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Biomedical subjects

L Bianchi

Publications and source records attributed to L Bianchi.

At least 145 records · Page 8Linked to original sources

Involvement of the proliferating cell nuclear antigen (PCNA) in DNA repair induced by alkylating agents and oxidative damage in human fibroblasts.

The involvement of the proliferating cell nuclear antigen (PCNA) in the process of DNA repair induced by alkylating agents or by oxidative damage was investigated in human quiescent fibroblasts by immunofluorescence and flow cytometry. Transition from soluble to the DNA-bound form of PCNA, was taken as the parameter to determine its involvement in repair DNA synthesis. Treatment with the alkylating agents methylmethane sulfonate and N-methyl-N'-nitro-N-nitrosoguanidine resulted in the rapid and dose-dependent increase in the nuclear binding of PCNA. Similar results were obtained with compounds such as hydrogen peroxide or tert-butyl hydroperoxide, which are known to induce oxidative DNA damage. Tert-butyl hydroperoxide may also generate malondialdehyde through a reaction of lipid peroxidation. This mutagenic and carcinogenic product has been previously shown to form adducts with DNA. Therefore, the possibility that tert-butyl hydroperoxide could induce DNA damage through this pathway was investigated by incubating cells directly in the presence of malondialdehyde. Such treatment resulted in an increase in immunofluorescence associated with nuclear-bound PCNA. The ability of oxidative and alkylating agents to induce the nuclear binding of PCNA was also assessed in proliferating cells. In these conditions, treatment with hydrogen peroxide or methylmethane sulfonate, resulted in an increase in nuclear-bound PCNA in the G1 and in the G2 + M compartments, but not in S phase. At longer times after treatment, PCNA immunostaining was reduced to basal levels, while an increase in nuclear binding of p21(waf1/cip1) protein was found in concomitance with cell-cycle arrest. These results indicate that agents inducing DNA base alterations in vivo, promote the nuclear binding of PCNA. These lines of evidence support the role of a PCNA-dependent reaction in the base excision repair system.

Alkylating Agents↗

Functional consequences of ROMK mutants linked to antenatal Bartter's syndrome and implications for treatment.

The antenatal variant of Bartter's syndrome is an autosomal recessive kidney disease characterized by polyhydramnios, premature delivery, hypokalemic alkalosis and hypercalciuria. It is genetically heterogeneous, having been linked recently to mutations in an ATP-sensitive, renal outer medullary K+channel, ROMK, and earlier to mutations in the Na-K-2Cl co-transporter, NKCC2. We characterized four of the mutations reported in three heterozygous ROMK variants of antenatal Bartter's and found that each expressed a distinct phenotype in Sf9 cells. One mutation expressed normal function and appears to be an allelic polymorphism. The other three mutations produced channels with significantly reduced K+fluxes. However, the mechanisms in each case were different and reflected abnormalities in phosphorylation, proteolytic processing or protein trafficking. The different mechanisms may be important in the design of appropriate therapy for patients with this disease.

Animals↗

Myxoid dermatofibrosarcoma protuberans: morphological, ultrastructural and immunohistochemical features.

Two uncommon cases of dermatofibrosarcoma protuberans with prominent myxoid changes are presented. The tumors appeared as large multinodular cutaneous plaques that arose at the sites of excision of previous tumors some years earlier. In addition to limited fibrous storiform features, focally observed in deep and peripheral portions of the tumors, a diffuse myxoid pattern could be observed. The latter consisted of homogeneous areas of rare, stellate or spindle-shaped cells, haphazardly scattered in abundant myxoid matrix. Cells of myxoid neoplastic tissue showed mainly a positive immunoreaction for fibrohistocytic markers and the absence either of muscular, neural or human progenitor cell antigens. Mitotic figures were fewer and cell proliferation rates were lower in myxoid as compared to those of typical dermatofibrosarcoma protuberans used as a control. The ultrastructural examination of myxoid areas revealed a prevalent fibroblast-like cell population showing dilated cytoplasmic vesicles, sometimes containing glycosaminoglycans-like substances. The extent of myxoid changes together with the characteristic morphological, ultrastructural and immunohistochemical features confirm that myxoid dermatofibrosarcoma protuberans is a distinct variant of this fibrohistiocytic tumor to be considered in the differential diagnosis among myxoid tumors of the skin.

Adult↗

Endogenous nitric oxide in patients with stable COPD: correlates with severity of disease.

BACKGROUND: Increased levels of exhaled nitric oxide (eNO) have been reported in asthmatic subjects but little information is available on eNO in patients with advanced chronic obstructive pulmonary disease (COPD). A study was undertaken to evaluate the levels of eNO in patients with stable COPD of different degrees of severity. METHODS: Peak and plateau values of eNO (PNO and PLNO, respectively) were evaluated in 53 patients with COPD and analysed according to the level of forced expiratory volume in one second (FEV1) and the presence of cor pulmonale (CP) (group 1, FEV1 < 35% predicted with CP, n = 15; group 2, FEV1 < 35% predicted without CP, n = 15; group 3, FEV1 > 35% predicted, n = 23). Seventeen normal subjects served as controls. RESULTS: All the patients with COPD had reduced levels of PLNO compared with the controls (mean (SD) 6.3 (3.0) and 9.4 (2.8) ppb, respectively). In groups 1 and 2 PLNO levels were significantly lower than in subjects in group 3 (5.5 (2.9), 5.7 (3.5), and 7.1 (2.7) ppb, respectively; p < 0.01 ANOVA). In all subjects % predicted FEV1 correlated slightly with PLNO but not with PNO. CONCLUSION: Patients with severe stable COPD have reduced levels of eNO compared with normal subjects. eNO levels are slightly related to the severity of airflow obstruction.

Aged↗

Kinematic coordination in human gait: relation to mechanical energy cost.

Twenty-four subjects walked at different, freely chosen speeds (V) ranging from 0.4 to 2.6 m s-1, while the motion and the ground reaction forces were recorded in three-dimensional space. We considered the time course of the changes of the angles of elevation of the trunk, pelvis, thigh, shank, and foot in the sagittal plane. These angles specify the orientation of each segment with respect to the vertical and to the direction of forward progression. The changes of the trunk and pelvis angles are of limited amplitude and reflect the dynamics of both right and left lower limbs. The changes of the thigh, shank, and foot elevation are ample, and they are coupled tightly among each other. When these angles are plotted one versus the others, they describe regular loops constrained on a plane. The plane of angular covariation rotates, slightly but systematically, along the long axis of the gait loop with increasing V. The rotation, quantified by the change of the direction cosine of the normal to the plane with the thigh axis (u3t), is related to a progressive phase shift between the foot elevation and the shank elevation with increasing V. As a next step in the analysis, we computed the mass-specific mean absolute power (Pu) to obtain a global estimate of the rate at which mechanical work is performed during the gait cycle. When plotted on logarithmic coordinates, Pu increases linearly with V. The slope of this relationship varies considerably across subjects, spanning a threefold range. We found that, at any given V > 1 m s-1, the value of the plane orientation (u3t) is correlated with the corresponding value of the net mechanical power (Pu). On the average, the progressive rotation of the plane with increasing V is associated with a reduction of the increment of Pu that would occur if u3t remained constant at the value characteristic of low V. The specific orientation of the plane at any given speed is not the same in all subjects, but there is an orderly shift of the plane orientation that correlates with the net power expended by each subject. In general, smaller values of u3t tend to be associated with smaller values of Pu and vice versa. We conclude that the parametric tuning of the plane of angular covariation is a reliable predictor of the mechanical energy expenditure of each subject and could be used by the nervous system for limiting the overall energy expenditure.

Adult↗

Motor patterns for human gait: backward versus forward locomotion.

Seven healthy subjects walked forward (FW) and backward (BW) at different freely chosen speeds, while their motion, ground reaction forces, and electromyographic (EMG) activity from lower limb muscles were recorded. We considered the time course of the elevation angles of the thigh, shank, and foot segments in the sagittal plane, the anatomic angles of the hip, knee, and ankle joints, the vertical and longitudinal ground reaction forces, and the rectified EMGs. The elevation angles were the most reproducible variables across trials in each walking direction. After normalizing the time course of each variable over the gait cycle duration, the waveforms of all elevation angles in BW gait were essentially time reversed relative to the corresponding waveforms in FW gait. Moreover, the changes of the thigh, shank, and foot elevation covaried along a plane during the whole gait cycle in both FW and BW directions. Cross-correlation analysis revealed that the phase coupling among these elevation angles is maintained with a simple reversal of the delay on the reversal of walking direction. The extent of FW-BW correspondence also was good for the hip angle, but it was smaller for the knee and ankle angles and for the ground reaction forces. The EMG patterns were drastically different in the two movement directions as was the organization of the muscular synergies measured by cross-correlation analysis. Moreover, at any given speed, the mean EMG activity over the gait cycle was generally higher in BW than in FW gait, suggesting a greater level of energy expenditure in the former task. We argue that conservation of kinematic templates across gait reversal at the expense of a complete reorganization of muscle synergies does not arise from biomechanical constraints but may reflect a behavioral goal achieved by the central networks involved in the control of locomotion.

Adult↗

Acute effects of deep diaphragmatic breathing in COPD patients with chronic respiratory insufficiency.

This study investigated the impact of deep diaphragmatic breathing (DB) on blood gases, breathing pattern, pulmonary mechanics and dyspnoea in severe hypercapnic chronic obstructive pulmonary disease (COPD) patients recovering from an acute exacerbation. Transcutaneous partial pressure of carbon dioxide (Ptc,CO2) and oxygen (Ptc,O2) and arterial oxygen saturation (Sa,O2), were continuously monitored in 25 COPD patients with chronic hypercapnia, during natural breathing and DB. In eight of these patients, breathing pattern and minute ventilation (V'E) were also assessed by means of a respiratory inductance plethysmography. In five tracheostomized patients, breathing pattern and mechanics were assessed by means of a pneumotachograph/pressure transducer connected to an oesophageal balloon. Subjective rating of dyspnoea was performed by means of a visual analogue scale. In comparison to natural breathing deep DB was associated with a significant increase in Ptc,O2 and a significant decrease in Ptc,CO2, with a significant increase in tidal volume and a significant reduction in respiratory rate resulting in increased V'E. During DB, dyspnoea worsened significantly and inspiratory muscle effort increased, as demonstrated by an increase in oesophageal pressure swings, pressure-time product and work of breathing. We conclude that in severe chronic obstructive pulmonary disease patients with chronic hypercapnia, deep diaphragmatic breathing is associated with improvement of blood gases at the expense of a greater inspiratory muscle loading.

Aged↗

Effects of proportional assist ventilation on exercise tolerance in COPD patients with chronic hypercapnia.

This study investigates the impact of proportional assist ventilation (PAV), a new mode of partial ventilatory support, on exercise tolerance and breathlessness in severe hypercapnic chronic obstructive pulmonary disease (COPD) patients. We also examined the effects of continuous positive airway pressure (CPAP) and pressure support ventilation (PSV). On two consecutive days, 15 stable hypercapnic COPD patients underwent four endurance tests on a cycle ergometer at 80% of their maximal workrate, receiving, via a nasal mask in random order, either: 1) sham ventilation (CPAP: 1 cmH2O); 2) CPAP (6 cmH2O); 3) PSV (inspiratory pressure support: 12-16 cmH2O; expiratory positive airway pressure (EPAP): 1 cmH2O); or 4) PAV (8.6+/-3.6 cmH2O x L(-1) and 3+/-1.3 cmH2O x L(-1)x s(-1) of volume and flow assistance, respectively plus EPAP: 1 cmH2O). Oxygen supply was standardized to maintain an arterial oxygen saturation (Sa,O2) of 92-93%. Breathing pattern and minute ventilation (by respiratory inductive plethysmography), pulse oximetry, end tidal partial pressure of CO2, cardiac frequency and sensations of dyspnoea and leg discomfort (by Borg scale) were monitored. In comparison to sham ventilation, PAV, PSV and CPAP were able to increase the endurance time (from 7.2+/-4.4 to 12+/-5.6, 10+/-5.2 and 9.6+/-4.6 min, respectively) and to reduce dyspnoea and oxygen flow to the nasal mask. However, the greatest improvement was observed with PAV. We conclude that PAV delivered by nasal mask can im-prove exercise tolerance and dyspnoea in stable hypercapnic COPD patients and hence this mode of ventilatory support may be useful in respiratory rehabilitation programmes.

Aged↗

Familial occurrence of pseudoxanthoma-elasticum-like papillary dermal elastolysis.

We report the morphological, immunohistochemical and ultrastructural cutaneous findings of two sisters, aged 72-74, with pseudoxanthoma-elasticum-like papillary dermal elastolysis (PDE), recently defined as an age-related condition. To our knowledge, these are the first familial cases of PDE reported in the literature. The lesions appeared as small, asymptomatic, soft papules around the neck and axillary regions. The affected skin revealed a marked decrease of normal elastic network of papillary dermis without alterations in either the relevant collagen or reticular dermis. Ultrastructural and immunohistochemical examinations showed activated dermal fibroblasts with abundant elongated dendritic cytoplasmic processes and the absence of myofibroblasts. The well documented avoidance of sun exposure (the patients are both nuns), the rare incidence of the disorder (only six cases reported), and the familial occurrence suggest that genetic or inherited predisposition should also be considered in the pathogenesis of PDE.

Aged↗

Nuclear association of cyclin D1 in human fibroblasts: tight binding to nuclear structures and modulation by protein kinase inhibitors.

The association of cyclin D1 with nuclear structures was investigated in normal human fibroblasts by using hypotonic detergent extraction procedures, immunofluorescence quantitation with flow cytometry, and Western blot analysis. About 20% of the total cellular levels of cyclin D1 was found to be tightly bound to nuclear structures, being the complex formation resistant to DNase I treatment and to high salt extraction. Maximal levels of the insoluble form of the protein were found in the middle to late G1 phase of the cell cycle. Cell fractionation and immunoprecipitation techniques after in vivo 32P-labeling showed that both soluble and nuclear-bound forms of cyclin D1 were phosphorylated. Both fractions were reactive to an anti-phosphotyrosine antibody, while only the latter was detectable with an anti-phosphoserine antibody. Treatment with the protein kinase inhibitor staurosporine, which induces a cell cycle arrest in early G1 phase, strongly reduced cyclin D1 phosphorylation. Concomitantly, the ratio of nuclear-bound/total cyclin D1 levels was reduced by about 60%, compared with the control value. The protein kinase A specific inhibitor isoquinoline-sulfonamide (H-89) induced a similar reduction in the ratio, with no significant modification in the total amount of protein. In contrast, both calphostin C and bisindolylmaleimide, specific inhibitors of protein kinase C, consistently increased by 30-50% the ratio of nuclear-bound/total amount of the cyclin protein. These results suggest that, during the G1 phase, formation of an insoluble complex of cyclin D1 occurs at nuclear matrix structures and that this association is mediated by a protein kinase A-dependent pathway.

Cell Division↗

Mapping the kidney potassium channel ROMK1. Glycosylation of the pore signature sequence and the COOH terminus.

ROMK1, also known as Kir 1.1, is an inwardly rectifying K+ channel and is the prototypical member of the large Kir gene family. The accepted model of Kir topology predicts intracellular NH2 and COOH termini, and two membrane-spanning segments, M1 and M2, connected by an intramembranous pore-forming segment, H5. The sequence of H5 is similar in voltage-dependent K+ channels and features a strictly conserved GY/FG in its mid-region, which has been proposed as the selectivity filter of the pore. We have been using N-glycosylation substitution mutants to map the extracellular topology of ROMK1 biochemically and have described several loci in H5 that were glycosylated. We now report glycosylation at loci Tyr144 and Phe146, which indicates that the signature GYG sequence (143-145) rather than being intramembranous is extracellular. The COOH terminus was predicted to begin at position 178, but contrary to the model, we observed that position 257 was glycosylated and surrounding positions at 199, 222, and 298 were unglycosylated. N-Glycosylation sequon substitution at the latter three positions abolished K+/Na+ selectivity. Our results suggest a major revision of the topology of ROMK1 with H5 and the pore signature sequence now completely extracellular. The COOH terminus appears to form two additional membrane-spanning segments and to contribute to the ion conduction pathway.

Amino Acid Sequence↗

Effect of cromakalim on the purinergic and cholinergic transmission in the rat detrusor muscle.

Contraction of the rat detrusor muscle is mediated by cholinergic and purinergic mechanisms. The present study was carried out to look at the influence of cromakalim, compared with atropine, suramin and nifedipine on the contractile response evoked by single shock and exogenous agonists (carbachol and ATP) in rat urinary bladder. Cromakalim was able to inhibit only partially the response to carbachol and profoundly affected the response to exogenous ATP. Atropine suppressed the response to carbachol and was inactive versus ATP. Suramin was inactive versus carbachol and was able to antagonize the response to ATP. Nifedipine proved to be a non-competitive antagonist versus carbachol (pD2 = 7.66 +/- 0.05) and deeply affected the response to ATP. Cromakalim inhibited only partially the first, purinergic, phase of the electrically evoked response but was able to inhibit in a concentration-dependent manner the second, cholinergic, phase (logIC50 = 6.87 +/- 0.05). Nifedipine blocked both the phases. Atropine blocked partially only the second phase. Suramin inhibited the first phase but, at least partially, also the second one. The combination of atropine and suramin enhanced the inhibition of the second phase. The antagonistic effect of suramin on the second phase could indicate an overlap of the purinergic and cholinergic components. The comparison between pre- and postjunctional effects indicates that cromakalim acts on purinergic transmission predominantly postjunctionally. On the contrary, the action on cholinergic transmission seems to occur mainly at prejunctional level. This conclusion can be relevant in view of the claimed importance of K+ channel openers in the treatment of urinary disorders.

Adenosine Triphosphate↗

Measurement of synthetic phenolic antioxidants in human tissues by high-performance liquid chromatography with coulometric electrochemical detection.

The antioxidants, 2-tert.-butyl-4-methoxyphenol (BHA) and its oxidative peroxidation product 2,2'-dihydroxy-3,3'-di-tert.-butyl-5,5'-dimethoxybiphenyl (di-BHA), 3,5-di-tert.-butyl-4-hydroxytoluene (BHT) and propyl gallate, were measured in plasma and tissue homogenates by HPLC and electrochemical detection, with a sensitivity down to 0.2 (BHA), 0.1 (di-BHA), 0.4 (BHT) and 1 (propyl gallate) ng ml(-1) of plasma or tissue homogenate. The data demonstrate that in man, at the current level of exposure to dietary antioxidants, significant amounts of BHA, BHT and propyl gallate are accumulated in the omentum. Furthermore, they provide the first evidence that the peroxidase-catalysed oxidation of BHA is operative in man.

Aged↗

Plasma tryptophan levels and tryptophan/neutral amino acid ratios in obsessive-compulsive patients with and without depression.

We have studied fasting plasma tryptophan (TRP) levels and tryptophan/large neutral amino acid (TRP/LNAA) ratios in 12 patients with obsessive-compulsive disorder (OCD) and 12 patients with OCD and a coexisting current diagnosis of major depressive disorder (OCD-MDD). Assessments were made at baseline and after 6 weeks of treatment with fluvoxamine. OCD-MDD patients had significantly lower baseline TRP levels and TRP/LNAA ratios than OCD patients. After 6 weeks of fluvoxamine treatment, OCD-MDD patients had significant increases in plasma TRP and TRP/LNAA ratio, whereas OCD patients had non-significant decreases. Our data suggest that a major depressive syndrome could be a state variable affecting the changes in plasma TRP and TRP/LNAA ratio in OCD patients.

Adult↗

Cromakalim blocks the purinergic response evoked in rat vas deferens by single-pulse electrical stimulation.

The present study was carried out to look at the influence of the K+ channel opener cromakalim, compared with suramin and prazosin, on the contractile response evoked by single-pulse field stimulation and exogenous agonists in epididymal and prostatic portions of rat vas deferens. In the epididymal portion suramin abolished the first phase of the response to single shock, prazosin deeply affected the second phase and a combination of both antagonists almost completely abolished both phases. Cromakalim was able to inhibit in a concentration-dependent manner the first purinergic phase (pD2 = 5.90 +/- 0.11), leaving practically unaffected the second, adrenergic phase. This inhibitory effect of cromakalim on the electrically evoked response was counteracted by glibenclamide. Cromakalim and prazosin, but not suramin, affected the response to exogenous noradrenaline. Suramin but not cromakalim was able to antagonize responses to alpha, beta-methylene-ATP. In the prostatic portion because of a less clear discrimination between adrenergic and purinergic phases of the electrically evoked response, the picture was less clear although the trend was identical. Cromakalim was not able to antagonize the response to ATP. It is concluded that in rat vas deferens cromakalim inhibits purinergic transmission by acting prejunctionally.

Adenosine Triphosphate↗

Influence of family history of hypertension on insulin sensitivity in lean and obese hypertensive subjects.

We evaluated the influence of family history of hypertension on insulin sensitivity in lean and obese hypertensive subjects (H): 40 lean [body mass index (BMI) < or = 25 kg m-2] H with normotensive parents (F-), 50 lean H with one or two parents hypertensive (F+), 30 obese HF- (BMI > or = 30 kg m-2) and 35 obese HF+. The four groups were comparable in terms of age, sex and ambulatory blood pressure values. We evaluated glucose, insulin and C-peptide before and 30, 60, 90 and 120 min after an oral glucose load, insulin sensitivity index (ISI, fasting glucose/insulin ratio), fasting insulin/C-peptide ratio (I/Cp). Glucose, fasting and during test, and I/Cp were similar among the four groups; insulin and C-peptide, fasting and stimulated, were significantly higher and ISI lower in obese H than in lean H; at similar BMI, insulin and C-peptide were significantly higher in F+ than in F-. Insulin directly correlated with night-time blood pressure only in lean HF-. The correlation between insulin and BMI was significantly closer in F-than in F+. In conclusion, family history of hypertension appears to play a relevant role in insulin sensitivity in hypertensive subjects also in the presence of obesity.

Adult↗

Profiles of the response to noradrenaline in the whole and bisected rat vas deferens.

1. The present study was carried out to look at the differences between the whole and bisected rat vas deferens in response to cumulative and non-cumulative administration of noradrenaline in terms of sensitivity and maximum response. An effort was made to quantify the parameters characterizing the various components of the mechanical response to single concentrations of the agonist. 2. The sensitivity, as measured by the -log EC50 value for noradrenaline, was significantly lower in the prostatic portion than in the whole vas deferens and epididymal portion. The maximum contractions reached by the epididymal and the prostatic half were 65.03 +/- 10.43% and 13.84 +/- 5.28% of the maximal contraction evoked by noradrenaline in the whole rat vas deferens. 3. Various concentrations of noradrenaline were tested as single concentrations in the three preparations. These components of the response to noradrenaline were individualized, i.e. an early rapid phasic component followed by a second slower tonic component with spikes superimposed. The time-course of these components, as well as their ratios, were different depending on the concentration of agonist tested and on which half of the vas deferens was considered. 4. The importance of oxidation of exogenous noradrenaline as well of the neuronal and extraneuronal uptake mechanisms was considered. EDTA was devoid of any action. Cocaine enhanced potency and the maximum contraction of noradrenaline and all the parameters related to the different phases of the contraction were increased. Hydrocortisone at the highest concentration employed (2 X 10-5 M) was able to reduce significantly the -log EC50 value of the cumulative concentration-response curve to noradrenaline and both the phasic and tonic components of the contradiction to noradrenaline (3 X 10-6 M). 5. In conclusion, our evaluation of the parameters of the mechanical response of the whole and bisected vas deferens to noradrenaline rationalize the, often contradictory, findings of the current literature. Chiefly, the attainment of a careful description of the features of the response to noradrenaline can offer a dependable approach to the study of the underlying mechanisms of the three components.

Adrenergic alpha-Agonists↗

Efficacy of fluvoxamine, paroxetine, and citalopram in the treatment of obsessive-compulsive disorder: a single-blind study.

Obsessive-compulsive disorder (OCD) has been successfully treated with proserotonergic agents for some years. Clomipramine was the first drug used, but several clinical trials have been conducted more recently to assess the antiobsessional efficacy of selective serotonin reuptake inhibitors (SSRIs). The aim of this study was to compare the antiobsessional efficacy of three SSRIs, fluvoxamine, paroxetine, and citalopram. Thirty obsessive-compulsive patients without comorbid axis I diagnoses except for tic disorder as assessed by DSM-III-R criteria gave informed consent and were recruited consecutively; they underwent a 10-week randomized treatment with fluvoxamine, paroxetine, or citalopram. Ratings were performed under blind conditions every 2 weeks from baseline to the end of the study and by the Yale-Brown Obsessive-Compulsive Scale, the National Institute of Mental Health-Obsessive-Compulsive Scale, the Clinical Global Impressions Scale, and the Hamilton Rating Scale for Depression. Quantitative and qualitative analyses of the antiobsessional efficacy of the three drugs were completed with analysis of variance with repeated measures and survival analysis. The results showed no significant differences between the three treatments. The preliminary conclusions drawn from this study concern the interchangeable antiobsessional effects of different SSRIs, although further studies of "cross-response" to these drugs are needed.

Adult↗