Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0016382 (flushing)
 6,387 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Increasing numbers of chemotherapeutic agents are being used to treat patients with cancer and various immunologically mediated and inflammatory disorders. Many of the drugs used have distinctive cutaneous side effects that range from relatively common ones, such as alopecia, stomatitis, and hyperpigmentation, to more unusual ones, such as radiation enhancement and recall phenomena, photosensitivity and hypersensitivity reactions, and phlebitis or chemical cellulitis. In addition, there are some rare complications such as diffuse sclerosis of the hands and feet, Raynaud's phenomenon, sterile folliculitis, and flushing reactions. By being aware of which drug may have caused a particular cutaneous reaction, dermatologists will be able to contribute to the care of patients with complex problems in a meaningful way.
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PMID:Cutaneous complications of chemotherapeutic agents. 664 64

We evaluated a totally implanted system consisting of a subcutaneous injection port connected to a silicone elastomer central venous catheter for vascular access, including blood drawing, in 35 patients with cancer. All patients lacked peripheral venous access sites and were undergoing aggressive chemotherapy programs. The cumulative duration of successful access exceeded 2,900 days (for individual patients: range, five to 203 days; median, 61 days). In no instance were infusions or injections unsuccessful. Blood-sampling attempts were successful 90% of the time. The system did not require flushing between uses, being filled with heparinized saline after each entry. There were no instances of irreversible catheter occlusion or shear and no system-related infections. Thus, this device appears to have advantages over other central venous catheters in terms of patient acceptance and lack of maintenance between uses.
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PMID:A totally implanted injection port system for blood sampling and chemotherapy administration. 671 82

Medullary cancer of the thyroid is rare but of unusual biologic interest. It originates in the thyroid parafollicular or C cells that are of neural crest origin and that secrete calcitonin. Calcitonin measurements, particularly after pentagastrim administration, are useful in detecting the tumor and following its progression. Ninety percent of medullary cancers are sporadic and 10% are familial; the latter may be associated with pheochromocytoma and parathyroid hyperplasia-adenoma. Initial symptoms of both the sporadic and familial varieties include thyroid mass, diarrhea, and less often, flushing. Uninvolved members of kindreds with the disease should be followed up by repeated measurements of calcitonin after pentagastrim and calcium infusion and should be treated when a positive test result is obtained. Therapy involves total thyroidectomy plus node dissection if indicated. In addition, postoperative radiation may reduce the recurrence rate.
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PMID:Medullary carcinoma of the thyroid. 684 63

The camptothecin analogues topotecan and irinotecan (CPT-11) are active anticancer drugs. This article reviews the accumulated results of clinical and laboratory studies performed with these agents at The Johns Hopkins Oncology Center. In a phase I clinical and pharmacology trial of topotecan given as a 30-min infusion daily for 5 days every 3 weeks, profound neutropenia precluded dose escalation above 1.5-2.0 mg/m2 per day, the maximum tolerated dose (MTD). The daily x5 schedule has been developed further with dose escalation using granulocyte-colony-stimulating factor support in patients who have kidney or liver dysfunction and given in combination with cisplatin. In addition, a phase I trial of topotecan given as a 5-day continuous intravenous infusion to patients with refractory leukemia has had promising antileukemic responses. A separate series of in vitro studies indicates that a modest degree of resistance to the cytotoxicity of topotecan can be mediated by P-glycoprotein. A phase I and pharmacology study of irinotecan given as a 90-min infusion every 3 weeks has defined an MTD of 240 mg/m2, with dose escalation being limited by several toxicities. These included an acute treatment-related syndrome of flushing, warmth, nausea, vomiting, and diarrhea; a subacute combination of nausea, diarrhea, anorexia, and weight loss; and/or neutropenia. Antitumor activity has been observed with topotecan and irinotecan in patients with a variety of solid tumors and refractory leukemia in our studies, which supports the widespread enthusiasm for this group of compounds.
Cancer Chemother Pharmacol 1994
PMID:Camptothecin analogues: studies from the Johns Hopkins Oncology Center. 752 Aug 44

A prototype of a totally implantable vascular catheter-port system was evaluated on its design using three animals of different species. The catheter was placed either intravenously or intra-arterially, and connected to the port which was retained outside the body. Parameters used for design evaluation or functionality testing were focused on the use and handling of the port-catheter system such as easiness of flushing, injection, blood sampling, septum stiffness to prevent blood reflux after pushing the septum, and possible diffusion of blood into the saline present in the port-catheter system. This pilot experiment showed that the septum of the prototype port system was too flexible, and that the distance between septum and base of the port was too short. These findings have led to a major improvement of the catheter-port system, currently successfully used in cancer chemotherapy.
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PMID:Ex vivo design evaluation of an implantable blood port system. 760 53

From September 1993 through March 1994, 30 cases of refractory carcinoma of the ovary and Fallopian tube were treated with Taxol. Complete response was seen in 4 and partial response in 8 cases with a response rate of 40%. The average length of remission was 5 months in CR and 3.9 months in PR. The major toxic side effect was decrease in total white cell count and in neutrophil count. Apart from flushing of face during Taxol infusion in 6 patients, no other allergic reaction was observed. Gastrointestinal, neurologic, liver and renal toxicities were mild. Taxol is a drug of choice in the treatment of patients with cancer of the ovary and Fallopian tube who are resistant to conventional chemotherapy.
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PMID:[A clinical report of refractory carcinoma of ovary and fallopian tube treated with taxol]. 765 6

Melphalan has a steep dose-response curve, but the use of high doses results in unacceptable myelosuppression. Strategies to circumvent this dose-limiting myelosuppression would allow for the administration of higher, more effective doses of melphalan. Amifostine (WR-2721) has been shown in preclinical studies to protect the bone marrow from the myelotoxicity of melphalan, and in clinical trials, to protect from the myelotoxicity of other alkylating agents. A Phase I trial of the combination of amifostine and melphalan was performed in children with refractory cancers to: (a) define the acute toxicities of amifostine and its maximum tolerated dose (MTD); and (b) to determine whether the dose of melphalan could be safely escalated when administered in combination with amifostine. Amifostine was administered i.v. as a 15-min infusion 30 min before melphalan. The starting dose of amifostine was 750 mg/m2, with planned dose escalations in 30% increments. Melphalan was administered as a 5-min infusion using the previously defined MTD in heavily pretreated patients, 35 mg/m2, as the starting dose. The dose of melphalan was escalated by 30% increments. Nineteen patients, ranging in age from 3 to 24 years (median, 15 years), were entered on trial. The dose of amifostine was escalated to 2700 mg/m2, which is approximately 3-fold higher than the adult recommended dose, without reaching a MTD. Fifteen patients experienced nondose-limiting (< 25%), transient decreases in blood pressure after the amifostine infusion. Other nondose-limiting toxicities of amifostine included mild nausea and vomiting, flushing, anxiety, diarrhea, and urinary retention. Six patients, three each at the 2100 and 2700 mg/m2 amifostine dose levels were treated with an escalated dose of melphalan (45 mg/m2). All of these patients experienced grade 4 neutropenia (< 500/mm3), and five of six patients had grade 4 thrombocytopenia. The duration of this dose-limiting myelosuppression exceeded 7 days in four of six patients. Although no dose-limiting (grade 3 or 4) toxicity was attributed to amifostine, significant anxiety and reversible urinary retention occurred at the two highest amifostine dose levels. A dose of 1650 mg/m2 for pediatric Phase II trials is recommended. High doses of amifostine, however, do not appear to allow for escalation of melphalan beyond its single agent MTD of 35 mg/m2.
Cancer Res 1995 Sep 15
PMID:A phase I trial of amifostine (WR-2721) and melphalan in children with refractory cancer. 766 82

The Cytospin method of fine needle aspiration cytology includes flushing the aspirate into 10 mL of Cytospin fluid; the cytocentrifuge preparations are then safely and conveniently prepared in the laboratory. Slides are stained with Papanicolaou stain and hematoxylin and eosin. From November 1989 through October 1992, 1,868 breast aspirates from palpable lumps were examined by this method at our institution. The method detected 398 of 441 cancers (90.2%); of the 43 that were undetected, 16 had inadequate aspirates, and 27 were falsely reported as negative (for a false-negative rate of 6.0%). There were no false positives; the positive predictive value for malignancy was 100%. The inadequacy rate was 14.8%. Excluding inadequate samples, the complete sensitivity was 95.2%, with 96.5% specificity. The Cytospin method of processing breast aspirates from palpable breast lumps is an acceptable alternative to conventional fine needle aspiration using direct smears. It is also highly convenient as an outpatient procedure, obviating the need for skillful preparation of direct smears.
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PMID:Fine needle aspiration cytology of the breast. A review of 1,868 cases using the Cytospin method. 799 83

Granisetron, a potent and selective 5-hydroxytryptamine receptor (5-HT3) antagonist was reported to be an effective antiemetic agent both in animal studies and in patients given highly emetogenic chemotherapy. A sample of 43 patients with breast cancer was accrued from September to November 1992 in a phase II study to assess the efficacy of granisetron in patients receiving FEC (5-FU, epirubicin, cyclophosphamide). Each patient received 3 mg intravenous granisetron as a single dose just prior to chemotherapy. Oral metoclopromide was prescribed to each patient as a rescue anti-emetic. The emetic episodes and degree of nausea were evaluated on a daily basis. Good control of emesis (0-2 episodes of vomiting) and nausea (mild or no nausea) was in the range 77%-98% and 77%-93% respectively. There was a complete response (no emetic episodes throughout the 6-day period) in 16 patients (37.2%). Onset of emesis tends to occur on day 1 and tend to subside after day 3; 85% of patients had onset of emesis in the first 2 days after chemotherapy. Control of emesis and nausea tends to improve after day 3, which could be the result of the reduced emetogenicity of the combination FEC with time. Altogether, 77% had good control of acute emesis; control of delayed emesis was better with 84% achieving a major response on day 2 after chemotherapy, which improved to more than 90% after day 4. Granisetron was generally tolerated with headache being the most common side-effect followed by constipation and flushing. This study suggests that granisetron is an effective and well-tolerated anti-emetic agent, which deserves randomised trials to elucidate its efficacy further.
Support Care Cancer 1994 May
PMID:Control of emesis by intravenous granisetron in breast cancer patients treated with 5-FU, epirubicin and cyclophosphamide. 803 7

7-Ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxycamptothecin (CPT-11; Irinotecan), a semisynthetic analogue of camptothecin (CPT) with broad preclinical antitumor activity, has demonstrated impressive activity in phase II trials in Japan in advanced small and non-small cell lung, colorectal, cervical, and ovarian carcinomas, as well as in refractory lymphomas and leukemias. In this phase I and pharmacological study, 90-min infusions of CPT-11 were administered every 3 weeks at doses ranging from 100 to 345 mg/m2 to patients with solid malignancies. Acute, severe, and refractory vomiting, diarrhea, and/or abdominal cramps associated with flushing, warmth, and diaphoresis occurred in the immediate posttreatment period at the 240-mg/m2 dose level in several patients who were not treated with premedications. The characteristics and temporal nature of these toxicities, the prompt resolution of symptoms following treatment with diphenhydramine, and the successful use of a premedication regimen consisting of ondansetron and diphenhydramine in preventing these acute effects suggest that vasoactive substances are involved in the mediation of these acute toxicities. With the routine use of these premedications, there was no single toxicity type that limited the escalation of CPT-11 doses. Instead, a constellation of severe hematological and gastrointestinal effects precluded the repetitive administration of CPT-11 at doses above 240 mg/m2, the maximum tolerated dose and recommended phase II dose on this schedule. Major responses were observed in patients with advanced colorectal, cervical, and renal cancers. The disposition of total CPT-11 in plasma was fit by a biexponential kinetic model with renal elimination accounting for 37 +/- 4% (SE) of total drug disposition. The Cmax for the active metabolite of CPT-11, 7-ethyl-10-hydroxycamptothecin (SN-38), was achieved at 2.2 +/- 0.1 h after treatment, and mean residence times for both CPT-11 and SN-38 were long, 9.1 and 10.0 h, respectively. Compared with topotecan, another CPT analogue under development, a larger proportion of total drug exposure was accounted for by the active lactone (closed-ring) forms of CPT-11 and SN-38; areas under the time-versus concentration curve for their respective lactone were 44 and 50% of areas under the time-versus-concentration curve for total CPT-11 and SN-38. Although intermittent dosing schedules appear to be superior to single dosing schedules for CPT and some CPT analogues in preclinical tumor models, the maintenance of biologically relevant concentrations of SN-38 for relatively long durations may negate the potential pharmacological benefits of intermittent and continuous administration schedules for CPT-11.(ABSTRACT TRUNCATED AT 400 WORDS)
Cancer Res 1994 Jan 15
PMID:Phase I and pharmacological study of the novel topoisomerase I inhibitor 7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxycamptothecin (CPT-11) administered as a ninety-minute infusion every 3 weeks. 827 79


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