to accumulate araCTP which paralleled a reduction in 3H-NBMPR binding. The second patient achieved complete remission with araC given in low dose (15 mg twice daily by subcutaneous injection) for 21 days at the time of a localised relapse in the mediastinum and pleura. These studies suggest that araC may have a place in the therapy of early stage T-lymphoblastic disease.

Adolescent

Proximal motor neuropathy, dermato-endocrine syndrome, and IgG kappa paraproteinemia.

The association of monoclonal paraproteinemia, neuropathy, and dermato-endocrine disturbances is well recognized in Japan, and it also occurs in white patients. Neuropathy in such patients is classically distal and sensorimotor, and the paraprotein almost always contains lambda light chains. A 58-year-old white man presented with severe progressive proximal motor neuropathy, dermato-endocrine changes, and an IgG kappa paraprotein. Over a 2 1/2-year period, treatment with melphalan and prednisolone produced improvement in the neuropathy and resolution of dermato-endocrine features with a corresponding decline in the serum paraprotein concentration. Subsequent reappearance of the paraprotein, despite treatment, was associated with clinical relapse.

Endocrine System Diseases

Chronic lymphatic leukemia developing in a patient with multiple myeloma: immunologic demonstration of a clonally distinct second malignancy.

A patient with multiple myeloma who subsequently developed chronic lymphocytic leukemia is reported. Initial studies demonstrated clinical and hematological features of multiple myeloma with an IgM lambda paraprotein. Skeletal disease was a significant presenting feature, although relapse occurred in extraosseous sites, particularly the pleura. He developed chronic lymphatic leukemia 31 months later and immunological studies showed the malignant lymphocytes to have kappa (Kappa) light chain surface immunoglobulin, demonstrating separate clonal origin of this patient's two B-cell malignancies.

Aged

Multiple cranial nerve palsies as the presenting feature of meningeal myelomatosis.

The case of a 69-year-old man with IgGK myeloma in whom meningeal myelomatosis with multiple cranial nerve palsies developed, is reported. Review of previously reported cases of clinically apparent meningeal myelomatosis indicates this rare complication frequently presents with cranial nerve palsies; currently available treatment is ineffective.

Adult

Use of the FAB criteria for the diagnosis of acute erythroleukaemia (AEL).

The criteria proposed by the French-American-British (FAB) Group for the diagnosis of acute erythroleukaemia (AEL), including the requirement for greater than or equal 30% marrow myeloblasts, were used in a review of patients with erythroleukaemia. Ten patients with AEL were identified, and a further twelve patients with marrows suggestive of AEL but having less than 30% myeloblasts were classified as having refractory anaemia with excess of blasts (RAEB). The AEL patients had a poor prognosis, poor response to chemotherapy, and none showed evolution to myeloblastic or monoblastic leukaemia. In contrast, the patients with RAEB appeared to survive longer, respond better to chemotherapy, and several evolved into typical myelogenous leukaemia. The FAB criteria subdivides patients with erythroleukaemia into groups with apparent clinicopathological and prognostic differences. Further studies using these or equally strict criteria are required.

Acute Disease

Acanthocytosis and haemolytic anaemia due to the McLeod blood group.

A fourteen-year-old boy presenting with marked acanthocytosis of the red blood cells and a compensated haemolytic anaemia was shown to have the McLeod blood type. Only three other individuals have been reported as having this abnormality of the Kell blood group system without evidence of chronic granulomatous disease. Serological typing for the McLeod phenotype should be undertaken in males with unexplained acanthocytosis, and CPK estimation may provide a screening test for this condition.

Acanthocytes