Biomedical subjects
Publications and source records attributed to A Bertuzzi.
The ablation of a post-traumatic superficial corneal nodule with an argon fluoride excimer laser is reported. Three months postoperatively the area had a smooth surface with no distortion of adjacent cornea.
After a mean follow up of 19 months, the visual characteristics of eyes with bifocal diffractive intraocular lenses (IOLs) ("bifocals") in one eye were compared with those of fellow eyes with monofocal IOLs ("monofocals") in 29 bilateral pseudophakic patients. All of the eyes had a distance-corrected acuity of 0.6 or more, but 24.1% of the bifocals and 48.3% of the monofocals had an acuity of 1.00. Near acuity with distance correction was J2 or more in 93.1% of the bifocals and in 17.4% of the monofocals (without correction: 79.3% and 41.4%, respectively). In 55.2% of the bifocals and 20.7% of the monofocals, the combined uncorrected acuity was 0.5 or more for distance and J2 or more for near. Fogging revealed a similar depth of focus in the monofocals and a similar distance focus in the bifocals. The bifocals had two peaks of acuity but no "plateau" between them. The eye with the monofocal IOL was preferred by 37.9% and the eye with the bifocal IOL by 10.3%. Vision in no eye was rated "poor." Visual disturbances were more frequent in the bifocals. No glasses were prescribed for 20.7% of all of these patients; 65.5% required bifocal glasses; 44.8% managed most of daytime without glasses.
Azelaic acid was the first dicarboxylic acid proposed as an alternative energy substrate in total parenteral nutrition. In this study, the pharmacokinetics of azelaic acid were investigated in 12 healthy volunteers, 7 receiving a constant infusion (10g over 90 min) and 5 a bolus dose (1g). The 24h urinary excretion and plasma concentration in blood samples taken at regular intervals were assayed by gas-liquid chromatography. Experimental data were analysed by a 2-compartment nonlinear model that describes both tubular secretion and cellular uptake in Michaelis-Menten terms. A high value of urinary excretion (mean 76.9% of infused dose) and a mean clearance of 8.42 L/h were found, suggesting the presence of tubular secretion. Estimating the population mean of the pharmacokinetic model parameters gave a maximal cellular uptake of 0.657 g/h. The model predicts that 90% of the maximal uptake should be reached in the plateau phase of a constant infusion of 2.2 g/h. The presence of extensive and rapid losses through urinary excretion, and the low estimated value of the maximal cellular uptake, indicate that azelaic acid is not suitable as an energy substrate for total parenteral nutrition.
We studied the in situ binding of propidium iodide to DNA in fixed human lymphocytes, using flow cytometry. Experimental data of fluorescence emission vs dye concentration and vs cell concentration were obtained. Data were interpreted by means of two different mathematical models specific for the staining reaction, and the binding parameters were obtained by "best-fitting" of the data. A model based on two classes of binding sites with different affinity constants gave the most satisfactory fitting. The accessibility of the in situ chromatin turned out to be reduced with respect to the non in situ accessibility for ethidium bromide as reported in the literature. The present study shows the usefulness of the flow-cytometric technique for probing DNA structure in intact cells.
The in vitro spontaneous mechanical and electrical activity of the non-pregnant rat uterine horn was investigated. An isometric isovolumic preparation was used to obtain records of intraluminal pressure, axial force, extracellular electrical activity and horn morphology. Mean intraluminal pressure was 28.6 cmH2O and mean force 2.5 g. Burst electrical activity was initiated at the ovarian end in 70% of the cases. Detailed analysis of electrical and mechanical events during a single contraction showed a preparatory phase involving the longitudinal muscle layer, followed by a stronger contractile event involving both longitudinal and circular layers. Moreover, the mechanical activity was modulated at the frequency of a component (0.16-0.20 Hz) of the slow electrical activity of the horn. Burst electrical activity appeared at five equidistant electrodes along the horn with variable delays: the highest delays (mean values 7.4 s for burst activity initiated at the ovarian end and 6.5 s at the vaginal end) were observed in the middle part of the horn. The spontaneous contraction of the segment appeared to be due to the activation of separate regions of the horn (i.e. an ovarian and a cervical region), more than to a propagated excitatory action.
Lonidamine (LND), an indazole-carboxylic acid derivative, was delivered alone and together with adriamycin (ADM) or hyperthermia to the human melanoma cell line M14, and cell survival was assessed. Cell cycle-specific effects were investigated by analyzing sequences of DNA content histograms by means of a suitable mathematical procedure. LND delivered for 1 h at a dose of 50 micrograms/ml did not affect proliferation and survival of the cells. Exposure of the cells for 1 h to ADM (1.0 microgram/ml) followed by LND for 1 h (50 micrograms/ml) produced the highest effect on the survival. Kinetic parameters were affected by the combined treatment slightly more than by ADM exposure alone. Simultaneous delivery of LND (50 micrograms/ml) with hyperthermia (42 degrees C, 1 h) reduced the survival and enhanced the block of cells in the G2M phase, as compared with the heat treatment alone. The effect of the treatments on cell survival appeared to be related to the perturbation of the G2M phase of the cycle.
The lithogenic character of human gallbladder bile was investigated by a mathematical model on the basis of a clinical data set. Each bile was described by means of the quaternary system bile salts--phospholipids--free fatty acids--cholesterol. Reporting a set of bile samples on the tetrahedron of concentrations, a clear separation emerged between the control bile, the bile from patients with gallstones, and the bile of subjects with gallbladder dyskinesia. This group was characterized by a largely increased content of free fatty acids.
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The rate of DNA synthesis along S phase is estimated from flow cytometric histograms on the basis of a mathematical model of a cell population. In the absence of loss, the model expresses the population kinetics in terms of DNA synthesis rate, S-phase influx, and population size. A single histogram is sufficient to determine the DNA synthesis rate when the population is in balanced exponential growth. Two suitably chosen histograms are necessary if the S-phase influx is exponential in a time interval longer than the S-phase duration. The analysis procedure was tested on published autoradiographic data and applied to three cultured cell lines (CM-S, 3LL, and M14 cells) that show various patterns of DNA distribution. In each case the cell-cycle fractions, the DNA synthesis rate, and the S-phase duration were obtained.
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A general expression for time sequences of DNA-fluorescence histograms from flow microfluorometry is given in this paper. Such expression is given in terms of the law of DNA growth along S phase, the flux of cells into S, and the efflux out of M. Special conditions of growth (e.g. the exponential steady-state growth), and the case of blocks in S phase are also analyzed. Some simulations of the expressions obtained are presented.
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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.
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).
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.
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.
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.
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.