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Biomedical subjects

V M Lauta

Publications and source records attributed to V M Lauta.

29 records · Page 2Linked to original sources
PubMed1990

Maintenance treatment with recombinant interferon alfa-2b in patients with multiple myeloma responding to conventional induction chemotherapy.

The use of interferon for the induction treatment of multiple myeloma has been shown to be effective in about 20 percent of patients. We studied its effects on long-term survival when it was used for maintenance treatment. Between April 1985 and May 1988, 101 patients with symptomatic multiple myeloma who had had a substantial objective response or a lesser objective response with disappearance of symptoms ("disease stabilization") after 12 courses of induction chemotherapy were randomly assigned to receive recombinant interferon alfa-2b as maintenance therapy (n = 50) or to receive no treatment (n = 51). As of December 1989, 66 of the 101 patients have relapsed (25 given interferon and 41 not treated). The median duration of response (from the time of randomization) was 26 months in the patients given interferon and 14 months in the untreated patients (P = 0.0002). A total of 37 patients have died (14 given interferon and 23 not treated). The median duration of survival (from randomization) was 52 months in the interferon group and 39 months in the control group (P = 0.0526). Among the patients who had had a substantial objective response to induction chemotherapy, the difference in survival time was statistically significant (P = 0.03526). Interferon had to be stopped because of toxic effects in 3 of 12 patients initially treated with 10 MU (megaunits) per square meter of body-surface area. After the dose was reduced to 3 MU per square meter, the only toxic effect was a mild influenza-like syndrome lasting two to three weeks. We conclude that maintenance treatment with interferon prolongs response and survival in patients with multiple myeloma who have responded to conventional induction chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

[ACE: physiopathology and role in the diagnosis and prognosis of systemic granulomatosis, neoplasms and lung toxicity caused by antineoplastic agents].

Several studies have been performed in the last ten-years on the biochemical and physiopathologic properties of angiotensin-converting enzyme (ACE). Human lung and kidney are a rich source of ACE and the enzyme is bound to the plasma-membrane of vascular endothelial cells; however, the small intestine and the choroid plexus are also particularly rich in ACE, where it is concentrated on the surface of cuboidal epithelial cells facing the cerebrospinal fluid. The ACE is a glycoprotein with a molecular weight of 150,000 daltons and it cleaves C-terminal dipeptides of several oligo-peptides, including angiotensin I and bradykinin. It catalyzes conversion of angiotensin I to angiotensin II and induces inactivation of bradykinin. Synthetic acylated tripeptides such as radiolabelled hippuryl-histidyl-leucine and hippuryl-glycyl-glycine have been found to be the most suitable substrates for determining the activity of ACE with radiochemical assays. The mean-normal values for ACE activity is 25 U/ml; there are no significant differences in ACE activity between different sexes and races, but there is significant decrease in adults. The measurement of ACE activity in sarcoidosis suggests the following results: 1) There is a relationship between the increased SACE and LACE activity and active disease and between normal ACE activity and inactive disease. 2) Normal or decreased ACE activity is useful for therapeutic evaluation of sarcoidosis. 3) Increased SACE activity can be a sensitive parameter for predicting clinical relapse of the disease. An increased SACE activity is found in a wide variety of non-sarcoid granulomatous diseases and non-granulomatous systemic diseases. A decreased SACE and LACE activity is found in non-granulomatous pulmonary diseases such as "Adult Respiratory Distress Syndrome", lung cancer and lung toxicity caused by antineoplastic drugs. Moreover, a low preoperative SACE is associated with poor prognosis in lung cancer and its levels may be useful for predicting clinical relapse of this disorder after operation. Finally, a low SACE activity is found in malignant lymphomas, leukemia and multiple myeloma. A relationship is also found between decreased enzyme activity and a poor prognosis and clinical relapse of these diseases.

Adolescent↗
PubMed1987

Early-onset diagnosis of lung toxicity caused by cyclophosphamide, melphalan and procarbazine therapy.

Lung function studies were performed in 33 patients with lymphomyeloproliferative diseases (25 cases of multiple myeloma and 8 cases of Hodgkin's disease) who received cyclophosphamide, procarbazine, and melphalan therapy. Lung function was investigated by spirometric tests, indicative tests of small airways disease, and diffusing capacity of the lung for carbon monoxide (DUCO). Indicative tests of small airways disease and other lung function tests such as forced expiratory volume in 1 second (FEV1), vital capacity (VC), total lung capacity (TLC) etc. were markedly improved in 18 patients (55%), whereas 24 patients (73%) showed a decreased diffusing capacity of the lung for carbon monoxide. Furthermore, most of the patients (77%-83%) showed contemporaneous involvement of spirometric tests and DUCO. The DUCO was also found more constantly impaired than other function tests because it had decreased with and without other spirometric tests. Impaired lung function tests were found to be related to a cumulative dose of antineoplastic drugs. The absence of increased lung toxicity was found to be related to several drugs administered in combination. In view of the absence of previous bronchopathies, lung involvement signs in multiple myeloma (25, 26) or lymphoma, and concomitant bronchopneumonias, the impaired functional tests could be ascibed to drug-induced lung toxicity. In the absence of clinical symptoms, roentgenographic and pathologic features, impaired lung function tests may play a role as early-onset signs of drug-induced lung toxicity.

Adult↗
PubMedDate not supplied

Pharmacological elements in clinical application of synthetic peptides.

The research carried out on the biological properties of synthetic peptides and the possibility of obtaining them in adequate amounts through the recombinant DNA technology allows their use as therapeutical agents. Procedures following the synthesis of peptides must be performed in order to verify their structure, conformation, immunogenicity and biological activity and to make them suitable for clinical applications. The size of synthetic peptides together with some modifications such as amidation, acetylation and sulfatation must be taken into consideration as they may have a significant impact on half-life, stability and biological activity. Endothelial, epithelial and enzymatic interference which may hinder the absorption of drugs must be evaluated in order to choose the most appropriate route of administration. The considerable bioavailability related to the intravenous route, the effectiveness of the circulation of the intramuscular route and the possibility of reaching specific targets by the intra-arterial route must also be taken into consideration. There is the possibility of applying transdermal therapeutic systems and transdermal iontophoresis only for peptides of low molecular weight. Among synthetic peptides provided with antianaemic activity, erythropoietin, growth factors and interleukin 3 must be mentioned because of their effectiveness both in optimal stimulation of melopoiesis after chemotherapy or bone-marrow transplantation and in the treatment of anaemia occurring during chronic renal failure. Furthermore, interferon alpha was shown to be one of the most used synthetic peptides provided with antiviral and antineoplastic activity. Remarkable results have been obtained in the treatment of chronic hepatitis C, haematological malignancies and some solid tumours. More recently, interleukin 2 has been tested in the treatment of melanoma and renal cancer, inducing a reasonable proportion of overall response rate. Finally, the antagonist of gonadotropin-releasing-hormone may be regarded as effective agent both in the treatment of prostate cancer and in the inhibition of luteinizing-hormone surges during controlled ovarian stimulation. Toxic side effects can be related to the administered dose as well as to metabolites derived from bacteria in which peptides have been synthesized.

Drug Administration Routes↗
PubMedDate not supplied

[Update on the use of interferons in clinical practice].

Discovered by Isaac and Lindemann as a substance able to induce a biological interference among viruses and host cells, interferon appeared to include three main antigenic classes: alpha, beta and gamma. There is a large variety of actions exhibited by different types of interferon and among them it is possible to distinguish an antiviral, antineoplastic, immunomodulatory or hormonal activity. Many years ago, the antiviral action seemed to be relative to some cellular membrane disorders, but later other mechanisms were stressed. Among them, it is worth describing the transcription and transduction of antiviral proteins like the oligoadenilsinthetase and proteinphosphokinase, able to cause the viral RNA breackage. The antineoplastic action is exerted by direct and indirect mechanisms. Direct mechanisms include an antiproliferative activity and the induction to cellular differentiation whereas the indirect ones involve the enhancement on tumor cell surfaces of some tumor associated antigens included in the I class of MHC system. The immunomodulatory action is exerted by the stimulation of macrophages, T cells and Killer cells cytotoxic activity. The list of viral diseases sensitive to interferon treatment includes condiloma acuminata, herpes zoster, chronic B and C hepatitis and Kaposi sarcoma AIDS-related. High proportions of overall response rate were observed among interferon treated patients with condiloma acuminata (80-100%). The use of interferon in the treatment of herpes zoster achieved good results regarding a shorter duration of the time spent to induce the chest pains and cutaneous symptoms disappearance when compared with that relative to other antiviral drugs. Results obtained in the treatment of chronic B and C hepatitis regard the disappearance of viral replication serological markers and the improvement of histological and enzymatic pattern. The effectiveness of interferon in the therapy of Kaposi sarcoma is demonstrated by the reduction of cutaneous symptoms and recurrent infectious diseases incidence. The use of interferon in treatment of solid tumors seems to play secondary role and, at any rate, to be adjuvant to chemotherapy. The administration of beta interferon as therapy of breast cancer seems to increase the estrogens and progesterone concentration in the neoplastic tissue and so it aims to improve the sensitivity to the tamoxifen treatment. The addition of interferon alpha both to 5-FU and cis-platinum seems to improve the proportion of overall response rate respectively in the treatment of colon cancer and head and neck cancer.(ABSTRACT TRUNCATED AT 400 WORDS)

Antineoplastic Agents↗
PubMedDate not supplied

[Clinical use of interferon].

It has been thought that there is a particular balance between interferon and humoral immunity in the specific antiviral activity exerted by these systems. A possible relationship has been observed between some interferon-related proteins and the interferon serum level and a predictive significance can be assigned to MxA protein regarding the progression of some haematological malignancies. Both natural and recombinant interferon have been shown to be effective in the treatment of T-cell cutaneous lymphoma and the myeloma cell expression of Bcl-2 oncoprotein correlates to the response to interferon therapy in multiple myeloma patients. It has been thought that the combined therapy including interferon and cis-retinoic acid might be effective in the therapy of metastatic melanoma and breast cancer, whereas the combination of interferon with other chemotherapeutic agents appears to be effective in the treatment of hepatocellular cancer. It has been confirmed that interferon-alpha is useful in the therapy of chronic hepatitis C and a better knowledge regarding the mechanism of action of beta interferon in the therapy of multiple sclerosis has been acquired. Finally, a remarkable report regards the effectiveness of interferon in the therapy of idiopatic dilated cardiomiopathy.

Humans↗