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Biomedical subjects

J Doyle

Publications and source records attributed to J Doyle.

At least 73 records · Page 4Linked to original sources

Does vitamin C cause hemolysis in premature newborn infants? Results of a multicenter double-blind, randomized, controlled trial.

OBJECTIVE: We tested the hypothesis that vitamin C supplementation of premature neonates is associated with hemolysis. STUDY DESIGN: A double-blind, randomized, controlled trial of vitamin C supplementation (50 mg/day) was undertaken in premature neonates (birth weight, 1000 to 1500 gm). Infants were randomly assigned to receive vitamin C (Ce-Vi-Sol) (n = 32) or placebo (n = 24) for 14 days. Twenty-three subjects per group were required to detect a difference of 1 SD in corrected carboxyhemoglobin values (alpha = 0.05, beta = 0.10). RESULTS: Day 14 vitamin C levels were lower in control subjects than in supplemented neonates (62 +/- 24 vs 125 +/- 62 micromol/L, p = 0.005). There was no difference in corrected blood carboxyhemoglogin concentrations (0.72 +/- 0.44 vs 0.72 +/- 0.23%; p = 0.95), other parameters of hemolysis, weight gain, blood sampled, presumed septic episodes, necrotizing enterocolitis, feeding intolerance, or transfusion. On day 14, bilirubin values were higher in control subjects than in the supplemented group (77 +/- 37 vs 55 +/- 33 micromol/L; p = 0.04). When a distant outlier in the nonsupplemented group was excluded (163 micromol/L), statistical significance was lost (73 +/- 32 vs 55 +/- 33 micromol/L; p = 0.09). CONCLUSION: Oral supplementation of premature infants with vitamin C is not associated with evidence of increased erythrocyte destruction, hyperbilirubinemia, or other morbidity.

Anemia, Hemolytic↗

Leukemia and/or myeloproliferative syndrome in neonates with Down syndrome.

Approximately 10% of newborn infants with Down Syndrome develop a form of megakaryoblastic leukemia which usually disappears spontaneously during the first months of life. The evidence that this "Transient Leukemia" is truly leukemia includes the following: it is clonal proliferation, it can be fatal and tissue infiltration of leukemic cells occurs. Also in approximately 25% of cases that recover, Acute Megakaryoblastic Leukemia will develop in the first four years of life, which, if not treated, is fatal. Evidence regarding the megakaryoblastic nature of the leukemic cells is presented as well as a description of the lethal forms of the disease. The study of Transient Leukemia is of considerable importance because it can provide insight into both the nature of leukemia and its relation to trisomy 21.

Biopsy↗

An improved limited sampling method for individualised busulphan dosing in bone marrow transplantation in children.

Busulphan (BU) pharmacokinetic (PK) studies in children undergoing bone marrow transplantation suggest that individual BU dosing may be necessary to optimise BU systemic exposure. Optimising BU systemic exposure may improve outcome and decrease toxicity in BMT. Because of practical limitations in obtaining blood from children and for financial reasons, a limited sampling method (LSM) is needed. However, such methods for BU have not been validated in children. In the present study, we individualized oral BU dosing in 10 children to target an area under the curve of BU (BU AUC) of 900-1400 microM/min based on BU AUC(0-infinity) calculated from nine serum BU concentrations performed after a BU test dose of 40 mg/m2. We validated a LSM using 3 BU concentrations to determine AUC. Six of nine patients studied (one patient non-evaluable), required their doses modified (3, lower; 3, higher). The mean percent dose change was 26.2% (range -33.3% to +45.3%). Our three sample LSM BU AUC(0-infinity) (1098 +/- 344, mean +/- 1 s.d.) correlated highly with our nine sample BU AUC(0-infinity) (1132 +/- 389, Pearson r = 0.98, P = 0.0001) and was not significantly different by t-test (P = 0.3). The mean percentage difference between the three sample LSM AUCs and the nine sample AUCs in each of our patients was 7.5%, (range -10.99% to +9.4%). Trough levels correlated extremely well with AUC (r = 0.95, P = 0.0001). Individual BU dosing, based on AUC, is necessary in most children to achieve targeted levels of BU therapy. An LSM of three BU concentrations performed at 0.5 h, 1 h and 6 h post-BU test dose closely predicts the AUC calculated from nine sampling points.

Alkylating Agents↗

Controlled pilot study of rapid amphotericin B infusions.

This pilot study compared the toxicity of a one hour with a four hour amphotericin B infusion in children. There were more severe chills in the former group on the first day of infusion, and more hypotension in the latter group over the study duration.

Adolescent↗

Analysis of the cost-effectiveness of paclitaxel as alternative combination therapy for advanced ovarian cancer.

PURPOSE: A phase III trial by the Gynecologic Oncology Group (GOG) provides strong evidence that a new alternative therapy--paclitaxel (Taxol; Bristol-Myers Squibb Co, Princeton, NJ) in combination with cisplatin (Platinol; Bristol-Myers Squibb Co)--is clinically more effective than the standard therapy using cyclophosphamide (Cytoxan; Bristol-Myers Squibb Co) in combination with cisplatin in the treatment of advanced ovarian cancer. We conducted a pharmacoeconomic analysis to determine whether the alternative paclitaxel-cisplatin (TP) therapy is cost-effective (CE) in comparison to standard cyclophosphamide-cisplatin (CP) therapy. METHODS: Using an economic model, we applied cost data figures to resource utilization data derived from the two arms of the GOG trial. We examined paclitaxel benefits in terms of increased mean survival time, as well as median survival time. Estimates of the cumulative proportion surviving in the trial were based on Kaplan-Meier procedures. RESULTS: Per year of life gained (YLG), TP therapy costs more ($19,820 more for inpatient treatment; $21,222 outpatient) than CP treatment. CONCLUSION: The TP regimen's increased mean survival cost per YLG (inpatient and outpatient settings) adds a substantial benefit at an acceptable cost compared with CP therapy.

Antineoplastic Agents↗

Audiological and psychological characteristics of a group of tinnitus sufferers, prior to tinnitus management training.

A profile of audiological and psychological characteristics, obtained before starting tinnitus management training, is presented for 96 subjects with tinnitus. Variability was marked in all measures. A history of headaches, neck or back pain, or balance problems was not related to the ability to cope with tinnitus. The coping strategies used to manage tinnitus were influenced by the beliefs held about tinnitus, but the coping strategies chosen were not necessarily effective. No gender differences were found in coping ability or overall stress levels, although there were gender differences on some psychological measures and stress influences. Subjects who had previously sought assistance differed from those who had not in the complexity of the tinnitus sounds, the level of emotional reaction and the use of coping behaviours.

Adaptation, Psychological↗

Managing tinnitus: a comparison of different approaches to tinnitus management training.

A series of studies examining the interaction between the characteristics of individual tinnitus sufferers and the effectiveness of the methods used to assist them has been conducted. The first of these studies provided a baseline description of 96 people with tinnitus, according to a range of audiological and psychological variables. In the present paper four differing tinnitus management programmes are described and the related changes in tinnitus perception reported three months after tinnitus management training. For the majority of subjects, the tinnitus was less annoying and less distressing three months after attending tinnitus management training. However, the majority of subjects reported no change in tinnitus loudness, or tinnitus awareness and no change in their tinnitus coping ability. Subjects receiving low level white noise stimulation reported greater improvement in tinnitus coping ability than subjects who received information and relaxation training, although there was no associated improvement in tinnitus awareness. Subjects' beliefs about tinnitus and preferred coping style may have influenced the reported benefit or otherwise of the differing tinnitus management techniques.

Acoustic Stimulation↗

A pharmacoeconomic comparison of UFT and 5-FU chemotherapy for colorectal cancer in South America.

The escalating role played by managed care organizations in the health-care system is reflected in the increased demand for cost-effectiveness analyses (CEAs) to assess the balance between economic impact and clinical efficacy. For example, the high incidence and costs associated with colorectal cancer in Latin America calls for a comprehensive economic evaluation to ensure appropriate allocation of limited health-care funds. In addition, the current call for a "societal" perspective of such analyses indicates the need for increased consideration of the concerns of both patient and health-care provider. The introduction of oral tegafur and uracil (UFT) provided the opportunity to evaluate the pharmacoeconomic advantage of the new agent compared with the standard fluorouracil (5-FU). Results of this study indicated an economic advantage for oral UFT vs a 5-FU-based regimen in the treatment of colorectal cancer in Brazil and Argentina. It was further noted that the mild toxicity profile of UFT reduced both the number of clinic visits and the need for venipuncture procedures. Noting that oral UFT may have a positive impact on quality of life in addition to its estimated economic benefit, it was concluded that prospective economic research and quality-of-life evaluations are needed to fully assess the pharmacoeconomic impact of oral UFT.

Argentina↗

Locations of human and mouse genes encoding the RFX1 and RFX2 transcription factor proteins.

RFX transcription factors constitute a highly conserved family of site-specific DNA binding proteins involved in the expression of a variety of cellular and viral genes, including major histocompatibility complex class II genes and genes in human hepatitis B virus. Five members of the RFX gene family have been isolated from human and mouse, and all share a highly characteristic DNA binding domain that is distinct from other known DNA binding motifs. The human RFX1 and RFX2 genes have been assigned by in situ hybridization to chromosome 19p13.1 and 19p13.3, respectively. In this paper, we present data that localize RFX1 and RFX2 precisely within the detailed physical map of human chromosome 19 and genetic data that assign Rfx1 and Rfx2 to homologous regions of mouse chromosomes 8 and 17, respectively. These data define the established relationships between these homologous mouse and human regions in further detail and provide new tools for linking cloned genes to phenotypes in both species.

Animals↗

Benign cervical leiomyoma leading to disseminated fatal malignancy.

A case study is reported of incomplete excision of a sessile leiomyoma of the posterior cervix followed by rapid tumor growth of the same region in a pregnancy commencing 2 months later. Cesarean section for placenta previa was followed 10 days later by hysterectomy for massive hemorrhage. The tumor was considered, following multiple review, to be a leiomyoma of the cervix with mitosis consistent with recent pregnancy. Widespread peritoneal recurrence occurred within 3 months requiring further laparotomy for excision of widespread tumor and ligation of internal iliac arteries. Death occurred 4 weeks later with widespread peritoneal occurrence. No postmortem was performed. The case emphasizes the rare potential for malignant change in histologically benign leiomyomas with no indications to this potential apart from biological behavior.

Adult↗

Endonasal premaxillary osteotomy.

In our hands, the endonasal premaxillary osteotomy is an improvement over the buccal sulcus tunnel and transpalatal techniques not only because of preservation of the blood supply but also because of improved visualization to the premaxilla. We have found the technique to be particularly useful in the bilateral cleft patient in whom the palate has been closed before Le Fort I osteotomy.

Cleft Lip↗

The effect of ketorolac on microvascular thrombosis in an experimental rabbit model.

This study was undertaken to evaluate the effect of ketorolac (Toradol), a potent cyclooxygenase inhibitor used for postoperative pain, on microvascular thrombosis in an established thrombosis model. Bilateral 3-mm arterial inversion grafts (n = 66) were constructed in the femoral arteries of New Zealand White rabbits. ALZET (ALZA Corporation, Palo Alto, Calif.) osmotic pumps were implanted in the external jugular veins for drug delivery. The blinded protocol called for the experimental animals to receive intravenous doses of ketorolac of 1.72 mg/kg per day (group 1) or 3.44 mg/kg per day (group 2), while control animals received equivalent volumes of saline. Patency was assessed at 7 days. Whereas 52 percent (13 of 25) of control vessels remained patent, 70 percent (14 of 20) and 86 percent (18 of 21) of group 1 and group 2 vessels, respectively, were patent at 1 week. This decrease in microvascular thrombosis with delivery of ketorolac was statistically significant (p = 0.0094). Ketorolac, at experimental doses approximating 9 and 18 mg IV q6h in a 70-kg man, demonstrated a statistically significant reduction in microvascular thrombosis. This study supports its use in clinical microvascular surgery.

Animals↗

Patient satisfaction with time use in audiological consultations.

An analysis of how time was used in and around 60 consultations was carried out for the purpose of exploring the relationship of time use to patient satisfaction. Sixty patients across two practice settings were surveyed, immediately following their interaction with the audiologist, regarding satisfaction with the consultation. Satisfaction was measured via: (1) a four-point scale, which yielded a satisfaction rating; and (2) a check list of satisfaction with 11 aspects of the consultation, which yielded a satisfaction score. Satisfaction ratings and scores were correlated significantly (rs = 0.76 corrected for ties, P = 0.0001). The majority of patients were either 'very satisfied' (63%) or 'satisfied' (31.6%) with the consultation experience. Temporal pictures of the consultations of 'very satisfied', 'satisfied' and 'dissatisfied' patients were clearly different. For the present sample it appeared that patient satisfaction ensued when the total consultation time was equal to or exceeded 0.6 of the sum of total consultation time and the time spent waiting at the clinic immediately prior to the consultation. Regression analyses showed that of the temporal variables studied, total consultation time (TCT) and the amount of time waiting immediately pre consultation (WT) contributed most to the variation in patient satisfaction ratings and scores. Forty-two per cent of the variance in satisfaction ratings and 36% of the variance in satisfaction scores could be explained by TCT/(WT + TCT).

Adult↗

The persisting communicative difficulties of 'remediated' language-impaired children.

This study addresses the effiacy of dismissal criteria used by speech and language pathologists by investigating communicative functioning in children declared 'remediated'. A battery of measures comprising the Language Assessment and Remediation Procedure (LARSP); the Behavioural inventory of Speech Act Performances (BISAP); the BISAP Addendum and the Devereux School Behaviour Rating Scale (DESB) was conducted on five children with language impairment who had been declared 'remediated'. Findings for certain 'remediated' subjects revealed persisting problems. The results suggest that decisions about dismissal from therapy may, in some cases, be premature and point to the need for a broad-based perspective concerning remediation dismissal decisions. An additional study on larger populations and the use of designs which investigate long term outcomes would further inform clinical decision-making concerning dismissal from therapy.

Child↗

Mismatch between aspects of hearing impairment and hearing disability/handicap in adult/elderly Cantonese speakers: some hypotheses concerning cultural and linguistic influences.

This paper addresses the observation that some Cantonese-speaking adults do not perceive a hearing problem even when hearing screening identifies hearing loss. A sample of 49 Cantonese speakers was surveyed about their self-perceptions of hearing prior to a 25 dB HTL pure-tone screening test. All 49 persons failed the screening test, yet 34 (69.4%) reported that they had no problems hearing during conversations. Persons who admitted hearing difficulties tended to have mean hearing levels in excess of 45 dB HTL. A number of hypotheses concerning cultural and linguistic influences are proposed as explanations for the apparent lack of significance of auditory sensitivity loss for some Cantonese speakers. Ways in which these hypotheses might be tested are suggested.

Aged↗

Co-amplification of MYCN and a DEAD box gene (DDX1) in primary neuroblastoma.

DEAD box proteins are putative RNA helicases that have been implicated in cellular processes involving alteration of RNA secondary structure, such as translation initiation and splicing. These proteins share eight conserved amino acid motifs, including Asp(D)-Glu-(E)-Ala(A)-Asp(D) which is part of a more extended motif. Recently, we have shown that the novel DDX1 gene containing a DEAD box motif maps to the same chromosome band as MYCN at 2p24 and is co-amplified with MYCN in retinoblastoma cell lines. Here, we show that the DDX1 gene is co-amplified with the MYCN gene in 2 of three neuroblastoma cell lines and that DDX1 RNA levels correlate with DDX1 gene copy number. Since amplification of MYCN is an indicator of poor prognosis in neuroblastoma, it was of interest to determine whether co-amplification with DDX1 occurred in clinical samples of neuroblastoma and whether such a finding carried any additional prognostic significance. We determined the gene copy number of DDX1 in 32 neuroblastoma patient samples (representative of all stages): 13 were MYCN amplified and 19 had normal copy numbers of the MYCN gene. Of the 13 neuroblastomas that were MYCN amplified, seven were also DDX1 amplified. Of the 19 that were not MYCN amplified, none were DDX1 amplified. This is the first example of a gene that is co-amplified with MYCN at a high frequency in neuroblastoma. While there was a trend towards a worse clinical outcome with co-amplification, the numbers were too small to reach significance.

Child↗