Inserting central venous catheters. Open technique has lower evidence of complications.
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Catheterization, Central Venous↗
Biomedical subjects
D M Richards
Publications and source records attributed to D M Richards.
Membrane proteins are critical targets in free radical mediated cytolysis.
The hypothesis that proteins are critical targets in free radical mediated cytolysis was tested using U937 mononuclear phagocytes as targets and iron together with hydrogen peroxide to generate radicals. Those conditions which, after a lag of approx. 30 min, led to drastic lysis were also associated with very rapid membrane depolarisation. Conversely, when the early membrane depolarisation was prevented (by the addition of chelator and catalase), so was lysis. A similar correlation between early membrane depolarisation and subsequent lysis was also observed when the cells were exposed to a toxin from Actinobacillus actinomycetemcomitans. Those conditions of radical attack which led to lysis normally caused substantial lipid peroxidation. However, depolarisation and subsequent lysis were not prevented even when lipid peroxidation was completely suppressed by exogenous antioxidant. ATP levels were not grossly affected within the critical first 30 min period. These data exclude lipids and ATP as the target for lytic damage. We argue therefore that proteins are probably amongst the primary targets in cytolysis by radicals.
Adenosine Triphosphate↗
The 5'-flanking regions of three pea legumin genes: comparison of the DNA sequences.
Approximately 1200 nucleotides of sequence data from the promoter and 5'-flanking regions of each of three pea (Pisum sativum L.) legumin genes (legA, legB and legC) are presented. The promoter regions of all three genes were found to be identical including the "TATA box", and "CAAT box', and sequences showing homology to the SV40 enhancers. The legA sequence begins to diverge from the others about 300bp from the start codon, whereas the other two genes remain identical for another 550bp. The regions of partial homology exhibit deletions or insertions and some short, comparatively well conserved sequences. The significance of these features is discussed in terms of evolutionary mechanisms and their possible functional roles. The legC gene contains a region that may potentially form either of two mutually exclusive stem-loop structures, one of which has a stem 42bp long, which suggests that it could be fairly stable. We suggest that a mechanism of switching between such alternative structures may play some role in gene control or may represent the insertion of a transposable element.
Base Sequence↗
Ceftazidime. A review of its antibacterial activity, pharmacokinetic properties and therapeutic use.
Ceftazidime is a new 'third generation' cephalosporin administered intravenously or intramuscularly. Similarly to other third generation cephalosporins it has a broad spectrum of in vitro activity against Gram-positive and Gram-negative aerobic bacteria, is particularly active against Enterobacteriaceae (including beta-lactamase-positive strains) and is resistant to hydrolysis by most beta-lactamases. Importantly, in vitro ceftazidime is presently the most active cephalosporin available against Pseudomonas aeruginosa, but it is less active against Staphylococcus aureus than first and second generation cephalosporins. Only larger comparative trials are likely to discern any statistically significant differences in clinical efficacy which may exist between ceftazidime and other antibiotics, but ceftazidime appears to be similar in efficacy to 'standard' comparative drugs in lower respiratory tract infections and complicated and/or chronic urinary tract infections among debilitated or hospitalised patients. Thus, in patients having Gram-negative infections at these sites and in whom the potential toxicity of the aminoglycosides is a concern, ceftazidime may be a valuable alternative in that it apparently lacks serious side effects and does not require routine drug plasma concentration monitoring. In fibrocystic patients having acute respiratory tract infections, ceftazidime is highly effective at both reducing symptoms of infection and temporarily reducing the sputum counts of Pseudomonas species. However, in these patients resistance to ceftazidime may develop, as seen with other beta-lactam antibiotics. In the treatment of fever of unknown origin or documented infections in immunocompromised adults and children, ceftazidime appears to be similar in efficacy to various 2- or 3-drug combinations. Nevertheless, the coadministration of an antibiotic having greater efficacy against Gram-positive bacteria should be considered in immunocompromised patients. Results from a small number of comparative trials suggest that ceftazidime may be as effective as the aminoglycosides in intra-abdominal, obstetric and gynaecological, and skin and soft tissue infections. However, further clinical experience, particularly a few well designed comparative studies, is needed to clarify the comparative efficacy in these conditions as well as in septicaemia/bacteraemia, meningitis, and bone and joint infections.
Aging↗
Ceftizoxime. A review of its antibacterial activity, pharmacokinetic properties and therapeutic use.
Ceftizoxime is a 'third generation' cephalosporin administered intravenously or intramuscularly. Like other third generation cephalosporins it has a wide spectrum of in vitro activity against Gram-positive and Gram-negative bacteria, is particularly active against Enterobacteriaceae (including beta-lactamase-positive strains), and is resistant to hydrolysis by beta-lactamases. However, the third generation cephalosporins are less active than earlier cephalosporins against staphylococci and so could not be considered the drugs of choice. Like many currently available third generation cephalosporins, ceftizoxime has limited activity against Pseudomonas aeruginosa, and thus cannot be recommended as sole treatment of known or suspected non-urinary tract pseudomonal infections. Similarly, although favourable clinical results have been obtained in patients treated with ceftizoxime for infections caused by mixed aerobic/anaerobic organisms (such as intra-abdominal, and obstetric and gynaecological infections), the relatively low in vitro activity of ceftizoxime (in common with most other third generation cephalosporins) against Bacteroides fragilis and enterococci may restrict its usage in situations where these organisms are the suspected or proven pathogens. Ceftizoxime appears to be similar in efficacy to several other cephalosporins in lower respiratory tract infections in elderly and/or debilitated patients, and in chronic and/or complicated urinary tract infections, 2 clinical situations in which third generation cephalosporins may have a major role. Ceftizoxime is also effective clinically and bacteriologically in skin, soft tissue, bone and joint infections, septicaemia/bacteraemia, meningitis and neonatal infections. However, a few large, well designed clinical comparisons of efficacy with aminoglycosides are needed before ceftizoxime can be recommended as an alternative in patients in whom potential aminoglycoside toxicity is a concern. Single intramuscular doses of ceftizoxime appear similar in efficacy to aqueous procaine penicillin G in gonorrhoeae due to nonpenicillinase-producing Neisseria gonorrhoea, and ceftizoxime is also highly effective against penicillinase-producing strains. Although only a few infections have been treated to date, ceftizoxime may be useful in the treatment of gonorrhoea in places where penicillinase-producing strains are common. Thus, ceftizoxime appears to be an effective addition to the growing number of third generation cephalosporins. However, further studies are needed to confirm its relative efficacy compared with other new cephalosporins, in particular cefotaxime.(ABSTRACT TRUNCATED AT 400 WORDS)
Anti-Bacterial Agents↗
Pirbuterol. A preliminary review of its pharmacological properties and therapeutic efficacy in reversible bronchospastic disease.
Pirbuterol is a beta-adrenoceptor agonist which differs structurally from salbutamol in the substitution of a pyridine ring for the benzene ring. In common with salbutamol, pirbuterol demonstrates both bronchodilatory and cardiovascular effects. Generally, improvements of up to 25% are noted in forced expiratory volume in 1 second (FEV1) [versus baseline or placebo] in asthmatic patients treated with pirbuterol for several months. In individual 12-week double-blind comparative studies, pirbuterol aerosol appeared similar to orciprenaline (metaproterenol) aerosol, and orally administered pirbuterol appeared similar to orally administered salbutamol in bronchodilator efficacy. However, well-designed long term comparative studies are needed to more clearly define the comparative efficacy of pirbuterol and alternative beta-adrenoceptor agonists.
Adrenergic beta-Agonists↗
Cefotetan. A review of its antibacterial activity, pharmacokinetic properties and therapeutic use.
Cefotetan is a new semisynthetic cephamycin antibiotic administered intravenously or intramuscularly. It has a broad spectrum of activity against Gram-negative aerobic and most clinically important Gram-positive and anaerobic bacteria, and is generally more active against Gram-negative bacteria than the 'first and second generation' agents. Cefotetan is particularly active against Enterobacteriaceae but has little activity against Pseudomonas aeruginosa. An extended plasma elimination half-life of about 3.5 hours, and relatively high achievable serum and tissue levels, enables cefotetan to be administered on a twice daily basis in the treatment of mild to severe infections. Cefotetan has shown good clinical efficacy in intra-abdominal, obstetric and gynaecological infections, postoperative wound infections, and infections in immunocompromised patients - all of which are often complicated due to their polymicrobial nature or by the presence of anaerobic pathogens. A satisfactory clinical response is achieved in over 90% of paediatric patients with acute otorhinolaryngological infections, whereas in the treatment of chronic disease, as with other agents, the efficacy is dramatically reduced. Like other cephalosporins, cefotetan is effective in treating patients with complicated urinary tract infections and lower respiratory tract infections. Its efficacy in urinary tract infections is at least as good as cefoxitin, although in this and some other clinical areas its activity relative to that of other cephamycins and cephalosporins remains to be assessed. Thus, with its convenient twice daily dosage schedule, cefotetan would appear to be a useful addition to a rapidly expanding group of antibacterial agents.
Bacteria↗
Norfloxacin. A review of its antibacterial activity, pharmacokinetic properties and therapeutic use.
Norfloxacin is one of the new 4-quinolone antibacterial agents. A fluorinated piperazinyl-substituted congener of nalidixic acid, it demonstrates a much wider in vitro antibacterial spectrum and greater potency than the parent compound. Its antibacterial activity against most Gram-negative pathogens is enhanced in comparison to nalidixic acid, but is similar to that of some of the other new 4-quinolones like enoxacin, and slightly less than that of ciprofloxacin. Unlike nalidixic acid, norfloxacin is also active against Pseudomonas aeruginosa and some Gram-positive organisms. In acute or uncomplicated urinary tract infections, norfloxacin has repeatedly been shown to be as effective as co-trimoxazole. Single studies have demonstrated a significantly better bacteriological cure rate with norfloxacin than with pipemidic acid, and similar cure rates with norfloxacin and both a nalidixic acid/sodium citrate mixture and amoxycillin. Similar results were found in a few studies comparing norfloxacin to pipemidic acid or amoxycillin in patients with chronic and/or complicated urinary tract infections. Norfloxacin is as effective as spectinomycin in gonorrhoea due to penicillin-resistant N. gonorrhoeae, and cures bacterial gastroenteritis caused by several gastrointestinal pathogens. Norfloxacin appears to be well tolerated and may have a low propensity to select for bacterial resistance during clinical use, although the latter needs further confirmation.
Antifungal Agents↗
Oxatomide. A review of its pharmacodynamic properties and therapeutic efficacy.
Oxatomide is an orally active H1-histamine receptor antagonist which, as appears to occur with some other antihistamines, also inhibits mast cell degranulation. Oxatomide has demonstrated response rates similar to those with other more established members of its drug class in a few studies of chronic urticaria and allergic rhinitis. Interestingly, some patients responding to oxatomide were said to be unresponsive to previously administered antihistamines. The effect of oxatomide was little different from placebo in clinical trials of bronchial asthma in adults. While somewhat more encouraging results have been reported in children with bronchial asthma when higher than presently recommended dosages were employed, and in follicular conjunctivitis, atopic dermatitis and food allergy, reports to date are largely preliminary in nature and additional well-controlled studies are needed to clarify the efficacy of oxatomide in such conditions. The drug has been generally well tolerated, but shares some of the familiar H1-histamine receptor antagonist side effects. As with other similarly acting drugs, the 2 primary side effects with oxatomide are drowsiness and weight gain. Thus, on the basis of present evidence, a trial with oxatomide seems a potentially useful alternative in patients with conditions known or thought to be allergic in nature, in whom more established treatments were ineffective or poorly tolerated.
Animals↗
Ceftriaxone. A review of its antibacterial activity, pharmacological properties and therapeutic use.
Ceftriaxone is a new 'third generation' semisynthetic cephalosporin with a long half-life which has resulted in a recommended once daily administration schedule. It is administered intravenously or intramuscularly and has a broad spectrum of activity against Gram-positive and Gram-negative aerobic, and some anaerobic, bacteria. The activity of ceftriaxone is generally greater than that of the 'first' and 'second generation' cephalosporins against Gram-negative bacteria, but less than that of the earlier generations of cephalosporins against many Gram-positive bacteria. Although ceftriaxone has some activity against Pseudomonas aeruginosa, on the basis of present evidence it cannot be recommended as sole antibiotic therapy in pseudomonal infections. Ceftriaxone has been effective in treating infections due to other 'difficult' organisms such as multidrug-resistant Enterobacteriaceae. Ceftriaxone was effective in complicated and uncomplicated urinary tract infections, lower respiratory tract infections, skin, soft tissue, bone and joint infections, bacteraemia/septicaemia, and paediatric meningitis due to susceptible organisms. In most of these types of infections once-daily administration appears efficacious. Results were also encouraging in a few patients with ear, nose and throat, intra-abdominal, obstetric and gynaecological infections, and adult meningitis, but conclusions are not yet possible as to the efficacy of the drug in these indications due to limited experience. A single intramuscular dose of ceftriaxone has been compared with standard therapy for gonorrhoea due to non-penicillinase-producing and penicillinase-producing strains of Neisseria gonorrhoeae and shown to be highly effective. In a few small trials the comparative efficacy of ceftriaxone and other antibacterials has been assessed in other types of infections and in perioperative prophylaxis in patients undergoing surgery. Few significant differences in response rates were found between therapeutic groups in these comparative studies, but larger well-designed studies are needed to more clearly assess the comparative efficacy of ceftriaxone and other antimicrobials, especially the aminoglycosides and other 'third generation' cephalosporins, and to confirm the apparent lack of serious side effects with ceftriaxone. If more widespread use confirms the safety and efficacy of ceftriaxone, it will offer an important alternative, particularly for the treatment of serious infections due to multidrug-resistant Gram-negative bacteria and in situations where the long half-life of the drug could result in worthwhile convenience and cost benefits.
Aging↗
Astemizole. A review of its pharmacodynamic properties and therapeutic efficacy.
Astemizole is an H1-histamine receptor antagonist with a long duration of action permitting once daily administration. Its efficacy in seasonal and perennial allergic rhinitis has been convincingly demonstrated, and several comparative studies suggest that astemizole is at least as effective as some other H1-histamine receptor antagonists. A few smaller studies have shown beneficial effects on the symptoms of allergic conjunctivitis and chronic urticaria (but not atopic dermatitis). While astemizole appears to share with other H1-histamine receptor antagonists a tendency to increase appetite and cause weight gain after prolonged use, it offers the important advantage of an absence of significant central nervous system depression or anticholinergic effects with usual doses. Thus, astemizole offers a worthwhile improvement in side effect profile over 'traditional' H1-histamine receptor antagonists, especially in patients bothered by the sedative effects of these drugs.
Animals↗
Piperacillin. A review of its antibacterial activity, pharmacokinetic properties and therapeutic use.
Piperacillin is one of the new generation of semisynthetic penicillins which can be administered intravenously or intramuscularly. It has a broad spectrum of activity against Gram-positive and Gram-negative aerobic and anaerobic bacteria. Although piperacillin has shown greater activity against beta-lactamase-producing organisms than the other penicillins, it is hydrolysed by the plasmid-mediated beta-lactamases (TEM-1). Activity against Pseudomonas aeruginosa is better than that of ticarcillin, carbenicillin and mezlocillin. Although only limited controlled studies have been reported, in those which have been conducted and in a larger number of open studies piperacillin was effective in the treatment of complicated urinary tract infections and lower respiratory tract infections, particularly pneumonia, caused by Gram-negative bacilli. Favourable clinical results have been obtained in patients with infections caused by mixed aerobic/anaerobic organisms (such as intra-abdominal infections) but the relatively average in vitro activity of piperacillin against Bacteroides fragilis may not indicate its usage in situations where this organism is the suspected or proven pathogen. Piperacillin in combination with an aminoglycoside or a 'third generation' cephalosporin gave encouraging results in the treatment of infections in immunocompromised patients, whilst its penetration into the diseased central nervous system and lack of toxicity indicate a potential value in the treatment of neonatal Gram-negative bacillary meningitis, particularly where the causative organism is Pseudomonas aeruginosa. Whether piperacillin alone is appropriate therapy for conditions usually treated with aminoglycosides (other than pseudomonal infections) needs additional clarification, but if established as equally effective in such conditions it has the advantages of its apparent lack of serious adverse effects and freedom from the need to undertake plasma concentration monitoring. These advantages would not, however, apply when considering one of the new (third generation) cephalosporins as alternative therapy in non-pseudomonal infections. Generally, however, it is still considered necessary to treat serious and complicated infections with combination therapy, either a cephalosporin, or in cases of resistance to P. aeruginosa an aminoglycoside.
Animals↗
Acyclovir. A review of its pharmacodynamic properties and therapeutic efficacy.
Acyclovir (aciclovir) is a nucleoside analogue antiviral drug related to cytarabine, idoxuridine, trifluridine and vidarabine. In common with these earlier antivirals, acyclovir is active against some members of the herpesvirus group of DNA viruses. The efficacy of topical acyclovir has been convincingly demonstrated in ocular herpetic keratitis, and in initial and primary initial genital herpes infection, but little or no clinical benefit was seen when non-primary initial genital infections were assessed separately. Acyclovir ointment demonstrated little benefit in recurrent genital herpes but topical acyclovir cream decreased the course of the infection by 1 to 2 days. Orally and intravenously administered acyclovir were beneficial in initial genital herpes infections, and oral therapy shortened the duration of recurrent infections by 1 to 2 days but did not ameliorate pain. In non-immunocompromised patients with recurrent herpes simplex labialis, generally little clinical benefit was seen with the use of topical acyclovir ointment even when therapy was initiated during the prodromal phase, while topical acyclovir cream effected small but significant improvements in the clinical but not the symptomological course of the disease. However, in immunocompromised patients, both intravenous and topical acyclovir shortened the clinical course of herpes simplex virus infections occurring mainly on the lips, oral mucosa and face, and prophylaxis with either oral or intravenous acyclovir suppressed the appearance of recurrent lesions from latent virus for the period of drug administration, but acyclovir did not eradicate latent herpesviruses. In non-immunocompromised patients, intravenous acyclovir was shown to decrease the acute pain of zoster, especially in the elderly, but postherpetic neuralgia was not ameliorated. When immunocompromised patients were studied, intravenous acyclovir inhibited the progression of zoster infections and shortened the healing time and duration of viral shedding in patients with cutaneous disseminated zoster. However, acute and post-herpetic pain were not significantly affected. Well designed controlled studies are underway to establish the efficacy of acyclovir in herpes simplex encephalitis and cytomegalovirus infections in immunocompromised patients, infections due to Epstein-Barr virus, and neonatal herpesvirus infections. Despite some aspects of the drug's use which require further clarification, acyclovir will make a major impact on the treatment of herpesviral infections. Barring unexpected findings with wider clinical use, it will become the agent of choice in several conditions.
Acyclovir↗
The role of the primary care physician in rural mental health.
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Humans↗
Physiological response to organophosphate residues in field workers.
The physiologic response of 21 male agricultural field workers exposed to foliage-borne Guthion residues was monitored during routine peach-thinning operations in a northern California orchard. Surveillance included daily venipuncture and urine collection to determine whole blood cholinesterase (CHE) activity and level of dialkylphosphate excretion for 3 baseline (nonexposed) and 5 normal work days. Foliage samples were obtained to measure dislodgeable and total Guthion residues. A decrease in group-mean CHE activity by 15% over the surveillance period was found. Apart from one worker who showed a consistent decrease in CHE activity, reaching a maximum of 30% below baseline at the end of the work week, daily changes in individual CHE activity were erratic. Group-mean dialkylphosphate excretion levels provided a semiquantitative indication of exposure to Guthion. Medical examination before and after the exposure period revealed an absence of clinical signs of organophosphate intoxication.
Adult↗
A controlled field trial of physiological responses to organophosphate residues in farm workers.
Blood acetylcholinesterase (ACHE) and pseudocholinesterase (PCHE) activity and urinary dialkyl phosphate (DAP) excretion were measured in a group of 15 male agriculture field workers during a five-day thinning operation in a Northern California peach orchard. Eight men were randomly assigned to work in a Guthion-treated plot, and seven men to work in an adjoining plot free from organophosphate residues. Foliage samples were taken to measure dislodgeable and total Guthion residues. The daily mean percent change in the ACHE and in the PCHE activity was less than -10.0 percent of baseline values for each group of men. Mean ACHE activity of workers in the Guthion treated plot was different from that of workers in the control plot on the fifth exposure day. The mean PCHE activity of workers in the Guthion treated plot was not different from that of workers in the control plot. Daily group-mean urinary metabolite excretion levels for workers exposed to Guthion residues were highly correlated with their daily group-mean percent change in ACHE activity. No urinary metabolites were detected in workers in the control plot. Decay in Guthion residues was markedly slower in this trial than in a comparable study conducted one year previously, emphasizing the difficulty in setting re-entry intervals based on time elapsed from pesticide application. Suggestions were made to extend the time interval of future studies on the human health effects of organophosphate residue exposure, and to further refine urinary metabolite surveillance methods toward the goal of establishing a threshold level of metabolites which would correspond to meaningful exposure to these pesticides residues.
Acetylcholinesterase↗