Adolescence spinal epidural abscess with neurological symptoms: case report,a lesson to be re-learnt

Epidural abscess of the spinal column is a rare condition that can be fatal if left untreated. It promptly progresses and can cause neurologic paralysis, urinary retention or cauda equina syndrome. Compromised immune system that occurs in patients with diabetes mellitus, AIDS, chronic renal failure, alcoholism, or cancer is a predisposing factor. It mostly occurs in adults. Here we would like to report a case of spontaneous pyogenic lumbar epidural abscess with neurological deficit diagnosed in a 15 year old boy. We treated this case successfully with surgical microscopic decompression and drainage.     

Whole‐brain atrophy as a measure of progression in premanifest and early Huntington's disease

Therapeutic trials in Huntington's disease (HD) are challenging as clinical progression is slow and variable and reliable biomarkers are lacking. We used magnetic resonance imaging and the brain boundary shift integral to quantify whole‐brain atrophy rates over 1 year in early and premanifest HD subjects, and controls. Early HD subjects had statistically significantly (P = 0.007) increased (threefold higher) rates of whole‐brain atrophy compared with controls. Higher atrophy rates were associated with longer CAG repeat length. MRI‐based measures of whole‐brain atrophy may have potential as a measure of progression in HD. © 2009 Movement Disorder Society     

Huntington's disease phenocopies are clinically and genetically heterogeneous

Huntington's disease (HD) classically presents with movement disorder, cognitive dysfunction and behavioral problems but is phenotypically variable. One percent of patients with HD‐like symptoms lack the causative mutation and are considered HD phenocopies. Genetic diseases known to cause HD phenocopies include HD‐like syndromes HDL1, HDL2, and HDL4 (SCA17). HD has phenotypic overlap with dentatorubral‐pallidoluysian atrophy, the spinocerebellar ataxias and neuroferritinopathy. Identifying the genetic basis of HD phenocopies is important for diagnosis and may inform the search for HD genetic modifiers. We sought to identify neurogenetic diagnoses in the largest reported cohort of HD phenocopy patients. Two hundred eighty‐five patients with syndromes consistent with HD, who were HD expansion‐negative, were screened for mutations in PRNP, JPH3, TBP, DRPLA, SCA1, SCA2, SCA3, FTL and FRDA. Genetic diagnoses were made in 8 subjects: we identified 5 cases of HDL4, 1 of HDL1 and 1 of HDL2. One patient had Friedreich's ataxia. There were no cases of DRPLA, SCA1, SCA2, SCA3, or neuroferritinopathy. HD phenocopies are clinically and genetically diverse and a definitive genetic diagnosis is currently possible in only a minority of cases. When undertaken, it should be clinically directed and patients and clinicians should be prepared for the low probability of reaching a genetic diagnosis in this group of patients. © 2008 Movement Disorder Society     

Autocrine human growth hormone expression leads to resistance of MCF-7 cells to tamoxifen

Tamoxifen is the most common antiestrogen used in the treatment of estrogen-positive breast cancer but its adverse effects and also resistance to this drug are serious challenges in the treatment of breast cancer. Characterization of mechanisms responsible for these adverse effects can lead to design of more efficient therapeutic strategies for the treatment of breast cancer. Here, we used a cellular model to evaluate the effects of autocrine expression of human growth hormone on responses of cells to tamoxifen. Our results imply for the first time that autocrine expression of growth hormone in human breast adenocarcinoma cell line, MCF-7, results in increase in cell proliferative capacity of cells even in the presence of tamoxifen. This effect may be due to up-regulation of G-coupled estrogen receptor, GPR30, which is activated by tamoxifen.     

Pagetoid squamous cell carcinoma in situ of the vulva: comparison with extramammary paget disease and nonpagetoid squamous cell neoplasia.

Pagetoid squamous cell carcinoma in situ (PSSCIS) is a variant of squamous cell intraepithelial neoplasia. Although PSSCIS is well-documented in the cutaneous skin and esophagus, cases of vulvar PSSCIS are rare. In the vulva, the main differential diagnosis is extramammary Paget disease (EMPD). We report 2 cases of vulvar PSSCIS along with the immunohistochemical and human papillomavirus (HPV) status of this disease compared with primary cutaneous EMPD of the vulva. Although PSSCIS and EMPD share CK7 and CK19 expression, PSSCIS is consistently mucin and carcinoembryonic antigen negative. In contrast to EMPD, both cases of PSSCIS strongly expressed p16 (INK4A) protein, consistent with RB1 protein dysregulation. However, integration of high-risk HPV was found in only 1 of the 2 PSSCIS cases. Given the morphological and immunohistochemical findings, we suggest that PSSCIS arises from a bidirectional stem cell capable of both squamous and glandular differentiation. Additionally, as with nonpagetoid squamous cell neoplasias of the vulvar, integration of high-risk HPV may occur in some, but not all, cases of PSSCIS.     

A RANDOMISED,DOUBLE-BLIND,PARALLEL-GROUP COMPARISON OF VENLAFAXINE AND DOTHIEPIN IN GERIATRIC PATIENTS WITH MAJOR DEPRESSION

This randomised, double-blind study conducted at nine sites in the UK and the Netherlands compared the safety and antidepressant efficacy of venlafaxine and dothiepin. Ninety-two geriatric patients (aged 64-87 years) with major depression were randomly assigned to receive either venlafaxine or dothiepin for up to 43 days. The dose of venlafaxine or dothiepin was titrated up to a maximum of 150 mg per day for the first 15 days, and thereafter could range from 50 to 150 mg per day. Adjusted mean scores on the MADRS and the HAM-D decreased significantly (p 0.05) from baseline to the end of the study in both groups. A response to therapy was observed in 60% of patients in the venlafaxine group and 53% of patients in the dothiepin group on the MADRS, and in 60% of patients in both groups on the HAM-D. Suicidal ideation scores on the MADRS were significantly (p=0.042) lower in the venlafaxine group at week 6. Treatment-emergent study events were the primary reason for withdrawal in only 7% of venlafaxine-treated patients and 8% of dothiepin-treated patients. The results confirm the efficacy and tolerability of venlafaxine for treating major depression in the elderly.     

Infusible platelet membrane microvesicles: a potential transfusion substitute for platelets

BACKGROUND: Several substitutes for intact, viable platelets have been used for transfusion, both to people and in animal models, with varied success. Infusible platelet membrane (IPM) is prepared from human platelets. IPM retains the glycoprotein (GP)lb receptor and has platelet factor 3 activity (procoagulant activity). However, factor V, serotonin, a cytoplasmic marker enzyme (purine nucleotide phosphorylase), GPIIb/IIIa complex, and HLA class I and II antigens are all absent in IPM. STUDY DESIGN AND METHODS: IPM is prepared from outdated platelets. The platelets were disrupted by freezing and thawing; they were washed and heated to inactivate possible viral contaminants, and then the sonicated membrane microvesicle fraction was separated and lyophilized. The hemostatic activity of IPM was measured by its ability to reduce the prolonged bleeding time in thrombocytopenic rabbits. RESULTS: Administration of IPM at a dose of 2 mg per kg results in a substantial reduction in the bleeding time. In a series of 23 experiments, a median preinjection bleeding time of 15 minutes was reduced to 6 minutes within 4 hours after IPM administration. Administration of IPM did show a mild enhancement in the thrombogenicity index, as measured in the Wessler rabbit model. This enhancement is, however, not significant, as a thrombogenicity index value of up to 0.6 is clinically acceptable. CONCLUSION: IPM may have clinical potential as a substitute for platelets in the treatment of bleeding due to thrombocytopenia.     

Evaluation of six commercial nucleic acid amplification tests for detection of Neisseria gonorrhoeae and other Neisseria species

Molecular detection of Neisseria gonorrhoeae in extragenital samples may result in false-positive results due to cross-reaction with commensal Neisseria species or Neisseria meningitidis. This study examined 450 characterized clinical culture isolates, comprising 216 N. gonorrhoeae isolates and 234 isolates of nongonococcal Neisseria species (n = 218) and 16 isolates of other closely related bacteria, with six commercial nucleic acid amplification tests (NAATs). The six NAATs tested were Gen-Probe APTIMA COMBO 2 and APTIMA GC, Roche COBAS Amplicor CT/NG and COBAS 4800 CT/NG tests, BD ProbeTec GC Qx amplified DNA assay, and Abbott RealTime CT/NG test. All assays except COBAS Amplicor CT/NG test where four (1.9%) isolates were not detected showed a positive result with all N. gonorrhoeae isolates (n = 216). Among the 234 nongonococcal isolates examined, initial results from all assays displayed some false-positive results due to cross-reactions. Specifically, the COBAS Amplicor and ProbeTec tests showed the highest number of false-positive results, detecting 33 (14.1%) and 26 (11%) nongonococcal Neisseria isolates, respectively. On the first testing, APTIMA COMBO 2, APTIMA GC, Abbott RealTime, and Roche COBAS 4800 showed lower level of cross-reactions with five (2.1%), four (1.7%), two (1%), and two (1%) of the isolates showing low-level positivity, respectively. Upon retesting of these nine nongonococcal isolates using freshly cultured colonies, none were positive by the APTIMA COMBO 2, Abbott RealTime, or COBAS 4800 test. In conclusion, the COBAS Amplicor and ProbeTec tests displayed high number of false-positive results, while the remaining NAATs showed only sporadic low-level false-positive results. Supplementary testing for confirmation of N. gonorrhoeae NAATs remains recommended with all samples tested, in particular those from extragenital sites.     

Imaging microglial activation in Huntington's disease

Activated microglia have been proposed to play a major role in the pathogenesis of Huntington's Disease (HD). PK11195 is a ligand which binds selectively to peripheral benzodiazepine binding sites, a type of receptor selectively expressed by activated microglia in the central nervous system. Using (11)C-(R)-PK11195 positron emission tomography (PET), we have recently shown in vivo evidence of increased microglial activation in both symptomatic and presymptomatic HD gene carriers and that the degree of microglial activation in the striatum correlates with the severity of striatal dopamine D2 receptor dysfunction measured with (11)C-raclopride PET. Our findings indicate that microglial activation is an early process in the HD pathology, occurring before the onset of symptoms. The close spatial and temporal relationship between microglial activation and neuronal dysfunction lends further support to the pathogenic link between the two processes in HD. Further longitudinal studies are needed to fully elucidate this link.