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Biomedical subjects

B Bannwarth

Publications and source records attributed to B Bannwarth.

At least 19 recordsLinked to original sources
PubMed2000

[Gastrointestinal tolerance of nonsteroidal anti-inflammatory agents].

Nonsteroidal anti-inflammatory drugs (NSAIDs) are effective antipyretic, analgesic and anti-inflammatory agents. One of the major concerns regarding the use of these compounds is the incidence of gastrointestinal (GI) adverse effects, ranging from dyspepsia to the serious and potentially life threatening complications of ulcers, haemorrhages, and perforations. Thus, the prevention and/or treatment of upper GI damage is estimated to increase the overall cost of NSAID therapy by at least 40%. The pathogenesis of NSAID-induced gastroduodenal mucosal injury appears to involve both topical and systemic mechanisms. The former is related to the acidic nature of most NSAIDs, which promotes the accumulation of ionised molecules (ion trapping) within the mucosal cells. Topical mucosal injury may also occur as a result of biliary excretion of active NSAID metabolites. The systemic effect has, however, the predominant role. It is mediated through cyclo-oxygenase (COX) inhibition and a subsequent decrease in gastroprotective prostaglandins. Fortunately, 2 forms of COX enzymes, designated COX-1 and COX-2, have been recognised. COX-1 appears to function as a house-keeping enzyme, whereas COX-2 is primarily induced by inflammatory stimuli and mitogens in various cells, including macrophages and synovial cells. Accordingly, the inhibition of COX-2 would result in anti-inflammatory effects, whereas gastroduodenal ulceration is thought to be related to the inhibition of COX-1. Animal data have suggested that nabumetone has a low ulcerogenic potential in comparison with other available NSAIDs. This feature was further supported by controlled clinical trials as well as epidemiological studies. The relative GI safety of nabumetone may be attributed to its lack of direct and indirect topical effects because of its nonacidic nature and absence of enterohepatic recirculation. Furthermore, the active metabolite [6-methoxy-2-naphthylacetic acid (6-MNA)] may be gastro-sparing as a result of its property of COX-2 preferential inhibition.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1999

[New nonsteroidal anti-inflammatory agents: nitric oxide donors and selective cyclooxygenase-2 inhibitors].

The use of non steroidal anti-inflammatory drugs as analgesic or anti-inflammatory agents is primarily limited by their toxicity to the gastrointestinal tract. Two strategies have been developed recently in order to improve the safety of these drugs. The first approach is the linking of a nitric oxide-releasing moiety to the available compounds. The rationale is that nitric oxide may prevent non steroidal anti-inflammatory drugs-induced ulcerations by preventing mucosal ischemia. The second approach is based on the discovery of two isoforms (COX-1 and COX-2) of the cyclo-oxygenase enzyme. It was hypothesized that the constitutively expressed COX-1 isoenzyme leads to the synthesis of prostaglandins with homeostatic functions whereas COX-2 is merely responsible for the production of prostaglandins mediating pain, fever and inflammation. Accordingly, selective COX-2 inhibitors have been developed. Clinical trials indicate that these compounds are roughly as effective as the available non steroidal anti-inflammatory agents without causing acute gastrointestinal damage. There is some evidence that both COX-1 and COX-2 isoforms are involved in the production of prostaglandins associated with inflammation and homeostatic functions. Finally, the true benefit/risk ratio of these new non steroidal anti-inflammatory drugs remains to be assessed.

Analgesics↗
PubMed1999

Influence of molecular lipophilicity on the diffusion of arylpropionate non-steroidal anti-inflammatory drugs into the cerebrospinal fluid.

The diffusion of seven arylpropionic acid non-steroidal anti-inflammatory drugs (NSAIDs) into the cerebrospinal fluid (CSF) has been investigated in male Wistar rats by means of quantitative structure-activity relationship (QSAR) study. After intraperitoneal administration of each drug (5 mg/kg), blood and CSF samples were collected at different times (0.5, 1, 3, and 6 h). The fraction bound to plasma proteins (fb) was determined using ultracentrifugation. The total (CT) and free (CF) plasma concentrations and the concentrations in CSF (CCSF) were measured by a reversed-phase high performance liquid chromatographic (RP-HPLC) method. The areas under the curve of the free plasma (AUCF) and CSF (AUCCSF) concentrations were calculated according to the trapezoidal rule. The overall drug transit into CSF was estimated by the ratio RAUC (AUCCSF: AUCF). The lipophilicity of the compounds was expressed as their polycratic capacity factors (log k'w) measured in a RP-HPLC system. The RAUC ranged from 0.24 to 6.58 and fb from 91.4 to 99.8%. The compounds with an intermediate lipophilicity value (3 < logk'w < 3.6) easily entered the CSF (RAUC > 1). A parabolic relationship was found between log k'w and log RAUC, emphasizing the role of molecular lipophilicity in the diffusion into CSF. Considering the fb value of each drug in regard to this non-linear relationship, it can be hypothesized that the diffusion rate of NSAIDs into the CSF depends primarily on the lipophilicity.

Animals↗
PubMed1999

Risk-benefit assessment of opioids in chronic noncancer pain.

Opioids have been accepted as appropriate treatment for acute and cancer pain, but their role in the management of chronic nonmalignant pain is the subject of much debate, mainly due to concerns about waning efficacy, the potential for neuropsychological impairment and the development of drug addiction. Controlled clinical trials demonstrated that opioids may be effective in both nociceptive and neuropathic noncancer pain, although the former responded more consistently than the latter. Gastrointestinal and CNS adverse effects were frequent in most studies. Observational studies have generated contradictory findings regarding efficacy and safety as well as the risk of drug addiction in patients with chronic noncancer pain receiving long term opioid therapy. However, they suggest that opioids may be effective in individual cases, whichever the pathophysiological mechanism of pain. Taken together, the available data indicate that the outcomes associated with opioid therapy vary markedly across patients experiencing chronic nonmalignant pain. The main consensus is that a subset of these patients may gain substantial benefit from opioid analgesics without requiring rapidly escalating doses or developing intolerable adverse effects or drug addiction. Prescribing guidelines have been developed to assist practitioners in selecting the appropriate patients and ensuring an acceptable risk : benefit ratio of opioid therapy. Finally, it must be emphasised that chronic pain is a complex entity wherein analgesics, including opioids, are only part of the treatment.

Analgesics, Non-Narcotic↗
PubMed1998

Propionibacterium acnes isolated from synovial tissue and fluid in a patient with oligoarthritis associated with acne and pustulosis.

This report describes the case of a patient with a 14-month course of severe oligoarthritis associated with acne. Pure cultures of Propionibacterium acnes were isolated from synovial tissue and synovial fluid specimens collected from the same joint after a 4-month interval. After 2 months of treatment with roxithromycin 300 mg/day, rifampicin 1,200 mg/day, and a nonsteroidal antiinflammatory drug (NSAID), followed by 4 months of treatment with azithromycin 1 gm/week and an NSAID, the synovitis persisted. Cultures of skin lesions and synovial fluid at this time were negative. Although P acnes has previously been isolated from bone specimens obtained from patients with osteitis associated with acne, this is the first report of the isolation of this microorganism from the synovial tissue of a patient with arthritis associated with acne. Our findings raise the question of the role of P acnes in the pathogenesis of arthritis associated with acne.

Acne Vulgaris↗
PubMed1998

Effect of dimethicone (polysilane gel) on the stereoselective pharmacokinetics of ketoprofen.

OBJECTIVE: Since dimethicone may be employed to improve gastrointestinal tolerability of non steroidal anti-inflammatory drugs (NSAIDs), we studied its influence on the pharmacokinetics of ketoprofen in subjects receiving a single oral dose of racemic ketoprofen. PATIENTS AND METHODS: In a cross-over experimental design, 12 healthy fasting volunteers were given a single oral dose (100 mg) of racemic ketoprofen, administered with or without dimethicone. The kinetic parameters measured were area under the concentration (AUC), maximum peak plasma concentration (Cmax), time to reach peak concentration (tmax), elimination half-life (t1/2), mean residence time (MRT) and urinary excretion for R and S enantiomers. RESULTS: Dimethicone reduced the peak concentration of both R and S ketoprofen by about 10% (P<0.05) and also induced a slight but non-significant increase in the mean time to achieve peak concentration. However, this treatment had no significant effect on the bioavailability and the elimination of R and S enantiomers, as shown by AUC, t1/2 and MRT values. The absorption patterns were equivalent for both ketoprofen isomers, since plasma pharmacokinetic parameters were similar. Nevertheless, the urinary recovery was significantly lower for R ketoprofen than for its antipode. The administration of dimethicone did not alter this stereoselectivity. CONCLUSION: The administration of dimethicone to alleviate the epigastralgic effects related to NSAIDs does not affect the efficacy of the treatment. Dimethicone did not significantly alter the bioavailability of ketoprofen, chosen as an example of an NSAID, especially that of the pharmacologically active S enantiomer.

Adult↗
PubMed1998

Passage of S-(+)- and R-(-)-ketoprofen across the human isolated perfused placenta.

Ketoprofen is a chiral non-steroidal anti-inflammatory drug (NSAID) available as a racemic (rac) mixture of S-(+)- and R-(-)-isomers. Its inhibitory effect on prostaglandin biosynthesis resides virtually in the S-form. Interestingly, R-ketoprofen does not undergo substantial metabolic inversion in humans. Though contraindicated during the last trimester of pregnancy, NSAIDs, including ketoprofen, are used as tocolytic agents in some cases. The S/R plasma concentration ratio was reported to average 2.3 in premature neonates whose mothers were given rac-ketoprofen and to be close to 1 in the maternal plasma. Thus, we investigated the placental transfer of rac-ketoprofen in vitro using Schneider's perfused human cotyledon model. Glucosed Earle solutions with and without human serum albumin (HSA) were used. Several maternal perfusates were tested with different rac-ketoprofen concentrations together with 20 mg L-1 of antipyrine as a reference substance. Ketoprofen enantiomers were assayed by a specific HPLC method with derivatization procedure. HSA concentrations in maternal perfusate influenced the placental transfer of ketoprofen enantiomers. In the absence of HSA in the maternal perfusate, the S-(+)/R-(-) concentration ratio was close to 1 in the fetal perfusate. By contrast, this ratio averaged 1.44 after addition of HSA 10 g L-1 on the maternal side. Similar results were found for dialysis experiments using an inert Spectrapor 2 membrane suggesting that the S-(+)-free concentration is superior to the R-(-)-free concentration in the presence of HSA. Direct measurements of the free concentrations by centrifugal ultrafiltration confirmed this hypothesis. Accordingly, the data observed in vivo may result, at least in part, from the stereoselective protein binding of ketoprofen.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1998

Genotypic characterization of seven strains of Mycoplasma fermentans isolated from synovial fluids of patients with arthritis.

We performed a genotypic characterization of seven strains of Mycoplasma fermentans which have been isolated from the synovial fluid of patients with rheumatoid arthritis (n = 2), spondyloarthropathy (n = 1), and unclassified arthritis (n = 4). We compared them to three reference strains (strains PG18 and K7 and incognitus strain) and to a clinical isolate from the urethra of a patient with nongonococcal urethritis. The characterization methods included electrophoresis of native DNA, arbitrarily primed PCR, and restriction fragment length polymorphism analysis following conventional and pulsed-field gel electrophoresis. Southern blot analysis with a probe internal to an insertion sequence was performed with the restriction products produced by the last two techniques. No extrachromosomal DNA sequences were detected. The M. fermentans strains identified by these methods did not present a unique profile, but they could be separated into two main categories: four articular isolates were genetically related to PG18 and the three other isolates, the urethral isolate, and the incognitus strain were related to K7. We also looked for the presence of the bacteriophage MAV1 (associated with the arthritogenic property of Mycoplasma arthritidis in rodents) in the M. fermentans strains. MAV1 DNA was not detected in either the clinical isolates or the reference strains of M. fermentans.

Adult↗
PubMed1998

Effect of balanced analgesia with buprenorphine on pain response and general anaesthesia requirement during lithotripsy procedures.

The effectiveness of a balanced analgesia with buprenorphine ketoprofen-propacetamol for pain control during extracorporeal shock wave lithotripsy (ESWL) was evaluated in order to reduce the requirements for general anaesthesia. Two hundred and ninety-one consecutive patients were included in a randomized, placebo-controlled, double-blind study. Patients in each group received midazolam 5 mg pre-operatively as premedication. The subjects then received either placebo (group 1), buprenorphine 0.3 mg (group 2) or the combination buprenorphine 0.3 mg plus ketoprofen 100 mg and propacetamol 2 g (group 3) intravenously (i.v.) at a constant rate. The treatment was started 45 min prior to ESWL. Pain was assessed using a three-point verbal scale: (0)no pain; (1) moderate pain; and (2) intense pain needing general anaesthesia. The patients assessed their pain intensity on a 0-100 mm visual analogue scale. Only 69% of group 1 patients received ESWL with midazolam premedication. Buprenorphine provided good analgesia in 87% of group 2 patients, while the combination buprenorphine-ketoprofen-propacetamol was effective in 99% of group 3 patients (P < 0.05). The incidence of nausea and vomiting was similar in the buprenorphine groups. No respiratory depression was reported. In conclusion, the buprenorphine-ketoprofen-propacetamol combination provided effective analgesia, allowing ESWL to be performed without the need for general anaesthesia.

Acetaminophen↗
PubMed1998

[Prescription of non-steroidal anti-inflammatory drugs].

Non steroidal anti-inflammatory drugs (NSAIDs) are widely prescribed and largely used over the counter, especially for analgesic purposes in the most commonly nociceptive painful disorders. Unfortunately, NSAID use is associated with a high rate of side effects which account for 9% to 25% of the reports to the drug surveillance centres all over the world. Interestingly, severe adverse events are partly preventable provided some recommendations are followed. First, individual risk factors (old age, gastrointestinal history, possible drug interaction, ...) should be carefully assessed in order to take particular preventive measures (coprescription of misoprostol or omeprazole, treatment of a preexisting dehydration, ...) or ensure specific monitoring. Second, NSAIDs should be used at the lowest effective dosage after consideration of safer alternatives. Third, NSAIDs should be combined with other analgesics with the aim of reducing NSAID dosage. Finally, the patients should be informed about the main side effects of NSAIDs.

Adult↗