Botulinum toxin treatment improves dysphagia in patients with oculopharyngeal muscular dystrophy and sporadic inclusion body myositis.

OBJECTIVE: Dysphagia can be troublesome in sporadic inclusion body myositis (sIBM) and oculopharyngeal muscular dystrophy (OPMD), but no established treatment exists. Cricopharyngeal muscle botulinum toxin injection has at case level been reported to be effective. We evaluated safety and efficacy of botulinum toxin injections in the cricopharyngeal muscle in patients with dysphagia due to sIBM or OPMD. METHODS: Participants were included from our outpatient clinic. Cricopharyngeal constriction was confirmed by laryngoscopy. After EMG confirmation of needle placement in the cricopharyngeal muscle, botulinum toxin A was injected in awake patients. An individualized dose of 5-10 units of botulinum toxin A was applied initially and titrated up a maximum of 3 times. Outcome measures were change in dysphagia questionnaire, timed cold-water swallow test and subjective dysphagia status (worse, unchanged, improved). Due to the need for individualized dosing and a limited number of available patients, an uncontrolled, un-blinded design was used. RESULTS: Thirteen patients, 3 with OPMD, received at least 1 injection. In the dysphagia questionnaire, all but 2 subjects, none with subjective worsening, improved (p < 0.001). Subjectively, seven felt an improvement, 4 no change and 2 a worsening. No overall change was seen the timed cold-water swallow test. No serious adverse events were observed. CONCLUSION: Botulinum toxin injection of the cricopharyngeal muscle in patients with OPMD and sIBM had a beneficial effect on dysphagia in most of the treated patients. Two of 13 patients experienced a temporary worsening not reflected in dysphagia score. Limitations are the un-blinded and un-randomized design and subjective assessments methods. PROSPECTIVE TRIAL REGISTRATION: EudraCT-number: 2014-002210-23.

Experimental findings on the nasal tract resonator in singing.

SUMMARY: Many professional operatic singers sing the vowel /a/ with a velopharyngeal opening.(1) Here resonatory effects of such an opening are analyzed. On the basis of CAT scan imaging of a baritone singer's vocal tract and nasal cavity system, including the maxillary sinuses, acoustic epoxy models were constructed, in which velopharyngeal openings were modeled by different tubes. The sound transfer characteristics of this model were determined by means of sine-tone sweep measurements. In an idealized (iron tube) model, the VPO introduced a zero in the transfer function at the frequency of the nasal resonance. In the epoxy models, however, the resonances of the nasal system, and hence the zero, were heavily damped, particularly when the maxillary sinuses were included in the nasal system. A velopharyngeal opening was found to attenuate the first formant in /a/, such that the relative level of the singer's formant increased. A similar effect was observed in a modified epoxy model shaped to approximate the vocal tract of an /u/ and an /i/, although it also showed a substantial widening of the first formant bandwidth. Varying the size of the velopharyngeal opening affected the transfer function only slightly. It seems likely that singers can enhance higher spectrum partials by a careful tuning of a velopharyngeal opening.

Reduced jaw opening from paradoxical activity of mandibular elevator muscles treated with botulinum toxin.

The aim of the study was the effect of injections with botulinum toxin A (BTX-A) on reduced jaw opening, caused by paradoxical, antagonistic activity of jaw elevator muscles after brain stem lesions. The study included a male (51 years) and a female (69 years) patient. Subjective assessment, clinical recordings, muscle blocks and electromyography (EMG) were used to diagnose paradoxical activity, and to plan, guide and evaluate the treatment. The paradoxical innervation pattern was unilateral in the male and bilateral in the female. The paradoxical activity during jaw opening amounted to 24-109% of the level during maximum biting, and bursts of paradoxical activity were also present during chewing. EMG-guided blocks and later BTX-A injections of the affected muscles increased the opening by 9-23 mm from pre-treatment values of 15-18 mm, and normalized chewing. The study proved BTX-A to be an effective treatment for reduced jaw opening caused by paradoxical activity. Treatment was optimized by EMG evaluation of the current activity of the jaw elevator muscles, permitting individual treatment plans with longer intervals between BTX-A injections and lower doses than with conventional treatment for oromandibular dystonia. Thus the treatment only had to be repeated one to two times per year to maintain acceptable jaw mobility.

[Botulinum toxin treatment of patients with oromandibular dystonia]. / Botulinumtoksin-behandling af patienter med oromandibulaer dystoni.

INTRODUCTION: Oromandibular dystonia (OMD) is a frequently disabling focal dystonia, which may be treated with injections of botulinum toxin in the affected muscles. The aim of the present study was to evaluate the population, effect and side-effects of patients treated in Denmark during a nine year period. METHODS: We evaluated all 45 consecutive patients treated with quantitative EMG guided injections of botulinum toxin for OMD. RESULTS: The OMD symptoms varied but were most often mixed symptoms (n = 13), jaw closing (n = 11) and jaw opening (n = 7). Thirty-two patients (71%) had other focal or generalised dystonia, and in 24 the additional dystonia were also treated with botulinum toxin. The 45 patients had a total of 277 treatments (mean 6.2 treatments pr. patient), each including one to six muscles. Marked effect was observed or experienced after 193 (70%) treatments, and 33 patients (73%) experienced at least one effective treatment. Side-effects occurred after 35 treatments (13%) experienced by a total of 16 patients (35.6%), most frequently as transient mild dysphagia. DISCUSSION: The study shows that botulinum toxin treatment of OMD, guided by quantitative EMG, is safe and effective.

Auditory function after continuous infusion of gentamicin to high-risk newborns.

Audiometry was performed at four years of age in 69 of 105 surviving children who had received continuous intravenous infusion of gentamicin during neonatal intensive care. A hearing loss of 20 dB was found in 2 of them (3%), corresponding to that shown in other studies of survivors following neonatal intensive care. Free field audiometry performed in another 7 children and questionnaires returned from 13 of the remaining 29 gave no suspicion of hearing loss. Thus there is no indication that continuous 24 hours intravenous infusion of gentamicin causes more hearing impairment than intermittent intravenous or intramuscular administration.

Effects of 3-deazaadenosine, an inducer of HL-60 cell differentiation, on human blood cells in vitro.

The adenosine analogue 3-deazaadenosine (c3 Ado) induces differentiation of human promyelocytic leukemia HL-60 cells in vitro. c3 Ado affects in vitro viability and growth of cells involved indirectly (cytokine-producing cells) and directly (transformed myeloid cells) in leukemic cell differentiation. Growth inhibition of proliferating cells is achieved at c3 Ado concentrations between 10-100 microM. Concentrations higher than 100 microM affect viability of proliferating and nonproliferating cells.

Surgical and speech results following palatopharyngoplasty operations in Denmark 1959-1977.

This study analysed surgical results from 600 palatopharyngoplasties (PPP), performed from 1959-77 by Dr. Poul Fogh-Andersen, Copenhagen, and the speech results in 140 of these cases. There were 205 cases of cleft lip and palate (CLP), 133 of cleft palate (CP), 104 of submucous cleft palate (SMCP), 138 of velopharyngeal insufficiency (VPI), and 20 cases of velar paresis. At surgery 62% were younger than ten years, and 5% were older than 30 years. Speech results were evaluated from pre- and postoperative tape recordings. Normal nasal resonance was obtained in 74%, improvement to mild symptoms in 24%. Submucous cleft palate cases had the highest rate of normalization, VPI cases the lowest. The cases with severest hypernasality had the lowest normalization rate. Age and operative procedure were of minor importance in relation to speech results, but surgical complications were fewer in subjects younger than ten years. Postoperative speech therapy was given to 38%, predominantly to subjects with compensatory voice and articulation problems.

The profile and severity of lithium-induced side effects in mentally healthy subjects.

In a double-blind, placebo-controlled, crossover design various side effects (= unwanted effects) during 6 months of therapeutic serum lithium levels (0.7-1.1 mmol/1) to nonpsychiatric patients were studied. The side effects were measured by self-rating scales and independent observer rating scales administered every 2-4 weeks throughout the study. After months of treatment, lithium induced hand tremor and thirst/polyuria; however, without any relationship to the serum levels of lithium. The frequency of tremor was highest in patients above the age of 60 years. No initial sedative-like lithium effect was found.

Long-term treatment of nasal polyps with beclomethasone dipropionate aerosol. I. Treatment and rationale.

Beclomethasone dipropionate is a potent corticosteroid, which when applied by a pressurized metered dose aerosol in the airways has pronounced anti-allergic effects with no risk of systemic steroid side effects at the recommended dosage. An impressive effect in hay fever and perennial rhinitis has been demonstrated. A double-blind short-term trial showed that the drug was effective in about 80% of patients suffering from moderate to severe nasal polyposis. A study of the long-term effects on the nasal mucosa is indicated.

[Long-term treatment of nasal polyps with beclomethasone dipropionate aerosol. III. Morphological studies and conclusions].

Morphological studies during the treatment of patients with nasal polyps with beclomethasone dipropionate aerosol for one year showed a trend towards a decrease in the number of eosinophils in nasal smears and falls in the increased concentrations of albumin, IgG and IgE in the nasal secretion. No change in the histological picture of the polypous tissue except increased density was observed. By scanning electron microscopy, no change in the surface structure of the nasal mucous membrane was noted. As morphological studies did not reveal any sign of adverse effects, beclomethasone dipropionate may be regarded as a valuable drug in the treatment of nasal polyps. The indications for its clinical use and supplementary therapy are discussed.

Long-term treatment of nasal polyps with beclomethasone dipropionate aerosol. II. Clinical results.

The effect of a one-year treatment with intranasal beclomethasone dipropionate in 33 patients with long-standing nasal polyps was determined. About 80% of the patients obtained good or excellent relief of symptoms. No adverse reactions of any importance occurred. It is suggested that intranasal beclomethasone dipropionate is close to the ideal basic treatment for patients with nasal polyps.

Lithium treatment of meniere's disease. Results of a double-blind cross-over trial.

21 patients with Meniere's disease participated in a double-blind, cross-over trial, with 6 months' lithium treatment and 6 months' placebo treatment. Even if the results were not completely unequivocal, no difference was found between lithium and placebo treatment. The results might imply that both other medical as well as surgical treatment of Meniere's disease exert a pure placebo effect; so far no controlled investigation has been published, establishing the value of surgical treatment of Meniere's disease.

Facial nerve paralysis caused by carcinoma developed in thorotrastoma in the parotid gland.

A carcinoma developed in a thorotrastoma of the right parotid gland and caused facial paralysis 28 years after a sialography with radioactive thorotrast. The literature is reviewed, and another case is reported in which facial nerve paralysis occurred without evidence of malignancy.

A follow-up examination of patients with pulmonary tuberculosis resected on suspicion of tumour.

Thoracotomy was performed in 91 patients who proved to have pulmonary tuberculosis. A short course of antituberculous chemotherapy was given preoperatively in 66 cases. The surviving 89 patients received antituberculous chemotherapy postoperatively, and were-re-examined from 1 to 14 years after the operation. No signs of dissemination or other tuberculous manifestations were found 1 year after termination of chemotherapy, even if preoperative treatment had not been given. One recurrence was seen 7 years after operation despite 9 months postoperative antituberculous chemotherapy. This was the only tuberculous manifestation. The survival rate was normal in the first 3 years compared with a corresponding Danish population, but became slightly reduced 10 years after operation. The quality of life did not seem to be significantly changed as estimated by the degree of disablement which could be correlated to the operation.

Glucose tolerance and serum lipids in man after long-term lithium administration.

Intravenous glucose tolerance and serum lactate concentration during the tolerance test were determined in the same 12 patients after 6 months of placebo and after 6 months of lithium treatment. At the end of these periods values of glucose, lactate, serum free fatty acids, and serum triglycerides were measured in fasting patients. Long-term lithium treatment had no influence on these parameters.

Surgical treatment of "tuberculoma". A follow-up examination of patients with pulmonary tuberculosis resected on suspicion of tumour.

On suspicion of tumour, thoracotomy was performed in 91 patients, who proved to have pulmonary tuberculosis. Short-term antituberculous chemotherapy was given pre-operatively in 66 cases. The 89 surviving patients received antituberculous chemotherapy after operation, and were examined one year after its termination. No signs of dissemination or other tuberculous manifestations were found, whether pre-operative therapy had been given or not.