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D Franceschi

Publications and source records attributed to D Franceschi.

At least 19 recordsLinked to original sources

A new approach for three-dimensional reconstruction of arterial ultrasonography.

This report describes a computerized approach that allows the creation of realistic three-dimensional arterial images from two-dimensional contiguous slices derived from a conventional ultrasound scan. Furthermore, the study assesses the method's feasibility and accuracy by performing in vitro cadaver artery three-dimensional reconstructions. Images are digitized into a computer, with a resolution of 512 x 480 pixels, and a dynamic range of 8 bits/pixel (256 gray scale). After edge enhancement with convolution filters through the original binary data, the intraluminal and outer edges are traced and converted to a polygon vector within a defined three-dimensional space. Serial cuts, 2 mm apart, are then "stacked" into a three-dimensional model, with interpolation of polyhedra between slices. Sixteen normal and arteriosclerotic distal aortic and common iliac arteries were obtained from fresh cadavers. Three-dimensional reconstruction models were compared with gross examination of the original artery. Anatomically accurate reconstructions were obtained, all with detailed surface information. Data analyzed included diameter, area, residual lumen, and percent stenosis. Pearson's coefficients determined for the pairs of data indicated excellent correlation (greater than or equal to 0.90) between separate measurements. With use of the described technology it is feasible to perform arterial three-dimensional reconstructions on a personal computer, with detailed and accurate surface information. The three-dimensional reconstruction method used can reliably and consistently reproduce the anatomic specimens.

Arteries

Protease priming of neutrophil superoxide production. Effects on membrane lipid order and lateral mobility.

Phagocyte superoxide (O2-) response is primed by a variety of physiologic compounds including the neutrophil secretory proteases cathepsin G and elastase. To study whether protease priming of neutrophil O2- response is related to changes in membrane physical state, we examined enzyme effects on the order and lateral mobility of lipid probes in intact neutrophil membranes. Exposure to cathepsin G (5 micrograms/ml) or elastase (10 micrograms/ml) caused a significant decrease in fluorescence anisotropy of the probe trimethylammonium diphenylhexatriene in neutrophil plasma membranes (0.279 to 0.256 for cathepsin G, 0.274 to 0.256 for elastase, p less than 0.02 for both), indicating a decrease in phospholipid chain order in the surface membrane bilayer. Cathepsin G and elastase also caused significant increases in membrane lipid lateral mobility as measured by excimer formation of the fluorescent probe 1-pyrenedecanoic acid (for cathepsin G, a 107% increase, and for elastase, a 44% increase in excimer/monomer fluorescence ratio, p less than 0.001). Enzyme effects on membrane structure were dependent on intact proteolytic activity, and were cell specific; the proteases had no effect on lipid order or lateral mobility in liposomes. In corollary studies, the possible association between the physical state of the polymorphonuclear leukocyte membrane and O2- generation was analyzed with the membrane modifying compounds, linoleic acid, ethanol, and cholesterol. Cell exposure to linoleic acid (1 microM) caused a significant decrease in lipid order and an increase in lipid lateral mobility along with increased O2- production to N-formyl-Met-Leu-Phe (fMLP) (191%) and phorbol myristate acetate (PMA) (39%), p less than 0.02 for each. 3 mM ethanol also augmented O2- response to fMLP (31%) and PMA (48%) and caused a significant decrease in lipid order, but did not affect lipid lateral mobility. Treatment with cholesteryl hemisuccinate (100 micrograms/ml) resulted in increased lipid order and decreased lipid lateral mobility, as well as decreased neutrophil superoxide response to fMLP (-61%, p less than 0.001) and PMA (-50%, p less than 0.02). We then examined whether modulation of membrane physical state may explain the mechanism of action of a known priming agent by studying the effects of low concentrations of a diacylglycerol. Cells treated with 10 microM 1-oleoyl-2-acetyl-sn-glycerol had a greater than 8-fold increase in superoxide response to fMLP (p less than 0.001) while demonstrating a significant decrease in lipid order (0.289 to 0.281, p less than 0.01) and a 50% increase in lipid lateral mobility (p less than 0.001).(ABSTRACT TRUNCATED AT 400 WORDS)

Adult

Not all nonpalpable breast cancers are alike.

Clinical and mammographic data of 1009 consecutive patients were correlated with histopathologic data of 1144 biopsy specimens of nonpalpable breast lesions to better define the presentation and biologic behavior of early breast cancer. Patients with malignant neoplasms (269 [24%] of 1144 specimens) were older (mean age, 62.1 years) than patients with benign lesions (mean age, 54.9 years). Furthermore, patients with invasive disease were older (mean age, 63.3 years) than patients with noninvasive disease (mean age, 58.5 years) with an overall increased risk of invasive cancer per year of 1.035. A 58% incidence of invasive cancer was detected for lesions characterized by calcifications, while the incidence of invasive cancer was 84% for isolated mass lesions (relative risk, 4.31 for masses). Isolated mammographic calcifications associated with cancer appeared in a younger population and were significantly associated with noninvasive ductal cancer. Breast cancer presenting as a mammographic mass appeared in an older group and was highly associated with the presence of invasive disease.

Adult

Outcome of complex vascular and orthopedic injuries of the lower extremity.

Thirty-two patients undergoing limb salvage procedures for complex vascular and orthopedic injuries of the lower extremity were studied in order to identify prognostic indicators for delayed amputation in this select group. A high incidence of nerve (38%), soft tissue (66%), and remote injury (47%) was noted. A comprehensive and integrated approach to vascular, orthopedic, and plastic reconstruction was utilized. Of the 32 patients studied, 1 (3.1%) died as a result of remote injury and sepsis. Amputation was required in 9 patients (28%), while 13 (56%) of the patients with limb salvage showed persistent functional or neurologic deficits. Infection was the most significant factor associated with amputation (p less than 0.0005) and was not avoided by the perioperative use of antibiotics. Delayed amputation resulted in a significant extension of total hospitalization (p less than 0.005). The authors favor an aggressive approach to limb salvage with IIIC injury but recommend early amputation in the presence of significant nerve disruption. An attentive use of tissue debridement, intravenous antibiotics, and early wound coverage is needed to limit infection.

Adolescent

Breast biopsy for calcifications in nonpalpable breast lesions. A prospective study.

We prospectively studied 239 consecutive patients who underwent breast biopsy for 277 nonpalpable lesions characterized by mammographic microcalcifications. Clinical and mammographic characteristics were correlated with histologic findings in an attempt to identify patients more likely to have early breast cancer. The distribution of clinical risk factors was equal between patients with benign or malignant outcomes. The predominant Wolfe pattern on mammography was P2 (38%); however, no relationship was observed between the Wolfe pattern and malignancy. A marked correlation was observed between malignancy and small lesions, more than 15 calcifications, and calcifications in a linear or branching pattern. Twenty-four percent (n = 67) of the biopsy specimens contained either ductal or lobular breast cancer. This study highlights the necessity of an aggressive approach toward suspicious calcifications found by mammography.

Biopsy

Mechanisms of oxygen free radical-induced calcium overload in endothelial cells.

Unregulated increases in intracellular calcium levels with subsequent cytoskeletal disruption have been implicated in tissue injury caused by oxygen free radicals (OFRs). The purpose of these experiments was to study the kinetics of free intracellular calcium in endothelial cells on exposure to exogenous OFRs and investigate the mechanisms of this altered homeostasis. Monolayers of endothelial cells were labeled with a calcium-sensitive probe and exposed to exogenous OFRs generated with hypoxanthine and xanthine oxidase. Intracellular calcium changes were monitored dynamically by continuous measurement of fluorescence with a spectrofluorometer. A sustained rise in intracellular Ca++ levels reaching a peak at 5 minutes was observed. This effect was blocked by superoxide dismutase and catalase. Removal of calcium from the medium or chelating the extracellular calcium with ethyleneglycoldiamine tetraacetate significantly blunted the response to OFRs (p less than 0.05). Preincubation of the cells with verapamil did not alter the observed increase in Ca++i. Addition of another divalent cation (Mn++) to the medium partially blocked the rise in calcium levels (p less than 0.05). Membrane potential measurements assessed fluorometrically, with the fluorescent probe bisoxonol, demonstrate a transient hyperpolarization of the plasma membrane on exposure to OFRs, temporally associated with the rise in [Ca++]i. In summary, OFRs cause an increase of intracellular calcium in endothelial cells. This response is dependent on extracellular calcium and independent of voltage-sensitive calcium channels. The increase can be partially inhibited by other divalent cations. These results suggest that the transformation of the plasma membrane components (lipid peroxidation and cross-linking of proteins) caused by OFRs may produce cation ionophores.

Animals

Biopsy of the breast for mammographically detected lesions.

We prospectively studied 718 women who underwent biopsy of the breast for suspicious, mammographically detected mammary lesions in an attempt to identify key clinical risk factors, as well as roentgenographic characteristics associated with the appearance of early carcinoma of the breast. Patients with a benign outcome had an average age of 55 years versus 63 years for patients with carcinoma of the breast. Seventy-six per cent of these patients had no previous history of mammary problems, 20 per cent had a positive family history for carcinoma of the breast, 58 per cent were premenopausal and 21 per cent had used birth control pills. Except for age (p less than 0.001), the distribution of clinical risk factors was equal among patients with benign or malignant outcomes. Suspicious mammographic findings included mass lesions (53 per cent), calcifications (36 per cent) and the association of both (11 per cent). The predominant Wolfe pattern on mammography was P1 (36 per cent). No relationship was observed between Wolfe pattern and malignant conditions. In this group of patients, mammography was poorly specific; however, the positive predictive value increased with age and is related to the age-specific prevalence of carcinoma of the breast. Eight hundred and twenty-five lesions were removed. Twenty-five per cent (n = 203) of the specimens taken at biopsy contained carcinoma. Stellate mass lesions were highly suggestive of a malignant growth (p less than 0.0001). No relationship between the size of the suspicious mammographic mass and the malignant lesion was observed. A marked correlation (chi-square test with Yate's correction) was observed between malignant tumor and lesions with a linear or branching pattern, more than 15 calcifications, or small sized calcifications. The presence of a mass with calcifications was associated with carcinoma in 34 per cent. The incidence of invasive carcinoma was much higher for mass lesions (81 per cent) than for suspicious calcifications (56 per cent) (p less than 0.0001).

Adult

Microcomputer image processing in gastrointestinal endoscopy.

A computer-based system was developed to handle information and endoscopic images in a clinical setting. The system is based on an 80286 AT computer whose topology includes a 16-bit color image capture/display graphics adapter and a 256 gray scale 8-bit digital image analysis processor. Using its color capabilities, one may initiate a picture database of patient's endoscopic images, x rays, and relevant clinical data. The computer-based imaging system allows instant access to this information and minimizes subjective evaluation, improving comparison and follow-up of treatments in a more objective manner. The image analysis components permit digital characterization of lesions, which allows online measurements and image enhancement. This is a cost-effective method of handling information and images in the clinical setting, facilitating endoscopic management and follow-up of the patient with gastrointestinal disease, as well as an effective research and teaching tool.

Computer Graphics

Effects of argon laser radiation on aortic endothelial cells: early membrane changes and proliferative response.

Membrane fluidity, transmembrane signaling responses, and proliferative characteristics of endothelial cells were studied to characterize biochemical and molecular changes after treatment with argon laser energy. Bovine aortic endothelial cells grown in monolayers were irradiated at 50, 100, and 200 J with an argon laser (wavelength, 488 and 514 nm). Proliferation, assayed by [3H]thymidine incorporation, was measured daily for 6 days. An initial lag phase was observed for irradiated cells when compared to nonirradiated controls (P less than 0.03), with eventual recovery by the third day. Membrane fluidity, determined by fluorescence anisotropy, was measured 1 hr after irradiation. A decrease in static rotational motion of 1,6-diphenyl-1,3,5-hexatriene (DPH) was noted in irradiated versus nonirradiated cells indicating a decrease in membrane fluidity (P less than 0.02). Dynamic studies of intracellular calcium and pH flux utilizing fluorescent probes demonstrated a preserved response to mitogenic stimulation. An increase in intracellular Ca2+ with a concomitant alkalinization of the intracellular milieu was observed in irradiated and non-irradiated cells in response to stimulation with endothelial cell growth factor (ECGF). These responses resemble those characterized for other mitogens. Argon laser energy applied to aortic endothelial cells decreases membrane fluidity early after irradiation. These alterations probably cause the initial lag observed in their proliferative response; however, the capacity to respond to exogenous mitogenic stimulation is maintained.

Animals

Risk factors associated with intravascular catheter infections in burned patients: a prospective, randomized study.

A prospective, controlled study of 101 intravascular catheter sites was undertaken to determine the importance of tubing manipulation and skin contamination in the etiology of catheter infection in burned patients. Catheters in place for 3 days were randomized to have the tubing changed every 24 or 48 hours. Catheters were removed at 72 hours and the tips cultured by the semi-quantitative technique of Maki. Hubs were cultured (by swab culture) at times of tubing change and at the time of catheter removal. Skin cultures of the area surrounding the catheter were done at the time of insertion and removal. Catheter tip infection was defined as 15 or more colony forming units. Positive cultures were found in 25.7% of the cases, and were most often due to Pseudomonas species (33%) and coagulase-negative Staphylococcus (29%). Infections occurred in 35% of arterial catheters, 27% of central, and 12% of peripheral venous catheters. No benefit was observed from changing the administration tubing at 24 hours vs. 48 hours. Hub cultures were positive 30% of the time at 24 hours, 39% at 48 hours and 41% at 72 hours. Although the isolated organisms correlated with tip cultures, false positive rates varied from 8 to 62%. Discriminant analysis showed no relationship between catheter infection and burn size or day postburn; however, the incidence of catheter infection correlated inversely with the distance of the catheter insertion site from the burn wound (p = 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

Enhanced in vivo therapy of pulmonary metastases with interferon and interleukin-2.

Interleukin-2 (IL-2) can mediate in vivo tumor regression at high doses. To enhance this efficacy, we studied the effect of adding a human hybrid recombinant interferon alpha A/D (rHuIFN-alpha-A/D) because of its known in vitro augmentation of immune-mediated tumoricidal activity. C56BL/6 mice bearing established pulmonary metastases induced by the iv injection of the methylcholanthrene-induced fibrosarcoma MCA 106 were treated for 12 days with intraperitoneal injections of (1) Hanks' balanced salt solution, (2) recombinant IL-2, (3) rHuIFN-alpha-A/D, and (4) a combination of IL-2 and HuIFN-alpha-A/D. IL-2 and interferon each had some antitumor activity. However, maximal reduction of pulmonary metastases consistently resulted from combining IL-2 with interferon. In two of four experiments, this combination was significantly better compared to either IL-2 or interferon treatment alone. The most potent regimen was 12 days of IL-2 (50,000 units bid) together with rHuIFN-alpha-A/D (50,000 units ip qd). No consistent pattern of proliferative or cytotoxic activity was found against a panel of stimulator and target cells. These results demonstrate enhanced antitumor efficacy of combining recombinant interferon alpha and IL-2 against established pulmonary metastases. Potential clinical applications are suggested by these data.

Animals

Interferon inhibition of IL-2-mediated lymphocyte proliferation.

Interleukin-2 (IL-2) combined with hybrid human alpha interferon (IFN-alpha A/D) mediates enhanced tumor regression compared with either agent alone. To elucidate the underlying mechanism of interaction of IL-2, with its known ability to induce expansion of T lymphocytes, and IFN-alpha A/D, with its antiproliferative activity, we studied splenocytes from normal and tumor-bearing C57BL/6 mice in 5-day cultures and measured proliferation by means of a standard 4-hour 3H-thymidine incorporation assay. Potent inhibition of IL-2-induced proliferation (usually greater than 90%) resulted from high concentrations of IFN (100 to 1000 U/ml). Splenocytes from both tumor-bearing and normal mice, cultured alone or with mitomycin-treated syngeneic tumor, MCA106, exhibited similar patterns of inhibition. Unexpectedly, allostimulation with DBA/2 (H-2d) stimulators and C57BL/6 (H-2b) responders showed enhanced proliferation, most pronounced at lower IFN concentrations. Time course of IFN action revealed minimal duration of exposure necessary for inhibition to be less than 24 hours. Microfluorometric cell analysis showed the striking increase in Thy-1+ cells (55% to 96%) induced by IL-2 with parallel increase in Lyt2+ cells but almost complete disappearance of L3T4+ cells. IFN reduced IL-2-induced increase in Lyt-2+ cells (61% to 31%). These results emphasize the complexity of IL-2 and IFN interaction and the potential for dose-related antagonistic effects. This may be important in the clinical use of this combination.

Animals

Technetium-99m methoxyisobutyl isonitrile (RP30) for quantification of myocardial ischemia and reperfusion in dogs.

This study was done to determine whether [99mTc]methoxyisobutyl isonitrile (RP30), a nonredistributing myocardial perfusion agent, could be used to quantify regional myocardial blood flow distribution during ischemia and reperfusion, employing sequential injections of tracer, tomographic imaging, and appropriate image subtraction. Dogs underwent transient (6 min) coronary artery occlusion, followed by two paired injections of RP30 and radioactive microspheres combined with tomographic imaging, the first during coronary occlusion and the second after 60 min of reperfusion. To obtain a true image representative of reperfusion, the first set of images was corrected for 99mTc decay and subtracted from the second. During occlusion, tissue microsphere content and scintigraphic RP30 activity in the center of the ischemic region (both expressed as a fraction of the nonischemic region) were closely correlated, although RP30 consistently exceeded microsphere content (0.43 +/- 0.03 vs. 0.24 +/- 0.04, p less than 0.01). Direct tissue counting of RP30 confirmed its relative excess in ischemic myocardium. Reperfusion was successful in 7/8 dogs, with an increase in RP30 activity to 0.98 +/- 0.04 compared to 0.89 +/- 0.03 for microspheres (p = N.S.). In one dog with microsphere-documented persistent ischemia, the RP30 defect was still present after reflow. Our results indicate that because of the lack of myocardial clearance and redistribution, repeat injections of RP30 can be used to quantify serial changes in regional myocardial blood flow.

Animals

The management of localized abdominal aortic dissections.

Aortic dissections limited to the abdominal aorta occur infrequently. We have identified four cases of abdominal aortic dissection and have reviewed these in combination with 43 previously reported cases to identify factors that influence the prognosis and management of this disease. Abdominal aortic dissections are similar to thoracic dissections in their presentation, with acute shearing pain and systolic hypertension occurring commonly. Although the diagnosis may be made by ultrasonography or CT scanning, angiography is the definitive diagnostic study. Factors found to be associated with high mortality include presentation with acute pain (p less than 0.0003), involvement of visceral vessels (p less than 0.02), and rupture (p less than 0.000002). Chronicity appears to be protective (p less than 0.04), although chronic dissections may present acutely. Although prosthetic replacement of the involved aorta is the treatment of choice in most cases, nonoperative management with regular follow-up can be considered in asymptomatic chronic dissections.

Aged

Microcomputer image processing for burn patients.

A computer-based system was developed to handle information and images in a clinical setting. The system is based on an 80286 AT computer, the topology of which includes a 16-bit color image capture/display graphics adapter and a 256 gray scale 8-bit digital image analysis processor. Using its color capabilities, we have created a picture database of patients' injuries, radiographs, and other relevant clinical data. The computer-based imaging system allows instant access to this information and minimizes subjective evaluation, making comparison of and follow-up of treatments more objective. The image analysis components permit digital characterization of the burn wound, enhancing our ability to quantitatively evaluate wound size, contracture, graft take, and re-epithelialization. This is a cost-effective method of handling information and images in the clinical setting as well as an effective research and teaching tool that facilitates management and follow-up care of the patient with burns.

Burns