Maternal polycystic ovary syndrome and the risk of autism spectrum disorders in the offspring: a population-based nationwide study in Sweden.

Although many studies indicate the interplay of genetic and environmental factors in the etiology of autism spectrum disorder (ASD), our limited understanding of the underlying mechanisms hampers the development of effective ways of detecting and preventing the disorder. Recent studies support the hypothesis that prenatal androgen exposure contributes to the development of ASD. This would suggest that maternal polycystic ovary syndrome (PCOS), a condition associated with excess androgens, would increase the risk of ASD in the offspring. We conducted a matched case-control study nested within the total population of Sweden (children aged 4-17 who were born in Sweden from 1984 to 2007). The sample consisted of 23 748 ASD cases and 208 796 controls, matched by birth month and year, sex and region of birth. PCOS and ASD were defined from ICD codes through linkage to health-care registers. Maternal PCOS increased the odds of ASD in the offspring by 59%, after adjustment for confounders (odds ratio (OR) 1.59, 95% confidence interval (CI) 1.34-1.88). The odds of offspring ASD were further increased among mothers with both PCOS and obesity, a condition common to PCOS that is related to more severe hyperandrogenemia (OR 2.13, 95% CI 1.46-3.10). Risk estimates did not differ between sexes. In conclusion, children of women with PCOS appear to have a higher risk of developing ASD. This finding awaits confirmation, and exploration of potentially underlying mechanisms, including the role of sex steroids in the etiology of ASD.

Feasibility and acceptability of a web-based HIV/STD prevention program for adolescent girls targeting sexual communication skills.

Adolescent girls are at substantial risk of sexually transmitted diseases including HIV. To reduce these risks, we developed Health Education And Relationship Training (HEART), a web-based intervention focused on developing sexual assertiveness skills and enhancing sexual decision-making. This study assessed the feasibility and acceptability of this new program and examined if perceived acceptability varied according to participant ethnicity, sexual orientation or sexual activity status. Participants were part of a randomized controlled trial of 222 10th-grade girls (Mage = 15.26). The current analyses included those in the intervention condition (n = 107; 36% white, 27% black and 29% Hispanic). HEART took approximately 45 min to complete and was feasible to administer in a school-based setting. Participants found the program highly acceptable: 95% liked the program and learned from the program, 88% would recommend the program to a friend and 94% plan to use what they learned in the future. The primary acceptability results did not vary by the ethnicity, sexual orientation or sexual activity status of participants, suggesting broad appeal. Results indicate that this new online program is a promising method to reach and engage adolescents in sexual health education.

Regression of oral lichenoid lesions after replacement of dental restorations.

The aim of the study was to determine the prognosis and to evaluate the regression of lichenoid contact reactions (LCR) and oral lichen planus (OLP) after replacement of dental restorative materials suspected as causing the lesions. Forty-four referred patients with oral lesions participated in a follow-up study that was initiated an average of 6 years after the first examination at the Department of Odontology, i.e. the baseline examination. The patients underwent odontological clinical examination and answered a questionnaire with questions regarding dental health, medical and psychological health, and treatments undertaken from baseline to follow-up. After exchange of dental materials, regression of oral lesions was significantly higher among patients with LCR than with OLP. As no cases with OLP regressed after an exchange of materials, a proper diagnosis has to be made to avoid unnecessary exchanges of intact restorations on patients with OLP.

Evaluation of an Online Sexual Health Program among Adolescent Girls with Emotional and Behavioral Difficulties.

OBJECTIVES: Adolescent girls with emotional and behavioral difficulties (EBDs) have a heightened risk of negative sexual health, including HIV, other sexually transmitted infections (STIs), and unplanned pregnancy. Few evidence-based sexual health interventions are available for adolescent girls with EBDs. This study tested the feasibility, acceptability, and efficacy of a brief, online sexual health program called HEART (Health Education and Relationship Training). METHODS: Forty-seven participants (M-age = 15.79; SD = 1.71; 62% Black, 23% Hispanic) recruited from community-based organizations in the southeastern U.S. were compared to a non-equivalent comparison group who received an attention-matched intervention. RESULTS: Findings support the feasibility of participant recruitment and program administration in community-based settings. Participants completed HEART in 44 minutes and experienced few technological difficulties. HEART was highly acceptable: most participants liked, learned from, and were engaged with the program. Further, 92% would recommend HEART to a friend and 98% would use what they learned in the future. At posttest, intervention participants had significantly higher communication intentions, communication skills, STI/HIV knowledge, sexual self-efficacy, condom attitudes, and condom norms than the comparison group (ps < .003; effect size ds = .38-1.65). Significant improvement in condom intentions was observed when comparing pretest to posttest scores among intervention participants only, t(46) = -3.21, d = 0.47. CONCLUSIONS: Findings support the feasibility, acceptability, and efficacy of HEART among adolescent girls with EBDs in community-based settings. This study also addresses the growing need for research into the transferability of sexual health interventions to facilitate evidence-based decision-making about program dissemination and implementation.

Changes in health over time in patients with symptoms allegedly caused by their dental restorative materials.

OBJECTIVES: In Sweden, many patients with symptoms allegedly caused by their dental materials have exchanged their restorations, but the effects of the exchange have been insufficiently investigated. Therefore, the aim of the study was to describe the change in health over time for these patients and the hypothesis was that the patients could be divided based on their symptoms and that the ability to recover differs between these groups. Furthermore, we also examined if other factors such as replacement of dental restorative materials and follow-up time had any impact on the perceived health status. METHODS: A questionnaire was sent to 614 patients who had been referred to the School of Dentistry, Umeå, Sweden, with symptoms allegedly caused by dental restorative materials. The response rate was 55%. RESULTS: The risk of having any further complaints was higher for patients with complex symptoms (P = 0.03) and these patients had exchanged their restorations to a significantly larger extent than the others (P = 0.03). The remaining complaints was more frequent among men (P = 0.02). Exchange of dental restorative materials had no significant impact on the ability to recover completely. However, the patients who had exchanged their restorations completely perceived a significantly larger alleviation of their symptoms than the others (P < 0.01), although the frequency of most of the symptoms had increased. CONCLUSIONS: Patients with complex symptoms had a more unfavorable long-term prognosis concerning persistent complaints than those with localized symptoms only. Furthermore, the results indicate that the patients might experience health improvements after removal of their dental restorative materials. The reason for this improvement, however, is unclear. Further analyses regarding other possible explanations than the 'odontological/medical' are needed.

Requests for medical advice from patients and families to health care providers who publish on the World Wide Web.

BACKGROUND: The Internet is a novel, rapidly growing means of worldwide public communication. METHODS: We reviewed all unsolicited electronic mail and other communications from nonmedical individuals requesting medical information over a 12-month period from the physician at 1 established site on the World Wide Web. This site was the only Internet site with a primary focus on cardiac arrhythmias. RESULTS: Seventy unsolicited inquiries were received from 39 patients and 20 family members (the sources of 11 inquiries are unknown) from 20 states, Washington, DC, and 9 foreign countries (locations of 15 inquiries are unknown). Follow-up was obtained in 22 cases. The inquiries concerned cardiological conditions in 67 cases (96%) and cardiac electrophysiologic conditions and procedures in 52 cases (74%). The goals of the inquiries were diagnosis (15), therapy (48), prognosis (1), and patient education (6). On follow-up of 22 cases, the people initiating the inquiries stated that they were reassured (16), consulted a general cardiologist (1), consulted a cardiac electrophysiologist (4), or visited a tertiary care electrophysiology center (1). CONCLUSIONS: The increasing use of the Internet by the general public seeking specific medical information for themselves and for their families suggests a widespread, unmet need for objective medical advice. This study demonstrates that the public can choose accurately whom to ask for subspecialty advice in the area of cardiovascular diseases. Professional societies and regulatory agencies should develop physician guidelines for providing medical advice over the Internet.

Validation of the EINTHOVEN model-based computerized electrocardiogram rhythm analysis system with three classes of clinical arrhythmias.

Rhythm analysis by commercial systems does not meet clinical needs well, because (1) differential diagnosis of complex rhythms is not performed, (2) common rhythms are often misdiagnosed, and (3) transitions between rhythms are not described. We have developed a model-based diagnostic software system named EINTHOVEN that is designed to address the above limitations. A demonstration is available on the World Wide Web at http:@einthoven.uokhsc.edu. The system has been validated using simple rhythms from introductory electrocardiogram (ECG) textbooks. We present here the results of evaluation with more complex rhythm strips taken from clinical records and intermediate-level ECG textbooks. Rhythm strips were described by the onset and offset of each electrical event (P wave, QRS complex, and T wave) and by a morphology classification for each event. The rhythms included a variety of supraventricular and ventricular rhythms. The analysis was considered correct if it named all correct diagnoses in a rhythm strip, incorrect if it completed the analysis and failed to name the correct diagnoses, and indeterminate if it failed to complete the analysis. The system was designed not to complete an analysis if it could not explain an entire rhythm by at least 1 pathophysiological model. The test rhythms were not used to develop the system. Forty-six of 56 test rhythms were diagnosed correctly, and 8 were not analyzed completely. The 2 incorrect diagnoses were atrial tachycardia with variable conduction (diagnosed as intermittent complete heart block) and atrial fibrillation (diagnosed as irregular junctional tachycardia). All 56 rhythms were diagnosed correctly after minor technical improvements to the system. The processing time of the system was 7.6-fold (range 1.5-to 16.9-fold) faster than the elapsed time of the individual records. These preliminary results suggest (1) that computer-based interpretation of complex rhythms is possible, (2) that further software development is necessary to reach a clinical level of accuracy, and (3) that there are no theoretical obstacles to achieving this goal.

The dose-dependent reduction in blood pressure through administration of magnesium. A double blind placebo controlled cross-over study.

Seventeen patients with a diastolic blood pressure over 90 mm Hg were recruited from a running health screening program to participate in a double blind cross-over study of magnesium supplementation (15 mmol Mg2+/day (Emgesan, Kabi Pharmacia) for 3 weeks, followed by 30 mmol Mg2+/day for another 3 weeks, finishing with 40 mmol Mg2+/day for a final 3 weeks). A significant decrease in the mean systolic blood pressure was recorded from 154.0 +/- 10.7 mm Hg to 146.1 +/- 16.9 mm Hg (P = .031) while the mean diastolic blood pressure decreased from 100.2 +/- 4.2 mm Hg to 92.0 +/- 6.6 mm Hg (P = .0001).

Use of clozapine to treat levodopa-induced psychosis in Parkinson's disease: retrospective review.

Levodopa-induced psychosis can complicate the treatment of Parkinson's disease (PD). In this retrospective, uncontrolled report, we describe our experience treating PD-related psychosis with clozapine, emphasizing those patients treated for longer than 1 year. Twenty-seven patients were treated, 14 for longer than 1 year. Most patients showed a rapid improvement from baseline within 1 month using the Clinical Global Impression and Global Psychosis Rating Scores. Five patients discontinued the drug due to side effects, but only two patients reported side effects after 6 months of treatment. Clozapine appears to be effective in treating PD related psychotic symptoms while not interfering with motor function.

Effects of peroral magnesium on plasma and skeletal muscle electrolytes in patients on long-term diuretic therapy.

Twenty patients on long-term diuretic therapy for arterial hypertension and/or congestive heart failure were given a supplementary dose of 15 mmol magnesium aspartate hydrochloride per day for 6 months. Nineteen patients, fulfilling the same admission criteria as the treatment group, served as controls. The addition of magnesium aspartate hydrochloride resulted in a significant rise of the cellular potassium and magnesium content and in a significant decrease of both systolic and diastolic blood pressure. It is concluded that supplementation with magnesium aspartate hydrochloride may effectively prevent the diuretic induced disturbances of electrolyte balance.

An algorithm for complete enumeration of the mechanisms of supraventricular tachycardias that use multiple atrioventricular, AV nodal, and/or Mahaim pathways.

The EINTHOVEN system is a model-based expert system that interprets the cardiac rhythm from the electrocardiogram. It simulates the expected behavior of realistic semi-quantitative cardiac models constructed by heuristic rules to generate interpretations that include both text descriptions and event-by-event causal explanations in the form of ladder diagrams. The simulation has been limited by an inability to predict all possible behaviors of hearts with more than one reentrant circuit. We now describe an algorithm that overcomes this limitation. Its output has been validated by an independent possibility-tree analysis. Timing and storage measurements are presented for models with up to three slow atrioventricular nodal pathways, four atrioventricular pathways, and a single atriofascicular (Mahaim) pathway. This is the first report in the literature of an algorithm that enumerates all possible mechanisms for reentrant supraventricular tachycardias that use atrioventricular, atrioventricular nodal, and/or atriofascicular pathways in humans.

Expert system reasoning about dynamic systems by semi-quantitative simulation.

Current symbolic knowledge representation techniques are inadequate for describing complex dynamic systems, which are time-varying and contain feedback loops. These systems are particularly difficult to represent when quantitative knowledge about the relationships within the system is incomplete. This paper describes a symbolic extension of the system dynamics method which can answer 'what if' questions about system dynamics models semi-quantitatively. The method consists of (1) definition of generic model 'building blocks' which map directly onto difference equations; (2) development of a symbolic causal model of a system in terms of the generic functional 'building blocks', any available quantitative or semi-quantitative parameters, and a set of generic default values; (3) automatic translation of the model into a system of first-order difference equations; and (4) numerical integration of the equations by standard methods. A complex model with semi-quantitative parameters, representing the human cardiovascular system, is used to illustrate the method. This method couples the descriptive abilities of mathematics with the symbolic power of causal inference methods by providing the same knowledge base for both computational levels. It also eases truth maintenance, knowledge acquisition, and explanation. It may prove useful for expert system development in a variety of application domains whose processes are time-varying and homeostatic.

Medical and social prognoses of non-specific building-related symptoms (Sick Building Syndrome): a follow-up study of patients previously referred to hospital.

OBJECTIVES: The aim of this study was to describe and analyse the medical and social prognoses of patients with non-specific building-related symptoms. METHODS: A follow-up questionnaire focusing on current medical and social status, care, treatment, other actions taken and personality traits was sent to 239 patients with non-specific building-related symptoms assessed during the period between 1986 and 1998 at University Hospital in Umeå, Sweden. The response rate was 79%. RESULTS: Fatigue, irritation of the eyes, and facial erythema were the most common weekly symptoms reported at follow-up. As females constituted 92% of the respondents, statistical analyses were restricted to women. The level and severity of symptoms decreased over time, although nearly half of the patients claimed that symptoms were more or less unchanged after 7 years or more, despite actions taken. Twenty-five percent of the patients were on the sick-list, and 20% drew disability pension due to persistent symptoms at follow-up. The risk of having no work capabilities at follow-up was significantly increased if the time from onset to first visit at the hospital clinic was more than 1 year. This risk was also significantly higher if the patient at the first visit had five or more symptoms. All risk assessments were adjusted for length of follow-up. Symptoms were often aggravated by different situations in everyday life. CONCLUSIONS: Long-lasting symptoms aggravated by environmental factors exist within this group of patients. The results support that early and comprehensive measures for rehabilitation are essential for the patients.

The EINTHOVEN system: toward an improved cardiac arrhythmia monitor.

Contemporary cardiac arrhythmia monitors, used commonly in intensive care settings, are highly sensitive to artifact, resulting in high false alarm rates, inability to detect P waves reliably, and crude rhythm interpretation. We report on two new approaches that address these problems: a noise preprocessor that characterizes the type and degree of artifact in an ECG, and a model-based rhythm interpretation algorithm.

Multihormonal induction of alpha 2u-globulin in an established rat hepatoma cell line.

A subclone of the FU5-5 rat hepatoma cell line has been isolated which is inducible more than several hundred fold for the 20,000 dalton form of the major rat urinary protein alpha 2u-globulin. The basal relative synthetic rate (RSR) in growth medium containing 10% fetal calf serum was less than 2 X 10(-6) of total protein synthesis. Both dexamethasone and insulin were necessary for induction, and yielded a maximum induced RSR of 4-8 X 10(-3). Triiodothyronine (T3), dihydrotestosterone (DHT), rat growth hormone (GH), and estrogen, all of which have been shown to influence the induction of alpha 2u-globulin in the intact rat, were without effect on the cell line. A factor present in fetal calf serum was also necessary for maximum induction, since dexamethasone plus insulin in serum-free medium raised the RSR to only 3 X 10(-5); exogenous T3, GH, and DHT could not substitute for this serum factor. The kinetics of induction by dexamethasone were slow, with a lag of approximately 48 hr followed by a period of increasing RSR for 6-20 days. Removal of dexamethasone from induced cells led to an exponential decline in the RSR (t 1/2 15 hr). The concentrations of dexamethasone and insulin that could yield half maximum induction were 5 X 10(-8)M and 3 X 10(-11)M, respectively. Higher concentrations of insulin, although still in physiological range (10(-9)M), inhibited induction. At yet higher insulin levels, beyond the physiological range, alpha 2u-globulin synthesis returned to maximum values. The lack of DHT, T3, and GH requirement for alpha 2u-globulin induction in this cell line may mean that a regulatory aberrancy has occurred in this transformed cell line, or, alternatively, that these hormones act indirectly in the intact animal. This cell line should prove useful for the study of the molecular events associated with alpha 2u-globulin induction and for genetic approaches to the problem of multihormonal regulation of gene expression.

Nonlinear heart model predicts range of heart rates for 2:1 swinging in pericardial effusion.

We analyze two mathematical models of Rigney and Goldberger (14) of heart swinging in large pericardial effusions. Both models represent the torques due to the outflow of blood from the heart. The first assumes that the duration of systole does not vary with heart rate (in beats/min), whereas the second assumes that it varies linearly with heart rate. We examine the motion of the heart for heart rates between 50 and 200 and for a range of initial positions and velocities. Both models predict that the heart swings once every other beat (2:1 swinging, giving rise to electrical alternans) in a discrete range of heart rates and swings once per beat otherwise; both models explain the appearance and disappearance of 2:1 swinging mathematically. The first model predicts a rate range from 105 to 116 for the occurrence of 2:1 swinging. The second model predicts the same qualitative behavior but with 2:1 swinging occurring at heart rates between 88 and 119, which agrees well with published clinical data showing 2:1 swinging at heart rates between 90 and 144. We describe an analysis program for ordinary differential equations that analyzed the models quickly and automatically.

A-to-D conversion from paper records with a desktop scanner and a microcomputer.

A novel method for digitizing signals contained in paper records is presented. This method is based on the use of an inexpensive optical scanner to translate the image on paper into a binary, bit map data structure. Several algorithms which recognize the signal line in the bit map and translate it into a series of numbers which are equivalent to the output of electronic analog-to-digital converters are described. The method was validated by comparison both with idealized test patterns of varying frequency content and with electronically digitized pressure and pressure time derivative tracings from chronically instrumented dogs. The root mean square error for the physiological signals was 3.5-3.9% of peak-to-peak full scale, corresponding to roughly 50% more than the thickness of the signal line on the paper.