Thromboembolism and breast cancer: the hidden risk for patient and physician.
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Aged↗
Biomedical subjects
A Forgione
Publications and source records attributed to A Forgione.
The new 4DDome prosthesis: an original light and partially absorbable composite mesh for hernia repair.
INTRODUCTION: The use of non-absorbable meshes for the repair of inguinal hernias has become standard; however, these meshes have been associated with complications including long-term postoperative pain. To this end, a new partially absorbable composite mesh has been developed, and the aim of this study was to investigate its efficacy in animal and human trials. MATERIALS AND METHODS: Sixty male Wistar rats were used to evaluate the behavior of the newly designed composite mesh. Composite meshes were implanted in the extra-peritoneal plane for 2, 4 and 8 weeks and compared to a standard polypropylene mesh. Forty patients with symptomatic inguinal hernias were treated using a new 4DDome designed prosthesis. Follow-up was by clinical and ultrasound examination at 1, 6 and 12 months. RESULTS: The animal study demonstrated that the inflammatory reaction associated with the new composite mesh was significantly lower than a standard polypropylene mesh, characterized by a lower macrophage infiltrate (P < 0.001). The mesh did not shrink over the 8-week period, unlike the polypropylene mesh (P < 0.05). The human study showed that there were three minor postoperative complications, no recurrences and the mesh was well tolerated. Follow-up with serial ultrasound showed that at 10 days and 1 month the dome was clearly visible in position; however, by 6 months it had flattened out, been partially absorbed and become incorporated into the repair. CONCLUSION: These experimental and clinical studies have validated the concept of the new 4DDome composite mesh. It was well tolerated and was associated with good short-term results. The combination of the dome shape and the new composite mesh means that less polypropylene is required and represents a significant advance in anterior hernia repair.
Animals↗
Anticholinergic syndrome due to 'Devil's herb': when risks come from the ancient time.
We describe a case of Mandragora autumnalis poisoning which occurred in a 72-year-old female patient who had eaten the venenous M. Autumnalis, picked near her home, mistaking it for the edible Borago Officinalis. M. Autumnalis is a solanaceous plant, common in the Sicilian countryside, which contains a variable concentration of solanum alkaloids, causing gastrointestinal irritation, and tropane alkaloids, with anticholinergic properties. Unluckily, M. Autumnalis is often mistaken for the edible B. Officinalis, likewise widespread in Sicilian countryside. The diagnosis of Mandragora poisoning was made on the basis of clinical symptoms and signs of anticholinergic syndrome associated with a history of vegetable meal of uncontrolled origin, moreover analysing the vegetable obtained from gastric lavage. Decontamination and symptomatic treatment were useful in our patient to control acute poisoning.
Cholinergic Antagonists↗
Two-stage totally minimally invasive approach for acute complicated diverticulitis.
OBJECTIVES: Surgical options for acute diverticulitis with peritonitis include Hartmann's procedure or resection and primary anastomosis with or without a stoma. Initial laparoscopic lavage and drainage can control the acute intra-abdominal sepsis to allow for a delayed definitive procedure in nonemergency conditions. Potential advantages include the avoidance of a laparotomy, stoma and local infections at the origin of dehiscence and incisional hernias. We evaluated this approach in a selected group of patients. METHODS: Patients with intra-abdominal pus secondary to diverticular perforation requiring surgery were included in the study. Patients with localized pus amenable to computerized tomography (CT)-guided drainage, faecal peritonitis, severe generalized peritonitis, and those in which the perforation was spontaneously visible were excluded. Standard demographic data, CT findings, intra-operative findings and postoperative outcomes were analysed. RESULTS: Ten patients were suitable for the approach. Mean patient age was 60.2 years. Mean body mass index was 28.2 m2/kg. Mean postoperative stay was 8.5 days and uneventful in all patients. One patient re-presented after 3 weeks with acute peritonitis requiring open sigmoidectomy. Six patients successfully underwent laparoscopic sigmoidectomy with primary anastomosis 2-3 months later. Two patients were not re-operated because of comorbidity and one refused surgery. CONCLUSIONS: A two-stage totally minimally invasive approach may be a safe alternative strategy for selected cases of acute complicated diverticulitis.
Acute Disease↗
Pharmacokinetics of a new extended-release nifedipine formulation following a single oral dose, in human volunteers.
This study aimed to define the pharmacokinetics of nifedipine following oral administration of a new extended-release formulation. Twelve healthy volunteers of both sexes, aged 39 +/- 4 years, were treated with a single oral tablet of a new extended-release formulation containing 40 mg of nifedipine. Samples of venous blood were taken before dosing, after 30 min and at 1, 2, 4, 8, 12, 16, 20 and 24 h after administration. Nifedipine concentration was measured by means of a high-performance liquid chromatography method. Noncompartmental pharmacokinetics parameters were then calculated. The plasma concentration of nifedipine increased slowly and in seven subjects biphasic peaks occurred. The mean values were as follows: t(max): 8.5 +/- 1.2 h; C(max): 36.55 +/- 6.76 ng/ml; AUC: 347.06 +/- 51.61 ng/h/ml; AUC 409.99 +/- 61.08 ng/h/ml; A(half-life): 2.26 +/- 0.36 h; D(half-life): 2.43 +/- 0.44 h; E(half-life): 4.62 +/- 0.79 h. Twenty-four hours after administration nifedipine was still detectable (3.17 +/- 0.67 ng/ml). Arterial blood pressure decreased and heart rate increased concurrently and proportionally to the increase in nifedipine concentration. Extended-release nifedipine formulations have better tolerability profiles than immediate-release formulations, which are at present not recommended in the treatment of hypertension, hypertensive crises or myocardial infarction. This new extended-release formulation has interesting pharmacokinetic parameters and may be effective in conditions in which dihydropyridine calcium channel blockers are indicated.
Administration, Oral↗
Mandibular deviations in TMD and non-TMD groups related to eye dominance and head posture.
This study was designed to determine whether eye-dominance affects head posture (rotation) and in turn, whether head posture is associated with mandibular frenum midline deviation, in both TMJ and control subjects. Eye dominance was determined using three tests: Porta, Hole, Point tests. Natural head posture was evaluated using the Arthrodial protractor. Mandibular frenum deviation was recorded as left, right or no deviation. Fifty female subjects were included in the study, 25 TMJ patients attending the Gelb Craniomandibular Pain Center and 25 non-TMJ control subjects. The findings indicate that eye dominance and direction of head rotation are strongly associated in both TMJ and control subjects. Further, in TMJ subjects mandibular deviation occurred in greater frequency than in controls and tends to occur in the contra lateral direction of head rotation.
Adult↗
Influence of the surgical treatment on local recurrence of rectal cancer: a prospective study (1980-1992).
BACKGROUND AND OBJECTIVES: The incidence of locoregional recurrences (LR) following radical surgery of rectal cancer varies from 5% to 30% according to the literature. The purpose of this prospective study was to compare the outcome of the Abdomino-Perineal Excision (APE) vs. the Anterior Resection (AR) in a consecutive series of 188 patients who underwent surgery for cure from 1980 to the end of 1992 (81 APE and 107 AR), followed for 5 years, evaluating their influence on the incidence of the recurrences. METHODS: The patients were enrolled at random in the two surgical groups, provided that a radical excision of the tumour, with only two limits: the level of the lesion from the anal verge and the presence of a severe incontinence instrumentally proven. TNM, Dukes staging, grading, and tumour location were statistically evaluated. Further primary suture vs. packing of the perineal wound in APE and handsewn vs. stapled anastomosis in AR were compared in relation with the incidence of LR. RESULTS: The overall local recurrence rate was 19.2% (32/167), in details 19.7% for APE and 18.5% for AR. Similar recurrence rates were observed following both procedures, matching the patients according to the Dukes stage and different details of techniques. A slight statistically significant difference was found as far as the tumour location is concerned in the group treated with anterior resection (p = <0.05) because of the higher recurrence observed in AR performed for tumours of the lower third of the rectum in comparison with the more proximal level. CONCLUSIONS: The AA conclude that the choice of the right surgical procedure in the rectal carcinoma depends on the characteristics of the tumour and the conditions of the patients, provided that the oncologic indications were respected, because recurrence and survival rate are independent from the surgical approaches.
Abdomen↗
l-Sulpiride, at a low, non-neuroleptic dose, prevents conditioned fear stress-induced freezing behavior in rats.
Antidepressant drugs are effective in anxiety states, including panic disorder. Both clinical and animal studies indicate that l-sulpiride, at low, non-neuroleptic doses, has antidepressant activity. The present study examined the effect of an antidepressant dose of l-sulpiride (4 mg/kg per day SC), compared with a well-established antidepressant drug (fluoxetine, 3 mg/kg per day SC), in a rat model of anticipatory anxiety/panic behavior: conditioned fear stress-induced freezing behavior. Long-term (26 days) administration of l-sulpiride almost completely abolished freezing, a similar effect being produced by fluoxetine (freezing duration, in seconds: controls, 148.1 +/- 29.6; l-sulpiride, 27.5 +/- 8.3; fluoxetine, 72.0 +/- 15.2). The same doses of l-sulpiride (4 mg/kg SC) and fluoxetine (3 mg/kg SC) had no effect when administered for shorter periods (1, 5, or 12 days). No effect was produced by the long-term (26 days) administration of a neuroleptic dose of l-sulpiride (20 mg/kg per day SC). These results demonstrate that long-term administration of low, non-neuroleptic doses of l-sulpiride, is highly effective in an animal model of anticipatory anxiety/panic behavior.
Animals↗
In vitro excitatory actions of corticotropin-releasing factor on rat colonic motility.
Corticotropin-releasing factor (CRF) has been shown to affect gastrointestinal functions, however, a direct effect of CRF on the intestine has not been demonstrated. To determine the direct effect of CRF and its antagonist alpha-helical-CRF9-41 (alpha-h-CRF) on the enteric nervous system, we studied the action of these substances on electrical and mechanical parameters of peristaltic activity on isolated distal colon of the rat. The effects of CRF were evaluated in vitro on rat isolated colonic segments in which intraluminal pressure, longitudinal displacement, ejected fluid volume and extracellular electrical activity were simultaneously recorded during colonic peristaltic reflex. The addition of CRF (10(-10) - 10(-8) M) to the bath fluid provoked a concentration-dependent increase of both mechanical and electrical peristaltic activity. The CRF-receptor antagonist alpha-h-CRF dose-dependently (10(-10) - 10(-7) M) induced a decrease of the colonic mechanical and electrical activity and prevented (10(-8) - 10(-6) M) CRF (10(-8) M) maximal effects. These results indicate: (a) CRF can exert its effects on colon functions by a direct action, (b) a specific CRF-receptor is present in the rat colon. Indeed, CRF effects are antagonized by the specific CRF antagonist alpha-h-CRF, (c) the fact the alpha-h-CRF displays an activity on its own reveals that colonic functions are controlled by an endogenous CRF tonic activity.
Animals↗
Chronic administration of l-sulpiride at low doses reduces A10 but not A9 somatodentritic dopamine autoreceptor sensitivity.
The effect of chronic treatment (twice daily for 21 days) with low doses of l-sulpiride (2 mg/kg i.p.) on the apomorphine-induced inhibition of A10 and A9 dopaminergic neurons was compared with the effect of chronic administration of the classic antidepressant desipramine (20 mg/kg i.p. daily for 21 days). Intravenous administration of apomorphine (0.01-0.04 mg/kg), to rats treated chronically with l-sulpiride, produced a reduction of the spontaneous firing rate of A9 dopaminergic neurons not significantly different from that observed in control (saline-treated) rats. In contrast, apomorphine at the same doses was more potent in inhibiting A10 firing in control rats than in l-sulpiride-treated subjects. On the other hand, desipramine-treated rats were found normosensitive (as compared to saline-treated rats) to the inhibitory properties of apomorphine in both A9 and A10 dopaminergic neurons. It is suggested that chronic l-sulpiride-induced reduction of autoreceptor sensitivity in the A10 region may contribute to its clinical antidepressant effect.
Animals↗
Chronic administration of l-sulpiride at non-neuroleptic doses reduces the duration of immobility in experimental models of "depression-like" behavior.
It has been shown that long-term administration of l-sulpiride induces a down-regulation of beta receptor-associated adenylate cyclase activity in the frontal cortex of rats, and adaptive response that is typically associated with the chronic administration of antidepressants. Here we show that in two animal models of "depression-like" behavior (forced swim in rats and tail suspension in mice), the long-term (21 days) administration of l-sulpiride at a non-neuroleptic dose (2 mg/kg IP twice a day) significantly decreases the duration of immobility, the effect being similar to that of desipramine (20 mg/kg IP). The same dose (2 mg/kg) of l-sulpiride, acutely administered, has no effect at all. On the other hand, either chronic (21 days) or acute administration of neuroleptic doses of l-sulpiride have an opposite effect, and indeed increase the duration of immobility. These results are an in vivo support to the in vitro findings suggesting that low doses of l-sulpiride may have antidepressant-like activity.
Animals↗
Pharmacotoxicological aspects of levosulpiride.
Levosulpiride is the levorotatory enantiomer of sulpiride, a substituted benzamide indicated as an antipsychotic, antidepressant, antiemetic and antidyspeptic drug, as well as for the treatment of somatoform disorders. In vivo sulpiride displays a number of neuroleptic properties which it shares with all typical neuroleptic drugs; however, it has also a number of divergent characteristics that set it apart as the principal compound of the so-called 'atypical neuroleptic agents'. The main mechanism of action of levosulpiride consists of blocking the D2 dopaminergic receptors, preferentially located on the presynaptic membranes in the dopaminergic pathways of the brain; this means that sulpiride is a selective autoreceptor blocker. The results of series of experimental trials conducted to evaluate the toxicologic characteristics of levosulpiride are presented. Both the acute, subacute, chronic and local toxicity trials, and the studies on reproduction toxicity, mutagenic potential and oncogenic/carcinogenic potential, demonstrate that levosulpiride is well tolerated by the animals tested (rats, mice, rabbits and dogs) at doses higher than those effective in human therapy. Moreover, the findings from the experimental studies on levosulpiride lead to exclude the toxicity from accumulation, tolerance, dependence or withdrawal syndrome. In conclusion, according to the evaluated preclinical studies, levosulpiride shows pharmacotoxicologic properties which make it suitable for the management of diseases for which the drug is indicated.
Animals↗
The effects of S(-) and R(+) sulpiride, metoclopramide, cisapride and domperidone on the small intestine suggest DA2-receptors are involved in the control of small intestinal transit time in rats.
To study the effect of intraperitoneal S(-)sulpiride (1-15 mg/kg), R(+)sulpiride (5-10 mg/kg), metoclopramide (1-15 mg/kg), cisapride (10 mg/kg) and domperidone (5-10 mg/kg) on intestinal progression, rats were given the test drug followed by oral lactulose. Their hydrogen excretion was used to calculate the small bowel transit time (SBTT) and maximum peak time (MPT). Metoclopramide (7.5 mg/kg) had the greatest effect on SBTT (-25%), followed by S(-)sulpiride and domperidone. S(-)sulpiride (10 mg/kg) had the greatest activity on the MPT (-35.2%) followed by metoclopramide. R(+)sulpiride and cisapride did not modify SBTT and MPT. In conclusion S(-)sulpiride is the isomer active on intestinal transit and DA2-receptors seem important targets in the modulation of intestinal progression, since S(-)sulpiride, metoclopramide and domperidone are DA2-receptor antagonists, and R(+)sulpiride and cisapride are not. The H2 breath test proved a valid method for measuring the effect of drugs on the small intestine in animals.
Animals↗
Low doses of l-sulpiride down-regulate striatal and cortical dopamine receptors and beta-adrenoceptors.
There is now clinical evidence that l-sulpiride has antidepressant effects when administered at low, non-neuroleptic doses. Down-regulation of beta-receptor-linked adenylate cyclase is a well-documented adaptive response to chronic administration of antidepressant drugs. In this study, we investigated dopamine receptor and beta-adrenoceptor changes induced by chronic administration of low doses of l-sulpiride. The data indicate that striatal D1 and D2 receptor function was desensitized by the treatment, which suggests that at low doses l-sulpiride preferentially blocks D2 autoreceptors, leading to increased dopamine release. l-Sulpiride also induced a selective down-regulation of beta-receptor-associated adenylate cyclase activity in the frontal cortex, but not in the striatum, which does not receive norepinephrine projections. Taken together these data suggest that cortical noradrenergic terminals may be endowed with dopamine D2 receptors controlling norepinephrine release and that blockade of this dopaminergic inhibitory modulation may be involved in the antidepressant effects of l-sulpiride.
2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
Possible mechanism of antidepressant effect of L-sulpiride.
L-Sulpiride is a dopamine (DA)-receptor blocker that acts as an antidepressant at low doses. We have reviewed evidence suggesting that the antidepressant effect of L-sulpiride may depend on the activation of DA transmission secondary to the blockade of DA autoreceptors.
Depressive Disorder↗
[Antiemetic effect of the levo isomer of sulpiride (L-sulpiride) in humans].
Vomiting represents one of the most dangerous complications of general anesthesia. L-sulpiride has been able to control this complication very effectively. We studied the effect on vomiting of two doses of L-sulpiride (50/100 mg). Both these doses have been effective in reducing the episodes of vomiting other than in preventing nausea and retching if considered versus controls and also versus droperidol at the doses of 5 mg (50 mg L-sul = 12%, 100 mg = 4%, droperidol = 20%, controls = 28%). L-sulpiride is an antagonist of dopamine on D2 receptors therefore inhibits the action of dopamine increasing the secretion of prolactin. During the surgical distress per se prolactin levels are increased. Together with the increment of catecholamines, high concentration of prolactin can evoke arrhythmias. In view of this possibility we studied the time course of the administration of the two doses of L-sulpiride and of droperidol on prolactin secretion. Both of the drugs increased the plasma levels of prolactin. Droperidol-induced increase in prolactin secretion was significant already at ten minutes after the administration reaching the peak after 20 minutes. L-sulpiride increased prolactin secretion reaching the maximum increase 20 minutes after the administration of 50 mg of the drug, and 30 minutes after the administration of 100 mg doses. The hyperprolactinemizing action of droperidol lasts for at least 8 hours, whereas L-sulpiride action lasts 4 hours.
Adolescent↗
Stereochemical pharmacokinetics of the 2-arylpropionic acid non-steroidal antiinflammatory drug flunoxaprofen in rats and in man.
Stereospecific serum assays of the non-steroidal antiinflammatory drug flunoxaprofen (S(+)-2-(4-fluorophenyl)-a-methyl-5-benzoxazoleacetic acid, Priaxim) were performed in rats after the oral administration of 10 mg/kg b.w. of the different enantiomeric forms of the drug or of the racemate in order to establish the occurrence and the rate of biotransformation of R(-)-flunoxaprofen to the S(+)-enantiomer, which is the pharmacologically active form. Preliminary observations of the enantiomeric blood levels were also made in man after a single oral dose (100 mg) of R(-)-flunoxaprofen or of the racemate. Blood was withdrawn at different time intervals up to 120 h in rats and up to 48 h in man and serum levels of flunoxaprofen enantiomers were determined by a HPLC method. The results obtained in the rat show that S(+)-flunoxaprofen serum levels following the administration of a single oral dose of flunoxaprofen reach about the same values (between 24 and 30 micrograms/ml at 18 h) whichever form was dosed (i.e. 10 mg/kg b.w. of S(+)- or R(+)-, or 5 mg/kg b.w. of S(+)- as the racemate). On the contrary, R(-)-flunoxaprofen serum concentrations fall to values lower than 5 micrograms/ml either after the administration of 10 mg/kg R(-)- or of 5 mg/kg R(-)- as the racemate; these serum R(-)-flunoxaprofen values are close to those observed after the administration of S(+)-flunoxaprofen which contains 5% R(-)- as an impurity (i.e. 0.5 mg/kg b.w.).(ABSTRACT TRUNCATED AT 250 WORDS)
Administration, Oral↗