Oral surgery in patients on oral anticoagulant therapy: a randomized comparison of different INR targets.
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Administration, Oral↗
Biomedical subjects
R Sacco
Publications and source records attributed to R Sacco.
Paraoxonase gene variants are associated with autism in North America, but not in Italy: possible regional specificity in gene-environment interactions.
Organophosphates (OPs) are routinely used as pesticides in agriculture and as insecticides within the household. Our prior work on Reelin and APOE delineated a gene-environment interactive model of autism pathogenesis, whereby genetically vulnerable individuals prenatally exposed to OPs during critical periods in neurodevelopment could undergo altered neuronal migration, resulting in an autistic syndrome. Since household use of OPs is far greater in the USA than in Italy, this model was predicted to hold validity in North America, but not in Europe. Here, we indirectly test this hypothesis by assessing linkage/association between autism and variants of the paraoxonase gene (PON1) encoding paraoxonase, the enzyme responsible for OP detoxification. Three functional single nucleotide polymorphisms, PON1 C-108T, L55M, and Q192R, were assessed in 177 Italian and 107 Caucasian-American complete trios with primary autistic probands. As predicted, Caucasian-American and not Italian families display a significant association between autism and PON1 variants less active in vitro on the OP diazinon (R192), according to case-control contrasts (Q192R: chi2=6.33, 1 df, P<0.025), transmission/disequilibrium tests (Q192R: TDT chi2=5.26, 1 df, P<0.025), family-based association tests (Q192R and L55M: FBAT Z=2.291 and 2.435 respectively, P<0.025), and haplotype-based association tests (L55/R192: HBAT Z=2.430, P<0.025). These results are consistent with our model and provide further support for the hypothesis that concurrent genetic vulnerability and environmental OP exposure may possibly contribute to autism pathogenesis in a sizable subgroup of North American individuals.
Aryldialkylphosphatase↗
Expression of adenylyl cyclase types III and VI in human hyperfunctioning thyroid nodules.
Hyperfunctioning thyroid nodules are characterized by the presence of spontaneous somatic mutations responsible for constitutive activation of the cAMP pathway. However, alterations affecting other elements of the cAMP signaling system may counteract the effects of the mutations. In this study, the expression of the adenylyl cyclase (AC) types III and VI was investigated by Western blot in 18 hyperfunctioning thyroid nodules; in 12 samples, we also assessed the presence of TSH receptor (TSHR) or gsp mutations and levels of AC VI and III mRNA. We found that the expression of nodular AC VI (but not AC III) was significantly lower (85.1% of normal, P=0.014) than the expression of both adenylyl cycles types of perinodular tissue from the same patients. Slightly, but not significant differences were detected in nodules with or without mutations and AC protein levels generally showed correlation with the levels of the transcripts detected by RT-PCR. In addition, AC III and AC VI expression levels within a given nodule were characterized by a significant positive correlation. These findings indicate that a diminished expression of AC type VI may be part of the mechanisms occurring in the hyperfunctioning nodules, independently of the presence of TSHR or gsp mutations, which influence the resulting phenotype.
Adenylyl Cyclases↗
Impact of laparoscopy on the management of an unusual case of nonpalpable testis in an adult patient.
BACKGROUND: In the past decade, cryptorchidism has generally been treated in the first 36 months of life using an inguinal approach, in the case of palpable testis, or using laparoscopy, in the case of nonpalpable testis. Nevertheless, before this period some children were managed incorrectly. This case report shows how laparoscopy and the collaboration between pediatric surgeons and urologists may lead to optimal results. CASE REPORT: A 19-year-old male was referred to our unit following routine medical examination for enrollment in the military service with a diagnosis of right cryptorchidism. The clinical history showed the anamnesis of right cryptorchidism diagnosed at birth as a right nonpalpable testis, confirmed at 2 years of age with clinical examination and computer tomography. The patient came to our attention to again undergo a clinical examination, ultrasonography, computed tomography, and magnetic resonance imaging. We found a left, well-positioned testis of 20 ml in volume and an empty right scrotum; all the instrumental examinations were negative. The patient was thus scheduled for a diagnostic laparoscopy. A pediatric surgeon with extensive experience in this pathology performed the procedure. The 10-mm 30 degrees optics introduced through the umbilicus showed a closed right inguinal ring, with no evidence of either vas deferens or inner spermatic vessels at the level of the inguinal region or pelvis. Two more trocars were introduced and a testis of 15 ml in volume was found under the ascending colon 10 cm away from the cecum. An orchiectomy was performed via laparoscopy. CONCLUSION: This case clearly shows that some males with nonpalpable testis may have been treated incorrectly in the prelaparoscopic era and may now have an intraabdominal testis. In addition, our experience shows that intraabdominal testis may sometime be in an unusual location, and a laparoscopic surgeon with experience in this pathology is fundamental to finding the testis. In the case of adults with nonpalpable testis, when echography, computed tomography, and magnetic resonance imaging are not useful, the only effective diagnostic procedure is laparoscopy.
Abdominal Cavity↗
Are extended biopsies really necessary to improve prostate cancer detection?
The aim of this study is to understand the value of specific sites in extended peripheral and transition zone biopsy schemes in order to define the optimal systematic biopsy regimen correlated with the percentage of positivity of each single bioptic site. A total of 165 consecutive patients underwent transrectal ultrasonography examination to detect prostate cancer followed by a lesion-directed and systematic 14-step biopsy scheme. The detection rate was examined for the lesion-directed and for each zone region biopsy. The frequency of positive biopsies in the various prostate regions was determined to evaluate the diagnostic yield of each biopsy site. Analysis was stratified for prostate-specific antigen (PSA), free-to-total PSA ratio, age, prostate size and digital rectal examination. The biopsy protocol detected 40% of patients (66/165) as positive and 55.1% (91/165) as negative for cancer. Standard sextant biopsy was expected to detect only 51 cancer on 66, lateral peripheral (PZ), transition (TZ) and central zone (CZ) biopsies only 56 cancer on 66, while the combination of sextant, PZ, TZ and CZ biopsies, for a total of 14 zone biopsies, detected 64 on 66 patients with cancer (97%) at recruitment. Sampling only the eight prostate regions with higher frequency of positive cancer biopsy was expected to detect 61 cancer patients against the 64 found with the 14-step scheme. This eight-biopsy regimen outperforms the conventional sextant regimen in cancer detection rate (93 vs 77%) and has an overall detection rate lower by only 3.1% (36.9 vs 40%) compared to the 14-biopsy regimen. This difference in detection rate is even smaller in patients with PSA values <10 ng/ml, age <70 y and prostate size <50 ml. This eight-biopsy scheme, including sampling in PZ and TZ toward the base, should be considered in an initial biopsy scheme to maintain a similar detection rate of an extensive biopsy scheme reducing the number of biopsies.
Biopsy↗
Thyrotropin receptor mutations and thyroid hyperfunctioning adenomas ten years after their first discovery: unresolved questions.
Ten years after the first description of activating mutations in the thyroid stimulating hormone receptor (TSHR) gene in sporadic autonomous hyperfunctioning thyroid adenomas, there is general agreement in assigning a major pathogenic role of this genetic abnormality, acting via the constitutive activation of the cAMP pathway, in both the growth and functional characteristic of these tumours. From the beginning, however, the pathophysiological and clinical relevance of somatic TSHR mutations has been debated and some arguments still exist against a fully causative role of these mutations and the practical value of detecting these mutations for the diagnosis, treatment and prognosis of thyroid hot nodules. Some major issues will be examined herein, including (a) the frequency of TSHR alterations in various reports showing that the genetic abnormality underlying the pathogenesis of a substantial subset of thyroid tumours has yet to be identified; (b) the limitations of the present experimental models, which suggest greater caution in the interpretation of in vitro results; (c) the still unresolved question of absence of genotype-phenotype correlation. Clarification of these issues may hopefully provide new and useful tools for improving the clinical management of this disease.
Adenoma↗
Novel hypotensive agents from Verbesina caracasana. 8. Synthesis and pharmacology of (3,4-dimethoxycinnamoyl)-N(1)-agmatine and synthetic analogues.
The more polar metabolites from the Venezuelan plant Verbesina caracasana, i.e., N(3)-prenylagmatine, (3,4-dimethoxycinnamoyl)-N(1)-agmatine, agmatine, and galegine (prenylguanidine), previously reported (Delle Monache, G.; et al. BioMed. Chem. Lett. 1999, 9, 3249-3254), have been synthesized following a biosynthetic strategy. The pharmacologic profiles of various synthetic analogues of (3,4-dimethoxycinnamoyl)-N(1)-agmatine (G5) were also analyzed, to shed some light on the structure-activity relationship of these compounds. Derivatives with the (E)-configuration and/or with a p-methoxybenzoyl moiety were found to be responsible for higher hypotensive effects, which were associated with a slight and, in some cases, not dose-related increase of cardiac inotropism, with variable and not significant chronotopic responses, and, only at higher doses, with effects of respiratory depression. Either an increase (to six) or a decrease (to two) of the number of methylene groups in the alkyl chain of (E)-G5 did not change blood pressure responses, while slightly increasing the positive inotropic ones. At pharmacological doses, all the studied compounds showed hypotensive and slight positive inotropic effects without relevant chronotropic and respiratory actions.
Agmatine↗
Results and complications of laparoscopic cholecystectomy in childhood.
BACKGROUND: The purpose of our study was to evaluate the results and complications of laparoscopic cholecystectomy in a case series of 110 infants. METHODS: Over a 5-year period (1993-98), we performed laparoscopic cholecystectomy in 110 pediatric patients. Surgery was performed at different institutions by three different surgeons. The patient population was composed of 69 girls and 41 boys; their ages ranged from 1 to 16 years (median, 8.5). All of the 110 children had symptomatic cholelithiasis, which was confirmed at ultrasound examination. An associated pathology was present in 27 patients (sickle cell disease in 17 cases, hereditary spherocytosis in seven cases, thalassemia in three); the other 83 infants were affected by idiopathic cholelithiasis. In 107 patients, the operation was performed using four ports; in three patients, it was done using five ports. In three patients, we also performed a concomitant splenectomy. RESULTS: Median duration of simple cholecystectomy was 45 min (range, 25-75) and hospital stay ranged from 1 to 10 days (median, 2). Only 15 children required drainage. We had 17 complications in our series (15.5%), including a gallbladder perforation during dissection in 11 patients, a fall of stones into the abdominal cavity during extraction in one patient, and a trocar orifice infection in the postoperative period in five patients. At a maximum follow-up of five years (range, 1-5), all patients were doing well. CONCLUSION: Laparoscopic cholecystectomy in children seems to be as effective as open surgery in cases of symptomatic cholelithiasis. In pediatric patients more than in adults, an accurate and precise dissection and a sound knowledge of possible congenital biliary abnormalities are essential to avoid any kind of complication.
Adolescent↗
Results and complications of laparoscopic surgery for pediatric varicocele.
BACKGROUND: The aim of this study was to evaluate the results and complications of laparoscopic varicocelectomy in children. METHODS: Over a 36-month period, 211 children underwent laparoscopic treatment of varicocele. Their ages ranged between 6 and 17 years; the varicocele was located on the left side in 209 cases (99.1%) and was bilateral in 2 (0.9%). In 195 patients the laparoscopic transperitoneal approach was used and in 16 retroperitoneoscopy was used. Thirty children (14.2%) underwent ligation of the veins alone, and 181 (85.8%) underwent ligation of testicular veins and artery. In 15 (7.1%) cases an additional procedure was applied during the same operation. RESULTS: Average operating time was 30 minutes and hospitalization about 24 hours. At an average follow-up of 26 months, there were 19 (9%) postoperative complications: 14 children had a left hydrocele, 3 children a scrotal emphysema, and 2 an umbilical granuloma. There were 5 recurrences of varicocele in our series: 2 (2 of 30, 6.6%) after the Ivanissevitch procedure, and 3 (3 of 181, 1.6%) after Palomo's. Testicular atrophy did not occur in any patient of this series. CONCLUSIONS: This preliminary experience shows that the results of the laparoscopic approach are comparable to those of the open approach. The ligation of testicular veins and artery is preferable to the ligation of the testicular veins alone. Hydrocele seems to be the most frequent postoperative complication and a potential problem, especially in children operated on with the Palomo procedure.
Adolescent↗
Distribution of hepatitis C virus serotypes and duration of infection in HCV infected subjects from a geographical area in Southeast Italy.
Hepatitis C virus serotypes and the duration of infection HCV positive subjects from a restricted geographical area in Italy, were evaluated. HCV serotypes were determined by Murex serotyping assay. Serotypes were detected in 592 (88.0%) of 669 samples. Type 1 proved to be the most frequent (48.9%), followed by types 2 (29%), 3(4.5%) and 4 (2.1%). The transmission of HCV 3 and 4 were observed only in the past 20 years whilst those of other types were recorded during 40 or more years. The results support the view that the prevalence of different HCV types of infection in one restricted geographical area may be associated with the source and duration of infection.
Adult↗
Transforming growth factor beta1 and soluble Fas serum levels in hepatocellular carcinoma.
In this study we assessed the usefulness of serum Transforming Growth Factor-beta1 (TGF-beta1) and soluble Fas (sFas) in distinguishing liver cirrhosis (LC) with and without hepatocellular carcinoma (HCC) as compared with alpha-fetoprotein (AFP). Serum TGF-beta1 and sFas levels were measured by ELISA in 51 LC patients, 54 patients with HCC and 30 healthy donors. Considering as a cut-off limit (mean+1SD of controls) 74 pg/ml and 637 pg/ml for TGF-beta1 and sFas, respectively, we computed serum concentrations of TGF-beta1 and sFas as a score (mean+/-SD). The positive frequency of serum TGF-beta1 levels in HCC patients (54%) was greater than in LC patients (26%) and healthy donors (3%). TGF-beta1 levels were higher in HCC (1.6+/-0.5) than in LC (1.1+/-0.2) (P<0.0001) and healthy donors (0.6+/-0.2). Using a cut-off limit of 82 pg/ml (mean+2SD), the positive frequency of TGF-beta1 was 20% in HCC patients. None of the controls and LC patients had TGF-beta1 levels higher than 82 pg/ml. The positive frequency of serum sFas levels was 100% in HCC patients, 98% in LC patients and 3% in healthy controls. Serum sFas levels were higher in HCC (2.5+/-0.7) than in LC (1.9+/-0.5) (P<0. 001) and healthy donors (0.6+/-0.3). No significant change of positive frequency was obtained by setting sFas cut-off at higher levels. sFas values did not correlate with TGF-beta1 levels. No relationship was found between TGF-beta1 amounts and AFP levels. However, in the 23% of HCC patients, with normal AFP values TGF-beta1 levels were higher than the cut off. These findings suggest the potential usefulness for TGF-beta1 assay in AFP-negative HCC.
Adult↗
Malignant pleural disease.
The vast majority of pleural neoplasms invade the pleura secondarily and can be seen in patients with bronchogenic carcinoma, breast cancer, lymphoma, and ovarian or gastric carcinoma. Primary pleural neoplasms are less common, although they have developed notoriety since the up-surge of malignant mesothelioma and the knowledge of its connection to asbestos exposure. Other malignant primary tumors include localized fibrous tumor and pleural liposarcoma. In most patients with diffuse malignant pleural disease the chest radiograph shows pleural effusion with or without pleural thickening. Computed tomography (CT) usually provides precise localization and extent of the disease and may be of value in assessing chest wall and mediastinal involvement. In specific situations, magnetic resonance (MR) may be useful as a problem-solving tool when CT findings of chest wall or diaphragmatic invasion are equivocal or in patients with contraindication to intravenous administration of ionic contrast material.
Asbestos↗
Optimising local therapy during oral surgery in patients with von Willebrand disease: effective results from a retrospective analysis of 63 cases.
Bleeding after dental extractions is very frequent in patients with von Willebrand disease (vWD) and in the past often necessitated transfusions with factor VIII/von Willebrand factor concentrates (vWFc). To evaluate the benefits of a standard local therapy on bleeding complications during oral surgery, 63 consecutive patients with vWD were analysed retrospectively. All types of vWD were included: type 1 (n=31), type 2 (n=22) and type 3 (n=10). All the patients had dental extractions or periodontal surgery at the same hospital by the same oral surgeons. All cases had been given tranexamic acid (TA) before and for 7 days after surgery. As additional local therapy fibrin glue (FG) was used during surgery in several patients. Additional systemic therapies were: desmopressin (DDAVP, 0.3 microg kg-1) and fVIII/vWF concentrates (vWFc, 40 U kg-1) given as a single dose before surgery. The 29 subjects (46%) treated locally did not bleed. Among the remaining cases, 24 (38%) were given DDAVP as additional systemic therapy and 6 (9.5%) received vWFc. There was bleeding after surgery in only two cases who had been given local FG (type 2 B) or systemic vWFc (type 3), but bleeding was stopped with an additional local application of FG. Our data suggest that a standard local therapy with TA and FG with DDAVP can prevent bleeding complications during oral surgery in the majority of patients (84%) with vWD and reduce the need for concentrates, with all their possible complications and high costs.
Adolescent↗
Hepatitis C virus serotypes in haemodialysis patients in South-East Italy.
Hepatitis C virus (HCV) infection is highly prevalent in haemodialysis patients. To date, only a few studies involving a small number of subjects have characterized HCV-infected dialysis patients by serotyping. The spread of HCV serotypes in 114 HCV-positive dialysis patients from the same geographical area was evaluated by Murex HCV serotyping assay. Serotypes were detected in 102 subjects (89.5%), with type 1 being the most frequent (37.7%), followed by types 2 (19.3%), 4 (8.8%) and 3 (7.9%). Types 5 and 6 were the least prevalent (3.5%). Ten samples (8.8%) revealed mixed infections: type 1 was detectable in all and the co-infecting HCV types were types 2, 3 and 4 in 3, 4 and 3 cases, respectively. These results suggest that the serotyping assay as an alternative method of distinguishing the major types of HCV, also for particular risk groups and especially in laboratories that lack the specific expertise to perform genotyping methods. Age-related differences in patients with type 5 compared with those with types 3 and 6 may provide evidence of a more recent spread of these latter types.
Adult↗
Bivariate binary data analysis with nonignorably missing outcomes.
One of the objectives in the Northern Manhattan Stroke Study is to investigate the impact of stroke subtype on the functional status 2 years after the first ischemic stroke. A challenge in this analysis is that the functional status at 2 years after stroke is not completely observed. In this paper, we propose a method to handle nonignorably missing binary functional status when the baseline value and the covariates are completely observed. The proposed method consists of fitting four separate binary regression models: for the baseline outcome, the outcome 2 years after the stroke, the product of the previous two, and finally, the missingness indicator. We then conduct a sensitivity analysis by varying the assumptions about the third and the fourth binary regression models. Our method belongs to an imputation paradigm and can be an alternative to the weighting method of Rotnitzky and Robins (1997, Statistics in Medicine 16, 81-102). A jackknife variance estimate is proposed for the variance of the resulting estimate. The proposed analysis can be implemented using statistical software such as SAS.
Biometry↗
sICAM-1, sCD95 and sCD95L levels in chronic liver diseases of different etiology.
The release of soluble circulating molecules represents a prominent feature during the course of immune-mediated clinical conditions. To further assess the relationship between serum concentrations of adhesion or apoptotic-related soluble structures and liver diseases, we evaluated the levels of intercellular adhesion molecule-1 (sICAM-1), Fas receptor (CD95) and Fas ligand (sCD95L) in a group of patients affected by Hepatitis C Virus (HCV)-induced chronic hepatitis (CH-C), HCV-positive liver cirrhosis with superimposed hepatocellular carcinoma (HCC), autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC) and alcoholic liver cirrhosis (ALC). Results show that sICAM-1 values were in all instances significantly elevated when compared to those seen in healthy donors. Similar findings were noted in subjects with liver diseases in terms of sCD95 concentrations, even if to a different degree of statistical significance. Finally, sCD95L amounts were augmented in AIH, PBC, ALC and CH-C in comparison to controls, while in the HCC counterpart sCD95L levels fell within normal range. All together, these findings emphasize the occurrence of circulating soluble molecules in patients with various chronic liver diseases, likely reflecting the involvement of several pathogenetic mechanisms.
Adult↗
p21WAF1/CIP1 protein expression in primary ovarian cancer.
p21WAF1/CIP1 protein is a cyclin-dependent kinase inhibitor, able to prevent the CDK2/cyclin E induced retinoblastoma protein (pRB) phosphorylation, thus inhibiting cell cycle progression at G1 phase. p21WAF1/CIP1 protein levels were examined in a series of 102 ovarian tissue samples including normal ovary, primary ovarian tumors, omental metastasis, recurrent disease and residual tumor after chemotherapy exposure, by Western blot analysis. The association of p21WAF1/CIP1 status with clinicopathological parameters and clinical outcome was also investigated. p21WAF1/CIP1 protein was detectable in 76 out of 102 (74%) ovarian tissue samples. We observed a significant trend of p21 levels to gradually increase from normal ovarian tissues (median 0 a.u.) through primary ovarian cancers (median 0.19 a.u.), omental metastases (median 0.33 a.u.) and recurrence of disease (median 0.44 a.u.) (p=0.015). In the group of stage III-IV ovarian cancer patients, p21-positive cases showed a more favourable prognosis with respect to p21-negative cases: the 3-year time to progression (TTP) rate was 58% for p21-positive compared with 33% of p21-negative cases (p=0.036). In conclusion, p21WAF1/CIP1 expression levels seem to be correlated with tumor status at the time of diagnosis and can predict TTP in a selected group of patients.
Adult↗
Hepatitis C virus-RNA, immunoglobulin M anti-HCV and risk factors in haemodialysis patients.
In order to evaluate hepatitis C virus-RNA (HCV-RNA), immunoglobulin M (IgM) anti-HCV and risk factors in haemodialysis patients, 180 subjects (45 HCV negative and 135 HCV positive) were studied. Sex, age, duration of dialysis, number of transfusions and ALT were also considered. HCV-RNA was determined by the Amplicor HCV test, and IgM anti-HCV by the Abbott HCV IgM EIA. These markers were present in 40% and 30.4% of anti-HCV positive subjects. The agreement between the two tests employed was 77%. The results showed a close association between HCV-RNA and IgM anti-HCV with abnormal ALT levels and between HCV-RNA and the number of transfusions. Both of these markers were different when correlated with age and time on dialysis, respectively. Therefore, IgM anti-HCV may also serve as a serological marker of HCV infection and a complementary marker of virus replication.
Adult↗