Lower urinary tract changes in young adults using ketamine.

PURPOSE: We identified the profile of lower urinary tract changes in ketamine users in the community. In addition, we identified the relative risks of dose, frequency of ingestion and duration of ketamine use for changes in lower urinary tract function. MATERIALS AND METHODS: A mobile medical assessment service was established at specific youth centers, and subjects who were known to social workers and who had a history of ketamine use were invited to participate in health screening. Lower urinary tract function was evaluated using the Pelvic Pain, Urgency and Frequency questionnaire, and uroflowmetry and ultrasonography. RESULTS: Use of ketamine more than 3 times weekly was significantly associated with lower voided volumes. Pelvic Pain, Urgency and Frequency questionnaire scores were significantly higher for ketamine use for more than 24 months compared to use for short durations (7.82 vs 6.00). The scores on the symptom and bother subscales of the Pelvic Pain, Urgency and Frequency questionnaire decreased progressively with increased duration of abstinence. For individuals after 1 year of abstinence the Pelvic Pain, Urgency and Frequency questionnaire scores were significantly lower and voided volumes were higher than those for active users. CONCLUSIONS: Ketamine users with at least a 2-year habit of 3 or more hits per week have altered bladder function that can be recognized and that causes bother. These early functional changes have the potential to normalize after 1 year of ketamine abstinence. This study provides a basis for the development of health promotion material that can be used in the community by welfare workers seeking to encourage drug cessation.

Agreement between initial and final diagnosis of first seizures, epilepsy and non-epileptic events: a prospective study.

BACKGROUND: Differentiating between first seizure, epilepsy and a non-epileptic event is a challenging clinical exercise for many physicians as it may lead to different therapeutic implications. This study aims to investigate the agreement between the initial diagnosis at the accident and emergency (A&E) department and the final diagnosis following inpatient neurological evaluation of seizure disorders. METHOD: A prospective observational study between April 2004 and June 2005 in a regional hospital in Hong Kong recruited 1701 patients from the A&E to neurology/medical wards with initial diagnoses/labels matching any one of 12 predefined keywords which were categorised as either "seizure specific" or "non-specific". RESULTS: Among the 1170 patients with "non-specific" initial diagnoses/labels, 58 (5%) were finally diagnosed as having had a first seizure or epilepsy. Among 531 patients with "seizure specific" initial diagnoses/labels, 27 (5.1%) were subsequently diagnosed as having had non-epileptic events. The kappa value for agreement between the initial and final diagnosis was 0.88. Of the 154 patients with a final diagnosis of first seizure, 34 (22%) had "non-specific" initial labels. Among these patients, components of the evaluation contributing to revision of diagnosis included retrieval of witness accounts (47%), epileptiform discharges on EEG (47%), short term monitoring in patients suspected of acute symptomatic seizures (28%) and panel discussion of cases (22%). CONCLUSION: There was generally a high degree of agreement between the initial and final diagnosis, but first seizures were often missed initially. Careful history taking, judicious use of EEG, selective short term monitoring and liaison with specialists are important in reaching an accurate diagnosis.

Plasma beta-globin DNA as a prognostic marker in chest pain patients.

BACKGROUND: Acute coronary syndrome may involve cell death and the release of nucleic acids into the circulation. We thus investigated whether plasma DNA concentrations are increased and determined its prognostic significance in patients with ACS. METHODS: Real-time polymerase chain reaction was used to quantitatively measure the beta-globin gene from blood samples taken from patients presenting to an emergency department with chest pain of probable cardiac cause. RESULTS: Samples from 58 patients with chest pain, and from 21 age- and sex-matched healthy control subjects were analysed. Compared with the control group, median plasma DNA concentrations were increased 1.5-fold in patients with minor cardiac injury, were increased further in patients with STEA and STEMI, and were the highest in those patients who died within 2 years (P=0.0005; post-hoc Dunn's, P<0.05). Median plasma DNA concentrations were higher in patients who later developed heart failure (1060 vs. 500 kGE/l; P=0.0095); higher in patients who later reinfarcted (1000 vs. 530 kGE/l; P=0.0298); higher in patients who had a cardiac arrest in that admission (1350 vs. 525 kGE/l; P=0.04); and were higher in patients who were readmitted within 6 months of discharge (725 vs. 475 kGE/l; P=0.04). CONCLUSION: Plasma DNA is a potential marker for post-ACS complications.

Extraocular muscles have fundamentally distinct properties that make them selectively vulnerable to certain disorders.

While skeletal muscles generally perform specific limited roles, extraocular muscles (EOMs) have to be responsive over a wider dynamic range. As a result, EOMs have fundamentally distinct structural, functional, biochemical and immunological properties compared to other skeletal muscles. While these properties enable high fatigue resistance and the rapid and precise control of extraocular motility, they might also explain why EOMs are selectively involved in certain disorders, such as chronic progressive external ophthalmoplegia (CPEO), myasthenia gravis and Graves' ophthalmopathy. This review first gives an overview of the novel myofibre classification in EOMs and then focuses on those properties that might explain why ophthalmoplegia should be so prominent in these disorders.

Optic neuropathies--importance of spatial distribution of mitochondria as well as function.

Optic neuropathies such as Leber's hereditary optic neuropathy, dominant optic atrophy and toxic amblyopia are an important cause of irreversible visual failure. Although they are associated with a defect of mitochondrial energy production, their pathogenesis is poorly understood. A common feature to all these disorders is relatively selective degeneration of the papillomacular bundle of retinal ganglion cells resulting central or caecocentral visual field defects. The striking similarity in the pattern of clinical involvement seen with these disparate disorders suggests a common pathway in their aetiology. The existing hypothesis that the optic nerve head has higher energy demands than other tissues making it uniquely dependent on oxidative phosporylation is not satisfactory. First, other ocular tissues such as photoreceptors, which are more dependent on oxidative phosporylation are not affected. Second, other mitochondrial disorders, which have a greater impact on mitochondrial energy function, do not affect the optic nerve. The optic nerve head has certain unique ultra structural features. Ganglion cell axons exit the eye through a perforated collagen plate, the lamina cribrosa. There is a sharp discontinuity in the density of mitochondria at the optic nerve head, with a very high concentration in the prelaminar nerve fibre layer and low concentration behind the lamina. This has previously been attributed to a mechanical hold up of axoplasmic flow, which has itself been proposed as a factor in the pathogenesis of a number of optic neuropathies. More recent evidence shows that mitochondrial distribution reflects the different energy requirements of the unmyelinated prelaminar axons in comparison to the myelinated retrolaminar axons. The heterogeous distribution of mitochondria is actively maintained to support conduction through the optic nerve head. We propose that factors that disrupt the heterogeneous distribution of mitochondria can result in ganglion cell death. Evidence for this comes from studies of cultured cells with the dominant optic atrophy mutation in which mitochondrial distribution is altered and from some forms of hereditary spastic paraparesis which are associated with optic atrophy. The responsible mutations do not affect ATP production until late in the disease but do affect mitochondrial arrangement, again showing that mitochondrial distribution as well as energy production by individual mitochondria may be important in the pathogenesis of ganglion cell death. Greater understanding of the factors localising mitochondria within the ganglion cell axon in particular the interaction with cytoskeleton is required to formulate new treatments. Boosting energy production alone may not be an effective treatment.

Clinical efficacy and safety of the orally inhaled neuraminidase inhibitor zanamivir in the treatment of influenza: a randomized, double-blind, placebo-controlled European study.

OBJECTIVES: To assess the clinical efficacy and safety of orally inhaled zanamivir in the treatment of influenza in a European primary care setting. METHODS: This was a randomized, double-blind, placebo-controlled trial in primary care and hospital clinics in 11 European countries. Patients aged > or = 12 years were recruited within 2 days of onset of typical influenza symptoms and received orally inhaled zanamivir 10 mg via a Diskhaler twice daily for 5 days or matching placebo. Influenza symptoms and temperature were recorded daily for 14 days. The primary endpoint was time to alleviation of clinically significant symptoms of influenza. Other endpoints included symptom severity, use of relief medications, time to return to normal activities, complications and investigator's assessment of symptoms. RESULTS: A total of 356 patients were recruited; 277 (78%) had laboratory-confirmed influenza and 32 (9%) were considered high-risk (i.e. elderly or with underlying medical conditions). Zanamivir significantly reduced the time to alleviation of symptoms versus placebo (median 5 days versus 7.5 days, P<0.001), a 33% reduction in duration of illness. Zanamivir significantly reduced the severity of several symptoms; improvements versus placebo were discernible after approximately 24 h. The proportion of patients who were afebrile after 24 h increased by 46% versus placebo. Similar treatment benefits were observed in the high-risk patients. Zanamivir was well tolerated, with an adverse event profile similar to that of placebo. CONCLUSIONS: Zanamivir is effective in reducing the duration and severity of influenza illness and is well tolerated. Zanamivir should therefore be a clinically valuable intervention in the management of influenza.

Computed tomography evaluation in acute stroke: retrospective study.

OBJECTIVE: To determine the accuracy with which 'frontline' hospital doctors interpret computed tomography brain scans. DESIGN: Retrospective study. SETTING: University teaching hospital, Hong Kong. PARTICIPANTS: Medical and emergency room doctors. MAIN OUTCOME MEASURE: Accuracy in correctly identifying features of acute stroke on 18 computed tomography brain scans. RESULTS: Computed tomography brain scan images showing easily detectable haemorrhage and infarct were identified in 91% and 90% of scans, respectively; but difficult-to-interpret scans with subtle features of haemorrhage or infarct were only correctly identified in 46% and 45% of readings, respectively. More experienced doctors did not perform better than junior doctors (P=0.69; 95% confidence interval, -1.84 to 2.73) and the mean total score for doctors from the emergency department did not differ significantly from that of doctors from the medical department (P=0.57; 95% confidence interval, -2.98 to 1.67). CONCLUSION: Early signs of infarct and small bleeds on computed tomography brain scans are not well recognised by doctors, regardless of clinical exposure or seniority. Ineligible patients may be treated with thrombolytic therapy as a result of such computed tomography scan misinterpretation.

Assessment of visual function in chronic progressive external ophthalmoplegia.

AIMS: To assess the visual function of patients with chronic progressive external ophthalmoplegia (CPEO) using the Visual Function Index (VF-14). To identify discriminatory questions that reflect visual disability in mitochondrial ocular myopathies. To investigate the relationship between visual impairment and the ocular parameters routinely measured in clinical practice. METHODS: We studied 40 CPEO patients. Each patient underwent ophthalmological assessment, including best-corrected visual acuity, ptosis measures, and fundus examination for pigmentary retinopathy, and orthoptic assessment including cover test in the primary position, assessment of diplopia, and measurement of uniocular fields of fixation using the Goldmann perimeter. Patients were interviewed by telephone by an independent observer and their visual function was assessed using the VF-14. RESULTS: A total of 38 patients (95%) were visually impaired. The mean VF-14 was 72 (95% CI 66-79). Patients reported having the most difficulty with reading small print and driving at night. No significant correlation was found between the VF-14 and ocular motility parameters, ptosis, or pigmentary retinopathy. CONCLUSIONS: CPEO is associated with significant visual impairment. Measures of visual disability should be included in studies of natural history and treatment of mitochondrial ocular myopathies.

Efficacy and safety of the neuraminidase inhibitor zanamivirin the treatment of influenza A and B virus infections.

The efficacy and safety of zanamivir, administered 2x or 4x daily over 5 days, was evaluated in the treatment of influenza infections. A total of 1256 patients entered the study; 57% of those randomized had laboratory-confirmed influenza infection. The primary end point, "alleviation of major symptoms," was created to evaluate differences in clinical impact. In the overall population with or without influenza infection, zanamivir reduced the median number of days to reach this end point by 1 day (P=.012 2x daily vs. placebo; P=.014 4x daily vs. placebo). The reduction was greater in patients treated within 30 h of symptom onset, febrile at study entry, and in defined high-risk groups. Zanamivir reduced nights of disturbed sleep, time to resumption of normal activities, and use of symptom relief medications. It was well tolerated. These results suggest that zanamivir can significantly reduce the duration and overall symptomatic effect of influenza.