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Biomedical subjects

J Byrne

Publications and source records attributed to J Byrne.

At least 37 records · Page 2Linked to original sources

Prognostic factors and secondary malignancies in childhood medulloblastoma.

PURPOSE: Little is known of the outcome of long-term survivors of childhood medulloblastoma, one of the most common pediatric malignancies. To determine the potential for secondary malignancies, a retrospective outcome evaluation in 88 consecutive cases of childhood medulloblastoma was performed. PATIENTS AND METHODS: The records of all patients with childhood medulloblastoma diagnosed at Children's National Medical Center in Washington, DC from 1969 through 1997 were reviewed. RESULTS: The median follow-up time was 92 months (range 6-257 months). Overall survival was 59% at 5 years and 52% at 10 years. Univariate analysis showed that age at diagnosis, extent of surgical resection, presence of metastatic disease (M stage), ventriculoperitoneal shunt placement within 30 days from diagnosis, posterior fossa radiation therapy dose, and adjuvant chemotherapy significantly affected survival. Although based on small numbers, the risk of second neoplasms was significantly increased in this cohort. Multiple basal cell carcinomas developed in the areas of radiation therapy in two patients; these patients also had nevoid basal cell carcinoma syndrome (NBCCS) diagnosed. One other patient died of glioblastoma multiforme 8 years after treatment of medulloblastoma. A meningioma developed in another patient 10 years after radiation therapy. CONCLUSION: As survival of medulloblastoma patients improves, increased surveillance regarding secondary malignancies is required, especially because radiation-induced tumors may occur many years after treatment. These two cases of NBCCS also illustrate the importance of considering the concomitant diagnosis of NBCCS in young patients with medulloblastoma. In those patients, alternative therapy should be considered to minimize radiation therapy-related sequelae.

Adolescent↗

Overexpression of 3-ketoacyl-acyl-carrier protein synthase IIIs in plants reduces the rate of lipid synthesis.

A cDNA coding for 3-ketoacyl-acyl-carrier protein (ACP) synthase III (KAS III) from spinach (Spinacia oleracea; So KAS III) was used to isolate two closely related KAS III clones (Ch KAS III-1 and Ch KAS III-2) from Cuphea hookeriana. Both Ch KAS IIIs are expressed constitutively in all tissues examined. An increase in the levels of 16:0 was observed in tobacco (Nicotiana tabacum, WT-SR) leaves overexpressing So KAS III when under the control of the cauliflower mosaic virus-35S promoter and in Arabidopsis and rapeseed (Brassica napus) seeds overexpressing either of the Ch KAS IIIs driven by napin. These data indicate that this enzyme has a universal role in fatty acid biosynthesis, irrespective of the plant species from which it is derived or the tissue in which it is expressed. The transgenic rapeseed seeds also contained lower levels of oil as compared with the wild-type levels. In addition, the rate of lipid synthesis in transgenic rapeseed seeds was notably slower than that of the wild-type seeds. The results of the measurements of the levels of the acyl-ACP intermediates as well as any changes in levels of other fatty acid synthase enzymes suggest that malonyl-ACP, the carbon donor utilized by all the 3- ketoacyl-ACP synthases, is limiting in the transgenic plants. This further suggests that malonyl-coenzyme A is a potential limiting factor impacting the final oil content as well as further extension of 16:0.

3-Oxoacyl-(Acyl-Carrier-Protein) Synthase↗

The reliability of a breastfeeding questionnaire.

This research project tests the reliability of a correctly constructed breastfeeding questionnaire. The questionnaire is designed to evaluate the impact of breastfeeding support services on breastfeeding initiation and duration and identify groups of women most at risk of premature weaning. The development of the questionnaire followed a seven-step plan to determine the accuracy of the data and the overall integrity of the questionnaire. Reliability was assessed using the test-retest method on twenty-one women with children between the age of one and three years. The statistic kappa was used to assess nominal data, while ordinal and ratio data were assessed using the correlation coefficient, Pearson's r. This study served as a preliminary analysis of the assertion that the correctly constructed breastfeeding questionnaire is an effective and efficient tool.

Adult↗

Prevalence of Müllerian duct anomalies detected at ultrasound.

The true prevalence of müllerian duct abnormalities is not well established. We used standard ultrasound examinations to establish the prevalence of müllerian duct abnormalities in girls and women who were evaluated for reasons unrelated to the presence of uterine anomalies. Prospective ultrasound examinations for nonobstetric indications in 2,065 consecutive girls and women (aged 8-93) showed that 8 had anomalies, including bicornuate uterus, septate uterus, and double uterus. In this first attempt to determine the prevalence of uterine anomalies in the general population, using noninvasive methodology, the rate of anomalies was 3.87 per 1,000 women (exact 95% confidence interval: 1.67-7.62), or approximately 1 in 250 women. This prevalence estimate may be greater than the true rate if selection biases are strong, or less than the true prevalence if ultrasound detection rates are low. As a first attempt to establish the prevalence by pelvic ultrasound in a consecutive series, these data may serve as a baseline estimate.

Adolescent↗

The distribution of caprylate, caprate and laurate in lipids from developing and mature seeds of transgenic Brassica napus L.

The composition and positional distribution of lipids in developing and mature transgenic Brassica napus seeds accumulating up to 7 mol% of caprylate (8:0), 29 mol% caprate (10:0) or 63 mol% of laurate (12:0) were examined. The accumulation of 8:0 and 10:0 resulted from over-expression of the medium-chain-specific thioesterase (Ch FatB2) alone or together with the respective chain-length-specific condensing enzyme (Ch KASIV). Seeds containing high levels of 12:0 were obtained from plants expressing bay thioesterase (BTE) alone or crossed with a line over-expressing the coconut lysophosphatidic acid acyltransferase (LPAAT), an enzyme responsible for the increase in acylation of 12:0 at the sn-2 position. In all instances, 10:0 and 12:0 fatty acids were present in substantial amounts in phosphatidylcholine during seed development with a drastic decrease of 80-90% in mature seeds. At all stages of seed development however, 8:0 was barely detectable in this membrane lipid. Altogether, these results indicate that these transgenic seeds exclude and/or remove the medium-chain fatty acids from their membrane and that this mechanism(s) is more effective with the shorter-chain fatty acids. Furthermore, seeds of 8:0- and 10:0-producing lines had only negligible levels of these fatty acids present in the sn-2 position of the triacylglycerols. In contrast, all 12:0-producing seeds had a substantial amount of this fatty acid in the sn-2 position of the triacylglycerols, suggesting that the endogenous LPAAT is able to acylate 12:0 if no other acyl-CoA species are available.

Brassica↗

Physician expressions of uncertainty during patient encounters.

Uncertainty is inherent in clinical medicine and may contribute to variability in physician practice patterns, patient satisfaction, and exchange of information. However, research on physician disclosure of uncertainty to patients is sparse. We measured the frequency of physician expressions of uncertainty to patients using audiotapes of visits to 43 physicians by 216 continuity patients in a university-affiliated general medicine clinic. We also analyzed the audiotapes using Roter Interaction Analysis. Physicians completed Gerrity's Physician's Reaction to Uncertainty scale and patients completed the Kranz Health Opinion Survey and a standardized satisfaction questionnaire. Physicians made verbal expressions of uncertainty in 71% of clinic visits. Physicians with greater self-rated reluctance to disclose uncertainty to patients made fewer expressions. Physicians who made more uncertainty expressions also used more positive talk and partnership building, and gave more information to patients. Physicians also expressed more uncertainty to patients with more education, greater desire for information, and more questions. Physician uncertainty expression were associated with greater patient satisfaction, but not independently of other physician verbal behaviors that were also associated with satisfaction.

Adult↗

Allogeneic haemopoietic stem cell transplantation for multiple myeloma or plasma cell leukaemia using fractionated total body radiation and high-dose melphalan conditioning.

We have evaluated the outcome of allogeneic haemopoietic stem cell transplantation for multiple myeloma using a conditioning regimen comprising fractionated total body irradiation and high-dose melphalan (110 mg/m2). The study comprised 25 patients (median age 49 years) who had been transplanted by either bone marrow (n = 13) or G-CSF mobilized peripheral blood stem cells (n = 12). Overall transplant-related mortality was 30% but was lower for patients < 50 years of age at transplant (21%). The main cause of treatment-related mortality was viral infection. Of the 19 patients evaluable post-transplant, 17 have so far achieved complete remissions. Currently, with a median follow-up of 3.4 years, 18 out of 25 patients are alive, of whom 15 are in continuing complete remission (CR) and 2 in second remission after suffering localized relapses, which were treated with radiotherapy and donor leucocyte infusions. Patients transplanted after 1 line of previous therapy, < 50 years of age and receiving peripheral blood stem cells (PBSC) rather than bone marrow (BM) had a superior outcome, although there was no statistically significant factor. We conclude that allogeneic transplantation should be considered as a potentially curative option for younger patients with myeloma and that the regimen using fractionated total body irradiation and melphalan has a high CR rate and a relatively low risk of treatment-related mortality, particularly in younger patients.

Adult↗

Physiologic responses to laparoscopic aortofemoral bypass grafting in an animal model.

OBJECTIVE: To measure and compare the physiologic, metabolic, and hemodynamic responses to aortofemoral bypass grafting by three techniques: open or conventional laparotomy, laparoscopic-assisted (minilaparotomy), and totally laparoscopic grafting. METHODS: Twenty-four laboratory-bred hounds were randomized to one of three groups (open, laparoscopic-assisted, or totally laparoscopic). Four sets of parameters were measured: hemodynamic (intraoperative continuous cardiac output monitoring), inflammatory or hematologic (serial leukocyte and platelet levels), metabolic responses (serial blood glucose, serum cortisol and insulin, plasma epinephrine, plasma norepinephrine, and dopamine levels), and catabolic (24-hour urinary nitrogen excretion). RESULTS: Cardiac output increased transiently with aortic cross-clamping, more in the laparoscopic-assisted and total laparoscopic groups than in the open group, but the differences were not significant. White blood counts nearly doubled within 12 hours of surgery but were similar in all three groups. Platelet counts decreased significantly in all three groups, but no significant intergroup effects were observed. Metabolic parameters (e.g., blood glucose, cortisol, and catecholamine) rose significantly during surgery but fell to normal within 24 hours, with no important difference between groups. For the first 24 hours, urinary urea excretion fell by 50% but returned to normal by 7 days in all three groups. CONCLUSIONS: In the experimental animal model, the hemodynamic, hematologic, and metabolic responses to laparoscopic and laparoscopic-assisted aortofemoral bypass grafting are similar to those produced by conventional laparotomy graft placement. These data call into question whether laparoscopic techniques for aortic surgery have a significant physiologic advantage in humans.

Animals↗

Focal amyotrophy in neurofibromatosis 2.

Neurofibromatosis type 2 (NF2) is an autosomal dominant disorder characterised by bilateral vestibular schwannomas and other CNS tumours including meningiomas and spinal schwannomas. Occasionally, peripheral neuropathy occurs in these patients but this is the first report of focal amyotrophy. Clinical, electrophysiological, and imaging data from four NF2 patients seen at a specialist neurofibromatosis clinic over a 4 year period are described in whom symptomatic focal amyotrophy preceded the diagnosis of NF2. Two presented with wasting and weakness of a single muscle group, several years before NF2 was diagnosed. In one patient a mononeuritis multiplex was the presenting feature of NF2, and in one patient focal wasting and weakness developed after the diagnosis of NF2 was made. In none of the four cases could a focal peripheral nerve or root neurofibroma be identified despite extensive imaging with MRI, and the limitations of neuroimaging for identifying a structural cause in patients with NF2 with a focal peripheral nerve lesion is discussed. It is likely that NF2 may affect peripheral nerve structures in a manner distinct from a compressive schwannoma.

Adolescent↗

Screening of abdominal aortic aneurysm: a pragmatic approach.

In order to evaluate the feasibility of a selective screening programme for abdominal aortic aneurysm (AAA) within an urban setting and assess its impact on the expected increase in workload for the local hospital(s), a population based, prospective study was performed. A total of 4823 men aged 65 years were invited for ultrasound examination of the abdominal aorta between January 1993 and April 1997 as part of a general practice-based aneurysm screening programme covering two districts with a general hospital each. All examinations were carried out by senior radiographers using a portable B mode grey scale machine and a 3.5 MHz curvi-linear array probe. Patients with a maximum aortic diameter of over 3 cm were annually recalled, those with over 4 cm were referred to hospital for an out-patient's appointment. Those with AAA greater than 5 cm were considered for surgery. Of those approached, 3497 (72.5%) took part in the study, 1206 (25%) did not attend and 120 (2.5%) were excluded by their general practitioners (GPs) on medical grounds. Of the men taking part, 3130 (89.5%) had an aortic diameter equal to or less than 2.5 cm, 196 (5.6%) between 2.6 and 3.0 cm, and 171 (4.9%) had aortic diameters greater than 3 cm--29 of whom had AAA greater than 5 cm with a mean diameter of 6.0 cm (range 5.1-9.0 cm). Of 127 men with an initial diameter of 3.1-4.0 cm (mean progression in size of 2.3 mm/year), 22 enlarged to > 4 cm and 3 to > 5 cm. Of 24 men with an initial diameter of 4.1-5.0 cm, 6 enlarged to > 5 cm. Some 69 (2%) patients were referred to hospital requiring a total of 125 consultations (1.8 consultations per patient); 21 underwent surgery and one died from rupture whilst awaiting surgery. Five patients refused their operation and two failed to attend the clinic (all > 5 cm) but remain well to date. No patient died following surgery. We conclude that, screening for AAA in men at age 65 years within an urban setting is feasible and well received by patients and GPs. Screening does not lead to a huge increase in terms of outpatient appointments and operations for AAA.

Aged↗

Elective abdominal aortic aneurysm operations--the results of a single surgeon series of 243 consecutive operations from a district general hospital.

BACKGROUND: There are few data on the morbidity and mortality of planned elective surgery for infrarenal abdominal aortic aneurysm (AAA) as a single surgeon series. This audit is of a consecutive series of AAA operations performed by one surgeon in one district general hospital over a 13-year period. METHODS: 243 patients were operated on for AAA between 1985 and 1998. Data were collected on the majority of patients prospectively. A reliable method was devised to identify all patients. Any missing complication and mortality data were then collected retrospectively. RESULTS: 13 patients died as a result of their operation (5.3%). In patients over the age of 80 years (36), five patients died (14%) and in the 207 patients under the age of 80 years, eight died (3.8%). Cardiac deaths were the most frequent cause (38%); 82 patients had recorded complications (34%). The operative mortality rate has increased in later years, (2.2% to 7.1%), largely due to an increase in the very elderly accepted for operation (12% to 16%), and a possible increase in co-morbidity. CONCLUSIONS: An acceptable and comparable mortality rate can be achieved in a district general hospital. The complication rate is high indicating the need for very intense medical and nursing care for these patients postoperatively. There is a considerable variance in mortality rates with age and risk even in the practice of one surgeon, indicating a need to be very knowledgeable and cautious in interpreting postoperative mortality data. This is the largest single surgeon series to date in the UK.

Aged↗

Human cyclophilin has a significantly higher affinity for HIV-1 recombinant p55 than p24.

The ability of cyclophilin to bind a panel of recombinant HIV-gag proteins was assessed using sensitive, quantitative, sandwich enzyme-linked immunosorbant assays (ELISAs). Significantly higher binding to cyclophilin was observed when recombinants contained at least 12 carboxy-terminal amino acids of p17 in addition to p24 sequences. These results indicate that the carboxy-terminus of p17 is important for optimal binding of cyclophilin to p24 and support the theory that cyclophilin acts on the uncleaved HIV-1 gag (p17-p24) precursor.

Gene Products, gag↗

Long-term genetic and reproductive effects of ionizing radiation and chemotherapeutic agents on cancer patients and their offspring.

The continuing search for a cure for cancer has lead to more aggressive therapies as new agents are developed with largely unknown late complications. Standard therapy for the majority of cancers today, following surgery, often consists of combinations of high doses of radiation and multi-drug therapy. Compared with exposures experienced by atomic bomb survivors, cancer survivors have been exposed to higher doses of partial body irradiation and combination chemotherapy over longer periods. Thus, cancer survivors provide a model system with which to evaluate the long-term effects on the human organism of high doses of agents known to damage DNA. Five-year survival after cancer diagnosis is now greater than 56%; more than 5 million Americans are considered cured of cancer. However, the late complications of cancer in long-term survivors has been poorly evaluated, especially in adults, and little is known of the most troubling possibility, that is, that the effects of cancer treatments could be passed on to the next generation. What little we know comes from studies of at most 5,000 survivors of childhood cancer, treated decades ago. So far, results are reassuring that with the means now available, we cannot detect clinical evidence of heritable damage. However, reproductive effects, including infertility, are common consequences of cancer therapy and may represent germ cell damage. We are just in the infancy of studies of germ cell mutagenesis in cancer survivors. The relatively small numbers of survivors, and the few types of exposures studied so far, provide only limited grounds for reassurance. More comprehensive, properly designed, studies of modern new agents are urgently need.

Abnormalities, Radiation-Induced↗

Titration of vasodilator therapy in chronic heart failure according to plasma brain natriuretic peptide concentration: randomized comparison of the hemodynamic and neuroendocrine effects of tailored versus empirical therapy.

BACKGROUND: Most patients with chronic heart failure (CHF) receive the same dose of angiotensin-converting enzyme (ACE) inhibitors because there is currently no measure of treatment efficacy. We sought to determine whether titration of vasodilator therapy according to plasma brain natriuretic peptide (BNP) concentration may be of value in the individual optimization of vasodilator therapy in CHF. METHODS AND RESULTS: Twenty patients with mild to moderate CHF receiving stable conventional therapy including an ACE inhibitor were randomly assigned to titration of ACE inhibitor dosage according to serial measurement of plasma BNP concentration (BNP group) or optimal empirical ACE inhibitor therapy (clinical group) for 8 weeks. Only the BNP-driven approach was associated with significant reductions in plasma BNP concentration throughout the duration of the study and a significantly greater suppression when compared with empiric therapy after 4 weeks [-42.1% (-58.2, -19.7) vs -12.0% (-31.8, 13.8), P =.03]. Both treatment strategies were well tolerated and associated with favorable neurohormonal and hemodynamic effects; however, in comparison between groups, mean heart rate fell (P =.02) and plasma renin activity rose (P =.03) in the BNP group when compared with the clinical group. CONCLUSIONS: Plasma BNP concentration may be chronically reduced by tailored vasodilator therapy in CHF. Furthermore, titration of vasodilator therapy according to plasma BNP was associated with more profound inhibition of the renin-angiotensin-aldosterone system and significant fall in heart rate when compared with empiric therapy.

Aged↗

Infrainguinal arterial reconstruction for claudication: is it worth the risk? An analysis of 409 procedures.

PURPOSE: Infrainguinal reconstruction traditionally has been reserved for patients with limb-threatening ischemia. Surgery for debilitating claudication, however, has been discouraged as a result of the perceived fear of bypass graft failure, limb loss, and significant perioperative complications that may be worse than the natural history of the disease. In this study, the results of infrainguinal reconstructions for claudication performed during the past 10 years were evaluated for bypass graft patency, limb loss, and long-term survival rates. METHODS: Data were collected and reviewed from the vascular registry, the office charts, and the hospital records for patients who underwent infrainguinal bypass grafting for claudication. RESULTS: From 1987 to 1997, 409 infrainguinal reconstructions were performed for claudication (9% of all infrainguinal reconstructions in our unit). The patient population had the following demographics: 73% men, 28% with diabetes, 54% smokers, and an average age of 64 years (range, 24 to 91 years). Inflow was from the following arteries: iliac artery/graft, 10%; common femoral artery, 52%; superficial femoral artery, 19%; profunda femoris artery, 16%; and popliteal artery, 2%. The outflow vessels were the following arteries: 165 above-knee popliteal arteries (40%), 150 below-knee popliteal arteries (37%), and 94 tibial vessels (23%). The operative mortality rate was 0%, and one limb was lost in the series from distal embolization. The primary patency rates were 62%, 77%, and 86% for above-knee popliteal artery, below-knee popliteal artery, and tibial vessel reconstructions at 4 years, and the secondary patency rates were 64%, 81%, and 90%, respectively. Cumulative patient survival rates were 93% and 80% at 4 and 6 years as compared with 65% and 52%, respectively, for infrainguinal reconstructions performed for limb salvage. CONCLUSION: Infrainguinal arterial reconstruction for disabling claudication is a safe and durable procedure in selected patients. These data indicate that concern for limb loss, death, and limited life span of the patients with this disease may not be warranted.

Adult↗