RESUMO
In 2015, the Nobel Committee for Physiology or Medicine, in its only award for treatments of infectious diseases since six decades prior, honoured the discovery of ivermectin (IVM), a multifaceted drug deployed against some of the world's most devastating tropical diseases. Since March 2020, when IVM was first used against a new global scourge, COVID-19, more than 20 randomized clinical trials (RCTs) have tracked such inpatient and outpatient treatments. Six of seven meta-analyses of IVM treatment RCTs reporting in 2021 found notable reductions in COVID-19 fatalities, with a mean 31% relative risk of mortality vs. controls. During mass IVM treatments in Peru, excess deaths fell by a mean of 74% over 30 days in its ten states with the most extensive treatments. Reductions in deaths correlated with the extent of IVM distributions in all 25 states with p < 0.002. Sharp reductions in morbidity using IVM were also observed in two animal models, of SARS-CoV-2 and a related betacoronavirus. The indicated biological mechanism of IVM, competitive binding with SARS-CoV-2 spike protein, is likely non-epitope specific, possibly yielding full efficacy against emerging viral mutant strains.
RESUMO
Many advances have recently been made in the development of chemotherapeutic agents for bacterial infections. As a consequence of problematic antimicrobial-resistant bacteria, research is now directed towards narrow-spectrum agents rather than broad-spectrum agents. Further, orally active agents have always been desirable, but today's cost-saving environment, in line with a desire to minimize treatment costs, values reduced administration costs and keeping patients out of the hospital. There has been a recent increase in research into orally active antibacterial agents, such as carbapenems and cephalosporins, and non-glycopeptide natural products.
Assuntos
Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Bactérias/efeitos dos fármacos , Infecções Bacterianas/tratamento farmacológico , Administração Oral , Antibacterianos/economia , Antibacterianos/farmacocinética , Infecções Bacterianas/microbiologia , Ensaios Clínicos como Assunto , Resistência Microbiana a Medicamentos , HumanosRESUMO
Together, interleukin-1 alpha (IL-1 alpha) and IL-1 beta primed human neutrophils for enhanced release of superoxide (O2-) stimulated by chemotactic peptide, chemokine, and plant lectin, and alone, each triggered O2- release in a dose-dependent manner. The maximal priming and triggering effect was obtained by high concentrations (50 to 500 ng/mL) of IL-1 alpha or IL-1 beta, though IL-1 beta was more effective than IL-1 alpha at suboptimal concentrations. Priming effect of IL-1 was very rapid and maximal within 10 minutes, whereas O2- release triggered by IL-1 was gradual and continued for 90 to 120 minutes. Combined stimulation of human neutrophils with IL-1 plus granulocyte colony-stimulating factor (G-CSF) or granulocyte-macrophage CSF (GM-CSF) resulted in additive priming effect, and combined stimulation of neutrophils with IL-1 plus G-CSF, GM-CSF, or tumor necrosis factor (TNF) resulted in additive triggering effect, even when the maximal concentration of each cytokine was used. These priming and triggering effects of IL-1 alpha and IL-1 beta on the respiratory burst in human neutrophils were completely inhibited by IL-1 receptor antagonist (IL-1ra). Furthermore, only the net effect of IL-1 was inhibited by IL-1ra, even when human neutrophil was stimulated with IL-1 plus other cytokines to release O2-. Present results indicate that IL-1 does stimulate the respiratory burst activity in human neutrophils via receptor-mediated mechanism and suggest that the post-IL-1-receptor signaling pathways linked to the activation system of the respiratory burst are independent from those utilized by other cytokines in human neutrophils.
Assuntos
Interleucina-1/farmacologia , Neutrófilos/fisiologia , Receptores de Interleucina-1/antagonistas & inibidores , Explosão Respiratória/efeitos dos fármacos , Adulto , Citocinas/farmacologia , Humanos , Ativação de Neutrófilo/efeitos dos fármacos , Transdução de SinaisRESUMO
The neutrophil superoxide (O2-)-producing capacity in 57 patients with chronic myeloproliferative disorders (MPDs) and eight patients with chronic myelomonocytic leukemia (CMML) was investigated. O2- release in neutrophils stimulated by chemotactic peptide was markedly increased in all types of chronic MPD, including chronic myelogenous leukemia in both chronic phase and blastic crisis, polycythemia vera, and essential thrombocythemia, but was normal in CMML, which is thought to be a myelodysplastic disorder rather than MPD. Increase in O2(-)-producing capacity in MPD was also observed when other receptor-mediated agonists such as interleukin-8 and concanavalin A were used, but not when phorbol ester, a direct activator of protein kinase C, was used as the triggering agonist of O2- release. Priming effects of granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage CSF (GM-CSF), and tumor necrosis factor (TNF) on chemotactic peptide-induced O2- release was observed in all patients with MPD and CMML, though fold enhancement of priming effects was much less in MPD compared with normal subjects. In addition, the priming effects of TNF were less than those of GM-CSF in 10 cases, whereas the priming effects of TNF were consistently and markedly greater than those of GM-CSF in normal subjects. Tyrosine phosphorylation of 42-kDa protein stimulated by G-CSF, GM-CSF, and TNF was observed in CML neutrophils to be identical to that in normal neutrophils. Present results indicate specific potentiation of the receptor-mediated route of signaling that is linked to the respiratory burst and downregulated responsiveness to cytokines in neutrophils in patients with all types of chronic MPD, suggesting in vivo priming of patient neutrophils via certain mechanism by cytokines or related stimuli in these hematological disorders.
Assuntos
Citocinas/farmacologia , Transtornos Mieloproliferativos/metabolismo , Neutrófilos/metabolismo , Receptores de Superfície Celular/metabolismo , Explosão Respiratória , Transdução de Sinais , Superóxidos/metabolismo , Concanavalina A/farmacologia , Humanos , Interleucina-8/farmacologia , Transtornos Mieloproliferativos/patologia , Ativação de Neutrófilo/efeitos dos fármacos , Neutrófilos/patologia , Receptores de Superfície Celular/agonistasRESUMO
Tumor necrosis factor (TNF), like granulocyte-macrophage colony-stimul ating factor (GM-CSF), rapidly primed human monocytes for enhanced release of superoxide (O-2) stimulated by receptor-mediated agonists, N-formyl-methionyl-leucyl-phenylalanine (FMLP) and concanavalin A (Con A), but not by phorbol myristate acetate (PMA), which bypasses the receptors to stimulate the cells. The optimal priming was obtained by pretreatment of suspended monocytes with 10 U/mL TNF for 10 minutes at 37 degrees C. The potency of the maximal priming effect was TNF> GM-CSF, and the combined effect of TNF and GM-CSF was greater than that of each cytokine alone. GM-CSF induced an increase in cytoplasmic pH but TNF did not. These findings suggest that TNF and GM-CSF activate monocytes through different mechanisms. TNF and GM-CSF by themselves never triggered O-2 release in suspended monocytes or monocytes adherent to endothelial cells, although both cytokines triggered massive release of O-2 in human neutrophils. In additions, TNF and GM-CSF induced tyrosine phosphorylation of a 42-kD protein in neutrophils but not in monocytes. These findings suggest that the TNF-receptor- or GM-CSF-receptor-mediated signaling pathways for triggering O-(2) release is active in neutrophils but inactive or defective in monocytes. TNF also enhanced phagocytosis of sialidase-treated autologous erythrocytes by monocytes, and this effect was further potentiated in the presence of autologous fresh serum. The significant enhancement of erythrophagocytosis was obtained at 1 U/mL TNF. At this concentration of TNF, the expression of C3bi-receptor (CD11b/CD18) was upregulated. These findings show that TNF rapidly primes human monocytes for enhanced release of O-(2) and erythrophagocytosis and suggest that TNF activates monocytes through autocrine or paracrine mechanisms at the inflammatory sites inasmuch as TNF is primarily produced by activated monocytes/macrophages.
Assuntos
Monócitos/fisiologia , Superóxidos/metabolismo , Fator de Necrose Tumoral alfa/fisiologia , Adulto , Complemento C3b/metabolismo , Concanavalina A/farmacologia , Citoplasma/fisiologia , Eritrócitos , Fator Estimulador de Colônias de Granulócitos e Macrófagos/farmacologia , Humanos , Concentração de Íons de Hidrogênio , N-Formilmetionina Leucil-Fenilalanina/farmacologia , Fagocitose , Fosfotirosina/metabolismo , Receptores de Adesão de Leucócito/metabolismo , Proteínas Recombinantes , Acetato de Tetradecanoilforbol/farmacologia , Fatores de TempoRESUMO
Granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin (IL) -3 induced tyrosine phosphorylation of 92-kDa protein in normal human monocytes. We identified this 92-kDa protein as STAT5, but not as STATs1, 3, and 6 nor c-fes and vav protooncogene products, and demonstrated its translocation to the nucleus, enhancement of specific DNA binding capacity, and potentiation of trancriptional activity by GM-CSF. N-formyl-methionyl-leucyl-phenylalanine (FMLP) and phorbol myristate acetate (PMA) induced tyrosine phosphorylation of 42- and 44-kDa proteins, which were identified as extracellular signal-regulated kinase (ERK), in human monocytes. In marked contrast to neutrophils and MO7e cells, GM-CSF did not induce tyrosine phosphorylation and activation of ERK in monocytes. Among upstream signaling molecules of ERK, Shc was constitutively associated with Grb2 and was not tyrosine-phosphorylated by GM-CSF and FMLP, and Sos1 and c-Raf-1 were not phosphorylated by GM-CSF, IL-3, TNF, and FMLP in monocytes, whereas all these signaling molecules were affected and/or utilized by GM-CSF in MO7e cells. In contrast to neutrophils, p38 was constitutively phosphorylated and agonist-dependent phosphorylation and activation was not detected in human monocytes. Superoxide release stimulated by FMLP was inhibited partially by PD98059 or SB203580, a specific inhibitor of ERK or p38 pathway, and was almost completely inhibited by the combination of both inhibitors, whereas PMA-induced superoxide release was resistant to these two inhibitors in monocytes. PD98059 inhibited GM-CSF-dependent proliferation of MO7e cells. Present results indicate trancriptional roles of STAT5 and functional roles of ERK and/or p38 in normal human monocytes stimulated by physiological receptor-mediated agonists GM-CSF and FMLP. Possible roles of ERK in proliferation of transformed cells were also suggested.
Assuntos
Citocinas/farmacologia , Proteínas do Leite , Monócitos/metabolismo , Neutrófilos/metabolismo , Transdução de Sinais , Adulto , Proteínas Quinases Dependentes de Cálcio-Calmodulina/antagonistas & inibidores , Proteínas Quinases Dependentes de Cálcio-Calmodulina/metabolismo , Linhagem Celular , Núcleo Celular/metabolismo , DNA/metabolismo , Proteínas de Ligação a DNA/metabolismo , Inibidores Enzimáticos/farmacologia , Fator Estimulador de Colônias de Granulócitos e Macrófagos/farmacologia , Humanos , Interleucina-3/farmacologia , N-Formilmetionina Leucil-Fenilalanina/farmacologia , Fosfotirosina/metabolismo , Proteínas Recombinantes/farmacologia , Fator de Transcrição STAT5 , Superóxidos/metabolismo , Acetato de Tetradecanoilforbol/farmacologia , Transativadores/metabolismoRESUMO
Cytochalasin B, despite its potent enhancing effect on superoxide (O2-) release triggered by N-formyl-methionyl-leucyl-phenylalanine (FMLP) and many other agonists, significantly inhibited O2- release triggered by interleukin 8 (IL-8) and platelet-activating factor in human neutrophils. Cytochalasin B also enhanced changes in membrane potential stimulated by FMLP but inhibited those stimulated by IL-8. Using IL-8 as a triggering agonist, we found that the priming effect of tumor necrosis factor (TNF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) on O2- release was slightly but significantly potentiated by cytochalasin B. O2- release triggered by TNF and GM-CSF was completely abolished by cytochalasin B. In contrast to these diverse effects of cytochalasin B on O2- release, changes in cytoplasmic pH stimulated by FMLP, IL-8, TNF, and GM-CSF were not or were only minimally affected by cytochalasin B. Unlike human neutrophils, human monocytes stimulated by FMLP showed inhibition of O2- release and changes in membrane potential in response to cytochalasin B, and the priming effect of TNF and GM-CSF on O2- release in human monocytes was completely abolished by cytochalasin B. These findings indicate the diverse effects of cytochalasin B on phagocytes and suggest distinct regulatory mechanisms according to the functions, agonists, and cell types.
Assuntos
Citocalasina B/farmacologia , Explosão Respiratória/efeitos dos fármacos , Adulto , Fatores Quimiotáticos/farmacologia , Humanos , Monócitos/efeitos dos fármacos , Monócitos/fisiologia , Neutrófilos/efeitos dos fármacos , Neutrófilos/fisiologia , Superóxidos/metabolismoRESUMO
Tumor necrosis factor (TNF), granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF) rapidly primed human neutrophils for enhanced superoxide (O2-) release, and membrane depolarization stimulated by chemotactic peptide (N-formyl-methionyl-leucyl-phenylalanine), interleukin 8, concanavalin A (Con A) and ionomycin. Combined stimulation of human neutrophils with the optimal concentrations of TNF plus GM-CSF showed no additive or synergistic effects according to the subsequent stimuli and within the parameters tested. Particularly, a high synergistic priming effect of these two cytokines was observed when Con A was used as a triggering agonist of O2- release. The priming of human neutrophils with the optimal concentrations of TNF plus G-CSF, however, always resulted in the same effect as TNF alone. TNF and GM-CSF triggered O2- release directly in human neutrophils for prolonged time periods, and combined stimulation of human neutrophils with the optimal concentrations of TNF plus GM-CSF triggered an added amount of O2- release. TNF and GM-CSF by themselves induced an increase in cytoplasmic pH (intracellular alkalinization), an important signaling event for functional activation of neutrophils, though combined stimulation of human neutrophils with the optimal concentrations of the two cytokines had no additive effects on cytoplasmic pH. The present results show cooperative interaction between TNF and GM-CSF in their stimulatory effects on particular functions in human neutrophils, and these synergistic effects are probably mediated via a mechanism distal to or independent of intracellular alkalinization.
Assuntos
Concanavalina A/farmacologia , Fator Estimulador de Colônias de Granulócitos e Macrófagos/farmacologia , N-Formilmetionina Leucil-Fenilalanina/farmacologia , Neutrófilos/fisiologia , Explosão Respiratória/fisiologia , Fator de Necrose Tumoral alfa/farmacologia , Humanos , Estimulação QuímicaRESUMO
We investigated tyrosine phosphorylation of proteins in primary human leukemic cells stimulated by macrophage colony-stimulating factor (M-CSF) in 60 patients with acute myeloid leukemia (AML) and 5 patients with chronic myelomonocytic leukemia and compared the findings for leukemic cells with those of normal human monocytes and bone marrow immature hematopoietic cells. M-CSF induced tyrosine phosphorylation of p140-200, p110, p60, p44, and p42 frequently, and that of p95 and p55 less frequently, in primary myeloid leukemic cells, whereas M-CSF-induced phosphorylation of proteins was not detected in the normal human hematopoietic cells tested. Of these phosphoproteins, p140-200 was phosphorylated in all patients who responded to M-CSF and was considered to be almost identical to Fms, a product of the c-fms proto-oncogene. M-CSF-induced tyrosine phosphorylation was observed frequently (89%) in AML of French-American-British class M4 and infrequently in all other subtypes of AML, including M5. In chronic myelomonocytic leukemia, M-CSF-induced protein phosphorylation was prominent in blast crisis but was not detected in the chronic phase. Both bone marrow immature cells and mature monocytes showed low responsiveness to M-CSF. These findings for responsiveness to M-CSF were correlated with the amount of Fms in each type of cell. We also identified tyrosine phosphorylation of Vav, Shc, and extracellular signal-regulated kinase by M-CSF in some cases. These findings clarified an M-CSF-specific pattern of protein tyrosine phosphorylation and the responsiveness to M-CSF of primary human myeloid cells. Particularly, enhanced phosphorylation responses to M-CSF and increased amounts of Fms protein were observed in restricted human hematopoietic cells with a premature myelomonocytic character.
Assuntos
Amidoidrolases , Leucemia Mieloide/patologia , Fator Estimulador de Colônias de Macrófagos/farmacologia , Proteínas de Neoplasias/metabolismo , Tirosina/metabolismo , Doença Aguda , Aminopeptidases/metabolismo , Técnicas de Cultura de Células , Células-Tronco Hematopoéticas/metabolismo , Humanos , Leucemia Mieloide/classificação , Leucemia Mielomonocítica Crônica/patologia , Proteínas de Neoplasias/efeitos dos fármacos , Fosforilação/efeitos dos fármacos , Proto-Oncogene Mas , Transdução de Sinais , Fator de Células-Tronco/farmacologiaRESUMO
We studied the biological features of eosinophils in a patient with chronic eosinophilic leukemia and a unique t(2:5)(p23;q35) translocation. Microscopic and cytochemical studies revealed no particular abnormalities, although more than 90% of the peripheral eosinophils had a density lighter than 1.080 g/ml. Clonogenic assay disclosed that myeloid progenitor cells possessed the translocation, although in vitro eosinophilopoiesis seemed normal, and there were also hematopoietic cells with a normal karyotype. In a surface marker study, EG1 was positive on 34.0% of the eosinophils, while EG2 positivity was only 0.5%. Eosinophilopoietic growth factors and adhesion molecules were virtually absent with the exception of GM-CSF and CD11b. Functional studies showed that chemotaxis for C5a was normal, although that for IL-2 or FMLP was attenuated. In addition, leukotriene C4 production was decreased while O2- production was intact. These findings indicated that our patient's eosinophils were not in an activated state despite their extreme hypodensity, and suggested that the leukemic eosinophils had slight defects of cellular function. These characteristics may have saved the patient from the multiple organ damage which occurs in typical hypereosinophilic syndrome.
Assuntos
Cromossomos Humanos Par 2/ultraestrutura , Cromossomos Humanos Par 5/ultraestrutura , Eosinófilos/patologia , Células-Tronco Neoplásicas/patologia , Translocação Genética , Adulto , Antígenos de Neoplasias/análise , Antígenos de Superfície/análise , Fatores Quimiotáticos/farmacologia , Quimiotaxia de Leucócito/efeitos dos fármacos , Terapia Combinada , Complemento C5a/farmacologia , Eosinófilos/efeitos dos fármacos , Foliculite/etiologia , Fator Estimulador de Colônias de Granulócitos e Macrófagos/farmacologia , Humanos , Hidroxiureia/uso terapêutico , Fatores Imunológicos/uso terapêutico , Interferon-alfa/uso terapêutico , Interleucinas/farmacologia , Leucotrieno C4/biossíntese , Masculino , N-Formilmetionina Leucil-Fenilalanina/farmacologia , Proteínas de Neoplasias/biossíntese , Células-Tronco Neoplásicas/efeitos dos fármacos , Oxigênio/metabolismo , Acetato de Tetradecanoilforbol/farmacologia , Ensaio Tumoral de Célula-TroncoRESUMO
The aminoglycoside phosphotransferase of Pseudomonas aeruginosa 21-75 was purified by affinity chromatography using dibekacin-Sephadex 4B or lividomycin A-Sepharose 4B followed by DEAE Sephadex A-50 chromatography. It had activities of both the known aminoglycoside 3'-phosphotransferases I and II, and transferred phosphate from ATP to the 3'-hydroxyl group of kanamycin A, ribostamycin and butirosin A and 5-hydroxyl group of lividomycin A. This enzyme was designated aminoglycoside 3'-phosphotransferase III. It showed strong substrate inhibition by kanamycin A and ribostamycin when their concentration exceeded 6 muM. Purification and characterization of this enzyme are reported.
Assuntos
Fosfotransferases , Aminoglicosídeos , Sulfato de Butirosina/farmacologia , Canamicina/farmacologia , Paromomicina/análogos & derivados , Paromomicina/farmacologia , Fosfotransferases/antagonistas & inibidores , Fosfotransferases/isolamento & purificação , Pseudomonas aeruginosa/enzimologia , Ribostamicina/farmacologiaRESUMO
Aminoglycoside 3'-phosphotransferases I and II in three strains of Pseudomonas aeruginosa were studied in comparison with those in two strains of R factor-carrying Escherichia coli. The strain TI-13 of P. aeruginosa produced the former and strain H-9 the latter. Strain B-13 produced the both enzymes. The 3'-phosphotransferases of type I in P. aeruginosa TI-13, B-13 and E. coli K12 J5 R11-2 were different from each other in chromatographic behavior, molecular weight, pH optimum, and Ii. The 3'-phosphotransferase of type II in P. aeruginosa H-9 and E. coli JR66/W677 showed the same behavior.
Assuntos
Fosfotransferases/biossíntese , Pseudomonas aeruginosa/enzimologia , Aminoglicosídeos , Sulfato de Butirosina/biossíntese , Cromatografia de Afinidade , Escherichia coli/enzimologia , Concentração de Íons de Hidrogênio , Canamicina/biossíntese , Peso Molecular , Neomicina , Paromomicina/análogos & derivados , Paromomicina/biossínteseRESUMO
Mongolian gerbils (Meriones unguiculatus) serve as an valuable model animal for several infectious diseases of medical and veterinary importance. Reagents available for characterization of the immune response of Mongolian gerbils are strictly limited. We describe three novel murine monoclonal antibodies (mAbs) to dendritic cells of Mongolian gerbils. These include HUSM-M.g.11 of IgG2b isotype, HUSM-M.g. 20 of IgG2a isotype, and HUSM-M.g.30 of IgG1 isotype. All of these mAbs had an identical profile of immunohistochemical reactions with various tissues taken from immune-naive Mongolian gerbils, and were intensively expressed on dendritic cells, including epidermal Langerhans cells, B-cell follicles, and the thymic reticulum. Positive reactions of the epidermis and intestinal mucosa with these mAbs were induced by cutaneous or intestinal infections with parasites. Competitive enzyme-linked immunosorbent assay and immunoblot analysis (western blotting) indicated that all of these mAbs recognize an identical peptide epitope on a molecule with approximate molecular mass of 29 kDa. These data suggest that the mAbs recognize major histocompatibility complex class-II molecules of gerbils. Use of described mAbs would facilitate characterization of immune responses as well as investigations on host responses to infections of medical and veterinary importance, using the gerbil model.
Assuntos
Anticorpos Monoclonais , Células Dendríticas/imunologia , Gerbillinae/imunologia , Animais , Western Blotting , Ensaio de Imunoadsorção Enzimática , Gerbillinae/anatomia & histologia , Antígenos de Histocompatibilidade Classe II/imunologia , Imuno-Histoquímica , Camundongos , Camundongos Endogâmicos BALB C , Linfócitos T/imunologiaRESUMO
In the winter of 1998-1999, we collected parasitological data from 54 wild carnivores in the north-western part of Tohoku region, Japan. These consisted of 38 martens (Martes melampus melampus), 14 raccoon dogs (Nyctereutes procyonoides viverrinus) and 2 foxes (Vulpes vulpes japonica). Collected helminth parasites were 11 nematode, 10 trematode, 3 cestode, and a single acanthocephalan species, including 5 hitherto unknown species for this research area or the mainland of Japan (Honshu). Mesocestoides paucitesticulus was for the first time recorded from martens as well as from carnivores distributed in Honshu. Brachylaima tokudai originally recorded from Urotrichus talpoides in the central part of Honshu was for the first time found from a raccoon dog.
Assuntos
Carnívoros/parasitologia , Helmintíase Animal/parasitologia , Helmintos/isolamento & purificação , Acantocéfalos/isolamento & purificação , Animais , Cestoides/isolamento & purificação , Feminino , Japão , Masculino , Nematoides/isolamento & purificação , Trematódeos/isolamento & purificaçãoRESUMO
Laryngeal lymphangioma is extremely rare. We have been able to find only seventeen cases reported in world literature. We recently, treated a patient suffering from laryngeal lymphangioma in our department. The female patient, aged 36, complained of hoarseness for several months. Indirect laryngoscopy revealed a growth on her right false vocal cord. Under general anesthesia, tracheostomy and laryngofissure were performed for removal of this neoplasm. The tumor was microscopically diagnosed as lymphangioma. The symptoms disappeared after surgery and there has been no recurrence. The pertinent literature on this rare disease is reviewed.
Assuntos
Neoplasias Laríngeas/cirurgia , Linfangioma/cirurgia , Adulto , Humanos , Neoplasias Laríngeas/patologia , Laringe/patologia , Linfangioma/patologia , Masculino , TraqueotomiaRESUMO
The following results were obtained in pharmacokinetic, bacteriological and clinical investigations of a cephem antibiotic for injection, cefozopran (SCE-2787, CZOP), administered to neonates and premature infants. 1. Pharmacokinetics (1) Half-lives (T 1/2's) of CZOP in 0-day-old (less than 24 hours after birth) neonates and premature infants were longer than those in 1-day-old or older infants. When half-lives were compared between 0-day-old neonates and 0-day-old premature infants, longer half-lives were observed in premature infants. (2) When CZOP was intravenously administered to 1-day-old or older neonates and premature infants at a dose of 20 mg/kg, no differences were noted in blood concentrations between neonates and premature infants from 30 minutes to 6 hours after administration as well as T 1/2's. (3) Blood concentration of CZOP administered at doses of 10, 20 and 40 mg/kg were dose-dependent. (4) Urine excretion rates of CZOP administered to 1-day-old or older neonates and premature infants were approximately 30 to 60% in the first 6 hours after administration. Urine excretion rates in 0-day-old neonates and premature infants were low. 2. Clinical results (1) Of a total of 136 cases to which CZOP was administered, clinical efficacy evaluation was possible in 96 cases, and safety evaluation in 132 cases. (2) The clinical efficacy rates were 78.6% (22/28) in 28 cases in which causative organisms were detected (Group A), and 97.1% (66/68) in 68 cases in which no such organisms were detected (Group B), with the total efficacy rate (Groups A and B) of as high as 91.7% (88/96). (3) Bacteriological evaluations were made with 33 strains isolated from the 28 cases of Group A. Elimination rates for Gram-positive and Gram-negative bacteria were 88.2% (15/17) and 92.3% (12/13), respectively, with the total elimination rate of 90.0% (27/30). No microbial substitution was noted. (4) As an adverse reaction, diarrhea was noted in one case (0.8%). Abnormal laboratory test values were noted in 15 cases (12.3%) including eosinophilia, elevated GPT, and elevated gamma-GTP. All of these abnormalities were transitory, and none of them critical. As a result of above pharmacokinetic and clinical investigations, CZOP is considered to be highly useful in the treatment of indicated infections in neonates and premature infants. It appears that 20 mg/kg of CZOP can be administered by intravenous injection or intravenous drip infusion to neonates and premature infants aged 0-day (less than 24 hours after birth) once or twice daily, to those aged 1 (24 or more hours after birth) to 7 days twice or three times daily, and to those aged 8 or more days three to four times daily, and that the dose can be increased up to 40 mg/kg in cases of critical or intractable infections.
Assuntos
Cefalosporinas/uso terapêutico , Doenças do Prematuro/tratamento farmacológico , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/microbiologia , Cefalosporinas/farmacocinética , Cefalosporinas/farmacologia , Feminino , Humanos , Recém-Nascido , Masculino , CefozopranRESUMO
In order to evaluate the usefulness of MRI in estimating bone marrow cellularity, we performed MRI of the lumbar spine in two patients with severe aplastic anemia, before and after successful treatment with antithymocyte globulin (ATG). Case 1, a 25-year-old man with idiopathic aplastic anemia, was treated with ATG 6 months after the onset. One month after treatment, his peripheral blood count and bone marrow cellularity recovered, and the MRI bone marrow pattern became normal. Case 2, a 78-year-old woman with drug-induced aplastic anemia, was treated with ATG 4 months after the onset. Three months after treatment, her peripheral blood count improved. Five months after treatment, her bone marrow cellularity recovered and the MRI bone marrow pattern was normal for her age. Seven months after treatment, when her peripheral blood count was almost normal, we observed hypercellular bone marrow restoration at the periphery of the vertebrae. MRI seems to be an effective method of evaluating bone marrow recovery in aplastic anemia.
Assuntos
Anemia Aplástica/terapia , Soro Antilinfocitário/uso terapêutico , Medula Óssea/patologia , Adulto , Idoso , Anemia Aplástica/diagnóstico , Feminino , Humanos , Imageamento por Ressonância Magnética , MasculinoRESUMO
Two patients with essential thrombocythemia were successfully treated by administering native alpha-interferon (alpha-IFN). One patient was a 38-year-old man in whom thrombocytosis was found accidentally. His platelet count on admission was 880,000/microliters and megakaryocytes increased. Three million units of alpha-IFN was administered subcutaneously everyday, and the platelet count decreased gradually to about 500,000/microliters within 2 weeks. The other patient was a 66-year-old woman who visited our hospital complaining of tenderness and swelling of the fingertips. Her platelet count was 1,610,000/microliters, and megakaryocytes increased and showed abnormal morphology. Six million units of alpha-IFN was administered subcutaneously every other day. The tenderness and swelling of the fingertips disappeared soon after the beginning of alpha-IFN administration. The platelet count decreased to about 500,000/microliters within 10 days, but she developed itching of the skin over the entire body. Therefore, alpha-IFN treatment was discontinued. It was suggested that alpha-IFN suppresses not only the maturation and proliferation of the progenitors of megakaryocytes but also the production of platelets from megakaryocytes. Administration of alpha-IFN should be considered in treating patients with essential thrombocythemia, because effects appear soon and alpha-IFN does not induce a second malignancy.
Assuntos
Interferon-alfa/uso terapêutico , Trombocitemia Essencial/terapia , Adulto , Idoso , Feminino , Humanos , Masculino , Contagem de Plaquetas , Trombocitemia Essencial/sangueRESUMO
A 62-year-old man was admitted to our hospital because of generalized lymphadenopathy, fever and skin eruptions. The histology of the right cervical lymph nodes showed immunoblastic lymphadenopathy (IBL)-like T cell lymphoma. His laboratory data were as follows: hemoglobin concentration 7.1 g/dl, red blood cells 1,850,000/microliters, reticulocytes 4.2%, total bilirubin 2.6mg/dl, direct bilirubin 0.5mg/dl, haptoglobin less than 10mg/dl, positive Coombs test. He was diagnosed as having IBL-like T cell lymphoma accompanied by autoimmune hemolytic anemia. He was successfully treated with combination chemotherapy (Pro-MACE), and lymph node swelling and hemolytic anemia disappeared. He has been in complete remission for more than 1 year.
Assuntos
Anemia Hemolítica Autoimune/complicações , Linfoma de Células T/complicações , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ciclofosfamida/administração & dosagem , Doxorrubicina/administração & dosagem , Etoposídeo/administração & dosagem , Humanos , Linfadenopatia Imunoblástica , Linfoma de Células T/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Prednisolona/administração & dosagem , Indução de RemissãoRESUMO
Obstructive Sleep Apnea Syndrome (OSAS) is children is commonly caused by upper airway obstruction, such as that caused by adeno-tonsillar hypertrophy. We report a rare case of SAS due to a nasopharyngeal tumor. The patient was a 10-year-old boy who complained of snoring and sleep apnea. The tumor was found in the nasopharynx and mesopharyngeal space. We diagnosed this case as OSAS by overnight sleep study (Apnea Hypopnea Index: AHI = 19.67). The tumor was removed under general anesthesia. Histopathology revealed features of nasopharyngeal angiofibroma. After removal of the tumor, his symptoms resolved completely. A follow-up overnight sleep study confirmed resolution of OSAS. At the last follow up, conducted 17 months after the operation there were no signs of tumor recurrence.