PubMed Health⌕ Search

Biomedical subjects

L R Wiseman

Publications and source records attributed to L R Wiseman.

46 records · Page 3Linked to original sources
PubMed1994

Ceftibuten. A review of its antibacterial activity, pharmacokinetic properties and clinical efficacy.

Ceftibuten is an orally active third generation cephalosporin which has a broad spectrum of in vitro antibacterial activity, encompassing the majority of Gram-negative pathogens and streptococci, and which shows greater stability than several other cephalosporins against bacteria producing extended-spectrum beta-lactamases. In clinical studies, ceftibuten (generally 400 mg/day in adults or 9 mg/kg/day in children, administered once daily) was effective in the treatment of acute uncomplicated or complicated urinary tract infections, demonstrating an efficacy similar to that of cefaclor (1500 mg/day), and similar or superior to that of cotrimoxazole (trimethoprim/sulfamethoxazole; 8/40 mg/kg/day) in children. The majority of patients with acute or chronic lower respiratory tract infections responded to treatment with ceftibuten, and response rates were similar to those achieved with cefaclor (750 or 1500 mg/day). Ceftibuten 9 mg/kg/day was at least as effective as cefaclor and as effective as amoxicillin/clavulanic acid (both 40 mg/kg/day) in children with acute otitis media, and was superior to phenoxymethylpenicillin (penicillin V; 25 mg/kg/day) in children and adolescents with streptococcal pharyngitis or scarlet fever caused by Group A beta-haemolytic streptococci. Ceftibuten was well tolerated in most patients, with adverse events (mostly mild to moderate gastrointestinal disturbances) generally occurring in 5 to 10% of patients. Thus, ceftibuten, with a once- or twice-daily oral dosage regimen, good tolerability profile and activity against a wide range of bacterial organisms, offers a promising alternative to other agents (including cefaclor, cotrimoxazole, amoxicillin/clavulanic acid, bacampicillin and phenoxymethylpenicillin) for the treatment of patients with urogenital and respiratory tract infections. Its place in therapy will be more clearly defined following further large comparative trials, in which it is likely to prove most useful in patients with infections caused by beta-lactamase-producing pathogens.

Adult↗
PubMed1994

Trandolapril. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in essential hypertension.

Trandolapril is a non-sulfhydryl prodrug which, after oral administration, is hydrolysed in the liver to its active diacid, trandolaprilat. Trandolaprilat inhibits the angiotensin converting enzyme (ACE) and displays similar pharmacodynamic properties to other ACE inhibitors, improving haemodynamic and cardiac parameters in patients with essential hypertension. Trandolapril 2 to 4mg once daily effectively controls blood pressure for at least 24 hours in patients with mild to moderate hypertension. In a small number of double-blind comparative trials, trandolapril had similar antihypertensive efficacy to that of atenolol, enalapril, hydrochlorothiazide, lisinopril and sustained release nifedipine, but was more effective than captopril. Combined therapy with trandolapril and hydrochlorothiazide or sustained release nifedipine had a significantly greater antihypertensive effect than either drug treatment alone. Further comparative trials are warranted to confirm these preliminary findings. The tolerability profile of trandolapril is similar to that of other ACE inhibitors, most adverse events being generally mild and transient in nature, and trandolapril lacks adverse effects on carbohydrate and lipid metabolism. Thus, trandolapril, with its favourable pharmacological profile and antihypertensive activity similar to that of agents currently used to treat patients with mild to moderate hypertension, is likely to provide a well tolerated option for the treatment of this disease. The results of ongoing and future clinical trials will determine its potential as a cardioprotective agent in patients following myocardial infarction.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1994

Porcine-derived lung surfactant. A review of the therapeutic efficacy and clinical tolerability of a natural surfactant preparation (Curosurf) in neonatal respiratory distress syndrome.

Porcine-derived lung surfactant (PLS; Curosurf) has shown efficacy in neonatal respiratory distress syndrome. PLS consists of phospholipids, mainly dipalmitoylphosphatidylcholine, the primary surface-active agent of natural lung surfactant, and pulmonary surfactant-associated proteins which facilitate spreading and adsorption of the surface-active agent at the air-alveolar interface. Intratracheal administration of a single dose of PLS 200 mg/kg significantly improves the survival rate and reduces the incidence of bronchopulmonary dysplasia at 28 days in premature infants (birthweight 700 to 2000g) with severe respiratory distress syndrome (fraction of inspired oxygen > or = 0.60). PLS also reduces the incidence of air leak events such as pulmonary interstitial emphysema and pneumothorax. The response rate may be further improved by administration of additional 100 mg/kg doses at 12-hour intervals to infants showing a poor response or relapse after a single dose. PLS prophylaxis reduces the incidence and severity of respiratory distress syndrome in premature infants at high risk of developing the disease; however, it remains unclear whether the eventual clinical outcome is similar or superior to that observed in infants who receive rescue treatment. PLS is well tolerated and does not appear to increase the incidence of complications of prematurity or respiratory distress syndrome, including patent ductus arteriosus and intraventricular haemorrhage. Although its effect on long term development require further investigation, early indications are that PLS is not associated with any long term adverse sequelae. Comparative trials are clearly warranted to determine the efficacy and tolerability of PLS relative to that of other available surfactant preparations, particularly to explore preliminary indications that a more rapid effect of natural surfactants such as PLS (compared with synthetic products) may correlate with improved clinical outcomes, and that PLS may result in fewer complications than synthetic preparations. Thus, available data show PLS to be a very effective agent for the treatment and prophylaxis of neonatal respiratory distress syndrome, and that it may have some advantages over synthetic preparations.

Animals↗
PubMed1993

Type I IGF receptor and acquired tamoxifen resistance in oestrogen-responsive human breast cancer cells.

Tamoxifen inhibited the oestrogen-stimulated proliferation of MCF-7 cells but had little effect on the oestrogen-stimulated proliferation of two tamoxifen-resistant variants (RL-3 and AL-1). The lack of oestrogen antagonist activity in the resistant cells was largely a result of an increased oestrogen agonist activity of tamoxifen on cell proliferation. Proliferation of the tamoxifen-resistant cells was also stimulated by 4-hydroxytamoxifen but not by ICI 164,384, a structurally distinct pure anti-oestrogen. Tamoxifen does not have increased oestrogen agonist activity for the induction of a series of oestrogen-regulated RNAs, and this suggests that the increased agonist activity may be restricted to key components involved in the proliferative response. Tamoxifen-stimulated cell proliferation was dependent on insulin-like growth factor I (IGF-1) in the resistant cells, suggesting that tamoxifen stimulates cell proliferation by sensitising cells to the proliferative effects of IGF-1. This may involve induction of the type-I IGF receptor.

Breast Neoplasms↗
PubMed1993

Formestane. A review of its pharmacodynamic and pharmacokinetic properties and therapeutic potential in the management of breast cancer and prostatic cancer.

Formestane (4-hydroxyandrostenedione) is an effective and competitive inhibitor of aromatase, the enzyme responsible for the conversion of androgens to estrone and estradiol. Significant reductions in plasma estradiol levels are observed following intramuscular administration of formestane to postmenopausal women with advanced metastatic breast cancer. Overall response rates to intramuscular formestane in these patients are approximately 25 to 30% and a further 20 to 30% of patients experience disease stabilisation during treatment. Response rates are improved in patients with hormone responsive tumours and in those who have responded to previous endocrine therapy. Soft tissue metastases generally show the best response to formestane treatment while visceral metastases (in particular liver) show a poor response. The median duration of response is usually between 7 months and 1 year. Formestane has been generally well tolerated in the relatively small clinical trials conducted to date with adverse effects reported in approximately 13% of patients following intramuscular administration. The most frequent adverse effects are local reactions at the injection site and systemic effects mainly related to the effect of the drug on the hormonal milieu. Thus, formestane is effective as a second-line endocrine treatment for advanced metastatic breast cancer in women with natural or artificially induced menopause, with apparent tolerability advantages over older agents such as aminoglutethimide; with wider study and experience it may yet challenge tamoxifen as a first-line endocrine therapy in metastatic breast cancer.

Androstenedione↗
PubMed1993

Cefprozil. A review of its antibacterial activity, pharmacokinetic properties, and therapeutic potential.

Cefprozil is an orally active cephalosporin which has demonstrated activity against a wide range of organisms in vitro. It is particularly active against the Gram-positive organisms Streptococcus pyogenes, pneumoniae and agalactiae and against methicillin-susceptible Staphylococcus aureus. Strains of methicillin-resistant S. aureus are not susceptible to cefprozil. Cefprozil is also moderately active against Haemophilus influenzae, Moraxella catarrhalis, Neisseria gonorrhoeae, many Enterobacteriaceae and certain anaerobic organisms, and is relatively stable to hydrolysis by a number of beta-lactamases. In comparative trials, the clinical and bacteriological efficacy of cefprozil 500mg or 20 mg/kg administered once or twice daily has been comparable with multiple daily dosage regimens of erythromycin in patients with tonsillitis or pharyngitis, with cefaclor and amoxicillin/clavulanate in lower respiratory tract infections, with amoxicillin/clavulanate and erythromycin in skin and skin-structure infections and with cefaclor in acute uncomplicated urinary tract infections. The clinical efficacy of cefprozil is similar to that of cefaclor in patients with tonsillitis or pharyngitis but the bacteriological efficacy of cefprozil is significantly greater than that of cefaclor. Cefprozil is clinically more effective than cefuroxime axetil in the treatment of lower respiratory tract infections and demonstrated greater efficacy than cefaclor in one of 2 comparative studies when administered twice daily in patients with skin and skin-structure infections. In children with acute otitis media, cefprozil 15 mg/kg twice daily was as effective as cefaclor or amoxicillin/clavulanate 13.3 mg/kg 3 times daily and was as effective as cefixime 8 mg/kg once daily. The most frequently reported adverse effects associated with cefprozil, diarrhoea and nausea, are usually mild to moderate in severity and discontinuation of treatment is rarely necessary. Thus, cefprozil with its convenient administration regimen appears to be a suitable alternative to cefaclor, cefixime, amoxicillin/clavulanate or erythromycin for the treatment of upper and lower respiratory tract infections, skin and skin-structure infections, and otitis media in children. While cefprozil has shown similar efficacy to cefaclor in the treatment of uncomplicated urinary tract infections, well-controlled clinical trials comparing its efficacy with that of cotrimoxazole (trimethoprim+sulfamethoxazole) in this indication are required.

Animals↗
PubMed1992

Indobufen. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in cerebral, peripheral and coronary vascular disease.

Indobufen is an inhibitor of platelet aggregation which acts by reversibly inhibiting the platelet cyclo-oxygenase enzyme. Improvements in walking distances and microcirculatory parameters have been achieved during therapy with indobufen in patients with peripheral vascular disease and intermittent claudication. Indobufen has been shown to be as effective as aspirin plus dipyridamole in preventing the reocclusion of coronary and femoro-popliteal artery bypass grafts and has been shown to significantly reduce platelet deposition on haemodialysis membranes. Initial studies have also indicated that indobufen may have a prophylactic effect on the incidence of secondary thrombotic events following transient ischaemic attack or mild stroke and may be effective in the prophylaxis of migraine. Indobufen is well tolerated following oral administration and has been associated with a low incidence of adverse effects rarely requiring withdrawal of treatment. Thus, available evidence indicates that indobufen may be an effective alternative to aspirin for the treatment of cerebral, peripheral and coronary vascular diseases with the advantage of a lower incidence of gastrointestinal effects compared to high dose aspirin, rendering indobufen more suitable for longer term therapy.

Cerebrovascular Disorders↗
PubMed1989

Effects of the antioestrogen, ICI 164,384, on oestrogen induced RNAs in MCF-7 cells.

The effects of ICI 164,384 on the expression of six oestrogen-regulated RNAs (pNR-1, pNR-2, pNR-13, pNR-17, pNR-25 and pNR-100) and the 46 kDa secreted protein were measured in MCF-7 cells. In marked contrast to tamoxifen, an antioestrogen commonly used in the treatment of breast cancer, ICI 164,384 administered alone had little or no effect on the RNAs or protein. ICI 164,384 completely inhibited the induction of the RNAs and 46 kDa protein by oestradiol. Although ICI 164,384 has an affinity for the human oestrogen receptor only slightly less than that of oestradiol, half maximal inhibition of oestradiol action was attained with between a 50 and 150-fold molar excess of ICI 164,384. The pNR-1 RNA is induced by tamoxifen but this induction was abolished by ICI 164,384. Thus, ICI 164,384 acts as a potent antioestrogen for the regulation of the expression of specific oestrogen-responsive genes in human breast cancer cells.

Breast Neoplasms↗
PubMed1989

Regulation of progesterone receptor mRNA by oestradiol and antioestrogens in breast cancer cell lines.

The induction of progesterone receptor mRNA by oestradiol and antioestrogens has been characterised in the MCF-7 breast cancer cell line. Progesterone receptor mRNA was induced more than 100-fold by oestradiol. The induction was half-maximal in the presence of 10(-10) M oestradiol and maximum levels were reached after 24 h treatment. Progesterone receptor mRNA was induced to 10% of the oestrogen-induced level by tamoxifen and its metabolite 4'-hydroxytamoxifen. The increase was half-maximal in the presence of 5 X 10(-8) M tamoxifen or 5 X 10(-10) M 4'-hydroxytamoxifen. In contrast, neither the benzothiophene antioestrogen LY117018 nor the 7 alpha-alkyl steroidal antioestrogen ICI 164,384 had any effect on progesterone receptor mRNA. The progesterone receptor mRNA was also induced by oestrogen in a T47D subline and in two other oestrogen-responsive breast cancer cell lines (ZR-75, EFM-19). Tamoxifen was a partial oestrogen for progesterone receptor mRNA induction in each of these cell lines. The large induction of the progesterone receptor mRNA by oestrogen in all 4 breast cancer cell lines supports the contention that the progesterone receptor may be a good predictive marker of hormonal response in human breast cancer.

Animals↗