Psychometric properties of the Observer Alexithymia Scale in a clinical sample.

The purpose of this study was to evaluate the psychometric properties of the Observer Alexithymia Scale (OAS; Haviland, Warren, & Riggs, 2000) in a clinical setting. Clinical and counseling psychologists used the OAS to rate outpatients (n = 192) with various Diagnostic and Statistical Manual of Mental Disorders (American Psychiatric Association, 1994) diagnoses. Reliability and validity data are similar to the initial nonclinical data (n = 819): OAS scores are reliable (coefficient alpha = .90), and the five-factor structure--Distant, Uninsightful, Somatizing, Humorless, and Rigid--was confirmed. Moreover, the OAS does a relatively good job of differentiating clinical from nonclinical cases. The OAS is psychometrically sound, and it appears to be a useful tool for collecting and evaluating observer data on the clinically relevant, everyday expressions of alexithymia.

An observer scale to measure alexithymia.

The authors developed a relatively brief observer alexithymia measure that can be used by patients' acquaintances and relatives. Items corresponding to the defining features of alexithymia (California Q-Set Alexithymia Prototype) were written, and the new instrument's psychometric properties were evaluated in 3 lay-rater samples. The 33-item Observer Alexithymia Scale (OAS) is internally consistent (coefficient alphas = 0.88 and 0.89) and stable (2-week test-retest reliability = 0.87). Moreover, it has an interpretable five-factor structure (based on exploratory and confirmatory factor analyses): distant, uninsightful, somatizing, humorless, and rigid. The OAS is a reliable instrument with a stable factor structure and good conceptual coverage and thus, it appears to be a useful tool for collecting observer data on the clinically relevant expressions of alexithymia that receive minimal attention.

Dural repair using acellular human dermis: experience with 200 cases: technique assessment.

OBJECTIVE: Many craniotomies require a watertight dural closure. When primary dural repair is not possible, a graft is necessary. Autograft material is not always easily accessible or available, necessitating the use of other material. We performed 200 craniotomies using an acellular human dermal graft (AlloDerm; LifeCell Corp., The Woodlands, TX) to determine its suitability as a dural substitute. METHODS: From June 1996 through March 1998, all patients at Allegheny General Hospital who required a dural substitute graft and in whom autograft harvest was impractical or impossible received the acellular dermal autograft. The running suture technique was used to form a watertight seal. RESULTS: After follow-up for a minimum of 1 year, seven patients have required subsequent surgery. Three patients developed cerebrospinal fluid leaks that were repaired without removing the dermal graft. Four patients developed wound infections that required debridement. In each patient, the graft seemed to be uninvolved in the infectious process and was left in place. The patients were administered antibiotics postoperatively, and there have been no recurrent infections. No adhesion formation or scarring was noted around or underneath the graft in any patient. CONCLUSION: AlloDerm is a reasonable alternative to the available dural graft materials. Its handling characteristics are similar to those of dura, it is biologically inert, and it does not produce adhesion formation.

On the field evaluation of athletic head injuries.

This article reviews the diagnosis and management of athletic-related head injury. Cerebral concussion, diffuse axonal injury, brain contusion, and the spectrum of intracranial hematoma is discussed. Emphasis is placed on the need to evaluate when it is prevented from further participation.

On the field evaluation of athletic neck injury.

This article reviews the on the field management of athletic cervical spine and spinal cord injury. The various types of injuries are discussed, as well as the team approach to evaluation, immobilization, and transport of the injured athlete. An overview of treatment rationale and decisions regarding the return of the spine-injured or spinal cord-injured player to competition is given. Emphasis is placed on the prevention of further injury by mishandling the injured athlete.

Association of genes within the major histocompatibility complex with attention deficit hyperactivity disorder.

The objective was to determine whether a relationship exists among the complement C4B gene, a DR region gene and attention deficit hyperactivity disorder (ADHD). Thirty-one subjects with ADHD, their mothers, all but 5 of their fathers, and 90 normal subjects living in northern Utah were studied. DR and C4B typing were performed by serologic HLA typing techniques and the DNA methods PCR-RFLP. The alleles of 2 genes, the null allele of the C4B gene and the beta 1 allele of the DR gene, encode for products involved in immune function and regulation. Each of these alleles was found to be significantly associated with ADHD. Moreover, approximately 55% of the ADHD subjects carried both of these alleles on 1 of their chromosomes, compared to only 8% of normal controls. Genes related to the immune system may be associated with development of the symptoms of ADHD.

Strong association of the third hypervariable region of HLA-DR beta 1 with autism.

We reported that the major histocompatibility complex (MHC) including the null allele of the C4B gene and the extended haplotype B44-C30-DR4 is associated with autism. We report now that the third hypervariable region (HVR-3) of certain DR beta 1 alleles have very strong association with autism. The HVR-3 of DR beta 1* 0401 or the shared HVR-3 alleles DR beta 1* 0404 and DR beta 1* 0404 and DR *0101, was expressed on extended haplotypes in 23 of 50 (46%) autistic subjects as compared to only 6 of 79 (7.5%) normal subjects. Another HVR-3 sequence, the DR beta 1* 0701 allele, was carried on extended haplotypes in 16 (32.0%) of the autistic subjects as compared to 8 (10.1%) of the normal subjects.

Immunogenetic studies in autism and related disorders.

The major histocompatibility complex comprises a number of genes that control the function and regulation of the immune system. One of these genes, the C4B gene, encodes a product that is involved in eliminating pathogens such as viruses and bacteria from the body. We previously reported that a deficient form of the C4B gene, termed the C4B null allele (no C4B protein produced) had an increased frequently in autism. In this study we attempted to confirm the increased incidence of the C4B null allele in autism and investigated the presence of a C4B null allele in two other childhood disorders, attention-deficit hyperactivity disorder and dyslexia (reading disability). In addition, we explored the relationship of autism to the DR beta 1 gene, a gene located close to the C4B in autism. We confirmed the finding of an increased frequency of the C4B null allele in autism and found that the related disorders also had an increased frequency of this null allele. In addition, two alleles of the DR beta 1 gene also had significantly increased representation in the autistic subjects.

Is decreased blood plasma concentration of the complement C4B protein associated with attention-deficit hyperactivity disorder?

OBJECTIVE: The complement system is a group of blood proteins that play an important role in defending against viral and bacterial infections. The objective of this investigation was to study the plasma levels of the C4B protein in attention-deficit hyperactivity disorder (ADHD) in an attempt to associate infections with the development of some cases of this disorder. METHOD: C4B plasma protein levels were studied using an enzyme-linked immunosorbent assay in a group of 23 subjects meeting DSM-III-R criteria for ADHD and a similar number of age- and sex-matched controls. Also studied were parents of the ADHD subjects. RESULTS: C4B plasma levels (157.0 micrograms/mL) in the ADHD subjects were significantly (p < .01) lower than those (239.3 micrograms/mL) in the normal age-matched subjects. Mothers of the ADHD subjects also had significantly lower C4B values compared with mothers of normal children. On the other hand, C4B values in the fathers were not significantly altered. CONCLUSIONS: Decreased C4B levels in ADHD, if replicated, may represent an important marker for ADHD (or a subgroup of ADHD). It also seems plausible that C4B levels are an important etiological factor for ADHD.

HLA-B27 binding of peptide from its own sequence and similar peptides from bacteria: implications for spondyloarthropathies.

The spondyloarthropathies are associated by an unknown mechanism with HLA-B27 and certain bacteria. HLA-B27 shares sequence with proteins from enteric bacteria. The B*2705 sequence contains a nonapeptide, LRRYLENGK, predicted to bind in the binding cleft of B27. Some nonapeptides from enteric organisms that share sequence with this nonapeptide of B27 also bind B27. These observations suggest an unappreciated mechanism for autoimmunity that may operate in the B27-associated spondyloarthropathies involving peptides bound to and derived from histocompatibility alleles.

DR-positive T cells in autism: association with decreased plasma levels of the complement C4B protein.

Autism is a developmental disorder characterized by severe communication, social and behavioral abnormalities. Over the past several years a fair amount of evidence has accumulated suggesting that some cases of autism may be associated with immune abnormalities and with products of the HLA complex including the C4B gene located in the class III region of HLA. This study sought additional evidence for an association of autoimmune processes with autism by investigating the presence of activated T cells in 26 autistic subjects. Fourteen of the autistic subjects had DR+ T cells, an indicator of activated T cells, but none of the autistic subjects had T cells expressing the interleukin-2 receptor, another indicator of T cell activation. Similar findings of incomplete or partial T cell activation have been reported in autoimmune disorders and in a recent study of autism. In the current investigation, the DR+ T cells were not found to be associated with age of the autistic patients but were inversely correlated with a decreased plasma level of the C4B protein. In conclusion, this study provides additional evidence for the involvement of an autoimmune mechanism in autism.

Increased frequency of the extended or ancestral haplotype B44-SC30-DR4 in autism.

Autism likely results from several different etiologies or a combination of pathological mechanisms. Recent studies suggest that this disorder may be associated with immune abnormalities, pathogen-autoimmune processes and perhaps the major histocompatibility complex (MHC). In a preliminary study we found that 22 autistic subjects had an increased frequency of the extended or ancestral MHC haplotype B44-SC30-DR4. The current study attempted to confirm this observation by studying 23 additional randomly chosen autistic subjects, most of their parents and 64 unrelated normal subjects. In agreement with earlier findings B44-SC30-DR4 was associated with autism. In combining the data from the original and current studies, B44-SC30-DR4 or a substantial fragment of this extended haplotype was represented in 40% of the autistic subjects and/or their mothers as compared to about 2% of the unrelated subjects. It is concluded that one or more genes of the MHC is (are) involved in the development of some cases of autism.

Decreased plasma concentrations of the C4B complement protein in autism.

OBJECTIVE: To determine complement C4 protein concentrations in the plasmas of autistic subjects and their family members. DESIGN: Cross-sectional study. SETTING: Center for Persons with Disabilities and the Department of Biology, Utah State University, Logan. PARTICIPANTS: Forty-two autistic subjects (34 males [81%] and eight females [19%]), 50 of their biologic parents, 21 siblings, and 105 normal subjects (56 females [53%] and 49 males [47%]; all white) living in northern Utah. INTERVENTIONS: None. METHODS: The enzyme-linked immunosorbent assay was used to determine C4 protein concentrations in autistic subjects. MAIN RESULTS: Plasma concentration (median, 14.7 g/L of the C4B protein) in autistic patients was significantly (P = .01) decreased compared with that of normal subjects (median, 22.4 g/L). The C4B concentrations in parents and siblings of autistic children were decreased, but not significantly. The C4A protein concentrations in the plasma of autistic subjects and their family members were normal. CONCLUSION: Decreased protein concentrations of C4B may be associated with autism.

A hypothesis for the HLA-B27 immune dysregulation in spondyloarthropathy: contributions from enteric organisms, B27 structure, peptides bound by B27, and convergent evolution.

Several human rheumatic diseases occur predominantly in persons who carry the histocompatibility (HLA) class I allele B27. They have also been related to Gram-negative enteric microorganisms. In addition, the recent recovery of peptides bound to B27 has allowed an understanding of the structural requirements for their binding. Using the accumulated data base of protein sequences, we have tested a series of hypotheses. First, we have asked whether the primary amino acid sequence of the hypervariable regions of HLA-B27 shares short sequences with the proteins of Gram-negative enteric bacteria. The data demonstrate that, unique among the HLA-B molecules, the hypervariable regions of HLA-B27 unexpectedly share short peptide sequences with proteins from these bacteria. Second, we have asked whether the enteric proteins tend to satisfy the structural requirements for peptide binding to B27 in those regions of the sequence shared with B27. This hypothesis also tends to be true, especially in an allelically variable part of the B27 sequence which is predicted to bind B27 if it were to be presented as a free peptide. We conclude that HLA-B27 and enteric Gram-negative bacteria have undergone a previously unappreciated form of convergent evolution which may be important in the process leading to these rheumatic diseases. Moreover, the regions of the enteric bacterial proteins which are contiguous with the short sequences shared with B27 tend to have structures which are also predicted to bind B27. These observations suggest a mechanism for autoimmunity and lead to the prediction that the B27-associated diseases are mediated by a subset of T-cell receptors, B27, and the peptides bound by B27.

Antibodies to myelin basic protein in children with autistic behavior.

Based on a possible pathological relationship of autoimmunity to autism, antibodies reactive with myelin basic protein (anti-MBP) were investigated in the sera of autistic children. Using a screening serum dilution of 1:400 in the protein-immunoblotting technique, approximately 58% (19 of 33) sera of autistic children (< or = 10 years of age) were found to be positive for anti-MBP. This result in autistics was significantly (p < or = .0001) different from the controls (8 of 88 or only 9% positive), which included age-matched children with normal health, idiopathic mental retardation (MR) and Down syndrome (DS), and normal adults of 20 to 40 years of age. Since autism is a syndrome of unknown etiology, it is possible that anti-MBP antibodies are associated with the development of autistic behavior.

Possible association of the extended MHC haplotype B44-SC30-DR4 with autism.

We previously reported that the complement C4B null allele appears to be associated with infantile autism. Since the C4B null allele is known to be part of the extended or ancestral haplotype [B44-SC30-DR4], we investigated the incidence of [B44-SC30-DR4] in 21 autistic children and their parents. This extended haplotype was increased by almost six-fold in the autistic subjects as compared with healthy controls. Moreover, the total number of extended haplotypes expressed on chromosomes of autistic subjects was significantly increased as compared with those expressed on chromosomes of healthy subjects. We conclude that a gene related to, or included in, the extended major histocompatibility complex may be associated with autism.

Increased frequency of the null allele at the complement C4b locus in autism.

Associations between C4 deficiency and autoimmune disorders have been found over the past several years. Since autism has several autoimmune features, the frequencies of null (no protein produced) alleles at the C4A and C4B loci were studied in 19 subjects with autism and their family members. The autistic subjects and their mothers had significantly increased phenotypic frequencies of the C4B null allele (58% in both the autistic subjects and mothers, compared with 27% in control subjects). The siblings of the autistic subjects also had an increased frequency of the C4B null allele, but this increase was not significant. The fathers had normal frequencies of this null allele. All family members had normal frequencies of the C4A null allele, all normal C4A and C4B alleles and all BF and C2 alleles.

Detection of maternal antibodies in infantile autism.

Maternal antibodies reactive with antigenic proteins expressed on the cell surface of paternal lymphocytes can be detected in couples with histories of more than one miscarriage or stillbirth. It is possible, but not proven, that these antibodies also react with tissues of the fetus and result in fetal death. Since many mothers of autistic children have a history of pregnancy disorder, antibodies were studied in 11 mothers of autistic children who were 6 years of age or younger. Six of the mothers had antibodies that reacted with lymphocytes of the autistic child. Five of these six mothers had a history of pregnancy disorder. Since antigens expressed on lymphocytes are found on cells of the central nervous system and, perhaps, other tissues of the developing embryo, it is suggested that aberrant maternal immunity may be associated with the development of some cases of infantile autism.