A mechanism for the analgesic effect of neurotensin as revealed by behavioral and electrophysiological techniques

Behavioral and electrophysiological techniques were used to examine the effects of local injections of neurotensin (NT) into the periaqueductal gray (PAG). The results of the behavioral experiments showed that injection of NT into the PAG produced dose-dependent analgesia that lasted for as long as 60 min and was not blocked by naloxone. However, electrolytic lesions of the nucleus raphe magnus (NRM) and its surrounding area, abolished the analgesic effect of NT. Electrophysiological experiments indicated that micro-pressure application of NT onto neurons in the PAG had a predominantly excitatory effect. Furthermore, it was shown that injection of NT into the PAG produced excitation of the NRM neurons. It is concluded that NT produces its analgesic effect by excitation of PAG neurons which leads to activation of the pain inhibitory system that originates from the NRM and its surrounding areas in the medulla.     

Termination of strict diet therapy in phenylketonuria. A study on EEG sleep patterns and computer spectral analysis

For several years and under various aspects we have studied diet termination in twenty-two early and late treated patients with phenylketonuria. Time of diet termination was the completed eighth year. For evaluation of possible functional CNS deficits, we applied psychometric tests, methods for testing psychomotor behavior and, in addition, neurophysiological parameters and registrations of sleep EEG. EEG morphology was studied visually and the rhythms of the different phases of sleep were quantified by computerized spectral analysis. EEG was studied during diet therapy when phenylalanine levels in blood were low and after a relatively short period of four months with elevated phenylalanine blood levels. At least two years after diet termination with correspondingly elevated phenylalanine blood levels the EEG was studied once more. Compared to the respective findings before diet termination in these patients there were no significant changes of the sleep EEG seen, neither on visual nor on spectral analysis. We have seen in this study minor EEG changes in early treated children and overtly pathological EEG changes in late treated PKU patients with cerebral damage, both before and after diet termination. Ultrastructural CNS defects may be the cause of these anomalies which do not respond to the actual biochemical situation at the age of eight to ten years. The morphology of such defects may include altered synaptic maturation and may occur already in an early phase before the diet therapy is implemented.     

Prediction of maxillary third molar impaction in adolescent orthodontic patients

The purpose of this study was to identify risk factors for maxillary third molar impaction in adolescent orthodontic patients. Radiographs made before treatment (T1) and after treatment (T2) and at a minimum of 10 years postretention (T3) of 132 patients that allowed accurate diagnosis of impaction vs eruption of one or both maxillary third molars were evaluated. Although univariate logistic regression revealed that the decision to extract premolars reduced the risk of impaction by 76% (P < .01), this parameter was not included in the final prediction model at T1. Multiple logistic regression analyses revealed that third molar impaction could be predicted at T1 according to the size of the retromolar space and the amount of mesial molar movement that will occur during active appliance therapy, reducing the risk of impaction by 22% and 34% for every millimeter increase in distance, respectively (P < .01). At T2, multiple logistic regression revealed that the odds of impaction were more than 60 times higher (P < .01) if the third molar was angulated mesially as compared with less than 30 degrees distally relative to the occlusal plane and almost five times (P < .05) higher if the third molar was angulated more than 30 degrees distally as compared with less than 30 degrees distally. Similar analyses at T2 showed 29% reduced risk of impaction for every millimeter increase in retromolar space and 18% reduced risk for every degree increase in angle MP/SN (P < .01).     

Isolated optic nerve lymphoma diagnosed by optic nerve biopsy

PURPOSE: To report a case of isolated optic nerve lymphoma diagnosed by optic nerve biopsy. DESIGN: Case report. METHODS: A 66-year-old woman was referred to the Neuro-Ophthalmology Service because of a decrease in visual acuity and right optic disk edema. RESULTS: A magnetic resonance image of the brain showed only enhancement of the optic nerve. An examination that included ANA, c-ANCA, p-ANCA, Lyme titers, FTA-ABS, ACE level, chest x-ray, and lumbar puncture was negative. Because of rapid progression on clinical examination and serial imaging, an optic nerve biopsy was performed, which showed B-cell lymphoma. CONCLUSION: Optic nerve lymphoma can be confused with a variety of inflammatory and neoplastic infiltrations of the optic nerve on clinical and radiographic examinations. Optic nerve biopsy can be valuable in diagnosing isolated optic nerve lymphoma if other diagnostic tests are unrevealing, but the procedure carries considerable risk of loss of visual acuity and should be recommended judiciously.     

Multifocal ERG in ethambutol associated visual loss

AIM: To determine the anatomical site and extent of electrophysiological dysfunction in patients with ethambutol associated visual loss. METHODS: A comparative case series. Four patients with ethambutol associated visual loss underwent multifocal electroretinography (mERG). Two patients had advanced visual loss while two had early signs of toxicity. The N1-P1, N1, P1 amplitudes, N1, and P1 latencies were compared to 10 age and sex matched controls. RESULTS: mERG abnormalities were detected in the ethambutol treated patients. The N1 amplitude was significantly lower in the ethambutol treated patients than in the control group. CONCLUSION: Ethambutol is possibly toxic to the retina, and not only the optic nerve. The multifocal ERG may be of value to diagnose and monitor patients taking ethambutol.     

Fractionated stereotactic radiotherapy for parasellar meningiomas: a preliminary report of visual outcomes

BACKGROUND/AIM: Fractionated stereotactic radiotherapy (FSRT) is a new treatment for brain tumours that are close to critical structures, such as the visual apparatus. This study aims to assess the visual outcomes for patients with parasellar meningioma following FSRT. METHODS: A retrospective, non-comparative case series of 13 patients with parasellar meningiomas who were treated in one institution with FSRT between January 1995 and January 2001. RESULTS: 13 patients (26 eyes) were followed for a mean of 2 years. Visual acuity improved in four eyes (12.5%), remained stable in 18 eyes (75%), and worsened in three eyes (12.5%). Visual field improved in 15 eyes (57%), remained stable in six eyes (23%), and worsened in four eyes (15%). No adverse visual outcome occurred as a result of radiation. CONCLUSION: These preliminary findings suggest that FSRT is a safe and effective treatment for parasellar meningiomas.     

Perceived effectiveness and side effects of intermaxillary fixation for diet control

Weight loss is one of the major side effects associated with intermaxillary fixation (IMF) following orthognathic surgery or jaw fractures. The aim of this study was to retrospectively interview patients treated with intermaxillary fixation for diet control (IMFDC) to collect base-line information regarding: (1) perceived effectiveness, patients' compliance and patients' satisfaction with the treatment; (2) the frequency of side effects associated with IMFDC. The results show that IMFDC significantly reduced weight by a mean of 6.8 kg during treatment, and a mean of 4.1 kg at a minimum of 1 month following IMFDC removal (P<0.0001). Only 32.5% of the patients complied with the planned period of IMFDC treatment while 70% were satisfied with the treatment results. The most common side effects were speech problems and oral-facial pain with a prevalence of 52.5 and 32.5%, respectively. IMFDC treatment is not effective for long-term weight reduction and may only be used for a very short period of time to initiate weight loss. Exercise and/or special diet programs are healthier and better means to treat obesity and maintain weight loss.     

The effects of diphenhydramine and SR142948A on periaqueductal gray neurons and on the interactions between the medial preoptic nucleus and the periaqueductal gray

The midbrain periaqueductal gray contains both neurotensin type-1 and type-2 receptors. Behavioral studies have shown that the analgesic effect of neurotensin is mediated through its interaction with the type-2 receptors. These receptors specifically bind the type-1 histamine antagonist, levocabastine. Recently, it has been shown that another histamine-1 antagonist, diphenhydramine, blocks the analgesic effect of neurotensin. In addition, it has been shown that a non-peptide neurotensin antagonist, SR142948A, binds to both types of neurotensin receptors and blocks the analgesic effect of exogenously applied neurotensin. Major afferents to the periaqueductal gray arise from the medial preoptic nucleus of the hypothalamus. This region contains neurotensinergic neurons, and the expression of neurotensin mRNA in this region increases following cold-water swim stress that leads to opioid-independent analgesia. The goal of this study was to determine whether the responses of periaqueductal gray neurons to stimulation of the medial preoptic nucleus are modified by local injection of diphenhydramine and SR142948A. Because the cellular basis of the effects of diphenhydramine on periaqueductal gray neurons had not been reported, we also examined the effects of diphenhydramine on the baseline-firing rate and synaptic transmission using in vivo and in vitro methods. The results of the in vitro studies indicate that diphenhydramine concentrations above 500 nM significantly reduce the baseline firing of the periaqueductal gray neurons without a significant effect on the frequency of postsynaptic potentials. At concentrations below 100 nM, diphenhydramine has little effect on the baseline-firing rate but partially blocks the response to neurotensin. The results of the in vivo studies showed similar effects of diphenhydramine. At high concentrations it inhibited periaqueductal gray neurons, but at low concentrations it had no effect on the baseline-firing rate and it blocked the response to neurotensin and to medial preoptic nucleus stimulation. Unlike diphenhydramine, SR142948A had virtually no effect on the baseline-firing rate but blocked the response to neurotensin and to stimulation of the medial preoptic nucleus. It is concluded that: (1) SR142948A, at a dose that completely blocks the effect of exogenously applied neurotensin on periaqueductal gray neurons, has little effect on their baseline-firing rates. (2) Because of its effect on the baseline-firing rate, only low doses of diphenhydramine can be used as an antagonist of the neurotensin analgesic effect. (3) Responses of periaqueductal gray neurons to medial preoptic nucleus stimulation is, in part, mediated by a neurotensinergic network within the periaqueductal gray.