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Biomedical subjects

J Doyle

Publications and source records attributed to J Doyle.

At least 109 records · Page 6Linked to original sources
PubMed1994

Concurrent RhGM-CSF does not offset myelosuppression from intensive chemotherapy: randomized placebo-controlled study in childhood acute lymphoblastic leukemia.

To determine whether recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) can offset the myelosuppressive effects of intensive chemotherapy, we carried out a double-blind placebo-controlled trial in which 40 patients with acute lymphoblastic leukemia (ALL) were randomized into two groups of 20 each. One group received rhGM-CSF (5.5 micrograms/kg SC) coadministered with chemotherapy and the other, placebo coadministered with chemotherapy from day 5 to day 11 and from day 19 to day 25 of the 28-day intensification phase of our institutional high-risk protocol for childhood ALL. The results indicate that, at the dose and schedule used, rhGM-CSF did not prevent neutropenia or shorten the number of days required to complete this phase of therapy. In addition, the treated and placebo groups showed no significant difference in absolute neutrophil counts, number of days with neutropenia, number of days with fever, number of days spent in hospital, or number of days on antibiotics during the 28-day study period. There was also no difference between the two groups in the number, type, or severity of infectious episodes. Two of 20 patients in the treatment group have relapsed, whereas none of the patients in the placebo group has yet relapsed (follow-up: 3-37 months), but these events were not statistically significant. We conclude that treatment with rhGM-CSF at the dose and schedule employed is not clinically beneficial.

Adolescent↗
PubMed1994

Letters of recommendation for surgical residencies: what they say and what they mean.

Screening of applicants and selection of interns for surgical residency programs continue to rely heavily on letters of recommendation from surgical faculty. To define important aspects of letters useful for screening and selection, letters written on behalf of housestaff with known performance and those of new applicants were circulated to a sample of 120 academic surgeons. Eighty letters, written on behalf of 42 students, were divided into 10 groups of 8; each group was sent to 12 individuals. Half of the letters were "open" (full letter-head and signature), and half were "text only" (i.e., no identification). Candidate names were omitted. Each faculty reviewer was asked to rank the candidate represented by each letter, for their program, on a scale of 1 to 5, and indicate key negative or positive phrases on individual letters. Reviewers were also asked to indicate the importance they generally ascribe in evaluating such letters to the school of origin, academic rank of the letter writer, personalization (of letter to reader), formal vs informal reference to the candidate, and mention of interest in specialty training. A response rate of 60% was obtained. Faculty reviewers stated explicitly that school of origin, personalization of the letter, and the academic rank of the writer are important factors influencing their ranking of candidate letters. The scores they gave to "open" and "text only" letters, however, do not differ significantly (P > 0.05). Letters were scored similarly, indicating that school of origin or writer may not be as critical as implied or believed.(ABSTRACT TRUNCATED AT 250 WORDS)

Correspondence as Topic↗
PubMed1994

Soft tissue and visceral sarcomas in Irish patients. Interim analysis of data obtained by the Dublin Soft Tissue Tumour Panel.

The Dublin Soft Tissue Sarcoma Panel was established in 1989 with a view to achieving a unified approach to diagnosis and management of soft tissue and visceral sarcomas. This interim report presents data on 265 prospectively-evaluated patients and on a separate retrospective series of 126 patients. The patients in the prospective series were treated by 93 different surgical and medical specialists. Tumours presented in all anatomic sites and ranged in size from 0.2 to 60 cm. Leiomyosarcoma was the commonest tumour type. Eighty-nine tumours were inoperable at clinical presentation. There was a consensus panel diagnosis in over 90%, non-neoplastic reactive lesions and primitive round cell tumours being the most difficult cases diagnostically. Management, including onward referral for chemotherapy or radiation therapy, was inconsistent. The 2-year survival figures were: 43% (1989-91) and 37% (1980-88). These findings should provide a basis for the evaluation of coherent treatment strategies for Irish sarcoma patients.

Adolescent↗
PubMed1994

Myelodysplasia and acute megakaryoblastic leukemia in Down's syndrome.

In this report we describe the clinical and hematologic features of 23 cases of myelodysplasia (MDS) or acute megakaryoblastic leukemia (AMKL) occurring in Down's syndrome. MDS was characterized by thrombocytopenia, abnormal megakaryocytopoiesis, megakaryoblasts (< 30%) in the marrow and abnormal karyotype, the most common of which was trisomy 8, found in 7/15 patients with MDS. Three of five patients achieved a complete remission with low dose cytosine arabinoside, vincristine and retinyl palmitate. The high cure rate and the distinctive features of the leukemic process in these cases suggest that this type of MDS and AMKL are unique to patients with Down's syndrome.

Adolescent↗
PubMed1994

Tumor necrosis factor-alpha (TNF-alpha), interferon-gamma, and interleukin-6 but not TNF-beta induce differentiation of neuroblastoma cells: the role of nitric oxide.

Tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), and interleukin-6 (IL-6), but not TNF-beta, can induce the in vitro differentiation of the neuroblastoma cell line N103 in a dose-dependent manner. Differentiation of N103 was accompanied by the arrest of cell growth and neurite formation. The induction of neuroblastoma cell differentiation by TNF-alpha and IFN-gamma can be specifically inhibited by a nitric oxide (NO) synthase inhibitor, L-NG-monomethylarginine. In contrast, the differentiation of N103 cells by IL-6 was not affected by L-NG-monomethylarginine. These results indicate that TNF-alpha and IFN-gamma, but not IL-6, induce the differentiation of neuroblastoma cells via NO. This is confirmed by the finding that the culture supernatants of N103 cells induced by TNF-alpha and IFN-gamma, but not that by IL-6, contained high levels of NO2-, the production of which was inhibited by L-NG-monomethylarginine. Furthermore, the differentiation of N103 cells can be induced directly in a dose-dependent manner by the addition of nitroprusside, a generator of NO, into the culture medium. These data therefore indicate that NO may be an important mediator in the induction of neuronal cell differentiation by certain cytokines such as TNF-alpha and IFN-gamma and that neuronal cells, in addition to the macrophage-like brain cells, can be induced by immunological stimuli to produce large quantities of NO.

Amino Acid Oxidoreductases↗
PubMed1994

Initial consultations in hearing aid clinics in Australia.

Fifty initial consultations in government hearing aid clinics were audiotape recorded and analyzed to study the behavior of audiologists and clients in the initial stages of hearing aid rehabilitation. Consultations averaged 34 minutes and showed a four-stage clinical routine in which clients appeared largely passive. Hearing aid fitting was initiated in 48 (96%) consultations. The consultations of individual audiologists differed significantly in total time, proportion of consultation time in which talk occurred, proportion of consultation time in which talk occurred, proportion of consultation time devoted to hearing assessment, and the number of clients' direct requests for information. Individual audiologists appeared to have one of two general patterns in hearing aid prescription. The study indicates a need for the further study of audiologist behavior and the relationship of that behavior to hearing aid rehabilitation outcomes such as client satisfaction and degree of hearing aid use.

Adult↗
PubMed1994

Idiopathic thrombocytopenia and neutropenia in childhood.

PURPOSE: Between 1975 and 1990, 13 patients seen at The Hospital for Sick Children, Toronto, Ontario, were noted to have concurrent idiopathic thrombocytopenia and neutropenia (ITN; platelet count < 150 x 10(9)/L; absolute neutrophil count < 1.5 x 10(9)/L). These patients all had normal marrow function and no evidence of systemic disease. PATIENTS AND METHODS: A detailed chart review was performed to define the clinical and laboratory features of these patients. RESULTS: Although this was a heterogeneous group of patients, they shared several common characteristics. The disease followed a chronic course with thrombocytopenia or neutropenia or both that persisted or recurred over the entire period of follow-up in all patients (18 months to 15 years). The disease was associated with splenomegaly in eight patients and lymphadenopathy in nine patients. Boys were affected more frequently than were girls (ratio 11:2). Thrombocytopenia improved temporarily during treatment with corticosteroids, i.v. immunoglobulin G, RhoGAM, and a variety of immunosuppressive agents; however, neutropenia tended to be much more resistant to these therapies. Splenectomy was ineffective in two children in whom the procedure was performed. Platelet of and neutrophil antibodies or both were detected in five of six patients who were tested, suggesting an autoimmune cause for the cytopenias. CONCLUSIONS: These findings suggest that ITN in childhood is distinct from immune thrombocytopenic purpura, particularly in terms of its chronicity and poor response to therapy.

Adolescent↗
PubMed1993

Pre-exposure of murine macrophages to lipopolysaccharide inhibits the induction of nitric oxide synthase and reduces leishmanicidal activity.

Murine macrophages produce nitric oxide (NO) from L-arginine on stimulation with lipopolysaccharide (LPS), alone or with interferon-gamma (IFN-gamma). The effect of incubation of macrophages with low concentrations of LPS on NO synthesis on subsequent stimulation was investigated, using a murine macrophage cell line, J774, and peritoneal macrophages from CBA mice. Cells which had been incubated with LPS produced significantly lower amounts of NO, and expressed lower levels of NO synthase activity, following stimulation with IFN-gamma and LPS, or with a high concentration of LPS. This effect was not reversed by tumor necrosis factor-alpha. The ability of CBA macrophages to kill the intracellular parasite Leishmania major was markedly reduced by pre-incubation with LPS. Reduced NO production by macrophages previously exposed to LPS is a manifestation of endotoxin tolerance, and may represent an important means of regulation of NO synthesis and thus a survival mechanism for intracellular parasites.

Amino Acid Oxidoreductases↗
PubMed1993

Transverse fracture of the patella in children.

We report two cases of transverse fracture of the patella in children. Contrary to the general belief that this fracture is common in children, we could not find any reported cases since 1973. Both of our cases were sports-related and each illustrates a different mechanism of injury.

Adolescent↗
PubMed1993

The increasing incidence of infantile hypertrophic pyloric stenosis.

Several reports have suggested that there is an increasing incidence of infantile hypertrophic pyloric stenosis (IHPS). We examined the incidence of IHPS in a stable population in the West of Ireland over a ten year period (1981-1990). During the 10 years of the study the number of live births per year did not alter significantly. The incidence of IHPS increased significantly from 0.87/1000 live births in 1981 to 5.10/1000 in 1990 (p < 0.001, Student's test), peaking in 1989 at 6.8/1000. There was no statistical correlation between the increasing incidence and feeding habits, birth rank, family history or gender distribution. The reason(s) for this increase remain unclear.

Female↗
PubMed1993

Effect of nasal continuous positive airway pressure during sleep on 24-hour blood pressure in obstructive sleep apnea.

Ambulatory blood pressure (BP) was measured noninvasively (Oxford Medilog ABP) at 15-minute intervals for 24 hours before and after 8 weeks of treatment with nasal continuous positive airway pressure (nCPAP) in 19 men with obstructive sleep apnea (OSA). We included both normotensive and hypertensive patients, but hypertensives were studied after withdrawal of antihypertensive drugs. Ambulatory BP before and after treatment was compared using patients as their own controls. Treatment with nCPAP was successfully established in 14 of the 19 patients (74%). Blood pressure fell significantly in patients who were successfully treated: 24-hour mean BP (systolic/diastolic) decreased from 141 +/- 18/89 +/- 11 mm Hg to 134 +/- 19/85 +/- 13 mm Hg (p < 0.05). The reduction in 24-hour mean systolic BP occurred during both day and night, but a significant fall in mean diastolic BP was only observed during the day. The mean blood pressure fell in both normotensive and hypertensive patients. Patients who were inadequately treated with nCPAP had no reduction in mean 24-hour BP. Effective treatment of sleep apnea with nCPAP was associated with a significant fall in both systolic and diastolic BP independent of changes in body weight or alcohol consumption, suggesting that sleep apnea was an independent factor contributing to elevated nighttime and daytime BP in these patients.

Blood Pressure↗
PubMed1992

Characterization and molecular analysis of nondisjunction in 18 cases of trisomy 21 and leukemia.

We recently began a cytogenetic and molecular study of nondisjunction in leukemic Down syndrome individuals to determine whether the mechanism by which the extra chromosome 21 originates predisposes the individual to leukemia. In the present report, we summarize our observations on 18 patients with trisomy 21 and acute or transient leukemia, including 11 patients with acute lymphocytic leukemia, three with acute myeloid leukemia, one with B-cell lymphoma, one with acute megakaryoblastic leukemia, and two with transient leukemia. Results of DNA marker studies of the parental origin of the extra chromosome 21 indicated that 16 of the 18 cases (89%) were maternally derived, a percentage similar to that seen among nonleukemic Down syndrome patients. We noted that most leukemic Down syndrome patients had one locus or more in which parental heterozygosity was maintained in the trisomic individual, indicating a meiotic rather than a mitotic origin for the trisomy.

Adolescent↗
PubMed1992

Augmentation of the accuracy of percutaneous electrode implantation by using a modified arthroscope to guide insertion.

Using a clear polyvinyl fluoride sheath over an arthroscope, inserted through a 1-cm stab incision, we have demonstrated the feasibility of visualizing the sciatic nerve and its branches in the feline model. The purpose of this technique is to allow visual control, without a large surgical incision, of the exact site of implantation of electrodes used for functional neuromuscular stimulation. Currently, we determine the optimum site for percutaneous electrode implantation by stimulating the target nerve or muscle with a 26-gauge probe needle until maximal response is obtained. This method lacks accuracy because there is no direct visualization of the location of the tip of the probe or the electrode. With the new technique, we identified nerves by their distinctive vascular markings and we followed the nerves with minimal disruption of the soft tissues. In this way, individual branches were identified and targeted for instrumentation, allowing selective stimulation of specific muscle groups.

Animals↗
PubMed1992

Candoxatril, a neutral endopeptidase inhibitor: efficacy and tolerability in essential hypertension.

OBJECTIVE: To examine the efficacy and tolerability of the neutral endopeptidase inhibitor, candoxatril (UK 79,300) as monotherapy in essential hypertension. DESIGN: Double-blind, placebo-controlled, parallel-group study of 28 days' duration. SETTING: Three hospital outpatient departments participating in the Glasgow Blood Pressure Clinic (Glasgow, UK). PATIENTS: Forty patients with essential hypertension with diastolic blood pressure 95-114 mmHg after a 2-4 week placebo run-in period. INTERVENTIONS: Twenty-eight days' treatment with candoxatril 200 mg twice daily or matching placebo capsules. MAIN OUTCOME MEASURES: Changes in supine and erect blood pressure, and volunteered side effects during double-blind treatment. RESULTS: When measured at the end of the dose interval, the fall in supine blood pressure following candoxatril was not significantly greater than that after placebo. Compared with placebo, a significant effect for candoxatril was seen only for systolic blood pressure in the erect posture; the fall in erect diastolic blood pressure attributable to candoxatril was insignificant. Median plasma atrial natriuretic peptide concentration increased in candoxatril-treated patients and decreased in the placebo group. No stimulation of the renin-aldosterone axis was seen. There was a non-significant trend towards greater urinary excretion of cyclic guanosine monophosphate after candoxatril. Mean plasma concentration of candoxatril at (UK 73,967--the active metabolite of candoxatril) reached a peak of 1010 +/- 437 ng/ml after acute dosing, and 1328 +/- 405 ng/ml after chronic dosing; time to maximum concentration was 2 h in each case. Candoxatril was well-tolerated; numbers of adverse events did not differ between active treatment and placebo. CONCLUSIONS: Although atrial natriuretic peptide levels were significantly increased, candoxatril 200 mg twice daily for 28 days did not produce a clinically relevant fall in blood pressure. Our results cast some doubt upon the role of neutral endopeptidase inhibition in the treatment of unselected hypertensive patients.

Antihypertensive Agents↗