Biomedical subjects

Alain Baumelou

Publications and source records attributed to Alain Baumelou.

8 recordsLinked to original sources

PubMed2006

Renal tubular drug transporters.

The kidney plays an important role in the elimination of numerous hydrophilic xenobiotics, including drugs, toxins, and endogenous compounds. It has developed high-capacity transport systems to prevent urinary loss of filtered nutrients, as well as electrolytes, and simultaneously to facilitate tubular secretion of a wide range of organic ions. Transport systems for organic anions and cations are primarily involved in the secretion of drugs in renal tubules. The identification and characterization of organic anion and cation transporters have been progressing at the molecular level. To date, many members of the organic anion transporter, organic cation transporter, and organic anion-transporting polypeptide families have been found to mediate the transport of diverse organic ions. It has also been suggested that ATP-dependent primary active transporters such as MDR1/P-glycoprotein and the multidrug resistance-associated protein family function as efflux pumps of renal tubular cells for more hydrophobic molecules and anionic conjugates. Tubular reabsorption of peptide-like drugs such as beta-lactam antibiotics across the brush-border membranes appears to be mediated by two distinct H+/peptide cotransporters: PEPT1 and PEPT2. Renal disposition of drugs occurs through interaction with these diverse secretory and absorptive transporters in renal tubules. Studies of the functional characteristics, such as substrate specificity and transport mechanisms, and of the localization of drug transporters could provide information regarding the cellular network involved in renal handling of drugs. Detailed information concerning molecular and cellular aspects of drug transporters expressed in the kidney has facilitated studies of the mechanisms underlying renal disposition as well as transporter-mediated drug interactions.

Animals↗

PubMed2005

[Medication use in older patients with chronic renal failure].

Adverse drug reactions in the elderly are of growing concern because of the increasing elderly population and the increasing numbers of medications prescribed to this group. Ageing and the frequent comorbid diseases in the elderly result in altered drug pharmacokinetics and pharmacodynamics increasing the risk of side effects. The decline in renal function affects the elimination of many drugs. Before prescribing an estimation of the glomerular filtration rate is of the highest importance. All the nomogramms and formulae are approximate in the oldest old. The Cockcroft and Gault formula is frequently used. Pharmacodynamic alterations are particularly important for the centrally active drugs that older people are more vulnerable to, for example increased and prolonged effects of anticholinergic, hypnotic and sedative drugs. Polypharmacy and self-medication is also common in these patients, with increased chance for drug-drug interactions. In France, the recent law on Public Health (August 09, 2004) requires for the next five years to decrease the frequency of inappropiate prescriptions in elderly people and of to decrease the frequency of the drug-induced hospitalisations. Undertreatment of the elderly is not the solution: it's necessary to optimize their medication: to well appreciate before prescription their motor and cognitive deficiencies interfering with compliance, to "start low and go slow" their medications, to review their drug consumption on a regular basis, to educate them and their family for a good observance.

Aged, 80 and over↗

PubMed2005

FHD: an index to evaluate drug elimination by hemodialysis.

BACKGROUND: In hemodialyzed patients, physicians have to (1) adjust drug dosage for a creatinine clearance lower than 10-15 ml/min and (2) know whether or not the drug will be removed by the dialysis session to decide whether it may be administered before or after the session on dialysis days. However, of several indices being used to evaluate drug removal by dialysis none is appropriate and we suggest a novel index named F(HD), which reflects the role of hemodialysis clearance of a drug in its overall clearance during the session. METHODS: Pharmacokinetic simulations were performed to test the influence of dialysis on the pharmacokinetics of some drugs, whether F(HD) was considered or not, to determine when to administer the drug. F(HD) was then calculated for several drugs and its value compared with other indices. Five hemodialysis patients from our department for whom the time of drug administration was determined according to F(HD) were included in a small study and their drugs' trough concentrations were monitored. RESULTS: F(HD) emphasized that considering hemodialysis clearance alone may lead to false interpretations of the potential dialyzability of some drugs. In our patients, who received their treatment according to the 'F(HD) rule', monitoring of trough levels gave satisfactory results. CONCLUSION: The use of the 'F(HD) rule' should be tested on a long-term administration basis to confirm our conclusion. F(HD )could be the index of choice to determine when to administer a drug, before or after the session, in hemodialysis patients.

Adult↗

PubMed2005

Renal disease in cardiovascular disorders: an underrecognized problem.

Chronic renal disease is generally appreciated as a major and rapidly growing health problem. In the United States alone, as many as 19.5 million people may have markers of early renal disease, and more than 660,000 people are expected to require renal replacement therapy by the year 2010. By contrast, the presence and pathological role of renal disease in patients with cardiovascular disease are somewhat underrecognized. Evidence now shows that even minor impairments in renal function, as indicated by measures including glomerular filtration rate and microalbuminuria, are common in cardiovascular disease states and predictive of cardiovascular events. Indeed, microalbuminuria may be a marker of systemic vascular disease rather than kidney dysfunction alone. In patients with hypertension, diabetes, metabolic syndrome, acute coronary syndromes, and stroke, markers of renal disease have proved to be at least as predictive of morbidity and mortality as conventional risk factors. Yet, chart reviews in a variety of clinical settings reflect poor recognition and management of renal disease in at-risk patients. Models for renal protection are based on the control of risk factors, particularly blood pressure, that are associated with renal and cardiovascular outcomes. Screening protocols for markers of renal disease should recognize the potential inaccuracy of serum creatinine concentrations and the preferability of glomerular filtration rate estimates that take age and gender into account. Pilot programs for screening high-risk populations have shown efficacy in detecting renal disease.

Biomarkers↗

PubMed2004

Herbs and the kidney.

The use of herbal therapy has increased dramatically in past years and may lead to renal injury or various toxic insults, especially in renal patients. In most countries, herbal products are not regulated as medicines. Herbal poisoning may be secondary to the presence of undisclosed drugs or heavy metals, interaction with the pharmacokinetic profile of concomitantly administered drugs, or association with a misidentified herbal species. Various renal syndromes were reported after the use of medicinal plants, including tubular necrosis, acute interstitial nephritis, Fanconi's syndrome, hypokalemia or hyperkalemia, hypertension, papillary necrosis, chronic interstitial nephritis, nephrolithiasis, urinary retention, and cancer of the urinary tract. It seems critical that caregivers be aware of the potential risk of such often underreported therapy and carefully question their patients about their use of this popular branch of alternative medicine.

Aristolochic Acids↗

PubMed2004

Antiretroviral and immunosuppressive drug-drug interactions: an update.

With the introduction of highly active antiretroviral therapy (HAART), human immunodeficiency virus (HIV) infection has become a chronic disease with more frequent end-stage organ failures. As a result, the question of transplantation in HIV patients is raised more often. However, some of the HAART regimen medications require elimination or metabolism via the P-glycoprotein (P-gp) and multidrug-resistant protein (MRP) transporters or via the cytochrome P450 enzyme system. Since these transporters and enzymes are also responsible for the clearance of immunosuppressive drugs, drug-drug interactions are likely to occur. Indeed, profound drug-drug interactions between protease inhibitors and immunosuppressive drugs have been observed and they required reductions in drug dosage. In contrast, HAART using nucleoside or nonnucleoside reverse transcriptase inhibitors without the use of protease inhibitors has been shown to produce less significant drug-drug interactions. It is thus crucial to take into account those potential pharmacokinetic and/or pharmacodynamic drug-drug interactions in order to avoid drug toxicity or a lack of efficacy. The aim of this work was to review and synthesize the international literature on this field in order to give practical recommendations on how to manage immunosuppressive drugs in HIV patients who get transplanted and on how to handle HAART therapy in transplant-recipient patients who get infected with HIV.

Acquired Immunodeficiency Syndrome↗

PubMed2003

Unusual IgM fibrillar deposits in glomerulonephritis: ultrastructural and diffraction studies in a case report.

Morphological examination of 2 renal biopsy specimens obtained from a 69-year-old woman with a nephrotic syndrome, high blood pressure, and a reduced glomerular filtration rate revealed, in ultrastructural study, a type of a glomerulonephritis with fibrillar deposits in a subendothelial position which were unusual in their immunoglobulin components (mainly IgM). The fibrillar components were of irregular size, 13 to 18 nm in diameter and presented a very particular "barbed wire" morphological aspect, not hitherto described. Diffraction studies and image analysis, revealed spiraled fibrils with regular alternating elements that we suggest may correspond to IgM molecules. The clinical (isolated renal symptoms) and laboratory (traces of 3 monoclonal components in the serum and 2 normal bone marrow biopsy specimens) data provided no evidence of hematopoietic malignancy, viral hepatitis or cryoglobulinemia.

Aged↗

PubMed2002

Primary chronic interstitial nephritis in Crohn's disease.

BACKGROUND & AIMS: In Crohn's disease, cases of interstitial nephritis with renal failure have been reported in connection with the use of mesalamine. METHODS: We observed 4 patients with severe interstitial nephritis proven by examination of kidney biopsy specimens. Renal failure was discovered before or simultaneously with the diagnosis of Crohn's disease, and patients were not treated with mesalamine. Impairment of renal function progressed to end-stage renal failure in 3 of the 4 patients. RESULTS: Our results show that the kidney can be an extraintestinal target of Crohn's disease. CONCLUSIONS: Several unanswered questions remain concerning the frequency of interstitial nephritis in patients with Crohn's disease, as well as the exact role of mesalamine in the development of chronic interstitial nephritis.

Adult↗