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Biomedical subjects

E Marchesi

Publications and source records attributed to E Marchesi.

At least 37 records · Page 2Linked to original sources
PubMed1996

Lack of T-cell-mediated recognition of the fusion region of the pml/RAR-alpha hybrid protein by lymphocytes of acute promyelocytic leukemia patients.

In previous studies, it was shown that the fusion region of the pml/RAR-alpha protein, expressed by acute promyelocytic leukemia (APL) cells, can be specifically recognized in vitro by donor (D. E. ) CD4 T cells in a HLA class II DR11-restricted fashion. We present here the results on the recognition of several pml/RAR-alpha peptides by APL patients expressing HLA DR11. The in vitro immunization of peripheral blood lymphocytes from four patients in remission (S. R., F. R., M. M., P. G.) with BCR1/25, a 25-mer pml/RAR-alpha, did not elicit either a polyclonal or a clonal immune response specific to the peptide. We then generated new donor anti-pml/RAR-alpha CD4(+) T-cell clones. These clones were tested for their recognition of BCR1/25. One clone (C3/5, CD3(+), CD4(+), CD8(-)) was selected for further analysis. Clone C3/5 showed specific proliferation, cytotoxicity, and cytokine (tumor necrosis factor alpha, granulocyte-macrophage colony-stimulating factor) production when challenged with autologous lymphoblastic cell lines pulsed with peptide BCR1/25. C3/5 cells developed specific proliferation and cytotoxicity when challenged with peptide-pulsed lymphoblastic cell lines and peripheral blood lymphocytes from the four DR11(+) APL patients. APL blasts, available only from patients F. R. and P. G., were not lysed by C3/5 and were unable to present peptide BCR1/25. Incubation of APL cells with IFN-gamma failed to induce HLA class II molecules and recognition by the C3/5 clone. Since APL cells do not express HLA class II molecules, we tested in two donors (D. E. and C. H. R.) and in patients S. R. and P. G. whether the use of 9-mer peptides (BCR1/9) would generate a CD8/HLA class I-restricted response. No peptide-specific T-cell line or clone could be generated from both donors and patients. These findings are discussed in relation to possible therapeutic approaches to the immunotherapy of APL.

Binding Sites↗
PubMed1995

Demonstrable cardiac reinnervation after human heart transplantation by carotid baroreflex modulation of RR interval.

BACKGROUND: After heart transplantation, respiration-synchronous fluctuations (0.18 to 0.35 Hz, high frequency [HF]) in RR interval may result from atrial stretch caused by changes in venous return, but slower fluctuations (0.03 to 0.15 Hz, low frequency [LF]) not due to respiration suggest reinnervation. In normal subjects, sinusoidal neck suction selectively stimulates carotid baroreceptors and causes reflex oscillations of RR interval. METHODS AND RESULTS: To evaluate the presence of reinnervation, we measured the power of RR-LF and RR-HF in 26 heart transplant recipients and 16 control subjects before and during sinusoidal neck suction at 0.1 Hz and 0.20 Hz (similar to but distinct from that of controlled respiration, 0.25 Hz) and before and during administration of atropine or beta-blocker (esmolol hydrochloride) by spectral analysis. All transplant recipients showed small respiratory HF fluctuations. Nonrespiratory LF fluctuations were present in 13 of 26 transplant recipients and increased with months since transplantation (r = .53, P < .01). HF neck suction induced a 0.20-Hz component in all 16 control subjects and none of the 26 transplant subjects. LF neck suction increased RR-LF (from 0.73 +/- 0.20 to 1.30 +/- 0.26 ln ms2, P < .001), similar to but less than in control subjects (from 6.12 +/- 0.21 to 8.27 +/- 0.21 ln ms2, P < .001). Atropine reduced all fluctuations in control subjects and blocked the HF increase caused by 0.20-Hz neck suction but not the LF increase during 0.10-Hz stimulation. Neck suction-induced changes in LF fluctuations persisted after administration of atropine in transplant recipients but were attenuated by esmolol hydrochloride, suggesting sympathetic rather than vagal reinnervation. CONCLUSIONS: The presence of baroreceptor-induced RR oscillations is evidence of functional, although incomplete, autonomic reinnervation.

Adrenergic beta-Antagonists↗
PubMed1995

Antiallergic activity of loratadine: inhibition of leukotriene C4 release from human leucocytes.

The H1 antagonist loratadine has the capacity to inhibit histamine release from human basophils. The aim of this study was to investigate whether loratadine can also inhibit leukotriene C4 (LTC4) release from human leucocytes. Basophil-enriched mononuclear cell suspensions were prepared by centrifugation of peripheral venous blood (n = 10) on discontinuous Percoll gradients. Leucocytes were stimulated with anti-IgE, N-formylmethionyl-leucyl-phenylalanine (FMLP) and Ca2+ ionophore A23187; immunoreactive (i) LTC4 release in the cell supernatant was measured by a competitive radioimmunoassay and histamine release was evaluated by an automated fluorometric technique. Loratadine, in the concentration range of 1-50 microM, exerted a dose-dependent inhibitory effect on IgE-mediated and IgE-independent histamine and iLTC4 release. The concentrations inhibiting 50% of histamine release were 30 microM (anti-IgE), 27 microM (FMLP) and 19 microM (Ca2+ ionophore A23187). The concentrations inhibiting 50% of iLTC4 release were 2.3 microM (anti-IgE). 11 microM (FMLP) and 1.7 microM (Ca2+ ionophore A23187). The inhibitory activity on iLTC4 release was optimal after preincubation for 2 h at 37 degrees C, and was no longer evident when leucocytes were stimulated 2 h after cell washing. Increased extracellular Ca2+ concentrations reduced the inhibitory activity of loratadine. These results indicate that loratadine has the capacity to inhibit the release of preformed and newly generated mediators from human basophil-enriched mononuclear cell suspensions.

Basophils↗
PubMed1995

Acute promyelocytic leukaemia cells resistant to retinoic acid show further perturbation of the RAR alpha signal transduction system.

Acute promyelocytic leukaemia (APL) cell lines resistant to all-trans retinoic acid (ATRA) have been previously derived from the NB4 cell line, and characterized as having lost the expression of the intact pml/RAR alpha fusion protein. To confirm the association between ATRA-resistance and alteration in the fusion protein at the clonal level, 16 clones were generated from ATRA-resistant APL cell lines. All clones show immunological (HLA class I and II, CD11b and c, CD13 and 33), molecular and growth features similar to the parental cell lines. To investigate whether the irradiation protocol used to generate the previously reported retinoic acid-resistant NB4.306 cell line induced additional alterations that could render these cells able to escape the anti-proliferative effect of retinoic acid (ATRA), an additional ATRA-resistant APL cell line, [NB4.007/6], was generated, under the selective pressure of ATRA, from the NB4 cell line without previous radiation. This cell line shows resistance to the anti-proliferative and differentiating action of ATRA. The NB4.007/6 cell line contains the t(15;17) chromosome translocation, shows the usual pml/RAR alpha hybrid DNA but expresses no detectable amount of the usual pml/RAR alpha protein in Western blot analysis, similarly to the NB4.306 cell line. Finally, the relative resistance to ATRA of NB4.306 and NB4.007/6 was evaluated by comparing the phenotypic (CD11b) changes induced by ATRA in these two lines with those induced in the parental, ATRA-sensitive, NB4 cell line. It is estimated that NB4.306 and NB4.007/6 are about 300 and 70 times less sensitive to ATRA than the original NB4 cell line.

Cell Line↗
PubMed1995

Loratadine in the treatment of cough associated with allergic rhinoconjunctivitis.

BACKGROUND: Antihistaminic treatment of allergic asthma or cough-type asthma, including cough associated with allergic rhinocojunctivitis, has been recently reconsidered prospectively since new very potent compounds, nonsedating with anti-allergic properties, are available. OBJECTIVE: The possible effectiveness of loratadine in the treatment of allergic cough was assessed in 20 patients with allergic rhinoconjunctivitis and cough due to Parietaria judaica during the pollen season (April to July 1993). METHODS: Allergic patients were enrolled in a double-blind, placebo-controlled, parallel-group, randomized study, and received loratadine 10 mg/d or placebo in oral tablets for 4 weeks. Occurrence and severity of conjunctival and nasal symptoms, severity and frequency of cough attacks were assessed daily by the patients together with peak expiratory flow evaluation performed twice a day, ie, in the morning and in the evening. Physicians evaluated conjunctival and nasal signs, and spirometry on admission (before treatment), 2 and 4 weeks after treatment. On admission methacholine challenge was also performed to assess PD20. Pollen counts were assessed during the study. RESULTS: According to patients' diary cards, ocular and nasal symptoms were progressively reduced by loratadine treatment (respectively P < .05 and P < .01), as well as cough frequency (P < .05) and cough intensity (P < .01). Peak expiratory flow rate, forced vital capacity, and forced expiratory volume in one second significantly decreased in the placebo-treated group (P < .01), while they were not modified in loratadine-treated patients, who remained normal. CONCLUSIONS: The study suggests that loratadine may be beneficial in the treatment of allergic cough, as well as in rhinoconjunctivitis. Further studies of this may be warranted.

Adult↗
PubMed1995

Presence of autoantibodies against oxidatively modified low-density lipoprotein in essential hypertension: a biochemical signature of an enhanced in vivo low-density lipoprotein oxidation.

OBJECTIVE: We have previously reported that low-density lipoproteins (LDL) isolated from patients with essential hypertension are more susceptible to in vitro oxidation than lipoproteins isolated from normotensive control subjects. In the present study we investigated the occurrence of in vivo LDL oxidation in hypertensive patients. DESIGN: The presence of antioxidatively modified LDL autoantibodies was taken as a suitable index of in vivo LDL oxidation because, after oxidative modifications, LDL express antigenic epitopes that elicit an immune response. The antibody titres were measured in plasma from untreated patients with newly diagnosed essential hypertension. METHODS: An enzyme-linked immunosorbent assay method was employed, using native LDL, Cu(2+)-oxidized LDL and malondialdehyde-derivatized LDL (MDA-LDL) as antigens. Human serum albumin and MDA human serum albumin were also used to monitor cross-reactivity with other oxidized molecules. The antibody titre was expressed as the ratio between anti-modified and anti-native antigen absolute values. RESULTS: The patients with essential hypertension had an antibody ratio significantly higher than control subjects with respect to anti-Cu(2+)-oxidized LDL immunoglobulins G and M, and with respect to anti-MDA-LDL immunoglobulins G and M. A significant positive correlation was found between anti-MDA-LDL and anti-Cu(2+)-oxidized LDL antibody titres. The anti-MDA human serum albumin antibody titre was not different in the two groups of patients. An inverse correlation was detected between the anti-MDA-LDL immunoglobulin M titre and the age of the patients. CONCLUSIONS: The results obtained are consistent with the view that, during the early phases of hypertension development, LDL undergo in vivo oxidation that is mirrored by the generation of autoantibodies against epitopes of oxidized LDL. The oxidation process appears specific for LDL and might be relevant both for the progression of hypertension and for the development of the atherosclerosis that often complicates hypertension itself.

Antibody Specificity↗
PubMed1994

Non-respiratory components of heart rate variability in heart transplant recipients: evidence of autonomic reinnervation?

1. Although the high-frequency fluctuations in R-R interval (respiratory sinus arrhythmia) observed in heart transplant recipients are not a reliable marker of reinnervation because of a previously shown direct mechanical effect of breathing, the presence of a non-respiration-related low-frequency oscillation reflects rhythms generated outside the heart, and thus could be neurally mediated. 2. To evaluate the presence of reinnervation, the spontaneous variability in R-R interval was investigated, supine and after passive tilting, in 23 heart transplant recipients (age 43 years, range 23-64 years) and in 25 normotensive control subjects by autoregressive spectral analysis of low- and high-frequency spontaneous fluctuations in R-R interval and respiration. The response of R-R interval to amyl nitrite inhalation was also evaluated in five heart transplant recipients and eight control subjects. 3. Detectable low-frequency oscillations, unrelated to respiration, were present in 13/23 heart transplant recipients, particularly in those who were transplanted at least 20 months earlier (11/14). The natural logarithm of the power of low-frequency fluctuations was markedly lower than in control subjects (0.75 +/- 0.21 versus 5.62 +/- 0.20 ms2, P < 0.001). The low-frequency but not the high-frequency fluctuations correlated with time since transplantation (r = 0.44, P < 0.05). The subjects with low-frequency fluctuations showed a sudden decrease in R-R interval with amyl nitrite linearly related to the decrease in mean blood pressure (r > or = 0.94). The slopes obtained in these heart transplant recipients were comparable (although of lower values) with those obtained in control subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Inhibitory effect of the H1 antagonist loratadine on histamine release from human basophils.

Loratadine is a powerful H1 antagonist commonly employed in the treatment of allergic disorders. The present study was performed to investigate whether loratadine, in addition to anti-H1 activity, is able to modulate histamine release from human basophils. Leukocyte suspensions were prepared by dextran sedimentation of peripheral venous blood drawn from 10 normal subjects. Leukocytes were stimulated with anti-IgE (1/5,000), N-formyl-methionyl-leucyl-phenylalanine (FMLP; 10 microM) and the Ca2+ ionophore A23187 (1 microM), and histamine release in the cell supernatants was measured by an automated fluorometric method. Loratadine, at concentrations ranging from 1 to 50 microM, exerted a dose-dependent inhibitory effect on IgE-mediated and IgE-independent histamine release. The concentrations inhibiting 50% of histamine release were 30 microM (anti-IgE), 29 microM (FMLP) and 24 microM (Ca2+ ionophore A23187). The inhibitory activity of loratadine was optimal after incubation for 2 h at 37 degrees C and the effect of the drug was no longer evident when leukocytes were stimulated 2 h after cell washing. Increased extracellular Ca2+ concentrations reduced the inhibitory activity of loratadine, indicating that external Ca2+ and loratadine have antagonistic effects on basophil histamine release. These results indicate that loratadine, in addition to H1 receptor blocking activity, has the capacity to inhibit histamine release from human basophils.

Adult↗
PubMed1994

Cardiovascular autonomic modulation in essential hypertension. Effect of tilting.

To better understand the role played by the autonomic nervous system in essential hypertension, we used autoregressive power spectrum analysis to study the noncasual oscillations in RR interval, blood pressure, and skin blood flow in 40 subjects with mild to moderate hypertension and in 25 age-matched control subjects at low frequency (index of sympathetic activity to the heart and the peripheral circulation) and high frequency, respiratory related (index of vagal tone to the heart). RR interval, respiration, noninvasive systolic blood pressure, and skin arteriolar blood flow were simultaneously and continuously recorded with subjects in the supine position and immediately after tilting. The low-frequency component was not significantly different in the two groups either at the cardiac level (control versus hypertensive subjects: 39.1 +/- 4.3 versus 39.9 +/- 3.7 normalized units [NU]) or at the vascular level (1.52 +/- 0.17 versus 1.69 +/- 0.13 ln mm Hg2). After head-up tilting, the RR interval fluctuations were less in hypertensive subjects (low-frequency components from 39.9 +/- 3.7 to 48.4 +/- 4.1 NU, P < .05; high-frequency components from 53.9 +/- 3.7 to 44 +/- 4 NU, P < .05) than in control subjects (low-frequency components from 39.1 +/- 4.3 to 64.4 +/- 4.9 NU, P < .001; high-frequency components from 56.0 +/- 4.5 to 31.2 +/- 4.6 NU, P < .001); the low-frequency components in systolic blood pressure increased similarly in hypertensive subjects (to 2.43 +/- 0.17 ln mm Hg2, P < .0001) and in control subjects (to 2.44 +/- 0.21 ln mm Hg2, P < .01), but the low-frequency components in skin blood flow increased only in control subjects (from 5.34 +/- 0.45 to 6.55 +/- 0.53 mm Hg2, P < .01), not in hypertensive subjects (from 5.55 +/- 0.34 to 5.60 +/- 0.35 ln mm Hg2). In hypertensive subjects with left ventricular hypertrophy, the low-frequency components in systolic blood pressure did not increase after tilting (from 1.75 +/- 0.33 to 2.05 +/- 0.41 ln mm Hg2). Baroreflex sensitivity, as assessed by spectrum analysis, was significantly lower in hypertensive than in control subjects (5.17 +/- 0.49 versus 13.18 +/- 2.44 ms/mm Hg, P < .001. Power spectrum analysis did not reveal an increased sympathetic activity or reactivity either at the cardiac or at the vascular level. The decreased baroreceptor sensitivity in hypertensive subjects could explain the reduced change in sympathovagal balance in the tilt position at the cardiac level. In hypertensive subjects without left ventricular hypertrophy, cardiopulmonary reflex deactivation induced by tilting and/or amplification of sympathetic nervous tone by arteriolar structural change could have preserved the sympathetic activation at the vascular level.

Adolescent↗
PubMed1994

[The noninvasive demonstration of functional reinnervation after heart transplantation].

Although RR interval variability appears to be an ideal method for assessing reinnervation after heart transplantation, it has been shown that respiratory sinus arrhythmia is caused by the mechanical effect of respiration on the right atrium. The neck-suction induces heart rate changes only by means of nervous reflex and its hemodynamic effect is local and hence appears as a useful method for assessing reinnervation. We tested the presence of autonomic reinnervation in 18 heart transplant recipients, compared to 12 donor-age-matched controls. We measured the power of RR interval low- (LF, around 0.1 Hz) and respiratory fluctuations (HF) before and during rhythmic neck-suction stimulation at 0.1 Hz and at a frequency (0.20 Hz) similar to, but distinct from, that of respiration (controlled at 0.25 Hz), before and during 0.04 mg/kg atropine infusion, using autoregressive spectral analysis of RR interval, respiration and neck pressure signals. The relationship between pairs of signals at each frequency was quantitatively assessed by bivariate coherence function. All transplanted subjects showed low-amplitude HF, related to respiration. Detectable LF (whose power was lower than in controls: 1.15 +/- 0.39 versus 6.08 +/- 0.27 1n-ms2, p < 0.001), non coherent with respiration, were present in 11/18 transplanted subjects, and correlated with months since transplantation (r = +0.59, p < 0.05). HF neck suction induced the presence of a 0.20 Hz fluctuation in 12/12 controls, distinct from and greater than the 0.25 Hz respiratory component (7.28 +/- 0.26 versus 6.69 +/- 0.74 1n-ms2, p < 0.01); this was not seen in any of the transplanted subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Metabolic risk factors in white coat hypertensives.

Metabolic disturbances such as hyperinsulinaemia, dislipoproteinaemia and glucose intolerance are often associated with essential hypertension and markedly affect cardiovascular morbidity in hypertensive patients. In order to shed some light on the prognostic significance of white coat hypertension (raised clinic and normal ambulatory blood pressure), we compared the metabolic profile in a group of white coat and sustained previously untreated hypertensives. We studied 84 newly detected hypertensive patients (49 men, 35 women, 47 +/- 8 years, range 28-59 years). Subjects with obesity (BMI > 30), NIDDM and target organ damage were excluded. Ambulatory blood pressure monitoring was performed by SpaceLabs 90207-31. Total cholesterol and triglycerides, LDL-cholesterol, HDL-cholesterol (HDL-C) and subclasses HDL2 and HDL3 cholesterol as well as apolipoprotein A1 and B were measured in fasting plasma. Glucose and insulin were determined in fasting and postload (glucose 75 g plasma. Twenty patients (24%, 8 men and 12 women) were classified as white coat hypertensives. No differences in age, BMI and waist to hip ratio were observed between white coat and sustained hypertensive patients. Plasma glucose and lipoprotein levels were similar in the two groups. Fasting and postload insulin levels were significantly lower in white coat hypertensives (fasting insulin 7.1 +/- 2.9 vs. 12 +/- 8.6 microU/ml, P < 0.02; insulin 120 minutes 48 +/- 27 vs. 65 +/- 41 microU/ml, P < 0.05); glucose/insulin rate was higher in white coat than in sustained hypertensive patients (15 +/- 7 vs. 11 +/- 7, P = 0.03).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Occurrence of resistance to retinoic acid in the acute promyelocytic leukemia cell line NB4 is associated with altered expression of the pml/RAR alpha protein.

The mechanism(s) by which acute promyelocytic leukemia (APL) cells acquire resistance to all-trans retinoic acid (ATRA) is poorly understood. We describe here an APL cell line, named NB4.306, that shows resistance to the anti-proliferative action of ATRA. This cell line is also operationally resistant to most ATRA-induced phenotypic modifications (CD11b, CD11c, CD13, and CD33). No significant differences in ATRA intracellular accumulation, efflux, or metabolism were found between NB4.306 and the parent NB4 cell line that could explain the observed resistance of the NB4.306 line. The NB4.306 cell line was found to be positive for the t15;17 translocation and showed the usual pml/RAR alpha fusion bands in both Southern and Northern blot assays, but expressed no detectable amount of the usual pml/RAR alpha protein, as assayed by Western blot analysis using an anti-RAR alpha antibody. These results were confirmed in 14 of 14 clones obtained from the NB4.306 cell line, while 30 of 30 clones obtained from the parental NB4 line expressed the usual 110-Kd fusion polypeptide. It is concluded that the occurrence of resistance to ATRA in the NB4.306 cell line is closely associated to the loss of expression of the intact pml/RAR alpha protein.

Blotting, Southern↗
PubMed1993

Adoptive immunotherapy of advanced melanoma patients with interleukin-2 (IL-2) and tumor-infiltrating lymphocytes selected in vitro with low doses of IL-2.

Freshly isolated tumor-infiltrating lymphocytes (TIL) from stage IV melanoma patients were cultured for 2 weeks with low doses of interleukin-2 (IL-2; 120 IU/ml), to select potentially for tumor-specific lymphocytes present in the neoplastic lesion, followed by high doses (6000 IU/ml) to achieve lymphocyte expansion. TIL were serially analyzed for their expansion, phenotype and cytotoxic activity against autologous and allogenic tumor cells. A preferential lysis of autologous melanoma cells was obtained in long-term cultures of 7/13 cases (54%), while the remaining ones showed a major-histocompatibility-complex-unrestricted, lymphokine-activated-killer(LAK)-like activity at the time of in vivo injection. Sixteen patients with metastatic melanoma were infused with TIL (mean number: 6.8 x 10(9), range: 0.35 x 10(9)-20 x 10(9)) and IL-2 (mean dose: 130 x 10(6) IU, range: 28.8 x 10(6)-231 x 10(6) IU); 1 complete and 3 partial responses were observed in 12 evaluable patients (response rate 33%). In all responding patients, injected TIL showed an in vitro preferential lysis of autologous tumor cells, while in no cases were TIL with LAK-like activity associated with a clinical response. The mean autologous tumor cytotoxic activity of TIL at the time of in vivo injection was significantly higher in responding patients in comparison to nonresponding ones, suggesting that a marked and preferential cytolysis of autologous tumor cells is associated with the therapeutic efficacy of TIL.

Adult↗
PubMed1993

Low-density lipoprotein oxidation in essential hypertension.

OBJECTIVES: To investigate the occurrence of enhanced low-density lipoprotein (LDL) oxidation as an additional factor promoting atherosclerosis progression in hypertensive patients. DESIGN: The oxidation of plasma LDL was investigated in a group of untreated patients with mild-to-moderate essential hypertension without clinically evident target organ damage and in a group of control subjects. METHODS: LDL oxidation was evaluated as both the susceptibility to oxidation in vitro and the presence of plasma anti-oxidized LDL antibodies (as an index for oxidation in vivo). RESULTS: LDL from hypertensive subjects exhibited enhanced susceptibility to oxidation in vitro as revealed by early and accelerated generation of conjugated dienes after exposure to CuSO4. Vitamin E concentration in LDL from hypertensive subjects was slightly but significantly decreased and its efficiency in protecting LDL from oxidation was impaired. Furthermore, a higher plasma anti-oxidized LDL titre was found in hypertensive patients. Subclass analysis revealed that the contemporary presence of hypercholesterolaemia did not significantly modify either the increased susceptibility of LDL to oxidation or the presence of plasma anti-oxidized LDL antibodies detected in hypertensive patients. Moreover, no correlation was found between LDL oxidation parameters and blood pressure values. CONCLUSIONS: LDL from hypertensive patients is more susceptible to oxidation in vitro and is more promptly oxidized in vivo. These findings suggest a possible participation of LDL oxidation in promoting and accelerating the atherosclerosis that often develops in hypertensive patients.

Adult↗
PubMed1993

Protective effect of loratadine on late phase reaction induced by conjunctival provocation test.

The protective effect of Loratadine, a new generation, non-sedating antihistamine, on clinical and cellular events during the early phase reaction (EPR) and late phase reaction (LPR) of the allergen-specific conjunctival provocation test (CPT) was assessed out of the pollen season in 20 seasonally allergic rhino-conjunctivitis patients. After a screening CPT, selected patients were randomized to Loratadine (10 mg OD) or matching placebo for 7 days. CPT was repeated following treatment. Clinical and cellular responses were evaluated by a symptom score and cell counting in conjunctival scrapings before, and 30 min and 6 h after challenge with allergen (one eye) or placebo (control eye). Conjunctival symptom severity following CPT was reduced at 30 min (EPR) and 6 h (LPR) after CPT in the Loratadine group compared to placebo group (p < 0.01), as was the total number of inflammatory cells (p < 0.001). In conclusion, Loratadine protects against the clinical and cellular EPR and LPR events consequent to CPT, showing antiallergic properties.

Allergens↗
PubMed1992

Perindopril versus captopril: efficacy and acceptability in an Italian multicenter trial.

The aim of this 3-month, double-blind, double-dummy, parallel group study was to compare the antihypertensive efficacy and acceptability of perindopril (4-8 mg/day) in 54 patients (30 males, 24 females, 25-68 years of age) and captopril (50-100 mg/day) in 54 patients (39 males, 15 females, 29-66 years of age) in the treatment of essential hypertension. In a subgroup of 38 patients a complete echocardiographic study was performed. The two groups had similar (ANOVA) blood pressure (BP), heart rate (HR), body mass index, and duration of hypertension. Supine and standing BP was significantly reduced by both drugs, without differences between them. Owing to poor control of BP, hydrochlorothiazide (25 mg/day) was added to 27% of patients on perindopril and to 41% of patients on captopril (p less than 0.05). Normalization of supine diastolic BP (less than or equal to 90 mm Hg) was obtained in 67% of patients on perindopril and in 47% of patients on captopril (p less than 0.01). No change in HR was detected. Only mild untoward effects were recorded. Left ventricular mass was significantly reduced by either drug, with no change in systolic function. In conclusion, perindopril and captopril, at these doses, were both well tolerated and on average reduced BP to a similar extent; however, treatment with perindopril showed that fewer patients needed the addition of a thiazide and BP became normal in a larger number of patients.

Adult↗
PubMed1992

Treatment of recurrent in transit metastases from cutaneous melanoma by isolation perfusion in extracorporeal circulation with interleukin-2 and lymphokine activated killer cells. A pilot study.

Chemoresistant melanoma cells are known to be susceptible in vitro to lymphokine activated killer (LAK) cells. To obtain a high LAK/tumour cell ratio in vivo and avoid systemic toxicity due to interleukin-2 (IL-2), we used IL-2 plus LAK cells in the treatment of in transit melanoma metastases of the limbs by isolation perfusion (IP). In vivo immunological modifications induced by this immunotherapeutic approach were also analysed. Six patients previously treated with IP in extracorporeal circulation with tumour cytotoxic drugs and presently relapsing or not responding, were submitted to locoregional adoptive therapy consisting of 5 days systemic administration of IL-2 (Proleukin, EuroCetus) (9-12 x 10(6) IU/m2/day c.i.). Autologous LAK cells were derived from leukapheresis and subsequent in vitro stimulation with IL-2; LAK cells were then given along with IL-2 (120-2400 IU/ml of perfusion priming) to the affected limb by IP. In addition, 7-16 x 10(9) LAK cells were administered by systemic infusion the day after together with IL-2 (9-12 x 10(6) IU/m2/day) by c.i. for 5 days. All patients concluded the treatment without major toxicity. The analysis of circulating lymphocytes obtained from extracorporeal circuit at different times revealed rapid disappearance of LAK cells, suggesting their extravasation and/or endothelial adhesion in perfused tissues. Clinical responses included four partial and one complete response; another patient had stable disease. All patients are presently alive. Follow-up after IP ranges from 8 to 22 months.

Adult↗