Potential aripiprazole-mediated extrapyramidal symptoms in an adult with developmental disabilities.

PURPOSE: A case of extrapyramidal symptoms (EPS) following administration of aripiprazole to a man with developmental disabilities who had never received antipsychotic medications and had no history of movement disorders is presented. SUMMARY: The patient was a 40-year-old male with developmental disabilities. He was nonverbal, profoundly mentally retarded, and diagnosed with obsessive compulsive disorder (OCD) and orthopedic problems. He developed episodic movements possibly consistent with EPS secondary to aripiprazole usage. The patient was antipsychotic naive before initiation of aripiprazole 5 mg daily. Concurrent medications at the time of EPS onset included oxazepam, baclofen, and citalopram. Baclofen and oxazepam were prescribed secondary to right-sided hemiparesis contractures. Aripiprazole, 5 mg daily, was initiated in November 2004 as an augmentation strategy for the diagnosis of OCD. Facial, tongue, and arm movements were first reported approximately five weeks after the initiation of aripiprazole. Initial symptoms resolved after approximately 24 hours. The dosage was increased to 10 mg daily two weeks later. Dystonic episodes continued on an intermittent basis, and the patient presented with lower-lip thrusting and upper-limb athetosis. These movements interfered with the patient's eating, chewing, and holding of utensils. Several of the standard treatment strategies for EPS were used. Initially, diphenhydramine hydrochloride 25 mg was administered orally every six hours. The patient's movements resolved following diphenhydramine administration. Aripiprazole was subsequently discontinued secondary to its lack of efficacy for OCD and the development of a movement disorder. CONCLUSION: A patient with developmental disabilities who had no history of movement disorders developed EPS following initiation of aripiprazole.     

A Chinese adolescent girl with Fechtner-like syndrome

We describe a 15-y-old girl with Fechtner-like syndrome, who is the first Chinese reported to have this rare syndrome. She presented with left homonymous hemianopia and neuroimaging revealed haemorrhage in both parietal and occipital lobes. Peripheral blood smear showed macrothrombocytopenia and intracytoplasmic inclusion bodies inside leucocytes. Thrombocytopenia and proteinuria responded to intravenous immunoglobulin and pulsed methylprednisolone. This case illustrates that life-threatening haemorrhage can occur in patients with Fechtner syndrome. Although there was no effective treatment reported in the literature, high dose steroid and immunoglobulin seemed to be useful in our patient. Our patient also had nephritic-nephrotic syndrome with renal insufficiency, which is unusual in adolescent female patients.     

SUICIDE ATTEMPT DUE TO METOCLOPRAMIDE-INDUCED AKATHISIA

Akathisia as a side-effect of metoclopramide has received increasing attention in consultation-liaison psychiatry in recent years. A case of metoclopramide-induced akathisia resulting in a suicide attempt is reported in order to highlight the suffering of such patients and the factors that lead to misdiagnosis.     

Rapid VAC high dose melphalan regimen, a novel chemotherapy approach in childhood soft tissue sarcomas

Forty-three children with malignant soft tissue sarcomas (IRS Groups II-IV) were treated with rapid dose delivery chemotherapy protocol comprising six courses of vincristine, adriamycin and cyclophosphamide, given in most cases within 8 weeks (Rapid VAC). This was followed in 36 patients by high dose melphalan with autologous bone marrow rescue. Twenty-six patients also received irradiation to the site of primary tumour. The Rapid VAC regimen was well tolerated and largely administered as an out-patient. There was one toxic death which occurred 2 months after high dose melphalan due to a combination of infection and possible anthracycline cardiomyopathy. Stages were, (Intergroup Rhabdomyosarcoma Study (IRS) system) Group, Group II--four patients. Group III--27 patients and Group IV--12 patients; International Society of Paediatric Oncology (SIOP) staging, Stage I--11, Stage II--13, Stage III--7, Stage IV--12. Actuarial survival at 5 years for all stages is 57% and event free survival 44%. For patients with non-metastatic diseases, 62% and 53% respectively. This treatment strategy utilises the philosophy of rapid drug delivery with high dose consolidation and enables all chemotherapy to be finished within a 4 month period. In general, a conservative approach was applied to both radiation and surgery to minimise late sequelae related to these treatment modalities. Although the small number of high risk patients in this study limits conclusions regarding efficacy in these subgroups the overall results with this regimen appear to be comparable to that with other approaches.     

High dose melphalan and total body irradiation with autologous marrow rescue in childhood acute lymphoblastic leukaemia after relapse

High dose melphalan (HDM 110-140 mg/m2) and total body irradiation (TBI, 10.5 Gy, single fraction) followed by infusion of autologous bone marrow (ABMT) was evaluated for toxicity and efficacy in 24 children with acute lymphoblastic leukaemia (ALL) in second (CR2) or third remission (CR3). Marrow was purged with Campath 1 in six children (four were children in CR3). All children had engraftment with a median of 30 days (range 18-70 days) to neutrophil count greater than 0.5 x 10(9)/l. Four children (16%) died from toxicity 1-4 months after autograft, two from pneumonitis, one from an intracerebral haemorrhage and one from sepsis. Apart from fever and mucositis the procedure was well tolerated. Nine of 17 children treated in CR2 remain in complete remission 6-72 months after ABMT (median 25 months). Seven of these have a follow-up of greater than 12 months. Three of the seven children treated in CR3 are alive 17, 22 and 29 months post ABMT. Seven children relapsed within 10 months (median 4 months) of the autograft. Only one relapse has occurred beyond 10 months. HDM and TBI followed by ABMT is a relatively well tolerated regimen and may contribute to survival in children with relapsed ALL.     

Detection of Cattle Naturally Infected with Anaplasma marginale in a Region of Endemicity by Nested PCR and a Competitive Enzyme-Linked Immunosorbent Assay Using Recombinant Major Surface Protein 5

A competitive enzyme-linked immunosorbent assay using recombinant major surface protein 5 (rMSP5-cELISA) of Anaplasma marginale was validated in a naturally infected cattle herd in an area of eastern Oregon where A. marginale is endemic. The true positive and negative A. marginale infection status of 235 randomly selected cattle was determined by using a nested PCR (nPCR) coupled with msp5 sequence analysis and hybridization. Judgment of the reliability of the nPCR and hybridization for detection of persistent infections was based on three observations. First, the nPCR was able to detect as few as 30 infected erythrocytes per ml. Second, the nPCR was able to consistently detect low levels of rickettsemia in seven carrier cattle experimentally infected with A. marginale. Third, msp5 sequence analysis showed >95% identity among 30 nPCR amplicons from cattle naturally infected with field strains of A. marginale. The nPCR and hybridization identified 151 infected and 84 uninfected cattle among the 235 animals tested. With a cutoff point of 28%, the rMSP5-cELISA showed a sensitivity of 96% and a specificity of 95%. These results indicate that the rMSP5-cELISA can sensitively and specifically detect cattle with naturally acquired persistent A. marginale infections and suggest that it is an excellent assay for epidemiological studies, eradication programs, and regulation of international cattle movement.     

The immunoprotective Anaplasma marginale major surface protein 2 is encoded by a polymorphic multigene family.

An Anaplasma marginale Florida msp-2 gene was cloned and expressed in Escherichia coli. Pulsed-field gel electrophoresis and Southern blot analysis revealed the presence of multiple msp-2 gene copies that were widely distributed throughout the chromosomes of all three strains examined. Genomic polymorphism among copies was greatest in the 5' end of msp-2 but also occurred in 3' regions. The presence of gene-copy-specific epitopes was indicated by the reactivity of the cloned msp-2 copy with some, but not all, monoclonal antibodies that bound native MSP-2. Multiple antigenically distinct MSP-2 molecules were expressed within strains and were coexpressed by individual A. marginale organisms. These results suggest that expression of polymorphic msp-2 gene copies is responsible for the significant percentages of A. marginale organisms within strains that do not react with individual anti-MSP-2 monoclonal antibodies. Sequence analysis revealed highly significant MSP-2 homology with two rickettsial surface proteins, A. marginale MSP-4 and Cowdria ruminantium MAP-1. Immunization with MSP-4 has been shown to induce protective immunity in a manner similar to that of immunization with MSP-2. These findings support the hypothesis that A. marginale surface proteins are targets of protective immune responses but are antigenically polymorphic.     

Detection of Anaplasma ovis infection in goats by major surface protein 5 competitive inhibition enzyme-linked immunosorbent assay.

A competitive inhibition enzyme-linked immunosorbent assay (ELISA) based on a major surface protein 5 (MSP5) B-cell epitope conserved among Anaplasma species was used to detect goats infected with Anaplasma ovis. We examined strains of A. ovis isolated from goats in Kenya and demonstrated that MSP5 and the target B-cell epitope, bound by monoclonal antibody ANAF16C1, were conserved. Sera from 149 goats in four regions of Kenya and from 302 goats in six U.S. states were tested for the presence of epitope-specific antibodies with the MSP5 competitive inhibition ELISA. Evidence that the assay can be used to detect A. ovis-infected goats includes the following: (i) 53 goats raised in confinement with arthropod control were all seronegative; (ii) six goats experimentally infected with A. ovis seroconverted at the same time that they developed detectable rickettsemia; (iii) seroconverted goats remained seropositive, consistent with the persistence of A. ovis in goats and the presence of anti-MSP5 antibody in cattle persistently infected with Anaplasma marginale; and (iv) 119 of 127 known A. ovis-infected goats in Kenya were seropositive. A. ovis infection, as determined serologically and by demonstration of infected erythrocytes, in goats from the four regions in Kenya was highly prevalent. In contrast, despite the presence of A. ovis and competent arthropod vectors in the United States, the prevalence of infection appeared to be very low. The high prevalence in Kenya and the occurrence of anemia in persistently infected goats may be impediments to current efforts to increase milk yields on small farms.