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PubMed2000

Physical and chemical properties of radionuclide therapy.

As more radionuclide therapies move from laboratory feasibility studies into clinical reality, it becomes increasingly important for the labeling chemistry to produce consistently a stable radiopharmaceutical that remains intact under the challenge of human catabolism. Similarly, once proof of principle is established to bring a radionuclide conjugate into clinical therapy trials, dosimetric estimates should be made to select the appropriate radionuclide properties, which are based on animal-specific or patient-specific pharmacokinetics and match a set of specific clinical endpoints. These properties may include the radionuclide physical half-life, radiolabeled conjugate biological uptake and clearance, product-specific activity, range and type of emissions, and resultant effects on tumor and normal tissue cellular survival. The immunologist and labeling chemist have now produced a variety of strategies that have potential to increase the therapeutic ratio (tumor-to-normal tissue dose ratio). The advent of normal tissue clearing agents, fragmented or chimerized carriers to improve targeting, and the method of bispecific or two-step and three-step targeting agents has increased the need for realistic modeling of the carrier in vivo to guide prospectively the competitive development of these radiopharmaceuticals. In this article, examples have been taken from the literature to elucidate the benchmark of success that careful experimental design has fostered to bring these agents into clinical practice by creative and logical methodologies.

Half-Life↗
PubMed1998

Current susceptibility patterns of anaerobic bacteria.

While antibiotic resistance among anaerobes continues to increase, the frequency of antimicrobial susceptibility testing for anaerobes is declining. Because anaerobic infections are often mixed and detailed bacteriology of the organisms involved may take some time, physicians must institute empiric therapy before susceptibility testing results are available. Also, economic realities and prudent use of resources mandate that careful consideration be given to the necessity for routine susceptibility testing of anaerobic bacteria. Determination of appropriate therapy can be based on published antibiograms; however, since patterns may vary within geographic regions and even within hospitals, it is strongly recommended that each hospital center periodically test their isolates to determine local patterns and detect any pockets of resistance. As a general guide, antibiograms from the last several years of susceptibility testing at the Wadsworth Anaerobe Laboratory are reported.

Bacteria, Anaerobic↗
PubMed1975

Changes in beliefs held by occupational therapy students before and after the first field experience.

Occupational therapy programs seek to integrate classroom theory and clinical reality. Early introduction of clinical contacts, concurrency of theory and practice, and coordinated program planning is directed to orderly growth and change in the occupational therapy student. It was hypothesized that, with complete integration of theory and practice, no sharp belief changes would occur during the first full-time field experience. Data from responses to social psychological instruments by one group of 28 occupational therapy seniors supported the hypothesis. There were no statistically significant changes in authoritarianism, dogmatism, or Machiavellianism during the first full-time field experience.

Attitude↗
PubMed1992

Pelvic inflammatory disease.

Pelvic inflammatory disease is a common serious complication of the sexually transmitted pathogens Neisseria gonorrhoeae and Chlamydia trachomatis. There are more than 800,000 cases of pelvic inflammatory disease annually accounting for approximately 200,000 hospital admissions for acute and chronic infections. Early accurate diagnosis and treatment are essential to prevent the serious sequelae including ectopic pregnancy, tubal disease infertility, chronic pain, and disability requiring multiple hospitalizations and surgery. Although clinical models to aid in the diagnosis and management of pelvic inflammatory disease have been developed by numerous investigators, all have lacked the sensitivity and specificity to be helpful to the clinician. Laparoscopy, considered by many to be the "gold standard" for diagnosis, is underutilized, and the definition of pelvic infection differs between investigators. Improved patient compliance and safety may be seen if single-agent therapy for acute pelvic inflammatory disease becomes a reality. In a small prospective randomized study, oral ofloxacin was as effective as cefoxitin plus doxycycline for outpatient treatment of chlamydial and gonococcal pelvic inflammatory disease. Treatment of tuboovarian abscess appears to be successful with single agent and combination therapy. Risk factors for developing postabortion endometritis continue to be identified, and the most efficacious prophylactic antibiotic regimen has not been determined to date.

Abortion, Legal↗
PubMed1990

Ovarian cancer.

Prevention, early detection, morbidity, and survival issues continue to challenge health professionals involved in the care of women with ovarian cancer. While advances in diagnosis, staging, and treatment have been made, survival rates remain grim. Continuing research in the areas of screening, diagnosis, and treatment is the key to improved survival. The hope of new drug therapy, such as cisplatin-taxol regimens, intraperitoneal therapy, immunotherapy, and bone marrow transplantation, needs further investigation to become reality. As new and potentially more toxic regimens are developed, the nurse must be knowledgeable about the therapies and adverse effects, and maintain a high level of clinical expertise in order to teach the patient, reinforce information, clarify misconceptions, and provide the patient with supportive physical and emotional care.

Carcinoma↗
PubMed2002

Combining antiplatelet and thrombolytic therapies for stroke.

Pharmacological therapy for acute nonhaemorrhagic stroke has become a reality over the last 5 years. Mechanistically, both thrombolytic (tissue plasminogen activator and urokinase) and antiplatelet (aspirin) monotherapy have demonstrated efficacy. However, unintended actions limit the extent of clinical improvement in each circumstance. For example, in addition to excess bleeding, tissue plasminogen activator therapy has been associated with complement activation, neuronal toxicity and laminin degradation, while aspirin may reduce nitric oxide synthase activity and cerebral blood flow. Attention is now directed toward improving the therapeutic index for each class of agents. Generally, while thrombolytic therapy is focused on developing agents with greater fibrin specificity and safety (that is, a reduction in intracranial haemorrhage rate), the development of antiplatelet agents is primarily focused on achieving greater potency. The latter is being investigated by combining agents with different mechanisms (aspirin and dipyridamole, aspirin and clopidogrel) as well as agents designed to block the glycoprotein IIb/IIIa receptor, the final common pathway for platelet aggregation. Thus, combination therapy using both thrombolytic and antiplatelet agents will further attempt to improve the therapeutic index by increasing potency and improving the safety profile. Anecdotal case studies support the merits of this approach and are consistent with the data reported for myocardial ischaemia and interventional strategies. It is anticipated that drug therapy directed at both thrombolytic and antiplatelet targets will ultimately result in a widened therapeutic window that will allow acute stroke therapy to be administrated to a much greater number of patients than is currently possible.

Animals↗
PubMed2004

Growth patterns reflect response to antiretroviral therapy in HIV-positive infants: potential utility in resource-poor settings.

Laboratory monitoring of HIV-infected children is the current standard of care in the United States to guide the appropriate use of antiretroviral therapy (ART). Although ART is becoming a reality in some developing countries, laboratory monitoring of ART is costly, necessitating creative approaches to monitoring. As an initial step to guide monitoring of HIV progression in low resource settings, we assessed the utility of the physical examination to predict clinical progression of HIV. We conducted a retrospective cohort study of HIV-infected children using data from Pediatric AIDS Clinical Trials Group Protocol 300. We developed a clinical predictive model, and compared the utility of the clinical model to the change in HIV RNA viral load as diagnostic tests of ART failure. The clinical model incorporated treatment regimen, age, and height velocity: a three-level clinical predictive model provided likelihood ratios of 0.3, 3.9, and 14. For decline in RNA the likelihood ratios were 0.2 (> 1 log decline), 1.4, and 3.5 (> log increase). We developed a simple clinical predictive model that was able to predict clinical progression of HIV after initiation of new ART. The clinical model performed similarly to using changes in HIV RNA viral load. These data should be validated internationally and prospectively, because the test subjects were from a resource rich environment and growth patterns in undernourished children may be impacted differently by HIV and its treatment. The model was most pertinent to children 36 months of age or younger, and was conducted in children receiving monotherapy and dual therapy.

Anti-HIV Agents↗
PubMed2000

Validation therapy for dementia.

BACKGROUND: Validation therapy is a "therapy for communicating with old-old people who are diagnosed as having Alzheimer's disease and related dementia". The approach was developed by Naomi Feil between 1963 and 1980. She classifies individuals with cognitive impairment as having one of four stages on a continuum of dementia: these stages are Malorientation, Time Confusion, Repetitive Motion and Vegetation. The benefits of Validation therapy for patients are reported by Feil as restoration of self worth, minimisation of the the degree to which patients withdraw from the outside world, promotion of communication and interaction with other people, reduction of stress and anxiety, stimulation of dormant potential, help in resolving unfinished life tasks, facilitation of independent living for as long as possible. These benefits are highly desirable and Validation therapy but there is a need to show them on the basis of substantive research yielding strong evidence across a number of well designed studies. The potential number of people that might benefit from the implementation of Validation therapy is considerable given the increasing incidence of dementia. OBJECTIVES: To evaluate the effectiveness of using validation therapy with people diagnosed as having senile dementia of the Alzheimer's type, other forms of dementia, or cognitive impairment. SEARCH STRATEGY: The Cochrane Controlled Trials Register was searched by the Cochrane Dementia and Cognitive Impairment Group Coordinator and relevant references were forwarded to the primary reviewer. The reviewers carried out independent searches of the following electronic databases - MEDLINE, EMBASE, Eureka, CINAHL, PSYCLIT, RLIN, SIGLE and SOCIOFILE. The following key terms were used in searches; validation-therapy, dementia, cognitive impairmnent, communication, and random*-control*. An author search using Feil and Naomi was also carried out. Personal contact was made with the Validation Institute, Cleveland, Ohio USA and unpublished studies were sought by direct contact with the relevant authors, or institutions. Key individuals who might provide further information regarding validation therapy were contacted. SELECTION CRITERIA: All randomised controlled trials (RCTs) and quasi-randomised controlled trials examining Validation therapy as an intervention for dementia were considered for inclusion in review. The criteria for inclusion/exclusion comprised systematic assessment of the quality of study design and the risk of bias, using a standard data extraction form. Outcome measures of cognitive and/or behavioural change were required. DATA COLLECTION AND ANALYSIS: Data were extracted independently by both reviewers, using a previously tested data extraction form. Authors were contacted for data not provided in the papers. Psychological scales measuring cognitive and behavioural changes were examined. Subcategory analysis was performed due to the diversity of the scales and the inability to combine data across studies. MAIN RESULTS: Only three studies were identifed that potentially met the inclusion criteria and only two small studies were able to be obtained. The Peoples 1982 study was not obtainable through a British Library loan because the cost was prohibitive. Data from 2 studies were entered using MetaView - Robb 1986, Toseland et al 1997, incorporating data on a total of 87 patients (32 in the experimental group, and 55 in the control groups (usual care 34 and social contact 21)). It was not possible to pool the data from the two included studies, and therefore, subcategory analyses were carried out. The analysis of the data failed to reveal statistically significant results although there were trends toward favouring validation therapy for some outcomes. (ABSTRACT TRUNCATED)

Alzheimer Disease↗
PubMedDate not supplied

Reality orientation training in an amnesic: a controlled single-case study (n = 572 days).

'Reality orientation training' (ROT) is a well-established therapy used with the elderly, especially those with dementia. It aims to improve orientation and reduce negative behaviours, e.g. confusion. ROT has been recommended for non-demented patients with acquired neurological impairment. However, this suggestion has not been investigated further in controlled trials. This paper describes an informal 24 h ROT programme with an amnesic subject (H.J.). It combined single-case experimental designs derived from behaviour therapy. Target behaviours were items of temporal orientation--current time/time of day, year, season, month and day of week. Orientation regarding the current date was not trained, and thus served as control variable for non-specific effects (e.g. spontaneous recovery). In order to improve oriented behaviour in different relevant situations outside the clinic, we chose 24 h ROT instead of formal therapeutic sessions. The patients' spouse offered 24 h ROT at home 7 days a week. This consisted of reminding the patient of orientation information, e.g. the current day of the week in different situations. Furthermore, negative behaviours such as irrelevant questions were ignored. The patients' spouse was trained and supervised to carry out this task in 27 sessions each lasting 10 min. For 14 weeks supervision was provided twice a week in the clinic (i.e. 2 x 10 min). Afterwards the spouse continued to apply ROT at home without further supervision in two follow-up periods. As expected, learning was slow but reliable. Generalization of improvement to another setting was shown (home vs clinic). Stable therapeutic gains over a long follow-up period could be demonstrated.(ABSTRACT TRUNCATED AT 250 WORDS)

Activities of Daily Living↗
PubMed2000

[From the great clinical studies to the management of the single patient. Medical therapy in the pre- and post-fibrinolytic era].

Medical therapy of myocardial infarction has changed over the last 30 years. The "lag phenomenon", i.e. the time lapsing from the appraisal of a new, relevant scientific evidence and its practical adoption, has been variable, and different from one treatment to another. It has been very short for GP IIb/IIIa receptor inhibitors in candidates for urgent coronary angioplasty after myocardial infarction, short for ACE inhibitors, and it has been also short for the decrease in the prescription of calcium channel inhibitors after controversial scientific evidence. This time lapse has been long for beta-blockers, that only now are used quite extensively in Italy: from less than 10% of hospitalized patients during the early '80s, to over 60% nowadays. This evolution of medical therapy has been progressive and continuous, has not been divided into two eras, and thrombolysis seems to have little to do with it. The extensive introduction of thrombolysis has simply divided patients with acute myocardial infarction into two subgroups, very different for clinical characteristics: candidates for this therapy, and "others". Candidates for thrombolysis have a much better prognosis, but for a "paradox effect" they have been studied much more than the others. Now, the bulk of publications concerning patients undergoing thrombolysis carries the risk of spreading the concept that myocardial infarction has changed. We do not think that this corresponds to reality. Probably, the concepts that have guided medical therapy have been very similar and unchanged over the years, and both medical and surgical plus coronary angioplasty therapies are today much more appropriately used than yesterday.

Adrenergic beta-Antagonists↗
PubMed2005

Is aggressive lipid-lowering effective and safe in the older adult?

With improvements in diet and health care over the last several decades, the elderly have become the fastest-growing segment of the U.S. population. Along with this progress, however, has come increasing morbidity, much of which is attributable to cardiovascular disease, and which is burdensome both to patients and to the health-care system. New medications, including HMG-CoA reductase inhibitors (statins) have the potential to prevent or delay the progression of disease and vascular events. Large, randomized, placebo-controlled trials continue to show that elderly patients benefit from statin therapy and that aggressive therapy is generally very safe in this population; however, statins remain under-used in older individuals. This paper reviews the benefits of statin therapy in the elderly and discusses the reality versus the perception of risk, selection of appropriate patients, and ways in which any risks that may exist can be minimized further.

Aged↗
PubMed2006

Advances in molecular diagnostics and therapeutics in head and neck cancer.

Extensive treatment-related morbidities and stagnant survival rates over the past few decades for patients with squamous cell cancer of the head and neck (SCCHN) emphasize the need for novel diagnostics and therapeutics based on the molecular characteristics of the tumor. The development of an early detection test remains largely preliminary. Much attention has recently been given to saliva-based early detection assays that use accepted tumor markers such as p53 and DNA methylation. Most of these studies have focused on feasibility as opposed to prospective clinical trials. To date, early detection saliva assays have failed to yield a high enough sensitivity and specificity for broad population-based screening. The use of saliva as a noninvasive, inexpensive, and accessible diagnostic substrate remains desirable. Unlike SCCHN diagnostics, molecular-targeted therapies for SCCHN will soon be a reality, with many more compounds in the pipeline. The most promising of these drugs target the epidermal growth factor receptor (EGFR), which is known to be overexpressed in squamous cell carcinomas. Cetuximab, a monoclonal EGFR antibody, has shown efficacy in combination with radiotherapy in advanced SCCHN in a recent phase III trial and is currently being petitioned for US Food and Drug Administration approval. Likewise, erlotinib, an EGFR tyrosine kinase inhibitor, has shown favorable results in phase II trials as monotherapy and in combination with chemotherapy. Gefitinib, another EGFR tyrosine kinase inhibitor, has shown efficacy as monotherapy, in combination with chemotherapy, and with chemoradiotherapy. At least two phase III trials of gefitinib in patients with advanced SCCHN are ongoing. Such low-toxicity, tumor-specific targeting strategies will soon be available for patients with head and neck cancer. The challenge is to establish assays to determine which patients are most likely to benefit from these agents.

Antibodies, Monoclonal↗
PubMed2004

Reduction of human anti-tetanus toxoid antibody in hu-PBL-SCID mice by immunodominant peptides of tetanus toxoid.

Immunotherapy of murine autoimmune and allergic diseases by administration of peptides corresponding to the dominant T cell epitope is a reality. However, problems remain in applying this therapy to reduce antibody responses in humans. To overcome these difficulties, a preclinical system was developed to test the effect of immunodominant peptides from a common antigen, tetanus toxoid (TT), on the long-term human anti-TT response. Individuals whose T cells proliferated against dominant TT peptides were identified. Peripheral blood leucocytes (PBL) from these donors were injected intraperitoneally (i.p.) into mice with severe combined immunodeficiency (SCID) that had been depleted of murine natural killer (NK) cells (hu-PBL-SCID mice). Peptides or PBS were injected i.p. before a further injection of PBL and immunization with TT. The concentration of human IgG and anti-TT in murine plasma was followed for 10 weeks. The total IgG was similar in both groups. By contrast, there was a statistically significant reduction in IgG anti-TT from eight weeks onwards. It is considered that the hu-PBL-SCID model system may provide a means by which the efficacy of peptide immunotherapy for reduction of pathological antibodies in humans can be examined.

Adult↗
PubMed2006

Molecular and pharmacological properties of human embryonic stem cell-derived cardiomyocytes.

Human embryonic stem cells (hESCs) can be coaxed to differentiate into specific cell types, including cardiomyocyte-like cells. These cells express cardiac-specific markers and display functional similarities to their adult counterparts. Based on these properties, hESC-derived cardiomyocytes have the potential to be extremely useful in various in vitro applications and to provide the opportunity for cardiac cell replacement therapies. However, before this can become a reality, the molecular and functional characteristics of these cells need to be investigated in more detail. In the present study we differentiate hESCs into cardiomyocyte-like cells via embryoid bodies (EBs). The fraction of spontaneously beating clusters obtained from the EBs averaged approximately 30% of the total number of EBs used. These cell clusters were isolated, dissociated into single-cell suspensions, and frozen for long-term storage. The cryopreserved cells could be successfully thawed and subcultured. Using electron microscopy, we observed Z discs and tight junctions in the hESC-derived cardiomyocytes, and by immunohistochemical analysis we detected expression of cardiac-specific markers (cTnI and cMHC). Notably, using BrdU labeling we also could demonstrate that some of the hESC-derived cardiomyocytes retain a proliferative capacity. Furthermore, pharmacological stimulation of the cells resulted in responses indicative of functional adrenergic and muscarinic receptor coupling systems. Taken together, these results lend support to the notion that hESCs can be used as a source for the procurement of cardiomyocytes for in vitro and in vivo applications.

Cell Differentiation↗
PubMed2005

[Eros and Psyche: everything you want to now about their discreet relationship].

For a follower of his liberating cause in the 20th century, it is a wholly technological destiny that now relegates medical sexology into treating the instrumental functions of Sexology. How is it possible to separate so radically the dancer from the dance? Hopefully the opportunity will arise again for physicians and sexologists to become builders of new psychological spaces. The author is suggesting a synthetic approach showing how sexuality is involved in life. The author even describes some heuristics he developed in the framework of a seminary guided by Professor Georges Abraham. Accordingly, the physician will be allowed to join the "dancers", or at least to find a path to the present realities leading further than codified perspectives of therapy.

Female↗
PubMed1995

Strategies of care for patients with dementia.

Strategies are available to help nurses care for patients with dementia in general wards and the community. Strategies include reality orientation, environmental modification, validation and resolution therapies and the use of reminiscence. Such approaches can lead to higher standards of care and a better quality of life for people with dementia.

Aged↗
PubMed2001

Gene therapy for inherited hyperbilirubinemias.

Crigler-Najjar syndrome type 1 (CN-1) is a potentially lethal condition, and is the only inherited disorder of bilirubin metabolism that needs treatment beyond the neonatal period. Currently, orthotopic liver transplantation is the only available cure for CN-1. Because the liver architecture is not disturbed in CN-1 and partial correction of bilirubin-UDP-glucuronosyltransferase (UGT1A1) activity is expected to be sufficient for protection against kernicterus, cell and gene therapies are being developed using the Gunn rat as an animal model of the disease. Ex vivo gene therapy based on the transplantation of genetically manipulated hepatocytes and in vivo gene transfer using recombinant adenovirus and Simian virus 40 (SV40)-based vectors have yielded significant success. The novel strategy of in vivo site-directed mutagenesis has also resulted in modest, but significant, correction of the genetic abnormality. Newer viral and nonviral gene delivery methods are being explored and have been discussed in brief. In summary, effective gene therapy methods have been validated in Gunn rats. Despite considerable remaining hurdles, gene therapy for CN-1 could become a clinical reality by the turn of this decade.

Animals↗