Advanced lung ventilation system (ALVS) with linear respiratory mechanics assumption for waveform optimization of dual-controlled ventilation.

The present paper describes the functional features of an advanced lung ventilation system (ALVS) properly designed for the optimization of conventional dual-controlled ventilation (DCV), i.e. with pressure-controlled ventilation with ensured tidal or minute volume. Considering the particular clinical conditions of patients treated with controlled ventilation the analysis and synthesis of ALVS control have been performed assuming a linear respiratory mechanics. Moreover, new airways pressure waveforms with more physiological shape can be tested on simulators of respiratory system in order to evaluate their clinical application. This is obtained through the implementation of a compensation procedure making the desired airways pressure waveform independent on patient airways resistance and lung compliance variations along with a complete real-time monitoring of respiratory system parameters leading the ventilator setting. The experimental results obtained with a lung simulator agree with the theoretical ones and show that ALVS performance is useful for the research activity aiming at the improvement of both diagnostic evaluation and therapeutic outcome relative to mechanical ventilation treatments.

Involvement of EGF in medroxyprogesterone acetate (MPA)-induced mammary gland hyperplasia and its role in MPA-induced mammary tumors in BALB/c mice.

In previous papers we have demonstrated that sialoadenectomy inhibited MPA-induced mammary tumorigenesis in BALB/c mice. To further explore the role of EGF in this experimental model, we evaluated its effects on mammary glands of sialoadenectomized (sialox) MPA-treated female mice and on tumor growth. MPA-treated sialox mice were injected s.c. (n = 3) or not (n = 6) with 5 microg EGF every 36 h for 45 days; MPA-treated sham-operated mice were used as controls (n = 6). Mammary glands from sialox MPA-treated mice are considerably less developed as compared with sham-operated animals. The exogenous administration of EGF restores the usual MPA-induced growth pattern of the glands, thus confirming a role for EGF either in mediating or cooperating with MPA in inducing the mammary architectural changes observed in MPA-treated mice. On the other hand, primary cultures of progestin-dependent (PD) ductal mammary adenocarcinoma in vivo tumor lines and of lobular progestin-independent (PI) tumor lines were used to evaluate the effect of EGF on tumor growth. In vitro EGF was found to stimulate cell proliferation of lobular PI tumor cells and of fibroblastic cells from both types of tumors at concentrations higher than 0.1-0.5 ng/ml and in the presence of 1-5% of charcoal-stripped fetal calf serum. Conversely, no proliferative effects were observed in ductal PD cells under the same experimental conditions, regardless of the presence of 10 nM MPA. It can be concluded that although EGF plays an important role in MPA-induced mammary carcinogenesis, it is not necessary in PD tumor growth.

Promoter effect of medroxyprogesterone acetate (MPA) in N-methyl-N-nitrosourea (MNU) induced mammary tumors in BALB/c mice.

The promoter effect of medroxyprogesterone acetate (MPA) on mammary carcinogenesis in female BALB/c mice was investigated using methylnitrosourea (MNU) as initiator. Nine out of 43 animals developed mammary carcinomas in the group treated with MNU (50 mg/kg) and MPA (administration of 40 mg every 3 months) starting 1 week after MNU administration. No tumors appeared in controls receiving only MNU or MPA during the time course of the experiment (9 months). The tumors were lobular adenocarcinomas showing different degrees of squamous differentiation with low or undetectable estrogen and progesterone receptors, and expressing epidermal growth factor receptors. These results support the hypothesis that MPA promotes the growth of MNU induced lesions.

A versatile mechanical ventilator (DIGIT) with high flow stability and a programmable inspiratory phase flow pattern.

The paper describes the general characteristics of a newly developed nonconstant-flow generator for automatic ventilation of the lungs. It is known that the application of very high pressure to high internal resistance leads to a very stable flow, in that the flow itself is unaffected by external load (patient) variations. The stability of the flow means that the inspiratory process can be controlled by means of the ventilated volume, thus extending DIGIT utilization to high resistance patients. The modulation of the flow is implemented via a digital electromechanical system, which allows the ventilator functions to be accurately programmed. The desired flow waveform is obtained by means of a series of pneumatic valves, the apertures of which are digitally controlled. The design is innovative in that it allows the flow waveform in each of the ten digitalized time steps into which each inspiratory phase is divided to be both programmed and controlled. Other ventilators commercially available and currently in use do not have this functional capability, as they are all designed to model the integral flow of the inspiratory waveform without being able to modify the subunit time steps of a single inspiratory phase. The paper also discusses the results of fundamental tests concerning the performance characteristics of the ventilator.

Effect of medroxyprogesterone acetate (MPA) and serum factors on cell proliferation in primary cultures of an MPA-induced mammary adenocarcinoma.

The effect of progesterone (Pg), medroxyprogesterone acetate (MPA), estradiol (E2), dihydrotestosterone (DHT) and dexamethasone (DEXA) was studied on the in vitro growth rate of a progestin-dependent (PD), estrogen-sensitive mammary tumor line originated in an MPA-treated BALB/c mouse (C4-HD), and on its estrogen-resistant variant (C4-HDR). The specificity of hormone action was further investigated using the anti-hormones RU-486 and hydroxyflutamide (FLU). Cell growth was evaluated in epithelial and fibroblast-enriched cultures using 3H-thymidine and/or autoradiography and immunocytochemistry. The results indicate that cell growth is directly stimulated by MPA and Pg at concentrations ranging from 10(-11) to 10(-7) M. RU486 prevented MPA-induced stimulation in concentrations 10 to 100 fold lower than those of MPA. When used alone, it inhibited cell proliferation only in concentrations higher than 10(-11) M. At nM concentrations, neither DEXA nor DHT stimulated 3H-thymidine uptake except DEXA at 100 nM. MPA-induced stimulation was not reverted by micromolar concentrations of FLU. As for E2 (10(-7)-10(-9) M) it prevented MPA stimulation only in cultures of estrogen-sensitive tumors. Progesterone receptors (PR) (475 +/- 115 fmoles/10(5) cells, n = 5) and estrogen receptors (ER) (ND-115 fmoles/10(5) cells, n = 5) were detected only in epithelial-enriched cultures. Serum from 7 day-MPA-treated mice induced a significant increase of 3H-thymidine uptake; an increase was also obtained with serum from untreated ovariectomized animals to which 1 nM-100 nM concentrations of MPA had been added. The stimulatory effect of the exogenous MPA was much lower than that of the serum obtained from MPA-treated animals. It is concluded that MPA stimulates cell growth of primary cultures of MPA-induced PD tumors via PR. The results provide support for a direct effect of MPA which may be mediated or potentiated by serum factors.

Effect of sialoadenectomy on medroxyprogesterone-acetate-induced mammary carcinogenesis in BALB/c mice. Correlation between histology and epidermal-growth-factor receptor content.

To evaluate the possible involvement of the salivary glands in the modulation of medroxyprogesterone (MPA)-induced mammary tumorigenesis, 48 sialoadenectomized virgin BALB/c female mice and 47 controls were treated with 40mg MPA depot s.c. every 3 months for 1 year. Mammary tumors developed in 11 sialoadenectomized and in 34 control mice with similar latencies. In both groups, 75% of the tumors were ductal and progestin-dependent (PD) while the remainder were lobular and progestin-independent (PI). Epidermal growth factor (EGF) levels were measured in salivary glands (SG-EGF) and serum (S-EGF) in both groups. MPA induced a significant increase in SG-EGF and in S-EGF that became evident only after 1 month of MPA treatment. No increase in S-EGF was detected in MPA-treated sialoadenectomized mice, indicating that salivary glands are the major source of S-EGF. The presence of EGF receptors (EGF-R) was investigated in ductal PD and PI tumor lines and compared with 8 PI tumor lines of lobular origin. A significant difference in EGF-R content was found between lobular and ductal tumors. No increase in EGF-R was noted when ductal tumors became autonomous. EGF-R did not correlate with tumor growth rate and there was an inverse correlation between EGF-R and steroid receptors. When the effect of sialoadenectomy on tumor growth was tested in vivo in syngeneic transplants of 2 ductal PD, 1 ductal PI and 2 lobular PI mammary adenocarcinomas, it was not found to be significant when compared with the controls. It may be concluded that SG-EGF plays an important role in the induction of mammary adenocarcinomas by MPA, while it has no significant effect on the growth of established tumors.

27 MHz hybrid evanescent-mode applicators (HEMA) with flexible heating field for deep and safe subcutaneous hyperthermia.

A new class of low-frequency electromagnetic applicators for hyperthermic treatment of superficial and subcutaneous tissues is described. These applicators employ an air-filled waveguide segment which is operating below the cut-off frequency, the evanescent modes of which are energized by suitable exciters to produce model field components. Direct radiators are integrated into the waveguide to generate additional direct field components. All field components may be combined in different power level ratio, phase, and orientation, to provide a composite heating field exhibiting a large variety of field sizes, shapes, and penetration features. The composite field emerging from the waveguide aperture propagates within the tissue to be heated through a non-critical air-gap. These versatile heating devices appear of potential interest to heat a variety of deep and localized subcutaneous tissues to therapeutic temperatures without injury to access fat layers of substantial thickness.

The freezing and thawing of water in poultry meat and vegetables irradiated by electrons at doses of 0.1-4 kGy.

Poultry meat and some vegetables, irradiated by 5 MeV electrons (0.1-4 kGy), were analysed by differential scanning calorimetry, from 24 h after irradiation. The temperature and enthalpy transitions of the water contained in the irradiated samples were measured and compared with those of unirradiated samples. We analysed 18 meat and 10 vegetable samples for each irradiation dose together with a similar number of unirradiated controls. The mean supercooling temperatures of water in the irradiated poultry meat samples and in some vegetables are significantly lower than those of controls. Moreover, the freezing enthalpies of the irradiated poultry breast are significantly lower than those of controls, while they are unchanged in the other cases. The mean ice melting temperatures and enthalpies are similar for all samples. The amount of the lowering of the water-ice transition depends on the nature of the sample and is highest in poultry breast and lowest in vegetables.

Evanescent-mode applicators (EMA) for superficial and subcutaneous hyperthermia.

Evanescent-mode waveguide aperture applicators are proposed for hyperthermic treatments of superficial and subcutaneous tissues. They consist of air-filled waveguide segments which are working below the cutoff frequency, and therefore support only evanescent transverse modes. These are excited by radiators of suitable symmetry and configuration to produce modal heating fields of selected cross-section. This field is emerging from the waveguide active aperture and enters the tissue to be heated through an air gap on non-critical length. These devices work in a very large range of frequencies, and are extremely simple to manufacture even with a variety of cross-section size and shape, on account of their air-filled feature. This enables to obtain good heating field flexibility with improved penetration. Their operation is safe and practical also on irregular and curved tissue surfaces.

Microstrip-antenna design for hyperthermia treatment of superficial tumors.

Microstrip antennas have many different advantages over other RF/MW radiative applicators employed for superficial hyperthermia treatment. This is mainly due to their compact and body-conformable structure as well as to printed circuit board techniques, both of which allow a wide design flexibility for superficial tumor heating. Among the wide variety of radiator configurations, three microstrip antennas of increasing complexity with electromagnetic and heating characteristics potentially suitable as applicators for superficial hyperthermia have been designed, developed, and tested in different radiative conditions: a microstrip disk, a microstrip annular-slot, and a microstrip spiral. Electromagnetic design criteria are presented together with the determinations of the applicator return loss versus frequency and thermograms of the near-field heating pattern in muscle-like phantom. The results are in good agreement with theory and indicate that: i) the operating frequency is either single or multiple according to the applicator-mode, "resonant" or "traveling-wave," and can be chosen in the useful frequency range for hyperthermia (200-1000 MHz) according to the tumor cross-section and depth; ii) the heating pattern flexibility increases going from the simple geometry disk to the annular-slot and spiral applicators; iii) a distilled-water bolus is required; iv) the annular-slot applicator exhibits the highest efficiency, while the spiral applicator provides the best performance.