Biomedical subjects

Peter Jensen

Publications and source records attributed to Peter Jensen.

14 recordsLinked to original sources

PubMed2006

Regulation of immunity by a novel population of Qa-1-restricted CD8alphaalpha+TCRalphabeta+ T cells.

Regulatory mechanisms involving CD8+ T cells (CD8 regulatory T cells (Tregs)) are important in the maintenance of immune homeostasis. However, the inability to generate functional CD8 Treg clones with defined Ag specificity has precluded a direct demonstration of CD8 Treg-mediated regulation. In the present study, we describe the isolation of functional lines and clones representing a novel population of TCRalphabeta+ Tregs that control activated Vbeta8.2+ CD4 T cells mediating experimental autoimmune encephalomyelitis. They express exclusively the CD8alphaalpha homodimer and recognize a peptide from a conserved region of the TCR Vbeta8.2 chain in the context of the Qa-1a (CD8alphaalpha Tregs). They secrete type 1 cytokines but not IL-2. CD8alphaalpha Tregs kill activated Vbeta8.2+ but not Vbeta8.2- or naive T cells. The CD8alphaalpha Tregs prevent autoimmunity upon adoptive transfer or following in vivo activation. These findings reveal an important negative feedback regulatory mechanism targeting activated T cells and have implications in the development of therapeutic strategies for autoimmune diseases and transplantation.

Animals↗

PubMed2005

A pilot randomized, controlled trial of an in-home drinking water intervention among HIV + persons.

Although immunocompromised persons may be at increased risk for gastrointestinal illnesses, no trials investigating drinking water treatment and gastrointestinal illness in such patients have been published. Earlier results from San Francisco suggested an association (OR 6.76) between tap water and cryptosporidiosis among HIV + persons. The authors conducted a randomized, triple-blinded intervention trial of home water treatment in San Francisco, California, from April 2000 to May 2001. Fifty HIV-positive patients were randomized to externally identical active (N = 24) or sham (N = 26) treatment devices. The active device contained a filter and UV light; the sham provided no treatment. Forty-five (90%) of the participants completed the study and were successfully blinded. Illness was measured using 'highly credible gastrointestinal illness' (HCGI), a previously published measure. There were 31 episodes of HCGI during 1,797 person-days in the sham group and 16 episodes during 1,478 person-days in the active group. The adjusted relative risk was 3.34 (95% CI: 0.99-11.21) times greater in those with the sham device. The magnitude of the point estimate of the risk, its consistency with recently published observational data, and its relevance for drinking water choices by immunocompromised individuals support the need for larger trials.

Adult↗

PubMed2004

CD8alphaalpha-mediated survival and differentiation of CD8 memory T cell precursors.

Memory T cells are long-lived antigen-experienced T cells that are generally accepted to be direct descendants of proliferating primary effector cells. However, the factors that permit selective survival of these T cells are not well established. We show that homodimeric alpha chains of the CD8 molecule (CD8alphaalpha) are transiently induced on a selected subset of CD8alphabeta+ T cells upon antigenic stimulation. These CD8alphaalpha molecules promote the survival and differentiation of activated lymphocytes into memory CD8 T cells. Thus, memory precursors can be identified among primary effector cells and are selected for survival and differentiation by CD8alphaalpha.

Animals↗

PubMed2004

Comparison of PCR-southern hybridization and quantitative real-time PCR for the detection of JC and BK viral nucleotide sequences in urine and cerebrospinal fluid.

The presence of the human polyomaviruses JCV and BKV in immunocompromised patients can lead to lethal diseases and conditions including progressive multifocal leukoencephalopathy (PML), interstitial nephritis, hemorrhagic cystitis, and kidney allograft rejection. Typically, detection of JCV and BKV in clinical samples has employed standard PCR amplification for viral nucleotide sequences, with subsequent confirmation for viral genome specificity of PCR products by southern blot hybridization. Here, we directly tested a validated PCR-southern protocol with a TaqMan real-time PCR protocol (Applied Biosystems) to assay clinical samples of urine and cerebrospinal fluid. We found equal specificity and sensitivity with both methods. However, real-time allowed for absolute viral-genome quantitation without the use of radionucleotides and was performed more rapidly, in as little as 24 h. Such advantages are important to consider in the effort to establish international standardization of controls for the detection of JCV and BKV, which would aid in screening confidence and the reliable assessment of anti-viral therapies.

BK Virus↗

PubMed2004

Cost assessment of a school-based mental health screening and treatment program in New York City.

Although school-based mental health screening and treatment programs have been proposed as a viable means of reaching youth with unmet mental health needs, no previous reports have attempted to comprehensively document the costs of such programs. The purposes of this report are (1) to estimate the cost of a school-based mental health screening and treatment program in a real-world school setting, and (2) to outline the methods and procedures that should be employed by future investigators to explore the costs of such programs. The program, located in a middle school in a low-income, largely Hispanic neighborhood in New York City, aimed to screen all students in Grades 6-8 for anxiety, depression, and substance use disorders. Most students in need of treatment were referred to the school-based treatment program, where social workers offered individual and group counseling. Economic evaluation methods and a before/after study design were used to assess the costs of the screening and treatment programs for 3 years of operation. Costs were estimated from the societal perspective, which includes all measurable program costs regardless of who bears the costs, and the school perspective, which includes only costs that would be borne directly by a school operating these programs. Data primarily came from administrative records and staff interviews. The total cost ranged from 106,125 dollars to 172,018 dollars for the screening program and from 420,077 dollars to 468,320 dollars for the treatment program. The cost of the screening program ranged from 149 dollars to 234 dollars per student and the cost of the treatment program ranged from 90 dollars to 115 dollars per session. These costs were estimated from the perspective of society. Applying economic cost analysis methods in a real-world school setting is challenging, but the process can generate useful estimates. Cost analyses and cost-effectiveness studies are needed in this area.

Adolescent↗

PubMed2004

AACAP 2002 research forum: placebo and alternatives to placebo in randomized controlled trials in pediatric psychopharmacology.

OBJECTIVE: The use of placebo in the pediatric age group has come under increasing scrutiny. At the 2002 Annual Meeting of the American Academy of Child and Adolescent Psychiatry, the Academy's Workgroup on Research conducted a research forum. The purpose was to identify challenges and their solutions regarding the use of placebo in randomized controlled trials in pediatric psychopharmacology. METHOD: Workgroups focused on problems and solutions in five areas: ethics and human subjects, research design and statistics, partnering with consumers, U.S. Food and Drug Administration and pharmaceutical industry perspectives, and psychosocial treatments. RESULTS: In many but not all circumstances, inclusion of a placebo control is essential to meet the scientific goals of treatment outcome research. Innovative research designs; involvement of consumers in planning and implementing research; flexibility by industry, academia, the National Institutes of Health, and regulatory agencies acting in partnership; and concomitant use of evidence-based psychosocial services can and should assist in making placebo-controlled trials acceptable. CONCLUSIONS: Properly designed placebo-controlled trials remain necessary, ethical, and feasible.

Adolescent↗

PubMed2004

Antiretroviral adherence in persons with HIV/AIDS and severe mental illness.

This study identified factors impacting adherence to human immunodeficiency virus (HIV) therapies in a sample of 46 persons diagnosed with HIV/acquired immune deficiency syndrome and severe mental illness who were receiving care through a day care program in Northern California. Comprehensive descriptions of factors and circumstances that influence adherence behaviors were obtained through critical incident interviews, and a taxonomy of adherence factors was determined. A chi2 analysis that examined differences between patient characteristics and major adherence factors found that planning was more likely to be reported by older persons taking HIV medications over longer periods. Nonwhite persons and those living alone were more apt to rely on the use of reminders and cues. Persons with bipolar disorder reported substantially more incidents of the impact of their symptoms on adherence to HIV therapies than persons with other psychiatric diagnoses. The taxonomy of adherence factors provides important information for developing relevant adherence education programs and an essential foundation for testing compliance interventions.

Acquired Immunodeficiency Syndrome↗

PubMed2003

Physiologic effects of intravenous fluid administration in healthy volunteers.

UNLABELLED: Dose regimens in perioperative fluid management are rarely evidence based. Therefore, we investigated responses to an IV fluid infusion in healthy volunteers to assess basic physiologic effects of a fluid infusion per se. In a prospective, double-blinded, cross-randomized study, 12 healthy volunteers with a median age of 63 yr (range, 59-67 yr) received an infusion of lactated Ringer's solution 40 mL/kg (median, 2820 mL) or 5 mL/kg (median, 353 mL; background infusion) in random order on two separate occasions. The study was designed to mimic the perioperative course with preoperative fasting, infusion of the fluid over 3 h in the morning, and additionally 24-h hospitalization under standardized conditions. Primary outcome assessments were pulmonary function (spirometry), exercise capacity (submaximal treadmill test), balance function (BalanceMaster), and weight. Infusion of 40 mL/kg of lactated Ringer's solution compared with the background infusion (5 mL/kg) resulted in a significant decrease in pulmonary function and a significant weight gain of median 0.85 kg (range, -0.2-1.6 kg; P = 0.003) persisting 24 h after the infusion. Exercise capacity and balance function were not influenced by fluid administration. These findings may serve as a basis for clinical studies applying the same type of fluid in different amounts to determine the optimal amount of perioperative fluid in various surgical procedures. IMPLICATIONS: Infusion of 40 mL/kg of lactated Ringer's solution in volunteers led to a significant decrease in pulmonary function and a significant weight gain for 24 h but without effects on exercise capacity. These findings may serve as basis information for clinical studies of perioperative fluid management.

Aged↗

PubMed2002

Barriers to health care research for children and youth with psychosocial problems.

CONTEXT: The 1999 surgeon general's report on mental health concluded that insufficient attention to mental health disorders is being paid in children's primary medical care services. This lack of attention has occurred despite considerable attention to this issue in the planning documents of many federal agencies. OBJECTIVE: To assess the extent to which federal agencies' portfolios of funded research grants were consistent with the directives for primary care-based mental health services for children and adolescents featured in their planning documents. DATA SOURCE: A cross-sectional review of the 66 749 abstracts listed in the April 2001 Computer Retrieval of Information on Scientific Projects (CRISP) database of currently funded research grants supported by the US Department of Health and Human Services. Abstracts were rated by whether they targeted primary care, examined behavioral or emotional issues, and examined or modified a facet of primary care. DATA SYNTHESIS: Of the 45 022 research abstracts in the CRISP database, 2720 (6%) contained the words children, adolescents, or youth. Sixty-three abstracts contained work on children, adolescents, or youth in primary care (0.14% of the portfolio). Of these 63 abstracts, only 21 (0.05% of the portfolio) addressed behavioral or emotional issues. Of the 21 projects, only 11 examined aspects of the primary care process. When the distribution of child and adult studies on the treatment of depression within primary care settings was examined, it was found that adults received 15 times the research attention compared with children. CONCLUSION: Even though the importance of primary care as a system for identifying and treating behavioral and emotional problems in children has been recognized for more than 20 years, little attention is being paid to this topic in the research portfolios of the National Institutes of Health and other federal agencies that support research.

Adolescent↗

PubMed2002

A turbo engine with automatic transmission? How to marry chemicomotion to the subtleties and robustness of life.

Most genomes are much more complex than required for the minimum chemistry of life. Evolution has selected sophistication more than life itself. Could this also apply to bioenergetics? We first examine mechanisms through which bioenergetics could deliver sophistication. We illustrate possible benefits of the turbo-charging of catabolic pathways, of loose coupling, low-gear catabolism, automatic transmission in energy coupling, and of homeostasis. Mechanisms for such phenomena may reside at the level of individual proton pumps, or consist of rerouting of electrons over parallel pathways. The mechanisms may be confined to preexisting components, or involve the plasticity of gene expression that is so characteristic of most living organisms. These possible benefits lead us to the conjecture that also bioenergetics has evolved more for sophistication than for necessity. We next discuss a hitherto unresolved enigma, i.e. that bioenergetics does not seem to be critical for the physiological state. To decide on how critical bioenergetics is, we quantified the control exerted by catabolism on important physiological functions such as growth rate and growth yield. We also determined whether a growth inhibition mostly affected bioenergetics (catabolism) or anabolism; if ATP increases with growth rate, then growth should be considered energy (catabolism) limited. The experimental results for Escherichia coli pinpoint the enigma: its energy metabolism (catabolism) is not critical for growth rate. These results might suggest that because it has no direct control over cell function, bioenergetics is unimportant. Paradoxically however, in biology, highly important mechanisms tend to have little control on cell function, precisely because of that importance. Sophistication in terms of homeostatic mechanisms has evolved to guarantee robustness of the most important functions: The most important mechanisms are redundant in biology. Bioenergetics may be an excellent example of this paradox, in line with the above conjecture. It may be highly important and sophisticated. We then discuss work that has begun to focus on the sophistication of bioenergetics. Homeostasis of the energetics of DNA structure in E. coli is extensive. It relies both on preexisting components and on responsive gene expression. The vastly parallel electron-transfer network of Paracoccus denitrificans engages in sophisticated dynamic and hierarchical regulation. The growth yield of the organism can depend on which terminal oxidases are active. Effective proton translocation may vary due to rerouting of electrons. We conclude that much sophistication of bioenergetics will be discovered in this era of functional genomics.

Adenosine Triphosphate↗

PubMed2002

[Tuberculous spondylitis--Pott disease--in a 33-year-old man from Greenland].

We report a case where tuberculous spondylitis was diagnosed in a 33-year-old man from Greenland. Very typically for Pott's disease, there was back pain, weight loss, and a characteristic kyphotic deformity. Computed tomography showed destruction of the thoracic vertebrae with paraspinal abscesses. The treatment was antituberculous therapy and surgery.

Adult↗

PubMed2002

Using state administrative and pharmacy data bases to develop a clinical decision support tool for schizophrenia guidelines.

Administrative and pharmacy data bases represent a largely untapped resource for clinical decision support and quality improvement. In this study, we examined the feasibility of using New York State Office of Mental Health (NYSOMH) data bases to develop an automated clinical report to support implementation of schizophrenia guidelines. First we reviewed the structure of existing data bases for capacity and limitations in supporting guideline implementation. Second, we identified schizophrenia guideline recommendations and adherence measures that would be the focus of our implementation. Third, a preliminary report was programmed, based on operational definitions of the guideline recommendations. Finally, we developed user groups to define content and format of new reports, through an iterative process of field testing, feedback, and revision. Our experience suggests that administrative and pharmacy data bases, despite their limitations, can be used to develop guideline-based clinical decision support tools for schizophrenia with high physician acceptability.

Antipsychotic Agents↗

PubMed2002

What research suggests for depressed women with children.

BACKGROUND: The strong association between maternal and offspring depression has been observed in numerous studies. Understanding this association has implications for early intervention and prevention. METHOD: Findings from our community-based epidemiologic studies and high-risk and longitudinal studies of families with depression are reviewed. RESULTS AND CONCLUSIONS: The childbearing years are the high-risk period for major depression in women. The offspring of depressed women are at high risk for depression. The risk begins before puberty in the offspring and is transmitted to the grandchildren. Depression that begins in childhood or adolescence is continuous and is associated with considerable morbidity. Despite the availability of efficacious treatment, the majority of depressed adults and children remain untreated. Without a clear commitment to mental health parity and an effective service system for intervention, little progress will occur in improving the treatment of depression. There are numerous opportunities for research on the etiology, treatment, and prevention of depression in mothers and their children.

Adolescent↗

PubMedDate not supplied

Postherniorrhaphy urinary retention--effect of local, regional, and general anesthesia: a review.

BACKGROUND AND OBJECTIVES: Postherniorrhaphy urinary retention (UR) may depend on the anesthetic technique. We therefore reviewed available published studies of UR in relation to anesthetic technique. METHODS: A Medline-based search (1966-November 2001) revealed 70 nonrandomized and 2 randomized studies. RESULTS: The incidence of UR was lower with local anesthesia (LA) (33 in 8991 patients, 0.37%, 95% confidence interval [CI] 0.24%-0.49%) compared with regional anesthesia (RA) (150 in 6191 patients, 2.42%, 95% CI 2.04%-2.81%) and general anesthesia (GA) (344 in 11471 patients, 3.00%, 95% CI 2.69%-3.31%). CONCLUSION: The low incidence of UR with LA is in accordance with the inhibitory effects of RA and GA on bladder function. Data from newer short-acting techniques of GA and RA are required to define the optimal anesthetic for inguinal herniorrhaphy.

Anesthesia↗