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[Physiopathology and clinical aspects of Menière's disease].

The most prominent changes in temporal bone histopathology of Menière's disease are hydrops-like extensions of the endolymphatic spaces. The endolymphatic hydrops seems to be the consequence of a diminished function or complete atrophy of the endolymphatic sac. The etiology or pathomechanism of perisaccular fibrosis or saccular degeneration is unknown. But as a consequence of experimental datas obtained by animal studies the pathogenesis of the endolymphatic hydrops can be explained by osmotic active forces which develope within the endolymphatic spaces after blockage of the endolymphatic aqueduct or sac: An increasing concentration of osmotic active endolymphatic components cause an influx of water from the perilymphatic (extracellular) environment so that the limiting membranes of the endolymphatic space have to extend (e.g. Reissner's membrane, saccular membrane). At any topographic location of the endolymphatic spaces these membranes can rupture followed by intermixing of potassium-rich endolymph with sodium rich perilymph. This leads to an acute or chronic intoxication of those sensory nerve elements which have close contact to perilymphatic fluid. The hypothesis of an osmotic induced accumulation of "water' during endolymphatic hydrops is supported by sometime striking results of the glycerol test. Nevertheless, the pathogenesis and etiology of Menière's disease remains obscure, as indicated by the diverging spectrum of the different conservative or surgical therapeutic methods in use.

Animals↗

Neurotoxicity to the basal ganglia shown by magnetic resonance imaging (MRI) following poisoning by methanol and other substances.

OBJECTIVE: To define specific brain magnetic resonance features in methanol intoxicated patients and to evaluate the clinical relevance of monitoring these features. BACKGROUND: During the past decade magnetic resonance imaging has proven to be an exquisitely sensitive modality in depicting subtle water changes in diseased areas of the brain, allowing the definition of high-risk structures in numerous pathological conditions. METHOD: Four patients admitted to our institution for acute methanol intoxication were repeatedly evaluated by brain magnetic resonance imaging or a combination of computed tomography and magnetic resonance imaging. Common features of initial brain status were shown in all four cases and compared to those of patients presenting with other intoxications or critical deprivation states. RESULTS: Preferential localization of methanol-induced lesions within the putamina was observed in all four cases. This finding is specific compared to intoxication by other substances like carbon monoxide, or in the critical phase of metabolic disorders. The striking regression of the putaminal lesions on follow-up magnetic resonance examinations correlated with complete neurological recovery and the absence of extrapyramidal disturbance. Two patients exhibited discrete symmetric additional lesions in the medial areas of the parieto-occipital lobes. In a third one, the occipital lesions were severe. All three suffered from permanent visual impairment. The fourth patient, in whom magnetic resonance examinations failed to reveal any occipital lesion, never complained of visual disturbance though signs of optic neuropathy were detected in the visual evoked potentials. CONCLUSION: Magnetic resonance imaging appeared as a well suited neuroimaging modality in methanol intoxicated patients both in revealing a specific pattern of brain lesions and in demonstrating valuable correlation between evolution of brain changes on magnetic resonance images and clinical outcome.

Adult↗

Interaction between glucose diet and ethanol on rat liver microsomal induction and liver plasma membrane damage in chronic hexachlorobenzene intoxication.

Male Wistar rats fed for 60 days a glucose diet containing 17.5 mmol hexachlorobenzene/kg show a less pronounced increase in serum parameters and microsomal cytochrome P-450 concentration and a lower decrease in liver plasma membrane 5'-nucleotidase, K+, Na+- and Mg++-adenosine triphosphatase activities than the controls fed standard diet + hexachlorobenzene. Addition of 10% ethanol to the drinking water eliminates the "glucose effect". The glucose diet and ethanol exert contrasting effects on microsomal enzyme induction and liver plasma membrane damage in hexachlorobenzene intoxication.

Animals↗

Lithium intoxication associated with acute renal failure.

Lithium can produce transient natriuresis, nephrogenic diabetes insipidus, and partial distal renal tubular acidosis. Lithium intoxication is commonly associated with mild renal insufficiency and may produce acute renal failure. We have described a case of acute renal failure in a patient with severe lithium intoxication, as well as cardiac arrhythmias and hypothyroidism, both of which have been reported to occur with lithium toxicity. Treatment with daily hemodialysis eventually produced complete recovery. Lithium clearance occurs quickly with hemodialysis, but a rebound effect occurs as lithium in intracellular water equilibrates with extracellular fluid. Prolonged dialysis may be required to reduce the blood lithium level to the therapeutic range. We conclude that lithium intoxication may produce severe reversible renal failure as a result of direct tubular epithelial damage.

Acute Kidney Injury↗

Lead intoxication during development: its late effects on kidney function and blood pressure.

Exposure to lead in early life may result in chronic renal disease in adulthood. To test this hypothesis, we gave Sprague-Dawley rats, from 3 to 9 weeks of age, either tap water or a 1% lead acetate solution, and we studied them (in pairs) 3 and 16 weeks after exposure; that is, at 12 and 25 weeks of age. Lead-intoxicated animals failed to grow. Their GFR's were lower compared with the matched controls and fell between 12 and 25 weeks of age from 4.8 +/- 0.3 to 3.3 +/- 0.4 ml/min/g dry kidney wt (P less than 0.01). Changes in RBF and single nephron GFR were proportional to changes in total kidney GFR, indicating that superficial and deep nephrons were equally affected. The blood pressure in the lead-exposed animals studied at 25 weeks of age was 143.2 +/- 3.7 mm Hg, a value significantly higher than that of 130.4 +/- 3.3 observed in controls (P less than 0.05). These results demonstrate that limited exposure to lead during development can result in progressive renal insufficiency and hypertension.

Animals↗

The effect of water deprivation on lithium clearance and lithium excretion fraction in lithium-polyuric rats.

The effect of water deprivation on lithium clearance was studied in rats with lithium-induced polyuria. During a 3-hr period of water deprivation, the rats lost water in amounts corresponding to about 10% of body weight. Lithium clearance fell to about 25% of the level observed in rats which were not water deprived. During shorter periods of water deprivation, the fall of lithium clearance was less. The decrease of lithium clearance was partly due to a fall of inulin clearance and partly due to a fall of fractional excretion of lithium. The decrease of the two variables contributed to the same extent to the decrease of lithium clearance. The findings support the suggestion that insufficient intake of water in patients with lithium-induced polyuria may lead to a rapid lowering of lithium clearance and, hence, to a rise of the serum lithium concentration and development of intoxication.

Animals↗

Voluntary consumption of ethanol and its consequences in C57 mice treated with 4-methylpyrazole.

Daily injections of the alcohol dehydrogenase inhibitor 4-methylpyrazole (4MP) were administered to C57BL/6J mice offered continuous free access to food, water and 10% v/v ethanol. There was a significant correlation (r = -0.82) between the rate of ethanol consumption during pretreatment and the effect of 4MP on subsequent intake. Mice drinking more than 2.5 g/kg per day decreased their intake, while subjects drinking less than this amount increased the quantity of ethanol self-administered. The elevated concentrations of plasma ethanol which resulted from voluntary consumption were sufficient to produce intoxication but did not induce physical dependence. Presenting mice with 10% ethanol as their only fluid or offering them a choice of water and saccharin-sweetened ethanol increased intake but failed to raise plasma ethanol to the concentrations observed in mice offered unflavored ethanol and water, and treated with 4MP. The evidence suggests that plasma ethanol does not limit voluntary drinking in untreated mice and that concentrations of 135 to 250 mg/dl are not avoided by C57 mice in a free-choice situation.

Alcohol Dehydrogenase↗

Activities associated with drownings in Imperial County, CA, 1980-90: implications for prevention.

Statewide surveillance in California determined that the highest drowning rate from 1980 through 1989 was for the rural, desert county of Imperial (21.9 drownings per 100,000 population). To identify activities associated with drowning in this county, the authors abstracted data from the county sheriff-coroner's reports. From 1980 through 1990, there were 317 unintentional drownings; 85 percent occurred in irrigation canals. The activity prior to drowning was known for 262 persons (83 percent), and the most common activity was illegal entry into the United States. Overall, 140 persons (53 percent) were illegal entrants. Ninety-three percent of illegal entrants drowned in the All American Canal; the monthly drowning rate increased as the monthly average water velocity in the canal increased (r = 0.36; P < 0.001). Forty-eight persons (18 percent) drowned while riding in or on a land vehicle (automobile, pick-up truck, motorcycle, dune buggy, or tractor), the second most common activity associated with drowning. Seventy percent of the 23 drivers had an alcohol concentration of 100 milligrams per deciliter or more, California's limit for intoxication. To reduce drownings in Imperial County, prevention strategies should target persons engaged in at-risk activities near bodies of water. These strategies should include the identification and use of effective canal safety devices.

Accidents, Traffic↗

The influence of lithium on calcium and magnesium homeostasis in serum and tissues of rats.

Lithium is used in medicine. However, its administration can have negative side effects, disturb the water-electrolyte equilibrium and affect the level of essential elements. For these reasons the influence of oral lithium intoxication at the dose of 150 mg Li dm(-3) on magnesium and calcium levels in serum and tissues of rats was investigated. The concentration of Mg and Ca in serum increased throughout the experiment. The concentration of magnesium in tissues decreased after three weeks in liver, kidney, brain and femoral muscle. The trend of the changes of calcium tissue concentration was opposite to the one observed in the case of magnesium.

Animals↗

Recovery following pulsed exposure to organophosphorus and carbamate insecticides in the midge, Chironomus riparius.

The importance of recovery following pulsed and continuous exposure was determined by measuring the acute toxicity of two organophosphorus (parathion and malathion) and four carbamate (aldicarb, carbaryl, carbofuran and propoxur) insecticides. Two 1-h pulses caused significantly fewer symptoms of intoxication than 2 h of continuous exposure if at least 2 to 6 h in clean water were provided between doses for the four carbamates. Two 1-h pulses were equally toxic as a single 2-h continuous exposure for the two organophosphorus insecticides. Acetylcholinesterase activity in midges given two 1-h pulses of carbaryl separated by 24 h in clean water showed reactivation to control levels between the two exposures. These results contribute to the belief that episodic exposure to insecticides is less toxic if recovery in clean water is provided.

Animals↗

A simple, safe, and efficient way to treat severe fluoride poisoning--oral calcium or magnesium.

PURPOSE: To examine the efficacy and safety of administration of calcium and magnesium orally and intraperitoneally to treat severe sodium fluoride intoxication. MATERIALS AND METHODS: Mice were initially gavaged a lethal dose of sodium fluoride (NaF) or water. Then, mice were treated with water or varying concentrations of calcium chloride (CaCl2) or magnesium sulfate (MgSO4) via intraperitoneal (IP) route or via oral route. Mice were monitored for 24 h, and the time of death was recorded. RESULTS: IP injections of large amounts of CaCl2 or MgSO4 were dangerous. All mice gavaged with water and then treated with oral CaCl2 or MgSO4 survived and displayed normal activity during the experiment. The survival rate of mice gavaged with a lethal dose of NaF and then treated with a high dose of oral CaCl2 or MgSO4 was significantly higher than those of using low dose. CONCLUSION: Oral administration of a high dose of CaCl2 or MgSO4 is a simple, safe, and effective adjunctive method for treating severe oral fluoride poisoning.

Administration, Oral↗

Aneuploidy is not induced by ethanol during spermatogenesis in the Chinese hamster.

Aneuploidy was scored in spermatogonial stages and at both meiotic divisions in male Chinese hamsters exposed to alcohol in vivo. After light ether anesthetization, the animals were intubated (by gastric tube) with 1.5 ml of 12.5% ethanol, whereas controls were given 1.5 ml of distilled water. Gonadectomy was performed 3.5-24 h after ethanol exposure. Ethanol-dosed animals were obviously intoxicated, as evidenced by a rolling gait; serum alcohol levels in 10 animals that were tested peaked 1-2 h after exposure. Among the animals exposed to ethanol, no significant difference over time in the rates of aneuploidy was observed. These data were pooled, and, when compared to control rates, no significant difference could be attributed to ethanol exposure. The aneuploidy found could therefore be interpreted as background rates, and these compared well with data previously published for the Chinese hamster. Several artifactual phenomena were observed: Up to 15% aneuploid spermatogonial metaphases were seen in test and control animals. These were attributed to the mechanical breaking-up of closely apposed groups of diploid spermatogonia. Significant numbers of artifactual diploid MII figures and hypohaploid MI and MII figures were also recorded. To address the possibility that a spermatogonial or other long-term effect could be detected, two animals (with controls) were dosed with 12.5% ethanol daily for 13 and 16 days before sacrifice. No aneuploidy attributable to ethanol was found at MII in these animals either.

Aneuploidy↗

Aluminium-induced anaemia in haemodialysis patients.

It appears well established that a microcytic, hypochromic anaemia is present in patients receiving regular haemodialysis treatment, who also suffer from chronic aluminium intoxication. This characteristic anaemia is slightly improved following deionization or reverse-osmosis treatment of dialysate water. Iron deficiency has been tentatively excluded as a cause of this anaemia by measurement of serum ferritin levels. The exact mechanisms involved in the pathogenesis of this anaemia are still to be fully elucidated but a disturbance in haem synthesis and porphyrin metabolism seems probable, and secondary effects of PTH in the bone marrow may be involved. Evidence has accumulated that aluminium is the most likely ion responsible for this anaemia but other ions, trace metals in excess or deficiency and potentially toxic substances cannot be excluded yet.

Aluminum↗