Circulating cardiac troponin-I autoantibodies in human plasma and serum.

We identified IgG reactive with human cardiac troponin-I (cTnI) in plasma and serum samples (N = 1930) from normal blood donors, and in sample cohorts characterized on the basis of clinical biomarkers associated with cardiac, infectious, and autoimmune diseases. cTnI and brain natriuretic peptide were the biomarkers chosen to reflect myocyte damage or left ventricular dysfunction, respectively. The infectious disease cohorts were serologically positive for antibodies to hepatitis B (natural infection), hepatitis C virus, and Chagas (i.e., T.cruzi). The autoimmune cohorts were represented by samples from diagnosed systemic lupus erythematosus (biomarker: dsDNA) and rheumatoid arthritis (biomarker: rheumatoid factor) subjects. The prevalence of IgG autoantibodies reactive with cTnI was high in the normal donor cohort (95/750, 12.7%). The prevalence in the other sample cohorts was not significantly different from that in the normal blood donors, with the exception of a slight increase in the rheumatoid factor cohort (28/137, 20.4%). The presence of anti-cTnI IgG in highly reactive samples was confirmed by inhibition with the antigen and further by screening with a library of peptides derived from the human cTnI amino acid sequence. Our data suggest that these autoantibodies are polyspecific, encompassing epitopes across the entire cTnI sequence, including the cardiac-specific amino terminal region.

Galantamine treatment in Alzheimer's disease with cerebrovascular disease: responder analyses from a randomized, controlled trial (GAL-INT-6).

Alzheimer's disease combined with cerebrovascular disease (AD with CVD) is associated with progressive decline, with CVD impacting AD onset and severity of progression. Subjects with confirmed diagnosis of AD with CVD were treated with galantamine during a six-month, randomized, placebo-controlled trial (N = 285). Responder analyses were performed for cognitive, behavioural and functional outcome measures. Galantamine treatment resulted in significantly greater cognitive and functional improvements compared with placebo at six months, and a significantly higher percentage of treatment responders. The proportion of responders demonstrating improved or maintained cognition on the 11-item AD assessment scale-cognitive subscale (ADAS-cog/11) was 60.5% for galantamine versus 46.0% for placebo (P = 0.013). The proportion of patients responding by at least four-points on the ADAS-cog/11 was significantly greater for the galantamine group compared with placebo (33.6% versus 17.2%; P = 0.003). Seventy-five percent of galantamine-treated subjects improved or remained stable as assessed by CIBIC-plus compared with 53.6% on placebo (P = 0.0006). Significantly higher responder rates were observed with galantamine for behaviour (64.9% versus 56.6%; P = 0.024), and numerically favourable responder rates were seen with galantamine for activities of daily living. Treatment-emergent adverse events were generally related with the gastrointestinal system (nausea 20% versus 10%; vomiting 12% versus 5%; galantamine and placebo groups, respectively). Three deaths occurred during double-blind treatment: 2 of 188 subjects receiving galantamine, and 1 of 97 subjects receiving placebo. These findings are consistent with a broad range of cognitive, functional and behavioural benefits with galantamine across the spectrum of AD and AD with CVD.

Galantamine in frontotemporal dementia and primary progressive aphasia.

BACKGROUND/AIMS: The treatment of frontotemporal dementia (FTD) has been mainly symptomatic. Small randomized or open-label case control studies of neurotransmitters have been inconclusive. We tried galantamine in the 2 most common varieties of FTD. METHOD: Thirty-six behavioral variety FTD and primary progressive aphasia (PPA) patients were treated in an open-label period of 18 weeks and a randomized, placebo-controlled phase for 8 weeks with galantamine. The primary efficacy measures were the Frontal Behavioral Inventory, the Aphasia Quotient of the Western Aphasia Battery, the Clinical Global Impression of Severity and the Clinical Global Impression of Improvement. RESULTS: No significant differences in behavior or language were found for the total group. A treatment effect (p = 0.009), in a subgroup of subjects with PPA in the global severity score, in favor of galantamine was detected in the placebo-controlled withdrawal phase but was not considered significant after correction for multiple comparisons. The language scores for the treated PPA group also remained stable compared to the placebo group, which showed deterioration. CONCLUSION: Galantamine is not effective in the behavioral variety of FTD, but a trend of efficacy is shown in the aphasic subgroup, which may be clinically significant. Galantamine appeared safe in FTD/PPA.

Rapid high-throughput detection of peroxide with an acridinium-9-carboxamide: a homogeneous chemiluminescent assay for plasma choline.

Hydrogen peroxide generated from the enzymatic oxidation of choline was detected using a chemiluminescent acridinium-9-carboxamide. The dose-response for choline (0-50 microM) was established in buffer and was applicable to the quantification of choline in human plasma. This homogeneous assay was performed in a 96-well microplate format and required minimal sample volume (1 microL) and analysis time (<5 s per well).

Homogeneous chemiluminescent assays for free choline in human plasma and whole blood.

Choline was oxidized in the presence of choline oxidase and the hydrogen peroxide generated was detected using a chemiluminescent acridinium-9-carboxamide. The dose response for choline (0-150 microM) was established in buffer and was validated for the quantification of choline in human plasma and whole blood. This homogeneous assay was performed in a 96-well microplate format and required minimal sample volume (4 microL) and short analysis time (<5s per well). The new assay(s) correlated well (R>0.98, plasma; R>0.97, whole blood) with LC-MS/MS.

Diffuse reflectance near-infrared spectroscopy as a nondestructive analytical technique for polymer implants.

A near-infrared spectroscopic method to quantify drugs or excipients within polymeric matrixes is proposed. Cylindrical implants were fabricated by a melt-mold technique containing various ratios of poly(epsilon-caprolactone) (PCL) and poly(ethylene glycol) (PEG) and various loadings of lomefloxacin HCl with a constant ratio (70:30 w/w) of PCL/PEG. Near-infrared (NIR) spectra were obtained on intact sections of larger implants using a Foss NIRSystems Model 5000 monochrometer equipped with a Rapid Content Analyzer. Spectral data were treated with second derivative transformation followed by linear regression and PLS to obtain correlation with lomefloxacin or PEG content. Lomefloxacin content was separately determined by UV analysis (287 nm) using a validated extraction procedure. The NIR method was tested by comparing predicted loadings of test implants with either theoretical values based on weight (PEG) or with UV analysis results (lomefloxacin). Second derivative spectral values at particular wavelength ratios (PEG, 2064 nm/1698 nm; lomefloxacin, 2172 nm/2226 nm and 1824 nm/1862 nm) yielded linear results for PEG or lomefloxacin content. PEG content determined by NIR spectroscopy was in excellent agreement with theoretical content. Lomefloxacin content determined by NIR spectroscopy was also in excellent agreement with UV analysis. NIR analysis is interpreted through the use of corresponding mid-infrared spectral data.

Hepatitis C virus and lichen planus: A case-control study of 340 patients.

Lichen planus (LP) has been associated with liver disease, particularly hepatitis C virus (HCV) infection, in several studies to date. Most of these reports, especially the larger series, were conducted in Europe. In addition, the type of LP associated with HCV was reported to be oral LP in most studies. We conducted a case-control study in a US metropolitan population known to have a low seroprevalence of HCV infection to explore the impact of geography and endemicity of HCV on the association between cutaneous LP and HCV. The study comprised 340 patients with cutaneous LP (as case ) against 577 patients with psoriasis (as control-1 ). Hepatitis antibody titers and liver function abnormalities were our main outcome measures. Prevalence of HCV antibody among 149,756 regional volunteer blood donors (as control-2 ) was also used for comparison. Twelve (55%) of 22 patients with LP tested for HCV were antibody positive. This was significantly higher than 25% of 40 psoriasis patients tested for HCV antibody (P =.04) or than 0.17% of blood donors tested for HCV antibody (P < 10(-5)). Thus a small but significant percentage of US patients with cutaneous LP had HCV antibody. Because LP may be the first presentation of HCV infection, it is important for clinicians to actively look for such infection in patients with LP.

Porphyria cutanea tarda and hepatitis C virus: a case-control study and meta-analysis of the literature.

BACKGROUND: Porphyria cutanea tarda (PCT) and hepatitis C virus (HCV) infection have been associated in several reports with the prevalence of HCV exhibiting considerable regional variation. However, most reports were confounded by selection bias and a regional prevalence of HCV in the populations studied. In the United States, only a few cases of this association have been reported to date. OBJECTIVE: We concluded a study to evaluate the association between PCT and HCV in a US population. We used a case-control study design to control the systemic error that may occur during a selecting process or sampling procedure. METHODS: We reviewed the medical records of Wishard Memorial Hospital, a county hospital serving metropolitan Indianapolis, Indiana, to perform a retrospective case-control study of 26 patients with PCT (as case) against 149,756 regional volunteer blood donors (as control-1) and 51 patients receiving methotrexate for psoriasis (as control-2). HCV antibody titers and other liver abnormalities were our main outcome measures. We then performed a weighted meta-analysis of 17 reports that had at least 17 patients in their study populations. RESULTS: Sixteen (94%) of 17 PCT patients tested for HCV were antibody positive. Among blood donors, only 255 or 0.17% were HCV antibody positive (P < 10(-5), two-sided chi-square test). Of 5 psoriasis patients tested for HCV, none were HCV antibody positive (P = .0002, two-sided Fisher's exact test). For geographic comparison, meta-analysis of the literature demonstrated a varying regional prevalence of HCV in PCT patients as follows: Northern Europe 17%, Australia/New Zealand 20%, and Southern Europe 65%. CONCLUSION: Although a marked geographic variation was found in the worldwide prevalence of HCV in PCT patients, a very large percentage of US patients with PCT had HCV infection. Our results emphasize the need for clinicians to actively look for HCV in patients with PCT.

Risk factors of non-melanoma skin cancer in United States veterans patients: a pilot study and review of literature.

OBJECTIVE: To identify risk factors of non-melanoma skin cancer (NMSC) in US veterans patients. BACKGROUND: There are an estimated one million new NMSC cases annually in the United States alone. While other studies with varying foci have evaluated risk factors in different subsets of the general populace, none have examined veterans as a group with potentially unique exposures and risks. METHODS: An investigation of risk factors for skin cancer through questionnaire and physical examination on 145 veteran patients with skin cancer and 59 veteran patients without a history of skin cancer was conducted. RESULTS: Parents' ethnicity, actinic keratosis on the face or other anatomic sites, solar elastosis of the neck, facial telangiectasias, age of first sunburn, and residency in Indiana were risk factors significantly associated with the development of skin cancer. Other possible risk factors included smoking and radiation therapy. CONCLUSIONS: We documented several risk factors which significantly increased the chance of developing skin cancer among veterans. These included ethnic background and solar damage of the skin among others. A review of the literature confirms these risks in the general population, but also further study is warranted to address risk factors like smoking and radiation, particularly in veterans populations. Identification of pertinent risk factors will help to identify high risk individuals, allow detection of new skin cancer at its earliest stage, and develop a profile of favorable lifestyle characteristics that reduce NMSC risk.

Case report: pancreatic cancer presenting with paraneoplastic gastroparesis.

Delayed gastric emptying has been observed in some patients with histologically proved pancreatic cancer without evidence of obstruction. The case of a 73-year-old women who had signs and symptoms of delayed gastric emptying is described. Workup included a gastric emptying study that showed 95% retention of the radiolabeled test meal after 2 hours (normal result, <70%). Abdominal computed tomography showed findings consistent with a pancreatic mass. Indirect immunofluorescence study of the patient's serum showed staining of Purkinje cell nuclei and prompted further evaluation for malignant masses. No other cause for the patient's gastroparesis was found, including obstruction. This case illustrates how gastroparesis with no other apparent cause, particularly in elderly patients, may represent a paraneoplastic syndrome. Pancreatic cancer should be included in the list of occult carcinomas that can manifest in this manner.

Detection of antibodies to Trypanosoma cruzi among blood donors in the southwestern and western United States. I. Evaluation of the sensitivity and specificity of an enzyme immunoassay for detecting antibodies to T. cruzi.

BACKGROUND: Chagas' disease or American trypanosomiasis, caused by infection with Trypanosoma cruzi, is a significant health problem in Latin America. In the United States, transfusions of T. cruzi-contaminated blood from Latin American immigrants may represent the major source of Chagas' disease. STUDY DESIGN AND METHODS: A new enzyme immunoassay (EIA) for the detection of antibody to T. cruzi was evaluated in the sera of blood donors from the southwestern and western regions of the United States. Serum samples had been screened and were negative for all tests required. Specimens that were repeatedly reactive in the Chagas antibody EIA were analyzed for seroreactivity by a confirmatory EIA and by radioimmunoprecipitation assay. RESULTS: Fourteen of the 13,309 donor samples (0.105%) were confirmed as being positive for antibody to T. cruzi. The Chagas antibody EIA showed improved sensitivity over the Chagas IgG enzyme-linked immunosorbent assay and two indirect hemagglutination assays. The Chagas antibody EIA had a specificity of 99.98 percent with negative samples. The sensitivity of the Chagas antibody EIA was 100 percent (80/80) in xenodiagnosed specimens and 100 percent (50/50) in specimens positive by consensus (i.e., reactive in EIA, indirect hemagglutination assay, and immunofluorescence assays). CONCLUSION: This Chagas antibody EIA meets the need for accurate and rapid identification of seroreactive samples in low-prevalence or endemic populations.

Detection of antibodies to Trypanosoma cruzi among blood donors in the southwestern and western United States. II. Evaluation of a supplemental enzyme immunoassay and radioimmunoprecipitation assay for confirmation of seroreactivity.

BACKGROUND: Chagas' disease, caused by the protozoan parasite Trypanosoma cruzi, is endemic to Latin America and may be transmitted in the United States via blood donated by infected immigrants. Blood-borne pathogens such as T. cruzi require supplemental testing for confirmation of seroreactivity. STUDY DESIGN AND METHODS: A study was undertaken to determine an optimal scheme for confirmation of seroreactivity in repeatedly reactive samples identified by the Chagas antibody enzyme immunoassay (EIA). The procedure for initial confirmation involves three purified antigens coated onto three separate polystyrene beads and uses an EIA format. If the sample is reactive with two of three or three of three antigens, it is confirmed as seroreactive. If none or one of three beads is reactive, the sample is indeterminate and subjected to a radioimmunoprecipitation assay (RIPA). The RIPA must demonstrate characteristic bands at 32, 34, and 90 kDa. RESULTS: When tested with sera from persons with potentially cross-reactive diseases (n = 39) or against a presumed negative population from southeast Wisconsin (n = 289), the confirmatory EIA had a specificity of 100 percent. Sensitivity was 100 percent (28/28) with xenodiagnosis-positive sera and 97.6 percent (80/82) with chagasic sera from Latin America. The RIPA showed a specificity of 100 percent in EIA-nonreactive samples (n = 100) and a sensitivity of 100 percent with both xenodiagnosis-positive (28/28) and chagasic (82/82) sera. CONCLUSION: The confirmatory EIA and the RIPA together provide a highly specific and sensitive means of confirming seroreactivity for antibodies to T. cruzi.

Pharmacokinetics of theophylline before and after nephrectomy in dogs.

The role of the kidneys in the elimination of theophylline was directly assessed using nephrectomized dogs. Data was analyzed by two different pharmacokinetic approaches. Analysis indicated that a given dosage regimen produced significantly different serum concentrations before and after nephrectomy. Model independent pharmacokinetic analysis failed to show a significant difference in parameters. A model dependent approach, using a nonlinear regression analysis employing a linear two-compartment model, demonstrated that the differences observed could be accounted for by a change in the first order elimination kinetics.

Effect of alteration of cerebrospinal fluid bulk flow on nicotine cerebrospinal fluid exit transfer kinetics.

This study was undertaken to determine if a compound which alters the bulk flow of cerebrospinal fluid (CSF) alters the elimination kinetics of a compound in the CSF. Acetazolamide was chosen as the CSF bulk flow-altering agent. It produces a relatively large effect on the flow process, affecting both choroidal and extrachoroidal CSF production, and has been shown to affect CSF flow following iv administration. The compound monitored was nicotine. Acetazolamide was administered orally for one week before and intravenously during the experiment. Nicotine was administered by a bolus injection directly into the CSF via the cisterna magna. The results indicate that the introduction of acetazolamide into the general circulation increases the rate of removal of nicotine from the CSF. Subjects receiving acetazolamide had elevated CSF pressures. The increase in CSF pressure associated with the administration of acetazolamide suggests pressure as a possible factor in the observed increase in the rate of removal of nicotine.

Men in occupational therapy.

The purpose of this study was to identify the characteristics of male occupational therapists so that better strategies for recruiting men into the profession can be developed and the problem of retaining men in the field can be addressed. Male occupational therapists were surveyed at 3-year intervals, in 1978, 1982, and 1985. Our survey results were compared with results of the 1969 American Occupational Therapy Association (AOTA) Member Data Survey reported by Jantzen (1973), the 1982 AOTA Member Data Survey, and an unpublished study by Watson (1983). The number of professional occupational therapists almost tripled from 1970 to 1985, whereas the increase in the proportion of men was only from 3.9% to 5%. The study showed that as a group, male occupational therapists today are younger, more likely to have advanced degrees, and less likely to be married than their 1969 counterparts. Additional data included employment data, educational data, and demographic information such as family position, education and occupation of parents, extracurricular activities in high school and college, factors influencing career choice, and goals for the future.