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Biomedical subjects

S Pace

Publications and source records attributed to S Pace.

At least 19 recordsLinked to original sources
PubMed2006

Improvement of uterine artery Doppler velocimetry indices after metroplasty in arcuate uteri.

OBJECTIVE: Our study aimed to evaluate the effect of metroplasty performed in arcuate uteri on uterine artery Doppler velocimetry. STUDY DESIGN: We performed uterine artery Doppler velocimetry transvaginally before and after metroplasty in 36 women with arcuate uteri. Pulsatility indexes (PI) of uterine arteries were calculated and the presence or absence of a protodiastolic notch was evaluated. RESULTS: Comparing Doppler indexes before and after metroplasty, we found that uterine artery impedance improves as assessed by lower mean PI. We observed that PI after intervention was significantly lower compared with indexes before for mean Doppler index evaluations (mean uterine PI pre: 2.07+/-0.61 and post: 1.49+/-0.24 [p<0.03]). No differences were observed as regards bilateral protodiastolic notch absence or presence. A protodiastolic notch was present in 22 out of 36 women before metroplasty (61%), and a notch was observed in 19 out of 36 (52%) after metroplasty. CONCLUSIONS: Our results suggest that, metroplasty, as well as making the uterine cavity wider, leads to better uterine perfusion.

Adult↗
PubMed2006

Regression rate of clinical HPV infection of the lower genital tract during pregnancy after laser CO2 surgery.

The objective of the study was to evaluate the effects of laser CO2 surgery during pregnancy to prevent clinical HPV infection recurrence after delivery and vertical infection. A case-control study was performed on 280 pregnant women affected by clinical HPV infection treated during pregnancy with 256 women treated three months after delivery. Follow-up was performed for a minimum of three colposcopic examinations for two years. Recurrence rates were calculated considering the number of positive findings for at least one colposcopic examination confirmed by biopsy after a negative control in a year. Statistical comparison of rates was performed by chi-squared and Fisher's exact test. Recurrence rates were higher in the women treated in postpartum (p < .01) than in the group treated during gestation (p < .005). Clinical HPV infections treated during the second trimester of pregnancy showed a sensitive decrease in recurrence-rate of infection. Rarity of respiratory papillomatosis makes conclusions inconsistent for the prevention of vertical infection.

Carbon Dioxide↗
PubMed2006

Septate uterus: reproductive outcome after hysteroscopic metroplasty.

OBJECTIVE: To evaluate hysteroscopic metroplasty and its effect on reproductive outcome. STUDY DESIGN: Seventy-five patients consulted for uterine septum between January 1996 to December 2000 at "La Sapienza" University in Rome were included in the study. RESULTS: Forty patients attempted pregnancy and a total of 30 spontaneous pregnancies resulted (75% pregnancy rate). The uterine cavity was normal at hysteroscopic follow-up in 68% of cases. CONCLUSION: Correction of uterine septum improves pregnancy outcome of patients. Broadening the indications for hysteroscopic metroplasty should be encouraged for patients who desire to conceive.

Abortion, Habitual↗
PubMed2003

Endoscopic treatment of intrauterine adhesions.

PURPOSE OF INVESTIGATION: The authors investigated the validity of hysteroscopy as a diagnostic and operative technique in cases of intrauterine adhesions. METHODS: 6,680 hysteroscopies were carried out between June 1987 and December 2000 with 201 patients presenting intrauterine adhesions. Only 75 patients underwent resection of the adhesions by hysteroscopy with 94.6% of functional restoration and 93.3% of anatomic resolution. RESULTS: At 2-month follow-up the uterine cavity was completely regular in 70 cases, while in four cases a second surgical treatment was necessary. CONCLUSION: Good anatomic results are obtained after hysteroscopic treatment of intrauterine adhesions, and pregnancy rates vary from 28.7 to 53.6%.

Adult↗
PubMed2003

[Controlled release vaginal dinoprostone for the induction of labour].

AIM: To study the efficacy and safety of controlled release dinoprostone (PGE2) for the induction of labour. METHODS: From March 2001 to August 2002, a total of 173 patients hospitalized for postdate pregnancy, maternal hypertension, intrauterine delayed growth, reduction of amniotic fluid, were studied. In 33 of these patients, a hydrogel strip containing 10 mg dinoprostone, inserted into the posterior fornix of the vagina and release PGE2 at constant rate of 0.3-0.4 mg/h was used. RESULTS: Indications for induction, mode and time of delivery, maternal, fetal and neonatal parameters anomalies are evaluated. In 23 patients dinoprostone was used for postdate pregnancy, in 4 for maternal hypertension, in 4 for oligohydramnios and in 2 for intrauterine delayed growth. In 2 cases, the vaginal insert was removed for hyperstimulation in 1 case and for abnormal fetal heart rate in the other case. After vaginal delivery, Apgar scores and umbilical artery pH values were evaluated without anomalies. Vaginal delivery within 24 hours occurred in 51.6% of patients and medium time to delivery was 17.5 (nulliparous) and 12.3 (multiparous) hours. Only one case of uterine hyperstimulation to PGE2 was recorded, and the induction was suspended. The cesarean section rate was 12% and vaginal delivery after 24 hours was 38.7%. CONCLUSION: The continuous release of PGE2 from the vaginal insert permits a controlled and safe induction of labour, minimal risk of hyperstimulation, fast and easy removal of drugs in cases of fetal or maternal anomalies, easy accetability for patients, but high cost.

Adult↗
PubMed2001

Potent antitumor activity and improved pharmacological profile of ST1481, a novel 7-substituted camptothecin.

Relevant drawbacks of the molecular structure and mechanism of the action of camptothecins are the instability of the E ring lactone and the reversibility of drug-target interaction. Such features are expected to limit the clinical efficacy of conventional camptothecins. In an attempt to overcome these limitations and to improve the pharmacological profile of camptothecins, a novel series of seven modified lipophilic analogues was synthesized based on the hypothesis that lipophilicity could promote a rapid cellular accumulation and stabilization of drug-target interaction. A novel analogue (ST1481) of the series, characterized by a potent antitopoisomerase and cytotoxic activity, was selected for preclinical development. A detailed preclinical study of ST1481 was performed in the H460 non-small cell lung tumor model using oral administration and various treatment schedules. Under all of the conditions, ST1481 exhibited an impressive efficacy in terms of tumor growth inhibition (tumor volume inhibition percentage > 99%), log(10) cell kill, rate of complete responses (including "cures"), and an improvement of the therapeutic index compared with topotecan (used as the reference drug). The cytotoxic potency was also reflected by the in vivo potency, because the drug activity was observed at doses as low as 0.25 mg/kg with the daily schedule. In contrast to topotecan, no cross-resistance to ST1481 was found in ovarian carcinoma cells overexpressing P-glycoprotein (A2780/DX). A similar trend in the improvement of activity was also observed in the same tumor model growing in vivo with a 100% rate of complete tumor regressions. A rapid intestinal absorption and good oral bioavailability were supported by in vivo distribution studies, because the peak values of drug accumulation were found from 1 to 2 h after administration. The relevant liver accumulation may account for a marked effect of ST1481 against liver metastases induced by the ovarian carcinoma IGROV-1. In conclusion, the results support the hypothesis that a potent lipophilic camptothecin with a proper substituent at the position 7 may have therapeutic advantages likely related to a rapid intracellular uptake and tissue distribution, stabilization of the drug-target complex, and good oral bioavailability. Overall, the results support the preclinical interest of ST1481 in terms of efficacy, potency, toxicity profile, and ability to overcome multidrug resistance.

Administration, Oral↗
PubMed2001

Characteristics of irreversible ATP activation suggest that native skeletal ryanodine receptors can be phosphorylated via an endogenous CaMKII.

Phosphorylation of skeletal muscle ryanodine receptor (RyR) calcium release channels by endogenous kinases incorporated into lipid bilayers with native sarcoplasmic reticulum vesicles was investigated during exposure to 2 mM cytoplasmic ATP. Activation of RyRs after 1-min exposure to ATP was reversible upon ATP washout. In contrast, activation after 5 to 8 min was largely irreversible: the small fall in activity with washout was significantly less than that after brief ATP exposure. The irreversible activation was reduced by acid phosphatase and was not seen after exposure to nonhydrolyzable ATP analogs. The data suggested that the channel complex was phosphorylated after addition of ATP and that phosphorylation reduced the RyR's sensitivity to ATP, adenosine, and Ca(2+). The endogenous kinase was likely to be a calcium calmodulin kinase II (CaMKII) because the CaMKII inhibitor KN-93 and an inhibitory peptide for CaMKII prevented the phosphorylation-induced irreversible activation. In contrast, phosphorylation effects remained unchanged with inhibitory peptides for protein kinase C and A. The presence of CaMKIIbeta in the SR vesicles was confirmed by immunoblotting. The results suggest that CaMKII is anchored to skeletal muscle RyRs and that phosphorylation by this kinase alters the enhancement of channel activity by ATP and Ca(2+).

Acid Phosphatase↗
PubMed2001

Successful diagnostic and surgical hysteroscopy for endometrial ossification.

PURPOSE OF INVESTIGATION: Diagnostic-operative hysteroscopy was successful in two cases of endometrial ossification, and fertility was restored. METHODS: A 30-year-old and a 32-year-old woman presented at our Department with a history of secondary infertility, complaining of pelvic pain, dysmenorrhea and polymenorrhea which lasted for about one year before admission. Previous ultrasound studies revealed the presence of two bright hyperechogenic bands with posterior shadowing. RESULTS: In both cases diagnostic-operative hysteroscopies were performed, displaying osseous fragments which were removed with resectoscopy, mainly mechanically. CONCLUSION: Hysteroscopic resection should be the elective treatment for endometrial ossification because it allows complete removal of osseous fragments and reduces the chance of residual synechia. The mean objective of hysteroscopy in endometrial ossification is the restitution of conceivement capability.

Adult↗
PubMed2000

Efficacy and toxicity profile of oral topotecan in a panel of human tumour xenografts.

On the basis of their mechanism of action (cell killing during DNA replication) and the potential reversibility of the drug effects, protracted therapy with camptothecins is reported to provide optimal antitumour effects. Furthermore, oral administration may be a useful modality for optimisation of treatment. The aim of this study was to compare the therapeutic profile of topotecan given orally or intravenously in human tumours xenografted into athymic nude mice. The drug topotecan was given according to an intermittent (every fourth day, four times) or daily (qdx5/weeklyx5-10 weeks; only orally) schedule. Tumour growth inhibition and persistence of drug effects were assessed and compared with untreated mice. In a panel of seven tumour xenografts, oral topotecan was at least as effective on three and significantly more effective on four tumours. Using the intermittent schedule, the maximum tolerated dose (MTD) was comparable for the two routes (15 mg/kg), but the toxicity profile suggested a better tolerability in terms of lethal effects after oral administration. The daily oral treatment of low drug doses allowed a higher cumulative dose to be delivered with improved antitumour efficacy (2/10 cured in a large cell lung cancer) and no evidence of toxicity. In spite of the low bioavailability of oral topotecan (23.5%), the persistent plasma levels of the drug suggest that the time of exposure to the drug is more critical than the plasma concentrations for antitumour efficacy. This interpretation is consistent with the increased efficacy of prolonged daily treatment with low-dose levels. The results may have implications for the future design of clinical studies.

Administration, Oral↗
PubMed2000

Pharmacokinetics of propionyl-L-carnitine in humans: evidence for saturable tubular reabsorption.

AIMS: Propionyl-L-carnitine (PLC) is an endogenous compound which, along with L-carnitine (LC) and acetyl-L-carnitine (ALC), forms a component of the endogenous carnitine pool in humans and most, if not all, animal species. PLC is currently under investigation for the treatment of peripheral artery disease, and the present study was conducted to assess the pharmacokinetics of intravenous propionyl-L-carnitine hydrochloride. METHODS: This was a placebo-controlled, double-blind, parallel group, dose-escalating study in which 24 healthy males were divided into four groups of six. Four subjects from each group received propionyl-L-carnitine hydrochloride and two received placebo. The doses (1 g, 2 g, 4 g and 8 g) were administered as a constant rate infusion over 2 h and blood and urine were collected for 24 h from the start of the infusion. PLC, ALC and LC in plasma and urine were quantified by h.p. l.c. RESULTS: All 24 subjects successfully completed the study and the infusions were well tolerated. In addition to the expected increase in PLC levels, the plasma concentrations and urinary excretion of LC and ALC also increased above baseline values following intravenous propionyl-L-carnitine hydrochloride administration. At a dose of 1 g, PLC was found to have a mean (+/- s.d.) half-life of 1.09 +/- 0.15 h, a clearance of 11.6 +/- 0.24 l h-1 and a volume of distribution of 18.3 +/- 2.4 l. None of these parameters changed with dose. In placebo-treated subjects, endogenous PLC, LC and ALC underwent extensive renal tubular reabsorption, as indicated by renal excretory clearance to GFR ratios of less than 0.1. The renal-excretory clearance of PLC, which was 0.33 +/- 0.38 l h-1 under baseline condition, increased (P < 0. 001) from 1.98 +/- 0.59 l h-1 at a dose of 1 g to 5.55 +/- 1.50 l h-1 at a dose of 8 g (95% confidence interval for the difference was 2.18,4.97). As a consequence, the percent of the dose excreted unchanged in urine increased (P < 0.001) from 18.1 +/- 5.5% (1 g) to 50.3 +/- 13.3% (8 g). The renal-excretory clearance of LC and ALC also increased substantially after PLC administration and there was evidence for renal metabolism of PLC to LC and ALC. CONCLUSIONS: Intravenous administration of propionyl-L-carnitine hydrochloride caused significant increases in the renal excretory clearances of PLC, LC and ALC, due to saturation of the renal tubular reabsorption process - as a consequence there was a substantial increase with dose in the fraction excreted unchanged in urine. Despite the marked increase in the renal clearance of PLC, total clearance remained unchanged, suggesting a compensatory reduction in the clearance of the compound by non excretory routes.

Absorption↗
PubMed2000

Pharmacokinetics of L-carnitine in patients with end-stage renal disease undergoing long-term hemodialysis.

OBJECTIVE: L-Carnitine is an endogenous molecule involved in fatty acid metabolism. Secondary carnitine deficiency may develop in patients with end-stage renal disease undergoing long-term hemodialysis because of dialytic loss. In these patients L-carnitine can be administered to restore plasma and tissue levels. The objective of this study was to evaluate the pharmacokinetics of intravenous L-carnitine in patients undergoing long-term hemodialysis. METHODS: Twelve patients undergoing three dialysis sessions/week received L-carnitine intravenously (20 mg x kg(-1)) at the end of each dialysis session for 9 weeks. Plasma samples were analyzed for L-carnitine, acetyl-L-carnitine, and total carnitine by HPLC. RESULTS: Under baseline conditions, the mean +/- SD predialysis plasma concentration of L-carnitine was 19.5 +/- 5.6 micromol/L, decreasing to 5.6 +/- 1.9 micromol/L at the end of the dialysis session. These concentrations were substantially lower than endogenous levels in healthy human beings. Under baseline conditions the extraction ratios of L-carnitine and acetyl-L-carnitine by the dialyser were 0.74 +/- 0.07 and 0.71 +/- 0.11, respectively. During repeated dosing, there was accumulation of L-carnitine in plasma, and after 9 weeks of dosing, the predialysis and postdialysis plasma levels were 191 +/- 54.1 and 41.8 +/- 13.0 micromol/L, respectively. The predialysis and postdialysis plasma levels of L-carnitine decreased once dosing was ceased but had not returned to pretreatment levels after 6 weeks. CONCLUSION: The study demonstrated that removal of L-carnitine by hemodialysis is extremely efficient and that patients undergoing hemodialysis had plasma concentrations that were substantially lower than normal, particularly during dialysis. During repeated administration of L-carnitine, the predialysis and postdialysis concentrations of the compound increased steadily, reaching an apparent steady state after about 8 weeks. It is proposed that this accumulation arose from the distribution of L-carnitine into a deep tissue pool that includes skeletal muscle.

Acetylcarnitine↗
PubMed1999

Gastrosparing effect of new antiinflammatory drug amtolmetin guacyl in the rat: involvement of nitric oxide.

The effect of the nonsteroidal antiinflammatory drug (NSAID) amtolmetin guacyl (AMG) on the gastric mucosa was studied in the rat by means of histological and functional techniques. AMG administered at 50-300 mg/kg intragastrically was virtually devoid of gastrolesive properties after either acute or repeated treatment. By contrast, its metabolite, tolmetin (TOL, 15-60 mg/kg, intragastrically) caused dose-dependent gastric damage after both treatments. Light and electron microscopy revealed that AMG induced minimal changes in the surface epithelium layer, without signs of vasocongestion or leukocytes adherence. AMG (50 mg/kg intragastrically) did not change basal gastric potential difference (PD), whereas acetylsalicylic acid and ibuprofen induced falls in PD of 22 and 27 mV, respectively. AMG (50 mg/kg intragastrically) reduced by 60% the fall in PD induced by 50% ethanol; this inhibition was dependent on the incubation time, and was maximal when AMG was given 4 hr before ethanol. AMG (100 mg/kg intragastrically) induced an increase in NO synthase type 2 (NOS2) activity, which was significantly different from control values, when AMG was administered 4 hr before the test. The metabolites of AMG, tolmetin, MED 5, and guaiacol were ineffective. Pharmacokinetic analysis of the residence time of AMG in the different areas of the gastrointestinal tract, revealed that AMG remains in the gastrointestinal tract at least for 4 hr, the time necessary for a maximal induction of NOS2 and for maximal protection against ethanol-induced damage. In conclusion, these data indicate that the nonsteroidal antiinflammatory drug amtolmetin guacyl is devoid of gastrolesive properties; this gastro-sparing effect seems to involve the production of nitric oxide, which can counteract the damaging effects due to prostaglandin inhibition. The presence in the stomach of the native molecule of amtolmetin guacyl seems to be necessary for the protective effect observed.

Animals↗
PubMed1997

Pearls, pitfalls, and updates in toxicology.

Pearls and pitfalls learned from our practical experiences caring for poisoned patients are presented. Clinical pearls include the following: using diagnostic tests to detect end-organ toxicity, applying physiologic principles to the management of hemodynamically unstable poisoned patients, and dealing with psychologic injuries from hazardous materials incidents. Recognizing serious complications from poisoning and adverse drug effects, including the serotonin syndrome, are offered as pitfalls. Pharmaceutical companies are rapidly developing and marketing new therapies. Therefore, updates on the evolving role of NAC as an antidote for acetaminophen poisoning, new psychotropic medications, and new antidotes were included in this article. These pearls, pitfalls, and updates are intended to provide practical information that is readily applicable to the clinical practice of emergency medicine.

Adverse Drug Reaction Reporting Systems↗
PubMed1997

Cervical intraepithelial neoplasia and bacterial vaginosis: correlation or risk factor?

Bacterial Vaginosis (B.V.) is a syndrome defined microbiologically where lactobacilli-dominated flora is exchanged with an abundant complex flora dominated by strict and facultative anaerobic bacteria, constituted by gardenerella, micrococci, streptococci and staphylocci. It has been suggested that B.V. could be important in the development of cervical intracpithelial neoplasias, because the abnormal micro flora can produce careinogenic nitrosamines. The aim of this investigation was to evaluate the correlation between CIN and B.V. in 1,008 patients (median age: 28 years, range 17-60) who were divided into two groups: the first group consisted of 504 patients affected by CIN of different degrees, the second of 504 patients without CIN. All patients were submitted to colposcopy, pap-tests, cytology of the cervical canal and microcolpohysteroscopy in the case of lesions invading the cervical canal. The diagnosis of B.V. is based on four criteria: presence of clue cells, pH 4.5, positive amine test and increased vaginal discharge. X2 Pearson analysis was applied for statistical evaluation of the data. Among the 504 patients in the first group (women affected by CIN of different degrees), 180/504 (36%) women presented B.V. Among the second group (504 women without CIN), 248/504 (49%) women presented B.V. The results of our study demonstrate that there is no significant correlation between CIN and B.V. In the first group of patients affected by CIN and B.V., B.V. was present in 36% of the cases, while in the second group of patients not affected by CIN. B.V. was present in 49% of the cases (P < 0.00005).

Adolescent↗
PubMed1997

[Diagnostic and therapeutic problems in tubal adenocarcinoma. Report of a case].

Primary adenocarcinoma of the Fallopian tube is one of the most rare tumours: its incidence varies from 0.5% to 1.1% of all gynecological neoplasias. In 1988 a total of 1,200 cases had been reported, the majority grouped in small series and/or individual case reports. The first case was reported by Renauld in 1847. The preoperative diagnosis has increased over the past forty years from 0.26% to 6.38%, and is still extremely low. The diagnosis of primary adenocarcinoma of the uterine tube is basically achieved by exclusion, and in fact the metastasization of the tubes by adjacent gynecological organs must be excluded. The trio of abdominal pain, leukorrhea, metrorrhagia is regarded by many authors as being pathognomonic of tubal adenocarcinoma. In about half of patients the interval between the onset of symptoms and histological diagnosis is 2-3 months, and in 30% less than one month. The authors report their experience of a case in a 62-year-old patient with typical symptoms of primary tubal adenocarcinoma.

Adenocarcinoma↗
PubMed1997

[Preliminary diagnostic evaluation of submucosal myoma using operative hysteroscopy].

BACKGROUND AND AIM: The authors aim to underline the importance of preliminary diagnostic evaluation in the treatment of submucous leiomyoma using hysteroscopy. MATERIALS AND METHODS: The study examined 18 patients monitored at the Institute of Obstetrics and Gynecology of "La Sapienza" University of Rome between January and December 1995 in whom it was possible to make a correct definition of the lesion to be treated (number, site, size, etc.) using 3 different diagnostic methods: hysteroscopy (HS), transvaginal scan (TSV) and transvaginal echohysterography (TVHS) The authors focused attention on three different parameters: leiomyoma size, extension (intracavity/intramural portion) and evaluation of the residual leiomyoma, which are essential for optimal endoscopic resection. RESULTS: HS enabled the number, size, site, origin, base, submucous portion and relations with tube operings to be evaluated, but did not allow the myometrial part of the lesion to be examined. CONCLUSIONS: Integration with TSV, even if this does not allow a precise definition of the extension, highlights the size, site, involvement of myometrial structure and relations with the perimetrium, thus allowing the possibility of evaluating the residual myometrium. Compared to the above methods, TVHS highlights the effective extension (namely the submucous/intramural portion) and localization of the neoformation.

Adult↗