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PubMed2001

Correlation of intact sensibility and neuropathic pain-related behaviors in eight inbred and outbred rat strains and selection lines.

In some rat strains, total hindpaw denervation triggers autotomy, a behavior of self mutilation presumably related to neuropathic pain. Partial sciatic ligation (PSL) in rats produces tactile allodynia and heat hyperalgesia but not autotomy. Our aims in this study were to examine: (1) whether sensibility of intact rats to noxious and non-noxious stimuli is strain-dependent; (2) whether sensibility of intact rats could predict levels of autotomy, or of allodynia and hyperalgesia in the PSL model; and (3) whether autotomy levels are correlated with levels of allodynia or hyperalgesia. Here we report that in two inbred rat strains (Lewis and Fisher 344), two outbred rat strains (Sabra and Sprague-Dawley) and four selection lines of rats (Genetically Epilepsy-Prone Rats, High Autotomy, Low Autotomy and Flinders Sensitive Line), tactile sensitivity and response duration to noxious heat of intact animals were strain-dependent. Levels of autotomy following hindpaw denervation and of allodynia and hyperalgesia in the PSL model were also strain-dependent. Thus, these traits are determined in part by genetic factors. Sensory sensibility of intact rats was not correlated with levels of autotomy following total denervation, or allodynia and hyperalgesia following partial denervation. We suggest that preoperative sensibility of intact rats is not a predictor of levels of neuropathic disorders following nerve injury. Likewise, no correlation was found between autotomy, allodynia and hyperalgesia, suggesting that neuropathic pain behaviors triggered by nerve injury of different etiologies are mediated by differing mechanisms.

Animals↗
PubMed2000

Abnormalities in cellular adhesion of neuroblastoma and fibroblast models of Lesch Nyhan syndrome.

Lesch Nyhan syndrome is a neurological paediatric condition characterized by mental retardation, choreathotosis and self-mutilation. Biochemically, this condition has been attributed to a deficiency in the purine enzyme, hypoxanthine guanine phosphoribosyltransferase, however, the way this affects the development of the nervous system is still unknown. Ma et al.(15) and Stacey et al.(25) found that hypoxanthine guanine phosphoribosyltransferase-deficient neuroblastoma, differentiated significantly more than cells with this enzyme. Here, we report that adhesion of hypoxanthine guanine phosphoribosyltransferase-deficient neuroblastoma as well as fibroblasts from patients with Lesch Nyhan syndrome, exhibited dramatically enhanced adhesion compared to control cells. This increase in adhesion was dependent upon the cell type, density of the cells and upon the substrate used. Development of the nervous system is dependent on adhesion, in particular in the processes of migration, nucleation, differentiation and fasciculation. Our results suggest that the increased adhesion of hypoxanthine guanine phosphoribosyltransferase-deficient neuroblastoma and fibroblasts in vitro underpins the neuropathology of Lesch Nyhan syndrome.

Animals↗
PubMed1995

Overview of equine pruritus.

Pruritus is a common complaint associated with equine dermatoses. Self-mutilation results in alopecia, excoriations, scaling, and crusting; the aesthetic appearance of the horse is often ruined and the horse may be unfit for riding or showing. This article specifically addresses those pruritic dermatoses caused by allergies, including food allergy/intolerance, atopy and contact allergy, as well as by two ectoparasites, stick-tight fleas and rhabditic mange. The clinical signs, diagnostic tests, and treatment recommendations are discussed for each disorder. Insect hypersensitivity and pruritus associated with the other more common ectoparasites are covered in depth elsewhere in this issue.

Animals↗
PubMed1986

Aggressive behavior problems.

Accurate diagnosis of the cause of aggression in horses is essential to determining the appropriate course of action. The affective forms of aggression include fear-induced, pain-induced, intermale, dominance, protective, maternal, learned, and redirected aggressions. Non-affective aggression includes play and sex-related forms. Irritable aggression and hypertestosteronism in mares are medical problems, whereas genetic factors, brain dysfunction, and self-mutilation are also concerns.

Affect↗
PubMed2000

New mutations of the HPRT gene in Lesch-Nyhan syndrome.

Lesch-Nyhan syndrome is an X-linked recessive disorder involving the purine metabolism, with resultant hyperuricemia, choreoathetosis, self-mutilation, and profound neurologic dysfunction. A deficiency of the enzyme hypoxanthine guanine phosphoribosyl-transferase is responsible for the disease. The human HPRT gene is located at Xq26-27 and consists of 57 base pairs. At least 2,000 mutations throughout the HPRT gene coding region from exon 1-9 have been reported. Four patients from three Chinese families were diagnosed with Lesch-Nyhan syndrome according to the clinical and laboratory findings. DNA studies revealed the first family (Patients 1 and 2) had a missense mutation in exon 3 of the HPRT encoding region. This novel mutation occurs in the hot spot of the HPRT gene. The second family (Patient 3) was found to have a missense mutation in exon 8 of the HPRT gene. The third family (Patient 4) carried a mutation in the splicing region of intron 4 of the HPRT gene. All three mutations were de novo.

Base Sequence↗
PubMed1998

Hereditary insensitivity to pain with anhidrosis.

Hereditary sensory neuropathy type IV is an autosomal-recessive disorder characterized by congenital insensitivity to pain and anhidrosis and resulting in recurrent hyperpyrexia, self-mutilation, recurrent infections, chronic osteomyelitis, bone and joint deformities, and limb amputations. Described is a child with signs as well as skin and nerve biopsy results compatible with this disease, emphasizing the importance of early diagnosis and appropriate medical and educational care to prevent complications.

Biopsy↗
PubMed2002

A genetic basis for obsessive grooming.

Excessive grooming behaviors, cleansing rituals, and self-mutilation are important features of a range of neuropsychiatric diseases including obsessive compulsive (OC)-spectrum disorders. In this issue of Neuron, Greer and Capecchi (2002) report that Hoxb8 mutant mice exhibit this behavioral phenotype. These Hoxb8 mutants will be valuable in exploring the genetics and pathophysiology of OC-spectrum disorders as well as strategies for their treatment.

Animals↗
PubMed2001

Treatment of the agitation of late-life psychosis and Alzheimer's disease.

In older as well as younger people, antipsychotic medication is commonly used to treat psychoses. In clinical practice, antipsychotic medication is also used to control severe behavioral disturbances such as agitation, wandering, self-mutilation, as well as assaultiveness. Neuroleptic and non-neuroleptic drug treatments are used to control severe agitation and disruptive behavior. Among typical neuroleptics, very low doses (e.g., 0.25 mg of haloperidol 1-4 times per day) may be effective and limit the development of severe extrapyramidal reactions. Recent experience suggests that the atypical neuroleptics, olanzaine, risperidone, and quetiapine, are also useful for controlling severe agitation in elderly demented nursing home residents. The benzamides are also known for the treatment of behavioral disturbances in Europe, but there is little experience in the U.S.A. Although research studies in this area are virtually nonexistent, growing clinical experience suggests that the following may be quite useful: 1) trazodone; 2) buspirone (Buspar); 3) anticonvulsants (e.g., valproate); and 4) beta-blockers.

Aged↗
PubMed1999

The treatment of cyclical behavioral changes in women with mental disabilities.

STUDY OBJECTIVE: This study aims to evaluate the frequency of occurrence of cyclical behavioral changes in women with mental retardation, as well as the effectiveness of several treatment modalities for this type of behavior. DESIGN: Retrospective chart analysis. SETTING: University of Michigan clinic for reproductive healthcare of women with mental disabilities. PARTICIPANTS: All clinic patients of reproductive age, presenting with cyclical behavioral changes in our clinic from November 1985 to October 1992. INTERVENTIONS: Medical treatment of cyclical behavioral changes. MAIN OUTCOME MEASURES: Presence and documentation of cyclical behavioral changes, level of retardation, type of behavior, treatment modalities and results. RESULTS: Ninety-three of 522 reproductive-age patients (18%) presented with cyclical behavioral changes. Good documentation with behavior charts was present in 46% of these records. Level of retardation among the women included: 57 (61%) severely, 12 (13%) moderately, and 1 (1%) mildly retarded. No level of retardation could be detected in 23 (25%) women. Aggressive behavior was noted in 35 (38%) women, self-mutilation in 20 (22%) a combination of both in 10 (10%) and other behavior in 28 (28%) women. Primary treatment was by physician preference. Of 46 patients who received nonsteroidal antiinflammatory drugs (NSAID), 30 (65%) showed improvement, 10 (21%) showed no improvement, and 2 patients (4%) showed worsening symptoms. Birth control pills were used in 15 patients; there were signs of improvement in 6 (40%), no improvement in 3 (20%), and worsening in 3 (20%). The use of depomedroxyprogesterone injections was successful in treating 6 of 9 patients (66%), and showed no improvement in 2 women. No statistically significant differences were found between these treatment modalities. CONCLUSIONS: Cyclical behavioral changes in women with mental retardation is a common problem (18%) and may be related to pain- possibly due to menstrual cramps, since 65% of the patients responded to NSAID. If treatment with NSAID is unsuccessful, birth control pills and depomedroxyprogesterone improved behavior in 40% to 66% of patients. Documentation is a key issue.

Adolescent↗
PubMed2001

Avian skin diseases.

Avian dermatology is an important part of avian practice. Feather plucking, or self-mutilation, is one of the most common and challenging syndromes seen in avian practices, yet our understanding of it has developed piecemeal. Psittacine circovirus, which causes psittacine beak and feather disease, can devastate breeding programs and cause masked distress to new bird owners and their young birds. Cutaneous neoplasms are increasing in incidence as veterinarians are seeing more older bird patients.

Animals↗
PubMed2000

Absent innervation of skin and sweat glands in congenital insensitivity to pain with anhidrosis.

OBJECTIVES: A case of a 10-year-old girl with congenital insensitivity to pain with anhidrosis (CIPA) is reported. METHODS AND RESULTS: Parents referred several hyperpyretic episodes without sweating occurring since birth, and insensitivity to pain, noticed when the child was 2 years old. Her body had many bruises and scars, bone fractures and signs of self-mutilation. Neurological examination was normal except for insensitivity to pain. Her IQ was 52. Electrical and tactile sensory nerve conduction velocities were normal. The patient was unable to detect thermal stimuli. Histamine injection evoked a wheal but not a flare; pilocarpine by iontophoresis did not induce sweat. Microneurography showed neural activity from A-beta sensory fibers while nociceptive and skin sympathetic C fiber nerve activity was absent. No small myelinated fibers and very rare unmyelinated fibers were found in the sural nerve. Immunohistochemistry showed a lack of nerve fibers in the epidermis and only few hypotrophic and uninnervated sweat glands in the dermis. CONCLUSIONS: The lack of innervation of the skin (C and A-delta fibers) appears to be the morphological basis of insensitivity to pain and anhidrosis, and is consistent with the loss of unmyelinated and small myelinated fibers in the sural nerve biopsy.

Child↗
PubMed2003

Preimplantation diagnosis of Lesch-Nyhan using mini-sequencing primer extension.

Lesch-Nyhan syndrome (LN) is a severe X-linked disorder of males characterized by hyperuricaemia, choreoathetosis, spasticity, mental retardation and self-mutilation. The disorder is caused by a wide spectrum of mutations distributed throughout the hypoxanthine phosphoribosyltransferase (HPRT) gene. Female carriers of LN display no clinical symptoms but are at 50% risk of passing on the affected gene to their male offspring. A couple who had a boy with LN were referred to Monash IVF for preimplantation genetic diagnosis (PGD) because the woman had undergone tubal ligation and the couple wanted to have another child. A test was developed for the causative mutation IVS8+6 T-->G mutation based on minisequencing primer extension that also incorporated the co-analysis of an informative tetranucleotide marker in intron 3 of the HPRT gene to identify allelic dropout. All four biopsied embryos from their first IVF cycle were diagnosed as unaffected, and transfer of two embryos in the cohort with the highest morphological quality resulted in a singleton pregnancy and the birth of a healthy girl. Direct mutation detection by mini-sequencing and parallel analysis of an informative linked marker provides an alternative strategy for molecular diagnosis of point mutations that will have useful application in PGD for other single gene disorders.

DNA Primers↗
PubMed1999

Cognitive functioning in Lesch-Nyhan syndrome: a 4-year follow-up study.

Lesch-Nyhan syndrome (LNS) is a rare disorder of metabolism caused by a defective gene on the X chromosome. It is typically characterized by choreoathetosis, hypertonia, hyperreflexia, and self-mutilation. The present study is a 4-year follow-up investigation of the cognitive status of six subjects with a mean age of 17 years 10 months (range 14 years 9 months to 23 years). The Stanford-Binet Intelligence Scale: IV was used. Each of the four domains assessed by this battery (verbal reasoning, abstract/visual reasoning, quantitative, and short-term memory) was compared with previous findings of the same subjects at their initial test and 2-year follow up; the aim being to gain further insight into the clinical course of LNS over time. The results suggest that while the subjects generally continued to acquire new information and skills over time, their standardized scores declined, indicating that a plateau was reached in their skill levels relative to their peers, as also seen in other developmental disabilities. Deficits were noted in working memory, particularly on tasks that involve considering multiple features simultaneously.

Adolescent↗
PubMed1986

Disorders of facial recognition, social behaviour and affect after combined bilateral amygdalotomy and subcaudate tractotomy--a clinical and experimental study.

A case of a 37-year-old patient, 10 years after bilateral amygdalotomy and subcaudate tractotomy for chronic self-mutilation, is described. The clinical picture revealed a complex mental state, including disorders of facial recognition, social behaviour, affect and elements of the Kluver-Bucy syndrome. Mild selective deficits were demonstrated psychometrically in the recognition of familiar and unfamiliar faces. Certain features have been described in rhesus monkeys, but have not previously been reported in humans. Primate studies are discussed, with particular reference to the role of the amygdala in facial recognition.

Adult↗
PubMed1999

History of childhood sexual or physical abuse in Japanese patients with eating disorders: relationship with dissociation and impulsive behaviours.

BACKGROUND: Empirical data regarding prevalence of sexual and physical abuse histories in Japanese patients with eating disorders is lacking, in contrast to Western countries. This study investigated the prevalence of traumatic events in Japanese patients with eating disorders, and examined the relationship between such traumatic events and clinical features. METHODS: Subjects consisted of 33 patients with anorexia nervosa restricting type (RAN), 40 patients with anorexia nervosa binge eating/purging type (AN-BP), 63 patients with bulimia nervosa purging type (BN) and 99 healthy controls. All were female and diagnoses were based on DSM-IV. The Physical and Sexual Abuse Questionnaire (PSA), Eating Disorder Inventory (EDI) and Dissociation Experience Scale (DES) were administered to all of the subjects. RESULTS: Paradoxically, victims of minor sexual abuse committed by Chikan (a Japanese word indicating a person who commits minor sexual crimes) were more prevalent among controls than among patients with RAN, AN-BP or BN. However, physical punishment histories tended to be more prevalent among patients with AN-BP or BN than among RAN or controls. Only AN-BP and BN patients with physical punishment histories had twofold higher scores for DES and significantly more frequent histories of self-mutilation (67% v. 33%) compared with patients without such histories. CONCLUSION: An abuse history is not essential or a prerequisite to developing an eating disorder in Japan.

Adolescent↗
PubMed1997

When to investigate for purine and pyrimidine disorders. Introduction and review of clinical and laboratory indications.

When to suspect and thus investigate for inborn errors of purine and pyrimidine metabolism is a dilemma for even the most observant investigator. Often parents of affected children, or a history involving siblings, can provide valuable clues. The recognition of new purine and pyrimidine disorders requires skill and serendipity. But even identifying known disorders can prove difficult, since they cover a broad spectrum of illnesses, can have more than one symptom, or lead to early death. This problem is compounded by the fact that they are relatively recently described and therefore often little known, either in the clinic or laboratory. The considerable heterogeneity in clinical expression within families as well as between families means that asymptomatic homozygotes may not be recognized or can present at any time from early childhood through adolescence up to their eighth decade. Consequently, all siblings should be screened. These disorders should be suspected in any case of unexplained anaemia, failure to thrive, susceptibility to recurrent infection, or neurological deficits with no current diagnosis, including autism, cerebral palsy, delayed development, deafness, epilepsy, self-mutilation, muscle weakness, the inability to walk or talk, and-unusual in children and adolescents-gout, sometimes with renal disease. Some disorders present with radiolucent kidney stones, in acute or chronic renal failure, alone or with any of the above, or as an intolerance/sensitivity to therapy (e.g. 5-fluorouracil in malignancies or azathioprine immunosuppression in organ transplantation), often with life-threatening consequences. Several parameters need to be evaluated to ensure correct diagnosis. Pitfalls which can mask diagnosis using only a single test are renal failure, blood transfusion, diet or drugs.

Biomarkers↗
PubMed2004

New age eunuchs: motivation and rationale for voluntary castration.

We used a survey posted on the Internet to explore the motivation of men who are interested in being castrated. Out of 134 respondents, 23 (17%) reported already having been castrated. The 104 (78%) individuals who said they had not been castrated were asked why they wanted to be castrated and why they had not actualized that desire. They were given multiple-choice answers to select from. The major reason (selected by 40% of respondents) for desiring castration was to achieve a "eunuch calm" and freedom from sexual urges; however, a large proportion (approximately 30%) of respondents found fantasies about being castrated sexually exciting and a similar percentage desired castration for the "cosmetic" appearance it achieved (which we interpret to mean scrotal removal along with an orchiectomy). This high interest in castration as either a sexual stimulus (a fetish) or a cosmetic enhancement was unexpected and contrasted with the more classically stated motivation for voluntary castration in the psychiatric literature, i.e., libido control and transsexualism. Internet discussion groups that serve these men may encourage them to act out their castration fantasies. Alternately, Internet discussions may give them a displacement outlet for their fantasies and decrease the risk of castration by nonmedically qualified "street-cutters" or by self-mutilation. Forty percent of our respondents claimed that they would have an orchiectomy, if it were cheap, safe, and simple. A quarter wanted to try chemical castration first, but 40% were embarrassed to talk to their doctors about their interest in castration. Information now available on the Internet provides these men with increasingly easy access to street-cutters and directions on how to perform surgical castrations, putting them at risk of permanent injury and disability. Physicians need to be aware of these risks.

Adult↗
PubMed2003

Anguish and despair in adolescents with eating disorders--helping to manage suicidal ideation and impulses.

Adolescents struggling against anorexia nervosa or bulimia nervosa often experience self-punishing thoughts and behaviors, including self-mutilation, and suicidal ideation and attempts. These arise out of the profound anguish and despair frequently experienced by these young people. This paper outlines four particularly salient clinical themes underlying this despair that have significant implications for treatment. A practice perspective is discussed which emphasizes empathic listening and the development of a strong therapeutic alliance with the adolescent. Treatment recommendations draw from narrative theory and practice, and from feminist perspectives. The paper also draws on cognitive therapy and on recent developments in the areas of spirituality and motivational enhancement. Involving the distressed adolescent's family is also addressed.

Adaptation, Psychological↗