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Biomedical subjects

A Bertuzzi

Publications and source records attributed to A Bertuzzi.

At least 55 records · Page 3Linked to original sources

Estimation of cell DNA synthesis rate from flow-cytometric histograms.

The rate of DNA synthesis along S-phase can be estimated on the basis of a simple model of a cell population, from a single FCM histogram under conditions of balanced exponential growth, and from two histograms suitably spaced in time under conditions of locally exponential S-phase influx. An algorithm that constructs a piecewise constant approximation of the synthesis rate and estimates the phase fractions from a single histogram is presented. The results of the application of the algorithm to a set of computer generated histograms in balanced exponential growth are reported.

Animals↗

Peristaltic transport of a solid bolus.

An analysis of the peristaltic propulsion of a solid spherical bolus enclosed in a contractile membrane is presented. The model is based on in vitro preparations of intestinal segments, and utilizes a simplified representation of the mechanical properties of the muscular coats of the wall. The sequence of deformed configurations of the membrane and the displacement of the bolus are obtained by numerical solution of the model equations. The analysis presented in this paper could be useful for other studies in biomechanics (e.g. uterine contraction and motion of red blood cells in narrow capillaries).

Gastrointestinal Motility↗

Some parameters of descending inhibition during colonic propulsion.

Isolated segments of rabbit distal colon were stimulated by distension of intraluminal balloons, with the aim of investigating the electrophysiological pattern of descending inhibition (DI) during the peristaltic reflex. Incidence, duration, and latency of DI were studied by varying the parameters of stimulation. A linear correlation was found between stimulus duration and DI duration for stimuli up to 10 s long. DI duration increased with the distance of the recording site from the stimulus up to 3 cm. A more complex relation was found between balloon volume and DI duration. Propagation velocity decreased with the distance from the stimulus. The relation between ascending excitation and DI was also studied: ascending excitation could always be suppressed by DI. DI was examined after addition of anticholinergics, ganglionic blocking agents, and tetrodotoxin to the organ bath. The results show that DI parameters are partially related to the stimulus characteristics and that propagation of DI is neurally mediated through nonadrenergic inhibitory nerves.

Animals↗

Evaluation of doxorubicin cardiotoxicity in patients treated intermittently with beta-methyldigoxin.

Twenty-one patients with various advanced neoplasms were treated with 60 to 75 mg/m2 of doxorubicin every 3 to 4 weeks and monitored by ECG and systolic time intervals (PEP/LVET) with the aim to establish whether a pretreatment with beta-methyldigoxin, administered intermittently, could prevent doxorubicin-induced cardiotoxicity. It was found that until patients received digitalis pretreatment the PEP/LVET ratio did not change significantly from mean basal values even after the highest cumulative dosages of doxorubicin. However, after interruption of the therapy with both drugs, PEP/LVET increased reaching a value not significantly different from that observed in a comparable group of patients treated only with doxorubicin. Moreover, of 9 patients who reached the cumulative limiting dose, 2 developed congestive heart failure. These results question the possibility that digitalis administered according to an intermittent treatment scheme may prevent doxorubicin cardiomyopathy.

Adolescent↗

Relationship among estrogen receptors, proliferative activity and menopausal status in breast cancer.

Kinetic and estrogen receptor (ER) determinations were performed on 357 primary breast cancers. The proliferative activity of the cell population was determined by the autoradiographic technique and expressed as [3H]thymidine labeling index (LI): the ER status was assessed by the absorption charcoal technique. From the overall analysis of the relationship between proliferative activity and ER status, by using the median LI value as cutoff of low and high proliferating tumors, a correlation between ER + status and low proliferative activity and between ER- status and high proliferative activity was observed in 64% of the cases. Menopausal status proved to be an important determinant of kinetic and ER features. In fact, the proliferative activity was always higher in ER--tumors than in ER + tumors within the same menopausal group, and a decrease in proliferative activity was observed from premenopause to postmenopause within ER + and ER--tumors. The analysis of the relation between ER levels and proliferative activity in ER + tumors also evidenced three main ER/LI clusters significantly related to premenopause, paramenopause and postmenopause. A particular indication of nodal involvement was evidenced for a cluster of tumors with low ER levels and high LI from postmenopausal patients. The three different, previously proposed kinetic groups of potential relevance for prognostic and therapeutic purposes were confirmed and more precisely defined by considering not only premenopause and postmenopause but also paramenopause.

Adult↗

Estrogen receptors in renal carcinoma.

The presence of estrogen receptors was determined in 31 cases of renal carcinoma by use of the charcoal absorption technique. In 26 of these cases, the 'normal' counterpart of the same kidney was also studied. In 13 normal and in 19 neoplastic samples, the values were undetectable; in the other cases, the values were very low. Progesterone and dihydrotestosterone receptors were also studied in four cses (both normal and neoplastic tissue) by use of a gel-filtration assay: all the samples were negative. These findings do not support the presence of significant amounts of estrogen receptors in kidney carcinoma.

Charcoal↗

Clinical data and estradiol receptor evaluation in breast cancer biopsies.

To determine the correlation between the response to the estradiol receptor test and some fundamental properties of the tumor and the host, a study was conducted on 337 patients. Primary carcinomas, including lobular carcinomas, and recurrences or metastases are characterized by similar frequencies of response to the estradiol receptor test (68% positive, 26% negative and 6% borderline), while normal breast tissue is characterized by a higher frequency of negative results (3% positive, 71% negative and 26% borderline). Postmenopausal patients show a shift of estradiol receptor levels towards higher values with respect to premenopausal patients. Contemporaneously, an increase in estradiol receptor concentrations with patient age is observed. The clinical stage appears in influence estradiol receptor content only in postmenopausal patients, for whom an increase in the tumor size is accompanied by a decrease in the estradiol receptor levels. The apparent association constant of the receptors assumes values ranging from 1.5 to about 300 X 10(9) M-1 and does not appear to be related to either the type of tumor tissue or to the clinical stage of the tumor, age, or menopausal status of the patients.

Adult↗

Evaluation of cardiac activity and pharmacokinetic analysis of 3H-adriamycin in patients pretreated with beta-methyldigoxin.

The consequences at the cardiac level of adriamycin treatment alone or in association with the cardiac glycoside beta-methyldigoxin, were evaluated with reference to the PEP/LVET ratio, heart rate, and minimum blood pressure. The variation usually seen in the PEP/LVET ratio when adriamycin is administered alone was not observed when pretreatment with beta-methyldigoxin was also given. A similar situation is found with variations in blood pressure and heart rate. From a pharmacokinetic point of view, this treatment scheme does not seem to affect the general behavior of the antibiotic.

Adult↗

An analysis of the peristaltic reflex.

A mathematical model describing the dynamics of the peristaltic reflex in an isolated intestinal segment is presented. The model is referred to a preparation that makes it possible to record the relevant mechanical and electrical variables during the course of the reflex. A simplified representation is used for the structure and the operation of the intrinsic nervous plexus, but the interaction between mechanical and elctrical events appears quite clearly and some features of the experimental data are well predicted.

Biomechanical Phenomena↗

Peristalsis in distal colon of the rabbit: an analysis of mechanical events.

The mechanical behavior of isolated segments of rabbit distal colon was studied by experimental and theoretical techniques. The isometric isovolumic preparation was adopted to obtain records of endoluminal pressure, force, and wall morphology during 59 spontaneous and 53 electrostimulated peristaltic contractions. On strips of longitudinal and circular muscle, excised from the same segments, the tension-velocity and tension-length relationships were also measured. To describe mechanical events occurring during propulsion, a mathematical model was developed that incorporates the measured characteristics of the muscle. In response to given waveforms for the activation of the two muscular coats, the solution of model equations provides the time courses of pressure, force, and wall morphology. A number of parameters measured in the experimental contractions (e.g., pressure and force peaks, time lag between the stimulus and the peaks, velocity of progression of the peristaltic wave) were compared with model outputs, and a similar pattern of response was found. Therefore the model made it possible to relate segment and strip experimental data and to investigate the temporal and quantitative relationship between the contraction of longitudinal and circular layer.

Animals↗

An improved criterion for the evaluation of estrogen receptor binding data in human breast cancer.

The evaluation of the data is an important step in performing the estrogen receptor test. For this reason an effort has been made to derive a more reliable threshold criteria. Among the parameters considered, Xo, Ka, and BI%, only the former 2 appear to be suitable to allow a proper evaluation of the results. From the analysis of different types of carcinomatous or normal breast specimens, limit values of these parameters have been recovered for positivity and negativity of the estrogen receptor test. We found all the samples showing Ka less than 1.5 x 10(9) M-1 or Xo less than 5 fmol/mg proteins to be negative, those characterized by low values of both the parameters were borderline, and all the remaining ones were positive.

Breast Neoplasms↗

Transvaginal assessment of fetal anatomy at 11 to 16 weeks of gestation in relation to fetal position.

OBJECTIVE: To investigate the ability of the high-frequency transvaginal scanning technique to assess embryo-fetal anatomy in early pregnancy in relation to fetal position and in comparison with transabdominal scan. METHODS: A study population of 1,402 pregnant women were examined by transvaginal ultrasonography performed at 10(+1) to 16(+0) weeks of pregnancy. At 14(+1) to 16(+0) weeks of gestation, an ultrasonographic examination was performed in 247 pregnant women by transvaginal and transabdominal route. The criteria necessary for an adequate visualization of fetal organs and structures were met. RESULTS: The visualization rate of complete fetal anatomy increased with increase in menstrual age and fetal position affected this possibility. A detailed brain anatomy was more easily viewed with the fetus in the cephalic or transverse position than in the breech position, whereas the thoracic and abdominal anatomy were viewed more easily with the transverse position compared to the cephalic or breech position. Complete surveys of fetal anatomy were possible in 50% and 62% of women with transabdominal scan and in 85% and 85% with transvaginal one at 15 and 16 weeks' gestation, respectively (p < 0.001). CONCLUSION: A detailed assessment of fetal structures was possible in most cases at 13 weeks of gestation. Fetal position can influence this capability. At 14(+1) to 15(+0) weeks' gestation more anatomical surveys were completed with a transvaginal scan compared to a transabdominal one and this was influenced by fetal position.

Female↗

Tissue uptake and oxidation of disodium sebacate in man.

In order to better ascertain its possible use as an alternative fuel substrate in total parenteral nutrition, sebacate (Sb) metabolism was studied in seven overnight-fasting healthy male volunteers, who received a constant iv infusion (99 mmoles over 8 hours) of disodium sebacate. Sb oxidation rate was determined using an isotopic sebacate (disodic salt of (1-10)14C-sebacic acid) infusion (100 mu Ci from the fourth to the eighth hour of the cold sebacate infusion). Blood samples were collected during and after sebacate infusion at intervals of 30 minutes and Sb serum concentrations were determined by high performance liquid chromatography. Excreted radioactivity (mu Ci/min) was measured by bubbling the expired air into an apparatus containing 3 mEq hyamine to trap CO2 from a 20-L Douglas-bag. CO2 production and O2 consumption were measured before and at 4 and 8 hours after starting the infusion. Twenty-four hour nitrogen excretion with urine was obtained. The RQ and the percent of calories derived from lipid oxidation were calculated by indirect calorimetry. The Sb serum level at the plateau phase was (mean +/- SD) 4.54 +/- 0.71 mumole/mL, the overall rate of tissue uptake was 180.89 +/- 4.50 mumole/min, and the percent oxidation was 6.14 +/- 0.44%. At the end of Sb infusion the RQ dropped to 0.839 +/- 0.043, the percent of calories due to sebacate oxidation was 1.59 +/- 0.52%, and the calories derived from lipids increased to 37.77 +/- 12.90%. These data show that a definite amount of the sebacate infused is oxidized in human tissues.

Adipates↗

Pharmacokinetic analysis of dodecanedioic acid in humans from bolus data.

BACKGROUND: Excretion and tissue uptake of dodecanedioic acid (C12), a proposed alternative fuel substrate, was investigated in humans by bolus experiments. METHODS: Seven overnight-fasting healthy male volunteers received i.v. a bolus (1 g) of C12. Blood samples were collected after C12 administration at intervals of 15 minutes, and C12 serum concentration was measured by high-performance liquid chromatography. C12 excretion in 24-hour urine was measured. Binding of C12 in human serum was determined in separate equilibrium dialysis experiments by means of an isotopic compound (disodic salt of (1,12)14C-dodecanedioic acid). A two-compartment model was used for describing C12 kinetics. RESULTS: The excreted amount of C12 in 24-hour urine was found to be, on the average, 1.62% of administered dose. The apparent number of binding sites per albumin molecule was 3.1 +/- 0.2 (estimate +/- SE) with an affinity constant of 6.4 +/- 1.8 mM-1. The distribution volume of central compartment was 5.56 +/- 3.13 L and that of peripheral compartment was 87.4 +/- 30.4 L. The rate constant of exchange between compartments was 4.60 +/- 3.50 L/min, that or urinary excretion 25.6 +2- 15.5 mL/min, and that of tissue uptake 2.17 +/- 0.86 L/min. CONCLUSIONS: These results are promising for C12 utilization in parenteral nutrition, because C12 elimination in urine is low whereas tissue uptake appears to be rather efficient.

Binding Sites↗

Pharmacokinetics of sebacic acid in rats.

The pharmacokinetics of disodium sebacate (Sb) was studied in Wistar rats of both sexes. Sebacate was administered either as intra-peritoneal (i.p.) bolus (six doses ranging from 10 mg to 320 mg) or as oral bolus (two doses: 80 and 160 mg). Plasma and urinary concentrations of Sb and urinary concentrations of Sb and its products of beta-oxidation (suberic and adipic acids) were measured by an improved method using gas-liquid chromatography/mass-spectrometry. A single compartment with two linear elimination routes was selected after no increase in significance was shown by an additional compartment and after a saturable mechanism was found to be unsuitable. Both renal and non-renal elimination parameters were obtained by Marquardt non linear fitting of plasma concentrations together with urinary elimination. The data reported are calculated from the analysis on the whole population of rats and referred to an average body weight (bw) of 100 g. The Sb half-time was 31.5 min. The tissue elimination rate was 0.0122 min-1. The overall volume of distribution was found to be 26.817 ml/100 g bw. The renal clearance was 0.291 ml/min/100 g of bw, which is much less than the value of GFR reported in literature (about 1 ml/min/100 g bw), suggesting the presence of Sb reabsorption from the ultrafiltrate. The value of Sb renal clearance was found to be a concentration-independent function, suggesting the presence of a passive back-diffusion. The relative bioavailability of the oral form compared to the i.p. form was 69.09%, showing a good absorption of the drug.

Administration, Oral↗