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Biomedical subjects

W A Robinson

Publications and source records attributed to W A Robinson.

At least 55 records · Page 3Linked to original sources
PubMed1991

Role of recombinant alpha-interferon in the treatment of advanced cutaneous malignant melanoma.

A total of 65 patients with advanced cutaneous malignant melanoma (MM) have now been treated with interferon alpha-2b (Intron A) at a dose of 10 million IU/m2 administered subcutaneously thrice weekly. Fifty-one patients were evaluable for response, and 4 of these (7.8%) achieved complete remission; 2 of these 4 remain so at 37 + and 54 + months. Six additional patients achieved a partial remission. All responders had subcutaneous, lymph node and/or pulmonary metastases only. In all responders, therapy was continued for a total of 12 months. The vast majority of patients experienced side effects, largely flu-like symptoms, mild leukopenia and mild hepatocellular dysfunction. No evidence of cumulative toxicity was observed. Our experience indicates that interferon alpha-2b is active in patients with advanced cutaneous MM.

Adult↗
PubMed1991

Phase II trial of piritrexim in metastatic melanoma using intermittent, low-dose administration.

A phase II trial of piritrexim (2,4-diamino-6[2,5-dimethoxybenzyl]-5-methyl pyrido-[2,3d] pyrimidine, 301U74; PTX) was conducted for patients with metastatic malignant melanoma using an intermittent, low-dose oral administration schedule. PTX was administered at a starting dose of 25 mg orally three times per day for 5 days weekly for 3 weeks followed by 1 week of rest. Thirty-one patients were entered onto the study. Among 31 patients assessable for response, there were two complete responses (CRs) and five partial responses (PRs) for a response rate (CR plus PR) of 23% (95% confidence limit, 10% to 42%). Five responses occurred in soft tissue lesions, and two responses occurred in lung lesions. The initial dose schedule was well tolerated. The dose-limiting toxicity was myelosuppression. PTX administered in this schedule appears to be active against malignant melanoma. Further clinical trials to confirm these results are underway.

Administration, Oral↗
PubMed1991

Single-dose murine monoclonal antibody ricin A chain immunotoxin in the treatment of metastatic melanoma: a phase I trial.

To determine the maximally tolerated dose of a ricin A chain-conjugated antimelanoma antibody (XomaZyme-Mel), 20 patients with metastatic melanoma were treated with escalating doses of the murine immunotoxin given as single intravenous infusion over 30 minutes. The starting dose was 0.6 mg/kg and was escalated in five groups to a maximum of 1.6 mg/kg. The maximally tolerated dose was 1.25 mg/kg as three of six patients treated at 1.6 mg/kg developed unacceptable toxicity. The dose-limiting toxicity consisted of profound fatigue, myalgias, and arthralgias. These occurred within 4 days and resolved in 7 to 10 days. Other non-dose-limiting toxicities encountered consisted of hypoalbuminemia, weight gain, peripheral edema, mild hypotension, and flu-like syndrome; the severity of these was also dose related. In addition, two allergic reactions occurred, one severe. There was one durable complete response of 12+ months' duration and one brief mixed response lasting 3 months. We conclude that the maximum tolerated single dose of XomaZyme-Mel is 1.25 mg/kg. Phase I studies evaluating 1.25 mg/kg given in multiple doses at 2- to 4-week intervals and phase II studies to determine the response rate of a single 1.25 mg/kg dose are warranted.

Adult↗
PubMed1990

Surgical treatment of brain metastases in malignant melanoma.

The authors report the results of a retrospective review of 13 patients who underwent 19 craniotomies for resection of metastatic malignant melanoma at the University of Colorado (Denver, CO) between 1983 and 1989. There was preoperative evidence of extracranial disease in 11 patients. Eight patients had more than one intracranial metastasis at operation. Intraoperative ultrasound was used in 18 of the 19 craniotomies to minimize surgical trauma to the brain. The 30-day mortality was zero. The 30-day morbidity was minimal. No patient acquired a new neurologic deficit as a result of surgery. All patients regained at least their preoperative level of functioning. Six of the patients who were living at the time of review have been followed for 4 to 25 months (median, 7.5 months). The seven patients who were dead at the time of review survived 4 to 18 months (median, 10 months). These results compare favorably with the survival of untreated patients with metastatic melanoma to the brain (median, 1 month), patients treated with radiation therapy alone (median, 2-4 months), and those treated with chemotherapy alone (median, 2-4 months). The excision of metastatic melanoma from the brain, although not curative, may increase survival in patients with this problem with little morbidity and mortality even in the presence of other metastases.

Adult↗
PubMed1990

Cigarette smoking, blast crisis, and survival in chronic myeloid leukemia.

We reviewed the records of all patients with chronic myeloid leukemia (CML) seen in the CML Clinic of the University of Colorado Health Sciences Center between 1968 and 1987 for a history of cigarette smoking. Patients who smoked for five or more pack/years within the ten years preceding, or after the diagnosis of CML, were defined as smokers. Adequate smoking histories were obtained on 122 patients. Eighty-seven of these were non-smokers and 35 were smokers by the above criteria. The smoking group had a higher predominance of males, an older median age, and were diagnosed earlier in the course of the 20 year study. Seventy-two patients had died at the time of analysis. All but one, a non-smoker, died from the development of blast crisis. The overall median actuarial survival was significantly reduced for smokers (35 months) as compared to non-smokers (47 months). This was particularly striking for patients who had succumbed to the disease, with a median survival of 30 months in smokers versus 46 months in non-smokers. Although various explanations could explain the differences noted, we conclude that cigarette smoking has an adverse effect on the development of blast crisis and survival in chronic myeloid leukemia.

Adolescent↗
PubMed1990

Malignant melanoma as a model for cancer education and prevention. 1989 Harvey lecture American Association for Cancer Education.

Cutaneous malignant melanoma is one of the most rapidly increasing and highly fatal cancers in the world today. Current estimates suggest that 1 in 90-100 Caucasians will develop MM by the year 2000, and 20%-30% will eventually die of the disease. The cause of the epidemic of malignant melanoma is clearly increasing exposure to the sun from lifestyle and clothing habits that have changed over the past 50 years. The disease occurs primarily in preexisting nevi in sun-exposed sites in specific high risk populations who can be, and have been, defined. These are primarily middle- and upper middle-class Caucasians with blue eyes, brown or blonde hair, and fair skin, with predominantly indoor occupations who spend, or have spent, considerable time outdoors in leisure and other activities. The presence of a clearly definable cause (exposure to the sun) in specific risk groups, the ease of early detection by simple means, and the devastating outcome of late diagnosis make malignant melanoma an ideal model for teaching the basic tenets of cancer causation, development, and prevention to the public and professionals alike.

Adult↗
PubMed1989

Prophylactic penicillin for intraoral wounds.

We conducted a prospective, double-blind, placebo-controlled study in adult patients to determine whether prophylactic penicillin prevents infection in intraoral lacerations secondary to minor trauma or seizures. Uninfected full-thickness, mucosal-only, or through-and-through wounds presenting within 24 hours of injury were considered. Management consisted of cleansing, irrigation, debridement, and closure as indicated: no topical antibiotics were applied. Patients were randomly assigned to receive penicillin VK 500 mg or identically appearing placebo four times daily for five days. Home wound care was standardized and patients were followed for a minimum of four or five days. Infection was assessed clinically. Seventy-six patients were enrolled and 62 completed the study. Penicillin (30) and placebo (32) groups were similar in all parameters except wound etiology; assault was more common in the placebo group (P = .02). Two infections occurred in patients receiving penicillin, and six infections were seen among placebo-treated patients (P = .05, beta = 0.17). When patients poorly compliant with therapy were eliminated from analysis, none of the penicillin-treated patients and five of the placebo-treated patients developed infections (P = .027). Our data suggest that patients with intraoral wounds may benefit from prophylactic penicillin if compliant with their therapy. More studies are needed to further delineate the usefulness of prophylactic antibiotics for these wounds.

Administration, Oral↗
PubMed1989

Intranasal administration of deferoxamine to iron overloaded patients.

We examined the effect of intranasal administration of deferoxamine on iron excretion in seven patients with iron overload secondary to chronic transfusion therapy. Deferoxamine was administered in doses of 0.75 to 3.0 gm given over 12 hours in a variety of dosing schedules. There was a probable, though not significant, dose response relationship between the amount of iron excreted and the dose administered. The amount of iron excreted was 10%-15% of that obtained using the same dosage of deferoxamine given by the subcutaneous route over the same time period. Hourly administration was more effective than less frequent administration. Addition of taurodeoxycholate to deferoxamine did not increase its absorption as measured by the levels of iron excretion. Side effects were few and consisted mainly of mild nasal irritation and a bad taste in the mouth. Nasal administration of deferoxamine may be a useful adjunct to iron chelation in patients receiving chronic transfusion therapy, particularly in those who are noncompliant with parenteral means of administration.

Administration, Intranasal↗
PubMed1989

Sequential use of indium-111 labeled monoclonal antibodies 96.5 and ZME-018 does not increase detection sensitivity for metastatic melanoma.

Two indium-111 labeled anti-melanoma murine monoclonal antibodies (MAb), 96.5 and ZME-018, each recognizing separate antigens on melanoma cells, were administered intravenously to 17 patients with melanoma in a sequential fashion to determine whether: 1) additional tumor sites could be imaged with the combination compared to a single Mab; 2) the first MAb influenced the biodistribution and tumor localization of the second; and 3) significantly toxicity occurred with the combination. Patients were randomized to receive either 96.5, followed by ZME-018, ZME-018 followed by 96.5, or each MAb followed by itself (controls). Infusions of the second MAb occurred 10 days after the first infusion. Gamma camera images were obtained 72 hours after each antibody infusion. There were 139 known metastatic sites of which 72 lesions were localized by either MAb for an overall sensitivity of 52%. The detection rate was higher when lesions only greater than 1.5 cm were considered. Imaging results were independent of MAb administration sequence. When ZME-018 was given as the first infusion, when ZME-018 was given as a second infusion (p = NS). However, mean sensitivities using 96.5 as the first or second infusion were 48% and 66% respectively (p = NS). There was not a significant number of sites detected by MAb 2 that were missed by MAb 1. Human anti-murine antibody (HAMA) response occurred in seven of eight patients studied; two patients who experienced toxicity had levels of HAMA greater than 2000 ng/ml. We conclude that the use of these two murine anti-melanoma monoclonal antibodies given in sequential fashion did not significantly change the imaging sensitivity from that seen with each individual antibody. Moreover, with the exception of one patient, mean plasma half-life of the MAb did not change significantly, suggesting that overall clearance mechanisms were not saturated by the consecutive doses of monoclonal antibody or significantly altered by the presence of HAMA.

Adult↗
PubMed1988

Use of differentiation-inducing agents in the myelodysplastic syndrome and acute non-lymphocytic leukemia.

The use of chemical agents that induce differentiation of malignant cells to normal cells has held great promise as an adjunct to standard chemotherapy. In vitro data has shown that 13-cis-retinoic acid can differentiate certain leukemia cell lines (e.g., HL-60) into stable granulocyte cells. In this study, oral 13-cis-retinoic acid was administered to four patients with the myelodysplastic syndrome (MDS) and to four patients with acute nonlymphocytic leukemia (ANLL). None of the MDS patients showed an hematologic response to the drug, while three of four ANLL patients responded with normalized peripheral blood counts. The side effects of the drug at 80-120 mg/d (dry skin, cheilitis, epistaxis) were self limiting.

Acute Disease↗
PubMed1988

Role of recombinant interferon alpha 2 and cimetidine in patients with advanced malignant melanoma.

Following recent reports suggesting that the addition of cimetidine to interferon may enhance response rates in patients with metastatic malignant melanoma, we have completed a Phase II study of the use of recombinant alpha 2 interferon and cimetidine in patients with advanced malignant melanoma and who had progressive disease following interferon therapy alone. We observed two partial responses, no complete responses, and two patients had stable disease. Toxicity encountered was analogous to that of interferon alone. We conclude that the additional of cimetidine to alpha interferon is not beneficial in the treatment of advanced metastatic malignant melanoma.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1988

Bone marrow granulopoietic response to scalds and wound infection in mice.

Phagocytic cell function is often suppressed after thermal injury. It has been suggested that one of the mechanisms of suppression is a direct effect of thermal injury upon these cells. In the present study we examined whether bone marrow haemopoietic stem cells were suppressed by thermal injury similar to the effect seen on mature haemopoietic cells. Results of both in vitro bone marrow cell cultures and in vivo spleen colony assays showed that granulopoiesis was not suppressed but activated early on day 3 following scald injury or scald plus wound infection in mice. In the latter group, stimulation of granulopoiesis persisted throughout the entire observation period of 9 days. These studies indicate that bone marrow pluripotent stem cells are capable of modulating their direction of differentiation according to body demand and deviate toward the granulocyte series following thermal injury.

Agranulocytosis↗
PubMed1988

Interleukin-1 enhances murine granulopoiesis in vivo.

Interleukin-1 (IL-1), a monokine involved in host response to infection and inflammation, has recently been shown to stimulate production of granulocyte-monocyte colony-stimulating factors (CSFs) from a variety of cell types in vitro. The purpose of this study was to investigate the effects of human IL-1 on granulopoiesis in vivo. CF1 female mice were injected with a single dose of either highly purified human IL-1 or recombinant human IL-1 alpha (rIL-1 alpha). Heat-inactivated IL-1 or rIL-1 alpha served as controls. Physiologic doses of the IL-1 preparations were initially established by evaluating neutrophil egress from bone marrow (BM). Significant peripheral neutrophilia developed 3 h after injection of 10 U (doubling units) purified IL-1, in association with decreased marrow neutrophils. Significant neutrophilia occurred 6 h after injection of 5 x 10(3) U (half-maximal units) rIL-1 alpha. Serum colony-stimulating activity (CSA) and BM colony formation (CFU-GM) were subsequently measured in standard agar culture at various times following injection. A significant rise in CSA occurred between 3 and 6 h after injection of purified IL-1, and a significant increase in BM CFU-GM developed 48 h after injection. Similar increases in CSA and CFU-GM occurred following injection of rIL-1 alpha. These results suggest that IL-1 may play an important role in the regulation of granulopoiesis in vivo by enhancing the production of CSFs required for myeloid proliferation.

Animals↗
PubMed1988

Malignant melanoma--profile of an epidemic.

Cutaneous malignant melanoma is occurring in epidemic proportions in the United States. To provide a profile of persons at risk and the epidemiologic features of malignant melanoma, we reviewed the records of 325 patients with cutaneous malignant melanoma seen at the University of Colorado Health Sciences Center between 1973 and 1983. Most patients had fair skin, brown or blonde hair, blue or green eyes, and had difficulty in suntanning. The majority of melanomas (72%) developed in preexisting nevi. In women, melanomas were most common on the extremities, and in men they occurred most frequently on the trunk, head or neck. The most frequently noted depth of invasion was Clark's level IV. At diagnosis, most of the patients (77%) were at stage I. We conclude that malignant melanoma constitutes a major disease problem in the western United States that is largely preventable with appropriate physician and patient education.

Adolescent↗
PubMed1987

Metastatic disease in patients with newly diagnosed malignant melanoma.

In patients with stage I Clark's level III and IV malignant melanoma (MM), recurrence rates of 30-60% can be expected after resection of the primary lesion. If metastatic disease could be detected early and treated in such patients, survival might be prolonged. Ninety patients (37 males and 53 females) with newly diagnosed, resected stage I cutaneous MM, levels III and IV, were evaluated for metastatic disease at diagnosis using a physical examination; CBC; SMA 18; chest films; brain computed tomography (CT) scan; and radioisotope liver, spleen, and bone scans. Forty-four patients had level III and 46 had level IV melanomas ranging in thickness from 0.65 to 4.5 mm. None of these 90 patients was found to have metastatic disease. Such tests are not useful and can be replaced by a history and physical examination with substantially improved cost effectiveness.

Humans↗