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Biomedical subjects

R Moriarty

Publications and source records attributed to R Moriarty.

10 recordsLinked to original sources
PubMed2000

Prevention of N-methyl-N-nitrosourea-induced mammary carcinogenesis in rats by 1alpha-hydroxyvitamin D(5).

BACKGROUND: Although the active form of vitamin D, i.e., 1,25-dihydroxyvitamin D(3), is a potent cell-differentiating agent, its use in cancer prevention or therapy is precluded because it induces excessive blood calcium levels (hypercalcemia). However, less calcemic or noncalcemic synthetic analogues of vitamin D(3) are poorly effective against mammary carcinogenesis. We synthesized an analogue of vitamin D(5), 1alpha-hydroxy-24-ethylcholecalciferol (1alpha-hydroxyvitamin D(5)), which was less calcemic than 1,25-dihydroxyvitamin D(3) and prevented the development of precancerous lesions in mammary glands. Here, we evaluate its efficacy in an experimental rat mammary carcinogenesis model. METHODS: Sprague-Dawley rats were treated with 1alpha-hydroxyvitamin D(5) beginning 2 weeks before carcinogen treatment. Animals received an intravenous injection of N-methyl-N-nitrosourea at 80 days of age and continued to receive dietary 1alpha-hydroxyvitamin D(5) for an additional 105 days. Tumor incidence and multiplicity were determined, and plasma concentrations of calcium and phosphorus were measured. The efficacy of 1alpha-hydroxyvitamin D(5) at different stages of carcinogenesis was determined in mouse mammary gland organ culture. All statistical tests were two-sided. RESULTS: The tumor incidence was reduced from 80% (95% confidence interval [CI] = 51.9%-95.7%) in control rats to 53.3% (95% CI = 26.6%-78.8%) and 46.6% (95% CI = 21.3%-73.4%) in rats treated with 1alpha-hydroxyvitamin D(5) at 25 microg/kg diet and 50 microg/kg diet, respectively. The tumor multiplicity was reduced from 1.6 tumors per rat to 1.2 (95% CI for the difference = -0.45 to 1.25; P=.34) and 0.8 (95% CI for the difference = 0.14-1.46; P =.02), respectively. There was no statistically significant increase in the plasma calcium or phosphorus concentration at either dose level. The vitamin D(5) analogue was effective during both the initiation and the promotion stages of mammary lesion formation in organ culture. CONCLUSION: Our findings indicate that 1alpha-hydroxyvitamin D(5) reduces the incidence of mammary carcinogenesis in vivo. This analogue appears to be a good candidate for further development as a chemopreventive agent.

Animals↗
PubMed2000

Fifteen-year minimum follow-up of a prostate brachytherapy series: comparing the past with the present.

OBJECTIVES: To report the overall survival for 126 patients more than 15 years after iodine-125 interstitial therapy; to report the biochemical progression status for those alive and clinically without evidence of disease for longer than 15 years; to document the upward migration of grade by date of grade assignment; to compare the tumor stage and grade profile of this mature series with our current experience; and to clarify the prostate-specific antigen (PSA) data when this series is used as a historical comparison. METHODS: The records of 126 patients who underwent interstitial therapy more than 15 years previously were reviewed for assessment of the current TNM stage and Gleason grade and the current PSA level for patients clinically free of disease. The tumor grade and stage of these patients were compared with those of the first 126 patients treated by transrectal ultrasound-guided brachymonotherapy at our center between January 1995 and January 1999. The methodology of our 1993 publication was also reviewed. RESULTS: Of the 16 patients clinically free of disease (13 still alive and 3 dead of other causes more than 15 years after therapy), a review of the initial diagnostic needle biopsy was unable to confirm the presence of tumor in 3 patients. Of the remaining 13, 4 had a PSA level of 0.2 ng/mL or less, 4 a PSA level between 0.21 and 0.9 ng/mL, and 5 a PSA level between 1 and 2.5 ng/mL. Re-evaluation of the histopathologic findings using current criteria increased the Gleason score and World Health Organization grade. Patients currently selected for brachytherapy have a lower Gleason grade and TNM stage than recorded for patients treated in the past. The actuarial progression probability curves using the 0.5 or less cutpoint published in 1993 represented the best possible outcome and cannot serve as a historical control for current series comparisons. CONCLUSIONS: For patients who were alive and clinically free of disease longer than 15 years after therapy, the biochemical PSA levels were low. This may be attributed to the therapeutic radiation effect. Whether the improved technology of current transrectal ultrasound-guided implants can extend these favorable results from a small minority to a significant majority and whether it can approach the therapeutic results of radical prostatectomy may be partially answered with a longer follow-up of the current series. The histopathologic criteria have been refined, and upgrading from the initially assigned grade is common. In some cases, a prostate cancer diagnosis could not be confirmed. These findings limit the ability to match patients across time and institution. The results of our 1993 report of biochemical chemical progression-free probability 10 years after iodine-125 implantation cannot be used as a comparator for current studies. Ultimately, a valid comparison between treatment options will only be achieved through a randomized controlled trial.

Brachytherapy↗
PubMed2000

Implicit and explicit memory in pregnant women: an analysis of data-driven and conceptually driven processes.

A study by Brindle, Brown, Brown, Griffith, and Turner (1991), reported that pregnant women showed impaired implicit memory (as measured by a stem completion task) in the presence of intact explicit memory. The present study was an attempt to replicate and extend this finding by employing a read/generate encoding manipulation across data-driven (word fragment completion and graphemic cued recall) and conceptually driven (semantic cued recall and category generation) tests. A total of 64 women (32 pregnant) were tested on both data-driven and conceptually driven tasks either directly or indirectly. No differences emerged between pregnant subjects and non-pregnant controls across tasks. Subjects experiencing their first pregnancy did report their memory in the previous 2 weeks as being considerably worse than normal.

Adult↗
PubMed1996

Upregulation of prostate-specific membrane antigen after androgen-deprivation therapy.

OBJECTIVES: To determine the expression of prostate-specific membrane antigen (PSMA) before and after androgen-deprivation therapy and to compare PSMA expression with prostate-specific antigen (PSA) expression. METHODS: We studied specimens from 20 patients with prostate cancer undergoing medical or surgical castration or combination androgen-deprivation therapy in whom matched pretreatment and post-treatment tissue specimens were available and 16 patients in whom only a post-treatment specimen was available. The expression of PSMA and PSA in the tissue specimens was determined by immunoperoxidase staining. The extent of staining was calculated by multiplying the percent of antigen-positive tumor cells by the staining intensity to arrive at a stain index for each biomarker. An in vitro study assessed the concentration of PSMA and PSA in extracts of LNCaP cells cultured in the presence or absence of androgen as determined by immunoassays and Western blot analysis. RESULTS: PSMA reactivity was found to be increased in 55% (11 of 20) of post-treatment primary tissues and 100% (4 of 4) of post-treatment metastatic specimens. In contrast, PSA expression was found to be decreased in 70% (14 of 20) of post-treatment primary and 100% (4 of 4) of post-treatment metastatic specimens. Neither type of androgen-deprivation treatment nor tissue sensitivity to androgen deprivation appeared to influence degree of biomarker expression. PSMA was found to be downregulated and PSA upregulated when LNCaP cells were cultured in the presence of testosterone or dihydrotestosterone. CONCLUSIONS: The enhanced expression of PSMA in tissues and LNCaP cells after androgen deprivation suggests that PSMA is upregulated in the majority of prostate carcinomas after androgen treatment. The high expression in metastatic tissues strongly suggests that PSMA may be a clinically useful target for antibody-and genetic-directed therapy of prostate cancer that recurs after androgen deprivation. The mechanism whereby androgens suppress the expression of PSMA, and the association of PSMA with the development of hormone-independent prostate cancers, will require further study.

Androgen Antagonists↗
PubMed1993

Age-adjusted CD4+ lymphocyte parameters in healthy children at risk for infection with the human immunodeficiency virus. The Military Pediatric HIV Consortium.

Values for CD4+ lymphocytes are reported to vary by age. We evaluated an ethnically diverse population of healthy children at risk for human immunodeficiency virus infection to establish normal ranges for age-adjusted CD4+ lymphocyte parameters. We identified a threshold of approximately 30% CD4+ lymphocytes which corresponded to a 5th percentile for all ages. It is important that no significant differences in absolute CD4+ lymphocyte counts on the basis of ethnic group were found.

Age Factors↗
PubMed1993

Immunization status of a military dependent population.

The immunization status of active duty pediatric dependents served by the National Naval Medical Center was surveyed to estimate the degree to which this group was in compliance with immunization requirements. Four hundred sixteen patients who presented consecutively to a pediatric acute care clinic had their medical and immunization records screened. Ten percent of patients did not have complete records of immunization. Of the 375 patients remaining, 52 (13.9%) were deficient in one or more required immunizations based on their current age. The highest rates of delay were seen for the Haemophilus influenza vaccine followed by measles, mumps, rubella, and diphtheria, tetanus, and pertussis. The most common reason for missing immunizations was parental unfamiliarity with the recommended schedule. This study suggests that a significant number of dependents in our catchment area were delayed in immunization and that accurate record keeping and patient education about immunizations needs to be improved.

Adolescent↗
PubMed1985

Candy flavoring as a source of salicylate poisoning.

Methyl salicylate (oil of wintergreen) in the form of candy flavoring was ingested by a 21-month-old male infant who subsequently developed vomiting, lethargy, and hyperpnea. A "swallow" of the solution resulted in a serum salicylate concentration of 81 mg/dL six hours after ingestion. The infant was treated with parenteral fluids and sodium bicarbonate and he recovered rapidly. Hazards associated with salicylate use in this form include lack of parental awareness of the substance's toxic potential, the attractiveness of the candy-like odor, and the availability of the liquid in non-child-resistant packaging containing potentially lethal quantities.

Candy↗
PubMed1975

Sampling problems in the micro determination of blood lead.

Sampling tube and fingertip contamination were found to present potential problems in the collection of samples for micro blood lead analyses. Large differences between micro screening and macro confirming lead levels were frequently observed when the time between collection of the two samples was 1-2 weeks. The magnitude of these differences decreased as macro blood lead concentration increased and were apparently a result of episodic lead ingestion in the population.

Ethanol↗