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Biomedical subjects

D Jones

Publications and source records attributed to D Jones.

At least 163 records · Page 9Linked to original sources
PubMed2000

Phase I trial of the anti-Lewis Y drug immunoconjugate BR96-doxorubicin in patients with lewis Y-expressing epithelial tumors.

PURPOSE: We conducted a phase I clinical trial of BR96-Doxorubicin (BR96-Dox), a chimeric anti-Lewis Y (Le(Y)) monoclonal antibody conjugated to doxorubicin, in patients whose tumors expressed the Le(Y) antigen. The study aimed to determine the toxicity, maximum-tolerated dose, pharmacokinetics, and immunogenicity of BR96-Dox. PATIENTS AND METHODS: This was a phase I dose escalation study. BR96-Dox was initially administered alone as a 2-hour infusion every 3 weeks. The occurrence of gastrointestinal (GI) toxicity necessitated the administration of BR96-Dox as a continuous infusion over 24 hours and use of antiemetics and antigastritis premedication. Patients experiencing severe GI toxicity underwent GI endoscopy. All patients underwent restaging after two cycles. RESULTS: A total of 66 patients predominantly with metastatic colon and breast cancer were enrolled onto the study. The most common side effects were GI toxicity, fever, and elevation of pancreatic lipase. At higher doses, BR96-Dox was associated with nausea, vomiting, and endoscopically documented exudative gastritis of the upper GI tract, which was dose-limiting at a maximum dose of 875 mg/m(2) (doxorubicin equivalent, 25 mg/m(2)) administered every 3 weeks. Toxicity was reversible and generally of short duration. Premedication with the antiemetic Kytril (granisetron hydrochloride; SmithKline Beecham, Philadelphia, PA), the antacid omeprazole, and dexamethasone was most effective in ameliorating GI toxicity. A dose of 700 mg/m(2) BR96-Dox (doxorubicin equivalent, 19 mg/m(2)) every 3 weeks was determined to be the optimal phase II dose when administered with antiemetic and antigastritis prophylaxis. BR96-Dox deposition on tumor tissue was documented immunohistochemically and by confocal microscopy. At the 550-mg/m(2) dose, the half-life (mean +/- SD) of BR96 and doxorubicin was 300 +/- 95 hours and 43 +/- 4 hours, respectively. BR96-Dox elicited a weak immune response in 37% of patients. Objective clinical responses were seen in two patients. CONCLUSION: BR96-Dox provides a unique strategy to deliver doxorubicin to Le(Y)-expressing tumor and was well tolerated at doses of 700 mg/m(2) every 3 weeks. BR96-Dox was not associated with the typical side-effect profile of native doxorubicin and can potentially deliver high doses of doxorubicin to antigen-expressing tumors. A phase II study in doxorubicin-sensitive tumors is warranted.

Adult↗
PubMed2000

CNS involvement in children with newly diagnosed non-Hodgkin's lymphoma.

PURPOSE: To determine the frequency of CNS involvement at diagnosis of non-Hodgkin's lymphoma (NHL), to characterize its pattern of presentation, and to determine its prognostic significance. PATIENTS AND METHODS: We reviewed the records of 445 children (1975 through 1995) diagnosed with NHL (small noncleaved cell NHL/B-cell acute lymphoblastic leukemia [SNCC NHL/B-ALL], 201 patients; lymphoblastic, 113; large cell, 119; other, 12). Tumor burden was estimated by serum lactate dehydrogenase (LDH) measurement and reclassification of disease stage irrespective of CNS involvement (modified stage). RESULTS: Thirty-six of 445 children with newly diagnosed NHL had CNS involvement (lymphoma cells in the CSF [n = 23], cranial nerve palsy [n = 9], both features [n = 4]), representing 13%, 7%, and 1% of small noncleaved cell lymphoma, lymphoblastic lymphoma, and large-cell cases, respectively. By univariate analysis, CNS disease at diagnosis did not significantly impact event-free survival (P =. 095), whereas stage and LDH did; however, children with CNS disease at diagnosis were at 2.0 times greater risk of death than those without CNS disease at diagnosis. In a multivariate analysis, CNS disease was not significantly associated with either overall or event-free survival, whereas both serum LDH and stage influenced both overall and event-free survival. Among cases of SNCC NHL/B-ALL, CNS disease was significantly associated with event-free and overall survival (univariate analysis); however, in multivariate analysis, only LDH had independent prognostic significance. Elevated serum LDH or higher modified stage were associated with a trend toward poorer overall survival among children with CNS disease. CONCLUSION: A greater tumor burden at diagnosis adversely influences the treatment outcome of children with NHL and CNS disease at diagnosis, suggesting a need for ongoing improvement in both systemic and CNS-directed therapy.

Adolescent↗
PubMed2000

Silent lacunar lesions detected by magnetic resonance imaging of children with brain tumors: a late sequela of therapy.

BACKGROUND: Cerebral lacunes, which generally appear on magnetic resonance imaging as foci of white matter loss, usually occur in adults after ischemic infarcts. We report the development of lacunes in children after therapy for brain tumors. PATIENTS AND METHODS: We reviewed the clinical characteristics and radiologic studies of 524 consecutive children with brain tumors treated over a 10-year period. We documented the neuropsychologic findings associated with lacunes and the factors predictive of lacunar development. RESULTS: Lacunes developed in none of the 103 patients observed or treated with surgery alone. Twenty-five of the 421 patients treated with chemotherapy or radiation therapy or both had lacunes. Patients were a median of 4.5 years old at the time of both diagnosis (range, 0.3 to 19.8 years) and radiotherapy (range, 1.5 to 20 years). Fourteen patients were treated with craniospinal irradiation, and 11 were treated with local radiotherapy. The median time from radiotherapy to the appearance of lacunes was 2.01 years (range, 0.26 to 5.7 years). For all patients, lacunes were an incidental finding with no corresponding clinical deficits. The factor most predictive of lacunar development was age less than 5 years at the time of radiotherapy (P =.010). There was no significant difference in estimated decline in intelligence quotient scores between patients with lacunes and age and diagnosis-matched controls. CONCLUSION: Lacunes may be caused by therapy-induced vasculopathy in children with brain tumors, with the most significant predictor being age less than 5 years at the time of radiotherapy.

Adolescent↗
PubMed2000

An isocentrically mounted stand for total body irradiation.

The purpose of this study was to construct a stand to support a patient for total body photon irradiation and to expedite the set-up and treatment by rotating the stand. As in other isocentric treatments, the midline dose is impacted less by source-to-skin distance variations. The method of immobilizing the patient is described. A 10 mm lucite plate is supported in front of the patient to increase skin dose. A matrix of holes in this plate serves to index the location of blocks used to shield the lungs. The dosimetry of the set-up is described, as is the production of tissue deficit compensators. The results of phantom studies and in vivo thermoluminescent dosimetry measurements are presented.

Equipment Design↗
PubMed2000

Childhood trauma, dissociation and self-harming behaviour: a pilot study.

OBJECTIVE: Childhood trauma is known to be an important antecedent in those who engage in deliberate self-harm (DSH). We aimed to explore the mediating mechanisms between childhood trauma and subsequent DSH in a sample of women detained in a high secure setting. METHOD: From a previous incidence study into DSH, we subdivided a group of 50 women as follows: non-harmers (N = 13), infrequent harmers (N = 22) and frequent harmers (N = 15). These three groups were then compared on several measures believed to be associated with DSH. RESULTS: The frequency of DSH was related to low self-esteem, increased dissociation, anger (both inwardly and outwardly directed), impulsivity, and a history of sexual and physical abuse. When these variables were entered into a path analytic model exploring the relationship between childhood trauma and subsequent DSH, two paths emerged: one major path which linked childhood sexual abuse to DSH via increased dissociation and another, more minor association, linking childhood sexual abuse via reduced self-esteem. CONCLUSION: This study shows a strong association between high levels of dissociation and an increased frequency of self-harming behaviour. This association is theoretically plausible and has therapeutic implications.

Adult↗
PubMed2000

Mesothelial cells in tuberculous pleural effusions of HIV-infected patients.

The scarcity of mesothelial cells is a well-known characteristic of tuberculous pleural effusions. We report three HIV-infected patients with tuberculous pleural effusions, in which mesothelial cells were found in significant numbers in the pleural fluid. Clinicians should be aware that the altered immune responses that occur in HIV-infected patients may affect the cytologic profile of tuberculous pleural effusions, and they should be cautious not to exclude this diagnosis based solely on the presence of mesothelial cells in the fluid.

AIDS-Related Opportunistic Infections↗
PubMed2000

Imaging of mucormycosis skull base osteomyelitis.

Skull base osteomyelitis (SBO) is typically bacterial in origin and caused by Pseudomonas, although the fungus Aspergillus has also rarely been implicated. SBO generally arises from ear infections and infrequently complicates sinonasal infection. Rhinocerebral Mucor infection is characteristically an acute, fulminant, and deadly infection also affecting the orbits and deep face and is associated with intracranial complications. Bony involvement is uncommon because of the angioinvasive nature of the fungus. More recently, chronic invasive Mucor sinusitis has been described. We report the unusual clinical and imaging features of a patient with biopsy-proven invasive mucormycosis arising from chronic isolated sphenoid sinus disease, who presented with extensive SBO and a paucity of deep facial, orbital, or intracranial involvement.

Biopsy↗
PubMed2000

Angiotensin-converting enzyme genotype affects the response of human skeletal muscle to functional overload.

The response to strength training varies widely between individuals and is considerably influenced by genetic variables, which until now, have remained unidentified. The deletion (D), rather than the insertion (I), variant of the human angiotensin-converting enzyme (ACE) genotype is an important factor in the hypertrophic response of cardiac muscle to exercise and could also be involved in skeletal muscle hypertrophy - an important factor in the response to functional overload. Subjects were 33 healthy male volunteers with no experience of strength training. We examined the effect of ACE genotype upon changes in strength of quadriceps muscles in response to 9 weeks of specific strength training (isometric or dynamic). There was a significant interaction between ACE genotype and isometric training with greater strength gains shown by subjects with the D allele (mean +/- S.E.M.: II, 9.0+/-1.7 %; ID, 17.6 +/-2.2 %; DD, 14.9+/-1.3 %, ANOVA, P 0.05). A consistent genotype and training interaction (ID DD II) was observed across all of the strength measures, and both types of training. ACE genotype is the first genetic factor to be identified in the response of skeletal muscle to strength training. The association of the ACE I/D polymorphism with the responses of cardiac and skeletal muscle to functional overload indicates that they may share a common mechanism. These findings suggest a novel mechanism, involving the renin-angiotensin system, in the response of skeletal muscle to functional overload and may have implications for the management of conditions such as muscle wasting disorders, prolonged bed rest, ageing and rehabilitation, where muscle weakness may limit function.

Adolescent↗
PubMed2000

Gravity, revised.

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Gravitation↗
PubMed2000

Asthma therapy.

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Journal Article↗