PubMed Health⌕ Search

Biomedical subjects

R Caruso

Publications and source records attributed to R Caruso.

At least 37 records · Page 2Linked to original sources
PubMed2001

Human herpesvirus 6 infection in neoplastic and normal brain tissue.

The presence and variant distribution of human herpesvirus 6 (HHV-6) was investigated by a nested polymerase chain reaction (PCR) in 118 biopsies from patients affected by nervous tissue tumor (115 primary tumors and 3 metastasis) and in 31 autopsy samples from the brain of healthy individuals. HHV-6 DNA sequences were detected in normal and neoplastic nervous tissue at a frequency of 32% and 37%, respectively. In both tissues, variant A was three times more frequent than the variant B. Peripheral blood lymphocytes (PBLs) derived from seven tumor affected patients contained the same variant as their respective brain sample, as judged by PCR. The expression of HHV-6 encoded immediate early protein p41 was detected by immunohistochemistry in neoplastic but not in normal brain. This may reflect viral reactivation from latency in immunocompromised patients. The seroepidemiological data indicated a frequency distribution of anti-HHV-6 antibodies in patients with brain tumors similar to that found in healthy donors.

Antibodies, Viral↗
PubMed2001

Pharmacokinetic study of the new cyclosporine-A formulation (Neoral) in adult allogeneic bone marrow transplant recipients.

BACKGROUND AND OBJECTIVES: A major problem encountered during oral cyclosporin-A (CsA) administration to prevent acute graft-versus-host-disease (GVHD) after allogeneic bone marrow transplantation (allo-BMT) is its irregular pharmacokinetics. The aim of this study was to evaluate the pharmacokinetics of Neoral, a new water-free microemulsion formulation of CsA. DESIGN AND METHODS: Eighteen patients aged over 18 were enrolled into the study. When able to eat normally after allo-BMT, patients received CsA orally and after 4 days a 12-hour CsA pharmacokinetic profile was constructed. Three patients received Sandimmune 10 mg/kg/day, 5 patients received Neoral 7.5 mg/kg/day and 10 patients Neoral 5 mg/kg/day. CsA concentration was analyzed on whole blood by high-performance liquid chromatography (HPLC). RESULTS: Neoral showed concentration-time profiles characterized by a smooth and faster rise to the Cmax value compared to that produced by Sandimmune. The comparison between pharmacokinetic parameters obtained in patients receiving Neoral 5 mg/kg/day or 7.5 mg/kg/day showed a proportional increase of the AUC (4776+/-1084 vs. 7746+/-2006 ng/mL h) and C(max) (1027+/-203 vs. 1514+/-231 ng/mL). In all patients to whom 7.5 mg/kg/day of Neoral were given, C(trough) levels were always above the threshold of 200 ng/mL. INTERPRETATION AND CONCLUSIONS: Our data suggest that oral administration of Neoral 7.5 mg/kg/day early after allo-BMT may represent an appropriate dose resulting in adequate CsA C(trough) levels without significant renal toxicity.

Adult↗
PubMed2001

Whole-blood calcineurin activity is not predicted by cyclosporine blood concentration in renal transplant recipients.

BACKGROUND: In transplant patients, current cyclosporine (CsA) dose monitoring with classic pharmacokinetics has demonstrated limitations. Evaluation of the activity of calcineurin (CN), the serine-threonine phosphatase enzyme target of CsA, has been proposed as a reliable way to optimize CsA dosing. METHODS: CN activity was measured in whole blood in an attempt to overcome the high variability of results obtained previously with peripheral blood mononuclear cells (PBMCs). We also explored, in vitro, a possible relationship between the CsA concentration and CN inhibition in whole blood. Finally, we assessed whether the CsA blood trough concentration correlates with whole-blood CN activity in kidney transplant recipients (n = 15) on maintenance immunosuppression with CsA. RESULTS: In 14 healthy individuals, less scattered CN activity values were documented in whole blood than in the PBMC fraction. Whole-blood CN activity was higher than the sum of the enzyme activity in each cell blood fraction. After ex vivo incubation of whole blood from healthy subjects (n = 5) with increasing concentrations of CsA (50-1000 microg/L for 1 h), a concentration-dependent inhibition of CN activity was found comparable to that in the PBMC fraction. Moreover, in 15 kidney transplant recipients, no relationship was found between CsA pharmacokinetic parameters and CN activity at time 0. However, a highly significant correlation was found between CN area under the CN activity-time curve, which represents the extent of the CN daily inhibition, and CN activity at time 0 (r = 0.79; P <0.01) and at 12 h postdosing (r = 0.96; P <0.01). CONCLUSIONS: Measuring CN activity in whole-blood samples is a reproducible method. In kidney transplant recipients, CsA trough concentrations do not predict baseline CN activity. Moreover, a single CN activity monitoring at baseline or at time 12 h post-CsA dosing may be a useful surrogate for the inhibition of this enzyme by CsA during 12 h.

Buffers↗
PubMed2001

The early growth response gene EGR-1 behaves as a suppressor gene that is down-regulated independent of ARF/Mdm2 but not p53 alterations in fresh human gliomas.

PURPOSE: EGR-1 is an immediate early gene with diverse functions that include the suppression of growth. EGR-1 is down-regulated many cancer cell types, suggesting a tumor suppressor role, and may critically involve the p53 pathway. The aim of this work was to measure the expression of EGR-1 and the p16/INK4a/ARF-Mdm2-p53 pathway status in fresh human gliomas. EXPERIMENTAL DESIGN: Thirty-one human gliomas with different grades of malignancy were investigated for Egr-1 mRNA and the protein expression, frequency, and spectrum of p53 gene mutations, mdm2 gene amplification, and p16/INK4a/ARF allele loss. RESULTS: The amplification of Mdm2 and the deletion of the p16/INK4a gene was found in 3 and 5 cases, respectively, whereas mutations of p53, including two novel mutations, were observed in 10 other cases. The three types of changes occurred strictly mutually exclusively, emphasizing that these genes operate in a common pathway critical to glioma progression. EGR-1 mRNA was significantly down-regulated in astrocytomas (14.7 +/- 5.1%) and in glioblastomas (33.6 +/- 10.0%) versus normal brain. Overall, EGR-1 mRNA was strongly suppressed (average, 15.2 +/- 13.9%) in 27 of 31 cases (87%), independent of changes in p16/INK4a/ARF and Mdm2; whereas 4 of 31 cases with residual EGR-1 expression as well as the highest EGR-1 variance segregated with p53 mutations. Immunohistochemical analyses confirmed the suppression of EGR-1 protein. CONCLUSIONS: These results indicate that EGR-1 is commonly suppressed in gliomas independent of p16/INK4a/ARF and Mdm2 and that suppression is less crucial in tumors bearing p53 mutations, and these results implicate an EGR-1 growth regulatory mechanism as a target of inactivation during tumor progression.

Blotting, Northern↗
PubMed2000

Phase I chemotherapy study of biochemical modulation of folinic acid and fluorouracil by gemcitabine in patients with solid tumor malignancies.

PURPOSE: This phase I biochemical modulation study evaluated the maximum-tolerated dose (MTD), toxicity, and effectiveness of the combination of folinic acid (FA)/fluorouracil (5-FU) followed by escalated dose levels of gemcitabine (FFG) in patients with advanced solid tumors. PATIENTS AND METHODS: Patients were refractory to primary treatment and/or without effective treatment options. Twenty-eight patients received an intravenous (IV) infusion of FA 100 mg/m(2) over 1 hour and a 5-FU 450 mg/m(2) IV bolus in the middle of the FA infusion. After the FA infusion, gemcitabine was administered at a steady rate of infusion of 10 mg/m(2)/min over initially 30 minutes and with increases of an additional 15 minutes at each given level. One cycle consisted of six weekly treatments followed by a 2-week rest. RESULTS: The MTD of gemcitabine was established at 900 mg/m(2) given over 90 minutes. Eight patients of 21 with metastatic colorectal cancer achieved responses (one complete response; seven partial responses), for a response rate of 38%. Responses were seen across the gemcitabine doses of 300 to 900 mg/m(2). One patient had prior treatment with FA/5-FU for advanced disease. Patients with colorectal carcinoma had a median survival of 18 months, and the patient with lung carcinoma has been alive for 24+ months. CONCLUSION: The combination chemotherapy of FFG was well tolerated and may benefit patients with advanced colorectal carcinoma. A phase II evaluation in this patient population is in progress.

Adult↗
PubMed2000

Cavernous angiomas of the nervous system in Italy: clinical and genetic study.

We performed a clinical and genetic study of patients affected by cavernous angiomas (CA) of the nervous system. We examined initial signs and symptoms in sporadic and familial cases. We obtained clinical, neuroimaging and genetic data on 15 Italian patients with CA of the nervous system with positive, doubtful or apparently negative family history. Genetic markers surrounding three different gene regions (7q, 3q and 7p) were analysed. In one small family, genetic linkage was consistent with all chromosome loci. In another family with the unusual association of cerebral and spinal CA, linkage with chromosome 7q and, likely, 7p was excluded, while linkage with locus 3q was possible. Our results indicate that Italian families with CA may show genetic heterogeneity. Non-specific and subtle onset symptoms hide the presence of CA within families. Patients with multiple CA may have silent cerebral lesions confirming the low penetrance of clinical signs in spite of radiological ones.

Adolescent↗
PubMed1999

Radiolucencies and cavitation in bronchioloalveolar carcinoma: CT-pathologic correlation.

Bronchioloalveolar carcinoma (BAC) is a polymorphic lung cancer the incidence of which is rising. The presence of intratumoral radiolucencies is an important feature of bronchioloalveolar carcinoma. The aim of this study was to present pictorially the spectrum of intratumoral radiolucencies visible in BAC. In 57 BACs studied with thin-slice CT, we identified six types of radiolucencies: (a) patent intratumoral bronchioles (air bronchiologram); (b) pseudocavitations; (c) cavitation; (d) serpentine radiolucencies; (e) internal alveologram; and (f) multiple cystic lesions.

Adenocarcinoma, Bronchiolo-Alveolar↗
PubMed1999

Tamoxifen and fenretinide in women with metastatic breast cancer.

BACKGROUND: Tamoxifen and fenretinide combination therapy has been shown to be an active treatment regimen in metastatic breast cancer patients. This pilot study sought to determine whether the addition of fenretinide to tamoxifen would be associated with antitumor activity in metastatic breast cancer patients who had been previously treated with tamoxifen or who had hormone receptor negative disease. The effect of this therapy on circulating plasma transforming growth factor-beta (TGF-beta) levels and serum lipids was also examined. PATIENTS AND METHODS: Thirty-one patients were treated with tamoxifen (20 mg p.o. daily), and fenretinide (400 mg p.o. daily with a 3-day drug holiday each month). Plasma TGF-beta testing was performed using isoform specific sandwich ELISA. RESULTS: Twenty four of the 31 patients were evaluable for an antitumor response including 14 estrogen receptor (ER) positive patients who had failed prior tamoxifen therapy, seven ER-negative patients, and three hormone therapy naive ER-positive patients. There were no objective antitumor responses; three patients had stable disease for 8, 8, and 24 months. Five patients (16%) discontinued therapy for toxicity (one for grade 3 skin rash and four for abnormal dark adaptation). There was a statistically significant decrease in total cholesterol (median change per patient of -13.5 mg/dl; p = 0.049, a 6.5% decrease), and an increase in HDL levels (median change per patient of +18 mg/dl, p = 0.0001, a 35% increase) with tamoxifen and fenretinide therapy. TGF-beta1 plasma levels were normal in 26 of 28 patients, and no changes in these levels post-treatment were demonstrated. CONCLUSIONS: Tamoxifen and fenretinide therapy is not an active combination in ER negative metastatic breast cancer or in patients whose disease has progressed on tamoxifen. This combination had a beneficial effect on total serum cholesterol and HDL levels with no associated rise in serum triglyceride levels. The 400 mg dose of fenretinide was associated with symptomatic nyctalopia in one-third of patients making it an unsuitable dose for use in breast cancer prevention studies.

Adult↗
PubMed1999

Increased plasma levels of fibrinogen in acute and chronic ischemic coronary syndromes.

BACKGROUND: The aim of this study was to evaluate the pathophysiological role of fibrinogen in patients with chronic or acute ischemic coronary syndromes on the basis of epidemiological and clinical evidences showing the importance of fibrinogen as a risk factor for cardiovascular diseases and atherosclerosis progression. METHODS: We evaluated the behavior of plasma fibrinogen in 310 hospitalized patients with 1) acute myocardial infarction (n = 98); 2) unstable angina (n = 87); 3) chronic ischemic heart disease (n = 75); and 4) in controls without myocardial ischemia (n = 50). Fibrinogen was evaluated, by using the Clauss method, on day 1 and 5 during in hospital-stay and at 6-month follow-up in patients suffering from acute myocardial infarction. RESULTS: Plasma levels of fibrinogen were higher in patients with chronic ischemic heart disease (335.3 +/- 81.2 mg/dl, p < 0.001) and especially in patients with acute myocardial infarction (454.72 +/- 69.5 mg/dl, p < 0.00001) and unstable angina (382.6 +/- 101.3 mg/dl, p < 0.00025) in comparison with controls (271.28 +/- 62.4 mg/dl). Q wave myocardial infarction showed higher levels of fibrinogen than non-Q wave (461.3 +/- 95.8 vs 422.5 +/- 71.3 mg/dl, p < 0.02). Patients with acute myocardial infarction showed a further increase in fibrinogen on day 5 in comparison with entry levels (525.88 +/- 87.3 vs 454.7 +/- 69.5 mg/dl, p < 0.00001) regardless of the fibrinolytic treatment. Patients who died (n = 6) or had severe arrhythmias (n = 4) during in-hospital stay as well as those with post-infarction angina (n = 20) showed higher fibrinogen levels. CONCLUSIONS: Our results confirm the role of fibrinogen as a risk factor for ischemic heart disease, especially in patients with unstable angina and acute myocardial infarction. In the latter, elevated fibrinogen values seem also to be associated with a worsen prognosis during hospitalization.

Acute Disease↗
PubMed1998

Sarcoma metastatic to the brain: a series of 15 cases.

METHODS: We report on 15 patients surgically treated for intraparenchymal brain metastases from sarcoma, including six osteosarcomas, five leiomyosarcomas, two malignant fibrous histiocytomas, and two alveolar soft-part sarcomas (ASPS). RESULT: Median survival after craniotomy was 9.3 months. Patients with a preoperative Karnofsky performance score of > 70 survived for 12.8 versus 5.3 months for those with a Karnofsky performance score < 70 (p=0.03). Patients with evidence of only lung metastases at the time of surgery (nine cases) survived 8.6 months, which was similar to the 10.4-month survival for patients with disease limited to the brain (p=0.1). The two patients with alveolar soft-part sarcomas are alive at 15 and 20 months after surgery. CONCLUSION: We conclude that surgery is effective in treating selected patients with sarcoma metastatic to the brain and that patients with metastasis from ASPS may have a relatively good prognosis if they are surgically treated. The complete removal of all brain metastases and a Karnofsky performance score > 70 are associated with a favorable prognosis; the presence of concurrent lung metastases is not a contraindication to surgery.

Adolescent↗
PubMed1998

Long-term survival in patients with supratentorial glioblastoma.

The authors report 11 patients with cerebral glioblastoma who lived at least 5 years after their initial diagnosis. There were 6 female and 5 male; the mean age was 39 years (range 24-55 years). All patients were treated surgically and postoperatively received whole-brain radiotherapy and chemotherapy. Five patients (45%) presented local recurrences after an average interval of 3.9 years from treatment. At average follow-up of 9 years (range 5-14 years), 7 patients (64%) were alive after an average interval of 8.1 years; 4 patients (36%) died from local relapse. Survival was influenced by patient age and, to a lesser degree, by treatment. A review of the literature, together with our own series, suggest that death from recurrence disease is unusual in glioblastoma patients who survive more than 5 years.

Adult↗
PubMed1998

Abbreviated kinetic profiles in area-under-the-curve monitoring of cyclosporine therapy. Technical note.

BACKGROUND: The new microemulsion formulation of cyclosporine (CsA-ME) displays more consistent pharmacokinetic properties than the original formulation and may allow successful implementation of an abbreviated area-under-the-curve (AUC) strategy. METHODS: Here we compared two limited sampling strategies in order to define the one that best predicts AUC after CsA-ME in 51 renal transplant recipients with stable renal function. Pharmacokinetics were based on analysis of blood samples collected over 12 hours after drug administration by high-performance liquid chromatography (HPLC). Predicted AUC was estimated by using a three-point (0, 1 and 3 hr) or a two-point (2 and 6 hr or 0 and 2 hr) sampling strategy. RESULTS: A simplified strategy with three time points of blood collection at 0, 1, and 3 hours after CsA-ME allowed adequate and accurate prediction of the daily exposure to CsA. AUC prediction with two-point sampling at 2 and 6 hours was less good with a very large error in prediction (only 59% of the estimated AUC were within the accepted range). This limitation was even more evident when the 0 and 2 hour time points were examined, in which only 51% of AUC estimates were included in the accepted range of variation (-10 to 10%). CONCLUSIONS: A limited strategy of three-point sampling taken early after dosing allows an excellent and perfectly reliable prediction of the actual AUC.

Adult↗
PubMed1998

AMPA/kainate antagonist LY293558 reduces capsaicin-evoked hyperalgesia but not pain in normal skin in humans.

BACKGROUND: Animal studies suggest that alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid-kainate (AMPA-KA) receptors are involved in pain processing. The effects of the competitive AMPA-KA antagonist LY293558 in two types of experimental pain in human volunteers, brief pain sensations in normal skin, and mechanical allodynia-pinprick hyperalgesia were studied after the injection of intradermal capsaicin. METHODS: Brief intravenous infusions of the competitive AMPA-KA antagonist LY293558 were given to 25 healthy volunteers to examine acute toxicity and analgesic effects. Fifteen volunteers then entered a double-blinded, three-period crossover study. In a Phase II study, LY293558 infusions (100% maximally tolerated dose vs. 33% maximally tolerated dose vs. placebo) began 10 min after intradermal injection of 250 microg capsaicin in volar forearm. Spontaneous pain, areas of mechanical allodynia and pinprick hyperalgesia, and side effects were determined every 5 min for 60 min. RESULTS: The median maximally tolerated dose was 1.3 +/- 0.4 (range, 0.9-2.0) mg/kg. Tests of cognitive and neurological function were unchanged. Dose-limiting side effects were hazy vision in 95% of volunteers and sedation in 40%. There were no significant changes in electrical or warm-cool detection and pain thresholds or heat pain thresholds. LY293558 had little effect on brief pain sensations in normal skin. Both high and low doses of LY293558 significantly reduced pain intensity, pain unpleasantness, and the area in which light brush evoked pain after intradermal capsaicin. There was a trend toward a dose-response effect of LY293558 on the area in which pinprick evoked pain after intradermal capsaicin, which did not reach statistical significance. CONCLUSIONS: The authors infer that AMPA-KA receptor blockade reduces the spinal neuron sensitization that mediates capsaicin-evoked pain and allodynia. The low incidence of side effects at effective doses of LY293558 suggests that this class of drugs may prove to be useful in clinical pain states.

Adult↗
PubMed1998

Treatment of acute idiopathic thrombocytopenic purpura in children. A retrospective evaluation of 120 cases.

Acute idiopathic thrombocytopenic purpura (AITP) in children is generally a benign disease with a high frequency of spontaneous remission. Nevertheless the debate over treating or not is still open, because of the high risk of hemorrhage as long as the platelet count remains below 20 x 10(9)/l. We have retrospectively evaluated 120 pediatric cases from our center, receiving different treatments at diagnosis: no treatment (76); IVIG: 400 mg/kg/d for 5 days (28); continuous oral PDN: 1-1.5 mg/kg/d for at least two weeks (16). No patients had been previously treated for AITP. Follow-up is up to fifty months. We found no significant differences as to the percentage of responses among the three groups. We conclude that waiting without treatment is safe and appropriate in most cases; whether the hemorrhagic risk suggests treatment, standard dose continuous oral PDN and IVIG may be equally effective, but IVIG may achieve a significantly faster rise in the platelet count. The timing of treatment and the cost/benefit ratio are discussed.

Acute Disease↗
PubMed1998

[Epidermoid cyst of the cranial vault. Neuroradiological and therapeutic considerations].

AIM: Intradiploic epidermoid cyst is a slow-growing tumor affecting only rarely the cranial bones. PATIENT: The authors describe a case of intradiploic epidermoid cyst of the cranial vault in which there was a predominantly intracranial extension. Roentgenographic and CT findings do not permit a differential diagnosis. Complete removal of the cyst and its capsule was accomplished, with complete recovery. CONCLUSION: Total removal oft the tumor and its capsule is associated with a very good long-term prognosis without recurrences.

Epidermal Cyst↗