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PubMed2002

Microstructural properties of bone in rat vertebra after long-term clodronate treatment.

Bisphosphonates (BPs) are known to increase bone mineral density, but it is not known how this increase manifests at low hierarchic levels of the bone structure. The present study aimed to clarify the effects of the long-term use of clodronate on the microstructure and chemical composition of bone. The second lumbar vertebral body (L2) in growing rats, subjected to 32 weeks' treatment with clodronate at either a therapeutic dose of 2 mg/kg, or a high dose of 10 mg/kg, or physiological saline (control group), was studied by scanning electron microscopy for morphology, by backscattered electron image (BSE) for density, and by energy dispersive spectrometry for material analysis. BSE images showed that the degree of mineralization in the different areas of trabecular bone of the vertebral body varied in both the control and the study groups, but this variation seemed to be different in the control and study groups. BSE analysis showed that there was more high-density bone (white area) in the low-dose clodronate group than in the controls, but the difference between the high-dose clodronate group and the control group was not significant. The density of the white area (high-density bone) was slightly increased in the low-dose clodronate group. There were no differences in the density of the gray area (low-density bone) between the groups. Neither the distribution of Ca, P, or Mg, nor the total mineral content, was affected by the clodronate treatment. Our results indicate that long-term clodronate treatment at the therapeutic level increases the proportion of high-density bone in the vertebral body in non-osteoporotic rats.

Analgesics, Non-Narcotic↗

PubMed1997

Effects of angiotensin-converting enzyme inhibitors on anemia and erythropoietin requirements in peritoneal dialysis patients.

In an attempt to assess the effect of angiotensin-converting enzyme inhibitors (ACEIs) on anemia and recombinant human erythropoietin (rHuEPO) requirements in peritoneal dialysis patients, we evaluated 5 patients treated with ACEIs for one year, and the results were compared with data from a control group (N = 5). In response to ACEIs, the mean hemoglobin value decreased progressively, reaching statistical significance after 6 months and thereafter (basal, 10.7 +/- 0.8; month 6, 10.3 +/- 0.9; month 12, 10.3 +/- 0.5 g/dL, p < 0.05), with no variations in the control group. The rHuEPO requirements experienced a progressive increase in ACEI-treated patients, from 4400 +/- 1516 U/week at basal to 8600 +/- 2880 U/week at the conclusion of the study (p < 0.01). Serum erythropoietin concentration remained stable during the study in both groups of patients. In conclusion, rHuEPO requirements necessary to maintain a stable hemoglobin concentration are greater in subjects under ACEI therapy. ACEI may be an important cause of resistance to rHuEPO, an effect not mediated by a decrease in endogenous erythropoietin.

Aged↗

PubMed1998

The monoamine oxidase-A gene and major psychosis in Japanese subjects.

BACKGROUND: Monoamine oxidase (MAO) is a critical enzyme in deamination of biogenic amines and may be involved in the pathophysiology of major psychosis, including mood disorder and schizophrenia. Recently, evidence for genetic association between the MAO-A gene and bipolar mood disorder was obtained in Caucasians. METHODS: We investigated the polymorphisms of the MAO-A gene, which may be related to enzyme activity (T/941/G, A/1609/G), with amino-acid change (A/1609/G), in Japanese patients with bipolar disorder patients (n = 132), unipolar major depression (n = 43), or schizophrenia (n = 95), and controls (n = 169). RESULTS: No difference in the allele frequencies or genotype distribution of the T/941/G variation was observed between any disease group and the control group. As for the A/1609/G variation, no G allele was found in the Japanese subjects. CONCLUSIONS: No evidence for the genetic association between the MAO-A gene and major psychosis was obtained in the Japanese subjects.

Adult↗

PubMed2002

Complexities in ETS-domain transcription factor function and regulation: lessons from the TCF (ternary complex factor) subfamily. The Colworth Medal Lecture.

The ETS-domain transcription factor family can be divided into a series of subfamilies. Elk-1 represents the founding member of the ternary complex factor (TCF) subfamily. By focusing on the TCF subfamily, we can demonstrate the complexities that exist in the function and regulation of ETS-domain transcription factors. This article focuses on Elk-1 in detail and summarizes the functions of other TCFs. The key themes covered include the domain structure of the TCFs, the mechanisms of complex formation with serum response factor, regulation of TCFs by mitogen-activated protein kinase cascades, and transcriptional regulatory properties of the TCFs. Finally, the emerging role of the TCFs in vivo is discussed. A picture is developing indicating that, while these proteins exhibit significant sequence and functional conservation, key differences in their structure and regulation are being identified which may relate to unique functions of these proteins in vivo.

Amino Acid Sequence↗

PubMed2004

Analysis of histamine release assays using the Bootstrap.

The data from several types of bioassays is usually presented as a quotient as an intuitive parameter and a means of comparing results between experiments. For the example we considered here, we look at experiments with an experiment-wide negative control used to generate percent activity quotients from each experimental group. We asked if there was a valid means to statistically evaluate the transformed rather than the raw data. The experimental system chosen was a dose response of the agonist compound 48/80, which causes release of histamine from mast cells, thus providing test data from replicates of n=24. Descriptive statistics, the Ryan-Joiner test for normality of distribution of data, and normal probability plots confirm the normality of the distribution of data at each dose level. In parametric analysis, when the control group was treated as an errorless constant, there was a distinct consistent bias in the standard error of the data of 10% or less, which was not present if the control group's mean was treated as a variable with experimental error. This would be of minor interest in qualitative studies and might be safely ignored, but might be of considerable importance in quantitative assessments of activity using confidence intervals. When using Bootstrap estimates of standard error and probability plots of the bootstrap samples, the transformed data does not deviate significantly from normality. The standard, bias-corrected percentile limits (BCa), and empirical percentile methods gave very similar results when using resampling statistics to generate the transformed data from groups of n=6. Sample size can be as low as n=4 and still provide useful results. Thus, we have shown that resampling (i.e., bootstrap, Monte Carlo method, computer-intensive methods) can produce the data transform as well as provide confidence intervals using this type of raw data in small groups (n=4 to 6), giving improved statistical analysis of the transformed data (ratio estimates) without accepting a bias from methodology ignoring variation in the control group.

Animals↗

PubMed1993

Excretion of urinary enzymes after extracorporeal shock wave lithotripsy: a critical reevaluation.

The excretion of the urinary enzymes alanine aminopeptidase, alkaline phosphatase, gamma-glutamyl-transferase and N-acetyl-beta-D-glucosaminidase, and the 99mtechnetium-diethylenetriaminepentaacetic acid isotope clearance were studied in 35 patients treated with extracorporeal shock wave lithotripsy (ESWL*). Enzyme measurements were made before and consecutively on days 1, 2 and 5, and at 3 months after treatment. A control group investigated at the same intervals was included. Posttreatment enzyme values were not significantly different from those before treatment except for alkaline phosphatase on day 1 after ESWL. Some individuals had short-term increases of enzymuria that were greater than biological variations in the control group. The transient changes of enzymuria after ESWL had no predictive value for kidney function, since no decreased renal function was observed in individual patients with high enzyme excretions after ESWL.

Acetylglucosaminidase↗

PubMed1997

[Influence of growth hormone (GH) and nutrition on neonatal growth].

OBJECTIVE: At present, growth regulating factors in the transition from fetal to postnatal life remain unknown. The purpose of this study was to analyze the influence of GH and nutrition on neonatal growth. PATIENTS AND METHODS: Serum and 24-hour urine GH levels, various anthopometric variables and daily energy and nutrient intake were measured in appropriate (AGA), large (LGA) and small for gestational age (SGA) newborn infants. These variables were measured at 1 (n = 98), 3 (n = 41) and 5 weeks of postnatal age (n = 8). RESULTS: The highest GH levels at the 1st week of postnatal life were obtained in preterm SGA infants (GHs: 61.4 +/- 20.0 microUI/m; GHu: 18.6 +/- 10.3 ng/kg/24 h). GH levels decreased in preterm infants, so that differences between groups failed to be significant at the third and fifth weeks of postnatal life. Urinary GH excretion did not show significant variations in the control group during the study (1st wk 3.0 +/- 3.5; 3rd wk 2.3 +/- 2.7; 5th wk 3.2 +/- 4.7 ng/kg/24 h). Daily protein intake had a direct relationship with both triceps skinfold and weight and head perimeter increase. SGA preterm infants showed a higher fat increase compared to AGA preterm infants. Serum and urinary GH levels were not related to the anthopometric variables studied. CONCLUSIONS: There are differences in GH secretion and body composition between SGA and AGA preterm infants. GH probably does not contribute to neonatal growth.

Anthropometry↗

PubMed1996

Resistance of the normal human microflora to mercury and antimicrobials after exposure to mercury from dental amalgam fillings.

The concentrations of mercury in saliva and feces and the resistance pattern of the gastrointestinal microflora were investigated for 20 subjects. Ten patients, with a mean number of 19 amalgam surfaces, had all amalgam fillings removed during one dental session. Ten subjects without amalgam fillings served as a control group. Saliva and fecal samples were collected before amalgam removal and 2, 7, 14, and 60 days afterward. Mercury levels in saliva and feces correlated significantly with the number of amalgam surfaces. No differences in the resistance pattern of the oral microflora were detected between the two groups. In the amalgam group there was an increase in the relative number of intestinal microorganisms resistant to mercury, ampicillin, cefoxitin, erythromycin, and clindamycin on days 7-14. This was not statistically significant in light of the normal variations of the control group. A significant correlation between the prevalence of mercury resistance and multiple antimicrobial resistance in intestinal bacterial strains was observed.

Adolescent↗

PubMed1993

The effect of chronic and acute exercise on immunity in rats.

The effects of exercise training and acute exercise on the immune system were investigated in rats. For chronic exercise training, the rats ran on a drum exerciser at the intensity of about 60-70% of maximal oxygen consumption (VO2max) for 30 min and then extended up to 60 min per day, 5 days per week for 10 weeks. The rats were at rest for 3 days before sacrifice. The mitogenic activity of spleen lymphocytes to concanavalin A (Con A) and staphylococcal enterotoxin B (SEB) decreased as compared to the sedentary control, while proliferative response to lipopolysaccharide (LPS) increased. The interleukin-2 (IL-2) production in the training group was reduced. The immunomodulatory effect after acute exercise has also been investigated and it showed profound enhancement of cell proliferation to Con A, SEB and LPS in mild (50% VO2max for 10 min) and moderate (70% VO2max for 10 min) exercise groups. The enhancing activity was less prominent after severe exercise (> 75%) VO2max until exhaustion). The IL2 production increased in all of these acute exercise groups. Nevertheless, there was no significant variation between exercise and control groups in the cell number per spleen and the percentages of various lymphocyte populations, i.e., total T, CD4+, CD8+ and IL-2R+ T cells as well as B cells. In summary, this study indicates that chronic exercise training may cause the reduction of T cell activity while acute exercise manifests an enhancing effect. However, B cell proliferation was elevated in both chronic and acute exercise groups.

Animals↗

PubMed1995

[The analysis of the gastric mucosa by computerized densitometry].

An analytical method of histologic imaging of the gastric mucosa by computerized densitometry based on the extraction of components of an image on the basis of its luminous density is described. A group of 10 healthy controls, a group of 10 subjects with gastric ulcer and 10 with duodenal ulcer were included in the study. The method was particularly useful in the identification of atrophic and hypertrophic processes. A decrease was found in the density of parietal and chief cells in atrophic gastritis of the gastric body. In atrophic gastritis of the gastric antrum a decrease was observed in global cell density of the antrum. Patients with gastric ulcer did not present variations versus the control group. In those with duodenal ulcers an increase was observed in the density of surface cell of the gastric body with no variation in the density of parietal and principal cells. This finding challenges the classical concept on the increase in parietal cell mass accompanying duodenal ulcers.

Adolescent↗

PubMed1997

Ultrasonic videodensitometric analysis of two different models of left ventricular hypertrophy. Athlete's heart and hypertension.

Absolute or relative increases in intramyocardial fibrosis accompany hypertrophy development in human hypertension. Myocardial texture analysis of two-dimensional echocardiographic gray-level distribution has been shown to identify alterations attributed to abnormal collagen content in several conditions. Therefore, this echocardiographic tool might help to identify those hypertensive individuals with abnormal interstitial collagen deposition, a condition that may promote and/or aggravate morbidity in this group of people who are at high risk for cardiovascular events. We compared male essential hypertensive subjects who had marked cardiac hypertrophy (left ventricular mass index adjusted for height > 2 SD of mean of control group) (group 1) with normotensive elite veteran athletes who had comparable cardiac hypertrophy (group 2) and sedentary normotensive subjects as controls (group 3). The groups (n = 14 each) were matched for age (+/- 2 years) and sex. We analyzed echocardiographic digitized data quantitatively by means of a calibrated 256 gray level digitization system to calculate midseptal and midposterior end-diastolic and end-systolic mean gray levels and to derive the so-called cyclic variation index, ie, the percent mean gray level variation during the cardiac cycle. Echocardiographic parietal and septal thicknesses and masses were evaluated according to the Penn convention. Left ventricular mass index (adjusted for height) overlapped between groups 1 and 2 (187.1 +/- 17.5 and 181.3 +/- 19.3 g/m, respectively; P = NS), whereas it was obviously smaller in control subjects (93.1 +/- 18.6 g/m; P < .001 for both). According to inclusion criteria, both septal and posterior wall thicknesses were comparable in athletes and hypertensive subjects, and they were higher than in the control group (P < .0001). The hypertensive subjects showed a significantly lower cyclic variation index than the control and athlete groups for both the septum (P < .001) and posterior wall (P < .001); no statistical difference was found between athletes and control subjects for this parameter. In conclusion, abnormalities of two-dimensional echocardiographic gray-level distribution are present in hypertensive hypertrophied individuals but seem unrelated to the degree of echocardiographic hypertrophy as such. An altered collagen network distribution or a decrease in capillary distribution in severe myocardial hypertrophy, secondary to pressure-volume overload in hypertension with other yet unknown mechanisms, could help to explain our findings. Further work is needed to establish the prognostic, clinical, and therapeutic implications of these findings.

Analysis of Variance↗

PubMed1980

Praecordial ECG-mapping in acute anterior myocardial infarction: the variability of ST segment, Q and R waves.

Praecordial ECG-mapping (forty-two unipolar leads) was carried out on sixteen patients with anterior acute myocardial infarction (AMI) and on ten control patients without AMI. The variability, chronometric changes and the error-of-measurement when measuring sigma ST, sigma Q and sigma R in an ECG-map were evaluated. The investigation demonstrated that there was a significant inter-individual variation of sigma ST, sigma Q and sigma R in both patient groups. In cases of AMI, the intra-individual variation of sigma St, sigma Q and sigma R was significantly greater than the variation in the error-of-measurement; this applied also to the control group, except for sigma ST which was of the same magnitude. Inducing measuring errors, which were brought about by changes in the position of the patient, were of the same magnitude as the itra-individual variation in the control group. The chronometric variation of sigma ST, sigma Q and sigma R were significant in the patients with AMI; this also applied to sigma ST in the control group, but not to sigma Q and sigma R. In patients with AMI, sigma ST and NST were correlated to heart rate, mean arterial blood pressure, the product of heart rate and systolic blood pressure, and respiratory rate. However, only the correlations between heart rate and sigma ST and NST, respectively, were of such a magnitude that they were of clinical relevance. Thus 37-42% of the variance in the ST segment within 14 days after the onset of the infarction can be explained by changes in the heart rate.

Adult↗

PubMed2006

Variations of the Amnionless gene in recurrent spontaneous abortions.

Recurrent spontaneous abortions (RSA) are estimated to affect 0.5-1% of couples trying to have a child. The causes of RSA are unknown in the majority of cases. This study aimed to determine whether homozygous mutations in the AMN gene in a fetus cause spontaneous abortions in humans, as they are known to cause spontaneous abortions in mice. The study was conducted by screening 40 couples and 5 women with three or more unexplained spontaneous abortions for heterozygous mutations in the AMN gene using denaturing high-performance liquid chromatography. Altogether, 3 exonic and 11 intronic sequence variations were found. There were no significant differences in the frequencies of the variations between the patients and a control group. One of the exonic variations was non-synonymous, and three of the variations may affect gene splicing. None of the putative phenotype-affecting variations were found in both partners in any couple. These results indicate that RSA in the couples studied cannot be explained by homozygous AMN mutations in the fetus. However, two couples had different, potentially deleterious variations in both partners. If these variations have a phenotypic effect, the RSA experienced by these couples may be caused by mutations in the AMN gene. In addition, birthplaces of the patients' ancestors revealed some clustering, suggesting that some patients may carry a founder mutation in another gene which may contribute to RSA.

Abortion, Habitual↗

PubMed1995

Comparison of the effects of nerve growth factor and superoxide dismutase on vascular extravasation in experimental burns.

Superoxide dismutase (SOD), a free-radical scavenger, inhibits the increase of vascular permeability in experimental burn lesions in rats. In this study the aim was to determine whether Nerve Growth Factor (NGF), which has been implicated in the modulation of some inflammatory reactions, behaves in an analogous way. The study compares the haematocrit (Ht) and haemoglobin (Hb) variations in three groups of rats treated respectively with saline solution, SOD and NGF, immediately after causing a 25 per cent dermal burn injury. Statistical comparison (Student's t test) of the Ht and Hb variations between the Control group (Ht and Hb increase) and the NGF group (Ht and Hb decrease), shows significant differences in the intervals between 15 and 60 min (P < 0.01) and between 60 and 120 min (P < 0.05). Although SOD is able to control extravasation in the immediate postburn period (basal-15 min), NGF has a comparable effect in subsequent periods. The overall action of NGF shows that this agent is able to maintain Ht and Hb values at basal levels even after 120 min postburn. These results seem to be the first evidence of an inhibitory effect of NGF on the vascular permeability in burn lesions.

Animals↗

PubMed1989

Plasma sex steroids and SHBG in patients with breast cancer and their relation to tumor oestrogen-dependency.

In order to evaluate the possible role of sex steroids in breast cancer and their relation to the presence of oestradiol receptors (ER), ER were quantified in 112 breast adenocarcinomas and 14 benign tumours. The sex hormones of the patients were determined in plasma: oestradiol (E2), progesterone, testosterone, androstenedione, as well as SHBG and gonadotrophins. The ER were evaluated in cytosolic and nuclear fractions. Steroids and gonadotrophins were determined by RIA. SHBG was determined by following a procedure of saturation with tritiated dihydrostestosterone. The mean levels of E2 in postmenopausal women with breast cancer was found to be significantly higher than of the control group. However, no significant variations for the rest of the steroids were seen among the patients with breast cancer and the control group or benign tumour. Nor was any relation found between the presence of ER and the hormonal steroids studied or SHBG. It is suggested that the possible influence of the sex steroids in the etiopathogenesis of breast cancer might be due to the greater production accompanied by a parallel metabolic clearance that would maintain their plasma levels.

Adenocarcinoma↗

PubMed2000

Seasonal variation in heart rate variability in asthmatic children.

Asthma is a "seasonal disease" with symptoms either aggravated by environmental changes during specific seasons or prevalent at certain times of the year for other reasons. We examined whether the heart rate variability (HRV) of asthmatic children changes by season. The HRV during a portion of one night (00:00-04:00) and day (12:00-16:00) and the entire 24h period (00:00-24:00) during each of the four seasons was analyzed. The data of 95 children with asthma and 106 healthy children, as controls, were assessed. In children with asthma during the 24h period, seasonal variation in the low-frequency (LF) band (0.04-0.15 Hz) and the high-frequency (HF) band (0.15-0.4 Hz) were detected (HF: F=6.81, p=.0003; LF: F=4.18, p= .008). The HF value in the summer was significantly higher than in autumn and spring (Scheffe test: autumn vs. summer, s = 4.46, p < .001: spring vs. summer, s = 2.86, p < .05), while the LF value in autumn was significantly lower than in summer (s = 3.42, p < .01). In the control group, no seasonal variation in HF, LF, or LF/HF was detected. The findings infer the HRV, a surrogate measure of autonomic nervous system function, of asthmatic children is more susceptible to seasonal changes brought about by either endogenous annual rhythms or environmental weather phenomena.

Adolescent↗

PubMedDate not supplied

[Effects of lobectomy on the auditory mid-latency response in temporal lobe epileptic patients].

AIM: Auditory mid-latency response (MLR) has been studied in temporal lobe epileptic patients in order to evaluate the relationship between the different components of this evoked response and their probable generators in the most rostral part of auditory pathway. PATIENTS AND METHODS: MLR was studied in eight patients with temporal lobe epilepsy before lobectomy, and 1, 6 and 12 months after the surgical treatment, and eight healthy subjects matched for age and gender. Recording electrodes were placed in Cz, T3 and T4 according to the international 10-20 system. Comparisons were carried out in terms of peak to peak amplitude, latency and interpeak intervals of the main components (Mann-Whitney U test, Wilcoxon test). RESULTS: Epileptic patients showed statistically significant prolonged latency of all components, and increased Pa-Pb interpeak interval duration respect to control group. No significant variations were found in the amplitude of the studied components. There were no differences between left and right lobotomized patients. However, a marked tendency to the shortening of latency was observed in the left group after the surgical treatment. CONCLUSIONS: The differences between the pre-surgical records of patients and controls reflect an impaired activity in the generating areas for MLR components. There appears to be a trend to a different behaviour after right or left lobectomy, probably related to the extension of the removed tissue.

Adult↗

PubMed1990

Prolonged treatment (18 months) of chronic hepatitis C with recombinant alpha-interferon in comparison with a control group.

The effectiveness of recombinant alpha-interferon was evaluated in chronic non-A, non-B hepatitis of parenteral transmission. Thirty patients were randomly allocated two groups: control group (without treatment) and treatment group (alpha-interferon 5 mega units thrice weekly for 2 months, and then 1.5 mega units until the eighteenth month). Retrospectively, 26 patients had anti-hepatitis C antibodies. After the first month, 40% of the treated patients had normal serum alanine aminotransferase levels, and no one in the control group (p less than 0.05). After 18 months of treatment, 40% (6/15) of treated patients and 7% (1/14) of controls had normal serum transaminases (p less than 0.05). Interferon was well tolerated. A decrease in the Knodell Index score on final biopsy was found in treated patients (p less than 0.05), with no variations in the control group. Relapse within 7 months after the end of treatment occurred in two out of six complete responders. Thus, recombinant alpha-interferon therapy given for 18 months normalizes serum transaminases and improves histological lesions in chronic hepatitis C of parenteral epidemiology. This long-term interferon schedule is well tolerated.

Adult↗