Advances in the management of victims struck by ruptured intracranial aneurysms

The advances in management of victims struck by the rupture of an intracranial aneurysm is reviewed. In the 1970s the management outcome was still far from acceptable; many victims who had 'recovered' following a major aneurysmal subarachnoid haemorrhage (SAH) succumbed or became crippled as the result of repeat bleeds and/or delayed SAH-induced ischaemic deterioration ('cerebral vasospasm'). The era of prosperity for microneurosurgery, the introduction of the calcium channel blocker nimodipine and the accumulation of cases in centres with a team of dedicated aneurysm surgeons form the basis of a recent breakthrough in the previously gloomy management outcome. With microsurgical techniques elective surgery can now be performed in the acute stage thereby preventing disastrous reruptures which occur frequently in the early phase after the first bleed. The concomitant use of nimodipine minimizes delayed SAH-induced ischaemic deterioration. Today a management regime including early operation combined with nimodipine has led to grossly improved results. Nevertheless cognitive disturbances and psychosocial maladjustment are frequent sequelae following a major aneurysmal bleed. Hope for further improvements could depend on the development of techniques which may allow identification of intracranial aneurysms before they rupture and increased knowledge of the aetiology of such cerebral arterial wall lesions.     

Nosology and diagnosis of Rett Syndrome

Rett Syndrome is one of the least commonly occurring autism spectrum disorders (ASD), but certainly one of the most devastating. A genetic profile has been identified, but checklists still have an important role for prescreening, especially before expensive genetic testing, and to provide precise strengths and weaknesses with respect to the core features of the disorder. Furthermore, research is now demonstrating subprofiles of genetic mutation which may be linked to profiles of behavioral responding and general symptom profiles. We review the literature on the nosology and assessment of Rett Syndrome in light of these developments. Specific symptoms and assessment techniques are discussed and potential future research avenues are reviewed with an eye to strengths and weaknesses of the current knowledge base.     

An Examination of Psychotropic Medication Side Effects: Does taking a greater number of psychotropic medications from different classes affect presentation of side effects in adults with ID?

This study examined whether the number of psychotropic medications an individual is taking across classes influences side effects among adults with Intellectual Disability (ID). Participants were 80 adults diagnosed with ID. Dependent variables were the composite score and domain scores of the Matson Evaluation of Drug Side-effects (MEDS), which is an instrument used to assess side effects. There were three levels of the independent variable: Group 1 – those taking zero psychotropic medications, Group 2 – those taking one psychotropic medication, and Group 3 – those taking two psychotropic medications across different medication classes. There was a significant main effect regarding number of psychotropic medication classes prescribed. Further analysis revealed that four of the nine MEDS domains had significantly different mean scores for number of psychotropic medication classes. For the majority of MEDS domains, such as Central Nervous System-General, Parkinsonism/Dyskinesia, and Behavioral/Akathesia domains, participants in the no psychotropic medication group had significantly lower mean scores than those in the one and two psychotropic medication groups. Only two MEDS domains, Cardiovascular and Hematologic Effects as well as Skin, Allergies, and Temperature, were significantly different between participants taking one psychotropic medication as compared with two psychotropic medications from different classes. Implications of these findings and recommendations for future research are discussed.     

Trend of Symptoms in Children Diagnosed with Autistic Disorder as Measured by the Autism Spectrum Disorders-Diagnostic for Children (ASD-DC)

Researchers have examined the progression of core symptoms in AD; however, the primary focus of lifespan research for children with ASD has been based on retrospective reports and the stability of diagnoses. The purpose of this study, then, was to conduct a cross sectional investigation of symptom expression of AD throughout the childhood years. Participants consisted of children ranging in age from 3 to 11 years old who were diagnosed with AD. The participants were partitioned into three age cohorts, with symptom endorsements of AD assessed through the Autism Spectrum Disorders-Diagnostic for Children (ASD-DC). Results indicated that symptoms of AD were no more pronounced at any one of the three age cohorts when compared to each other. Additionally, a non-significant linear trend was found, indicating that symptoms of AD in childhood remain stable and chronic. Implications of these findings and future directions for research in this area are discussed.     

Challenging behaviors should not be considered depressive equivalents in individuals with intellectual disabilities. II. A replication study

Previous research has proposed behavioral equivalents for depression, but evidence for behavioral equivalents has been contradictory. The relationship between a measure of depression and several proposed behavioral equivalents of depression was assessed in 693 adults living in a large residential setting. Most were adults with severe or profound intellectual disability. The frequency of language-based measures of depression was very low. A scale to assess depression was constructed based on an item analysis of a larger pool of items. Both item and factor analysis and correlations between scores on the depression scale and individual maladaptive behavior items showed little or no relationship between proposed behavioral equivalents and depression. No support was found for behavioral equivalents of depression. This replicated the findings of Tsiouris, Mann, Patti, and Sturmey (2003). Practitioners are cautioned against using maladaptive behaviors as evidence of depression in people with severe or profound intellectual disabilities.     

Aneurysmal subarachnoid haemorrhage: overall outcome and incidence of early recurrent haemorrhage despite a policy of acute stage operation

A series of 480 patients who were alive upon admission following an aneurysmal subarachnoid haemorrhage (SAH) is reported. These patients represented 40% of the total Swedish incidence during a 3-year period. The three neurosurgical referral centres covering this population had a similar policy of early diagnosis and acute state surgery in all patients considered of having a potential to survive without permanent disabling cerebral malfunction. At 2-year follow up 45% showed a good neurological recovery, the morbidity was 25% and the mortality was 30%. Some more lives might have been saved with an improved ultra-early referral system since there were 21 initially good-to-fair risk patients (4% of the total SAH population) who rebled fatally before surgery and within 48 h. For comparison, in the Kingdom of Denmark, with a general policy of delayed operation, out of 1076 patients who were alive upon admission, 27.5% made a good recovery, while the morbidity was 27%, and the mortality was 45.5%.     

Activity of mitozolomide (NSC 353451), a new imidazotetrazine, against xenografts from human melanomas, sarcomas, and lung and colon carcinomas

The chemosensitivity of human tumor xenografts to mitozolomide, 8-carbamoyl-3-(2-chloroethyl)imidazo[5-1-d]-1,2,3,5-tetrazin-4(3H) -one, was studied in 3 different assay systems. In concentrations of 1 to 500 micrograms/ml, mitozolomide completely inhibited the colony-forming ability in soft agar of cell suspensions from sarcomas, melanomas, lung and colon cancers, and a mammary carcinoma. When a panel of tumors of the different histological types was tested for its sensitivity to mitozolomide in vitro, in the 6-day subrenal capsule assay in conventional mice, and, in some cases, as s.c. growing tumors in nude mice, good agreement between the different assay systems was seen. In most cases, a very pronounced antitumor effect was observed. The efficacy of mitozolomide was as good or better than that of the drugs clinically used against the tumor types tested. Tumor size measurements and histological examinations indicated that nude mice carrying a melanoma, a small cell lung cancer, and an osteosarcoma were cured of their tumors. The approach here used for evaluating the effect of a new drug on human cancers may be useful for selecting the tumor types which primarily should be studied in clinical trials. The results indicate that clinical responses to mitozolomide may be anticipated in sarcoma, melanoma, small cell lung cancer, and possibly in colon cancer.     

Radiolocalization of xenografted human malignant melanoma by a monoclonal antibody (9.2.27) to a melanoma-associated antigen in nude mice

A murine monoclonal antibody (9.2.27), directed to a Mr 250,000 glycoprotein-chondroitan sulfate proteoglycan complex, was radiolabeled with 125I and assessed for radiolocalization in tumor and normal tissues of normal and tumor-bearing nude mice. The 125I-9.2.27 localized in vivo preferentially in Mr 250,000 antigen-expressing human melanomas (FMX-Met, SESX) but not in low antigen-expressing tumors (LOX-L) xenografted in nude mice. The imaging index of tumor cells was positively correlated with the antigen density of the various melanoma cell lines as measured by flow cytometry. The nonspecific immunoglobulin RPC-5 of the same IgG2a subclass as 9.2.27 did not specifically localize to xenografts of melanoma. The total amount of 125I-9.2.27 accumulated in the tumor was directly correlated with tumor size. However, the specific radioactivity (cpm/g) in smaller tumors was higher than that in larger tumors. Nonspecific uptake and circulating antibody levels differed between normals and tumor-bearers. The organs of the reticuloendothelial system of normal mice accumulated more labeled antibody than did those of tumor bearers, and conversely, tumor bearers had higher levels of circulating labeled antibody in the blood than normals. The circulating labeled antibody in tumor bearers was still monomeric but had no detectable antigen-binding capacity.