Nursing guidelines and discharge planning for patients receiving recombinant interleukin-2.
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Cardiovascular Diseases↗
Biomedical subjects
G Caliendo
Publications and source records attributed to G Caliendo.
New drugs on the horizon.
The agents covered in this article are useful in a wide range of illnesses, including infections, cancers, cardiovascular and gastrointestinal diseases, and others. One of the major forces driving the development of new drugs is the use of biotechnology. Biotechnology encompasses the techniques of recombinant DNA and monoclonal antibody technologies to produce protein drugs that have not been previously available in sufficiently pure form or in adequate quantities. As new drugs are developed, the authors hope that intensified efforts will be geared towards the development of unique drugs that offer important therapeutic gains.
Acquired Immunodeficiency Syndrome↗
Colonic ischemia complicating immunotherapy with interleukin-2 and interferon-alpha.
Colonic ischemia (CI) is a rare complication of high-dose interleukin-2 (IL-2) immunotherapy. This complication occurred in three of 141 patients (2.1%) with metastatic cancer treated with high-dose IL-2 therapy; CI only developed in patients receiving interferon-alpha (IFN) with IL-2 (three of 21, 14%) compared with none of 120 in those patients receiving IL-2 alone (P equals 0.0009). Severe diarrhea (greater than or equal to 7 bowel movements/day) also was significantly more common in patients receiving IFN with IL-2 (six of 21, 29%) than in those receiving IL-2 alone (three of 120, 2.5%, P equals 0.001) and preceded the clinical diagnosis of CI in all three patients. Three of nine patients with severe diarrhea had CI. Hematochezia occurred in four patients, all of whom received IFN with IL-2; three had CI, and the other patient had nonspecific colitis. Differences in vasopressor use did not explain the increased risk of CI in patients receiving IFN; those receiving IFN with IL-2 required phenylephrine less often than patients receiving IL-2 alone (P equals 0.01). The administration of lymphokine-activated killer (LAK) cells had no significant effect on the incidence of CI, severe diarrhea, peritonitis, or vasopressor use; two of three patients with CI, however, had their ischemic episode within 24 hours after the last of three LAK cell infusions. In conclusion, CI is an unusual complication of high-dose IL-2 and IFN immunotherapy. In patients receiving such combination therapy, severe diarrhea is a risk factor for the subsequent occurrence of CI.
Carcinoma, Renal Cell↗
Perfusion of rat colon with sennosides, rhein and rheinanthrone. Concentration-related histamine release.
Rat colon perfused intraluminally in vitro and in vivo released histamine into the perfusates. Histamine release was increased by rhein 0.1-10 micrograms/ml and much more by rheinanthrone 0.1-10 micrograms/ml but not by sennosides A or B 1-10 micrograms/ml. The effect of rhein and rheinanthrone was reduced by tritoqualine 20 mg/kg. This raises the possibility that laxation by senna and its derivatives involves histamine formation.
Animals↗
Relationships between octanol-water partition data, chromatographic indices and their dependence on pH in a set of beta-adrenoceptor blocking agents.
A thorough investigation on the dependence of octanol/water distribution coefficients (log D) of basic and amphiprotic beta-blocker drugs on pH and pKa values has been carried out. An attempt is made to clarify the factors which govern the chromatographic parameters (log k') in reversed-phase high performance liquid chromatography (RPLC) in terms of chemical structure and of distribution coefficients. The correlations between log D and log k' of different compounds show that the bulkiness and the branching of nitrogen substituent are controlling factors in RPLC measurements. Finally, an ion pair chromatographic system is considered for the prediction of octanol/water partition coefficients.
Adrenergic beta-Antagonists↗
On the use of 1H-NMR and 13C-NMR chemical shifts in a QSAR of benzotriazole derivatives.
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Carbon Isotopes↗
Using computer databases to predict and avoid drug-drug interactions in the cancer patient requiring psychotropics.
Psychotropic drug interactions with medical prescriptions is an essential knowledge base for the practicing oncologist as well as the psychiatrist. This paper describes a method to identify, understand, and develop a conceptual framework to codify psychotropic-medical drug interactions; a systemic approach for updating this key database, and a software system to assist in the management of this ever unfolding sphere of knowledge; and, a set of instruments to provide ongoing developments in this important area. Since many of the trials either for oncological medications or psychotropic drugs did not include studies comparing these two domains, their interactions often only become known with their utilization and subsequent reporting.
Adverse Drug Reaction Reporting Systems↗
Phase II trial of merbarone in patients with malignant brain tumors.
The standard treatment for patients with primary malignant glioma includes surgical resection, radiotherapy, and nitrosourea. Despite this multimodality approach, adults with newly diagnosed glioblastoma multiforme (GBM) and high-grade astrocytoma have a median survival duration of 50 weeks and 150 weeks respectively. Chemotherapy has had a limited impact on the survival of these patients. Merbarone (5-phenylcarboxamide-2-thiobarbituric acid) is a nonsedating derivative of barbituric acid that crosses the blood brain barrier. Antitumor activity of merbarone has been described against L1210, B16 melanoma cell line and the M5076 sarcoma cells in phase I studies. Merbarone inhibits DNA synthesis and tumor growth by inducing single strand breaks in DNA. It also inhibits RNA and protein synthesis. We evaluated merbarone in a phase II trial in patients (pts) with recurrent or refractory GBM (7 pts) and high grade anaplastic astrocytoma (7 pts). Fourteen patients (nine males, five females) were treated with merbarone at a dose of 1000 mg per m2 per day by continuous intravenous infusion for 5 days every 3 weeks. Every patient received at least two cycles of treatment. No complete or partial responses were observed, although one patient had stable disease lasting 20 weeks. Our conclusion is that merbarone is ineffective against GBM and high-grade anaplastic astrocytoma at the dose and schedule in which it was administered in this trial.
Adult↗
Synthesis and biological activity of pseudopeptides inhibitors of Ras farnesyl transferase containing unconventional amino acids.
A study was performed on the structure-activity relationships of a series of phenol derivatives, CVFM analogs, derived from the two most active compounds of a first series (1A and 1B) of inhibitors of Ras farnesyl transferase (FTase) that we have recently described. We report the synthesis and the activity of a second series of compounds in which the phenylalanine residue was replaced by unconventional aromatic and non-aromatic amino acids, with varying electronic, lipophilic, steric and conformational properties. The compounds showed to be significantly less active than reference compounds against FT, with the only exception of derivative 3A (IC50 = 3 microM), which is slightly more active than 1A but not 1B. Subsequently we tested the effects of compounds 1A, 1B and 3A, 3B on the anchorage-dependent growth of two epithelial cell lines of rats, FRTL-5 and the same line v-Ha-ras transformed. Compound 3A derived from lead compound 1A, showed an appreciable selectivity against transformed cells. In contrast, compounds derived from derivative 1B had only a modest cellular activity.
Alkyl and Aryl Transferases↗
Cardiac drug and psychotropic drug interactions: significance and recommendations.
Understanding cardiac drug interactions with concurrent psychotropic prescriptions is essential for the practicing cardiologist and primary care physician, as well as for the psychiatrist. There has been an explosive use of new drugs in both psychiatry and cardiology without widespread knowledge of their potential interactions. The increasing tendency toward poly-pharmacy, the use of psychotropic medications by cardiologists and primary care physicians caring for cardiac patients, and the growth of the aging population present major challenges for the practitioner. Finally, there is a need to have models/paradigms for predicting potential drug interactions--e.g., the Cytochrome p450 schema. This paper describes a method to identify, understand, and codify the interactions between psychotropic and cardiac drugs, a systematic approach for updating this key database and specific cardiac-psychotropic drug interactions. Specifically, this paper 1) details the interactions, 2) addresses the level of their clinical significance, 3) describes the potential mechanism(s) of the interactions, and 4) offers recommendations to the clinician. Since the majority of the original clinical trials, either for cardiac medications or psychotropic drugs, do not include studies comparing these two drug domains contemporaneously, their interactions often become known only with their combined use in the clinical arena, using the patient as "guinea pig," and through subsequent reporting.
Cardiovascular Agents↗
Synthesis and structure-activity of antisense peptides corresponding to the region for CaM-binding domain of the inducible nitric oxide synthase.
Nitric oxide synthase (NOS) catalyses the conversion of L-arginine to nitric oxide (NO) which plays an important role in the regulation of cellular functions and intracellular communications. Three distinct isoforms of NOS have so far been identified, two constitutive and one inducible. All three mammalian isoforms of NOS contain putative CaM-binding domains with the canonical composition. In this paper we report the synthesis and the inhibitory activity on rat neuronal and lung inducible NOS of antisense peptides corresponding to the antisense strand read in 3' to 5' (CALM 1) or 5' to 3' (CALM 2) direction of the region encoding for the CaM-binding domain of the inducible NOS isoform (residues 503-522). CALM 1 inhibited, at all the concentrations tested (0.01-1 mM), both the inducible and constitutive NOS (IC(50) 98 microM and 56 microM, respectively), while CALM 2 (0.01-1 mM) was ineffective on both isoforms. The acetylation of CALM 1 at its amino terminal (CALM 8) completely abolished its inhibitory activity. We also synthesized and analysed the activity of amino terminal truncated analogues (CALM 3-7) of CALM 1, which selectively inhibited the inducible isoform, although less potently than the parent compound. The pentapeptides (CALM A-D) deriving from the cleavage of CALM 1 were ineffective, except the pentapeptide CALM C corresponding to the residues 513-517, which was as potent as the parent compound (IC(50) 65 microM).
Amino Acid Sequence↗
Cardiac drug and psychotropic drug interactions: significance and recommendations.
Understanding cardiac drug interactions with concurrent psychotropic prescriptions is essential for the practicing cardiologist, primary care physician, and psychiatrist. There has been an explosion in the use of new drugs in both psychiatry and cardiology without widespread knowledge of their potential interactions. The increasing tendency toward polypharmacy, the use of psychotropic medications by cardiologists and primary care physicians caring for cardiac patients, and the growth of the aging population present major challenges for the practitioner. Finally, there is a need to have models and paradigms for predicting potential drug interactions-the cytochrome P450 schema. This article describes a method to identify, understand, and codify the interactions between psychotropic and cardiac drugs, a systematic approach for updating this key database, and specific cardiac-psychotropic drug interactions. Specifically, this paper 1) details the interactions, 2) addresses the level of their clinical significance, 3) describes the potential mechanism(s) of the interactions, and 4) offers recommendations to the clinician (Appendix). Because the majority of the original clinical trials, either for cardiac medications or for psychotropic drugs, did not include studies comparing these two drug domains contemporaneously, their interactions often become known only with their combined use in the clinical arena, using the patient as "guinea pig" and through subsequent reporting.
Animals↗
Synthesis by microwave irradiation and binding properties of novel 5-HT(1A) receptor ligands.
This work reports the synthesis by microwave irradiation and the binding tests on the 5-HT(1A), 5-HT(2A) and 5-HT(2C) receptors of new substituted piperazines in order to identify selective ligands for 5-HT(1A) subtype receptor. Conventional heating and microwave irradiation of the reactions was compared. Synthesis by microwave irradiation gave the desired compounds in better yields than those obtained by conventional heating. The overall times for the syntheses were considerably reduced. Some resulting active compounds (29 and 39) were characterised by a good selectivity profile for the 5-HT(1A) subtype receptor. The more active compounds were selected and further evaluated for their binding affinities on D(1), D(2) dopaminergic and alpha(1), alpha(2) adrenergic receptors. The compound with higher affinity and selectivity for the 5-HT(1A) over all the considered receptors was the 3-[4-[4-(1,2,3,4-tetrahydronaphthyl)-1-piperazinyl]butan]-benzotriazinone (-)29 (5-HT(1A) K(i)=36 nM, other receptors not active).
Animals↗
Outpatient subcutaneous interleukin-2 and interferon-alpha for metastatic renal cell cancer: five-year follow-up of the Cytokine Working Group Study.
PURPOSE: A phase II trial of outpatient subcutaneous (SC) interleukin-2 (rIL-2) plus interferon-alpha (IFN-alpha 2B) was performed in patients with metastatic renal cell cancer. A 5-year follow-up of that Cytokine Working Group study is presented. PATIENTS AND METHODS: Forty-seven patients meeting eligibility criteria of previous Cytokine Working Group studies were treated on an outpatient basis with SC rIL-2 (Chiron, Emeryville, CA), 5 x 10(6) IU/m2/dose q 8 hr x 3, then daily, 5 days per week, and IFN-alpha 2B (Schering-Plough, Kenilworth, NJ), 5 x 10(6) IU/m2/dose three times weekly for 4 weeks. After a 2- to 4-week break, patients were scheduled to continue treatment for up to six cycles. RESULTS: There were two complete and six partial responders (17% response rate, 95% CI: 8%-31%). Median duration of response was 12 months (range 1-49+ months), with complete responses of 15 and 49+ months. Responding sites of disease included lung, nodes, soft tissue, bone, and liver. Dose and schedule were adjusted to control toxicity at grade 2/3 levels, with 50% requiring dosage alterations. Grade 2/3 toxicity included fatigue, nausea/vomiting, diarrhea, anorexia, fluid overload, rash, CNS, injection site pain, chest pain/palpitations (including atrial fibrillation requiring treatment, two patients), and hypotension. Grade 4 toxicity included dehydration (seven patients), vomiting (one patient), and irreversible renal failure with crescentic glomerulonephritis requiring dialysis (one patient). CONCLUSION: SC rIL-2 plus IFN-a2B is tolerated in the outpatient setting with frequent dose adjustments. The overall response rate of this regimen is similar to that seen with high-dose rIL-2 alone; however, the response duration appears to be shorter.
Adult↗