Diversity of Xanthomonas campestris Isolates from Symptomatic Crucifers in New York State.

To assess the diversity of Xanthomonas campestris spp. infecting crucifers in New York, 154 isolates were collected over 10 years across the state. The goal was to determine if isolates of the pathogen were overwintering in New York and serving as primary inoculum in subsequent years, or if novel isolates were entering the state each year. Pure cultures of isolates were characterized using multilocus sequence analysis (MLSA), a greenhouse pathogenicity assay, repetitive element-polymerase chain reaction (Rep-PCR) using the BOX-A1R primer, and enzyme-linked immunosorbent assay. The MLSA scheme proved to be more efficient than Rep-PCR for a large sample population and for comparison with global isolates. X. campestris isolated from crucifers in New York comprised of X. campestris pv. campestris and X. campestris pv. raphani, with X. campestris pv. raphani being predominately isolated from transplants. Evidence for unique haplotypes persisting on the same farm for several years due to improper seedbed rotations was documented in addition to novel haplotypes being spread throughout states through infected transplants and seed. Rep-PCR confirmed the high diversity of X. campestris and was used to generate 15 unique fingerprint patterns from isolates collected in the first 5 years. A worldwide comparison of isolates suggests that the X. campestris pv. campestris population appears to be very homogenous with dominant haplotypes persisting for extended periods and being globally disseminated.

Differential effect of Huntington's and Parkinson's diseases in programming motor sequences of varied lengths.

BACKGROUND: Parkinson's disease (PD) and Huntington's disease (HD) patients have difficulties executing sequential movements. Attention control and short-term memory probably play an important role in programming sequential movements. To investigate the contribution of these cognitive factors to programming and executing visuomotor sequences in HD and PD patients a computerized version of the Corsi Block Tapping-Test was employed. METHODS: the performance of 11 patients with early stage PD, 11 HD patients with borderline to mild caudate atrophy and 20 healthy subjects was compared. The task was a reaction time task where targets were illuminated in groups of sequences increasing from 2 items to 5 items. Subjects reproduced the sequence (pressing the illuminated target) in the same order of appearance. Reaction Times and movement times were recorded. RESULTS: PD patients had increasing difficulties in programming and executing series greater than three components. HD patients did not differ significantly from the controls, although they showed a tendency to lose accuracy in the longer series. Both patient groups did not differ in their attention span. CONCLUSIONS: In PD although the spatial information may be well stored, they have difficulty accessing it when their attention is overloaded, leading to poor encoding and slow information processing. This process interferes with programming and execution of movement sequences. HD patients in the early stages of the illness seem to have more attention resources than PD patients, so that they start to show more problems in executing visuomotor sequences with longer movement sequences than PD patients.

The benzamide tiapride: treatment of extrapyramidal motor and other clinical syndromes.

The benzamide derivative tiapride (Tiapridex, Synthelabo) has a highly selective antagonistic effect on striatal adenylate cyclase-independent dopamine-2 receptors. Its in vitro binding affinity is especially high for dopamine receptors which have been sensitized by pre-incubation with dopamine. The involvement of altered dopamine receptor sensitivity in several extrapyramidal dys- and hyperkinesia has been hypothesized. By its high affinity for these receptors, without any affinity for other neurotransmitter receptors of the brain, tiapride is especially well suited for the treatment of movement disorders related to functional dopamine hyperactivity. Even at higher doses, tiapride does not exceed a D2-receptor occupancy of 80%, which is in accordance with the finding that tiapride rarely causes acute extrapyramidal syndromes and has, up to now, never implicated in inducing tardive dyskinesias. On the contrary, clinical studies demonstrate its excellent efficacy in neuroleptic-induced tardive dyskinesia, L-Dopa-induced dyskinesias, psychomotor agitation in geriatric patients and choreatic movement disorders. Since tiapride is not available in the USA as yet, most of the studies concerning tiapride have been carried out in Europe. In a recent study, based on objective measurements, tiapride effectively controlled choreatic movements in patients suffering from Huntington's disease (HD). Tiapride is well tolerated in daily doses between 300 and 1200 mg. Adverse events are generally rare and mild.

Velocity modulation and rhythmic synchronization of gait in Huntington's disease.

This study analyzed the ability of patients with Huntington's disease (HD) to modulate gait velocity without external sensory cues and in response to an auditory rhythmic cue within a frequency entrainment design. Uncued gait patterns of 27 patients were first assessed during normal, slower, and faster self-paced walking. During rhythmic trials, metronome and musical beat patterns were delivered at rates 10% slower and 10-20% faster than baseline cadence to cue gait patterns. After the rhythmic trials, patients were retested at normal gait speed without rhythm. Gait velocities in the patients with HD were below normal reference values in all ranges. Patients were able to significantly (p <0.05) modulate their gait velocity during self-paced and rhythmic metronome cueing but not during music. The ability to modulate gait velocity was retained regardless of the severity of the disease. Gait velocity declined with an increase in disability and chorea score. The disability score differentiated better between gait velocity of moderately and severe patients than chorea score. Slowness of gait was significantly correlated only with disability score and not with chorea. Patients had more difficulty producing adequate step rates than stride lengths during normal and fast walking speeds. After the rhythmic trials, unpaced gait velocity remained significantly (p <0.05) higher than baseline. This carry-over effect was not seen after the uncued trials. Synchronization ability was deficient in all patients, deteriorated with severity of disease, and was already compromised in patients with soft disease signs. Rhythmic tracking of music declined more with severity of disease than metronome tracking. In summary, patients were able to modulate velocity with and without external cues. Velocity adaptations to the external rhythm in music and metronome were achieved without exact synchronization between step cadence and rhythmic stimulus.

Motor learning by imagery is differentially affected in Parkinson's and Huntington's diseases.

Studies of motor imagery and motor learning have thus far been concerned only with its effects on healthy subjects. Therefore, in order to investigate the possible involvement of the basal ganglia, the effectiveness of motor imagery in the acquisition of motor constants in a graphomotor trajectorial learning task was examined in 11 non-demented mildly affected Huntington's disease (HD) patients and 12 non-demented Parkinson's disease (PD) patients. The patients received, after baseline, 10 min of motor imagery training, followed by a motor practice phase. Additionally, a test battery for visual imagery abilities was administered in order to investigate possible relations between visual and motor imagery. The results showed that imagery training alone enabled the HD patients to achieve a significant approach to movement isochrony, whereas the PD patients showed no marked improvements, either with motor imagery or with motor practice. Furthermore, the PD patients had more difficulties than the HD patients in solving the visual imagery tasks. Subsequent correlational analysis revealed significant relationships between the degree of caudate atrophy in the HD patients and their performance in the visual imagery tasks. However, there were no substantial correlations between the performance on the visual imagery tasks and the improvement of motor performance through motor imagery, which indicates that visual and motor imagery are independent processes. It is suggested that the dopaminergic input to the basal ganglia plays an important role in the translation of motor representations into motor performance, whereas the caudate nucleus atrophy of the HD patients does not seem to affect motor imagery, but only the visual imagery process. Furthermore, the deficits found in PD patients might also be related to their limited attentional resources and difficulties in employing predictive motor strategies.

Neurophysiological abnormalities in the Westphal variant of Huntington's disease.

The Westphal variant of Huntington's disease (HD) is a distinct clinical entity of HD characterized by a rigid-hypokinetic syndrome and is often associated with a juvenile onset of disease. Definite genetic differences between the subtypes of HD have not been delineated so far. Here we present the results of a battery of neurophysiological tests including somatosensory-evoked potentials, blink reflexes, long-latency reflexes, and measurement of saccadic velocities in a Westphal HD patient. Although quantitative assessment of his motor performance showed a severe hypokinetic syndrome resembling Parkinson's disease, the results of somatosensory-evoked potentials and blink reflexes were indistinguishable from results obtained in hyperkinetic HD patients. Long-latency reflexes, however, which are typically absent in hyper-kinetic HD patients, were retained in this patient. It is concluded that neurophysiology in HD patients is not a mere reflection of the patient's symptomatology but can give insight into the underlying pathophysiological process.

Huntington's disease: N-methyl-D-aspartate receptor coagonist glycine is increased in platelets.

Experiments in vertebrates and striatal tissue cultures have provided evidence for a neuroexcitotoxic cause for the neurodegeneration in Huntington's disease (HD), via N-methyl-D-aspartate (NMDA) receptors. Glycine in vitro increases the response of NMDA receptors to its agonists via the NMDA receptor-associated glycine receptor, and the same effect has been observed in vivo. Significantly increased levels of glycine have previously been found in the cerebrospinal fluid of patients with HD. In this present study glycine was measured in platelets and plasma of patients with HD and in controls by high-pressure liquid chromatography. Mean glycine concentration was significantly increased (P < or = 0.01) in platelets in HD compared to controls, though plasma glycine was normal. A possible role for glycine in the pathogenesis of HD, based on the excitotoxicity hypothesis of HD, is discussed.

Decreased plasma alanine and isoleucine in Huntington's disease.

Amino acid concentrations in plasma of patients with Huntington's disease (HD) were determined in 16 patients and 21 age- and sex-matched healthy controls. Alanine and isoleucine were significantly decreased in HD plasma whereas arginine, histidine, leucine, lysine, ornithine, proline, serine, threonine, tyrosine, and valine showed no significant changes. Our findings confirm the decreases of alanine and isoleucine that were described in plasma and cerebrospinal fluid by other investigators. A possible defect in cellular uptake or metabolism of neutral amino acids seems to be a consistent feature of HD.

Associative learning in degenerative neostriatal disorders: contrasts in explicit and implicit remembering between Parkinson's and Huntington's diseases.

The performances of 12 patients with Parkinson's disease (PD), 16 with Huntington's disease (HD), and young and old healthy controls were assessed on a number of tests of verbal and nonverbal declarative memory, on a test of nonmotor conditional associative learning (words and colors), and on a number of reaction time (RT) tasks. The RT tasks consisted of cued simple and choice reactions. The relationship between the precue and the imperative stimulus in the S1-S2 paradigm was nonarbitrary in the first series and arbitrary in the second series. The series with arbitrary S1-S2 associations was repeated across two successive blocks of trials. The rationale of the study was to investigate the function of the basal ganglia "complex loop," and it was postulated that HD patients would show greater deficits because of greater involvement of the caudate nucleus. The patients with HD had the slowest RTs. Across the two blocks with arbitrary S1-S2 associations, the patients with HD but not PD nevertheless showed evidence of learning in their precued RTs. In contrast, the patients with PD were better able to remember the associations in free recall than were the HD patients. It is concluded that patients with PD have relatively greater deficits in procedural learning, whereas those with HD have relatively more impairments in declarative memory, and the greater level of cognitive impairment in HD overall is interpreted as being due to more serious damage to the caudate loop.

Huntington's disease: the neuroexcitotoxin aspartate is increased in platelets and decreased in plasma.

The neural degeneration observed in the striata of patients with Huntington's disease (HD) can be reproduced by excitatory NMDA receptor agonists such as aspartate and glutamate in striatal cell cultures and in striata of vertebrates injected with these substances. Therefore, we decided to investigate the role of aspartate and glutamate in HD. Aspartate, glutamate, glutamine, and phenylalanine were measured in platelets and plasma of HD patients and age- and sex-matched healthy controls (C), using HPLC methods. In HD platelets the mean aspartate concentration was significantly (p < 0.01) increased (8.9 +/- 3.8 (SD) nmol/mg protein, n = 28) compared to C (4.6 +/- 1.4 (SD) nmol/mg protein, n = 24), whereas plasma aspartate was significantly (p < 0.01) decreased in HD (0.092 +/- 0.023 (SD) mg/dl, n = 16) versus C (0.179 +/- 0.109 (SD) mg/dl, n = 21). The increase in platelet aspartate should be a direct or indirect consequence of the dominant gene defect in HD. It might therefore be present in neurons as well, especially since platelets share many characteristics with neurons. Hence, chronically increased release of aspartate with consecutive overstimulation of postsynaptic neurons via NMDA receptors might be responsible for the damage observed in striatal target cells of corticostriatal glutamatergic and aspartatergic projection fibers in HD.

SPECT with HMPAO compared to PET with FDG in Huntington disease.

OBJECTIVE: It is the aim of this study to compare the performance of 99mTc-d,l-hexamethylpropyleneamine oxime (HMPAO) SPECT with that of [18F]fluorodeoxyglucose (FDG) PET in detecting striatal dysfunction as it occurs in Huntington disease (HD). MATERIALS AND METHODS: For the determination of regional cerebral glucose consumption, the PET camera PC-4096 was used; the cerebral uptake of HMPAO was measured using the three-head SPECT camera TRIAD. Eight patients with manifest HD, seven subjects at risk for HD, and nine normal individuals were included in the study. In both modalities data evaluation was performed using caudate-to-whole-slice (C/S) ratios. The patients' data were compared to 95% confidence intervals determined in the nine controls. RESULTS: The PET and SPECT C/S values correlated significantly (n = 24; r = 0.87; p < 0.0001). The C/S values were significantly reduced in PET in all eight and in SPECT in seven of the eight HD patients studied. Five of the seven at-risk subjects had normal C/S values in PET and SPECT, one showed reduced C/S values in both diagnostic methods, and the remaining at-risk individual showed a reduced C/S value in PET only. Thus, concordant results between PET and SPECT were obtained in seven of eight patients and six of seven at-risk subjects studied, corresponding to an 87% accuracy of SPECT in the detection of striatal dysfunction as compared to the "gold standard" PET. CONCLUSION: With use of a multidetector camera, HMPAO-SPECT comes near the performance of FDG-PET in the diagnosis of striatal dysfunction as it occurs in HD.

Striatal glucose consumption in chorea-free subjects at risk of Huntington's disease.

Controversial data have been reported with regard to the diagnostic value of the positron emission tomographic (PET) measurement of striatal glucose consumption (rCMRGlc) in chorea-free subjects at risk of Huntington's disease (HD). For further clarification of this issue we measured striatal and cerebellar rCMRGlc in 27 chorea-free subjects at risk of HD, 20 patients with manifest HD and 20 control subjects, using PET and 18F-fluorodeoxyglucose. In 6 of the at-risk subjects cerebellar ratios of striatal rCMRGlc were decreased below the corresponding 99% confidence limit determined in the controls. This indicates that the PET measurement of rCMRGlc may, indeed, be valuable in establishing the diagnosis of incipient HD in presymptomatic at-risk subjects.

Pre- and postcentral somatosensory evoked potentials in Huntington's disease: effects of stimulus repetition rate.

We recorded frontal, central and parietal somatosensory evoked potentials (SEPs) to median nerve stimulation in 20 patients with Huntington's disease (HD) and in a group of normal controls. Two stimulus repetition rates, 1 Hz and 5 Hz, were employed. In HD patients the early cortical potentials (latency range 20-30 ms) at all 3 recording locations were replaced by a widespread, broadly configured N20-25 deflection, while later potentials at 40-80 ms did not significantly differ from those of normals. In contrast to the early P22, P27 and N30 potentials in normals, the N20-25 potential in the patients was not significantly modified by changing the stimulus repetition rate. At 40-80 ms the stimulus rate effects were similar in the patients and normals. The results show that early pre- and postcentral SEPs are both pathological in HD, while later frontal and parietal components can be totally preserved. The early N20-25 in HD is possibly a subcortical potential, seen due to unmasking in the absence of early cortical deflections.

Comparison of somatosensory evoked potentials with striatal glucose consumption measured by positron emission tomography in the early diagnosis of Huntington's disease.

Both somatosensory evoked potentials (SEP) and striatal glucose consumption (rCMRGlc) measured by positron emission tomography (PET) have been reported to be abnormal early in the course of Huntington's disease (HD). To compare their diagnostic value, SEP and rCMRGlc were measured in a group of 18 first degree off-spring of HD families: 6 had manifest HD with chorea and the remaining 12 individuals were chorea-free subjects at risk for HD. In five patients with manifest disease, both SEP and striatal rCMRGlc were significantly abnormal, defined in SEP as having either a bilaterally absent frontal N30 amplitude or a reduction of the parietal N20/P25 amplitude below 1 microV on at least one side; in PET as exhibiting a reduction of the cerebellar ratio (CR) of both caudate and lentiform rCMRGlc below the 99% confidence limits of these variables determined in 20 normal volunteers. The remaining patient with manifest HD had questionably abnormal SEP and significantly reduced indices of striatal rCMRGlc. The five persons at risk for HD who had normal SEP also had normal striatal rCMRGlc; those three at-risk patients with abnormal SEP also had a reduction of the CR of both caudate and lentiform rCMRGlc. Of the remaining four individuals at risk for HD who had questionably abnormal SEP, three had CR values of striatal rCMRGlc in the normal range and one a reduction of the CR of lentiform rCMRGlc. In at-risk patients, the SEP diagnosis correlated significantly with caudate (r = -0.8; p < 0.002) and lentiform (r = -0.76; p < 0.005) rCMRGlc. These data indicate a parallel deterioration of SEP and striatal rCMRGlc early in the course of HD even before the development of chorea.

Impairment of temporal organization of speech in basal ganglia diseases.

Absolute and relative speech timing were examined in patients suffering from Parkinson's, Huntington's, and Wilson's disease. The task was to speak a standard sentence 10 times, first slowly, and then successively faster up to maximum rate. All patient groups had low maximal speech rates and showed decreased variability of speech rate. The duration of pauses between words was the same as in normals and the relative time structure of the test sentence was basically preserved. For comparison, two cases with nonfluent aphasia had even slower speech rates, large increases in pause duration, and major changes in relative speech timing. The results show the same type of alterations of the temporal organization of speech as those characteristic for rapid alternating limb movements in such patients. They support the view that the speech and skeletomotor systems share common neural control modes despite fundamental biomechanical differences. The common denominator between the speech and the skeletomotor disturbances in basal ganglia diseases may be the undamping and slowing of a fast central oscillator.

Motor responses evoked by magnetic brain stimulation in Huntington's disease.

In 34 patients with manifest Huntington's disease (HD), and in 21 first-degree offspring without clinical signs or symptoms, the sizes, central motor latencies (CMLs) and variation in latencies of EMG responses (MEPs) following transcranial magnetic brain stimulation were studied in muscles of the upper and lower extremities. In subgroups of patients and their offspring median and tibial nerve somatosensory evoked potentials (SEPs) and electrically elicited long-loop reflexes (LLRs) in hand muscles were also investigated. Increased MEP thresholds were observed in 10% of the HD offspring, while CML, latency variability and MEP amplitudes always lay within normal range. In contrast, SEPs were abnormal in 33%. In HD patients MEPs were found to be abnormal in up to 72% of patients when all available response parameters were taken into consideration. MEP abnormalities correlated with the duration of motor symptoms and the severity of choreic motor activity. When both MEPs and SEPs were evaluated, abnormalities could be detected in 91% of all HD patients. We suggest that abnormal MEPs might reflect an altered excitability of the cortico-spinal system as a consequence of basal ganglia dysfunction, rather than a structural damage of the investigated descending pathways. To localize the pathological mechanism responsible for altered LLRs, a "loop analysis" was performed by recording LLRs, MEPs and SEPs in the same patients. Alterations of LLRs correlated best with abnormal SEPs and might therefore be explained by reduced somatosensory input to the motor cortex.

Exclusion of atrial thrombus by transesophageal echocardiography.

To determine whether transesophageal echocardiography (TEE) is useful in ruling out the presence of atrial thrombus, we performed TEE in 20 patients immediately before valve replacement or valve repair and within 3 days of an autopsy in one patient. Mitral stenosis was the predominant lesion in three patients, mitral regurgitation was seen in 11 patients, five patients had mitral prosthesis malfunction, one patient had a tricuspid prosthesis malfunction, and one patient had aortic stenosis. Eight patients were in atrial fibrillation. Four patients demonstrated spontaneous contrast in the associated atria. Nine patients were receiving oral anticoagulation. Mean left atrial diameter was 5.3 +/- 1.3 mm. TEE revealed no evidence for atrial thrombus in 18 of the 21 patients; this finding was confirmed by careful inspection of the atria including the appendages. TEE demonstrated a left atrial thrombus in two patients and a right atrial thrombus in another (confirmed at the time of surgery or at autopsy). In all cases transthoracic echocardiography was negative. Our data suggest that TEE is useful in ruling out atrial thrombus, and therefore may be a useful test preceding interventions associated with an increased risk of embolism from the atria such as cardioversion, mitral valvuloplasty, or valve replacement.

Transesophageal echocardiography in patients with mechanical circulatory assistance.

Transesophageal echocardiography was used to assess myocardial function and to detect complications after mechanical circulatory support for 8 patients with cardiogenic shock. In 3 of 8 patients, serial transesophageal echocardiography documented improvement of systolic ventricular function, and it was possible to wean these 3 patients from the ventricular assist device. In all patients, transesophageal echocardiography added clinically important information including the extent of left and right ventricular dysfunction (6 patients), presence of atrial or ventricular thrombus (5 patients), presence of pericardial effusion or clot (2 patients), and verification of the position of the intravascular device (1 patient). Thus, transesophageal echocardiography may provide clinically useful information regarding both the underlying cardiac disease and potential complications from the mechanical circulatory assistance.

Value of transesophageal echocardiography as an adjunct to transthoracic echocardiography in evaluation of native and prosthetic valve endocarditis.

To determine if transesophageal echocardiography provides better visualization of valvular vegetations than transthoracic echocardiography, we used both methods to evaluate 24 consecutive patients (mean age, 54 years; 15 female patients and nine male patients) referred for symptoms suggestive of infectious endocarditis. Ten of the 24 patients had one or more valvular prostheses. Echocardiograms were classified as positive or negative based on visualization of valvular vegetations or abscesses. Of ten patients with a final diagnosis of infectious endocarditis on extended follow-up, transthoracic echocardiography was positive in five patients. Transesophageal echocardiography not only yielded abnormal findings in all ten of these patients, but also revealed additional information in four of the five patients with abnormal transthoracic echocardiographic examinations. Among the 14 patients who, on subsequent follow-up, were found not to have infectious endocarditis, transthoracic echocardiography was normal in 13 and falsely abnormal in one. Transesophageal echocardiography revealed no evidence of infectious endocarditis in any of these patients. The ten patients who were determined to have infectious endocarditis all had positive blood cultures and no alternative cause for their clinical presentation; in seven patients in this group who underwent operative or postmortem evaluation, infectious endocarditis was confirmed. All patients without infectious endocarditis were demonstrated to have other causes for their clinical presentation. We conclude that transesophageal echocardiography is a highly valuable test in the work-up of patients with suspected infectious endocarditis, especially those patients with inconclusive or normal transthoracic echocardiograms. In addition, transesophageal echocardiography may be of benefit to patients with previously documented infectious endocarditis and a complicated clinical course in whom additional cardiac lesions are suspected but not demonstrated by transthoracic echocardiography.

Transesophageal color Doppler echocardiography of the normal St. Jude Medical mitral valve prosthesis.

Transesophageal color flow Doppler findings are reported in 36 patients with a St. Jude Medical mechanical mitral valve prosthesis who had no auscultatory evidence for prosthetic valve dysfunction. Multiple jets consistent with mitral regurgitation originating from the central and lateral portion of the prosthesis were found in all patients. Maximum jet length ranged from 11 to 51 mm (mean 21 +/- 9 mm). Maximum jet area ranged from 0.2 to 4.1 cm3 (mean 1.2 +/- 0.9 cm2). The color M-mode Doppler interrogation showed two distinct components of the regurgitant jet: brief early systolic flow consistent with valve closure followed by holosystolic regurgitant flow consistent with transvalvular leakage. Four patients (11%) had a maximum regurgitant jet length exceeding 30 mm and absence of early systolic closure regurgitant flow by M-mode color imaging, suggesting clinically silent paravalvular leakage. Two pin-sized paravalvular suture line defects were confirmed in one patient at cardiac transplantation. We conclude that transesophageal echocardiography is a highly sensitive method for detection of mitral regurgitation in the St. Jude Medical mitral prosthesis. Clinically silent paravalvular leakage should be suspected if the maximum jet length exceeds 30 mm and color M-mode interrogation fails to demonstrate an early systolic closure regurgitant flow component.