The linker region of breast cancer resistance protein ABCG2 is critical for coupling of ATP-dependent drug transport.

The ATP-binding cassette (ABC) transporters of class G display a different domain organisation than P-glycoprotein/ABCB1 and bacterial homologues with a nucleotide-binding domain preceding the transmembrane domain. The linker region connecting these domains is unique and its function and structure cannot be predicted. Sequence analysis revealed that the human ABCG2 linker contains a LSGGE sequence, homologous to the canonical C-motif/ABC signature present in all ABC nucleotide-binding domains. Predictions of disorder and of secondary structures indicated that this C2-sequence was highly mobile and located between an α-helix and a loop similarly to the C-motif. Point mutations of the two first residues of the C2-sequence fully abolished the transport-coupled ATPase activity, and led to the complete loss of cell resistance to mitoxantrone. The interaction with potent, selective and non-competitive, ABCG2 inhibitors was also significantly altered upon mutation. These results suggest an important mechanistic role for the C2-sequence of the ABCG2 linker region in ATP binding and/or hydrolysis coupled to drug efflux.

Phase transition in poly(vinylidene fluoride) investigated with micro-Raman spectroscopy.

The phase transition from the non-polar alpha-phase to the polar beta-phase of poly(vinylidene fluoride) (PVDF) has been investigated using micro-Raman spectroscopy, which is advantageous because it is a nondestructive technique. Films of alpha-PVDF were subjected to stretching under controlled rates at 80 degrees C, while the transition to beta-PVDF was monitored by the decrease in the Raman band at 794 cm(-1) characteristic of the alpha-phase, along with the concomitant increase in the 839 cm(-1) band characteristic of the beta-phase. The alpha-->beta transition in our PVDF samples could be achieved even for the sample stretched to twice (2x-stretched) the initial length and it did not depend on the stretching rate in the range between 2.0 and 7.0 mm/min. These conclusions were corroborated by differential scanning calorimetry (DSC) and X-ray diffraction experiments for PVDF samples processed under the same conditions as in the Raman scattering measurements. Poling with negative corona discharge was found to affect the alpha-PVDF morphology, improving the Raman bands related to this crystalline phase. This effect is minimized for films stretched to higher ratios. Significantly, corona-induced effects could not be observed with the other experimental techniques, i.e., X-ray diffraction and infrared spectroscopy.

[Photography methods in general and esthetic surgery: clinical significance and impact on surgical performance]. / Fotografia estemporanea in chirurgia generale ed estetica. Significato clinico ed impatto sulla performance chirurgica.

The authors outline and emphasize the use of Polaroid technique in the surgical practice, either in emergency room (pre-, intra- and postoperative photography) or in plastic-reconstructive surgery, where informed consent is needed on the basis of surgical plan. Polaroid photos are suitable to be enclosed in the patient record as well as in the legal documentation. The Polaroid Macro-5SLR camera is specifically useful in the medical practice to improve the doctor-patient relationship.

[Imaging quality of a digital Konica Regius 336 system for thoracic radiology]. / Qualità dell'immagine di un sistema digitale Konica Regius 336 per Radiologia Toracica.

INTRODUCTION: Digital radiographic systems permit to optimize execution, depiction and storage of radiological images. Since a Regius 336 digital system (Konica Corp., Tokyo, Japan) devoted to chest radiography was recently installed in the Radiology Department of S. Anna Hospital in Como, Italy, we investigated its performance relative to image quality. MATERIAL AND METHODS: Konica Regius 336 is a computed radiography system made of a phosphorescence detector plate which is scanned with an infrared semiconductor laser beam. The radiographic image obtained from the detector is subjected to image processing, which allows a stable output and the nonlinear curve typical of conventional radiographic systems. Image quality was assessed based on the following parameters: dose, contrast, noise, and spatial resolution. As reference, we assessed the same parameters on a Cronex 88 analogic chest-changer (DuPont Pharma, North Billerica, Mass, USA). RESULTS: The Regius 336 air kerma values were always higher than the analogic ones (about 10%), both with and without a chest phantom; noise was also greater than in analogic images, sometimes even doubled. The optical densities of a step wedge and the spatial resolution of the digital chest-changer are independent of the X-ray tube voltage consequent to broader optical latitude. Inversely, the analogic images of the wedges show great optical density variability as a function of the X-ray tube voltage (in a range of 2). The modulation transfer functions of the two systems have the same trend. DISCUSSION AND CONCLUSIONS: The performance of the Konica Regius 336 is nearly equivalent to that of an analogic system. The main advantages of the digital system are a standard output, lower consumption of radiographic films, higher productiveness and better image quality standard level.

[The current state of the diagnostics of breast diseases in Lombardy]. / Indagine conoscitiva sulla situazione attuale della diagnostica senologica nella Regione Lombardia.

PURPOSE: The SIRM study group for senology in Lombardy set the following goals: to quantify the number of radiologist working in public radiology centers and in private credited hospitals in Lombardy; to quantify the number of radiologists working in diagnostic senology and the mean time they devote to this field; to survey the diagnostic equipment used for senology purposes and check its adequacy. MATERIAL AND METHODS: We considered 58 centers of senology diagnostic imaging in the radiology departments of general hospitals in 8 Lombardy provinces. First we evaluated the screening programs for early breast cancer detection carried out with clinical mammography. All data were evaluated with reference to female residents aged 40 to 69, to the average adherence rates reported in the literature, to the protocols adopted in different centers relative to the examination frequency. Mammography was always associated with a physical examination and then the patient was submitted to radiological investigations to make the final diagnosis. The form we used for data report is summarized in Table I. RESULTS: In the centers for diagnostic senology we surveyed in 1998, in all 182,724 mammograms, 58,686 breast US examinations and 7,097 needle biopsies for cytology or microhistology were performed; 35.5% of the female population which should have been screened actually underwent the examination and 32.6% of them was also submitted to breast US, while 3.88% underwent FNAB. Sixty-three mammographic units and 62 US units were operated by 152 radiologists. An average 2,900 radiographic investigations per mammographic unit were performed yearly. Each radiologist reported an average 1,202 mammograms a year. Refer to the tables for detailed data reporting by province. Thirty-six per cent of radiologists presently reads more than 1,500 breast examinations a year. The radiologists working in diagnostic imaging in senology devote an average 20% of their working time to this field. As for the technical adequacy of mammographic and US equipment relative to some reference levels reported in detail in the paper, only 42% of the former and 48% of the latter were up to standards. DISCUSSION AND CONCLUSIONS: Despite the massive work done in the field of senology, the estimated needs of the female population have not been met yet, given the increased demand for senologic examinations and women's growing awareness of the need of early breast cancer diagnosis. The answer to this problem lies in a political health care policy that should promote the current clinical programs increasing both instrumental and human resources. Alternatively screening programs could be planned on a regional basis, with the pro of reaching a larger female population and that of a more homogeneous methodological approach. Our data indicate that breast cancer detection is best achieved with clinical and screening tools: the former can be easily promoted in a short time and could thus make our first goal, while the latter, which is more complex, could be implemented later. Thus, a growing clinical activity could make a very good basis for high quality breast screening programs. Finally, it is necessary to guarantee high quality standards for equipment, methods and training of medical and nonmedical staff.

[An experimental study of the use of synthetic meshes in large abdominal eventrations]. / Studio sperimentale sull'applicazione di reti sintetiche in corso di grandi sventramenti addominali.

BACKGROUND: The aim of this study is to evaluate the biocompatibility of Angimesh mesh (polypropilene) in rats, usually used to replace or to strengthen the abdominal fasciae. METHODS: We made an abdominal longitudinal incision of skin and muscles in 20 rats was carried out and two muscular semilunae removed. The incision was occluded with Angimesh mesh fixed by ethilcyanoacrilate glue (first group of rats) or with suture stitches (second group of rats). The animals were sacrificed after 80 days and the stability of the mesh and the presence of endoperitoneal adhesion were evaluated macroscopically, and microscopically the fibrogenesis and inflammation answer. RESULTS: Two rats of the first group and seven of the second group died before 30 days. The mesh was more steady when fixed by suture. Adhesion in the contact sites between the mesh and the peritoneum was found. Histology did not show any inflammation reaction but showed a fibrogenic answer. CONCLUSIONS: The cyanoacrilate non-toxicity has been confirmed also in this application. Angimesh mesh showed good biocompatibility and resulted ideal for the synthesis of large abdominal resections.

[The prevention of adhesions in surgery. A clinical review and experimental contribution]. / Prevenzione delle aderenze in chirurgia. Revisione clinica e contributo sperimentale.

BACKGROUND: The well-known soft tissue healing properties in some rat models as well as the modulating fibroblasts activity of heterologous collagen led us to the hypothesis that it is possible to prevent the peritoneal adhesions in the rat by interposition of the collagen after peritoneal surgery. METHODS: In this study, the use of Type I heterologous collagen in different physical forms (1% gel, lyophilized sponge, dehydrated film) for the postoperative peritoneal adhesions prevention has been evaluated. In the second part of the experiment; the 1% gel heterologous collagen including the recombinant tissue plasminogen activator (rtPA) has been applied. RESULTS: The results of both the experiments don't show any improvement in the number and the quality of the adhesions. CONCLUSIONS: It is cannot be excluded that, increasing the rtPA concentration it is possible to obtain better results, but the great cost and its potential systemic toxicity are limiting factors for its widespread use in order to prevent peritoneal adhesions.

[Lipoemulsification. A histological study on the action of ultrasound, access site and adipose tissue]. / Lipoemulsificazione. Studio istologico sull'azione degli ultrasuoni, sulla via di accesso ed il tessuto adiposo.

A new mini-invasive technique for the lysis of subcutaneous adipose tissue has emerged in recent years. This directly applies ultrasounds to the tissue by titanium probes. Ultrasounds act on parenchyma tissues, saving the structure and integrity of the blood vessels. Our study show histological features of the subcutaneous adipose tissue evolution just ultrasound-treated up to 30 days after surgery. Five obese female patients underwent the treatment by anesthesia. Before surgery the sites to treat were topically injected with sterile, hypotonic, apyrogen saline solution added with adrenaline, Biopsies have been taken intraoperatively from the border cutis of the holes made for the introduction of the titanium probes and from the subcutaneous adipose tissue. Biopsies have also been taken during a follow-up at 2, 5, 15 and 30 days postoperatively. Drains were positioned in the treated sites for at least 72 hours. The same sites were sutured so at to make later follow-up biopsies easier. Histological specimens were considered according to three dying methods: eosin-haematoxylin, Gomori and acetic orcein. We observed, as a confirmation the safety of the adipose tissue blood vessels, and the substitution of the destroyed adipose tissue with a microfibrillar connective tissue not subject to a sclerogenic evolution.

[Lipoemulsification versus lipoaspiration. Comparison of intraoperative blood loss and surgery time]. / Lipoemulsificazione verso lipoaspirazione. Confronto fra le perdite ematiche intraoperatorie ed i tempi operativi.

Blood loss due to liposuction is one of the main problems in this kind of surgery, blood volume being up to 30%-35% of the whole liposucked volume. We studied the possible lower impact of ultrasound lipolysis in order to obviate this non negligible problem. For this purpose we treated 10 patients, females, aged between 28 and 55, such obese to overweight between 50% and 200%. These patients underwent ultrasound lipolysis surgery after any dietetic or any other treatment against obesity. No patient dropped out of the study. Each patient was treated, under general anesthesia, in a region included between an imaginary horizontal line passing through the umbilicus and another one through the middle of the femur. Thirty minutes after a bilateral infiltration with an epinephrine solution (1:500000 diluted, 28 C) 2 1 volume each side, the right side was treated with the liposucking cannula (0.4 cm diameter), the left one underwent ultrasound lipolysis with a titanium probe (0.5 cm diameter, SMEI Casale Monferrato, Italy). A liposucking probe every 10 minutes into the left side was inserted. Haemoglobin was detected (according to the method of Goodpasture) in the liposucked material. The result showed a statistically significant difference between the blood rate in the lipoaspirate and that one in the ultrasound lysed material. Ultrasound lipolysis is slower than lipoaspiration, but it also shows less risk of hemorrhage and fat embolism.

[Mullerian duct cysts. Description of two cases with a minimally invasive therapeutic approach]. / Cisti del dotto di Müller. Descrizione di due casi con approccio terapeutico minimamente invasivo.

Among cystic lesions of the male pelvis, the müllerian duct cyst represents the most commonly recognized abnormality. These lesions are midline in location and should not be confused with the big or cystic utricle because of its different embryologic development. The cysts are usually small and asymptomatic. Two cases of big and symptomatic müllerian cysts treated by minimal invasive approach consisting of aspiration and endoscopic marsupalization are presented.

[The interstitial photocoagulation with laser light of liver tumors]. / Fotocoagulazione interstiziale con luce laser dei tumori del fegato.

INTRODUCTION: Interstitial laser photocoagulation (ILP) is a recent interventional procedure performed under US or CT guidance which is capable of inducing thermal necrosis in solid tumors. We have used this technique for about 2 years to treat primary and secondary liver cancers. MATERIALS AND METHODS: Thirty-five patients, 20 of them with liver metastases and 15 with HCC, have been examined: 59 lesions in all, ranging in diameter 10 to 65 mm. Forty-nine lesions have been followed-up for at least 2 months and 25 for at least 6 months. The treatment was performed positioning one to six (18-21 G) modified Chiba needles in the lesions to be treated, according to their sizes, under US or CT guidance. The optical fibers (400-800 mu) were then inserted and the Laser was fired to administer 1,000 Joule/session, with 5-10 W power range. The US and CT patterns of the ILP-treated lesions are reported. RESULTS: Dynamic CT examinations 2 months after treatment showed complete tumor destruction in 77.5% of the lesions. The best results were obtained in the lesions < 3 cm phi; in particular, 32/38 lesions (84.2%) < 3 cm and with at least 2 months' follow-up exhibited complete necrosis, as did 6 of 11 lesions (54.6%) over 3 cm phi. When residual tumor tissue was demonstrated, further ILP sessions were useless. We observed only few complications which resolved spontaneously in all cases. CONCLUSIONS: At present, ILP remains an experimental procedure: further studies on larger series of patients and comparison with the results of other interventional procedures are needed to confirm its efficacy in treating primary and secondary liver cancers.

Vitamin E added silicone gel sheets for treatment of hypertrophic scars and keloids.

BACKGROUND: Trauma of various origins can induce a connective tissue disorder that leads to keloids. This condition has yet not been clearly distinguished from scars and hypertrophic scars. Only electronmicroscopic and biochemical data can help to do this. Among some more or less therapeutic approaches, the use of silicon (polydimethylsiloxane) plates, wrapped on the keloid surface, has been reported effective by some authors. These authors also demonstrated that it is not the mechanical pressure that is the mechanism of action, but a direct action on fibroblasts and a hyperhydration of subcutaneous tissue. The authors of this study conceived that the silicon plate may be able to improve the transdermal penetration of a compound such as vitamin E. This vitamin is capable of preserving some important morphologic and functional features of biological membranes by means of its phytilside chain of the molecule acting as a stabilizer of lysosomal membranes. MATERIALS AND METHODS: Eighty patients of both sexes, aged between 18 and 63 years, who had hypertrophic scars and keloids, were admitted to the trial. The patients were randomized to two groups in a simple-blinded study. Group A: Forty patients whose scars have been covered with silicon plates with added vitamin E. Group B: Forty patients treated with simple silicone gel sheets. No pressure bandages were used, only tape fixing the sheet for 10 hours overnight. The trial lasted for 2 months. The results were recorded at 4 and 8 weeks, evaluating the improvement according to a Scott-Husskinson scale. For objective assessment photos were taken. The results were analyzed by the chi-square test. RESULTS: At the end of the first month, group A had improved by more than 50% in 85% of cases, whereas the improvement in group B was 55% (P < 0.01). At the end of the second month, 95% of patients in group A had improved by 50%, whereas 75% had improved by 50% in group B (P < 0.05). CONCLUSIONS: Vitamin E added to the silicon plate scored better than the simple silicon plate at the end of both periods. We have reported the successful combined action of vitamin E and silicone gel sheets in scar treatment, especially in the short-term prophylaxis of hypertrophic scars or keloids.

[Ultrasonic suction lipectomy. A mini-invasive treatment of obesity]. / La liposcultura con ultrasuoni. Un trattamento miniinvasivo dell'obesità.

The safety of ultrasounds lipolysis in the treatment of local obesity and lipodystrophies versus suction lipectomy (less blood loss because of a lower impact on blood vessels network, and less mortality) induced us to combine these mini-invasive techniques in the treatment of obese patients. Between 1991 and 1994 we treated 205 patients (146 females, 59 males, 18-59 range age), affected by 1st degree obesity (44.4%), 2nd degree obesity (27.3%) and 3rd degree obesity (28.3%), accordingly to the following schedule: 1) general anesthesia; 2) subdermal infiltration of the operating sites of a cold sodium chloride (0.9%) epinephrine solution (1:10(5), 8 degrees C); 3) 0.5 cm cutaneous incisions; 4) introduction of titanium tips as ultrasounds source; 5) insertion of suction lipectomy probes to remove the adipose tissue destroyed by ultrasounds; 6) drainage of the wide subcutaneous space; 7) setting of elastic bandages. Mortality was zero and very low side effects have been observed. We report an improvement of blood glucose and triglycerides level and blood pressure 30 days after surgery. Fair late postoperative improvement of the blood glucose tolerance test have been seen in 3 cases.

[Cetyltrimethylammonium naproxenate as vaginal lavage in the therapy of vulvovaginal dystrophies in the postmenopause]. / Il naprossenato di cetiltrimetilammonio lavanda vaginale nella terapia delle distrofie vulvo-vaginali in post-menopausa.

A peculiar aspect of the postmenopausal period is atrophy of the lower genital tract, vagina and vulva. This is due to estrogen deficiency and is accompanied by vaginal pH elevation, lower number of lactobacilli and increased incidence of aspecific vulvovaginitis. We tested a new vaginal douche with an antibacterial-anti-inflammatory (non antibiotic-nonsteroidal) principle, cetyltrimethylammonium naproxenate 0.223% as an adjunct to classical estrogen topical replacement therapy. We treated 34 menopausal patients (mean age 67 yrs) in a double parallel controlled (15 A only estrogen topical therapy vs 19 B topical estrogen plus cetyltrimethylammonium naproxenate douches uid) study for 30 days. A significant reduction of symptoms was obtained in both groups although a faster reduction has been seen in the group treated with both drugs (= B). In conclusion a better replacement of physiological pH with reappearance of lactobacilli, a selective action on vaginal pathogens, a faster symptom remission and an higher psychophysical welfare can be attributed to the vaginal douche used in adjunct to classical estrogen topical therapy.

[Pilonidal cysts: the state of the art and the authors' personal experiences]. / Cisti pilonidali stato dell'arte ed esperienze personali.

After a historical review of the pathogenesis and several therapies suggested for the treatment of pilonidal cysts the authors report the results of a retrospective study performed in the Department of Surgery during a period of four years, with at least 12 months follow-up. This study involved 53 patients (35 males and 15 females, 23 years average age) affected by pilonidal cyst. These patients were treated for a month with antibiotic therapy and underwent surgery by general anaesthesia. Before surgery blue methylene was injected in the cyst. Between 4 months and 2 years 5.7% of operated patients relapsed. After 10 days antibiotic therapy they underwent surgery again by local anaesthesia and then they followed an open treatment protocol including collagen and silver sulfadiazine, healing by delayed wound closure. Furthermore a depilating cream for the border of the wound was suggested to the patient. These patients healed in a period between 4 weeks and 2 months. No relapses were observed after at least 12 months. In our opinion there is the rationale to suggest an open treatment of relapsed pilonidal cyst based on the use of heterologous lyophilized collagen and silver sulfadiazine: it is well accepted by the patient and effective in relapses.

[The diagnostic contribution of direct radiographic enlargement and of echography in the study of breast neoplasms]. / Contributo diagnostico dell'ingrandimento radiografico diretto e dell'ecografia nello studio delle neoplasie mammarie.

To compare the diagnostic value and the role of plain radiographic magnification and of ultrasonography (US) in breast cancer evaluation, 83 malignant tumors were studied with mammography, plain radiographic magnification and US. Microcalcifications were not included in our study. All tumors subsequently underwent histology or cytology. In our series, the malignant nature of the lesion was unquestionably proved in 53% of cases while a possible malignancy was suspected in 36% and a benign nature was incorrectly suspected in 11% of cases with mammography. The diagnostic value of plain radiographic magnification was compared with that of US; breast patterns, mammographic and clinical findings were considered. As for breast patterns, plain radiographic magnification was more accurate in evaluating fatty breast than both mammography and US, allowing the correct diagnosis of 58% of questionable mammographic findings, vs. 33% of US. On the contrary, US was more accurate in dense breasts, allowing the correct diagnosis of 77.7% of mammographic misdiagnoses vs. 33.3% only of plain radiographic magnification. As far as mammography is concerned, US was more accurate than plain radiographic magnification in the assessment of round masses (71.4% vs. 38.1%, respectively), whereas plain radiographic magnification was more accurate than US in stellate masses (100% vs. 92.7%, respectively). As far as clinical findings are concerned, plain radiographic magnification sensitivity was substantially the same in the assessment of symptomatic and asymptomatic lesions (91.5% vs. 89%, respectively), whereas US sensitivity was higher in symptomatic (97%) than in asymptomatic (69%) lesions. The rate of false-negative US diagnoses (14.4%) was higher than those of mammography and of plain radiographic magnification. Negative US findings must be considered with caution and are not sufficient to settle a radiologic doubt.