Search

A 67 year old man with the myasthenic syndrome associated with small cell bronchogenic carcinoma was treated with a new drug, 4-aminopyridine. The muscle weakness showed marked improvement and electrophysiological examinations demonstrated restoration of neuromuscular transmission. [ABSTRACT FROM AUTHOR]

A 67 year old man with the myasthenic syndrome associated with small cell bronchogenic carcinoma was treated with a new drug, 4-aminopyridine. The muscle weakness showed marked improvement and electrophysiological examinations demonstrated restoration of neuromuscular transmission. [ABSTRACT FROM PUBLISHER]

A new drug, 4-aminopyridine, was prepared for use in humans and tested by repeated injections in six patients with myasthenia gravis. The drug caused improvement of muscle strength and neuromuscular transmission as demonstrated by clinical observations and repetitive electrical nerve stimulation. The drug was effective in cases without any other treatment as well as in cases undergoing treatment with anticholinesterases. It is concluded that 4-aminopyridine may be of value as a supplementary drug in the treatment of myasthenia gravis. [ABSTRACT FROM AUTHOR]

Four cases are described to demonstrate the extrapyramidal clinical syndrome sometimes appearing in chronic amphetamine users. The symptoms are dominated by choreiform or athetoid movements, ataxia and disturbances of gait. The syndrome develops during amphetamine abuse and may be observed also during abstinence. The symptoms usually disappear within a week when the drug is discontinued, but may remain for years. [ABSTRACT FROM AUTHOR]

Background: Physical inactivity is a main cause of childhood obesity which tracks into adulthood obesity, making it important to address early in life. Physical activity on prescription (PAP) is an evidence-based intervention that has shown good effect on physical activity levels in adults, but has not been evaluated in children with obesity. This project aims to evaluate the prerequisites, determinants, and feasibility of implementing PAP adapted to children with obesity and to explore children's, parents', and healthcare providers' experiences of PAP., Methods: In the first phase of the project, healthcare providers and managers from 26 paediatric clinics in Region Västra Götaland, Sweden, will be invited to participate in a web-based survey and a subset of this sample for a focus group study. Findings from these two data collections will form the basis for adaptation of PAP to the target group and context. In a second phase, this adapted PAP intervention will be evaluated in a clinical study in a sample of approximately 60 children with obesity (ISO-BMI > 30) between 6 and 12 years of age and one of their parents/legal guardians. Implementation process and clinical outcomes will be assessed pre- and post-intervention and at 8 and 12 months' follow-up. Implementation outcomes are the four core constructs of the Normalization Process Theory; coherence, cognitive participation, collective action, and reflexive monitoring; and appropriateness, acceptability, and feasibility of the PAP intervention. Additional implementation process outcomes are recruitment and attrition rates, intervention fidelity, dose, and adherence. Clinical outcomes are physical activity pattern, BMI, metabolic risk factors, health-related quality of life, sleep, and self-efficacy and motivation for physical activity. Lastly, we will explore the perspectives of children and parents in semi-structured interviews. Design and analysis of the included studies are guided by the Normalization Process Theory., Discussion: This project will provide new knowledge regarding the feasibility of PAP for children with obesity and about whether and how an evidence-based intervention can be fitted and adapted to new contexts and populations. The results may inform a larger scale trial and future implementation and may enhance the role of PAP in the management of obesity in paediatric health care in Sweden., Trial Registration: ClinicalTrials.gov Identifier: NCT04847271 , registered 14 April 2021., (© 2022. The Author(s).)

Background: Patients with eating disorders may experience a severe and enduring course of illness. Treatment outcome for patients provided with inpatient treatment is reported as poor. Research to date has not provided consistent results for predictors of treatment outcome. The aims of the study were to investigate rates of remission at follow-up after inpatient treatment, symptom change from admission to follow-up, and predictors of treatment outcome., Methods: The follow-up sample consisted of 150 female adult former patients (69.4% of all eligible female patients) with eating disorders. Mean age at admission was 21.7 (SD = 4.9) years. Diagnostic distribution: 66% (n = 99) anorexia nervosa, 21.3% (n = 32) bulimia nervosa and 12.7% (n = 19) other specified feeding or eating disorder, including binge eating. Data were collected at admission, discharge and follow-up (mean 2.7 (SD = 1.9) years). Definition of remission was based on the EDE-Q Global score, body mass index and binge/purge behavior. Paired T-tests were performed to investigate change over time. Univariate and multivariate logistic regressions were estimated to investigate predictors of remission., Results: At follow-up, 35.2% of the participants were classified as in remission. Significant symptom reduction (in all patients) (p <  0.001) and significant increase in body mass index (BMI) (in underweight participants at admission) (p <  0.001) was found. Increased BMI (p <  0.05), the level of core eating disorder symptoms at admission (p <  0.01) and reduced core eating disorder symptoms (p <  0.01) during inpatient treatment were found significant predictors of outcome in the multivariate model., Conclusions: All participants had an eating disorder requiring inpatient treatment. Approximately one-third of all participants could be classified as in remission at follow-up. However, most participants experienced significant symptom improvement during inpatient treatment and the improvements were sustained at follow-up. Increased probability of remission at follow-up was indicated by lower core ED symptoms at admission for all patients, raised BMI during admission for patients with AN, and reduced core ED symptoms during inpatient treatment for all patients. This finding contributes important information and highlights the importance of targeting these core symptoms in transdiagnostic treatment programs.

In recent years, it has become evident that neural stem cells in the adult mammalian brain continuously generate new neurons, mainly in the hippocampus and olfactory bulb. Although different growth factors have been shown to stimulate neurogenesis in the adult brain, very little is known about the role of neuropeptides in this process. Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide with pleiotropic effects acting through three receptors to which it has high affinity, namely, PACAP receptor 1 (PAC1), vasoactive intestinal peptide (VIP) receptor 1, and VIP receptor 2. We show that PAC1 is expressed in the neurogenic regions of the adult mouse brain, namely the ventricular zone of the lateral ventricle and the hippocampal dentate gyrus. Cultured neural stem cells isolated from the lateral ventricle wall of adult mice express PAC1 and proliferate in vitro in response to two PAC1 agonists, PACAP and Maxadilan, but not VIP at physiologic concentrations, indicating PAC1 as a mediator of neural stem cell proliferation. Pharmacologic and biochemical characterization of PACAP-induced neural stem cell proliferation revealed the protein kinase C pathway as the principal signaling pathway, whereas addition of epidermal growth factor synergistically enhanced the proliferating effect of PACAP. Further in vitro characterization of the effect of PACAP on neural stem cells showed PACAP capable of stimulating ex novo in vitro formation of multipotent neurospheres with the capacity to generate both neuronal and glial cells. Finally, intracerebroventricular infusion of PACAP increases cell proliferation in the ventricular zone of the lateral ventricle and the dentate gyrus of the hippocampus. We conclude that PACAP, through PAC1, is a potent mediator of adult neural stem cell proliferation., (Copyright 2004 Wiley-Liss, Inc.)

Purpose: The purpose of this study was to investigate the association between temporomandibular joint (TMJ) pain and histological changes in TMJs with disc displacement., Method: Samples from capsules and posterior disc attachments from 27 TMJ pain patients who underwent surgery were compared with samples from seven asymptomatic persons., Results: On logistic regression analysis, retrodiscal tissues from the painful joints demonstrated a significantly higher density of fibroblasts, presence of narrowed and obliterated arterial lumens, and a significantly lower distribution of elastic fibers., Conclusion: The results indicate that there is a difference between painful and asymptomatic joints at the microscopic level.

Purpose: This study compares the histologic features of the lateral capsule and lateral and central posterior disc attachment of temporomandibular joints (TMJs) in young and elderly persons., Material and Methods: Samples were removed from 36 joints belonging to young persons (mean age, 30 years; age range, 16 to 39 years) and 29 joints belonging to elderly persons (mean age, 69 years; age range, 58 to 78 years). Twelve joints from elderly persons had altered disc position, whereas none of the young joints had this condition. Six-micrometer-thick sections were stained with hematoxylin-eosin and the Fränkel method (for elastic fibers). Logistic regression analysis using a likelihood-ratio test was applied for comparisons between groups and to avoid the confounding effect of differences in disc position and gender., Results: A significantly lower density of fibroblasts was observed in elderly persons in all the three areas investigated. In addition, elderly persons demonstrated a significantly lower distribution of vascular tissue and a significantly higher presence of dense connective tissue in the central third of the posterior disc attachment., Conclusion: This study shows that retrodiscal tissues, which may eventually function as an articular disc during altered disc position, are susceptible to age-related connective tissue changes.

The purpose of this autopsy study was to test the hypotheses that temporomandibular joint (TMJ) arthrosis is more common in women than in men, increases with age, and is more common in edentulous persons than in those with natural teeth. Two hundred forty-eight TMJs removed at autopsy from 224 fresh cadavers were investigated macroscopically with dissection or cryosectioning. Age was found to be a significant factor in prediction of TMJ arthrosis (p < 0.001) and of disk perforation (p < 0.05). No significant association was found between morphologic changes in the TMJ and the factor of sex for the whole group. Disk displacement and disk perforation were, however, more common in the joints of women than men in the group of persons 80 years of age or older (p < 0.05). There were significant associations (p < 0.001) between arthrosis, disk displacement, disk deformation, and disk perforation. There were no statistically significant differences in the prevalence of morphologic changes in the joints from persons with 10 or more natural teeth in each jaw compared with those from persons without natural teeth. The results of this study showed that TMJ arthrosis is more frequent in older than in younger persons. TMJ disk displacement generally appears necessary for the development of perforations. The findings of this study indicate that sex and dentition are not major factors for the development of TMJ pathosis in elderly individuals.

Comparisons among several temporomandibular joint autopsy studies indicate that the frequency of arthrosis and disk displacement is higher in elderly persons. The aim of this study was to investigate type, frequency, and location of morphologic changes in temporomandibular joint autopsy specimens divided into two groups according to age and to determine the differences between the two groups. For this purpose 68 temporomandibular joints were removed from 37 persons at autopsy. Group I (young) consisted of 36 specimens belonging to 19 persons with a mean age of 30 years (range, 16 to 39 years). Group II (elderly) consisted of 32 specimens from persons with a mean age of 68 years (range, 55 to 78 years). Significant differences between the two groups were observed with respect to several of the morphologic changes that were evaluated. The results of this study suggest that the frequency of morphologic changes such as deviation in form, arthrosis, perforations, disk displacement, disk deformation, and adhesions is higher in the temporomandibular joints of elderly persons.

Numerous temporomandibular joint autopsy studies have been presented in the literature for the last two decades, but signs and symptoms of temporomandibular disorders before death were not available. To investigate the clinical significance of morphologic changes in the temporomandibular joint, 19 persons were clinically examined for signs and symptoms of temporomandibular disorders. The temporomandibular joints were subsequently analyzed macroscopically at autopsy and statistically associated with history and clinical findings. The average time between clinical examination and autopsy was 12 months. Signs and symptoms of temporomandibular disorders were not common findings for these persons. Morphologically, 31 of the 34 joints showed different forms of changes such as deviation in form, arthrosis, disk displacement, disk deformation, and adhesions. Crepitation showed a significant association with arthrosis. It was concluded that the association between pain and dysfunction and joint morphology is complex and gross morphologic alterations can be present in the absence of temporomandibular joint pain and dysfunction.

Thirty-three patients with an arthrographically documented anterior disk displacement without reduction were randomly assigned to be treated with upper joint space lavage or to serve as controls in an 8-week clinical trial. Pain was evaluated by the patients on a visual analog scale at rest and after chewing gum. The clinical examination followed a standardized protocol. Improvements in pain and mouth opening were found in both the lavage and control group after 8 weeks, but there were no statistically significant differences between the treatment and control groups. It was concluded that upper joint space lavage after arthrography seems to be ineffective to decrease pain and to increase mouth opening in patients with anterior disk displacement without reduction.

A flat occlusal splint has been extensively used in the treatment of patients with temporomandibular joint disk displacement without reduction, but no studies with untreated controls have assessed its effect. We randomly assigned 51 patients with temporomandibular joint pain and arthrographically verified disk displacement without reduction to be treated with a flat occlusal splint or to serve as untreated control subjects in a 12-month clinical trial. Pain symptoms disappeared in about one third of the patients in each group. Another third of the patients in the control group improved. Sixteen percent of the patients in the control group and 40% of the patients treated with a flat occlusal splint were worse at the end than at the beginning of the study. Joint pain and muscle tenderness decreased more frequently in the nontreatment controls than in the treatment group. A statistically significant benefit of a flat occlusal splint over nontreatment control subjects could not be identified in this study of patients with painful disk displacement without reduction. The use of a flat occlusal splint in this patient group should therefore be reconsidered.

This study investigated the frequency and distribution of clinical signs of temporomandibular joint (TMJ) internal derangement in an adult non-TMJ patient population. Four hundred three persons who participated in an epidemiologic investigation were examined for clinical signs of TMJ internal derangement by four examiners who followed a standardized form. Clinical signs of internal derangement were found in 76 persons (19%). Twenty-nine persons (7%) had reciprocal clicking and 47 (12%) had a history of clicking replaced by limitation of mouth opening with deviation to the affected side. Reciprocal clicking was associated with TMJ pain during mouth opening and with limitation of jaw movement. A history of clicking replaced by limitation of mouth opening with deviation to the affected side was associated with pain during mouth opening, limitation of opening, and palpatory tenderness of the TMJ. The study indicates that clinical signs of TMJ internal derangement are present in nearly one fifth of non-TMJ patients. Those with clinical signs of internal derangement frequently also have subjective symptoms but they have not sought treatment for these symptoms.

To study the correlation between single fibre EMG jitter and endplate potential amplitude we examined neuromuscular transmission in rats paralysed with botulinum toxin type A with single fibre EMG (SFEMG) in vivo and with intracellular microelectrode techniques in vitro. In muscles that were not completely paralysed SFEMG showed an increased neuromuscular jitter on nerve stimulation and in these muscles endplate potentials were of reduced amplitude. When the nerve stimulation frequency increased the jitter decreased. Intravenous injection of drugs that increase the acetylcholine release and endplate potential amplitude markedly reduced the jitter and the frequency dependence disappeared.

The anterior repositioning splint is widely used to treat temporomandibular joints with reciprocal clicking. This treatment was compared to a flat occlusal splint and to an untreated control group. The anterior repositioning splint decreased joint pain at rest, during chewing, and during protrusion. Reciprocal clicking was eliminated and palpatory tenderness of the joint and muscles was reduced. This favorable effect was of short duration. The majority of the patients reported pain and clicking and demonstrated tenderness following removal of the splint after 6 weeks' treatment. The flat occlusal splint decreased joint tenderness but did not affect clicking or muscle tenderness. In the control group the clicking remained and the frequency of muscle tenderness increased. The results indicate that temporomandibular joints with reciprocal clicking can be successfully treated by positioning the mandible anteriorly. Since the symptoms returned when the splint was removed a more permanent change of mandibular position seems necessary.

Rabbits injected with purified acetylcholine (ACh) receptor protein produce antibodies against the receptor and develop generalized muscle weakness. The compound muscle action potentials show a decremental fall in amplitude with repetitive nerve stimulation. Both the weakness and the decrement is counteracted by reversible cholinesterase inhibitors. Intracellular recordings from muscle endplates show that the amplitude of the miniature end-plate potentials is considerably reduced. A reduced binding of neurotoxin to muscles from immunized rabbits was observed. Nerve impulses release a normal number of ACh packages (quanta) from the motor nerve terminals. The muscle weakness in immunized rabbits thus has the same features as the muscle weakness in myasthenia gravis and may be a good animal model of myasthenia gravis.

4-Aminopyridine (4-AP) powerfully increases transmitter release from motor nerve terminals of rat and frog skeletal muscle in response to single nerve impulses. The drug also enhances transmitter release during repetitive nerve activity but, at D-tubocurarine-blocked endplates, only the first impulses cause increased transmitter release at stimulation frequencies at or above 50 Hz. At magnesium- and botulinum-poisoned endplates, 4-AP potentiates transmitter release at every stimulus during tetanic nerve stimulation and restores neuromuscular transmission. Spontaneous transmitter release in the rat is not affected by the drug, but at some frog endplates miniature endplate potential (mepp) frequency increases. The drug has no post-synaptic action, as evidenced by its lack of effect on amplitude or time course of mepps. Decreasing the temperature from 37 to 15 degrees C does not abolish the effect of 4-AP on neuromuscular transmission. In the presence of 4-AP, single nerve impulses produce repetitive spontaneous activity in the nerve terminal of the frog nerve-muscle preparation. Experiments on the mode of action of 4-AP suggest that the drug increases transmitter release by enhancing the influx of calcium ions during depolarization of the nerve terminal.

Seven patients with temporomandibular joint disk displacement were treated with disk-repositioning onlays, and changes in the mandibular position were studied by means of roentgen stereophotogrammetry. A wide range of changes in mandibular position was seen at cementation of the onlays and during the observation period. On an average, recapturing of the disk and cementation of the onlays lowered the mandible by 2.5 mm and protruded it by 0.5 mm. During the observation period of 7 months the mandible had a tendency to resume its original position. The relapse was 80% in the sagittal plane, 70% in the transverse plane, and 12% in the vertical plane. It was concluded that disk-repositioning onlays can be used to lower the mandible with a relatively small relapse. Changes in the horizontal plane, however, seem to be less stable.

It has been suggested in the literature that reciprocal temporomandibular joint clicking progresses to locking, but little information is available on the longitudinal course of this stage of internal derangement. Seventy patients with reciprocal clicking were therefore followed for 3 years. Reciprocal clicking remained unchanged in fifty patients (71%) and disappeared in twenty patients (29%). Fourteen patients (20%), in whom clicking disappeared, attained normal mouth opening, whereas locking developed in six patients (9%). At the initial examination, these six patients had more pain, more frequent joint tenderness, greater frequency of missing molar support and more often dental abrasion on the affected side than the patients who did not develop locking. It was concluded that reciprocal clicking does not usually progress to locking. However, locking is more likely to occur in patients who initially have pronounced pain, joint tenderness, dental abrasion, and no molar support on the affected side.

Sixty-three patients with an arthrographic diagnosis of disk displacement with reduction were randomly assigned to three treatment groups: (I) onlays to maintain disk repositioning, (II) flat occlusal splint, or (III) untreated controls. Guidance for construction of the disk-repositioning onlays was established during arthrography to obtain a recaptured disk position relative to the condyle. The onlays were cemented to the teeth and maintained the new intercuspal position anteriorly and inferiorly. The flat occlusal splint was used at night only and was adjusted to maintain a maximal occlusal contact in centric relation and centric occlusion. Clinical examinations were performed before and after 6 months of treatment. The disk-repositioning onlays improved joint function and reduced joint and muscle pain when compared with the flat occlusal splint and with nontreatment. The signs and symptoms in the flat occlusal splint group were no different from those in the control group. It is concluded that disk-repositioning onlays are effective in reducing pain and dysfunction associated with disk displacement with reduction in patients in whom the disk can be maintained in a normal relationship to the condyle with the aid of such onlays. The symptoms, however, returned when the onlays were removed after 6 months; this raises the question of whether a permanent change in the intercuspal position is necessary for long-term success.

To gain further knowledge about the differences between normal and pathologic anatomy of the temporomandibular joint disk, we examined histologically disks obtained at autopsy from 10 symptom-free persons and compared our findings with observations involving 17 surgically removed disks. The surgical patients had internal derangement and severe long-standing temporomandibular joint pain and dysfunction. The normal disks were biconcave, whereas the surgically removed disks were deformed and thicker than the normal disks. Chondrocytes (4 joints), a surface layer of proliferative connective tissue (4 joints), vessels (2 joints), and splitting (4 joints) were seen in the surgical specimens but not in the normal specimens. The surgical specimens also showed higher maximal density of fibroblasts and vessels. It was concluded that surgically removed temporomandibular joint disks demonstrated several histologic alterations that were not seen in normal disks. These characteristics may serve as the basis for development of a histologic grading of pathologic conditions of the temporomandibular joint disk and the posterior disk attachment.