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Biomedical subjects

I Judson

Publications and source records attributed to I Judson.

64 records · Page 4Linked to original sources
PubMed1993

2'-Chlorodeoxyadenosine: evaluation of a novel predominantly lymphocyte selective agent in lymphoid malignancies.

2'-Chlorodeoxyadenosine (2CDA) is a purine analogue selectively active against both resting and dividing lymphoid cells. Twenty-one patients with a variety of previously treated lymphoid malignancies received a total of 41 courses of 2CDA (0.1-0.15 mg/kg/day over 7 days continuous intravenous infusion) on compassionate grounds. The profile of the patient population was as follows: low grade non-Hodgkin's lymphoma (NHL) = 8, intermediate grade NHL = 2, transformed (intermediate grade NHL) = 6, Hodgkin's disease = 1, lymphoplasmacytoid NHL = 3 and lymphoblastic NHL = 1. The overall response rate was 53%, with three patients attaining complete remission (CR) and eight partial remission (PR). Three of 16 patients with primary resistant or resistant recurrent disease entered either CR (1) or PR (2). Ten patients had no response or progressive disease. The latter group was comprised of patients who had extensively pre-treated lymphoplasmacytoid tumours and/or poor performance status (WHO grades 2-4). The median duration of response is 6 months (range 1 to 12 months). Treatment was well tolerated and the chief toxicities were leucopenia and thrombocytopenia which were most pronounced when there was bone marrow involvement. As a result of dose limiting myelotoxicity, a dose escalation to 0.15 mg/kg/day was possible on just three occasions. These data confirm other reports of the activity of 2CDA in low grade NHL and indicate it may have activity in Hodgkin's disease. There was no demonstrable activity in poor performance status patients or those with extensively pre-treated lymphoplasmacytoid tumours.

Adult↗
PubMed1993

Platinum complexes in cancer medicine: pharmacokinetics and pharmacodynamics in relation to toxicity and therapeutic activity.

The study of the pharmacokinetics and pharmacodynamics of platinum based anti-cancer drugs has done much to direct their development, at both preclinical and clinical levels. The clinical development of cisplatin depended on an understanding of its mechanism of action. The amelioration of the renal toxicity of cisplatin with sodium chloride infusion and forced diuresis is thought to rely on a common ion effect to suppress the formation of aquated species in the renal tubule. Studies of the modulation of cisplatin toxicity with other agents have followed, although none has yet achieved widespread acceptance. Following the demonstration of the important clinical role for cisplatin, studies of the relationship between toxicity and the reactivity of the leaving groups led to the development of the less toxic but equally effective analogue, carboplatin. The clinical development of carboplatin has in turn been strongly influenced by the studies of its pharmacokinetics, with pharmacokinetically guided dosing now being standard in many cancer centres and also being widely used in current clinical trials. Pharmacokinetic studies in animals have demonstrated that it is possible to make analogues that have good oral bioavailability. Apart from the convenience of oral administration, there is also the suggestion that these molecules may possess activity against certain cisplatin resistant cell lines. For the future, the development of sensitive methodologies whereby the exact types of platinum-DNA adducts formed can be characterized may allow the reason for the remarkable anti-tumour activity of these complexes to be elucidated and further, more selective compounds to be designed. The history of the development of platinum compounds emphasizes the importance of performing intensive pharmacokinetic, pharmacodynamic and mechanistic studies in concert with the clinical development of any class of agents.

Antineoplastic Agents↗
PubMed1992

High-dose busulfan in patients with myeloma.

PURPOSE: To evaluate the use of high-dose busulfan (HDB) with autologous bone marrow transplantation (ABMT) in patients with myeloma. PATIENTS AND METHODS: Fifteen patients received HDB (16 mg/kg), eight of whom received high-dose melphalan (HDM) but had experienced a short remission or progression-free interval. Two patients had received HDM on two previous occasions, one had no response to low-dose melphalan, and four had impaired renal function (edathamil clearance < 40 mL/min). All patients received induction chemotherapy before HDB. RESULTS: Two patients were in complete remission (CR) after induction chemotherapy before HDB. Of the remaining 13 patients, four (31%) achieved CR and two (15%) achieved a partial remission for an overall response rate of 46%. There were three treatment-related deaths, but the toxicity was otherwise predictable and manageable. CONCLUSIONS: In heavily pretreated patients, HDB results in a relatively high response rate. It can also be used safely in patients with renal impairment who are not suitable for HDM.

Adult↗
PubMed1991

Anthrapyrazole CI941: a highly active new agent in the treatment of advanced breast cancer.

Thirty-one patients with advanced breast cancer were treated with CI941, an anthrapyrazole structurally related to mitoxantrone. Patients had not previously been treated with anthracyclines or mitoxantrone, and 15 patients had not received any previous cytotoxic chemotherapy. CI941 was given at a dose of 50 mg/m2 by intravenous bolus injection every 21 days. Thirty patients were assessable for response, and all were assessable for toxicity. Two patients (7%) had complete responses (CRs), and 17 (56%) achieved partial responses (PRs; overall response rate, 63%; 95% confidence interval, 46% to 81%). The response rates in patients with and without prior chemotherapy were 63% and 64%, respectively. The median response duration was 37 weeks from start of treatment, with a maximum response duration of greater than 70 weeks. Median survival has not yet been reached. Leukopenia was the most frequently encountered toxicity, with a World Health Organization (WHO) grade greater than 3 occurring in 74% of courses. Thrombocytopenia and anemia were negligible. Only 10 patients (32%) had alopecia severe enough to wear a wig. There were no cardiac symptoms or events in any patient, but a slight median fall in left ventricular ejection fraction (LVEF) of 6% (from +7 to -12) during stress and 6% (from +14 to -14) at rest occurred. Other toxicities were mild, and the drug was generally well tolerated. CI941 is a very active and well-tolerated new agent in the treatment of advanced breast cancer, with neutropenia being the main toxicity.

Adult↗
PubMed1990

How many tests are required in the diagnosis of palpable breast abnormalities?

Palpable breast nodules in 143 patients attending our primary diagnosis breast clinics were assessed by clinical examination, needle cytology, mammography, ultrasonography and magnetic resonance imaging (MRI). The diagnostic accuracy of all test combinations was compared with the final diagnosis of malignant or benign disease. Two-test combinations increased the sensitivity of diagnosis over that of the individual tests to between 93% and 100% except for MRI/mammography and MRI/cytology. The combinations of three or more tests increased the sensitivity further, but at the expense of an increased false-positive rate. MRI does not appear to have an important role in the primary diagnosis of breast cancer. Mammography is necessary because of the possibility of occult or multifocal disease. Clinical examination was associated with a high false-positive rate. The combination of cytology and ultrasound was best at correctly diagnosing malignancy, but in this series only 42% of patients underwent ultrasound examination. The role of breast ultrasound together with needle aspiration cytology for the diagnosis of malignancy in palpable breast nodules deserves further evaluation.

Adult↗
PubMed1990

The value of computed tomographic (CT) scan surveillance in the detection and management of brain metastases in patients with small cell lung cancer.

One hundred and twenty-seven consecutive patients presenting with small cell lung cancer were entered into a whole-brain CT scan surveillance study, starting at presentation and repeating at 3-monthly intervals for 2 years as an alternative to prophylactic cranial irradiation (PCI). The aim of the study was to detect CNS metastases at an early asymptomatic stage in the hope that prompt CNS radiotherapy could achieve long-term control; at the same time unnecessary PCI with its potential long-term morbidity could be avoided. CNS metastases were found in 56 patients (44%) including 16 (13%) at diagnosis and 40 at a median of 4 months (range 1-27 months) after completing chemotherapy. No patient developed CNS disease while on chemotherapy. Thirty-six patients were asymptomatic at diagnosis (group A) but 20 developed clinical CNS relapse between scans (group B) (interval relapse). Despite prompt radiotherapy 56% of patients in group A and 60% of patients in group B died with active CNS disease. Likewise, there was no survival difference between patients in group A, group B or those who never developed CNS disease. Regular 3-month CT scan surveillance is therefore not an effective substitute for PCI.

Brain Neoplasms↗
PubMed1990

Mussel culture and the accumulation of domoic acid.

The cultured mussel industry of Prince Edward Island had never experienced a toxic disease problem until November of 1987. With the successful use of the long-line culture system, the yearly production of fresh mussels to the gourmet food market had risen to close to 3.2 million pounds (1.46 million kg) of product. The physiology of this sessile bivalve and its method of feeding and location in the estuary leave it prone to the accumulation of a widely distributed biotoxin. Eastern Prince Edward Island became the epicentre of domoic acid-intoxicated mussels as early as 10 November 1987 (retrospective samples) during an intense bloom of the diatom Nitzschia. Mussels were able to accumulate large amounts of the domoic acid with little effect on their own well-being. Despite being in low water temperatures (below 4 degrees C) and under thick ice cover, the levels of the toxin decreased and were undetectable in about 6 weeks. The following year the toxin was detected in much smaller amounts, and the levels of toxin accumulation demonstrated a variable lag time with the increase in concentration of Nitzschia available in the water column. The sales of Prince Edward Island cultured mussels have rebounded to about 140% of the pre-domoic acid crisis.

Animals↗