Effects of parathyroid hormone on Wnt signaling pathway in bone.

The Wnt signaling pathway has recently been demonstrated to play an important role in bone cell function. In previous studies using DNA microarray analyses, we observed a change in some of the molecular components of the canonical Wnt pathway namely, frizzled-1 (FZD-1) and axil, in response to continuous parathyroid hormone (PTH) treatment in rats. In the present study, we further explored other components of the Wnt signaling pathway in rat distal metaphyseal bone in vivo, and rat osteoblastic osteosarcoma cells (UMR 106) in culture. Several Wnt pathway components, including low-density lipoprotein-receptor-related protein 5 (LRP5), LRP6, FZD-1, Dickkopf-1 (Dkk-1), and Kremen-1 (KRM-1), were expressed in bone in vivo and in osteoblasts in vitro. Continuous exposure to PTH (1-38) both in vivo and in vitro upregulated the mRNA expression of LRP6 and FZD-1 and decreased LRP5 and Dkk-1. These effects in UMR 106 cells were associated with an increase in beta-catenin as measured by Western blots and resulted in functional activation (three to six-fold) of a downstream Wnt responsive TBE6-luciferase (TCF/LEF-binding element) reporter gene. Activation of the TBE6-luciferase reporter gene by PTH (1-38) in UMR 106 cells was inhibited by the protein kinase A (PKA) inhibitor, H89. Activation was mimicked by PTH (1-31), PTH-related protein (1-34), and forskolin, but both PTH (3-34) and (7-34) had no effect. These findings suggest that the effect of PTH on the canonical Wnt signaling pathway occurs at least in part via the cAMP-PKA pathway through the differential regulation of the receptor complex proteins (FZD-1/LRP5 or LRP6) and the antagonist (Dkk-1). Taken together, these results reveal a possible role for the Wnt signaling pathway in PTH actions in bone.

Effects of middle ear effusion on the vestibular system in children.

Vertigo and dizziness are not common in childhood, but are probably present more often than was formerly thought. These symptoms caused mainly by otitis media and middle ear effusion, two of the most common diseases in children, have been neglected for a long time, both in the literature and in practice, until recently. The purpose of this study was to determine objectively the incidence of balance-related symptoms in children with long-lasting middle ear effusion and to discover whether these symptoms resolve after the insertion of ventilation tubes. One hundred thirty-six children, ages 4 to 9 years, were given electronystagmographic tests and the Bruininks-Oseretsky tests for motor proficiency before and after tube ventilation of the middle ear. The results were compared with those in 74 healthy children with no history of middle ear diseases. Pathologic findings were found in 58% of the children with chronic middle ear effusion, as compared with only 4% of the control group. The symptoms and signs of balance disturbances resolved in 96% of the children after ventilation tube insertion. The results of this study indicate that balance-related symptoms often encountered in young children may result from chronic middle ear effusion and that these symptoms will resolve after evacuation of the effusion and ventilation of the middle ear.

Prophylactic treatment after ventilation tube insertion: comparison of various methods.

Otitis media is recognized as one of the most common diseases of childhood. Insertion of tympanostomy tubes for the treatment of otitis media is the most frequently performed otologic operation, and postoperative otorrhea is its most common complication. Many authors have suggested various reasons for posttympanostomy otorrhea, and many different prophylactic treatments were proposed in recent years to prevent this bothersome and frustrating complication. This retrospective study was designed to investigate and compare the efficacy of various prophylactic treatments and to define the most effective method of reducing the rate of postoperative otorrhea.

The epiglottis and obstructive sleep apnoea syndrome.

Obstructive sleep apnoea syndrome (OSAS) is caused by obstruction or narrowing of the airway at various levels. The repair of one site only will not alleviate the syndrome if there are obstructions in other sites. Epiglottis prolapse during inspiration is an unusual cause of airway obstruction and a rare cause of OSA. Twelve cases of OSAS due to an abnormal epiglottis are presented. We present our approach to the diagnosis using fibre-optic examination of the hypopharynx, and our treatment using endoscopic carbon dioxide laser partial epiglottidectomy. We found in our series that in 11.5 per cent of patients who failed the uvulopalatopharyngoplasty procedure, the reason was a narrow airway at the hypopharyngeal level caused by an abnormal epiglottis. It is our suggestion that in these cases a laser partial epiglottidectomy should be performed. The results of this study show that partial epiglottidectomy can increase the cure rate of patients with obstructive sleep apnoea syndrome by 10-15 per cent.

Use of assisted reading to increase correct reading rates and decrease error rates of students with learning disabilities.

The effects of assisted reading on 3 elementary students with learning disabilities were evaluated using a multiple baseline design. Data were collected from the students' oral reading from their basal texts. The results indicated an increase in number of words read correctly as well as a decrease in the number of words read incorrectly when assisted reading was used in the classroom.

Vestibular dysfunction in a child with embryonic exposure to accutane.

Children with a history of embryonic exposure to Accutane (isotretinoin) are at great risk for major physical malformations, brain malformations, and decreased intelligence. A case is presented of a 4-year 7-month-old black male with a history of embryonic exposure to Accutane who was born with embryopathy that includes bilateral major ear deformities. The child has a significant bilateral conductive hearing loss, and, in addition, a left sided sensorineural loss. Vestibular function testing revealed evidence of peripheral and central vestibular dysfunction. A course of diphenhydramine hydrochloride and Donnatal (phenobarbital, hyoscyamine sulfate, atropine sulfate, and scopolamine hydrobromide) significantly alleviated the symptoms of vestibular dysfunction. Otologic management of these children should include clinical documentation of the external deformities, evaluation of cochlear function, and early auditory habilitation. Vestibular function should also be evaluated in all children with a history of embryonic exposure to isotretinoin.

Effect of middle ear effusion on the vestibular labyrinth.

Although middle ear effusion was once described as the most common cause of vestibular disturbance in children, the association between glue ear and symptoms of dysequilibrium has never been quantified objectively. In this study the effect of middle ear effusion on the vestibular system of the inner ear was studied in a select group of children suffering from long lasting effusion in the middle ear with no evidence of infection at least one year prior to the study. The results were compared with results obtained from otitis free children, as well as from examinations of children after the insertion of ventilating tubes. The results of this study confirm the assumption that middle ear effusion has an adverse effect on the vestibular system, which can be resolved following the insertion of ventilation tubes. This effect may also contribute to the adverse effect that otitis media has on a child's development.

[Evaluation of VIIIth nerve disorders in learning-disabled children].

Recent research indicates that a subclinical VIIIth nerve defect can be a major contributing factor to, if not a cause of learning disabilities. A battery of tests developed for evaluation of VIIIth nerve function is presented. These tests include assessment of vestibular function and evaluation of auditory figure ground abilities. 70 primary school children diagnosed as learning-disabled by child study teams were tested using this battery. 94% had abnormal findings in the electronystagmographic test and 22% in the auditory figure ground test. This battery of tests can detect subclinical defects in learning-disabled children which can be alleviated by a combination of proper medical treatment and an appropriate educational plan.

Effective intravenous cyclosporin therapy in a patient with severe Crohn's disease on parenteral nutrition.

We report a patient with severe Crohn's disease and the short bowel syndrome on parenteral feeding who was not responding to conventional therapy and underwent treatment with cyclosporin (CyA) given initially intravenously and subsequently orally in each of two courses. Plasma drug concentrations were largely kept within the therapeutic range but wide variability was observed on oral therapy. Improvement both clinically and by objective assessment, was observed on intravenous CyA therapy, but was not sustained when the drug was given orally for several months. None of the side effects observed resisted treatment or was severe enough to warrant discontinuation of therapy. These findings suggest that there may be a place for intravenous CyA therapy in patients with severe Crohn's disease who do not respond to conventional therapy or to oral treatment with CyA.

Evaluation of a high pressure liquid chromatographic technique for metoclopramide analysis.

High-dose metoclopramide has found an established place in the prophylaxis of nausea and vomiting which may be induced by cancer chemotherapy. A simple reliable high pressure liquid chromatographic technique for the measurement of this drug in serum has been developed and evaluated. The methodology will find application in the study of metoclopramide pharmacokinetics and in the monitoring of high-dose metoclopramide therapy in individual patients with neoplastic disease.

Qualitative measurement of drugs.

It has been noted for several years that certain drugs produce abnormal test results in patients who are administered the electronystagmograph (ENG) test. Drug specific waveforms, termed drug evoked potentials (DEP), have been identified by using the ENG for alcohol, marijuana, cocaine, tranquilizers, amphetamines, barbiturates, opiates, hallucinogens, caffeine, aminophylline, dopamine, several gases and approximately 75 combinations of drugs (N = 821). Tests for double blind diagnosis of drug intake as well as tests for repeatability within the same subject were conducted. Subjects included surgical candidates, healthy volunteers, and neonates (N = 248). Drugs tested were ketamine hydrochloride, fentanyl, sodium pentothal, cocaine, dextroamphetamine, sodium seconal, morphine sulfate, phenobarbital, and meperidine. Placebos of dextrose in water and sucrose tablets were also used (N = 25). Analysis of the waveforms produced by surgical candidates and healthy volunteers revealed no false negatives or false positives. Analysis of waveforms produced by neonates whose mothers had been administered meperidine demonstrated a diminishing effect over the course of a 3 day period. Results of repeated studies revealed reliability within subject. One subject who was administered dextroamphetamine did not produce a wave consistent with amphetamine with a dosage of 5 mg. He did, however, produce an amphetamine wave when administered 10 mg of dextroamphetamine. These findings suggest a dose related effect, indicating the need for establishment of minimal levels of detection. Results indicate that with refinement and further research, this method could be used for identification of drugs diagnostically.

A non-invasive method of qualitative and quantitative measurement of drugs.

Methods for quick qualitative and quantitative evaluation of drug intake are needed, especially during emergency situations such as drug overdose and alcohol intoxication. The electronystagmograph was used in an attempt to develop a non-invasive method for identification of drug intake, and to study the effects of alcohol and other drugs on the vestibular system. Results of the study reveal that alcohol, diazepam, opiates, barbiturates, cocaine, marijuana, and hallucinogenic drugs produce a characteristic printout pattern which can be evaluated qualitatively. This method is a practical, non-invasive, objective procedure that provides rapid assessment of quality of drug intake. Its potential uses are extensive, including such possibilities as evaluation of drug intake in emergency drug overdose situations, monitoring anesthesia during surgery, evaluating drug intake in women about to deliver, (as well as the effects on the newborn), and determining whether or not persons who are being tested on a polygraph are under the influence of drugs.