Rectus abdominis myocutaneous flaps for perineal reconstruction: modifications to the technique based on a large single-centre experience.

INTRODUCTION: Perineal wound breakdown with delayed wound healing represents a significant cause of morbidity following surgery and radiotherapy to the perineum. The rectus abdominis myocutaneous (RAM) flap has been used increasingly to reconstruct the perineum with good effect. We describe our six-year experience of reconstruction of the perineum with the RAM flap and share some surgical adjuncts we believe are useful. METHODS: We conducted a retrospective case note review of all patients who underwent a reconstruction of the perineum using the RAM flap between August 2003 and October 2009. Indications for the flap, complication rates and outcomes were all observed. RESULTS: We conducted 16 RAM flap procedures, 15 of which (94%) were primary repairs and 1 (6%) a secondary repair. Three (19%) developed donor site hernias, two (12.5%) developed minor perineal wound infections, eight (50%) developed minor perineal wound breakdown and in one (6%) flap failure was observed. No perineal hernias were observed. There were no surgical mortalities. CONCLUSIONS: The RAM flap has a high success rate and an acceptable morbidity rate and is a useful tool in the reconstruction of complex perineal wounds. Modifications to the standard surgical technique may reduce complications and improve the versatility of this flap.

An audit of the tetanus immunisation status of plastic surgery trauma and burns patients.

This study audits the tetanus immunisation management of plastic surgery trauma patients by their referring Accident and Emergency departments, and compares this to nationally published guidelines. We assessed 269 burns and trauma patients, referred from across South Wales, using a questionnaire together with their Accident and Emergency notes or letter. The precise question(s) that had been asked regarding the tetanus immunisation status of the patient, and the immunisation management based on the results of those questions, were recorded. The accurate tetanus immunisation status of the patient was established, the wound was assessed and further management was given as indicated. Only 16 patients had been asked whether they had received a course of tetanus, and 41 patients were not questioned about their tetanus immunisation status by the referring Accident and Emergency department. As a consequence of more accurate questioning, 73 patients (27%) required further action after their arrival in the Plastic Surgery unit. This audit has demonstrated that the management of tetanus immunoprophylaxis in plastic surgery trauma patients cannot be confidently left to the referring Accident and Emergency department but should form an integral part of the treatment at the admitting unit.

Preservation of denervated muscle form and function by clenbuterol in a rat model of peripheral nerve injury.

The effects of clenbuterol in preserving the form and function of muscle after unilateral sciatic nerve division and epineural repair were investigated in a rat model. The drug (a beta2-adrenoceptor agonist) was administered daily for six weeks by gastric gavage (10 microg/kg body weight), interrupted every 5 days by a 2 day omission of dosing to avoid drug desensitization. Clenbuterol reduced the loss of wet weight, total protein, muscle fibre cross sectional area and (in part) contractile forces in denervated hindlimb muscles, with most effects lasting until reinnervation. The effects were dependent on muscle type, with slow-twitch oxidative muscle (soleus) and mixed-fibre (gastrocnemius) showing greater sensitivity to the drug than fast-twitch muscle (extensor digitorum longus). Anabolic effects on the contralateral innervated muscles tended to be small. The results suggest a potential for the adjuvant use of selective beta -adrenoceptor agonists in the management of peripheral nerve injuries in humans.

The use of a bilaminate artificial skin substitute (Integra) in acute resurfacing of burns: an early experience.

Integra artificial skin provides immediate full-thickness reconstruction for cutaneous burns. The clinical outcome appears to be superior in terms of final function and cosmesis. Consequently the use of such a skin substitute is being heralded as the future treatment of choice, particularly for massive burns where autologous donor skin is limited. The three cases reported here describe the senior author's early experience with Integra and highlight some of the difficulties and successes encountered. A high rate of dermal graft loss and slow epidermal engraftment have tempered the original enthusiasm, but with growing experience the final outcome justifies the continued use of Integra in our unit.

The Kendrick extrication device used for pediatric spinal immobilization.

Immobilizing a child presents a unique challenge for emergency medical services (EMS) personnel in addition to those challenges faced when immobilizing an adult. Most equipment commonly carried by EMS personnel is sized for adult use and as a result does not routinely provide adequate static or dynamic immobilization of a child. In addition, children often resist immobilization and can free themselves from standard strapping techniques. These problems have led to the modification of existing equipment and the development of several pediatric-specific devices. An ideal pediatric immobilization device would be one that uses an existing piece of equipment, is of limited additional cost, is routinely used by EMS providers, could be easily modified to immobilize a child, could easily be taught to EMS providers, and provides excellent static and dynamic immobilization. The Kendrick extrication device (KED) used as the authors describe meets these goals of an ideal pediatric immobilization device.

Ossification in the rectus sheath following free rectus flap.

Heterotopic ossification (HO) is a rare complication of laparotomy wounds. In this report, we describe an unusual presentation of ossification within the closed sheath following the harvest of a free rectus flap for lower limb reconstruction. Of specific interest to this case is that access to the rectus was gained through a lower transverse approach. Furthermore, the extremities of this incision were utilised for harvest of cancellous bone from the iliac crests. Given that one explanation for HO is intraoperative seeding it is of note that no problem was encountered in the wound intimately associated with the bony disruption.

Peripheral gangrene associated with fulminating meningococcal septicaemia. Is early escharotomy indicated?

We present a case of a 3-month-old boy presenting with fulminating meningococcal septicaemia associated with extensive peripheral gangrene requiring amputation of three limbs. The surgical management options and the role of early fasciotomy are discussed.

Certified first responder: a comprehensive model for pediatric training.

The purpose of this document is to present a general approach to educating the First Responder in Emergency Pediatric Care. The First Responder is especially important in the emergency care of the sick or injured child. The majority of mortality and morbidity associated with pediatric emergencies is a result of airway and ventilatory compromise. In addition, most airway and ventilation problems can be corrected with only basic life support interventions that are within the scope of practice of the First Responder. As a result, it is of paramount importance to assure that the First Responder is adequately trained in the initial care of the pediatric patient. This document will review some of the key objectives and topics which the First Responder needs to understand in order to adequately care for children until further emergency care arrives. Templates for lesson plans and suggested activities for training the First Responder are also presented.

The use of pH adjusted lignocaine in controlling operative pain in the day surgery unit: a prospective, randomised trial.

We report the results of a randomised, case matched, controlled, double blind study on 40 patients undergoing correction of their prominent ears, comparing efficacy of pH adjusted lignocaine to lignocaine alone in controlling operative pain. Each patient received commercial lignocaine in one ear and the same preparation reconstituted with 1 ml of 8.4% sodium bicarbonate in the other ear according to our randomisation protocol. 30 patients were studied to compare the difference between the buffered and commercial preparation infiltrated at room temperature. A further 10 patients were studied to assess the benefit the buffered preparation at room temperature had over commercial lignocaine warmed to body temperature. Linear analogue pain scores for discomfort at infiltration and during the operation itself were analysed. Buffered lignocaine imparts a significant reduction in pain on infiltration, compared to the commercial preparation at both room and body temperature. Both preparations were equally effective in obliterating pain during the operation itself.

Lornoxicam. A review of its pharmacology and therapeutic potential in the management of painful and inflammatory conditions.

Lornoxicam (chlortenoxicam), a new nonsteroidal anti-inflammatory drug (NSAID) of the oxicam class with analgesic, anti-inflammatory and antipyretic properties, is available in oral and parenteral formulations. It is distinguished from established oxicams by a relatively short elimination half-life (3 to 5 hours), which may be advantageous from a tolerability standpoint. Data from preliminary clinical trials suggest that lornoxicam is as effective as the opioid analgesics morphine, pethidine (meperidine) and tramadol in relieving postoperative pain following gynaecological or orthopaedic surgery, and as effective as other NSAIDs after oral surgery. Lornoxicam was also as effective as other NSAIDs in relieving symptoms of osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, acute sciatica and low back pain. Lornoxicam has a tolerability profile characteristic of an NSAID, with gastrointestinal disturbances being the most common adverse events. Limited clinical experience to date suggests that, as with a number of other NSAIDs, lornoxicam may provide a better-tolerated alternative or adjuvant to opioid analgesics for the management of moderate to severe pain. It has also demonstrated potential as an alternative to other NSAIDs for the management of arthritis and other painful and inflammatory conditions. These preliminary findings require confirmation in further comparative and long term studies.

Pantoprazole. A review of its pharmacological properties and therapeutic use in acid-related disorders.

Pantoprazole is an irreversible proton pump inhibitor which, at the therapeutic dose of 40mg, effectively reduces gastric acid secretion. In controlled clinical trials, pantoprazole (40mg once daily) has proved superior to ranitidine (300mg once daily or 150mg twice daily) and equivalent to omeprazole (20mg once daily) in the short term (< or = 8 weeks) treatment of acute peptic ulcer and reflux oesophagitis. Gastric and duodenal ulcer healing proceeded significantly faster with pantoprazole than with ranitidine, and at similar rates with pantoprazole and omeprazole. The time course of gastric ulcer pain relief was similar with pantoprazole, ranitidine and omeprazole, whereas duodenal ulcer pain was alleviated more rapidly with pantoprazole than ranitidine. Pantoprazole (40mg once daily) showed superior efficacy to famotidine (40mg once daily) in ulcer healing and pain relief after 2 weeks in patients with duodenal ulcer in a large multicentre nonblinded study. In mild to moderate acute reflux oesophagitis, significantly greater healing was obtained with pantoprazole than with ranitidine and famotidine, whereas similar healing rates were seen with pantoprazole and omeprazole. Pantoprazole showed a significant advantage over ranitidine in relieving symptoms of heartburn and acid regurgitation. Reflux symptoms were similarly alleviated by pantoprazole and omeprazole. Preliminary results indicate that triple therapy with pantoprazole, clarithromycin and either metronidazole or tinidazole is effective in the treatment of Helicobacter pylori-associated disease; however, these findings require confirmation in large well-controlled studies. Pantoprazole appears to be well tolerated during short term oral administration, with diarrhoea (1.5%), headache (1.3%), dizziness (0.7%), pruritus (0.5%) and skin rash (0.4%) representing the most frequent adverse events. The drug has lower affinity than omeprazole or lansoprazole for hepatic cytochrome P450 and shows no clinically relevant pharmacokinetic or pharmacodynamic interactions at therapeutic doses with a wide range of drug substrates for this isoenzyme system. In conclusion, pantoprazole is superior to ranitidine and as effective as omeprazole in the short term treatment of peptic ulcer and reflux oesophagitis, has shown efficacy when combined with antibacterial agents in H. pylori eradication, is apparently well tolerated and offers the potential advantage of minimal risk of drug interaction.

Lamotrigine. An update of its pharmacology and therapeutic use in epilepsy.

Lamotrigine is an antiepileptic agent which blocks voltage-dependent sodium channels, thereby preventing excitatory neurotransmitter release. Clinical evidence indicates that lamotrigine is effective against partial and secondarily generalised tonic-clonic seizures, as well as idiopathic (primary) generalised epilepsy. As monotherapy, lamotrigine 100 to 300 mg/day has similar medium term (30 to 48 weeks) efficacy to carbamazepine 300 to 1400 mg/day and phenytoin 300 mg/day against partial onset seizures and idiopathic generalised tonic-clonic seizures in adults with newly diagnosed epilepsy, and appears to be better tolerated than the older agents. As adjunctive therapy, lamotrigine (50 to 500 mg/day) has shown efficacy in short term ( < or = 6-months) placebo-controlled studies in adults with refractory partial epilepsy, reducing total seizure frequency (by < or = 60%) and producing improvement ( > or = 50% reduction in seizure frequency) in < or = 67% of patients. Both simple and complex partial seizures and secondarily generalised tonic-clonic seizures are reduced by lamotrigine, with generalised seizures (particularly absence seizures, atonic seizures and Lennox-Gastaut syndrome) tending to be more responsive than partial seizures. This reduction in seizure frequency is sustained on long term ( < or = 3 years) therapy and is reportedly accompanied by an improvement in psychological well-being. In children with refractory multiple seizure types, lamotrigine ( < or = 15 mg/kg/day; 400 mg/day) has proved effective as add-on therapy, with approximately equal to 40% of patients showing > or = 50% reductions in seizure frequency and approximately equal to 10 % achieving abolition of seizures after 3 months' treatment. Generalised seizures, including atypical and typical absence seizures, atonic and tonic seizures and Lennox-Gastaut syndrome are most responsive. The most common adverse events associated with lamotrigine are primarily neurological, gastrointestinal and dermatological. Maculopapular or erythematous skin rash, occasionally severe, occurs in approximately equal to 10% of patients and is the most common cause of treatment withdrawal. The risk of rash can, however, be minimised through adoption of a low, slow dosage titration schedule on initiating therapy. As monotherapy, lamotrigine produces less drowsiness than carbamazepine or phenytoin, and less asthenia and ataxia than phenytoin. Clinical experience would therefore suggest that lamotrigine is a particularly effective and generally well tolerated broad-spectrum agent for adjunctive treatment of both partial epilepsy and idiopathic generalised epilepsy in adults and children. Initial indications point to the drug filling an increasingly important future role in the monotherapy of newly diagnosed epilepsy.

Artesunate. A review of its pharmacology and therapeutic efficacy in the treatment of malaria.

Artesunate is an antimalarial agent, available in oral, rectal and parenteral formulations, that provides a rapid clinical effect in patients with Plasmodium falciparum malaria. The rapidity of effect, availability of an intravenous and intramuscular formulation and convenient dosage regimen make artesunate an ideal candidate for the treatment of severe malaria, including cerebral disease. While some results have been promising, there is no clear evidence to date that artesunate reduces mortality in patients with cerebral malaria to any greater extent than standard quinine therapy. When given as monotherapy, treatment should be continued for at least 5 to 7 days to prevent recrudescence. Combination therapy with mefloquine allows artesunate to be administered over 3 days or less, with a satisfactory clinical outcome maintained. Although optimal dosages remain to be determined, this combination continues to provide the rapid onset of clinical effect observed with artesunate monotherapy, but decreases the rate of recrudescence to 2% (i.e. radical cure rate of 98%) when used as treatment in patients with uncomplicated malaria from areas with a high risk of multidrug-resistance falciparum malaria. Although assessment of tolerability is complicated by the difficulty of distinguishing between disease- and treatment-related events, artesunate and artesunate-mefloquine combinations appear to be well tolerated in adults and children. Indeed, it is possible that prior administration of artesunate may reduce the incidence of mefloquine-induced vomiting. Clinical findings to date have not revealed any pattern of resistance to artesunate after use of the drug. However, given the history of the development of resistance to other antimalarial drugs, the use of artesunate should be restricted to areas of multidrug resistance, the drug should be used in combination with a longer acting agent such as mefloquine, and it should be used in regimens that provide radical cure rates of 90 to 100%. If used according to these treatment principles, artesunate will provide a well tolerated and valuable addition to the current extremely limited treatment options for multidrug-resistant falciparum malaria, a widespread parasitic disease associated with considerable mortality.

Oxybutynin. A review of its pharmacodynamic and pharmacokinetic properties, and its therapeutic use in detrusor instability.

Oxybutynin possesses anticholinergic and spasmolytic properties, which together form the basis for its use as a therapeutic option in patients with overactive detrusor function--either idiopathic detrusor instability (DI) or detrusor hyperreflexia. Of the symptoms of detrusor overactivity, urge incontinence is often the most distressing to the patient. Urge incontinence and other subjective parameters (urinary frequency, urgency) improve in tandem with objective (cystometric) measures (maximum detrusor pressure during filling, volume at first desire to void, maximum bladder capacity) in ambulatory, including elderly, patients treated with oxybutynin. However, on the basis of results of limited investigations, the drug appears ineffective in elderly institutionalised individuals. Relative to other anticholinergic drugs, oxybutynin appears at least as effective as propantheline and similar in efficacy to propiverine in small trials, although these results are not definitive. Further investigation of intravesical oxybutynin may lead to this route becoming an option in patients with pre-existing catheters. Adverse effects--dry mouth, constipation, blurred vision--related to the anticholinergic activity of oxybutynin occur frequently and can be sufficiently troublesome to necessitate treatment discontinuation in up to 25% of patients, depending on the dosage. Increases in residual urine volume suggesting urinary retention (undesirable in patients with idiopathic DI), also can develop in some oxybutynin recipients. In summary, oxybutynin is one of the few drugs proven to be beneficial in some patients with overactive detrusor function. Despite the occurrence of unwanted anticholinergic effects in many patients, and apparent lack of efficacy in the elderly institutionalised population, oxybutynin should be considered for the drug of first choice in patients with detrusor overactivity, including the elderly ambulatory population, when pharmacological therapy is indicated.

Cabergoline. A review of its pharmacological properties and therapeutic potential in the treatment of hyperprolactinaemia and inhibition of lactation.

Cabergoline is a synthetic ergoline which shows high specificity and affinity for the dopamine D2 receptor. It is a potent and very long-acting inhibitor of prolactin secretion. Prolactin-lowering effects occur rapidly and, after a single dose, were evident at the end of follow up (21 days) in puerperal women, and up to 14 days in patients with hyperprolactinaemia. In the only comparative study to date, cabergoline 0.5 to 1.0 mg twice weekly was more effective than bromocriptine 2.5 to 5.0 mg twice daily in the treatment of hyperprolactinaemic amenorrhoea, restoring ovulatory cycles in 72% of women and normalising plasma prolactin levels in 83%, compared with 52 and 58%, respectively, for bromocriptine. In the prevention of puerperal lactation, a single dose of cabergoline 1.0mg was as effective as bromocriptine 2.5mg twice daily for 14 days. A significantly lower incidence of rebound lactation in the third postpartum week was seen with cabergoline. Unpublished data suggest cabergoline 0.25mg twice daily for 2 days is effective in suppressing established puerperal lactation in about 85% of women. Nausea, vomiting, headache and dizziness are characteristic adverse events of the dopaminergic ergot derivatives. Cabergoline appears to be better tolerated than bromocriptine in both patients with hyperprolactinaemia and postpartum women. Most patients intolerant of other ergot derivatives can tolerate cabergoline. Bromocriptine use in the puerperium has been associated with an increased risk of serious thromboembolic events. However, there are no such reports with cabergoline and whether these events will become associated with other dopaminergic agents is unknown. The teratogenic potential of cabergoline has not been extensively investigated in humans. Ten congenital abnormalities have been reported in 199 cabergoline-associated pregnancies. Although there is no pattern to these abnormalities, the limited experience with cabergoline in pregnancy means the drug cannot be considered as a first-line therapy for the treatment of infertility associated with hyperprolactinaemia. At this stage of its development, cabergoline will prove useful in patients with hyperprolactinaemia who have failed treatment with, or are intolerant of, other dopamine agonists such as bromocriptine. If drug treatment is required for the prevention or suppression of puerperal lactation, cabergoline offers significant advantages over bromocriptine and should become the drug treatment of first choice for this indication.

Torasemide. An update of its pharmacological properties and therapeutic efficacy.

The pharmacological properties and therapeutic use of the high-ceiling loop diuretic torasemide (torsemide) were previously reviewed in Drugs in 1991, the following being a re-examination of the role of the drug in the light of data that have subsequently become available (particularly in the management of oedematous disorders). Torasemide produces a more prolonged water and electrolyte excretion than equipotent diuretic doses of furosemide (frusemide), but does not increase kaliuresis to the same extent. Dosages of torasemide of 2.5 to 5 mg/day do not affect plasma renin activity or aldosterone release to a clinically significant extent, although torasemide 20mg increases plasma renin levels, angiotensin II activity and urinary dopamine and prostaglandin E excretion. Studies published since the previous review have confirmed the efficacy of low dosages of torasemide (2.5 to 5 mg/day) in the treatment of hypertension, and have shown it to be effective when administered orally at a dosage of 5 to 20 mg/day in the management of congestive heart failure. Dosages of up to 400 mg/day increased urinary volume excretion and natriuresis in patients with chronic renal failure. Bodyweight and peripheral oedema were reduced by torasemide 10 to 200 mg/day as monotherapy, and 5 to 20 mg/day when coadministered with spironolactone, in patients with nephrotic syndrome. Dosages of 10 to 40 mg/day, either as monotherapy or in conjunction with an aldosterone antagonist, reduced ascites, oedema and bodyweight in patients with hydropically decompensated liver failure. Adverse effects due to torasemide are usually mild and transient in nature. No evidence of ototoxicity has been demonstrated in humans, and torasemide does not appear to affect blood glucose levels, serum uric acid concentrations, or serum potassium levels at dosages below 5 mg/day. Thus, additional evidence has accumulated for the clinical efficacy of torasemide in the management of mild to moderate essential hypertension and oedematous conditions which require diuretic therapy. Further studies are now required to confirm the long term efficacy and tolerability of torasemide, and to investigate the place of the drug in therapy relative to cardiovascular agents other than furosemide and the thiazide diuretics.

Etidronic acid. A review of its pharmacological properties and therapeutic efficacy in resorptive bone disease.

Etidronic acid is an orally and intravenously active bisphosphonate, which is believed to inhibit resorption of bone via a number of cellular mechanisms, including alteration of osteoclastic activity. In studies of patients with symptomatic Paget's disease, etidronic acid 5 to 20 mg/kg/day administered orally rapidly decreased the biochemical indices of bone turnover. Mineralisation defects in forming bone may be avoided by the use of an initial dosage of 5 mg/kg/day for up to 6 months; dosages above 10 mg/kg/day should be limited to 3 months' duration, and dosages greater than 20 mg/kg/day should be avoided. Although 3-day intravenous therapy with etidronic acid 7.5 mg/kg/day has shown superior efficacy to rehydration and forced diuresis in the management of hypercalcaemia of malignancy, the efficacy of the drug is lower than that of the newer bisphosphonates, pamidronic acid and clodronic acid. Clinical studies involving postmenopausal women with established osteoporosis have indicated that oral etidronic acid 400 mg/day for 14 days as part of a 90-day cycle, repeated for up to 3 years, increases the bone mineral density (BMD) of the lumbar vertebrae and appears to reduce the incidence of vertebral fracture. Published data suggest that etidronic acid shows similar efficacy to hormone replacement therapy (HRT) in these respects. The above dosage also appears to be effective in preventing corticosteroid-induced osteoporosis when administered as part of an intermittent, cyclical regimen. Etidronic acid in higher dosages (10 to 20 mg/kg/day orally) is effective in reducing the incidence of heterotopic ossification and its ensuing complications in both neurological and post-surgical patients. Etidronic acid is well tolerated by the majority of patients, with gastrointestinal complaints reported most commonly, but tends to delay the normal mineralisation of forming bone when administered continuously at higher dosages for prolonged periods. This is of little consequence where short term treatment is involved, but may be detrimental to those patients receiving longer courses of therapy. This effect may be minimised or avoided by using the lowest effective dosage for as short a time as possible (as in the above recommendations for Paget's disease), or by the use of intermittent cyclical therapy (as in the management of osteoporosis). Etidronic acid therefore retains a role in the management of resorptive bone disease, particularly in the treatment of Paget's disease, the prevention of heterotopic ossification, and as a second-line option in postmenopausal osteoporosis. However, the development of newer bisphosphonates requires that these compounds be continually compared and re-evaluated.

Loratadine. A reappraisal of its pharmacological properties and therapeutic use in allergic disorders.

Loratadine is a long-acting antihistamine agent, exhibiting partial selectivity for peripheral histamine H1-receptors. To date, loratadine has been evaluated in allergic rhinitis, urticaria and, to a limited extent, in asthma. In several large controlled comparative clinical studies, loratadine was superior to placebo, faster acting than astemizole and as effective as azatadine, cetirizine, chlorpheniramine (chlorphenamine), clemastine, hydroxyzine, mequitazine and terfenadine in patients with allergic rhinitis and chronic urticaria. The clinical effectiveness of loratadine in asthma is at present unclear. Loratadine is well tolerated. At dosages of 10 mg daily, commonly reported adverse events were somnolence, fatigue and headache. Sedation occurred less frequently with loratadine than with azatadine, cetirizine, chlorpheniramine, clemastine and mequitazine. Serious ventricular arrhythmias, as reported with some other second generation histamine H1-receptor antagonists, have not been observed with loratadine to date. Thus, loratadine, with its attributes of once daily administration, fast onset of action and essentially nonsedating properties, would appear to be an appropriate first-line agent for the treatment of allergic rhinitis or urticaria.

Risperidone. A review of its pharmacology and therapeutic potential in the treatment of schizophrenia.

Risperidone, a benzisoxazol derivative, is a novel antipsychotic agent which combines potent serotonin (5-hydroxytryptamine) 5-HT2 and dopamine D2 receptor antagonism. Development of the drug was stimulated by reports that the selective serotonin 5-HT2 antagonist ritanserin improved the negative symptoms of schizophrenia and decreased extrapyramidal symptoms when combined with haloperidol. The relatively low incidence of extrapyramidal symptoms with risperidone may reflect a preferential action on mesolimbic rather than nigrostriatal dopaminergic pathways. Recent clinical investigation suggests that risperidone is of at least comparable efficacy to haloperidol and perphenazine in improving the symptoms of acute and chronic schizophrenia on short term administration. Advantages offered by risperidone over haloperidol include a faster onset of antipsychotic action, a lower incidence of extrapyramidal effects and possibly greater efficacy against the negative symptoms of schizophrenia. If these benefits prove to be maintained during long term therapy, risperidone is likely to make a significant contribution to the treatment of schizophrenia.