PubMed Health⌕ Search

Biomedical subjects

T J Doyle

Publications and source records attributed to T J Doyle.

At least 19 recordsLinked to original sources
PubMed1998

Serial proton magnetic resonance spectroscopic imaging, contrast-enhanced magnetic resonance imaging, and quantitative lesion volumetry in multiple sclerosis.

Serial magnetic resonance (MR) studies that included proton MR spectroscopic imaging (MRSI), contrast-enhanced MR imaging (MRI), and lesion volumetric studies were performed on 25 multiple sclerosis (MS) patients with mild to modest clinical deficits. Each patient was scanned at varying intervals for up to 2 years, resulting in a total of 124 usable MR sessions. In these longitudinal studies, metabolic changes were observed on MRSI for some subjects before the appearance of lesions on MRI scanning. Regional changes in metabolite levels were observed to be dynamic and reversible in some patients. Transient changes in N-acetylaspartate (NAA) levels were sometimes found in acute plaques and indicate that a reduced NAA level does not necessarily imply axonal loss. An inverse correlation between the average NAA within the spectroscopic volume and the total lesion volume in the whole brain was observed. This negative correlation implies that NAA can serve as an objective marker of the disease burden. Strong lipid peaks in the absence of gadolinium enhancement and MRI-defined lesions were observed in 4 patients. This observation suggests that demyelination can occur independent of perivenous inflammatory changes and supports the presence of more than one pathophysiological process leading to demyelination in MS.

Adult↗
PubMed1998

Viral hemorrhagic fevers and hantavirus infections in the Americas.

Several arenaviruses and hantaviruses have been isolated in the Americas during the last 4 decades. These are rodent-borne viruses responsible for the South American hemorrhagic fevers (SAHF) and hantavirus pulmonary syndrome (HPS). Although rare, SAHF and HPS are serious illnesses with high mortality rates. Most viral isolates found in the Americas represent New World lineages of their respective viral families. Their presence in the Western hemisphere is likely ancient, their relationship with their rodent hosts is likely coevolutionary, and their recent detection forebodes the likelihood of detecting additional arena- and hantaviral species in the Americas.

Americas↗
PubMed1998

Analysis of host cells associated with the Spv-mediated increased intracellular growth rate of Salmonella typhimurium in mice.

The 90-kb virulence plasmid of Salmonella typhimurium encodes five spv genes which increase the growth rate of the bacteria within host cells within the first week of systemic infection of mice (P. A. Gulig and T. J. Doyle, Infect. Immun. 61:504-511, 1993). The presently described study was aimed at identifying the host cells associated with Spv-mediated virulence by manipulating the mouse host and the salmonellae. To test the effects of T cells and B cells on the Spv phenotype, salmonellae were orally inoculated into nude and SCID BALB/c mice. Relative to normal BALB/c mice, nude and SCID BALB/c mice were unaffected for splenic infection with either the Spv+ or Spv- S. typhimurium strains at 5 days postinoculation. When mice were pretreated with cyclophosphamide to induce granulocytopenia, there was a variable increase in total salmonella infection, but the relative splenic CFU of Spv+ versus Spv- S. typhimurium was not changed after oral inoculation. In contrast, depletion of macrophages from mice by treatment with cyclophosphamide plus liposomes containing dichloromethylene diphosphate resulted in equivalent virulence of Spv+ and Spv- salmonellae. To examine if the spv genes affected the growth of salmonellae in nonphagocytic cells, an invA::aphT mutation was transduced into Spv+ and Spv- S. typhimurium strains. InvA- Spv+ salmonellae were not significantly affected for splenic infection after subcutaneous inoculation compared with the wild-type strain, and InvA- Spv- salmonellae were only slightly attenuated relative to InvA+ Spv- salmonellae. Invasion-defective salmonellae still exhibited the Spv phenotype. Therefore, infection of nonphagocytes is not involved with the Spv virulence function. Taken together, these data demonstrate that macrophages are essential for suppressing the infection by Spv- S. typhimurium, by serving as the primary host cell for Spv-mediated intracellular replication and possibly by inhibiting the replication of salmonellae within other macrophages.

Agranulocytosis↗
PubMed1997

Systemic infection of mice by wild-type but not Spv- Salmonella typhimurium is enhanced by neutralization of gamma interferon and tumor necrosis factor alpha.

The spv genes of the virulence plasmid of Salmonella typhimurium and other nontyphoidal serovars of S. enterica are involved in systemic infection by increasing the replication rate of the bacteria in host tissues beyond the intestines. We considered the possibility that the Spv virulence function is to evade suppression by the host response to infection. To examine this possibility, gamma interferon (IFN-gamma) and/or tumor necrosis factor alpha (TNF-alpha) were neutralized in BALB/c mice by intraperitoneal administration of monoclonal antibodies. Neutralization of IFN-gamma and/or TNF-alpha resulted in increased splenic infection with wild-type salmonellae after oral inoculation; however, Spv- salmonellae were defective at increasing splenic infection in cytokine-depleted mice. The use of a temperature-sensitive marker plasmid, pHSG422, indicated that neutralization of IFN-gamma caused less killing of wild-type S. typhimurium, while neutralization of TNF-alpha resulted in an increased in vivo replication rate for wild-type salmonellae. These results demonstrate that the Spv virulence function is not to evade suppression of bacterial infection normally mediated by IFN-gamma or TNF-alpha.

Animals↗
PubMed1997

The association of drinking water source and chlorination by-products with cancer incidence among postmenopausal women in Iowa: a prospective cohort study.

OBJECTIVES: This study assessed the association of drinking water source and chlorination by-product exposure with cancer incidence. METHODS: A cohort of 28,237 Iowa women reported their drinking water source. Exposure to chlorination by-products was determined from statewide water quality data. RESULTS: In comparison with women who used municipal ground-water sources, women with municipal surface water sources were at an increased risk of colon cancer and all cancers combined. A clear dose-response relation was observed between four categories of increasing chloroform levels in finished drinking water and the risk of colon cancer and all cancers combined. The relative risks were 1.00, 1.06, 1.39, and 1.68 for colon cancer and 1.00, 1.04, 1.24, and 1.25 for total cancers. No consistent association with either water source or chloroform concentration was observed for other cancer sites. CONCLUSIONS: These results suggest that exposure to chlorination by-products in drinking water is associated with increased risk of colon cancer.

Chlorine↗
PubMed1997

Officers, trustees, directors beware! IRS-imposed 'intermediate' sanctions can be severe.

The IRS pushed for intermediate sanctions for some time. It now has them, and we should assume that it will use them. If you're an insider to a 501(c)(3) or 501(c)(4) organization, who is compensated by or has business dealings with the organization, or if you are an officer, director, or trustee of such an organization, study the intermediate sanctions law and congressional comment on it. Think through its possible applications and ramifications. With the assistance of legal counsel, you may also want to carefully review your organization's indemnification policies and understand how they relate to intermediate sanctions taxes. Finally, keep your ear to the ground for further IRS interpretations and application of this important new tax law.

Humans↗
PubMed1996

Tea consumption and cancer incidence in a prospective cohort study of postmenopausal women.

Tea has consistently been shown to inhibit the occurrence of tumors in experimental animals. The evidence for such a beneficial effect in humans, however, is limited. The authors examined the association between non-herbal tea consumption and cancer incidence in a prospective cohort study of 35,369 postmenopausal Iowa women. In this cohort, information on the frequency of tea drinking and other dietary and lifestyle factors was collected by mailed survey in 1986. After 8 years of follow-up, 2,936 incident non-skin cancer cases were ascertained in this cohort through the State Health Registry of Iowa. Proportional hazards regressions were used to derive adjusted relative risks and 95% confidence intervals for the association between tea consumption and cancer incidence. After controlling for confounding factors, the authors found that regular tea consumption was related to a slight, but not statistically significant, reduced incidence of all cancers combined. Inverse associations with increasing frequency of tea drinking were seen for cancers of the digestive tract (p for trend, 0.04) and the urinary tract (p for trend, 0.02). For women who reported drinking > or = 2 cups (474 ml) of tea per day, compared with those who never or occasionally drank tea, the relative risk for digestive tract cancers was 0.68 (95% confidence interval (CI) 0.47-0.98) and for urinary tract cancers, 0.40 (95% CI 0.16-0.98). Similar inverse associations were seen for specific digestive and urinary tract cancers, although site-specific analyses were not statistically significant. No appreciable association of tea drinking was found with melanoma, non-Hodgkin's lymphoma, or cancers of the pancreas, lung, breast, uterine corpus, or ovary. This study suggests that tea, one of the most popular beverages consumed worldwide, may protect against some cancers in postmenopausal women.

Aged↗
PubMed1995

Accelerated fractionation radiotherapy and concomitant chemotherapy in patients with stage IV inoperable head and neck cancer.

BACKGROUND: Stage IV inoperable head and neck cancer has a 2-year mortality rate of greater than 70% when treated with conventional radiotherapy. A Phase II study was undertaken to evaluate the effects of concomitant chemotherapy and accelerated, interrupted, twice-a-day radiotherapy on tumor response, locoregional control, survival, and morbidity. METHODS: Thirty-four patients with Stage IV inoperable squamous cell carcinoma of the head and neck and a minimum follow-up of 36 months were evaluated. Concomitant chemoradiotherapy was administered during weeks 1, 3, and 5 (with planned breaks during weeks 2 and 4), consisting of cisplatin 60 mg/m2 on day 1, continuous 5-day infusion of 5-fluorouracil, 750 mg/m2 per day, and radiotherapy, 2 Gy twice a day, more than 6 hours apart, followed by 3 days of radiation therapy alone (final "boost") in week 6, for a total dose of 70 Gy and treatment duration of 5 1/2 weeks (38 days). RESULTS: Twenty-seven patients achieved a clinical complete response (82%). Actuarial locoregional control at 3 years was 73% and the actuarial 3-year survival probability, including all deaths, was 38%. All locoregional recurrences were manifested within 12 months. Of the 20 deaths, 12 were tumor related (locoregional and/or metastatic), 3 were treatment related, and 5 were due to other causes. Acute toxicity consisted of grade 3 mucositis and dysphagia and grade 2-3 leukopenia, not requiring treatment interruption or cessation. CONCLUSION: Concomitant accelerated radiation therapy and chemotherapy is a feasible treatment approach in this prognostically poor patient population, yielding dramatic tumor responses and impressive locoregional control at the cost of somewhat increased acute toxicity. Although serious late complications have not been observed, caution should be exercised in view of the relatively short follow up.

Adult↗
PubMed1995

Retinol, antioxidant vitamins, and cancers of the upper digestive tract in a prospective cohort study of postmenopausal women.

Very few prospective studies have reported previously on the association of micronutrient intake and the risk of cancers of the upper digestive tract (mouth, pharynx, esophagus, and stomach) in western populations. During 7 years of follow-up in the Iowa Women's Health Study, from 1986-1992, 59 of the 34,691 at-risk cohort members developed cancers of the upper digestive tract. The association of retinol and antioxidant vitamins (carotene and vitamins C and E) were evaluated separately for cancers of the mouth/pharynx/esophagus (n = 33) and stomach (n = 26). After adjustment for age, smoking, and total energy intake, higher intakes of carotene and vitamins C and E were related to lower risks of both oral/pharyngeal/esophageal and gastric cancers, while retinol was associated with lower risk of gastric cancer only. The dose-response relation between gastric cancer risk and intake of carotene was clear and statistically significant, with relative risks of 0.6 and 0.3, respectively, observed among women in the upper two versus the lowest tertiles of intake. This study provides further evidence that higher intake of antioxidant vitamins may be important in the prevention of cancers of the upper digestive organs.

Aged↗
PubMed1995

Dietary intake of energy and animal foods and endometrial cancer incidence. The Iowa women's health study.

To assess the relations of dietary intake of energy and animal foods to endometrial cancer risk, dietary analyses were performed using data from a prospective cohort study of over 23,000 postmenopausal Iowa women who responded to a mailed questionnaire in 1986 and were followed through the end of 1992 for cancer incidence and total mortality. Usual intakes of 127 food items were measured by a semiquantitative food frequency questionnaire. After 7 years of follow-up, 216 incident endometrial cancer cases had been ascertained. There was no statistically significant association of dietary intake of energy and most animal foods with endometrial cancer incidence over the 7-year follow-up period. Stratified analyses, however, suggested that intake of energy from plant foods may be inversely associated with endometrial cancer risk in the latter years of follow-up (trend test, p = 0.03), while high intake of energy and foods from animal sources related to slightly, but not statistically significantly, elevated risks of this cancer in the earlier years of follow-up. The only significant dose-response relation observed in food group analyses was for processed meat and fish, for which a significant 50% excess risk of endometrial cancer was found among women in the highest versus the lowest tertile of intake. This study suggests that dietary intake of energy and most animal foods is not related to or is only weakly related to the risk of endometrial cancer among postmenopausal US women.

Cohort Studies↗
PubMed1995

Relative concentrations of proton MR visible neurochemicals in gray and white matter in human brain.

The relative distributions of N-acetylaspartate (NAA) + N-acetylaspartylglutamate (NAAG), creatine + phosphocreatine (Cr/PCr), and choline (Cho) in the gray and white matter of human brain were determined by utilizing proton magnetic resonance spectroscopic imaging (SI). The SI data was processed using an automated spectroscopic image processing algorithm, and image segmentation was performed using a supervised technique. Linear regression analysis indicated that the NAA + NAAG (2.01 ppm) and Cr/PCr (3.02 ppm) peaks are greater in gray matter compared with white matter. The large intersubject variation observed in the Cho (3.20 ppm) resonance prevented the assessment of its regional distribution with confidence.

Adult↗
PubMed1995

Automated proton spectroscopic image processing.

An automatic data processing and display protocol for proton magnetic resonance spectroscopic imaging is described. The spectroscopic images are generated using the fitted peak areas of phased metabolite resonances using the Levenberg-Marquardt algorithm. This automated spectroscopic image processing is tested and evaluated using phantom and human brain data. This algorithm is robust, simple to use, and minimizes user bias in processing and quantifying serial changes of metabolite levels in brain tissue.

Algorithms↗
PubMed1993

The Salmonella typhimurium virulence plasmid increases the growth rate of salmonellae in mice.

The virulence plasmids of Salmonella typhimurium and other invasive Salmonella serovars have long been associated with the ability of these bacteria to cause systemic infection beyond the intestines in orally inoculated animals. Genetic analysis of virulence genes on the high-molecular-weight plasmids has revealed that no more than five genes spanning a 6.2-kb region are sufficient to replace the entire plasmid for conferring virulence. However, the exact virulence function(s) encoded by these genes has not been elucidated. In this report, we measured the possible effect of the virulence plasmid on the growth rate of S. typhimurium in mice by two complementary procedures. The first procedure used segregation of a temperature-sensitive plasmid in vivo to provide a measure of bacterial divisions and the number of recovered marker plasmid-containing salmonellae as a measure of killing. In the second procedure, aroA deletions were transduced into virulence plasmid-containing and plasmid-cured S. typhimurium. Since AroA- salmonellae are inhibited for growth in vivo, if the virulence plasmid affected only growth rate, no difference in the recoveries of the paired AroA- strains would be seen. Virulence plasmid-containing S. typhimurium segregated the marker plasmid more rapidly than did the virulence plasmid-cured strain, and AroA- derivatives of both strains were recovered equally from mice. Therefore, the S. typhimurium virulence plasmid increased growth rate but had no detectable effect on killing or bacterial movement into deep tissues. To examine whether the plasmid accomplished this function by affecting the intracellular/extracellular location of bacteria, orally infected mice were injected with gentamicin to kill the extracellular bacteria. Wild-type and plasmid-cured S. typhimurium strains were equally resistant to gentamicin in vivo and hence most likely located intracellularly to equal degrees. When wild-type and plasmid-cured S. typhimurium strains were sequestered within peritoneal chambers in mice, the resulting extracellular growth was equal. Therefore, the virulence plasmid increases the growth rate of S. typhimurium in mice, probably within mouse cells.

Animals↗
PubMed1993

A successful physician-led multidisciplinary approach to process improvement for inpatient chemotherapy.

In 1991, Henry Ford Hospital established a physician-led, multidisciplinary chemotherapy DRG task force charged with examining and improving the clinical and support processes relating to inpatient chemotherapy. While the goal of this effort was to improve cost management, quality improvement philosophy and methods were applied. This task force developed two short-stay protocols, reducing the length of hospitalization from three days to one for high-dose cisplatin regimens, and from five to only two days for combined chemotherapy/radiation therapy regimens. This article shares insights regarding the types of improvements and methods that were used, the effective involvement of physicians, and the use of administrative and staff support to accelerate the improvement effort and leverage clinicians' time.

Cisplatin↗
PubMed1990

MPTP, MPDP+ and MPP+ cause decreases in dopamine content in mouse brain slices.

MPTP causes a Parkinson's disease-like syndrome in which the dopamine content of the nigrostriatal system decreases. We have studied the relationship between physiological changes and dopamine content using a brain slice preparation developed for electrophysiological studies of corticostriate and nigrostriatal synaptic transmission. We report that MPTP, MPDP+ and MPP+ cause significant decreases in dopamine content of mouse brain slices. We also report that compounds (pargyline and GBR-12909) which block MPTP's toxicity in vivo and prevent non-reversible changes in synaptic transmission are not able to alter MPTP's ability to decrease slice dopamine contents. This indicates that the dopamine content in slices may not be causally related to the non-reversible decrease in synaptic transmission or in vivo neurotoxicity.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1988

MPTP in mice: treatment, distribution and possible source of contamination.

Mice were treated daily with [3H]MPTP (30 mg/kg, 1 uCi, s.c.) for 1, 3, and 10 days to determine the fate and localization of tritiated compounds. An untreated mouse was housed either in the same cage ("cage-mate control") or in an adjacent cage separated by mesh-wire ("near-neighbor control"). The radioactivity measured in blood, brain, liver, and remaining body of [3H]MPTP-treated mice was dependent on the total dose of the drug the animals received and did not vary with the type of tissue analyzed. Significant amounts of radioactivity were found in the tissues of the "cage-mate control" mice, but not of the "near-neighbor control" mice. The route of transmission appears to be through the urine, as the urine of [3H]MPTP-treated mice was highly radioactive after the drug injection. Only traces of radioactivity were found in their feces and there was no increase in the background radiation in the environment of the cages, indicating that the tritiated compounds were not exhaled. Proper disposal of urinary products of MPTP-treated animals is therefore necessary to reduce the risk of possible drug contamination in humans.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗