Polymorphisms in glutathione-S-transferase genes (GST-M1, GST-T1 and GST-P1) and susceptibility to prostate cancer among male smokers of the ATBC cancer prevention study.

Glutathione-S-transferase (GST) genes encode a family of detoxification enzymes that offer protection against endogenous and exogenous sources of reactive oxygen species (ROS). Germline variations in GST genes may alter the catalytic efficiency of GST isoenzymes leading to a potential increase in susceptibility to the genotoxic effects of ROS and electrophilic substances. A nested case-control study design was used to examine the association between the polymorphic GST genes and prostate cancer risk among Finnish male smokers of the ATBC Cancer Prevention Study. A case-case analysis was used to determine the association between these genetic polymorphisms and prostate cancer progression. Germline DNA was obtained from 206 prostate cancer cases and 194 controls frequency matched on age, intervention group and study clinic. Cases and controls were genotyped for three GST genes using MALDI-TOF mass spectrometry or multiplex polymerase chain reaction (PCR). Relative to the wild-type genotype, we observed a 36% reduction in prostate cancer risk associated with the GST-M1-null genotype (odds ratio (OR) 0.64, 95% confidence interval (CI) 0.43, 0.95). Unlike GST-M1, GST-T1-null (OR 0.74, 95% CI 0.42, 1.33) and GST-P1*B (OR 1.10, 95% CI 0.72, 1.69) were not strongly associated with prostate cancer risk. We did not observe any significant associations between the selected polymorphic GST genes and tumour grade or stage. In conclusion, we did not observe a direct association between polymorphic GST-T1 or GST-P1 and prostate cancer risk. Our observation of a relatively strong inverse association between the GST-M1-null genotype and prostate cancer risk needs to be confirmed in larger association studies.     

Acoustic variations in reading produced by speakers with spasmodic dysphonia pre-botox injection and within early stages of post-botox injection.

Acoustic analysis of a reading passage was used to identify the abnormal phonatory events associated with adductor spasmodic dysphonia (ADSD) pre- and postinjection of Botulinum Toxin A (Botox). Thirty-one patients (age 22 to 74 years) diagnosed with ADSD were included for study. All patients were new recipients of Botox, and the examination of their voice occurred before and after their initial injection of Botox. Acoustic events were identified from reading samples of the Rainbow Passage produced by each of the patients. These events were examined from sentences containing primarily voiced sound segments. Dependent variables included the number of phonatory breaks, frequency shifts, and aperiodic segments--all variables previously defined by the investigators. Additionally, calculated variables were made of the percentage of time these events occurred relative to the duration of the cumulative voiced segments. A sex- and age-matched control group (+/-2 years) was included for statistical comparison. Results indicated that those with ADSD produced more aberrant acoustic events than the controls. Aperiodicity was the predominant acoustic event produced during the reading, followed by frequency shifts and phonatory breaks. Within the ADSD group, the number of atypical acoustic events decreased following Botox injection. It is important that the occurrence of specific abnormal acoustic events was sufficient to differentiate the disordered speakers from the controls following as well as preceding initial Botox injection, as indicated by discriminant function analysis. This paper complements our previous work using this acoustic analysis method for defining the abnormal events present in the voice of those with ADSD and further suggests that these measures can be used in conjunction with perceptual impressions to differentiate speakers on the basis of initial severity.     

The antiviral drug amantadine has a direct inhibitory effect on T-lymphocytes

We investigated the effect of the antiviral drug amantadine (AmTd) on polyclonal activation of thymic-dependent (T) and thymic-independent (B) lymphocytes from normal mice. In the present studies, T-lymphocytes are defined by their response to concanavalin A (Con A) and B-lymphocytes by their response to lipopolysaccharide (LPS). Polyclonal activator-induced lymphocyte proliferation was assessed by quantifying cellular incorporation of tritiated thymidine. The results show that, in a dose-dependent manner, AmTd exhibits at least 2-fold greater inhibitory activity against Con A-responding T-cells than against LPS-responding B-cells. Further, several findings demonstrate that AmTd has a direct inhibitory effect on T-lymphocytes. First, AmTd pulse treatment of isolated T-cells, but not accessory cells, abolished the T-cell response to Con A. Second, AmTd pulse treatment of the cytotoxic T-lymphocyte line, CTLL-2, markedly reduced their ability to undergo IL-2-induced proliferation. Third, proliferation of T-cells which had already undergone activation by ConA was inhibited by AmTd. Further, the finding that addition of IL-1, IL-2 or both to cultures failed to reverse inhibition of the response to ConA argues that AmTd did not interfere with endogenous production of these lymphokines. Possible implications of these findings are discussed.     

Nonepileptic Posttraumatic Seizures

Summary: Purpose: Epileptic posttraumatic seizures (PTSs) are a well-recognized consequence of head injury (HI), but HI and nonepileptic seizures (NESs) have not been related. We describe a significant subset of patients with NESs who had their seizures attributed to HI.
Methods: We reviewed the records of all patients diagnosed with NES at the University of Maryland Medical Center over a 6-year period (1989–1995) and selected patients with seizures attributed to a head injury occurring ≥3 years before the onset of their seizures.
Results: Of 157 patients with video-EEG confirmed NES, 37 (24%) had the onset of their seizures attributed to an HI. Their average age was 34 years (range, 15–56 years); 68% were women. Nonepileptic PTS usually developed within the first year after HI (89%). Convulsive symptoms were present in 54%. Whereas epileptic PTSs characteristically follow severe HI, the majority (78%) of our patients with nonepileptic PTSs sustained only mild HI. Before their HI, 76% of our patients were employed, working in the home, or students, but only 11% could continue those activities after developing nonepileptic PTSs.
Conclusions: Nonepileptic PTSs are frequently mistaken for epileptic PTSs and result in serious disability. The misdiagnosis of nonepileptic PTSs leads to ineffective and inappropriate treatment. Patients with intractable seizures after HIS, articularly mild HIS, should be carefully evaluated for NESs.     

Classification of anti-FcepsilonRI and anti-IgE autoantibodies in chronic idiopathic urticaria and correlation with disease severity

BACKGROUND: Circulating autoantibodies against FcepsilonRI, IgE, or both occur in approximately one third of patients with chronic idiopathic urticaria (CIU), but not all autoantibodies initiate histamine release. OBJECTIVE: We sought to classify patients with CIU into subsets on the basis of serum bioactivity and immunoreactivity and to examine the relationship between newly defined subtype and disease severity. METHODS: Sera from patients with CIU (n = 78), dermog-raphism (n = 15), and cholinergic urticaria (n = 10) and sera from healthy subjects (n = 39) were analyzed by means of Western blot analysis for anti-FcepsilonRI autoantibodies and for histamine release from basophils and dermal mast cells. In vivo reactivity of autologous serum was tested by means of intradermal injection, and CIU severity was determined on the basis of clinical interview. RESULTS: We classified sera from patients with CIU into 5 subsets: immunoreactive histamine-releasing anti-FcepsilonRI autoantibodies (n = 20 [26%]); immunoreactive anti-FcepsilonRI autoantibodies without histamine-releasing activity (n = 12 [15%]); anti-IgE-like autoantibodies (n = 7 [9%]); serum containing a mast cell-specific histamine-releasing factor (n = 7 [9%]); and sera with no identifiable factor (n = 32 [41%]). Patients with serum histamine-releasing activity had more severe urticaria than patients without such activity. Positive skin test responses to autologous sera were associated with histamine-releasing anti-FcepsilonRI autoantibodies but not with non-histamine-releasing anti-FcepsilonRI autoantibodies. Neither healthy subjects nor patients with dermographism or cholinergic urticaria had his-tamine-releasing anti-FcepsilonRI autoantibodies. CONCLUSION: These data support the specificity of functional anti-FcepsilonRI autoantibodies to CIU. The identification of distinctive subsets of patients suggests that other pathogenic mechanisms occur in CIU in addition to direct ligation of FcepsilonRI by autoantibodies causing dermal mast cell degranulation. Elucidating these mechanisms might lead to new treatments for CIU.