Interorgan relationships in alcoholic intoxication]

It is suggested, on the basis of 315 necropsies of patients who died of drunkenness and alcoholism and examination of 300 rats with acute and chronic alcoholic intoxication, to distinguish an "alcoholic disease" as a separate nosological entity. The stages of this disease are drunkenness, alcoholism and alcoholic abstinence syndrome. Multiple organ pathology is characteristic for the disease with obligatory microangiopathy, alcoholic encephalo-, cardiomyo- and hepatopathy. The development of the disease follows a principle of vitium cordis at which the changes in certain organs result in the progression of pathological lesions in other organs. The course of the disease is characterized by periods of remission and exacerbation provoked either by a regular alcohol consumption or by an alcoholic abstinence syndrome. Toxic effects of alcohol, acetaldehyde and catecholamines are main factors in the pathogenesis of lesions in various organs.     

Morphological characteristics of chronic hepatopathy in combination of HCV and chronic alcoholic intoxication

Biopsies from 35 patients and autopsy material from 20 patients who died of chronic hepatopathy were studied. Hydropic dystrophy and inflammation were predominant in HCV infection. Chronic alcoholic intoxication (CAI) was characterized by diffuse large-droplet fat dystrophy and liver fibrosis. In combination of HCV-infection with CAI sclerotic processes were pronounced and therefore liver cirrhosis is more frequent than in other groups.     

The diagnostics of arrhythmogenic right ventricular dysplasia by an endomiocardial biopsy and the role of viruses in the pathogenesis of disease

The comparative histologic, morphometric and immunohistochemical investigation of a right ventricular myocardium from 3 groups of patients has been carried out. The first group has included 12 patients with an arrythmogenic right ventricular dysplasia (ARVD) confirmed by an endomyocardial biopsy. The second group has consisted of 7 healthy people died a violent death. The third group has included 7 patients with a chronic alcoholism died from an acute alcoholic intoxication. The patients with ARVD and a chronic alcoholism have had an evident adiposis, a moderate fibrosis, and muscle atrophy with only 65% of cardiac hystiocytes. The patients with a chronic alcoholism have had only dystonia of intramural arteries. The cardiac hystiocytes of patients with ARVD have infected by enteroviruses (100%), parvoviruses B19 (58%), adenoviruses (25%), and hepatitis virus C (16%). 83% of observations have had a mixed viral infections.     

Ultrastructure of the human heart sinus node in alcoholic cardiomyopathy under acute alcohol intoxication and without it

An electron-microscopic study of the sinus nodes (SN) was conducted in the hearts of 8 males aged 32-60 who had suddenly died of alcoholic cardiomyopathy in the background of acute alcohol intoxication (4 cases) or without it (4 cases). The hearts of matched-for-age 7 males and 1 female whose cause of sudden death was other than cardiac served as control. It appeared that all the components of the sinus nodes from hearts of the study group underwent chronic or acute destructive changes. The latter were seen both in dark and clear SN conducting myocytes. There were also defects in neurohumoral regulation of the myocytic function due to nervous and microcirculatory SN disturbances. SN connective tissue was affected too. Relevance of the elicited SN changes to cardiac rhythm derangement and to the mechanism of sudden cardiac death is discussed.     

Sclerosing hyaline necrosis in noncirrhotic chronic alcoholic hepatitis.

A group of 18 chronic alcoholic patients who had sclerosing hyaline necrosis in noncirrhotic livers was compared with a group of 12 similar individuals with acute alcoholic hepatitis, but no centrilobular fibrosis. In cases with sclerosing hyaline necrosis, the most characteristic features were portal hypertension with very large, tender livers and unusually high glutamic-oxalacetic transaminase values; these were associated with centrilobular fibrosis and abundant alcoholic hyalin. Three of these patients died within two years and in two of these, early cirrhosis was found at necropsy. In the cases of acute alcoholic hepatitis, hepatomegaly was the most conspicuous finding, and only a single patient died; death here was unrelated to hepatic disease, the liver being unremarkable at necropsy. Patients who had sclerosing hyaline necrosis tended to remain ill for significantly longer periods. These observations, in conjunction with evidence gathered from the literature, seem to suggest that sclerosing hyaline necrosis is an obligatory step in the natural evolution of alcoholic hepatic disease, especially in cases that evolve into cirrhosis.     

Glucose consumption by the rat brain in ethanol intoxication and the abstinence syndrome]

The effect of acute and chronic alcohol intoxication and of the syndrome of ethanol withdrawal on the consumption of glucose by the brain of rats was studied by means of intravascular ethanol infusion. Infusion of ethanol into the internal carotid artery had no effect on glucose consumption by the brain, while its infusion into the femoral vein reduced consumption twofold. The effect was completely removed by the inhibitor of alcohol dehydrogenase pyrazole. Chronic intoxication also caused a twofold decrease of glucose utilization by the brain of rats. Infusion of ethanol into the internal carotid artery of rats who were in a state of alcoholic intoxication led to increase of glucose consumption by the brain to the control level. Infusion of ethanol into the femoral vein in this case had no effect on glucose consumption by the rat brain. Utilization of glucose by the brain diminished to an equal degree in rats suffering from the syndrome of ethanol withdrawal and in animals who were in a state of alcoholic intoxication. Infusion of ethanol, both intraarterial and intravenous, had no effect on glucose consumption by the brain. Activation and inhibition of the function of external respiration were encountered in equal concentrations of ethanol in blood flowing from the brain, whatever the method of its infusion.     

Morphogenesis of pneumonia in alcoholic intoxication]

A single moderate dose of ethanol given to 120 Wistar male rats inhibits general immune defence and may facilitate the development of pneumonia. No morphological changes are found in the surfactant system in acute alcoholic intoxication. In chronic alcoholic intoxication with a pronounced withdrawal syndrome, apart from the decrease of general immune defence, lung surfactant system is damaged due to the direct ethanol effect on type II pneumocytes. These are the leading factors in the pneumonia pathogenesis characterized by a grave course and tendency to the abscess formation.     

Focal nodular hyperplasia of the liver

Report about 19 cases of focal nodular hyperplasia of the liver observed from 1971 to June 1981. The autopsy cases are 7 women between 19 and 62 years of age. The intake of oral contraceptives over a long time period was known in 4 cases; once a node was detected in a 19-year-old woman after a normal pregnancy (death from amniotic fluid embolism), once in a 62-year-old woman who had a longterm diabetes, and once in a 47-year-old woman who died from acute alcoholic intoxication; probably contraceptives had not been taken. The biopsy cases are 11 women between 27 and 50 years of age and a man 25 years of age. Ten times the nodes were found on occasion of cholecystectomy, once during gastric resection, and once during vagotomy. 4 women took oral contraceptives for 5 to 101/2, 2 others for about 2 years. A 34-year-old woman had 7 pregnancies one shortly after the other. 4 women did not use oral contraceptives. In 12 of 18 women a hormonal induction seems possible, in 10 cases by oral contraceptives and in 2 cases by pregnancies. Complications such as bleedings we did not find.     

Neurologic sequelae of domoic acid intoxication due to the ingestion of contaminated mussels

In late 1987 there was an outbreak in Canada of gastrointestinal and neurologic symptoms after the consumption of mussels found to be contaminated with domoic acid, which is structurally related to the excitatory neurotransmitter glutamate. We studied the neurologic manifestations in 14 of the more severely affected patients and assessed the neuropathological findings in 4 others who died within four months of ingesting the mussels. In the acute phase of mussel-induced intoxication, the patients had headache, seizures, hemiparesis, ophthalmoplegia, and abnormalities of arousal ranging from agitation to coma. On neuropsychological testing several months later, 12 of the patients had severe anterograde-memory deficits, with relative preservation of other cognitive functions. Eleven patients had clinical and electromyographic evidence of pure motor or sensorimotor neuronopathy or axonopathy. Positron-emission tomography of four patients showed decreased glucose metabolism in the medial temporal lobes. Neuropathological studies in the four patients who died after mussel-induced intoxication demonstrated neuronal necrosis and loss, predominantly in the hippocampus and amygdala, in a pattern similar to that observed experimentally in animals after the administration of kainic acid, which is also structurally similar to glutamate and domoic acid. We conclude that intoxication with domoic acid causes a novel and distinct clinicopathologic syndrome characterized initially by widespread neurologic dysfunction and then by chronic residual memory deficits and motor neuronopathy or axonopathy.     

Coping with inner feelings and stress: heavy alcohol use in the context of alexithymia.

The authors conducted a population study to assess the relationship between heavy alcohol consumption and alexithymia, defined as difficulty in identifying and expressing feelings. The study sample consisted of 2,297 middle-aged men from eastern Finland. The proportion of men who reported either frequent intoxication or unpleasant aftereffects of heavy drinking increased linearly with alexithymia. Alexithymia and the heavy acute intake of different sorts of alcoholic drinks were also consistently associated. Long-term heavy use, taking into account both the dose and frequency, was also linearly related to the alexithymia measure. In multivariate models to assess whether high alcohol consumption in alexithymic individuals might relate to stress, the authors found nothing to support the stress-dampening hypothesis.     

Causes of the people death from drunkenness and alcoholism

We analyzed causes of 1008 people death, who abused by alcohol. Among them 2 groups were separated out: people died due to drunkenness and due to alcoholism. The structure of the death was similar in the both groups, however depended on alcoholism stages. The major cause of the death in group of drunkenness people was acute heart insufficiency, less commonly--lung pathology, and very rarely--brain vessels pathology and liver cirrhosis. In group of people, who died due to alcoholism, lung pathology was the major cause of these deaths, acute heart insufficiency was occurred less commonly, and very rare brain pathology because of delirium tremens or alcohol withdrawal syndrome, as so liver cirrhosis with complications. Hemorrhagic pancreonecrosis after alcoholic excess was found out in both groups, but it was more often in people, who died due to drunkenness. Obtained results show importance of chronic alcoholism identification as a disease with several stages including drunkenness and alcoholism.     

Significance of nonspecific histopathologic changes in the myocardium in sudden coronary death

Informative value of non-specific histopathological myocardial changes was determined on the material of 31 autopsy cases of a sudden coronary death (SCD) and comparison of two groups: 18 observations of violent death and 17 observations of an acute alcoholic intoxication. Informative value was assessed using Kullback's criterion. Large- and small-focal cardiosclerosis and cardiomyocyte hyperthrophy were of a high informative value for SCD. Sclerosis of the intramural arteries, congestion on venas and capillaries, muscle fiber fragmentation had an informative value for SCD versus a violent death, and haemorrhages for SCD versus an alcoholic group. Cardiomyocyte vacuolisation and wavelike deformation of muscle fibers were of a low informative value. Cardiomyocyte atrophy and lymphohistiocytic infiltration were informative for SCD when compared to a violent death and for an alcoholic group when compared to SCD. Endothelial proliferation of the microcirculation vessels, myolysis, sludge-phenomenon, lypofuscinosis, stromal lipomatosis were of informative value for the alcoholic group and not for SCD.     

Alcoholic lesions of the brain

Brains of 117 alcoholics admitted in the state of alcoholic coma or abstinence syndrome with an increase of blood pressure or development of acute psychosis were studied. The changes in the human brain were compared with those occurring in the brains of 30 rats with chronic alcoholic intoxication and formation of withdrawal syndrome. It is shown that in alcoholic coma and different manifestations of abstinence syndrome vascular and cellular changes take place, that can be attributed to the action of ethanol or its metabolites, as well as catecholamines. In the brain of the animals studied the same cellular and vascular changes were found as in the mentioned alcohol-induced manifestations in man. Progression of cephalic changes due to withdrawal syndrome is associated with more marked structural changes of the hemato-encephalic barrier.     

Nonalcoholic steatohepatitis: a study of 49 patients

Nonalcoholic steatohepatitis (NASH) refers to an alcoholic hepatitis-like histologic pattern found in nonalcoholic patients. A review of 543 liver biopsies diagnosed as alcoholic hepatitis yielded 49 cases of NASH. The patients were commonly middle-aged women who were obese and often diabetic. NASH was usually discovered because of abnormal liver function tests or hepatomegaly noted during evaluation of other medical problems. Histologic examination revealed the same spectrum of changes found in alcoholic hepatitis, including cirrhosis in eight patients. Follow-up information was available for 39 patients after an average length of 3.8 years. Only one patient developed hepatic decompensation or died with liver failure or portal hypertension. Repeat histologic material was available for 13 patients after a mean 3.5 years of follow-up. Five patients showed progression of fibrosis, with cirrhosis developing in two, but the other eight patients demonstrated little morphologic change. These findings indicate that NASH is, in general, a clinically mild and biologically low-grade condition, but with the potential to progress and evolve into cirrhosis in some patients. The factors promoting progression are unclear.     

Structural alterations in the human brain in acute alcohol intoxication

Various regions of the brain were studied in 14 patients who suddenly died and in 20 patients who died from ethanol intoxication. Severe circulatory disorders with pronounced vascular pathology, blood diseases, degenerative and necrotic neurocytic changes were shown to develop in ethanol intoxication. The area of neurocytes in the hemispheric cortex, thalamus, and cerebellum reduced due to the death of some of them. In the medulla, they were found to be more resistant to ethanol. The diameter of capillaries in the studied regions of the brain decreased due to the fall in cerebral arterial tonicity, the number of these vessels on the standard area increased, which is due to the compensatory dilatation of reserve capillaries.     

The Area of Ground Glass Opacities of the Lungs as a Predictive Factor in Acute Paraquat Intoxication

Even though plasma paraquat (PQ) levels have known to be an informative predictor, many patients succumb at low PQ levels in acute PQ intoxication. This study was designed to see whether the high resolution computerized tomography (HRCT) of the lungs would be a predictive measure in acute PQ intoxication. HRCT of the lungs was obtained from 119 patients with acute PQ intoxication on 7 days after PQ ingestion. The areas with ground glass opacities (GGOs) were evaluated at five levels with the area measurement tool of the picture archiving and communication systems. Among 119 patients, 102 survived and 17 died. The plasma PQ levels were significantly higher in the non-survivors than in the survivors (2.6±4.0 µg/mL vs. 0.2±0.4 µg/mL, P=0.02). The area with GGOs was 2.0±6.4% in the survivors and 73.0± 29.9% in the non-survivors (P<0.001). No patients survived when the area with GGOs was more than 40% but all of the patients survived when the area affected by GGOs was less than 20%. In conclusion, the area of GGOs is a useful predictor of survival in acute PQ intoxication, especially in patients with low plasma PQ levels.     

Five-year mortality in lithium-treated manic-depressive patients.

A hundred and thirty-three affective disorder patients who received prophylactic treatment with lithium were followed prospectively for 5 years and their mortality was recorded. Twenty-two patients died during the period, 13 from natural causes and nine from definite or probable suicide. The observed mortality was significantly greater than the expected overall, and also when natural causes and suicide were considered independently. No patients died from lithium intoxication or lithium-induced side effects. Patients who died from suicide were all bipolars or suffered from affective disorder with uncertain polarity. They were significantly younger than the patients who died from natural causes, they tended to lead isolated lives and they suffered a violent death. The older patients who died from natural causes had often had physical illness and alcohol abuse prior to the start of lithium treatment. The results of the study speak in favour of the establishment of comprehensive treatment programmes possibly in the framework of specialised affective disorder clinics.     

Pathogenesis and morphogenesis of alcoholic disease

Experimental, autopsy, and clinical findings call for a new clinical entity, namely, alcoholic disease. The disease has three stages: I) repetitive acute alcohol intoxications; II) drunkenness; and III) alcoholism and alcoholism-Related complications. The organs determining the pathogenesis and outcome of alcoholic disease are the liver, heart, lungs, and brain. In chronic alcohol intoxication, lesions in these organs develop in a cascade manner according to the principle of a vicious circle. Pathological changes in the internal organs arise against the background of progressive microangiopathy that by itself is an imoportant pathogenic component of the disease. The results obtained show that changes developing in the internal organs during the second stage are reversible or well compensated, whereas those occurring at the third stage are irreversible in a vast majority of cases and often fatal. There are reasons to consider the problem out of the context of the fight against alcoholism, which, in principle, is an irreversible pathological condition, but from the viewpoint of the proposed concept of alcoholic disease. Trnaslated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 122, No. 12, pp. 604–610, December, 1996     

Pulmonary aspergillosis and the importance of oxalate crystal recognition in cytology specimens

A 62-year-old man, previously healthy but alcoholic, and who was clinically thought to have bacterial pneumonia, presented with a pulmonary infiltrate in the right apex, and suddenly died of exsanguinating hemoptysis. Sputum cultures yielded Aspergillus niger and Candida krusei while sputum cytology revealed numerous birefringent crystals in a background of acute inflammatory exudate. Autopsy findings showed invasive aspergillosis with a large mycetoma-containing cavity in the lung that was associated with localized massive oxalosis. This case further substantiates the fact that the presence of calcium oxalate crystals in pulmonary biopsy and cytology specimens can be regarded as an important diagnostic aid in the diagnosis of pulmonary aspergillosis due to A niger.     

The effects of alcohol on prose memory

The present study examined the effects of acute alcoholic intoxication on prose memory. Intoxicated and sober subjects listened to six narrative passages at different presentation rates. Immediately after listening to a tape-recorded version of each story, subjects orally recalled it. The results demonstrated that sober subjects recalled more than intoxicated subjects, but subjects from both groups favored the main ideas in their recalls. However, at the fastest presentation rate, intoxicated subjects showed some diminished sensitivity to the semantic structure of prose. It was suggested that alcohol induced deficits in prose memory may result from a general slowing in the rate with which text is encoded into working memory.