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J Fowler

Publications and source records attributed to J Fowler.

At least 19 recordsLinked to original sources
PubMed2004

Insights into the evolution of Yersinia pestis through whole-genome comparison with Yersinia pseudotuberculosis.

Yersinia pestis, the causative agent of plague, is a highly uniform clone that diverged recently from the enteric pathogen Yersinia pseudotuberculosis. Despite their close genetic relationship, they differ radically in their pathogenicity and transmission. Here, we report the complete genomic sequence of Y. pseudotuberculosis IP32953 and its use for detailed genome comparisons with available Y. pestis sequences. Analyses of identified differences across a panel of Yersinia isolates from around the world reveal 32 Y. pestis chromosomal genes that, together with the two Y. pestis-specific plasmids, to our knowledge, represent the only new genetic material in Y. pestis acquired since the the divergence from Y. pseudotuberculosis. In contrast, 149 other pseudogenes (doubling the previous estimate) and 317 genes absent from Y. pestis were detected, indicating that as many as 13% of Y. pseudotuberculosis genes no longer function in Y. pestis. Extensive insertion sequence-mediated genome rearrangements and reductive evolution through massive gene loss, resulting in elimination and modification of preexisting gene expression pathways, appear to be more important than acquisition of genes in the evolution of Y. pestis. These results provide a sobering example of how a highly virulent epidemic clone can suddenly emerge from a less virulent, closely related progenitor.

Bacteriophages↗
PubMed2003

Can ulnar artery velocity changes be used as a preoperative screening tool for radial artery grafting in coronary artery bypass?

Radial artery harvesting for coronary revascularization may result in digit ischemia if collateral circulation is inadequate. The purpose of this study was to compare changes in ulnar artery flow velocity during radial artery compression (RAC) with changes in first- and second-digit pressures during RAC, a previously validated predictor of digital ischemia. Photoplethysmography was used to measure first- and second-digit arterial pressures before and during RAC on 80 extremities. Color flow duplex imaging was used to measure distal ulnar artery peak systolic velocity before and during RAC. Seventy-eight of eighty extremities had a slight increase in ulnar artery velocity with RAC. There was no correlation between ulnar artery velocity changes and digit pressure changes. Measurement of ulnar artery velocity during RAC is not a useful predictor of digit pressure changes. Measurement of segmental upper extremity pressures with first- and second-digit pressure measurement during radial artery compression should remain the preferred preoperative screening tool for radial artery harvest prior to CABG.

Adult↗
PubMed2002

Current value of peritoneal tap in blunt abdominal trauma.

This study aimed to establish the diagnostic value of paracentesis (peritoneal tap) in the assessment of patients with blunt abdominal trauma. Paracentesis, using a four-quadrant puncture technique, was performed in blunt abdominal trauma victims presenting to the emergency department of a tertiary-care university medical centre. Pregnant patients, those under 18 or those having an abdominal scar were excluded from the study. All patients then underwent one of the following procedures as indicated: emergency ultrasound, abdominal computed tomography scan, diagnostic peritoneal lavage or laparotomy. Paracentesis results were compared with the results of other tests and surgery in diagnosing haemoperitoneum. Haemoperitoneum was confirmed surgically in six of the seven patients with a positive paracentesis. Nine out of 65 patients with positive clinical findings but negative taps underwent surgical intervention, and abdominal bleeding was confirmed in eight. Three seriously injured patients died before diagnostic studies or laparotomy could be performed. In conclusion, a positive paracentesis result may be used to guide decision-making in the setting of blunt abdominal trauma if other diagnostic methods are unavailable. Its high false-negative rate limits its overall usefulness.

Abdominal Injuries↗
PubMed2001

Polymorphism of the human muc genes.

Mucins encoded by the MUC genes share the common feature of having an extensive tandem repeat region that encompasses a large proportion of the coding sequence. In many of the genes this tandem repeat region shows a great deal of allelic length variation and recently studies have demonstrated person to person variation in pattern of nucleotide or amino-acid changes in the repeat units. The length and sequence variability will be discussed in this review, as will its role in disease susceptibility.

Humans↗
PubMed2001

Prediction of cognitive decline in normal elderly subjects with 2-[(18)F]fluoro-2-deoxy-D-glucose/poitron-emission tomography (FDG/PET).

Neuropathology studies show that patients with mild cognitive impairment (MCI) and Alzheimer's disease typically have lesions of the entorhinal cortex (EC), hippocampus (Hip), and temporal neocortex. Related observations with in vivo imaging have enabled the prediction of dementia from MCI. Although individuals with normal cognition may have focal EC lesions, this anatomy has not been studied as a predictor of cognitive decline and brain change. The objective of this MRI-guided 2-[(18)F]fluoro-2-deoxy-d-glucose/positron-emission tomography (FDG/PET) study was to examine the hypothesis that among normal elderly subjects, EC METglu reductions predict decline and the involvement of the Hip and neocortex. In a 3-year longitudinal study of 48 healthy normal elderly, 12 individuals (mean age 72) demonstrated cognitive decline (11 to MCI and 1 to Alzheimer's disease). Nondeclining controls were matched on apolipoprotein E genotype, age, education, and gender. At baseline, metabolic reductions in the EC accurately predicted the conversion from normal to MCI. Among those who declined, the baseline EC predicted longitudinal memory and temporal neocortex metabolic reductions. At follow-up, those who declined showed memory impairment and hypometabolism in temporal lobe neocortex and Hip. Among those subjects who declined, apolipoprotein E E4 carriers showed marked longitudinal temporal neocortex reductions. In summary, these data suggest that an EC stage of brain involvement can be detected in normal elderly that predicts future cognitive and brain metabolism reductions. Progressive E4-related hypometabolism may underlie the known increased susceptibility for dementia. Further study is required to estimate individual risks and to determine the physiologic basis for METglu changes detected while cognition is normal.

Aged↗
PubMed2001

Is alpha/beta for prostate tumors really low?

PURPOSE: Brenner and Hall's 1999 paper estimating an alpha/beta value of 1.5 Gy for prostate tumors has stimulated much interest in the question of whether this ratio (of intrinsic radiosensitivity to repair capacity) is much lower in prostate tumors than in other types of tumors that proliferate faster. The implications for possibly treating prostatic cancer using fewer and larger fractions are important. In this paper we review updated clinical data and present somewhat different calculations to estimate alpha/beta. METHODS AND MATERIALS: Seventeen clinical papers published from 1995 to 2000 were reviewed to obtain estimates of biochemical control from radiotherapy alone using external beam, I-125 implants, or Pd-103 implants. The focus was on intermediate risk patients. Three methods of estimating alpha/beta were employed. First, a simple two-step graphical comparison of isoeffective doses from external beam and implant modalities was made, to see which value of alpha/beta predicted the observed identity of biologic effect. Second, the same data were subjected to Direct Analysis (maximum likelihood estimation), from which an estimate of alpha/beta and also of the T(12) of repair of sublethal damage in the tumors (both with confidence intervals) were obtained. Third, preliminary clinical data comparing two different sizes of high-dose boost doses were analyzed in which significantly different bNED was observed at 2 years. RESULTS: The second method gave the definitive result of alpha/beta = 1.49 Gy (95% CI 1.25-1.76) and T(12) = 1.90 h (95% CI 1.42-2.86 h). The first method gave a range from 1.4 to 1.9 Gy and showed that if mean or median dose were used instead of prescribed dose, the estimate of alpha/beta would be substantially below 1 Gy. The third method, although based on early follow-up, was consistent with low values of alpha/beta in the region of 2 Gy or below. The estimate for T(12) is the first value reported for prostate tumors in situ. CONCLUSIONS: All the estimates point toward low values of alpha/beta, at least as low as the estimates of Brenner and Hall, and possibly lower than the expected values of about 3 Gy for late complications. Hypofractionation trials for intermediate-risk prostatic cancer appear to be indicated.

Algorithms↗
PubMed2001

A new approach to dose escalation in non-small-cell lung cancer.

PURPOSE: To describe the radiobiological rationale for dose-per-fraction escalation in non-small-cell lung cancer (NSCLC) and to devise a novel Phase I scheme to implement this strategy using advanced radiotherapy delivery technologies. METHODS AND MATERIALS: The data from previous dose escalation trials in NSCLC are reanalyzed to establish a dose-response relationship in this disease. We also use data relating prolongation in treatment time to survival to compute the potential doubling time for lung tumors. On the basis of these results, and using a Bayesian model to determine the probability of pneumonitis as a function of mean normalized lung dose, a dose-per-fraction escalation strategy is developed. RESULTS: Standard approaches to dose escalation using 2 Gy per fraction, five fractions per week, require doses in excess of 85 Gy to achieve 50% long-term control rate. This is partly because NSCLCs repopulate rapidly, with a 1.6% per day loss in survival from prolongation in overall treatment time beyond 6 weeks, and a cell doubling time of only 2.5 to 3.3 days. A dose-per-fraction escalation strategy, with a constant number of fractions, 25, and overall time, 5 weeks, is projected to produce tumor control rates predicted to be 10%-15% better than 2 Gy per fraction dose escalation, with equivalent late effects. This Phase I clinical study is divided into three parts. Step 1 examines the feasibility of the maximum breath-holding technique and junctioning of tomotherapy slices. Step 2 treats 10 patients with 30 fractions of 2 Gy over 6 weeks and then reduces duration to 5 weeks using fewer but larger fractions in 10 patients. Step 3 will consist of a dose-per-fraction escalation study on roughly 50 patients, maintaining 25 fractions in 5 weeks. Bayesian methodology (a modification of the Continual Reassessment Method) will be used in Step 3 to allow consistent and efficient escalation within five volume bins. CONCLUSION: A dose-per-fraction escalation approach in NSCLC should yield superior outcomes, compared to standard dose escalation approaches using a fixed dose per fraction, for a given level of pneumonitis and late toxicity. Highly conformal radiotherapy techniques, such as intensity modulated radiotherapy (IMRT) and helical tomotherapy with its adaptive capabilities, will be necessary to achieve significant dose-per-fraction escalation without unacceptable lung and esophageal morbidity.

Carcinoma, Non-Small-Cell Lung↗
PubMed2001

Accelerated hyperfractionated irradiation for advanced head and neck cancer: effect of shortening the median treatment duration by 13 days.

BACKGROUND AND PURPOSE: Optimal treatment duration of altered fractionation schedules in head and neck cancer is still undefined. A retrospective study on local tumor control, survival, and complications of accelerated hyperfractionated irradiation in head and neck cancer was undertaken to investigate whether there was an advantage in further shortening overall time from 6.5 weeks. METHODS: Four hundred nineteen consecutive male patients treated with radiation alone for cure 1987-1998 were analyzed. Patients with stage I, or treated also with brachytherapy implants or chemotherapy, were excluded. Treatment with accelerated hyperfractionation was performed twice daily, at a median of 1.6 Gy/fraction, to a total median dose of 68 Gy in 39 days. The patient population was divided into two groups: those with < or =39 days overall treatment time (group A, n = 227; median, 33 days) and those with >39 days (group B, n = 192; median, 46 days). Group A received a significant median tumor dose reduction of 7% compared with group B. RESULTS: The 7-year actuarial local control (LC) rates were 59% and 48% for groups A and B, respectively (p =.02). The actuarial LC rates for T1-2 patients were 79% and 74% at 7 years for groups A and B, respectively (p = NS). Similarly, for T3-4 patients, they were 47% and 35% (p =.02), respectively. The 7-year actuarial disease-free survival (DFS) rates for groups A and B were 39% and 26% (p =.01), respectively. For stage II patients, DFS was 62% and 60% at 7 years (p = NS) for groups A and B, respectively. And similarly, for stage III-IV patients, DFS was 33% and 20% (p =.04), respectively, at 7 years. LC and DFS rates at 7 years for T4 and stage IV patients, respectively, were significantly improved in group A. Cox regression analyses for LC showed that both T stage and overall time were significant prognostic factors. Similarly, UICC clinical stage and overall time were significant prognostic factors for DFS. There was no difference in acute morbidity between the two groups: 3% of patients in both groups required tube or parenteral feeding. The 7-year actuarial probability of RTOG/EORTC grades 3-5 late effects was 15% and 13%, respectively, for each group (p = NS). CONCLUSIONS: This study, with the limitations of a retrospective study, has shown a significant improvement in local tumor control and disease-free survival, in patients treated with shorter overall treatment times (median, 33 days) with an accelerated hyperfractionated irradiation schedule compared with those treated with a median duration of 46 days. No significant enhancement of acute reactions and late morbidity were observed with the shorter schedule.

Adult↗
PubMed2001

Perspectives on prostate cancer diagnosis and treatment: a roundtable.

This roundtable was held September 30, 2000. It addressed, first of all, the accuracy and proper interpretation of the available prostate-specific antigen assays. Dr. Brawer presented data to demonstrate the specificity of the complexed prostate-specific antigen assay. Dr. Stamey counterpoised evidence that pretreatment prostate-specific antigen levels less than 9 ng/mL are attributable to benign prostatic hyperplasia and therefore are of little value as an indicator of when to initiate treatment for prostate cancer. The other roundtable participants offered reviews and new data regarding hormonal therapy as primary or adjunctive treatment of prostate cancer. Dr. Fowler presented a large retrospective series of men with locally advanced prostate cancer for whom androgen ablation was the primary therapy. Dr. Droller discussed his center's experience in integrating hormonal therapy with brachytherapy. Finally, Dr. Messing reviewed and critiqued the evidence that the combination of hormonal and radiation therapy improves survival.

Aged↗
PubMed2001

Validation of Toolkit After-Death Bereaved Family Member Interview.

The purpose of this study was to examine the reliability and validity of the Toolkit After-Death Bereaved Family Member Interview to measure quality of care at the end of life from the unique perspective of family members. The survey included proposed problem scores (a count of the opportunity to improve the quality of care) and scales. Data were collected through a retrospective telephone survey with a family member who was interviewed between 3 and 6 months after the death of the patient. The setting was an outpatient hospice service, a consortium of nursing homes, and a hospital in New England. One hundred fifty-six family members from across these settings participated. The 8 proposed domains of care, as represented by problem scores or scales, were based on a conceptual model of patient-focused, family-centered medical care. The survey design emphasized face validity in order to provide actionable information to health care providers. A correlational and factor analysis was undertaken of the 8 proposed problem scores or scales. Cronbach's alpha scores varied from 0.58 to 0.87, with two problem scores (each of which had only 3 survey items) having a low alpha of 0.58. The mean item-to-total correlations for the other problem scores varied from 0.36 to 0.69, and the mean item-to-item correlations were between 0.32 and 0.70. The proposed problem scores or scales, with the exception of closure and advance care planning, demonstrated a moderate correlation (i.e., from 0.44 to 0.52) with the overall rating of satisfaction (as measured by a five-point, "excellent" to "poor" scale). Family members of persons who died with hospice service reported fewer problems in each of the six domains of medical care, gave a higher rating of the quality of care, and reported higher self-efficacy in caring for their loved ones. These results indicate that 7 of the 8 proposed problem scores or scales demonstrated psychometric properties that warrant further testing. The domain of closure demonstrated a poor correlation with overall satisfaction and requires further work. This survey could provide information to help guide quality improvement efforts to enhance the care of the dying.

Adult↗
PubMed2001

Ondansetron versus diclofenac sodium in the treatment of acute ureteral colic: a double blind controlled trial.

The aim of this study is to compare the effectiveness of the 5-HT3 antagonist, ondansetron and a non-steroidal anti-inflammatory agent, diclofenac sodium, as a pain reliever in the treatment of acute ureteral colic. Sixty four patients with severe or moderate pain who were clinically diagnosed as having ureteral colic associated with microscopic or gross hematuria were included in the study. Thirty three patients were administered ondansetron and 31 patients were administered diclofenac sodium. Exclusion critera were known kidney or liver disease causing dysfunction, known hypersensitivity to ondansetron or diclofenac sodium, pregnancy, lactation, duodenal ulcer or bleeding. After pain assessment with a verbal scale and a visual analog scale (VAS), we randomized patients and administered 8 mg ondansetron intravenously to 33 patients and 75 mg diclofenac sodium intramuscularly to 31 patients and pain scores were recorded every 15 minutes. If significant pain relief was not achieved within 60 minutes, i.v. meperidine was given as rescue pain medication. Ondansetron was effective as a primary pain reliever in 14 (42.4%) patients, whereas 19 patients required additional medication. Diclofenac sodium was effective as a primary pain reliever in 24 (77.4%) patients, whereas 7 patients required additional medication. Ondansetron was not superior to diclofenac sodium in relieving pain in patients with acute ureteral colic.

Acute Disease↗
PubMed2001

Effect of TNP-470 (AGM-1470) on the growth of rat rhabdomyosarcoma tumors of different sizes.

Potential anticancer therapy with the fumagillin analog TNP-470 was investigated in the present project using subcutaneously growing rhabdomyosarcomas in rats. Specifically, influences of different tumor sizes at the start of treatment as well as dose/schedules were evaluated with this angiogenesis inhibitor. The results show a significant (p = < or = 0.01) reduction of the growth rate, even for relatively large-sized (> 7 cm3) tumors, when 50 mg/kg TNP-470 was used every other day for up to 3 or 5 injections. With 30 mg/kg TNP-470 injections, effects were seen only with tumors measuring < 7 cm3. The histologic examinations demonstrate an increase in necrosis, both in the center and in the peripheral part of TNP-470-treated tumors. Overall, both tumor volume and drug dose determine treatment outcome with the rat rhabdomyosarcoma. The results suggest that angiogenesis inhibitors could represent a valid component in the treatment of progressive tumor growth, also of large tumors as often encountered in clinics. The antivasculature therapy might also improve hypoxia/necrosis-related therapeutic approaches.

Angiogenesis Inhibitors↗
PubMed2001

Gold allergy in North America.

OBJECTIVE: To determine the prevalence of allergic reactions to gold among patients tested by the North American Contact Dermatitis Group (NACDG) from 1996 to 1998. METHODS: This is a prospective analysis of patch test results from the 12 centers that comprise the NACDG. Gold was tested as gold sodium thiosulfate (0.5% in petrolatum [pet]), along with 49 other screening allergens, in patients presenting with possible contact dermatitis. RESULTS: Of 4,101 patients tested, 388 (9.5%) had a positive patch test result to gold. Women accounted for 62.8% of the subjects tested and 90.2% of patients positive to gold (P < .0001). The most common sites of dermatitis in gold-allergic patients were the hands (29.6%), face (19.3%), and eyelids (7.5%). Nickel and cobalt allergies, respectively, also were present in 33.5% and 18.3% of gold allergic individuals, as compared with 14.2% and 9.0% of the total population. Gold was the only positive reaction in 15.2% of the 388 patients. CONCLUSION: Gold is a more common allergen than previously reported and might cause facial and eyelid dermatitis. Hypersensitivity to gold is statistically linked to female gender and to allergic reactions to nickel and cobalt.

Allergens↗
PubMed2000

Improved results with accelerated hyperfractionated radiotherapy of advanced head and neck cancer.

A retrospective study on local tumor control, survival, and complications of conventional irradiation vs. accelerated hyperfractionated irradiation in patients with selected head and neck cancer sites was undertaken. A total of 1,007 consecutive patients treated with radiation alone for cure from 1974-1997 were analyzed. Excluded were female patients, patients with T1 stage of the vocal cord, and patients also treated with brachytherapy implants. There were 637 patients treated with conventional fractionation once daily (QD) in 1974-1997, at a median 2.1 Gy/fraction, to a total median dose of 71.4 Gy in a median overall time of 54 days. As was common before the mid-1980s, 39% and 22% of patients had overall times exceeding 8 and 9 weeks, respectively; 370 patients were treated with accelerated hyperfractionation twice daily (BID) from 1987-1997, at a median of 1.6 Gy/fraction, with an interfraction interval of 4-6 h, to a total median dose of 68 Gy in 40 days. Both schedules were well-balanced with respect to their pretreatment characteristics. Patients were not randomized into QD or BID. The 10-year actuarial probability of local control was 37% vs. 56% for QD and BID, respectively (P < 0.001), which reflects an increase of 19% or a 51% reduction in the local failure rate. Multivariate analysis revealed that T-stage, QD or BID schedule, and overall treatment time were significant independent factors for achieving local tumor control. The 10-year actuarial probability of cause-specific disease-free survival was 25% and 30% for QD and BID, respectively (P = 0.012). Acute morbidity was slightly higher with the BID schedule: patients requiring tube or parenteral feeding were 2.4% for BID and 0.5% for QD (P = 0.01). The 10-year actuarial probability of RTOG/EORTC Grades 3-5 late effects was 13% for both QD and BID. The lack of increase in late complications was most probably due to the lower total dose and dose per fraction in the BID schedule. This study has shown that accelerated hyperfractionated irradiation using two doses of 1.6 Gy each treatment day for less than 6 weeks in advanced head and neck cancer in male patients provides significantly better local tumor control and cause-specific disease-free survival, without increased late morbidity, than conventional fractionation delivered at the previously relaxed overall times of 7 weeks, but sometimes exceeding 8 or 9 weeks. Int. J. Cancer (Radiat. Oncol. Invest.) 90, 80-91, 2000.

Adult↗