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Biomedical subjects

M Lombardo

Publications and source records attributed to M Lombardo.

At least 37 records · Page 2Linked to original sources

Clinical trial of the efficacy and safety of oral etretinate with calcipotriol cream compared with etretinate alone in moderate-severe psoriasis.

BACKGROUND: The aim of this clinical trial was to assess the efficacy and safety of calcipotriol cream associated with oral etretinate compared with etretinate alone in the treatment of moderate-severe psoriasis. METHODS: This controlled multicenter trial, within patients (hemiparts), enrolled 86 in- or out-patients (62 males, 24 females), mean (+/-SD) age 57.1 +/- 14.2 years, with psoriasis vulgaris on both sides of the body, and mean (+/-SE) baseline PASI score (Psoriasis Area and Severity Index) 30.7 +/- 0.9. All patients took oral etretinate 50 mg/day and applied calcipotriol cream (50 microg/g) on one half of their body twice a day. Treatment was continued for 9 weeks, and patients were seen every 3 weeks. RESULTS: At the end of the first 3 weeks the PASI score indicated a significant clinical difference between the two sides of the body (P < 0.001, ANOVA), with a reduction of 50.7% in the score for the calcipotriol-treated half, compared with a 39% reduction for the untreated half. By the 9th week of treatment the PASI score was 81.4% lower on the treated half, and 70.3% on the untreated side (P < 0.001, ANOVA). CONCLUSIONS: These findings suggest that patients with moderate-severe psoriasis might benefit from treatment with etretinate plus calcipotriol, with the aim of achieving a faster response and an overall smaller total dose of etretinate.

Administration, Oral↗

[Primary ureteral amyloidosis].

OBJECTIVE: Two additional cases of primary ureteral amyloidosis are described. The current literature and clinical classification of the disease are reviewed. METHODS: Over a period of 18 months, we observed two cases of organic ureteral stenosis whose etiology was difficult to determine. The first case warranted a nephroureterectomy due to the condition of the compromised urinary tract. Analysis of the surgical specimen showed histological evidence of ureteral amyloidosis. In the second case, the previous experience allowed a preoperative diagnosis to be made, an exceptional situation that permitted conservative surgery. Characterization of the amyloid proteins was done in both cases with immunochemical study by Western Blot. RESULTS: Two patients with primary ureteral amyloidosis were surgically treated. The first case underwent complete excision of the urinary tract. The second case, who had a single kidney, was treated by conservative surgery. In both cases we identified a fragment of the lambda light chain of immunoglobulin by Western Blot characterization as previously reported in localized amyloidosis. CONCLUSIONS: Although ureteral amyloidosis is an infrequent disease, it should be seriously considered in the differential diagnosis of organic ureteral stenosis in order to avoid unnecessary excision. To our knowledge, these are the first cases of ureteral amyloidosis with immunochemical characterization of the amyloid protein.

Aged↗

Efficacy of two different ProMACE-CytaBOM derived regimens in advanced aggressive non-Hodgkin's lymphoma. Final report of a multicenter trial conducted by GISL.

BACKGROUND AND OBJECTIVE: To compare the efficacy of ProME(Epidoxorubicin)CE-CytaBOM (PE-C) and ProMI(Idarubicin)CE-CytaBOM (PI-C) in the treatment of adult patients with aggressive non Hodgkin's lymphoma in a multicenter randomized controlled trial performed by 18 centers of the Italian Lymphoma Study Group (GISL). DESIGN AND METHODS: One hundred and twenty-eight and 122 patients were randomly assigned to receive either 6 courses of PE-C or PI-C, respectively. Some patients achieving complete remission with induction therapy participated in another randomized study comparing no further therapy versus maintenance therapy consisting of four blocks of two drugs. RESULTS: The rate of CRs was 62% and 64% for patients treated with PE-C and PI-C, respectively (p = 0.51). The 5-year relapse-free survival was 60% for PE-C and 53% for PI-C (p = 0.29). The estimated relapse-free disease survival rates at 4 years were 75% for patients in the consolidation group and 57% for those in the observation group (p = 0.11). Patients alive in first complete remission 4 years after study entry were estimated to be 39% in the PE-C arm and 38% in the PI-C arm (p = 0.90). The 3-year and 5-year estimated survival rates were 61% and 55% for the PE-C group and 56% and 47% for the PI-C group (p = 0.26). Fatal toxicities occurred in 7 patients (2.9%) with active disease and in 4 patients (1.7%) in complete remission. Stage (p = 0.04), bulky disease (p = 0.02), serum LDH (p = 0.0006), serum albumin (p = 0.0051), hemoglobin (p = 0.0011), performance status (p = 0.0001), International prognostic index (p < 0.0001) and the index proposed by the French group G.E.L.A. (p < 0.0001) were of prognostic value. In a multivariate analysis (Cox regression model) alternatively IPI alone or G.E.L.A. index plus performance status emerged as independent prognostic factors. INTERPRETATION AND CONCLUSIONS: The present study indicates that epirubicin and idarubicin in a combined chemotherapy regimen, have similar activities. The toxic profile also indicates the safety of both anthracyclines at the dosages employed, suggesting their possible dose escalation in a combined chemotherapy setting. PE-C and PI-C were both effective and feasible regimens in an outpatient setting, with acceptable cardiovascular toxicity. The trend toward a better outcome in patients undergoing consolidation therapy after the achievement of a complete remission, warrants further investigation.

Adolescent↗

Long-term effects of angiotensin-converting enzyme inhibitors and calcium antagonists on the right and left ventricles in essential hypertension.

To compare the effects of chronic antihypertensive treatment on left and right ventricular structure and function, 24 patients with mild to moderate, never-treated hypertension were randomized to receive fosinopril (20 mg daily) or amlodipine (10 mg daily) for 12 months. At baseline and subsequently at the end of third, sixth, and twelfth months, each patient underwent an integrated echocardiographic study and noninvasive ambulatory blood pressure monitoring. Both drugs significantly reduced blood pressure, casual or monitored (p < 0.01), and left ventricular mass index (from 125 +/- 32 to 100 +/- 12 gm/m2 [p < 0.02] with amlodipine and from 106 +/- 18 to 89 +/- 10 gm/m2 [p < 0.02] with fosinopril). The decrease in left ventricular mass was essentially caused by a reduction of ventricular thickness. Free right ventricular wall thickness was also lowered in both groups, more consistently with amlodipine (from 8.0 +/- 2.1 to 6.4 +/- 0.8 mm; p < 0.01), without an increase in plasma natriuretic peptide and insulin concentrations or heart rate. With both treatments, the decrease in ventricular mass was not associated with impairment of systolic function, whereas a trend toward an improvement of Doppler echocardiographic indexes of biventricular diastolic function was observed. In conclusion, both amlodipine and fosinopril induced similar qualitative effects on anatomy and function of both ventricles. The clinical meaning of these observations must be defined further by means of adequately sized prospective trials.

Adult↗

Endogenous estrogen and acetylcholine-induced vasodilation in normotensive women.

Acute exogenous estrogen administration enhances endothelial function in postmenopausal women. To evaluate the effect of endogenous estrogen on endothelium-dependent vasodilation, in 10 fertile normotensive women (age range 45 to 51 years) we studied the changes in forearm blood flow (strain-gauge plethysmography) induced by intrabrachial acetylcholine (0.15, 0.45, 1.5, 4.5, 1.5 micrograms.100 mL-1.min-1), an endothelium-dependent vasodilator, or sodium nitroprusside (1, 2, 4 micrograms.100 mL-1.min-1), an endothelium-independent vasodilator, in basal conditions and within 1 month after ovariectomy. As control subjects, 10 matched healthy women were also evaluated. In basal condition, vasodilation to acetylcholine and sodium nitroprusside was similar in patients and control subjects. Ovariectomy was followed by endogenous estrogen deprivation (from 71.6 +/- 31.3 to < 12 pg/mL) and was associated with a significant (P < .01) reduction in acetylcholine-induced vasodilation compared with baseline (maximum percent increase in forearm blood flow: baseline 568.2 +/- 47.1%; ovariectomy 309.5 +/- 37.4%); the response to sodium nitroprusside was unaffected by ovariectomy (maximum percent increase in forearm blood flow: baseline 526.4 +/- 36.5%; ovariectomy 454.7 +/- 47.2%; P = NS). In 6 of 10 patients, the study was repeated after 3 months of estrogen replacement therapy (17 beta-estradiol, 50 micrograms/d by transdermal patches). Exogenous estrogen restored acetylcholine-induced vasodilation (maximum percent increase in forearm blood flow: 548.9 +/- 43.1%; P < .01 versus ovariectomy), which was no longer different from baseline, whereas the response to sodium nitroprusside was not affected (maximum percent increase in forearm blood flow: 480.2 +/- 39.3%; P = NS). These results suggest a protective role of endogenous estrogen on endothelium-dependent vasodilation in the forearm vascular bed of normotensive women.

Acetylcholine↗

Color Doppler analysis in oligo- and amenorrheic women with polycystic ovary syndrome.

The objective of this study was to determine whether amenorrheic women have more severe blood flow variations and clinical-endocrinological patterns in comparison with oligomenorrheic polycystic ovary syndrome (PCOS) patients. Twenty oligomenorrheic women (cycle length > 35 days; Group I), and 20 amenorrheic women (no vaginal bleeding for at least 6 months; Group II) were submitted to ultrasonographic evaluation of ovarian volume, follicle distribution, number and diameter, color Doppler analysis of uterine and intraovarian blood flow, hormonal assay of different compartments, and plasma evaluation of lipid profile. The number of subcapsular small-sized follicles, and the ovarian volume, androstenedione and luteinizing hormone (LH) plasma levels, and the LH/follicle-stimulating hormone (FSH) ratio were significantly higher in the amenorrheic group compared with the oligomenorrheic patients. Furthermore, significantly lower high-density lipoprotein (HDL) and HDL/total cholesterol ratio were observed in Group II compared with Group I. In addition, in Group II, higher resistance in the uterine arteries and lower impedance to blood flow in the intraovarian arteries have been shown. The assessment of ovarian morphology by transvaginal ultrasound and Doppler flow analysis of both intraovarian and uterine arteries in patients with PCOS may provide an insight into the pathological state and the degree of progression of the disease.

Adult↗

Albuminuria and transferrinuria in essential hypertension. Effects of antihypertensive therapy.

The objectives of this study were to evaluate the effects of an ACE inhibitor (fosinopril) and a calcium antagonist (amlodipine) on the urinary albumin and transferrin excretion and their relationship to the blood pressure in essential hypertension. Twenty-four never-treated patients (mean age, 46.4 +/- 8.9 years) with a diastolic blood pressure between 90 and 114 mm Hg and normal renal function, randomly received amlodipine or fosinopril and, if the diastolic blood pressure was not normalized, doxazosin was added to the therapy. Twenty-four-hour ambulatory blood pressure monitoring and 24-h urine collection for albumin and transferrin measurements were performed before and after 3 and 6 months of therapy. Diastolic blood pressure was normalized in 23 patients (96%). Before treatment, microalbuminuria was present in 50% of patients. In the amlodipine and fosinopril group, antihypertensive therapy significantly decreased blood pressure and, only in the fosinopril group, albuminuria. Transferrinuria did not change significantly in both groups. Fosinopril lowered albuminuria in all patients, whereas amlodipine only in half of patients. Albuminuria, but not transferrinuria, was significantly correlated to the ambulatory blood pressure. This correlation was more pronounced for systolic than for diastolic pressure. In essential hypertensive patients with normal renal function, a high prevalence of microalbuminuria can be observed. Albuminuria appears to correlate with ambulatory blood pressure, particularly with systolic pressure. Intrarenal hemodynamic changes seem to play a more important role than systemic blood pressure decrease in the reduction of albuminuria. Transferrinuria does not seem a useful marker to follow-up nondiabetic hypertensive patients with early signs of glomerular dysfunction.

Adult↗

The impact of rufloxacin given as prophylaxis to patients with cancer on their oral and faecal microflora.

A single dose of 200 mg/day rufloxacin was investigated for preventing infection and for its impact on the commensal flora in a pilot study of 62 patients undergoing cytotoxic treatment for cancer. No infection caused by Gram-negative bacilli occurred among 54 assessable patients but prophylaxis was replaced by empirical treatment for fever in 19 cases and because of an adverse event, in a further three cases. The remaining 32 patients completed prophylaxis. The number of oral Branhamella spp., faecal Enterobacteriaceae and Bacteriodes spp. were significantly reduced whereas there was little effect of rufloxacin on the numbers of the other oral and faecal microflora. However, resistance to rufloxacin increased among both oral viridans streptococci, coagulase negative staphylococci and the faecal enterococci. These preliminary data suggest that selective oral antimicrobial prophylaxis for patients with cancer might be achieved with once-daily rufloxacin.

Administration, Oral↗

Randomized trial of 5-fluorouracil and high-dose folinic acid with or without alpha-2B interferon in advanced colorectal cancer.

We evaluated the role of low-dose alpha-2b interferon, added to chemotherapy, for advanced colorectal cancer; we randomized patients, to either a combination chemotherapy of 5-fluorouracil (5-FU) and high-dose folinic acid (HDFA) or the same regimen plus interferon. Between January 1990 and March 1992, 100 untreated patients (PTS) with advanced colorectal cancer, 53 men and 47 women, with an ECOG performance status (PS) of < or = 3, were randomized to either HDFA 200 mg/m2 iv bolus and 5FU 370 mg/m2 in 15-min iv infusion days 1-5 every 4 weeks (arm A), or the same chemotherapy plus IFN 3 x 10(6) IU subcutaneously three times a week in chemotherapy intervals (arm B). A total of 97 PTS are evaluable for response, toxicity, and survival; 3 PTS are not evaluable in arm B for major protocol violations. PTS characteristics were well balanced in both arms for age (median, 64 years), disease-free survival, and disease site. ECOG PS was 0 in 28% of PTS in arm A and in 13% in arm B. Response rates were as follows: arm A, 40%; and arm B, 23%. Median time to failure was as follows: 10.2 months arm A versus 9 months arm B. Median survival was as follows: 13.3 months arm A versus 10.9 months arm B. Grade 3 haematological toxicity was 9% of PTS in both arms. Gastrointestinal toxicity was as follows: 17% arm A versus 22% arm B. The cost of drugs expressed per m2/month was $60 in arm A and $390 in arm B. The results show that IFN at the schedule and doses employed adds no benefit to the combination of 5FU/HDFA.

Adult↗

Celiac disease in Down's syndrome with HLA serological and molecular studies.

The association between Down's syndrome (DS) and celiac disease (CD) has been confirmed by several authors. The sensitivity and specificity of antigliadin antibodies (AGAs), the clinical features of subjects with DS and CD (DS-CD+), the incidence of CD, and the results of serological and molecular class I and II HLA typing were determined in a sample of 57 Sicilian subjects with DS. Six (10.5%) and 17 subjects (29.8%) showed high levels of IgA AGAs and IgG AGAs, respectively. AGAs sensitivity and specificity were lower than in the population without DS. Ten people with DS were submitted to jejunal biopsy, and seven (12.2%) showed CD according to ESPGAN criteria. All seven patients were put on gluten-free diet, followed by rapid disappearance of symptoms. Class I and II HLA serological and molecular typing was carried out in seven DS-CD + subjects, 22 people with DS without CD (DS-CD-), five subjects with CD without DS, and 20 controls. Between DS-CD + and DS-CD- subjects, no statistically significant difference regarding serum HLA class I antigens was found. DQA1*0101 allele appears significantly in DS-CD + patients and deserves to be searched for in a larger sample to assess its meaning in the DS-CD association.

Adolescent↗

Prolonged streptokinase infusion in patients with unstable angina: results of a randomized, placebo-controlled clinical trial.

BACKGROUND: The purpose of this study was to assess the efficacy both of prolonged (48 h) and of short-duration (1 h) administrations of streptokinase in patients with unstable angina. In unstable angina, thrombosis is a dynamic process that waxes and wanes for hours and even days. The majority of previous studies have investigated the efficacy of short-duration thrombolytic regimens. METHODS: One hundred patients with acute unstable angina were randomly allocated to receive placebo, 1,500,000 U streptokinase during 1 h or 250,000 U streptokinase during 1 h and then a prolonged infusion of 100,000 U for the next 48 h. All of the treatments included intravenous heparin administration for 72 h. RESULTS: No death occurred in the study population. One of 34 patients treated with placebo (2.9%), three of 33 treated with streptokinase during 1 h (9.0%) and three of 33 treated with streptokinase during 48 h (9.0%) had a myocardial infarction. Refractory angina occurred in nine, three and seven patients receiving placebo, streptokinase during 1 h and streptokinase during 48 h, respectively. Kaplan-Meier analysis showed that the total probability for a patient to be free of cumulative events did not differ among the three groups of patients (NS). Fourteen patients (41%) receiving placebo, 15 patients (45%) receiving streptokinase during 1 h and 14 patients (42%) receiving streptokinase during 48 h had ischaemic episodes detected by Holter monitoring during the first 72 h after hospital admission (NS). Two patients receiving streptokinase during 48 h required blood transfusion, and a greater incidence of minor bleeding (P < 0.05) and adverse events (P < 0.02) was observed in patients receiving prolonged streptokinase administration than in those receiving streptokinase during 1 h or placebo. CONCLUSIONS: In patients with acute unstable angina, the administration of two different regimens of streptokinase significantly reduces the probability neither of developing cardiac events during hospitalization nor of ischaemia detected by Holter monitoring in the early phase after hospital admission. Although the sample size of the study provided sufficient power to exclude only a large difference in effect size, it did allow us to detect a significantly higher incidence of bleeding in the group of patients treated with prolonged streptokinase infusion.

Aged↗

Corticotropin-releasing factor-binding protein: origins and possible functions.

Corticotropin-releasing hormone-binding protein (CRFBP) is a 37-kD protein of 322 amino acids, containing one putative N-glycosylation site and 11 cysteines, 10 of which remain in the mature molecule (298 amino acids) and result essential for the action. CRFBP protein gene has been cloned and mapped to the distal region of chromosome 13 and loci5q in the mouse and human genomes. CRFBP is the only example of a neuropeptide-binding protein. It is produced in human and rat brain, and in human liver and placenta. In brain, the central distribution of CRFBP shares some regional overlap with CRF receptor-bindings sites. Additionally, in hypothalamic and limbic structures, CRFBP has been identified in association with CRF-expressing cell groups. CRFBP has been also demonstrated in the human placenta and related membranes. Indeed, amniotic epithelium, chorionic cytotrophoblast, and maternal decidua also show intense positive CRFBP mRNA signals. Circulating CRFBP levels in healthy nonpregnant individuals show the same range values as in maternal plasma collected during the first and second trimesters of pregnancy. A rise in CRFBP levels at 30-35 weeks of pregnancy with a dramatic decrease at 38-40 weeks have been shown. At postpartum, CRFBP levels in maternal plasma reach the nonpregnant concentrations. Recombinant and native CRFBP neutralize the ACTH-releasing activity of human CRF in cultured pituitary or placental cells and, additionally, may block the activity of CRF on human pregnant endometrium prostaglandin release and on human myometrium contractility in vitro. These findings suggest that CRFBP may play a role in modulating the functions of CRF in human pregnancy.

Body Fluids↗

Kaposi's sarcoma with primary bone lesions in an HIV-seronegative man.

Classic Kaposi's sarcoma, with primary bone lesions, is described in an HIV-seronegative man. The bone involvement, painful lytic lesions in the right leg and both feet, was shown by magnetic resonance and histology not to be contiguous with the skin lesions. Chemotherapy with vinblastine and doxorubicin, significantly reduced the skin and bone lesions, and pain also improved.

Adult↗

[Nutritional status of patients on chronic hemodialysis].

The objective was to determine the nutritional status (NS) in a population undergoing chronic hemodialysis (CHD), and correlate it with dialysis dose and morbimortality. A total of 55 patients, 27 men and 28 women, aged 47 +/- 15 and with a history of CHD of 54.6 +/- 47.6 months were evaluated. NS was classified into: adequate, mild malnutrition, moderate malnutrition and severe malnutrition. A score based on usual laboratory data (total iron-binding capacity [TIBC], albumin and cholesterol), clinical evaluation and anthropometric measurements (body mass index [BMI], mid brachial circumference, tricipital fold [TF], mid brachial muscle circumference [MBMC]), was used. In addition, a 7-days' intake auto-registration plan was conducted, and protein catabolic rate (PCR) was determined. Calorie intake was of 27 +/- 13 kcal/kg/day and protein intake was of 1.2 +/- 0.5 g/kg/day. No correlation was found between the latter and PCR. 49.1% of patients had moderate to severe malnutrition, only 9 patients had an adequate NS. However anthropometric measurements showed that TF, MBMC and BMI were normal in 54.5%, 45%, and 72.7% of patients, respectively. No correlation was found between NS and age onset of CHD, sex, creatinine, dialysis dose (Kt/V x = 1.24 +/- 0.12), PCR and morbidity. A longer history of dialysis was associated with a worse NS (p < 0.01). In addition, NS significantly correlated with albumin (p < 0.01) and mortality (p < 0.05). The estimated death risk was 9.45 times higher in patients with moderate and severe malnutrition.

Energy Intake↗

RT-PCR diagnosis of patients with acute nonlymphocytic leukemia and inv(16)(p13q22) and identification of new alternative splicing in CBFB-MYH11 transcripts.

As acute nonlymphocytic leukemia (ANLL) with inv(16) (p13q22) or t(16;16)(p13;q22) has been shown to result from the fusion of transcription factor subunit core binding factor (CBFB) to a myosin heavy chain (MYH11), we sought to design methods to detect this rearrangement using reverse transcriptase-polymerase chain reaction (RT-PCR). In all of 27 inv(16)(p13q22) and four t(16;16)(p13;q22) cases tested, a chimeric CBFB-MYH11 transcript coding for an in-frame fusion protein was detected. In a more extensive RT-PCR analysis with different primer pairs, we detected a second new chimeric CBFB-MYH11 transcript in 10 of 11 patients tested. The CBFB-MYH11 reading frame of the second transcript was maintained in one patient but not in the others. We show that the different CBFB-MYH11 transcripts in one patient arise from alternative splicing. Translation of the transcript in which the CBFB-MYH11 reading frame is not maintained leads to a slightly truncated CBFB protein.

Adolescent↗