Biomedical subjects
M Spitzer
Publications and source records attributed to M Spitzer.
[Comprehension of metaphoric speech by healthy probands and schizophrenic patients. An experimental psychopathologic contribution to concretism].
The comprehension of auditorily presented sentences with a metaphoric content was investigated in three experimental studies. Experiments 1 and 2 established the time course in control subjects: At 400 ms after prime offset only the concrete meaning was activated, whereas 1200 ms after prime offset both concrete and metaphoric meaning were active. Experiment 3 demonstrated a heightened activation of the concrete meaning and no activation of the metaphoric meaning in schizophrenic patients. These results resolve the dispute over the use of concepts by schizophrenic patients (overinclusive versus underinclusive), and can be related to the neurobiology of working memory and of associative semantic memory. The three experiments may serve as paradigms of how the method of mental chronometry can be applied in the field of psychopathology.
Associative semantic network dysfunction in thought-disordered schizophrenic patients: direct evidence from indirect semantic priming.
The characteristics of the spread of semantic activation in associative networks in normal subjects, thought-disordered (TD) and nonthought-disordered (NTD) schizophrenic patients with respect to time and semantic distance are examined. Direct and indirect semantic priming effects at two stimulus onset asynchronies (SOA) in a lexical decision task reveal that semantic associations spread further and faster in TD schizophrenic patients than in normal controls and in NTD schizophrenic patients. From a methodological point of view, indirect semantic priming at short prime-target intervals appears to be the best indicator of associative network dysfunction. The findings are discussed within the framework of current research on the effect of dopamine on the signal-to-noise ratio in cortical neural networks. Data suggest that semantic associative memory operates at a comparatively lower signal-to-noise ratio in thought-disordered schizophrenic patients.
Is human papillomavirus-related disease an independent risk factor for human immunodeficiency virus infection?
We sought to determine the prevalence of human immunodeficiency virus (HIV) infection in a population of women with human papillomavirus (HPV)-related diseases attending a colposcopy clinic who had no other CDC-defined risk factors for HIV. Study patients included all new patients attending our colposcopy clinic who were found to have histologic evidence of condyloma or cervical intraepithelial neoplasia. Those patients not already known to be HIV-positive were offered testing for HIV. Demographic information was obtained on all patients. Results were compared to data from anonymous testing of our own obstetrical population. One hundred forty of 208 women (67.3%) were either previously known to be HIV-positive or agreed to be tested. Sixteen (11.4%) were HIV-positive. Eight of the HIV-positive women were not previously known to be HIV-positive and 6 of the 8 had no definable risk factors for HIV infection. This is 4.6% of the women not already known to have a CDC-defined risk factor for HIV. The rate of HIV infection in our obstetrical population is 1.6%. In women without other definable risks for HIV infection and who had HPV-related disease the relative risk of HIV infection in our population was 2.94 (95% confidence interval 1.21-6.94; P < 0.031). In areas where HIV is endemic there is a high prevalence of HIV infection in women with HPV-related disease. Even in women without another definable risk factor for HIV, HPV-related disease may serve as a marker for an increased risk of HIV infection in this population.
The psychopathology, neuropsychology, and neurobiology of associative and working memory in schizophrenia.
A large number of psycholinguistic findings on how human beings store lexical information suggest the existence of associative memory, which may be characterized by a large capacity and a long duration. Its anatomical basis supposedly is, at least in part, the frontal lobes, and some of its functional characteristics have been tentatively linked to dopamine release. Working memory has a limited capacity, lasts only for seconds and is relevant for goal-directed behavior. Its anatomical basis in the frontal cortex is established and strong evidence suggests the involvement of dopaminergic pathways. Experimental evidence using several lexical decision tasks and a delayed response task is provided to demonstrate that some characteristic features of schizophrenic thinking--in particular the rapid shift of associations, the indirect relationship of associations, the overly abstract or overly concrete use of concepts, the lack of context-sensitivity and of general integrative function and intellectual capacity--can be explained in terms of an activation or disinhibition of associative memory, and of a dysfunctional working memory. The findings serve as an example of schizophrenia research in a cognitive neuroscience framework.
Relation of arterial pressure waveform to left ventricular and carotid anatomy in normotensive subjects.
OBJECTIVES: The purpose of this study was to examine the relation of the central arterial pressure waveform to left ventricular and carotid structure. BACKGROUND: The pressure waveform in the central arteries is affected by reflection of the pressure wave from the periphery. When reflected waves merge with the incident wave during systole, a late systolic peak and increment in systolic blood pressure are observed. The consequent increase in hemodynamic load may stimulate left ventricular and vascular adaptive changes. METHODS: Sixty-seven normotensive adults were studied by noninvasive techniques. Anatomy and function of the left ventricle and carotid artery were investigated by ultrasonography. Pressure waveforms were recorded by an external tonometer applied to the carotid artery, and waveform shape was expressed by the augmentation index, calculated from the difference between the maximal systolic pressure and that at the inflection between early and late systolic pressure peaks divided by the pulse pressure. Subjects were assigned to groups with a dominant early (group 1, augmentation index < or = 0) or dominant late systolic peak (group 2, augmentation index > 0). RESULTS: Left ventricular mass index was significantly higher in group 2 than in group 1, a difference that persisted after controlling for the confounding effects of gender, age and blood pressure. Carotid wall thickness and regional arterial stiffness were significantly increased in group 2, but differences disappeared in the analysis of covariance for age. CONCLUSIONS: Left ventricular and carotid artery structure are related to the shape of the central pressure waveform. Although the increase in left ventricular mass seen in subjects with a dominant late systolic peak pressure appears to be directly related to the shape of the pressure waveform, changes in the structural and physical properties of the carotid artery appear to be more closely related to the aging process.
Indirect semantic priming in schizophrenic patients.
Schizophrenic patients and normal controls performed a lexical decision task involving the recognition of words which were preceded (primed) by either associated, indirectly associated, or non-associated words. In contrast to normal control subjects who showed no indirect semantic priming effect at an inter-stimulus interval (ISI) of 0 ms, a trend towards such an indirect semantic priming effect was found in schizophrenic patients. With a longer ISI of 500 ms, an indirect semantic priming effect was obtained in both groups. In the framework of network models of semantic memory, the results are interpreted as further evidence for an increase in activation or decrease in inhibition in the spreading of associational activation in schizophrenic patients.
Psychological effects of MDE in normal subjects. Are entactogens a new class of psychoactive agents?
The so-called entactogens 3,4-methylenedioxymethamphetamine ([MDMA] also known as "Ecstasy," or "Adam") and its analog 3,4-methylenedioxyethamphetamine ([MDE] also known as "Eve") exert similar psychotropic effects in humans. Two double-blind placebo-controlled psychometric studies with normal control subjects were conducted. Placebo or MDE (140 mg) was administered orally to eight male volunteers at 1:30 P.M. and to six subjects (3 male, 3 female) at 11 P.M. Psychologic tests and clinical ratings were performed 1 hour before the administration of the drugs, as well as 2, 5, and 24 hours after drug intake and 7 days thereafter in the first study. In the second study, measures were taken at times -1, +8.5, +24 hours, and +7 days. The majority of the psychotropic effects resembled those that have already been described in anecdotal reports. The substance produced a partially controllable state of enhanced insight, empathy, and peaceful feelings. All subjects displayed a general stimulation with increased psychomotor drive, logorrhea, and facilitation of communication. One of the fourteen volunteers developed a toxic psychosis. One volunteer displayed a dysphoric reaction, one suffered from episodes of anxiety for some days after the experiment. The findings support the hypothesis that MDMA and MDE represent a novel pharmacologic class.
[Extension of the concept of extracorporeal fertilization by cryopreservation of impregnated oocytes].
Cryopreservation of human embryos within in-vitro fertilization treatment was already proposed in 1977 by Edwards and Steptoe. Today, this procedure is used worldwide by several teams as a standard method to enhance the success rate of IVF. In spite of this, there are many disadvantages of the freezing of embryos, furthermore it is legally prohibited in Germany. We report on a new concept for treatment, which includes the freezing of impregnated oocytes after IVF and their transfer in subsequent cycles. From 109 out of 120 patients who were treated with a long acting GnRH analogue or a contraceptive pill before IVF stimulation, "supernumerary" impregnated oocytes could be frozen. Twenty-three pregnancies resulted after immediate embryo transfer, and thirty patients, who returned for the transfer of cryopreserved oocytes, became pregnant. Neither the IVF pre-treatment, nor the stimulation in the transfer cycles of frozen oocytes with clomiphene citrate, influenced the success rate significantly. Combining the 53 pregnancies, a cumulative pregnancy rate of 49% can be calculated per IVF stimulation treatment. This means a doubling of the success rate, compared with routine IVF treatment. Although there are still problems to be solved, as, for instance, the insufficient implantation rate of 7% after the transfer of frozen/thawed cells, we consider cryopreservation of pronuclear oocytes a useful and promising supplement of IVF treatment. There is no further need for the freezing of embryos.
[Semantic activation phenomena in healthy probands and in schizophrenic patients. Analysis on the level of word pairs].
Semantic priming in normal controls and schizophrenic patients can be demonstrated in lexical decision tasks. Data from such a lexical decision task are analyzed with special respect to the question as to whether associative processes in schizophrenic patients are characterized by the occurrence of entirely new associations or by the intrusion of normal associations, i.e., associations which can be found in normal subjects. The analysis of the semantic priming effects of single word pairs demonstrates little qualitative differences between the associations of normals and of schizophrenic patients. This finding provides further support for Maher's hypothesis of activated normal associations in schizophrenic patients. From a methodological perspective, the item-by-item analysis of lexical decision task data can be used to optimize this method.
[Significance of historical and current hallucinogenic research in psychiatry].
Research in experimental psychosis has a long tradition extending through several stages. With the world wide abuse of psychoactive substances it came to an abrupt end. Systematic questions within this framework of research are still unresolved, and research on newly developed compounds is almost completely lacking. A review of the pharmacological and psychological effects of various psychoactive agents is provided, and results of recent experimental studies on arylalkylamines are discussed. It is argued that from a systematic as well as from a methodological viewpoint the traditional approach of experimental psychosis represents a valuable tool in psychiatric research.
The use of large-loop excision of the transformation zone in an inner-city population.
OBJECTIVE: To determine whether large-loop excision of the transformation zone (LLETZ) can be used in our population to treat patients in a routine colposcopy clinic without diminishing the capability to see the large number of patients who require care, and to compare these results to our previous experience with laser surgery. METHODS: Patients found to have squamous intraepithelial lesions on colposcopically directed biopsies were offered treatment with LLETZ during counseling regarding their biopsy findings. Procedures included "ablation equivalents" and "cone biopsy equivalents" using local anesthesia. Follow-up examinations were used to determine cure and included cytology, colposcopy, and directed biopsies when indicated. The cure rate was compared to our previous experience with laser surgery. RESULTS: Two hundred thirty-six patients were treated in the colposcopy clinic without diminishing the capability to see all patients requiring care. Complications were few. The mean (+/- standard deviation) follow-up period was 50.7 +/- 25.3 weeks. The overall cure rate of 91.3% (95% confidence interval [CI] 87.1-95.5) was not influenced by the severity of the disease, but positive endocervical margins significantly lowered the cure rate to 69.2% compared with those who had negative margins. Before this series, only 73.1% of our patients scheduled for laser surgery returned for treatment. Assuming a 90% cure rate among those who returned, this means that the actual cure rate was only 65.8%. The likelihood of cure was 1.37 times greater (95% CI 1.27-1.52; P < .0001) using LLETZ in the clinic at the time the patient was counseled regarding her biopsy findings than using laser at a later date. In 33 patients, the LLETZ specimen showed no evidence of disease. The relative risk of negative histology was 3.31 (95% CI 1.78-6.13; P < .001) when LLETZ was done for a discrepancy between cytology and histology as opposed to any other indication. Cancer was found on the LLETZ specimen in four patients (two microinvasive, two frankly invasive), but was not suspected preoperatively in any of the patients. CONCLUSION: In our inner-city clinic, treatment with LLETZ at the time the patient was counseled regarding her biopsy findings improved the actual cure rate. The LLETZ procedure can be done safely in a clinic setting without diminishing the capability to care for a large number of patients.
[Associative networks, formal thought disorders and schizophrenia. On the experimental psychopathology of speech-dependent thought processes].
Association psychology research in psychiatry dates back to Kraepelin, Aschaffenburg and C.G. Jung. Findings of the 1950s and 60s in this field suggest that semantic memory is organized in the form of a network. New results of experimental psychiatric studies indicate that schizophrenic symptoms, in particular formal thought disorders, are in part the result of an unfocussed activation or disinhibition of such associational network structures: The phenomenon of semantic priming is more pronounced in schizophrenic patients than in normals. Moreover, the phenomenon of indirect semantic priming on short stimulus onset asynchrony can be seen only in schizophrenic patients. The study of spontaneous speech further suggests the activation of structures responsible for the storage and processing of meaning. Increase in semantic priming, similar to that observed in schizophrenia, can further be observed in normal subjects on awakening from REM sleep. The findings are discussed in the framework of recent findings on the neurobiological causes of schizophrenia. They can be related structurally to an involvement of the frontal lobe, and functionally to disturbances of dopaminergic transmission. Methods such as the investigation of priming effects in lexical decision tasks, as well as concepts from the domain of cognitive neuroscience such as neural networks and the spreading activation model of lexical access, can help to bridge the gap between phenomenological psychopathology and neurobiology.
[Successful hyposensitization treatment of a patient with schizoaffective psychosis and carbamazepine allergy].
For the prevention of relapse in a 25 year old man with schizoaffective psychosis, lithium was prescribed but had to be discontinued because the patient developed psoriasis. Carbamazepine was started but had to be discontinued as the patient developed a generalized substance-induced skin rush. A six-week desensitization procedure with increased oral doses, starting with 1 mg per day, allowed relapse prevention with carbamazepine on a usual dosage. To our knowledge, this is the first report of a successful desensitization of a psychiatric patient with carbamazepine allergy.
Mescaline-induced psychopathological, neuropsychological, and neurometabolic effects in normal subjects: experimental psychosis as a tool for psychiatric research.
The psychological, neuropsychological, and neurometabolic effects of the hallucinogenic agent mescaline were investigated in 12 normal men who were volunteers. Mescaline produced an acute psychotic state 3 1/2-4 hr after drug intake, as measured by the Brief Psychiatric Rating Scale (BPRS) and Paranoid Depression Scale (PDS). The Assessment of Altered States of Consciousness (APZ) questionnaire revealed specific effects of mescaline in the visual system. Neuropsychological effects were studied with a face/nonface decision task with known right-hemisphere advantage, in which mescaline induced a decrease of functioning of the right hemisphere. In functional brain imaging using single photon emission computed tomography (SPECT), mescaline produced a "hyperfrontal" pattern with an emphasis on the right hemisphere, which was correlated with mescaline-induced psychotic psychopathology. Our findings question the validity of the concept of hypofrontality as an explanation for schizophrenic symptomatology. The study of psychoactive substances under controlled laboratory conditions has the methodological advantage of intraindividual control, and hence, minimal variability of data.
[Relations of model and drug-induced psychoses to schizophrenic diseases].
From the clinical point of view, substance-induced psychosis can be rather similar to schizophrenia. However, the question whether phenomenological resemblances represent similar underlying causal mechanisms is unsolved. Whereas the interest in experimentally induced psychosis was purely academic until the mid-1960s, the widespread use of "recreational" drugs provided this research with an important practical impact. With respect to a given case the differential diagnosis between schizophrenia and drug-induced psychosis it is often problematic. The differences in psychopathology refer to the disturbances of experience in general (Ichstörungen), the character of the hallucinations and the quality and quantity of the alterations of consciousness. Contrary to the sharp distinctions which used to be drawn between schizophrenia and drug-induced psychotic states, we hold that these states are rather similar, and may even represent a common underlying pathology. Hence, the renewed interest in the study on experimentally induced psychotic states using advanced methodology seems justified.
Parallel cardiac and vascular adaptation in hypertension.
BACKGROUND: Although vascular damage in the noncoronary circulation is a major cause of complications in hypertension, relatively little is known of the in vivo geometry and function of the arterial circulation in patients with uncomplicated hypertension or of their relation to left ventricular hypertrophy, a marker of enhanced risk of cardiovascular complications. METHODS AND RESULTS: Wall thickness and internal diameter of the common carotid artery and the presence of atherosclerosis within the extracranial carotid arteries were determined by ultrasound in 43 asymptomatic hypertensive patients and 43 normotensive subjects matched for sex, age, and body size. Vascular stiffness was estimated from simultaneous superimposed carotid pressure waveforms obtained with an external solid-state transducer. Left ventricular size and function were determined echocardiographically. Compared with normal subjects, hypertensive patients had greater left ventricular absolute and relative wall thicknesses, left ventricular mass, and carotid absolute and relative wall thicknesses (p < 0.005). Carotid intimal-medial thickness exceeded the 95th percentile of normal values in 28% of hypertensive patients (p < 0.01). Carotid atherosclerosis was equally prevalent within the two blood pressure groups and was associated with older age, larger left ventricular and carotid wall thicknesses, and carotid diameter. Despite similar carotid pulse pressures, vascular stiffness was significantly increased in the hypertensive patients. Among the population as a whole, significant relations existed between cardiac and vascular wall thicknesses and internal dimensions. In multivariate analyses, these relations were statistically independent of age and blood pressure. CONCLUSIONS: The present study documents the presence of geometric and functional changes within the common carotid artery in uncomplicated hypertension that parallel findings within the left ventricle. The potential contribution of these changes to the cardiovascular complications of hypertension, particularly in the setting of left ventricular hypertrophy, is unknown.
Reconquest of the subjective.
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