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Comparisons of target-based reaching vs memory-based (pantomime) reaching have been used to obtain insight into the visuomotor control of reaching. The present study examined the contribution of gaze anchoring, reaching to a target that is under continuous gaze, to both target-based and memory-based reaching. Participants made target-based reaches for discs located on a table or food items located on a pedestal or they replaced the objects. They then made memory-based reaches in which they pantomimed their target-based reaches. Participants were fitted with hand sensors for kinematic tracking and an eye tracker to monitor gaze. When making target-based reaches, participants directed gaze to the target location from reach onset to offset without interrupting saccades. Similar gaze anchoring was present for memory-based reaches when the surface upon which the target had been placed remained. When the target and its surface were both removed there was no systematic relationship between gaze and the reach. Gaze anchoring was also present when participants replaced a target on a surface, a movement featuring a reach but little grasp. That memory-based reaches can be either gaze anchor-associated or gaze anchor-independent is discussed in relation to contemporary views of the neural control of reaching.

The Dual Visuomotor Channel theory of reaching proposes that a reach-to-grasp act integrates a Reach, directed toward the extrinsic properties of the target (location), and a Grasp, directed toward the intrinsic properties of the target (size and shape). Previous studies of reach-to-grasp report that the Grasp is altered in pantomime tasks made from a starting position with digit 1 and digit 2 closed and proximal to the target. The present study extends the analysis of real versus pantomime reaching to a task that featured both a Reach and a Grasp, having a starting position with the hand open and proximal to the body. For a real reach, seated participants reached for a doughnut ball (food item) located on a pedestal at arms distance, with the intent of bringing the doughnut ball to the mouth for eating. Participants also made four pantomime reaches with: (1) the doughnut ball removed from the pedestal, (2) the doughnut ball and pedestal moved to the side of the reach location, (3) the doughnut ball and pedestal absent, and (4) the participants wearing vision-occluding glasses. There were two main findings. First, the presence of task-related cues, platform, doughnut ball, and room influenced the kinematics of the Reach and Grasp. Second, the compound structure of a real reach, in which flexion/extension of the arm featured in the Reach and flexion/extension of the digits featured in the Grasp are out of phase, changed in pantomime such that these features of Reach and Grasp became in phase. The results show that pantomime reaching is influenced not only by task-related percepts but also by central mechanisms ordinarily related to integrating the Reach and the Grasp.

Prehension, the act of reaching to grasp an object, is central to the human experience. We use it to feed ourselves, groom ourselves, and manipulate objects and tools in our environment. Such behaviors are impaired by many sensorimotor disorders, yet our current understanding of their neural control is far from complete. Current technologies for investigating human reach-to-grasp movements often utilize motion tracking systems that can be expensive, require the attachment of markers or sensors to the hands, impede natural movement and sensory feedback, and provide kinematic output that can be difficult to interpret. While generally effective for studying the stereotypical reach-to-grasp movements of healthy sighted adults, many of these technologies face additional limitations when attempting to study the unpredictable and idiosyncratic reach-to-grasp movements of young infants, unsighted adults, and patients with neurological disorders. Thus, we present a novel, inexpensive, and highly reliable yet flexible protocol for quantifying the temporal and kinematic structure of idiosyncratic reach-to-grasp movements in humans. High speed video cameras capture multiple views of the reach-to-grasp movement. Frame-by-frame video analysis is then used to document the timing and magnitude of pre-defined behavioral events such as movement start, collection, maximum height, peak aperture, first contact, and final grasp. The temporal structure of the movement is reconstructed by documenting the relative frame number of each event while the kinematic structure of the hand is quantified using the ruler or measure function in photo editing software to calibrate 2 dimensional linear distances between two body parts or between a body part and the target. Frame-by-frame video analysis can provide a quantitative and comprehensive description of idiosyncratic reach-to-grasp movements and will enable researchers to expand their area of investigation to include a greater range of naturalistic prehensile behaviors, guided by a wider variety of sensory modalities, in both healthy and clinical populations.

Reach-to-grasp movements feature the integration of a reach directed by the extrinsic (location) features of a target and a grasp directed by the intrinsic (size, shape) features of a target. The action-perception theory suggests that integration and scaling of a reach-to-grasp movement, including its trajectory and the concurrent digit shaping, are features that depend upon online action pathways of the dorsal visuomotor stream. Scaling is much less accurate for a pantomime reach-to-grasp movement, a pretend reach with the target object absent. Thus, the action-perception theory proposes that pantomime movement is mediated by perceptual pathways of the ventral visuomotor stream. A distinguishing visual feature of a real reach-to-grasp movement is gaze anchoring, in which a participant visually fixates the target throughout the reach and disengages, often by blinking or looking away/averting the head, at about the time that the target is grasped. The present study examined whether gaze anchoring is associated with pantomime reaching. The eye and hand movements of participants were recorded as they reached for a ball of one of three sizes, located on a pedestal at arms' length, or pantomimed the same reach with the ball and pedestal absent. The kinematic measures for real reach-to-grasp movements were coupled to the location and size of the target, whereas the kinematic measures for pantomime reach-to-grasp, although grossly reflecting target features, were significantly altered. Gaze anchoring was also tightly coupled to the target for real reach-to-grasp movements, but there was no systematic focus for gaze, either in relation with the virtual target, the previous location of the target, or the participant's reaching hand, for pantomime reach-to-grasp. The presence of gaze anchoring during real vs. its absence in pantomime reach-to-grasp supports the action-perception theory that real, but not pantomime, reaches are online visuomotor actions and is discussed in relation with the neural control of real and pantomime reach-to-grasp movements.

Epstein-Barr virus (EBV) causes infectious mononucleosis and can lead to lymphoproliferative diseases. We evaluated the effects of valganciclovir on oral EBV shedding in a randomized, double-blind, placebo-controlled study. Twenty-six men received oral valganciclovir or daily placebo for 8 weeks, followed by a 2-week "washout period" and then 8 weeks of the alternative treatment. Valganciclovir reduced the proportion of days with EBV detected from 61.3% to 17.8% (relative risk, 0.28; 95% confidence interval [CI], .21-.41; P < .001), and quantity of virus detected by 0.77 logs (95% CI, .62-.91 logs; P < .001). Further investigations into the impact of valganciclovir on EBV-associated diseases are needed.

Human herpesvirus 8 (HHV-8) replication increases the risk of Kaposi sarcoma (KS). Highly-active antiretroviral therapy (HAART) reduces the incidence of KS, and regimens that contain protease inhibitors (PIs) may be particularly effective.To determine whether PI-based HAART regimens may more effectively inhibit HHV-8 shedding compared to regimens without PIs.Prospective, observational study of 142 HIV-1 and HHV-8 co-infected men conducted in Seattle, Washington. Quantitative HHV-8 PCR testing was performed on daily swabs of the oropharynx, the primary site of HHV-8 replication. Associations between antiretroviral regimen and detection of HHV-8 DNA in swabs were evaluated using generalized estimating equations.HHV-8 DNA was detected in 3016 (26%) of 11,608 specimens collected. PI-based HAART was associated with a statistically significantly lower frequency of detection (RR 0.2; 95% CI 0.1-0.5) compared to ART-naïve persons, whereas HAART without a PI was not (RR 0.7; 95% CI 0.4-1.3). Compared to ART-naïve persons, there was also a trend toward lower quantities of HHV-8 detected during treatment with HAART regimens that contained a PI. These associations between PIs and measures of HHV-8 shedding could not be attributed to use of nelfinavir, which inhibits HHV-8 replication in vitro, and were independent of CD4 count and HIV plasma viral load (VL).HAART regimens that contain PIs appear to decrease HHV-8 shedding compared to NNRTIs. Further study of PI-based HAART is warranted to determine the optimal regimens for prevention and treatment of KS.

Objective: To determine whether rapidly cleared episodes of herpes simplex virus (HSV) reactivation occur in HIV-infected adults. Methods: Twenty HSV-2―seropositive, HIV-seropositive adults, including 9 (45%) who were also HSV-1 seropositive, collected oral and anogenital swabs for HSV DNA polymerase chain reaction 4 times a day for 60 days. Samples were positive for HSV if we detected ≥150 copies of HSV DNA/mL of specimen. Results: Median HSV shedding episode duration was 7.5 (range 4-253) hours for oral and 11 (range 4-328) hours for anogenital reactivation. Thirty-five percent of oral and 29% of anogenital reactivations lasted ≤6 hours, and 59% of oral and 53% of anogenital reactivations lasted ≤12 hours. Seven of 9 participants who shed orally and 10 of 15 who shed anogenitally had ≥1 reactivation lasting ≤6 hours. The median maximum level of HSV DNA detected in an episode increased with episode duration for both oral and anogenital episodes. Concurrent oral and anogenital shedding occurred more frequently than expected: oral HSV shedding was detected on 17% of time points with anogenital but 1% of time points without anogenital, shedding (P < 0.001). Conclusions: Rapidly cleared episodes of oral and anogenital HSV shedding occur in HIV-infected persons, supporting the hypothesis that frequent anogenital mucosal immune activation caused by HSV-2 is present in HIV coinfected persons, potentially contributing to HIV infectiousness.

The effect of highly active antiretroviral therapy (HAART) on control of herpes simplex virus (HSV) in human immunodeficiency virus (HIV) type 1– infected subjects is not known. Among 28 HAART-treated and 49 untreated subjects with HIV-1 and HSV-2 infections mucosal HSV shedding (median 18% and 29% of days positive for HSV DNA respectively; P = .08) and HSV DNA level (median 56250 and 50000 copies/mL respectively; P = .20) were similar. Treated subjects reported significantly fewer days with HSV lesions compared with untreated subjects (2.8% vs. 11.3% of days respectively; P = .001). Thus mucosal HSV shedding and HSV-2 reactivation were still frequent among treated subjects even though HAART was associated with fewer days with HSV lesions. (authors)

Trains of repetitive transcranial magnetic stimulation (TMS) at 10-30 Hz and intensities of 90-120% motor threshold were delivered through a figure of eight coil over the motor cortex while normal subjects made either rapid, self-terminated (ballistic) wrist movements or maintained the position of their wrist at a fixed angle. Movement kinematics and EMG activity in antagonistic forearm muscles were analysed. In the ballistic task, repetitive TMS had little effect on the velocity or acceleration of the initial segment of the movement, although it induced large terminal oscillations (tremor) around the target position at frequencies between 4.4 and 7.2 Hz. The likelihood that tremor would occur increased with increasing stimulus intensities or frequencies. It was maximal with stimulation over the forearm area, and decreased with stimulation over the leg area, or over parietal sites; there was no tremor during stimulation of cervical nerve roots. The frequency of the induced tremor was independent of the rate of stimulation and did not depend on the presence of excitatory and inhibitory motor responses to the stimulus. Stimulation could also induce tremor of the same frequency in the fixed task, but only during co-contraction of forearm muscles. The amplitude of tremor was proportional to the level of co-contraction. Clinically, the tremor induced by repetitive TMS appeared very similar to cerebellar tremors. In order to confirm this we investigated two cerebellar patients, one with autosomal dominant cerebellar ataxia and the other with multiple sclerosis. Both of them had a terminal tremor of 6-7 Hz in the wrist movement task. In the holding task, the amplitude of their postural tremor increased with the level of co-contraction in forearm muscles. Since the frequency of repetitive TMS-induced tremor was independent of stimulus parameters, we conclude that it represents some intrinsic property of the CNS. We suggest that the tremor is caused by disruption of cortical processes involved in terminating a voluntary movement or maintaining a posture. Similarities to cerebellar patients suggest that repetitive TMS may cause tremor by interfering with adaptive cerebellar afferent inflow to motor cortex. Repetitive TMS-induced tremor, therefore, may represent a model of some forms of cerebellar tremor in man.

We report the case of a 35-year-old woman who developed headache and psychosis and gradually became comatose within 3 weeks after a flu-like infection. MRI revealed bifrontal demyelination consistent with acute disseminating encephalomyelitis (ADEM). Two different cerebrospinal fluid samples were positively tested for Legionella cincinnatiensis by direct sequencing of a PCR-amplified Legionella-specific fragment. This result made it possible to interpret the initial symptoms as Pontiac fever. We think it most likely that this is a case of ADEM following the very rare situation of a systemic infection with L. cincinnatiensis. A review of the literature on Legionella-associated encephalopathy suggests that some of these cases may also have had ADEM.

A versatile photochemical method of labeling human antibodies is described. Labeling is achieved by photolyzing 4-azido-2,3,5,6-tetrafluoro-14C-methylbenzoate and the B72.3 human antibody in a buffer at physiological pH. The photochemically produced nitrene presumably inserts into bonds in the hydrophobic part of the antibody resulting in > 75% attachment of the photoprobe. An immunoassay of B72.3 with mucin (B72.3 antigen) reveals > 97% retention of immunoreactivity and suggests that photochemical labeling is a viable alternative for the conjugation of biomolecules.

N-alkyl derivatives of perfluoroarylazides are excellent candidates for photolabeling of proteins since they have absorption spectra in the 340-350 nm range permitting photolabel absorption without direct protein photolysis. The [14C]-N-methylamino derivative of 4-azido-tetrafluorobenzonitrile has been used to demonstrate that 80% of the photo-induced nitrene transient becomes covalently attached to HSA during photolysis. Multiwavelength detection of the photoprobe-protein separation by size exclusion chromatography is shown to be an effective tool for assessing the conjugation of the photoprobe to the protein.

James Stacy Taylor advances a thorough argument for the legalization of markets in current (live) human kidneys. The market is seemly the most abhorrent type of market, a market where the least well-off sell part of their body to the most well off. Though rigorously defended overall, his arguments concerning exploitation are thin. I examine a number of prominent bioethicists' account of exploitation: most importantly, Ruth Sample's exploitation as degradation. I do so in the context of Taylor's argument, with the aim of buttressing Taylor's position that a regulated kidney market is morally allowable. I argue that Sample fails to provide normative grounds consistent with her claim that exploitation is wrong. I then reformulate her account for consistency and plausibility. Still, this seemingly more plausible view does not show that Taylor's regulated kidney market is prohibitively exploitative of impoverished persons. I tack into place one more piece of support for Taylor's conclusion. (wc. 148).

BACKGROUND: Human herpesvirus-8 (HHV-8) replication is critical in the induction and maintenance of Kaposi sarcoma, primary effusion lymphoma, and some cases of Castleman disease. In vitro and observational studies suggest that ganciclovir inhibits HHV-8 replication, but no randomized clinical trials have been conducted. METHODS: A total of 26 men infected with HHV-8 were randomized to receive 8 weeks of valganciclovir administered orally (900 mg once per day) or 8 weeks of placebo administered orally. After a 2-week washout period, participants in each group received the study drug they had not yet taken (either valganciclovir or placebo), for 8 additional weeks. Oral swab samples were collected daily during the study, and HHV-8 and CMV DNA were quantified by real-time PCR. RESULTS: A total of 16 human immunodeficiency virus (HIV)-positive men and 10 HIV-negative men enrolled in and completed the study. Of the 3,439 swab samples that participants had been expected to provide, 3029 (88%) were available for analysis. HHV-8 was detected on 44% of swabs collected from participants who were receiving placebo, compared with 23% of swabs collected from participants who were receiving valganciclovir (relative risk [RR], 0.54 [95% confidence interval {CI}, 0.33-0.90]; P = .02). Valganciclovir reduced oropharyngeal shedding of cytomegalovirus by 80% (RR, 0.20 [95% CI, 0.08-0.48]; P < .001). Shedding of HHV-8 and shedding of cytomegalovirus were independent. Hematologic, renal, or hepatic toxicities were no more common among participants who received the active drug, compared with those who received placebo, though participants who received valganciclovir reported more days of diarrhea. CONCLUSIONS: Valganciclovir administered orally once per day is well tolerated and significantly reduces the frequency and quantity of HHV-8 replication.

To test the hypothesis that there is no difference between adults with Class I crowded (CICR), Class III (CIII), and Class I normal (CIN) occlusions with respect to (1) arch widths, (2) width of the maxillary and mandibular arches, (3) gender dimorphism within groups, and (4) gender comparisons.Samples of 39 CICR subjects, 40 CIII subjects, and 40 CIN subjects were studied. All subjects were white Americans with no history of orthodontic treatment. An analysis of variance and Duncan's test statistically compared the groups and genders.The CICR group had mean maxillary and mandibular intermolar and alveolar arch widths significantly smaller than the CIN group. The CIII group had mean maxillary intermolar and alveolar arch widths significantly smaller than the CIN group. Mean maxillary and mandibular intercanine arch widths were similar in the three groups. The CICR and CIN groups had similar mean maxillary/mandibular intermolar and alveolar differences significantly larger than the negative differences observed in the CIII group. Gender dimorphisms were identical in the CIII and CIN groups. The CICR group differed by not having a gender dimorphism in the maxillary alveolar width and having a gender dimorphism in the mandibular intercanine width. Gender comparisons between groups were similar in intercanine widths but differed in other widths.The hypothesis was rejected by the findings of this study.

Functionalization of perfluoro aryl azides by bifunctional chelating agents (BFCAs) capable of forming high specific activity complexes with (99m)Tc (for gamma-imaging) and (188)Re (for radiotherapy) is described. The synthesis of multidonor BFCAs containing N(2)S(2), N(4), and N(3)S donor groups containing imidazole, pyridine, and pyrazine functionalities that may be important for tuning the pharmacokinetic parameters is also described. Functionalization of perfluoro aryl azides at various sites on BFCAs yields novel bifunctional photolabile chelating agents (BFPCAs) that are useful for covalent attachment to biomolecules. A representative Re-BFPCA 8a in a model solvent, diethylamine, proceeded to give a high yield of intermolecular NH insertion product without the decomplexation of the metal ion from 8a. All products originated from the photolysis of 8a in diethylamine are characterized by analytical techniques, and a plausible mechanism of formation of different photolytic products is suggested. The high yield of intermolecular NH insertion of Re-BFPCA 8a is extended to labeling of human serum albumin (HSA) and Fab fragments under aqueous conditions. The photolabeling technology developed here offers a new way to attach diagnostically and therapeutically useful radiotracers (e.g., (99m)Tc, (188)Re) to Fab fragments for potential noninvasive imaging and therapy of cancer.

In the presence of an intracoronary thrombus, percutaneous coronary intervention (PCI) will frequently lead to complications. Glycoprotein IIb/IIIa blockade as adjunct to PCI is very effective in patients with non-occlusive clots and biochemical evidence of platelet micro-embolization. Thrombotically-occluded vessels still remain a major clinical problem. This provides a rationale for thrombus debulking prior to PCI. A powerful antiplatelet agent used in combination with a thrombus debulking strategy and stenting of the underlying ruptured plaque offers the potential for further enhancement of PCI. Protection against embolization could potentially be optimized with the use of anti-embolization devices and covered stents.

The purpose of the present study was to analyse specific advantages of calculated parameter images and their limitations using an optimized echo-planar imaging (EPI) technique with high spatial and temporal resolution. Dynamic susceptibility contrast magnetic resonance imaging (DSC-MRI) was performed in 12 patients with cerebrovascular disease and in 13 patients with brain tumours. For MR imaging of cerebral perfusion an EPI sequence was developed which provides a temporal resolution of 0.68 s for three slices with a 128 x 128 image matrix. To evaluate DSC-MRI, the following parameter images were calculated pixelwise: (1) Maximum signal reduction (MSR); (2) maximum signal difference (delta SR); (3) time-to-peak (Tp); and (4) integral of signal-intensity-time curve until Tp (SInt). The MSR maps were superior in the detection of acute infarctions and delta SR maps in the delineation of vasogenic brain oedema. The time-to-peak (Tp) maps seemed to be highly sensitive in the detection of poststenotic malperfused brain areas (sensitivity 90%). Hyperperfused areas of brain tumours were detectable down to a diameter of 1 cm with high sensitivity (> 90%). Distinct clinical and neuroradiological conditions revealed different suitabilities for the parameter images. The time-to-peak (Tp) maps may be an important advantage in the detection of post-stenotic "areas at risk", due to an improved temporal resolution using an EPI technique. With regard to spatial resolution, a matrix size of 128 x 128 is sufficient for all clinical conditions. According to our results, a further increase in matrix size would not improve the spatial resolution in DSC-MRI, since the degree of the vascularization of lesions and the susceptibility effect itself seem to be the limiting factors.

The efficiency of photolabeling of HSA and IgG with [14C]methyl 4-azido-2,3,5,6-tetrafluorobenzoate has been studied using size exclusion chromatography in conjunction with liquid scintillation counting. Labeling efficiencies of 78% for HSA and 82% for IgG have been determined. The extent of bond insertion into proteins exceeds the C-H insertion efficiency in cyclohexane with less wastage into anilinium and azo side products. These results suggest that the photoprobe accesses hydrophobic regions of both proteins prior to photolysis.

The processing of blood alcohol measurements by alcohol dehydrogenase method (ADH) was improved by using a tailored software program. The program is written in Turbo BASIC and requires an IBM Personal Computer (PC/XT/AT) or compatible with at least 640K memory and a graphic adapter (EGA or Hercules). All features of the program are available from the menu bar with pull down menus. The program stores on disk or harddisk the optical density values measured with an HITACHI spectrophotometer. After the measurement the calculation of alcohol concentration is accomplished by the program. The results can be transferred and further handled with database systems (e.g. DBASE III). Stored values are used to calculate the reproducibility of calibration and the precision of single determinations.

Between 1965 and 1979, 34 patients with organic hyperinsulinism were examined angiographically. By observing the following points it should be possible to diagnose tumours greater than 1 cm, whatever their position in the pancreas: 1) Use of high performance generators and tubes which permit one to employ fine focus, low kv and high mAs. 2) Optimum imaging systems (carbon fibre table top, high intensity screens). 3) Selective catheterisation, large quantities of contrast per unit time and adequate duration of the filming sequence. 4) Pharmacoangiography and subtractions may be valuable in some cases.

The method of flash photolysis was used to identify the transient absorption spectrum and to characterize the decay kinetics of the indole triplet of human serum albumin. This protein was studied because it contains a single indole side chain which is deeply buried in an expandable oily region and because the phosphorescence of the homologous indole in bovine serum albumin could not be detected at ambient temperatures. The transient was identified on the following basis: (i) its triplet-triplet absorption spectrum was similar to those previously reported for indole and tryptophan; (ii) it was quenched by small quantities of oxygen; and (iii) it was photobleached by 370- to 700-nm light. In a nitrogen-saturated solution at room temperature, the indole triplet decays exponentially for more than a factor of 10 with a lifetime of 0.5 msec. These observations suggest that, because of its exponential decay and relatively long lifetime, the triplet will be more valuable than the indole singlet as an intrinsic reporter group for the study of the structure and dynamics of proteins in solution.

We report on a data base system for general registration including blood alcohol results which is in operation at the Institute of Forensic Medicine at Heidelberg University since january 1987. It is run on personal computers using dBase III plus as data base software. Working with the system has been adapted to the mode of operation hitherto. It's main purpose is to offer a general mean to standardize the documentation of results in the different fields of forensic medicine. At present it is run parallel with the registration by means of hand-written books. It's main advantage is the rapid search for all occurring names and files. Blood alcohol results are typed at the screen and printed out on the institute's standard form, with the expert's opinion being composed of text blocks. The essential data are extracted and transferred to the data base. A network of personal computers at different locations in the institute will be installed in the near future. A print-out of the data base will replace the hand-written registration, and the registration files will be completed by result files.

From 1965 to 1973, 82 patients were operated on for mediastinal tumor. 42.7% of them were incidental radiological findings. Preoperatively, 66% of the mediastinal tumors were not morphologically confirmed. The lethality of the operation was 1.22%. Thymomas (29.3%) were the most frequent findings. 34.2% were malignant. While most patients with benign mediastinal tumors are cured by the operation, the 5 year survival rate for those with malignant tumors was 22%. Further special investigative procedures should only follow a guiding survey radiography in two planes if they can be expected to provide essential information on operability, operational tactics and approach.