The monitoring of the effects of food components on immunoreactivity in experimental animals.
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Allergens↗
Biomedical subjects
K Miller
Publications and source records attributed to K Miller.
Pharmacokinetics of pentoxifylline and its metabolites in healthy mice and in mice infected with Candida albicans.
Pentoxifylline has immunomodulatory properties and has been shown to decrease organ damage and improve survival in animals with gram-negative sepsis or endotoxemia. This effect is mediated by a reduction in endotoxin-induced production of tumor necrosis factor alpha (TNF-alpha) by the host. In earlier studies, we observed an unexpected increase in mortality in mice infected with Candida albicans that were given pentoxifylline even though concentrations of TNF-alpha in serum were not affected. The current study was designed to determine whether the pharmacokinetics of pentoxifylline and its metabolites were altered in C. albicans-infected mice and, if so, whether these changes could have contributed to the increased mortality. Noninfected mice and mice infected with C. albicans were treated with pentoxifylline (60 mg/kg of body weight) intraperitoneally every 8 h. Serum was collected from animals after one (day 0), four (day 1), or seven (day 2) injections of pentoxifylline or saline (controls). The first dose was administered 6 h after C. albicans infection. Serum was pooled. Concentrations of pentoxifylline and metabolites I, IV, and V were determined by capillary gas chromatography. Renal function and hepatic profiles were assessed. Pharmacokinetic parameters (maximum concentration of pentoxifylline in serum, half-life, and area under the concentration-time curve from 0 h to infinity [AUC(0)-infinity]) for all noninfected mice were similar and did not differ from those for day 0-infected mice. For day 1-infected mice, values of these three pharmacokinetic parameters for pentoxifylline and metabolite I were increased two- to fourfold over values for noninfected and day 0-infected mice. For metabolites IV and V, the AUC(0)-infinity was increased approximately eightfold over control values. In addition, day 1-infected mice demonstrated evidence of renal and hepatic dysfunction. In summary, C. albicans infection produced marked changes in the pharmacokinetics of pentoxifylline and its metabolites in the mice. The high concentrations of pentoxifylline and its metabolites in serum attained in infected mice may have contributed to the increased mortality of mice with systemic candidiasis.
Adjuvants, Immunologic↗
Retroviral diversity and distribution in vertebrates.
We used the PCR to screen for the presence of endogenous retroviruses within the genomes of 18 vertebrate orders across eight classes, concentrating on reptilian, amphibian, and piscine hosts. Thirty novel retroviral sequences were isolated and characterized by sequencing approximately 1 kb of their encoded protease and reverse transcriptase genes. Isolation of novel viruses from so many disparate hosts suggests that retroviruses are likely to be ubiquitous within all but the most basal vertebrate classes and, furthermore, gives a good indication of the overall retroviral diversity within vertebrates. Phylogenetic analysis demonstrated that viruses clustering with (but not necessarily closely related to) the spumaviruses and murine leukemia viruses are widespread and abundant in vertebrate genomes. In contrast, we were unable to identify any viruses from hosts outside of mammals and birds which grouped with the other five currently recognized retroviral genera: the lentiviruses, human T-cell leukemia-related viruses, avian leukemia virus-related retroviruses, type D retroviruses, and mammalian type B retroviruses. There was also some indication that viruses isolated from individual vertebrate classes tended to cluster together in phylogenetic reconstructions. This implies that the horizontal transmission of at least some retroviruses, between some vertebrate classes, occurs relatively infrequently. It is likely that many of the retroviral sequences described here are distinct enough from those of previously characterized viruses to represent novel retroviral genera.
Amino Acid Sequence↗
Imaging modalities in Peyronie's disease. An intrapersonal comparison of ultrasound sonography, X-ray in mammography technique, computerized tomography, and nuclear magnetic resonance in 20 patients.
OBJECTIVE: Peyronie's disease is an ill-understood condition afflicting men in their 40s with the reported age ranging from 18 to 68 years. It is characterized by a plaque in the tunica albuginea which leads to penile deformity making sexual intercourse difficult if not impossible and is often accompanied by severe pain upon erection in the early stage; erectile dysfunction is present in about 2% of cases. Diagnosis rests upon medical history, clinical examination with plaque palpation and autophotography in two planes. These diagnostic steps are not plaque-specific and therefore we wanted to assess which imaging modalities would allow for an objective determination of the plaque status. MATERIALS AND METHODS: We evaluated 20 patients with Peyronie's disease. All patients underwent clinical examination including autophotography and the subsequent use of the following imaging techniques: (1) ultrasound (US) using a 7.5-MHz transducer with a profile for semiquantitative density analysis; (2) X-ray in mammography technique in two planes; (3) computerized tomography (CT) with a density profile, and (4) magnetic resonance imaging (NMR). RESULTS: (1) Degree of deviation: Penile deviation ranged from 15 degrees to 63 degrees. It was best assessed using radiography in mammography technique reflecting the results obtained by autophotography. (2) Calcifications: Plaque calcifications were seen in 12 patients, 8 had no calcifications but thickening of the tunica albuginea only, 2 also had a fibrosis of the corpus cavernosum distant to the plaque. Calcifications were visualized using ultrasound sonography (12/12), radiographically (12/12), CT (12/12), NMR (9/12). Thickening of the tunica albuginea only was visualized using ultrasound sonography (7/8), radiographically (0/8), CT (2/8), NMR (6/8). (3) Morphological pattern in ultrasound: Three distinct patterns could be detected: (type 1) the plaque appeared as a thickening of the tunica albuginea without acoustic shadowing and only minimal density increase in the histogram profile; (type 2) moderately calcified plaque with typical ultrasound shadow but minimal density increase in the density profile; (type 3) severely calcified plaque with typical acoustic shadowing and density increase in the histogram profile. (4) Plaque inflammation: Only NMR with gadolinium DTPA showed periplaque inflammation. CONCLUSIONS: High-resolution ultrasound sonography is the best imaging modality in assessment of plaques. NMR is the modality of choice to monitor the inflamed plaque. X-ray in mammography technique and CT are not necessary in daily routine.
Calcinosis↗
Transdermal testosterone administration in women with acquired immunodeficiency syndrome wasting: a pilot study.
Although human immunodeficiency virus (HIV) disease is increasing rapidly among women, no prior studies have investigated gender-based therapeutic strategies for the treatment of acquired immunodeficiency syndrome (AIDS) and its complications in this population. Markedly decreased serum androgen levels have been demonstrated in women with AIDS and may be a contributing factor to the wasting syndrome in this population. To assess the effects of androgen replacement therapy in women with AIDS wasting, we conducted a randomized, placebo-controlled, pilot study of transdermal testosterone administration. The primary aim of the study was to determine efficacy in terms of the change in serum testosterone levels, safety parameters and tolerability. A secondary aim of the study was to investigate testosterone effects on weight, body composition, quality of life, and functional indexes. Fifty-three ambulatory women with the AIDS wasting syndrome defined as weight less than 90% of ideal body weight or weight loss of more than 10% of the preillness maximum, free of new opportunistic infection within 6 weeks of study initiation, and with screening serum levels of free testosterone less than the mean of the normal reference range (< 3 pg/mL) were enrolled in the study. Subjects were age 37 +/- 1 yr old (mean +/- SEM), weighed 92 +/- 2% of ideal body weight, and had lost 17 +/- 1% of their maximum weight. CD4 count was 324 +/- 36 cells/mm3, and viral burden was 102,382 +/- 28,580 copies. Subjects were randomized into three treatment groups, in which two placebo patches (PP), one active/one placebo patch (AP group), or two active patches (AA group) were applied twice weekly to the abdomen for 12 weeks. The expected nominal delivery rates of testosterone were 150 and 300 microg/day, respectively, for the AP and AA groups. Forty-five subjects completed the study (PP group, n = 13; AP group, n = 14; AA group, n = 18). Two additional subjects from the PP group and two from the AP group were included in the intent to treat analysis. Serum free testosterone levels increased significantly from 1.2 +/- 0.2 to 5.9 +/- 0.8 pg/mL (AP) and from 1.9 +/- 0.4 to 12.4 +/- 1.6 pg/mL (AA) in response to testosterone administration (P < 0.0001 for comparison of AA vs. PP and AP vs. PP; normal range, 1.3-6.8 pg/mL). Testosterone administration was generally well tolerated locally and systemically, with no adverse trends in hirsutism scores, lipid profiles, or liver function tests. Weight increased significantly in the AP group (1.9 +/- 0.7 kg) vs. the PP group (0.6 +/- 0.8 kg; P = 0.043), but did not increase significantly in the AA group (0.9 +/- 0.4 kg; P = 0.263 vs. PP, by mixed effects model assessing the interaction of time and treatment on all available data, one-tailed test). Improved social functioning (P = 0.024, by one-tailed test) and a trend toward improved pain score (P = 0.059) were observed in the AP vs. the PP-treated patients (RAND 36-Item Health Survey questionnaire). Five of six previously amenorrheic patients in the AP group had spontaneous resumption of menses compared to only one of four amenorrheic patients in the AA group (P = 0.045 for comparison of actual number of periods during the study). This study is the first investigation of testosterone administration in women with AIDS wasting. We demonstrate a novel method to augment testosterone levels in such patients that is safe and well tolerated during short term administration. At the lower of the two doses administered in this study, testosterone therapy was associated with positive trends in weight gain and quality of life. Higher, more supraphysiological, dosing was not associated with positive trends in weight or overall well-being. These data suggest that testosterone administration may improve the status of women with AIDS wasting. Further studies are needed to assess the effects of testosterone on weight in HIV-infected women and to define the optimal therapeutic window for test
Administration, Cutaneous↗
The average dose-area product at intravenous urography in 205 adults.
The intravenous urography (IVU) is the most important and most frequently performed radiological examination in urology. This prospective study determined the dose-area product as a measurement of radiation dose in 205 adult patients undergoing IVU. Average dose-area product was 1017 cGy cm2. An average 3.7 radiographs were obtained per patient. Tomographic views were required in only 8.8% of cases. Radiation dose is dependent not only on the number and size of the obtained radiographs, but on the physical constitution of the patient. The dose-area products measured show a clear relationship to the body weight of the patient.
Adolescent↗
Aromatic hydrocarbon receptor polymorphism: development of new methods to correlate genotype with phenotype.
Differential CYP1A1 inducibility, reflecting variations in aromatic hydrocarbon receptor (AHR) affinity among inbred mouse strains, is an important determinant of environmental toxicity. We took advantage of the Ahr polymorphism in C57BL/6 and DBA/2 mice to develop an oligonucleotide-hybridization screening approach for the rapid identification of DNA sequence differences between Ahr alleles. Oligonucleotides containing single-base changes at polymorphic sites were immobilized on a solid support and hybridized with C57BL/6 or DBA/2 AHR cDNA radiolabeled probes. The observed hybridization patterns demonstrate that this approach can be used to detect nucleotide differences in the Ahr coding region with very high accuracy. In parallel experiments, we used a yeast two-hybrid system to assess phenotypic differences in AHR function. AHR activation, as measured by beta-galactosidase reporter activity in Saccharomyces cerevisiae strain SFY526, was determined following treatment with varying doses of the AHR ligand beta-naphthoflavone (BNF). We found that the C57BL/6 AHR has about a 15-fold higher affinity for BNF than the DBA/2 AHR, in much better agreement with results reported for whole-animal studies than the values observed by in vitro ligand-binding assays. Using C57BL/6 and DBA/2 AHR chimeric proteins, we also confirmed the previously reported observation that an A375V change is principally responsible for the high- to low-affinity AHR phenotype. There has been no straightforward method to reliably and reproducibly phenotype large numbers of humans for CYP1A1 inducibility or AHR affinity. Screening human AHR cDNAs by oligonucleotide-hybridization and yeast two-hybrid methodologies will be invaluable for the rapid and unequivocal determination of changes in DNA sequence and receptor-ligand affinities associated with human AHR polymorphisms.
Animals↗
Hospital-wide standardization effort nets big savings.
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Cost Savings↗
Redesigning primary care via member profiles.
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Arizona↗
Innovative informatics education: aligning theory and practice through strategic partnership.
The University of Victoria School of Health Information Science (HINF) and The Toronto Hospital (TTH) have formed a strategic partnership to align current information management theory with practical experience. The fourth year undergraduate course in Information Management and Technology was redesigned to include a joint research project with TTH. Staff from TTH were paired with groups of 2-3 students to explore current information management issues. Technology such as electronic mail and conference calls enabled timely communication. Final results were presented via video conference at the end of the term and jointly graded by the professor and hospital staff. Over the three years, a variety of projects have been undertaken and the approach has been refined. Each year offered new insight to both students and staff. Findings include several key success factors: senior level support, early planning, timely communication, access to technology, and opportunity for staff and student feedback. This partnership offers strategic advantages to both organizations in innovation, mutual learning, recruiting, and partnership. Next steps include expansion of the project to a regional model and seminars on current information management topics for TTH staff.
Canada↗
Laparoscopic retroperitoneal lymph node dissection in clinical stage I nonseminomatous germ cell tumor: a minimal invasive alternative.
OBJECTIVE: To evaluate modified laparoscopic retroperitoneal lymph node dissection (LRPLND) performed for stage I nonseminomatous germ cell tumor. METHODS: Between December 1993 and January 1996, modified unilateral laparoscopic retroperitoneal lymph node dissection was performed on 13 patients with nonseminomatous germ cell tumor of the testis. In 8 patients, the tumor was on the right side, and in 5, on the left. RESULTS: The procedure was completed in 12 patients at a mean operating time of 292 min (range: 210-400 min). The mean estimated blood loss was 250 ml. The mean hospital stay was 6.4 days. Conversion to open surgery was required in one patient because of an uncontrollable venous bleeding. No other major complications occurred. Antegrade ejaculation was preserved in 10 patients, and the last 3 patients have not yet been addressed now. CONCLUSIONS: Our results demonstrate that LRPLND is an accurate and reliable staging procedure with low morbidity, which allows quick patient discharge and rapid return to normal activity. For further evaluation, long follow-up in larger groups of patients is required.
Adult↗
AstraZeneca and breast cancer advocacy: why is advocacy a good idea for business and for cancer associations, and how does such an alliance work for mutual benefit?
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Journal Article↗
Higher cerebrospinal fluid MHPG in subjects with dementia of the Alzheimer type. Relationship with cognitive dysfunction.
The authors sought to determine the relationships between cerebrospinal fluid (CSF) levels of three neurotransmitter monoamine metabolites and cognitive function. CSF was collected from subjects with dementia of the Alzheimer's type ([DAT] n = 28) and control subjects (n = 10) for determination of CSF 5-hydroxyindole acetic acid (5-HIAA), 3-methoxy-4-hydroxy-phenylglycol (MHPG), and homovanillic acid (HVA) levels. All subjects underwent systematic assessment to determine cognitive function. Subjects with DAT had higher concentrations of CSF MHPG. In the overall sample, cognitive function was inversely correlated with CSF levels of MHPG but not with 5-HIAA or HVA. Within the DAT sample, these correlations did not achieve significance.
Aged↗
[Concentration of copper and ceruloplasmin in serum of patients treated for epilepsy].
In 54 epileptic patients (28 females and 26 males) aged 21-48, serum copper (Cu) and ceruloplasmin (Crl) concentrations were assessed. Comparing with control group mean serum Cu and Crl concentrations were significantly increased. We suspect that antiepileptic drugs may influence the serum Cu and Crl concentrations by hepatic enzymes induction. Clinical picture of epilepsy and treatment duration does not influence serum Cu and Crl concentrations.
Adult↗
Comparison of human telomerase RNA and telomerase activity in urine for diagnosis of bladder cancer.
New, noninvasive methods for the early detection of urothelial carcinomas of the urinary bladder are needed for the diagnosis, follow-up, and screening of patients with bladder cancer. Detection of the enzyme telomerase in urine could offer these new diagnostic possibilities. The standard technique for detecting telomerase activity is the telomeric repeat amplification protocol (TRAP assay). Because of the instability of the ribonucleoprotein telomerase in an aggressive medium, such as urine, investigations conducted to date have yielded nonuniform or even contradictory findings. This study compares the detection of human telomerase RNA (hTR) by reverse transcriptase-PCR (RT-PCR) with detection of telomerase activity by the TRAP assay in the diagnosis of urothelial carcinoma of the urinary bladder. Sedimented cells obtained from urine of 30 patients with urothelial carcinoma, 15 patients with benign urological disorders, 3 patients as part of follow-up for malignant disease, and 20 healthy subjects were examined for the presence of hTR and for telomerase activity (TRAP). In patients with bladder cancer, telomerase activity was detected by the TRAP assay in only 2 of 30 specimens (7%). However, increased levels of hTR were detected by RT-PCR in 25 of the same 30 cases (83%). For patients with benign urological disorders, such as urolithiasis or urinary tract infections, hTR was detected in samples obtained from 4 of 15 patients (27%). Low hTR expression levels were found in 15% of the healthy controls. The detection of hTR by RT-PCR represents a promising new method for detecting malignant cells in urine.
Humans↗
Is detrusor instability a premature variant of normal micturition reflex?
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Adult↗
Differential utilization of CCR5 by macrophage and T cell tropic simian immunodeficiency virus strains.
Certain chemokine receptors serve as cofactors for HIV type 1 envelope (env)-mediated cell-cell fusion and virus infection of CD4-positive cells. Macrophage tropic (M-tropic) HIV-1 isolates use CCR5, and T cell tropic (T-tropic) strains use CXCR4. To investigate the cofactors used by simian immunodeficiency viruses (SIV), we tested four T-tropic and two M-tropic SIV env proteins for their ability to mediate cell-cell fusion with cells expressing CD4 and either human or nonhuman primate chemokine receptors. Unlike HIV-1, both M- and T-tropic SIV envs used CCR5 but not CXCR4 or the other chemokine receptors tested. However, by testing a panel of CCR5/CCR2b chimeras, we found that the structural requirements for CCR5 utilization by M-tropic and T-tropic SIV strains were different. T-tropic SIV strains required the second extracellular loop of CCR5 whereas a closely related M-tropic SIV strain could, like M-tropic HIV-1 strains, use the amino-terminal domain of CCR5. As few as two amino acid changes in the SIV env V3 domain affected the regions of CCR5 that were critical for fusogenic activity. Receptor signaling was not required for either fusion or infection. Our results suggest that viral tropism may be influenced not only by the coreceptors used by a given virus strain but also by how a given coreceptor is used.
Animals↗
Effect of saponin on the transmucosal passage of beta-lactoglobulin across the proximal small intestine of normal and beta-lactoglobulin-sensitised rats.
The ability of saponins and glycoalkaloids to permeabilise the mammalian intestinal barrier has been previously demonstrated in vitro, leading to the hypothesis that membranolytic saponins may facilitate transfer to the tissues of otherwise excluded macromolecules. An enhanced uptake of, for instance, potentially allergenic species from the lumen is one of the factors that may affect the induction of food allergy, and its presentation in already sensitised individuals. In the experiments described here, an increase in the transmucosal uptake of the milk allergen beta-lactoglobulin (beta LG) was assessed in non-sensitised and sensitised Brown Norway rats in the presence of Gypsophila saponin. Isolated jejunal loops were exposed in vivo to either beta LG followed by saponin, saponin followed by beta LG or the two compounds simultaneously. Portal vein blood samples were collected and assayed for beta LG and rat mucosal mast cell protease (RCMP II) activity. Mucosal tissue was also examined histologically and assayed for histamine content. Sham-operated animals, exposed to physiological buffer alone, were included as controls and beta LG measurements corrected for this component which was negligible. No transfer of beta LG occurred in the absence of saponin in non-sensitised rats, whereas a significant enhancement was observed in the presence of saponin. beta LG was detected in the portal circulation of sensitised rats exposed to beta LG alone; however addition of saponin to the intestinal lumen further enhanced this uptake, possibly by an independent mechanism. Histological examination of the mucosal epithelium exposed to saponin revealed damage, especially at the villus tips. Mucosal histamine and serum RCMP II concentrations were consistent with the differences observed between sensitised and non-sensitised animals. It is concluded that exposure to food constituents capable of permeabilising the mucosal epithelium may increase the risk of sensitisation to dietary antigens.
Animals↗