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Biomedical subjects

G Lotti

Publications and source records attributed to G Lotti.

At least 19 recordsLinked to original sources

Fracture of posterior-stablized tibial insert in a Genesis knee prosthesis.

We report a case of acute failure of a Genesis total knee arthroplasty (Smith and Nephew Orthopaedics, Memphis, TN) resulting from fracture of the eminence of the polyethylene posterior-stabilized tibial insert implanted in a revision procedure. A hyperflexion movement was responsible for shear stress on the insert with subsequent breakage. The correct diagnosis was obtained by arthroscopy, and the open substitution of the broken insert led to complete recovery of the prosthesis. This is the first report of mechanical breakage of a Genesis prosthesis.

Aged↗

Characterization of the binding of the RNA-binding protein AUF1 to the human AT(1) receptor mRNA.

An important mechanism of regulation of the expression of the AT(1) receptors is the modulation of the mRNA stability. AUF1, a human RNA-binding protein, may play an important role. Since AUF1 seems to bind to AU-rich regions of the 3'-untranslated region of the mRNAs, we verified the nucleotide sequence of human AT(1) receptor 3'-untranslated region and we found possible binding sites. In addition we evaluated the expression of the AUF1 protein in human vascular smooth muscle cells: the administration of both isoproterenol and angiotensin II induced a significant increase of total anti-AUF1 immunoreactive isoforms. At the same time angiotensin II induced a significant decrease in the AT(1) receptor mRNA abundance. Moreover, we found that recombinant human AUF1 protein binds to human AT(1) receptor riboprobes. The protein was able to bind to the distal portion of the 3'-untranslated region, and also to the coding region. Since the clinically relevant AT(1) receptor polymorphism is located in the 3'-untranslated region, we created two DNAs, corresponding to the A and C polymorphism, without any differences. Our data demonstrate the presence of AUF1 in human vascular smooth muscle cells and its modulation by activation of the beta-adrenergic and the AT(1) pathways, a and specific binding of AUF1 to the human AT(1) receptor mRNA, suggesting a role of this protein in the modulation of the AT(1) receptor expression.

3' Untranslated Regions↗

Acetylcholine-induced, calcium-dependent norepinephrine outflow from peripheral human lymphocytes.

Catecholamines (CA) were studied in peripheral human lymphocytes, as well as in the supernatants, after incubation with L-tyrosine and L-dihydroxyphenylalanine (L-Dopa) for 1 h. The effect that the addition of acetylcholine (ACh), Veratridine, lonomycin or KCI had on the outflow of norepinephrine (NE) from lymphocytes was also studied. The effect of the addition of methoxyverapamil (D600, a Ca2+ channel blocker) and cholinergic antagonists had on the ACh-induced NE outflow was assessed. CA were determined by HPLC-ECD, both in the supernatant and in the cell lysates. L-Tyrosine and L-Dopa significantly (P < 0.01) increased intracellular NE. Neither L-tyrosine, L-Dopa, nor vehicle induced a detectable outflow of NE to the supernatants. ACh [120 microM], Veratridine [100 microM], Ionomycin [10 microM] and KCl [50 mM] (with or without the simultaneous addition of L-tyrosine or L-Dopa) all induced a detectable outflow of NE to the supernatant when added 5 min before the end of incubation. NE was not detectable in the supernatant when the chemicals were added 10 to 20 min before the end of the incubation. When the chemicals were added at lower concentrations, erratic secretion or no secretion whatsoever was observed. D600 [100 microM] was able to significantly (P < 0.01) reduce the ACh-induced NE outflow. Tetraethylammonium (nicotinic antagonist), but not atropine (muscarinic antagonist), significantly (P < 0.001) decreased the ACh-induced NE outflow. The outflow of NE from peripheral human lymphocytes was seen. NE secretion seems to be ACh- and calcium-dependent since Veratridine, Ionomycin and KCl are able to induce Ca2+ entry by means of various mechanisms. The Ca2+ channel blocker employed in this study (D600) reduced the ACh-dependent NE outflow. We can conclude that both ACh (through nicotinic receptors) and calcium are involved in the outflow of NE from peripheral human lymphocytes.

Acetylcholine↗

L-tyrosine and nicotine induce synthesis of L-Dopa and norepinephrine in human lymphocytes.

Catecholamines (CA) were studied in peripheral human lymphocytes in basal conditions as well as after L-tyrosine and/or acetylcholine (ACh) stimulation. Nicotinic and muscarinic receptor activation and blockade were assessed. CA were determined after ultrasonic cell disruption in peripheral lymphocytes after incubation (1 h at 37 degrees C) with the chemicals employed. L-tyrosine significantly increased (P < 0.01) L-Dopa and norepinephrine (NE) content of lymphocytes. ACh in the low microM range did not modify, whereas ACh (60 microM) and (120 microM) significantly increased (P < 0.01), both L-Dopa and NE intracellular levels. L-tyrosine plus ACh (60 microM) or (120 microM) significantly increased (P < 0.01) intracellular L-Dopa and NE versus control, versus L-tyrosine alone and versus ACh alone. The increase was higher than the algebraic sum of the individual increases. Nicotine (250 microM), but not muscarine (50 microM), significantly increased L-Dopa and NE in lymphocytes. Tetraethylammonium (500 microM) (nicotinic blocker), but not atropine (100 microM) (muscarinic blocker), inhibited the ACh-mediated increase of intracellular L-Dopa and NE. These data show that lymphocyte synthesis of CA is under nicotinic control. Since intracellular L-Dopa after L-tyrosine plus ACh increased 6-fold versus basal, 2-fold versus L-tyrosine alone and 3-fold versus ACh alone, it is concluded that ACh might regulate CA synthesis in lymphocytes through an activation of the rate limiting enzyme tyrosine hydroxylase.

Acetylcholine↗

Ambulatory blood pressure monitoring: how reproducible is it?

We tested the reproducibility of ambulatory blood pressure monitoring (ABPM) by the use of agreement plots. Thirty-two normotensive volunteers underwent ABPM on four separate days (interval 28 days), on the same typical weekday. Sleeping time was restricted to the ABPM nighttime subperiod from 11:00 PM to 7:00 AM. Twenty-four-hour average values-both systolic and diastolic-daytime average values, and nighttime average values, as well as standard deviation (SD) values, were analyzed for differences (analysis of variance). Adaptation occurred from the first to the fourth ABPM, ie, average 24 h, daytime, and nighttime values were lower (-1 to -3 mm Hg) during the fourth recording than the first (P < .05 to P < .01). The agreement analysis showed a surprisingly high agreement among the four data sets (ie, differences from +/-2.54 to +/-5.92 mm Hg; +/-2 SD of the distribution). We concluded that reproducibility of ABPM seems excellent, but adaptation may occur, even in normotensive volunteers under research conditions. Caution must be paid before labeling a patient as hypertensive, because initial ABPM may yield higher values than later monitorings.

Adult↗

Catecholamine content and in vitro catecholamine synthesis in peripheral human lymphocytes.

We studied the catecholamine (CA) content in peripheral human lymphocytes and the ability of these cells to synthesize CA in vitro. CA were separated by high performance liquid chromatography (HPLC) and determined in the supernatant by electrochemical detection as well as being determined after ultrasonic cell disruption in mononuclear leukocytes, adherent cells (monocytes/macrophages), total lymphocytes, and B- and T-cell enriched fractions. T lymphocytes contained L-Dopa and norepinephrine (NE), whereas B lymphocytes contained only L-Dopa. Lymphocytes seem to be able to synthesize NE from both L-tyrosine and L-Dopa added to the incubation medium in concentrations similar to the peripheral venous plasma (i.e. 5 x 10(-5) m and 10(-8) m, respectively). The addition of D-Dopa did not increase intracellular NE. alpha-methyl-p-L-tyrosine, benserazide, disulfiram, and fusaric acid (which are inhibitors of the enzymatic pathway) all decreased the synthesis of NE. After the addition of [3H]-L-Dopa (10(-8) m and 10(-7) m) to the incubation medium, [3H]-NE and [3H]-dopamine appeared. By increasing the concentration of L-Dopa in the medium (< 10(-6) m), CA were detected in the supernatant as well. These data show that peripheral human T lymphocytes contain and are able to synthesize CA from normal precursors in physiologic concentrations, i.e. a CA synthetic pathway is shown in nonneural cells. These data seem to support the hypothesis of autocrine and paracrine loops in the regulation of lymphocyte activity in lymphocytes taken from human cerebrospinal fluid (as suggested by other authors).

Adult↗

Reproducibility of ambulatory blood pressure monitoring.

OBJECTIVE: To investigate whether blood pressure monitoring is reproducible. DESIGN: Reproducibility of ambulatory blood pressure monitoring data was assessed by means of traditional and relatively new statistical methods, namely correlation coefficients, regression analysis and agreement analysis. METHODS: Ninety-one normotensive and hypertensive, uncomplicated outpatients underwent monitoring twice (mean interval 241 days). Data were analysed for reproducibility, correlation, difference and adaptation. Analyses were performed to verify the reproducibilities of the diagnosis of hypertension and of the treatment assessment. RESULTS: Ambulatory blood pressure monitoring is highly reproducible in terms of traditional statistics, but not in terms of the agreement analysis (error as high as 18 mmHg), although it performs better than does office sphygmomanometry (error as high as 38 mmHg). Reproducibility is acceptable in normotensive subjects and in patients who respond to treatment, but untreated hypertensives and those who do not respond to treatment show a worse ratio. CONCLUSION: The reproducibility of ambulatory blood pressure monitoring requires improvement. We do not know how many repeated measurements we need before diagnosing hypertension. Spontaneous variability of blood pressure interferes with blood pressure reproducibility. Diagnosis and treatment assessment in hypertension must take into account poor reproducibility.

Journal Article↗

Effects of opioid substances on cAMP response to the beta-adrenergic agonist isoproterenol in human mononuclear leukocytes.

The effects of different opioid substances on isoproterenol and forskolin-stimulated cyclic AMP (cAMP) intracellular accumulation, and on the binding of 125I-pindodol (IPIN) to beta 2-adrenoceptors were studied in human mononuclear leukocytes (MNL). The opioids used were alpha-endorphin, beta-endorphin, tau-endorphin, DAGO (a mu receptor agonist), dermenkephalin (a delta receptor agonist and morphine. Only morphine was able to increase the cAMP response to isoproterenol. The EC50 of isoproterenol for cAMP accumulation was shifted leftward by morphine; this effect was blocked by naloxone. On the contrary, the cAMP response to forskolin, direct activator of adenylate cyclase, was similar in the control test with respect to the experiments with morphine. The five opioid peptides induced no changes in the dose-response curves with isoproterenol and forskolin. Furthermore, none of the opioids induced changes in the IPIN binding. Our data show that morphine is able to exert a significant enhancement of the response of beta 2-adrenergic receptors to isoproterenol in human mononuclear leukocytes. This effect seems to be mediated by mu opioid receptors and seems to involve G protein.

Adult↗

Yohimbine effects on blood pressure and plasma catecholamines in human hypertension.

The purpose of this study has been to test the hypothesis of an alpha 2-adrenoreceptor alteration in human essential hypertension. The design of the study involved the oral administration of 10 mg yohimbine, an alpha 2-adrenergic antagonist, to 25 healthy volunteers and 29 sex- and age-matched untreated hypertensive patients. Volunteers and patients were studied twice in random order, after placebo or yohimbine treatment, in supine and upright positions. Arterial pressure and heart rate were monitored by servoplethysmomanometry, and venous plasma catecholamines were determined by HPLC with electrochemical detection. Yohimbine induced a significant increase in diastolic pressure only in the hypertensive patients. Plasma norepinephrine was increased significantly in both yohimbine-treated groups, but the percent increase of plasma norepinephrine after the standing test was decreased significantly only in the healthy yohimbine-treated subjects. Plasma dopamine was increased significantly only in the healthy yohimbine-treated subjects. The response of plasma dopamine to the upright position was modified only in the healthy yohimbine-treated subjects. The decrease observed after 2 min of standing was abolished, showing the involvement of alpha 2-adrenoreceptors in the physiologic response of plasma catecholamines in healthy volunteers. Our data may be consistent with some in vivo evidence of an alpha 2-adrenoreceptor desensitization or an alteration in the balance of alpha-adrenoreceptors in human hypertension.

Adult↗

[Bone metastasis of leiomyosarcoma. Apropos of a case].

INTRODUCTION: Bone leiomyosarcoma is a rare tumor, whether it may be primary or secondary. The authors report on the case of a woman, aged 67, admitted in January 1992 complaining of pain in the left hip and the upper end of the femur. CASE REPORT: In 1985 the patient underwent surgical excision of a soft tissue tumor in the right thigh, histologically diagnosed as a benign fibrous tumor. This lesion recurred locally four times and repeated excisions were performed throughout the years, always with a histological diagnosis of a benign lesion. On admission to hospital, the physical examination as well as laboratory data and plain roentgenograms were unremarkable. Both tomography and MRI showed a lesion in the upper end of the left femur. An isotopic bone scan showed marked increased uptake in the left hip extending to the femoral diaphysis. An open biopsy was performed for histology, immunohistochemistry and electron microscopy. A diagnosis of metastatic leiomyosarcoma was made. The retrospective histological examination of specimens of the soft tissue tumor excised in 1985 showed the same immunohistochemical features of the contralateral leiomyosarcoma. On this basis, one stage resection of the left hip and the upper end of the femur was performed and a Kotz modular prosthesis was inserted. Postoperative healing was achieved without any complications and the function of the operated limb was satisfactory. Three months after the operation pulmonary lesions were noted on chest radiographs and CT scan. The patient died two years after the first admission for widespread metastasis. DISCUSSION: In the reported case, the bony metastasis appeared to be the presenting finding of the soft tissue tumor of the contralateral thigh. This presentation is rare in previously published series. The misdiagnosis of the primary tumor had caused local recurrences, and an increased malignity occurred. According to the literature, a soft tissue leiomyosarcoma can be easily confused with other spindle cell lesions. Therefore an accurate histological and ultrastructural diagnosis is necessary for adequate surgical treatment.

Aged↗

[Moxonidine vs. captopril in minor to intermediate hypertension. Double-blind study of effectiveness and tolerance].

In a randomized double-blind study, the antihypertensive efficacy and tolerance of the imidazoline receptor agonist, moxonidine, were compared with those of the ACE inhibitor, captopril. Included in the trial were 50 ambulatory patients with mild-to-moderate hypertension, who were treated for 4 weeks with either 0.2-0.4 mg moxonidine, or 25-50 mg captopril daily. Both substances clearly reduced hypertension; no statistically significant difference was seen between the two groups. Under moxonidine, the mean blood pressure while seated decreased from 176/101 mm Hg to 155/91 mm Hg by the end of treatment; under captopril the corresponding figures were 170/99 and 150/89 mm Hg. Minor transient side effects, for the most part with a doubtful relationship to the treatment, were seen in 5 patients (20%) of the moxonidine group, and in 8 patients (32%) of the captopril group. Thus, in this study, moxonidine and captopril proved to have equivalent antihypertensive efficacy and good tolerability.

Administration, Oral↗

Evidence for interactions between HLA system class I and beta-adrenergic receptors in human mononuclear leukocytes.

In order to determine the possible interactions between histocompatibility leukocyte antigen (HLA) -class I antigens and beta-adrenergic receptors, we evaluated the effects of anti-HLA class I monoclonal antibodies on beta-adrenoceptor-mediated intracellular production of cAMP in human mononuclear leukocytes. Moreover, we studied whether anti-HLA class I monoclonal antibodies inhibit the binding of a specific radioligand to the beta-adrenoceptors, and, conversely, whether both isoproterenol and propranolol interfere with the binding (evaluated by a cytofluorometric assay) of the anti-HLA class I monoclonal antibodies to the cell membrane. Our results showed that anti-HLA class I monoclonal antibodies induced a significant beta-adrenergic-dependent increase in intracellular cAMP whereas anti-HLA class II and antimelanoma monoclonal antibodies were ineffective. Moreover anti-HLA class I monoclonal antibodies inhibited, in part, the specific binding of a beta-adrenergic radioligand, although they did not induce the internalization of the beta-adrenoceptors. On the other hand, both isoproterenol and propranolol induced a significant decrease in the peripheral blood mononuclear cell expression of HLA-class I molecules. Our data suggest that important interactions between major histocompatibility complex gene products and the beta-adrenergic receptors may occur in human cells.

Adult↗

Effects of intravenous epinine administration on left ventricular systolic performance, coronary hemodynamics, and circulating catecholamines in patients with heart failure.

Twenty-six patients with mild to moderate heart failure were studied to determine the effects of epinine infusion (at a rate producing plasma levels similar to those measured after oral administration of 100 mg of the prodrug ibopamine) on left ventricular (LV) function (14 patients), and coronary flow and circulating catecholamines (12 patients). The only significant hemodynamic change at an infusion rate of 0.5 microgram/kg/min was a 9% (p less than 0.05) decrease in systemic vascular resistance (SVR). At an infusion rate of 1 microgram/kg/min (mean free epinine plasma levels 14.3 +/- 3.7 ng/ml), heart rate (HR), dP/dtmax (1,405 +/- 255 to 1,490 +/- 320 mm Hg, NS), (dP/dt)/DP40, and the relaxation rate remained unchanged, but the ejection fraction (EF) increased from 32 to 38% (p less than 0.001), cardiac output (CO) increased, and SVR decreased by 22% (p less than 0.05). In a separate group of 12 patients, epinine infusion at rates of 0.5-1 microgram/kg/min produced no significant changes in coronary blood flow or myocardial oxygen uptake. At these infusion rates, arterial norepinephrine (NE) and dopamine (DA) levels decreased slightly and arterial and coronary sinus epinephrine increased. In conclusion, epinine, at concentrations similar to those achieved during therapeutic use of ibopamine, had negligible effect on myocardial contractility and relaxation rate in heart failure patients. Cardiac pump function was improved by a decrease in SVR rather than by inotropic stimulation. The data also suggest that these low concentrations of epinine may modulate the sympathetic nervous system, but further studies are needed to determine whether this effect could have clinical significance.

Adult↗

[Viral and/or intraepithelial lesions of the lower female genital tract: diagnostic and prognostic value of in situ molecular hybridization].

Fourteen patients (mean age 37 years) suffering from viral and/or intraepithelial cervico-vagino-vulvar pathologies underwent colposcopic and cyto-histological tests and molecular hybridization. The following types of HPV were assayed: 6/11-16/18-31/35/51 in cytological tissues (exocervical scraping) and biopsy material immersed in paraffin and fixed in formalin buffered with 10% PBS. The aim of the study was to identify different types of HPV using molecular hybridisation in situ. The paper reports the results and correlations with colposcopic, cytological and histological diagnosis, and then discuss the clinico-biological and prognostic aspects of this method.

Adult↗

Norepinephrine-induced plasma dopamine decrease in man: pharmacological evidence of the involvement of alpha 2-adrenoceptors.

OBJECTIVE: The purposes of this study were: (1) to test whether intravenous infusion of norepinephrine can affect plasma dopamine levels; and (2) to explore to what extent dopamine-2 or alpha 2-receptors play a role in this response. DESIGN: Norepinephrine infusion in man was performed to test whether the increase in norepinephrine during sympathetic stimulation can affect dopamine release. Specific antagonists of presynaptic dopamine-2 and alpha 2-receptors were administered to test the receptor(s) involved in this possible regulatory phenomenon. METHODS: Plasma catecholamine levels were investigated in seven normal subjects before and after administration of domperidone (dopamine-2 antagonist), yohimbine (alpha 2-antagonist) and norepinephrine. RESULTS: Both oral domperidone and yohimbine induced a significant increase in both plasma norepinephrine and plasma dopamine. Norepinephrine infusion induced a significant decrease in plasma dopamine. Pretreatment with domperidone only partially counteracted this inhibitory effect of norepinephrine infusion, whereas yohimbine fully counteracted it. CONCLUSIONS: Our data show that norepinephrine may act as a hormone at plasma concentrations as low as 450 pg/ml. The norepinephrine-induced plasma dopamine decrease seems to be alpha 2-adrenoceptor-mediated. This norepinephrine effect may be involved in the physiologic decrease in plasma dopamine that we demonstrated in the upright position in normal subjects.

Administration, Oral↗

Hysteroscopy as an elective tool in abnormal uterine bleeding in perimenopausal women.

Abnormal Uterine Bleeding is a very frequent pathology particularly in perimenopausal age (> or = 45 years). The Authors report the experience of the 2nd Department of Ob/Gyn. of Rome University "La Sapienza" from January 1985 up to September 1991. The hysteroscopic evaluation of 789 patients in perimenopausal age is reviewed. The Authors analyze in detail the main cause of metrorrhagia describing the hysteroscopic aspect and relative incidence. Finally, some considerations concerning the great usefulness that a simple and accurate diagnostic investigation such as hysteroscopy represents in a routine diagnostic procedure, are reported.

Aged↗

[Diagnostic and therapeutic aspects of endometrial polyps].

The diagnostic and therapeutic utility of hysteroscopy in intracavity uterine pathologies is now widely recognised. The Authors have evaluated the efficacy of hysteroscopy in 640 patients in a study of endometrial polyps for which the endoscopic technique represents the elective form of therapy, avoiding excessive trauma to the patient and preserving the endometrial mucosa intact. The results obtained are fully discussed. Hysteroscopic resection of polyps was carried out in 49 patients in a day-hospital setting and without further complications.

Adult↗