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Both aberrant vascular reactivity to acute cardiovascular stress and epigenetic mechanisms such as microRNA (miR) may underlie the increased propensity for African Americans (AA) to develop cardiovascular disease. This study assessed racial differences in acute induced endothelial inflammation and related miRs. Cultured human umbilical vein endothelial cells (HUVECs) derived from AA and Caucasian Americans (CA) were exposed to influenza vaccine to determine changes in inflammatory markers, endothelial nitric oxide synthase (eNOS), and miR expression/release. Endothelial function [flow-mediated dilation (FMD)], circulating IL-6, and circulating miR were also measured in young, healthy AA and CA individuals before and after receiving the influenza vaccine. There were no significant racial differences in any parameters at baseline. The vaccine induced increases in IL-6 release (24%

Madsen et al . question the reliability of calibrated radiocarbon ages associated with human footprints discovered recently in White Sands National Park, New Mexico, USA. On the basis of the geologic, hydrologic, stratigraphic, and chronologic evidence, we maintain that the ages are robust and conclude that the footprints date to between ~23,000 and 21,000 years ago. Madsen et al . ( 1 ) question the veracity of calibrated radiocarbon ages used to constrain the antiquity of human trackways discovered recently at White Sands National Park (WHSA) Locality 2, New Mexico, USA ( 2 ). The ages were derived from seeds of the aquatic plant Ruppia cirrhosa , which they suggest may suffer from hard-water (or reservoir) effects, making them too old, potentially by thousands of years. We were well aware of this possibility, investigated it, and presented several lines of evidence that argued against such a problem. Here we respond to each of their four primary points.

Pre-participation physical evaluation and its vision screenings have been the mainstay of medical clearance for competitive play for decades. The ability of screening to address athlete's sports-specific vision needs is unknown.Fifty-eight intercollegiate football players consented to participate in a comprehensive, sports-specific eye examination in addition to the standard pre-participation vision screening. Sensitivity, specificity, and positive and negative predictive values were determined for screening's ability to detect athletes whose vision might improve with correction, athletes who had significant ocular findings that impact safety, and either of the two conditions together. The effect no recent eye examination added to pre-participation vision screening results was evaluated for change in screening yield. Descriptive statistics of the cohort and associations with no recent comprehensive eye examination were generated.The pre-participation vision screening was able to identify three athletes not meeting visual acuity requirements for medical clearance to play without a comprehensive assessment. A failed screening was poorly able to identify athletes who might benefit from improved acuity (sensitivity, 9.1%; specificity, 100%), have sports-specific significant ocular findings (sensitivity, 10.5%; specificity, 97.3%), or have either together (sensitivity, 7.5%; specificity, 100%). Sixty percent (33/55) of athletes reported never having a comprehensive examination or one within the last 10 years. Fifty-eight percent (34/58) had improved best-corrected visual acuity after comprehensive examination, and 81% (47/58) had improved acuity or a sports-specific significant finding.The pre-participation vision screening was largely able to identify athletes meeting the minimum visual acuity requirement for athlete clearance. It poorly identified those who might benefit from improved vision with refractive correction and those in whom sport-specific significant eye findings were noted. Comprehensive eye care had a clear benefit for the majority of athletes tested. This benefit needs to be balanced with the potential added costs and time constraints to players and athletic department staff.

Repeated exposure to a high-fat meal triggers inflammation and oxidative stress, contributing to the onset of cardiometabolic diseases. Regular exercise prevents cardiometabolic diseases and a prior bout of acute endurance exercise can counteract the detrimental cardiovascular effects of a subsequent high-fat meal. Circulating microRNAs (ci-miRs) are potential mediators of these vascular effects through regulation of gene expression at the posttranscriptional level. Therefore, we investigated the expression of ci-miRs related to vascular function (miR-21, miR-92a, miR-126, miR-146a, miR-150, miR-155, miR-181b, miR-221, miR-222) in plasma from healthy, recreationally to highly active, Caucasian adult men after a high-fat meal with (EX) and without (CON) a preceding bout of cycling exercise. Ci-miR-155 was the only ci-miR for which there was a significant interaction effect of high-fat meal and exercise (p=0.050). Ci-miR-155 significantly increased in the CON group at two (p=0.007) and four hours (p=0.010) after the high-fat meal test, whereas it significantly increased in the EX group only four hours after the meal (p=0.0004). There were significant main effects of the high-fat meal on ci-miR-21 (p=0.01), ci-miR-126 (p=0.02), ci-miR-146a (p=0.02), ci-miR-181b (p=0.02), and ci-miR-221 (p=0.008). Collectively, our results suggest that prior exercise does not prevent high-fat meal-induced increases in vascular-related ci-miRs.

An outbreak of norovirus GGII.4 2006b affected an Austrian 600-bed healthcare facility from 15 to 27 March 2009. A total of 204 patients, residents and staff fitted the outbreak case definition; 17 (8.3%) were laboratory-confirmed. Foodborne origin was suspected in the 114 patient and resident cases with onset 15-18 March. A case-cohort study was performed to test the hypothesis that consumption of dishes offered on 14, 15 and 16 March (risk days) was associated with increased risk of infection. Data on food exposure of 62% (317/510) of the patient and resident cohort were available for a simultaneous retrospective cohort study. The case-cohort analysis revealed that consumption of sliced cold sausage offered on 15 March [odds ratio (OR): 3.98; 95% confidence interval (CI): 1.18-14.1], a meat dish with salad (adjusted OR: 2.2; 95% CI: 1.19-4.08) and a rolled spinach pancake (adjusted OR: 2.17; 95% CI: 1.27-3.71) on 16 March were independent risk factors. It is likely that one of the five asymptomatic excretors among the kitchen staff on duty on the risk days was the source of food contamination. The case-cohort study design was found to be a valid alternative to the retrospective cohort study design for the investigation of a suspected foodborne outbreak in a large cohort.

The purpose of this study was to explore the rationale provided by program directors and general managers of health/fitness facilities for low adherence to nationally accepted standards related to pre-activity cardiovascular screening procedures (PACSPs) for members and clients of personal trainers. Qualitative interviews were conducted with the directors/managers in a Midwest region representing 76 facilities who indicated they did not conduct PACSPs for members and clients of personal trainers. Analysis of the rationale provided revealed 6 major clusters: (1) Purpose or need for screening; (2) time and staffing; (3) barrier to participation; (4) personal responsibility for health and actions; (5) legal issues; and (6) company or franchise policy that categorized the reasons for low adherence to PACSPs. These findings highlight the need to increase awareness of the relevance of PACSPs among health/fitness managers, staff members, and current exercise science students as well as engage those in risk management for informed dialogue for consistent application of the standard of care.

This investigation determined the number of health/fitness facilities within a Midwestern region conducting pre-activity cardiovascular screening procedures (PACSPs) consistent with American Heart Association/American College of Sports Medicine (AHA/ACSM) standards. Interviews were conducted with 123 commercial, community, corporate, and academic settings (84% response rate), with 40 (33%) facilities requiring members to complete a pre-activity screening device. Of those, 20 (50%) required physician clearance for "at-risk" members prior to physical activity participation. Personal training clients completed a pre-activity screening device at 50 (61%) facilities, with 32 (64%) requiring physician clearance for at-risk clients. The data were analyzed by setting, with corporate facilities having a significantly higher (P=.0049) adherence rate with AHA/ACSM standards than other facilities. Data were compared with previous studies and indicated a decrease in the number of facilities conducting PACSPs. Findings indicate that health/fitness personnel need to become aware of the relevance of conducting PACSPs.

Background Despite increased attention, conventional views of obesity are based upon individual behaviors, and children and parents living with obesity are assumed to be the primary problem solvers. Instead of focusing exclusively on individual reduction behaviors for childhood obesity, greater focus should be placed on better understanding existing community systems and their effects on obesity. The Milwaukee Childhood Obesity Prevention Project is a community-based coalition established to develop policy and environmental change strategies to impact childhood obesity in Milwaukee, Wisconsin. The coalition conducted a Group Model Building exercise to better understand root causes of childhood obesity in its community. Methods Group Model Building is a process by which a group systematically engages in model construction to better understand the systems that are in place. It helps participants make their mental models explicit through a careful and consistent process to test assumptions. This process has 3 main components: (1) assembling a team of participants; (2) conducting a behavior-over-time graphs exercise; and (3) drawing the causal loop diagram exercise. Results The behavior-over-time graph portion produced 61 graphs in 10 categories. The causal loop diagram yielded 5 major themes and 7 subthemes. Conclusions Factors that influence childhood obesity are varied, and it is important to recognize that no single solution exists. The perspectives from this exercise provided a means to create a process for dialogue and commitment by stakeholders and partnerships to build capacity for change within the community.

A number of investigators have observed that the use of 4-hydroperoxycyclophosphamide (4-HC) in multiwell plate cytotoxicity assays can be associated with toxicity to cells in wells that contain no drug. Previous reports have implicated diffusion of 4-HC decomposition products, and acrolein in particular, as the active species. Purpose: The purpose of this study was to elucidate the species responsible for the airborne cytotoxicity of 4-HC, and to devise ways to minimize such effects in chemosensitivity assays. Methods: To this end, analogues of 4-HC were synthesized to identify the contributions of individual cyclophosphamide metabolites to cytotoxicity. The analogues were then tested for activity against three human breast tumor cell lines (including a line resistant to 4-HC), and one non-small-cell lung carcinoma line. Cytotoxicity was evaluated by assays that quantitate cellular metabolism and nucleic acid content. Results: Didechloro-4-hydroperoxycyclophosphamide, a compound that generates acrolein and a nontoxic analogue of phosphoramide mustard, gave no cross-well toxicity. In contrast, a significant neighboring well effect was observed with phenylketophosphamide, a compound that generates phosphoramide mustard but not acrolein. Addition of authentic chloroethylaziridine reproduced the airborne toxicity patterns generated by 4-HC and phenylketophosphamide. Increasing the buffering capacity of the growth medium and sealing the microtiter plates prevented airborne cytotoxicity. Conclusions: Since it is unlikely that phosphoramide mustard is volatile, these findings implicate chloroethylaziridine rather than acrolein as the volatile metabolite of 4-HC that is responsible for airborne cytotoxicity. The fact that chloroethylaziridine is generated in amounts sufficient to volatilize, diffuse across wells and cause cytotoxicity indicates that it is an important component in the overall cytotoxicity of 4-HC in vitro. Furthermore, these findings suggest that chloroethylaziridine may also contribute to the toxicity of cyclophosphamide in vivo.

Previous investigations demonstrated three taxonomic groups among 22 clinical isolates of Mycobacterium smegmatis. These studies were expanded to 71 clinical isolates, of which 35 (49%) (group 1) were identical to five ATCC reference strains including the type strain ATCC 19420T. Twenty-eight isolates (39%) were group 2, and eight isolates (11%) were group 3. Isolates of groups 2 and 3 were most often associated with post-traumatic or post-surgical wound infections including osteomyelitis, were susceptible to sulfamethoxazole, amikacin, imipenem and the tetracyclines, variably resistan to clarithromycin, and susceptible (group 1), intermediately resistant (group 2) or resistant (group 3) to tobramycin. The three groups were similar by routine biochemical and growth characteristics, but had different mycolic acid dimethoxy-4-coumarinylmethyl ester elution patterns by HPLC and different PCR-restriction enzyme patterns of a 439 bp fragment of the hsp-65 gene. Group 3 isolates differed from group 1 by 18 bp by 16S rRNA sequencing and exhibited < 25% homology by DNA-DNA hybridization, being most closely related to Mycobacterium mageritense. The 16S rRNA of group 1 and group 2 isolates differed by only 3 bp, but by DNA-DNA hybridization they exhibited only 40% homology. The following names are proposed: Mycobacterium goodii sp. nov. for group 2 isolates (type strain ATCC 700504T = M069T), Mycobacterium wolinskyi sp. nov. for group 3 isolates (type strain ATCC 700010T = M0739T) and Mycobacterium smegmatis sensu stricto for group 1 isolates.

Because hematopoietic stem cells are rich in aldehyde dehydrogenase (ALDH) activity, we developed a fluorescent substrate for ALDH, termed BODIPY aminoacetaldehyde (BAAA), and tested its potential for isolating primitive human hematopoietic cells. A population of cells with low orthogonal light scattering and bright fluorescence intensity (SSCloALDHbrcells) could be readily fractionated from human umbilical cord blood cells costained with BAAA and the multidrug-resistance inhibitor verapamil. The SSCloALDHbrpopulation was depleted of lineage-committed cells, 40–90% pure for CD34+CD38lo/−cells, and enriched 50- to 100-fold for primitive hematopoietic progenitors detected in short- and long-term culture analyses. Together, these observations indicate that fractionating human hematopoietic stem cells on the basis of ALDH activity using BAAA is an effective method for isolating primitive human hematopoietic progenitors. This technique may be useful for isolating stem cells from other tissues as well.

A scotochromogenic acid-fast bacillus was isolated from a lymph node of a 2-year-old female. On the basis of conventional testing, the mycobacterium appeared to be Mycobacterium scrofulaceum. Its mycolic acid profile, however, was not identical to that of Mycobacterium scrofulaceum but was similar to that of Mycobacterium interjectum. Direct sequencing of the 16S rRNA gene revealed a unique nucleic acid sequence, suggesting that the isolate represents a previously undescribed pathogenic species.

Purpose.Drawing from self-determination theory, this study investigated adults' perceptions of the process of long-term maintenance of physical activity and how it may relate to their self-identity.Design.Qualitative study included 22 in-depth interviews and participants' recorded personal reflective journals.Setting.Health/fitness facility in a Midwestern city.Participants.Purposeful sample of 12 adult (age range 29–73 years) members who had engaged in regular physical activity for at least 3 years.Methods.Data were collected on participants' perceptions of processes associated with physical activity maintenance. Grounded theory data analysis techniques were used to develop an understanding of participants' long-term physical activity adherence.Results.Analysis revealed three themes organized around basic psychological need satisfaction: (1) Relatedness included receiving and giving support. (2) Competence included challenge and competition, managing weight, and strategies for health management. (3) Autonomy included confidence in the established routine, valuing fitness status, and feeling self-directed. The final theme of physically active self included the personal fit of an active lifestyle, identity as an active person, and attachment to physical activity as life enhancing.Conclusion.Our results suggest that long-term physical activity adherence may be strengthened by promotion of the individual's basic psychological need satisfaction. Adherence is most likely to occur when the value of participation becomes internalized over time as a component of the physically active self.

A distinct group of slowly growing mycobacteria was identified on the basis of growth characteristics, biochemical and lipid profiles, and nucleic acid analyses. The isolates showed growth at 22 to 37 degrees C, yellow pigmentation, and negative tests for Tween 80 hydrolysis, nicotinic acid, nitrate reductase, and urease; tests for arylsulfatase, pyrazinamidase, and heat-stable catalase were variable. Analysis of cellular fatty acids by gas-liquid chromatography and mycolic acids by thin-layer chromatography and high-performance liquid chromatography indicated a distinctive pattern which was unlike those of other species. Determination of the 16S rRNA gene sequence showed a unique sequence closely related to Mycobacterium simiae and M. genavense. On the basis of DNA homology studies, we suggest that these organisms are representatives of a novel species, for which the name M. lentiflavum sp. nov. is proposed.

It is well-established that at pH 7.4, intramolecular 1,3-N-alkylation reactions in isophosphoramide mustard (IPM) and phosphoramide mustard (PM) produce electrophilic alkylating agents with aziridinyl moieties. To investigate the role of 1,5-intramolecular cyclizations in the chemistry of IPM and PM, the five-membered ring phospholidine products of these reactions were independently synthesized and characterized by (31)P NMR. In 0.33 M BisTris, pH 7.4, 37 degrees C, the intramolecular O-alkylation product of IPM [2-(2-chloroethylamino)-2-tetrahydro-2H-1,3,2-oxazaphospholidine-2-oxide (11)] had a chemical shift of delta 33.0 and a half-life of 3.3 h. The O-alkylation product of PM [2-amino-3-(2-chloroethyl)tetrahydro-2H-1,3,2-oxazaphospholidine-2-oxide (12)] displayed a chemical shift of delta 30.6 and a half-life of 26.9 h. For both IPM and PM, 1,5-N-alkylation provides the same product [1-(2-chloroethyl)-2-hydroxy-tetrahydro-2H-1,3,2-diazaphospholidine-2-oxide (13)]. Because of its instability, 13 was generated in situ and was not isolated; however, the chemical shift (delta 33.0) and reactivity (half-life 0.3 h at 25 degrees C) of the species attributed to 13 were consistent with the assigned structure. Resonances with (31)P NMR chemical shifts indicative of 11 or 12 did not appear in reaction solutions of IPM or PM. The compound assigned as 13 gave hydrolysis products that were not found in reaction solutions of IPM or PM. The collective data supported the conclusion that intramolecular 1,5-alkylations do not contribute to the chemistry of IPM or PM in aqueous solutions at pH 7.4, 37 degrees C. Conversely, 11 and 12 were found to be the major if not exclusive products formed in DMSO solutions of the respective cyclohexylammonium salts of IPM and PM. Both 11 and 12 were relatively noncytotoxic against a series of cell lines, but there were differences in mutagenicities. Chinese hamster ovary cells were exposed to 11 or 12 for one half-life of each compound; 11 was nonmutagenic up to 500 microM, while 12 (500 microM) was mutagenic with 246 mutant colonies/10(6) surviving cells.

This article reports the results of research that examined a randomized group of 118 Jewish seniors who were clients of one of three Jewish social service agencies in New York City. They were interviewed by four Clinical Pastoral Education residents at the Jewish Institute for Pastoral Care. During the interview, participants were asked to respond to the questions contained in the Brief Depression Scale, Version 3 of the UCLA Loneliness Scale, and the Index of Core Spiritual Experience—INSPIRIT. A statistically significant positive correlation was found between the depression and loneliness scores, r(116) = .56, p< .001. Spirituality was not correlated with either of these scales. Both depression and loneliness were significantly higher among women, among people who had physical impairments and those who had been victims of Nazi persecution. Depression and loneliness were inversely related to participants' ability to venture out of their house and to their relationship with their families. Having a sense of meaning or purpose in life was also inversely related to depression and loneliness. Spirituality tended to be higher among women, those participants with more years of religious education, and those with physicals impairments, but only the gender effect was statistically significant.

Differentiation agents that induce neoplastic cells to regain a normal phenotype and/or cause growth arrest without significantly affecting normal cells represent an attractive option for cancer treatment. Analogues of short chain fatty acids, such as phenylbutyrate (PB), have been studied as clinically relevant agents. In an attempt to improve its pharmacokinetic profile, structural modifications of PB and other fatty acids have been studied. We hypothesize that strategic isotopic modification of PB would result in a longer half-life and thus translate into a more potent differentiation agent for clinical use. Using a colon cancer model, we demonstrated that 2,2,3,3-tetradeuterated PB (D4PB) significantly increased induction of apoptosis and inhibition of cell proliferation as compared with PB and butyrate. Difference in potency could not be explained by the effect of D4PB on the expression of specific regulatory proteins of the apoptotic cascade or from the inhibitory effect of D4PB on histone deacetylase activity. Interestingly, exposure of HT-29 colon cancer cells to D4PB resulted in a slowing of S transit, in contrast to butyrate and PB, which induced a G2/M cell cycle block. This difference in cell cycle effect may explain the differences seen in the potency of the phenotypic changes seen with treatment with D4PB. Further studies are needed to elucidate the mechanisms underlying effects of D4PB on the cell cycle. © 2002 Wiley-Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 91:1054–1064, 2002

The reservoir and transmission route of Mycobacterium kansasii are largely unknown. In addition, culturing of M. kansasii from human sources is not proof of disease because it may represent colonization rather than infection. Unfortunately, investigation of the epidemiology and pathogenicity of M. kansasii is complicated by evidence of heterogeneity within the species. A comprehensive study by detailed genotypic analysis of a large collection of M. kansasii isolates (n = 276) from various geographical sources within Europe was conducted. Five defined subtypes of M. kansasii were identified; of these subtypes, type I represents the most common isolate from humans. Although phylogenetic analysis confirmed its relationship to the other M. kansasii types, significant sequence divergence was found at the 16S-23S intergenic spacer. Analysis of the chromosomal polymorphism of type I demonstrated a marked clonal structure for this particular organism. Because M. kansasii is becoming a significant pathogen among immunodeficient hosts, future epidemiological and pathogenicity studies should take into consideration both the heterogeneity within the species and the apparent clonality of the most prevalent M. kansasii isolates infecting humans.

Previous studies have indicated that the conventional tests used for the identification of mycobacteria may (i) frequently result in erroneous identification and (ii) underestimate the diversity within the genus Mycobacterium. To address this issue in a more systematic fashion, a study comparing phenotypic and molecular methods for the identification of mycobacteria was initiated. Focus was given to isolates which were difficult to identify to species level and which yielded inconclusive results by conventional tests performed under day-to-day routine laboratory conditions. Traditional methods included growth rate, colonial morphology, pigmentation, biochemical profiles, and gas-liquid chromatography of short-chain fatty acids. Molecular identification was done by PCR-mediated partial sequence analysis of the gene encoding the 16S rRNA. A total of 34 isolates was included in this study; 13 of the isolates corresponded to established species, and 21 isolates corresponded to previously uncharacterized taxa. For five isolates, phenotypic and molecular analyses gave identical results. For five isolates, minor discrepancies were present; four isolates remained unidentified after biochemical testing. For 20 isolates, major discrepancies between traditional and molecular typing methods were observed. Retrospective analysis of the data revealed that the discrepant results were without exception due to erroneous biochemical test results or interpretations. In particular, phenotypic identification schemes were compromised with regard to the recognition of previously undescribed taxa. We conclude that molecular typing by 16S rRNA sequence determination is not only more rapid (12 to 36 h versus 4 to 8 weeks) but also more accurate than traditional typing.

We have investigated the use of DNA amplification by PCR for the detection of mycobacteria in clinical specimens, with the gene encoding the 16S rRNA as a target. Following generic amplification of mycobacterial nucleic acids, screening was done with genus-specific probe; this was followed by species differentiation by use of highly discriminating probes or nucleic acid sequencing. In a prospective 18-month evaluation, criteria to select specimens for PCR analysis were defined. Of a total of 8,272 specimens received, 729 samples satisfied the criteria and were subjected to DNA amplification. Clinical specimens included material from the respiratory tract (sputa and bronchial washings), aspirates, biopsies, and various body fluids (cerebrospinal, pleural, peritoneal, and gastric fluids). After resolution of discrepant results, the sensitivity of the PCR assay was 84.5%, the specificity was 99.5%, the positive predictive value was 97.6%, and the negative predictive value was 96.4%. The sensitivity and negative predictive value of culture (with a combination of broth and solid media) were 77.5 and 94.8%, respectively. In conclusion, this PCR assay provides an efficient strategy to detect and identify multiple mycobacterial species and performs well in comparison with culture.

A new type of slowly growing, nonphotochromogenic mycobacterium was recovered from two patients with disseminated disease. The growth characteristics, acid fastness, acids were consistent with those for Mycobacterium species. The results of biochemical investigations, lipid analyses, and comparative 16S rRNA sequencing showed that these isolates represent a new slowly growing Mycobacterium species which is named Mycobacterium conspicuum.

The Mycobacterium chelonae-like organism (MCLO) is a recently described member of the Mycobacterium fortuitum complex which causes posttraumatic skin infections and catheter sepsis. This taxon is a distinct group biochemically and has a unique mycolic acid profile as determined by high-performance liquid chromatography. Its phylogenetic relationships to other mycobacteria, however, have not been studied previously. We sequenced 1,062 bp of the 16S rRNA genes from three MCLO strains obtained from the American Type Culture Collection and compared our results with the sequences of previously described taxa of rapidly growing and slowly growing mycobacteria. Two biochemically typical strains (ATCC 49650T [T = type strain] and ATCC 49651) had identical sequences, while the sequence of a biochemically atypical strain (ATCC 49649) differed by 4 bp from the sequence of the two typical strains. The Hamming distances between these MCLO strains and related rapidly growing mycobacteria are comparable to the Hamming distances among taxa of rapidly growing mycobacteria established as species by DNA-DNA hybridization. We propose the name Mycobacterium mucogenicum sp. nov. for this new taxon because of the highly mucoid nature of most isolates on solid media.

Clarithromycin is a potent macrolide that has been used for treating infections with nontuberculous mycobacteria. Pairs of susceptible and resistant Mycobacterium intracellulare strains were obtained from patients with chronic pulmonary M. intracellulare infections undergoing monotherapy with clarithromycin. Nucleotide sequence comparisons of the peptidyltransferase region in 23S rRNAs from parental and resistant strains revealed that in three of six resistant strains, for which the MIC was > 32 micrograms/ml, a single base was mutated (Escherichia coli equivalent, A-2058-->G, C, or U). As the modification of adenine 2058 by dimethylation is a frequent cause of macrolide resistance in a variety of different bacteria, we suggest that mutation of A-2058 confers acquired resistance to clarithromycin in M. intracellulare.

Advanced tumors of the head and neck are often treated with combined radiochemotherapy. The chemotherapeutic agents used should be active in this tumor type and its adverse effects should not overlap with those of the radiation treatment.Published studies were reviewed and discussed on the basis of these principles.Initially, single agents such as 5-fluorouracil (5-FU) and methotrexate were used in combination with radiotherapy. These combinations caused an improved local tumor control but also an increased mucosal reaction. For mitomycin C it has been shown in a randomized trial that local tumor control was improved without concomitant increased normal tissue toxicity. Also cisplatin and carboplatin were studied in combination with radiotherapy. Unfortunately, there are no results of randomized studies available but these agents do not seem to increase mucosal toxicity. The standard chemotherapy of squamous cell carcinomas of the head and neck is cisplatin and 5-FU. Many studies have been conducted with this chemotherapy in combination with radiotherapy. To this day it has not been shown that the results of an effective radiation treatment or an effective chemotherapy can be improved by these experiments. The explanation for that is that either the chemotherapy or the radiotherapy cannot be given at full dose because the regimen would become too toxic.5-FU containing polychemotherapy regimens should not be combined with radiation any more because it is known that 5-FU increases the mucosal reaction. Agents that could be studied in the future either alone or in combination with cisplatin or carboplatin are etoposide and taxol.

Mycobacterium-like organisms, isolates 2081/92 and 4185/92, were recovered from a lymph node of a child with chronic lymphadenitis. The growth characteristics, acid-fastness, and mycolic acids of the isolate were consistent with those for Mycobacterium species. The isolates were biochemically distinct from described Mycobacterium species, although they most closely resembled M. scrofulaceum. Comparative 16S rDNA sequencing showed that these isolates represent a new slow-growing Mycobacterium species which is named M. interjectum. Our results demonstrate the importance of 16S rDNA sequencing for recognizing the diversity of species within the genus Mycobacterium.

Clinical isolates of Mycobacterium spp. were identified by direct sequence determination of 16S rRNA gene fragments amplified by polymerase chain reaction. Identification was based on a hypervariable region within the 16S rRNA gene in which mycobacterial species are characterized by species-specific nucleotide sequences. A manually aligned data base including the signature sequences of 52 species of mycobacteria easily allowed rapid and correct identification. The results of this study demonstrate that polymerase chain reaction-mediated direct sequence determination can be used as a rapid and reliable method for the identification of mycobacteria in the clinical laboratory. In addition, the prompt recognition of previously undescribed species is now feasible.

The data on a twenty-three year old woman who had an atrial septal defect and a myocardial infarction are presented. Factors predisposing to early coronary artery disease were not evident. Catheterization revealed a large atrial septal defect with a pulmonic flow two and a half times the systemic flow. Cineangiography revealed an occlusion of the anterior descending branch of the left coronary artery, the remaining left and the right coronary arteries being normal.

Teletherapy sources such as cobalt 60 and cesium 137 have been used for localizing studies in conjunction with radiation therapy for some time. In fact, one of the few references in the literature (1) points out that, under certain circumstances, radiography with these high-energy sources can provide diagnostic information beyond that provided by routine radiography. In view of the obvious advantages to using the teletherapy source for radiographic localization, it is surprising that so little has appeared concerning the procedure in the literature. This may well be due to the equally obvious limitation imposed on a radiographic system in which the energy of the radiation results in practically 100 per cent Compton interaction with the subject. Since Compton interactions are essentially independent of atomic number, the resulting differentials in absorption for the various structures in the human body are not very large and contrast, therefore, is at a minimum. In high-energy radiography, the proper filmi...

Antibodies to histones of the IgG-class are specific for SLE and can be shown in 23% of the sera. They are not associated with clinical symptoms of SLE, but with dsDNA-antibodies.

This article describes in detail a variety of home equity conversion plans and discusses their relevance for social security beneficiaries, as well as for the aged in general. Under these plans, a dormant asset--accumulated home equity--is converted into current retirement income. The plans vary: Some are debt instruments; others involve the sale and leaseback of the residence. Some provide income for a fixed term; others offer a lifetime annuity. Some include a public subsidy; others are free of governmental involvement. The advantages and disadvantages of these plans, as well as examples of how they operate and their respective income potential, are discussed in this article. The relevance of home equity conversion plans for social security beneficiaries is illustrated by means of data from the Retirement History Study. These data allow comparison of various demographic groups in terms of their dependence on social security benefits. Each group is examined in terms of available home equity and home equity potential under several conversion plans.

This article, which is based on data from the Social Security Administration's 1978 Survey of Survivor Families With Children, examines the continuity of health care coverage held by families headed by widows from the time of the husband's death to the interview. The data are presented by duration of widowhood and kind of coverage the family had before the husband died. Over this period, it was found that new kinds of coverage, such as the widow's job-related health insurance or directly purchased protection, often replaced the former coverage. At the time of the interview, about three-fourths of the families had coverage, including government assistance such as Medicaid. Whether or not the young survivor families had coverage was affected by the widow's current employment status and by family income. Premiums varied by type of policy: those with individual policies paid more (and received less extensive coverage) than did those with group policies. Compared with the general population, the widows and their children were in poorer health, generally used physician services less, and had somewhat higher expenditures for health care.

The Mycobacterium tuberculosis ahpC gene, encoding the mycobacterial orthologue of alkylhydroperoxide reductase, undergoes an unusual regulatory cycle. The levels of AhpC alternate between stages of expression silencing in virulent strains grown as aerated cultures, secondary to a natural loss of the regulatory oxyR function in all strains of the tubercle bacillus, and expression activation in static bacilli by a yet undefined mechanism. The reasons for this unorthodox regulatory cycle controlling expression of an antioxidant factor are currently not known. In this work, M. tuberculosis H37Rv and Mycobacterium smegmatis mc(2)155 ahpC knockout mutants were tested for sensitivity to reactive nitrogen intermediates, in particular peroxynitrite, a highly reactive combinatorial product of reactive nitrogen and oxygen species, and sensitivity to bactericidal mechanisms in resting and activated macrophages. Both M. tuberculosis ahpC::Km(r) and M. smegmatis ahpC::Km(r) showed increased susceptibility to peroxynitrite. In contrast, inactivation of ahpC in M. tuberculosis did not cause increased sensitivity to donors of NO alone. M. tuberculosis ahpC::Km(r) also showed decreased survival in unstimulated macrophages, but the effect was no longer detectable upon IFNgamma activation. These studies establish a specific role for ahpC in antioxidant defences involving peroxynitrite and most likely additional cidal mechanisms in macrophages, with the regulatory cycle likely contributing to survival upon coming out of the stationary phase during dormancy (latent infection) or upon transmission to a new host.