Cytogenesis in the adult rat dentate gyrus is increased following kindled seizures but is unaltered in pharmacological models of absence seizures.

The production of new neurons continues throughout adulthood in the dentate gyrus of the hippocampal formation, and is believed to play a role in hippocampus-dependent learning and memory. Seizure-induced changes in adult neurogenesis have been examined primarily in convulsive rodent seizure models, but not in models of nonconvulsive absence seizures. This study examined progenitor cell proliferation in the gamma-hydroxybutyrate (GHB) model of typical absence seizures and the AY-9944 model of atypical absence seizures, and compared these results with changes seen in the rat amygdala kindling model. Kindled subjects were found to have 189% more proliferating cells than sham-kindled control subjects, whereas no significant difference was found between the GHB or AY-9944 model and control subjects. These results suggest that changes in adult neurogenesis in models of absence seizures do not occur, and that seizure-induced enhancement of neurogenesis could depend on the characteristics of the seizure discharge.

Cochlear and trigeminal systems contributing to the startle reflex in rats.

The startle reflex is evoked by strong acoustic or tactile stimuli, or by electrical stimulation of acoustic or tactile pathways. To dissociate the contributions of acoustic and tactile pathways, stimulating electrodes were placed in adjacent cochlear and trigeminal nuclei. The currents needed to evoke startle-like responses were an order of magnitude lower in ventral trigeminal sites (12-80 microA for a 0.1-ms pulse) than in cochlear nucleus sites (150-800 microA). At low threshold sites in both areas, brief acoustic stimuli were followed 0-4 ms later by a single electrical pulse and the current required to evoke startle was measured at several interstimulus intervals. Summation between the acoustic and electrical stimuli for startle was strong in both cochlear and trigeminal sites. Collision effects were found in the anteroventral cochlear nucleus when the electrical stimulus followed the ipsilateral acoustic stimulus by 2.0 ms, suggesting that acoustic startle is mediated by axons in the anteroventral cochlear nucleus. Collision effects were found at 4.0 ms if the electrical stimulus was presented in the contralateral pontine reticular formation, suggesting that acoustic signals mediating startle mainly cross to the pontine reticular formation. Collision effects were not found in medial or posterior sites in the cochlear nucleus, or trigeminal sites, suggesting that the neurons that mediate startle in these sites do not mediate acoustic startle. Therefore, acoustic startle is mediated through high threshold cochlear nucleus sites, while low threshold sites are non-acoustic, probably as a result of trigeminal or vestibular stimulation.

Axons and synapses mediating electrically evoked startle: collision tests and latency analysis.

Davis et al. proposed that the primary acoustic startle reflex is mediated by synapses in the ventral cochlear nucleus (VCN), lateral lemniscus (LL) and caudal pontine reticular formation (PnC). The collision test was used here to estimate the locations of synapses mediating startle-like responses in these sites, and the conduction times between and across these synapses. Conditioning (C) and test (T) pulses were delivered to pairs of sites in chloral hydrate anaesthetized rats, and current thresholds for, and latencies of, hindlimb EMG responses were determined. When sites are axonally connected, thresholds increase at the same positive and negative C-T intervals ('symmetric collision'), but when sites are connected by strong synapses, thresholds increase at asymmetric C-T intervals. (i) Asymmetric collisions between VCN and contralateral PnC centered on a C-T interval of + 0.5 ms suggest a monosynaptic connection in ventrolateral pons (VLP), near LL. (ii) Asymmetric collisions between VCN and contralateral medulla centered on a C-T interval of + 0.85 to + 1.0 ms suggest a disynaptic connection. (iii) Asymmetric collisions between VLP and ipsilateral medulla centered on a C-T interval of 0.2-0.4 ms suggest a monosynaptic connection in PnC, as shown previously in freely behaving animals [32]. (4) Symmetric collisions between VLP and rostral PnC, and between caudal PnC and medulla suggest fast axonal connections. Latency differences between electrode pairs were generally similar to collision-derived conduction times. From these, conduction times and transmission times were estimated for each axon bundle and synapse in the circuit.

Kindling-induced neurogenesis in the dentate gyrus of the rat.

Kindling, a form of neuronal plasticity produced by repeated low intensity electrical brain stimulation, leads to epileptic seizures. To address possible causes of this phenomenon, we have prepared amygdala-kindled animals and measured neurogenesis, by bromodeoxyuridine incorporation. Early, when focal seizures were present, there was no evidence of a change in the rate of hippocampal neurogenesis. In contrast, during the later phases of kindling, when secondary generalization was well established and motor seizures were present, neurogenesis was enhanced by 75-140%, depending on the hippocampal region. Double labelling with the neuron-specific marker TOAD-64 demonstrated the presence of numerous new-born granule neurons in the kindled animals. We propose that the newly-born neurons contribute to the cellular changes and behavioral symptoms associated with this type of epileptiform brain plasticity.

Diagnosis and assessment of pectoralis major rupture by dynamometry.

Four patients with pectoralis major ruptures underwent clinical and dynamometric assessment and one patient underwent late surgical repair. The operation is described. Dynamometry proved a useful and objective method of estimating the loss of strength and indicating patients who might benefit from surgical repair.

Surgical stabilisation of the lower limb in osteogenesis imperfecta using the Sheffield Telescopic Intramedullary Rod System.

The Sheffield Expanding Intramedullary Rod System was developed after experiencing problems with existing rod systems in the management of osteogenesis imperfecta. Between 1986 and 1996 we treated 74 bones in the lower limb in 28 children at a median follow-up of 5.25 years. We have reviewed 24 children with a total of 60 rods. Before surgery, all children had had multiple fractures of the lower limb. At review eight patients had experienced no further fractures, but three had suffered five or more subsequently. Before initial stabilisation, 15 children had never walked, and only three (13%) used walking as their main means of mobility. After surgery, half of those who showed motor arrest were able to walk (p = 0.016). The number of patients able to walk, with or without aids, increased to 17 (p = 0.0001). We have experienced no evidence of epiphyseal damage after the procedure, and complication rates requiring rod exchange have been low (7%).

Effect of Escherichia coli O78 endotoxin on plasma lipids in the domestic fowl.

The injection of fasting nine- to 10-week-old chickens with endotoxin from a pathogenic avian strain of Escherichia coli (1 mg/kg iv) reduced the triglyceride, cholesterol and phospholipid content of the plasma 2 to 5 h afterwards. This effect was similar to that of an E coli infection and opposite to that produced in mammals. There was a transient rise in the cholesterol level within the first hour.

The influence of Escherichia coli O78 endotoxin on carbohydrate metabolism in the domestic fowl.

The injection of endotoxin isolated from a pathogenic avian strain of Escherichia coli (1 mg/kg intravenously) accelerated the depletion of liver glycogen in fasting nine- to 10-week-old chickens within the first hour and concurrently reduced their plasma inorganic phosphate levels. These changes were attributed to increased glycogenolysis and were followed by hypoglycaemia and a large increase in the lactate content of the plasma which appeared to be caused by enhanced glucose oxidation and reduced gluconeogenesis. The plasma glucose level returned to normal within three hours and simultaneous changes in the plasma urate and albumin content indicated that glucose was being synthesised from amino acids and that albumin was being catabolised to provide them.

Restoration of forearm rotation following malunited fractures: Baldwin's operation.

The technique and results of a series of 38 Baldwin's operations (excision of the ulnar neck) are described. This is a simple and effective procedure to restore forearm rotation following malunited fractures of the distal forearm.

Delay in diagnosis of slipped upper femoral epiphysis.

Treatment of slipped upper femoral epiphysis (SUFE) is directed at preventing progressive slippage, minimizing deformity and avoiding avascular necrosis and chondrolysis. Delay in treatment adversely affects long-term outcomes. In a retrospective study we assessed delays between symptom onset and evaluation of the patient in an orthopaedic department. 27 patients aged 10-16 years were grouped by source of referral (general practitioner or accident and emergency department), and hips were classified as stable or unstable according to ability to bear weight. The 27 children had 37 affected hips, 31 stable and 6 unstable. In the 20 patients referred by general practitioners, mean delay from symptom onset to orthopaedic evaluation was 119 days (range 2-504); in the 7 referred from accident and emergency departments it was 95 days (1-482). In the latter group the slips were more likely to be acute and unstable. 9 (45%) of the patients in the general-practitioner group had hip radiography before referral, all correctly diagnosed though not all the examinations included the recommended frog-lateral views. Long delays between onset and diagnosis of SUFE are most likely in patients with mild symptoms, able to bear weight on the hip. Any adolescent with undiagnosed hip or knee pain that has lasted more than a week should undergo radiological investigation of the hip, with frog-lateral as well as anteroposterior views.

Hormone replacement therapy acceptability to Nottingham post-menopausal women with a risk factor for osteoporosis.

In Nottingham we have assessed the acceptability of oral hormone replacement therapy (HRT) for an at risk group of post-menopausal women for osteoporosis. One hundred post-menopausal women between the ages of 50 and 70 years who had sustained a distal radial fracture were offered oral HRT. There was a 36% overall uptake of HRT with 9% of patients unable to take HRT because they had medical contraindications. The uptake in the 50-55 year age group was 54%. We conclude that in prospective studies of HRT for osteoporosis up to 50% of patients may not wish to take HRT and therefore study design should allow for this level of uptake.

Kindled seizures enhance young neuron survival in the adult rat dentate gyrus.

New neurons continue to be generated throughout adulthood in the dentate gyrus of mammals. This process of neurogenesis is believed to play a role in some forms of learning and memory. Hippocampal-dependent learning tasks have been shown to specifically enhance the survival of new granule neurons. The present study examined the effects of kindled seizures in rats on the survival of young neurons born before the kindling began. Kindled seizures within the perforant path input to the dentate gyrus triggered between 1 and 2 weeks following the injection of bromodeoxyuridine (BrdU), were found to increase the number of BrdU and NeuN co-labeled cells in the granule cell layer by 128% 1 month later. The number of co-labeled cells was not correlated with measures of seizure severity. These results demonstrate that kindled seizures enhance the survival of new born neurons in the adult rat dentate gyrus which may reflect the actions of an activity-dependent mechanism normally involved in hippocampal-dependent learning and memory.

Rupture of the anterior cruciate ligament--a quiet epidemic?

One hundred and seventeen consecutive patients with 119 anterior cruciate deficient knees presenting to a knee clinic were studied to analyse an apparent poor diagnosis rate by referring doctors. The diagnosis had been made by the original treating physician in only 9.8 per cent of cases. Thirty per cent of the patients had been seen by an orthopaedic consultant without the diagnosis being made. Thirty-six patients had undergone 51 invasive investigations, including arthroscopy, without the diagnosis being made. This was despite 90 per cent of patients having a typical history and all having unequivocal physical signs. The average delay in diagnosis was 21 months.

Heterogenous properties of dentate granule neurons in the adult rat.

Postnatal neurogenesis contributes substantially to the neuronal population of the adult dentate gyrus. We report here that the neurons located in the deep aspects of the granule cell layer, near the proliferative zone, have different properties from those located in the superficial layers. The former group of neurons, tentatively designated as young, can be readily identified in a standard hippocampal slice preparation by morphological, immunohistochemical, and electrophysiological criteria. Electrophysiological recordings and imaging with Lucifer yellow from these neurons in the standard hippocampal slice preparation showed one or two main dendrites and conically shaped branches possessing varicose protrusions. These features are in agreement with the appearance of the same population of young neurons immunopositive for TOAD-64, a marker for immature neurons. In disinhibited slices, these putative young neurons are distinguished from the mature neurons, located in the superficial granule cell layer, by showing paired pulse facilitation and having a lower threshold for induction of long-term potentiation. The putative young neurons are completely unaffected by GABA(A) inhibition and always display robust long-term potentiation. In contrast, the mature neurons never produce long-term potentiation when the GABA(A) inhibition is intact. We propose that the heterogeneity of the functional properties of the granule neurons is related to the ongoing neurogenesis in the adult animals.

Neurogenesis in the dentate gyrus of the rat following electroconvulsive shock seizures.

Electroconvulsive shock (ECS) seizures provide an animal model of electroconvulsive therapy (ECT) in humans. Recent evidence indicates that repeated ECS seizures can induce long-term structural and functional changes in the brain, similar to those found in other seizure models. We have examined the effects of ECS on neurogenesis in the dentate gyrus of the adult rat using bromodeoxyuridine (BrdU) immunohistochemistry, which identifies newly generated cells. Cells have also been labeled for neuronal nuclear protein (NeuN) to identify neurons. One month following eight ECS seizures, ECS-treated rats had approximately twice as many BrdU-positive cells as sham-treated controls. Eighty-eight percent of newly generated cells colabeled with NeuN in ECS-treated subjects, compared to 83% in sham-treated controls. These data suggest that there is a net increase in neurogenesis within the hippocampal dentate gyrus following ECS treatment. Similar increases have been reported following kindling and kainic acid- or pilocarpine-induced status epilepticus. Increased neurogenesis appears to be a general response to seizure activity and may play a role in the therapeutic effects of ECT.

Critical flicker frequency responses in visual cortex.

Critical flicker frequency (CFF) threshold is defined as the frequency at which a flickering light is indistinguishable from a steady, non-flickering light. CFF is useful for assessing the temporal characteristics of the visual system. While CFF responses are believed to reflect activity in the central visual system, little is known about how these temporal frequencies are processed in the visual cortex. The current paper estimated the CFF threshold for cells in the rat visual cortex by recording single unit responses to flickering stimuli. Results showed that: (1) there was a broad range of temporal tuning, (2) CFF threshold was lower in simple cells than in complex and hypercomplex cells, and (3) there was no significant difference in CFF threshold between areas 17 and 18.