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Biomedical subjects

F W Gunz

Publications and source records attributed to F W Gunz.

At least 19 recordsLinked to original sources

Evidence following splenic radiotherapy for a highly dynamic traffic of CFU-GM between the spleen and other organs in chronic granulocytic leukaemia.

Five patients with Ph1 +ve chronic granulocytic leukaemia and massive splenomegaly were given induction therapy with splenic irradiation, and their peripheral blood leucocyte count and granulocyte macrophage progenitor (CFU-GM) concentration monitored during the following six hours. In each patient there was a greater fall in CFU-GM than would have been expected from the fall in leucocyte count, but no evidence of a plasma inhibitor was found to explain the disproportionate reduction in CFU-GM. The difference between the estimated and observed decrease in CFU-GM/1 following splenic irradiation indicates a highly dynamic traffic of CFU-GM from the spleen to other organs in chronic granulocytic leukaemia.

Adult

Significance of secondary cytogenetic changes in patients with Ph-positive chronic granulocytic leukemia in the acute phase.

The karyotypic abnormalities in 29 patients in the acute phase of Ph-positive chronic granulocytic leukemia are described. Of 18 Giemsa banded samples, 11 showed one or more of the typical additional abnormalities found in the acute phase, namely +Ph, +8, or i(17q). Survival data from these patients was combined with three published series providing 135 patients and the effect of one, two, or three of these abnormalities tested. The prognosis was significantly worse in patients with two or more additional abnormalities, compared with those with one or none. Analysis of the subset of patients with only one additional abnormality [+Ph or +8 or i(17q)] suggested a worse prognosis in those with +8 than in those with +Ph or i(17q), although the differences were not significant. There also was a trend for patients in whom all metaphases showed abnormalities in addition to the Ph chromosome to have a worse prognosis than those in whom some or all metaphases contained the Ph only. However, this trend just failed to reach a 5% level of significance.

Adult

The need for palliative care services in a general hospital.

A population census in a major Sydney teaching hospital showed that, at any one time, between 5% and 10% of inpatients were in the terminal stages of their disease and, thus, were in need of palliative care. These needs challenge conventional patterns of practice in large hospitals and illustrate the magnitude of the problems arising from the generally observed trend towards hospitalization of the dying.

Hospitals, General

Dying of cancer. Factors influencing the place of death of patients.

An analysis of factors influencing the place of death of patients seen by two medical oncology units is reported. There were 1295 recorded deaths of patients from the Royal Prince Alfred Hospital, Sydney, and 688 from The Royal North Shore Hospital of Sydney during 1979-1981; the places of death were known in 1724 instances (87%). Of these, 73% of patients died in hospital, 9% died in terminal nursing care (TNC) institutions, and the remainder at home. Factors influencing the place of death were the place of residence, age, home circumstances-social support, diagnosis, and interval from first contact with the medical oncology unit. Our data indicate that a complex interrelation of these factors determines the place of death. Improvements in community services may allow more patients with cancer to die at home or in TNC institutions, but a substantial proportion of these will still die in major hospitals. Therefore, there is a need for the improvement of palliative care services in these institutions.

Adult

Isotypic discordance of paraproteins and lymphocyte surface immunoglobulins in myeloma.

B lymphocyte surface immunoglobulins (Smlg) were studied in 24 patients with multiple myeloma by means of anti-isotypic antisera, and their heavy and light chain isotypes were compared in each patient with those of the paraprotein. In 21 patients, lymphocyte Smlg consisted of only one light chain type, and in 16 of only 1 heavy chain type. However, the Smlg and paraprotein heavy and light chain types were identical in only 5 patients while in 6 they differed in heavy and light chain types, in 7 in light chain type, and in 4 in heavy chain type. In 2 patients with light chain myeloma, Smlg light chains were isotypically the same as the paraprotein. Isotypic discordance between paraprotein and Smlg may signify the proliferation of a second malignant clone with failure to differentiate into secreting plasma cells. Alternatively, it is conceivable that the lymphocyte Smlg could have the same idiotypic specificity as the paraprotein despite the isotypic differences, but this will require further studies using anti-idiotypic antisera.

Adult

Hypogammaglobulinaemia associated with abnormalities of both B and T lymphocytes in patients with chronic lymphatic leukaemia.

The underlying basis for hypogammaglobulinaemia in patients with chronic lymphatic leukaemia (CLL) was investigated by measurement if immunoglobulin produced in vitro in cultures of pokeweek mitogen-stimulated B and T lymphocytes. B and T cells were separated by sheep red blood cell rosette techniques and, by culture of these cells from CLL patients in various combinations with B or T cells from normal subjects, it was possible to measure independently the function of B lymphocytes and the helper or suppressor function of T lymphocytes. By these methods it was found that the B lymphocytes of six of eight patients failed to produce immunoglobulins in vitro. B lymphocytes from two patients appeared to produce immunoglobulins in vitro. T lymphocytes from five of the eight patients had low or undetectable helper T cell function and in six patients their T lymphocytes had excessive suppressor activity in comparison to T lymphocyte populations from normal subjects. Whether the primary abnormality in the CLL T cell populations was a deficiency of helper T cells or excess of suppressor T cells was uncertain from these studies. These results suggest that immunoglobulin production by B lymphocytes from most patients with CLL was abnormal but also that T cells from CLL patients may be abnormal in respect to their role in immunoglobulin production at an early stage of the disease. These findings may assist in understanding the pathogenesis of this disease and lead to new approaches in treatment.

Agammaglobulinemia

Extreme leucocytosis and prognosis of newly diagnosed patients with acute non-lymphocytic leukaemia.

A group of 87 consecutive patients with acute non-lymphocytic leukaemia (ANLL) who had been treated with large doses of hydroxyurea (HU) as a preliminary to protocol combination chemotherapy is reviewed. The outcome in patients whose initial leucocyte count was 100x10(9)/L or higher (HC group) is compared with that in the majority who had lower leucocyte counts. Contrary to reports in the literature, patients in the HC group had the same chance of achieving remission as the rest, and the survival of the responders was equally long in both groups. There were no deaths from intracerebral haemorrhage in the reportedly high-risk HC group, a fact which was attributed to the administration of HU to all new patients. Hydroxyurea rapidly lowered the leucocyte count in nearly all patients with ANLL and appeared to be a valuable addition to protocol therapy of this disease.

Acute Disease

A cytogenetic study of eight human melanoma cell lines.

Eight cell lines established originally at the Queensland Institute of Medical Research from human malignant melanoma explants have been studied by means of cytogenetic techniques. All showed abnormalities characteristic for each individual line and consisting of marker chromosomes and of changes in ploidy due to the addition of extra copies of normal chromosomes. Repeat cultures of some lines after one or two years contained most of the markers which had characterized the original samples; additional chromosome abnormalities were also found. An anlysis of the break points concerned in the production of markers showed preferential involvement of chromosomes 1 and 5, with a prevalence of centromeric breaks on No. 1. These findings add further weight to the evidence suggesting that changes in chromosome 1 may be of special significance in the pathogenesis of some solid tumours.

Cell Line

Contacts among patients with hematological malignancies.

A survey was carried out in 2 country areas of New South Wales with the aim of defining contacts among patients with lymphoma, leukemia and myeloma, and of determining whether these were more numerous than among matched controls from the same localities. Cases were identified from records of the N.S.W. Central Cancer Registry and of local doctors and hospitals. 184 cases were found, corresponding to the expected number, and 145 patients, as well as the same number of controls, were interviewed. Of the 290 patients and controls surveyed 111 (38.3%) had had one or more contacts with other patients or controls (37.9% of patients and 38.6% of controls). There were 24 case-case pairs involving contacts among 33 individual patients, 23 control-control pairs involving 36 individuals, and 38 case-control pairs involving 66 individuals. A statistical analysis using a weighting system showed that numbers, closeness and duration of contacts among patients and patients did not differ significantly from those expected. These results thus provide no evidence in favor of the hypothesis that the diseases were transmitted from patient to patient in the survey areas.

Australia

Thirteen cases of leukemia in a family.

Thirteen cases of leukemia, 12 of them acute, occurred in 3 generations of a family comprising 293 members. Individual cases could not be linked to the possession of any of a range of genetic markers. Cytogenetic studies showed no constitutional chromosome abnormalities. Preliminary results of virologic studies suggested the presence of oncornaviruses in at least 1 leukemic individual in this family. This aggregation of leukemia cases likely resulted from a genetic, probably polygenic, predisposition, in association with the activity of leukemogenic factors whose nature remains to be clearly defined.

Adolescent

Contamination of human melanoma cell lines by mouse L cells.

Five of 8 cell lines from human melanomas originally established elsewhere were found to consist exclusively of mouse cells when examined in our laboratory some months after their receipt. Cytogenetic studies, including G- and C-banding, showed that the mouse cells in all cultures had originated from a single cell line, identified as the L-line. Contamination probably occurred, one year before its discovery, in a laboratory where L cells and human melanoma cells were briefly kept in the same incubator.

Animals

Marrow culture studies in adult acute leukemia at presentation and during remission.

Culture of bone marrow and/or blood cells in a semisolid agar system from 43 adults with acute nonlymphoblastic leukemia at first presentation showed two distinct growth patterns at 14 days. In 53% of patients cells failed to grow (type O), while in the remainder an abnormal growth pattern (type B) with small numbers of diffuse colonies and excessive numbers of cell clusters was seen. The response following chemotherapy was significantly better in the patients whose cells failed to grow. Serial culture studies, performed in 9 patients throughout remissions of 100-1112 days, which had been maintained by intermittent chemotherapy, showed wide fluctuations in proliferative activity. These ranged from no growth to marked proliferation with predominance of clusters and small numbers of diffuse colonies, indistinguishable from the type B pattern seen in 47% of patients at first presentation. The possibility is discussed that the periods of failure to grow, and/or those in which a type B pattern emerged, represented sporadic reactivation of leukemic cells.

Adolescent