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Biomedical subjects

F Mantovani

Publications and source records attributed to F Mantovani.

At least 37 records · Page 2Linked to original sources

Expression of HMGI(Y) proteins in squamous intraepithelial and invasive lesions of the uterine cervix.

The expression of nuclear proteins high mobility group (HMG) I and HMGY was investigated in intraepithelial and invasive lesions of the uterine cervix. Human carcinoma cell lines C-41, ME-180, and CaSki were used for testing protein expression in neoplastic cells from the cervix. Morphological grading of the dysplasias (CIN 1, CIN 2, and CIN 3) and invasive carcinomas from formalin-fixed paraffin-embedded samples parallels the degree of nuclear immunostaining obtained using a polyclonal antibody raised against the amino-terminal region of HMGI(Y) proteins. The immunostaining obtained with HMGI(Y) antibody was compared with that observed using the antibody Ki-67, and the results were similar. We suggest the use of HMGI(Y) antibody in clinical oncology as a useful marker of intraepithelial lesions and invasive carcinomas.

Antibodies, Monoclonal↗

[Surgery in day hospital: scrotal surgery].

Actually scrotal ambulatory surgery represents a necessity for the surgeon because of the more and more greatest request to admittance and because of the impossibility to admit patients with less severe diseases. Ambulatory treatments allows psychological advantage, less discomfort, less hospital complications for the patients and a reduction of sanitary expense. Light general anaesthesia with concomitant administration of local anaesthesia is performed in our Institute. Surgical treatment must be short, with low haemorragic risk, scarcely algogenic and aseptic. Since January 1994 till December 1997, 484 patients underwent scrotal ambulatory surgery in our Institute. We reported one cardiac black and two lypothymia attacks associated with anaesthesia. Therefore combined general anaesthesia results a valid technique but unvoid of complications. Ambulatory surgery for scrotal surgery represents a sure advantage for patients and for the sanitary expense.

Adolescent↗

[Male and female urinary incontinence: treatment in day surgery].

Incontinence isn't itself a disease but the feature of possible urinary tract alterations or outside of it. Incontinence is frequent above all in the elderly but it can be on charge of both sexes at every age. In Italy, according to recent evaluations, people affected with this disease would be more than 4 millions. Incontinence is therefore an important failure for its health aspects but also for economic and social ones. The problem is to evaluate if incontinence can't be prevented and as consequence needs only an assistance management, or it can be considered a preventable disease able to be cured, as we deeply believe, suggested also by the positive results of new therapeutical procedures, in association with traditional surgery and rehabilitation such as injectables or mini-invasive quick operations such as colpocleisis or percutaneous vaginal colposuspension (PVC), matters of this presentation and always performed according to correct diagnosis and indication. Bovine dermal collagen highly purified, poorly viscous and easily injectable, despite traditional rehabilitation and surgery, is a further procedure, endoscopic and minimally invasive to treat stress incontinence. Collagen is employed to perform a bladder neck plasty, increasing urethrosphincterial competence, to obtain continence without the creation of an obstruction. Genital prolapse, that is hysterocolpocele or simple vaginal vault prolapse, has course in high proportion (37%) in elderly (after 80 years). Surgical management of severe failures of continence and often also of the voiding function, such as: hyscuria with vesicoureteral reflux, obstinate constipation related to severe genital prolapse with allied rectocele is often hardly performed in elderly owing to the age and general health conditions: colpoclesis is a vaginal surgical approach that can be easily performed by the urologist too, it is an effective alternative to permanent catheterization or maxipad to be offered to the patient to improve her quality of life. In between the above maintained procedures takes place the percutaneous vaginal colposuspension (PVC). It is an original technique made up in our Institute to treat incontinence by the bladder neck resuspension to Cooper ligament according to a complete miniinvasive retropubic tension free transvaginal colposuspension, in local anaesthesia and complementary light narcosis in Day Surgery. Urinary incontinence is today a disturbance easy to be cured thanks to injectables and to miniinvasive surgical procedures as reported in this presentation concerning the most advanced approaches to its management.

Aged↗

[Urethral implantation of collagen in the treatment of urinary incontinence. Comparison of transurethral and periurethral approach].

BACKGROUND: In mini-invasive surgery for the treatment of urinary incontinence injectable substances such as politef, autologous fat or bovine collagen, which can increase urethral resistance or support the sphincteric one are particularly used. It's a simple procedure in which patients may undergo local anesthesia, in short time and in "day hospital" regimen. Collagen, used as an injectable bulking agent, is the gold standard for this surgical technique because of complete biocompatibility, no evidences of adverse immunogenic effects, foreign-body reaction, migration of injected material, and because of higher fluidity which allows the use of thin needles compared to Politef (polytetrafluoroethylene) where an injection device is requested. Bovine collagen is partially reabsorbed within 24-36 months and a reinjection is often necessary. Although autologous fat is cheaper than bovine collagen, its injection shows more difficulties due to the need of higher needle diameter and time to store and prepare the material to inject. METHODS: The results obtained by two different approaches: transurethral injection of collagen and periurethral injection of collagen have been studied. A total of 48 patients underwent collagen injection for treatment of urinary incontinence: 24 treated by transurethral approach and 24 by periurethral approach. Follow-up at 6, 12, 24 months after treatment includes: objective exam, PAD test, functional evaluation, complete urodynamic evaluation (uroflow, cystomanometry, LPP, pressure/flow study, UPP). RESULTS: No clinical differences between peri/trans-urethral approach were found although collagen injection via transurethral technique need fewer material, reducing cost of treatment: an efficacy of treatment in 80% of patients and restoration of a complete urinary continence in 50% of patients was obtained. Although no clinical differences were demonstrated between the two different sites of injection, transurethral approach can be used similarly in both sexes even if without a modified resector as "injection device" it's more difficult to inject collagen in the right position, at the level of bladder neck submucosa. Perineal approach, exclusive of female sex, realizes the procedure without bleeding of urethral mucosa and no waste of collagen, though a longer period of training by surgeon is requested. After four years of experience the authors agreed that with an adequate injection device (modified resector), transurethral approach should be preferred, thus depending on the possibility to inject collagen in a correct position, just under bladder neck mucosa, which is possible to manage with this technique, in order to reduce reabsorption process of collagen and to obtain a longer efficacy of treatment reducing the number of reinjection and of course the cost of treatment. Collagen injection should be considered within an integrated therapeutical picture together with topic and systemic pharmacotherapy, physiotherapy, not excluding surgery techniques such as implantation of an artificial sphincter device in man or a sling procedure in woman. CONCLUSIONS: The urethral collagen injection for the treatment of urinary incontinence is a safe, durable and valid technique to improve urinary continence through a non obstructive effect increasing urethral resistance. Performed under local anesthesia this procedure allows the treatment of patients who may not be candidates suitable for general anesthesia and conventional surgery.

Adult↗

[Correction of acquired penile curvatures].

Penile acquired curvatures are related to the effects of the evolution of Peyronie's disease or to the results of conservative treatments. All the others (post-traumatic, post surgical) are quite rare and often therapeutically similar. More than 50% of penile acquired curvatures can today take advantage from pharmacophysical managements thanks to the technological progresses of industry and of the personal experience (cavernopharmacoperfusion) both being clinically suitable application for the effective results: more than 60% of stop in progression with decrease of the recurvatum enough to resume comfortable sexual intercourse. Last, when erectile failure is present, we suggest prosthesis implant preferring flexible-malleable device such as AMS 600. More recently we started an effective experience with the new silicone elastomers of Subrini (Virilis II). Both implants never required complementary surgery of the plaque to achieve straightening and sexual activity of satisfactory level.

Calcinosis↗

High mobility group I proteins interfere with the homeodomains binding to DNA.

Homeodomains (HDs) constitute the DNA binding domain of several transcription factors that control cell differentiation and development in a wide variety of organisms. Most HDs recognize sequences that contain a 5'-TAAT-3' core motif. However, the DNA binding specificity of HD-containing proteins does not solely determine their biological effects, and other molecular mechanisms should be responsible for their ultimate functional activity. Interference by other factors in the HD/DNA interaction could be one of the processes by which HD-containing proteins achieve the functional complexity required for their effects on the expression of target genes. Using gel-retardation assay, we demonstrate that two members of the high mobility group I (HMGI) family of nuclear proteins (HMGI-C and HMGY) can bind to a subset of HD target sequences and inhibit HDs from binding to the same sequences. The inhibition of the HD/DNA interaction occurs while incubating HMGI-C with DNA either before or after the addition of the HD. The reduced half-life of the HD.DNA complex in the presence of HMGI-C, and the shift observed in the CD spectra recorded upon HMGI-C binding to DNA, strongly suggest that structural modifications of the DNA are responsible for the inhibition of the HD.DNA complex formation. Moreover, by co-transfection experiments we provide evidence that this inhibition can occur also in vivo. The data reported here would suggest that HMGI proteins may be potential regulators of the function of HD-containing proteins and that they are able to interfere with the access of the HD to their target genes.

3T3 Cells↗

Evaluation of the in vivo genotoxic potential of three carcinogenic aromatic amines using the Big Blue transgenic mouse mutation assay.

Three genotoxic mouse carcinogens, 4-chloro-o-phenylenediamine (4-C-o-PDA), 2-nitro-p-phenylenediamine (2-N-p-PDA), and 2,4-diaminotoluene (2,4-DAT), were tested in the Big Blue transgenic mouse mutation assay. Each experiment consisted of a vehicle control group with ten Big Blue C57BL/6 mice, five of either sex, and an equally sized group treated with a high dose of the test chemical. In addition, four animals were treated with the vehicle and six animals with the test compound for the measurement of bromodeoxyuridine (BrdU) incorporation to determine cellular proliferation. Prior to the mutagenicity experiments, the maximally tolerated dose of each compound was determined using nontransgenic C57BL/6 mice. Based on these results the doses used in the main study were 200 mg/kg/day for 4-C-o-PDA, 150 mg/kg/ day for 2-N-p-PDA, and 80 mg/kg/day for 2,4-DAT. Animals were treated for 10 days over a 2 week period and were killed 10 days after the ast treatment. In an additional experiment with 2,4-DAT, animals were killed 28 days after treatment. Since all three chemicals are liver carcinogens in the mouse, the DNA of the liver was analyzed using the standard procedures for the Big Blue assay. Hepatocyte proliferation was assessed by immunohistochemical detection of proliferating cell nuclear antigen (PCNA) and, in some studies, by measuring BrdU incorporation. 4-C-o-PDA and 2-N-p-PDA did not induce an increase in PCNA expression when measured 10 days after the last treatment. There was no increase in BrdU incorporation immediately after treatment with 4-C-o-PDA or with 2,4-DAT. However, 10 days after the last treatment with 2,4-DAT, a strong mitogenic effect was found with both techniques, i.e., in the PCNA and BrdU assays. 4-C-o-PDA, a liver carcinogen in both genders of mice, induced a small, statistically significant increase of the mutant frequencies in females. No increase was found in males. 2-N-p-PDA, which has been reported to induce liver tumors only in females, was found positive in males and was clearly negative in females. 2,4-DAT, a liver carcinogen in female mice, was positive in females and negative in males when the animals were killed 10 days after the last treatment. After an expression time of 28 days, 2,4-DAT induced a statistically significant increase in both sexes. The effect in females was marginally stronger than after 10 days' expression time and almost identical to the effect observed in males under these test conditions. In conclusion, the experiments showed that the Big Blue assay detects the genotoxicity of the three carcinogenic monocyclic aromatic amines tested. However, it seems that the sex specificity of the carcinogenic effects of these compounds is not reflected by the mutagenicity data in Big Blue mice.

Animals↗

[New trends in the surgical treatment of penile carcinoma].

With the current oncological emphasis on radical treatment allied to minimal invasiveness, choice of treatment relies on precise clinical staging. The corpora cavernosa of the penis represent a well defined anatomical structure distinct from the corpus spongiosum and the glans which are tightly connected to one another. In case of primary penile tumour the T.N.M. classification of the American Joint Committee on Cancer includes in the T2 stage both infiltration of the corpus spongiosum and of corpora cavernosa. Jackson's classification seems to be more pertinent as it limits to stage 1 cases involving the glans and corona and classifies as stage 2 cases limited to the corpora cavernosa. Partial penectomy can prove overly invasive, yet insufficiently radical, if the anatomical continuity of the spongious tissue is not considered. Carcinoma of the glandular corpus spongiosum without cavernosal involvement indicates glandulectomy with partial uretrectomy and apical cavernous-urethrostomy. Preserving the corpora cavernosa is an option of great relevance to the quality of life of the patient: erectile ability and stand-up micturition are not affected and the patient keeps complete sexual ability and orgasmic sensation. In case of scrotal or public involvement, emasculation with hemipelvectomy must be attempted; if indicated, it can be followed by radiotherapy. Perineo/abdominal reconstruction can be followed by urinary diversion with adjuvant chemotherapy. In selective cases neophallic reconstruction can be later attempted using the inferior abdominal rectum muscle.

Adult↗

[Radical surgical treatment of Peironie disease by excision of the plaque and dermal graft allowing conservation of erection].

The surgical treatment of the La Peyronie disease is the complet excision of the fibrom plaque followed by dermal skin grafts. This technique is applied for stabilised cases in which coït has become uneasy due to the deformation of the penis. A complete isolation of the vasculonervous dorsal pedicle guaranties a good erection. In 15 years this technique was applied in 400 cases followed during 2 years. In 7% of cases a recidive of the incurvation occurs. In 20% the erection was unsatisfactory.

Adult↗

[Ileal neobladder in women: Milano's technique].

In the female patient with transitional cell carcinoma the risk of urethral recurrence is very low, when the bladder neck is histologically free of tumour. On the other hand urinary continence can be maintained if the lower half of the urethra together with the nerve supply is preserved. On this basis orthotopic bladder reconstruction was applied also in a female patient. In order to preserve urinary continence minimal dissection was performed anterior to the proximal urethra; in addition pubourethral ligaments were left intact. On the other hand to prevent chronic urinary retention arising from downward displacement of the reservoir a colposacropexy was performed. At 3 weeks the filling cystogram demonstrated a well shaped and compliant reservoir. No downward displacement of the reservoir was observed in upright position. Neither reflux nor residual urine could be demonstrated by voiding cystourethrogram. The woman achieved diurnal and nocturnal continence at 3 month.

Carcinoma, Transitional Cell↗

[Seminal obstructions of the inflammatory origin].

Presence of bacteria in the sperm is often associated to a reduction of fertility in relationship with a decrease in number and motility of spermatozoa and with an augmentation of the abnormal spermatic cells. In the most severe cases, chronic and complicated phlogosis may lead to obstruction of seminal pathways with consequent azoospermia. Clinical features of seminal phlogosis are extremely variable both in acute and chronic evolutions. In every case the first diagnostical step is sperm count and seminal complete analysis which can give evidence of phlogistic alteration in quantity and quality of spermatic cells with a typical presence of an excess in white blood cells (leukospermia) as consequence of infection. The great variety in clinical and bacteriological aspects and the particular biological features of the organs involved, as the prostate, makes treatment a difficult problem to solve with particular regard to the choice of an effective antibiotic which pharmacokinetic has to result suitable for the microorganism as well as for the tissue of the infection site. All those efforts are indispensable to reduce the too frequent therapeutical failures in the management of seminal phlogistic pathology with complications of organic but also physiological relevancy for the patient and the partner too, such as azoospermia.

Anti-Bacterial Agents↗

[Nonsurgical and endoscopic therapy in obstructive azoospermia].

The endoscopic therapy has an elective role in the distal obstructive azoospermia for urogenital carrefour pathologies both organics and functional and differently in the resection and/or aspiration with sperm recovery forms. Resolutely attends to the symptomatology and positively to the fertility re-establishment, in front of a short sickness-rate. The Authors describe the different techniques with relative indications, results and complications. Instead medical therapy has a role in the obstructive above all post infection and post inflammatory lesions prevention. Furthermore propose to oneself the goal to improve the seminal quality by the improvement of the semen fertilization capacity and to reduce the affections symptomatology. Finally concurs with the sperm selection techniques to fertility potential wealth.

Endoscopy↗

Isolation and characterization of the gene coding for murine high-mobility-group protein HMGI-C.

The HMGI-C protein is a nuclear factor expressed in human and rodent neoplastic cells which has been shown to be involved in the process of cell transformation. We have previously isolated the cDNA encoding murine HMGI-C and now we report the cloning and analysis of the mouse Hmgi-c gene. The gene is at least 50 kb long, contains five exons, and each of the three DNA-binding domains is encoded by a different exon. The location of exon-intron junctions was determined and shown to follow the GT-AG rule. The sequence revealed that the overall organization is similar to the gene encoding human HMGI(Y), the other member of the HMGI family, suggesting that HMGI genes probably evolved through gene duplication and exon shuffling events from an ancestral gene. A highly homologous pseudogene is also present in the mouse genome. Our results on Hmgi-c structure provide basic information to carry out further studies on the regulation of its expression.

Amino Acid Sequence↗

[Radical perineal and retropubic prostatectomy: comparison of technics].

Today we may consider radical perineal prostatectomy as an example of mild invasive surgery compared with the retropubic. Technique is found less traumatic account of the precision of the approach, the accuracy of hemostasis and urethral bladder suture and the speed of postoperative handling. The only disadvantage related with the impossibility of transperineal pathological lymph node staging can today be satisfactory overcome after the advent of laparoscopic lymph node methods which permits safe non invasive preoperative hystological examination. The authors show the technique of laparoscopic and surgical therapy, concluding that perineal prostatectomy is a better approach toward retropubic radical prostatectomy, if combined with preoperative laparoscopic pelvic lymphadenectomy.

Humans↗

[Revascularization: light and shadow].

Advances in the knowledge of penile haemodynamics make evidence of two fundamental mechanisms in the physiology of erection: 1) arterial vasodilatation; 2) blockage of venous outflow. Therefore peripheric vasculogenic erectile impotence presents two pathogenetic possibilities: 1) from insufficient arterial flow; 2) from increased venous outflow. It is therefore very important to make the correct diagnosis of the patient with erectile disturbances in order to determine an appropriate therapy. The following examinations are routine tests carried out at our Institution: NPT test, basal and dynamic Doppler-sonography, OOE-OME (evaluation of output obtaining and maintenance erection), basic and dynamic cavernosography, digital angiography, dynamic NMR. After an accurate diagnostic assessment medical treatment can begin, based essentially on the cavernous infusion of vasoactive drugs, in light forms; surgery is resorted to severe cases, or in cases of failure of medical therapy. Proposed operations may be divided into 3 groups: 1) arterio-cavernous by-pass; 2) arterio-arterial by-pass; 3) venous surgery. Since 1978 the successive experiences of the Authors in this field and the better knowledge of penile vascular structures have led to a standardization of the methods used, with partly original techniques (epigastro-dorsal antiflow and orthoflow double by-pass), which, with selective application, have raised the percentage of pulsing anastomoses at 18 months of 82%.

Follow-Up Studies↗

[Radical surgery and conservation of erection in Peyronie's disease].

The radical surgical option we propose for Peyronie's disease consists in removing the sclero-hyanolitic focus (plaque) and replacing it by an autologous dermal graft taken from the upper outer thigh area. Between 1981 and 1994, we operated 564 patients with Induration penis plastica (IPP), 418 of whom underwent plaque excision and dermal grafting. All could be assessed at two-year follow-up. Two main complications were observed: penile flexure relapse (71 Pts, 17% of cases), and erectile dysfunction with decreased corporal rigidity (84 Pts, 20% of cases). A mild deviation of the penis can occur some months after surgery and it is not due to disease progression (as it should have evolutive characteristics) but is mere scar retraction (44 Pts, 76% of examined relapsed flexures). The degree of this graft retraction is linked to the individual's histologic response and can be due to an idioptic tissular response or to an insufficient size of the patch. In some cases, the post-op penile flexure can result from a progression of disease (14 Pts, 24% of examined relapses flexures) and can be due either to a new "focus" or to an incomplete removal of the previous plaque. As the patient will date the onset of a possible postoperative erectile deficit from the time of the operation, it is advisable to assess preoperatively the real erectile ability of all patients. Furthermore, a post-op impaired erectile response (84 Pts, 20%) could result from a subalbuginear fibrosis of the erectile tissue that leads to a caverno-occlusive dysfunction (60%). In more than 35% of patients we found a psychogenic component, due to post-surgical stress, that involves an adrenergic hypertone with peripherical vasoconstriction. In few cases (4%) the post-op erectile dysfunction is the consequence of peroperative arterial damages that results in hypoaesthesia of the glans (injury of dorsal arteries) or in failure to obtaining corporal rigidity (damage of cavernosal arteries). A review of our experience involving plaque excision and dermal grafting led us to propose this option in case of mechanical disturbance during coitus and when the association of erectile dysfunction can be excluded.

Follow-Up Studies↗

[Island flap in the surgical treatment of hypospadias].

Surgery of hypospadias represents an interesting field of innovatory ideas. Many methods may be suitable and many modifications can be performed. There is no one method for all kinds of hypospadias. It is necessary to find the right method for each patient. The result often depends upon the experience of the surgeon with a particular method. The choice between straightening and urethroplasty in one or two stages depends on cost-benefit ratio and evolution at distance of the straightening must be taken into account as well tissue consumption imposed by the urethroplasty, with one stage straightening that makes reintervention very difficult. In the latter case, a multi-stage operation will be necessary with flaps for urethroplasty after the straightening, or, in a more developed penis, a shortening operation according to Nesbit. With two-stage method, in case of relapsed curvature, this can easily be treated, if tissue is available. For a good result of urethroplasty the ability of surgeon, a constant calibration of the canal, plenty of elastic tissue for the neo-urethra, care not to suture on these planes, are highly important. In our opinion Duplay's method observes these requisites. Two-stages surgery allows easy correction of any eventual relapsing incurvature, with no problems for the following urethroplasty. One-stage surgery allows the problems to be resolved in a single surgical Step, but involves the risk of tissue consumption and proximal stricture.

Follow-Up Studies↗