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Biomedical subjects

D Cunningham

Publications and source records attributed to D Cunningham.

At least 37 records · Page 2Linked to original sources
PubMed1991

Phase I immunotoxin trial in patients with B-cell lymphoma.

Fifteen patients with refractory B-cell lymphoma were treated in a Phase I dose escalation clinical trial with a highly potent immunotoxin consisting of the Fab' fragment of a monoclonal anti-CD22 antibody (RFB4) coupled to chemically deglycosylated ricin A chain. All patients had low, intermediate, or high grade non-Hodgkin's lymphoma. The immunotoxin was administered i.v. in two to six doses at 48-h intervals. The peak serum concentration and the t1/2 were not dose dependent among patients and averaged 1.3 micrograms/ml and 86 min, respectively. Three patients made antibody against A chain, and a fourth made antibody against both A chain and mouse immunoglobulin. Antibody responses were low (less than or equal to 85 micrograms/ml) in three patients and were not detected until 1 mo after treatment. The maximum tolerated dose of the immunotoxin was 75 mg/m2. Dose-related toxicities included vascular leak syndrome, fever, anorexia, and myalgia. Dose-limiting toxicities included pulmonary edema and/or effusion, expressive aphasia, and rhabdomyolysis (resulting in reversible kidney failure). There was no evidence of liver dysfunction. Partial responses were achieved in 38% of evaluable patients, and in those patients who had greater than 50% CD22+ tumor cells, 50% of the patients achieved a partial response. Clinical responses were not related to tumor grade and were generally transient, lasting between 1 and 4 mo.

Adult↗
PubMed1991

Mutation in the gene encoding the alpha chain of platelet glycoprotein Ib in platelet-type von Willebrand disease.

Platelet-type von Willebrand disease (PT-vWD) is an autosomal dominant bleeding disorder characterized by abnormally enhanced binding of von Willebrand factor (vWF) by patient platelets. Although the platelet glycoprotein (GP) Ib/IX complex is known to constitute the platelet's ristocetin-dependent receptor for vWF, a unique structural abnormality within this complex has not previously been identified in PT-vWD. Using the polymerase chain reaction to amplify genomic DNA coding for the alpha chain of GP Ib (GP Ib alpha) and then sequencing the amplified DNA following cloning into M13mp18 and M13mp19 phage vectors, we have found a single point mutation in the GP Ib alpha coding region of PT-vWD DNA resulting in the substitution of valine for glycine at residue 233. This substitution within the vWF-binding region of GP Ib alpha is likely to exert a significant influence on the conformation of the resulting protein. Competitive oligonucleotide primer assay for this mutation showed a homozygous wild-type pattern in genomic DNA from the 161 normal volunteers studied and from 6 phenotypically normal members of a PT-vWD family. All 7 affected members of this family studied were heterozygous for the mutant allele. Platelet GP Ib alpha mRNA reverse-transcribed and studied by competitive oligonucleotide primer assay showed similar expression of the mutant and wild-type alleles in the affected PT-vWD patients. Absence in the normal population, tight linkage with phenotypic expression of disease, and absence of any additional abnormality of GP Ib alpha in these patients identify the glycine-to-valine substitution as a point mutation underlying functional abnormality of the vWF receptor in PT-vWD.

Alleles↗
PubMed1991

High-energy catheter ablation of cardiac arrhythmias: an outmoded technique in the 1990s.

Catheter ablation has become an accepted technique for creating complete heart block in patients with drug refractory supraventricular tachycardias. However, it remains experimental for other indications, such as ablation of accessory pathway or ventricular tachycardia. The use of high energy defibrillator discharges is associated with adverse effects which greatly contribute to the limitations of the technique. Advances in technology have led to newer methods, such as radiofrequency and low energy capacitive discharge, which hold significant advantages over the conventional high energy technique, to the extent that the use of defibrillator discharges should now be considered outmoded and potentially damaging. Radiofrequency is the technique of choice for accessory pathway ablation and modification of AV conduction, and low energy capacitive discharge is the preferred method for creation of complete heart block. There are currently no acceptably safe and efficacious catheter techniques for treating ventricular tachycardia, and more research needs to be done in this area. The potential for the success of these techniques depends to an extent on the creation of new standards of practice for catheter ablation. There has been no unbiased comparative assessment of the different techniques, and consequently no consensus exists on the preferred technique and technologies which should be used. Only within the framework of these standards can the technique achieve significant clinical utility.

Arrhythmias, Cardiac↗
PubMed1991

Prothrombin mRNA is expressed by cells of the nervous system.

Thrombin, a serine protease of the blood coagulation system, has additional effects on cells in vitro. It is mitogenic for fibroblasts and astrocytes and contributes to the regulation of neurite outgrowth and astrocyte stellation. Until now the expression of thrombin or its precursor prothrombin in tissues other than liver has not been demonstrated conclusively because of difficulty in avoiding serum contamination. Using sensitive mRNA detection methods, we show here that prothrombin is expressed not only in the liver, but also in the brain throughout development. Polymerase chain reaction, Northern, and in situ hybridization studies demonstrate the presence of prothrombin transcripts in the olfactory bulb, the cortex, the cerebellum, and other regions of the rat and human nervous system, as well as in neural cell lines. These results support an involvement of (pro)thrombin in the regulation of cellular events in the nervous system.

Animals↗
PubMed1991

Alfacalcidol is a nontoxic, effective treatment of follicular small-cleaved cell lymphoma.

Thirty-four patients with progressive low grade non-Hodgkin's lymphoma were treated with 1 microgram oral alfacalcidol daily. Complete response was seen in four patients and a partial response in four patients with an overall response rate of 24%. Median duration of response was 14 months. Disease stabilised in ten other patients (29%) and 16 patients (47%) had tumour progression. In the sub-group of patients with follicular, small-cleaved cell-lymphoma the overall response to treatment was 29%. Apart from one patient who had a mild transitory elevation of serum calcium there was no recorded toxicity from alfacidol. These results indicate that alfacalcidol has significant antitumour activity in patients with low grade non-Hodgkin's lymphoma of the follicular, small-cleaved cell type.

Calcitriol↗
PubMed1991

Molecular monitoring of low grade non-Hodgkin's lymphoma by gene amplification.

Molecular monitoring by the polymerase chain reaction was used to detect and follow minimal disease in working formulation category B and C on non-Hodgkin's lymphoma. Rearrangement of the bcl-2 gene served as the target for gene amplification. Thirty patients were studied. Bone marrow histology was compared to PCR analysis of bone marrow aspirate and blood. PCR upstaged disease status in approximately 50% of patients. Results are shown from a patient whose disease was followed with PCR during chemotherapy from initial remission to relapse. We conclude that PCR of bone marrow and blood can be used to upstage disease status in low grade lymphoma and PCR of blood may be used to monitor response to treatment with obvious patient benefit. The general approach of molecular monitoring provides a means for appraising therapies in the setting of subclinical disease.

Base Sequence↗
PubMed1991

Low energy catheter ablation of a posteroseptal accessory pathway associated with a diverticulum of the coronary sinus.

A 23-year-old man was resuscitated from ventricular fibrillation and subsequently shown to have the Wolff-Parkinson-White syndrome. Electrophysiological study demonstrated a posteroseptal accessory pathway, and coronary sinus angiography demonstrated that this was associated with a diverticulum of the coronary sinus. Catheter ablation was performed using a new low energy system. Five shocks were delivered within the coronary sinus diverticulum, with a cumulative energy of 39 joules (J). Accessory pathway conduction was blocked successfully, and there were no complications.

Adult↗
PubMed1991

Low energy catheter ablation of right ventricular outflow tract tachycardia.

A 38 year old woman with a structurally normal heart presented with near syncope and had right ventricular outflow tract tachycardia. She was intolerant of antiarrhythmic medication and underwent low energy catheter ablation. Six non-arcing shocks of 25 J were delivered to the right ventricular outflow tract. No further ventricular tachycardia occurred during a follow up of seven months without antiarrhythmic treatment.

Adult↗
PubMed1991

Successful intracardiac electrical conversion of atrial flutter in patients with complex congenital heart disease.

Sixteen patients presenting on 21 occasions with atrial flutter in association with complex congenital heart disease were treated by intracardiac stimulation techniques combined with activation mapping. Nineteen episodes of atrial flutter were successfully converted to sinus rhythm. In the remaining two episodes atrial fibrillation was induced with spontaneous conversion to sinus rhythm within 12 hours in one episode and immediate DC cardioversion to sinus rhythm in the other. Intracardiac stimulation techniques were highly successful in this group and allowed reliable conversion to sinus rhythm without general anaesthesia and high energy cardioversion. In patients with atrial flutter associated with congenital heart disease intracardiac stimulation techniques should be tried first.

Adolescent↗
PubMed1991

Comparison of interleukin-6 levels in the bone marrow of multiple myeloma patients with disease severity and clonogenicity in vitro.

Fifteen of 25 bone marrow aspirates from 23 patients who presented or had been treated for multiple myeloma at the Royal Marsden Hospital produced myeloma colonies (MY-CFUc) in vitro. There was no correlation between disease severity and the level of interleukin-6 (IL-6) in bone marrow plasma nor was there any evidence that the level of IL-6 was higher in bone marrow aspirates from patients whose tumour produced MY-CFUc in vitro compared with those who did not. The mean level of IL-6 in the whole group of patients was 0.41 ng/ml (range 0.1-0.66 ng/ml), a value similar to that found in plasma from normal donor bone marrow, 0.42 ng/ml (range 0.14-0.62 ng/ml). Separation of peripheral blood cells from serum 24 h after collection, compared with 2 h after collection, resulted in a substantial increase of IL-6 in the serum. The results suggest that levels of IL-6 in bone marrow plasma is not a monitor of disease severity in multiple myeloma (MM) and that the collection and separation of blood and/or bone marrow samples into the cellular and aqueous components should be performed using standardized conditions to minimize inter-sample variation resulting from the release of IL-6 from the cellular components.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

Biotechnology awareness study, Part 1: Where scientists get their information.

A model study, funded by the National Library of Medicine (NLM) and conducted by the Southeastern/Atlantic Regional Medical Library (RML) and the University of Maryland Health Sciences Library, attempted to assess the information needs of researchers in the developing field of biotechnology and to determine the resources available to meet those needs in major academic health sciences centers. Nine medical schools in RML Region 2 were selected to participate in a biotechnology awareness study. A survey was conducted of the nine medical school libraries to assess their support of biotechnology research. To identify the information needs of scientists engaged in biotechnology-related research at the schools, a written survey was sent to the deans of the nine institutions and selected scientists they had identified. This was followed by individual, in-depth interviews with both the deans and scientists surveyed. In general, scientists obtained information from three major sources: their own experiments, personal communication with other scientists, and textual material (print or electronic). For textual information, most study participants relied on personal journal subscriptions. Tangential journals were scanned in the department's library. Only a few of these scientists came to the health sciences library on a regular basis. Further, the study found that personal computers have had a major impact on how biotechnologists get and use information. Implications of these findings for libraries and librarians are discussed.

Awareness↗
PubMed1991

Biotechnology awareness study, Part 2: Meeting the information needs of biotechnologists.

The second part of the biotechnology awareness study focused on health sciences libraries and how well they are meeting the needs of biotechnologists working in the study's nine medical centers. A survey was conducted over a three-month period to assess the demand for biotechnology-related reference services at nine libraries and the sources the librarians used to answer the questions. Data on monographic and current serial holdings were also collected. At the end of the survey period, librarians were asked for their perceptions about biotechnology research at their institutions and in their geographic areas. Their responses were compared to the responses the scientists at the nine schools gave to the same or similar questions. Results showed few biotechnology-related reference questions were asked of the librarians. The recorded questions dealt with a range of biotechnology subjects. MEDLINE was used to answer 77% of the questions received during the survey period. More detailed notes in MeSH and a guide to online searching for biotechnology topics were suggested by the librarians as ways to improve reference service to this group of researchers. Journal collections were generally strong, with libraries owning from 50% to 87% of the titles on a core list of biotechnology journals compiled for this study. All libraries subscribed to the five titles most often cited by the scientists surveyed. Generally, librarians were unaware of the biotechnology-related research being done on their campuses or in their geographic areas.

Awareness↗
PubMed1991

Management of vomiting associated with cytotoxic therapy.

Recent advances in the understanding of emesis have resulted in the development of serotonin 3 receptor antagonists. The careful use of these drugs and other conventional antiemetic agents can substantially reduce the nausea and vomiting associated with chemotherapy and improve the quality of life for cancer patients undergoing treatment.

Antiemetics↗
PubMed1990

Dexamethasone can potentiate the anti-emetic action of a 5HT3 receptor antagonist on cyclophosphamide induced vomiting in the ferret.

A new group of selective 5HT3 antagonists are proving to be effective anti-emetics for cytotoxic and radiation induced vomiting in both animal models and man. Current anti-emetic regimens often benefit from combination therapy, in particular the efficacy of metoclopramide (which can be a weak 5HT3 antagonist), can be improved by combination with dexamethasone, another anti-emetic. Hence it was of interest to evaluate whether a 5HT3 receptor antagonist GR38032F could be improved by combination with dexamethasone. Vomiting induced by cyclophosphamide in the ferret was observed after pre-treatment with dexamethasone alone or in combination with GR38032F. Animals were also observed for signs of 'nausea'. Dexamethasone alone proved a weak anti-emetic in this system but did have significant effects on 'nausea'. GR38032F has previously been shown to be capable of totally controlling emesis due to cyclophosphamide in the ferret. Here a dose of GR38032F that is not 100% effective was employed; this was shown to have effects on 'nausea' but most interestingly its anti-emetic action was increased by combination with dexamethasone. This may be important for the minority of patients whose vomiting is not completely controlled by GR38032F alone.

Animals↗
PubMed1990

Aromatase inhibition in advanced prostatic cancer: preliminary communication.

We report the results of the first use of a steroidal aromatase inhibitor, 4-hydroxyandrostenedione (4-OHA, CGP 32349), in the palliation of patients with advanced, hormone resistant, prostatic cancer. Twelve of 19 patients (63%), who had relapsed following castration and other therapies, gained significant pain relief following weekly intramuscular injections of 4-OHA. Five patients (31%) experienced a transient 'tumour flare', represented by an increase in bone pain soon after commencing treatment. The mechanism of action of 4-OHA in palliating patients with advanced prostatic cancer is obscure at present, but may represent an important new treatment modality which may lead to greater insight into prostatic biology.

Aged↗