Repeated administration of the monoamine reuptake inhibitor BTS 74 398 induces ipsilateral circling in the 6-hydroxydopamine lesioned rat without sensitizing motor behaviours

BTS 74 398 (1-[1-(3,4-dichlorophenyl)cyclobutyl]-2-(3-diaminethylaminopropylthio)ethanone monocitrate) is a monoamine reuptake inhibitor that reverses motor deficits in MPTP-treated (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) common marmosets without provoking established dyskinesia. However, it is not known whether BTS 74 398 primes the basal ganglia for dyskinesia induction. In this study, the ability of BTS 74 398 to sensitize 6-hydroxydopamine (6-OHDA)-lesioned rats for the production of abnormal motor behaviours and the induction of striatal DeltaFosB were determined in comparison with l-3,4-dihydroxyphenylalanine methyl ester (L-dopa). Acute administration of BTS 74 398 induced a dose-dependent ipsilateral circling response in unilaterally 6-OHDA-lesioned rats whereas L-dopa produced dose-dependent contraversive rotation. The ipsilateral circling response to BTS 74 398 did not alter during 21 days of administration. In contrast, L-dopa treatment for 21 days caused a marked increase in rotational response. Repeated administration of both L-dopa and BTS 74 398 increased general motor activity and stereotypic behaviour. In L-dopa-treated rats, orolingual, locomotive, forelimb and axial abnormal movements developed whereas BTS 74 398 produced only locomotion with a side bias but no other abnormal movements. Sensitization of circling responses and the development of abnormal movements in 6-OHDA-lesioned rats have been associated with the potential of dopaminergic drugs to induce dyskinesia. Furthermore, striatal DeltaFosB immunoreactivity, shown to correlate with dyskinesia induction, was increased by L-dopa but was unaffected by repeated BTS 74 398 administration. The lack of such changes following repeated BTS 74 398 treatment suggests that it may be an effective antiparkinsonian therapy that is unlikely to produce involuntary movements.     

Primary hyperaldosteronism with normokalaemia secondary to an adrenal adenoma (Conn's syndrome) in a 12 year-old boy

A 12-1/2 year-old boy presented to the Accident Department following an episode of dizziness and was found to be hypertensive. Investigations revealed primary hyperaldosteronism secondary to an adrenal adenoma (Conn's syndrome). He had normal electrolytes during the period of investigation and potassium concentrations were > or = 4.2 mmol/l on all but one occasion. The hypertension resolved following excision of the adrenal tumour. Normokalaemia with potassium >4.0 mmol/l is very unusual in patients with Conn's syndrome and has not been described in childhood before. Primary hyperaldosteronism needs to be considered in hypertensive children even when potassium concentrations are well within the laboratory reference range.     

Borjeson-Forssman-Lehmann syndrome and multiple pituitary hormone deficiency

We describe two brothers with Borjeson-Forssman-Lehmann syndrome and the 22A-->T (Lys8X) PHF6 mutation, who presented with the symptoms and signs of multiple pituitary hormone deficiency. Biochemical investigations and radiology confirmed growth hormone (GH), thyroid stimulating hormone (TSH) and adrenocorticotrophic hormone (ACTH) as well as gonadotrophin deficiency. They were also found to have optic nerve hypoplasia. This family suggests that the BFL gene product may play an important role in midline neuro-development including the hypothalamo-pituitary axis.     

Topical phenylephrine increases anal canal resting pressure in patients with faecal incontinence

INTRODUCTION: The internal anal sphincter receives a stimulatory alpha(1) adrenergic innervation. Use of an adrenergic agonist may therefore have a role in treating patients with faecal incontinence. METHODS: Ten patients (seven females, median age 66 years) with passive faecal incontinence related to weak internal anal sphincter were studied. All patients had intact anal sphincters as assessed by endoanal ultrasound. Phenylephrine gel was applied in a double blind manner in concentrations of 0%, 10%, 20%, 30%, and 40% (Slaco Pharma (UK) Ltd, Watford, UK) on separate days. Maximum resting anal pressure (MRP), anodermal blood flow, blood pressure, and pulse rate were measured before, and one and two hours after application. RESULTS: All concentrations of phenylephrine gel increased median MRP (43, 48, 54, 65, and 70 cm H(2)O, for placebo, 10% (p=0.122), 20% (p=0.170), 30% (p=0.002), and 40% (p=0.004), respectively at one hour; comparisons with placebo). This was sustained at two hours. There was a clear dose-response relationship at one hour. Higher concentrations raised median MRP to within the normal range (> 60 cm H(2)O). At two hours, all concentrations greater than 20% increased the pressure to a similar degree, suggesting that the exact concentration may be important for the initial effect but given a certain threshold is less important after a period of time. Toxicity was rare. Two patients experienced transient perianal burning which settled within a few minutes. There was no significant effect on anodermal blood flow, blood pressure, or pulse rate. CONCLUSION: This study has demonstrated the feasibility of using topical phenylephrine to raise resting anal tone in patients with faecal incontinence. Randomised controlled trials are required to assess the efficacy of this agent.     

Topical ketorolac tromethamine 0.5% ophthalmic solution in ocular inflammation after cataract surgery

PURPOSE: To compare the efficacy and safety of ketorolac 0.5% ophthalmic solution with its vehicle in the treatment of ocular inflammation after cataract surgery and intraocular lens implantation. DESIGN: Multicenter clinical study. PARTICIPANTS: One hundred four patients were prospectively randomized, 52 patients in treatment group, 52 patients in control group. METHODS: Patients received either ketorolac or vehicle four times daily in the operated eye for 14 days starting the day after surgery in a prospective, double-masked, randomized, parallel group study. Only patients with moderate or greater postoperative inflammation the day after surgery were enrolled. MAIN OUTCOME MEASURES: The main outcome measures include inflammation (cell, flare, ciliary flush), intraocular pressure and visual acuity. RESULTS: Ketorolac was significantly more effective than vehicle in reducing the manifestations of postoperative ocular inflammation, including: anterior chamber cells (P: = 0.002) and flare (P: = 0.009), conjunctival erythema (P: = 0.010), ciliary flush (P: = 0.022), photophobia (P: = 0.027), and pain (P: = 0.043). Five times as many patients were dropped from the study for lack of efficacy from the vehicle group (22/52) than from the ketorolac group (4/52; P: = 0.001). Ketorolac was found to be equally as safe as vehicle in terms of adverse events, changes in visual acuity, intraocular pressure, and biomicroscopic and ophthalmoscopic variables. CONCLUSIONS: Ketorolac tromethamine 0.5% ophthalmic solution was significantly more effective than vehicle in the treatment of moderate or greater ocular inflammation following routine cataract surgery, while being as safe as vehicle.     

Attitudes and use of alternative therapies in UK prostate cancer patients-isn't it time we were in the know?

With increasing media interest in prostate cancer and the availability of data to patients from support groups and the Internet, the knowledge and use of alternative therapies by patients is becoming more common. The purpose of our study was to quantify patient awareness and use of alternative therapies for the prevention and treatment of prostate cancer in the UK. In May 2000, we performed a survey of men attending our urology outpatient clinic for prostate cancer evaluation or follow-up. All men diagnosed with and those at high risk (abnormal prostate specific antigen) for prostate cancer were eligible for the study. Each eligible patient was then sent an anonymous 25-item questionnaire to explore their knowledge and use of various alternative therapies for prostate cancer. Out of 195 patients who were sent the questionnaire, 168 responded, for a response rate of 86%. One hundred and sixty-four were analysed. Eight-two out of 164 (50%) were aware of alternative therapies for prevention/treatment of prostate cancer, the most common were tomatoes/tomato-based products and low-fat diet. There were 27 (16.5%) respondents taking alternative therapies for their prostate. Private patients were more aware (60.4% private vs 46.2% NHS) of complimentary therapies and were more likely to take them (27.9% private vs 12.4% NHS) than National Health Service patients. The majority of patients (60%) had not informed their GP or urologist. Fifteen therapies and 12 medication sources were recorded. Asked if doctors should discuss non-prescribed therapies, even if there is no proven benefit, 62% said 'yes' while 29% said 'no'. Alternative therapy use for prostate cancer is likely to increase. If we don't ask patients specifically whether they are taking them, patients are unlikely to tell us. Urologists and clinical oncologists treating men with prostate cancer need to be aware of alternative therapies and have some understanding of any benefit or harm, not only to be able to answer patient's questions and offer advice, but also to consider interactions with other treatments.Prostate Cancer and Prostatic Diseases (2001) 4, 235-241.     

Novel CHST6 nonsense and missense mutations responsible for macular corneal dystrophy

PURPOSE: To identify the underlying mutations in two unrelated British families with macular corneal dystrophy (MCD) by screening the carbohydrate sulfotransferase (CHST6) gene. DESIGN: Case reports and results of DNA analysis. METHODS: Two subjects from two British families with MCD were studied. The genetic status of CHST6 was determined for all members of these MCD families. In addition, sulfated keratan sulfate (KS) assay from the probands was also undertaken. CHST6 gene was amplified by polymerase chain reaction (PCR). The PCR products were analyzed by sequencing and restriction digestion. Enzyme-linked immunosorbent assay (ELISA) was performed to assess KS presence in serum. RESULTS: Four compound heterozygous mutations were identified, three of which are novel. The ELISA showed that the probands were of MCD type I. CONCLUSIONS: These novel mutations are expected to result in loss of CHST6 function, which would account for the MCD phenotype.