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Biomedical subjects

S Baron

Publications and source records attributed to S Baron.

At least 109 records · Page 6Linked to original sources

Granulocytic macrophage colony stimulating factor restores in vitro growth of granulocyte-macrophage bone marrow hematopoietic progenitors in dyskeratosis congenita.

In vitro 14-day cultures of bone marrow from a patient with dyskeratosis congenita showed virtually no growth of colonies. The addition of recombinant granulocyte-macrophage colony stimulating factor (rGM-CSF) promoted a significant increase in the number of GM colonies (CFU-GM). Interleukin 3 also increased GM colony formation but to a lesser extent. GM-CSF may have a therapeutic implication for pancytopenia in dyskeratosis congenita.

Adult↗

[Clinical and pharmacokinetic study of ceftizoxime in newborn infants and children].

Ceftizoxime was evaluated in the treatment of 49 children and 15 neonates. The average dosage was 150 mg/kg/d for newborns and 115 mg/kg/d for children, administered IV, 3 or 4 times daily. Clinical and bacteriological cure was achieved in 93% children and 92% neonates. The clinical and biological tolerance was very good. Pharmacokinetic parameters were studied in 17 patients, including 2 neonates. In children the mean serum peak was 40 mug/ml and the mean half life was 2.2 +/- 0.6 H, after a dose of 30 mg/kg. In both neonates the half life was 3.1 H and 3.6 H. In urine, mean concentration of 4 g/l has been obtained in the first 2 hours after IV.

Adolescent↗

[Clinical and pharmacokinetic study of imipenem/cilastatin in children and newborn infants].

Imipenem, a new carbapenem (thienamycin) beta lactam antibiotic which is clinically used in a 1:1 combination with cilastatin, an inhibitor or renal metabolism of imipenem, was evaluated in 25 patients; 11 children and 14 neonates. A mean daily dose of 60 mg/kg was given to children and the dose in neonates was 50 mg/kg. Clinically, 21 patients were cured, two failed to respond to treatment and two were not evaluable. Pharmacokinetic studies were performed in the 11 children and in 10 of the neonates. The mean elimination half-life of imipenem was 0.87 h in children and 2.1 h in neonates. The mean cilastatin elimination half-life was 0.73 h in children and 5.1 h in neonates. This difference in half-life between children and neonates is similar to the one noted between healthy adults and adults with renal insufficiency. No accumulation of imipenem was seen in neonates studied on the first and fifth days of treatment.

Adolescent↗

[Tonsil diffusion of cefixime in children].

Cefixime is a new oral cephalosporin antibiotic, with broad-spectrum of activity, near than of third generation cephalosporin, especially against betelactamase producers bacteria. Cefixime has been assayed with microbiological method in tonsils of 21 children (mean age 59 months). Tonsillectomy was performed 5 hours after a third dose of 4 mg/kg cefixime. Plasma levels were evaluated 10 hours after the second dose, with mean level of 0.84 micrograms/ml (0 to 1.35). Blood level was evaluated after third dose, during amygdalectomy was 1.24 micrograms/ml (0.1 to 3.9). Tonsils levels were: for right tonsils 0.74 micrograms/g and for left tonsils 0.53 micrograms/g. Cefixime was not detected in both tonsils of 6 children, and in one of the two tonsils in 11 of them. The tonsils penetration of cefixime was about 1 microgram/g in the case where cefixime was detectable. This penetration is not regular as for other betalactam antibiotics in relation with fibrosis of tonsils tissue inhibiting a good diffusion of antibiotic.

Cefixime↗

[Pharmacokinetics of prednisolone in children. Study of a correlation with tolerability and therapeutic effect in nephrosis].

In patients with nephrotic syndrome the response to corticosteroids and the way these drugs are tolerated are extremely variable. The purpose of this study was to investigate possible correlations between the pharmacokinetic values of prednisolone and the main clinical criteria of effectiveness and safety. The study was performed on 18 children under corticosteroid therapy: 16 with nephrotic syndrome and 2 with a systemic disease. Measurements were performed by radiocompetition with transcortine after an oral dose of 1 mg/kg bodyweight. Pharmacokinetic values varied considerably, with peak plasma levels ranging from 1.2 to 6.1 micrograms/ml between 20 and 120 minutes, and T 1/2 values of 77 to 648 minutes. Within this scattering of values, some patients were clearly outside the mean T 1/2 value (3.1 +/- 1 hours) due to a particularly fast or slow metabolisation of the drug. In patients with nephrotic syndrome no correlation was found between pharmacokinetic values and criteria of clinical effectiveness, such as the time and dosage required to obtain remissions and the duration of these remissions. Hypoalbuminaemia had no influence on the metabolism of prednisolone. In contrast, there was a correlation between pharmacokinetic values and side-effects, since patients who presented with side-effects also had a significantly greater area under plasma concentration versus time curves. This pharmacokinetic test may be used when corticosteroids produce unusual or unexplainable therapeutic results or adverse reactions.

Child↗

Role of interferon in leukocyte histamine release caused by common respiratory viruses.

Asthmatic attacks are often precipitated by viral respiratory infections. The mechanism of virus-induced asthma is still unclear. Interferon could be an important mediator in virus-induced hypersensitivity reactions, because interferon is induced by some respiratory viruses, and it can enhance IgE-mediated histamine release in vitro. We studied the effect of common respiratory viruses, including both interferon inducers and non-interferon inducers, on IgE-mediated leukocyte histamine release. Leukocytes from healthy, nonallergic donors were exposed to different strains of respiratory viruses, and basophils were challenged with antibody to IgE to release histamine. We found that the viruses are capable of enhancing IgE-mediated histamine release in the presence or absence of interferon. Our results suggest that although interferon may play a role in virus-induced hypersensivity reactions, other mechanisms probably also play a significant role.

Basophils↗

Hemoglobinuria detection in 195 urology patients.

There is a definite need for the development of a specific and sensitive diagnostic test for the detection of hematuria in patients with bladder and kidney cancer. It is well established that hemoglobin in the urine may be indicative of bladder and/or kidney cancer as well as other types of lesions of the urinary tract. We have developed a specific and sensitive immunological assay for the detection of human hemoglobin in urine. This test has several important advantages over the currently used chemical tests. A mouse monoclonal antibody specific for human hemoglobin was produced and used in the development of a double-antibody biotinylated enzyme-linked immunosorbent assay (ELISA) that specifically detected hemoglobin in the urine of 195 urology patients. The results from this assay were compared with data from an evaluation of the same specimen using a polyclonal antibody biotinylated ELISA (PE) as well as a dipstick test in a blind screening study. The monoclonal antibody biotinylated ELISA (ME) possessed a much higher level of sensitivity and specificity over the dipstick test. In addition, we determined that monoclonal as well as polyclonal antibody can detect not only normal hemoglobin but also abnormal hemoglobins in urine. Of the total 195 urology patients in all diagnostic categories, the ME test was positive for detection of hemoglobin in 28 more patients (35% more) than were detected by the dipstick test. Importantly, four of these 28 patients detected by the ME but undetected by the dipstick were patients with bladder or kidney cancer.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Osteoclast-like cells grow in cultures of multipotent hematopoietic progenitors in thrombocytopenia and absent radii (TAR) syndrome.

Cultures of bone marrow multipotent hematopoietic progenitors were performed in a case of TAR syndrome and normal bone marrow. It was found that clones of large multinucleated cells formed after 2 weeks of cultures from the TAR bone marrow but not in that of control subjects of the same age. Those cells contained a tartrate-resistant acid phosphatase activity and were negative for both monocytes and megakaryocytic markers. The data suggest that the multinucleated cells have several characteristics of osteoclasts. It was also found that growth of multipotent and megakaryocytic colonies was reduced when compared with normal control subjects (36 and 24%, respectively). This new finding of osteoclast or osteoclast-like cells derived from cultures of bone marrow hematopoietic precursors in TAR syndrome is discussed in relation to the lack of megakaryocytic characteristics in this disorder.

Abnormalities, Multiple↗

Treatment of neuroleptic malignant syndrome with diphenhydramine.

A case report of a patient with neuroleptic malignant syndrome is described. Of note is the fact that both central and peripheral manifestations of the syndrome responded to diphenhydramine and suportive therapy alone. A brief review of therapy is also discussed.

Adult↗

EL-4 metastases in spleen and bone marrow suppress the NK activity generated in these organs.

The relationship between metastatic cells in the spleen and bone marrow of tumor-bearing mice and the NK activity generated in vitro by cells obtained from these organs was investigated. EL-4 lymphoma and B16 melanoma cells injected intraperitoneally into syngeneic mice (10(6) cells/animal) killed the recipients in 16 days. These tumors had a different metastatic profile: EL-4 metastasized to the spleen and bone marrow while B16 did not. The number of metastatic cells was evaluated by plating spleen or bone-marrow cells of tumor-bearing mice in agarose cultures; in parallel, the ability of spleen and bone-marrow cells to generate NK activity in vitro was assessed. The presence of 10(5) EL-4 cells/10(6) spleen or bone-marrow cells correlated with a total lack of NK activity in these organs; in contrast, no decrease in NK activity was evident in the spleen or bone marrow of B16-bearing mice. The removal of metastatic EL-4 cells (by antibody and complement) from the spleen or bone marrow did not rescue the NK activity. The lack of NK activity in spleen and bone marrow colonized by metastatic cells was not due to induction of a suppressor cell in the host. Metastatic EL-4 cells appeared to have a direct and irreversible suppressive effect on the generation of NK activity by spleen or bone marrow. A possible cause-effect relationship between metastatic colonization of lymphoid organs and suppression of local NK activity is considered.

Animals↗

Condyloma acuminatum: epidemiological, clinical and therapeutic aspects.

Condyloma acuminatum, CA or genital warts, are benign fibro-epithelial tumors with a predilection for moist environments, especially mucosal surfaces. This sexually transmitted disease (STD) is increasing rapidly in incidence. The lesions are associated with a number of human papillomavirus (HPV) types. Some HPV types are closely linked with genital (especially cervical) dysplasia and neoplasia. Treatment consists of such traditional modalities as podophyllin, cryotherapy or surgical excision and, more recently, administration of interferon (IFN).

Condylomata Acuminata↗

Patients with condyloma acuminatum exhibit decreased interleukin-2 and interferon gamma production and depressed natural killer activity.

Peripheral blood mononuclear cells were obtained from 20 untreated condyloma acuminatum patients and from an equal number of sex- and age-matched controls and assayed for cell surface antigen expression, natural killer activity, and lymphokine production. Patient peripheral blood mononuclear cells had significantly lower helper-to-suppressor T-cell ratios (Leu3/Leu2) (P less than 0.05) and significantly higher percentages of Leu 2+ Tac+ cells (activated suppressor/cytotoxic cells) (P less than 0.05) and Leu 2+ OKM1+ cells (suppressor cells) (P less than 0.01). Natural killer activity of condyloma acuminatum patients was significantly lower (P less than 0.05) than that of controls. Production of interleukin-2 and interferon gamma, but not interferon alpha, was significantly (P less than 0.01) decreased in condyloma acuminatum patients. There was an inverse correlation between the in vitro production of interleukin-2 and interferon gamma and the percentage of Leu 2+ OKM1+ cells (suppressor) (P less than 0.01). Thus, patients with condyloma acuminatum differ from controls by demonstrating decreased natural killer-cell activity, decreased production of lymphokines which enhance natural killer-cell activity (i.e., interferon gamma and interleukin-2), and an increased proportion of T cells with a suppressor phenotype.

Adult↗

Nondetectable levels of interferon gamma is a critical host defense during the first day of herpes simplex virus infection.

Previous studies have demonstrated the importance of IFN alpha/beta in resistance to primary viral infections. However, the role of IFN gamma in primary infections is unclear. The present studies were undertaken to determine whether IFN gamma induction was an important early host defense against primary HSV infection. The approach was to block the IFN gamma response with antibodies to IFN gamma prior to infection and at various times post-infection (p.i.). The data indicates that treatment of mice with anti-IFN gamma prior to infection enhanced mortality (89% vs 37%). Anti-IFNs given at various times post HSV challenge proved most effective within the first 24 h of infection. The above results suggest for the first time that IFN gamma mediates important host defense(s) early during primary HSV infection. Similar results were obtained using antibody to IFN alpha/beta.

Animals↗

Do the interferons act singly or in combination?

Our views of interferon production and action have evolved from the simple to the complex. We review evidence that interferon-gamma (IFN-gamma) may induce a portion of its antiviral activity through the induction of another interferon. This is shown by demonstrating IFN-alpha in the supernatant fluids of IFN-gamma-treated mouse cells and showing that, under certain conditions, the antiviral activity of IFN-gamma in mouse and human cells can be reduced by antibody to IFN-alpha or IFN-beta, respectively. Induction of mouse spleen, bone marrow, and peritoneal exudate cells also results in their production of IFNs-alpha and/or -beta. In addition, new preliminary data indirectly suggests the presence of IFN-gamma in poly(IC):poly(LC)-treated mouse cells. In both of these systems, the maximal antiviral activity appears to develop as a consequence of the induction of a second interferon.

Animals↗

Interferon review.

Although IFN proteins were recognized first for their potent antiviral properties, it has now been established that they may profoundly affect other vital cellular functions. The IFNs are divided into three main classes, alpha, beta, and gamma, and are defined by their differences in amino acid sequences, physicochemical properties, and induction by different agents from different cell types. The inducing agents include viruses, bacteria, bacterial products, polymers, low molecular weight compounds, and antigens or mitogens. Studies on the mechanisms of action of IFNs have mainly been focused on their antiviral actions. However, many of the facts revealed by these studies are equally relevant for understanding other actions of IFN. IFNs are extremely potent, they interact with specific receptors, and they induce the expression of specific genes, the products of which mediate their various actions. There is almost a complete lack of knowledge of what happens between the interaction of IFN with its receptor and induction of new RNA synthesis. However, we are beginning to understand how some of the IFN-inducible enzymes impair viral replication. The discovery of the dsRNA-dependent enzymes has implications beyond the IFN system. It is quite possible that they are used for other physiologic regulatory systems as well. The identities and functions of many other IFN-inducible proteins remain to be elucidated. Principally, IFNs alpha and beta are cytokines in that they may be produced by the cellular components of the immune system and have immunoregulatory effects on the cells of the immune system. These effects include enhancement of surface structures such as histocompatibility antigens, pleiotropic hormone-like effects, and stimulation or inhibition of the activities of a number of different effector cells such as B cells, T cells, macrophages, and natural killing cells. IFN levels may be below detection and yet mediate important biologic functions. Perhaps the most interesting IFN subtype regarding immunoregulation is IFN gamma, which is a product of T lymphocytes. Few drugs have stimulated as much research interest or clinical promise as the IFNs. Clinical trials in patients have shown most promise in coryza, herpes virus infections, papilloma virus tumors, hairy cell leukemia, multiple myeloma, and renal cell carcinoma. IFN gamma employed alone and in combination with IFN alpha may dramatically increase IFN's activity. IFN treatment combined with chemotherapy also may give enhanced antitumor activity.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Interferon-induced cytolysis correlates with the degree of transformation of epidermal cells.

The cytolytic activity of interferon (IFN) was evaluated for its ability to distinguish between paired sets of nontumorigenic/tumorigenic epidermal cells (JB-1/JB-8; D1/D11a) as well as a set consisting of nonpromotable, promotable, and tumorigenic epidermal cell lines (JB-6 clones 30, 21, and RT101). The viability of the cell types was measured in a microassay using histoplates. IFN-gamma and IFN-alpha/beta, when employed singly, demonstrated an equivalent and limited effect on the viability of all cell lines. Treatment of nontumorigenic and nonpromotable cell lines with the combination of IFN-gamma + IFN-alpha/beta also caused only a limited effect on cell viability, whereas treatment of tumorigenic and promotable cell lines with the combination of IFNs caused a marked decrease in cell viability. Thus, the cytolytic effect of IFNs employed in combination but not singly was discriminatory between tumorigenic and nontumorigenic cells as well as between promotable and nonpromotable cells. Addition of cytotoxic effector cells was found to have a relatively moderate effect on the survival of target cells that were treated with IFN-gamma or IFN-alpha/beta separately. Addition of cytotoxic effectors to target cells treated with the IFNs in combination had a discriminatory effect. Nontumorigenic and nonpromotable cells were moderately affected; the tumorigenic and the promotable cells, however, were markedly affected, resulting in their complete (or nearly complete) eradication. The results demonstrate that combination IFN treatment: has a discriminatory cytolytic effect on tumorigenic and promotable cells in contrast to their nontumorigenic and nonpromotable counterparts; and when added to cytotoxic effector cells can completely eradicate tumorigenic and promotable cells while having a significantly lesser effect on nontumorigenic and nonpromotable cells.

Animals↗

Fenbufen induced pure red cell aplasia in rheumatoid arthritis.

Pure red cell aplasia occurred after fenbufen administration in a patient with severe rheumatoid arthritis. In vitro studies were performed to determine the pathogenesis of the selective red cell aplasia. No cellular or humoral inhibitory mechanisms were demonstrated on growth of erythroid and multipotent bone marrow progenitors. Also, no direct effect of fenbufen alone or in combination with IgG and/or patient serum was found. It is possible that a metabolite of the drug formed from its metabolism was responsible for the aplasia and that the target marrow cell precursor affected is later than both erythroid bone marrow progenitors (BFU-E and CFU-E) and therefore not apparent in our studies. Recovery upon cessation of fenbufen suggests its implication in the pure red cell aplasia.

Aged↗