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Biomedical subjects

M Partinen

Publications and source records attributed to M Partinen.

At least 19 recordsLinked to original sources

Positron emission tomography study of human narcolepsy: no increase in striatal dopamine D2 receptors.

We investigated dopamine D2 receptors in the caudate nucleus and putamen with positron emission tomography in seven patients with narcolepsy and seven healthy controls by using [11C]raclopride as a ligand. We applied an equilibrium method and Scatchard principle to give a quantitative estimation of the number (Bmax) and dissociation constant (Kd) of the receptors. Both the Bmax and Kd were within the normal range in the caudate nucleus and putamen in narcoleptic patients. We found no evidence for increased D2 receptor binding in narcolepsy.

Adolescent

Familial aggregates in obstructive sleep apnea syndrome.

Obstructive sleep apnea syndrome (OSAS) was diagnosed in157 subjects based on clinical symptoms, physical evaluation, cephalometric x-ray films, and polysomnography. These index cases identified 844 living first-degree relatives. Mailings were sent to 792 (94%). The mailing consisted of two identical questionnaires, one for the family member of the index case and one to be given to a friend (not a relative) of approximately the same age. In response, we received 531 (63%) questionnaires from relatives and 198 (25%) questionnaires from age-matched nonrelated friends, which were used as a control group. A more extensive investigation was performed on first-degree relatives of the index group living in the San Francisco Bay Area or vicinity. Two hundred seventy-nine relatives (100%) were identified. One hundred sixty-six subjects (59%) as well as 69 age-matched friends (ie, 41% of the 166 relatives and 25% of the potential total group) agreed to participate in further studies. These subjects had interviews, clinical investigations, and nonattended ambulatory monitoring. Cephalometric x-ray films could be obtained on only 22 of 166 participating relatives and 6 of 69 friends. Body mass index was not a differentiating measure between relatives and friends. Odds ratios (ORs) were calculated from the questionnaiare data. The report of tiredness, fatigue, and sleepiness did not distinguish family members from friends. The OR, however, progressively increases when there is a positive history of near nightly loud snoring (OR = 1.78; 95% confidence interval [CI] 1.25-2.54) or a positive history of daytime sleepiness in conjunction with near nightly loud snoring (OR = 3.11; 95% CI = 1.94-4.99). The investigation in the Bay Area indicated that, when first-degree relatives were compared with friends, the complaint of daytime tiredness, sleepiness, or both with the presence of a high and narrow(ogival) hard palate sharply differentiated between friends and relatives (OR = 10.9, 95, CI = 5.31-22.5). An Epworth Sleepiness Scale score of 9 or greater with the presence of another symptom associated with OSAS, and a respiratory disturbance index greater than 5 (number of apneas and hypopneas per hour of sleep > 5) gave an OR of 45.6 (95% CI = 18.8-11.0). Disproportionate craniofacial anatomy was common in familial groups with OSAS. Craniofacial familial features can be a strong indicator of risk for the development of OSAS.

Adolescent

Comparison of effects on sleep of lovastatin and pravastatin in hypercholesterolemia.

The effects on sleep of lovastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor administered as a lipophilic lactone prodrug, and pravastatin, an inhibitor administered in its active, hydrophilic, open-acid form, were compared by polysomnographic sleep monitoring. Twenty-four men with primary hypercholesterolemia (low-density lipoprotein 4 to 7 mmol/liter) each received 2 of the following 3 treatments in a randomized, incomplete block, crossover design study: lovastatin (40 mg/day), pravastatin (40 mg/day), and placebo. Test drug was administered once daily for 4 weeks during each half of the crossover study. Subjective sleep assessments were obtained throughout each treatment period, and polysomnographic recordings were obtained at the end of the 4-week treatment periods. Treatment periods were separated by a 1-week washout. Lovastatin did not differ from placebo regarding any polysomnographic parameter except "number of entries to wake," for which it produced fewer entries (i.e., change was in the direction of improvement). Pravastatin did not differ from placebo regarding any polysomnographic measures, but was associated with worsening in relation to lovastatin in the following parameters: sleep efficiency, entries to wake, percent rapid eye movement sleep, wake time during sleep, and total wake time. For each of these 4 parameters, although neither drug showed marked differences from placebo, the mean change in the lovastatin group was in the direction of improved sleep, whereas the change in the pravastatin group was in the direction of disturbed sleep. Neither lovastatin nor pravastatin had any effect on subjective, qualitative sleep ratings.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

The prevalence of narcolepsy: an epidemiological study of the Finnish Twin Cohort.

We investigated the prevalence of narcolepsy using a well-defined white population previously used for epidemiological investigations: the Finnish Twin Cohort. The Cohort consists of 13,888 monozygotic and dizygotic twin pairs born before 1958. There were 16,179 individuals who participated in the study, with a 77.3% response rate. The study methodology included a questionnaire covering sleep and alertness, the Ullanlinna Narcolepsy Scale (UNS), a scale specifically developed and tested for the study, telephone interviews, and finally, clinical evaluation, polygraphic recording, and HLA blood typing. Seventy-five subjects were selected for telephone interviews and laboratory evaluations based on data from both questionnaires. Five of them were strongly suspected of narcolepsy, but laboratory data identified only 3. All were dizygotic (fraternal) twins discordant for the disease with a negative family history and presence of DR2 DQw1 (i.e., DRw15 DQw6, new World Health Organization classification). The prevalence of narcolepsy in the Finnish population is 0.026% (95% confidence interval, 0.0-0.06). This prevalence is lower than that reported in studies performed without polygraphic recording and is close to that reported in 1945 in the black U.S. population. The tools developed to perform this study, the largest population study of its kind yet performed, can now be used for other population investigations.

Adult

The effect of four-day round trip flights over 10 time zones on the sleep-wakefulness patterns of airline flight attendants.

To study the effect of a four-day-round trip flight on the sleep-wakefulness of airline flight attendants, subjective sleep-wakefulness and autonomic sleep phases were measured. Forty flight attendants (mean age 33 years, range 21-50) kept daily logs on sleepiness, the time when going to bed, and sleep quality. In addition, the autonomic sleep phases of 21 subjects were studied by the static charge sensitive bed (SCSB) method. After the westward flight, the subjects went to bed approximately 1-3 h local time earlier during the first few days and were very sleepy compared to the week before the flight. There was a significant increase in the number of awakenings and in the feeling of 'not being at all rested' in the mornings. After the return flight eastwards, the subjects were very sleepy on the first evening but slept rather well for about 11 h. During the three following days, sleep restlessness, difficulties in falling asleep, and the feelings of sleepiness in the mornings increased compared to the week before the flights. Four days after the return flight, sleep length and the quality of sleep were, on average, the same as before the flights. According to the SCSB method, there were only small changes in the autonomic sleep phases due to the flights. After the westward flight, quiet sleep increased and intermediate sleep decreased compared to the sleep before the flight. The results indicate that most flight attendants have significant disturbances in sleep quality after transmedian flights. Sleep disturbances increase after both westward and eastward transmedian flights, but differ from each other in specific features.

Adult

The effect of four-day round trip flights over 10 time zones on the circadian variation of salivary melatonin and cortisol in airline flight attendants.

The effects of four-day round flights (Helsinki-Los Angeles-Seattle-Helsinki) were studied on the circadian rhythms of salivary melatonin (MT) and cortisol (COR) in 35 flight attendants. The mean age of the subjects was 33 +/- 7 years (median 34, range 21-50). Five 24 h profiles of unstimulated saliva were collected at 2 h intervals (except at 04:00) before, during, and after the four day flight. Salivary MT and COR were determined by radioimmunoassay. Both MT and COR exhibited a clear circadian rhythm with acrophases before the flight at 03:03 (MT) and 09:08 (COR). Two days after the westward flight from Helsinki to Los Angeles, the MT rhythm (circadian acrophase) had delayed 4 h 51 min and the COR rhythm 3 h 55 min compared to the control day before the flight. Two days later, during the last day in the USA, the MT rhythm had delayed 5 h 59 min and the COR rhythm 5 h 29 min as compared to the situation before the flight. After four days of the eastward flight from Seattle to Helsinki, the circadian acrophase of MT was still 1 h 35 min delayed compared to the control day before the westward flight. The results indicate that the restitution time of five days at the home base is on the average proper for recovery, if a four day round flight over 10 time zones takes four days or less. The resynchronization rate of salivary hormones after westward, outgoing flights is faster than the resynchronization rate after the eastward return flights.

Adult

Controversies in the diagnosis of narcolepsy.

The diagnosis of narcolepsy can be problematic. Most sleep laboratories use polygraphic testing to establish the diagnosis. One polygraphic recording followed by a single multiple sleep latency test (MSLT) is used to differentiate the causes of syndromes with complaints of daytime somnolence. Prospective investigations have demonstrated that patients with periodic leg movements or upper airway resistance syndrome may present abnormal sleep latencies and more than one sleep onset rapid eye movement period (SOREMP) during MSLT. On the other hand, investigations of patients with daytime sleepiness and cataplexy have shown that the MSLT may not show more than one SOREMP. The combination of history of cataplexy and more than one SOREMP during MSLT is the best clinical determinant of narcolepsy. History of daytime sleepiness and presence of more than one SOREMP during MSLT, however, is a poorer discriminant of narcolepsy than history of cataplexy, particularly in an aging population.

Adolescent

Twin studies in narcolepsy.

The genetic basis of narcolepsy is reflected by the strong association to human leukocyte antigen DR2 (most specifically to DQB1-0602) and the occasional familial occurrence, with several modes of transmission. At present, 12 monozygotic pairs with at least one affected twin have been reported. Of the three pairs considered concordant, the only well-documented pair is DR2 negative. Of the nine discordant pairs five are well documented, and all of these are DR2 positive. We performed a questionnaire study using a validated measure of narcoleptic symptoms (the Ullanlinna narcolepsy scale or UNS). The questionnaire was sent to 2,191 monozygotic twin pairs included in the Finnish Twin Cohort. In 225 pairs neither of the twins responded. In 1,550 pairs both twins responded, but in the answers of 228 pairs there were some missing data concerning the UNS items. Not a single case suggestive of narcolepsy was found. Narcolepsy in monozygotic twins is very rare. These facts support the hypothesis of a multifactorial etiology with a strong influence of nongenetic environmental factors.

Adult

Epidemiology of narcolepsy.

The prevalence of narcolepsy is usually presented at about 50/100,000. There are, however, marked differences of about 2,500-fold between the lowest and the highest reported prevalence. This discrepancy is at least partly explained by differences in the study populations and methods. There are, however, no earlier population-based epidemiological studies with polygraphically confirmed diagnoses. We studied the occurrence of symptoms resembling the two main manifestations of narcolepsy, i.e. abnormal sleep tendency and emotion-associated muscular weakness, in an adult twin cohort (n = 16,179) with a questionnaire. A total of 3.2% met the minimal diagnostic criteria of the International Classification of Sleep Disorders for narcolepsy. Eleven questionnaire items assessing the main manifestations of narcolepsy formed a measure called the Ullanlinna Narcolepsy Scale (UNS), which has been validated. The UNS score was calculated for 11,354 subjects. Those (n = 75) having a UNS score equal or higher than the lowest value in a narcolepsy patient group were studied. Thirty-one of them (fulfilling also the minimal diagnostic criteria) were interviewed, and those suspected of having narcolepsy (n = 5) were evaluated in the sleep laboratory. In three subjects the narcolepsy diagnosis was verified (all dizygotic, nonfamilial and human leukocyte antigen DR2/DQB-0602 positive), giving a prevalence of 0.026% in the adult Finnish (Caucasian) population.

Adult

Dopamine D2-receptors in human narcolepsy: a SPECT study with 123I-IBZM.

Increased dopamine D2 receptor binding in basal ganglia has been reported in human narcolepsy. These studies have been based on post-mortem material of 8 patients, most of them also medicated for narcolepsy. We studied six narcoleptics without stimulant or anticataplectic medication. The patients had an unambiguous history of cataplexy, and they were also studied polygraphically. Single photon emission computed tomography (SPECT) imaging was performed. The D2 receptor density was determined by using 123I-iodobenzamide (IBZM). The control subjects were 8 unmedicated Parkinson patients with one-sided (hemiparkinsonian) clinical symptoms. The D2 receptor density in them is known to be normal or somewhat increased compared to healthy normals. The striatum/frontal D2 activity ratio was 1.331 +/- 0.084 (with phantom study correction 2.101 +/- 0.300) in the narcoleptic patients, and in the parkinsonian controls 1.321 +/- 0.052 (2.067 +/- 0.185) for the asymptomatic side and 1.335 +/- 0.025 (2.117 +/- 0.090) for the symptomatic side (i.e. contralateral to the side with the clinical extrapyramidal signs). There was no statistical difference between the groups or between the symptomatic and asymptomatic side in the Parkinson patients. Thus, our results differ from the earlier post-mortem studies.

Adult

Natural evolution of snoring: a 5-year follow-up study.

INTRODUCTION: The natural evolution of snoring was studied in a middle-aged population in Finland. MATERIAL AND METHODS: A questionnaire was mailed to a stratified random sample of 1600 people aged 36-50 years in 1985 with a response rate of 75.2%; 53% of them completed also the 5-year-follow-up questionnaire. Clinical examinations (N = 36) and whole-night polygraphic recordings (N = 22) were made to habitual (every or almost every night) snorers and daily sleepy persons. RESULTS: A total of 626 persons completed the 5-year-follow-up questionnaire. The prevalence of habitual snoring among men was 28.3-43.8% and among women 6.3-18.8%, increasing with age. Sleepiness was common: doze-off at the wheel was reported by 23% of snorers and traffic accidents because of sleepiness by 4.5%. Hypertension was clearly more common (p = 0.002) among habitual snorers, but the self-reported rates of strokes and coronary heart disease were not increased in this study. None of the snorers had been investigated because of their snoring or sleepiness during the five years. In polygraphic recordings 11/22 showed an oxygen desaturation index (ODI4) more than 5/h; active treatment was started for 8 of them. The observed prevalence of sleep apnea syndrome with ODI4 > 10 was 1.1% in this study. CONCLUSIONS: Snorers, even with clear sleepiness, are passive in seeking help for their symptoms. Physicians should actively diagnose this treatable condition impairing the quality of life and increasing the risk of traffic accidents and vascular diseases.

Accidents, Traffic

Light treatment for seasonal affective disorder: theoretical considerations and clinical implications.

The concept of seasonal affective disorder (SAD) includes any depression whose onset is related to a certain season. Reduced environmental light is hypothesized to be the main precipitating factor of winter depression. Light treatment is used to prevent the onset of depressive episodes and to reduce depressive symptoms in patients with depression during winter months. The mechanisms of action which lead to the well-documented antidepressant response are still unknown. Several hypotheses of the pathogenesis of SAD are discussed, and the clinical practice of light treatment is reviewed.

Circadian Rhythm

Selegiline in the treatment of narcolepsy.

We treated 17 narcolepsy patients in a placebo-controlled, double-blind, crossover trial with 10-, 20-, 30-, and 40-mg daily doses of selegiline, a monoamine oxidase inhibitor widely used in Parkinson's disease. There was a dose-dependent as well as a statistically and clinically significant improvement in narcoleptic symptoms and polygraphic measures. At 40 mg, there was a 36% reduction in the number of daytime sleep episodes and a 34% reduction in their duration (compared with placebo, mean values). The number of excessive sleepiness episodes decreased by 43%, and the duration decreased by 47%. The number of cataplectic attacks was reduced by 89%. On the multiple sleep latency test, the REM sleep latency increased from 5.0 to 13.3 minutes, and the number of sleep-onset REM periods decreased from 3.1 to 0.6. Sleep (S1) latency was not changed. No intolerable adverse events occurred. The effective dose range was 20 to 40 mg, requiring a low-tyramine diet, which was easy to maintain. In conclusion, selegiline alleviates both main symptoms of narcolepsy--the abnormal sleep tendency and cataplexy. Thus, treatment with selegiline makes it possible to avoid polypharmacy and to use a potent stimulant without known addiction risk.

Adolescent

Snoring and cardiovascular risk factors.

The association of snoring with some cardiovascular risk factors was studied cross-sectionally by a postal survey among 3750 males aged 40-59 years. In univariate analyses, snoring associated statistically significantly (P < 0.01) with hypertension, smoking, obesity, heavy alcohol use, physical inactivity, dyspnoea, hostility and morning tiredness. In a multiple logistic regression model adjusted by age, snoring associated significantly with smoking, obesity, physical inactivity, hostility and morning tiredness. When smoking was excluded from the multivariate model, alcohol use was also associated significantly with snoring. The association of snoring with smoking, and with obesity seemed to be almost independent from other studied correlates of snoring. Our results indicate that in further studies on predictive value of snoring with regard to coronary heart disease and stroke, the associations of snoring with hypertension, smoking, obesity, heavy alcohol use, physical inactivity and hostility have to be considered, as these risk characteristics may cause confounding effects.

Adult

Effects of light treatment on sleep structure in seasonal affective disorder.

Twelve outpatients with seasonal affective disorder (depression, winter type) were treated by 1 h of bright light exposure for five mornings. The intervention produced a significant reduction in depression scores, but no change was seen in the sleep electroencephalographic variables recorded after light treatment. Significant changes were seen, however, in ratings of subjective sleepiness. The acrophase of the circadian sleepiness rhythm was phase advanced, the mean level of the sleepiness rhythm was diminished, and the mean values of sleepiness scores were reduced at 8 and 10 a.m. This minimal influence of bright light on sleep structure is unlikely to explain the well-documented antidepressant effect.

Adult