Sensitivity and specificity of the Rey Dot Counting Test in patients with suspect effort and various clinical samples.

The Rey Dot Counting Test was administered to 100 patients with suspect effort drawn from two separate settings (personal injury/disability, n=86; prison hospital, n=14) and to 251 subjects in nine clinical groups (head injury, learning disability, right and left cerebrovascular accident, schizophrenia, older normals, depressed elderly, and mild and moderate dementia). Sensitivity of cut-offs for individual test scores (mean grouped dot counting time, ratio of mean grouped to ungrouped dot counting time, and number of errors) differed markedly across the two suspect effort groups (e.g., 28-100%), indicating that noncredible patients drawn from different settings employ somewhat differing approaches in their fabrication of cognitive symptoms. Use of a cut-off of > or =17 applied to a combination score (mean ungrouped dot counting time+meangrouped dot counting time+number of errors) resulted in 100% sensitivity in the forensic suspect effort group and 75% sensitivity in the civil litigation/disability suspect effort group, while maintaining specificity of > or =90% for the clinical groups combined (excluding moderate dementia).     

Cranial neuropathy associated with primary amyloidosis

We report 6 patients for whom cranial neuropathy was a major manifestation of primary amyloidosis. In 3 of the 6, multiple cranial nerves were involved. All had tissue biopsy documentation of amyloidosis. In 2, nerve biopsy also confirmed amyloidosis. All had renal involvement manifested by proteinuria. Primary systemic amyloidosis must be considered in the differential diagnosis of cranial neuropathy, especially when proteinuria is present.     

Microglia enhance manganese chloride-induced dopaminergic neurodegeneration: Role of free radical generation

Exposure to elevated levels of manganese has been shown to cause neuronal damage in the midbrain and the development of Parkinsonian symptoms. Activation of microglia and release of neurotoxic factors in particular free radicals are known to contribute to neurodegeneration. We have recently reported that manganese chloride (MnCl₂) stimulates microglia to produce reactive oxygen species (ROS). The aim of this study is to determine the role of microglia in the MnCl₂-induced degeneration of dopaminergic (DA) neurons that are particularly vulnerable to oxidative insult. MnCl₂ (10-300 μM; 7 days) was markedly more effective in damaging DA neurons in the rat mesencephalic neuron-glia cultures than the neuron-enriched (microglia-depleted) cultures. In addition, the microglia-enhanced MnCl₂ toxicity was found to be preferential to DA neurons. The microglial enhancement of DA neurotoxicity was further supported by the observation that replenishment of microglia to the neuron-enriched cultures significantly increased the susceptibility of DA neurons to the MnCl₂-induced damage. Analysis of the temporal relationship between microglial activation and DA neurodegeneration revealed that MnCl₂-stimulated microglial activation preceded DA neurodegeneration. Mechanistically, MnCl₂ (10-300 μM) stimulated a concentration- and time-dependent robust production of ROS and moderate production of nitric oxide but no detectable release of tumor necrosis factor-alpha and interleukin-1beta. Application of free radical scavengers including superoxide dismutase/catalase, glutathione, N-acetyl cysteine and an inhibitor of nitric oxide biosynthesis significantly protected DA neurons against the MnCl₂-induced degeneration. These results demonstrate that microglial activation and the production of reactive nitrogen and oxygen free radicals promote the MnCl₂-induced DA neurodegeneration.     

Laryngeal cancer incidence among workers exposed to acid mists (United States)

In 1992, the International Agency for Research on Cancer (IARC) determined that sufficient evidence existed to classify sulfuric acid mists as a human carcinogen, based primarily on six human studies. Possible mechanisms include irritation of epithelial cells in conjunction with cigarette smoking, or a direct genotoxic effect due to a modification of cellular pH. We have followed 1,031 men exposed to acid mists in the steel industry in the United States, via mailed questionnaire and telephone interview, extending by 10 years a prior follow-up of this cohort. These workers averaged 9.2 years of exposure, with an average first year of exposure of 1949. The primary exposure was to sulfuric acid mist, although part of the cohort was exposed to other acid mists. Fourteen laryngeal cancers were observed in the cohort compared with 5.6 expected based on US rates, with follow-up through 1994. A 14 percent upward adjustment in expected cancers due to differences in tobacco and alcohol consumption led to 6.4 laryngeal cancers expected, yielding a rate ratio of 2.2 (95 percent confidence interval=1.2-3.7). Our findings are consistent with previous findings from this cohort and from most other studies, and tend to confirm IARC's classification of acid mists as a human carcinogen. The occupational exposures of this cohort were at least an order of magnitude higher than usual ambient exposures in urban air.     

Using Fyrite to monitor incubator carbon dioxide levels

Purpose The Fyrite analyzer (Bacharach, Incorporated) was evaluated to ascertain whether it would perform within the range specified by the manufacturer (±0.5%). Fyrite analyzer samples were compared to control samples obtained using an infrared CO ₂ monitor (Ohmeda, Model Number 5200).Methods Ten Fyrite analyzer measurements from each of three incubators were obtained using two different analyzers by three investigators for a total of 60 measurements per investigator. Twenty control measurements for each of the three incubators were obtained using an infrared monitor calibrated at the 5.0% CO ₂ level.Results Fyrite analyzer values fell outside of an acceptable range (Control mean CO ₂ ±0.5%) for 7 of 60 (11.7%) observations for Incubator 1 and 4 of 60 (6.7%) observations for Incubator 2. (Incubator 3 had no values outside the range.) The Fyrite analyzers were significantly different from each other (P=0.002). The three investigators (I) differed significantly from the control (I1 and I3, P<0.001; I2, P=0.02) as well as from each other (I1 vs I2, P<0.001; I1 vs I3, P<0.001; I2 vs I3, P<0.016).Conclusions Use of an infrared monitor for incubator calibration and monthly CO ₂ checks in concert with daily use of the Fyrite as a monitoring tool only is the better method.Presented at the 50th Annual Meeting of the American Fertility Society, San Antonio, Texas, November 5–10, 1994.     

Idiotypic cross-reactivity of immunoglobulins expressed in Waldenstr?m's macroglobulinemia, chronic lymphocytic leukemia, and mantle zone lymphocytes of secondary B-cell follicles

Monoclonal antibodies (MoAbs) specific for autoantibody-associated cross-reactive idiotypes (CRIs) of Waldenstr?m's IgM react frequently with the surface Ig (slg) expressed by leukemia cells of patients with chronic lymphocytic leukemia (CLL). Evaluation of the molecular basis for this cross-reactivity indicates that such CRIs are encoded by conserved antibody variable region genes (V genes) that have undergone little or no somatic hypermutation. We find that such anti-CRI MoAbs stain a subpopulation of cells within the mantle zones surrounding the germinal centers of normal human tonsil. In contrast, MoAbs specific for variable region subgroup determinants react with cells in both the mantle zones and germinal centers of secondary B-cell follicles. To test whether mantle zone B cells not reactive with existing anti-CRI MoAbs may express slg bearing as-yet-unrecognized CRIs present on Igs produced by neoplastic cells of some patients with Waldenstr?m's macroglobulinemia or CLL, we immunized mice with purified Waldenstr?m's IgM that have been characterized for their variable region subgroups using subgroup-specific antisera raised against synthetic peptides. The supernatants of hybridomas generated from the splenocytes of immunized mice were screened for their ability to stain a subpopulation of mantle zone lymphocytes in human tonsil. With this approach, two new anti-CRI MoAbs were identified, designated OAK1 and VOH3. OAK1 binds to a CRI present on a subset of kappa light chains of the VK1 subgroup. VOH3 recognizes a CRI determinant(s) present on a subset of antibody heavy chains of the VH3 subgroup. Flow cytometric analyses demonstrated that OAK1 specifically binds leukemia cells from 5 to 20 patients (25%) with kappa light chain expressing CLL. In addition, VOH3 reacted with the leukemia cells from 1 of 17 (6%) patients tested. The success of these methods demonstrates that the variable regions of the Igs produced by mantle zone B cells share idiotypic determinants with Igs expressed in B-cell CLL (B-CLL) and Waldenstr?m's macroglobulinemia.     

Cardiovascular responses to a hot tub bath.

This study was conducted to determine the cardiovascular effects of 15 minutes of hot tub immersion at 39 degrees C. Five college-age subjects (4 males and 1 female) volunteered to participate in this study. Assessments were made while sitting first in a chair for 5 minutes and then in the hot tub for 15 minutes. Oxygen consumption (VO2) and cardiac output (Q) measurements were made using a Medical Graphics CPX/D metabolic analyzer. Cardiac output was determined at minute 15 using the indirect CO2 rebreathing procedure. The data were analyzed using the analysis of variance with repeated measures, which indicated that at minute 15, heart rate (HR) and Q were increased, which increased VO2. The increase in Q was due to the heart rate (HR) response and the decrease in systemic vascular resistance (SVR). Mean arterial pressure (MAP) and systolic blood pressure (SBP) were decreased while double product (DP) was increased. There were no changes in stroke volume (SV) or arteriovenous oxygen difference (a-vO2 diff). These findings indicate that the HR and Q responses are necessary to the increase in metabolism (VO2). Hot tube use within these time and temperature constraints should reduce concern over hot tub safety in college-age subjects.