Early effects of tetraethylammonium chloride on the contractile properties of isolated rabbit basilar arteries

The acute vascular effects of tetraethylammonium chloride (TEA) were examined on annular segments of rabbit basilar arteries. Contractions induced by the potassium channel blocker were compared with those obtained for potassium chloride, 5-hydroxytryptamine (5-HT) and norepinephrine (NE). The greater magnitude of the contractions was of the following order: [K+] greater than 5-HT greater than TEA greater than NE. High concentrations of TEA alone (10(-2) M) generated spontaneous oscillatory contractions in cerebral vessels that were normally quiescent. Low concentrations of TEA (10(-8)-10(-6) M), which had no vasomotor properties per se, enhanced the contractile response of submaximal concentrations of 5-HT (10(-7) M) and NE (3 X 10(-6) M) and attenuated the contraction produced by 60 mM [K+]. An increased vascular response to the amines was still evident up to 3 h after the addition of TEA despite frequent rinsing with fresh buffer solutions. On arteries precontracted with TEA (10(-2) M), but not high [K+], the subsequent addition of 5-HT (10(-7) M) still induced a powerful constriction. Repeated concentration-response curves for [K+] were reproducible and, in the presence of TEA (10(-8) or 10(-6) M), the curve was displaced to the right in a competitive manner. A higher concentration of TEA (10(-4) M) was devoid of any blocking properties on the [K+]-induced response whereas, at 10(-3) M TEA, the response was potentiated, as evidenced by a shift of the curve to the left. Interactions between TEA and the cumulative response to 5-HT were difficult to interpret. Repeated exposures of the artery to 5-HT resulted in an increased maximal response with each determination (EAm = 127 +/- 9% and 149 +/- 14% of control values following the second and third applications, respectively). With TEA (10(-6) M), the increase in the maximal contractile effect noted previously was not observed. Contractions induced by single concentrations of TEA (10(-2) M) or [K+] (60 mM) were calcium dependent, were abolished completely in a calcium-free medium, and were depressed by the calcium antagonist nimodipine. 5-Hydroxytryptamine-induced contractions (10(-5) M) were less sensitive to withdrawal of calcium from the extracellular medium (31 +/- 6% relative to the maximal response at 4 mM calcium). Hence, an acute reduction in potassium conductance in cerebrovascular smooth muscle produced by TEA has complex, concentration-dependent effects and reproduces only part of the spectrum of effects of cisternal injection of blood on cerebrovascular reactivity.     

A case of affective disorder associated with the misuse of 'anabolic steroids'.

In the pursuit of gains in muscle size and strength, body-builders may mistakenly use illicit drugs believing them to be anabolic steroids. The case described illustrates the physical and psychological dangers of such behaviour.     

Nonrhinologic headache in a tertiary rhinology practice.

OBJECTIVE: Our goal was to determine the etiology of headache in patients who were referred for sinus evaluation but were found to have no evidence of rhinosinusitis on computed tomography (CT) of the sinuses and on endoscopic examination. METHODS: Data were collected prospectively from 100 patients with headache but with normal sinus CT and endoscopic examination. Headache and 20-Item Sino-Nasal Outcomes Test (SNOT-20) scores of patients with the chief complaint of headache and who requested further neurologic evaluation (group I) were compared with the scores of patients who did not list headache as a significant symptom (group II) and with the scores of patients without headache (group III). RESULTS: The most common neurologic diagnosis for group I patients (n = 36) was migraine headaches (58%). These patients also had higher mean SNOT-20 scores (24 +/- 3.3) compared to group II patients with mild headache (14.6 +/- 2.3) or group III patients without headache (12.4 +/- 2.1). CONCLUSION: Migraine was the most common type of headache in patients with normal sinus CT treated for presumed rhinosinusitis as the cause of the headache. Patients with headache as their chief complaint that required further neurologic evaluation had overall higher SNOT-20 scores than nonheadache patients, indicating greater disability of their overall quality of life index.     

9p21 and 13q14 dosages in ependymomas. A clinicopathologic study of 101 cases.

Ependymomas are glial neoplasms whose clinical behavior is difficult to predict based on histology alone. Recently, a comparative genomic hybridization study identified frequent chromosome 9p and 13q losses in anaplastic ependymomas, suggesting that p16 and RB alterations may be involved in tumor progression. In order to test this hypothesis further, 101 myxopapillary, conventional, and anaplastic ependymomas (51 spinal and 50 intracranial tumors) were tested for RB and p16 deletions using fluorescence in situ hybridization. Clinical follow-up, ranging from 2 to 198 months (median 46 months), was obtained in 90 cases (91%). RB and p16 deletions were seen in 22 of 92 (24%) and 22 of 89 (25%) informative cases, respectively. Polysomies were more frequent in the grade I and II spinal tumors, consistent with prior reports of increased aneuploidy in such cases. No significant genetic associations were seen with tumor grade, recurrence, or death, suggesting that 9p and 13q deletions do not play a prominent role in the malignant progression of ependymomas, as has been implicated in other glioma subtypes.     

Attenuation of exercise induced asthma by local hyperthermia.

BACKGROUND: Prior treatment with local hyperthermia has been shown to prevent mast cell degranulation and leucocyte histamine release, and to reduce mortality and cellular infiltrates in a model of acute lung injury. Local hyperthermia is effective in reducing the symptoms of the common cold and perennial and seasonal allergic rhinitis, nasal patency also being improved in rhinitis. It is possible that these effects are mediated by common anti-inflammatory mechanisms, and that this treatment may be effective in the treatment of asthma. The effect of prior local hyperthermia on the response to exercise challenge and histamine bronchoprovocation was therefore examined. METHODS: In a randomised, double blind, placebo controlled, crossover study, 10 asthmatic subjects with exercise induced asthma used machines delivering 40 1/minute of fully humidified air at either 42 degrees C (active treatment) or 31 degrees C (placebo treatment) for 30 minutes' tidal breathing. For each pretreatment, at two week intervals they underwent exercise challenges starting one and 24 hours after starting the inhalations. After a further two weeks the protocol was repeated with histamine substituted for the exercise challenges. RESULTS: The mean (SE) maximum percentage fall in forced expiratory volume in one second (FEV1) was significantly lower one hour after treatment with air at 42 degrees C (30.8% (3.1%)) than after treatment with air at 31 degrees C (22.3% (2.9%)). There was no significant effect on exercise challenge at 24 hours, or on histamine challenge at either time point, though there were nonsignificant trends towards protection with exercise at 24 hours and with histamine at one hour. CONCLUSION: In asthmatic subjects the response to exercise challenge is significantly attenuated one hour after treatment with local hyperthermia. This treatment warrants further investigation in the treatment of clinical asthma and other inflammatory disorders.     

Ubiquitin is associated with abnormal cytoplasmic filaments characteristic of neurodegenerative diseases.

Several degenerative diseases of the nervous system are characterized by the presence of neuronal inclusions. Most of these inclusions are made of abnormal filaments and share epitopes with cytoskeletal proteins. One of these inclusions, the neurofibrillary tangle of Alzheimer disease, has recently been shown to contain ubiquitin, a regulatory protein thought to play a role in the degradation of abnormal proteins. We carried out light and electron microscopic immunocytochemistry with several polyclonal and monoclonal antibodies to investigate the presence of ubiquitin in neuronal inclusions of neurodegenerative diseases. Ubiquitin was present not only in paired helical filaments that form the neurofibrillary tangle of Alzheimer disease, but also in the filamentous components of the inclusion characteristic of Parkinson disease, Pick disease, and progressive supranuclear palsy. In contrast, ubiquitin was not detected in other neuronal inclusions often found in aging and in Alzheimer disease, such as Hirano bodies and granulovacuolar degeneration. Reactivity with monoclonal antibodies suggests differences in the ubiquitin-acceptor proteins present in the inclusions studied. It is concluded that ubiquitin is selectively present in neuronal inclusions of degenerative diseases.