Multidimensional daily diary of fatigue-fibromyalgia-17 items (MDF-fibro-17): part 2 psychometric evaluation in fibromyalgia patients.

BACKGROUND: The Multidimensional Daily Diary of Fatigue-Fibromyalgia-17 instrument (MDF-Fibro-17) has been developed for use in fibromyalgia (FM) clinical studies and includes 5 domains: Global Fatigue Experience, Cognitive Fatigue, Physical Fatigue, Motivation, and Impact on Function. Psychometric properties of the MDF-Fibro-17 needed to demonstrate the appropriateness of using this instrument in clinical studies are presented. METHODS: Psychometric analyses were conducted to evaluate the factor structure, reliability, validity, and responsiveness of the MDF-Fibro-17 using data from a Phase 2 clinical study of FM patients (N = 381). Confirmatory factor analyses (CFA) were performed to ensure understanding of the multidimensional domain structure, and a secondary factor analysis of the domains examined the appropriateness of calculating a total score in addition to domain scores. Longitudinal psychometric analyses (test-retest reliability and responder analysis) were also conducted on the data from Baseline to Week 6. RESULTS: The CFA supported the 17-item, 5 domain structure of this instrument as the best fit of the data: comparative fit index (CFI) and non-normed fit index (NNFI) were 0.997 and 0.992 respectively, standardized root mean square residual (SRMR) was 0.010 and the root mean square error of approximation (RMSEA) was 0.06. In addition, total score (CFI and NNFI both 0.95) met required standards. For the total and 5 domain scores, reliability and validity data were acceptable: test-retest and internal consistency were above 0.9; correlations were as expected with the Global Fatigue Index (GFI) (0.62-0.75), Fibromyalgia Impact Questionnaire (FIQ) Total (0.59-0.71), and 36-Item Short Form Health Survey (SF-36) vitality (VT) (0.43-0.53); and discrimination was shown using quintile scores for the GFI, FIQ Total, and Pain Numeric Rating Scale (NRS) quartiles. In addition, sensitivity to change was demonstrated with an overall mean responder score of -2.59 using anchor-based methods. CONCLUSION: The MDF-Fibro-17 reliably measures 5 domains of FM-related fatigue and psychometric evaluation confirms that this measure meets or exceeds each of the predefined acceptable thresholds for evidence of reliability, validity, and responsiveness to changes in clinical status. This suggests that the MDF-Fibro-17 is an appropriate and responsive measure of FM-related fatigue in clinical studies.

Multidimensional daily diary of fatigue-fibromyalgia-17 items (MDF-fibro-17). part 1: development and content validity.

BACKGROUND: Fibromyalgia (FM), a disorder characterized by chronic widespread pain and tenderness, affects greater than five million individuals in the United States alone. Patients experience multiple symptoms in addition to pain, and among them, fatigue is one of the most bothersome and disabling. There is a growing body of literature suggesting that fatigue is a multidimensional concept. Currently, to our knowledge, no multidimensional Patient Reported Outcome (PRO) measure of FM-related fatigue meets Food and Drug Administration (FDA) requirements to support a product label claim. Therefore, the objective of this research was to evaluate qualitative and quantitative data previously gathered to inform the development of a comprehensive, multidimensional, PRO measure to assess FM-related fatigue in FM clinical trials. METHODS: Existing qualitative and quantitative data from three previously conducted studies in patients with FM were reviewed to inform the initial development of a multidimensional PRO measure of FM-related fatigue: 1) a concept elicitation study involving in-depth, open-ended interviews with patients with FM in the United States (US) (N = 20), Germany (N = 10), and France (N = 10); 2) a cognitive debriefing and pilot study of a preliminary pool of 23 items (N = 20 US patients with FM); and 3) a methodology study that explored initial psychometrics of the item pool (N = 145 US patients with FM). RESULTS: Five domains were identified that intend to capture the broad experience of FM-related fatigue reported in the qualitative research: the Global Fatigue Experience, Cognitive Fatigue, Physical Fatigue, Motivation, and Impact on Function. Seventeen of the original pool of 23 items were selected to best capture these five dimensions. These 17 items formed the basis of a newly developed multidimensional PRO measure to assess FM-related fatigue in clinical trials: the Multidimensional Daily Diary of Fatigue-Fibromyalgia-17 (MDF-Fibro-17). CONCLUSION: Qualitative analysis, and preliminary quantitative item level data, confirmed that FM-related fatigue is multidimensional and provided strong support for the content validity of the MDF-Fibro-17. The next stage was to quantitatively evaluate the measure to confirm the factor structure, psychometric properties, sensitivity to change, and meaningful change. This has been conducted and is being reported separately.

Anaphylaxis to artesunate?

Artesunate, an artemissin derivative is a highly efficacious and relatively safe antimalarial agent. Common adverse reactions to artemissin derivatives are nausea, vomiting, anorexia and dizziness. More serious but less-frequent toxic effects of artesunate use are neutropenia, anemia, hemolysis, elevated liver enzymes and severe allergic reactions. However, anaphylactic reaction to artesunate is a rare entity. Here, we report a case of anaphylaxis to parenteral artesunate and its successful management in a female patient to whom intravenous artesunate was administered during surgery under general anesthesia.

Predictors of tobacco smoking and smokeless tobacco use among adults in Bangladesh.

INTRODUCTION: To examine predictors of current tobacco smoking and smokeless tobacco use among the adult population in Bangladesh. MATERIALS AND METHODS: We used data from the 2009 Global Adult Tobacco Survey (GATS) in Bangladesh consisting of 9,629 adults aged ≥15 years. Differences in and predictors of prevalence for both smoking and smokeless tobacco use were analyzed using selected socioeconomic and demographic characteristics that included gender, age, place of residence, education, occupation, and an index of wealth. RESULTS: The prevalence of smoking is high among males (44.7%, 95% confidence interval [CI]: 42.5-47.0) as compared to females (1.5%, 95% CI: 1.1-2.1), whereas the prevalence of smokeless tobacco is almost similar among both males (26.4%, 95% CI: 24.2-28.6) and females (27.9%, 95% CI: 25.9-30.0). Correlates of current smoking are male gender (odds ratio [OR] = 41.46, CI = 23.8-73.4), and adults in older age (ORs range from 1.99 in 24-35 years age to 5.49 in 55-64 years age), less education (ORs range from 1.47 in less than secondary to 3.25 in no formal education), and lower socioeconomic status (ORs range from 1.56 in high wealth index to 2.48 in lowest wealth index. Predictors of smokeless tobacco use are older age (ORs range from 2.54in 24-35 years age to 12.31 in 55-64 years age), less education (ORs range from 1.44 in less than secondary to 2.70 in no formal education), and the low (OR = 1.34, CI = 1.0-1.7) or lowest (OR = 1.43, CI = 1.1-1.9) socioeconomic status. CONCLUSION: Implementation of tobacco control strategies needs to bring special attention on disadvantaged group and cover all types of tobacco product as outlined in the WHO Framework Convention on Tobacco Control (FCTC) and WHO MPOWER to protect people's health and prevent premature death.

Efficient multilevel brain tumor segmentation with integrated bayesian model classification.

We present a new method for automatic segmentation of heterogeneous image data that takes a step toward bridging the gap between bottom-up affinity-based segmentation methods and top-down generative model based approaches. The main contribution of the paper is a Bayesian formulation for incorporating soft model assignments into the calculation of affinities, which are conventionally model free. We integrate the resulting model-aware affinities into the multilevel segmentation by weighted aggregation algorithm, and apply the technique to the task of detecting and segmenting brain tumor and edema in multichannel magnetic resonance (MR) volumes. The computationally efficient method runs orders of magnitude faster than current state-of-the-art techniques giving comparable or improved results. Our quantitative results indicate the benefit of incorporating model-aware affinities into the segmentation process for the difficult case of glioblastoma multiforme brain tumor.

Non-patient factors related to rates of ruptured appendicitis.

BACKGROUND: Adult rates of ruptured appendicitis vary from 13.2 to 41.9 per cent in urban hospitals, despite controlling for individual factors. This suggests an effect of hospital organization. Surgeons report that appendicectomies may be delayed because of lack of access to operating rooms. METHODS: Combining interviews with hospital personnel and information from medical records for 1998-1999, a cross-sectional study using logistic regression, taking hospital clustering of patients into account, was conducted on 861 patients from 12 hospitals. Hospitals were grouped into organizational models. The diagnostic information was recoded to ensure interhospital validity. RESULTS: Hospitals with high activity and volumes of patients, but without an operating room designated for urgent surgery, were associated with a significantly higher risk of peritonitis (P<0.050). Time to surgery was very long in all hospitals, particularly time after departure from the emergency department and for elderly patients. CONCLUSION: Organizational characteristics, in unfavourable combinations, influence the course of time-dependent diseases such as appendicitis. Difficulties in gaining access to operating rooms, even for urgent operations, have emerged. Delays in treatment must be addressed when planning healthcare reforms.

Microencapsulation of Zanthoxylum limonella oil (ZLO) in glutaraldehyde crosslinked gelatin for mosquito repellent application.

Glutaraldehyde (GA) crosslinked gelatin (G) microcapsules containing Zanthoxylum limonella oil (ZLO) were prepared by coacervation technique. The effect of various parameters such as variation of oil-loading, gelatin concentration and degree of crosslinking on release rate of oil were studied. Scanning electron microscopy (SEM) was used to understand the surface characteristics of microcapsules. FTIR-results indicated the absence of any significant interaction between polymer and oil.

Removal of iron from groundwater by ash: a systematic study of a traditional method.

A traditional method for removal of iron from ground water by using ash has been systematically investigated. Ashes from five different sources, viz., banana rind, banana pseudostem, banana leaf, rice husk and bamboo has been studied. The principle applied is enhanced precipitation of iron at high pH caused by ash. The study included laboratory analysis of some relevant chemical parameters of the ashes and the efficiency of the ashes in removing iron from prefabricated water with respect to quantity of ash and corresponding increase in pH of water. The ash of banana pseudostem has been found to be most suitable for removal of iron. A low-cost and easily made iron removal system for household use has been designed and tested in the laboratory. The ash of banana pseudostem has been found to remove iron to below 0.3ppm without increasing the pH above the acceptable limit. The optimum values of the different parameters for removal of iron are 200-300mgl(-1) ash, 1.0lh(-1) flow rate and 1h of contact time with ash for groundwater having [Fe] of about 2.20ppm. The amount of ash can be increased for groundwater having higher [Fe] and can be decreased gradually during continuous use of the system. Acceptability of the method has been examined based on chemical analysis of the treated water. Increase in the essential minerals such as Ca, K has been observed in the water after treatment. The designed iron removing system is expected to be suitable for household use.

Acute toxicity and cardio-respiratory effects of 2-deoxy-D-glucose: a promising radio sensitiser.

OBJECTIVE: To evaluate the acute toxicity of 2-deoxy-D-glucose (2DG) by oral (p.o.) and intravenous (i.v.) routes, and also the cardio-respiratory effects following high doses of 2DG in animal models. METHODS: The LD50 of 2DG (in water) was determined in rats and mice by p.o. route and in mice by i.v. route. The effect of 2-DG (250 mg/kg, 500 mg/kg, and 1000 mg/kg, i.v.) was studied on various cardio-respiratory parameters viz., mean arterial blood pressure, heart rate and respiratory rate in anaesthetised rats. The effect of 2DG (500 mg/kg, 1000 mg/kg, and 2000 mg/kg, p.o.) was also studied on various respiratory parameters viz., respiratory rate and tidal volume in conscious rats and mice using a computer program. RESULTS: The p.o. LD50 of 2DG was found to be >8000 mg/kg in mice and rats, and at this dose no death was observed. The LD50 in mice by i.v. route was found to be 8000 mg/kg. At this dose 2 out of 4 mice died and the death occurred within 6 h. A significant increase in the body weight was observed after p.o. administration of 2DG in rats at 500 mg/kg, 1000 mg/kg, and 2000 mg/kg doses. There was no significant change in the body weight at 4000 mg/kg and 8000 mg/kg by the p.o. route in rats and up to 8000 mg/kg by p.o. as well as i.v. routes in mice. Intravenous administration of 2DG (250 mg/kg, 500 mg/kg, and 1000 mg/kg) in anaesthetised rats showed a time-dependent decrease in the mean arterial blood pressure. There was no change in the heart rate in any of the treatment groups. The tidal volume was not changed significantly by p.o administration in conscious rats, but a significant decrease in the respiratory frequency at 500 mg/kg and 1000 mg/kg doses was observed. In the mice also there was no change in the tidal volume after p.o, administration, but the respiratory frequency decreased significantly at 2000 mg/kg dose. CONCLUSION: 2DG is a safe compound but can cause a fall in the blood pressure and a decrease in respiratory frequency at high doses.

Clostridium schirmacherense sp. nov., an obligately anaerobic, proteolytic, psychrophilic bacterium isolated from lake sediment of Schirmacher Oasis, Antarctica.

A novel obligately anaerobic, proteolytic bacterium, designated AP15T, was isolated from lake sediments of Schirmacher Oasis, Antarctica. The bacterium produced maximum cell mass between 5 and 10 degrees C in an anaerobic basal medium containing 0.5 % tryptone and peptone. The strain grew optimally at a pH around 8.0 and tolerated NaCl up to a concentration of 7.5 %. It contained diphosphatidylglycerol as the major phospholipid and C(15 : 0), C(16 : 0) and C(17 : 0) as the major cellular fatty acids. Several amino acids, including arginine, leucine, isoleucine, cysteine, glutamate and serine, supported growth. Glutamate was degraded to acetate, propionate, CO2 and H2. In addition, the strain degraded carbohydrates including glucose, raffinose, adonitol, ribose and rhamnose. The main fermentation products during growth on glucose were H2, CO2, formate, acetate, propionate and isovalerate. The DNA G+C content of the bacterium was 24 mol%. On the basis of a phylogenetic analysis, strain AP15(T) is identified as a close relative of Clostridium subterminale ATCC 25774T, with which it shares 99.5 % similarity at the 16S rRNA gene sequence level; however, it exhibits a low DNA-DNA binding value (55 %) to this strain at the whole-genome level. In addition to showing other major differences with respect to C. subterminale and other members of the genus Clostridium, AP15T also exhibits phenotypic differences. On the basis of these differences, strain AP15T is identified as representing a novel species of the genus Clostridium, for which the name Clostridium schirmacherense sp. nov. is proposed. The type strain is AP15T (=DSM 17394T = JCM 13289T).

The Quebec Association of Gastroenterology position paper on colorectal cancer screening - 2003.

Colorectal cancer is a leading cause of death and the third most common cancer in Canada. Evidence suggests that screening can reduce mortality rates and the cost effectiveness of a program compares favourably with initiatives for breast and cervical cancer. The objectives of the Association des gastro-entérologues du Québec Task Force were to determine the need for a policy on screening for colorectal cancer in Quebec, to evaluate the testing methods available and to propose one or more of these alternatives as part of a formal screening program, if indicated. Fecal occult blood testing (FOBT), endoscopy (including sigmoidoscopy and colonoscopy), barium enema and virtual colonoscopy were considered. Although most clinical efficacy data are available for FOBT and sigmoidoscopy, there are limitations to programs based on these strategies. FOBT has a high false positive rate and a low detection yield, and even a combination of these strategies will miss 24% of cancers. Colonoscopy is the best strategy to both detect and remove polyps and to diagnose colorectal cancer, with double contrast barium enema also being a sensitive detection method. The Task Force recommended the establishment, in Quebec, of a screening program with five- to 10-yearly double contrast barium enema or 10-yearly colonoscopy for individuals aged 50 years or older at low risk. The program should include outcome monitoring, public and professional education to increase awareness and promote compliance, and central coordination with other provincial programs. The program should be evaluated; specific billing codes for screening for colorectal cancer would help facilitate this. Formal feasibility, effectiveness and cost-effectiveness studies in Quebec are now warranted.

[Could we trust clinical statistics from data banks of the National Health Service (NHS)?]. / Peut-on se fier aux statistiques fournies par les banques de données émanant du ministère de la santé?

Can we accept the statistics provided by the Ministry of Health, which uses large computerized databases? Through MEDECHO, the Ministry provides to hospital managers, reports cards on different interventions. These reports compare different hospitals performances. Surgeons involved in the process hesitate to accept this information. Using the results of the performance of cholecystectomy provided by this system (Gr: A), we compared the same cohort (1 April-31 December 1996 = 346 cholecystectomies) but using specific criteria determined as relevant to our surgeons (Gr: B). The rate of complication gives a crude aftermath and no attempt was used to adjust for severity. The MEDECHO data are adjusted for severity. The global rate of complications is similar Gr: A 11%, Gr: B 12%. Major complication rate for pulmonary embolism, hemorrhage and biliary duct trauma are identical. The rate of surgical site infection is higher in Gr: B (5% vs. 2%). The patients are seen in the outpatient clinic and these observations are not included by the analytical system unless the patient has been readmitted. For our hospital, the MEDECHO data are valid and reliable even though they underestimated the wound infection rate. These results could be explained by an appropriate interpretation of the code system by the archivist and by the surgeons' precision to complete the summary sheet of hospitalization. We can conclude that these data can be used as a means to evaluate the quality of outcome of a surgical service.

Classic Kaposi's sarcoma associated with human herpesvirus 8 infection in a 13-year-old male: a case report.

PURPOSE: Classic Kaposi's sarcoma (KS) is rare in children. Although its etiology is not fully understood, human herpesvirus 8 (HHV-8) is present in the angiogenic lesions. We report an HIV-negative, 13-year-old patient of Sicilian descent with HHV-8-associated classic KS to facilitate the diagnosis and treatment of this entity in children. EXPERIMENTAL DESIGN: DNA was extracted from the skin specimen of the patient and analyzed via PCR assay and Southern blot hybridization for HHV-8 DNA. The amplified HHV-8 DNA was cloned, sequenced, and compared with the prototype HHV-8-KS330/BAM. RESULTS: The patient presented with purpuric lesions on the distal lower extremities and the tip of his nose, associated with thrombocytopenia and leukopenia, suggesting an immune-mediated cytopenia. While on prednisone, he developed marked vascular proliferation in the groins. Biopsy of the skin lesions showed KS, and HHV-8 was detected in the tissues by PCR. Sequence analysis of the amplified DNA was homologous to the prototype HHV-8-KS330/BAM. His HHV-8 strain was the A subgroup, the type associated with Mediterranean classic KS. Stopping prednisone and treatment with IFN-alpha and IgG resulted in regression of the groin lesions. CONCLUSIONS: This report emphasizes the importance of recognizing classic KS in children and avoiding immunosuppressive therapies in indolent classic KS. The diagnostic and therapeutic strategies were effective and well tolerated.

Prevalence of HTLV-I-associated T-cell lymphoma.

In order to assess the prevalence rate of HTLV-1-associated T-cell lymphomas and human retrovirus infection in general, approximately 21,000 individuals representing various patient populations, retroviral risk groups, and blood donors were examined for HTLV-I, HTLV-II, HIV-1, or HIV-2 infection using serologic and PCR assays. The prevalence rates among volunteer blood donors were 0.02% and 0% for HTLV and HIV, respectively. Significantly increased HTLV prevalence rates were observed among paid blood donors, African American health care clinic patients, Amerindians, recipients of HTLV-positive cellular blood products, intravenous drug users, sexual contacts and family members of HTLV-positive people, and patients with primary thrombocytosis and other-than-low-grade non-Hodgkin's lymphoma (NHL). Among some of these groups there were significant differences in the prevalence of HTLV-I versus HTLV-II. The eight HTLV-positive NHL patients all had mature, high-grade, CD4+ T-cell lymphomas with clonally integrated HTLV-I, for a prevalence of 4% among other-than-low-grade NHL patients. Seven of the eight died from their disease within 2 years despite treatment. Interestingly, two groups at risk for HTLV infection, namely needle stick victims and recipients of HTLV-infected and/or pooled plasma products, showed no evidence for infection. Significantly increased HIV-1 prevalence was observed among paid blood donors, African Americans, homosexuals, female prostitutes, hemophiliacs, and other-than-low-grade NHL patients. Only one patient was infected with HIV-2. Of the nine HIV-positive, other-than-low-grade NHL patients, seven HIV-1 positives had B-cell lymphomas, one HIV-1 positive had an HTLV-I-positive CD4+ T-cell lymphoma, and one infected with HIV-2 had a CD4+ T-cell lymphoma that was HTLV negative. The data indicate that HTLV-I lymphoma, while uncommon, is not necessarily rare among other-than-low-grade NHL cases in the United States and, given its poor prognosis, should probably be studied separately in clinical trials.

Toxic effects of arsenic (III) on some hematopoietic and central nervous system variables in rats and guinea pigs.

OBJECTIVE: To evaluate the effects of arsenic (III) exposure on porphyrin metabolism and the central nervous system supplemented with data on the effect of hepatic and renal tissues of rats and guinea pigs. METHODS: Rats and guinea pigs were exposed to 10 or 25 ppm arsenic in drinking water for 16 weeks. RESULTS: Following chronic arsenic (III) exposure, delta-aminolevulinic acid dehydratase activity in blood showed a significant reduction as did the total cell counts (RBC and WBC) and reduced glutathione with increased urinary delta-aminolevulinic acid. Zinc protoporphyrin, a sensitive indicator of iron deficiency and impairment of heme biosynthesis, showed a significant increase in arsenic exposure. The hepatic delta-aminolevulinic acid dehydratase and delta-aminolevulinic acid synthetase activity increased in chronic arsenic (III) exposure in rats and guinea pigs. Significant changes in the steady-state level of three major neurotransmitters, dopamine, norepinephrine, and 5-hydroxytryptamine, and monoamine oxidase were observed following chronic arsenic (III) exposure. CONCLUSION: At low doses (10 and 25 ppm in drinking water), the effects of arsenic on hematopoietic indices and whole-brain neurotransmitter concentrations were more prominent in guinea pigs than in rats with some variability in the dose response.

Ultraviolet-B radiation impacts light-mediated turnover of the photosystem II reaction center heterodimer in Arabidopsis mutants altered in phenolic metabolism.

Ultraviolet-B (UV-B) radiation can have a negative impact on the growth and development of plants. Plants tolerant to UV-B alleviate these effects using UV-screening pigments that reduce the penetration of UV-B into mesophyll tissue. Little is known about the relative contribution of specific phenolic compounds to the screening capacity of leaves. The D1 and D2 proteins constituting the photosystem (PS) II reaction center heterodimer are targets of UV-B radiation and can be used as an in situ sensor for UV penetration into photosynthetic tissue. Degradation of these proteins occurs under very low fluences of UV-B, and is strongly accelerated in the presence of visible light. Using the D1-D2 degradation assay, we characterized UV-B sensitivity of Arabidopsis mutants (tt4, tt5, and fah1) that are genetically altered in their composition of phenolic compounds. We found that changes in phenol metabolism result in altered rates of PSII reaction center heterodimer degradation under mixtures of photosynthetically active radiation and UV-B. A comparison of D2 degradation kinetics showed increased UV sensitivity of the Landsberg (Landsberg erecta) tt5 mutant relative to the Landsberg tt4 mutant and the Landsberg wild type. Despite a lack of flavonoid accumulation, the tt4 mutant is not particularly UV sensitive. However, the tolerance of this mutant to UV-B may reflect the increased accumulation of sinapate esters that strongly absorb in the UV range, and may thus protect the plant against environmentally relevant UV-B radiation. This sinapate-mediated protection is less obvious for the tt4 mutant of Columbia ecotype, indicating that the relative contribution of particular phenolics to the total screening capacity varies with the genetic background. The role of sinapate esters in UV screening is further substantiated by the results with the fah1 mutant where absence of most of the sinapate esters results in a significantly accelerated degradation of D2 under mixed light conditions. Because the latter mutant is not expected to be deficient in flavonoids, the relative contribution of flavonoids as protectants of PSII reaction center heterodimer against UV-B damage in Arabidopsis needs to be re-evaluated vis-a-vis screening by simple phenolics like sinapate esters.

The complete genomic sequence of a BLV strain from a Holstein cow from Argentina.

DNA was extracted from the peripheral blood of a seropositive, PCR-positive, BLV-infected Holstein cow (No. 38) from Argentina. The DNA was amplified via PCR with a series of overlapping primers encompassing the entire BLV proviral DNA. The amplified BLV ARG 38 DNA was cloned, sequenced, and compared phylogenetically to three other full-length BLV sequences. Characterization of its deduced proteins and its relationship to other members of the PTLV/BLV genus of retroviruses are discussed.

Coamplification of 3-hydroxy-3-methylglutaryl coenzyme A reductase genes in methotrexate-resistant human leukemia cell lines.

Methotrexate (MTX)-resistant K562 human myelocytic leukemia sublines with 20- and 200-fold amplified dihydrofolate reductase (DHFR) genes localized to homogeneously staining regions (HSRs) on the long arms of chromosomes 5, 6, and 19 were used to examine whether other genes mapping close to the DHFR genes were coamplified. The gene for 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, located on chromosome 5q13.3-14, was coamplified 4-14-fold, corresponding to the levels of resistance exhibited by these cells. Similar observations were made with a MTX-resistant subline of the promyelocytic leukemia cell line, HL-60R, with 200 gene copies of DHFR. These observations indicate a tight linkage of DHFR and HMG-CoA genes on chromosome 5q.

The safe use of epidural anesthesia after subcutaneous injection of low-dose heparin in general abdominal surgery.

OBJECTIVE: To determine if epidural anesthesia after the subcutaneous injection of low-dose unfractionated heparin (LDUH) in patients who undergo elective bowel surgery is safe with respect to hemorrhagic complications. DESIGN: A prospective cohort study. SETTING: Two hospitals affiliated with the Université de Montréal. PATIENTS: Fifty patients scheduled for elective bowel surgery. INTERVENTION: Subcutaneous injection of 5000 units of LDUH and elective surgery for colonic carcinoma, chronic diverticulosis or inflammatory bowel disease. MAIN OUTCOME MEASURES: Activated partial thromboplastin time (APTT), anti-IIa and anti-Xa heparin levels measured before and 2 and 4 hours after injection of LDUH. RESULTS: In no case was the heparin anti-IIa or anti-Xa level higher than 0.20 U/mL, which is considered a significant detectable level of heparin. CONCLUSION: LDUH given subcutaneously is not associated with significant detectable heparin levels, so epidural anesthesia should be safe when performed 2 hours after LDUH injection in patients who undergo general abdominal surgery in the absence of any other impairment of hemostasis.

Comparative performances of an HTLV-I/II EIA and other serologic and PCR assays on samples from persons at risk for HTLV-II infection.

BACKGROUND: HTLV-I and HTLV-II are related exogenous pathogenic human retroviruses. Until recently, ELISAs based on HTLV-I antigens have been used to screen for the presence of HTLV-I or -II antibodies. The HTLV-I-based assays have not been as sensitive in detecting antibodies to HTLV-II as in detecting antibodies to HTLV-I. The Abbott HTLV-I/HTLV-II ELISA uses a combination of HTLV-I and HTLV-II antigens to detect antibodies to the whole HTLV group. The performance of this ELISA was compared to that of several HTLV-I-based serologic assays and an HTLV-II PCR assay in cohorts of South American Indians and New York City IV drug users (IVDUs) in whom HTLV-II is endemic. STUDY DESIGN AND METHODS: Sera from 429 South American Indians and New York City IVDUs were evaluated for HTLV antibodies by the use of three ELISAs (rgp21-enhanced HTLV-I/II, Cambridge Biotech; Vironostika HTLV-I/II, Organon Teknika; and HTLV-I/HTLV-II, Abbott), and a Western blot (WB) assay. Peripheral blood leukocyte DNA from each person was analyzed for HTLV-I and HTLV-II pol DNA via PCR. The HTLV-II PCR-positive samples were further subtyped via cloning and sequencing and/or oligomer restriction. RESULTS: Two hundred four samples (48%) were positive for HTLV-II by serologic and/or PCR assays. All of the positive samples from the Indians and approximately one-third of the positive samples from the IVDUs were of the HTLV-IIB subtype. Comparative analyses indicate that the sensitivity and specificity of the various assays were: PCR, 98 and 100 percent; Abbott HTLV-I/HTLV-II, 78 and 95 percent; Cambridge Biotech HTLV-I/II, 76 and 96 percent; Vironostika HTLV-I/II, 71 and 98 percent; and WB, 73 and 100 percent, respectively. CONCLUSION: There were no significant differences among the sensitivities and specificities of the HTLV-I/II ELISAs (p values, 0.056-0.438). The WB and PCR assays were much more specific than the other serologic assays (p