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PubMed1997

Prostate specific antigen levels during radical radiation therapy and the prediction of outcome in localized carcinoma of the prostate.

There has been substantial interest in the effect of radiation therapy upon serum prostate specific antigen (PSA) levels in patients managed by radiation therapy and their ability to predict the eventual outcome. At our institute, an observational prospective longitudinal study was begun in 1989 to identify prognostic factors for biochemical relapse from among several variables, including PSA levels measured prior to treatment, during treatment, and post-treatment, and to summarize what happens to PSA levels over the course of treatment with radical radiation therapy. A total of 142 patients with adenocarcinoma of the prostate (T1-4, N0, M0) were radically irradiated (6-7 weeks) between February 1989 and January 1991. Serum PSA levels were recorded weekly during radiation therapy in 117 patients. Of these 117, weekly PSA measurements ranged in completeness from 95 to 113 cases. A number of statistical tests were performed on the data with investigative/ exploratory intent. There were 60 biochemical relapses documented in the whole group of 142 patients, with a maximum follow-up of 4.6 years and median follow-up of 3.3 years. Of the candidate prognostic variables tested by univariate analysis, the following emerged as statistically significant (i.e. P < 0.05): each of the four pretreatment factors (absolute PSA value, dichotomous PSA (normal versus above normal), T category and Gleason score); the treatment variables namely, the end-of-treatment PSA, the slope of PSA, and the absolute change in PSA from pretreatment to the end of treatment; and, among post-treatment variables, the first follow-up PSA, the absolute change in PSA from pretreatment to first follow-up, and the return to normal of an above-normal pretreatment PSA by first follow-up. The majority of these factors were then subjected to multivariate Cox proportional hazards (PH) regression analyses. The end-of-treatment PSA and T category were consistently identified as independently statistically significant factors associated with biochemical relapse. The Gleason score was selected less consistently, and never when defined on a categorical scale. Therefore, using a Cox PH model with the variables of end-of-treatment PSA and T category, both defined on a categorical scale, we developed three prognostic groups with good, intermediate and poor prognoses (chi 2 TREND = 40.7; P < 0.0001). Their 3-year biochemical relapse-free rates, for example, were: 91%, (standard error (SE) 5%); 64% (SE 9%); and 24% (SE 6%), respectively. However, substitution of the baseline value of PSA, which was also strongly associated with outcome, and using the data from all 142 patients, provided similarly distinct prognostic groups (chi 2 TREND = 41.6; P < 0.0001), with corresponding 3-year relapse-free rates of: 92% (SE 4%); 79% (SE 7%); and 30% (SE 6%). Mean weekly PSA levels measured during treatment were found to have a negatively sloping or decreasing tendency. A statistically significant decrease in PSA occurred from pretreatment to the end of treatment (t116 = 7.5; P < 0.0001); the geometric mean of the ratio of end-of-treatment PSA to PSA at pretreatment was 0.7 (95% CI 0.6-0.8). The end-of-treatment PSA and T category emerged as independently statistically significant prognostic variables predicting biochemical relapse. Using the fitted Cox PH model with these two variables, three distinct prognostic groups were identified. The results using pretreatment PSA instead of end-of-treatment PSA produced similarly distinct prognostic groups. Mean weekly PSA levels measured during treatment exhibited a decreasing tendency, and a statistically significant decrease in PSa from pretreatment to the end of treatment was observed.

Adenocarcinoma↗
PubMed2005

Intermediate phenotypes in schizophrenia: a selective review.

Studies aiming to identify susceptibility genes for schizophrenia and other complex psychiatric disorders are faced with the confounds of subjective clinical criteria, commonly occurring phenocopies, significant between-subject variability of candidate traits, and the likelihood of allelic and locus heterogeneity that has been shown to define the genetics of other complex human brain and somatic disorders. Additionally, research aimed at identification of the molecular origins of schizophrenia must also deal with the confounding nature of the human brain. Unlike organs with a few common cellular phenotypes, transcriptomes, and proteomes, individual neurons are often distinct from one another in all of these respects. In this review, we present recent work testing the assumption that studies of genetic susceptibility in complex polygenic disorders such as schizophrenia might be enhanced by the identification of intermediate phenotypes related to more fundamental aspects of brain development and function. Progress in the identification of meaningful intermediate phenotypes in schizophrenia has been made possible by the advent of newer methods in cognitive neuroscience and neuroimaging, and the use of combined multimodal techniques.

Brain↗
PubMed2002

The influence of protein structure on the products emerging from succinimide hydrolysis.

Proteins are vulnerable to spontaneous, covalent modifications that may result in alterations to structure and function. Asparagines are particularly labile, able to undergo deamidation through the formation of a succinimide intermediate to produce either aspartate or isoaspartate residues. Although aspartates cannot undergo deamidation they can form a succinimide and result in the same products. Isoaspartyls are the principal product of succinimide hydrolysis, accounting for 65-85% of the emerging residues. The variability in the ratio of products emerging from succinimide hydrolysis suggests the ability of protein structure to influence succinimide outcome. In the H15D histidine-containing protein (HPr), phosphorylation of the active site aspartate catalyzes the formation of a cyclic intermediate. Resolution of this species is exclusively to aspartate residues, suggestive of either a succinimide with restrained hydrolysis, or an isoimide, from which aspartyl residues are the only possible product. Deletion of the C-terminal residue of this protein does not influence the ability for phosphorylation or ring formation, but it does allow for isoaspartyl formation, verifying a succinimide as the cyclic intermediate in H15D HPr. Isoaspartyl formation in H15D Delta85 is rationalized to occur as a consequence of elimination of steric restrictions imposed by the C terminus on the main-chain carbonyl of the succinimide, the required point of nucleophilic attack of a water molecule for isoaspartyl formation. This is the first reported demonstration of the influence of protein structure on the products emerging from succinimide hydrolysis.

Aspartic Acid↗
PubMed2004

The fractional urinary fluoride excretion of adolescents and adults under customary fluoride intake conditions, in a community with 0.6-mg F/L in its drinking water.

AIMS: To assess the fractional urinary fluoride excretion (FUFE) relative to the customary daily fluoride (F) ingestion in adolescents and adults aged 11-75 years, and to explore the influence that some metabolic variables, such as the F-dose (mg F/kg body weight), rate of urinary fluoride excretion, age and body weight, might have on FUFE values. DESIGN: The fluoride ingestion and urinary excretion of 92 volunteers aged 11-75 years, resident in Santiago, Chile, were measured. In Santiago, the water is fluoridated to a concentration of between 0.5 and 0.6 mg/l. Individual FUFE values were calculated as the ratio between the total amount of F excreted with the urine and the total amount of F ingested, over a 24-hour period. RESULTS: The average FUFE values did not differ significantly among adults (ANOVA; p > 0.31). The average 24-hour FUFE value for adults was 0.75; 95% C.I. = 0.70-0.80, while the corresponding value for adolescents was 0.35; 95% C.I. = 0.30-0.40. Individual FUFE values were fitted by a multiple regression model using the rate of F urinary excretion and the inverse of the F dose as significant predictors (R2 = 0.79). CONCLUSIONS: Results obtained suggest that among adults residing in an area with an intermediate F-exposure, FUFE values do not depend on age. A relatively simple multiple regression model appears to explain 79% of the variability of the individually measured FUFE values. Further studies in areas with different F exposures are needed to refine the proposed model.

Adolescent↗
PubMed2002

Occurrence of a sibling species complex within neotropical lymnaeids, snail intermediate hosts of fascioliasis.

The delimitation of cryptic species within the genus Lymnaea, which are the main vectors of fascioliasis, remains a topic of controversy. An analysis of genetic variability based on 12 enzyme loci revealed different fixed alleles at 9 loci between two sympatric samples of Lymnaea viatrix at the type locality in Lima, Peru. The absence of heterozygotes within this locality indicates the presence of isolated populations or cryptic species within L. viatrix. Significant genetic differences were also found between these two L. viatrix samples from Lima and other populations of L. viatrix in South America and in addition to species such as L. truncatula, L. cubensis and L. columella. Moreover, the lack of variability within each Lymnaea samples studied indicates the existence of a high selfing rate in each species.

Animals↗
PubMed1985

Effect of variable glutathione peroxidase activity on H2O2-related cytotoxicity in cultured aortic endothelial cells.

Primary cultures of porcine aortic endothelial cells were used to assess the effects of O2 intermediates produced by 10-40 mU/ml xanthine oxidase (XO; +2 mM hypoxanthine) or 25-100 mU/ml glucose oxidase (GO; +5 mM glucose). A 60-min incubation in the presence of the enzyme systems resulted in a dose-dependent toxic effect with evidence of cytolysis (increased LDH release) and cell loss (decrease in DNA and protein content), when these indexes were measured 24 hr after completion of the enzyme reaction. Decreased [3H]thymidine incorporation into DNA was the most sensitive index of cell dysfunction for both enzyme systems. The effects of various scavengers and enzymes indicated that H2O2 was the main O2 intermediate involved in the cytotoxicity resulting from the XO-hypoxanthine reaction. Increased glutathione peroxidase activity associated with the addition of 2 X 10(-7) M selenomethionine to culture medium had a partial protective effect which could be related to an increased rate of H2O2 degradation. Evidence for increased DNA synthesis after injury was found in cells previously exposed to XO-hypoxanthine, the degree of increase in [3H]thymidine incorporation being dependent on the intensity of the initial cytotoxicity. Cultured endothelial cells provide a useful tool to evaluate the role of O2 intermediates in endothelial cell injury, to test the effects of protective agents, and to study the repair process.

Animals↗
PubMed1986

Variability of expression and arrangement of cytokeratin and neurofilaments in cutaneous neuroendocrine carcinomas (Merkel cell tumors): immunocytochemical and biochemical analysis of twelve cases.

Twelve specimens of cutaneous neuroendocrine carcinomas (Merkel cell tumors) available as fresh tissue were analyzed for intermediate filament (IF) expression by immunocytochemical and biochemical methods. In immunofluorescence microscopy, most cases were positive for both simple-epithelium-type cytokeratins and the neurofilament L- and M-polypeptides. Several different IF staining patterns ranging from presence of plaque-like structures (fibrous bodies) only to nearly exclusive expression of delicate cytokeratin fibrils could be distinguished. In immunoelectron microscopy the labeling for both cytokeratin and neurofilament polypeptides seemed evenly distributed among the IFs of the fibrous bodies. In primary culture, tumor cells maintained the coexpression of both IF types. Desmoplakin-positive true desmosomes were found in 5 specimens. Biochemically, cytokeratins nos. 8, 18 and, variably, 19, as well as IT protein and, in many specimens, the neurofilament L-protein and a putative neurofilament M-protein were detected. Only traces of the neurofilament H-polypeptide were found. Our results show that a coexpression of cytokeratin IFs and neurofilaments in variable patterns is a characteristic feature of cutaneous neoendocrine carcinomas; occasionally, however, neurofilaments may be very scarce. The biological, histogenetic and diagnostic implications are discussed.

Adult↗
PubMed1995

Kinetics of interaction of partially folded proteins with a hydrophobic dye: evidence that molten globule character is maximal in early folding intermediates.

Interaction with 8-anilino-1-naphthalenesulfonate (ANS) is widely used to detect molten globule states of proteins. We have found that even with stable partially folded states, the development of the fluorescence enhancements resulting from such interactions can be relatively slow and kinetically complex. This is probably because initial binding of the dye can induce subsequent changes in the protein structure, so that the ultimate resulting fluorescence enhancement is not necessarily a good, nonperturbing probe of the preexisting state of the protein. When ANS is used to study folding mechanisms the problem is compounded by the difficulty of distinguishing effects due to the development of dye interactions from those due to the changing populations of folding intermediates. Many of these complications can be avoided by experiments where the ANS is introduced only after folding has been allowed to proceed for a variable time. The initial fluorescence intensity after mixing, resulting only from rapid and therefore hopefully relatively nonperturbing interactions with the protein, can be monitored at different refolding times to provide a better reflection of the progress of the reaction, uncomplicated by dye interaction effects. Such studies of the folding of carbonic anhydrase and alpha-lactalbumin have been compared with conventional single-mix experiments and large discrepancies observed. When ANS was present throughout refolding, time-dependent changes attributed to the formation or reorganization of protein-ANS complexes were clearly superimposed on those associated with the actual progress of refolding, and the folding kinetics and population of intermediates were also substantially perturbed by the dye. Thus, it is clear that the pulse method, though cumbersome, should be used where refolding reactions are to be probed by dye binding. The results emphasize that fluorescence enhancement tends to be greatest in early intermediates, in contrast to what, for carbonic anhydrase at least, might appear to be the case from the more conventional experiments. Later intermediates in the folding of both of these proteins actually induce little fluorescence enhancement and therefore may be quite different in nature from equilibrium molten globule states.

Anilino Naphthalenesulfonates↗
PubMed2001

High dose radiation delivered by intensity modulated conformal radiotherapy improves the outcome of localized prostate cancer.

PURPOSE: We present the long-term outcome and tolerance of 3-dimensional (D) conformal and intensity modulated radiation therapy for localized prostate cancer. MATERIALS AND METHODS: Between October 1988 and December 1998, 1,100 patients with clinical stages T1c-T3 prostate cancer were treated with 3-D conformal or intensity modulated radiation therapy. Patients were categorized into prognostic risk groups based on pretreatment prostate specific antigen (PSA), Gleason score and clinical stage. Sextant biopsies were performed 2.5 years or greater after treatment to assess local control. PSA relapse was defined according to the consensus guidelines of the American Society for Therapeutic Radiation Oncology. Late toxicity was classified according to the Radiation Therapy Oncology Group morbidity grading scale. Median followup was 60 months. RESULTS: At 5 years the PSA relapse-free survival rate in patients at favorable, intermediate and unfavorable risk was 85% (95% confidence interval [CI] +/- 4), 58% (95% CI +/- 6) and 38% (95% CI +/- 6), respectively (p <0.001). Radiation dose was the most powerful variable impacting PSA relapse-free survival in each prognostic risk group. The 5-year actuarial PSA relapse-free survival rate for patients at favorable risk who received 64.8 to 70.2 Gy. was 77% (95% CI +/- 8) compared to 90% (95% CI +/- 8) for those treated with 75.6 to 86.4 Gy. (p = 0.04) [corrected]. The corresponding rates were 50% (95% CI +/- 8) versus 70% (95% CI +/- 6) in intermediate risk cases (p = 0.001), and 21% (95% CI +/- 8) versus 47% (95% CI +/- 6) in unfavorable risk cases (p = 0.008) [corrected]. Only 4 of 41 patients (10%) who received 81 Gy. had a positive biopsy 2.5 years or greater after treatment compared with 27 of 119 (23%) after 75.6, 23 of 68 (34%) after 70.2 and 13 of 24 (54%) after 64.8 Gy. The incidence of toxicity after 3-D conformal radiation therapy was dose dependent. The 5-year actuarial rate of grade 2 rectal toxicity in patients who received 75.6 Gy. or greater was 14% (95% CI +/- 2) compared with 5% (95% CI +/- 2) in those treated at lower dose levels (p <0.001). Treatment with intensity modulated radiation therapy significantly decreased the incidence of late grade 2 rectal toxicity since the 3-year actuarial incidence in 189 cases managed by 81 Gy. was 2% (95% CI +/- 2) compared with 14% (95% CI +/- 2) in 61 managed by the same dose of 3-D conformal radiation therapy (p = 0.005). The 5-year actuarial rate of grade 2 urinary toxicity in patients who received 75.6 Gy. or greater 3-D conformal radiation therapy was 13% compared with 4% in those treated up to lower doses (p <0.001). Intensity modulated radiation therapy did not affect the incidence of urinary toxicity. CONCLUSIONS: Sophisticated conformal radiotherapy techniques with high dose 3-D conformal and intensity modulated radiation therapy improve the biochemical outcome in patients with favorable, intermediate and unfavorable risk prostate cancer. Intensity modulated radiation therapy is associated with minimal rectal and bladder toxicity, and, hence, represents the treatment delivery approach with the most favorable risk-to-benefit ratio.

Adenocarcinoma↗
PubMed1993

Screening for gestational diabetes mellitus: a critical review.

Gestational diabetes mellitus (GDM) occurs in 1% to 3% of pregnant women. Generally, the clinical focus in these cases is on intermediate outcomes such as macrosomia, hypoglycemia, or hypocalcemia. Only macrosomia is consistently associated with gestational diabetes, yet the risks of macrosomia such as shoulder dystocia and birth injury are highly variable. The screening test and the reference standard, the oral glucose tolerance test, are problematic in that there are no standardized testing procedures or definitive criteria for diagnostic interpretation and poor reproducibility of test results. There have been no methodologically sound randomized controlled trials of therapy for GDM. Studies that attempted randomization show, however, that therapy reduces the incidence of macrosomia, which is an intermediate outcome. A critical review of the literature revealed that there is insufficient evidence to justify routine screening for gestational diabetes. A reassessment of the relation between maternal glucose levels in pregnancy and neonatal outcomes is needed to determine if there are correctable adverse outcomes. In the meantime, management should be based on careful assessment of each individual pregnancy.

Diabetes, Gestational↗
PubMed1995

Improved cardiac risk stratification in major vascular surgery with dobutamine-atropine stress echocardiography.

OBJECTIVES: This study sought to optimize preoperative cardiac risk stratification in a large group of consecutive candidates for vascular surgery by combining clinical risk assessment and semiquantitative dobutamine-atropine stress echocardiography. BACKGROUND: Dobutamine-atropine stress echocardiography has been used for the prediction of perioperative cardiac risk in a small group of patients scheduled for elective major vascular surgery on the basis of the presence or absence of stress-induced regional left ventricular wall motion abnormalities. METHODS: Clinical risk assessment and dobutamine-atropine stress echocardiography were performed in 302 consecutive patients presenting for major vascular surgery. The extent and severity of stress wall motion abnormalities and the heart rate at which they occurred, in addition to the presence of wall motion abnormalities at rest, were assessed. RESULTS: The absence of clinical risk factors (angina, diabetes, Q waves on the electrocardiogram, symptomatic ventricular tachyarrhythmias, age > 70 years) identified a low risk group of 100 patients with a 1% cardiac event rate (unstable angina). Dobutamine-atropine stress echocardiographic findings were positive in 72 patients. Twenty-seven patients had a perioperative cardiac event (cardiac death in 5, nonfatal infarction in 12, unstable angina pectoris in 10); all 27 patients had positive stress test results (positive predictive value 38%, negative predictive value 100%). The semiquantitative assessment of the extent and severity of ischemia did not provide additional prognostic information in patients with positive test results. In contrast, the heart rate at which ischemia occurred defined a high risk group with a low ischemic threshold (38 patients with 20 events [53%]) and an intermediate risk group with a high ischemic threshold (34 patients with 7 events [21%]). All 5 patients with a fatal outcome and 8 of 12 with a nonfatal myocardial infarction were in the high risk group with a low ischemic threshold. CONCLUSIONS: Clinical variables identify 33% of patients at very low risk for perioperative complications of vascular surgery in whom further testing is redundant. In all other candidates, dobutamine-atropine stress echocardiography is a powerful tool that identifies those patients at intermediate risk and a small group at very high risk. Risk stratification with a combination of clinical assessment and pharmacologic stress echocardiography has the potential to facilitate clinical decision making and conserve resources.

Adult↗
PubMed1986

Histochemical staining characteristics of normal horse skeletal muscle.

The histologic and histochemical staining characteristics of the triceps brachii (long head), extensor carpi radialis, gluteus medius, vastus lateralis, biceps femoris, semimembranosus, semitendinosus, and extensor digitorum longus muscles of 8 Thoroughbreds, 2 Quarter Horses, 1 Arabian, 1 Paso Fino, and 1 Shetland Pony are described. Muscle fiber morphology, staining distribution and intensity, amount of IM connective tissue, number of IM blood vessels and IM nerves, calcium-activated adenosine triphosphatase activity (CaATPase), percentage of fibertype population, percentage of relative fibertype area, mean fiber diameter, nonspecific esterase activity, alkaline phosphatase activity, and acid phosphatase activity were evaluated, using 10 common histochemical and histologic stains. Two fiber types (I, II) and 3 subtypes (IIA, IIB, IIC) were observed, using CaATPase-, nicotinamide-adenine dinucleotide-tetrazolium reductase-, periodic acid-Schiff hematoxylin-, and nonspecific esterase-stained frozen serial muscle sections. Type I muscle fibers in general had low CaATPase activity, high oxidative capacity, low glycogen capacity, and low esterase activity. Type IIA muscle fibers had high CaATPase activity, intermediate oxidative capacity, high glycogen concentration, and high esterase activity. Type IIB fibers had high CaATPase activity, low oxidative capacity, high glycogen concentration, and a high esterase activity. Type IIC muscle fibers had high CaATPase activity, high oxidative capacity, variable glycogen concentration, and high esterase activity. Type II (IIA and IIB) muscle fibers predominated in the muscles. The percentage of muscle fiber population, mean minimal muscle fiber diameter, and percentage of relative muscle fiber area were determined for each sampled muscle. Type IIA and IIB muscle fibers predominated in the percentage of muscle fiber population and percentage of relative muscle fiber area. Type IIB muscle fibers had the greatest minimal fiber diameter, type IIA muscle fibers had intermediate minimal fiber diameter, and type I muscle fibers had the smallest minimal fiber diameter. The percentage of relative muscle fiber area was less variable (P less than or equal to 0.05) than the percentage of muscle fiber population. Mean muscle fiber diameter did not significantly differ between breeds. Alkaline and acid phosphatase activities were at low levels in all muscles biopsied and were limited to the IM connective tissue fibrocytes, macrophages, and capillaries.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed2000

Is there any difference between intermediate-acting and long-acting calcium antagonists in diurnal blood pressure and autonomic nervous activity in hypertensive coronary artery disease patients?

Recently, there have been some reports indicating that calcium antagonists induce a reflex increase in sympathetic activity, triggering cardiac events, especially in coronary artery disease (CAD) patients. In this study, we assessed heart rate (HR) variability (HRV) using power spectral analysis of the 24-h RR interval in 25 hypertensive outpatients with CAD treated with nifedipine. We compared blood pressure (BP), HR, and HRV variation in the same patients substituting benidipine (long-acting) for nifedipine (intermediate-acting). There were no significant differences in 24-h, daytime, nighttime, and morning BP between the nifedipine phase and the benidipine phase. HRV parameters (LF: low frequency power, HF: high frequency power, LF/HF ratio) also showed no significant differences in 24-h, daytime, nighttime, and morning LF, HF, and LF/HF ratio between the nifedipine phase and the benidipine phase. Blood pressure, HR, and HRV parameters, except the LF component from 2 to 4 h after nifedipine administration (the most effective duration), showed no differences compared to before administration. The LF component after the nifedipine administration was lower than before administration. In conclusion, in hypertensive patients with CAD, whose BP levels were well-controlled by twice-daily use of intermediate-acting nifedipine, switching from nifedipine to a long-acting calcium antagonist, benidipine, maintained well-controlled BP levels to a similar degree, but it may not have additional benefit in sympatho-vagal balance.

Autonomic Nervous System↗
PubMed1997

Antigenic and molecular analyses of the variability of bovine respiratory syncytial virus G glycoprotein.

Antigenic variation among eight bovine respiratory syncytial virus (BRSV) isolates was determined using monoclonal antibodies (MAbs) specific for the attachment (G) protein. Two major (and one intermediate) subgroups were identified, as well as one strain that did not fit any pattern. The subgroups could also be differentiated on the basis of the Mr of the F protein cleavage product, F2. The nucleotide sequence of the G gene of seven of the BRSV strains was determined and compared with published G gene sequences. Subgroups A and A/B were more closely related in protein sequence than subgroups A and B or subgroups A/B and B. These results could not be correlated with those obtained by the determination of the Mr of the F2 polypeptide. Multiple sequence alignments showed a high level of amino acid identity at the inter-subgroup level (85% identity between subgroup A and subgroup B strains), similar to the intra-subgroup human (H)RSV identity, suggesting that the BRSV isolates form a continuum rather than distinct subgroups. However, unusual variability was observed within the immunodominant domain (amino acids 174-188) in contrast with the situation in HRSV strains belonging to the same subgroup.

Amino Acid Sequence↗
PubMed1987

Dynamics of the upper urinary tract: II. The effect of variations of peristaltic frequency and bladder pressure on pyeloureteral pressure/flow relations.

The dynamics of pyeloureteral flow is described when there is no peristalsis and for peristalsis of high and intermediate frequencies, on the assumption that the ureter is uniform except in the mid-ureter and at the outlet. The possibility of upstream transmission of bladder pressure variations to the renal pelvis is considered. The overall behaviour depends on three principal variables, the maximum tube pressure in the contraction waves, the intrinsic peristaltic carrying capacity and the peristaltic frequency f, expressed in the form fT where T is the time for a peristaltic contraction wave to sweep through the ureter. At intermediate peristaltic frequencies (fT less than but comparable with one) oscillatory flow patterns can occur, in which periods of peristaltically driven flow alternate with extraperistaltic periods of flow through the open ureter. The kidney is better isolated from bladder pressure variations when the peristaltic frequency is high, but high peristaltic frequency can by itself lead to elevated renal pelvic pressure if the flow rate is high. Experimental observations in pigs are presented to support these conclusions.

Animals↗
PubMed2003

Imbalance between lipoxin A4 and leukotriene B4 in chronic mastitis-affected cows.

Persistent accumulation of inflammatory cells in the udder, with neutrophils being the predominant cell type, is a characteristic feature of chronic mastitis in dairy cows. Leukotriene (LT) B4 is a potent chemotactic agent, known to induce recruitment and accumulation of neutrophils in the bovine mammary gland. The LTB4-stimulated neutrophil functional responses are closely opposed by lipoxin (LX) A4, which promotes the resolution of inflammation. We thus hypothesized that the chronic inflammation of the udder could be associated with an unfavorable ratio between these two eicosanoids and that the persistence of neutrophil accumulation could be due to an increase in LTB4 synthesis and/or an impaired LXA4 production. In an attempt to verify this hypothesis, we first measured LXA4, LTB4, and their ratio in the milk of healthy and acute and chronic mastitis-affected quarters. Next, we studied the relationships between these variables and the degree of udder inflammation as assessed by somatic cell count measurement. The LTB4 concentration was low in healthy quarters, drastically increased in acute mastitis, and reached intermediate levels in chronic mastitis-affected quarters. However, whereas LXA4 concentration was highly increased in acute mastitis, healthy and chronic quarters had similarly low values. The LXA4:LTB4 ratio was thus significantly lower in chronic mastitis-affected cows. The LTB4 concentrations measured in chronic quarters were highly correlated to somatic cell count and to milk neutrophil and macrophage numbers. A weaker correlation was observed between LXA4 and these variables. For both eicosanoids, the highest correlation was observed with the number of neutrophils. These results show the existence of an LXA4:LTB4 imbalance in chronic mastitis-affected cows because of low LXA4 concentrations. Further studies are needed to determine whether administration of LX or stable analogs could have therapeutic potential in the control of chronic bovine mastitis.

Acute Disease↗
PubMed1997

[Multivariate analysis on prognostic factors of non-Hodgkin's lymphoma].

OBJECTIVE: To predict the prognostic factors and to improve the response and survival in intermediate-grade and high-grade non-Hodgkin lymphoma (NHL). METHODS: 200 patients with intermediate-grade and high-grade NHL were treated with chemotherapy. A multivariate Cox model was used to analyse the prognostic factors that significantly affect the treatment outcome. The variables examined included: sex, age, clinic stage of disease, B symptoms, extranodal sites, bone marrow involvement, tumor bulk, performance status (ECOG) and malignancy grades. RESULTS: Multivariate analysis showed that performance status, the number of extranodal sites, pathologic malignancy grade and tumor bulk were significantly independent prognostic factors. These factors were put together to construct a prognostic index formula. The index partitioned the patients into low risk group (PI -2.43(-)-1.30), intermediate risk group (PI -1.29-1.0) and high risk group (PI > 1.0) giving 5-year survival rates of 76.0%, 21.6% and 7.4%, respectively. CONCLUSION: The prognostic index formula and subgroups could serve as a reference to distinguish patients requiring more intensive chemotherapy and autologous stem cell transplantation from those who should be treated with standard regimens in order to improve the prognosis.

Adolescent↗
PubMed2005

Staphylococcus aureus strain designation by agr and cap polymorphism typing and delineation of agr diversification by sequence analysis.

The allelic variations of the regulatory operon agr (groups I-IV) and the cap polymorphism (capsular types 5 and 8) were used as a typing scheme for rapid strain designation in Staphylococcus aureus. In combining 10 agr subgroups resolved by restriction fragment length polymorphism (RFLP) analysis with the two cap polymorphisms 12 types could be defined. To assess whether this type designation is informative for the population structure of the species S. aureus, agr and cap types were determined in clonal lineages defined by pulsed-field gel electrophoresis (PFGE) of a collection of 219 isolates. agr groups and cap types were both linked to certain clone complexes. However, little correlation was found between the two polymorphic loci. By PFGE cluster analysis 11 prevalent and 52 sporadic clones were defined. Most of the prevalent clones (9/11) could be discriminated by agr/cap typing. Thus, this technique allows a first subdivision of isolates and an inter-center comparable designation of S. aureus clones preceding a more detailed clonal analysis by PFGE or multi-locus sequence typing (MLST). To get insight into agr diversification, sequence analysis of the variable and conserved part of agr from selected S. aureus clones was performed. Strains of agr-I displayed the highest sequence divergence on the nucleotide and amino acid level, suggesting an early diversification of this group. When analyzing the relationship between the four agr interference groups we could show: (i) one intermediate between agr-I and agr-IV alleles; (ii) agr-IV sequences seem to bridge the agr-I and -III groups and (iii) two cases of horizontal transfer of the variable gene cassette from an agr-I strain to an agr-II strain. Thus, stepwise evolutionary progression and rare events of recombination were evident in the diversification of the agr locus.

Alleles↗