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Biomedical subjects

M Meregalli

Publications and source records attributed to M Meregalli.

At least 37 records · Page 2Linked to original sources
PubMed1988

Immunomodulation and Sézary syndrome: experience with thymopentin (TP-5).

The clinical, histological and immunological effects of long-term treatment with thymopentin (TP-5), administered 50 mg i.v. three times a week on alternate days, in four patients with Sézary syndrome is reported. In all four cases reduction of itching, oedema, scaling and thickening, and clearing of erythroderma were noted after 2 months treatment. Peripheral blood Sézary cells decreased in three cases. Reduction or suspension of the drug was followed by a clinical relapse. A loss of epidermotropism and a reduction in cell infiltrates were observed together with a dramatic reduction in epidermal and dermal Langerhans cells. An increase in the proliferative response to mitogens and in IFN-gamma production, and the expression of activation antigens in PHA stimulated cultures occurred after 3 months. HNK-I+ cells increased both in the peripheral blood and in the dermis following a transient increase in IL-2 receptors, suggesting that clinical response in TP-5 treated patients may be mediated by an increased production of IL-2 and consequent generation of cytotoxic cells or release of lymphokines able to augment NK activity.

Adjuvants, Immunologic↗
PubMed1988

Human myeloma: several subsets of circulating lymphocytes express plasma cell-associated antigens.

Peripheral blood lymphocytes from 9 monoclonal gammopathies of undetermined significance (MGUS) and 27 multiple myelomas (MM) were studied with a panel of monoclonal antibodies (MoAb) that recognize B and T lymphocytes and plasma cells. No difference in the percentage of B lymphocytes, identified by B1 and B4 MoAb, was observed in MGUS and MM patients versus normal controls. However, high percentages of circulating lymphocytes expressing plasma cell-associated antigens were detected in MM (HAN-PC1+ = 29.4 +/- 20.4%; TEC-T10+ = 27.8 +/- 19.2%) whereas they were in the normal range in MGUS (HAN-PC1+ = 8.8 +/- 5.8% p = 0.006; TEC-T10+ = 5.7 +/- 4.7% p less than 0.001). Almost identical results were obtained using PCA-1 MoAb in 17 of these patients. TEC-T10+ and PCA-1+ lymphocytes were sorted and re-analyzed with phycoerythrin conjugated MoAb in 3 healthy subjects, 2 MGUS, and 4 MM patients. In normal subjects and in MGUS the majority of PCA-1+ cells belonged to the B lineage (Leu 2-, Leu3-, Leu 15-, HLA-Dr+), whereas the majority of TEC-T10+ cells are represented by activated T cells and NK cells (Leu 15+). In MM an abnormal expansion of T lymphocytes was chiefly responsible for the high values of lymphocytes expressing plasma cell-associated antigens. Moreover, in MM a clinical evaluation showed a correlation between the presence of these lymphocytes and an aggressive disease. Indeed, they can be considered a useful prognostic marker.

Antibodies, Monoclonal↗
PubMed1987

Double-blind comparison of once-daily bopindolol and atenolol for mild-to-moderate hypertension.

In order to compare the medium term antihypertensive effectiveness and tolerability of atenolol with those of bopindolol (LT 31-200), a new non-selective beta-blocker with slight PAA (partial agonist activity), a randomized double-blind study was performed. Thirty-one outpatients with mild-to-moderate essential hypertension (WHO stage I-II) were enrolled and after a placebo run-in randomly allocated to bopindolol (1 to 4 mg/day) or atenolol (50 to 200 mg/day). The dose was titrated according to the individual pressor responses, and thereafter it was kept constant until the end of the treatment (12 weeks). Both drugs induced statistically significant decreases in SBP, DBP and HR, both in resting conditions and during an ergometric test. Accordingly, most patients achieved the main goal of the therapy, i.e., supDBP less than or equal to 90 mmHg, 11/15 (74%) with bopindolol versus 8/13 (62%) with atenolol. There were no significant differences between the effects of the two compounds. Resting airway resistance (expressed as Peak Expiratory Flow) was not influenced by the treatments. The antihypertensive efficacy was still evident after 12 months in 8 patients who were evaluated for non-comparative long-term effectiveness of bopindolol monotherapy, and improvements in plasma lipid profiles were also observed. Side effects were relatively mild and transient, with two patients in the atenolol group discontinuing therapy (one for inefficacy and one because of undesirable reactions) and one dropped out in the bopindolol group (late evidence of not fulfilling inclusion criteria).(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗
PubMed1986

[2 cases of metabolic acidosis during therapy of portosystemic encephalopathy with branched-chain amino acids].

Two patients known to be suffering from liver cirrhosis were admitted to hospital in a state of coma. The apparent ineffectiveness of treatment with branched chain amino acids was found in reality to be due to the onset of metabolic acidosis. The suspension of treatment and balancing of the metabolic imbalance with an infusion of bicarbonate solutions led to lessening of the neurological symptomatology.

Acidosis↗
PubMed1985

Functional properties in Sézary cells with an unusual phenotype.

The immunological and functional characteristics of Sézary cells with an unusual phenotype are reported. The clinical, histologic, and hematologic picture was typical for Sézary syndrome. Studies with monoclonal antibodies showed that 80% Sézary cells had an CD3+, CD4+, CD5+, CD7-, CD8-, Leu-7+, Leu-8-, Leu-11-, OKM1- phenotype. By two-color immunofluorescence assay 80% FACS-sorted Leu-7+ cells coexpressed CD4 antigen and did not express the myeloid antigen OKM1, CD8, and antigens characteristic of immature T cells. The cells had no NK activity but did display a high helper activity. Unseparated and FACS-sorted Leu-7+ and Leu-7- Sézary cells did not respond to mitogens but were able to grow in the presence of exogenous IL-2. FACS sorted Leu-7- cells, cultured for 7 days in the presence of 20% IL-2, acquired the receptors for Leu-7. IL-2 and IFN-gamma production was studied in unseparated Leu-7+ and Leu-7- FACS-sorted Sézary cells. IL-2 production was lower than in normal cells. The addition of PHA or PHA plus TPA led to an increase in IL-2 production. Also IFN-gamma production was marked lower than in normal controls but increased after 7-day culture in exogenous IL-2. In conclusion in this case the Sézary cells may represent a neoplastic expansion of the CD3+, CD4+, CD5+, Leu-7+, Leu-11- subpopulation which is equivalent to the 2-4% of the Leu-7+ population in normal lymphocytes.

Aged↗
PubMed1985

A single blind comparison of dihydroergotoxine mesilate and clonidine for treatment of hypertensive emergencies.

The effectiveness and safety of dihydroergotoxine mesylate (DHT) and clonidine (CLO) as acute antihypertensive treatments were studied in a single-blind randomized controlled study of 28 patients hospitalized after abrupt increases in mean blood pressure (MAP) to more than 150 mmHg, with concomitant symptoms related to hypertensive status (16 patients). Intravenous infusion of 1.5 mg DHT significantly reduced both systolic (SBP) and diastolic (DBP) blood pressure from 227 +/- 2/128 +/- 2 mmHg to 160 +/- 4/94 +/- 2 mmHg by 1 hour after the onset of infusion (p less than 0.01). In patients given CLO, BP values fell from 221 +/- 3/123 +/- 3 mmHg to 166 +/- 5/95 +/- 3 mmHg after 150 minutes. After that BP values did not change significantly up to 6 hours after both treatments. One hour after the onset of infusion, mean heart-rate (HR) had decreased by 15 beats/min in the DHT group and by 10 beats/min in the CLO-group. Twenty-one per cent of the patients given DHT and 78% of the patients given CLO complained of mild or moderate side-effects. The results of this study showed that DHT is an effective and well tolerated agent for the treatment of hypertensive emergencies and can be used safely even when continuous monitoring of blood pressure cannot be carried out.

Aged↗
PubMed1984

Changes in T and B lymphocyte subpopulations before, during and after chemotherapy for malignant melanoma.

The behaviour of T and B lymphocyte subpopulations before, during and after chemotherapy with DTIC or CCNU was studied in 87 melanoma patients. The effect on immune status of DTIC administered as adjuvant therapy was also reported. The immunosuppressive effect was found to be higher in patients with normal pretreatment T-cell values than in patients with low pretreatment values, and it was higher in metastatic than in nonmetastatic patients. Where T and B lymphocyte subpopulations were assessed in 10 metastatic patients after each course of chemotherapy, a progressive reduction of T-lymphocytes was observed, indicating a cumulative effect of the drugs with advancing course. The reduction of T lymphocytes was mainly due to the decrease of OKT4+ cells. A normalization of T lymphocyte subpopulations was observed after the suspension of therapy. No significant decrease in the number of B cells was observed in the DTIC treated metastatic patients, whereas a significative reduction in the absolute number was found in those treated with CCNU.

Aged↗
PubMed1983

The prognostic value of T-lymphocyte levels in malignant melanoma. A five-year follow-up.

Serial immunologic tests (active E-rosettes = T-Ea; total E-rosettes = T-Et; total lymphocytes and null cells) were performed every 3 months for 5 years on 113 melanoma patients. A significant reduction in absolute T-Ea, T-Et, null cells, and total lymphocytes was noted in the patients who died, by comparison with those who are still alive. The latter presented a significant reduction in absolute T-Et only, plus a significant increase in null cells when compared with normals. The 38 patients without metastases, at the end of the study, presented a reduction in T-Et and an increase in null cells compared with the normals, while the 75 patients with metastases presented a reduction in T-Et, null cells and total lymphocytes when compared with the patients without metastases and a reduction in T-Ea, T-Et, and total lymphocytes when compared with the normals. Null cells show a linear decrease in patients who died and a linear increase in those who survived. A total of 80.2% of patients with a fall in T-Et displayed metastases usually within 2 to 10 months (mean, 6.8). Patients with normal T-Ea, T-Et, and total lymphocyte values showed a significant prolonged survival when compared to those with lower values. In addition, survival seemed to be always a function of immunologic test values, irrespective of the tumor site.

Adult↗
PubMed1983

Thymostimulin therapy in melanoma patients: correlation of immunologic effects with clinical course.

Thirty-two nonmetastatic melanoma patients with low T-lymphocyte values were treated with a thymic extract, thymostimulin (TS) (8 patients), DTIC (8 patients), or surgery alone (16 patients). In the 8 patients receiving TS, active E-rosette (T-Ea) and total E-rosette (T-Et) counts rose to normal levels and there was a significant rise in IgM and IgD receptors. Six out of eight patients treated with TS showed no evidence of metastases after 34 months, while 7/8 patients on DTIC and 13/16 patients on surgery alone developed metastases. Twenty metastatic patients with low T-lymphocyte values received either DTIC plus TS or DTIC alone. Total lymphocyte, T-Ea, and T-Et counts did not increase in either group nor was there a significant difference between the group on DTIC plus TS and the group on DTIC alone. The survival rate of patients on DTIC plus TS did not differ significantly from that on DTIC alone.

Adult↗
PubMed1983

T-cell subsets in melanoma patients evaluated by anti-T-cell monoclonal antibodies.

Functional T-cell subpopulations have been evaluated in the peripheral blood of 124 melanoma patients (71 non-metastatic and 53 metastatic) using monoclonal antibodies: OKT3, OKT4, OKT8, every 2 months for 1 year. The levels of OKT3+ cells were significantly lower in metastatic patients than in normal controls and they decreased in the advanced phases of the disease. Percentages and absolute OKT4+ cell values were reduced in metastatic patients only, while a significant reduction in OKT8+ cells was noted in both long-surviving, non-metastatic and metastatic patients. The ratio of OKT4+/OKT8+ cells was increased in non-metastatic patients and in patients remaining metastasis-free for 4 years after resection of their metastases. Patients with prolonged survival show normal T-helper cells and low T-suppressor cells with a significant increased ratio OKT4/OKT8. In the patients who developed visceral metastases and in those who died the progressive reduction in total T cells is mainly due to the decrease in OKT4+ cells.

Adult↗
PubMed1980

The in vitro effect of a calf thymus extract on the peripheral blood lymphocytes of patients with warts.

T and B lymphocyte populations were evaluated in forty-one patients with multiple recurring warts. Active rosettes (T-Ea) and total T lymphocytes (T-Et) were significantly decreased. The in vitro effect of a calf thymus extract (TP-I) on peripheral blood lymphocytes was evaluated in thirty-three patients. A statistically significant increase in E-rosette forming cells was observed in twenty-three patients (69%). Serum blocking factors were not found in the patients with a positive response to TP-I, which suggests the possibility of a thymic hormone deficiency. In the case of non-responders to TP-I, on the other hand, an anti-lymphocyte antibody capable of directly blocking the hormone receptors on the undifferentiated lymphocytes may be postulated.

Adolescent↗
PubMedDate not supplied

The hemochromatosis gene affects the age of onset of sporadic Alzheimer's disease.

In the present study we analysed the genotype of HFE, the gene involved in hemochromatosis, in 107 patients with sporadic late-onset AD and in 99 age-matched non-demented controls. We observed that patients carrying the mutant HFE-H63D allele had a mean age at onset of 71.7 +/- 6.0 years versus 76.6 +/- 5.8 years of those who were homozygous for the wild-type allele (p = 0.001). The frequency of the HFE-H63D mutation was highest (0.22) in the patients aged <70 years at the time of disease onset, whereas it was 0.12 in those with disease onset at an age of 70-80 years, and 0.04 in those aged more than 80 years. The APOE genotype did not significantly modify the effect of HFE on age at onset. We conclude that mild disturbances of iron homeostasis associated with a common genetic determinant may interact with other pathogenic mechanisms involved in AD. HFE mutations may anticipate AD clinical presentation in susceptible individuals.

Age of Onset↗
PubMedDate not supplied

Increasing doses of 5-fluorouracil and high-dose folinic acid in the treatment of metastatic colorectal cancer.

AIMS AND BACKGROUND: Combined 5-fluorouracil (5FU) and folinic acid (FA) is the first-line treatment of metastatic colorectal cancer. The aims of this study were to individualize the dose of 5FU in a weekly schedule in which the maximum tolerated dose of 5FU is administered to each patient, and to evaluate the impact of increasing 5FU doses on response and survival. METHODS: Thirty-two patients (30 evaluable for response) with metastatic colorectal cancer were treated with weekly intravenous doses of FA 150 mg/m2 and a fast infusion of 5FU, at an initial dose of 600 mg/m2 which was increased by 60 mg/m2 every week until the appearance of a side effect, in order to determine the maximum tolerated dose for the patient. RESULTS: We obtained 11 objective responses (36.7%, median survival 22 months) and 15 disease stabilizations (50%, median survival 15 months); there were four cases of progressive disease (13.3%, median survival 4 months). The overall survival was 15 months. Twenty-eight patients (87.5%) tolerated 5FU doses of 720 mg/m2 or more. CONCLUSIONS: Weekly 5FU with high-dose FA modulation can be individualized by dose escalation. A 5FU dose of 720 mg/m2 per week seems to be critical, as higher doses are no more effective and lead to severe side effects. This schedule gives good results in terms of response, even though the complete response rate remains low.

Adult↗
PubMedDate not supplied

Alcohol dehydrogenase: an autoantibody target in patients with alcoholic liver disease.

The link between alcohol consumption and liver disease is not direct and several factors including autoimmunity to hepatocyte components have been implicated. We have previously identified alcohol dehydrogenase (ADH) as an autoantigen in autoimmune liver disease and in a proportion of patients with alcoholic liver disease. The aim of the present study is to investigate the association between the presence of anti-ADH antibodies, alcohol consumption and severity of liver damage in alcoholic patients. The presence of antibodies to human ADH beta2 and horse ADH was investigated in 108 patients with documented history of alcohol consumption and alcohol related liver disease, 86 being active alcohol abusers and 22 on sustained alcohol withdrawal, 39 with non-alcohol related disease and 22 normal subjects. Antibodies to either ADH form were more frequently detected in active alcohol abusers (55/86, 64%) than in patients on sustained alcohol withdrawal longer than 6 months (1/8, 13 %, P < 0.005), HBV infection (2/8, 25 %, P=0.03), non-alcohol related disease (9/29, 23 %, P < 0.0001) and in normal controls (3/22, 14 %, P < 0.0001); were more frequent in patients with cirrhosis than in those with steatosis (26/34, 76 % vs 34/64, 53 %, P=0.02); and were associated with elevated levels of ALT (anti-ADH beta2, P < 0.05), immunoglobulin A (P < 0.05) and gamma-glutamyl transpeptidase (P=0.01). Anti-ADH antibody positive serum samples were able to inhibit the enzymatic activity of ADH. These findings suggest that anti-ADH antibodies may be triggered by alcohol consumption and act as a disease activity marker in alcoholic liver disease.

Adult↗
PubMedDate not supplied

A psychoneuroendocrine study of brain dopaminergic sensitivity in locally limited or metastatic cancer patients.

In addition to the occurrence of pain, the evidence of a diminished capacity to feel pleasure is one of the most common cancer-related symptoms. Recent advances in psychoneuroendocrinological knowledge has shown that the perception of pleasure is mainly mediated by the dopaminergic pathways in the brain. Moreover, it has also been demonstrated that the brain dopaminergic sensitivity may be clinically explored by evaluating the endocrine response to the administration of dopaminergic agents, such as apomorphine, which consists of a decline in PRL concentrations and an increase in GH and cortisol levels. The present study was performed to evaluate dopaminergic sensitivity by the administration of apomorphine in cancer patients in an attempt to document possible cancer-related neuroendocrine anomalies, which could explain the psychological status of the patients. The study included 24 cancer patients (breast cancer: 12; colorectal cancer: 7; non-small cell lung cancer: 5), 12 of whom showed distant organ metastases. Apomorphine was given orally at 0.01 mg/kg b.w., by collecting venous blood samples before and after 20 and 60 minutes. A normal decline in PRL levels was seen in both non-metastatic and metastatic cancer patients. No cortisol increase in response to apomorphine was achieved and the lack of cortisol response was particularly evident in metastatic patients. No GH rise occurred in either metastatic or non-metastatic cancer patients. Finally, no significant difference in the endocrine response to apomorphine was seen in relation to the histotype of tumor. The results of this study show that the neoplastic disease is characterized by neurochemical alterations involving pleasure-related dopaminergic pathways, which are more evident in the metastatic disease, without particular differences in relation to tumor histotype. Therefore, the psychological condition of cancer patients would not depend only on psychological factors, but it could be due at least in part to cancer-related neuroendocrine alterations involving the dopaminergic system.

Adult↗