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T Doyle

Publications and source records attributed to T Doyle.

At least 19 recordsLinked to original sources
PubMed2004

Programmed -1 ribosomal frameshifting in the SARS coronavirus.

Programmed -1 ribosomal frameshifting is an alternate mechanism of translation used by coronavirus to synthesize replication proteins encoded by two overlapping open reading frames. For some coronaviruses, the mRNA cis-acting stimulatory structures involved in this process have been characterized, but their precise contribution to ribosomal frameshifting is not completely understood. Recently, a novel coronavirus was identified as the causative agent of the severe acute respiratory syndrome. This review describes the mRNA motifs involved in programmed -1 ribosomal frameshifting in this virus.

Amino Acid Sequence↗
PubMed2003

Cyclizine.

Explore the source record for details and available documents.

Antiemetics↗
PubMed2002

Paget's disease in New Zealand: evidence for declining prevalence.

The prevalence rate of Paget's disease in New Zealand is believed to be among the highest in the world, but recent data suggest that it may have decreased in recent decades. We estimated the current prevalence of Paget's disease in subjects of European origin (>55 years of age) in two New Zealand cities (Dunedin and Auckland) based on review of nearly 2000 pelvic radiographs. Prevalence rate increased with age (p = 0.022) and was higher in men (p = 0.014), but there was no significant difference between the two cities. The Dunedin data were compared with a 1983 survey from the same city, and prevalence was approximately half its previous level (p = 0.012). In Auckland, the prevalence of an isolated raised plasma alkaline phosphatase level (>150 U/L, normal range <120 U/L) was estimated in over 80,000 blood samples processed at a community laboratory. The prevalence of "biochemical Paget's disease," as assessed by this surrogate marker, was very similar to that observed in the radiographic survey in Auckland for subjects <80 years of age, but not for older subjects. We conclude that the prevalence of Paget's disease in New Zealand has declined over the past two decades, indicating that there are important environmental determinants in its development. Biochemical estimates of the prevalence of Paget's disease agree well with radiographic estimates, except in the elderly. The method used herein offers an alternative way of determining the prevalence of Paget's disease.

Aged↗
PubMed2001

Long-term results of local recurrence after breast conservation treatment for invasive breast cancer.

PURPOSE: The outcome for women with a local failure after breast conservation treatment is not well described in the literature. Because local recurrence is a potentially salvageable event, this study was performed to evaluate the outcome of patients with local recurrence after breast conservation surgery and definitive radiation treatment. METHODS AND MATERIALS: The study population consisted of 112 patients with ipsilateral breast tumor recurrence. There were 100 isolated local recurrences and 12 local-plus-regional recurrences. There were 93 invasive local recurrences and 19 DCIS (ductal carcinoma in situ) local recurrences. Local recurrences were detected by physical examination alone in 42 patients, mammography alone in 47 patients, and both modalities in 23 patients. All patients were initially treated with breast conservation treatment with or without systemic therapy and subsequently treated at the time of local recurrence with salvage mastectomy with or without systemic therapy. The mean and median follow-up times after local recurrence were 49 and 44 months, respectively. RESULTS: For the entire group of 112 patients, the overall survival at 10 years after local recurrence was 69%, the cause-specific survival was 71%, and the freedom from distant metastases was 47%. For the 93 patients with an invasive local recurrence, the overall survival at 10 years was 64%, cause-specific survival was 67%, and freedom from distant metastases was 44%. For the 93 patients with an invasive local recurrence, interval from diagnosis to local recurrence (< or =2 years vs. 2.1-5 years vs. >5 years) predicted for overall survival at 5 years (65% vs. 84% vs. 89%; p = 0.03). Method of detection of local recurrence (physical examination vs. mammography vs. both methods) also predicted for 5-year overall survival (73% vs. 91% vs. 93%, respectively; p = 0.04). On multivariable analysis, interval from diagnosis to local recurrence was an independent predictor of overall survival (p = 0.03). Method of detection of local recurrence (physical examination vs. mammography vs. both methods) was borderline in predicting for 5-year cause-specific survival (73% vs. 91% vs. 93%, respectively; p = 0.06). Similarly, interval from diagnosis to local recurrence (< or =2 years vs. 2.1-5 years vs. >5 years) was a borderline predictor of 5-year cause-specific survival (65% vs. 84% vs. 89%; p = 0.08). No factors that predicted for freedom from distant metastases were identified. There were three second locoregional failures on the chest wall. Two of the 19 patients with a DCIS local recurrence have died of metastatic breast cancer. Death was probably not related to their local recurrence, but rather a result of persistent risk from an invasive primary cancer. CONCLUSIONS: This analysis provides long-term data after salvage treatment for patients who experience local recurrence after breast conservation treatment. The variables of method of detection and interval from diagnosis to local recurrence are identified as having prognostic significance for overall and cause-specific survival. In view of the potential for long-term survival, aggressive attempt at salvage treatment is warranted for the patient with local recurrence after breast conservation treatment. Second local recurrence after salvage mastectomy is an uncommon event. Although DCIS local recurrences may not in themselves cause an increase in the risk of mortality, the risk from the primary invasive cancer persists.

Adult↗
PubMed2001

Modified Norwood operation for hypoplastic left heart syndrome.

BACKGROUND: We examined early results in infants with hypoplastic left heart syndrome undergoing the Norwood operation with perioperative use of inhaled nitric oxide and application of extracorporeal membrane oxygenation. METHODS: Medical records were reviewed retrospectively. RESULTS: Between April 1997 and March 2001, 50 infants underwent a modified Norwood operation for hypoplastic left heart syndrome. Mean age at operation was 7.5 +/- 5.7 days, and mean weight was 3.1 +/- 0.5 kg. Five infants had a delayed operation because of sepsis. The mean diameter of the ascending aorta by echocardiography was 3.6 +/- 1.8 mm. Ductal cannulation was used to establish cardiopulmonary bypass in all patients. Mean circulatory arrest time was 39.4 +/- 4.8 minutes. The size of the pulmonary-systemic shunt was 3.0 mm in 6 infants, 3.5 mm in 37, and 4.0 mm in 7. Infants with persistent hypoxia (partial pressure of oxygen < 30 mm Hg) received nitric oxide after they were weaned from cardiopulmonary bypass. Extracorporeal membrane oxygenation was initiated in 8 infants in the pediatric intensive care unit primarily for low cardiac output and in 8 in the operating room because of the inability to separate them from cardiopulmonary bypass. The 30-day mortality rate was 22% (11 of 50 patients), and the hospital mortality rate was 32% (16 of 50 patients). Mean follow-up was 17 months. Ten patients (20%) underwent stage-two repair, with one operative death. One survivor had a Fontan procedure, and 2 underwent heart transplantation, with one death. CONCLUSIONS: Early application of extracorporeal membrane oxygenation for hemodynamic instability and selective use of nitric oxide for persistent hypoxia in the immediate postoperative period may improve survival of patients with hypoplastic left heart syndrome. Renal failure requiring hemofiltration during extracorporeal membrane oxygenation (p < 0.05) and cardiopulmonary arrest in the pediatric intensive care unit (p < 0.05) were predictors of hospital mortality.

Administration, Inhalation↗
PubMed2001

The dose distribution of medium energy electron boosts to the laryngectomy stoma.

An en face, medium energy electron boost of approximately 10 Gy is often given to stomal and peristomal tissues. Because the boost is considered a simple treatment, CT-based treatment planning is rarely used. Further, the results of such a plan might be inaccurate, as the complex dose distribution surrounding the stoma air cavity is poorly modeled by many treatment planning systems. We constructed three phantoms-two with a central vertical cavity to mimic the size and shape of the stoma and proximal trachea and one with a cavity inclined at 45 degrees to the horizontal to better simulate anatomy. These were used to investigate the dose distribution surrounding the stoma. In all cases, the entrance to the stoma opening was centered in a field defined by a 7-cm circular cutout and the phantom was irradiated at a source-surface distance (SSD) of 100 cm with either vertically incident 9- or 12-MeV electrons. Film measurements were made at a range of depths below and lateral to the cavity. For the vertical cavity phantoms, diode measurements were performed and isodose plans using CT scans of the phantoms were generated on a modern treatment planning system. For these two phantoms, the combined effects of lateral scatter from surrounding material and reduced equivalent thickness for electrons which pass directly through the cavity increases the dose within a centimeter of the bottom of cavity by as much as 50% for 9 MeV and 70% for 12 MeV. In material at the shallower ("superior") end of the inclined cavity, a 40-50% overdose was noted. The dose increase is geometry dependent and is not predicted by the available treatment planning system. The potential of such a dose increase to affect normal tissues such as the neopharynx should be considered.

Electrons↗
PubMed2001

True aneurysm of a femoropopliteal vein graft.

Aneurysmal dilatation of saphenous vein grafts mostly represent thin-walled pseudoaneurysms at anastomotic sites. True aneurysmal dilatation of femoropopliteal bypass vein grafts is rare. We report this unusual case, which was repaired with a prosthetic graft.

Aged↗
PubMed1998

Co-occurrence of abuse of different drugs in men: the role of drug-specific and shared vulnerabilities.

BACKGROUND: Previous research has demonstrated genetic and environmental influences on abuse of individual substances, but there is less known about how these factors may influence the co-occurrence of abuse of different illicit drugs. METHODS: We studied 3372 male twin pairs from the Vietnam Era Twin Registry. They were interviewed using the Diagnostic Interview Schedule, Version III, Revised to investigate the extent to which the abuse of different categories of drugs occurs together within an individual, as well as the possibility that genetic and environmental factors are responsible for observed co-occurrence. Co-occurrence was quantified using odds ratios and conditional probabilities. Multivariate biometrical modeling analyses were used to assess genetic and environmental influences on co-occurrence. RESULTS: Abusing any category of drug was associated with a marked increase in the probability of abusing every other category of drugs. We found evidence for a shared or common vulnerability factor that underlies the abuse of marijuana, sedatives, stimulants, heroin or opiates, and psychedelics. This shared vulnerability is influenced by genetic, family environmental, and nonfamily environmental factors, but not every drug is influenced to the same extent by the shared vulnerability factor. Marijuana, more than other drugs, was influenced by family environmental factors. Each category of drug, except psychedelics, had genetic influences unique to itself (ie, not shared with other drug categories). Heroin had larger genetic influences unique to itself than did any other drug. CONCLUSION: There are genetically and environmentally determined characteristics that comprise a shared or common vulnerability to abuse a range of illicit drugs.

Adult↗
PubMed1998

Interaction of beta-L-2',3'-dideoxy-2',3'-didehydro-5-fluoro-CTP with human immunodeficiency virus-1 reverse transcriptase and human DNA polymerases: implications for human immunodeficiency virus drug design.

The work reported in this article has evaluated the relative molecular activity of the 5'-triphosphate of a novel beta-L-nucleoside with an unsaturated ribose residue, beta-L-2', 3'-dideoxy-2',3'-didehydro-5-fluorocytidine (beta-L-Fd4CTP), with that of beta-L-2',3'-dideoxy-5-fluorocytidine (beta-L-FddCTP) and 2', 3'-dideoxycytidine (ddCTP), on DNA strand elongation by human immunodeficiency virus-1 reverse transcriptase (HIV RT) and human DNA polymerases alpha (pol alpha), beta (pol beta), gamma (pol gamma), and epsilon (pol epsilon). The concentrations of beta-L-Fd4CTP that inhibited the yield of products by 50% were 0.20 micro M, 1.8 micro M, and 4.0 micro M for HIV RT, pol gamma, and pol beta, respectively. The beta-L-Fd4CTP at a concentration as high as 40 micro M had no inhibitory effect on pol epsilon, but could inhibit pol alpha by 10-20% at 20 micro M. The Km and relative Vmax values of beta-L-Fd4CTP, beta-L-FddCTP, and ddCTP for incorporation into the standing start point of 5'-[32P]-oligonucleotide primer annealed with M13mp19 phage DNA by HIV RT and human DNA polymerases were evaluated. The efficiency of incorporation (Vmax/Km) of beta-L-Fd4CTP by HIV RT was about 4-fold and 12-fold higher than that of ddCTP and beta-L-FddCTP, respectively. In contrast, the Vmax/Km ratio of beta-L-Fd4CTP for pol gamma was 7-fold lower than that of ddCTP, but 4-fold higher than that of beta-L-FddCTP. Pol alpha could use beta-L-Fd4CTP as a substrate, but only at a high concentration (>20 micro M). Incorporation of beta-L-Fd4CTP by pol epsilon could not be detected. A hypothesis about the preferable recognition of the 2',3'-dideoxy-2',3'-didehydro- structure of beta-L-Fd4CTP to that of the 2',3'-dideoxy-structure of beta-L-FddCTP by HIV RT is discussed.

Anti-HIV Agents↗
PubMed1997

Reversible acute renal failure induced by losartan in a renal transplant recipient.

A 56-year-old man who received a live-related renal transplant in 1988 was started in 1995 on the selective angiotensin II antagonist losartan (Dupont-Merke) to treat worsening hypertension. Two months later because of pulmonary oedema, loop diuretics were started. Within two weeks, serum creatinine had increased from 245 to 571 mumol/l, and the patient became oliguric. A systolic bruit was noted over the graft. Renal angiography showed a 90% stenosis of the transplant renal artery. Losartan was withdrawn, with prompt improvement in renal function. A successful percutaneous transluminal angioplasty performed a few days later resulted in further improvement in renal function accompanied by a significant diuresis.

Acute Kidney Injury↗
PubMed1996

Movement of yeast cortical actin cytoskeleton visualized in vivo.

Fusion proteins between the green fluorescent protein (GFP) and the cytoskeleton proteins Act1p (actin), Sac6p (yeast fimbrin homolog), and Abp1p in budding yeast (Saccharomyces cerevisiae) localize to the cortical actin patches. The actin fusions could not function as the sole actin source in yeast, but fusions between the actin-binding proteins Abp1p and Sac6p complement fully the phenotypes associated with their gene deletions. Direct observation in vivo reveals that the actin cortical patches move. Movement of actin patches is constrained to the asymmetric distribution of the patches in growing cells, and this movement is greatly reduced when metabolic inhibitors such as sodium azide are added. Fusion protein-labeled patches are normally distributed during the yeast cell cycle and during mating. In vivo observation made possible the visualization of actin patches during sporulation as well.

Actins↗
PubMed1995

Pulmonary vein stenosis.

Pulmonary vein stenosis (PVS) is a rare disorder. Accurate diagnosis often requires anatomical examination. We report four children with pulmonary vein stenosis. Autopsy showed bilateral lesions in two patients who were thought clinically to have unilateral disease. A diagnosis of PVS was made at autopsy in the third case. Intimal and medial fibromuscular proliferation was noted in extrapulmonary and intrapulmonary veins. Some of the fibromuscular proliferation were eccentric, resembling organized thrombi. In one case a focal organizing thrombus was found in a clinically unobstructed but anatomically narrowed veno-atrial junction. In another case injection of contrast medium into the stenotic pulmonary vein (PV) showed anastomosis between PV and bronchial vessels as well as small pulmonary arteries. Bilateral hypertensive arteriopathy was observed in unilateral and bilateral PVS. Our histological finding of intrapulmonary venous lesions in the lobes in which PVS was not detected clinically suggests that during surgical correction of unilateral PVS multiple biopsies of the opposite lung may help to evaluate possible bilateral disease. Our study also suggests that thrombosis in a stenotic pulmonary vein may further compromise the lumen and contribute to the progression of pulmonary vein obstruction. The possible pathogenesis of bilateral pulmonary hypertensive arteriopathy in unilateral PVS also is discussed.

Biopsy↗
PubMed1994

A comparison of American Speech-Language Hearing Association guidelines for obtaining speech-recognition thresholds.

This study compared two approaches for measuring speech-recognition thresholds (SRTs): the ASHA (1979) and ASHA (1988) guidelines. The subjects were 30 veterans with impaired hearing. Contrary to prior reports, the ASHA (1979) approach was found to be slightly less time consuming than the ASHA (1988) approach. The ASHA (1979) approach also yielded slightly better pure tone average (PTA)-SRT agreement than the ASHA (1988) approach for two of three generally accepted measures for comparing these tests; the third measure yielded equivalent results. Although statistically significant, the differences between these guidelines in test time and PTA-SRT agreement were small and are considered to be clinically insignificant.

Adult↗
PubMed1994

Resistance and disease in Brugia malayi infection of ferrets following prior infection, injection of attenuated infective larvae and injections of larval extracts.

A partial resistance expressed by a 53% to 78% reduction in lymphatic filariae from a challenge infection was induced in ferrets (Mustela putorius furo) by a prior infection and by injection of radiation attenuated infective larvae (L3) but not by injections of lyophilized microfilariae (mf) or L3. Equivalent acquired resistance was demonstrated with and without overt filarial disease. A prior infection resulted in peripheral lymphoedema in approximately one-third of the amicrofilaraemic resistant ferrets following challenge infection and injection of attenuated larvae resulted in inflammatory responses characteristic of a hyper-responsive syndrome in one-half of the amicrofilaraemic ferrets. Injections of lyophilized mf inhibited microfilaraemia and promoted development of lymphostatic disease. A limited examination of immune responses and histopathology suggested that disease in partially resistant ferrets was associated with high TH2 dependent responses directed, at least in part, to mature filariae and to mf. Mechanisms of resistance were not identified.

Animals↗