Randomized feasibility trial of replacing or discarding the nail plate after nail-bed repair in children.

BACKGROUND: Nail-bed injuries are the most common hand injury in children. Surgical dogma is to replace the nail plate after repairing the nail bed. Recent evidence suggests this might increase infection rates and returns to clinic. The aim of this feasibility trial was to inform the design and conduct of a definitive trial comparing replacing or discarding the nail plate after nail-bed repair. METHODS: This study recruited participants from four hand units in the UK between April and July 2015. Participants were children under the age of 16 years with a nail-bed injury requiring surgery. They were randomized to either having the nail plate replaced or discarded after nail-bed repair. The follow-up method was also allocated randomly (postal versus clinic). Information was collected on complications at 2 weeks and 30 days, and on nail-plate appearance at 4 months using the Zook classification. Two possible approaches to follow-up were also piloted and compared. RESULTS: During the recruitment phase, there were 156 potentially eligible children. Sixty were randomized in just over 3 months using remote web-based allocation. By 2 weeks, there were two infections, both in children with replaced nail plates. The nail-replaced group also experienced more complications. There was no evidence of a difference in return rates between postal and clinic follow-up. CONCLUSION: Recruitment was rapid and nail-bed repair appeared to have low complication and infection rates in this pilot trial. The findings have led to revision of the definitive trial protocol, including the mode and timing of follow-up, and modification of the Zook classification.

Clinical variation in the treatment of trigger finger: An international survey of orthopaedic and plastic surgeons.

Trigger finger is a common condition affecting the hand. Therapeutic variability surrounds the management of trigger finger, especially in the mild cases. The aim of this study was to survey secondary care surgeons to describe the current management of trigger fingers. The steering group developed a survey for hand surgeons. Following piloting, the survey was distributed to hand surgeons in the United Kingdom and The Netherlands. A total of 713 plastic surgeons and orthopaedic surgeons were invited to participate in the online survey and 440 (62%) surgeons completed the survey. In both mild and moderate cases of trigger finger, steroid injection was the preferred treatment option. Open surgery was the treatment of choice for severe cases. However, there was variation in delivery of care, including type and dosage of steroid, site of injection, interval between injections, maximum number of injections, type of incision and treatment of patients with diabetes or rheumatoid arthritis. This highlights the need for a better evidence base for the treatment of trigger fingers.

Tenosynovial giant cell tumours of the hand: A multicentre case-control study.

Many factors have been proposed to contribute to the risk of recurrent tenosynovial giant cell tumours (TSGCT); however, we remain unable to predict those at risk, which formed the rationale for this multicentre retrospective case-control study of 28 patients with recurrence. We included cases of recurrence in a 1:1 ratio matched for age and sex with controls over 10 years. Using Cox regression, we present hazard ratios (HRs) for recurrence with 95% confidence intervals (CIs). Out of 285 cases, 28 individuals developed recurrence after a median of 2.4 years. Recurrent TSGCT had a higher mitotic count/mm2 in the primary tumour (median increase of 3 [IQR 1, 7]). Mitotic count in the primary tumour was associated with the risk of recurrence (adjusted HR 1.1 [95% CI 1.1, 1.2]) meaning that for every additional mitosis, the risk of recurrence increased by 10% per annum. We recommend a prospective cohort study to validate our findings.

Neurochemical and autonomic pharmacological profiles of the 6-aza-analogue of mianserin, Org 3770 and its enantiomers.

The neurochemical and autonomic pharmacological profile of 1,2,3,4,10, 14b-hexahydro-2-methyl-pyrazino[2,1-a]pyrido[2,3-c]pyrido[2, 3-c] [2] benzazepine [+/-)Org 3770) and the related antidepressant drug, mianserin, have been compared. The uptake of [3H]noradrenaline ([3H]NA) in vitro was weakly affected by (+/-)Org 3770 (pKi = 5.6) in contrast to mianserin (pKi = 7.4). Both (+/-)Org 3770 and mianserin facilitated the release of [3H]NA in slices of cortex. The effects of NA mediated by alpha 2-adrenoceptors on the release of both [3H]NA or [3H]serotonin ([3H]5-HT) were antagonized by (+)Org 3770 with pKi values of 8.4 and 8.1, respectively. However, (-)Org 3770 only antagonized the effect of NA on the release of [3H]5-HT (pA2 = 7.7). The binding of [3H]rauwolscine to alpha 2-adrenoceptors was inhibited by (+/-)Org 3770 and mianserin with identical affinity (pKi = 7.0), whereas the binding of [3H]prazosin to alpha 1-adrenoceptors was less potently affected by (+/-)Org 3770 (pKi = 6.4) than by mianserin (pKi = 7.1). A similar difference was found for alpha 1- and alpha 2-adrenoceptors in vas deferens of the rat. The binding of [3H]mianserin to 5-HT2 receptors was less potently blocked by (+/-)Org 3770 (pKi = 8.1) than by mianserin (pKi = 9.4) while the binding of [3H]mepyramine to histamine-1 receptors was more potently affected by (+/-)Org 3770 (pKi = 9.3) than by mianserin (pKi = 8.75). The binding of [3H]quinuclidinylbenzilate to muscarinic cholinergic receptors was blocked equally by (+/-)Org 3770 (pKi = 6.1) and mianserin (pKi = 6.3). Similar data on tryptamine-D, histamine-1 and muscarinic cholinergic receptors in isolated organs were obtained. A prominent role for the blockade of alpha 2-adrenoceptors in the therapeutic effects of mianserin and (+/-)Org 3770 in depression is suggested, probably excluding a role of inhibition of the uptake of NA.

Beclomethasone dipropionate: II: Allergic rhinitis and other conditions.

At doses similar to those used in the treatment of chronic bronchial asthma, intranasal beclomethasone dipropionate is effective in alleviating nasal symptoms of seasonal allergic and perennial rhinitis in about three-quarters of patients. Eye symptoms are not relieved. The carry-over effect of the evening dose is useful in preventing early morning attacks of sneezing. Intranasal beclomethasone dipropionate is useful in controlling symptoms persisting after polypectomy and may possibly delay or eliminate the need for the surgical removal of nasal polyps, which may shrink after several weeks or months of treatment.

Beclomethasone dipropionate inhaler: a review of its pharmacology, therapeutic value and adverse effects. I: Asthma.

Beclomethasone dipropionate is a topically active corticosteroid used as an adjuvant in the control of chronic asthma when given by inhalation as an aerosol. It is not intended for treatment of acute attacks. It appears that the main difference between beclomethasone dipropionate and other corticosteroids previously used by inhalation is its high topical activity together with a lower systemic activity due to metabolic inactivation of the swallowed portion of the dose. Clinical experience has shown that at doses of 200 to 600mug daily, beclomethasone dipropionate inhaler is preferable to oral corticosteroids, because of lack of side-effects, when adult patients and children who are inadequately controlled by full doses of sodium cromoglycate and bronchodilators, are first considered to need maintenance corticosteroids. Inhaled beclomethasone dipropionate can allow a worthwhile reduction in maintenance doses of systemic corticosteroids in many patients already receiving these drugs and can replace systemic steroids entirely in some patients, particularly when their initial dose of steroids is less than 10mg daily of prednisone or its equivalent. Substitution should be attempted when the patient's asthma is well controlled on their usual doses of systemic steroids and full doses of other adjuvant therapy. Withdrawal of systemic corticosteroids should be performed slowly and carefully. Because recovery from impaired adrenocortical function caused by prolonged systemic steroid therapy is usually slow, special care is necessary for 9 to 12 months after transfer to beclomethasone dipropionate aerosol until the hypothalamo-pituitary-adrenal axis has sufficiently recovered to cope with emergencies such as trauma, surgery, severe infections or an acute attack of asthma. It is essential that additional therapy including high doses of systemic corticosteroids be used immediately to control any acute exacerbation of asthma which occurs during maintenance therapy with beclomethasone dipropionate aerosol. Tests of adrenal function suggest that beclomethasone dipropionate at dosages of 400 to 800 mug daily has little or no adverse effect. The most common side-effect associated with the continuous use of beclomethasone dipropionate inhaler has been oropharyngeal candidiasis, which appears to be dose-related and more common in women than in men. Systemic steroid withdrawal effects, like being generally unwell, and exacerbation of underlying allergic diseases such as allergic rhinitis, have been reported after substitution of beclomethasone dipropionate inhaler for systemic steroids. However, systemic withdrawal effects seldom occur if systemic steroids are withdrawn slowly.

Naproxen: a review of its pharmacological properties and therapeutic efficacy and use.

Naproxen2, (+)-6-methoxy-alpha-methyl-2-naphthalene acetic acid, is a new non-steroidal anti=inflammatory agent advocated for use in rheumatiod arthritis, degenerative joint disease and ankylosing spondylitis. Published data suggest that in rheumatiod arthritis, naproxen 500mg daily comparable in efficacy with moderate doses of aspirin (3.6 to 4g daily) or 150mg daily of indomethacin, but generally causes fewer and milder side-effects than these drugs at the dosages used and can be given less frequently (12-hourly). Encouraging intial results have been reproted from its use in other inflammatory joint disorders, including acute gout and juvenile rheumatiod arthritis. It has compared favourably with indomethacin in ostioarthrosis of the hip of knee. Its exact place in the management of ankylosing spondylitis remains to be determined.

Clotrimazole: a review of its antifungal activity and therapeutic efficacy.

Clotrimazole 2, a synthetic imidazole derivative, is primarily used locally in the treatment of vaginal and skin infections due to yeasts and dermatophytes. In vitro, it is most active against Candida spp., Trichophyton spp., Microsporum spp. and Malazzesia fuffur (Pityrosporon orbiculare). In addition, it has some in vitro activity against certain Gram-positive bacteria, and at very high concentrations has activity against Trichomonas spp. In the treatment of vaginal candidiasis, clotrimazole vaginal tablets have produced cure rates comparable with those of conventional nystatin vaginal tablets. There have been no published comparisons with nystatin vaginal cream or foaming vaginal tablets - nystatin dosage forms preferred by some clinicians. Cootrimazole has also been successful in patients who had failed to respond to other antifungal agents such as nystatin and amphotericin B. Results in trichomonal vaginitis are not impressive. Skin infections caused by Candida or dermatophytes have been effectively treated with topical application of clotrimazole. In comparative trials, clotrimazole cream has been as effective as Whitfield's ointment and tolnaftate in the treatment of dermatophytoses, and as effective as nystatin in cutaneous candidiasis. Clotrimazole topical preparations are generally well tolerated, but local irritation has necessitated withdrawal of therapy in a few cases. Candidal septicemia and urinary and pulmonary candidiasis have been cured with oral clotrimazole therapy. Results in other types of serious fungal infections, including pulmonary aspergillosis, have been disappointing. A limiting factor in oral clotrimazole therapy is the high incidence of gastro-intestinal disturbances and neurological reactions.

Miconazole: a review of its antifungal activity and therapeutic efficacy.

Miconazole2, a synthetic imidazole derivative, is a new topical antifungal agent for use in the local treatment of vaginal, and skin and nail infections due to yeasts and dermatophytes. It is particularly active against Candida spp., Trichophyton spp., Epidermophyton spp., Microsporum spp. and Pityrosporon orbiculare (Malassezia furfur), but also possesses some activity against Gram-positive bacteria. In vaginal candidiasis, miconazole vaginal cream has produced higher cure rates than conventional nystatin vaginal tablets or amphotericin B vaginal cream. There have been no published comparisons with nystatin vaginal cream or foaming vaginal tablets - the nystatin dosage form preferred by some clinicians. The vaginal cream has also achieved a cure where previous nystatin or natamycin therapy had failed. Miconazole has proved equally effective in both Candida and dermatophyte infections of the skin, but as yet there have been no published comparisons with other antifungal agents. However, it has been successfully used in chronic skin infections which had not responded satisfactorily to other agents such as natamycin and pecilocin. Preliminary experience with oral and intravenous miconazole therapy in systemic candidiasis is promising. Miconazole preparations are well accepted and tolerated.

Fenfluramine: a review of its pharmacological properties and therapeutic efficacy in obesity.

Fenfluramine has been used for a number of years as a short-term adjunct to diet in the management of obesity. Controlled studies and clinical experience have shown that it possesses anorectic activity at least as good as that of other therapeutically useful drugs of its type, but like these drugs it has only a limited role in the overall management of obesity. Tolerance to the anorectic effects of fenfluramine may possibly develop more slowly than to other chemically related drugs in patients with refractory obesity. The mechanism of its anorectic action is probably by an effect on the appetite control centres in the hypothalamus, rather than by an effect on glucose and lipid metabolism. However, its effect in enhancing glucose uptake into skeletal muscle may be of advantage in diabetes mellitus, preliminary studies suggesting that it is of potential use in maturity-onset obese diabetics who cannot be adequately controlled by dietary measures alone. The starting dosage in obesity of 40mg daily should be increased gradually over 2 to 4 weeks to 60 to 120mg. In general, little extra benefit is gained by higher dosage. When a course of therapy is to be discontinued, fenfluramine dosage should be reduced gradually over a period of 2 to 4 weeks in order to avoid mood depression which has occurred in some patients on abrupt withdrawal of the drug. With these recommendations, the majority of patients tolerate fenfluramine satisfactorily, although some patients may have to discontinue the drug because of troublesome gastro-intestinal problems, diarrhoea, drowsiness or dizziness. Unlike other amphetamine-derived anorectics, fenfluramine is not a central stimulant in therapeutic doses, and it probably has little abuse potential.

Metoclopramide: a review of its pharmacological properties and clinical use.

Metoclopramide, 4-amino-5-chloro-2-methoxy-N-(2-diethyl-aminoethyl) benzamide, is advocated for use in gastro-intestinal diagnostics, and in treating various types of vomiting and a variety of functional and organic gastro-intestinal disorders. Published data have indicated that metoclopramide assists radiological identification of lesions in the small intestine, facilitates duodenal intubation and small intestine biopsy, and eases emergency endoscopy in upper gastro-intestinal haemorrhage. Metoclopramide reduces post-operative vomiting and radiation sickness, and ameliorates some types of drug-induced vomiting. It may provide symptomatic relief in dyspepsia and possibly in vertigo, reflux oesophagitis and hiccups, but further controlled trials are needed to confirm the efficacy of metoclopramide in these proposed areas of use. It promotes gastric emptying prior to anaesthesia. Its effects in healing gastric ulcer and preventing relapse of duodenal ulcer remain unproven. Side-effects are few and transient, though alarming extrapyramidal reactions can occur in a small proportion of patients receiving therapeutic doses but more usually following excessive doses in young subjects. They respond rapidly to withdrawal of the drug.

Hydrocortisone 17-butyrate: a new topical corticosteroid preliminary report.

Hydrocortisone 17-butyrate is a new non-fluorinated topical corticosteroid for use in psoriasis, eczema and other inflammatory dermatoses. In double-blind paired comparisons with other topical corticosteroids, the efficacy of hydrocortisone 17-butyrate 0.1% has generally been indistinguishable from that of triamcinolone acetonide 0.1%, fluocinolone acetonide 0.025% or betamethasone 17-valerate 0.1% in patients with eczema or psoriasis. When applied to the face of patients with atrophy superimposed on rosacea and perioral dermatitis resulting from prolonged use of fluorinated topical corticosteroids, hydrocortisone 17-butyrate 0.1% did not prevent the beneficial effect of systemic tetracycline nor the disappearance of telangiectasis, and tended to be more effective than hydrocortisone 1%. This result suggests that hydrocortisone 17-butyrate may be suitable for long-term use on facial lesions, although the occurrence of moderate rebound eruption in about 10% of patients indicates the need for caution. The findings suggest that hydrocortisone 17-butyrate may be less liable to cause skin atrophy and adrenal suppression than some other potent topical corticosteroids, but trials to date have been too short to allow definite conclusions regarding possible long-term effects and have not involved infants or children.

Dantrolene sodium: a review of its pharmacological properties and therapeutic efficacy in spasticity.

Dantrolene sodium or dantrolene1 is 1([5-(nitrophenyl)furfurylidend] amino) hydantoin sodium hydrate. It is indicated for use in chronic disorders characterised by skeletal muscle spasticity, such as spinal cord injury, stroke, cerebral palsy and multiple sclerosis. Dantrolene is believed to act directly on the contractile mechanism of skeletal muscle to decrease the force of contraction in the absence of any demonstrated effects on neural pathways, on the neuromuscular junction, or on the excitable properties of the muscle fibre membranes. Controlled trials have demonstrated that dantrolene is superior to placebo in adults or children with spasticity from various causes, as evidenced by clinical assessments of disability and daily activities, and by muscle and reflex responses to mechanical and electrical stimulation. It is somewhat less effective in patients with multiple sclerosis than in those with spasticity from other causes. There has been a general clinical impression in controlled trials that dantrolene caused less sedation than would have been expected from therapeutically comparable doses of diazepam. In 2 controlled trials, there was no significant difference between dantrolene and diazepam in terms of reductions in spasticity, clonus, and hyperreflexia, but side-effects such as drowsiness and inco-ordination occurred significantly more frequently on diazepam. Long-term studies have indicated continuing benefit for patients taking dantrolene, though the incidence of side-effects has often been high and there has been a suggestion of exacerbation of seizures in children with cerebral palsy. Dantrolene may be of value in the medical treatment of spasm of the external urethral sphincter due to neurological and non-neurological disease, and animal studies suggest a potential use in the management of malignant hyperpyrexia. Chemical evidence of liver dysfunction may occur in 0.7 to 1% of patients on long-term treatment with dantrolene, with symptomatic hepatitis in 0.35 to 0.5% and fatal hepatitis in 0.1 to 0.2%. The drug commonly causes transient drowsiness, dizziness, weakness, general malaise, fatigue and diarrhoea at the start of therapy. Muscle weakness may be the principal limiting side-effect in ambulant patients, particularly in those with multiple sclerosis, and therapy could be hazardous in patients with pre-existing bulbar or respiratory weakness. The dosage of dantrolene has been fixed in most controlled trials, though long-term studies have indicated the need for individualisation of dosage. The initial dose is usually 25mg once daily, increasing to 25mg two, three or four times daily, and then by increments of 25mg up to as high as 100mg two, three or four times daily. The lowest dose compatible with optimal response is recommended.

Doxepin up-to-date: a review of its pharmacological properties and therapeutic efficacy with particular reference to depression.

Doxepin is closely related in structure and general pharmacological properties to other tricyclic antidepressant drugs such as amitriptyline and imipramine. It combines antidepressant activity with a sedative effect and in this respect resembles amitriptyline, with which it shares a similar profile of clinical action. The mood elevating effect of doxepin appears to be similar to that of amitriptyline but is probably less marked than that of imipramine and in some studies has been slower to take effect than imipramine. At dosages which have achieved a similar overall response rate, doxepin tends to cause fewer or less troublesome side-effects than imipramine, amitriptyline or amitriptyline-prephenazine. The more marked sedative properties of doxepin make it more useful than imipramine in depressed patients with sleep distrubances and in depression associated with anxiety. The benzodiazepines remain the drugs of choice in anxiety states. but when anxiety is accompained by significant depression, doxepin is more effective than chlordiazepoxide or diazepam. Doxepin is usually well tolerated, and in particular by the elderly and those with cardiovascular disease. Side-effects are similar in nature to those of other tricyclic antidepressants, with dry mouth, drowsiness and constipation being the most common. Postural hypotension is uncommon. Although doxepin appears to cause fewer cardiovascular side-effects in usual therapeutic doses, it has an intrinsic cardiotoxicity on overdosage similar to other tricyclics.

Fenoprofen: a review of its pharmacological properties and therapeutic efficacy in rheumatic diseases.

Fenoprofen1 (dl-2-[3-phenoxyphenyl]propionic acid) is a new non-steroidal anti-inflammatory, antipyretic, analgesic agent advocated for use in rheumatoid arthritis, degenerative joint disease, ankylosing spondylitis and gout. Published data suggest that in rheumatoid arthritis, fenoprofen 2.4 g daily is comparable in effectiveness with moderate doses of aspirin (3.6 to 4 g daily), but generally causes fewer and milder side-effects at the dosages used. In published comparisons with other non-steroidal anti-inflammatory agents of the same chemical group, it is closely comparable with naproxen in effectiveness but tends to cause more minor side-effects than naproxen. However, as no one of the non-steroidal anti-inflammatory agents is the most suitable drug for all patients requiring such therapy, fenoprofen should be considered along with the other drugs of its type in the initial treatment of the arthritic patient. Fenoprofen has compared favourably with phenylbutazone in osteoarthrosis of the hips and with aspirin in osteoarthrosis of the shoulders, hips, knees and spine. Its exact place in the management of gout and ankylosing spondylitis remains to be determined.

Sodium valproate: a review of its pharmacological properties and therapeutic efficacy in epilepsy.

Sodium valproate has a broad spectrum of anticonvulsant activity, but is structurally unrelated to conventional antiepileptic drugs. Its proposed mode of action is mediated through effects on the function of brain gamma-aminobutyric acid (GABA). However, the elevations in brain and cerebellar GABA, and the concomitant reductions in levels of cyclic guanosine monophosphate, occur in animals at dose levels which are unlikely to be achieved during treatment of epileptic patients.

Hexoprenaline: a review of its pharmacological properties and therapeutic efficacy with particular reference to asthma.

Hexoprenaline1, N,N-[2-(3,4-dihydroxyphenyl)-2-hydroxyethyl] hexamethyl-enediamine, sulphate is a selective beta2-adrenoreceptor agonist which is active in man as a bronchodilator by the oral or intravenous routes and by inhalation. It is indicated for use in the treatment of bronchospasm associated with obstructive airways diseases, including asthma, bronchitis and emphysema. Clinical experience and double-blind studies have established that hexoprenaline is an effective bronchodilator. It major advantage over many other many other brochodilators of equal efficacy is its generally low production of side-effects, particularly tremor, palptitations, and tachycardia. In comparative trials, it has generally been rated as superior to orciprenaline or trimetoquinol, but comparisons with salbutamol have provided equivocal results. Oral hexoprenaline was superior to fenoterol as long-term maintenance therapy is asthma, principally because its somewhat lesser bronchodilatory effects were more than compensated for by a lesser incidence of side-effects.

Low-dose clonidine: a review of its therapeutic efficacy in migraine prophylaxis.

The demonstration that long-term administration of relatively low doses of clonidine decreased the responsiveness of blood vessels to vasodilator and vasoconstrictor drugs in animals led to its investigation in the prevention of migraine in man. Results of placebo-controlled and open therapeutic trials have shown that clonidine in low dosages (75 to 150 mug daily) is useful in preventing migraine headaches in about 30%-50% of patients. A 50% or greater reduction in headache frequency or headache indices has been reported in 40% of patients in controlled and open studies. Thus clonidine, like other drugs used in the interval therapy of migraine, can be expected to be effective in only a proportion of patients. Although clonidine has not been compared directly with other drugs used in the prophylactic treatment of migraine, the general clinical impression is that it is less effective then pizotifen or methysergide. Because it is relatively well tolerated at dosages of 75 to 150 mug daily it is worthy of a trial, particularly in patients considered to need prophylactic migraine therapy for the first time, and when migraine occurs in association with hypertension. At the dosages used in migraine prophylaxis, which are almost invariably lower than used in hypertension, clonidine does not cause hypotension and can be used in patients with cardiovascular disease. The principal side-effects are drowsiness and dry mouth which tend to diminish as treatment continues.

Tobramycin: a review of its antibacterial and pharmacokinetic properties and therapeutic use.

SYNOPSIS: Tobramycin is a new aminoglycoside antibiotic with a broad antibacterial spectrum in vitro, and pharmacokinetic properties similar to those for gentamicin. Tobramycin is more active than gentamicin against Pseudomonas aeruginosa and active against many gentamicin resistant strains, but is not active against enterobacteriaceae resistant to gentamicin. Theoretically, tobramycin has an advantage over gentamicin against infections caused by P. aeruginosa, but any advantage in clinical practice has yet to be adequately demonstrated. Clinical experience with tobramycin is considerably less than with gentamicin. Whilst tobramycin appears to offer no clear advantages over gentamicin against sensitive organisms it is indicated in infection caused by strains of P. aeruginosa which are resistant to gentamicin, but sensitive to tobramycin. Like gentamicin, tobramycin acts synergistically with corbenicillin and the cephalosporins. The efficacy of the tobramycin-carbenicillin combination has been shown in endocarditis caused by P. aeruginosa which was unresponsive to gentamicin plus carbenicillin. Ototoxicity and nephrotoxicity similar to that seen with other animoglycosides have been encountered in therapeutic trials with tobramycin and wider clinical experience is necessary to determine the relative incidence of these side-effects with gentamicin and tobramycin used under similar conditions. Antimicrobial activity: In comparative studies, in vitro, tobramycin is more active than gentamicin against clinical isolates of Pseudomonas aeruginosa. Similarly, the inhibitory index, which is the ratio between the serum concentration attained at usual therapuetic doses and the minimum inhibitory concentration, for Pseudomonas aeruginosa is higher for tobramycin than for gentamicin. Against Gram-negative bacteria other than Pseudomonas spp. the spectrum of activity of tobramycin is similar to that of gentamicin. For most species the activity of tobramycin is slightly less than that of gentamicin. Gentamicin is consistently more active than tobramycin against Serratia marcescens. Like other aminoglycoside antibiotics, tobramycin is active in vitro in low concentrations against Staphylococcus aureus. Tobramycin is essentially inactive against Streptococcus pyogenes, Streptococcus faecalis and Streptococcus pneumoniae (pneumococci). Maner aminoglycosides and of other antibiotics against various bacteria in vitro, but comparisons between studies cannot always be interpreted literally because the activity of many antibiotics in vitro, including tobramycin, is influenced by the nature of the culture media and the presence of certain salts. The sensitivity of P. aeruginosa to tobramycin is influenced by the magnesium, and calcium content of the culture media whilst that of all species is reduced by sodium ions. Wide variations in the concentration of these ions may result in divergent MIC values and an inappropriate choice of antibacterial agent to treat pseudomonas infection...

Pimozide: a review of its pharmacological properties and therapeutic uses in psychiatry.

Pimozide 1-(1-[4,4-bis(4-fluorophenyl)butyl]-4-peperidinyl)-2-benzimidazolone, is the first of a new series of psychotropic drugs, the kiphenylbutylpiperidines. It is advocated for once-daily use as maintenance therapy in chronic schizophrenia and for the treatment of psychic and functional disorders induced by personality traits. Published data suggest that in chronic schizophrenia, pimozide 4 to 6mg daily is indistinguishable from maintenance doses of chlorpromazine, fluphenazine, flupenthixol, perphenazine, or thioidazine. Patient groups have usually been to small to allow statistically significant differences to be apparent, but in some trials pimozide was significantly superior to trifluoperzine and to haloperidol. On present evidence, pimozide has no place in the hyperactive, aggressive type of patient or in treating the acute phase of schizophrenia, probably because of its relative lack of sedative properties compared with many antipsychotic drugs. The incidence and severity of extrapyramidal reactions with pimozide are low, but suitably designed controlled studies are needed to determine whether its use leads to a reduction in the requirement for antiparkinsonian medication. In anxious patients, pimozide seems to offer no advantages over currently available anxiolytic agents, either in terms of efficacy or incidence of side-effects. Claims for a specific effect against anxiety associated with psychosis or disturbed personality traits remain unproven.