Thyroid FNA diagnostics in a real-life setting: Experiences of the implementation of the Bethesda system in Finland.

INTRODUCTION: The Bethesda system is widely accepted for thyroid FNA diagnostics, but has scarcely been analysed in relation to clinical background data. Our aim was to analyse the thyroid FNA diagnostic process in view of clinical data, and to assess the validity of the Bethesda system during the first year of implementation. METHODS: There were 415 thyroid FNAs taken from 363 patients during October 2011-September 2012 in the Pirkanmaa Hospital District, Finland. The median age of the patients was 59 years, and the female-to-male ratio 4:1. Clinical data were collected from patient registries, and thyroid FNA and histopathological data from the pathology registry. RESULTS: The Bethesda categories were represented as follows: 94 non-diagnostic cases (26%); 177 benign (49%); 32 atypia of undetermined significance/follicular lesion of undetermined significance (9%); 31 follicular neoplasm (9%); 20 suspicious for malignancy (5%); and nine malignant cases (2%). Only 23 (24%) of the non-diagnostic samples and 18 (56%) of the atypia of undetermined significance/follicular lesion of undetermined significance led to repeat FNA. Thyroid cancer was histopathologically diagnosed in 28 cases (8%). When the categories requiring surgical treatment were considered true positive findings, the sensitivity of the Bethesda system was 90%, and specificity was 70%. Interobserver accuracy was 86%. CONCLUSIONS: Already during the first year of implementation, the Bethesda system proved reliable in evaluating the risk of thyroid malignancy. Nevertheless, the clinical judgement of the indication of ultrasound/FNA and management according to the FNA findings need improvement. The relatively high proportion of non-diagnostic FNAs could be diminished by obtaining the samples by radiologists experienced in ultrasound-guided FNA techniques.

High-sensitivity C-reactive protein and ankle brachial index in a finnish cardiovascular risk population.

High-sensitivity C-reactive protein (hsCRP) has been previously linked to different forms of vascular disease. However, some studies have not found any relationship between hsCRP and atherosclerosis. Also, studies investigating correlation between hsCRP and ankle brachial index (ABI) are scarce. We studied hsCRP in a cardiovascular risk population with a special interest in correlation between hsCRP and ABI. All men and women aged 45 to 70 years from a rural town Harjavalta, Finland were invited to participate in a population survey. Diabetics and people with known vascular disease were excluded. Seventy-three percent (n = 2085) of the invited persons participated and 70% of the respondents (n = 1496) had at least one risk factor to cardiovascular diseases. These subjects were invited to further examinations. From them we measured ABI, hsCRP, leukocyte count, glucose tolerance, systemic coronary risk evaluation (SCORE), body mass index (BMI), and waist circumference. Mean hsCRP was 1.9 mg/L. Smokers had higher hsCRP (mean 2.2 mg/L) than nonsmokers (mean 1.8 mL/L). hsCRP in women was higher than in men (mean 2.0 mg/L versus 1.8 mg/L). Mean ABI was 1.10, and the prevalence of peripheral arterial disease was 3.1%. ABI correlated weakly with hsCRP (r = -0.077, p = 0.014), leukocyte count (r = -0.107, p = 0.001), and SCORE (r = -0.116, p = 0.001). It did not have correlation between age, weight, BMI, or waist circumference. hsCRP correlated with BMI (r = 0.208, p < 0.0001) and waist circumference (r = 0.325, p < 0.0001). When we excluded subjects with hsCRP >10 mg/L, ABI no longer correlated with hsCRP. In a cardiovascular risk population, hsCRP has only a weak correlation with ABI, and this correlation disappeared when we excluded subject with hsCRP >10 mg/L. Instead, hsCRP was correlated to the measures of obesity (waist circumference and BMI), indicating its role as a marker of adipose tissue-driven inflammation. hsCRP does not seem to be a suitable screening method for peripheral arterial disease.

Hormonal deficiencies during and after Puumala hantavirus infection.

Previous reports have described panhypopituitarism associated with severe cases of hemorrhagic fever with renal syndrome (HFRS), but the prevalence of hormonal deficiencies after nephropathia epidemica (NE), a milder form of HFRS, has not been studied. This study was conducted in order to determine the prevalence of hormonal defects in patients with acute NE and during long-term follow-up. Fifty-four patients with serologically confirmed acute NE were examined by serum hormonal measurements during the acute NE, after 3 months, and after 1 to 10 (median 5) years. Thirty out of 54 (56%) patients had abnormalities of the gonadal and/or thyroid axis during the acute NE. After a median follow-up of 5 years, 9 (17%) patients were diagnosed with a chronic, overt hormonal deficit: hypopituitarism was found in five patients and primary hypothyroidism in five patients. In addition, chronic subclinical testicular failure was found in five men. High creatinine levels and inflammatory markers during NE were associated with the acute central hormone deficiencies, but not with the chronic deficiencies. Hormonal defects are common during acute NE and, surprisingly, many patients develop chronic hormonal deficiencies after NE. The occurrence of long-term hormonal defects cannot be predicted by the severity of acute NE.

Cervical hip fracture in a Finnish population: incidence and mortality.

BACKGROUND AND AIMS: Our aim was to describe the incidence of cervical hip fractures and to describe the relationships between selected background variables and mortality at 30 days, 6 months, and 3 years postoperatively. MATERIAL AND METHODS: The basic material consisted of population-based data set of patients aged 65 years or older who had sustained a hip fracture and were treated operatively between 1999 and 2000. Out of these, we identified 266 consecutive patients with cervical hip fracture. RESULTS: The age-adjusted incidence of cervical hip fractures in women was 1.3-fold compared to men. In age-adjusted analysis, occurrence of chronic lung disease, cardiovascular disease or 2-5 comorbidities, male gender, the need for 2-person mobility assistance, and poor ambulation postoperatively were associated with excess mortality at least at one evaluation point. CONCLUSIONS: Only chronic lung disease and male gender were independent predictors of increased mortality at each follow-up assessment in multivariate analysis.

The impact of proximal femur geometry on fracture type--a comparison between cervical and trochanteric fractures with two parameters.

INTRODUCTION: Only a few studies have tested the ability of proximal femur geometry parameters to discriminate between cervical hip fractures and those of the trochanter. The main objective of this study was to evaluate the geometrical differences between these two fracture types by measuring the neck shaft angle (NSA) and the femoral neck axis length (FNAL). We also compared the distributions of these parameters and the distributions of fracture type by gender. MATERIAL AND METHODS: A retrospective analysis was made in a population-based material of 428 hip fractures collected during a two-year period from 1999 to 2000 (323 women and 105 men aged 65 years or older). NSA and FNAL were manually measured from pelvic radiographs. RESULTS: No significant differences in NSA or FNAL were found between cervical and trochanteric hip fractures in women or in men. Men had significantly higher NSA and FNAL than women. Age was not related to these geometrical parameters. The distributions by fracture type were similar in both genders. CONCLUSIONS: The different pathogenesis of cervical and trochanteric hip fractures cannot be explained by NSA or FNAL. A standardized measurement setup is needed when evaluating the role of hip geometry in fracture patients.

Incidence of hip fractures among the elderly in Satakunta, Finland.

BACKGROUND AND AIMS: The aim was to describe the incidence rate of hip fractures in the elderly in a specific region in Finland and circumstances around them. MATERIAL AND METHODS: Retrospective analysis of 461 women and men aged 65 or older undergoing an operation for hip fracture during a two-year period between 1999 and 2000. 80 variables in all were obtained from the hospital discharge register and patient documents. RESULTS: The age-specific incidence of hip fractures was higher in women than in men (women 6.88/1000 person/y vs. 3.50/1000 person/y). Prior to the fracture, patients were primarily doing well; 63.4% lived at home and 65.1% used no mobility equipment or aids. Altogether 41.9% of hip fractures occurred in institutions. Both women and men more often suffered their injury indoors (91.1% and 75.7% respectively), and only a slight seasonal variation was observed. More than every fourth (26.9%) had experienced a previous fracture. CONCLUSIONS: The age-specific incidence of hip fractures was higher in women than in men. The fractures took place mostly indoors and often in institutions. Therefore the measures that impact on indoor safety are particularly important for the elderly.

Effects of lifelong ethanol consumption on drinking behavior and motor impairment of alcohol-preferring AA and alcohol-avoiding ANA rats.

The effects of drinking ethanol throughout a lifetime on voluntary drinking behavior and ethanol-induced motor impairment were studied in alcohol-preferring AA (Alko, Alcohol) and alcohol-avoiding ANA (Alko, Non-Alcohol) rats of both sexes. At the age 3 months, the rats were tested for individual voluntary ethanol (10% vol./vol.) intake and ethanol-induced motor impairment (2 g/kg, i.p.). The rats were housed in group cages, half of them having 12% (vol./vol.) ethanol as the only source of fluid and the other half having free access to water. Food was always available for all animals. At the age of 23 months, their individual voluntary ethanol intake and ethanol-induced motor impairment were tested again. During forced drinking, the females of both strains consumed more ethanol than did the males. The ethanol consumption of the AA and ANA females and the ANA males increased significantly (P < .001) with age, but a slight decrease was seen in the ethanol consumption of the AA males. Time x strain interaction showed a significant (P < .05) difference in the ethanol consumption of male rats, with the AA males having a slight decrease in ethanol consumption with age, whereas the ANA males increased their ethanol consumption. After 19 months of forced ethanol exposure, AA males significantly decreased their individual voluntary ethanol consumption, and individual voluntary ethanol consumption by ethanol-exposed AA males was more pronounced (P < .001) than that of the AA rats that had free access to water (P < .05). For the female AA rats, those having free access to water significantly decreased their voluntary ethanol consumption (P < .05), but those having ethanol only did not. No significant changes in voluntary ethanol consumption with age or with different exposures were seen in the ANA rats. Body weights were higher in the groups having access to water than in the ethanol-only groups, but the differences were not significant within the AA and ANA strains. The ANA rats were significantly heavier in all groups. These results indicate that the voluntarily nondrinking ANA rats can drink almost as much ethanol as the voluntarily drinking AA rats when they are forced to drink ethanol and that lifelong forced ethanol drinking does not change their inherent drinking habits. When sensitivity to ethanol was measured with the tilting-plane test, the old AA female rats were more sensitive to ethanol than were the young ones. The young ANA females were more sensitive than the AA females when tested at 4 months. In males, aging did not produce any differences in ethanol sensitivity.

Dose-dependent decrease in glial fibrillary acidic protein-immunoreactivity in rat cerebellum after lifelong ethanol consumption.

The effects of aging and lifelong ethanol consumption on astrocytic morphology and glial fibrillary acidic protein-immunoreactivity (GFAP-IR) in the cerebellar vermis obtained from ethanol-preferring Alko, Alcohol (AA) rats were analyzed by using computer-assisted image analysis. The ethanol-consuming animals (both male and female) were given ethanol (10%-12%, vol./vol.) as the only available fluid for 21 months (3-24 months), whereas the young (3 months) and the old (24 months) controls received water. In the male rats, but not in the female rats, an age-related decrease in GFAP-IR was found in folia II, VII, and X of the molecular layer, and in turn, an age-related increase was found in folium X of the granular layer, indicating opposite changes in GFAP-IR for male rats due to aging in adjacent brain regions. In the female rats, 21 months of daily average ethanol consumption of 6.6 g/kg resulted in decreased GFAP-IR in folium VII of the molecular layer, and the decrease in cerebellar GFAP-IR correlated with the average daily ethanol intake (r=-.886, P=.019) when folia II, IV, VII, and X were analyzed together. No effect of ethanol on GFAP-IR was detected in the granular layer or in the central white matter of the female rats. There was no change in GFAP-IR in any of the three cerebellar layers of the male rats with average daily ethanol consumption of 3.2 g/kg. These results indicate that the Bergmann glial fibers are the GFAP-expressing structures of the cerebellum most sensitive to moderate-to-heavy chronic ethanol exposure and that this effect is dose dependent.

User satisfaction with teleconsultations for surgery.

We carried out a prospective study of realtime videoconferencing in surgical consultations. Videoconferencing equipment at the Satakunta Central Hospital, Pori, was connected by ISDN at 384 kbit/s to two health centres in the cities of Kankaanpää and Huittinen (55 and 60 km from Pori, respectively). A document camera was used to transmit images of radiographs and paper documents. Fifty patients who needed a surgical consultation were examined by a doctor in the health centres, and the surgeon interviewed and observed the physical examination by videoconference. The consultation time ranged from 12 to 23 min (mean 15 min). Technically the equipment functioned reliably and the quality of the video-picture was good. According to the consulting surgeon, the decision made in the videoconference was reliable in 48 cases (96%). According to the doctors in the health centres, the consultation was useful in 49 cases (98%) and was considered satisfactory in one. The doctors thought that the teleconsultation was as reliable as an outpatient appointment in 49 cases (98%). The educational benefit of the consultation was excellent or good in 38 cases (76%). The overall satisfaction of patients was very good or good in 45 cases (96%). All patients, except one, avoided travelling to a face-to-face appointment because they received a definite treatment decision during the teleconsultation.

Evidence of acetaldehyde-protein adduct formation in rat brain after lifelong consumption of ethanol.

Acetaldehyde, the first metabolite of ethanol, has been shown to be capable of binding covalently to liver proteins in vivo, which may be responsible for a variety of toxic effects of ethanol. Acetaldehyde-protein adducts have previously been detected in the liver of patients and experimental animals with alcoholic liver disease. Although a role for acetaldehyde as a possible mediator of ethanol-induced neurotoxicity has also been previously suggested, the formation of protein-acetaldehyde adducts in brain has not been examined. This study was designed to examine the occurrence of acetaldehyde-protein adducts in rat brain after lifelong ethanol exposure. A total of 27 male rats from the alcohol-preferring (AA) and alcohol-avoiding (ANA) lines were used. Four ANA rats and five AA rats were fed 10-12% (v/v) ethanol for 21 months. Both young (n = 10) and old (n = 8) rats receiving water were used as controls. Samples from frontal cortex, cerebellum and liver were processed for immunohistochemical detection of acetaldehyde adducts. In four (two ANA, two AA rats) of the nine ethanol-exposed rats, weak or moderate positive reactions for acetaldehyde adducts could be detected both in the frontal cortex and cerebellum, whereas no such immunostaining was found in the remaining five ethanol-treated rats or in the control rats. The positive reaction was localized to the white matter and some large neurons in layers 4 and 5 of the frontal cortex, and to the molecular layer of the cerebellum. Interestingly, the strongest positive reactions were found among the ANA rats, which are known to display high acetaldehyde levels during ethanol oxidation. We suggest that acetaldehyde may be involved in ethanol-induced neurotoxicity in vivo through formation of adducts with brain proteins and macromolecules.

A new method for surgical consultations with videoconference.

BACKGROUND: The aim of our prospective study was to examine the technical ability and the medical suitability of a realtime teleconferencing system in surgical consultations. METHOD: A personal computer-based-videoconferencing system was used over an architecture of the IP (Internet Protocol) over ATM (Asynchronous Transfer Mode) area network connecting Satakunta Central Hospital, Pori with a health center in the community of Noormarkku (15 km apart from Pori). A document camera was used for transfering the radiographs and paper documents. The material consisted of 50 patients who needed surgical consultation. The patients were examined by a physician in the health center of Noormarkku, and the surgeon interviewed and observed the physical examination with the aid of teleconference. RESULTS: Technically the videoconferencing system functioned reliably, and the visual quality of the videopicture was good after more powerful personal computers (Pentium II with a 266 MHz prosessor and 64 Megabits RAM-memory) were changed for the videoconferencing system. All patients, except one, saved the travelling to the face-to-face appointment because they got a definite decision of the treatment already at the videoconsultation. According to the opinion of the consulting surgeon, the decision which was made in the teleconference was good or very good, except in one case very poor. The physicians of the health centers were satisfied both with the decisions of the treatment of their patients and with the educational effect of a consultation where two physicians are present at the same time. All patients thought that it was good to be in consultation with two doctors. CONCLUSION: Surgical videoconsultations are a reliable method and a real alternative to sending a patient to a distant place for consultation.

Effects of ageing and intermittent ethanol exposure on rat locus coeruleus and ethanol-withdrawal symptoms.

In this study, the effects of ethanol and age on the morphology of the locus coeruleus (LC) and on the severity of ethanol-withdrawal symptoms were studied during a 5-week intermittent ethanol exposure. Young (3-4 months) and old (29-30 months) male Wistar rats were given highly intoxicating doses of ethanol by intragastric intubations for 4 days, followed by a 3-day ethanol-withdrawal period. This 7-day cycle of ethanol exposure and withdrawal was repeated five times. A non-treated group and a sucrose-fed group of both ages were used as control groups. The severity of ethanol-withdrawal symptoms (rigidity, tremor, irritability, hypoactivity) was rated up to 62 h after the last dose of ethanol. The intoxication level was higher in the old, compared with the young, rats, despite the smaller doses of ethanol given to the old animals. There was no significant difference between the age groups in the severity of the ethanol-withdrawal syndrome. The LC quantitative studies were performed using unbiased stereological methods. The results showed that there was no difference between the age groups in the LC total neuron numbers of the non-treated control groups. The 5-week intermittent ethanol exposure significantly reduced the LC neuron numbers and LC neuronal density in the old ethanol-exposed animals, compared with the sucrose-fed control animals. In the young rats, the ethanol-induced neuron loss did not reach statistical significance. According to the ANCOVA, the difference in the ethanol-induced LC neuronal loss between the age groups may be due to the difference in the intoxication levels. Interestingly, the sucrose intubations were also found to decrease the LC neuronal numbers in the young rats, compared with the non-treated young control group. It was concluded that ageing did not significantly affect the severity of ethanol-withdrawal symptoms or ethanol-induced loss of LC neurons in Wistar rats.

Effects of continuous versus intermittent ethanol exposure on rat sympathetic neurons.

BACKGROUND: Binge ethanol exposure is known to induce degeneration of central nervous system (CNS) neurons. Sympathetic hyperactivity has been related to ethanol withdrawal symptoms, but the effects of repeated withdrawals on peripheral sympathetic neurons have not been studied previously. METHODS: The effects of continuous versus intermittent ethanol consumption on sympathetic neurons of the superior cervical ganglion (SCG) were studied in male Wistar rats. Two-month-old rats were divided into three groups: one group with ethanol (10% v/v) as the drinking fluid throughout the 51/2-month experiment (continuous, n = 9), one group drinking ethanol on 4 days/week and water on 3 days/week (intermittent, n = 9), and a control group (n = 9) with water as the only available fluid. All groups had food ad libitum. SCG volume, neuron density, and total number of neurons were measured by using unbiased morphometric methods. RESULTS: As the mean daily ethanol consumption did not differ between the two ethanol-exposed groups (continuous 5.7 g/kg/day versus intermittent 5.8 g/kg/day), the total dose of ethanol consumed was 42% smaller in the intermittent group. The total number of SCG neurons decreased by 28%, and neuron density by 23%, in the intermittent group compared with the control group, whereas no significant neuron loss was observed in the continuous group. The volume of the SCG was similar in all study groups. The results suggest that repeated ethanol withdrawals, rather than ethanol exposure per se, are deleterious to sympathetic neurons. CONCLUSIONS: Ethanol-induced degeneration of neurons is not only related to the amount of ethanol consumed, but also to the patterns of drinking.

Effects of dexmedetomidine on rat locus coeruleus and ethanol withdrawal symptoms during intermittent ethanol exposure.

In the present study, the neuroprotective effects of dexmedetomidine on rat locus coeruleus were studied during a 5-week intermittent ethanol exposure. Male Wistar rats (3 to 4 months old) were given ethanol or isocaloric sucrose by intragastric intubations three times a day for 4 days, which was followed by a 3-day withdrawal period. This 7-day cycle of ethanol exposure and withdrawal was repeated five times. Dexmedetomidine (at a dose decreasing from 30 microg/kg to 10 microg/kg, s.c.) was given to the treatment group during the withdrawal phase. The results showed that, during the 5-week experiment, dexmedetomidine significantly relieved the ethanol withdrawal syndrome, measured as the sum of the three most specific symptoms (rigidity, tremor, and irritability). The total neuron number of locus coeruleus (LC) decreased in the ethanol-treated group by 24%, compared with the nontreated control group and by 11%, compared with the sucrose-treated control group. Interestingly, the LC neuron numbers were found to decrease in the sucrose-intubated rats as well, compared with the nontreated control group. Dexmedetomidine was found to relieve ethanol-induced neuronal loss in the LC. Dexmedetomidine might be a new interesting alternative in the treatment of ethanol withdrawal syndrome, particularly due to its possible neuroprotective effects in the central nervous system.

Effects of lifelong ethanol consumption on rat sympathetic neurons.

In this experiment we studied the effects of aging and lifelong ethanol consumption on rat peripheral sympathetic neurons. The aim was to find out the possible differences in the vulnerability to ethanol-induced neuronal degeneration between rats of both genders, or between the alcohol-avoiding (ANA) and the alcohol-preferring (AA) lines of rat. The superior cervical ganglia (SCG) of 40 male and 41 female AA and ANA rats were analyzed. The ethanol-exposed groups had 12% ethanol as the only available fluid from 3 to 24 months of age. The young (3 months) and old (24 months) control groups had water instead. SCG neuronal density, volume, and total neuron number were measured by unbiased morphometric methods. No gender difference was seen in either the volume of the SCG or in the SCG neuron number. The volume of the ganglion was significantly increased with age, but the total neuron number did not change. Neuronal density was significantly decreased with age, but lifelong ethanol consumption induced no further decrease. SCG neuron number in the ethanol-exposed groups did not differ from the age-matched or young control groups, but a significant negative correlation (r = -0.70, p<0.01) was seen between individual ethanol consumption and the number of SCG neurons in the female rats. The amount of lipopigment in the SCG was increased in the ethanol-exposed male rats. These results suggest that the peripheral sympathetic neurons are rather resistant to ethanol-induced degeneration, and that no major gender or line differences exist in this respect.

Influence of chronic ethanol consumption on arterial tone in young and aged rats.

The aim of this work was to evaluate the effects of long-term ethanol consumption on arterial responses in vitro in young and aged rats. Therefore, Wistar rats (ages 3 and 29 mo, respectively) were allocated to six groups: control-young, sucrose-young, ethanol-young, control-aged, sucrose-aged, and ethanol-aged. The ethanol-fed groups were given 25% ethanol by intragastric gavage three times a day 4 days a week. Responses of mesenteric arterial rings were examined in standard organ chambers after 5 treatment weeks. In norepinephrine-precontracted arterial rings, endothelium-dependent relaxations to acetylcholine, as well as endothelium-independent relaxations to isoproterenol, were attenuated in aged rats when compared with young controls. Relaxation responses to isoproterenol, but not to acetylcholine and nitroprusside, were clearly improved by ethanol treatment in both young and aged rats. The cyclooxygenase inhibitor diclofenac, which reduces the synthesis of dilating and constricting prostanoids, enhanced the relaxation to acetylcholine in all three aged rat groups but was without significant effect in the young rats. In the presence of the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester the relaxation to acetylcholine in control and sucrose-fed aged rats was markedly reduced compared with control rats, whereas in the young controls and in both young and aged ethanol-exposed groups, distinct relaxations to higher concentrations of acetylcholine were still present. The endothelium-independent relaxations to cromakalim, a hyperpolarizing vasodilator acting via ATP-sensitive potassium channels, were also markedly augmented by ethanol feeding in both young and aged rats. In conclusion, ethanol consumption in both young and aged rats was associated with markedly improved arterial relaxations to isoproterenol and cromakalim, as well as clearly augmented relaxation to acetylcholine during inhibition of cyclooxygenase and nitric oxide synthase. These findings suggest that especially the potassium channel-related component of arterial relaxation was augmented by long-term ethanol exposure.

Using IP-videoconferencing systems in a surgery consulting.

In this paper we describe how to use IP-videoconferencing systems in medical surgery consulting. We started to think about how we could use special doctor's services without patients having to travel a long way. The answer to this question is that the information goes from one place to another, not the patient. First we had a pilot project, where we used the 3xISDN transmission rate and now we are using ATM. We have here in Satakunta a local area network between our Satakunta Central Hospital and the Health Care Center in Noormarkku and Kankaanpää, so we have very good environment to do this kind of research. Our network is quite fast, we can use the 10 Mbps bitrate and in this network there are no other activities in this moment, so there are not any interferences. There is a surgery specialist in the hospital and a doctor in the health care center with a patient. The specialist looks at the monitor, where there is a videopicture of the patient from the health care center. Then the specialist makes the treatment plan for the patient.

Lifelong ethanol consumption and loss of locus coeruleus neurons in AA and ANA rats.

The effects of lifelong ethanol exposure and aging on the morphology of the locus coeruleus (LC) were studied in the AA (Alko, Alcohol) and ANA (Alko, Nonalcohol) rats of both sexes. The ethanol-consuming (EtOH) rats were given 12% (v/v) ethanol as the only drinking fluid from 4 to 22 months of age, whereas the young (3-month-old) and aged (24-month-old) controls had only water available. The total LC neuron numbers were obtained by using the unbiased disector method. In the AA line, as we have previously reported. the EtOH female and male rats displayed a 26-30% loss of LC neurons compared with the controls. In the ANA line, the EtOH females had 30% fewer LC neurons than the controls (EtOH 1579 +/- 377 vs. controls 2264 +/- 269, ANOVA p < 0.01), whereas the EtOH males showed no neuron loss compared to the controls (EtOH 1848 +/- 525 vs. controls 2216 +/- 152, ANOVA NS). However, taking into account (sex by line ANCOVA) the markedly higher ethanol intake of the female rats in both lines, no gender or line differences in the ethanol-induced LC degeneration were detected. Neither was there any difference in LC neuron numbers between the young and old control rats of either line of rats. In conclusion, chronic alcohol consumption, not aging per se, damages the LC neurons in experimental animals.

Dexmedetomidine alleviates ethanol withdrawal symptoms in the rat.

The effect of dexmedetomidine, a selective alpha 2-adrenoceptor agonist, on ethanol withdrawal symptoms was studied in chronically ethanol-fed rats. After a 4-day ethanol intoxication period the rats were given s.c. injections of dexmedetomidine (3, 10, or 30 micrograms/kg) or saline (control group) at 10, 16, 22, and 39 h after the last dose of ethanol. The severity of ethanol withdrawal symptoms (rigidity, tremor, irritability, hypoactivity) was rated up to 58 h, blind to the treatments. The results showed that dexmedetomidine at doses 10 and 30 micrograms/kg significantly diminished the severity of the ethanol withdrawal reaction as measured by the sum score of the three most specific withdrawal signs (rigidity, tremor, and irritability). Dexmedetomidine at 10 micrograms/kg was the most effective dose, especially in the latter half of the withdrawal period (23-58 h after last dose of ethanol). The results suggest that dexmedetomidine in the treatment of ethanol withdrawal symptoms should be further studied.

Dexmedetomidine, diazepam, and propranolol in the treatment of ethanol withdrawal symptoms in the rat.

In this study, the effects of dexmedetomidine, a selective alpha 2-adrenoceptor agonist, on ethanol withdrawal symptoms, were compared with those of diazepam and propranolol. The rats were given highly intoxicating doses of ethanol for 4 days. After the intoxication period, rats were divided into four equal groups: a dexmedetomidine-treated group (30 micrograms/kg, sc), a diazepam-treated group (2 mg/kg, sc), a propranolol-treated group (5 mg/kg, sc), and a control group with no medication. Medication was given in the withdrawal phase-2, 8, 14, and 20 hr after the onset of the withdrawal symptoms. The severity of the ethanol withdrawal symptoms (rigidity, tremor, irritability, and hypoactivity) was observed up to 33 hr after the onset of the ethanol withdrawal symptoms. Both dexmedetomidine and diazepam significantly relieved tremor compared with the control group. Diazepam reduced irritability significantly, compared with the control group. When measured as the sum score of the three most specific withdrawal signs (rigidity, tremor, and irritability), dexmedetomidine and diazepam significantly relieved the ethanol withdrawal reaction. Propranolol attenuated tremor, but was inefficient against other withdrawal symptoms. Dexmedetomidine may thus represent a new effective drug in the treatment of the ethanol withdrawal syndrome.