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Biomedical subjects

N Coombe

Publications and source records attributed to N Coombe.

9 recordsLinked to original sources
PubMed1999

Phase II clinical trial of didemnin B in patients with recurrent or refractory anaplastic astrocytoma or glioblastoma multiforme (NSC 325319).

The activity of didemnin B, a natural product derived from the Caribbean Tunic was assessed in 16 patients with Glioblastoma multiforme. Didemnin B was administered intravenously by a short infusion at a dose of 4.3 mg/m2 and subsequently escalated to 6.3 mg/m2. No anti-tumor activity was observed. Toxicity consisted of fatigue, weakness, stomatitis, mild blood count changes, nausea and vomiting and occasional fever. Based on these results further studies with didemnin B in patients with Glioblastoma multiforme are not recommended.

Adult↗
PubMed1994

Urologic complications of high-dose chemotherapy and bone marrow transplantation.

OBJECTIVE: This study reviews the incidence and management of cyclophosphamide-induced hemorrhagic cystitis in a group of patients who received high-dose chemotherapy and bone marrow transplantation. METHODS: The records of 217 consecutive patients undergoing bone marrow transplantation were reviewed. The incidence, degree, and management of hematuria in this group of pancytopenic and immunocompromised patients were recorded. RESULTS: Despite prophylaxis, cystitis developed in 58 of these 217 patients (27%). In 12 patients (6%) the cystitis was severe. These patients had gross hematuria, clot retention, and drop in hematocrit necessitating blood transfusion. These patients were managed with continuous bladder irrigation, alum irrigation, and when less aggressive approach was unsuccessful, with intravesical formalin instillation. Alum irrigation was used in 5 patients, and was successful in only 1 patient. Six patients required intravesical formalin instillation to control the hematuria. Formalin solution 2-5% was instilled initially. When lower-concentration formalin failed, 5-10% formalin was used progressively. CONCLUSIONS: Patients with bone marrow transplantation in whom severe hemorrhagic cystitis develops should be managed aggressively early. Intravesical formalin appears to be the most effective regimen in controlling profuse, persistent hematuria.

Adolescent↗
PubMed1994

Phase I-II trial of high dose Ara-C, carboplatinum, etoposide and steroids in patients with refractory or relapsed lymphomas.

Thirty-three patients, including 20 with non-Hodgkin's lymphomas (NHL) and 13 patients with Hodgkin's disease, were treated with a combination of high dose Ara-C 3 gm/m2 over 3 h, carboplatinum 300 mg/m2 over 15 min, etoposide 300-750 mg/m2 continuous infusion over 24 h and solumedrol 1250 mg. Probantheline was given prophylactically. The etoposide dose was escalated from 300 mg/m2 to 600 mg/m2 to 750 mg/m2. The median age was 44 years (range 28-63). Median Karnofsky performance status was 80 (range 60-100). Patients treated included: primary refractory six, first relapse 14, > first relapse seven, and resistant relapse six. Responses were seen in 11 patients (33%; 95% CI 17-49). Of note, no responses were seen in ten patients receiving < 750 mg/m2 etoposide vs. 11/23 patients receiving 750 mg/m2 etoposide (p = 0.013). Responses were seen in patients who were refractory to previous chemotherapy and occurred in all sites. Toxicity was tolerable with most patients not requiring hospitalization following chemotherapy. Two patients died on study: one of Guillain-Barre syndrome and the other of a sudden death. Severe mucositis was not observed. High dose etoposide based salvage chemotherapy offers a greater probability of response than lower dose etoposide. This regimen is well tolerated and can be administered with relatively brief hospitalization.

Adult↗
PubMed1993

Propantheline prevention of mucositis from etoposide.

Mucosal toxicity is dose limiting for etoposide. This may be related to the direct effects of etoposide on the mucosa. Twelve patients receiving etoposide 1800 mg/m2 as part of a myeloablative pre-transplant regimen were randomized to receive propantheline 30 mg or placebo orally every 6 h for six doses. Mucositis was less frequent (2 of 6 vs 5 of 6) and less severe (p = 0.05) in the propantheline arm. There were no differences in tumor response or survival between the two groups. Propantheline is an anticholinergic that causes xerostomia by decreasing salivation. Propantheline may reduce the salivary excretion of etoposide and could reduce its toxic effects on the mucosa. Propantheline is effective in reducing the incidence and severity of mucositis in patients receiving high-dose etoposide.

Adult↗
PubMed1992

A phase I pharmacokinetic study of recombinant human tumor necrosis factor administered by a 5-day continuous infusion.

Nineteen patients with advanced cancer were entered into a phase I clinical trial of Tumor Necrosis Factor (TNF) which was designed to determine the pharmacokinetic profile, safety, and maximal tolerated dose (MTD) of the recombinant human cytokine in vivo. TNF was administered by continuous infusion for 24 hours followed by pharmacokinetics and a 120-hour infusion repeated every 3 weeks. The initial dose was 40 micrograms/m2 and was ultimately escalated to 200 micrograms/m2. A total of forty 5-day cycles were administered to 18 of these patients; and all were evaluable for toxicity. Toxicities in this trial included fever, chills, rigors, hypotension, headaches, seizures, lethargy, weight loss, and malaise. At all dose levels, but more significantly at the highest doses, hematological toxicities were observed and grade 3 neurotoxicity (headache and confusion), and hypotension were noted. Two patients expired during the study, and this was felt to be related to septic episodes. Because of these severe toxicities, 160 micrograms/m2 was defined as the MTD. At 160 micrograms/m2 peak serum levels occurred within 5-20 minutes of initiation and were not detectable 1 hour later. No anti-tumor responses were observed. No measurable plasma levels of TNF were observed with the administration of doses of 80 micrograms/m2. This dose level could be further studied in phase II studies alone and in combination with other agents, utilizing a continuous infusion schedule.

Adenocarcinoma↗
PubMed1989

Lack of protection against bacterial infections in patients with advanced cancer treated by biologic response modifiers.

A survey of patients with advanced cancer treated by biologic response modifiers (BRMs), including (i) recombinant interleukin-2 and lymphokine-activated killer cells, (ii) recombinant interleukin-2 and alpha interferon, and (iii) tumor necrosis factor, was done. A total of 52 patients were reviewed. A total of 73 courses of BRMs were administered. Prior to the initiation of therapy, all patients were infection free and not receiving antibiotics. Twelve patients developed bacteremia during treatment with these BRMs. Five of these 12 patients had catheter-related bacteremia. Six patients had bacteremic infections without an obvious source, and one patient had a urinary tract infection with bacteremia. Staphylococcus epidermidis accounted for six of the isolates. Other organisms were Staphylococcus aureus, group B streptococci, viridans group streptococci, and gram-negative bacilli. This was an unexpectedly high incidence of bacterial infections in patients treated with BRMs. These BRMs have been previously shown to be efficacious against infections (by bacteria and other intracellular organisms) in experimental animals. In this study BRMs did not influence host defense mechanisms or offer protection against bacterial infections.

Bacterial Infections↗
PubMed1989

Acute promyelocytic leukemia: a 5-year experience with new antileukemic agents and a new approach to preventing fatal hemorrhage.

Forty-six induction courses were administered to 32 patients with acute promyelocytic leukemia. There were 28 males and 18 females with a median age of 39.5 (range 19-68). Twelve patients were previously untreated, 32 were in relapse, and 2 were refractory to primary induction chemotherapy. Heparin 7.5-10 units/kg/h by continuous infusion, 4-6 units of platelets and 1-2 units of fresh-frozen plasma (FFP) every 12 h were given to all patients. Previously untreated patients received either daunorubicin, idarubicin or mitoxantrone in combination with cytarabine (Ara-C). For relapsed and refractory patients, regimens included amsacrine with high-dose cytarabine (Amsa/HiDac), homoharringtonine (HHT) alone, or with Ara-C, mitoxantrone and bisantrene. Hemorrhagic complications occurred in only 1 out of 46 courses (2%). Complete remission rates (CR) were as follows: previously untreated 83% (10/12), relapsed 66% (21/32), primary refractory 50% (1/2). Amsa/HiDac resulted in a 71% (10/14) CR and HHT-based regimens achieved a 46% (6/13) CR. These regimens are effective and the value of their incorporation into primary therapy should be studied. The use of heparin with platelet and FFP transfusions every 12 h reduces the risk of hemorrhage during induction therapy.

Adult↗
PubMedDate not supplied

Rat bites support need for in-home control: an epidemiologic study of rat bites in New York City, 1974-1978.

Rat bite reports in New York City during the years 1974-1978 were analyzed by time, place and person characteristics. Rat bites showed a general decline over the five-year period, from 226 reported bites in 1974 to 162 reports in 1978 (2/100,000 population). The decrease in reported bites from areas with active rodent control programs was twice the decrease from areas without such programs. The highest rates were reported from the health districts of the Lower East Side of Manhattan and the Williamsburg-Greenpoint section of Brooklyn. Rat bite rates in reported incidents are highest in children under age five, with no significant difference between sexes. Of the 1069 reported rat bites for the five-year period, 41.4% occurred on the hand, particularly the fingers, and 87.9% occurred indoors. The use of rat bite reports is a mechanism to identify high risk groups and areas of rodent infestation as well as indicating the success of rodent control programs.

Age Factors↗