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Two modes of pseudorabies virus neuroinvasion and lethality in mice.

We describe two distinct modes of neuroinvasion and lethality after murine flank inoculation with virulent and attenuated strains of pseudorabies virus (PRV). Mice infected with virulent (e.g., PRV-Becker, PRV-Kaplan, or PRV-NIA3) strains self-mutilate their flank skin in response to virally induced pruritus, die rapidly with no identifiable symptoms of central nervous system (CNS) infection such as behavioral abnormalities, and have little infectious virus or viral antigen in the brain. In distinct contrast, animals infected with an attenuated PRV vaccine strain (PRV-Bartha) survive approximately three times longer than wild-type PRV-infected animals, exhibit severe CNS abnormalities, and have an abundance of infectious virus in the brain at the time of death. Interestingly, these animals have no skin lesions and do not appear pruritic at any time during infection. The severe pruritus and relatively earlier time until death induced by wild-type PRV infection may reflect the peripheral nervous system (PNS) and immune responses to infection rather than a fatal, virally induced CNS pathology. Based on previously characterized afferent (sensory) and efferent (motor) neuronal pathways that innervate the skin, we deduced that wild-type virulent strains transit through the PNS via both afferent and efferent routes, whereas PRV-Bartha travels by only efferent routes in the PNS en route to the brain.

Animals↗

Fenfluramine in Prader-Willi syndrome: a double blind, placebo controlled trial.

A double blind trial was conducted to determine the effect of fenfluramine on the weight and behaviour of patients with the Prader-Willi syndrome. Fifteen subjects, aged 5.5 to 27 years, received the placebo and the active drug, each for a period of six weeks. The dose of fenfluramine varied according to the age of the patient. Treatment with fenfluramine was associated with significant weight loss, improvement in food related behaviour, and a decrease in aggressive behaviour directed towards others. Skin picking and other self mutilation were unaffected by the drug. None of the subjects suffered from any side effects while taking the drug. These findings suggest that short term treatment with fenfluramine may have a role in the management of some patients with Prader-Willi syndrome. It could be used during periods when exposure to large amounts of food cannot be avoided and aggressive behaviour is particularly difficult to contain. It may also be useful in those whose lives are threatened by the complications of obesity.

Adolescent↗

Chromosome subband 17p11.2 deletion: a minute deletion syndrome.

Interstitial deletion of the short arm of chromosome 17 was detected in three unrelated patients with mental retardation and multiple congenital malformations. These patients were identified at a single centre over a six month period suggesting that del(17) (p11.2p11.2) is not a rare constitutional chromosome rearrangement. Comparison of the phenotypic features in a total of 19 patients with del(17)(p11.2p11.2) shows a consistent clinical phenotype with moderate to severe mental retardation, microbrachycelphaly, prominent forehead, broad face, flat midface, prognathism, short, broad hands, and behavioural anomalies such as self-mutilation. The sex ratio is unremarkable, parental ages are normal, and survival is usually unimpaired. Chromosome resolution of at least 500 bands appears necessary to detect this deletion.

Abnormalities, Multiple↗

Stereotaxic amygdalotomy and basofrontal tractotomy in psychotics with aggressive behaviour.

Twelve patients with personality disorders or chronic schizophrenia in whom aggressive-destructive behaviour was a prominent feature were treated by bilateral stereotaxic electrocoagulation of the amygdala. In two of the patients a cingulectomy and in five of the patients a frontal lobotomy had been performed several years previously without effect. In 11 of the patients the amygdalotomy resulted in disappearance of, or marked reduction in, their aggressive episodes. In two patients with frequent self-mutilations and reactive psychotic episodes these symptoms disappeared after an additional basofrontal tractotomy by Knight's method.

Adult↗

Use of the modified acrylic external fixator in 54 dogs and 28 cats.

This paper describes the use of acrylic resin instead of a Kirschner clamp for treating bone fractures. The technique is cheaper than using Kirschner external skeletal fixator and allows greater flexibility for pin placement. It is also less prone to self mutilation by dogs than the entirely acrylic external fixator. The modified acrylic fixator gave results similar to those obtained with the Kirschner external fixator, when used in 54 dogs and 28 cats.

Acrylic Resins↗

Congenital insensitivity to pain with anhidrosis in Taiwan: a morphometric and genetic study.

Congenital insensitivity to pain with anhidrosis (CIPA) is characterized by insensitivity to pain, anhidrosis, recurrent hyperpyrexia, mild mental retardation, and self-mutilating behavior. We report 2 brothers, aged 20 and 18 years, who suffered from phenotypes of CIPA. Both brothers had a branch site mutation in intron 7 (IVS7-33 T-->A) of the neurotrophic tyrosine kinase receptor type 1 gene. The electrophysiological studies showed no significant abnormal findings in sensory evoked potentials, motor evoked potentials to transcranial magnetic stimulation, or heart rate variations; sympathetic skin responses were absent. Morphometric study of their sural nerve histopathology revealed normal myelinated fiber density, 8,082 fibers/mm2 and 5,637 fibers/mm2 (normal 6,141 +/- 421); decreased unmyelinated fiber density, 2,537 fibers/mm2 and 2,211 fibers/mm2 (normal 28,578 +/- 8,669); increased axon size, 4.41 +/- 1.59 microm and 5.33 +/- 1.48 microm (normal 3.73 +/- 1.45), and increased axon diameter (A)/myelin thickness (M) ratio (A/M), 3.47 +/- 1.42 and 2.70 +/- 1.07 (normal 2.49 +/- 0.93). Scatterplot analysis of the G ratio (axon diameter:fiber diameter) did not show consistent results in the relationship between axon size and myelin thickness. In conclusion, the neuropathy of our CIPA patients included a marked reduction of small myelinated and unmyelinated fibers and a relatively increased axon size. This is the first CIPA family encountered in Taiwan.

Adolescent↗

A case with 47,XXY,del(15)(q11;q13) karyotype associated with Prader-Willi phenotype.

Herein we present the case of a 12-year-old boy who attended our clinic for obesity and hyperphagia. As a newborn he was noted to have diffuse muscular hypotonia and poor sucking response. At the age of 11 years, he was admitted to hospital for respiratory insufficiency. He had personality disorders characterized by temper tantrums and violent outbursts including self-mutilation. Physical evaluation revealed marked central obesity, he had small hands and feet, and also genital hypoplasia. Of the biochemical parameters, hyperglycemia and a low serum testosterone level must be emphasized. The patient fulfills the clinical criteria of typical Prader-Willi syndrome. Cytogenetic and fluorescence in situ hybridization analysis showed a karyotype 47,XXY, del(15)(q11;q13). To our knowledge this is the first report of the aforementioned genotype expressed as Prader-Willi phenotype in childhood.

Child↗

Posttraumatic stress symptoms in victims of childhood incest.

The relationship between posttraumatic stress disorder (PTSD) and the experience of severe childhood incest was investigated in a comparison of 97 adult female victims of incest and 65 matched controls. It appeared that 62% of the incest victims and none of the controls met the DSM-III-R criteria for PTSD. The best predictor for the development of PTSD appeared to be the subjective reaction at the time of the event, consisting of anxiety, freezing and dissociation. The incest victims also displayed other psychiatric symptoms, such as self-mutilation and conversions. Although the relation incest-PTSD is quite obvious, the diagnosis may easily be missed because the symptoms may be masked by other psychiatric phenomena.

Adolescent↗

The effects of azathioprine (imuran) on purine synthesis in clinical disorders of purine metabolism.

Azathioprine, a purine analogue, significantly suppressed the purine synthesis de novo of two gouty patients manifesting overproduction of uric acid, as well as three of four gouty patients who showed normal uric acid production. This suppression is taken as evidence that phosphoribosyl-pyrophosphate amidotransferase, the rate-controlling step in purine synthesis de novo, has a normal sensitivity to feedback inhibitors in the patients who responded to the drug.Two children afflicted with the familial disorder of hyperuricemia, choreo-athetosis, and self-mutilation described by Lesch and Nyhan showed no reduction in the activity of the biosynthetic pathway in response to azathioprine. This inability to respond to azathioprine can be directly related to the absence in these patients of the enzyme hypoxanthine-guanine phosphoribosyltransferase which is required for conversion of the drug or its metabolites to the biochemically active ribonucleotide form.

Journal Article↗

Dissociation as a mediator of psychopathology among sexually abused children and adolescents.

OBJECTIVE: This study investigated the role of dissociation as a mediator of mental health outcomes in children with a history of sexual abuse. METHOD: The study group consisted of 114 children and adolescents (ages 10-18 years) who were wards of the Illinois Department of Children and Family Services and were living in residential treatment centers. Interviews, provider ratings, and chart reviews were used to assess the relationship of childhood abuse history, dissociative responses, and psychopathology. RESULTS: Sexual abuse history was significantly associated with dissociation, whereas a history of physical abuse was not. Both sexual abuse and dissociation were independently associated with several indicators of mental health disturbance, including risk-taking behavior (suicidality, self-mutilation, and sexual aggression). Severity of sexual abuse was not associated with dissociation or psychopathology. Analysis of covariance indicated that dissociation had an important mediating role between sexual abuse and psychiatric disturbance. These results were replicated across several assessment sources and varied perspectives. CONCLUSIONS: The findings suggest a unique relationship between sexual abuse and dissociation. Dissociation may be a critical mediator of psychiatric symptoms and risk-taking behavior among sexually abused children. The assessment of dissociation among children may be an important aspect of treatment.

Adolescent↗

Childhood trauma, dissociation, and psychiatric comorbidity in patients with conversion disorder.

OBJECTIVE: The aim of this study was to evaluate dissociative disorder and overall psychiatric comorbidity in patients with conversion disorder. METHOD: Thirty-eight consecutive patients previously diagnosed with conversion disorder were evaluated in two follow-up interviews. The Structured Clinical Interview for DSM-III-R, the Dissociation Questionnaire, the Somatoform Dissociation Questionnaire, and the Childhood Trauma Questionnaire were administered during the first follow-up interview. The Structured Clinical Interview for DSM-IV Dissociative Disorders was conducted in a separate evaluation. RESULTS: At least one psychiatric diagnosis was found in 89.5% of the patients during the follow-up evaluation. Undifferentiated somatoform disorder, generalized anxiety disorder, dysthymic disorder, simple phobia, obsessive-compulsive disorder, major depression, and dissociative disorder not otherwise specified were the most prevalent psychiatric disorders. A dissociative disorder was seen in 47.4% of the patients. These patients had dysthymic disorder, major depression, somatization disorder, and borderline personality disorder more frequently than the remaining subjects. They also reported childhood emotional and sexual abuse, physical neglect, self-mutilative behavior, and suicide attempts more frequently. CONCLUSIONS: Comorbid dissociative disorder should alert clinicians for a more chronic and severe psychopathology among patients with conversion disorder.

Adolescent↗

Characteristics of patients with serious suicidal intentions who ultimately commit suicide.

Patients in a long-term follow-up study who had made a serious suicide threat or attempt before admission were further studied to determine if there were characteristics that discriminated between those who ultimately committed suicide and those who did not. The results showed that patients who committed suicide were more likely to have a DSM-III axis I diagnosis, to be male, and to be discharged against medical advice. Those alive at follow-up were more likely to have a borderline personality disorder, to be female, impulsive, and self-mutilating, to be discharged with medical advice, and to have a healthier postdischarge course.

Bipolar Disorder↗

Major depression in patients with borderline personality disorder: a clinical investigation.

OBJECTIVE: Borderline personality disorder (BPD) is characterized by a high frequency of comorbidity with major depressive disorder (MDD). This study aimed to compare the clinical characteristics of 2 groups of patients with MDD: those with concomitant BPD and those with other concomitant personality disorders. METHODS: We assessed 119 outpatients, using a semistructured interview for demographic and clinical features, the Structured Clinical Interview for DSM-IV, Hamilton anxiety and depression scales, the Zung Self-Rating Depression Scale (ZSDS), the Social and Occupational Functioning Assessment Scale (SOFAS), the Sheehan Disability Scale, and the Revised Childhood Experiences Questionnaire. We performed a regression analysis, using the number of criteria for BPD as the dependent variable. RESULTS: Severity of BPD was positively related to the ZSDS score, to self-mutilating behaviours, and to the occurrence of mood disorders in first-degree relatives; it was negatively related to the SOFAS score and age at onset of MDD. CONCLUSIONS: Patients with comorbid MDD and BPD present differential characteristics that indicate a more serious and impairing condition with a stronger familial link with mood disorders than is shown by depression patients with other Axis II codiagnoses.

Adult↗

Psychotherapy of the characterologically difficult patient.

The increasing number of characterologically difficult patients in psychiatric practices has produced a plethora of theoretical formulations, treatment strategies and techniques. The major shifts in theoretical emphasis from drive theory to object relations theories and self-psychology has encouraged many psychiatrists to treat these patients in psychotherapy. The heterogeneity and variability of clinical profiles represented in this group of patients, however, still prevents prescription of "the" treatment of choice for this patient population. A major focus on treatment considerations in this paper is the assessment process with emphasis on determining the capacities for inter-personal relationships, psychological mindedness, empathy and psychological soothing of self and others. The advisability of establishing a "contract" as a prerequisite to treatment is suggested as an important factor in determining outcome. Other particular treatment issues are addressed such as frequency of sessions, "secrets", premature provocation of intense affect, medications, consultations, hospitalization, self-mutilation, substance abuse and indications for termination. The complex vissicitudes of the transference and countertransference processes with this group of patients is pointed out especially those feelings of helplessness and range sometimes experienced in the counter-transference. Long term intensive psychotherapy with many of these patients probably still belongs to the area of therapeutic heroics. Hard evidence for good and poor outcome is scarce and therapeutic zeal is too often based on anecdotal testimonial from adherents of one approach or another.

Adaptation, Psychological↗

Incomplete oedipism and chronic suicidality in psychotic depression with paranoid delusions related to eyes.

Self-enucleation or oedipism is a term used to describe self-inflicted enucleation. It is a rare form of self-mutilation, found mainly in acutely psychotic patients. We propose the term incomplete oedipism to describe patients who deliberately and severely mutilate their eyes without proper enucleation. We report the case of a 32-year-old male patient with a five-year history of psychotic depression accompanied by paranoid delusions centered around his belief that his neighbors criticized him and stared at him. A central feature of his clinical picture was an eye injury that the patient had caused by pouring molten lead into his right eye during a period of deep hopelessness and suicidality when the patient could not resolve his anhedonia and social isolation. Pharmacotherapy and psychotherapy dramatically improved his disorder.

Journal Article↗

Relationships between pain and schizophrenia.

In an examination of the phenomenology of pain in 78 patients with schizophrenia, 29 had current pain complaints. Of these 13 had an appropriate physical cause, leaving 16 with pain of seemingly psychological origin. The head, leg and back were the commonest sites. Complaints were most often described in sensory terms. Pain plausibly related to a specific delusion or hallucinatory process occurred only once, and no gross examples of insensitivity to noxious stimuli or to self-mutilation were seen. Patients with schizophrenia may have less pain than those with anxiety or depression but certainly do experience pain both from physical and psychological causes. The influence of phenothiazines on pain experience is uncertain.

Adult↗

Psychosocial treatment for severe personality disorder. 36-month follow-up.

BACKGROUND: In a previous report a step-down psychosocial programme for severe personality disorders was found to be more effective at expected termination of treatment than a longer in-patient treatment with no planned after-care. AIMS: To evaluate the clinical effectiveness of these two psychosocial specialist programmes over a 3-year follow-up period. METHOD: Two samples allocated to the in-patient treatment and to the step-down programme were compared prospectively on symptom severity, social adjustment, global assessment of mental health and other clinical indicators at 6, 12, 24 and 36 months after intake. RESULTS: Improvements were significantly greater in the step-down programme for social adjustment and global assessment of mental health. Patients in the programme were found to self-mutilate, attempt suicide and be readmitted significantly less at 24- and 36-month follow-up than patients in the in-patient group. CONCLUSIONS: Improvements associated with specialist residential treatment continued 2 years after discharge. A step-down model has significant advantages over a purely in-patient model.

Adult↗

Utilization of purines by an HPRT variant in an intelligent, nonmutilative patient with features of the Lesch-Nyhan syndrome.

The patient, H.Chr.B., was among the first reported with hyperuricemia and central nervous system symptoms. He has been found to have a variant of hypoxanthine guanine phosphoribosyl transferase (HPRT; E.C.2.4.2.8) distinct from the enzyme present in patients with the Lesch-Nyhan syndrome. The patient had chroeoathetosis, spasticity, dysarthric speech, and hyperuricemia. However, his intelligence was normal and he had no evidence of self-mutilation. There was no activity of HPRT in the lysates of erythrocytes and cultured fibroblasts when analyzed in the usual manner. Using a newly developed method for the study of purine metabolism in intact cultured cells, this patient was found to metabolize some 9% of 8-14C-hypoxanthine, and 90% of the isotope utilized was converted to adenine and guanine nucleotides. In contrast, cells from patients with the Lesch-Nyhan syndrome were virtually completely unable to convert hypoxanthine to nucleotides. The patient's fibroblasts were even more efficient in the metabolism of 8-14C-guanine, which was utilized to the extent of 27%, over 80% of which was converted to guanine and adenine nucleotides. The growth of the cultured fibroblasts of this patient was intermediate in media containing hypoxanthine aminopterin thymidine (HAT), whereas the growth of Lesch-Nyhan cells was inhibited and normal cells grew normally. Similarly in 8-azaguanine, 6-thioguanine, and 8-azahypoxanthine, the growth of the patient's cells was intermediate between normal and Lesch-Nyhan cells. These observations provide further evidence for genetic heterogeneity among patients with disorders in purine metabolism involving the HPRT gene. They document that this famous patient did not have the Lesch-Nyhan syndrome.

Adenine↗