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Biomedical subjects

D S Gordon

Publications and source records attributed to D S Gordon.

At least 37 records · Page 2Linked to original sources

Assessment of endocrine function after transsphenoidal surgery for Cushing's disease.

OBJECTIVE: We assessed the endocrine outcome after transsphenoidal surgery for Cushing's disease. DESIGN: Five-year (mean) follow-up (range 1 month-12 years) of patients undergoing transsphenoidal surgery for Cushing's disease between 1977 and 1990; review of case notes, current clinical and biochemical assessment including 24-hour urinary free cortisol. SETTING: Northern Ireland. SUBJECTS: Forty-one patients (33F: 8M); mean age at diagnosis 39.1 years (9-72 years). MAIN OUTCOME MEASURES: Measurements of early post-operative 0800 h serum cortisol and 24-hour urinary free cortisol at least 24 hours after withdrawal of oral hydrocortisone therapy. This was followed by low dose dexamethasone testing. Current 24-hour urinary free cortisol measurements. Retrospective definition of cure. RESULTS: Twenty-seven patients were either cured or improved by surgery, 14 were considered definite failures. Of 19 patients cured, eight had unmeasurable early post-operative 0800 h serum cortisol levels while of 15 tested, 13 had complete suppression with dexamethasone and two suppressed normally but to still measurable levels (39 and 60 nmol/l respectively). Seventeen patients in total have subsequently had bilateral adrenalectomy of whom two have developed Nelson's syndrome. Seven of the 41 patients were shown to have definite cyclical cortisol secretion first diagnosed post-operatively in three patients. Hormone deficiency included TSH (5), LH/FSH (1), cortisol (1) and ADH (temporary in 7, permanent in 1). In all, seven patients had some type of permanent hormonal deficiency post-operatively. CONCLUSIONS: Transsphenoidal surgery offers a worthwhile cure rate without the necessity of life-long endocrine therapy. Post-operative endocrine assessment must be rigorous so that early further management can be planned in the significant percentage of patients in whom cure is not achieved. Early complete suppression on low dose dexamethasone testing is very suggestive of cure but repeated and long-term monitoring of 24-hour urinary free cortisol is advisable.

Adenoma↗

A local census of dementia sufferers.

The results of a census of all dementia sufferers known to institutional and community services in Angus are reported. A total of 859 sufferers were identified compared with an expected 1013 based on EURODEM prevalence rates. After allowing for cross-boundary flow to institutions, it was estimated that the true identification rate was 80% (809/1013). Of the estimated total 1063 sufferers (including cross-boundary flow): 26% were in hospital, 27% in residential or nursing homes, 27% in the community and known to services (often the GP), and 19% in the community and not known to services (or, at least, not returned by them in the census). With the co-operation of all concerned, a census approach can yield useful information at a much lower cost than a full survey.

Age Factors↗

Autologous bone marrow transplantation in acute leukemia with marrow purged with alkyl-lysophospholipid.

Alkyl-lysophospholipids are anticancer agents that are selectively toxic to leukemic cells and relatively sparing of normal bone marrow cells. Thus, they would be likely candidates for purging remission marrows before autologous bone marrow transplant. One of the more promising agents is edelfosine, which could be safely used for purging without prolonging marrow recovery. Assays for marrow progenitor cells were performed before and after purging and cryopreservation in 64 patients. There was no significant reduction in colony formation after purging when compared with unpurged cryopreserved marrow, but there was a significant reduction after cryopreservation. Twenty-four patients with acute leukemia in second (16 patients) or third remission (3 patients), early relapse (3 patients), or in first remission with successfully treated extramedullary relapse (2 patients) received marrow-ablative chemotherapy and total body irradiation followed by infusion of marrow purged for 4 hours with 50 to 100 micrograms/mL of edelfosine. There were 9 lymphoblastic and 15 myelogenous leukemia patients. The median time to granulocyte recovery to 500/microL was 26 and 33 days for the 50 and 75 microgram/mL doses, respectively. The patient whose marrow was purged at the dose of 100 micrograms/mL failed to engraft. The median time to platelet recovery to 25,000/microL was 45 and 37 days for the 50 and 75 micrograms/mL doses, respectively. Twenty-nine percent of the patients remain disease free from 131 to 1,291 days, with a median of 356 days. These results have established that purging with 75 micrograms/mL of edelfosine is a safe dose and is recommended for a phase II trial.

Adolescent↗

Late intensification therapy in adult acute lymphoid leukemia. The Southeastern Cancer Study Group Experience.

One hundred ninety-two evaluable patients were treated on a multicenter protocol for adult acute lymphoid leukemia to determine in a prospective randomized fashion if late intensification chemotherapy beginning after about six months of treatment would improve remission duration and survival. The complete remission rate was 60%. The median remission duration was 13.5 versus 25.9 months (P = 0.31) for standard maintenance therapy and late intensification, respectively, and the median survival was 17.5 versus 34.7 months (P = 0.19) respectively. Although there was a suggestion that the late intensification strategy was helpful, relapse proved to be common during the early phases of treatment; thus, insufficient numbers of patients were available at the randomization point to conclusively address the possible value of late intensification. Intensive therapy earlier in remission should be evaluated.

Adolescent↗

Intravenous immunoglobulin therapy in systemic lupus erythematosus-associated thrombocytopenia.

Seven patients with thrombocytopenia and systemic lupus erythematosus were treated with intravenous (IV) doses of human immunoglobulin to assess clinical response and to examine the mechanism of action of IV immunoglobulin in these patients. Five of 7 patients had a greater than 50% increase in their platelet counts. Four of these patients had a sustained benefit of at least 6 months duration. The initial effectiveness of IV immunoglobulin therapy was not dependent on the reduction of levels of circulating platelet-binding IgG or circulating immune complexes.

Antigen-Antibody Complex↗

Ophthalmological and other toxicities related to cytosine arabinoside and total body irradiation as preparative regimen for bone marrow transplantation.

Cytosine arabinoside, 3 g/m2, every 12 h for 6 days, followed by fractionated total body irradiation, 200 cGy twice daily for 3 days, was administered to 39 adult patients undergoing bone marrow transplantation. Allogeneic transplant patients received cyclosporin and methotrexate for prophylaxis of graft-versus-host disease. There were 21 autologous transplants (16 with acute leukemia, four with an advanced stage of chronic myelocytic leukemia, and one with lymphoma) and 18 allogeneic transplants (14 with acute leukemia, two with an advanced stage of chronic myelocytic leukemia and two with myelodysplastic syndrome). Toxicities were compared between the two groups. There was a significantly greater degree and duration of mucositis and a greater frequency of radiation-type retinopathy developing in the allogeneic group, predominantly in those having had radiation for prophylaxis or treatment of central nervous system leukemia. Seven of 11 acute leukemic patients who received autologous transplants in remission survive. Two of seven acute leukemias who received allogeneic transplants while in remission survive. Although the increased morbidity, retinitis and mucositis, observed in the allogeneic group indicates that this regimen when combined with methotrexate and cyclosporin is too toxic, the results in autologous transplantation in acute leukemia in remission are encouraging.

Bone Marrow Transplantation↗

Ascertainment and natural history of treated acromegaly in Northern Ireland.

The prevalence of known cases of acromegaly in Northern Ireland in 1984 was 6.3 per 100,000 population. The incidence of newly-diagnosed cases over the preceding 25 years was 5.5 patients per year, or 0.4 patients per 100,000 population per year. This rate would be equivalent to about 200 new cases per year in the United Kingdom. Four options have been available to most of these patients--surgical hypophysectomy (transfrontal or transsphenoidal), pituitary radiotherapy (usually external cobalt beam), drug treatment with bromocriptine, or no treatment. Choice of treatment has been mainly influenced by tumour size, with the larger pituitary adenomas having surgery initially. No single form of treatment has been successful in achieving a clinical remission or cure in more than a minority of cases. The most successful outcome has been where total pituitary ablation has been achieved. Life-table analysis for the whole group shows life expectancy which is not markedly different for that of an age-matched population from Northern Ireland. Morbidity related to long term osteoarthritis and treatment complications remain a major problem. The incidence of malignant tumours is higher than would be expected.

Acromegaly↗

[Granular biogenic amine-containing cells of the rat endometrium as components of the system of mononuclear phagocytes].

To 10 non-inbred white mature rats 24 h before sacrifice 7.0 ml of Indian ink colloid solution has been injected intraperitoneally. Histochemical reactions of Falk-Hillarp (catecholamines, serotonin) have been performed on nonfixed cryostat slices of the uterus, those of Cross, Even, Rost (histamine) against non-specific esterase and acid phosphatase. Before carrying out these reactions, the slices have been examined under luminescent microscope LUMAM-I3 by means of luminescent and usual illumination in order to reveal cells, possessing autoluminiscence and containing phagocyted Indian ink particles. Presence of autoluminescence, phagocyted material, catecholamines and serotonin, histamine, nonspecific esterase, acid phosphotase, prostaglandin E2 in the same granular cells of the rat endometrium have been stated. All cellular properties revealed are specific for macrophages. A conclusion is made that granular biogenic amine-containing cells of endometrium can be considered as belonging to the system of mononuclear phagocytes.

Animals↗

Cesarean prophylaxis: a comparison of cefamandole and cefazolin by both intravenous and lavage routes, and risk factors associated with endometritis.

This study included 207 patients in a double-blind, prospective randomized trial of cefazolin versus cefamandole single-dose prophylaxis by both intravenous (IV) and lavage routes in patients laboring with ruptured membranes who eventually had nonelective cesareans. No significant differences (P less than .05) were noted in the rates of infectious morbidity (cefazolin IV: six of 47, 13%; cefazolin lavage: nine of 59, 15%; cefamandole IV: six of 47, 13%; cefamandole lavage: six of 54, 11%). The incidence of operative complications in the patients developing endometritis (eight of 22, 36%) was significantly different (P less than .004) from that in the group who did not develop endometritis (21 of 185, 11%). Cefazolin by IV and lavage routes of administration appears to be as effective as cefamandole by either route of administration.

Cefamandole↗

Factors affecting survival in allogeneic bone marrow transplantation.

From 1979 to 1988, 82 allogeneic and 2 syngeneic bone marrow transplants (BMT) were performed in 78 patients (age range 13-49 years) with the following diagnoses: acute myelogenous leukemia (AML) (21 patients); acute lymphoblastic leukemia (ALL) (15 patients); chronic myelocytic leukemia in chronic, accelerated, or blastic phase (CML-CP, AP or BC) (25 patients); myelodysplastic syndrome (MDS) (1 patient); multiple myeloma (MM) (1 patient); Hodgkin's disease (HD) (1 patient); diffuse poorly differentiated lymphoma (DPDL) (1 patient); aplastic anemia (AA) (13 patients). Univariant analyses were carried out to determine factors of importance in predicting outcome. AML patients receiving transplants in remission had 12/19 (63%) survivors. Only one of seven ALL patients receiving transplants in remission survives free of disease, and none of eight patients receiving transplants in relapse survived. Six ALL patients relapsed. In CML, 6 of 16 (40%) patients receiving transplants in CP survive; two of nine patients (22%) in AP or BC survive. Of the 13 aplastic anemias, 8 (62%) survive. Graft-vs.-host disease (GVHD) was evaluated in 75 patients, 24 of 33 (73%) who developed GVHD died, compared to 24 of 44 (55%) who did not develop GVHD. Of the 30 patients given the combination of methotrexate (MTX) plus cyclosporine (CSP), only 23% developed GVHD, compared to 58% of those not given the combination. Interstitial pneumonia (IP) occurred in 16 patients and was fatal in 15. The introduction of daily acyclovir and weekly intravenous gamma globulin in 1985 was associated with little reduction in the frequency of IP (from 20% to 18%). However, survival increased from 21% to 47%.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Bilateral inferior petrosal sinus sampling as a routine procedure in ACTH-dependent Cushing's syndrome.

Bilateral inferior petrosal sinus sampling was successfully performed in 12 of 13 consecutive patients with ACTH-dependent Cushing's syndrome. Ten of the patients subsequently had transsphenoidal pituitary microsurgery. Eight patients in whom the inferior petrosal sinus to peripheral vein ACTH level ratio was 1.5 or greater were found to have a pituitary adenoma. One of the remaining two patients who had ratios less than 1.5 had pituitary hyperplasia while the other had no identified abnormality. In five of the patients with pituitary tumour a ratio above 1.5 was present on only one side. Bilateral petrosal sampling is therefore always necessary. Tumour localization within the pituitary was only poorly predicted by either petrosal sinus sampling (four of eight) or computed tomography scanning (three of eight). If petrosal sinus sampling is used early in the differential diagnosis of ACTH-dependent hypercortisolism, then the use of other differential diagnostic tests may not always be necessary.

Adenoma↗

Oncogene expression and cytotoxic activity of tumor necrosis factor against human cancer cells.

We studied the effect of recombinant tumor necrosis factor (TNF) on selected leukemic and breast cancer cell lines. Based on their sensitivity to TNF in the presence or absence of cycloheximide (CHX), these cell lines could be categorized into three phenotypes: SS, cells that are spontaneously sensitive to TNF; RS, cells that are normally resistant to TNF but are killed in the presence of CHX; and RR, cells that are resistant to TNF irrespective of the presence of CHX. The effect of TNF on expression of c-myc, N-ras, and Ha-ras oncogenes was also studied in these cell lines. Transient, minimal suppression of c-myc was observed in one cell line (Raji), and an inconsistent stimulation of c-myc in another (MCF-7.OCI). No correlation was observed between the effect on oncogene expression and TNF sensitivity.

Adenocarcinoma↗

Preclinical studies on deoxycoformycin and deoxyadenosine as pharmacologic T cell purging tools.

Deoxycoformycin (dCf) is a potent toxin to T lymphocytes in human peripheral blood and bone marrow. In the presence of deoxyadenosine (dAdo), dCf inhibits T cell function as measured by DNA synthesis induced by stimuli in the rank order of mixed lymphocyte culture greater than murine monoclonal antibody OKT3 greater than phytohemagglutinin. Approximately two logs of human bone marrow T cells were removed by 24 h of incubation with dCf and dAdo at doses that preserved colony-forming ability of the treated marrow. A semi-closed system of isolating mononuclear cells in large volumes using density gradient centrifugation was developed. Using this system, it was found that dCf and dAdo could remove about two logs of T lymphocytes after 24 h of incubation when the cells were incubated in large volumes at a relatively high concentration (10(7) cells/ml). This system appears well suited for purging T lymphocytes from human bone marrow before clinical transplantation.

Adenosine Deaminase Inhibitors↗

Transient bone marrow aplasia associated with non-A, non-B hepatitis.

We describe two patients who developed aplastic anemia early in the course of non-A, non-B hepatitis. Spontaneous rapid recovery of bone marrow function occurred in both patients. Although early bone marrow transplantation has been recommended as the treatment of choice in hepatitis-associated aplastic anemia, these patients illustrate the need for a period of expectant observation before undertaking bone marrow transplantation in such patients.

Adolescent↗

Leukemia of non-T lineage natural killer cells.

An unusual case of an aggressive leukemia of natural killer (NK) cells occurred in a 65-year-old male. Clinical characteristics of this case included hepatosplenomegaly, ascites, marrow infiltrate with leukemic cells, and a WBC up to 82.8 X 10(9) before therapy. One year before his presentation he had been noted to have a WBC of 12.1 X 10(9) with 78% lymphocytes, and 6 months before had noted intermittent fever and weight loss. He and his brother had well documented hereditary cold urticaria. The patient was treated with a modification of ProMACE CYTABOM regimen and had prompt regression of the leukemia with associated acute tumor lysis. Renal, hepatic, and marrow failure predominated during a terminal course that ended 22 days after therapy was commenced, and at autopsy there was no evidence for leukemic cell infiltrate in the liver, spleen or marrow. The leukemic cells were large granular lymphocytes by light and electron microscopic criteria, and had the following immunophenotype: CD2+, DR+, Leu7+, NKH1+, CD11+, CD3-, CD5-, CD4-, CD8-, CD16-. The cells displayed high antibody-dependent cell-mediated cytotoxicity (ADCC) and NK activity, and had a high rate of spontaneous proliferation in vitro that was not augmented by phytohemagglutinin (PHA), concanavalin A (Con A), or pokeweed mitogen (PWM). Southern analysis of DNA from leukemic cells revealed normal germline arrangements for the beta and gamma chains of the T cell antigen receptor and immunoglobulin heavy chain genes. The majority of metaphases were clonally abnormal revealing consistent rearrangements involving extra material attached to the long arms of chromosomes 5 and 11.

Aged↗

[Luminescence-histochemical analysis of the histamine-containing cells in the lobule of the thymus].

By means of the luminescent-histochemical method of S. A. M. Cross, S. W.-B. Ewen and E. W. D. Rost [9] in the premedullary zone of the thymus lobule cortex histamine-containing cells have been found; they have different form, size, luminescent colour. The histamine-containing cells differently react to introduction of biologically active substances: histamine, noradrenaline, acetylcholine. Their amount depends on sex and age of the animals.

Acetylcholine↗

Acoustic neuroma surgery in Northern Ireland 1976-1986.

Forty acoustic neuromas have been removed surgically between 1976 and 1986. The condition was unilateral in 32 and bilateral in four. There were 31 large, four medium and five small tumours. Excision was complete in 16 and incomplete in 24. Of the incomplete removals 14 were subtotal leaving microscopic remnants, eight were partial capsular and two were intracapsular. Follow-up ranged from two months to ten years (median 3.5 years).There was one early death in an 83-year-old. The overall incidence of post-operative complete facial paralysis was 20% but reached 55% for large tumours when excision was complete. Twenty-eight patients had hearing before operation and in eleven patients some preservation of hearing was possible (39%). In these, the excision was complete in three, subtotal in four, partial capsular in three and intracapsular in one.Of the unilateral tumours, there have been three recurrences requiring repeat surgery. All were initially incompletely excised. Two were of an invasive nature causing considerable erosion of the petrous temporal bone making complete excision impossible. For the bilateral tumours a deliberate incomplete excision was first performed on one side to ensure preservation of hearing. Further excision on this side was then left until such time as hearing was lost. Complications included CSF otorhinorrhoea (5%), persistent but temporary nausea and vomiting (10%), meningitis (5%), facial numbness (5%) and hoarseness and dysphagia (3%).

Adolescent↗