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Biomedical subjects

D Cunningham

Publications and source records attributed to D Cunningham.

At least 37 records · Page 2Linked to original sources
PubMed1994

Management of carcinomas of the upper gastrointestinal tract.

Patients with oesophageal, gastric, and pancreatic carcinomas present a common and difficult problem for the clinician. Surgery is the best option for curative treatment but overall survival figures remain low. Recent improvements in our understanding of the biology of these tumours and improvements in their clinical staging, along with the development of combined modality approaches to local-regional disease, have led to renewed optimism that survival figures may be improved. This is particularly so for oesophageal and gastric carcinomas. In addition, there have been advances in the palliative management of all three tumours. This article examines some of these developments and looks at future prospects.

Adult↗
PubMed1994

Placebo-controlled phase III trial of lenograstim in bone-marrow transplantation.

Haemopoietic growth factors are accepted as accelerating haemopoietic recovery after bone-marrow grafting, yet no large randomised trials have been published that convincingly show benefit. Lenograstim (glycosylated recombinant human granulocyte colony-stimulating factor) was given to 315 patients after bone-marrow transplantation in a prospective randomised placebo-controlled multicentre trial. 1 day after bone-marrow infusion, 163 patients received lenograstim 5 micrograms/kg per day by 30-min infusion, and 152 patients received placebo daily for 28 days or until neutrophil recovery. 137 patients had lymphoma, 35 myeloma, 85 acute lymphoblastic leukaemia, and 58 a solid tumour. Patients were stratified by age and by type of bone-marrow transplantation (BMT). Neutrophil recovery to above 10(9)/L for 3 consecutive days was seen earlier in lenograstim-treated patients (16 vs 27 days, p < 0.001). Time to neutrophil recovery above 0.5 x 10(9)/L was reduced (14 vs 20 days, p < 0.001). The difference was significant both in autograft (20 vs 14 days, p < 0.001) and allograft (20 vs 14 days, p < 0.01) patients, in children (20 vs 13 days, p < 0.001), and adults. Lenograstim-treated patients had fewer days of infection, and of antibiotic administration, and also spent less time in hospital. However, clinical and microbiological sepsis was similar in both groups. There was no significant toxicity ascribed to lenograstim. Survival was the same at days 100 and 365. In patients undergoing autologous or allogeneic BMT for neoplastic disease, lenograstim significantly reduced duration of neutropenia and led to earlier hospital discharge.

Adjuvants, Immunologic↗
PubMed1994

Application of scanning force microscopy to chromosome analysis.

The application of scanning force microscopy (SFM) to the imaging and analysis of chromosomes is described. This relatively new microscopical technique has been used to provide high-resolution, three-dimensional images of uncoated and unstained human chromosomes in which surface features less than 50 nm have been resolved. Comparison of SFM images with light microscopy data has permitted identification of specific chromosomes, and images of a chromosome showing a cytogenetic abnormality are presented. These preliminary results demonstrate that this technique has potential applications in the imaging and analysis of chromosome structure.

Chromosomes, Human↗
PubMed1994

A characteristics protein highly expressed in guinea pig inner ear, defined by monoclonal antibody WH-1.

A new monoclonal antibody (termed WH-1; isotype IgG2b) was established using a homogenate of dissected guinea pig cochleas (N = 60) as immunogen. Western blotting and sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) identified the WH-1 antigen as a protein or glycoprotein with M(r) approximately 40 kDa. Immunoperoxidase treatment of histologic cryosections of guinea pig cochlea, followed by light microscopic examination, revealed strong positive staining at three sites: (i) parts of Hensen's stripe, marginal band, covering net, and Kimura's membrane (within the tectorial membrane [TM]); (ii) Deiters' cells, pillar cells, Hensen's cells, and stereocilia of outer hair cells (within the organ of Corti); (iii) interdental cells, inner and outer sulcus cells, Reissner's membrane, and surface membrane of stria vascularis epithelium. Similar staining patterns were observed for cryosections of rat and mouse cochleas. Only a trace quantity of cross-reacting protein was detectable in brainstem. The protein was not detectable in tongue extract by Western blotting. However, sections of brainstem and tongue did show positive immunohistological staining with WH-1. Localization of WH-1 antigen was further examined by electron microscopy. WH-1 positivity on outer hair cell stereocilia, certain sites on the TM, interdental cell surface, Reissner's membrane epithelia, and inner and outer sulcus cells was confirmed. WH-1 antigen was not detected on inner hair cell stereocilia by light or electron microscopy. The localization of WH-1 antigen on outer hair cell stereocilia and TM suggests that it may play some role in adhesion between these structures.

Animals↗
PubMed1994

Comparison of the effect of heparin and aspirin versus aspirin alone on transient myocardial ischemia and in-hospital prognosis in patients with unstable angina.

OBJECTIVES: This study compared the effects of heparin and aspirin versus aspirin alone on transient myocardial ischemia and in-hospital prognosis in patients with unstable angina. BACKGROUND: Transient myocardial ischemia occurring in patients with unstable angina is associated with an adverse prognosis. Heparin and aspirin are two drugs used frequently in the treatment of this condition, but the effect of combination therapy versus aspirin alone on transient myocardial ischemia is unknown. METHODS: Two hundred eighty-five consecutive patients with unstable angina were randomized to receive either intravenous heparin plus oral aspirin (150 mg once daily) (Group H + A) or aspirin alone (Group A). Patients also received a beta-adrenergic blocking agent, diltiazem and intravenous nitrates. ST segment monitoring was performed for the 1st 48 h of treatment. Patients were followed up for the duration of their in-hospital stay. RESULTS: One hundred fifty-four patients (30 women, mean [+/- SEM] age 58.3 +/- 0.8 years) received heparin and aspirin (Group H + A), and 131 patients (26 women, mean age 60.6 +/- 0.8 years) received aspirin only (Group A). ST segment monitoring (11,622 h) yielded 244 episodes of transient myocardial ischemia of a total duration of 7,819 min. There were no significant differences between the two treatment arms in the number of patients with transient myocardial ischemia (27 [18%] in Group H + A vs. 31 [24%] in Group A), number of episodes (96 in Group H + A vs. 148 in Group A) or total duration of transient myocardial ischemia (2,911 min in Group H + A vs. 4,908 min in Group A). The incidence of in-hospital myocardial infarction or death was significantly higher in patients with transient myocardial ischemia (53% vs. 22%, p < 0.0001). Five of the six deaths occurred in patients with transient myocardial ischemia. Event-free survival from myocardial infarction or death was similar in both treatment groups. Preadmission therapy with aspirin was associated with a lower in-hospital infarction rate (19% vs. 34%, p = 0.01). CONCLUSIONS: The presence of transient myocardial ischemia in patients with unstable angina is associated with a significantly higher incidence of myocardial infarction or death in hospital. Combined therapy with heparin and aspirin compared with aspirin alone makes no difference in the development of these events, nor does it reduce the development of transient myocardial ischemia.

Adult↗
PubMed1994

Haematological toxicity of radiotherapy following high-dose chemotherapy and autologous bone marrow transplantation in patients with recurrent Hodgkin's disease.

17 patients with recurrent Hodgkin's disease received 21 courses of radiotherapy (RT) 1-23 months after high-dose chemotherapy and autologous bone marrow transplantation. WHO grade III-IV haematological toxicity, of median duration 38 days (range 4-236), was observed following 10 courses of radiotherapy in 9 patients. This haematological morbidity could be predicted with an 80.0% sensitivity when the pre-RT white cell count was < 5 x 10(9)/l or the platelet count < 100 x 10(9)/l. It occurred in 9/11 patients with initial stage III-IV disease, including all 6 given extended radiotherapy fields, but in no patients with initial stage II disease (chi 2 = 9.35, P < 0.005). Age, histology, the presence of B symptoms, performance status, previous radiotherapy or chemotherapy, the interval between autologous bone marrow transplantation and radiotherapy, the high-dose regimen used, and the radiotherapy dose or field size, did not appear to affect haematological toxicity. The median survival was 18 months from the date of starting radiotherapy. 7 patients remain alive and progression-free 8-51 months (median 21 months) after radiotherapy. Radiotherapy may contribute to durable remissions in patients with relapsed or residual Hodgkin's disease after autologous bone marrow transplantation, but significant haematological toxicity may be expected in those with mild pancytopaenia prior to radiotherapy, particularly with initial stage III or IV disease.

Adolescent↗
PubMed1994

A pilot study of intraperitoneal cisplatin in the management of gastric cancer.

BACKGROUND: This phase II trial was designed to evaluate the feasibility, toxicity, relapse pattern and survival following adjuvant intraperitoneal cisplatin in patients with gastric cancer at high risk of relapse. PATIENTS AND METHODS: Patients who had undergone complete surgical resection of adenocarcinoma of the stomach and who had positive serosa and/or regional lymph nodes and/or peritoneal washings has insertion of either a Tenckhoff catheter or temporary peritoneal dialysis catheter and were treated with cisplatin 60 mg/m2 intraperitoneally every 21 days for 4-6 courses. Peritoneal lavage or cytology was done before each treatment. RESULTS: Eighteen patients were studied. Seventeen patients had serosal involvement, 11 had regional lymph node involvement and 2 had positive peritoneal washings before treatment. The median number of courses of chemotherapy was 4 (range 2-6). Radioisotope tracer studies (6 patients) showed good distribution throughout the peritoneal cavity. No WHO grade 3/4 toxicity was seen. Twelve patients (67%) have relapsed, 6 (33%) intra-abdominally, 4 (22%) with hepatic metastases and 2 (11%) outside the abdominal cavity. The median survival was 17 months. CONCLUSIONS: Cisplatin can be administered safely as adjuvant therapy to patients with gastric cancer, however, as single agent therapy the pattern of relapse and subsequent death was similar to that expected. The occurrence of distant metastases may argue for systemic rather than local adjuvant treatment.

Adenocarcinoma↗
PubMed1994

Protracted venous infusion 5-fluorouracil and interferon-alpha in advanced and refractory colorectal cancer.

BACKGROUND: The management of patients with advanced colorectal cancer remains dependent on the optimal use of 5-Fluorouracil (5-FU). Enhanced 5-FU activity can be achieved by either adding a modulator or by altering the administration schedule, in particular using a protracted venous infusion. Based on encouraging phase II data using bolus 5-FU and interferon-alpha, we designed a study to investigate the activity of this modulator in patients with colorectal cancer refractory to protracted venous infusion 5-FU. PATIENTS AND METHODS: Patients with advanced colorectal cancer were treated with 5-FU (300 mg/m2/day) given as a protracted venous infusion via an indwelling central venous catheter and portable battery driven pump. At the time the tumour became refractory to 5-FU, interferon-alpha was added and further outcome evaluated. RESULTS: One hundred twenty-four patients were entered on the study, 118 of whom had measurable disease. Fifty-two patients had previously received chemotherapy. The overall tumour response rate with infusional 5-FU was 33% (38/118), however in previously untreated patients was 42% (29/69) and 18% in those given prior chemotherapy (9/49). At the point of refractory disease 64 patients had interferon-alpha added to the 5-FU. Five patients (8%) showed an objective partial response following interferon-alpha addition. Patient toxicities on infusional 5-FU included hand-foot erythroderma, stomatitis and diarrhoea. There were only 15 episodes of grade 3 or 4 toxicity. The addition of interferon-alpha gave fever, lethargy, myelosuppression and depression, but did not increase the incidence or severity of 5-FU related toxicities. Of 67 patients with tumour related pain, 53 (79%) had an improvement in their symptoms. Median survival of the whole group was 7.5 months. CONCLUSIONS: Protracted venous infusion 5-FU is an active and well tolerated palliative treatment for advanced colorectal cancer. The addition of interferon-alpha at the point of 5-FU refractory disease resulted in further significant response in a small number of patients. Further randomised studies, including quality-of-life end-points, are needed before the use of interferon-alpha can be recommended as a modulator of 5-FU in the clinical setting.

Adult↗
PubMed1994

A phase II study in advanced gastro-esophageal cancer using epirubicin and cisplatin in combination with continuous infusion 5-fluorouracil (ECF).

PURPOSE: A phase II study was performed in patients with unresectable or metastatic gastric cancer evaluating the efficacy of a new chemotherapy schedule combining epirubicin and cisplatin with a continuous ambulatory infusion of 5-fluorouracil (ECF). PATIENTS AND METHODS: One hundred thirty-nine consecutive, previously untreated patients were given ECF. Of these, 128 had measurable disease. Epirubicin (50 mg/m2 i.v.) and cisplatin (60 mg/m2 i.v.) were administered every three weeks for 8 cycles during a 21 week continuous i.v. infusion of 5-fluorouracil (200 mg/m2/day). In total 773 cycles of chemotherapy were given. RESULTS: Objective tumour responses was seen in 91 (71%) of the 128 patients with measurable disease, of which 15 (12%) had a complete response. Twenty patients with locally advanced disease responding to ECF had attempted resection of the primary--11 (55%) were completely removed, 4 of these had no residual tumour in the resected specimen. The overall median survival was 8.2 months with 1 and 2 year survivals of 30% and 10% respectively. Grade 3 or 4 emesis occurred in 13%, stomatitis in 7%, diarrhoea in 4%, infection in 6%, leucopenia in 21% and thrombocytopenia in 8% of patients. Myelosuppression delayed treatment in 39 (5%) of the 773 cycles. Six of the 139 patients (4.3%) had treatment related deaths. There was no measurable reduction in quality of life during chemotherapy, while 67% of the 66 patients with dysphagia had complete resolution of this symptom. CONCLUSIONS: The ECF regimen displays high anti-tumour activity with moderate toxicity in patients with gastric cancer and in some cases enabled resection of previously inoperable tumours.

Adenocarcinoma↗
PubMed1994

An animal model of visual loss from orbital hemorrhage.

Intraorbital hemorrhage may arise spontaneously or following orbital or periorbital surgery or trauma and may be associated with visual loss or impairment. This project was designed to evaluate the ophthalmic effects and underlying mechanism(s) associated with visual impairment secondary to intraorbital hemorrhage. An experimental surgical procedure was developed to simulate intraorbital hemorrhage. A reversible state of unilateral visual loss secondary to acutely increased intraorbital volume was induced and maintained under general anesthesia for either 90, 120, or 180 min duration in nine adult nonhuman primates (NHPs) (Macaca arctoides). Color funduscopic photography, i.v. fluorescein angiography, electrophysiological testing, and tonometry were obtained during baseline, experimental, and follow-up procedures. The globes and optic nerves were obtained for histopathologic evaluation. One of three animals in the 180 min experimental group exhibited clinical and histopathological changes of optic neuropathy 6 weeks after the experimental procedure. Optic neuropathy is one of several proposed etiologies for producing visual loss secondary to intraorbital hemorrhage. This study offers a reliable, safe, and reversible technique to study the effects of acutely increased intraorbital volume in nonhuman primates. The animal model described may be useful for evaluating mechanism(s) involved with visual impairment in other acquired optic neuropathies.

Animals↗
PubMed1994

Natural killer cell activity in early human pregnancy.

Natural killer (NK) cell activity was determined in 41 women during the first trimester of pregnancy. NK cytotoxicity was similar between the study subjects and nonpregnant controls and was not a reflection of a change in the circulating number of cells or density in culture. Although NK cells may play a role in maternal immune status in advanced pregnancy, NK cells do not appear to be crucially involved in the first trimester, when reproductive wastage usually occurs.

Cytotoxicity, Immunologic↗
PubMed1994

High-dose melphalan and autologous bone marrow transplantation as consolidation in previously untreated myeloma.

PURPOSE: We report the results of intensive chemotherapy with high-dose melphalan (HDM) following conventional-dose cytoreductive chemotherapy in previously untreated patients with myeloma. PATIENTS AND METHODS: From 1986 to 1991, 53 previously untreated patients with myeloma received HDM 200 mg/m2 plus methylprednisolone 1.5 g daily (MP) for 5 days with autologous bone marrow transplantation (ABMT) after cytoreductive chemotherapy. RESULTS: At the time of HDM administration, responses to induction therapy were complete remission (CR) in nine patients, partial remission (PR) in 38, and no response (NR) in six. Following HDM, all but one patient responded, with 40 patients achieving a CR (75%). There was one treatment-related death following HDM. The median time to reach a WBC count more than 1,000/microL and platelet count more than 25,000/microL was 19 days (range, 13 to 30) and 24 days (range, 15 to 55), respectively. The median duration of response has not been reached at 20 months, and it is significantly longer for patients in CR than for those in PR (P < .025). Currently, with a median follow-up duration of 31 months (range, 6 to 58), 12 patients are dead and 40 are alive, and the estimated probability of survival at 54 months is 63%. Multivariate analysis found hemoglobin (Hb) more than 10 g/dL (P = .012), and stage A disease (P = .001) at diagnosis to be favorable indicators for survival. CONCLUSION: Myeloma patients who are able to receive HDM plus ABMT following conventional chemotherapy achieve a high proportion of CRs, which may be associated with prolonged survival.

Adult↗
PubMed1994

High-dose melphalan for multiple myeloma: long-term follow-up data.

PURPOSE: To present long-term follow-up data of patients with myeloma treated with high-dose melphalan HDM, including an assessment of prognostic factors. PATIENTS AND METHODS: Between November 1981 and April 1986, 63 previously untreated patients with multiple myeloma received HDM 140 mg/m2 without autologous bone marrow transplantation. RESULTS: The overall response rate was 82% (51 of 62), with 32% (20 of 62) patients entering complete remission (CR). The median duration of response was 18 months, and six patients remain alive and free from disease progression at 60+ to 84+ months. Improvements in quality of life associated with remission were immediate in terms of pain grade (89% of patients) and performance status (92%), and later in terms of bone healing (29%). Currently, at a median follow-up duration of 74 months (range, 63 to 100) since HDM, 23 patients are alive with a median survival duration of 47 months, and 35% of patients are expected to be alive at 9 years. Apart from early-stage disease, no factors were found to predict long-term survival. No second malignancies or other late side effects have been recorded. CONCLUSION: Single-agent HDM without autologous bone marrow transplantation is a feasible therapeutic option in myeloma, and is associated with a high objective response rate, relatively long remission durations, and good symptom control.

Adult↗
PubMed1994

Fludarabine in lymphoproliferative disorders: the Royal Marsden Hospital experience.

Fludarabine 25 mg/m2 was given on five consecutive days every four weeks to 85 patients with B- and T-cell malignancies. The median number of courses given was five. All patients except one had received previous chemotherapy. The overall response rate in non-Hodgkin's lymphoma (NHL) was 50% (five complete responses (CR) and 19 partial responses (PR)). The response rate in chronic lymphocytic leukemia (CLL) was 43% (four CR and 12 PR). Responses were seen in all groups of B-cell malignancies, but no T-cell malignancies (n = 4) responded. The median duration of CR has not been reached and the median duration of PR was 14 months for NHL and 16 months for CLL. The median survival from starting fludarabine for patients who achieved a CR or PR in NHL has not been reached and the median duration of PR in CLL was 23 months. The median duration of survival in non-responders was five months. Fludarabine was well tolerated and the main toxicity was myelosuppression. Our results suggest that even in patients who have never responded to any chemotherapy, regardless of the number of treatment regimens previously given, there is a 36% chance of response. In addition, this is the first report of fludarabine activity in Franklin's disease.

Adult↗