[Concerning "Trainee in internal medicine. Does the future general internist need participation in sciences?" by P.W. Straub (Schweiz. med. Wschr. 1991; 121: 1435-1438)].
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Gasoline↗
Biomedical subjects
T Reich
Publications and source records attributed to T Reich.
An extension of the acquaintanceship procedure in family studies of mental disorder.
The acquaintanceship procedure is a method for obtaining a control group matched to relatives of probands on demographic variables. Relatives are asked to name six acquaintances who are the same gender, and who are about the same age and social class as themselves. An acquaintance is randomly selected from this list and contacted for recruitment. Rates of mental disorder in this group are assumed to approximate general population rates in a group with these demographic characteristics. This report focuses on an extension of the acquaintanceship procedure in which "super-normal" controls are used in a family study design. Two questions were addressed: (1) Does the acquaintance group (n = 166), as a whole, show a higher rate of illness than the relatives of acquaintances with no mental disorder (n = 129)? (2) Is there a relationship between mental disorder in acquaintances and in providers of acquaintance names? The prevalence of mental illness was significantly greater among acquaintances compared to relatives of "never ill" acquaintances. There was no evidence of assortative selection. We concluded that using the relatives of well acquaintances is a cost-effective control selection methodology which maximizes the detection of intergenerational transmission in family studies of mental disorder.
Adult↗
Patterns of lifetime drug use among intravenous drug users.
To obtain a clearer description of the natural history of intravenous drug use (IVDU), 92 intravenous drug users (IVDUs), not selected through treatment or contact with the legal system, were identified. Concerning lifetime use, central nervous system (CNS) stimulants were the most common class of drug to be injected (by 72.8% of IVDUs), followed by opiates (by 50.0% of IVDUs). Mean age of onset of IVDU in this sample was 18.5 years, following initiation of alcohol use by an average of 4.6 years and cannabis use by an average of 2.1 years. Any history of IVDU in this sample indicated substantial lifetime use of illicit drugs and early onset of psychoactive substance use.
Acquired Immunodeficiency Syndrome↗
Lifetime complications of drug use in intravenous drug users.
Ninety-two intravenous drug users (IVDUs) were identified from a study of 1,640 relatives of treated alcoholics and felons. Nearly all of the IVDUs (90%) reported a lifetime history of some degree of physical, psychological, or social difficulty related to drug abuse, but only 35% had ever received treatment for drug abuse. Overall, compared to subjects with a history of substantial illicit drug use who had never injected, IVDUs were significantly more likely to report all drug-related problems assessed. Even in populations of drug users not selected through treatment, any history of intravenous (IV) drug use is strongly indicative of a lifetime occurrence of complications of drug use.
Adult↗
A secular increase in child and adolescent onset affective disorder.
Both longitudinal and cross-sectional studies utilizing population and family study samples have found evidence for a secular increase in major affective disorders in adults. Applying techniques used in cross-sectional studies in adults to family study data of children and adolescents, the authors demonstrate evidence of a parallel secular increase for child and adolescent onset affective disorders. Normal and depressed prepubertal probands were identified. All full siblings were directly interviewed for lifetime episodes of affective disorder. Analysis of the siblings (probands not further analyzed in this article) by the Cox proportional hazards model demonstrates that the risk for affective disorder is higher in siblings born more recently.
Bias↗
Reduced alpha 1- and beta 2-adrenoceptor-mediated positive inotropic effects in human end-stage heart failure.
1. alpha 1-Adrenoceptor (phenylephrine in the presence of propranolol) and beta 2-adrenoceptor (fenoterol)-mediated positive inotropic effects were investigated in human ventricular preparations isolated from five non-failing (prospective organ donors) and from eight explanted failing hearts with end-stage idiopathic dilative cardiomyopathy (NYHA IV). 2. For comparison, the nonselective beta-adrenoceptor agonist isoprenaline, the phosphodiesterase (PDE) inhibitor 3-isobutyl-1-methylxanthine (IBMX), the cardiac glycoside dihydroouabain, and calcium were studied. 3. Furthermore, the influence of IBMX on adenosine 3':5'-cyclic monophosphate (cyclic AMP) PDE activity as well as total beta-adrenoceptor density, beta 1- and beta 2-adrenoceptor subtype distribution, and alpha 1-adrenoceptor density were compared in nonfailing and failing human heart preparations. The radioligands (-)-[125I]-iodocyanopindolol for beta-adrenoceptor binding and [3H]-prazosin for alpha 1-adrenoceptor binding were used. 4. The inotropic responses to calcium and dihydroouabain in failing human hearts were unchanged, whereas the maximal alpha 1- and beta 2-adrenoceptor-mediated positive inotropic effects were greatly reduced. The inotropic effects of the other cyclic AMP increasing compounds, i.e. isoprenaline and IBMX, were also reduced to about 60% of the effects observed in nonfailing controls. The potency of these compounds was decreased by factors 4-10. 5. The basal PDE activity and the PDE inhibition by IBMX were similar in nonfailing and failing preparations. 6. The total beta-adrenoceptor density in nonfailing hearts was about 70 fmol mg-1 protein. In failing hearts the total number of beta-adrenoceptors was markedly reduced by about 60%. The betal/beta2-adrenoceptor ratio was shifted from about 80/20% in nonfailing to approximately 60/40% in failing hearts which was due to a selective reduction of beta1-adrenoceptors. The beta2-adrenoceptor population remaining unchanged. alpha-Adrenoceptor density was increased from about 4 fmol mg-' protein in nonfailing to 10 fmol mgprotein in failing hearts.7. Changes in PDE activity and adrenoceptor downregulation cannot completely explain the reduced positive inotropic effects of alpha 1- and beta 2-adrenoceptor agonists in failing human hearts. This supports the hypothesis that impairment of other processes such as the coupling between receptor and effector system, i.e. the respective G-proteins, are equally important in end-stage heart failure.
3',5'-Cyclic-AMP Phosphodiesterases↗
Psychiatric comorbidity and suicidality among intravenous drug users.
BACKGROUND: Prevalence of lifetime psychiatric comorbidity and history of attempted suicide among intravenous drug users was investigated. METHOD: One thousand sixty-two relatives of hospitalized alcoholics, felons, and control subjects were administered a structured interview that gathered data on lifetime psychiatric symptoms and psychoactive drug use. Psychiatric diagnoses were based on interview information, medical records, and family history data. Comparisons were made between 411 subjects who used no illicit drugs, 329 cannabis users, 230 subjects who had used psychoactive drugs other than cannabis more than five times but had never injected drugs, and 92 intravenous drug users. RESULTS: Any history of injecting drugs increased the odds of being diagnosed with antisocial personality disorder by a factor of 21.01, alcoholism by 4.42, and unipolar depression by 3.02. A diagnosis of antisocial personality disorder increased the odds of having injected drugs by a factor of 27.19, while diagnoses of alcoholism or unipolar depression conveyed odds for injecting drugs of 4.62 and 3.70, respectively. Intravenous drug use was associated with an 8.27-fold increase in odds for a suicide attempt compared with no drug use. CONCLUSION: Rates of alcoholism, depression, and antisocial personality disorder, but not other psychiatric disorders (other than drug dependence), are significantly elevated in intravenous drug users. Moreover, among drug users, the decision to inject is differentially made by those with antisocial personality disorder. A history of suicide attempt is common among intravenous drug users, but injecting appears to convey little additional risk above substantial but non-intravenous drug use.
Adolescent↗
Alcoholism and alleles of the human D2 dopamine receptor locus. Studies of association and linkage.
The association of the A1 allele of the D2 dopamine receptor gene with alcoholism was examined by comparing 32 unrelated white alcoholics with 25 unrelated white controls and by analysis of 17 nuclear families in multigenerational pedigrees of alcoholics in whom the A1 allele was segregating. All subjects had structured psychiatric interviews. Clinical assessment and genotyping were carried out independently. Thirteen (41%) of the 32 alcoholics carried the A1 allele compared with three (12%) of the 25 controls. The association with the A1 allele was significant when controls were compared with a subset of 10 alcoholics with severe medical problems (60% vs 12%), but not less severe cases. However, regardless of clinical severity or subtype, there was no evidence of linkage or cosegregation of the A1 allele and increased susceptibility to alcoholism in informative pedigrees. The possible association in the general population without linkage in families may be explained either by chance variation in our small samples or a modifying effect of the A1 allele that increases severity. Further study of the role of the D2 receptor gene in alcoholism is warranted.
Alcoholism↗
Current perspectives on the genetics of unipolar depression.
Evidence regarding the heritability of unipolar depression is evaluated. The data reviewed here support the involvement of genetic factors in the etiology of unipolar depression and its suitability for independent genetic inquiry, despite our inability to identify the mode(s) of transmission or identify a candidate locus. Continued progress in testing etiologic hypotheses requires (a) clarification of the mode of transmission; (b) resolution of phenotypic and potential genotypic heterogeneity; (c) general agreement on a "gold standard" for assessment of the unipolar phenotype; (d) the continued application of available quantitative methods to take into account the effects of ascertainment bias, sex effects, cohort effects, and variable/late age at onset; and (e) incorporation of quantitative indicators correlated with liability in multivariate analysis to improve the stability/validity of phenotypic determinations in segregation and linkage analysis. We present several recommendations regarding the extension of current methodologies in human population and quantitative genetics to help resolve these issues.
Chromosome Mapping↗
The relationship of solvent use to other substance use.
One hundred thirty solvent abusers were retrospectively identified from a family study containing 286 alcoholics, 157 felons, 60 control subjects, and 1,640 of their relatives. Comprehensive data regarding psychiatric diagnosis and drug use were gathered using the Home Environment Lifetime Psychiatric Record. Solvent abuse was very strongly associated with having a diagnosis of Antisocial Personality Disorder and was consistently associated with polysubstance abuse. Solvent abusers were more likely to be male, or lower socioeconomic status, and younger than those without a reported history of solvent abuse. Contrary to current understanding, solvent use did not clearly precede other substance use; rather, alcohol and cannabis use tended to occur first, followed by use of solvents. Solvent users were 5 to 10 times more likely than nonusers to report abuse of opioids, stimulants, depressants, and hallucinogens.
Adult↗
Epidemiological perspectives on children of alcoholics.
Because alcoholism is a highly heritable condition, children of alcoholics, especially sons, are at much higher risk than the general population for developing the disorder. Furthermore, secular trends are apparent for both sons and daughters of alcoholics, such that alcoholism has become more prevalent over time, increasing the morbid risk in offspring of alcoholics. Increases in prevalence of disorders known to be associated with alcoholism, such as conduct disorder, depression, and drug abuse, have also been found in younger cohorts, as well. At the genetic level, alcoholism appears to be heterogeneous, raising the possibility that alcoholism may be a product of numerous different kinds of gene-environment interactions. Further advances in our understanding of alcoholism will come from molecular genetic studies and longitudinal studies of high-risk populations.
Alcoholism↗
Solvent use and psychiatric comorbidity.
From a family study of 286 alcoholics, 157 felons, 60 control subjects, and 1640 of their relatives, 130 solvent users were retrospectively identified. Risk for diagnosis of antisocial personality disorder was significantly elevated for all solvent users. Relatives, though not probands, were more likely to receive diagnoses of alcoholism and secondary depression, but this relationship appeared to be mediated by the presence of antisocial personality disorder. Solvent users were not at increased risk for primary depression or other psychiatric illnesses. Subjects reporting any solvent use also had significantly increased risk of suicidal ideation and suicide attempt compared to non-users, with half of the solvent users reporting suicidal ideation and 30% reporting a history of suicide attempt. However, risk for suicidal ideation and suicide attempt among solvent users appeared to covary with presence of antisocial personality disorder, alcoholism, and secondary depression rather than being specifically associated with solvent use.
Adult↗
No evidence for linkage between chromosome 5 markers and schizophrenia.
Linkage between chromosome 5 markers and schizophrenia has been proposed for a small number of Icelandic and English families. Three subsequent reports have failed to replicate this report. To increase the number of tested kindreds, we collected seven North American families with schizophrenia and genotyped them at 4 loci that span the region 5p13-5q11-14, including the two markers used in the single positive linkage report. The data were analyzed with models of affection status similar to those utilized in the positive report. We observed no evidence of linkage between these markers and psychiatric disorders, regardless of the definition of affection status. Additionally, we can exclude most of the region for linkage with schizophrenia in these families. This and other negative reports of linkage between schizophrenia and chromosome 5 markers suggest that genetic defects in this region are rarely, if ever, etiologically related to schizophrenia.
Chromosomes, Human, Pair 5↗
[An in vitro test procedure for evaluating dental restoration systems. 1. A computer-controlled mastication simulator].
This article describes the development and testing of a computer-controlled chewing simulator which is able to simulate the wear mechanisms and temperature changes that can occur in the mouth. It was further evaluated if the opposing cusps used in this chewing simulator should be metallic or if natural enamel was preferential. The results indicated that the machine fulfilled the parameters concerning chewing motion and thermal changes reported in the literature. Furthermore it was shown that natural enamel cusps must be used as the opposing dentition. The chewing simulator will form a part of an in-vitro test, which will allow the evaluation of dental restorative systems under clinically relevant conditions.
Computer Simulation↗
NIMH Collaborative Program on the Psychobiology of Depression: clinical.
As part of the National Institute of Mental Health Collaborative Program of Depression study, data were collected on 2,225 first-degree relatives of 612 probands. A subset consisting of 187 families of bipolar patients was made available to participants of Genetic Analysis Workshop 5 (GAW5). A description of these data, including sample sizes, diagnoses, and a summary of published analyses, is given.
Adult↗
Segregation and linkage analyses of bipolar and major depressive illnesses in multigenerational pedigrees.
Data were collected on six large multigenerational pedigrees, four ascertained through a proband with major depression and two ascertained through a proband with a bipolar form of illness. Diagnoses were made using the SADS-L structured interview and Research Diagnostic Criteria (RDC). Complex segregation analyses were conducted on the bipolar and the major depression pedigree sets using a model allowing for both major locus and polygenic inheritance; in these analyses a variety of diagnostic schemes and assumptions concerning the lifetime population prevalence were examined. Linkage analyses on standard markers were conducted using parameters for transmission of susceptibility to illness derived from the segregation analyses. Results of the segregation analyses were quite sensitive to the diagnostic and prevalence assumptions. In the pedigrees ascertained through probands with a bipolar form of illness, we were unable to discriminate between major gene and polygenic inheritance. The data were compatible with Mendelian major gene transmission of susceptibility to illness when bipolar and schizoaffective manic diagnoses were considered as affected and the lifetime population prevalence was between 0.04 and 0.06. Outside this narrow prevalence range, or when additional diagnoses, such as major depression or hypomania, were included as expressions of liability to disease, major gene transmission of susceptibility to disease could be rejected. Similarly, in the pedigrees ascertained through probands with major depression, it was not generally possible to discriminate between major gene and polygenic transmission of susceptibility to illness. For a diagnostic scheme including only major depression as a manifestation of susceptibility to illness, there was a narrow range of lifetime population prevalence values (female prevalence ranging from 0.20 to 0.25, male prevalence set to 1/2 female prevalence) which yielded results compatible with major gene transmission. Linkage analyses for all markers yielded negative or inconclusive results. In one bipolar pedigree a lod score of 1.65 was found with a marker in chromosome 1 recommending further studies of this chromosome.
Adult↗
Schizophrenia and the question of genetic heterogeneity.
Despite major advances in psychiatric diagnosis during the past 20 years, boundaries of the schizophrenic syndrome remain elusive. Moreover, in pedigrees containing cases of schizophrenia there are marked between-pedigree differences with respect to prognosis, familial patterns of psychiatric illness, drug response, and especially association of affected status with a specific chromosomal locus. Such between-pedigree differences suggest the syndrome may be made up of several different diseases. Linkage of affected status to specific loci may aid in resolving genetic heterogeneity. Large multigenerational informative pedigrees may permit the separation into those that do and do not link to a genomic locus of interest. Admixture analysis of smaller informative pedigrees may permit separation of linked and unlinked pedigrees on the basis of differences in the recombination fraction. Finally, biological "markers" can be used before the genetic analysis to separate putative linked and unlinked pedigrees. The combined study of genetic linkage and clinical heterogeneity will aid in the resolution of etiological heterogeneity of schizophrenia and the delineation of meaningful diagnostic boundaries.
Genetic Linkage↗
Cerebral cortical and white matter reactivity to carbon dioxide.
We measured cerebrovascular reactivity to carbon dioxide in the cerebral cortex and the subcortical white matter of 12 healthy adult volunteers (four young subjects aged 21-24, four middle-aged subjects aged 34-40, and four elderly subjects aged 62-85 years). Blood flow was computed from the concentration history of xenon-133 in the volume of interest measured with an ultrapure germanium detector array. End-tidal PaCO2 ranged from 35.4 to 42.6 mm Hg. The mean +/- SD baseline blood flows in the cerebral cortex were 60 +/- 7, 51 +/- 9, and 33 +/- 4 ml/100 cm3/min in the young, the middle-aged, and the elderly subjects, respectively; the corresponding subcortical white matter baseline blood flows were 21 +/- 1, 22 +/- 3, and 16 +/- 5 ml/100 cm3/min. Mean +/- SD cerebrovascular reactivities to carbon dioxide in the cerebral cortex were 2.03 +/- 0.58, 1.36 +/- 0.41, and 0.72 +/- 0.19 ml/100 cm3/min/mm Hg PaCO2 for the young, the middle-aged, and the elderly subjects, respectively; the corresponding reactivities in the subcortical white matter were 0.69 +/- 0.11, 0.59 +/- 0.17, and 0.36 +/- 0.41 ml/100 cm3/min/mm Hg PaCO2. Blood flow and cerebrovascular reactivity in the cerebral cortex of the young subjects were significantly higher than those for white matter and significantly higher than those in the elderly subjects (p less than 0.001). Age vs. blood flow (for the cortex) and age vs. cerebrovascular reactivity (for both cortical gray and subcortical white matter) also showed significant linear correlation (p less than 0.05). However, the age-related changes in white matter blood flow and cerebrovascular reactivity were slow, and the differences among the age groups were not statistically significant.
Adult↗