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D Atkins

Publications and source records attributed to D Atkins.

At least 37 records · Page 2Linked to original sources
PubMed2000

Interleukin-7 or interleukin-15 enhances survival of Mycobacterium tuberculosis-infected mice.

Both antigen-presenting cells and immune effector cells are required to effectively eradicate or contain Mycobacterium tuberculosis-infected cells. A variety of cytokines are involved to ensure productive "cross talk" between macrophages and T lymphocytes. For instance, infection of macrophages with mycobacteria leads to effective interleukin-7 (IL-7) and IL-15 secretion, and both cytokines are able to maintain strong cellular immune responses of alpha/beta and gamma/delta T cells. Here we show that either cytokine is able to enhance survival of M. tuberculosis-infected BALB/c mice significantly compared to application of IL-2, IL-4, or phosphate-buffered saline (as a control). Enhanced survival could be achieved only when IL-7 or IL-15 was delivered as a treatment (i.e., 3 weeks postinfection), not when it was administered at the time of infection. Increased survival of M. tuberculosis-infected animals was observed following passive transfer of spleen cells harvested from M. tuberculosis-infected, IL-7- or IL-15-treated animals, but not after transfer of spleen cells obtained from mice which received either cytokine alone. Histological examination revealed that IL-7 and IL-15 failed to significantly impact on the number and composition of granulomas formed or the bacterial load. Our data indicated that administration of IL-7 or IL-15 to M. tuberculosis-treated animals resulted in a qualitatively different cellular immune response in spleen cells as reflected by increased tumor necrosis factor alpha and decreased gamma interferon secretion in response to M. tuberculosis-infected antigen-presenting cells.

Adoptive Transfer↗
PubMed2000

Lipid screening in women.

Evidence of the benefits of lowering cholesterol in various populations continues to grow, but questions persist about screening and treatment of lipid disorders in women. In this paper, we review the distinct features of the epidemiology of lipids and coronary heart disease in women and data from recent long-term treatment trials specific to women. Although data from primary prevention trials in women remain sparse, recent trials demonstrating benefits of cholesterol reduction across a broad range of cholesterol levels and cardiac risk in men and women bolster the conclusion that benefits may extend to asymptomatic women who are otherwise at high risk for coronary disease. Periodic lipid screening beginning in middle age will identify most women who are at high enough risk to merit drug therapy or more intensive individual lifestyle interventions. More detailed consideration of age, diabetes, blood pressure, specific lipid levels, or the ratio of total cholesterol to high-density lipoprotein cholesterol, and other risk factors can more accurately estimate individual risk of coronary heart disease and identify high-risk women most likely to benefit from lipid reduction. Advice about healthy diet, weight control, and physical activity can benefit all women, but authorities differ on the benefits of routine lipid screening in low-risk younger women.

Adult↗
PubMed2000

Pregnancy and inflammatory bowel disease: current management.

Inflammatory bowel disease primarily affects adolescents and young adults, presenting management concerns for obstetricians caring for these women during pregnancy. Interdisciplinary care by the obstetrician and gastroenterologist and selection of individual courses of management produce pregnancy outcomes that approach those of an unaffected population. Routine medical management using glucocorticoids, metronidazole, and asacol derivatives as well as more aggressive therapy using immunomodulators azathioprine and 6-mercaptopurine are shown to be of low risk to the fetus. Effective medical management greatly reduces need for surgical intervention during pregnancy. An understanding of current management perspectives assures positive pregnancy outcomes for mother and infant.

Adolescent↗
PubMed2000

Evaluation of the cellular uptake of hexitol nucleic acids in HeLa cells.

Two major hurdles to the widespread use of synthetic nucleic acids as drugs are the biological stability of the compounds and efficiency of cellular penetration. Recent advances in the chemistry of nucleic acids has given rise to highly stable derivatives with an anhydrohexitol backbone. This report addresses the cellular uptake of these molecules. We show that the uptake of HNA in the absence of a carrier is very low but HNA is efficiently internalized with a range of transfection reagents.

Fluorescent Dyes↗
PubMed1999

Eating disorders in adolescents and young women with spina bifida.

This is the first report of the association of spina bifida and eating disorders. Five patients were diagnosed rather late in the course of their illness. They all had been overweight premorbidly and had been urged to lose weight for years in order to improve their mobility. As they dieted, they experienced their weight loss as a source of power that could somehow compensate for their losses and neurologic limitations. They responded to a multidisciplinary intervention. Clinicians taking care of patients with spina bifida need to be cognizant that they may be at risk of developing an eating disorder. Such awareness should influence the quality of nutritional counseling (prevention aspect) and the clinical assessment of sudden weight loss (early intervention).

Adolescent↗
PubMed1999

Antimalarial antisense activity of hexitol nucleic acids.

Antisense oligonucleotides and ribozymes have shown promise both as antimalarial agents and as tools for identifying genes vital for parasite survival. This task is urgent due to the ineffectiveness of current drug regimes on the most virulent human malarial parasite, Plasmodium falciparum. The development of new ways to modify and/or protect conventional phosphodiester oligonucleotides to improve nuclease resistance is also important. We assessed the effect of antisense oligonucleotides containing phosphorylated anhydrohexitols in suppressing the growth of P. falciparum in culture. The modified oligonucleotides were able to inhibit parasite growth in a sequence-specific manner, but not as well as the phosphorothioated antisense oligonucleotides, which are effective antimalarials at submicromolar concentrations. Two reasons are suggested: the absence of RNase H activation and differences in membrane transport.

Animals↗
PubMed1999

A systematic review of treatments for the painful heel.

OBJECTIVE: To establish the efficacy for treatments of pain on the plantar aspect of the heel. METHODS: Systematic review of the published and unpublished literature. Electronic search of Medline, BIDS and the Cochrane database of clinical trials. An assessment of the quality of the reporting was made of studies included in the review. MAIN OUTCOME MEASURE: patients' pain scores. STUDY SELECTION: randomized controlled trials, published or unpublished, that evaluated treatments used for plantar heel pain. Foreign language papers were excluded. RESULTS: Eleven randomized controlled trials were included in the review. These evaluated some of the most frequently described treatments (steroid injections and orthoses) and some experimental therapies (extracorporeal shock wave therapy and directed electrons). The methodological assessment scores of the published trials were low; small sample sizes and failure to conceal the treatment allocation from study participants prevents more definitive statements about the efficacy of treatments. In 10 of the included trials, patients in both the intervention and control arms reported improved pain scores at the final outcome measure. CONCLUSIONS: Although much has been written about the treatment of plantar heel pain, the few randomized controlled trials involve small populations of patients and do not provide robust scientific evidence of treatment efficacy.

Fasciitis↗
PubMed1999

Steroid injection for heel pain: evidence of short-term effectiveness. A randomized controlled trial.

OBJECTIVES: To compare the effectiveness of a steroid injection (25 mg/ml prednisolone acetate) with a local anaesthetic control in the treatment of heel pain and to determine any advantage for patients' comfort of using a posterior tibial nerve block to anesthetize the heel prior to infiltration. METHODS: A double-blind randomized controlled trial using a 2 x 2 design in a hospital-based rheumatology clinic. Subjects comprised 106 patients with heel pain referred by general practitioners and other rheumatologists working in Camden and Islington Health Authority. MAIN OUTCOME MEASURES: heel pain reduction at 1, 3 and 6 months, and patient comfort at the time of injection. All outcomes were measured using a 10 cm visual analogue scale. RESULTS: A statistically significant reduction in pain was detected at 1 month (P=0.02) in favour of steroid injection, but thereafter no differences could be detected. Patient comfort was not significantly affected by anaesthesia of the heel (P=0.5). CONCLUSIONS: A steroid injection can provide relief from heel pain in the short term. There appears to be no increase in patient comfort from anaesthetizing the heel prior to infiltration.

Adult↗
PubMed1999

Infundibuloneurohypophysitis in children. A report of 2 cases.

Two children with diabetes insipidus secondary to a chronic inflammatory infiltrate of the infundibulum - infundibuloneurohypophysitis - are presented. Features unique to these cases are contrasted with prior case reports. The differential diagnoses of diabetes insipidus and inflammatory pituitary disorders are discussed. Recommendations for diagnosis and treatment are proposed.

Adolescent↗
PubMed1999

Avalanche deaths in the United States: a 45-year analysis.

OBJECTIVE: To describe the demographic characteristics and patterns of death of persons killed in snow avalanches over a 45-year study period. METHODS: The national avalanche database was the source of data in this retrospective, descriptive study. RESULTS: A total of 440 victims were killed in 324 fatal avalanches, of which 87.7% were fully buried, 4.7% were partially buried, and 7.6% were not buried. The average age was 27.6 +/- 10.6 years, and 87.3% were men. Victims who died included climbers (25.5%), backcountry skiers (22.7%), out-of-bounds skiers (10.0%), snowmobilers (6.8%), in-bounds skiers (5.2%), residents (4.5%), ski patrollers (3.6%), workers (3.6%), and motorists (3.0%). Over the 45-year study period there appear to be decreases in the deaths of in-bounds skiers, highway workers, and motorists. Increasing fatalities were observed among out-of-bounds skiers, snowmobilers, ski patrollers, and backcountry skiers. Most deaths occurred in Colorado (33.0%), Washington (13.2%), and Alaska (12.0%). CONCLUSIONS: Avalanche fatalities have increased over the last 45 years. Climbers, backcountry skiers, out-of-bounds skiers, and more recently snowmobilers constitute the majority of the victims. The decrease in deaths among groups that benefit from avalanche control programs supports the benefit of avalanche prevention strategies. Further study is needed to assess the impact of avalanche safety education for individuals who travel in remote and uncontrolled terrain.

Adolescent↗
PubMed1998

Second trimester abortion using prostaglandin E2 suppositories with or without intracervical Laminaria japonica: a randomized study.

OBJECTIVE: To compare the abortifacient efficacy of vaginal prostaglandin (PG) E2 suppositories with and without pretreatment with intracervical PGE2 gel and Laminaria japonica. METHODS: One hundred seventy-five women between 16 and 20 weeks' gestation requesting abortion were divided randomly into three groups. Forty-one received PGE2 vaginal suppositories alone to induce abortion, 72 had Laminaria placed 24 hours before vaginal PGE2, and 62 were given intracervical 0.5 mg PGE2 gel plus Laminaria 24 hours before vaginal PGE2. Maternal demographic characteristics, induction to delivery time, number of suppositories required, and complications were analyzed. RESULTS: The mean maternal age, gravidity, parity, race, and gestational age were similar among groups. Ninety-five percent of all women delivered within 24 hours. The induction to delivery time was significantly longer in the PGE2-only women (mean +/- standard deviation 689+/-319 minutes) compared with that of those receiving PGE2 plus Laminaria (487+/-321 minutes) and PGE2 plus Laminaria plus gel (547 +/-374 minutes, P = .01). There was a statistically significant difference in the number of suppositories needed to complete the abortion process. The PGE2-only group required more suppositories (median three, range 1-8) compared with PGE2 plus Laminaria (median 3, range 1-3) and PGE2 plus Laminaria plus gel (median 2.5, range 1-9; P = .001). Patients in the PGE2 plus Laminaria plus gel group reported more pain associated with placement (median pain score 4, range 0-10) compared with PGE2 plus Laminaria (median 2, range 0-9; P = .003). There was a lower incidence of febrile episodes in the PGE2-only group (29%) compared with PGE2 plus Laminaria (68%) and PGE2 plus Laminaria plus gel (54%, P = .002). CONCLUSION: Placement of Laminaria japonica 24 hours before PGE2 vaginal suppository-induced abortion resulted in a significantly shorter induction-to-delivery time, and pretreatment with Laminaria japonica decreased the number of suppositories required to complete abortion. Pretreatment with intracervical PGE2 gel increased pain associated with Laminaria placement and did not improve the efficacy of the procedure.

Abortion, Induced↗
PubMed1998

Broadening the evidence base for evidence-based guidelines. A research agenda based on the work of the U.S. Preventive Services Task Force.

Evidence-based evaluations of clinical preventive services help define priorities for research in prevention as part of primary health care. In this article, we draw on our experiences with the U.S. Preventive Services Task Force (USPSTF) to outline some major areas where research is needed to define the appropriate use of specific screening tests, counseling interventions, immunizations, and chemoprophylaxis. Areas of particular importance included research to: (1) Identify effective and practical primary care interventions for modifying personal health practices of patients, especially around issues such as diet, exercise, alcohol and drug use, and risky sexual behavior; (2) Clarify the optimal periodicity for certain screening tests and counseling interventions; (3) Identify practical ways to allow patients to share decision-making about preventive care, especially for services of possible but uncertain benefit; (4) Examine the most sensitive and efficient ways to identify high-risk groups who may need different services than the average population; and (5) Expand the use of decision-analysis and cost-effectiveness analysis to help identify optimal use of clinical preventive services. Given the difficulty of large, prospective trials, we discuss the use of alternative research designs to fill in critical gaps in the evidence for the effectiveness of specific services. Finally, we note several issues of increasing importance that may need to be addressed by future work of the USPSTF: what are the most reliable and effective ways to (1) measure and (2) improve the delivery and quality of preventive care provided in the primary care setting.

Decision Support Techniques↗
PubMed1998

The U.S. Preventive Services Task Force: putting evidence-based medicine to work.

The U.S. Preventive Services Task Force is a prominent example of evidence-based medicine put to work. The Guide to Clinical Preventive Services and its Canadian counterpart distill thousands of articles into easily understood guidelines for the busy clinician. Rather than dictating practice, it provides the scientific base for prevention services. The second fundamental part of evidence-based medicine is the filtering of that evidence through the clinical skill of the clinician. Only the clinician can judge the applicability of the evidence and the preferences of the woman and her family. Some common preventive practices in women's health lack a scientific basis. Others clearly work. To maximize benefit, clinicians should emphasize and encourage prevention strategies that are effective. These include cervical cytology screening, blood pressure screening, urine cultures in early pregnancy, testing for phenylketonuria, and discouraging smoking. No health program can be reviewed in a vacuum. This is especially true in the managed care era. Clinicians must ask what benefit would have accrued had the same amount of time and money been spent on alternative programs. If practices with only a class C recommendation draw money and resources from other programs of proven worth (e.g., class A recommendations), then the former have a net negative impact on women's health. The Task Force report helps women, clinicians, payers, and policymakers make these important decisions.

Breast Neoplasms↗
PubMed1997

Inhibition of Plasmodium falciparum proliferation in vitro by ribozymes.

Catalytic RNA (ribozymes) suppressed the growth of the human malarial parasite Plasmodium falciparum in vitro. The phosphorothioated hammerhead ribozymes targeted unique regions of the P. falciparum carbamoyl-phosphate synthetase II gene. The P. falciparum carbamoyl-phosphate synthetase II gene encodes the first and limiting enzyme in the pathway, and its mRNA transcript contains two large insert regions absent in other carbamoyl-phosphate synthetases, including that from humans. These inserts are ideal targets for nucleic acid therapy. Exogenous delivery of ribozymes to cultures reduced malarial viability up to 55% at 0.5 microM ribozyme concentrations, which is significantly greater than control levels (5-15% reduction), suggesting a sequence-specific inhibition. This inhibition was shown to be stage-specific, with optimal inhibitions being detected after 24 h, coincident with maximal production of the carbamoyl-phosphate synthetase enzyme in the course of the life cycle of the parasite. A decrease in total carbamoyl-phosphate synthetase activity was observed only in cultures treated with the ribozymes. The task of developing alternative therapeutic agents against malaria is urgent due to the evolution of drug-resistant strains of P. falciparum, the most virulent of all human malarial parasites. Another critical issue to be addressed is the possibility of eliminating or reducing any systemic toxicity to the host, which can potentially be provided by nucleic acid therapy. This work is the first reported assessment of the ability of ribozymes as antimalarials. Ribozyme inhibition assays can also aid in identifying important antimalarial loci for chemotherapy. The malarial parasite can, in turn, be a useful in vivo host to study the catalysis and function of new ribozyme designs.

Animals↗