A primer on the mechanics of P-glycoprotein the multidrug transporter.

P-glycoprotein (P-gp) the multidrug transporter is a well-characterised member of the super-family of ATP-binding cassette (ABC) transporters, and mediates the clearance of xenotoxins against steep concentration gradients at the expense of ATP hydrolysis. The primary function of this protein is to prevent the uptake of toxic compounds from the gut into the body, and to protect vital structures such as the brain, cerebrospinal fluid, testis, foetus and bone marrow against toxins. Although P-gp transports a wide range of compounds, which is advantageous, it can also be a disadvantage and may interfere with the delivery of drugs to target tissues resulting in multidrug resistance. In the present review: (i) we consider our current understanding of the structure of P-glycoprotein, (ii) discuss substrate binding and its coupling to ATPase activity, (iii) provide insight into key features which define P-glycoprotein substrates/inhibitors and the ability to predict potential substrates in silico, (iv) provide an overview of existing models of pump function and (v) present emerging concepts into the regulation of P-glycoprotein expression, with particular reference to multidrug resistance.     

Limbal nodules in Sweet's syndrome

Sweet's syndrome is acute febrile neutrophilic dermatosis. Conjunctivitis and episceritis have been described with it before. A case of Sweet's syndrome, described here, was found to have limbal nodules with histology similar to the skin lesions. This is the first report of this association.     

Successful outcome following anastomosis of a severed trochlear nerve in the middle fossa

Complete return of function has been obtained following neurosurgical repair of a trochlear nerve inadvertently divided during the clipping of a basilar tip aneurysm. To date this is the second case reported in the literature. The technique of repair and the method of recording the return of function is discussed.     

The influence of pre-exercise glucose ingestion on endurance running capacity.

Drinking a concentrated glucose solution less than 1 h before the start of prolonged submaximal exercise has been reported to reduce endurance capacity during cycling. The purpose of this study was to re-examine the influence of pre-exercise ingestion of a concentrated glucose solution on endurance running capacity. Nine recreational runners (five men and four women) ran to exhaustion on a level treadmill, at speeds equivalent to 70% VO2max, on two occasions separated by at least 1 week. The runners ingested either a solution containing 75 g of glucose in 300 ml of water (G trial), or 300 ml of sweetened water (P trial) 30 min before each trial. As a consequence, the blood glucose concentrations were 55% higher at the beginning of the G trial compared with those recorded for the P trial (G trial, mean(s.e.) blood glucose = 6.3(0.7) mmol l-1 versus P trial, mean(s.e.) blood glucose = 4.1(0.3) mmol l-1; P < 0.01). Nevertheless, there were no differences in the running times to exhaustion between the two trials (G trial, mean(s.e.) 133.79(11.0) min versus P trial, mean(s.e.) 121.16(8.1) min). The results of this study show that ingesting a 25% glucose solution 30 min before exercise does not reduce the endurance capacity of recreational runners when the exercise intensity is equivalent to 70% VO2max.     

Prospective study of 210 consecutive cases of endocapsular phacoemulsification using the AM0 SI-30NB 3-piece foldable lens

Purpose: To assess the acceptability of clinical outcome achieved with use of the SI-30NB lens, as well as the incidence of any lens related complications.
Methods: This prospective study evaluated 210 consecutive eyes undergoing endocapsular phacoemulsification cataract surgery (EPECS), with implantation of the AM0 SI-30NB foldable three-piece lens, commencing with the first patient in our practice receiving this implant. There was 99% follow-up for at least three months, with a mean of nine months, and a range of three to 14 months. Incisions were a maximum of 3.2 mm in size, and this allowed minimisation of astigmatism, and maximisation of early visual rehabilitation.
Results: The final visual acuity results were excellent, with 95% of cases achieving corrected vision of 6/12 or better. All cases without pre-existing ocular pathology achieved corrected vision of 6Y6, apart from a single case which achieved 6/9, but the patient died before follow-up. The lens-related complication rate was less than 1% (two patients). No decentration of any other implant ocurred, and no patient complained of edge glare. There were no cases of iris chafing or pigment dispersion. Only three patients (1.4%) required Yag posterior capsulotomy in the first 14 months of the study. Central bag-bag fixation was achieved in 206 of the 210 cases in the study (98%).
Conclusion The results achieved using the SI-30NB lens with a small incision phaco procedure were excellent. Lens-related complications occurred in only two cases and very few cases have had problems with posterior capsular opacification.     

MUSICAL HALLUCINATIONS ASSOCIATED WITH RECURRENCE OF A RIGHT OCCIPITAL MENINGIOMA

SUMMARY The case of an 84-year-old woman who experienced musical and visual hallucinations after recurrence of a right occipital meningioma is reported.     

ACUTE PSYCHOSIS ASSOCIATED WITH ABRUPT WITHDRAWAL OF CARBAMAZEPINE FOLLOWING INTOXICATION

SUMMARY Carbamazepine is regularly used in the treatment of trigeminal neuralgia. Although exacerbation of psychosis has been described following abrupt discontinuation of carbamazepine in chronic schizophrenics, a withdrawal syndrome has not been reported previously in patients treated for trigeminal neuralgia. The case presented here suggests that abrupt withdrawal of toxic concentrations of carbamazepine may precipitate a withdrawal reaction, which is manifest some days after discontinuation of the drug. Therefore it may be advisable to withdraw therapy slowly in these situations.     

Aspects of growth hormone control in diabetes

Growth Hormone (GH) has been implicated in the development of retinal new vessels that characterise diabetic proliferative retinopathy. Formerly, pituitary ablation was successful in causing such new vessels to regress but this approach has been largely superseded by panretinal photocoagulation. A clearer understanding of the GH abnormalities in diabetes might not only shed light on the process of retinal new vessel formation but could also provide a means for pharmacological suppression of GH in those patients not fully responding to laser photocoagulation. In this review, GH control in diabetes is considered with particular reference to studies in patients with diabetic retinopathy.