Postprandial hypotension and orthostatic blood pressure responses in elderly Parkinson's disease patients

OBJECTIVE: To investigate the change in systolic blood pressure (SBP) induced by meals and to compare their impact on the orthostatic SBP response in elderly Parkinson's disease with that in control patients. DESIGN: Ten elderly patients suffering from Parkinson's disease were compared with 10 age-matched elderly control patients. METHODS: The postprandial SBP change was measured by means of ambulatory blood pressure monitoring with the patient in the supine position. Orthostatic SBP responses were measured the next day by means of active standing and passive head-up tilting tests performed before and after the patients had their lunch. RESULTS: In Parkinson's disease patients, a postprandial SBP drop of 27 mmHg in the supine position was found compared with a drop of 8 mmHg in controls. In Parkinson's disease patients, that drop was moderately correlated to the orthostatic SBP responses and significantly correlated to the preprandial supine baseline SBP level. The orthostatic fall in SBP was greater with passive than with active standing and with both it was greater in Parkinson's disease patients than in the control subjects. The fall in orthostatic blood pressure was reduced by a previous meal. In contrast, there was no difference in orthostatic heart rate responses between the patients and the controls. CONCLUSIONS: Parkinson's disease patients demonstrated a significant postprandial drop in SBP and a tendency towards orthostatic hypotension, which was not worsened by the meal, probably owing to a stronger sympathetic activation. Postprandial supine SBP change and orthostatic SBP responses were only moderately associated in Parkinson's disease patients. In addition to autonomic dysfunction, an increased baseline SBP level might contribute to both phenomena.     

Iodine-123-beta-CIT and iodine-123-FPCIT SPECT measurement of dopamine transporters in healthy subjects and Parkinson's patients

Iodine-123-beta-carbomethoxy-3 beta-(4-iodophenyltropane) (CIT) has been used as a probe of dopamine transporters in Parkinson's disease patients using SPECT. This tracer has a protracted period of striatal uptake enabling imaging 14-24 hr postinjection for stable quantitative measures of dopamine transporters, and it binds with nanomolar affinity to the serotonin transporter. Iodine-123 fluoropropyl (FP)CIT is an analog of [123I]-beta-CIT and has been shown to achieve peak tracer uptake in the brain within hours postinjection and to provide greater selectivity for the dopamine transporter. The purpose of the present study was to compare [123I]-beta-CIT with [123I]-FPCIT in a within-subject design. METHODS: Six Parkinson's disease patients and five healthy control subjects participated in one [123I]-beta-CIT and one [123I]-FPCIT SPECT scan separated by 7-21 days. Controls were imaged at 24 hr postinjection 222 MBq (6 mCi) [123I]-beta-CIT and serially from 1-6 hr postinjection 333 MBq (9 mCi) [123I]-FPCIT. Two imaging outcome measures were evaluated: (a) the ratio of specific striatal activity to nondisplaceable uptake, also designated V"3, at each imaging time point; and (b) the rate of striatal washout of radiotracer expressed as a percent reduction per hr for [123I]-FPCIT. In addition, venous plasma was obtained from the five control subjects after the [123I]-FPCIT injection for analysis of radiometabolites. RESULTS: Both [123I]-FPCIT and [123I]-beta-CIT demonstrated decreased striatal uptake in Parkinson's disease patients compared with the controls with a mean of V"3=3.5 and 6.7 for [123I]-beta-CIT (Parkinson's disease and controls, respectively) and a mean of V"3=1.34 and 3.70 for [123I]-FPCIT (Parkinson's disease and controls, respectively). For [123I]-beta-CIT, the mean Parkinson's disease values represented 52% of the control uptake, while the mean [123I]-FPCIT value for Parkinson's disease patients was 37% of the control values. Analysis of [123I]-FPCIT time-activity curves for specific striatal counts showed washout rates of 8.2%/hr for Parkinson's disease and 4.9%/hr for controls. CONCLUSION: These data suggest that SPECT imaging with [123I]-FPCIT visually demonstrates reductions in striatal uptake similar to [123I]-beta-CIT. iodine-123-FPCIT washed out from striatal tissue 15-20 times faster than [123I]-beta-CIT, and estimates of dopamine transporter loss in Parkinson's disease patients were higher for [123I]-FPCIT than for [123I]-beta-CIT. This was most likely due to the faster rate of striatal washout and establishment of transient equilibrium binding conditions at the dopamine transporter, which the modeling theory suggests produces an overestimation of dopamine transporter density with relatively greater overestimates in healthy control subjects by [123I]-FPCIT.     

Activity in the parietal area during visuomotor learning with optical rotation

Regional cerebral blood flow (rCBF) was measured in six subjects to study changes of activity in the parietal cortex during learning of a visually guided pointing task with a discrepancy of visuomotor coordination and to determine whether reorganization affects the parietal activity after learning. During the early stage of learning, the right posterior parietal cortex showed a significant increase in rCBF. During the late stage, on the other hand, significant activation was noted in the postcentral gyrus of the right hemisphere. These results support a role for the posterior parietal cortex in remapping visuomotor coordinates and suggest the involvement of the human postcentral gyrus in retaining sensorimotor coordinates, considered to relate to the self image of the hand.     

Stereotaxy during intravenous anesthesia with propofol

BACKGROUND: Abnormally high levels of saccadic distractibility have been demonstrated to occur in patients with schizophrenia. Converging evidence implicates frontal cortical dysfunction as a mechanism; however, much of the neuropharmacology of saccadic distractibility has not yet been established. METHODS: We measured antisaccade, no-saccade, and visually guided saccade components in healthy subjects following single doses of lorazepam 2 mg, chlorpromazine 50-100 mg, and placebo. Visual analogue rating scales (VARS) provided a subjective measure of sedation. RESULTS: Lorazepam, but not chlorpromazine, was shown to cause an increase in saccadic distractibility in both the antisaccade and no-saccade tasks. Peak visually guided saccade velocity was decreased by lorazepam and chlorpromazine in a dose-dependent manner, with corresponding changes seen in VARS. Lorazepam, unexpectedly, did not affect peak antisaccade velocity. The background level of antisaccade directional errors was 6.43%, which is relatively low compared to control groups in patient studies. CONCLUSIONS: These results support the view that abnormal saccadic distractibility in patients with schizophrenia is not due to an acute effect of antipsychotic medication. The use of benzodiazepines and the level of task practice are highlighted as possible confounding variables in patient studies. The implications of these results for the current neuropathological theories of abnormal saccadic distractibility are discussed.     

Influence of automatic word reading on motor control

We investigated the possible influence of automatic word reading on processes of visuo-motor transformation. Six subjects were required to reach and grasp a rod on whose visible face the word 'long' or 'short' was printed. Word reading was not explicitly required. In order to induce subjects to visually analyse the object trial by trial, object position and size were randomly varied during the experimental session. The kinematics of the reaching component was affected by word presentation. Peak acceleration, peak velocity, and peak deceleration of arm were higher for the word 'long' with respect to the word 'short'. That is, during the initial movement phase subjects automatically associated the meaning of the word with the distance to be covered and activated a motor program for a farther and/or nearer object position. During the final movement phase, subjects modified the braking forces (deceleration) in order to correct the initial error. No effect of the words on the grasp component was observed. These results suggest a possible influence of cognitive functions on motor control and seem to contrast with the notion that the analyses executed in the ventral and dorsal cortical visual streams are different and independent.     

Neuropsychological and motor functioning after unilateral anatomically guided posterior ventral pallidotomy. Preoperative performance and three-month follow-up

This study presents baseline and 3-month follow-up motor and neuropsychological data for 22 patients with Parkinson's disease (PD) who underwent anatomically guided unilateral posterior ventral pallidotomy (PVP). Postsurgical improvements were seen in psychomotor speed, fine motor accuracy, and dyskinesia, whereas grip strength decreased on the side contralateral to the surgery. No change was detected in overall level of cognitive functioning, nor were changes demonstrated in memory, language, or working memory when the entire sample of patients was evaluated. When the group was divided on the basis of side of surgery, patients with left-sided pallidotomies showed a decline in verbal fluency. Patients and caregivers reported improvement in psychosocial functioning. These initial findings of improved motor performance and largely unaffected cognitive functions are consistent with results obtained with functional PVP and provide support for the use of anatomically guided posterior ventral pallidotomy in the treatment of motor symptoms of PD.     

Changing bone marrow micro-environment during development of acute myeloid leukaemia in rats

The high incidence of serious chest infections in patients with Parkinson's disease is unexplained, but an impairment in cough reflex may have a role. Maximal voluntary cough (MVC) and reflex cough (RC) to inhalation of ultrasonically nebulized distilled water were analyzed in patients with Parkinson's disease and age-matched control subjects by monitoring the integrated electromyographic activity (IEMG) of abdominal muscles. The peak amplitude of IEMG activity (IEMGP) was expressed as a fraction of the highest IEMGP value observed during MVC corrected to account for possible losses in abdominal muscle force due to reduced central muscle activation. Cough intensity was indexed in terms of both the IEMGP and the ratio of IEMGP to the duration of the expiratory ramp (TEC), i.e., the rate of rise of IEMG activity. Cough threshold was slightly higher in patients than in control subjects, but the difference failed to reach statistical significance. Compared with control subjects, patients displayed a lower IEMGP during maximal expiratory pressure maneuvers (PEmax), MVC, and RC (p always < 0.01); TEC during RC was longer (p < 0.01) than in controls. Consequently, the rate of rise of IEMG activity during cough was always lower in patients (p < 0. 01), especially during RC. Finally, PEmax, and both the peak and rate of rise of IEMG activity during RC were inversely related to the level of clinical disability (Spearman rank correlation coefficient, rs = -0.88, -0.86, and -0.85, respectively, p always < 0.01). The results indicate that the central neural mechanisms subserving the recruitment of motor units and/or the increase in their frequency of discharge during voluntary and, even more markedly, RC are impaired in patients with Parkinson's disease.     

Stage I non-Hodgkin''s lymphoma treated with doxorubicin-containing chemotherapy with or without radiotherapy

Assess the feasibility of proton MR spectroscopic imaging (1H-MRSI) of the striatum (putamen and caudate nucleus) in patients with Parkinson's disease and evaluate striatal neuronal density. Proton MRSI of the striatum and thalamus with 2 cc spatial resolution was performed in 10 patients with Parkinson's disease, 1 patient with atypical parkinsonism, and 13 control subjects. Single voxel proton MR spectra with signals from choline metabolites (Cho), creatine metabolites (Cr), and the putative neuronal marker, N-acetyl-aspartate (NAA), were obtained from the putamen and thalamus, but not the caudate nucleus, of patients with parkinsonism and control subjects. Metabolite rations in controls and patients were: in putamen NAA/Cho 1.70 +/- 0.25 vrs 1.74 +/- 0.32, NAA/Cr 2.80 +/- 0.79 vrs 2.36 +/- 0.42, Cho/Cr 1.63 +/- 0.25 vrs 1.39 +/- 0.3; in thalamus, NAA/Cho 1.78 +/- 0.15 vrs 1.62 +/- 0.22, NAA/Cr 2.78 +/- 0.34 vrs 2.64 +/- 0.41, Cho/Cr 1.57 +/- 0.25 vrs 1.65 +/- 0.28. There were no statistically significant differences between patients and controls. The putaminal NAA/Cho ratio of the single subject with atypical parkinsonism was lower than that of 9 of the 10 patients with classic Parkinson's disease and 11 of the 13 control subjects. Likewise, the putaminal NAA/Cr ratio in the single subject with atypical parkinsonism was lower than that of 7of the patients with guided selection of spectra from very small brain volumes, is a technique that can be used to evaluate neuronal density in individual subcortical gray nuclei in the brains of patients with parkinsonism. Using this technique, we have shown that Parkinson's disease produces no change in relative levels of the neuronal marker, NAA, in the putamen.     

The effect of pictorial illusion on prehension and perception

The present study examined the effect of a size-contrast illusion (Ebbinghaus or Titchener Circles Illusion) on visual perception and the visual control of grasping movements. Seventeen right-handed participants picked up and, on other trials, estimated the size of "poker-chip" disks, which functioned as the target circles in a three-dimensional version of the illusion. In the estimation condition, subjects indicated how big they thought the target was by separating their thumb and forefinger to match the target's size. After initial viewing, no visual feedback from the hand or the target was available. Scaling of grip aperture was found to be strongly correlated with the physical size of the disks, while manual estimations of disk size were biased in the direction of the illusion. Evidently, grip aperture is calibrated to the true size of an object, even when perception of object size is distorted by a pictorial illusion, a result that is consistent with recent suggestions that visually guided prehension and visual perception are mediated by separate visual pathways.     

Prospective memory: when reminders fail

The present study examined fingertip forces during the replacement and release of an instrumented object on a table in eight subjects with Parkinson's disease (PD) both off and on medication and eight age-matched control subjects. Subjects performed the task at (1) their preferred speeds and (2) as fast as possible. During performance of the task at preferred speed, the duration of object replacement, the rate, and duration of force decrease following table contact for PD subjects were similar to that observed in the control subjects and were unaffected by medication. In contrast, the rates were significantly lower and durations longer in the PD subjects when the task was performed as fast as possible irrespective of medication. A similar result was obtained when subjects were asked to release their pinch force from predefined force levels while the object was fixed to the table surface. These results emphasize the importance of considering task requirements in order to delineate the specific task parameters associated with the movement impairments in Parkinson's disease.     

Altered serial position learning after frontal lobe lesion

The serial position function is a powerful and highly reliable feature of human learning, with well-described primacy and recency effects. We tested the hypothesis that frontal lobe lesions in patients would disrupt the serial position function since such patients are known to have disturbed temporal ordering, learning in the presence of interference, encoding and organizational approaches to learning. Performance was compared in patients with focal, acquired lesions of frontal and non-frontal cortices, using a standardized paradigm of verbal list learning. Results indicated a similar pattern of performance on first trial learning for the two groups. However, across learning trials, frontal lesion subjects failed to maintain significant primacy and recency effects. Non-frontal lesion subjects consistently showed the expected U-shaped serial position curve across all trials. Subjective organization in learning was particularly deficient in the dorsolateral frontal lesion subjects. We propose that serial position effects are qualitatively different after frontal lobe lesion, being transitory and prone to alteration by the cumulative effects of disturbed temporal-spatial processing across learning trials.     

Apparent decrease in population clearance of theophylline: implications for dosage

Tthe antisaccade eye movement task, which has been linked to frontal lobe function, presents a target in one visual field and asks subjects to move their eyes to the same location in the opposite field. The task requires inhibition of the reflexive prosaccade to the cue, initiation of the antisaccade to the opposite field, and visuo-spatial memory of the cue location. Forty-two subjects from 19-79 years of age performed this task and a control task, visually guided saccades to the cue itself, to determine which functions are affected by aging. The time to initiate antisaccades increased linearly with age at a rate greater than the time to initiate visually guided saccades. This difference suggests that the processing time to inhibit the incorrect movement to the cue is selectively increased with age. Older subjects also made more incorrect prosaccadic movements to the cue, a finding consistent with the loss of inhibitory processing capacity. The accuracy of movements did not change, which suggests that visuo-spatial memory is unaffected by aging.     

Functional brain electrical activity mapping in boys with attention-deficit/hyperactivity disorder

BACKGROUND: Symptoms of attention-deficit/hyperactivity disorder (ADHD) have been associated with frontal lobe deficits. We used a novel brain electrical imaging method to investigate rapid and continuous changes in brain activity during the continuous performance task (CPT) in normal boys and in boys with ADHD. The amplitude and latency topography of the steady-state visually evoked potential (SSVEP) were examined while subjects performed the "X" version of the CPT (CPT-X; the reference task) and the "A-X" version of the CPT (CPT-AX). METHODS: Seventeen boys meeting DSM-III-R criteria for ADHD and 17 age-matched controls participated in the study. Brain electrical activity was recorded from 64 scalp sites. During the reference task, subjects pressed a microswitch on the unpredictable appearance of the letter X. During the CPT-AX, subjects were required to press the microswitch on the appearance of the letter X only if an A had preceded it. RESULTS: In the interval between the appearances of the A and the X of the correct trials of the CPT-AX, control boys showed transient reductions in SSVEP latency at right prefrontal sites. By contrast, boys with ADHD showed no change or an increase in prefrontal SSVEP latency at right prefrontal sites. CONCLUSION: Our results suggest increased speed of prefrontal neural processing in children without ADHD following a priming stimulus, and a deficit in such processes in children with ADHD.     

PET studies on brain monoamine transporters with carbon-11-beta-CIT in Parkinson's disease

The cocaine analog 2 beta-carbomethoxy-3 beta-[4-iodophenyl]tropane (beta-CIT) labeled with 11C was used to study dopamine reuptake sites with PET. METHODS: Three normal subjects and nine patients with Parkinson's disease were investigated. Each of them underwent a dynamic PET scan (25 timeframes over 80 min) with [11C]-beta-CIT. A dose of 102.5-211.3 MBq (2.77-5.71 mCi) of this ligand was administered intravenously and a PET examination with an ECAT 931/08 PET camera was carried out. Ratios between the striatal/cortical/thalamic/midbrain and cerebellar uptake of this radioligand were calculated. RESULTS: The highest accumulation of [11C]beta-CIT was observed in the caudate and putamen, though there was some uptake in the thalamus and the midbrain. Cortical uptake was negligible. Carbon-11-beta-CIT accumulated significantly less in the putamen of the Parkinson's patients than in the normal subjects. The putamen-to-cerebellum ratio in the Parkinson's patients was 1.59 +/- 0.04 and 1.80 +/- 0.13s (p = 0.028) in the normal subjects. In the caudate, there was no significant difference between the Parkinson's patients and the normal subjects. CONCLUSION: These results imply that [11C]beta-CIT is a useful compound for carrying out a PET examination of the function of the presynaptic monoaminergic neurons both in normal and pathological brains.     

Control of pigeons' spatial search by graphic landmarks in a touch-screen task.

Pigeons learned to peck an unmarked 2-cm–2 target area, defined by 4 visually distinct graphic landmarks, on a color monitor with an attached touch frame. The configuration of landmarks and target area was constant during training, but their location on the screen varied across trials. The presence, relative location, and features of the landmarks were manipulated on probe trials. Most birds showed control by only 1 or 2 of the landmarks, and some birds displayed surprisingly accurate search with a single landmark. For individual birds, landmark-removal tests were very consistent with landmark-shift tests in indicating which landmark or landmarks controlled search. However, the dominant landmark varied across birds. Manipulation of landmark color and shape revealed that control was based exclusively on color. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Test/retest reproducibility of iodine-123-betaCIT SPECT brain measurement of dopamine transporters in Parkinson's patients

Iodine-123-beta-CIT has been used as a probe of dopamine transporters in Parkinson's disease patients using SPECT. We studied the test/retest reproducibility of SPECT measures in Parkinson's disease patients and healthy controls obtained after injection of [123I])beta-CIT in part to assess the utility of this tracer for longitudinal evaluation of striatal dopamine transporters as a marker of disease progression. METHODS: Seven Parkinson's disease patients and seven healthy control subjects participated in two [123I]beta-CIT SPECT scans separated by 7-21 days. Subjects were imaged at 24 hr post injection of 360 MBq (9.7 mCi) of [123I]beta-CIT. Two outcome measures were evaluated; 1) the ratio of specific striatal (activity associated with DA transporter binding) to nondisplaceable uptake, also designated V3," and 2) the total specific striatal uptake (%SSU) expressed as a percentage of injected radiotracer dose. For both measures, test/retest variability was calculated as the absolute difference of test minus retest divided by the mean of test/retest and expressed as a percent. In addition, the reproducibility of left and right striatal asymmetry and putamen:caudate ratios were determined. RESULTS: The two outcome measures demonstrated excellent test/retest reproducibility for both the Parkinson's disease and healthy subject groups with variability of striatal V3" = 16.8 +/- 13.3% and percent striatal uptake = 6.8 +/- 3.4% for Parkinson's disease patients and V3" = 12.8 +/- 8.9% and %SSU = 7.0 +/- 3.9% for control subjects. There were no statistically significant differences in test/retest variability between control subjects and Parkinson's disease patients for either outcome measure. The reproducibility of left/right asymmetry indices and putamen-to-caudate ratios showed no patient versus control subject differences. The asymmetry index had greater test/retest variability than the other outcome measures. CONCLUSION: These data suggest that SPECT imaging performed at 24 hr postinjection of [123I]beta-CIT permits calculation of reliable and reproducible measures of dopamine transporters in both Parkinson's disease patients and control subjects and supports the feasibility of using [123I]beta-CIT in the evaluation of disease progression in Parkinson's disease.     

Human theta class glutathione transferase: the crystal structure reveals a sulfate-binding pocket within a buried active site

Depressive illness has been reported to interfere with effortful processing, which requires conscious attention. The aim of this study was to evaluate divided attention in depressed patients, as a function of the degree of difficulty of the task performed. Tasks designed to measure unimodal and bimodal reaction times were presented to 10 patients with major depression and 10 normal control subjects. Performance was evaluated both before treatment when the patients were depressed and after treatment when they had recovered. Unlike the unimodal trials, the bimodal reaction time tasks were designed to evaluate decision-making under conditions in which attention was divided between two perceptual channels. Reaction times were measured under two different conditions in order to assess the extent of the response delay induced by divided attention, modality shifting, and decision processing. During simple response tasks, the depressed patients displayed significantly greater lengthening of reaction times when their attention was divided between two perceptual channels. This cross-modal delay effect occurred both for stimuli of the same modality and when shifting between modalities. The cross-modal delay effect was evident only for the choice tests in both the depressed and the recovered patients, but only the recovered patients were as accurate as the control subjects. These results suggest that the need for decision processing in depressed patients results in a failure to allocate the mental resources required to complete interchannel shifting, when attention is divided between two perceptual channels. These data are consistent with the hypothesis that attentional regulation is impaired in major depression.     

Bilateral interactions in saccade programming. A saccade-latency study

Subjects were required to make a saccade to a target appearing randomly 4 degree to the left or right of the current fixation position (1280 trials per experiment). Location cues were used to direct visual attention and start saccade preparation to one of the two locations before target onset. When the cue indicated the target location (valid trials), the generation of express saccades (visually guided saccades with latencies around 100 ms) was strongly facilitated. When the opposite location was cued (invalid trials), express saccades were abolished and replaced by a population of mainly fast-regular saccades (latencies around 150 ms). This was found with a peripheral cue independently of whether the fixation point was removed before target onset (gap condition; experiment 1) or remained on throughout the trial (overlap condition; experiment 2). The same pattern also was observed with a central cue that did not involve any visual stimulation at a peripheral location (experiment 3). In the case where the primary saccade was executed in response to the cue and the target appeared at the opposite location, continuous amplitude transition functions were observed: starting at about 60-70 ms from target onset onward, the amplitude of the cue-elicited saccades continuously decreased from 4 degree to values below 1 degree. The results are explained by a fixation-gating model, according to which the antagonism between fixation and saccade activity gives rise to multimodal distributions of saccade latencies. It is argued that allocation of visual attention and saccade preparation to one location entails a successive disengagement of the fixation system controlling saccade preparation within the hemifield to which the saccade is prepared and a partial engagement of the opposite fixation system.     

P50 suppression among schizophrenia and normal comparison subjects: a methodological analysis

The present report investigated the relationship between P50 suppression and habituation among 20 schizophrenia and 20 normal comparison subjects. Subjects were presented with clicks delivered over headphones in a S1-S2 paradigm (clicks were separated by 500 msec; average intertrial interval was 8 sec). There were 60 total trials; the data were analyzed separately for the first and second 30 trials. The groups did not differ either on the number of usable trials or on the morphology of their P50 responses. Consistent with previous reports, schizophrenia patients demonstrated deficient P50 suppression. The overall suppression effect was not due to a group difference on S1 P50 amplitudes, but was associated with schizophrenia patients having smaller S1-S2 P50 amplitude difference scores than normal comparison subjects. Furthermore, the suppression effect appears to be more pronounced during the first than during the second block of trials. Thus, it may be important to evaluate changes in P50 responses over time among schizophrenia and normal comparison subjects.     

Gingival recession and exposure of barrier membrane: effect on guided tissue regeneration of Class II furcation defects

The purpose of the present study was to evaluate the effect of barrier membrane exposure on the success of guided tissue regeneration in Class II furcation defects. Twenty-six subjects with mandibular Class II furcation defects received initial periodontal therapy followed by guided tissue regeneration surgery. The membrane was placed and the flaps were repositioned so that the membrane was totally submerged. Membranes were removed 4 to 6 weeks later, at which time the extent of their exposure was recorded. An overall improvement in all clinical parameters was observed for all subjects 1 year after surgery. Half of the patients had experienced no membrane exposure, while the other 13 subjects had experienced mild to pronounced exposure; both groups showed similar improvement in all clinical and surgical parameters. In light of the comparable results obtained in exposed sites, and the anatomic difficulties sometimes encountered in covering a membrane completely, in some of these cases the membrane may be left only partially submerged. This approach will allow for tighter occlusal "seal" of the tooth-membrane interface and preservation of the keratinized gingiva.