Psychological stress during in vitro fertilization and embryo transfer is influenced by the patients' background and gender.

Purpose: This study evaluated the changes in psychological stress during in vitro fertilization and embryo transfer (IVF-ET) and the relationship of such stress to the patients' background and gender. Methods: Sixty couples undergoing IVF-ET were administered the State-Trait Anxiety Inventory-JYZ (STAI) test at six different points during IVF-ET procedures. Anxiety scores at each time point were recorded and analyzed according to gender, fertility status, and duration of treatment. Results: The median state anxiety score for women increased following induction until oocyte collection, after which it temporarily declined and then increased again until the pregnancy test. No such changes were noted in men. Scores for women who had undergone a shorter period of IVF treatments were higher while state and trait anxiety in men increased with a prolonged treatment period. Unsuccessful treatment increased the state and trait anxiety of women. Conclusions: Psychological stress changed periodically depending on the duration of the patients' treatment and fertility status also influenced anxiety levels. These findings will prove helpful in guiding psychological therapy and counseling for couples attempting to conceive by in vitro fertilization.

Mutational analysis of the hepatitis C virus E1 glycoprotein in retroviral pseudoparticles and cell-culture-derived H77/JFH1 chimeric infectious virus particles.

Cell entry by enveloped viruses is mediated by viral glycoproteins, and generally involves a short hydrophobic peptide (fusion peptide) that inserts into the cellular membrane. An internal hydrophobic domain within E1 (aa262-290) of hepatitis C virus (HCV) may function as a fusion peptide. Retrovirus-based HCV-pseudotyped viruses (HCVpp; genotype 1a) containing Ala or Pro substitutions at conserved amino acid positions within this putative fusion peptide were generated. Mutation of conserved residues significantly reduced efficiency of HCVpp entry into Huh-7 cells. The majority of amino acid substitutions appeared to disrupt necessary interactions between E1 and E2. For some mutants, reductions in HCVpp-associated E1 were associated with the incorporation of a high molecular weight, hyperglycosylated E2 that displayed decreased CD81-binding. Other entry-deficient mutants displayed normal E1E2 incorporation into pseudoparticles and normal CD81-binding, and therefore might affect viral fusion. One mutant (S283P) consistently displayed two- to threefold higher infectivity than did wild-type. Three mutations that decreased HCVpp infectivity also reduced levels of HCVcc infectious virus production. However, the S283P mutation had a different effect in the two systems as it did not increase production of infectious HCVcc. This comprehensive mutational analysis of the putative HCV fusion peptide provides insight into the role of E1 in its interaction with E2 and in HCV entry.

Psychosocial factors are independent risk factors for the development of Type 2 diabetes in Japanese workers with impaired fasting glucose and/or impaired glucose tolerance.

AIMS: We prospectively studied Japanese workers with impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT) and analysed possible risk factors for diabetes, including psychosocial factors such as stress. METHODS: The participants were 128 male Japanese company employees (mean age, 49.3 +/- 5.9 years) with IFG and/or IGT diagnosed by oral glucose tolerance test (OGTT). Participants were prospectively studied for 5 years with annual OGTTs. The Kaplan-Meier method and Cox's proportional hazard model were used to analyse the incidence of diabetes and the factors affecting glucose tolerance, including anthropometric, biochemical and social-psychological factors. RESULTS: Of 128 participants, 36 (28.1%) developed diabetes and 39 (30.5%) returned to normal glucose tolerance (NGT) during a mean follow-up of 3.2 years. Independent risk factors for diabetes were night duty [hazard ratio (HR) = 5.48, P = 0.002], higher fasting plasma glucose (FPG) levels within 6.1-6.9 mmol/l (HR = 1.05, P = 0.031), stress (HR = 3.81, P = 0.037) and administrative position (HR = 12.70, P = 0.045), while independent factors associated with recovery were lower FPG levels (HR = 0.94, P = 0.017), being a white-collar worker (HR = 0.34, P = 0.033), non-smoking (HR = 0.31, P = 0.040) and lower serum alanine aminotransferase (ALT) levels (HR = 0.97, P = 0.042). CONCLUSIONS: In addition to FPG levels at baseline, psychosocial factors (night duty, stress and administrative position) are risk factors for Type 2 diabetes, while being a white-collar worker, a non-smoker and lower serum ALT levels are factors associated with return to NGT in Japanese workers with IFG and/or IGT.

Pharmacokinetics of zonisamide and drug interaction with phenobarbital in dogs.

The purposes of the present study were to elucidate the pharmacokinetics of zonisamide, determine the presence of a drug interaction with phenobarbital, and evaluate how long any interaction lasted after discontinuation of phenobarbital in dogs. Five dogs received zonisamide (5 mg/kg, p.o. and i.v.) before and during repeated oral administration of phenobarbital (5 mg/kg, bid, for 30-35 days). Zonisamide (5 mg/kg, p.o.) was also administered 8, 10, and 12 weeks after discontinuation of phenobarbital. Blood was sampled until 24 h after each zonisamide administration and serum concentrations of zonisamide were determined. Repeated phenobarbital decreased the maximum serum concentration, area under the serum concentration vs. time curve, apparent elimination half-life, and bioavailability of zonisamide. Total clearance increased. Time to maximum serum concentration and volume distribution were not changed. The maximum serum concentration and area under the serum concentration vs. time curve of zonisamide continued to be low until 10 weeks after the discontinuation of phenobarbital. They were restored to the same serum concentration as before phenobarbital administration 12 weeks after the discontinuation of phenobarbital. These data suggested that repeated administration of a clinical dose of phenobarbital enhanced the clearance of zonisamide and the enhanced clearance lasted at least 10 weeks after the discontinuation of phenobarbital. Caution may be necessary when zonisamide is given with phenobarbital and when antiepileptic therapy is changed from phenobarbital to zonisamide.

[The present studies of the development of HCV vaccine].

After isolation of a hepatitis C virus genome in 1989, all donated blood samples have been analyzed by a sensitive screening system, which brought us 'safety transfusion' (free from HCV). However it is likely that about 170 million people around the world, more than 2 million people in Japan have already infected with HCV. Despite the numerous efforts, the lack of efficient cell culture system makes it difficult to develop HCV vaccine. Some novel strategies are engineered day by day that might be useful tools. Hereafter we must clarify the mechanisms of replication and infection in depth, to develop a vaccine that clear HCV from carrier.

Intraoperative measurement of arterial blood flow using a transit time flowmeter: monitoring of hemodynamic changes during cerebrovascular surgery.

BACKGROUND: The purpose of this study was to examine the utility and reliability of arterial flow measurements made with a transit time ultrasonic flowmeter for monitoring blood flow changes during intracranial and carotid surgery. METHOD: A total of 25 patients underwent intra-operative arterial blood flow measurements. The pulsatile flow curve and mean flow values were obtained using 1- to 6-mm transit time probes with a dual channel flowmeter. Four cases underwent aneurysm clipping, 11 cases superficial temporal artery (STA)--middle cerebral artery (MCA) bypass, 2 cases external carotid artery (ECA)--radial artery--MCA bypass for aneurysm trapping, and 8 cases carotid endarterectomy. In aneurysm clipping, blood flow in the branches distal to the aneurysm was measured before and after clipping. Blood flow in the STA was measured before and after STA-MCA anastomosis, and blood flow in the internal carotid artery (ICA) cervical portion was measured during carotid endarterectomy. Blood flow in the MCA and STA was monitored during radial artery grafting. FINDINGS: Blood flow in the STA was elevated after STA-MCA anastomosis. However, post-operative hyperperfusion syndrome was found in some cases whose flow elevation was over 50 ml/min. Also in one case of carotid stenosis, of which blood flow of ICA was elevated to 400 ml/min after carotid endarterectomy, hyperperfusion syndrome was found after surgery. In the cases of MCA aneurysm clipping, decreasing of M2 flow was detected when clipping caused bifurcation stenosis. INTERPRETATION: We found transit time flow measurement useful for management of cerebrovascular surgery: the technique was simple to use and provided stable, reliable results. The method was able to reveal distal branch flow diminution in aneurysm clipping, or residual flow during temporary clipping in aneurysm surgery, and has the potential to predict post-operative complications such as hyperperfusion by signalling over-elevation of donor artery flow in bypass surgery or ICA flow in carotid surgery.

Low-intensity pulsed ultrasound initiates bone healing in rat nonunion fracture model.

Low-intensity pulsed ultrasound exposure has been shown clinically to shorten the fracture repair process and to induce healing of nonunions in humans, but its mechanism of action remains unclear. In this study we investigated the effect and mechanism of low-intensity pulsed ultrasound on nonunion fracture healing in rat tibias. A consistently reproducible nonunion was produced in rat tibias by muscle interposition without osteotomy. This model was produced by creating a closed tibial fracture with only the distal end of the tibialis anterior muscle interposed into the fracture site. One limb was noninvasively exposed to low-intensity pulsed ultrasound (a 200-millisecond burst of sine waves of 1.5 MHz, repeating at 1.0 kHz) for 20 minutes daily. The incident intensity was approximately 30 mW/cm2. Rats were killed at intervals between 2 and 6 weeks. The events were assessed by radiographs, microfocus X-ray computed tomograms, and histologic examination. After 6 weeks of exposure, 7 of 14 nonunion fractures showed healing on radiologic assessment. The results of three-dimensional microfocus X-ray computed tomographic reconstruction and histologic examination also supported this finding. On the other hand, all control tibias remained in a state of nonunion during the same period. These results indicate that low-intensity pulsed ultrasound promotes healing in the rat nonunion fracture model.

Cell fusion activity of hepatitis C virus envelope proteins.

To examine the cell fusion activity of hepatitis C virus (HCV) envelope proteins (E1 and E2), we have established a sensitive cell fusion assay based on the activation of a reporter gene as described previously (O. Nussbaum, C. C. Broder, and E. A. Berger, J. Virol. 68:5411-5422, 1994). The chimeric HCV E1 and E2 proteins, each consisting of the ectodomain of the E1 and E2 envelope protein and the transmembrane and cytoplasmic domains of the vesicular stomatitis virus G glycoprotein, were expressed on the cell surface. Cells expressing the chimeric envelope proteins and T7 RNA polymerase were cocultured with the various target cell lines transfected with a reporter plasmid encoding the luciferase gene under the control of the T7 promoter. After cocultivation, the cell fusion activity was determined by the expression of luciferase in the cocultured cells. The induction of cell fusion requires both the chimeric E1 and E2 proteins and occurs in a low-pH-dependent manner. Although it has been shown that HCV E2 protein binds human CD81 (P. Pileri, Y. Uematsu, S. Campagnoli, G. Galli, F. Falugi, R. Petracca, A. J. Weiner, M. Houghton, D. Rosa, G. Grandi, and S. Abrignani, Science 282:938-941, 1998), the expression of human CD81 alone is not sufficient to confer susceptibility to cell fusion in the mouse cell line. Treatment of the target cells with pronase, heparinase, or heparitinase reduced the cell fusion activity induced by the chimeric envelope proteins. These results suggest (i) that both HCV E1 and E2 proteins are responsible for fusion with the endosomal membrane after endocytosis and (ii) that certain protein molecules other than human CD81 and some glycosaminoglycans on the cell surface are also involved in the cell fusion induced by HCV.

The enzyme that synthesizes tetrahydrobiopterin from 6-pyruvoyl-tetrahydropterin in the lemon mutant silkworm consists of two carbonyl reductases.

Tetrahydrobiopterin plays an important role in the biosynthesis of certain neurotransmitters. Using DEAE-Sepharose FF column chromatography, we separated the enzyme that synthesizes tetrahydrobiopterin from 6-pyruvoyl-tetrahydropterin [which is different from sepiapterin reductase (EC 1.1.1.153)] in the lemon mutant of the silkworm Bombyx mori into two fractions, which were named carbonyl reductase I (CR I) and carbonyl reductase II (CR II). The CR I enzyme converted 6-pyruvoyl-tetrahydropterin to 6-lactoyl-tetrahydropterin, while CR II converted 6-pyruvoyl-tetrahydropterin to 1'-hydroxy-2'-oxopropyl-tetrahydropterin, both reactions occurring only in the presence of NADPH. Neither of the two carbonyl reductases alone was able to catalyze the conversion of 6-pyruvoyl-tetrahydropterin to tetrahydrobiopterin in the presence of NADPH. However, when CR I was mixed with CR II in the reaction mixture, 6-pyruvoyl-tetrahydropterin was reduced to tetrahydrobiopterin in the presence of NADPH. Moreover, CR I catalyzed the formation of tetrahydrobiopterin from 1'-hydroxy-2'-oxopropyl-tetrahydropterin, while CR II converted 6-lactoyl-tetrahydropterin to tetrahydrobiopterin, both reactions occurring only in the presence of NADPH. Our results suggest that there are two potential routes for formation of tetrahydrobiopterin from 6-pyruvoyl-tetrahydropterin in the lemon mutant silkworm. In the first route, 1'-hydroxy-2'-oxopropyl-tetrahydropterin is formed from 6-pyruvoyl-tetrahydropterin by CR II and then reduced to tetrahydrobiopterin by CR I, both reactions occurring only in the presence of NADPH. In the other route, 6-pyruvoyl-tetrahydropterin is reduced to 6-lactoyl-tetrahydropterin by CR I and then converted to tetrahydrobiopterin by CR II, both reactions occurring only in the presence of NADPH.

[Validation and optimization of the use of standardized arterial input function in N-isopropyl-p[123I]iodoamphetamine cerebral blood flow SPECT].

UNLABELLED: Use of a standardized arterial input function and calibrating it by a single blood sample has been proposed to assess quantitatively cerebral blood flow using N-isopropyl-p[123I]iodoamphetamine (IMP) and single-photon emission computed tomography. This study was intended to validate this approach using a larger number of measured arterial radioactivity curves in the clinical setting. METHOD: Arterial input function was measured for 50 patients at rest following the i.v. IMP, and its inter-subject variation was assessed. Difference between smokers and non-smokers in addition to effects of acetazolamide administration were particularly investigated. We also evaluated the accuracy of the calibration procedures by means of either a single blood sample or a continuous arterial blood withdrawal sampling for an early period. RESULTS: Inter-subject variation of the observed arterial input function appeared not to show large variations among the 50 patients, thus suggesting the validity of using the standardized arterial input function for the IMP SPECT study. There was a significant difference in the shape of the arterial input function between the smokers and non-smokers, but the calibration at an optimized sampling time provided the area-under-the curve (AUC) that was not significantly different between the two groups. The arterial input function after the acetazolamide showed no significant difference as compared with the shape at rest. The calibration of the standardized input function by means of the early integration of individual curve did not show better accuracy except for a short period of AUC (i.e., < 20 min) for longer integration period > 10 min. CONCLUSION: Thus, use of the standardized arterial input function has been validated for the IMP SPECT study. The single blood sampling procedure for calibrating the standardized input function has also been validated, and has been shown to provide better accuracy compared with the continuous withdrawal procedure.

[Digital recording in neurosurgery].

The purpose of this study is to examine the image quality of multi-media for digital recording of surgical procedure using an operating microscope in neurosurgery. For video recording, high vision recording, digital video recording and analogue VHS recording were used. For still pictures, an analogue camera with 35 mm silver halide film and a micro-digital camera were used. The quality of photographs taken with a microdigital camera was superior to the quality of those taken with the conventional 35 mm film camera. The micro-digital camera system is superior to the conventional 35 mm camera in neurosurgery in its quality and success rate. In video recording, high vision analogue recording was superior to any other media as far as its image quality is concerned although its practical convenience is limited and cost performance is not always good. On the other hand, digital video can record high quality images, including still pictures, with satisfactory quality to the neurosurgeon. These digital recording media are also space saving for storing the huge amount of data obtained during surgery and the cost-performance is superior to that of the conventional method. In the near future, most of surgical procedures are supposed to be expected using digital media.

Intra-operative premature rupture of the cerebral aneurysms. Analysis of the causes and management.

The causes and management of intra-operative premature rupture are analysed and discussed. During the past 6 years, the authors, performed 398 consecutive direct surgical interventions for ruptured cerebral aneurysms. Intra-operative premature rupture is defined as a rupture which occurs before the securing of the parent arteries or the neck of the aneurysm and is out of control, at least temporarily. The causes and management were retrospectively analyzed by reviewing video tape recordings. Intra-operative premature ruptures which met the above definition occurred in 24 cases (6.0%). The causes were as follows: 1.) dural opening and arachnoid opening (8.3%), 2.) haematoma removal (12.5%), 3.) brain retraction (16.7%), 4.) aneurysm dissection (62.5%). A double suction technique was used to control bleeding and haemostasis with a small piece of cotton or a temporary clip, performed in 20 cases (83.3%). However, in cases with premature rupture immediately after the dural or arachnoid opening, the extension of the haematoma into the subarachnoid space resulted in severe brain swelling and partial resection of the brain had to be done to secure temporary clipping. The double suction technique and primary haemostasis using a small piece of cotton or temporary clip resulted in good outcome even in cases with premature rupture. However, very early premature rupture also occurred although its incidence was extremely rare. The removal of part of the brain can secure the working space but the outcome was poor.

Bladder wall radiation dose in humans from fluorine-18-FDOPA.

UNLABELLED: PET, in conjunction with 18F-fluorodopa (FDOPA), has become the standard technique to assess basal ganglia degeneration in patients with movement disorders. Based on published dosimetry data, the injected dose of FDOPA is limited to 111 Mbq (3 mCi) because of exposure to the bladder wall, which is the critical organ for such studies. These dosimetry studies are based on mathematical models for the bladder radioactivity accumulation and clearance when the subjects were asked to void approximately 2 hr after the intravenous injection of FDOPA. In this study, we improved the radiation dose estimate to the bladder wall using dynamic PET to image the bladder during the uptake phase as well as before and after voiding. METHODS: The subjects were tested on a new protocol. They were hydrated preinjection and given a first bladder void break at 40 min postinjection and a second void at the end of study at 120 min. RESULTS: The MIRD model, applied to the data collected from 10 adults of both sexes, yielded an average absorbed dose of 0.15 +/- 0.08 mGy/MBq (0.57 +/- 0.28 rad/mCi). CONCLUSION: This absorbed dose is significantly lower than previous estimates and allows for FDOPA injections up to 333 Mbq (9 mCi).

Discovery of a new tetrahydrobiopterin-synthesizing enzyme in the lemon mutant of the silkworm Bombyx mori.

A new tetrahydrobiopterin-synthesizing enzyme, which is different from sepiapterin reductase (EC 1.1.1.153), was discovered in the integument of the lemon mutant of the silkworm Bombyx mori. This enzyme converted 6-pyruvoyltetrahydropterin to tetrahydrobiopterin, an essential cofactor in the hydroxylation of aromatic amino acids, in the presence of NADPH. The reaction proceeded via 6-lactoyltetrahydropterin and 1'-hydroxy-2'-oxopropyltetrahydropterin as intermediates. The molecular mass of this enzyme was estimated to be 40 kDa. N-Acetylserotonin, a potent inhibitor of sepiapterin reductase, slightly inhibited the enzymatic reaction. In the presence of 0.5 mM N-acetylserotonin, the formation of tetrahydrobiopterin by sepiapterin reductase purified from the normal strain silkworm was completely inhibited. However, the formation of tetrahydrobiopterin by the enzyme purified from the lemon mutant was inhibited by only about 50%. These results suggest an alternative biosynthetic pathway to tetrahydrobiopterin.

Cerebral metabolic topography in unilateral temporal lobe epilepsy.

OBJECTIVE: Fluorodeoxyglucose positron emission tomography (FDG-PET) studies of temporal lobe epilepsy (TLE) generally report interictal hypometabolism in the vicinity of the seizure focus. Yet, other evidence suggests that interictal metabolic abnormalities might extend to remote brain areas. We used FDG-PET to evaluate metabolism in selected regions distant from the focus in TLE. SUBJECTS: Twenty adult patients with medically intractable TLE were selected by criteria favoring a unilateral mesiobasal temporal focus. Structural imaging in this sample were normal except for medial temporal sclerosis in 13 patients. Twenty normal volunteers were controls. DESIGN: PET imaging was performed interictally. Regional glucose metabolism normalized by global metabolism was analyzed using t tests and correlation analysis. RESULTS: Ipsilateral to the seizure focus, metabolism was depressed compared with normal in the temporal pole (p = 0.001), but relatively elevated in the mesiobasal region (p = 0.005). Contralateral to the focus, metabolism was elevated in lateral temporal cortex (p = 0.0003) and mesiobasal regions (p = 0.0001). Metabolic correlation between ipsilateral and contralateral mesiobasal regions was similar in normal subjects (r = 0.74) and patients (r = 0.68). In contrast, correlations were abnormal between temporal poles and other temporal lobe subregions, both ipsilateral and contralateral to the seizure focus. CONCLUSIONS: Relative to normal values, both elevations and depressions of metabolism exist interictally in TLE. Such abnormalities, and accompanying changes in interregional correlations, may have wide spatial distribution. These findings are atypical among PET studies but are consistent with other physiologic, anatomic, and neuropsychological investigations of TLE.

[Pharmacokinetics of transbronchially injected flconazole in pulmonary aspergillosis].

A 68-year-old woman had a pulmonary aspergilloma in the left upper lobe, with old cavitary pulmonary tuberculosis. Surgery was not possible because of marginal ventilation, and the patient was treated by transbronchial injection of Fulconazole. After five injections of 50 mg of Fulconazole, the fungus ball had decreased in size. To study the pharmacokinetics of Fulconazole after transbronchial injection, its concentration in serum was measured. The values of serum Fulconazole concentration were 0.7 microgram/ml at 1 h, 0.8 microgram/ml at 4 h, 0.8 microgram/ml at 8 h, 0.7 microgram/ml at 12 h, 0.7 microgram/ml at 24 h, and 0 microgram/ml at 48 h after transbronchial injection. These results indicate that Fulconazole was absorbed well. Furthermore, these values are equal to those obtained after intravenous administration of 50 mg and are higher than those obtained after intravenous administration of 25 mg. Fulconazole may have been absorbed via the bronchial epithelium, because of destruction of alveoli, connective tissue proliferation in the cavitary wall and secondary bronchiectasis.

Anatomic and physiological considerations in pallidotomy for Parkinson's disease.

Our ongoing study of ventral pallidotomy for the control of Parkinson's disease in selected patients has provided the opportunity to explore the topographical and somatotopic organization of the human globus pallidus. Utilizing microelectrode techniques we have obtained recordings which were correlated with data from MPTP-parkinsonian primates. In addition, we performed pre- and post-operative FDG/PET scans in these patients. Our studies reveal similarities between the MPTP-parkinsonian primate model and human Parkinson's disease in terms of physiologic recordings and responses. However, we have encountered significant differences between dominant and non-dominant hemisphere representations, particularly for the hand, in the human. In addition, our PET studies confirmed, as in previous parkinsonian primate models, glucose hypermetabolism in the lenticular area of Parkinson's disease patients. This hypermetabolism is dramatically altered by creation of a lesion in the globus pallidus medialis. This is demonstrated by follow-up PET scans which reveal not only a decrease in metabolism of the operated lenticular region, but also in the frontal cortical projections. These combined observations of the cellular activity in the globus pallidus and the observed changes in PET metabolism support the selection of the pallidum for lesioning and control of Parkinson's disease, and offer insight into the underlying physiology of this disorder. The above physiological and PET data will be clinically correlated with our ongoing series of 35+ patients.

The metabolic topography of parkinsonism.

We used [18F]fluorodeoxyglucose/positron emission tomography (18F-FDG/PET) and a statistical model of regional covariation to study brain topographic organization in parkinsonism. We studied 22 patients with Parkinson's disease (PD), 20 age-matched normal volunteers, and 10 age- and severity-matched patients with presumed striatonigral degeneration (SND). We used FDG/PET to calculate global, regional, and normalized metabolic rates for glucose (GMR, rCMRglc, rCMRglc/GMR). Metabolic parameters in the three groups were compared using an analysis of variance, with a correction for multiple comparisons, and discriminant analysis. The scaled subprofile model (SSM) was applied to the combined rCMRglc dataset to identify topographic covariance profiles that distinguish PD patients from SND patients and normals. GMR, rCMRglc, and rCMRglc/GMR were normal in PD; caudate and lentiform rCMRglc/GMR was reduced in the SND group (p < 0.01). SSM analysis of the combined group of patients and normals revealed a significant topographic profile characterized by increased metabolic activity in the lentiform nucleus and thalamus associated with decreased activity in the lateral frontal, paracentral, inferior parietal, and parietooccipital areas. Individual subject scores for this profile were significantly elevated in PD patients compared with normals and SND patients (p < 0.001) and discriminated the three groups. In the PD group, subject scores for this factor correlated with individual subject Hoehn and Yahr (H & Y) scores (p < 0.02), and with quantitative rigidity (p < 0.01) and bradykinesia (p < 0.03) ratings, but not with tremor ratings. SSM analysis of right-left metabolic asymmetries yielded a topographic contrast profile that accurately discriminated mildly affected PD patients (H & Y Stage I) from normals. Our findings demonstrate that abnormal topographic covariance profiles exist in parkinsonism. These profiles have potential clinical application as neuroimaging markers in parkinsonism.