PubMed Health⌕ Search

Biomedical subjects

M Spinelli

Publications and source records attributed to M Spinelli.

At least 19 recordsLinked to original sources
PubMed2006

Prevalence of the A1555G (12S rRNA) and tRNASer(UCN) mitochondrial mutations in hearing-impaired Brazilian patients.

Mitochondrial mutations are responsible for at least 1% of the cases of hereditary deafness, but the contribution of each mutation has not yet been defined in African-derived or native American genetic backgrounds. A total of 203 unselected hearing-impaired patients were screened for the presence of the mitochondrial mutation A1555G in the 12S rRNA gene and mutations in the tRNASer(UCN) gene in order to assess their frequency in the ethnically admixed Brazilian population. We found four individuals with A1555G mutation (2%), which is a frequency similar to those reported for European-derived populations in unselected samples. On the other hand, complete sequencing of the tRNASer(UCN) did not reveal reported pathogenic substitutions, namely A7445G, 7472insC, T7510C, or T7511C. Instead, other rare substitutions were found such as T1291C, A7569G, and G7444A. To evaluate the significance of these findings, 110 "European-Brazilians" and 190 "African-Brazilians" unrelated hearing controls were screened. The T1291C, A7569G and G7444A substitutions were each found in about 1% (2/190) of individuals of African ancestry, suggesting that they are probably polymorphic. Our results indicate that screening for the A1555G mutation is recommended among all Brazilian deaf patients, while testing for mutations in the tRNASer(UCN) gene should be considered only when other frequent deafness-causing mutations have been excluded or in the presence of a maternal transmission pattern.

Black People↗
PubMed2004

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↗
PubMed2003

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↗
PubMed2002

CD10 is a marker for cycling cells with propensity to apoptosis in childhood ALL.

CD10 constitutes a favourable prognostic marker for childhood acute lymphoblastic leukaemia. Since correlations between CD10, cell cycle and apoptotic abilities were demonstrated in various cell types, we investigated whether differences existed in the cycling/apoptotic abilities of CD10-positive and CD10-negative B acute lymphoblastic leukaemia cells. Twenty-eight cases of childhood acute lymphoblastic leukaemia (mean age of 6.8 years) were subdivided into two groups according to high (17 cases, 93.2+/-4.5%, MRFI 211+/-82 CD10-positive cells) or low (11 cases, 11.5+/-6.2%, MRFI 10+/-7 CD10-negative cells) expression of CD10. CD10-positive acute lymphoblastic leukaemia cells were cycling cells with elevated c-myc levels and propensity to apoptosis, whereas CD10-negative acute lymphoblastic leukaemia cells had lower cycling capacities and c-myc levels, and were resistant to apoptosis in vitro. A close correlation between all these properties was demonstrated by the observations that the few CD10-positive cells found in the CD10-negative acute lymphoblastic leukaemia group displayed elevated c-myc and cycling capacities and were apoptosis prone. Moreover, exposure of CD10-positive acute lymphoblastic leukaemia B cells to a peptide nucleic acid anti-gene specific for the second exon of c-myc caused inhibition of c-myc expression and reduced cell cycling and apoptotic abilities as well as decreased CD10 expression.

Antigens, CD↗
PubMed2002

Sacral neuromodulation and pregnancy.

PURPOSE: Sacral neuromodulation is effective for lower urinary tract dysfunction. However, despite its increasing use and a preponderance of female patients treated to our knowledge its effect in pregnant women and developing fetuses remains unknown. Therefore, we obtained information on patients on sacral neuromodulation who then achieved pregnancy. MATERIALS AND METHODS: Data were obtained using a standard questionnaire from 4 physicians with a total of 6 eligible patients. We recorded patient urological history, indication for neuromodulation, pregnancy course, the mode of delivery and neonatal health. We also noted the timing of implant deactivation and reactivation. RESULTS: In 5 patients the stimulator was deactivated between weeks 3 and 9 of gestation, after which 2 with a history of urinary retention had urinary tract infection. In another case, stimulation was discontinued 2 weeks before conception. The only noted complication developed in a pregnancy in which birth was premature at 34 weeks. Three patients underwent normal vaginal delivery, including 1 in whom subsequent implant reactivation did not resolve voiding dysfunction. In 3 cases elective cesarean section was performed. All neonates were healthy. CONCLUSIONS: When a patient on neuromodulation achieves pregnancy, the stimulation should be deactivated. If implant deactivation leads to urinary related complications that threaten the pregnancy, reactivation should be considered. Elective cesarean section should be discussed since it is possible for sacral lead damage or displacement to occur during vaginal delivery.

Adult↗
PubMed2001

Neuromodulation for fecal incontinence: outcome in 16 patients with definitive implant. The initial Italian Sacral Neurostimulation Group (GINS) experience.

PURPOSE: Sacral nerve modulation appears to offer a valid treatment option for some patients with fecal incontinence and functional defects of the internal anal sphincter or of the striated muscle. METHODS: Sixteen patients with fecal incontinence (4 males; mean age, 51.4 (range, 27-79) years) with intact or surgically repaired (n = 1) anal sphincter underwent permanent sacral nerve stimulation implant. Cause was traumatic in two patients, and associated disorders included scleroderma (2 patients) and spastic paraparesis (1 patient); eight (50 percent) of the patients also had urinary incontinence, and two (12.5 percent) had nonobstructive urinary retention. All patients were selected on the basis of positive findings from at least one peripheral nerve evaluation. The stimulating electrode was positioned in the S2 (1 patient), S3 (14 patients), or S4 (1 patient) sacral foramen. RESULTS: Mean follow-up was 15.5 (range, 3-45) months. Mean preimplant Williams score decreased from 4.1 +/- 0.9 (range, 2-5) to 1.25 +/- 0.5 (range, 1-2) (P = 0.01, Wilcoxon test), and the number of incontinence accidents for liquid or solid stool in 14 days decreased from 11.5 +/- 4.8 (range, 2-20) before implant to 0.6 +/- 0.9 (range, 0-2) at the last follow-up. Important manometric data were an increase in mean maximal pressure at rest of 37.7 +/- 14.9 mmHg (implantable pulse generator 49.1 +/- 18.7, P = 0.04) and in mean maximal pressure during squeeze (prestimulation 67.3 +/- 21.1 mmHg, implantable pulse generator 82.6 +/- 21.0, P = 0.09). CONCLUSIONS: Neuromodulation can be considered an option for fecal incontinence. However, an accurate clinical and instrumental evaluation and careful patient selection are required to optimize outcome.

Adult↗
PubMed2001

Flt-3 and its ligand are expressed in neural crest-derived tumors and promote survival and proliferation of their cell lines.

Flt-3 ligand (FL) is a cytokine that promotes the survival, proliferation, and differentiation of hematopoietic progenitors in synergy with other growth factors, such as stem cell factor. Previously we have demonstrated that stem cell factor and its receptor c-kit are expressed in neural crest-derived tumor cells and that a c-kit block induces their apoptosis. Here we have evaluated the expression of flt-3 and its ligand in 12 neuroectodermal tumor cell lines from neuroblastoma (NB), neuroepithelioma (NE), Ewing sarcoma (ES), and peripheral neuroectodermal tumor (PNET) and in 38 biopsies: 19 from NB and 19 from ES and PNET. RT-PCR demonstrated the expression of flt-3 and FL in all lines. Coexpression was observed in 42% of NB and in 74% of ES and PNET biopsies. Flow cytometry confirmed the presence of membrane and cytoplasmic flt-3 and membrane FL in all lines, whereas soluble FL protein was not measurable in their supernatants. Microphysiometric demonstration of acidification of the medium provided evidence of the specific response of cell lines to FL stimulation. Specific flt-3 phosphorylation after FL treatment was also demonstrated by Western blotting analysis. In cells growing in RPMI plus 1% fetal calf serum, FL revealed a significant proliferating activity, more evident in NB and NE lines (mean increase of viable cells, 73 +/- 26% after 1 day). Treatment with flt-3 antisense oligonucleotides significantly inhibited cell growth. FL also displayed an antiapoptotic activity: after a 12-hour culture in the presence of 0.1% fetal calf serum, FL caused a 50% reduction of apoptotic cells. These results provide further evidence that neuroectodermal and hematopoietic cells share common regulatory pathways, and could be of interest in the clinical management of neuroectodermal tumors.

Base Sequence↗
PubMed2001

[Benign unclassified tumor of the gonadal stroma: importance of alpha-inhibin expression].

We present a begin unclassified gonadal stroma tumor in a 62 year-old menopausal woman. We discuss the differential diagnosis with the most frequent fibromas and thecomas and with the rarer sclerosing stromal tumor of the ovary. The immunohistochemical staining for alpha-inhibin was important to confirm the origin of the spindle-cell proliferation from undifferentiated (unclassified) ovarian gonadal stroma.

Actins↗
PubMed2001

[Neurofibromatosis (NF1) and neuroleprosy: immunoreaction against pathologic Schwann-cells. Physiopathogenetic observations].

BACKGROUND: We reviewed the literature evaluating the immune reaction in neurofibromatosis (NF1) and neuroleprosy, so as to underline the immunopathegenetic parallelism and the possible therapeutic implications regarding the treatment of these two disorders. In particular we evaluated the systemic modifications and the local fibrotic events that lead to nerve damage in NF1 and complete neuronal destruction as in leprosy. METHODS: With the above aim in mind we studied the histology, histochemistry and immunohistochemistry (Schwann cells and immunoglobulins) of four plexiform neurofibroma, one common neurofibroma and one case of borderline neuroleprosy (BT). RESULTS: Two plexiform neurofibromas showed an evident immune reaction that was antibody mediated with numerous IgG; the remaining neurofibromas represented other stages of disease evolution and disease quiescence and thus showed a scarce immune reaction with a reduced presence of immunoglobulins. All the neurofibromas showed the presence of fibrous bundles. In the case of neuroleprosy (BT), the immune reaction was modest, immunoglobulins were present and fibrotic transformation on neuronal fibers was observed. CONCLUSIONS: Being that pathologic Schwann cell are the site of immune reactions that can become abnormal (at times with autoimmune reactions), clinical as well as biochemical surveillance of leprous neuropathy and NF1 could allow for a timely modification of the abnormal reaction with selective immunomodulators. The inactivation of the mycobacterial RNA polymerase or of the NF1 gene could offer hope for controlling disease activity and disease evolution of the two disorders.

Adolescent↗
PubMed2001

Chronic sacral neuromodulation in patients with lower urinary tract symptoms: results from a national register.

PURPOSE: The Italian Register was created in February 1997 to collect the national results of sacral neuromodulation. All Italian centers at which sacral neuromodulation is performed were invited to participate in our study. We present the results from retrospective and prospective registers. MATERIALS AND METHODS: A total of 196 patients underwent permanent implantation of sacral neuromodulation and were enrolled in the Italian register. There were 18 males and 75 females in the retrospective, and 28 males and 75 females in the prospective studies. Student's t test was used to compare paired values, and the Wilcoxon rank sum and nonparametric tests were used when necessary. RESULTS: Mean incontinent episodes daily plus or minus standard deviation for patients with detrusor instability went from 5.4 +/- 3.9 to 1.1 +/- 1.6 (median 5 and 0, respectively) at 12-month followup (p <0.001). For idiopathic retention average residual volume decreased from 277 to 108 cc (median 287 and 80, respectively), and 50% of patients stopped catheterization and another 13% catheterized once daily at 1-year after implantation. With neurogenic voiding disturbances, the results fluctuated with time from a minimum of 33% to a maximum 66% of patients who did not catheterize at 6-month followup and 12 months after implantation, respectively. At 12-month followup, 50% of patients with hyperreflexia had less than 1 incontinent episode daily. The problem was completely solved in 66% of patients in the retention group. Of patients in the urge incontinent population 39% were completely dry and 23% had less than 1 incontinent episode daily. CONCLUSIONS: Sacral neuromodulation is effective therapy for treating lower urinary tract symptoms resistant to less invasive therapy.

Adolescent↗
PubMed2001

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↗
PubMed2001

Quality of life assessment in patients who undergo sacral neuromodulation implantation for urge incontinence: an additional tool for evaluating outcome.

PURPOSE: We investigated the impact of sacral neuromodulation on quality of life and assessed the importance of quality of life for determining the success of sacral neuromodulation in patients with detrusor hyperactivity, including instability and hyperreflexia. We also compared it with parameters documented in a voiding diary. MATERIALS AND METHODS: From May 1998 to December 2000, 82 female and 31 male patients 17 to 79 years old (mean age 51.1) with urge incontinence (63), urgency/frequency (5), voiding disturbance (41) and pelvic pain (4) resistant to conservative treatment were enrolled in a national prospective registry after showing a positive response to percutaneous nerve evaluation testing. Of the patients 47 who were 32 to 79 years old (mean age 59.2) with urge incontinence due to detrusor instability and 16 who were 27 to 51 years old (mean age 51.5) with hyperreflexia were asked to complete a validated self-reporting incontinence domain specific quality of life questionnaire before, and 3, 6, 9, 12, 18, 24 and 36 months after implantation. RESULTS: Compared with baseline the quality of life index significantly improved at each followup, which strongly correlated with the decrease in the number of incontinence episodes. CONCLUSIONS: Evaluating quality of life may be an additional useful tool for assessing the results of sacral neuromodulation for urge incontinence. Our study confirms that sacral neuromodulation is effective therapy for urge incontinence that can have a positive effect on patient quality of life.

Adolescent↗
PubMed2000

Carcinosarcoma of the parotid gland: cytological, clinicopathological and immunohistochemical study of a case.

Manifesting a putative origin from a pleomorphic adenoma, carcinosarcoma of the salivary gland is a heterologous neoplasm in which a sarcomatous and a carcinomatous component coexist. We present a parotid gland carcinosarcoma in a 77-year-old man with peculiar morphological findings. Fine-needle aspiration cytology allowed a preoperative diagnosis of poorly differentiated carcinoma. At histologic examination, the tumor showed biphasic differentiation with an epithelial component made up of well-differentiated keratinizing squamous carcinoma and ductal-type adenocarcinoma, and a mesenchymal component, revealing focal areas of osteosarcoma and myoepithelial malignant proliferation. Carcinosarcoma is a very rare malignant neoplasm, accounting for 0.16% of malignant salivary gland tumors: only 60 cases have been reported, some of which arose "de novo", i.e., without clinico-pathologic evidence of a pre- or co-existing pleomorphic adenoma.

Aged↗