Biomedical subjects

J E Morgan

Publications and source records attributed to J E Morgan.

At least 37 records · Page 2Linked to original sources

PubMed2002

Remodelling the filtration bleb.

AIMS: To report remodelling of enlarged dysmorphic filtration blebs with conjunctival compression sutures and autologous blood injection. METHODS: A retrospective analysis of consecutively recruited patients with enlarged and dysmorphic filtration blebs who were managed with conjunctival compression sutures and subconjunctival autologous blood injections. Under topical anaesthesia, conjunctival (8.0-9.0 Nylon or 8.0 Vicryl) compression sutures were placed either side of blebs that were not showing signs of spontaneous resolution. In each case up to 0.75 ml of autologous blood was then injected into the areas of the bleb to be flattened. Supplemental injections of autologous blood were given in clinic as required. RESULTS: In 11 eyes of 11 patients, conjunctival compression sutures were placed and autologous blood was injected, on average, 568 days following filtration surgery (range 41-2023). Supplemental autologous blood injections were required in eight patients, with three injections being given in one patient. In each case, the sutures were well tolerated and satisfactory compression of the conjunctiva was achieved. The highest intraocular pressure following injection was 25 mm Hg (mean 17.3, SD 4.2) and in none of the cases did blood enter the anterior chamber or parts of the filtration bleb bounded by the sutures. CONCLUSION: Conjunctival compression sutures with autologous blood provide a simple and effective means for remodelling the filtration bleb. The procedure can be performed under topical anaesthesia and does not hinder further bleb surgery, should this be required.

Aged↗

PubMed2002

A multicentre evaluation of the diagnostic efficiency of serological investigations for C1 inhibitor deficiency.

AIM: To determine the diagnostic efficiency of assays routinely used in the investigation of hereditary angio-oedema. METHODS: Over a four year period, 1144 samples were received for analysis from 907 patients suspected of C1 inhibitor deficiency. Analyses were performed for C4 and C1 inhibitor (functional and immunochemical). Notes were reviewed retrospectively on patients with low serological indicators to determine diagnosis. RESULTS: These are the first data to indicate the sensitivity, specificity, and predictive values of the assays most frequently used to screen for C1 inhibitor deficiency. A combination of low C4 and low C1 inhibitor function has 98% specificity for C1 inhibitor deficiency in this population and a 96% negative predictive value, and is thus a very effective screen. All patients with untreated C1 inhibitor deficiency had a low C4 value. CONCLUSIONS: All patients considered for a diagnosis of C1 inhibitor deficiency should have serum examined to measure both C4 and functional C1 inhibitor. If either is normal at presentation this essentially excludes a diagnosis of C1 inhibitor deficiency. These tests can be performed sequentially. If C4 is normal it is not necessary to proceed to C1 inhibitor analysis. If C1 inhibitor function and C4 are both low then a repeat sample should be obtained to confirm the findings.

Angioedema↗

PubMed2001

Role of the PR intermediate in the reaction of cytochrome c oxidase with O2.

The first discernible intermediate when fully reduced cytochrome c oxidase reacts with O2 is a dioxygen adduct (compound A) of the binuclear heme iron-copper center. The subsequent decay of compound A is associated with transfer of an electron from the low-spin heme a to this center. This reaction eventually produces the ferryl state (F) of this center, but whether an intermediate state may be observed between A and F has been the subject of some controversy. Here we show, using both optical and EPR spectroscopy, that such an intermediate (P(R)) indeed exists and that it exhibits spectroscopic properties quite distinct from F. The optical spectrum of P(R) is similar or identical to the spectrum of the P(M) intermediate that is formed after compound A when two-electron-reduced enzyme reacts with O2. An unusual EPR spectrum with features of a CuB(II) ion that interacts magnetically with a nearby paramagnet [cf. Hansson, O., Karlsson, B., Aasa, R., Vänngård, T., and Malmström, B.G (1982) EMBO J. 1, 1295-1297; Blair, D. F., Witt, S. N., and Chan, S. I. (1985) J. Am. Chem. Soc. 107, 7389-7399] can be uniquely assigned to the P(R) intermediate, not being found in either the P(M) or F intermediate. The binuclear center in the P(R) state may be assigned as having an Fe(a3)(IV)=O CuB(II) structure, as in both the P(M) and F states. The spectroscopic differences between these three intermediates are evaluated. The P(R) state has a key role as an initiator of proton translocation by the enzyme, and the thermodynamic and electrostatic bases for this are discussed.

Animals↗

PubMed2001

Electron and proton transfer in the arginine-54-methionine mutant of cytochrome c oxidase from Paracoccus denitrificans.

Arginine 54 in subunit I of cytochrome c oxidase from Paracoccus denitrificans interacts with the formyl group of heme a. Mutation of this arginine to methionine (R54M) dramatically changes the spectral properties of heme a and lowers its midpoint redox potential [Kannt et al. (1999) J. Biol. Chem. 274, 37974-37981; Lee et al. (2000) Biochemistry 39, 2989-2996; Riistama et al. (2000) Biochim. Biophys. Acta 1456, 1-4]. During anaerobic reduction of the mutant enzyme, a small fraction of heme a is reduced first along with heme a(3), while most of heme a is reduced later. This suggests that electron transfer is impaired thermodynamically due to the low redox potential of heme a but that it still takes place from Cu(A) via heme a to the binuclear site as in wild-type enzyme, with no detectable bypass from Cu(A) directly to the binuclear site. Consistent with this, the proton translocation efficiency is unaffected at 1 H(+)/e(-) in the mutant enzyme, although turnover is strongly inhibited. Time-resolved electrometry shows that when the fully reduced enzyme reacts with O(2), the fast phase of membrane potential generation during the P(R )()--> F transition is unaffected by the mutation, whereas the slow phase (F --> O transition) is strongly decelerated. In the 3e(-)-reduced mutant enzyme heme a remains oxidized due to its lowered midpoint potential, whereas Cu(A) and the binuclear site are reduced. In this case the reaction with O(2) proceeds via the P(M) state because transfer of the electron from Cu(A) to the binuclear site is delayed. The single phase of membrane potential generation in the 3e(-)-reduced mutant enzyme, which thus corresponds to the P(M)--> F transition, is decelerated, but its amplitude is comparable to that of the P(R)--> F transition. From this we conclude that the completely (4e(-)) reduced enzyme is fully capable of proton translocation.

Arginine↗

PubMed2001

A new immunodeficient mouse model for human myoblast transplantation.

Design of efficient transplantation strategies for myoblast-based gene therapies in humans requires animal models in which xenografts are tolerated for long periods of time. In addition, such recipients should be able to withstand pretransplantation manipulations for enhancement of graft growth. Here we report that a newly developed immunodeficient mouse carrying two known mutations (the recombinase activating gene 2, RAG2, and the common cytokine receptor gamma, gammac) is a candidate fulfilling these requirements. Skeletal muscles from RAG2(-/-)/gammac(-/-) double mutant mice recover normally after myotoxin application or cryolesion, procedures commonly used to induce regeneration and improve transplantation efficiency. Well-differentiated donor-derived muscle tissue could be detected up to 9 weeks after transplantation of human myoblasts into RAG2(-/-)/gammac(-/-) muscles. These results suggest that the RAG2(-/-)/gammac(-/-) mouse model will provide new opportunities for human muscle research.

Animals↗

PubMed2001

Antisense-induced exon skipping and synthesis of dystrophin in the mdx mouse.

Duchenne muscular dystrophy (DMD) is a severe muscle wasting disease arising from defects in the dystrophin gene, typically nonsense or frameshift mutations, that preclude the synthesis of a functional protein. A milder, allelic version of the disease, Becker muscular dystrophy, generally arises from in-frame deletions that allow synthesis of a shorter but still semifunctional protein. Therapies to introduce functional dystrophin into dystrophic tissue through either cell or gene replacement have not been successful to date. We report an alternative approach where 2'-O-methyl antisense oligoribonucleotides have been used to modify processing of the dystrophin pre-mRNA in the mdx mouse model of DMD. By targeting 2'-O-methyl antisense oligoribonucleotides to block motifs involved in normal dystrophin pre-mRNA splicing, we induced excision of exon 23, and the mdx nonsense mutation, without disrupting the reading frame. Exon 23 skipping was first optimized in vitro in transfected H-2K(b)-tsA58 mdx myoblasts and then induced in vivo. Immunohistochemical staining demonstrated the synthesis and correct subsarcolemmal localization of dystrophin and gamma-sarcoglycan in the mdx mouse after intramuscular delivery of antisense oligoribonucleotide:liposome complexes. This approach should reduce the severity of DMD by allowing a dystrophic gene transcript to be modified, such that it can be translated into a Becker-dystrophin-like protein.

Animals↗

PubMed2001

Orbital cellulitis caused by Fusobacterium necrophorum.

PURPOSE: To report the case of a previously healthy young female who developed orbital cellulitis caused by Fusobacterium necrophorum. We are unaware of previous reports of this condition caused by the same anaerobic, gram-negative, nonsporeforming bacterium and could find no reference to it in a computer search using MEDLINE. METHODS: Case report. RESULTS: In the case of orbital cellulitis presented here, the patient required 3 sinus debridement operations and 30 days of intravenous antibiotics. Despite this, her vision did not fully recover. CONCLUSION: F. necrophorum is capable of causing severe orbital disease that requires aggressive and prompt treatment to preserve sight.

Adolescent↗

PubMed2001

The effects of astigmatism and working distance on optic nerve head images using a Heidelberg Retina Tomograph scanning laser ophthalmoscope.

PURPOSE: To determine effects of astigmatism and working distance on optic nerve head images in normal patients using the Heidelberg Retina Tomograph. METHODS: The optic disks of 51 normal healthy subjects, aged 19 to 44 years, were imaged through dilated pupils. Subjects with 0.75 DC or less of astigmatism were imaged without correction at a working distance of 15 mm. They were then re-imaged with a cylindrical correction of +3.00 DC at 90 degrees axis (n = 20). Naturally astigmatic subjects with more than 1.00 DC were imaged without correction and then re-imaged once this was neutralized with their appropriate spectacle prescription (n = 15). The effects of working distance were studied using subjects with 0.75 DC or less (n = 16). Two working distances were used, 15 and 25 mm. At each session the means of three topographic images were taken from which standard deviations and parameters were recorded. Parameters analyzed included cup shape measure, rim area, and inferior temporal rim volume. Z-profile full width at half maximum was calculated from one image per subject for each condition. RESULTS: No significant difference was found in the measured parameters of the optic disk for any astigmatic condition or changes in working distance (P >.05), (paired t test). Both the standard deviation of the mean topographic images and the Z-profile half-maximum width of the axial intensity profile were significantly greater with induced astigmatism of +3.00 DC (P values 0.3 and.00, respectively). CONCLUSIONS: Optic disk parameters are not significantly affected by uncorrected astigmatism (up to 2.50 DC) or working distance. The algorithm used by the Heidelberg Retina Tomograph to generate topographic maps is sufficiently robust that astigmatism up to 2.50 DC does not require correction.

Adult↗

PubMed2001

The pattern electroretinogram (PERG) with contralateral corneal reference.

The pattern electroretinogram (PERG) is a sensitive test for investigation of the proximal retina. For monocular recording, the contralateral corneal reference (CCR) electrode position has been suggested as a possible alternative to the conventional ipsilateral temporal reference (ITR). We therefore compared the effect of these electrode positions on 26 subjects (median age 45.5 years, IQR 24.5-61.5). The signals were recorded monocularly with DTL nylon fibre electrodes. The visual stimuli were high contrast 19' black-white checkerboard patterns, reversing 4 times/s. PERG responses obtained from the CCR gave larger amplitudes and the increase in amplitude was statistically significant (P < 0.001). Because the CCR signal is larger, new normative ranges must be established to avoid false negative results.

Adult↗

PubMed2001

The Humphrey optical coherence tomography scanner: quantitative analysis and reproducibility study of the normal human retinal nerve fibre layer.

BACKGROUND/AIMS: To determine the reproducibility of the Humphrey optical coherence tomography scanner (OCT), software version 5.0, for measurement of retinal nerve fibre layer (RNFL) thickness in normal subjects and to compare OCT measurements with published histological thickness of the human RNFL. METHODS: Three independent measurements were obtained at each session for one eye from 15 normal subjects with a mean age of 30.8 (SD 10.9) years. Scans were taken in the peripapillary retina using the default setting (1.74 mm radius from centre of the optic disc) and were repeated 1 week later. Additional scans were obtained at the optic nerve head (ONH) margin overlying the scleral rim, for comparison with available histological data on the human RNFL. RESULTS: For the 1.74 mm circular scan, the mean coefficient of variation (COV) for the global RNFL thickness measurement was 5% (SD 3%). This increased to 8% (3%) for quadrant measurements and to 9% (3%) with further subdivision into 12 segments. Significant differences (p<0.05) between sessions were only found when the data were divided into segments. The mean RNFL thickness for the 1.74 mm scan was 127.87 (9.81) microm. The RNFL was maximal at the superior disc pole, 161.44 microm (14.8), and minimal at the temporal pole, 83.1 (12.8) microm. Peak thickness values occurred superior temporal and inferior temporal to the vertical axis. RNFL thickness for every sector of the disc was greatest at the margin of the optic disc (mean 185.79 microm; SD 32.61). Although the variation in RNFL thickness around the disc follows published histology data, the OCT underestimates RNFL thickness by an average of 37% (SD 11; range 21-48%). CONCLUSION: The OCT provides reproducible measurement of the retinal structures that are consistent with the properties of the RNFL. However, comparison with available studies of RNFL thickness in the human suggests that in its present form, the OCT underestimates RNFL thickness. Further refinement of this technology is required to improve the accuracy with which the OCT measures retinal nerve fibre layer thickness.

Adult↗

PubMed2001

Stable strontium accumulation by earthworms: a paradigm for radiostrontium interactions with its cationic analogue, calcium.

The accumulation of stable strontium and its chemical analogue calcium by four species of earthworm, representing three distinct ecophysiological groups inhabiting celestite (SrSO4)-rich natural soils, was investigated. An increase in soil strontium concentration over a four-orders-of-magnitude range was accompanied by an increase in earthworm tissue strontium concentration. In contrast, no relationship between soil and tissue calcium concentrations was apparent, indicating that this essential cation is strongly regulated within earthworm tissues but that nonessential strontium burdens are not physiologically regulated. Concentration factors for strontium ranged from 0.1 to 1.42, with an inverse relationship between this parameter and soil strontium concentration. The use of concentration factors and discrimination coefficients lead to the conclusion that earthworms discriminate against strontium accumulation at increased soil calcium concentrations, such that strontium would be predicted to be more efficiently accumulated by worms inhabiting acidic, calcium-poor soils. Although few consistent trends in strontium and calcium concentration were apparent between earthworm species, the species with the highest calcium turnover (i.e., the litter-inhabiting Lumbricus rubellus) typically accumulated higher concentrations of strontium than representatives of contrasting ecophysiological classes. These findings are considered in the context of the distribution, retention, and cycling of radiostrontium in soils.

Animals↗

PubMed2001

The s-cone PHNR and pattern ERG in primary open angle glaucoma.

PURPOSE: To compare the sensitivity of the photopic negative response (PhNR) from the shortwave (S)-sensitive and the long (L)- and medium (M)-wave-sensitive cone electroretinograms (ERGs), with the pattern electroretinogram (PERG) in the early stages of primary open-angle glaucoma (POAG). METHODS: Eighteen patients under treatment for diagnosed POAG and 19 normal control subjects were investigated. S-cone ERGs were elicited using adaptation to 650-nm light to suppress L-cone activity, and substitution between 450 nm and 535 nm to silence M-cone response at luminances higher than rod saturation. PhNRs from the L&M-cone pathways were elicited by a 200-msec pulse of red light (650 nm) on a continuous blue (450 nm) background. PERGs were recorded in accordance with the International Society for Clinical Electrophysiology of Vision (ISCEV) standard. RESULTS: Each method showed a statistically significant difference in the two groups. The S-cone PhNR was the most sensitive test and provided the most statistically significant results, with the largest area enclosed by the receiver operating characteristic (ROC) curve. CONCLUSIONS: The findings indicate that all three types of ERG may be useful in glaucoma investigation. The L- and M-cone PhNRs may have a role in monitoring established glaucoma. The previously reported high sensitivity of the PERG was confirmed. Extensive diffuse damage to S-cone bipolar and bistratified ganglion cells appears to occur at a very early stage in POAG, owing to a pressure-related mechanism, and the S-cone PhNR was the most sensitive test. It may in future have an important role in diagnosis and monitoring of early glaucoma. Further investigation of this possibility is recommended.

Aged↗

PubMed2000

Electrogenic reactions of cytochrome bd.

Cytochrome bd is one of the two terminal quinol oxidases in the respiratory chain of Escherichia coli. The enzyme catalyzes charge separation across the bacterial membrane during the oxidation of quinols by dioxygen but does not pump protons. In this work, the reaction of cytochrome bd with O(2) and related reactions has been studied by time-resolved spectrophotometric and electrometric methods. Oxidation of the fully reduced enzyme by oxygen is accompanied by rapid generation of membrane potential (delta psi, negative inside the vesicles) that can be described by a two-step sequence of (i) an initial oxygen concentration-dependent, electrically silent, process (lag phase) corresponding to the formation of a ferrous oxy compound of heme d and (ii) a subsequent monoexponential electrogenic phase with a time constant <60 mus that matches the formation of ferryl-oxo heme d, the product of the reaction of O(2) with the 3-electron reduced enzyme. No evidence for generation of an intermediate analogous to the "peroxy" species of heme-copper oxidases could be obtained in either electrometric or spectrophotometric measurements of cytochrome bd oxidation or in a spectrophotometric study of the reaction of H(2)O(2) with the oxidized enzyme. Backflow of electrons upon flash photolysis of the singly reduced CO complex of cytochrome bd leads to transient generation of a delta psi of the opposite polarity (positive inside the vesicles) concurrent with electron flow from heme d to heme b(558) and backward. The amplitude of the delta psi produced by the backflow process, when normalized to the reaction yield, is close to that observed in the direct reaction during the reaction of fully reduced cytochrome bd with O(2) and is apparently associated with full transmembrane translocation of approximately one charge.

Carbon Monoxide↗

PubMed2000

Binding of O(2) and its reduction are both retarded by replacement of valine 279 by isoleucine in cytochrome c oxidase from Paracoccus denitrificans.

The crystal structure of the heme-copper oxidases suggested a putative channel of oxygen entry into the heme-copper site of O(2) reduction. Changing a conserved valine near this center in cytochrome bo(3) of Escherichia coli to isoleucine caused a significant increase in the apparent K(M) for oxygen with little or no change in V(max), suggesting that oxygen diffusion had been partially blocked [Riistama, S., Puustinen, A., García-Horsman, A., Iwata, S., Michel, H., and Wikström, M. (1996) Biochim. Biophys. Acta 1275, 1-4]. To study this phenotype further using rapid kinetic methods, the corresponding change (V279I) has been made in cytochrome aa(3) from Paracoccus denitrificans. In this mutant, the apparent K(M) for oxygen is 8 times higher than in the wild-type enzyme, whereas V(max) is decreased only to approximately half of the wild-type value. Flow-flash kinetic measurements show that the initial binding of oxygen to the heme of the binuclear site is indeed much slower in the mutant than in the wild-type enzyme. However, the subsequent phases of the reaction with O(2) are also slow although the pure heme-to-heme electron transfer process is essentially unperturbed. It is suggested that the mutation sterically hinders O(2) entry into the binuclear site and that it may also perturb the structure of local water molecules involved in proton transfer to this site.

Amino Acid Substitution↗

PubMed2000

Scanning laser polarimetry of the normal human retinal nerve fiber layer: a quantitative analysis.

PURPOSE: To provide a quantitative comparison of retardation values obtained with the scanning laser polarimeter (Nerve Fiber Layer Analyzer; Laser Dignostic Technologies, San Diego, California) in normal subjects, with the known histologic properties of the human retinal nerve fiber layer. METHODS: Scanning laser polarimetry was performed on 48 normal subjects. The retardation values obtained from each eye were processed to remove reflections from the optic nerve head vasculature and to derive peripapillary polar retardation profiles. The location of the maximum and minimum retardation values superior and inferior to the disk was determined. Retardation values were also determined along lines running radially from the center of the optic disk to through the points of maximal retardation. RESULTS: Retardation values were greater in the superior and inferior quadrants of the peripapillary retinal nerve fiber layer compared with the nasal and temporal quadrants. Superiorly, peak retardation values were nasal to the vertical meridian by 22.9 degrees (SD, 17.5) in right eyes and by 15.7 degrees (SD, 17.7) in left eyes. Inferiorly, the peak showed a closer correspondence with the vertical meridian, lying nasal to this by 0.8 degrees (SD, 14.9) in right eyes and temporal to this by 2.8 degrees (SD, 15.4) in left eyes. Radial analysis showed that the peak retardation occurred approximately (0.5 to 0.7 disk diameters from the optic disk margin) at the superior and inferior aspect of the disk. The degree of modulation of retardation around the optic disk was less than would be expected from the variation in peripapillary nerve fiber layer thickness seen histologically. CONCLUSION: The location of the peak retardation values shows reasonable agreement with the angular location of the peak values of nerve fiber layer thickness published for humans. By contrast, the modulation of retardation values around the disk and the change with eccentricity from the optic disk center differ from the anatomic data. The Nerve Fiber Layer Analyzer appears to measure a correlate of nerve fiber layer thickness, but it is important that any discrepancies between the retardation and anatomic data are recognized in the clinical interpretation of polarimetric data.

Adult↗

PubMed2000

Optic nerve head structure in glaucoma: astrocytes as mediators of axonal damage.

Increased intraocular pressure (IOP) is recognised as the principal risk factor for the development of glaucomatous cupping of the optic disc. The hypothesis that it disrupts the function of retinal ganglion cell axons by increasing mechanical forces on the lamina cribrosa of the optic nerve head has received considerable experimental support. However, many patients with glaucoma will have progressive cupping even though the IOPs remain within the normal range, suggesting that mechanical compression is unlikely to be the sole cause of optic nerve damage. Clinical studies have emphasised the role of other factors, such as optic nerve head ischaemia, in generating optic disc cupping. One of the outstanding problems in understanding optic nerve head dysfunction in glaucoma has been the elucidation of the pathways that could integrate the effects of IOP and ischaemia to generate the characteristic changes seen. This review considers the role that optic nerve head astrocytes might play in the initiation of axon damage, based on the hypothesis that these cells are sensitive to mechanical or ischaemic factors and are important for the maintenance of retinal ganglion physiology. It discusses their role in the remodelling of the structure of the lamina cribrosa and the effect that this might have on axon function. Recent evidence has shown that the modulation of astrocyte activity, for example by the reduction of the production of nitric oxide, may prevent retinal ganglion cell death in ocular hypertension. The possibility that astrocyte-axon interactions are important in the development of glaucomatous optic neuropathy suggests new avenues of therapeutic intervention, not related to the control of IOP, that would prevent retinal ganglion cell death in glaucoma.

Astrocytes↗

PubMed2000

Retinal ganglion cell death in experimental glaucoma.

AIMS: To determine whether parasol retinal ganglion cells (magnocellular pathway) are selectively lost in the primate model of glaucoma. METHODS: Ocular hypertension was induced in one eye of six Macaca fascicularis monkeys for 6-14 weeks. The retinal ganglion cells in these eyes were labelled retrogradely with the tracer horseradish peroxidase (HRP) implanted into the optic nerve and subsequently examined in retinal whole mount preparations. The degree of retinal ganglion cell loss was estimated from Nissl stained tissue by comparison with the contralateral untreated control eye. RESULTS: In the three glaucomatous retinas with the best labelling 1282 cells could be classified, of which 182 were parasol cells and 1100 were midget cells. Linear regression analysis did not demonstrate a significant reduction in the proportion of parasol to midget cells with increasing cell loss (regression slope 0.023, 95% CI -0.7 to 0.11). Compared with the control eye the cell soma of the remaining retinal ganglion cells in glaucomatous eyes were reduced in size by 20% for parasol cells (p=0.003) and by 16% for midget cells (p <0.001). CONCLUSION: The results of this study do not support the hypothesis that selective loss of parasol retinal ganglion cells occurs in experimental glaucoma. In addition, the change in cell soma size distributions following ocular hypertension suggests that both parasol and midget retinal ganglion cells undergo shrinkage before cell death.

Animals↗

PubMed2000

Clinical and neuropsychological profiles of obsessive-compulsive schizophrenia: a pilot study.

This pilot study compared characteristics of obsessive-compulsive (OC) schizophrenic patients and a matched non-OC schizophrenic control group. The OC-schizophrenic group required more intensive clinical interventions and had a poorer clinical course, lower levels of functioning, and longer periods of hospitalization. They showed greater negative symptoms and more impaired executive functioning. These findings suggest OC-schizophrenic patients may have an atypical set of clinical and neuropsychiatric characteristics, perhaps constituting a subgroup within the schizophrenia spectrum. Pathophysiology and possible treatment implications require further study.

Adult↗