[Participatory research in Cuenca Lechera, Departamento de San José].
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Community Participation↗
Biomedical subjects
R Palumbo
Publications and source records attributed to R Palumbo.
Enzyme deficiency and tumor suppressor genes: absence of 5'-deoxy-5'-methylthioadenosine phosphorylase in human tumors.
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Animals↗
Pharmacokinetics of glucosamine in man.
The pharmacokinetics of glucosamine sulfate (CAS 29031-19-4) was investigated in 6 healthy male volunteers (2 per administration route) using 14C uniformly labelled glucosamine sulfate and administering it in single dose by intravenous (i.v.), intramuscular (i.m.) or oral route. The results show that after i.v. administration the radioactivity due to glucosamine appears in plasma and is rapidly eliminated, with an initial t1/2 of 0.28 h. 1-2 h after administration the radioactivity due to glucosamine disappears almost completely and is replaced by a radioactivity originating from plasma proteins, in which glucosamine or its metabolites are incorporated. This radioactivity reaches a peak after 8-10 h and then declines with a t1/2 of 70 h. About 28% of the administered radioactivity is recovered in the urine of the 120 h following the administration and less than 1% is recovered in the feces. After i.m. administration similar pharmacokinetic patterns are observed. After oral administration a proportion close to 90% of glucosamine sulfate is absorbed. Free glucosamine is not detectable in plasma. The radioactivity incorporated in the plasma proteins follows pharmacokinetic patterns which are similar to those after i.v. or i.m. administration, but its concentration in plasma is about 5 times smaller than that after parenteral administration. The AUC after oral administration is 26% of that after i.v., or i.m. administration. The smaller plasma levels of radioactivity after oral administration are probably due to a first pass effect in the liver which metabolizes a notable proportion of glucosamine into smaller molecules and ultimately to CO2, water and urea.(ABSTRACT TRUNCATED AT 250 WORDS)
Administration, Oral↗
Metastatic bone tumors. Nonsurgical treatment. Outcome and survival.
Of 683 (16.1%) consecutive patients investigated from October 1984 to December 1985, 110 had various malignant tumors and secondary bone involvement. In 82 of 110 patients (74.5%), the primary tumor was located in the breast, and the percentage of clinical and radiographic objective responses (OR) of their bone lesions (42.7% and 22.8%, respectively) was higher than for cancer in other sites (clinical OR, 21.4%; radiographic OR, 15.8%). The average survival time of 82 breast cancer patients was 87.4 months, or 38 months from the diagnosis of the bone metastases. Of the 110 patients with bone metastases, 60 patients (54.5%) had secondary spinal involvement. The clinical and radiographic OR (38.4% and 30.2%) were better in the patients with vertebral metastases than in the patients with bone metastases in other sites (clinical OR, 36%; radiographic OR, 9.1%). The average survival time of the patients with vertebral involvement was 99.4 months, or 40.4 months from the time of diagnosis of the bone metastases. From the results obtained, in terms of OR and survival for patients with bone metastases, early and aggressive treatment should be considered to improve the patients' life quality.
Adolescent↗
Ifosfamide plus epirubicin at escalating doses in the treatment of locally advanced and/or metastatic sarcomas.
A total of 46 consecutive patients were entered into this study to assess the efficacy and toxicity of an epirubicin/ifosfamide combination in treating locally advanced and/or metastatic adult sarcomas (38 soft-tissue sarcomas and 7 bone sarcomas in 45 evaluable patients). Epirubicin was given at escalating doses (from 50 to 100 mg/m2) as an intravenous (i.v.) bolus on day 1, and ifosfamide was given i.v. at 1.2 g/m2 daily on days 1-5. Cycles were repeated every 4 weeks. The overall response rate was 38% (17 of 45 patients), reaching 42% (16 of 38) in the soft-tissue sarcoma group and 44% (17 of 39) in patients who had not been treated previously. In all, 4 complete responses (CRs, 9%) and 13 partial responses (PRs, 29%) were obtained. Most responses (about 68%) were reached within the first 2 cycles. The high-dose intensity of epirubicin (P < 0.04), the histologic type (P < 0.03), the presence of metastatic lesions only (P < 0.01), and the lack of previous treatment (P < 0.04) were found to be positively correlated with the probability of response. The median duration of response was 8 months. The median survival period was 10 months for all evaluable patients and 21 months for those achieving CRs and PRs (P < 0.01). The tumor grade, performance status, and extent of disease at entry into the study correlated with survival. The treatment was well tolerated; no case of sepsis occurred, and neither acute nor cumulative cardiotoxicity was observed. Epirubicin in combination with ifosfamide is therefore effective in advanced and/or metastatic disease with acceptable toxicity. The activity of this combination as compared with that of either of the two drugs given alone at optimal doses needs to be evaluated in prospective randomized trials.
Adolescent↗
Deficiency of 5'-deoxy-5'-methylthioadenosine phosphorylase activity in malignancy. Absence of the protein in human enzyme-deficient cell lines.
The absence of 5'-deoxy-5'-methylthioadenosine phosphorylase (MTAase) activity in malignant cells, and the putative localization of its gene, suggest that this enzyme deficiency might be due to a genomic alteration also involving a tumour-suppressor gene. We studied the possible occurrence of inactive forms of the protein in two MTAase-negative cell lines, namely K562 and Jurkat, by immunochemical methods. Two highly specific antisera, directed against different epitopes of the phosphorylase [Della Ragione, Oliva, Gragnaniello, Russo, Palumbo & Zappia (1990) J. Biol. Chem. 265, 6241-6246], were used to carry out immunotitration and immunoblotting analyses, as well as to investigate the biosynthesis of the enzyme. No MTAase protein was detected by Western-blotting technique performed under conditions where all the phosphorylase-positive samples gave a clear band at the MTAase subunit molecular mass. No cross-reacting material was observed by a sensitive immunotitration method which permitted the detection of as low as 0.5 ng of protein. Moreover, the results obtained by [35S]methionine-labelling experiments ruled out phosphorylase biosynthesis in the negative cell lines. Altogether, these data suggest that an alteration at the gene level hampering the specific mRNA biosynthesis or resulting in an untranslatable mRNA is the cause of the enzyme deficiency in the MTAase-negative cell lines studied.
Antibody Specificity↗
Isolation and characterization of human embryonic osteoblasts.
Human osteoblasts were obtained by migration and proliferation of cells from embryonic membranous bone on glass fragments. Light and electron microscopy analyses revealed a typical osteoblast-like appearance with high protein synthesis activity. The cells showed high alkaline phosphatase activity that was associated with plasma membranes and matrix vesicles and was 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] responsive. In contrast to the adult osteoblasts, embryonic cells could not produce detectable levels of osteocalcin, not even in the presence of 1,25(OH)2D3. Osteoblasts grown in multilayers produced a thick extracellular matrix, mainly composed of type I collagen, that mineralized in the presence of 10 mM beta-glycerophosphate. Because of their intrinsic osteogenic capacity, embryonic osteoblasts represent a valuable model for studying the mineralization process in vitro. In addition, the embryonic origin of these cells renders them a precious experimental system for the elucidation of mechanisms at the basis of differentiation of osteoblastic lineage.
Alkaline Phosphatase↗
Progressive 13-cis-retinoic acid dosage in the treatment of oral leukoplakia.
16 patients with oral leukoplakia were treated with oral 13-cis-retinoic acid. The initial dose, given for 3 months, was 0.2 mg/kg/day, increasing by a further 0.2 mg/kg/day in successive 3 month cycles. The maximum dosage reached at 1.0 mg/kg/day, was given to only 2 patients (who received a total of 15 months treatment). However, 10 patients completed the cycle at 0.8 mg/kg/day (12 months treatment in total), but treatment could not continue due to toxicity (grade I and II), which was cutaneous, mucosal, and haematological (hypertriglyceridemia and hypercholesterolemia). There was grade III toxicity in the skin and mucosa in only 1 case, a patient treated at a dose of 1.0 mg/kg/day. The toxicity was reversible in all cases. 14 of the patients completed the trial. In 4 there were improvements graded as partial responses (PR) obtained at 0.2 mg/kg/day (3PR) and 0.6 (1PR) and there was one complete response (CR) obtained at 0.4 mg/kg/day. Overall there was thus an objective response rate of 36% who showed 50% or more reduction in lesion size. After the retinoic acid treatment was stopped, patients were followed-up for 12 months; 2 patients showed regression of the responses obtained after 6 and 9 months. This study shows that oral treatment with 13-cis-retinoic acid at low dosages is efficacious and with minimal toxicity. It also shows that it is not feasible to treat these patients at doses above 0.8 mg/kg/day for long periods--mainly due to poor compliance.
Adult↗
99mTc-DTPA-surfactant inhalation in adult respiratory distress syndrome (ARDS): a new diagnostic-therapeutic tool.
ARDS is a life-threatening pulmonary disease with a rapidly progressive decline due mainly to multi-organ failure. Death occurs in 50-75% of ARDS cases. The diagnosis and therapy should start in the first six days of this fatal disease when mortality is at its lowest level. The 99mTc-DTPA-measured pulmonary alveolar epithelial permeability (PAEP) is strikingly increased in ARDS even in comparison to heavy smokers. Furthermore, surfactant inhalation has been shown to be of therapeutic value. In five ARDS patients with increased PAEP (T0.5 = 12% pred.) 20 mg/kg of aerosolized surfactant determined a dramatic improvement in blood gases and PAEP (51.8% pred.) No patient remained dependent on ventilatory treatment.
Administration, Inhalation↗
Doxorubicin (or epidoxorubicin) combined with ifosfamide in the treatment of adult advanced soft tissue sarcomas.
The results of the association of doxorubicin plus ifosfamide in the treatment of locally advanced and/or metastatic adult soft tissue sarcomas as reported in the literature from 1986 up to the present time are reviewed. The data confirm the effectiveness of the association doxorubicin plus ifosfamide, with an objective response rate of 33.25% (range, 22% to 42%), with 9.3% of complete responses. The highest percentages were reported in studies using doses of doxorubicin of 60 mg/m2 or higher, with a suggested dose-response correlation. The pattern is generally well tolerated, with a prevalently haematological toxicity. Results being equal, the use of epidoxorubicin seems to allow a lower incidence of high grade leukopenia, and an higher dose-intensity of the drug administered. The two randomized studies by EORTC and ECOG indicate superiority of this combination compared to doxorubicin on its own or with other polychemotherapeutic regimens containing doxorubicin, without ifosfamide. However, the actual contribution of ifosfamide deserves further investigation. The impact on long-term disease-free survival is, however, poor and median survival time ranges from 8 to 12 months in responder patients. Future studies should be aimed at increasing the dosages of the drugs without a significant increase of toxicity, by administering them in continuous infusion or by the use of growth factors.
Antineoplastic Combined Chemotherapy Protocols↗
Treatment of oral leukoplakia with beta-carotene.
Over the past few years, beta-carotene has progressively gained ground as a drug chosen in the treatment of oral leukoplakias, thus making it possible to reduce the use of 13-cis-retinoic acid, which was shown by many studies to be highly toxic while beta-carotene has proved to have no significant side effects and hence to be much more suitable in oral premalignancy. In 1989, a phase II study of patients showing oral leukoplakias and treated with beta-carotene (90 mg/day) was begun. A total of 23 patients (aged between 17 and 85) were included in the study and 18 (8 male and 10 female) were evaluated. Eight patients (44.4%) had objective responses (6 complete, 2 partial). Four CR and a PR appeared unexpectedly within 2-7 months after the end of the therapy. The lesions were macroscopically and histologically examined at entry; in the evaluated patients, two types of alterations were found: atypical hyperplasia (16 patients) and dysplasia (2 patients). No signs of significant toxicity were detected; only in 1 patient treatment had to be interrupted for 1 week. The results of this study show the fair efficacy of beta-carotene against oral leukoplakias, but further confirmations through controlled clinical studies are needed.
Adult↗
[Potassium canrenoate and the combination of potassium canrenoate-butizide in the therapy of light to moderate arterial hypertension].
The aim of the study was to evaluate the antihypertensive effect of K-canrenoate, alone or in combination with butizide, in mild to moderate essential hypertensives. Fifteen patients (supine diastolic blood pressure ranging from 95 to 114 mmHg) received K-canrenoate 50mg/die (step 1). In patients with supine diastolic blood pressure greater than 90 mmHg therapeutic regimen was modified at two-week intervals according to the following design: K-canrenoate 100 mg/die (step 2), K-canrenoate 50 mg + butizide 5 mg/die (step 3), K-canrenoate 100 mg + butizide 10 mg/die (step 4). Blood pressure control was achieved in 2 patients treated with K-canrenoate alone (step 2) and in 8 patients on a combined regimen (step 3), and it was maintained throughout the whole trial period (12 weeks); step 4 did not achieve the goal of therapy in the remaining 5 subjects. A statistically significant increase in triglyceridemia (123.2 +/- 42.1 vs 158.3 +/- 62 mg/dl) and uricemia (4.6 +/- 0.9 vs 5 +/- 0.9 mg/dl) was observed at the end of the follow-up period. Serum potassium levels remained stable in all patients. Therefore, K-canrenoate in combination with butizide is an effective and well tolerated drug in the treatment of mild to moderate essential hypertension.
Adult↗
In vitro effects of beta-carotene on human oral keratinocytes from precancerous lesions and squamous carcinoma.
Human keratinocytes, obtained from bioptic specimens of healthy and preneoplastic oral mucosa, and from human cell lines from oral cavity tumors (KB and SCC-25) were treated with beta-carotene (10 microM). The colony forming efficiency (CFE), the proliferation rate and the frequency of micronucleated cells were measured in these cultures. CFE was significantly reduced (p less than 0.05) by beta-carotene treatment in cells from healthy mucosa and in KB cells. Decreases (p greater than 0.05; NS) were also observed in cells from pathological mucosa and in SCC-25 cells. Cell proliferation rate was not substantially affected by beta-carotene in all cultures. Finally, a decreased frequency of micronucleated cells was found in treated cultures, but significant reductions (p less than 0.05) were only observed in cultures from oral mucosa (healthy and pathological) as well as in KB cell cultures. Our results indicate that beta-carotene is able to reduce the clonogenic activity (CFE), even if it does not seem to influence cell proliferation, and that it has a protective effect against genotoxic damage.
Adolescent↗
Physicochemical and immunological studies on mammalian 5'-deoxy-5'-methylthioadenosine phosphorylase.
5'-Deoxy-5'-methylthioadenosine phosphorylase (MTAase) was purified to homogeneity (10,000-fold) from bovine liver with a recovery of 12%. The pure protein shows a molecular weight of about 98,000 +/- 3,000 and is composed of three apparently identical subunits. Several physicochemical features have been investigated including hydrodynamic properties, amino acid composition, and secondary structure. In particular, the CD spectrum of the protein indicates a very low alpha-helical content and a large percent of beta-structure and random coil. The pure protein was used to raise specific rabbit antisera but, because of the scarce antigenic properties of the native enzyme, different chemically modified forms were prepared and employed as immunogens. Among the antibodies obtained, those to keyhole limpet hemocyanin-MTAase recognize both the native and the denatured enzyme and are also active against the human protein. Therefore, they were employed as a tool to investigate the occurrence of inactive forms of MTAase in two human malignant cell lines lacking this enzymatic activity. The results obtained with K562 and Jurkat cells indicate that the protein is absent in these phosphorylase-deficient cell lines.
Amino Acids↗
Fate of human albumin microsphere and spherocyte radioaerosols in the human tracheobronchial tree.
Human albumin microspheres (99mTc-HAM; 7-25 microns) and spherocytes (99mTc-S; 4-4.5 mu) are particles used for lung mucociliary clearance (MCC) measurements. If radiolabelled HAM aerosols are sent through an airway model to a screen, they appear peripherally distributed, whereas S present a more central and homogeneous distribution. The radioscanning evaluation of particle sedimentation in saline-filled tubes shows quite a different behavior pattern for S, HAM, and surfactant-coated HAM (S-C HAM). In these experimental conditions, S-C HAM and HAM floating properties were better than those of S. This could be explained by physical-chemical factors. Looking for the fate of organic particles after inhalation, we performed multiple bronchial biopsies in seven bronchitic patients, 2 h following inhalation of HAM and S. Scanning electron microscopy revealed that most of S was floating on the mucus layer, while HAM appeared deeply imbedded inside the mucus and partially digested. The same study performed on three bronchitic patients after S-C HAM inhalation, shows that S-C HAM float like S. In vitro, the time-course of tryptic digestion is similar for HAM and for S. However, in vivo, the different location of each particle on the bronchial surface might lead to a different digestion by trypsin and by PZ-peptidase, which are dosable in pathologic mucus. In our opinion, if HAM are coated with surfactant, this should improve the mucus-HAM interaction, thus helping to control variability in lung radioaerosol MCC studies.
Aerosols↗
Immunoscintigraphy in the follow up of patients with ovarian cancer.
Our case series concerns eight patients affected by epithelial cancer of the ovary. The immune scintigraphical examination with B 72.3-I-131 monoclonal antibody was carried out as a follow-up after surgical therapy with chemo- and/or radio-therapy. The results were compared with traditional diagnostic methods (CT, pelvic echography etc.). The immunoscintigraphy confirmed the presence of local relapses in seven patients, correlating positively with the results of conventional enquiries. The conclusions, although relating to a limited number of cases, are satisfactory and seem to indicate important diagnostic possibilities to the end of follow-up in patients affected by ovarian cancer.
Adult↗
Immunoscintigraphy of adenocarcinomas by means of radiolabeled F(ab')2 fragments of an anti-carcinoembryonic antigen monoclonal antibody: a multicenter study.
F(ab')2 fragments of anti-carcinoembryonic antigen (CEA) monoclonal antibody F023C5, determined to be more suitable than intact IgG and Fab fragments for immunoscintigraphy, were labeled with 131I or conjugated to DTPA for instant 111In-labeling, and administered i.v. (2-3 mCi/0.5 mg) to 509 patients in 11 nuclear medicine departments: 284 patients had gastrointestinal adenocarcinomas, 204 had nongastrointestinal adenocarcinomas and 21 were control; serum CEA was elevated in 169 patients, normal in 115, and not determined in 225. The following results were obtained: (a) no adverse reactions; (b) tumor imaging in 324 patients (in particular, in 81.5% CEA-seropositive and in 69.0% CEA-seronegative patients); (c) no significant difference in sensitivity among the results of the 11 departments; (d) no significant difference in overall sensitivity between 131I-and 111In-labeled immunoradiopharmaceuticals; (e) the fraction of documented lesions imaged was 73.3% in CEA-seropositive and 53.7% in CEA-seronegative patients; (f) the detection of liver metastases was hampered, particularly when using the 111In-labeled reagent, by nonspecific radioactivity uptake; (g) the major cause of negative immunoscintigraphy results was a lack of CEA in tumor lesions, as documented by immunohistochemistry; (h) lesion size is also important since the sensitivity was 64% for lesions up to 2 cm in diameter and 84% for larger lesions; (i) many "unexpected" radiolocalizations were recorded. Most were identified as occult tumor lesions. In 35 patients, this finding contributed to the early detection of tumor recurrences.
Adenocarcinoma↗
Normal reference values for regional pulmonary peripheral airspace epithelial permeability. Influence of pneumonectomy and the smoking habit.
Peripheral airspace epithelial permeability (PAEP) to diethylentriaminopentacetate (DTPA), an index of pulmonary integrity, was measured in 3 groups of subjects for different purposes: (1) to establish vertical regional reference values; (2) to determine the physiological role of acute doubling of total pulmonary blood flow; (3) to quantify the pulmonary epithelial damage in smokers and the possibility of lung protection by an agent stimulating surfactant production. This study broadens previous knowledge of PAEP. First of all, regional reference values are given for young normal nonsmoking subjects and the existence of a vertical gradient of PAEP is confirmed. Furthermore, this study shows that this gradient is independent of the vertical blood flow gradient, since an acute increase of total blood flow in pneumonectomized patients does not modify the regional distribution of PAEP. Finally, it is confirmed that the cigarette smoker's lung is more permeable than the controls and that probably a drug-stimulating surfactant production gives some protection against damage due to chronic smoking.
Adult↗