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Biomedical subjects

D C Heaton

Publications and source records attributed to D C Heaton.

At least 37 records · Page 2Linked to original sources

Intranasal amphotericin B reduces the frequency of invasive aspergillosis in neutropenic patients.

PURPOSE: To retrospectively study the prophylaxis of invasive aspergillosis in neutropenic patients and to relate the frequency of this fungal disease to any causal or modifying factors that could be identified. PATIENTS AND METHODS: Between 1977 and 1988, 130 patients underwent 158 intensive treatment episodes to control acute leukemia, lymphoma, and aplastic anemia, and the frequency of complicating aspergillus infection was determined. RESULTS: Proven invasive aspergillus infections occurred in 22 cases, 12 of which were fatal. Invasive aspergillosis was suspected in a further 16 cases and all these patients recovered with amphotericin B treatment. Colonization by Aspergillus in the absence of clinically significant infection was seen in 31 treatment episodes. Invasive aspergillosis involved mainly the upper and lower respiratory tract and skin. Control of the infection was closely related to the control of the underlying disease, with subsequent return of normal marrow function and resolution of neutropenia. The incidence of aspergillus infection has decreased dramatically since 1985, most probably due to the introduction of intranasal amphotericin B. This occurred despite the persistence of aspergillus spores in the hematology ward air during the 1986 to 1988 period. CONCLUSION: Intranasal aerosolized amphotericin B may protect against invasive aspergillosis, even when neutropenic patients are cared for in conventional wards without HEPA filtration.

Administration, Intranasal↗

Busulphan/cyclophosphamide conditioning for bone marrow transplantation may lead to failure of hair regrowth.

Following the introduction of bulsulphan and cyclophosphamide (BUCY) conditioning in our unit in 1987, a number of patients noted incomplete scalp hair regrowth following bone marrow transplantation (BMT). Between August 1987 and May 1989, 22 patients had undergone allogeneic or autologous BMT in our unit and we recalled for detailed assessment the 14 who were alive and well at least 6 months post grafting. Six patients had experienced incomplete hair regrowth of varying severity 7-27 months following BMT. All those affected had received BUCY conditioning and the four most severely affected were allogeneic BMT recipients. No patient had received any post-BMT chemotherapy or radiation. None of the patients had evidence of graft-versus-host disease. No laboratory test abnormalities distinguished the affected from the unaffected patients. Despite the relatively small number of patients, our results suggest that BUCY has caused permanent damage to the hair follicles of the affected patients. Prolonged alopecia may markedly impair the quality of life for long-term survivors of BMT and this unexpected complication also has significant medicolegal implications.

Adolescent↗

Treatment of hairy cell leukaemia with recombinant alpha interferon.

Eleven patients with progressive hairy cell leukaemia (three nonsplenectomised) were treated with recombinant alpha-2 interferon (Intron-A or Roferon-A) subcutaneously three times per week at a dosage of 3 x 10(6) units. Ten patients completed at least ten weeks of therapy and could be evaluated; one patient died of haemorrhage from severe thrombocytopenia after only three weeks treatment. Nine of the ten patients responded and all of these are regarded as good partial remissions (normalisation of all blood parameters but still discernible hairy cells in the marrow). Responding patients have all been followed for a median of two years and in one case 3 1/2 years since commencement of therapy. The patients are all transfusion independent and free of infection. We conclude that alpha-2 interferon therapy for progressive hairy cell leukaemia is effective therapy in both splenectomised and nonsplenectomised patients.

Adult↗

Essential thrombocythaemia and the Philadelphia chromosome.

Six adult patients presented with clinical features of essential thrombocythaemia. Five of the patients, although Ph-positive, have maintained these features without evidence of leukaemia; in one case for 9 years. A sixth patient developed leukaemic blast crisis following a persistently high platelet count over 4 years. Her cells were Ph-negative, but hybridization of gene probes to chromosomes in situ and to leukaemic DNA showed that the abl oncogene had moved to the breakpoint cluster region (bcr) on the normal chromosome 22. This patient has the same molecular gene change as occurs in some cases of Ph-negative chronic myeloid leukaemia (CML) whose leukaemic cells likewise show no evidence of chromosomal translocation. Molecular studies are essential for the correct diagnosis of these patients. The Ph genomic lesion appears to have a range of leukaemic expression which includes thrombocythaemia as well as chronic myeloid leukaemia and acute lymphatic leukaemia.

Adult↗

Chromosome abnormalities in chronic lymphocytic leukemia revealed by cytochalasin B and Epstein-Barr virus.

Peripheral blood lymphocytes from eight patients with chronic lymphocytic leukemia (CLL) were cultured with Epstein Barr virus (EBV) and cytochalasin B. All eight cytochalasin B cultures had analyzable metaphases whereas only six of the EBV cultures were successful. Furthermore, the number of abnormal metaphases and the mitotic indices were greater in the cytochalasin B cultures than in the EBV cultures. Trisomy 12, alone or in combination with other abnormalities, was the most frequent cytogenetic finding. Structural abnormalities of chromosomes #6 and #14 were also found. Cytochalasin B appears to be an effective mitogen for demonstrating abnormal metaphases in patients with CLL.

Aged↗

Influence of spinal and general anaesthesia on haemostasis during total hip arthroplasty.

One hundred and one patients with osteoarthritis were randomly allocated to undergo total hip arthroplasty under either spinal (subarachnoid) or general anaesthesia. Venous blood was sampled before, during and after surgery and on the 5th day after operation to study the haemostatic mechanism. There were no preoperative differences between the two anaesthetic groups. Although there was pronounced individual variability, similar patterns of change in coagulation, platelets and fibrinolysis were seen in both groups. However, there were significant differences between the two groups in platelet count, thrombin production, and Factor VIIIRAg in the intra- and immediate postoperative periods. Also, compared with general anaesthesia, there was less intraoperative activation of fibrinolysis, as measured by the euglobulin clot lysis time, with spinal anaesthesia. These differences suggest slight modification of the haemostatic response to surgery with spinal anaesthesia, which could be consistent with a neuroendocrine mechanism. By the 5th day both groups exhibited a very similar "hypercoagulable" postoperative state.

Aged↗

Ph-negative chronic myeloid leukaemia.

An analysis of five patients with Philadelphia chromosome (Ph) negative chronic myeloid leukaemia (CML) revealed that two were clinically and haematologically identical to Ph-positive CML whereas three should be reclassified as chronic myelomonocytic leukaemia (CMML). At a molecular level the first two patients showed the same juxtaposition of c-abl and bcr genes as is seen in Ph-positive CML. These genomic changes were not seen in the other three patients. Observations on these five patients suggest that the clinical course and prognosis of the rare patient who carries the Ph 'molecular defect' but lacks the Philadelphia chromosome is no different from Ph-positive CML.

Adult↗

Assessment of D dimer assays for the diagnosis of deep vein thrombosis.

Sixty-two patients with suspected deep vein thrombosis were subjected to venography and to plasma D dimer assay by both rapid latex agglutination and enzyme immunoassay methods. The latex agglutination method was insensitive to the presence of deep vein thrombosis. In contrast, the enzyme immunoassay method was sensitive although of low specificity and for technical reasons not suitable for performance as an emergency test.

Adult↗

Allogeneic bone marrow transplantation at Christchurch 1979-1985.

Twelve bone marrow transplants have been carried out at Christchurch since 1979 in five patients with aplastic anaemia and seven with acute leukaemia. Five patients are currently alive at 77, 69, 63, 45, and seven months post-transplant. Acute and chronic graft versus host disease have been major problems and its clinical features and management are described. Long term follow-up data is presented on the four patients currently alive at between three to six years post-transplant. The practical problems we have experienced by carrying out bone marrow transplants without special funding have been considerable and the implications of this are discussed.

Adolescent↗

Danazol therapy in haemophilia.

Three patients with severe haemophilia A and one patient with moderately severe Christmas disease were given danazol and placebo in a double blind cross over trial to study the effects on haemostatic variables and bleeding tendency. In each case there was a shortening of the activated partial thromboplastin time (APTT) and euglobulin clot lysis time (ECLT) during danazol therapy but factor VIII and IX levels did not show any consistent change and there was no improvement in the bleeding tendency.

Adult↗

Still's disease associated with Coxsackie infection and haemophagocytic syndrome.

At the onset of Still's disease (systemic-onset juvenile arthritis) in a 12-year-old girl, serological evidence of Coxsackie B virus infection was found. Two weeks later she developed a haemophagocytic syndrome which was then treated with cytotoxic therapy. Her arthritis is still active six years later.

Antineoplastic Combined Chemotherapy Protocols↗

Host origin of in vitro bone marrow fibroblasts after marrow transplantation in man.

Two female patients who received bone marrow transplants from male donors showed the donor karyotype in all blood cells cultured with phytohemagglutinin and in all cells of bone marrow aspirate after direct or 24-hour culture preparation for cytogenetic study. The donor origin of myeloid cells was demonstrated specifically by identifying the male karyotype in the dividing cells of granulocyte/macrophage colonies in soft agar. Only the host female karyotype was found in fibroblast cell populations from cultured bone marrow aspirate. Bone marrow aspirate from transplant patients contained cells of host origin and cells of donor origin; both will proliferate in culture.

Anemia, Aplastic↗

Familial thrombocytopenia associated with platelet autoantibodies and chromosome breakage.

An extended family is described in which three members had thrombocytopenia. These affected members had chromosomal changes resembling those found in Fanconi's anaemia, though they lacked the development defects associated with that syndrome. One had bone-marrow hypoplasia and died of squamous cell carcinoma of the mouth at the age of 27. In addition, all three had platelet autoantibodies not found in any other family members tested. There was no linkage between the thrombocytopenia and HLA groups. The nature of the association of thrombocytopenia, platelet autoantibodies and chromosomal abnormalities in this family remains doubtful.

Adolescent↗

Nonrandom cytogenetic changes in New Zealand patients with acute myeloid leukemia.

Bone marrow clones with abnormal chromosomes were observed in 56% of 66 patients with forms of acute myeloid leukemia [French-American-British (FAB) M1-M6]. Acute myeloblastic leukemia (AML, M1 and M2) was the most common form, and 65% of these patients showed chromosomal abnormalities compared with 41% of patients with acute myelomonocytic leukemia (AMMoL, M4). The recognized nonrandom chromosomal abnormalities found were trisomy 8, monosomy 5 or 7, trisomy 1q, t(6;9), t(8;21), t(15;17), and abnormalities in 17q. There was also a strong involvement of chromosome No. 11: Abnormalities were found in eight patients when their leukemia was diagnosed and in a further three patients during the course of karyotypic evolution. Six of these patients had AMMoL or AMoL. Complex or multiple clones were found in 37% of AML patients at diagnosis. Our AML patients had a reduced frequency of abnormalities in chromosome No. 5 or 7 and an increased frequency of abnormalities in chromosome No. 8 compared with studies reported in other countries (p = 0.01). This difference suggests that in New Zealand AML might be caused by factors different from those operating in more industrialized centers.

Bone Marrow↗