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At least 217 records · Page 12Linked to original sources
PubMed2003

Structured treatment interruptions in HIV infection: benefit or disappointment?

Many investigators are and have been studying the impact of structured treatment interruptions in HIV patients on subsequent viral control, HIV-specific cellular and humoral immunity, improvement of quality of life, and reduction of side effects and costs. Although varying treatment schedules have been followed and few clinical trials of different cohort size have been completed, tentative conclusions can already be drawn. Firstly after the initiation of treatment during acute infection followed by structured treatment interruptions, some patients maintained low level viremia during many months, such control of viremia has not been observed after the initiation of treatment during chronic infection followed by structured treatment interruptions. Second, structured treatment interruptions lead to an increase in frequencies of HIV-specific CD8(+) T-cell populations, however, these frequencies are not above pretreatment frequencies in chronically infected patients. Third, HIV-specific CD4(+) T-cell responses can be induced or enhanced during structured treatment interruptions but this augmentation was usually only transient. Finally, selection of drug-resistant virus variants may occur during structured treatment interruptions but clinical resistance to treatment has been quite rare. The initial hopes that structured treatment interruptions would substantially enhance immune control in the absence of therapy have not been confirmed, particularly in patients who initiated therapy during chronic infection. Additional immune-stimulatory interventions are now being considered and tested, such as administration of cytokines or vaccination. Furthermore, the demonstration of reduced side effects or costs due to structured treatment interruptions awaits the completion of large, comparative studies with a follow-up of several years.

Anti-HIV Agents↗
PubMed2004

Single-enantiomer drugs: elegant science, disappointing effects.

Most new drugs are marketed as single enantiomers but many older agents are still available in racemic form. As these drugs reach the end of their patent life manufacturers become interested in marketing single enantiomer equivalents. This is called 'chiral switching' and it has been claimed that it will bring clinical benefits in terms of improved efficacy, more predictable pharmacokinetics or reduced toxicity. We reviewed the clinical evidence and prices for three recently marketed single enantiomer versions of widely used racemic drugs: escitalopram, esomeprazole and levosalbutamol. Claims of increased efficacy were based on comparisons of non-equivalent doses and any advantages seemed small and clinically unimportant. Prices of esomeprazole and levosalbutamol were higher than their racemic alternatives and we predict that these prices will remain high despite the market presence of generic versions of the racemates. Patent protection and a perception of superiority based on promotion rather than evidence will maintain price premiums for single enantiomer drugs that are not justified on the basis of clinical performance.

Albuterol↗
PubMed2003

Pharmacogenomics and "individualized drug therapy": high expectations and disappointing achievements.

Since 1965 there have been more than 800 pharmacogenetics/genomics reviews - most suggesting that we are on the verge of offering individualized drug therapy to everyone. However, there are numerous reasons why this approach will be extremely difficult to achieve in the foreseeable future. Drug treatment outcome represents a complex phenotype, encoded by dozens, if not hundreds, of genes, and affected by many environmental factors; therefore, we will almost always see a gradient of response. Phenotyping assays of blood enzyme activities (if feasible) are generally more successful than DNA genotyping for predicting unequivocal outcomes of drug therapy in each and every patient. Phenotyping with probe drugs has generally not succeeded, because of the overlapping substrate specificities not only of drug-metabolizing enzymes but also transporters, receptors, ion channels, transcription factors, and other drug targets; drug-drug interactions, enzyme induction and inhibition, and multiple (enzyme, transporter, second-messenger, signal transduction) pathways also present enormous problems. Genotyping to predict drug disposition, efficacy, toxicity, and clinical outcome has been proposed, but the success of genotyping in individualized drug therapy currently appears unlikely because of the many shortcomings (frequency of DNA variant sites, ethnic differences, admixture) and complexities (plasticity of the genome, multiple mechanisms for determining sizes and locations of haplotype blocks) of this approach. Genomics is an important tool in basic research; yet, it is unrealistic to include genotyping within the realm of tests available to the practicing clinician in the foreseeable future. The same can be said for transcriptomics and proteomics, which also rely on available sources (tumors, biopsies, excreta). The newly emerging fields of metabonomics and phenomics might offer solutions to anticipating and decreasing individual risk for adverse drug reactions in each individual patient; however, tests based on these approaches are not expected to become available to the practicing clinician for at least the next 5-10 years.

Humans↗
PubMed1992

Chemotherapy for gastrointestinal cancer: new hopes or new disappointments?

Since the end of the eighties relevant progress has been made in the treatment of gastrointestinal tract cancer, as well in advanced disease as in the adjuvant setting. The neoadjuvant treatment of localized esophageal and gastric cancer is of high interest, and especially the adjuvant treatment of colorectal cancer provides a realistic hope for further progress in the years not too far ahead. Results of recent studies with implications for future trials are discussed.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1988

Extraarticular repair of the unstable knee. Disappointing 6-year results of the Slocum and Ellison operations.

Thirty-nine clinically unstable knees caused by anterior cruciate ligament rupture were evaluated 5-8 years after medial and lateral extraarticular stabilization according to Slocum and Ellison. At the follow-up, 10 knees had been subjected to an intraarticular anterior cruciate ligament reconstruction, and one knee was not available for follow-up. The mean Lysholm score for the 28 reexamined knees was 84 out of a maximum of 100 points. Activity scores were generally low, and all the knees had increased anterior drawer instability. The combination of the pes anserinus and lateral extraarticular repair did not give acceptable long-term results.

Adolescent↗
PubMed2006

Antioxidants and hormones as antiaging therapies: high hopes, disappointing results.

No single agent has been shown to truly reverse aging or increase longevity in humans. This article reviews the evidence of efficacy (or lack thereof) for two types of agents touted as antiaging therapies: antioxidants (vitamin E, vitamin C, and carotenoids) and hormones (growth hormone, testosterone, dehydroepiandrosterone, and vitamin D).

Aging↗