Acute anxiety and depression induced by loss of sensation and muscle control after botulinum toxin A injection.
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Biomedical subjects
Publications and source records attributed to M Spitzer.
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Healthy subjects performed a lexical decision task in a semantic priming paradigm while event-related potentials (ERPs) were recorded from 64 channels. Semantic distance between prime and target was varied by including directly, indirectly, and nonrelated word pairs. At centro-parietal electrodes an N400 to nonrelated pairs was elicited bilaterally which was sensitive only to direct, but not to indirect semantic priming. These N400 priming effects were mirrored by the RT data. At inferior fronto-temporal sites directly related words showed ERP priming effects over both hemispheres. However, indirectly related words only elicited ERP priming effects over the right hemisphere. These results support the hypothesis that the right hemisphere semantic system is involved in processing of remote semantic information.
The cortical organization of executive control was investigated using event-related potentials (ERPs). ERPs were collected while subjects performed a go/no go task that required response inhibition. First, around 260 ms after stimulus onset, an effect of response inhibition on ERPs was observed over inferior prefrontal areas. Generators in these regions were confirmed by source analysis. Later, between 300-600 ms after stimulus onset, a left lateralized fronto-central ERP effect was found which differed in topography from a non-specific effect of task difficulty. Source analysis indicated that generators in anterior cingulate and left premotor areas also contributed to this effect. Orchestrated activation of prefrontal areas and the anterior cingulate subserves executive function whereas relatively late activity of the left premotor cortex is involved in motor control.
Repetition blindness is the failure to report the detection of repeated items in rapid visually presented lists. It can be explained in terms of either a processing limitation or an active inhibitory process. In two studies conducted in either English or German language we set out to induce repetition blindness under various conditions in a total of 47 control subjects and 30 schizophrenic patients. The patients displayed the phenomenon to at least the same degree as normal control subjects. These results render unlikely accounts of repetition blindness which involve processes known to be dysfunctional in schizophrenic patients. Moreover, the study provides an example of how the performance of schizophrenic patients can constrain theories of normal cognition.
In an effort to reduce the false-negative rate of cervical cytologic findings, several new technologies have recently evolved. Automated cytologic testing (PapNet, AutoPap 300 QC) proposes to rescreen negative conventional cytologic findings to identify smears likely to be false negative. Fluid-based monolayers (ThinPrep, CytoRich) propose to reduce the false-negative rates by optimizing the collection and preparation of cells. Human papillomavirus deoxyribonucleic acid testing by Hybrid Capture has been proposed for a variety of screening and triage roles. Visual screening after application of acetic acid is done by cervicography by use of a photographic technique, whereas in speculoscopy the screening is done by direct visualization of the cervix by the primary care provider. Polarprobe uses biophysical parameters and a computer algorithm to give an instantaneous prediction of the likelihood of cervical disease. Each of these techniques, as well as the clinical experience with them, is reviewed. Current and possible future uses are discussed with regard to both clinical usefulness and cost-effectiveness.
OBJECTIVE: Our purpose was to determine the ability of different indications for cone biopsy to predict the presence of disease in the cone specimen and the utility of conization for low-grade disease. STUDY DESIGN: The records were reviewed of all patients who had an excisional cone biopsy at Queens Hospital Center between 1984 and 1995. Data were gathered regarding cytologic studies, visualization of the transformation zone, colposcopically directed biopsy, and endocervical curettage. The indications for the cone procedure were grouped as being for treatment (biopsy-proved disease) (indication A), discrepancy between cytologic and histologic diagnoses (indication B), positive endocervical curettage results (indication C), and transformation zone not fully visualized (indication D), and combinations of the above. RESULTS: Two thousand nine hundred sixty-nine records were reviewed. Of these, 604 had cone biopsies. Three hundred twenty-three of 355 (91%) cone biopsies done for indication A alone had disease on the cone specimen (defined as any grade of dysplasia or condyloma). Forty of 47 (85.1%) cone biopsies done for indication B alone had disease of the cone specimen. Forty-three of 46 (93.5%) cone biopsies done for indication C alone had disease on the cone specimen. Ninety-one cone procedures were done for a combination of indications A and D, with 87 (95.6%) showing disease on the cone specimen. Thirty-one procedures were done for a combination of indications B and D, with 25 (80.6%) showing disease on the cone specimen. Cone procedures were done on 32 women for a combination of indications C and D, and 30 (93.8%) had disease on the cone specimen. Two cone procedures were done because of the colposcopic appearance alone; one had high-grade disease on the cone specimen. Age did not help to predict the likelihood that disease would be found on the cone specimen. The data were then reanalyzed to determine the likelihood of finding high-grade disease (cervical intraepithelial neoplasia grades 2 or 3 or invasive cancer) on the cone specimen. Overall, those with preoperative high-grade cytologic or histologic characteristics (cervical intraepithelial neoplasia grades 2 or 3) were much more likely to have high-grade disease (277/371 [74.7%]) than were those with preoperative low-grade cytologic or histologic characteristics (condyloma or cervical intraepithelial neoplasia grade 1) (49/233 [21.0%]) (p < 0.001). CONCLUSION: Neither age nor the preoperative grade of disease are good discriminators of the likelihood that disease will be found on a conization specimen. However, patients who have high-grade disease on the preoperative evaluation are much more likely than those with only low-grade disease to have high-grade dysplasia or cancer on a subsequent conization.
OBJECTIVE: To determine the time it takes for prolactin (PRL) levels to increase after initiation of therapy with haloperidol (a neuroleptic medication) and the pattern and extent of the increase. METHODS: Seventeen individuals scheduled to be given treatment with neuroleptic drugs were enrolled. Baseline blood specimens were collected for PRL and TSH levels. Follow-up samples for PRL determinations were obtained every 3 days for 18 days after initiation of haloperidol therapy. RESULTS: There were 17 subjects: 14 women and three men. Two of the subjects were found to have hyperprolactinemia due to hypothyroidism and were excluded from the basic study. The 15 remaining subjects all had normal baseline PRL levels and normal TSH values. The PRL levels in all 15 showed a similar pattern: a rapid increase in PRL levels in the first 6-9 days, followed by a plateau that remained, with minor fluctuations, throughout the study. The highest mean peak level of PRL was 37.4 ng/mL and the maximum was 77 ng/mL. The two individuals with hypothyroidism had somewhat elevated baseline PRL levels; although they showed the same initial pattern of increase after haloperidol administration, their PRL levels reached values well above 100 ng/mL. CONCLUSION: There is a distinct pattern of response of PRL to haloperidol. The PRL level increases for 6-9 days, then plateaus, the peak being between 30 and 50 ng/mL, and always remains below 77 ng/mL. In our study, levels that continued to increase, or increased above 77 ng/mL, indicated the presence of hypothyroidism. The patterns and levels of the increase were uninfluenced by the therapeutic dose of the medication given. Given that the patients in our study with elevated levels of TSH had such high levels of PRL, all patients should have TSH determinations at the initiation of therapy with neuroleptic medications such as haloperidol.
Functional magnetic resonance imaging (fMRI) was used to examine the pattern of cortical activity during a picture naming task. Subjects (n=12) had to covertly name either animals or furniture items. Functional scanning was performed using a conventional 1.5-Tesla whole-body MRI system. Images obtained during naming the two categories were compared using a non-parametric test. The study revealed evidence for domain-specific lexical regions in left middle, right middle and inferior frontal areas, as well as in superior and middle temporal areas. The results corroborate neuropsychological data and demonstrate directly and non-invasively in human volunteers that semantic representations in frontal and temporal areas are, to some degree, localized and possibly implemented as multiple maps. A completely distributed storage of semantic information is rendered unlikely.
The psychological, neuropsychological, and neurometabolic effects of the hallucinogenic agent mescaline were investigated in 12 normal male volunteers. Between 3 1/2 and 4 hours after drug intake, mescaline produced an acute psychotomimetic state, as measured by the BPRS and PDS-P. The APZ questionnaire revealed the specific effects of mescaline in the visual system. Neuropsychological effects were studied with a face/non-face decision task with known right hemisphere advantage, in which mescaline induced a decrease in functioning of the right hemisphere. In functional brain imaging using SPECT, mescaline produced a "hyperfrontal" pattern with an emphasis on the right hemisphere, which was correlated with mescaline-induced psychotomimetic psychopathology. Our findings question the validity of the concept of hypofrontality as an explanation for acute psychotic symptomatology.
Human experimental research with hallucinogenic drugs is potentially able to identify linking variables between the psycho(patho)logical conditions and neurobiological alterations involved in both pharmacologically induced and naturally occurring acute psychotic states. A number of methodological aspects should be considered when planning modern experimental studies with hallucinogenic drugs. The issues of subject selection, repeated measures, and adequate control groups are discussed in this paper. Examples of recent experimental studies are presented which take these aspects into account. The first study examined psychopathological changes, facial expression and semantic priming effects during a psilocybin-induced state. In the second study, semantic priming effects after intake of psilocybin, 3,4-methylenedioxyethylamphetamine (MDE), and d-methamphetamine were investigated. Results confirmed time-dependent effects of psilocybin and the restriction of increased priming effects in the psilocybin group.
Mental disorders are characterised by psychopathological symptoms which correspond to functional brain states. Functional magnetic resonance imaging (fMRI) is used for the non-invasive study of cerebral activation patterns in man. First of all, the neurobiological principles and presuppositions of the method are outlined. Results from the Heidelberg imaging lab on several simple sensorimotor tasks as well as higher cognitive functions, such as working and semantic memory, are then presented. Thereafter, results from preliminary fMRI studies of psychopathological symptoms are discussed, with emphasis on hallucinations, psychomotoric phenomena, emotions, as well as obsessions and compulsions. Functional MRI is limited by the physics underlying the method, as well as by practical constraints regarding its use in conjunction with mentally ill patients. Within this framework, the problems of signal-to-noise ratio, data analysis strategies, motion correction, and neurovascular coupling are considered. Because of the rapid development of the field of fMRI, maps of higher cognitive functions and their respective pathology seem to be coming within easy reach.
BACKGROUND: In schizophrenia, disturbances in the development of physiological hemisphere asymmetry are assumed to play a pathogenetic role. The most striking difference between hemispheres is in language processing. The left hemisphere is superior in the use of syntactic or semantic information, whereas the right hemisphere uses contextual information more effectively. METHOD: Using psycholinguistic experimental techniques, semantic associations were examined in 38 control subjects, 24 non-thought-disordered and 16 thought-disordered people with schizophrenia, for both hemispheres separately. RESULTS: Direct semantic priming did not differ between the hemispheres in any of the groups. Only thought-disordered people showed significant indirect semantic priming in the left hemisphere. CONCLUSIONS: The results support: (a) a prominent role of the right hemisphere for remote associations; (b) enhanced spreading of semantic associations in thought-disordered subjects; and (c) disorganisation of the functional asymmetry of semantic processing in thought-disordered subjects.
OBJECTIVE: To determine the levels of CA-125 throughout pregnancy and the puerperium to establish a baseline, thereby indicating what values may be indicative of the pathologic conditions usually associated with elevated CA-125 levels. STUDY DESIGN: A prospective, longitudinal study was carried out on a consecutive series of pregnant women to determine their CA-125 levels throughout pregnancy and during the puerperium. Blood was drawn at four- to six-week intervals for clinically indicated tests. The residual sera were kept frozen, and subsequently CA-125 measurements were determined by radioimmunoassay. RESULTS: Of 34 women enrolled in the study, 20 completed the evaluations throughout pregnancy and in the puerperium. The remaining 14 had evaluations for varying portions of their pregnancies but not throughout pregnancy or during the puerperium. The results in these two groups were compared and found not to be statistically significantly different. For the group as a whole, the levels of CA-125 were high, with wide fluctuations in the first trimester; the levels in the early first trimester (five to eight weeks) were particularly high, with a mean of 55.8 and median of 36.2 (range, 6.9-251.2) U/mL. The levels then dropped and remained < 35 U/mL through the rest of pregnancy (including immediately prior to delivery). Another peak, with wide fluctuations, occurred soon after delivery, with a mean of 39.8 and median of 41.9 (range, 10.7-296.7) U/mL. In the late postpartum period (2-10 weeks after delivery) there was a return to baseline levels in all subjects. CONCLUSION: This study showed that there is a distinct pattern in CA-125 levels during pregnancy and the puerperium. Due to the wide fluctuations in CA-125 levels in very early pregnancy and the immediate postpartum period, CA-125 values during these periods are not useful for clinical correlation with the pathologic conditions known to be associated with elevated levels of CA-125. However, further study is needed to determine whether extreme values in the first trimester or elevated levels after the first trimester are diagnostic or predictive of any conditions related to pregnancy.
OBJECTIVE: To determine whether women who require tuboplasty for infertility and have associated uterine leiomyomas that require removal should have the myomectomy done concurrently. STUDY DESIGN: Eighty-nine infertility patients underwent tuboplasty alone for proximal tubal obstruction, 30 others were treated by both myomectomy and tuboplasty during the same operation, and 15 others underwent tuboplasty, leaving the myomas in situ. The tuboplasty in all cases consisted of tubal resection and anastomosis (TRA). The pregnancy rates and outcomes in the three groups were compared. RESULTS: Of the 89 patients who underwent TRA alone, 74.2% (66 patients) became pregnant, and of those 66, 15.2% had a spontaneous miscarriage, 24.2% developed an ectopic pregnancy, and 60.6% achieved a viable birth. By comparison, of 30 patients who had both TRA and myomectomy, 63.6% (19 patients) conceived, and of those 19, 15.8% miscarried, 26.3% developed ectopic pregnancies, and 57.9% achieved viable births. Of 15 patients who underwent TRA leaving the myomas in situ, 73% (11) became pregnant, and of those 11, 45% (5) miscarried, 18% (2) had ectopic pregnancies and 36% (4) gave birth to viable infants. The incidence of pregnancies, ectopic gestations, miscarriages and viable births in the three groups showed no statistical differences. CONCLUSION: When myomectomy is indicated, because of the lack of disadvantages of performing it at the time of tuboplasty, the combined surgical approach should be the procedure of choice rather than leaving the myomas in situ for their removal in a separate operation at a later date.
The general reduction of P300 amplitude in response to auditory oddball stimuli is one of the most consistently replicated biological observations in schizophrenic patients. Several groups have reported a P300 asymmetry in schizophrenic patients, others have not been able to replicate this finding. In order to clarify this issue, we examined the effect of stimulus discriminability on P300 amplitude distribution in schizophrenic patients and in age-matched normal control subjects, using two different auditory oddball paradigms. The detection of the target tone was either simple or difficult, due to manipulation of pitch disparity. The P300 amplitude was comparatively smaller in the schizophrenic patient group compared to the healthy controls and in the difficult task compared to the simple. The schizophrenic patients showed a specific P300 amplitude reduction over left temporal electrode sites when the simple paradigm was used. The difficult paradigm did not elicit asymmetrical P300 amplitudes in schizophrenic patients.
OBJECTIVE: The objective was to determine if repeating a Pap smear at the time of an initial colposcopy has sufficient clinical benefit to justify its clinical and financial costs. METHODS: The records were reviewed of all patients who had an initial colposcopy at Queens Hospital Center between 1984 and 1995. Data were gathered regarding the referral cytology, the cytology done at the time of colposcopy, and the results of any biopsies which were taken. The terminology for cytology and histology done prior to 1989 was adjusted to the Bethesda classification system. A repeat Pap smear was defined as clinically valuable if it would have changed the patient's management, i.e., if it suggested more advanced disease than the referral Pap and that the disease was not identified on the colposcopically directed biopsy. RESULTS: Two thousand nine hundred sixty-nine records were reviewed. In 139 cases, no Pap smear was repeated at the time of colposcopy. Of the remaining 2830 women, only 1347 (47.6%) showed exact correlation between their referral Pap smear and the Pap done at the time of colposcopy. In another 1016 (35.9%), the Pap at colposcopy was within one grade of the referral Pap. In 312 women, the Pap at the time of colposcopy was a higher grade than the referral Pap. However, in 236, the higher grade of disease was detected by the colposcopically directed biopsy. Of the remaining 76 women, 58 had a normal biopsy, but their Pap at the time of colposcopy showed low-grade squamous intraepithelial lesions (44) or high-grade squamous intraepithelial lesions (HGSIL) (14). Seventeen others had a biopsy showing low-grade dysplasia while the Pap at the time of colposcopy showed HGSIL. In 1 patient, the repeat Pap showed malignant cells while the biopsy showed a high-grade lesion. Based on the triage protocols at our institution, this means that a repeat Pap at the time of colposcopy would have indicated a cone biopsy in 31 patients (1.1%) and more careful follow-up of another 44 patients (1.6%). Skipping the repeat Pap smear would not have resulted in any missed cancers. In our series of 2830 patients, the cost savings of skipping the repeat smear would have been $68,580 or $24.23 per patient. On a national level, skipping the repeat smear would save more than $24,000,000 annually. CONCLUSION: Using current triage protocols at our institution, repeating the Pap smear at the time of an initial colposcopy would have changed the management in 2.7% of patients and indicated a conization in only 1.1% of patients. It is doubtful that this justifies its cost and the potential detrimental effects on the colposcopic examination.
Within the past 10 years, computer simulations of neural networks have yielded new insights into the nature of information-processing neural systems. Since 1987, more and more network models relevant to psychiatry have been published, and such models have meanwhile been proposed for almost every psychopathological phenomenon. This paper provides an introduction to the theory of neural networks and gives examples of discoveries made via computer simulations. Network models of psychopathological phenomena are discussed with respect to formal thought disorder and delusions. The relevance of neural network models for psychopathological research and theory formulation is highlighted and it is argued that neural network modeling in psychopathology does not merely introduce a few mathematical gimmicks, but rather represents the beginning of a new basis for psychopathology.