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Biomedical subjects

M Lazzeri

Publications and source records attributed to M Lazzeri.

At least 19 recordsLinked to original sources

Characterization of kinin receptors in human cultured detrusor smooth muscle cells.

BACKGROUND AND PURPOSE: Kinins have an important role in inflammatory cystitis and in animal pathophysiological models, by acting on epithelium, fibroblasts, sensory innervation and smooth muscle. The aim of this study was to characterize the receptors responsible for direct motor responses induced by kinins on human detrusor. EXPERIMENTAL APPROACH: Human detrusor cells from biopsies were isolated and maintained in culture. B(1) and B(2) kinin receptors were characterized by means of radioligand and functional experiments (PI accumulation and PGE(2) release). KEY RESULTS: [(3)H]-[desArg(9)]-Lys-BK and [(3)H]-BK saturation studies indicated receptor density (B(max)) and K (d) values of 19 or 113 fmol mg(-1), and 0.16 or 0.11 nM for the B(1) or B(2) receptors, respectively. Inhibition binding studies indicated the selectivity of the B(1) receptor antagonist [desArg(9)Leu(8)]-Lys-BK and of the B(2) receptor antagonists Icatibant and MEN16132. [DesArg(9)]-Lys-BK and BK induced PI accumulation with an EC(50) of 1.6 and 1.4 nM and different maximal responses (E(max) of [desArg(9)]-Lys-BK was 10% of BK). BK also induced prostaglandin E(2) release (EC(50) 2.3 nM), whereas no response was detected with the B(1) receptor agonist. The incubation of detrusor smooth muscle cells with interleukin 1beta (IL-1beta) or tumour necrosis factor-alpha (TNF-alpha) (10 ng ml(-1)) induced a time-dependent increase in radioligand-specific binding, which was greater for the B(1) than for the B(2) receptor. CONCLUSIONS AND IMPLICATIONS: Human detrusor smooth muscle cells in culture retain kinin receptors, and represent a suitable model to investigate the mechanisms and changes that occur under chronic inflammatory conditions.

Bradykinin↗

Raman spectrum of graphene and graphene layers.

Graphene is the two-dimensional building block for carbon allotropes of every other dimensionality. We show that its electronic structure is captured in its Raman spectrum that clearly evolves with the number of layers. The D peak second order changes in shape, width, and position for an increasing number of layers, reflecting the change in the electron bands via a double resonant Raman process. The G peak slightly down-shifts. This allows unambiguous, high-throughput, nondestructive identification of graphene layers, which is critically lacking in this emerging research area.

Journal Article↗

Penile carcinoma in patients with genital lichen sclerosus: a multicenter survey.

PURPOSE: In this observational descriptive study we reviewed the histology and the clinical records of 130 patients with LS involving the male genitalia to determine the presence of premalignant or malignant lesions. MATERIALS AND METHODS: A total of 130 male patients (from 1991 to 2001) with genital LS were treated at our centers. Mean patient age at diagnosis was 42.5 years. In all patients with a clinical diagnosis of LS, the histology was reexamined to look for evidence of LS, applying strict histological criteria. All cases of histologically proven epithelial malignancy, namely SCC, VC and EQ, were reviewed to confirm the presence of neoplastic changes and ascertain the degree of SCC differentiation. RESULTS: Of 130 men 11 (8.4%) with genital LS showed premalignant or malignant histopathological features including 7 (64%) with SCC, 2 (18%) with VC, 1 (9%) with EQ and 1 (9%) with SCC associated with VC. In 6 of 11 patients (55%) the histological study showed the presence of epithelial dysplasia. CONCLUSIONS: Survival of patients with penile carcinoma depends on early diagnosis and treatment, and all patients with genital LS should be observed closely to detect the development of neoplastic or preneoplastic lesions as early as possible.

Adolescent↗

Ion recombination correction for very high dose-per-pulse high-energy electron beams.

The parallel-plate ionization chamber is the recommended tool for the absorbed dose measurement in pulsed high-energy electron beams. Typically, the electron beams used in radiotherapy have a dose-per-pulse value less then 0.1 cGy/pulse. In this range the factor to correct the response of an ionization chamber for the lack of complete charge collection due to ion recombination (ksat) can be properly evaluated with the standard "two voltage" method proposed by the international dosimetric reports. Very high dose-per-pulse electron beams are employed in some special Linac dedicated to the Intra-Operatory-Radiation-Therapy (IORT). The high dose-per-pulse values (3-13 cGy/pulse) characterizing the IORT electron beams allow to deliver the therapeutic dose (10-20 Gy) in less than a minute. This considerably reduces the IORT procedure time, but some dosimetric problems arise because the standard method to evaluate ksat overestimates its value by 20%. Moreover, if the dose-per-pulse value >1 cGy/pulse, the dependence of ksat on the dose-per-pulse value cannot be neglected for relative dosimetry. In this work the dependence of ksat on the dose-per-pulse value is derived, based on the general equation that describes the ion recombination in the Boag theory. A new equation for ksat, depending on known or measurable quantities, is presented. The new ksat equation is experimentally tested by comparing the absorbed doses to water measured with parallel-plate ionization chambers (Roos and Markus) to that measured using dose-per-pulse independent dosimeters, such as radiochromic films and chemical Fricke dosimeters. These measurements are performed in the high dose-per-pulse (3-13 cGy/pulse) electron beams of the IORT dedicated Linac Hitesys Novac7 (Aprilia-Latina, Italy). The dose measurements made using the parallel-plate chambers and those made using the dose-per-pulse independent dosimeters are in good agreement (<3%). This demonstrates the possibility of using the parallel-plate ionization chambers also for the very high dose-per-pulse (> 1 cGy/pulse) electron-beam dosimetry.

Algorithms↗

Kohn anomalies and electron-phonon interactions in graphite.

We demonstrate that graphite phonon dispersions have two Kohn anomalies at the Gamma-E(2g) and K-A'1 modes. The anomalies are revealed by two sharp kinks. By an exact analytic derivation, we show that the slope of these kinks is proportional to the square of the electron-phonon coupling (EPC). Thus, we can directly measure the EPC from the experimental dispersions. The Gamma-E(2g) and K-A'1 EPCs are particularly large, while they are negligible for all the other modes at Gamma and K.

Journal Article↗

Intravesical infusion of resiniferatoxin by a temporary in situ drug delivery system to treat interstitial cystitis: a pilot study.

PURPOSE: Interstitial cystitis (IC), a syndrome characterized by motor and sensory dysfunction of the lower urinary tract, represents a diagnostic and therapeutic challenge even to highly skilled physicians. We investigated the technical feasibility and the clinical efficacy of a prolonged intravesical instillation of RTX by in situ drug delivery system in patients with IC. MATERIAL AND METHODS: 5 female patients (mean age 48.7 years) received a prolonged infusion of a saline solution containing 10nM of resiniferatoxin at the flow rate 25microl/h by the MiniMed 407C Infusion Pump (MiniMed Sylmar, CA, USA), connected to sovrapubic 5Fr mono Pigtail catheter, for 10 days. All patients reported frequency, nocturia and urgency, and symptoms of pelvic pain for at least six months. They showed the absence of urinary tract infection within the last three months, the absence of functional disorders of lower urinary tract and no other vesical or urethral pathology. The pre-treatment (PT) frequency/volume (FV) chart and a pain score (VAS score) were recorded. Patients were evaluated after 30 days from the end of infusion (primary end point, PEP) and after three months (secondary end point, SEP). RESULTS: At PEP frequency reduced from 11.3+/-1.39 to 7.4+/-1.51 (p<0.01) and nocturia from 3.6+/-0.54 to 1.2+/-0.44 (p<0.01). A highly significant reduction of pain score was observed at PEP: it decreased to 2.4+/-0.54 from 6.7+/-0.83 (p<0.01). The pain score remained significantly lower at SEP (3.2+/-0.44 p<0.05). Nocturia was also statistically reduced at SEP (1.9+/-0.74) as well as frequency (8.7+/-1.76). No side effects were reported during the infusion as well as after the removal of the catheter. CONCLUSION: The present study demonstrates that the prolonged intravesical instillation of a drug by in situ drug delivery system is a feasible procedure and seems to support the efficacy of RTX in the treatment of IC patients. However further studies are necessary and mandatory to confirm our results and to define the exact action mechanism of prolonged infusion of RTX, the dosage and the treatment schedule.

Administration, Intravesical↗

A minimally invasive method to evaluate 131I kinetics in blood.

The dose limiting factor for 131I therapy in patients with thyroid cancer is myelotoxicity, thus an accurate determination of radioiodine activity in the red marrow is of paramount importance. The reference method for red marrow dosimetry in radiometabolic therapy is based on the measurement of radioiodine kinetics, particularly the activity/time curve in blood. Such a measurement requires withdrawal of blood samples at various times after 131I administration. This procedure involves some potential risk from the radiation protection point of view, such as possible contamination of personnel with blood and disposal of the radioactive blood samples (and syringes). We present here a minimally invasive method to evaluate radioiodine kinetics in the blood, which only requires one blood sample and a set of measurements on the patient's thigh made with a collimated NaI(Tl) probe. The method has been validated in four patients treated with 131I for thyroid cancer.

Adult↗

Interim outcomes of dorsal skin graft bulbar urethroplasty.

PURPOSE: We update our interim results of bulbar urethroplasty using a skin graft placed on the dorsal urethral surface. MATERIALS AND METHODS: A total of 45 patients with an average age of 45 years underwent dorsal onlay skin graft urethroplasty between January 1994 and December 2000. Of the patients 23 had undergone an average of 2.6 prior endoscopic procedures (range 1 to 14). Preoperative evaluation include clinical history, physical examination, retrograde and voiding urethrography, and ultrasonography. In all patients the bulbar urethra was opened along its dorsal surface, the graft was sutured, splayed and quilted to the corpora cavernosa, and the urethra was rotated to cover the graft. In all patients was used penile skin as substitution material. Mean graft length was 4.7 cm (range 2.5 to 11). Three weeks after surgery voiding cystourethrography was performed. RESULTS: Average followup was 71 months (range 41 to 110). Clinical outcome was considered a failure when postoperative instrumentation was needed, including dilation. Of 45 cases 33 (73%) were classified as successful and 12 (27%) were failures. The 12 failures were treated with internal urethrotomy (1), end-to-end-anastomosis (1), skin graft urethroplasty (2) and 2-stage urethroplasty (6). Six of the 12 initial failures had a satisfactory final outcome. The remaining 6 patients refused further surgical procedures and received a definitive perineal urethrostomy. CONCLUSIONS: Penile skin grafts used as a dorsal onlay for bulbar urethral reconstruction in a homogeneous series of patients showed a tendency to deteriorate with time. Longer followup is required to compare penile skin with buccal mucosa as substitute materials for bulbar urethral reconstruction.

Adult↗

Anterior urethral strictures.

The surgical treatment of adult anterior urethral strictures has developed continuously. Recently considerable changes have been introduced, involving the cause of the urethral disease and surgical techniques. The criteria for selecting the reconstructive surgical technique are presented according to the cause and a new classification of urethral strictures. The main surgical procedures are presented and fully illustrated, with an updated and comprehensive review of recent publications.

Humans↗

Neurophysiological evidence may predict the outcome of sacral neuromodulation.

PURPOSE: Chronic stimulation of the sacral nerves has now become one of the most accepted stimulation therapies for functional lower urinary tract symptoms refractory to conservative treatment. Despite the existence of a large amount of literature on sacral neuromodulation (SNM) showing a fairly high percent of significant improvement in clinical outcome there are few experimental studies of SNM stimulus parameters and/or neurophysiological monitoring. We evaluated the specific action of SNM on the primary sensory cortical area. Somatosensory evoked potentials (SEPs) of the pudendal and posterior tibial nerves were evaluated in patients implanted with a monolateral permanent quadripolar electrode. MATERIALS AND METHODS: A total of 24 patients underwent stage 1 monolateral sacral nerve implantation. Three SEP patterns were evaluated; namely before implantation, 1 month after stage 1 with stimulation set at 21 Hz and again with a pulse rate of 40 Hz. RESULTS: In all patients SNM produced a significant decrease in pudendal SEP latency of the first positive deflection between baseline SNM stimulation at different pulse rates at the ipsilateral and contralateral implant sites. This finding was evidence of the effect of S3 SNM on the cortical sensory area and the specificity of pudendal SEPs in measuring how SNM modulates the afferent pathway from the spinal nerve to the cortical sensory area. CONCLUSIONS: Our study confirms previous observations that SNM acts by the afferent pathway at the cortical site level and it sheds light on so-called idiopathic lower urinary tract symptoms. A modification of SEPs induced by SNM seems to be a prognostic factor of clinical outcomes. The action of SNM on the afferent pathway from the sacral area to the somatosensory cortex is specific and neurophysiological evaluation via pudendal SEPs provides evidence to this effect.

Adolescent↗

Stress-driven reconstruction of an oxide surface: the anatase TiO(2)(001)-(1 x 4) surface.

The recently discovered (1 x 4) reconstruction of the stoichiometric anatase TiO(2)(001) surface is studied via first principles density functional calculations. We propose a new structural model for this reconstruction, which is energetically much more favorable than all the other available models, including the unreconstructed (1 x 1) surface. In this model, rows of TiO(3) species periodically replace rows of surface bridging oxygens of the (1 x 1) surface, thus leading to a relief of the large surface tensile stress present on that surface. The corresponding empty-state charge density distribution correctly describes the experimental scanning tunneling microscopy images.

Journal Article↗

Study of the correlation between administered activity and radiation committed dose to the thyroid in 131I therapy of Graves' disease.

Substantial reduction in the thyroid volume (up to 70-80%) after 131I therapy of Graves' disease has been demonstrated and reported in the literature. Recently a mathematical model of thyroid mass reduction during the first month after therapy has been developed and a new algorithm for the radiation committed dose calculation has been proposed. Reduction of the thyroid mass and the radiation committed dose to the gland depend on a parameter k, defined for each subject. The calculation of k allows the prediction of the activity to administer, depending on the radiation committed dose chosen by the physician. In this paper a method for calculating k is proposed. The calculated values of k are compared to values derived from measurements of the changes in thyroid mass in twenty-six patients treated by 131I for Graves' disease. The radiation committed dose to the thyroid can be predicted within 21%, and the radioiodine activity to administer to the patient can be predicted within 22% using the calculated values of k. The thyroid volume reduction during the first month after therapy administration can be also predicted with good accuracy using the calculated values of k. The radiation committed dose and the radioiodine activity to administer were calculated using a new, very simple algorithm. A comparison between the values calculated by this new algorithm and the old, classical Marinelli-Quimby algorithm shows that the new method is more accurate.

Algorithms↗

Long-term outcome of urethroplasty after failed urethrotomy versus primary repair.

PURPOSE: A urethral stricture recurring after repeat urethrotomy challenges even a skilled urologist. To address the question of whether to repeat urethrotomy or perform open reconstructive surgery, we retrospectively review a series of 93 patients comparing those who underwent primary repair versus those who had undergone urethrotomy and underwent secondary treatment. MATERIALS AND METHODS: From 1975 to 1998, 93 males between age 13 and 78 years (mean 39) underwent surgical treatment for bulbar urethral stricture. In 46 (49%) of the patients urethroplasty was performed as primary repair, and in 47 (51%) after previously failed urethrotomy. The strictures were localized in the bulbous urethra without involvement of penile or membranous tracts. The etiology was ischemic in 37 patients, traumatic in 23, unknown in 17 and inflammatory in 16. To simplify evaluation of the results, the clinical outcome was considered either a success or a failure at the time any postoperative procedure was needed, including dilation. RESULTS: In our 93 patients primary urethroplasty had a final success rate of 85%, and after failed urethrotomy 87%. Previously failed urethrotomy did not influence the long-term outcome of urethroplasty. The long-term results of different urethroplasty techniques had a final success rate ranging from 77% to 96%. CONCLUSIONS: We conclude that failed urethrotomy does not condition the long-term result of surgical repair. With extended followup, the success rate of urethroplasty decreases with time but it is in fact still higher than that of urethrotomy.

Adolescent↗

Urodynamic and clinical evidence of acute inhibitory effects of intravesical nociceptin/orphanin FQ on detrusor overactivity in humans: a pilot study.

PURPOSE: Management of neurogenic incontinence is complex and available treatments are not satisfactory. Nociceptin/orphanin FQ, a recently discovered neuropeptide, has been reported to inhibit the voiding reflex in the rat. These experimental results prompted us to investigate the urodynamic and clinical effects of intravesical instillation of nociceptin/orphanin FQ in humans. MATERIAL AND METHODS: Our study involved 5 normal subjects (group 1) with a mean age of 40.4 years (range 21 to 54) and 9 patients (group 2) 40.4 years (24 to 54). All patients in group 2 presented with detrusor hyperreflexia refractory to standard therapy. They were invited to undergo a filling cystometrogram with saline solution and after 30 minutes, a new one with a solution containing 1 microM. nociceptin/orphanin FQ. The urodynamic parameters that were recorded included bladder capacity, volume threshold for the appearance of detrusor hyperreflexia and maximum bladder pressure. Clinical and urodynamic followup was performed after 15 days. The data were statistically analyzed with 1-way analysis of variance followed by the Dunnett test for multiple comparison considered statistically significant with p <0.05. RESULTS: Intravesical instillation of 1 microM. nociceptin/orphanin FQ in group 1 did not produce significant functional changes. This infusion in group 2 produced a statistically significant increase in mean bladder capacity and volume threshold for the appearance of detrusor hyperreflexia from 164 plus or minus standard deviation (SD) 84 to 301 +/- 118 and 93 plus or minus SD 41 to 231 +/- 104 ml. (p <0.05, respectively). Mean maximum bladder pressure decreased from 79 plus or minus SD 25 to 54 +/- 44 cm. water but was not statistically significant (p = 0.19). After 15 days an absence of clinical improvement was noticed in group 2, and the urodynamic control did not show any significant changes compared to the values before nociceptin/orphanin FQ treatment. No severe symptomatic reactions were observed during infusion of 1 microM. nociceptin/orphanin FQ. CONCLUSIONS: Our results demonstrate that nociceptin/orphanin FQ is able to elicit a robust inhibitory effect on voiding reflex in group 2 but not 1. The ideal dosage, route of administration of nociceptin/orphanin FQ and treatment interval are not yet established.

Administration, Intravesical↗

Characterization of bradykinin B(2) receptor antagonists in human and rat urinary bladder.

The effect of three selective bradykinin B(2) receptor antagonists, MEN11270 (H-DArg-Arg-Pro-Hyp-Gly-Thi-c(Dab-DTic-Oic-Arg)c(7gamma-1 0alpha)), Icatibant (H-DArg-Arg-Pro-Hyp-Gly-Thi-Ser-DTic-Oic-Arg-OH), and FR173567 ((E)-3-(6-acetamido-3-pyridyl)-N-[N-[2, 4-dichloro-3-[(2-methyl-8-quinolinyl) oxymethyl] phenyl]-N-methylaminocarbonylmethyl]acrylamide) was evaluated in the human and rat urinary bladder in vitro and in vivo in anaesthetized rats. Bradykinin evoked a concentration-dependent contraction of human (pD(2)=7.2) and rat (pD(2)=7.7) detrusor muscle strips. In human preparations, all the antagonists tested produced a rightward-shift in the concentration-response curve for bradykinin. Schild plot analysis yielded pK(B) values of 8.4, 8.4 and 8.6 for MEN11270, Icatibant, and FR173567, respectively. In the rat preparations the three antagonists (at 100 nM concentration), produced a shift to the right which gave apparent pA(2) values of 8. 2, 8.0 and 8.1 for MEN11270, Icatibant, and FR173567, respectively. In anaesthetized rats, both MEN11270 and Icatibant (1-10 nmol/kg i.v. ) dose dependently reduced the bradykinin (100 nmol/kg i.v.)-induced urinary bladder contraction, their effect being prompt and long-lasting. In contrast, FR173567 (100 nmol/kg i.v.) produced a partial and short-lasting inhibition of bradykinin-induced bladder contractions. The present findings indicate that all the antagonists tested recognize with similar potencies the bradykinin B(2) receptors expressed in the detrusor muscle of both humans and rats. MEN11270 and Icatibant possess a higher potency and longer duration of action in vivo than FR173657, suggesting that the activity of this non-peptide antagonist in vivo is hampered by factors unrelated to its affinity for bradykinin B(2) receptors.

Aged↗

Influence of thyroid volume reduction on calculated dose in radioiodine therapy of Graves' hyperthyroidism.

Administration of radioactive iodine (131I) is an effective treatment for hyperthyroidism due to Graves' disease. Recently several investigators have shown that the success of this therapy may depend on the absorbed dose to the thyroid. Thyroid dose varies inversely with the mass of the gland. Much experimental evidence demonstrates that a reduction of the thyroid volume (mass) may occur after radioiodine therapy. In this work we evaluate the influence of the volume reduction on the calculation of the absorbed dose to the thyroid. A mathematical model of thyroid mass reduction after 131I therapy is presented, based on masses evaluated with ultrasonography of ten patients treated in the endocrinology department of our hospital. This model was applied to the general formula for calculation of the thyroid doses in these patients. The dose values obtained considering a reduction of thyroid mass after the treatment are often quite different from those obtained without considering change in mass (from 9% to 30% greater). We conclude that the consideration of thyroid mass reduction is important for an accurate estimation of the calculated dose.

Graves Disease↗

Intravesical resiniferatoxin for the treatment of hypersensitive disorder: a randomized placebo controlled study.

PURPOSE: Present therapeutic approaches to control hypersensitive disorder of the lower urinary tract and bladder pain are clinically and scientifically unsatisfactory. We performed a randomized placebo controlled study with followup after 1 and 3 months using intravesical resiniferatoxin to treat hypersensitive disorder and bladder pain. MATERIALS AND METHODS: We prospectively randomized 18 patients into 2 groups to receive a single dose of 10 nM. resiniferatoxin intravesically (group 1) or a placebo saline solution only (group 2). All patients had at least a 6-month history of frequency, nocturia, urgency and symptoms of pelvic pain as well as no urinary tract infection within the last 3 months, functional disorders of the lower urinary tract, or other vesical or urethral pathology. Pretreatment voiding pattern and pain score were recorded. Patients were evaluated after 30 days (primary end point) and 3 months (secondary end point). RESULTS: The 2 groups were adequately homogeneous in regard to patient age, sex ratio, disease duration, voiding pattern and pain score. At the primary end point mean frequency plus or minus standard error of mean was decreased from 12. 444 +/- 0.70 voids to 7.111 +/- 0.67 and nocturia from 3.777 +/- 0. 27 to 1.666 +/- 0.16 (p <0.01). We observed a lesser significant improvement in mean frequency in group 1 at the secondary end point to 10.444 +/- 0.94 voids (p <0.05). No significant modification was noted in patients assigned to placebo. Mean pain score significantly decreased in group 1 at the primary end point from 5.555 +/- 0.29 to 2.666 +/- 0.23 (p <0.01) but not at the secondary end point (4.777 +/- 0.66, p >0.05). No statistically significant improvement in mean pain score was observed in placebo group 2. During resiniferatoxin infusion 4 group 1 patients noticed a light warm or burning sensation at the suprapubic and/or urethral level. CONCLUSIONS: Intravesical resiniferatoxin may significantly improve the voiding pattern and pain score in patients with hypersensitive disorder and bladder pain. Because resiniferatoxin did not cause a significant warm or burning sensation at the suprapubic and/or urethral level, it may be considered a new strategy for treating hypersensitive disorder and bladder pain. However, further studies are necessary to confirm our results and define the resiniferatoxin mechanism of action, dose and necessary treatment schedule.

Administration, Intravesical↗