Reliability of the Otago photoscreener A study of a thousand cases

The Otago photoscreener is a 35 mm single lens reflex camera in which the flash light comes from a narrow ring around the outer margin of its lens. The margin is also the limiting aperture of the optic system and in the centre of the lens is a flickering fixation light. In a colour photograph taken at a distance of 66 cm from the face of the subject who is accurately focusing on and fixing the camera fixation light with both eyes, the fundus reflex in each pupil is very dark red and the corneal light reflexes are symmetrical. If either or both eyes are not appropriately focused or fixing, the fundus reflex is brighter and yellow or white. This article describes a prospective trial of the performance of the Otago photoscreener in a series of 1000 infants with actual or suspected amblyopia, refractive error or strabismus. In this study photoscreening showed a sensitivity of 94% and a specificity of 79%. Photoscreening also identified some cases of esotropia and of refractive error which were missed on clinical examination. In this series photoscreening passed as normal three children with mild to moderately severe amblyopia. This represents les than 1 % of the clinically abnormal children.     

Complex I deficiency is associated with 3243G:C mitochondrial DNA in osteosarcoma cell cybrids

143B.206 rho degrees cells were repopulated with mitochondria from a MELAS patient harbouring a mixture of 3243G:C and 3243A:T mitochondrial DNA. A number of biochemical assays were performed on selected cybrids with various proportions of the two types of mitochondrial DNA. These assays revealed a marked decrease in oxygen consumption with pyruvate, a complex I substrate, in cybrids containing 60% to 90% 3243G:C mitochondrial DNA. Moreover, these cybrids showed decreased synthesis of a number of polypeptides in a mitochondrial in vitro translation assay. A cybrid line with a very high level of 3243G:C mitochondrial DNA (95%) had additional deficiencies in complexes III and IV and there was a marked generalised decrease in mitochondrial translation in this cybrid. The observation of complex I deficiency is consistent with previously reported enzymatic measurements of muscle homogenates from MELAS patients with the 3243G:C mutation.      

Spontaneous intramural haematoma of the oesophagus: Radiologic recognition

Spontaneous intramural haematoma of the oesophagus (SIHO) is an uncommon disorder. It presents usually with acute chest pain followed by dysphagia. This condition may mimic spontaneous rupture of the oesophagus (Boerhaave Syndrome), dissection of the thoracic aorta or acute myocardial infarction. Hence early accurate confirmation of the diagnosis by radiology is vital for the appropriate acute management. The condition is frequently mistaken for acute myocardial infarction which may prompt inappropriate thrombolytic therapy. The appearances on contrast studies of oesophagus and on CT scanning are characteristic. Despite this, the diagnosis may easily be missed, if appropriate careful radiological technique is not used. This paper reports three consecutive cases of SIHO managed in one institution. These cases illustrate that early gastrografin contrast radiology followed by barium contrast radiology and if necessary by thoracic CT is diagnostic in all cases of this condition.     

Sympathoneural and skeletal muscle contributions to plasma dopa responses in pithed rats.

Dihydroxyphenylalanine (DOPA) in plasma has been thought to originate from sympathetic nerve endings and to reflect catecholamine biosynthesis, because changes in DOPA levels follow pharmacologically- or environmentally-induced manipulations that alter turnover of the sympathetic neurotransmitter, norepinephrine (NE). Skeletal muscle may be an additional, non-neural source of circulating DOPA. In the present study we examined sympathoneural and skeletal muscle contributions to DOPA in arterial plasma in pithed rats. Electrical stimulation of the spinal cord causes discharges of sympathetic post-ganglionic neurons, with attendant release of NE into the bloodstream, and discharges of spinal motoneurons, which causes diffuse contraction of skeletal muscle. Stimulation of the spinal cord rapidly elevated arterial plasma concentrations of NE, dihydroxyphenylglycol (DHPG), and DOPA. Pre-treatment with curare, a skeletal muscle relaxant, did not affect the NE and DHPG responses but attenuated the DOPA responses by about 50%. Administration of chlorisondamine, a ganglionic blocker, abolished NE and DHPG responses to cord stimulation, and DOPA responses were decreased by about 90%. Adrenal-demedullation did not affect the stimulation-induced DOPA responses. The results demonstrate that in pithed rats undergoing spinal cord stimulation, DOPA is released into the bloodstream. Since this response is markedly inhibited after ganglionic blockade and also attenuated after skeletal muscle paralysis, the results provide indirect evidence that DOPA formed in sympathetic neurons can be stored in a non-neuronal pool and released during skeletal muscle contraction.     

Inhibition of morphine tolerance development by a substance P-opioid peptide chimera

The neuropeptide substance P (SP), apart from its traditional role in spinal nociceptive processing, is an important regulatory effector of opioid-dependent analgesic processes. The present study stems from our original findings indicating that 1) pharmacologically administered SP mediates a strong inhibitory activity on the development of morphine tolerance in rats, and that 2) a novel SP-opioid peptide chimera YPFFGLM-NH(2), designated ESP7, produces opioid-dependent analgesia without tolerance development. To further examine the effects of simultaneous activation of two distinct opposing spinal systems on opioid tolerance and the mechanisms underlying chimeric peptide function, a second SP-opioid chimera was synthesized. This chimera, designated ESP6 (YPFFPLM-NH(2)), contains overlapping domains of endomorphin-2 and SP, respectively. ESP6 is distinguished from ESP7 by a glycine to proline substitution at position 5. Intrathecal administration of morphine sulfate (MS) with ESP6 leads to a prolongation of MS analgesia over a 5-day period. The analgesia produced by ESP6 and MS is opioid receptor-dependent, due to the ability of naltrexone to block the analgesic response. Furthermore, when ESP6 and MS are administered with concurrent NK-1 receptor blockade, a decay in analgesic potency similar to that seen with MS alone results. The presence of a proline in ESP6 appears to reduce its conformational flexibility, limit its potency at the micro-opioid receptor, and hinder its analgesic effectiveness alone. However, ESP6 represents a novel adjuvant for the maintenance of opioid analgesia over time and provides a means to predict the pharmacological properties of a chimera from its structure.     

Deprenyl in Parkinson disease

(-)Deprenyl, a specific monoamine oxidase subtype B inhibitor (MAOI-B), has been reported to be a safe and valuable adjunct to conventional treatment of parkinsonism. A double-blind, clinical comparison of (-)deprenyl with placebo was undertaken in 11 parkinsonian patients; the efficacy of 10 mg daily was studied over 4 weeks. In four cases the clinical score for parkinsonian deficits improved during deprenyl therapy, and in five it deteriorated; there was no change in one patient. Two subjects failed to complete the study. (-)Deprenyl induced euphoria and insomnia. It was concluded that any advantages deriving from the use of (-)deprenyl in parkinsonism are limited, and probably dominated by its elevation of mood. Biochemical analysis failed to reveal any significant increase in platelet or plasma catecholamine concentrations during deprenyl therapy. There was, however, a significant decrease in plasma epinephrine (p < 0.05) and platelet MAO activity (p < 0.005).