Cardiotoxin from cobra venom increases the level of phosphatidylinositol 4-monophosphate and phosphatidylinositol kinase activity in two cell lines.

In rat basophilic leukemia-2H3 (RBL-2H3) and Madin-Darby canine kidney (MDCK) cells, cardiotoxin from cobra venom induced a marked decrease in the level of [3H] phosphatidylinositol and a corresponding increase in the level of [3H]phosphatidylinositol 4-monophosphate over the course of 20 min as demonstrated in cells that had been labeled to equilibrium with [3H]inositol. The effect was dependent on the concentration (5-30 micrograms/ml) of the toxin. In plasma membrane-enriched fractions isolated from the two cell lines, the cardiotoxin enhanced the endogenous activity of phosphatidylinositol kinase especially at temperatures above 14 degrees C. In RBL-2H3 cells, cardiotoxin also induced release of substantial amounts of histamine and lactate dehydrogenase. The release of histamine, but not of lactate dehydrogenase, was totally dependent on external calcium and this release probably represented an exocytotic response of the cells to cardiotoxin. Although, initially, treatment with the toxin did not impair antigen-induced hydrolysis of inositol phospholipids or prevent the antigen-induced rise in the concentration of cytosol Ca2+, prolonged exposure to the toxin did result in a progressive loss of responsiveness of RBL-2H3 cells to antigen.

Migrating esophageal foreign bodies.

UNLABELLED: Ingested foreign bodies which migrate extraluminally, although rare in occurrence, are fraught with the potential to cause life-threatening complications. PURPOSE OF THE STUDY: To discuss the management of this pathology. MATERIAL AND METHODS: A series of four patients with such occurrences is presented. CONCLUSION: A discussion on the safe management of such seemingly innocuous foreign bodies allows the authors to propose a therapeutical algorythm.

Metastatic angiosarcoma to the thyroid.

BACKGROUND: Angiosarcoma (AS) in non-alpine areas is exceptionally rare, and so is metastatic AS to the thyroid. The difficulties and controversies associated with its diagnosis and management are highlighted in this case report. METHOD: Case report. RESULTS: A Chinese gentleman with AS metastatic to the thyroid presented a year after radiotherapy to his scalp AS. There was rapid expansion of the metastasis over 2 weeks and invasion of the pyriform fossa caused dysphagia and haemoptysis. The diagnosis was established by paraffin histology of the tumour post-hemithyroidectomy, after repeated fine-needle aspiration cytology was not diagnostic. Patient opted for external beam radiotherapy to the pyriform fossa instead of pharyngolaryngectomy. Residual pyriform tumour was treated with brachytherapy delivered via nasogastric tube. Unfortunately, the patient died 4 months later due to cardiac failure which was unrelated to his oncologic condition. CONCLUSION: AS metastatic to the thyroid is possible. The unexpectedly acute presentation and difficulties associated with diagnosis and management are highlighted. A useful method of delivering brachytherapy to the pyriform fossa is described.

Mastoparan increases membrane bound phosphatidylinositol kinase and phosphatidylinositol 4-monophosphate kinase activities in Madin-Darby canine kidney cells.

Synthetic wasp venom Mastoparan induced an increase of [3H] inositol phosphates levels and a corresponding decrease of [3H]inositol phospholipids levels in Madin-Darby canine kidney (MDCK) cells. The effect was dose (5-100 micrograms/ml) and time (1 to 15 min) dependent. Mastoparan also enhanced the endogenous activity of phosphatidylinositol kinase and phosphatidylinositol 4-monophosphate kinase. The effect was dose (25-75 micrograms/ml) and time dependent (1 to 15 min).

Mastoparan inhibits rat renal NaK-ATPase activity.

Rat renal NaK-ATPase was inhibited by mastoparan in a dose dependent fashion. This inhibition reached completion within 30 seconds. Due to mastoparan's rapid effects on NaK-ATPase activity, this inhibition does not appear to involve either a decrease in the rate of synthesis or an increase in their degradation of NaK-ATPase since these processes require a latency period of at least several minutes. In addition, the phosphoenzyme intermediate formed in the presence of mastoparan was greater than that formed in its absence further indicating that inhibition of NaK-ATPase by mastoparan is not due to a decrease in the number of NaK-ATPase. A possible mechanism for the inhibition is that mastoparan stabilizes the phosphoenzyme intermediate and reduces the Vmax of the enzyme by decreasing the rate of turnover of existing enzyme sites. Neomycin, an inhibitor of inositol phospholipid metabolism, was also found to attenuate the inhibition of Na,K-ATPase by mastoparan, suggesting that the mechanism of this inhibition may involve degradation of the phosphatidylinositol "pool".

Inhibition of alpha-aminoisobutyric acid uptake by mastoparan in Madin-Darby Canine Kidney cells.

Mastoparan, a wasp venom, was found to inhibit Na(+)-dependent net alpha-aminoisobutyric acid (AIB) uptake in Madin Darby Canine Kidney (MDCK) cells. Mastoparan also produced a significant increase in AIB efflux when compared to controls. Pretreatment of MDCK cells with 2 mM neomycin attenuated mastoparan's inhibition of net AIB uptake and completely suppressed mastoparan-mediated increases in AIB efflux when compared to controls. These data suggest that mastoparan's inhibition of net AIB uptake involves more than a single basic mechanism.

Surgical management of septal perforation: an alternative to closure of perforation.

The surgical closure of septal perforations remains a distinctive challenge to the otorhinolaryngologist. This is demonstrated by the modest success in most techniques. An alternative method, involving surgical enlargement of the perforation with posterior edge repair, is described and the outcome is investigated. Thirteen patients with perforations of up to 50 mm in size underwent this technique. A questionnaire interview was conducted and symptom scores were obtained. The length of hospitalization, follow-up period and post-operative complications were evaluated as were measures of morbidity. The results showed a significant improvement in the symptom scores for nasal crusting, epistaxis and overall discomfort. This technique is straightforward and is especially suitable for larger perforations. The successful improvement in symptoms and an associated low morbidity makes it a complement to alternative surgical closure techniques.

Spontaneous cerebrospinal fluid otorrhoea via oval window: an obscure cause of recurrent meningitis.

Spontaneous cerebrospinal fluid (CSF) leak via the oval window is uncommon and can result in recurrent bacterial meningitis. Current understanding of spontaneous CSF otorrhoea is reviewed and a diagnostic algorithm is presented. A seven-year-old boy presented with bilateral congenital deafness and recurrent meningitis. High-resolution computed tomography (HRCT) of the temporal bone showed a labyrinthine deformity and communication between the internal auditory canal (IAC) and the cochlea. Subtotal petrosectomy with closure of the external acoustic meatus and eustachian tube was performed. Post-operatively, the child had no further episodes of meningitis. This rare and obscure cause of recurrent childhood meningitis requires a high index of suspicion and the use of diagnostic tools, especially HRCT.

Clinics in diagnostic imaging (100). Migrated pharyngeal fish bone.

A 71-year-old man presented with a suspected swallowed fish bone. The lateral radiograph of the neck showed a curvilinear radio-opaque density in the swollen pre-vertebral soft tissues. The diagnosis of a migrated fish bone was confirmed on computed tomography and during subsequent surgery. The patient made a good recovery. As calcified normal structures, particularly the laryngeal cartilages, can mimic abnormal radio-opaque foreign bodies, it is important to be able to recognise the normal calcified structures seen on the neck radiograph. A sound knowledge of radiological anatomy is required in order to avoid unnecessary investigation and to provide prompt and appropriate management.

Impact of tinnitus as measured by the Tinnitus Handicap Inventory among tinnitus sufferers in Singapore.

INTRODUCTION: The effects of tinnitus on quality of life (QOL) have never been extensively studied in Singapore. We describe the characteristics of tinnitus and its impact on QOL as measured by the Tinnitus Handicap Inventory (THI) in a series of ear, nose and throat clinic patients. METHODS: A total of 327 patients who attended a tinnitus counselling clinic completed the THI questionnaire, a self-report measure with 25 items grouped into functional, emotional and catastrophic subscales. RESULTS: The mean age of the 134 female and 193 male patients was 48.9 years. 36.7 percent of these patients had bilateral tinnitus and 64.6 percent had symptoms for less than one year. 270 patients had hearing loss, 74 percent of whom presented with bilateral high frequency hearing loss. Most patients (84.1 percent) perceived only one type of sound. The total THI score distribution was: 107 (33 percent) patients had THI less than 16, 100 (31 percent) had THI 18 to 36, 59 (18 percent) had THI 38 to 56, and 61 (19 percent) had THI more than 58. There were no differences in the overall THI and subscale scores between the patients' gender, those with or without hearing loss, and those with unilateral or bilateral tinnitus. However, significantly higher total THI and all subscale scores were found among patients who were hearing more than one type of tinnitus sound. The areas of concern that were commonly reported by the patients in this series were a lack of control over tinnitus, frustration and stress. CONCLUSION: Tinnitus patients who hear multiple sounds tend to have a higher THI and subscale scores. The management of tinnitus should address common areas of concern, and may include counselling. The THI is a potential screening tool to determine if patients require counselling. A series of THI assessments can be used to chart the progress of treatment.

Neomycin inhibits mastoparan-induced lactate dehydrogenase release, ethidium bromide accumulation, and intracellular fluorescein depletion in MDCK cells.

Mechanisms of cell death induced by toxins probably involve one or more processes such as inhibition of protein synthesis and impairment of plasma membrane integrity leading to an increase in membrane permeability. Since one of the possible actions of mastoparan, a cationic tetradecapeptide from wasp venom, is to perturb membrane phospholipids resulting in an increase in membrane permeability, we studied the effect of chemically synthesized mastoparan on lactate dehydrogenase release (LDH), ethidium bromide and fluorescein accumulation in Madin-Darby Canine Kidney (MDCK) cultured cells. Our results demonstrated that mastoparan induced cytosolic LDH release, ethidium bromide accumulation and intracellular fluorescein depletion in MDCK cells. Neomycin, a polycationic aminoglycoside, interacts with anionic polyphosphoinositides at the plasma membrane. Since both mastoparan and neomycin are cationic peptides and react with the negatively charged membrane phospholipids, we studied the interaction of these two peptides on membrane permeability. Our results demonstrated that neomycin inhibited mastoparan-induced LDH release, ethidium bromide accumulation and intracellular fluorescein depletion.

Effect of triiodothyronine on system A amino acid transport in cells of rat submandibular gland.

The effect of L-3,5,3'-triiodothyronine (T3) on alpha-aminoisobutyric acid (AIB) transport in isolated cell suspensions of rat submandibular gland was investigated. The uptake of ATB by these cells appeared to require extracellular Na+ and was inhibited by ouabain (10(-3) M). Cell suspensions from thyroidectomized rats which have been given three successive doses of T3 on alternate days (50 micrograms/100 g BW) showed a significant increase in AIB uptake compared with cells isolated from thyroidectomized rats treated with diluent. Efflux of AIB from the cell suspension was not affected by T3. There was no significant changes in AIB uptake 12 h after a single injection of T3 (50 micrograms/100 g BW). However, there was a significant 49% and 65% increase in AIB net uptake at 24 and 48 h, respectively, after T3 treatment. Under similar conditions, the cell suspension showed a 48% increase in NaK-ATPase activity at 12 h and to a peak of 61% at 24 h. Therefore, changes in NaK-ATPase activity preceded the changes in AIB net uptake upon treatment with T3, implying that AIB uptake is probably mediated, at least in part, by the activity of NaK-ATPase.

Effects of triiodothyronine on resting membrane potential of primary cultured rat submandibular gland cells.

The effect of triiodothyronine (T3) on the resting membrane potential was measured in primary cultured rat submandibular gland cells. The resting membrane potential was 29.5 +/- 0.71 mV. The hormone T3, at concentrations of 10(-9) M or greater, hyperpolarized the cells 5.8 mV (p less than 0.05). Hyperpolarization was complete within 24 hours. Ouabain (1 mM) depolarized the cells 5.9 mV. Cells exposed to T3 and ouabain had the same membrane potential as cells treated with ouabain alone. These data suggest that the hyperpolarization observed can be, in part, attributed to triiodothyronine-induced synthesis of (Na-K)-adenosine triphosphatase.