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PubMed2005

Pulmonary mucoepidermoid carcinoma with prominent tumor-associated lymphoid proliferation.

We report 6 cases of low-grade pulmonary mucoepidermoid carcinoma displaying a striking lymphoplasmacytic infiltrate. All six tumors had a typical pulmonary mucoepidermoid carcinoma presentation as a polypoid endobronchial mass involving the proximal bronchi. The patients were 3 females and 3 males with a mean age of 33 years (range, 5-61 years). Half of the patients were asymptomatic, while half experienced mild symptoms of pneumonia, asthma-like symptoms, or hemoptysis. No tumor-related deaths were observed, with a mean follow-up of 51 months. The tumor size ranged from 2.1 to 3.4 cm (mean, 2.9 cm). The tumors characteristically displayed an elaborate tubulocystic epithelial component composed of intermediate, epidermoid, and mucus-producing cells, and variable numbers of clear cells, multinucleated giant cells, columnar cells, and oncocytic cells. The tumors' lymphoplasmacytic infiltrate with occasional Russell bodies was sufficiently intense to raise concern of a low-grade lymphoma. All tested tumors were immunoreactive with CK7 while nonreactive with TTF-1 and CK20. Recognition of this histologic variant is important for a correct diagnosis of low-grade pulmonary mucoepidermoid carcinoma. The dense lymphoplasmacytic infiltrate is similar to that previously described in salivary glands as tumor-associated lymphoid proliferation.

Adult↗
PubMed1999

Mycobacterium wolinskyi sp. nov. and Mycobacterium goodii sp. nov., two new rapidly growing species related to Mycobacterium smegmatis and associated with human wound infections: a cooperative study from the International Working Group on Mycobacterial Taxonomy.

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 resistant 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 = MO69T), Mycobacterium wolinskyi sp. nov. for group 3 isolates (type strain ATCC 700010T = MO739T) and Mycobacterium smegmatis sensu stricto for group 1 isolates.

Adolescent↗
PubMed1996

"Phase examination" an assessment of consultation skills and integrative knowledge based in general practice.

The undergraduate medical curriculum at Linköping was changed and problem-based learning introduced in 1986. As a consequence the need for new examinations arose. To assess the students' consultation skills, ability to use theory in practice and skills in problem-based learning, a new examination called 'phase examination' was designed and introduced. The examination results of a 4-year student cohort are presented here, including descriptive statistics and correlations between phase examinations 1 and 2, as well as a semester examination consisting of modified essay questions and an objective structured clinical examination. The construct validity of the phase examination was tested by factor analysis. In general, low correlation between the three examinations were found, and interpreted as a result of inter-case and inter-rater variability. The factor analysis identified two factors in both phase examinations--one representing the solving of a learning task, the other consultation skills. The variables concerning the use of knowledge had an intermediate position, more connected to the solving factor in phase 1 and the consultation factor in phase 2. With the close connection of theory and practice in the phase examination, both by its design and the pairing of examiners (one general practitioner and one basic scientist), these examinations can be an important learning experience for both students and teachers. The deficiencies in the reliability of the phase examinations is, in our view, compensated by its directing and supporting effect on students' learning and its face and construct validity.

Clinical Competence↗
PubMed1994

Increased walking variability in elderly persons with congestive heart failure.

OBJECTIVES: To determine the effects of congestive heart failure on a person's ability to walk at a steady pace while ambulating at a self-determined rate. SETTING: Beth Israel Hospital, Boston, a primary and tertiary teaching hospital, and a social activity center for elderly adults living in the community. PARTICIPANTS: Eleven elderly subjects (aged 70-93 years) with well compensated congestive heart failure (NY Heart Association class I or II), seven elderly subjects (aged 70-79 years) without congestive heart failure, and 10 healthy young adult subjects (aged 20-30 years). MEASUREMENTS: Subjects walked for 8 minutes on level ground at their own selected walking rate. Footswitches were used to measure the time between steps. Step rate (steps/minute) and step rate variability were calculated for the entire walking period, for 30 seconds during the first minute of the walk, for 30 seconds during the last minute of the walk, and for the 30-second period when each subject's step rate variability was minimal. Group means and 5% and 95% confidence intervals were computed. MAIN RESULTS: All measures of walking variability were significantly increased in the elderly subjects with congestive heart failure, intermediate in the elderly controls, and lowest in the young subjects. There was no overlap between the three groups using the minimal 30-second variability (elderly CHF vs elderly controls: P < 0.001, elderly controls vs young: P < 0.001), and no overlap between elderly subjects with and without congestive heart failure when using the overall variability. For all four measures, there was no overlap in any of the confidence intervals, and all group means were significantly different (P < 0.05).

Adult↗
PubMed1999

Prognostic value of dipyridamole thallium imaging after acute myocardial infarction in older patients.

OBJECTIVE: To assess the utility of intravenous dipyridamole thallium testing for predicting major cardiac events following acute myocardial infarction in older patients. DESIGN: Prospective cohort study with a median follow-up of 18 months. SETTING: A university teaching hospital. PARTICIPANTS: 73 patients aged 65 years and older with enzymatically confirmed acute myocardial infarction (mean age 75 years, 56% male, 71% white). MEASUREMENTS: All patients underwent a detailed clinical assessment, an echocardiogram, and an intravenous dipyridamole thallium stress test before hospital discharge. The study endpoint was death or nonfatal reinfarction during the follow-up period. RESULTS: Overall, 24 patients (33%) died or developed recurrent myocardial infarction during follow-up. Among 44 patients with a reversible thallium defect, 19 (43%) reached the study endpoint, compared with only five of 29 patients (17%) without reversible ischemia (P = .04). On multivariate analysis, independent prognostic variables included non-use of aspirin at hospital discharge (P = .002), decreased left ventricular systolic function (P = .009), non-use of a beta-blocker at hospital discharge (P = .013), and reversible ischemia on thallium scintigraphy (P = .025). The relative risks for death or reinfarction associated with non-use of aspirin, non-use of a beta-blocker, left ventricular dysfunction, and reversible ischemia were 2.65, 2.39, 2.01, and 2.51, respectively. Patients with three or four of these risk factors had an 83% probability of death or reinfarction, compared with 41% in patients with two risk factors and 6% in patients with one or no risk factor (P < .001). CONCLUSION: Intravenous dipyridamole thallium imaging provides independent prognostic information in older patients with acute myocardial infarction. Moreover, the combination of clinical, echocardiographic, and dipyridamole thallium variables effectively stratifies older postinfarction patients into high-, intermediate-, and low-risk categories for death or recurrent myocardial infarction.

Aged↗
PubMed2002

Evidence for fractal correlation properties in variations of peripheral arterial tone during REM sleep.

Previous studies utilizing detrended fluctuation analysis (DFA) of heart rate variability during sleep revealed a higher fractal exponent during rapid eye movement (REM) sleep than non-REM sleep. The aim of this study was to determine whether the same difference exists in the variations of peripheral arterial tone (PAT). Finger pulse wave measured by a novel plethysmographic technique was monitored during sleep in 12 chronic heart failure patients, 8 heavy snorers, and 12 healthy volunteers. For each subject, at least two 15-min time series were constructed from the interpulse intervals and from pulse wave amplitudes during REM and non-REM sleep. Fractal scaling exponents of both types of time series were significantly higher for REM than non-REM sleep in all groups. In each of the groups and in both sleep stages, the fractal scaling exponents based on pulse wave amplitude were significantly higher than those based on pulse rate variability. A repeat of the analysis for short-, intermediate-, and long-term intervals revealed that the fractal-like exponents were evident only in the short- and intermediate-term intervals. Because PAT is a surrogate of sympathetic activation, our results indicate that variations in sympathetic activation during REM sleep have a fractal-like behavior.

Adult↗
PubMed1984

Evaluation of a system for serial biopsy of cerebral cortical tissue in an awake goat.

No techniques to date have been developed that allow investigators to obtain serial, rapidly frozen brain tissue samples in unanesthetized animals. The design and methods for implantation of cranial windows in goats are described in detail. The cranial window allows one direct and repeated access to the cerebral cortical surface. With each window, a parietal cortical area of 7.9 cm2 (minus the dura) is available for biopsy. Serial tissue samples are obtained using a suction-freezing system. Samples (100-250 mg) are frozen in less than 1 s. Up to six samples can be taken from each site. Goats were studied over a period of 2-5 days. No signs of sampling or immobilization stress were present as evidenced by a relatively constant level of arterial catecholamines and CO2 partial pressure (PCO2). Local cerebral blood flow (CBF) in the tissue under the window was of the same magnitude as that in other cerebral cortical regions and was unaffected by serial sampling. Levels of labile phosphates and of some glycolytic and tricarboxylic acid cycle-associated intermediates were minimally influenced by serial sampling. Greater variability in metabolite levels was seen for biopsies taken 2-5 days apart than for biopsies taken at 1- to 2-min intervals. However, variations within animals were less than variations among animals. This was especially true for acutely biopsied samples. The described methods provide a model for studies of cerebral metabolism in unstressed goats where anesthetic influences are avoided and where each animal can be utilized as its own control.

Animals↗
PubMed1984

Pituitary-thyroid hormone economy in healthy aging men: basal indices of thyroid function and thyrotropin responses to constant infusions of thyrotropin releasing hormone.

In order to assess the effects of aging, as distinct from those of thyroid disease or extrathyroidal illness, on certain indices of thyroid function, we studied 74 healthy, ambulatory men recruited from the Baltimore Longitudinal Study on Aging. We determined basal serum values of T4, T3, rT3, thyroxine-binding globulin (TBG), and T3 resin uptake (T3RU) and calculated the free T4 index (FT4I = T4 X T3RU/100), free T3 index (FT3I = T3 X T3RU/100), and T4/TBG ratio for each subject. We used an ultrasensitive RIA to measure variations in basal concentrations of TSH within the normal range. We then infused TRH at a constant rate (0.4 microgram/min iv) for 240 min into 63 of the same men; serum samples, collected at 15-min intervals during the infusion, were analyzed for TSH by routine RIA. Subjects were divided into 3 groups according to age; A (n = 26, mean age = 39.4), B (n = 23, mean age = 60.0), and C (n = 25, mean age = 79.6). Analysis of variance with Duncan's multiple range test and regression analysis were used to evaluate data. There was no significant (P greater than 0.05) variation with age of basal serum values of T4, TBG, or T3RU. Comparison of groups A and C showed significant decreases of mean values of serum T3 (-11%, P less than 0.05), FT3I (-13%, P = 0.02), FT4I (-11%, P less than 0.01), and T4/TBG ratio (-12%, P less than 0.01) and an increase in serum TSH (+38%, P less than 0.05). For these variables, the mean values for group B were intermediate between, but not significantly different from, those of A and C. Regression analysis showed significant correlations of age with T3, FT3I, FT4I, T4/TBG, and TSH at P levels similar to those obtained by Duncan's test. No elderly individual exhibited a baseline elevation of TSH (greater than 7 microU/ml) or depression of T4 (less than 5 micrograms/dl), suggesting that primary hypothyroidism was not present in our old group. The basal TSH concentration did not correlate significantly with any index of thyroid function except with FT3I in group C (r = -0.43, P less than 0.05). In all age groups the TSH responses to TRH exhibited a biphasic pattern with early and late peaks.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1979

alpha 1-Antitrypsin deficiency and susceptibility to lung disease.

This subject concerns the complex interrelationship of a genetically determined protein deficiency, enzymes which are inhibited by that protein, environmental challenges such as cigarette smoke and industrial pollutants, and the occurrence of obstructive lung disease (Fig. 1). Unequivocal establishment of an etiological role for AAT deficiency, especially of intermediate degree, has proven to be difficult. Confounding variables such as enzyme concentration in PMN and PAMs, duration of exposure to potential environmental hazards, differences in laboratory methods utilized in measuring AAT and in studying pulmonary function all require investigation. The definitive study, incorporating all of these and other factors, has yet to be conducted. No single, clear-cut conclusion can be drawn from analysis of present studies. In those circumstances in which heterozygotes appear to be predisposed to COPD, phenotypic screening of the population at potential risk, such as industrial workers may be appropriate. Conversely, in conditions in which no association is demonstrated, such screening would not be justified. Perhaps, the best one can do is to suggest a "Scotch verdict"; that is, the issue of causation is not proven.

Animals↗
PubMed2006

Empirical support for optimal virulence in a castrating parasite.

The trade-off hypothesis for the evolution of virulence predicts that parasite transmission stage production and host exploitation are balanced such that lifetime transmission success (LTS) is maximised. However, the experimental evidence for this prediction is weak, mainly because LTS, which indicates parasite fitness, has been difficult to measure. For castrating parasites, this simple model has been modified to take into account that parasites convert host reproductive resources into transmission stages. Parasites that kill the host too early will hardly benefit from these resources, while postponing the killing of the host results in diminished returns. As predicted from optimality models, a parasite inducing castration should therefore castrate early, but show intermediate levels of virulence, where virulence is measured as time to host killing. We studied virulence in an experimental system where a bacterial parasite castrates its host and produces spores that are not released until after host death. This permits estimating the LTS of the parasite, which can then be related to its virulence. We exposed replicate individual Daphnia magna (Crustacea) of one host clone to the same amount of bacterial spores and followed individuals until their death. We found that the parasite shows strong variation in the time to kill its host and that transmission stage production peaks at an intermediate level of virulence. A further experiment tested for the genetic basis of variation in virulence by comparing survival curves of daphniids infected with parasite spores obtained from early killing versus late killing infections. Hosts infected with early killer spores had a significantly higher death rate as compared to those infected with late killers, indicating that variation in time to death was at least in part caused by genetic differences among parasites. We speculate that the clear peak in lifetime reproductive success at intermediate killing times may be caused by the exceptionally strong physiological trade-off between host and parasite reproduction. This is the first experimental study to demonstrate that the production of propagules is highest at intermediate levels of virulence and that parasite genetic variability is available to drive the evolution of virulence in this system.

Animals↗
PubMed2002

Circadian rhythms in airline pilots submitted to long-haul transmeridian flights.

BACKGROUND: Circadian rhythms shift out of phase after transmeridian flights. Desynchronization between body rhythms and the environment is linked to jet lag, which depends on age, flight direction, and number of time zones crossed. METHODS: To investigate this problem in airline pilots, we performed a multivariate analysis of their circadian systems during Madrid-Mexico-Madrid flights (-7 time zones, n = 12) and Madrid-Tokyo-Madrid flights (+8 time zones, n = 21). Telemetry was used to record pilots' activity, skin temperature, and heart rate, obtaining 6 d of continuous data, including 2 d before the flight, the flights themselves, 2 d at the stopover, and 1 d after the return flight. Time series were analyzed by cosinor, and the resulting parameters of the rhythms were compared by ANOVA and Tukey contrasts in every category formed by the age groups (under and over 50 yr old) and flight direction groups. Subjective time estimation of short, intermediate, and long intervals was recorded. Other psychological variables were measured, including anxiety, tiredness, and performance. RESULTS AND CONCLUSIONS: Activity/rest and heart rate rhythms appeared to be linked to a "weak oscillator." Temperature rhythms manifested a rigid response after the phase shifts of the light/dark cycle, closely related to the biological clock. Subjective time appreciation tended to be overestimated without exhibiting a clear circadian component, but attributable to fatigue and stress. Psychometric evaluation showed that desynchronization affected all the pilots. Some results showed an age-related variability with a more marked influence in younger pilots. No consistent effects regarding flight direction were found.

Activity Cycles↗
PubMed1992

[Antibiotic sensitivity of forty-four strains of group EF4 bacteria: study of minimum inhibitory concentrations using the agar dilution method].

EF4 bacteria are found in animal saliva and may contaminate bite wounds. Minimum inhibitory concentrations of 36 antimicrobials against 44 EF4 strains were determined using dilution in Mueller-Hinton agar. EF4 bacteria were susceptible to aminopenicillins, carboxypenicillins, ureidopenicillins, third-generation cephalosporins, fluoroquinolones, rifampicin, and trimethoprime-sulfamethoxazole. Susceptibility was intermediate for penicillin G, low for macrolides and variable for aminoglycosides. EF4 bacteria were resistant to lincomycin and trimethoprime. Routine prophylactic treatment of bite-induced Pasteurella infections using an aminopenicillin or a cycline also protects against EF4 infection of the wound.

4-Quinolones↗
PubMed2004

Allochronic differentiation among Daphnia species, hybrids and backcrosses: the importance of sexual reproduction for population dynamics and genetic architecture.

Seasonal dynamics of the abundance, sexual reproduction and genetic architecture in a Daphnia hyalina-galeata hybrid complex were studied in the large and deep Lake Constance. We found evidence for the occurrence of first and second order hybridization. Our study revealed strong differences between the parental species not only regarding their seasonal dynamics, genetic architecture and diversity, but also their sexual reproductive behaviour. The overwintering D. hyalina showed low genetic diversity, no genetic differentiation during the season, and reproduced sexually in autumn, whereas D. galeata reached higher levels of genetic diversity, reproduced sexually in early summer, and exhibited changes in genetic structure during the season, but was only present from spring to autumn. However, in both species sexual reproduction was a rare event, and daphnids, including hybrids, reproduced predominantly asexually. This allows long-term persistence of hybrids as well without continuing hybridization events. Within all variables studied, F1 and F2 hybrids showed an intermediate pattern, whereas proposed backcross hybrids were more similar to their respective parentals. These differences in phenotype as well as significant differences in pairwise Fst values between parentals suggest that gene flow seems to be relatively low in the Lake Constance hybrid system. We found evidence for unidirectional introgression by backcrossing from D. galeata to D. hyalina and found a decrease in at least one of the proposed introgressed alleles in the hyalina-backcross while the season progressed. Our findings suggest allochronic differentiation within this hybrid population and different microevolutionary trajectories of the parental species, which will be discussed in the light of the ongoing reoligotrophication process of Lake Constance.

Animals↗
PubMed1991

Neuroanatomy in fragile X females: the posterior fossa.

The relative homogeneity of the neuropsychiatric phenotype in individuals with fragile (fra) X syndrome suggests that there are consistent central nervous system (CNS) abnormalities underlying the observed cognitive and behavioral abnormalities. In this study, the neuroanatomy of the posterior fossa and other selected CNS regions in 12 young fra X females were compared with those of a group of 12 age-, sex-, and IQ-matched females without evidence of the fra X syndrome. Fra X females were shown to have decreased size of the posterior cerebellar vermis and increased size of the fourth ventricle, findings that are identical to those previously reported for fra X males. When compared with fra X male and nonfra X control groups, the distribution of the posterior-vermis and fourth-ventricle variables for the fra X female group was intermediate. These results support the hypothesis that the fra X genetic abnormality leads to hypoplasia of the posterior cerebellar vermis, a neuroanatomical variation of potential importance to both developmental and neuropsychiatric syndromes.

Adolescent↗
PubMed1988

Lymphocytic angiitis following streptokinase therapy.

A palpable, purpuric, nonpruritic eruption occurred in a 64-year-old man nine days after he received intravenous streptokinase therapy, which was successful in treating acute myocardial infarction. Perivascular mononuclear and eosinophilic infiltration was noted on routine staining of skin biopsy specimens: immune complexes, fibrin, and complement deposition in the skin microvasculature were demonstrated on immunofluorescent studies. These findings confirm the diagnosis of lymphocytic angiitis induced by streptokinase. Intermediate-type hypersensitivity reactions to streptokinase apparently have variable levels of severity. Clinicians who use streptokinase as a therapeutic agent should be aware of this potentially serious complication.

Fluorescent Antibody Technique↗
PubMed1988

Mammalian protein secretion without signal peptide removal. Biosynthesis of plasminogen activator inhibitor-2 in U-937 cells.

Plasminogen activator inhibitor-2 (PAI-2) is a serine protease inhibitor that regulates plasmin generation by inhibiting urokinase and tissue plasminogen activator. The primary structure of PAI-2 suggests that it may be secreted without cleavage of a single peptide. To confirm this hypothesis we have studied the glycosylation and secretion of PAI-2 in human monocytic U-937 cells by metabolic labeling, immunoprecipitation, glycosidase digestion, and protein sequencing. PAI-2 is variably glycosylated on asparagine residues to yield intracellular intermediates with zero, one, two, or three high mannose-type oligosaccharide units. Secretion of the N-glycosylated species began by 1 h of chase and the secreted molecules contained both complex-type N-linked and O-linked oligosaccharides. Enzymatically deglycosylated PAI-2 had an electrophoretic mobility identical to that of the nonglycosylated precursor and also to that of PAI-2 synthesized in vitro in a rabbit reticulocyte lysate from synthetic mRNA derived from full length PAI-2 cDNA. The amino-terminal protein sequence of secreted PAI-2 began with the initiator methionine residue. These results indicate that PAI-2 is glycosylated and secreted efficiently without the cleavage of a signal peptide. PAI-2 shares this property with its nearest homologue in the serine protease inhibitor family, chicken ovalbumin, and appears to be the first well characterized example of this phenomenon among natural mammalian proteins.

Animals↗
PubMedDate not supplied

Effect of semduramicin, salinomycin, and monensin on performance, shank pigmentation, and coccidial lesions in broiler chickens in floor pens.

The effects of 25 ppm semduramicin, 66 ppm salinomycin, 110 ppm monensin, and unmedicated treatments on performance, shank pigmentation, and coccidial lesion scores in broiler chickens were evaluated in two floorpen trials in the United States. On day 24 of each test, birds in each treatment were inoculated via the feed with a mixture of recent field isolates of Eimeria spp. at a dose rate calculated to provide 2 x 10(5) E. acervulina, 3 x 10(4) E. maxima, and 2 x 10(4) E. tenella sporulated oocysts per bird. Weight gain and feed conversion were significantly (P < or = 0.05) improved in the semduramicin-treated broilers in comparison with the monensin-treated and unmedicated broilers. These performance variables for the salinomycin-treated birds were intermediate between the semduramicin- and monensin-treated birds. Shank pigmentation scores were significantly (P < or = 0.05) improved in the three anticoccidial treatments compared with unmedicated birds, with the highest scores (P < or = 0.05) occurring in the semduramicin-treated broilers. Semduramicin was more efficacious (P < or = 0.05) than salinomycin in controlling upper intestinal lesions and more efficacious than monensin in controlling mid-intestinal lesions. All three drugs were comparable in controlling lesions in the ceca.

Animals↗
PubMed1995

Poly(adenosine diphosphoribose) polymerase in peripheral blood leukocytes from normal donors and patients with malignancies.

A two-color flow cytometric technique was developed to analyze poly(ADP-ribose) polymerase (PADPRP) in different individuals as a function of different physiological or pathological conditions and to establish the basis for determining whether enzyme deficiency may predispose to degenerative or malignant disorders. Peripheral blood granulocytes were devoid of enzyme activity, whereas mononuclear cells had variable amounts. PADPRP was highest in B cells, intermediate in T cells, and lowest in monocytes. This pattern of enzyme distribution and relative enzyme content of different types of cells was remarkably constant in normal subjects. In a series of 66 normal donors there was no significant biological variation in enzyme content as a function of age, race, or sex. The mean PADPRP values in peripheral blood mononuclear cells from 81 random patient samples obtained from an ambulatory oncology clinic did not differ significantly from normal subjects. However, groups of patients with breast cancer, lymphocytic malignancies, and esophageal cancer were observed to have below normal levels for peripheral blood mononuclear cell PADPRP.

Adult↗