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Risk stratification and prognosis of patients with known or suspected coronary artery disease by use of supine bicycle exercise stress echocardiography.

BACKGROUND: The aim of this study was to assess the long-term predictive values of supine bicycle exercise stress echocardiography (ESE), and the ESE additional role compared to other traditional clinical and rest echocardiographic variables, in 607 patients with low, intermediate and high pretest risk of cardiac events. METHODS: Clinical status and long-term outcome were assessed for a mean period of 46 months (range 12-60 months). ESE was performed for the diagnosis of suspected coronary artery disease (CAD) in 267 patients (43.9%), and for risk stratification of known CAD in 340 patients (56.1%). At baseline, the mean value of wall motion score index (WMSI) was 1.22 +/- 0.36, and the mean left ventricular ejection fraction was 58.5 +/- 10.9%. RESULTS: ESE was positive for ischemia in 210 patients (34.9%), while ECG was suggestive for ischemia in 157 patients (25.8%). During the test only 97 patients (15.9%) experienced angina. At peak effort, the mean WMSI was 1.38 +/- 0.46. A low workload was achieved by 158 patients (26.1%). During the follow-up period there were 222 events, including 82 hard events (36.9%), 48 deaths (21.6%) and 34 acute non-fatal myocardial infarction (15.3%). At stepwise multivariate model, cigarette smoking (p < 0.01), peak WMSI (p < 0.001), ESE positive for ischemia (p < 0.001) and low workload (p < 0.01) were the only independent predictors of cardiac death, while positive ESE, peak WMSI, angina during the test and hypercholesterolemia were the only independent determinants of hard cardiac events. The cumulative 5-year mean survival rate according to ESE response was 95.9% in patients with negative ESE, and 83.7% in patients with positive ESE (log rank 13.6; p < 0.00001). CONCLUSIONS: ESE yields prognostic information in known or suspected CAD, especially in patients with intermediate pretest risk level. The combined evaluation of clinical variables and other ESE variables, such as peak WMSI and exercise capacity, may further select patients at greatest risk of cardiac death in the overall population.

Coronary Artery Disease↗

Recombination between an expressed immunoglobulin heavy-chain gene and a germline variable gene segment in a Ly 1+ B-cell lymphoma.

The early stages of murine B-cell differentiation are characterized by a series of immunoglobulin gene rearrangements which are required for the assembly of heavy(H) and light(L)-chain variable regions from germline gene segments. Rearrangement at the heavy-chain locus is initiated first and consists of the joining of a diversity (DH) gene segment to a joining (JH) gene segment. This forms a DJH intermediate to which a variable (VH) gene segment is subsequently added. Light-chain gene rearrangement follows and consists of the joining of a VL gene segment to a JL gene segment: once a productive light-chain gene has been formed the cell initiates synthesis of surface immunoglobulin M (sIgM) receptors (reviewed in ref. 1). These receptors are clonally distributed and may undergo further diversification either by somatic mutation or possibly by continued recombinational events. Such recombinational events have been detected in the Ly 1+ B-cell lymphoma NFS-5, which has been shown to rearrange both lambda and H-chain genes subsequent to the formation of sIgM (mu kappa) molecules. Here we have analysed a rearrangement of the productive allele of NFS-5 and found that it is due to a novel recombination event between VH genes which results in the replacement of most or all of the coding sequence of the initial VHQ52 rearrangement by a germline VH7183 gene. Embedded in the VH coding sequence close to the site of the cross-over is the sequence 5' TACTGTG 3', which is identical to the signal heptamer found 5' of many DH gene segments. This embedded heptamer is conserved in over 70% of known VH genes. We suggest that this heptamer mediates VH gene replacement and may play an important part in the development of the antibody repertoire.

Animals↗

Variability in surface antigen expression of human breast epithelial cells cultured from normal breast, normal tissue peripheral to breast carcinomas, and breast carcinomas.

Single-cell heterogeneity and variability in expression of several surface antigens on human mammary epithelial cells in short-term culture were studied with immunofluorescence techniques, using polyclonal and monoclonal antibodies. The cultures, derived from normal breast, a fibroadenoma, a gynecomastia, normal breast tissue peripheral to breast carcinomas, and breast carcinomas and their metastases, were studied after one passage in vitro. The percentage of positive cells varied considerably from one tissue sample to another in all categories from normal to malignant, although there was an overall trend toward a decreasing percentage of positive cells of malignant tissues. The relative antigen content varied 3- to 8-fold among individual samples of cells from normal, peripheral, and carcinoma tissue, while the mean values in the three categories were similar. The single-cell variability in relative antigen content was considerable in all individual samples of normal, peripheral, and carcinoma tissues, as reflected in the high coefficients of variation. However, the coefficients of variation were significantly higher for cells from carcinoma and peripheral tissues [69 +/- 10% (S.E.) and 75 +/- 9%, respectively] than for cells from normal breast (48 +/- 5%). By analyzing in clonal colonies the appearance of quantitative variants in expression of a specific surface antigen, detected with a monoclonal antibody, the carcinoma cells were found to have a 10-fold higher rate of phenotypic variability (mean, 1.21 X 10(-2)/cell/generation) than did cells from normal breast (mean, 0.119 X 10(-2)) and one gynecomastia (0.045 X 10(-2)). Mammary epithelial cells from apparently "normal" tissue peripheral to a carcinoma had an intermediate rate of phenotypic variability (mean, 0.310 X 10(-2)) that was significantly higher than that of the normal tissue.

Adenofibroma↗

Size variability of the Y chromosome distal C-band in Brazilian Indians and Caucasoids.

Densitometric measurements of the Y chromosome distal heterochromatin were performed on 183 Indians and 21 Caucasoids living in Brazil. No significant intratribal intervillage variation was observed, but the tribal averages were different, ranging from 0.81 to 1.32 mu. The Caucasoid mean presented an intermediate value. Wide intrapopulation variability occurs, as well as a suggestion of bimodality in the measurements obtained among the Indians of the Amazon region. Surprisingly a positive correlation was found between this variable and the C-band size of chromosome 16, as well as between it and the heteromorphism index of chromosome 1.

Adult↗

Effects of cadmium on the control and internal regulation of oxidative phosphorylation in potato tuber mitochondria.

The effect of cadmium on the distribution of control over oxidative phosphorylation in potato tuber mitochondria was quantified by measuring control coefficients using top-down metabolic control analysis. Oxidative phosphorylation was divided into three subsystems, namely substrate oxidation, the phosphorylation reactions and the proton leak. The control exerted by each of these subsystems over the system fluxes, the value of the protonmotive force and the effective P/O ratio was quantified in the presence of different concentrations of free cadmium (up to 21 microM). Cadmium is known to stimulate the proton leak and inhibit the substrate oxidation reactions, but it had little effect on the distribution of control over the system variables except to shift the pattern to lower rates. Control exerted by particular subsystems appeared to change or to stay the same as cadmium was varied, depending on whether the control coefficients were presented as a function of respiration rate or protonmotive force. The regulatory strength of protonmotive force on the system variables was also calculated, as partial internal response coefficients. These coefficients changed with ATP turnover rate and with cadmium concentration, showing how the internal regulation of oxidative phosphorylation shifts under different conditions. The values of control coefficients and partial internal response coefficients show where control lies and how intermediates regulate the system variables under different conditions of ATP demand and external effector (i.e. cadmium) concentration. However, they are not useful for identifying the sites of action of external effectors, for which elasticity and regulation analysis must be used.

Cadmium↗

Serological and genetic characterisation of bovine respiratory syncytial virus (BRSV) indicates that Danish isolates belong to the intermediate subgroup: no evidence of a selective effect on the variability of G protein nucleotide sequence by prior cell culture adaption and passages in cell culture or calves.

Danish isolates of bovine respiratory syncytial virus (BRSV) were characterised by nucleotide sequencing of the G glycoprotein and by their reactivity with a panel of monoclonal antibodies (MAbs). Among the six Danish isolates, the overall sequence divergence ranged between 0 and 3% at the nucleotide level and between 0 and 5% at the amino acid level. Sequence divergences of 7-8%, 8-9% and 2-3% (nucleotide) and 9-11%, 12-16% and 4-6% (amino acid) were obtained in the comparison made between the group of Danish isolates and the previously sequenced 391-2USA, 127UK and 220-69Bel isolates, respectively. Phylogenetic analysis showed that the Danish isolates formed three lineages within a separate branch of the phylogenetic tree. Nevertheless, the Danish isolates were closely related to the 220-69Bel isolate, the prototype of the intermediate antigenic subgroup. The sequencing of the extracellular part of the G gene of additional 11 field BRSV viruses, processed directly from lung samples without prior adaption to cell culture growth, revealed sequence variabilities in the range obtained with the propagated virus. In addition, several passages in cell culture and in calves had no major impact on the nucleotide sequence of the G protein. These findings indicated that the previously established variabilities of the G protein of RS virus isolates were not attributable to mutations induced during the propagation of the virus. The reactivity of the Danish isolates with G protein-specific MAbs were similar to that of the 220-69Bel isolate. Furthermore, the sequence of the immunodominant region was completely conserved among the Danish isolates on one side and the 220-69Bel isolate on the other. When combined, these data strongly suggested that the Danish isolates belong to the intermediate subgroup.

Amino Acid Sequence↗

A risk model for ovarian carcinoma patients using CA 125: time to normalization renders second-look laparotomy redundant.

BACKGROUND: We evaluated the incorporation of CA 125 normalization times into a prognostic model based on pretreatment variables in patients with ovarian carcinoma to determine if they could render second-look laparotomy (SLL) redundant. METHODS: A total of 54 consecutive patients with ovarian carcinoma who underwent SLL between 1985 and 1990 were included in this analysis. At diagnosis, all of the patients had abnormal CA-125 serum levels, which fell to within the normal range during chemotherapy. Cox's model was used to select pretreatment variables relevant for prognosis. The influence of the time to normalization of CA 125 (< or = vs. > 1 months) and the capability of SLL results to modify prognostic prediction, were also evaluated. RESULTS: The size of the residual tumor at the beginning of therapy, and Eastern Cooperative Oncology Group (ECOG) performance status (PS) were independently predictive of survival. The time to normalization of CA 125 serum levels (analyzed either as -a continuous or as a two-category variable) also had an independent prognostic role when included in the model. When we examined the inclusion of both CA 125 parameter and SLL into the model together, we found that only CA 125 continued to have an independent prognostic relevance. On the basis of the two pretreatment parameters (PS and tumor size) and of this response parameter (time to normalization of CA 125 values) we selected six subgroups of patients having different outcomes (log rank test of equality over-strata < 0.001). Patients with good prognostic pretreatment variables, and those with intermediate prognosis at the beginning of therapy who showed a quick normalization of CA 125, had an 80% 5-year survival, compared with 16% 5-year survival in the remaining patients. (P < 0.0001). CONCLUSIONS: Our data suggest that the survival of patients with advanced ovarian carcinoma could be accurately predicted by considering some pretreatment variables and time to CA 125 normalization together, without performing SLL. Our risk model, however, needs to be validated by larger prospective trials, to draw any definitive conclusions about the abandonment of surgically defined response.

Biomarkers, Tumor↗

Effects of variations in the temporal distribution of reinforcements on interval schedule performance.

Pigeons were exposed to variable-interval and fixed-interval schedules and schedules approximating variable-interval and fixed-interval schedules. The probabilities of the variable-interval and fixed-interval components in a mixed fixed-interval variable-interval schedule in Experiment I and the minimum and maximum interreinforcement intervals in Experiment II in a variable-interval schedule were manipulated to create intermediate schedule contingencies and contingencies approximating simple variable-interval or fixed-interval contingencies. Maximal control by time as defined by quantitative indices of the temporal pattern of response occurred as fixed-interval contingencies were approximated and minimal control occurred as variable-interval contingencies were approximated. Changes in the temporal pattern of response were systematically related to changes in the temporal distribution of reinforcements with both procedural definitions for manipulating the temporal distribution of reinforcements.

Journal Article↗

Ultrastructure of the rat urothelium in en face section.

We examined en face the fine structure of rat urothelium and describe here some unique subcellular features distinguishable in the various tissue layers by this technique. The most striking finding is that large, compact fibrous bundles lie in the cytoplasm at both sides of the superficial cell tight junction for the entire length around it apical surface. Basal to these bundles, an intricate series of desmosomes alternates with other specialized elaborations of the plasma membrane. These desmosomes anchor the extensive filamentous network that interconnects the nucleus, flattened superficial vesicles, and plaques of the lumenal membrane. En face sections of the urothelium show that large numbers of vesicles form inthe intermediate cell Golgi complexes and are then stored just under the apical membrane. These intermediate vesicles are smaller, more round, and less variable in size than superficial vesicles. After intermediate cells reach the superficial layer, the vesicles mature, undergoing modifications that apparently increase their tendency to fuse.

Animals↗

Direct demonstration of cytokeratin filaments by electron microscopy in K562 cell lines in liquid culture.

Our previous study suggested the presence of cytokeratins in the supernatant of human K562 erythroleukemic cell line. In this study we confirm, by using an electron microscopy technique, that K562 cells contain typical intermediate tonofilaments with the characteristics of cytokeratins. After variable intervals of liquid culture, K562 cells have been examined for their clonogenic ability by immunostaining and ultrastructural study. K562 cells showed variable amounts of medium-sized filaments (intermediate filaments) of 10 nm mean size, having the submicroscopic pattern consistent with tonofilaments, arranged as electron-dense curve-shaped bundles, in perinuclear position independently from the different growth phases. A pool of monoclonal antibodies against cytokeratins confirmed the presence of cytokeratins in immunostaining, while the cytofluorimetric analysis showed an unexpected positivity of the CD34 antigen, associated with the typical adhesion molecule VLA5. In conclusion, the immunostaining with monoclonal antibodies and the ultrastructural findings suggest the expression of epithelial features in human K562 leukemic cells.

Cell Culture Techniques↗

Heart failure diagnosis in primary health care: clinical characteristics of problematic patients. A clinical judgement analysis study.

BACKGROUND: Early detection of chronic heart failure has become increasingly important since the introduction of effective treatment. However, clinical diagnosis of heart failure is known to be difficult, especially in mild cases or early in the course of the disease. The purpose of this study is to analyse how patient characteristics contribute to difficulties in diagnosing systolic heart failure. METHODS DESIGN: A Clinical Judgement Analysis study of 40 case vignettes based on authentic patients, including relevant clinical data except echocardiography. SETTING: Primary health care and two cardiology outpatient clinics in Stockholm. SUBJECTS: 70 participants with different types of clinical experience; 27 specialists in general practice, 22 cardiologists, and 21 medical students. MAIN OUTCOME MEASURES: The assessed probability of heart failure for each case vignette, and the disagreement between the participants. The number of clinical variables (cues) indicative of heart failure in the case vignettes. RESULTS: The ten case vignettes with the least diverging assessments more often had increased relative cardiac volume and atrial fibrillation. No further specific clinical patterns could be found in subgroups of the case vignettes. The ten case vignettes with the most diverging assessments were those with an intermediate number of clinical variables. The case vignettes with the least diverging assessments more often represented patients with cardiac enlargement and atrial fibrillation. CONCLUSION: Diagnosing mild heart failure is difficult, as these patients are not easy to characterise. In our study, a larger number of positive cues resulted in more diagnostic conformity among the participants, and the most important information was cardiac enlargement. The importance of more objective diagnostic methods in diagnosing suspected cases of heart failure should be emphasised.

Cardiology↗

Learning to vary and varying to learn.

We compared two sources of behavior variability: decreased levels of reinforcement and reinforcement contingent on variability itself. In Experiment 1, four groups of rats were reinforced for different levels of response-sequence variability: one group was reinforced for low variability, two groups were reinforced for intermediate levels, and one group was reinforced for very high variability. All of the groups experienced three different reinforcement frequencies for meeting their respective variability contingencies. Results showed that reinforcement contingencies controlled response variability more than did reinforcement frequencies. Experiment 2 showed that only those animals concurrently reinforced for high variability acquired a difficult-to-learn sequence; animals reinforced for low variability learned little or not at all. Variability was therefore controlled mainly by reinforcement contingencies, and learning increased as a function of levels of baseline variability. Knowledge of these relationships may be helpful to those who attempt to condition operant responses.

Animals↗

Evolution of keratin genes: different protein domains evolve by different pathways.

Intermediate filaments are composed of a family of proteins that evolved from a common ancestor. The proteins consist of three domains: a central, alpha-helical domain similar in all intermediate filaments, bracketed by two domains that are variable in length and structure. Within the intermediate-filament family, several subfamilies have been recognized by immunologic and nucleic acid hybridization techniques. In this paper we present the sequence of the genomic DNA coding for a 65-kilodalton human keratin and compare it with the sequences of other intermediate-filament proteins. While the central, alpha-helical domains of these proteins show homologies that indicate a common ancestor, the sequences of the variable terminal domains indicate that the variable domains evolved through a series of tandem duplications and possibly by gene-conversion mechanisms.

Amino Acid Sequence↗

Diversity in expression of myosin heavy chain isoforms and M-band proteins in rat muscle spindles.

The composition of adult rat soleus muscle spindles, with respect to myosin heavy chain isoforms and M-band proteins, was studied by light-microscope immunohistochemistry. Serial sections were labelled with antibodies against slow tonic, slow twitch, fast twitch and neonatal myosin isoforms as well as against myomesin, M-protein and the MM form of creatine kinase. Intrafusal fiber types were distinguished according to the pattern of ATPase activity following acid and alkaline preincubations. Nuclear bag1 fibers were always strongly stained throughout with anti-slow tonic myosin, were positive for anti-slow twitch myosin towards and in the C-region but were unstained with anti-fast twitch and anti-neonatal myosins. The staining of nuclear bag2 fibers was in general highly variable. However, they were most often strongly stained by anti-slow tonic myosin in the A-region and gradually lost this reactivity towards the poles, whereas a positive reaction with anti-slow twitch myosins was found along the whole fiber. Regional staining variability with anti-neonatal and anti-fast myosins was apparent, often with decreasing intensity towards the polar regions. Nuclear chain fibers showed strong transient reactivity with anti-slow tonic myosin in the equatorial region, did not react with anti-slow twitch and were always evenly stained by anti-fast twitch and anti-neonatal myosins. All three intrafusal fiber types were stained with anti-myomesin. Nuclear bag1 fibers lacked staining for M-protein, whereas bag2 fibers displayed intermediate staining, with regional variability, often increasing in reactivity towards the polar regions. Chain fibers were always strongly stained by anti-M-protein. The MM form of creatine kinase was present in all three fiber types, but bag1 fibers were less reactive and clear striations were not observed, in contrast to bag2 and chain fibers. Out of 38 cross sectioned spindles two were found to have an atypical fiber composition (lack of chain fibers) and a rather diverse staining pattern for the different antibodies tested. Taken together, the data show that in adult rat soleus, slow tonic and neonatal myosin heavy chain isoforms are only expressed in the muscle spindle fibers and that each intrafusal fiber type has a unique, although variable, composition of myosin heavy chain isoforms and M-band proteins. We propose that both motor and sensory innervation might be the determining factors regulating the variable expression of myosin heavy chain isoforms and M-band proteins in intrafusal fibers of rat muscle spindles.

Animals↗

Effects of isotretinoin (13-cis-retinoic acid) on the development of mouse limbs in vivo and in vitro.

Isotretinoin (13-cis-RA) is known to be teratogenic in humans and laboratory animals. The relatively low potency of 13-cis-RA in NRMI mice in comparison to the all-trans isomer has been proposed to be due to minimal transfer across the placenta (Creech-Kraft et al., '87). To further delineate the teratogenic potential of 13-cis-RA, a dose-response, temporal study was conducted in vivo and in vitro using submerged limb culture and image analysis evaluation of development. Dose-dependent embryotoxicity was produced by treatment on GD 7, while later treatments produced inconsistent effects on resorption rate and fetal weight. Treatment on either GD 7 or GD 8 produced a number of malformations in dose-dependent manner. Most common were tail and cleft palate defects, which were produced by 13-cis-RA on each of the days tested (GD 7-GD 11), with peak malformations occurring on GD 9 and GD 10 for tail and cleft palate, respectively. Most limb defects were produced after GD 10 and GD 11 exposure. The observed frequency of defects confirmed that in ICR mice 13-cis-RA is about 10-fold less potent than all-trans-RA as a limb teratogen (Kwasigroch and Kochhar, '80; Kochhar and Penner, '87). Effects observed via image analysis following maintenance of limbs in serum-free culture medium were dose dependent. Low dose treatment produced occasional polydactyly. The intermediate dose caused somewhat variable region-dependent increases in cartilaginous bone anlagen area. The high dose of 13-cis-RA produced irregular limb outlines, a reduction in bone anlagen area, and an inhibition of alcian blue staining of cartilage without affecting morphogenesis of bone anlagen. These results confirm that, when the effects of the administered doses are evaluated, 13-cis-RA is a much less potent teratogen in comparison to the all-trans isomer. More importantly, the results show that retinoids can enhance (at low and intermediate doses), depress (at high doses), or eliminate (high dose) chondrogenenic expression during limb morphogenesis in vitro. This indicates that retinoids such as 13-cis-RA can manipulate events in development in a variety of ways (i.e., produce malformations, interfere with chondrogenic expression without affecting morphogenesis, and stimulate growth) in a dose- and time-dependent manner. Although the ability of RA to act as a true morphogen has recently been questioned (Wanek et al., '91; Noji et al., '91), the results presented here support the position that RA can modulate the development of the limb (and probably other organ systems) in several vertebrate species.

Abnormalities, Drug-Induced↗

Expression of p53, bcl-2, E-cadherin, matrix metalloproteinase-9, and tissue inhibitor of metalloproteinases-1 in paired primary tumors and brain metastasis.

The objectives of this study were to: (a) characterize the immunohistochemical expression of p53, bcl-2, E-cadherin (EC), matrix metalloproteinase-9 (MMP-9), and tissue inhibitor of metalloproteinases-1 (TIMP-1) in brain metastases; (b) compare immunohistochemical (IHC) expression of brain metastases with their primary tumors; and (c) assess the prognostic value of expression of these markers. Tumors from 35 patients with brain metastasis were studied for IHC expression of p53, bcl-2, EC, MMP-9, and TIMP-1. In 17 cases, primary tumors were also available for study. In brain metastases, p53 was positive in 91% of cases and intermediate in 9%, MMP-9 was positive in all cases, TIMP-1 was intermediate in 6% and negative in 94% of cases, EC expression was positive in 86% of cases and intermediate in 14%, and bcl-2 was variable. All primary tumors were positive for p53 and MMP-9, 3% were intermediate for TIMP-1 and 97% were negative, 65% were positive for EC and 35% were intermediate, whereas bcl-2 expression was variable. Neither p53, bcl-2, TIMP-1, or EC staining correlated with overall survival or survival with brain metastases. No assessment of survival differences could be made for MMP-9 because of its overexpression in all tissues. This study found that MMP-9 and p53 were markedly overexpressed in primary tumors and matched brain metastasis, TIMP-1 expression was negative in the majority of specimens, whereas EC expression was maintained in both primary tumors and brain metastases and bcl-2 expression was variable. This study suggests that the functional balance of MMP-9 and TIMP-1 is shifted toward extracellular matrix degradation in brain metastases and that deregulation of cell cycle control by p53 also exists in brain metastases. The high expression of EC may indicate the importance of adherence at late stages of metastasis but requires further study.

Adult↗

Response of desert biological soil crusts to alterations in precipitation frequency.

Biological soil crusts, a community of cyanobacteria, lichens, and mosses that live on the soil surface, occur in deserts throughout the world. They are a critical component of desert ecosystems, as they are important contributors to soil fertility and stability. Future climate scenarios predict alteration of the timing and amount of precipitation in desert environments. Because biological soil crust organisms are only metabolically active when wet, and as soil surfaces dry quickly in deserts during late spring, summer, and early fall, the amount and timing of precipitation is likely to have significant impacts on the physiological functioning of these communities. Using the three dominant soil crust types found in the western United States, we applied three levels of precipitation frequency (50% below-average, average, and 50% above-average) while maintaining average precipitation amount (therefore changing both timing and size of applied events). We measured the impact of these treatments on photosynthetic performance (as indicated by dark-adapted quantum yield and chlorophyll a concentrations), nitrogenase activity, and the ability of these organisms to maintain concentrations of radiation-protective pigments (scytonemin, beta-carotene, echinenone, xanthophylls, and canthaxanthin). Increased precipitation frequency produced little response after 2.5 months exposure during spring (1 April-15 June) or summer (15 June-31 August). In contrast, most of the above variables had a large, negative response after exposure to increased precipitation frequency for 6 months spring-fall (1 April-31 October) treatment. The crusts dominated by the soil lichen Collema, being dark and protruding above the surface, dried the most rapidly, followed by the dark surface cyanobacterial crusts (Nostoc- Scytonema- Microcoleus), and then by the light cyanobacterial crusts (Microcoleus). This order reflected the magnitude of the observed response: crusts dominated by the lichen Collema showed the largest decline in quantum yield, chlorophyll a, and protective pigments; crusts dominated by Nostoc-Scytonema-Microcoleus showed an intermediate decline in these variables; and the crusts dominated by Microcoleus showed the least negative response. Most previous studies of crust response to radiation stress have been short-term laboratory studies, where organisms were watered and kept under moderate temperatures. Such conditions would give crust organisms access to ample carbon to respond to imposed stresses (e.g., production of UV-protective pigments, replacement of degraded chlorophyll). In contrast, our longer-term study showed that under field conditions of high air temperatures and frequent, small precipitation events, crust organisms appear unable to produce protective pigments in response to radiation stress, as they likely dried more quickly than when they received larger, less frequent events. Reduced activity time likely resulted in less carbon available to produce or repair chlorophyll a and/or protective pigments. Our findings may partially explain the global observation that soil lichen cover and richness declines as the frequency of summer rainfall increases.

Analysis of Variance↗

Does hormonal manipulation in conjunction with permanent interstitial brachytherapy, with or without supplemental external beam irradiation, improve the biochemical outcome for men with intermediate or high-risk prostate cancer?

OBJECTIVE: To determine whether hormonal manipulation improves the biochemical outcome for men with intermediate or high-risk prostate cancer and undergoing permanent brachytherapy with or without supplemental external beam radiation therapy. PATIENTS AND METHODS: From April 1995 to August 2000, 350 patients with intermediate-risk (225 men; a Gleason score of >or= 7 or a prostate specific antigen, PSA, level of >or= 10 ng/mL or clinical stage >or= T2b) or high-risk features (125 men; two or three of a Gleason score of >or= 7 or PSA >or= 10 ng/mL or clinical stage >or= T2b) underwent transperineal ultrasonography-guided permanent brachytherapy. No patient underwent pathological lymph node staging. Of these patients, 293 received supplemental external beam radiation therapy (EBRT), 141 received hormonal manipulation, with 82 having hormonal therapy for 4 months) regimens, supplemental EBRT, isotope and dosimetric variables. RESULTS: For intermediate-risk patients, the 6-year actuarial BDF survival rates were 98%, 96% and 100% for hormone naïve, cytoreductive and adjuvant treatment, respectively (P = 0.693); for high-risk patients the respective values were 79%, 94% and 92% (P = 0.046). When stratified by pretreatment PSA, hormonal manipulation improved the outcome for patients with a PSA of >or= 10 ng/mL (P = 0.019), but not for those with < 10 ng/mL (P = 0.661). Hormonal status was not statistically significant in predicting biochemical outcome when stratified by Gleason score. The follow-up in hormone-naïve patients was significantly longer than that in hormonally manipulated patients, at 55 (20) vs 43 (15) months (P < 0.001). In a multivariate analysis only the Gleason score predicted failure in intermediate-risk patients, while pretreatment PSA, the use of hormonal manipulation and Gleason score predicted the outcome in high-risk patients (P = 0.035). For both hormone-naïve and hormonally manipulated BDF patients, the median PSA level after implantation was < 0.1 ng/mL. CONCLUSION: In patients treated by permanent prostate brachytherapy, hormonal manipulation improved the biochemical outcome for those at high-risk and those with an initial PSA of >or= 10 ng/mL, but not for those with intermediate-risk features. The use of hormonal therapy for> 4 months conferred no additional biochemical advantage over short-course regimens. Because the follow-up in hormone-naïve patients was longer than that for those receiving hormonal manipulation, additional follow-up will be mandatory to confirm the durability of these findings.

Antineoplastic Agents, Hormonal↗