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Biomedical subjects

J Kavanagh

Publications and source records attributed to J Kavanagh.

At least 55 records · Page 3Linked to original sources
PubMed1993

Genetic therapy of human neoplastic disease.

Molecular biology has provided clinical investigators and basic scientists with the tools to identify those changes present within neoplastic hematopoietic and epithelial cells that lead to the evolution of unregulated patterns of cell growth. This information has made possible the development of therapy that involves genetic modification of either the normal hematopoietic cells (for chemoprotection), or the tumor cells themselves to suppress the growth of these cells. This article will summarize the clinical and laboratory data that is evolving in this area.

Animals↗
PubMed1993

Multiple nodules of intermediate trophoblast following hydatidiform moles.

After removal of a complete hydatidiform mole, seven patients developed an unusual complication characterized by a proliferation of intermediate trophoblast-forming nodules in the endometrium or myometrium. The patients were examined because of vaginal bleeding or mildly elevated human chorionic gonadotrophin (HCG) titers. Three patients were cured by hysterectomy, one by endometrial curettage, one by endometrial curettage plus chemotherapy, and one (who also had choriocarcinoma) by multiple doses of chemotherapy after hysterectomy; the seventh patient was lost to follow-up. These nodules probably represent a mild form of postmolar trophoblastic disease.

Adult↗
PubMed1990

Phase I evaluation of thio-TEPA in combination with cisplatin for advanced gynecologic malignancies.

Thirty-five patients with advanced gynecologic malignancies were entered into a phase I study evaluating thio-TEPA in combination with cisplatin (50 mg/m2) intravenously every 4 weeks. Thirty-four patients were evaluable for toxicity and response, and one was evaluable for toxicity only. Median age was 53 years (range 28-72), and performance status less than or equal to 2. Prior treatment included chemotherapy in 21 patients, radiation in 15, hormonal therapy in 3, and immunotherapy in 1. Thio-TEPA was given to three or more patients at each of the following dose levels: 15, 20, 25, 30, 40, 50, and 60 mg/m2. Thio-TEPA's primary toxicity was myelosuppression; at 50 mg/m2, grade 3 or 4 granulocytopenia occurred in 13 of 17 cycles, and grade 3 or 4 thrombocytopenia occurred in 8 of 17 cycles. The maximum tolerated dose (MTD) of thio-TEPA was 40 mg/m2; in 35 cycles at this dose, grade 3 or 4 granulocytopenia occurred in 19, and grade 3 or 4 thrombocytopenia occurred in 10 cycles; median granulocyte nadir was 1100 (range 110 to 3600) and median platelet nadir was 90,000 (range 10,000 to 289,000). Fifteen patients received three or more cycles at one dose level; cumulative myelosuppression was observed in 11. Two cases of partial alopecia occurred at 40 and 60 mg/m2 thio-TEPA. Responses were as follows: complete response, 5; partial response, 7; stable disease, 14; progressive disease, 8. In 16 patients with ovarian cancer (15 of whom had previously received cisplatin), there were 4 complete responses and 5 partial responses (overall response rate of 56%). The thio-TEPA dose recommended in combination with cisplatin (50 mg/m2) in phase II trials is 40 mg/m2. Cumulative hematologic toxicity may occur with this regimen.

Agranulocytosis↗
PubMed1988

Neurologic complications of pelvic intraarterial chemoembolization performed with collagen material and cisplatin.

In three patients neurologic complications developed after chemoembolization procedures were performed with cisplatin and a new collagen material. Three patients with dominant unilateral stage III cervical carcinoma were entered into an investigative protocol attempting to control regional disease and pain with chemoembolization. All three patients had previously undergone surgery, radiation therapy, and intraarterial chemoembolization or chemoinfusion. Each case was complicated by neurologic deficits. A collagen material was administered that acts at a precapillary level and reduces the likelihood of collateral flow. The size of the material enables it to embolize the small feeding vessels of the spinal cord and peripheral nerves. The patients in this study also had predisposing factors to neurologic sequelae including the previous therapy and the contributing neurotoxicity of cisplatin. The neurologic complications in these patients are not easily explained by knowledge of the neurovascular anatomy. Even with meticulous technique, intraarterial chemoembolization of the pelvis with cisplatin and collagen can be complicated by serious neurologic deficits.

Adult↗
PubMed1987

The transport and metabolism of bovine IgM.

IgM is present in cows milk, is able to bind secretory component (SC), has a purported role as a secretory immunoglobulin in other species and has been identified with various antibody functions in cows milk. To determine the origin of cows milk IgM, we administered extrinsic 131I-IgM to lactating cows with cannulated bile and parotid ducts and studied the kinetics of its disappearance from serum and its appearance in milk, bile and parotid saliva for 60 hr post-injection. Pentameric IgM appeared to require a long equilibration time and disappeared from serum with a T1/2 of 40 hr. The transport of IgM into bile also appeared biphasic. Results showed that no 131I-IgM was transported intact into parotid saliva and that most radioactivity in milk and bile after 6 hr was in the form of low mol. wt, TCA-precipitable fragments rather than of the size of a pentamer. During the first 24 hr only 0.83% of the administered dose reached the milk in pentameric form, nevertheless, isotope dilution calculations indicated that nearly all milk IgM was derived from serum. During a 12 hr collection period, corresponding to one milking, greater than 200 mg of serum IgM is secreted in milk. During the first 24 hr, only 0.70% of the administered IgM reached the bile as a pentamer. It was calculated that 50% of the pentameric IgM in bile, 3 hr after administration, was serum-derived. Twenty-five per cent of the IgM appearing in bile and ca 10% of the IgM appearing milk, becomes associated with secretory component. A hypothesis to explain the degradation associated with this inefficient transport mechanism is presented.

Animals↗
PubMed1987

Phase I trial of caracemide using bolus and infusion schedules.

We conducted a phase I trial of caracemide, a new chemotherapeutic agent, which is active in the MX1 (mammary) and CX1 (colon) human tumor xenografts. Using a 5-day bolus schedule, dose-limiting toxicity consisting of burning perioral pain associated with flushing, nasal stuffiness, and excess lacrimation was seen at 650 mg/m2/day. Using a 5-day continuous-infusion schedule, dose-limiting toxicity in the form of changes in affect, lethargy, disorientation, and cognitive dysfunction with electroencephalogram abnormalities was noted at 800 mg/m2/day. The recommended phase II dose levels are 525 mg/m2/day using the 5-day bolus schedule and 650 mg/m2/day using the continuous-infusion schedule. Because of venous pain at the site of infusion, the drug must be delivered via central venous access. The pathophysiology of both the peripheral and central side effects of caracemide may be related to increased cholinergic activity.

Adult↗
PubMed1986

Clinical pharmacology of 4-demethoxydaunorubicin (DMDR).

DMDR, a daunorubicin derivative with a higher therapeutic index and lower cardiotoxicity than either the parent drug or doxorubicin, is active when given PO in experimental animals. We studied its pharmacokinetics in ten patients receiving DMDR IV or PO or IV and PO sequentially at 10-12.5 mg/m2. DMDR and its metabolites were quantified by high-performance liquid chromatography and fluorometry. In nine patients who received DMDR IV the unchanged drug disappeared from the plasma biphasically with a mean terminal half-life of 27.0 +/- 5.5 h, an apparent volume of distribution of 63.9 +/- 12.61 kg-1, and a total clearance of 1.9 +/- 0.41 kg-1 h-1. In 24 h only 5.1% +/- 1.1% of the dose was excreted in the urine. In comparison, in 19 studies the plasma half-life of DMDR given PO was 34.8 +/- 6.7 h, 2.3% +/- 1.3% was excreted in the urine in 24 h, and the maximum plasma drug concentration was reached in about 1 h. The bioavailability of DMDR given PO was about 39% according to comparison of the areas under the plasma DMDR concentration versus time curves for the two routes, but 45% according to comparison of the 24-h cumulative urinary excretion rates. In one patient with severe liver dysfunction following oral administration, the plasma DMDR half-life was 56.8 h, more than twice the average length. By either route, the drug was quickly metabolized to one major metabolite, DMDR-ol. The plasma half-life of DMDR-ol was 72.5 +/- 24.7 h, or 35.7 +/- 7.4 when DMDR was administered IV or PO. In the plasma, DMDR-ol always exceeded DMDR in concentration. Moreover, the 24 h cumulative urinary excretion of DMDR-ol as a percentage of the dose of DMDR administered was 7.8 following IV and 7.4 following PO administration.

Daunorubicin↗
PubMed1986

Phase II study of ifosfamide in cervical cancer.

Thirty patients with symptomatic, progressive squamous cell carcinoma of the uterine cervix no longer amenable to surgery or radiotherapy were entered in a phase II study of ifosfamide (IFX). Patients were treated with IFX (5 g/m2 iv given over 24 hours) and concomitant mesna (total dose, 9.2 g/m2 iv given over 36 hours) every 21 days. One complete response (duration, 10+ months) and nine partial responses were observed, with an overall median response duration of 6.5 months. The median survival of responding patients was 11 months. Objective response rates for lesions arising in previously irradiated sites (four of 22) were significantly lower than for lesions arising in nonirradiated sites (15 of 28) (P = 0.018). There were two treatment-related deaths: one due to leukopenia-associated infection in a patient with peritonitis and severe central nervous system toxicity and one due to central nervous system toxicity without complicating factors. One other patient developed severe but reversible encephalopathy. In all remaining patients hemorrhagic cystitis and hematological and gastrointestinal toxic effects were predictable and manageable. Treatment was delayed for 1 week due to toxicity on seven of 101 occasions: four of these delays were due to mild, reversible impairment of renal function and three were due to leukopenia. Complete though reversible alopecia occurred in 22 of 30 patients. The results indicate that IFX is active in cervical cancer and deserves further study in this setting.

Adult↗
PubMed1986

Domiciliary chemotherapy for malignant disease.

A prospective trial was carried out comparing hospital-based chemotherapy with domiciliary chemotherapy. Fifteen women received cisplatin combination regimens to treat gynecologic cancers. The first course was given in a hospital inpatient setting, and subsequent courses were given to each patient in her domicile. Seventy-four courses were given at home under the direction of a nurse trained to administer chemotherapy. There were no extravasations or anaphylactic reactions. In the period immediately following the at-home administration, no patient required hospitalization for dehydration or for adverse reactions to the chemotherapy. Written interviews with patients and family members were conducted after completion of the course of treatment. No patient wanted to return to the hospital environment. All patients preferred to be treated at home, usually because of the increased privacy, convenience, and lessened anxiety.

Adult↗
PubMed1985

An approach to modifying self-report instruments.

The Rasch model, a simple latent trait model was applied to responses to a 21-item self-report instrument. Items were assigned values reflective of interval scale measurement. To modify the instrument, items below the calibrated mean were eliminated. The proposed revision contains fewer items with known scale values and only those items that are the strongest indicants of the variable in question. The present work suggests that the Rasch and similar models are useful for increasing the measurement properties of self-report instruments.

Adult↗
PubMed1984

Chemotherapy of cervical carcinoma: use of Tc-99m-MAA infusion to predict drug distribution.

Nineteen patients with cervical cancer had infusion of Tc-99m-macroaggregated albumin particles (MAA) via bilateral internal iliac artery catheters to aid in dividing chemotherapeutic dose appropriately between the two catheters. Unequal drug distribution was used to minimize extrapelvic complications (local gluteal burns) by reducing the dose to the side with the greatest gluteal perfusion, or to increase the dose to the tumor regions that showed heightened perfusion. Pulmonary uptake, due primarily to arteriovenous shunting in the tumor bed, was seen in all patients. The authors suggest that bulk reduction of locally advanced cervical carcinoma in patients without prior irradiation may be achieved by intra-arterial chemotherapy with tolerable toxicity.

Antineoplastic Agents↗
PubMed1984

Mycobacterium bovis infection in primates in Dublin Zoo: epidemiological aspects and implications for management.

An outbreak of tuberculosis in non-human primates was successfully contained in the isolation area of Dublin Zoo. A Mayotte lemur, a lion-tailed macaque, a Patas monkey and a Siamang gibbon developed tuberculosis, and Mycobacterium bovis was isolated from all but the lemur, from which lesions were not cultured. Procedures for the prevention of tuberculosis in primate collections and for the management of outbreaks are discussed. The need for typing of the isolated pathogen is emphasized.

Animals↗
PubMed1982

The last epidemic.

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Allied Health Personnel↗