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Biomedical subjects

J Cassidy

Publications and source records attributed to J Cassidy.

At least 163 records · Page 9Linked to original sources
PubMed1991

Comparison of dexamethasone and ondansetron in the prophylaxis of emesis induced by moderately emetogenic chemotherapy.

A multicentre, randomised, double-blind, cross-over trial was done to compare the efficacy and safety of a serotonin receptor antagonist--ondansetron--and dexamethasone in the prophylaxis of acute and delayed emesis and nausea induced by moderately emetogenic non-platinum-containing chemotherapy regimens. Patients were treated as outpatients and received intravenous ondansetron 4 mg or dexamethasone 8 mg before chemotherapy and oral maintenance (ondansetron 4 mg every 6 h and dexamethasone reducing from 4 mg to 1 mg 6-hourly between days 1 and 5) for 5 days. 112 patients were treated (38 men, 73 women, 1 with no gender recorded; age range 30-73 years) and 100 were evaluable for cross-over analysis. Patients taking ondansetron or dexamethasone reported no significant difference in complete and major control of acute (83% vs 79%, p = 0.46) or delayed (82% vs 88%, p = 0.214) emesis (vomiting plus retches). Significantly more patients on dexamethasone (87%) than on ondansetron (72%) reported control of delayed nausea (days 2-5) (p = 0.003). Both drugs were well tolerated with no significant difference in the number of adverse events, and this is reflected by similar patient preference for ondansetron (40%) and dexamethasone (30%) (p = 0.244). Both drugs offer adequate out-patient control of chemotherapy-induced emesis; however, dexamethasone has an advantage in the control of delayed nausea, and also in terms of cost and resource allocation.

Acute Disease↗
PubMed1991

Phase I study of the anthrapyrazole biantrazole: clinical results and pharmacology.

In a phase I study the anthrapyrazole biantrazole (Warner-Lambert Company) was given to 41 patients with tumour refractory to existing therapy. The drug was given i.v. weekly for 3 weeks, with a 3-week interval between courses. At the 1st week a full pharmacokinetic study was performed, and at weeks 2 and 3, blood samples were taken at 1 and 6 h following treatment to check for drug accumulation. Biantrazole pharmacokinetics were linear with respect to the AUC (r = 0.924) over the full range of doses studied (4-36 mg/m2) but exhibited large inter-patient variations at each dose level. Elimination was triphasic, comprising two rapid early phases and a long terminal half-life (mean, 14.1 +/- 7.8 h). There was no evidence of drug accumulation over the 3-week treatment period. Approximately 12% of the parent drug was excreted unchanged in the urine together with two non-circulating, more water-soluble metabolites. Biantrazole was well tolerated but did cause moderate emesis at doses of greater than 18 mg/m2 and mild alopecia. The dose-limiting side effect was leucopenia, with no other major toxicity being observed. One patient developed biventricular failure that was not clearly related to biantrazole administration. On the present schedule, the recommended dose of biantrazole is 24 mg/m2. No response were seen in this patient population.

Adolescent↗
PubMed1991

The importance of added albumin during continuous intravenous infusion of interleukin-2 with alpha-interferon.

We treated 14 patients (4 malignant melanoma/10 renal carcinoma) with a combination of continuous infusion interleukin-2 (IL-2) and subcutaneous alpha-interferon. Variable concentrations of albumin were added to the infusion of IL-2. The toxicity of this regimen seems to be related to the percentage of albumin added to the IL-2 infusion. Partial responses were observed in 3 cases. Interestingly, 1 patient's response appeared dependent on the addition of human serum albumin. The mechanism of these effects is unknown, but the use of albumin with IL-2 should be carefully investigated in future studies.

Adolescent↗
PubMed1991

Phase I and pharmacokinetic study of D-verapamil and doxorubicin.

The calcium antagonist verapamil (a mixture of D- and L-racemers) is a potent modulator of the multi-drug resistance phenotype in vitro at a concentration of 6 microM. Clinical studies have shown dose-limiting toxicity of hypotension and heart block when plasma levels approach the concentrations active in vitro. Previous data indicate that the D-isomer is less cardioactive than the L-isomer but they appear to be equipotent in reversing drug resistance in vitro. In an attempt to increase plasma verapamil concentrations, we have treated ten patients (total of 27 courses) with oral D-verapamil (DVPM), 150-300 mg 6 h, and doxorubicin i.v. 70 mg m2 q 3 weeks. Hypotension (supine systolic BP less than 100 mmHg or a fall in systolic BP of greater than 30 mmHg) occurred in 5/6 patients at 1200 mg day DVPM, in 1/5 at 800 mg day, and in 1/5 at 600 mg day. PQ prolongation (greater than 0.23 s) was demonstrated in 2/5 patients at 800 mg day DVPM. Plasma levels of DVPM and its active metabolite norverapamil were measured and, combining these, levels of 3-4 microM were achieved at 1200 mg day DVPM; however this dose is likely to lead to unacceptable toxicity in the outpatient setting. Using an oral outpatient schedule of administration, an appropriate dose of DVPM is 800 mg day. This provides a combined plasma level (for VPM and DVPM) of 2-3 microM. If DVPM is to prove useful as a resistance modulator, it may require to be administered intravenously with careful inpatient monitoring and support.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1991

Synthetic polymers conjugated to monoclonal antibodies: vehicles for tumour-targeted drug delivery.

(N-(2-Hydroxypropyl)methacrylamide (HPMA)) copolymers have seen extensive development as sophisticated lysosomotropic drug carriers. They can be used for site-specific drug delivery by incorporation of appropriate targeting groups and here we report their conjugation to antitumour monoclonal antibodies (the murine IgG, antibody B72.3 and its Fab' and Fab'2 fragments) and assessment as vehicles for tumour-specific drug delivery. Conjugates were synthesised containing an average 5 copolymer units (Mw 20kD) per antibody molecule. Kinetics of elimination and body distribution of radiolabelled conjugates in mice were substantially modified compared with native antibody and fragments, showing prolonged circulation in the bloodstream. Notably, the half-time for bloodclearance of the Fab' fragment (35min) was extended ten-fold following conjugation (6h). The conjugates provoked only a low immune response in A/J mice, following three injections in adjuvant (IgG titre-1 less than 100), and were resistant (up to 50%) to proteolytic degradation by preparations of rat liver lysosomal enzymes. The parent antibody targeted efficiently to human colorectal carcinoma (LS174T) xenografts in nude mice (up to 25%/g); the conjugates, however, showed no tumour-targeting, probably due to masking by polymer chains (which are attached by non-specific aminolysis). Conjugates designed to maintain immunoreactivity following linkage through oxidised carbohydrates are currently being synthesised. Nevertheless, the conjugates display increased rates of extravasation, compared with proteins of the same hydrodynamic size, and the decreased charge is anticipated to accelerate diffusion through tumour interstitium.

Acrylamides↗
PubMed1991

Successive Salmonella give and Salmonella typhi infections, laboratory-acquired.

A case of laboratory-acquired typhoid fever is described. The case was complicated by a self-limiting Salmonella give gastroenteritis which may also have been laboratory-acquired and which occurred during the incubation period of the Salmonella typhi infection. The symptoms of typhoid were not sufficiently severe for the patient to seek medical attention and she was recovering from the infection when the typhoid bacillus was isolated from her stools. The mode of transmission of the S. typhi was presumed to be a laboratory infection from an unknown source. Although there was no obvious breakdown in safe laboratory techniques, the infecting dose of S. typhi is known to be small and the dangers of handling specimens which may contain this bacterium are emphasized.

Adult↗
PubMed1991

The role of the nurse in clinical cancer research.

Although advances have been made in the treatment of a number of cancers, no standard effective treatment exists for many forms of the disease. To answer remaining questions about cancer therapy, patients are encouraged to enter clinical trials that test new therapies or combinations of therapies. These trials take place not only in cancer centers and large university hospitals, but also in community hospitals and private offices throughout the country. The nurse can be an active participant in these trials as both the patient advocate and the liaison between the patient and the physician or the nurse researcher responsible for conducting the clinical investigation. Each protocol contains specific guidelines that include eligibility requirements, detailed treatment regimens, patient evaluations, and data collection schedules. The regulatory issues or Institutional Review Board (IRB) approval, informed consent, toxicity reporting, and maintenance of accurate records for investigational drug accountability are also part of the research process. A nurse who is well informed on these issues is an asset to the successful completion of any clinical study.

Clinical Protocols↗
PubMed1990

Phase I and pharmacokinetic study of intraperitoneal thioTEPA in patients with ovarian cancer.

A total of 15 patients with residual ovarian cancer confined to the peritoneal cavity after first-line systemic chemotherapy were treated with triethylene-thiophosphoramide (thioTEPA) in a phase I study. A total of 50 courses of thioTEPA were given intraperitoneally in doses ranging from 30 to 80 mg/m2. The dose limiting toxicity was myelosuppression, which occurred at 80 mg/m2 and was frequently prolonged. Short-lived nausea and vomiting was easily controlled, and there was no local toxicity. Three patients remain free of disease progression at 6, 6 and 12 months. ThioTEPA concentrations were measured by gas chromatography. Peritoneal fluid concentrations declined rapidly in a first-order fashion, with a half-life of 0.96 +/- 0.1 h. A mean of 93% of the drug was absorbed during the 4-h dwell time. Peak plasma levels were achieved 30-60 min after drug instillation and were substantially lower than corresponding peritoneal levels. A pharmacokinetic advantage for intraperitoneal delivery was detected for peak drug concentration (24.9 +/- 8.5) and AUC (9.2 +/- 4.8). Based on this study, the recommended dose for intraperitoneal thioTEPA is 60 mg/m2 every 3-4 weeks. However, the rapid absorption of this drug from the peritoneum, secondary to thioTEPA's small molecular weight and lipophilic nature, suggests that it has only a limited role in intraperitoneal therapy.

Adult↗
PubMed1990

Suramin-induced polyneuropathy.

We report the development of a severe polyneuropathy in 4 of 38 patients who were receiving parenteral suramin therapy for the treatment of various underlying malignancies. In 2 of these patients, the neuropathy progressed to generalized flaccid paralysis with bulbar and respiratory involvement, requiring endotracheal intubation and ICU monitoring. EMG and nerve conduction studies showed evidence of conduction block, suggestive of a demyelinating polyneuropathy. After several weeks, both patients improved clinically. The other 2 patients developed a reversible neuropathy with flaccid paresis of the limbs but without bulbar or respiratory compromise. No immediate response to plasmapheresis was noted. All 4 patients demonstrated an elevated CSF protein in the acute phase of their neuropathy, which declined or returned to normal during recovery. The development of polyneuropathy correlated with the maximum plasma suramin level, with an estimated 40% risk of developing neurotoxicity in those patients whose maximum level was 350 micrograms/ml or greater. No correlation could be made with the total dose of suramin administered or with the duration of therapy. Two of these 4 patients manifested tumor shrinkage while receiving suramin therapy. We conclude that suramin, a promising antineoplastic agent, is capable of inducing a severe sensorimotor polyneuropathy which appears to be related to the plasma concentration of suramin. Serial measurement of the plasma concentration during suramin therapy is recommended.

Adult↗