RESUMEN

Bisphosphonates are potent inhibitors of osteoclastic activity and reduce the disease-related skeletal complications when they are used in combination with chemotherapy in patients with multiple myeloma (MM). Pamidronate also inhibits apoptosis of primary osteoblastic cells and probably induces apoptosis on human MM cells and osteoclasts. It has been reported that interferon-alpha (IFN-alpha) decreases bone resorption and that low doses of IFN-alpha result in a significant increase in serum osteocalcin (OSC). The aim of this study was to determine the effects of pamidronate treatment on biochemical markers of bone resorption [cross-linked N-telopeptides of type I collagen (NTx)], bone formation [bone alkaline phosphatase (BAP) and OSC], disease activity [beta2-microglobulin, CRP, paraprotein], and interleukin-6 (IL-6) in patients with MM in plateau phase under IFN-alpha maintenance. The above parameters were evaluated in 28 patients (13 M, 15 F, median age 70 years) during maintenance treatment, before the addition of pamidronate and after 1, 3, 6, 9, 12, and 14 months of the combined therapy. The addition of pamidronate to maintenance treatment resulted in a significant reduction of NTx, IL-6, beta2-microglobulin, CRP from the 3rd month and paraprotein from the 6th month of treatment, whereas BAP and OSC were significantly increased from the 6th month. These changes continued during the 14-month follow-up of the combined treatment. Multivariate analysis showed a significant negative correlation between changes of BAP and OSC and the patients' age. The greater increase of the bone formation markers was observed in younger patients. These results suggest that, in addition to the inhibition of osteoclastic activity, pamidronate in combination with IFN-alpha was shown to induce bone formation in patients with MM in the plateau phase.

Asunto(s)

Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Difosfonatos/uso terapéutico , Interferón-alfa/uso terapéutico , Mieloma Múltiple/tratamiento farmacológico , Osteogénesis/efectos de los fármacos , Anciano , Anciano de 80 o más Años , Fosfatasa Alcalina/metabolismo , Biomarcadores/análisis , Biomarcadores/sangre , Biomarcadores/orina , Resorción Ósea/inducido químicamente , Resorción Ósea/prevención & control , Resorción Ósea/orina , Proteína C-Reactiva/análisis , Colágeno/orina , Colágeno Tipo I , Difosfonatos/administración & dosificación , Femenino , Humanos , Interferón-alfa/administración & dosificación , Masculino , Persona de Mediana Edad , Mieloma Múltiple/metabolismo , Mieloma Múltiple/patología , Estadificación de Neoplasias , Osteocalcina/sangre , Pamidronato , Paraproteinemias , Péptidos/orina , Inducción de Remisión , Microglobulina beta-2/sangre

RESUMEN

AIM: Bisphosphonates are potent inhibitors of osteoclastic activity and are used in the treatment of multiple myeloma (MM) in combination with chemotherapy. The effect of pamidronate on markers of bone resorption [cross-linked N-telopeptides of type I collagen (NTx)], markers of bone formation [serum alkaline phosphatase (BAP) and osteocalcin (OSC)], interleukin-6 (IL-6), beta2-microglobulin, CRP, paraprotein and disease-related pain and skeletal events has been evaluated in 62 newly diagnosed patients with MM. PATIENTS AND METHODS: The patients were randomly assigned to two groups: the first included 32 patients under chemotherapy and pamidronate (group I) and the second 30 patients on chemotherapy only (group II). Pamidronate was administered at a monthly dose of 90 mg iv, and the above parameters were evaluated at the beginning of this study and after 1, 3, 6, 9, 12 and 14 months of treatment. RESULTS: The addition of pamidronate to chemotherapy resulted in a significant reduction of NTx, IL-6 and paraprotein from the 3rd month and of beta2-microglobulin, CRP and pain from the 6th month of treatment. No changes of NTx, IL-6, beta2-microglobulin, CRP or skeletal events were observed in patients of group II, while paraprotein was significantly reduced after 6 months of treatment. The differences in NTx, IL-6, paraprotein and beta2-microglobulin were statistically significant between the two groups. Multivariate analysis revealed a significant correlation between changes of NTx, changes of IL-6 in both groups and reduction of pain and paraprotein in group I. CONCLUSIONS: These results suggest that pamidronate may have a synergistic action with chemotherapy in decreasing osteoclastic activity, in reducing markers of myeloma activity and myeloma related pain and in improving the quality of life in patients with MM.

Asunto(s)

Remodelación Ósea/efectos de los fármacos , Difosfonatos/farmacología , Mieloma Múltiple/complicaciones , Mieloma Múltiple/tratamiento farmacológico , Anciano , Fosfatasa Alcalina/orina , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Protocolos de Quimioterapia Combinada Antineoplásica/toxicidad , Biomarcadores/orina , Resorción Ósea/tratamiento farmacológico , Resorción Ósea/etiología , Resorción Ósea/orina , Proteína C-Reactiva/orina , Colágeno/orina , Colágeno Tipo I , Difosfonatos/administración & dosificación , Difosfonatos/toxicidad , Evaluación de Medicamentos , Femenino , Humanos , Interleucina-6/orina , Masculino , Persona de Mediana Edad , Mieloma Múltiple/metabolismo , Análisis Multivariante , Osteocalcina/orina , Dimensión del Dolor/efectos de los fármacos , Pamidronato , Paraproteínas/orina , Péptidos/orina , Factores de Tiempo , Microglobulina beta-2/orina

RESUMEN

Surveillance data on 12,944 bacterial isolates derived from nosocomial infections, reported to the Department of Microbiology and Infectious Diseases of the Hellenic Air Force and VA General Hospital over a 9-year period (1986-1994), were analyzed by the use of a microbial infection control software system. Overall, the isolation rate of Escherichia coli decreased from 25.2% in 1986 to 18.2% in 1994 and Proteus spp. from 5.3 to 2.6%. Remarkably, Pseudomonas spp. increased from 7.2 to 11.3%, Enterobacter spp. from 1.6 to 5.1%, Klebsiella spp. from 5.9 to 7.8% and Enterococcus spp. from 3 to 7.4%. Interestingly, the above phenomenon was paralleled by a significant increase in resistance rate to various antibiotics. Specifically, Staphylococcus aureus and coagulase-negative staphylococci, though they did not display any significant variation in isolation rates, showed an alarming increase in resistance rate to oxacillin, from 11 and 21% in 1986 to 51 and 75% in 1994, respectively. Enterococcus spp. sensitivity to vancomycin remained unlatered at 90%. The above-mentioned serious shift towards more resistant bacteria should be a matter of consideration.

Asunto(s)

Bacteriemia/microbiología , Infección Hospitalaria/microbiología , Infecciones por Enterobacteriaceae/microbiología , Hospitales Militares , Infecciones por Klebsiella/microbiología , Infecciones por Pseudomonas/microbiología , Farmacorresistencia Microbiana , Grecia , Hospitales con 300 a 499 Camas , Humanos , Pruebas de Sensibilidad Microbiana , Infecciones del Sistema Respiratorio/microbiología , Infección de la Herida Quirúrgica/microbiología , Infecciones Urinarias/microbiología

RESUMEN

The significance of Streptococcus agalactiae as an aetiological agent in vaginitis was evaluated. A total of 6226 samples from women who presented with vaginal symptoms was examined. The presence of >10 leucocytes/high-power field (h.p.f.) was taken to be the criterion of active infection. S. agalactiae was isolated from 10.1% of these samples. The isolation rates of other common pathogens such as Candida spp., Gardnerella vaginalis and Trichomonas spp. were 54.1%, 27.2% and 4.2%, respectively, in the same group of patients. In contrast, the isolation rates of these micro-organisms in the group of patients who had no infection (<10 leucocytes/h.p.f.) were 4.2%, 38.3%, 33% and 0.5%, respectively. In the majority of samples from which S. agalactiae was isolated, it was the sole pathogen isolated (83%) and its presence was associated with an inflammatory response in 80% of patients. Furthermore, the relative risk of vaginal infection with S. agalactiae (2.38) in patients with purulent vaginal discharge was greater than that of Candida spp. infection (1.41) and lower than that of Trichomonas spp. infection (8.32). These data suggest that S. agalactiae in symptomatic women with microscopic evidence of inflammation should be considered a causative agent of vaginitis.

Asunto(s)

Infecciones Estreptocócicas/microbiología , Streptococcus agalactiae/patogenicidad , Vaginosis Bacteriana/etiología , Vaginosis Bacteriana/microbiología , Adolescente , Adulto , Estudios de Evaluación como Asunto , Femenino , Humanos , Persona de Mediana Edad , Serotipificación , Streptococcus agalactiae/clasificación , Streptococcus agalactiae/aislamiento & purificación

RESUMEN

We have proposed that significant subsets of individuals with IgA deficiency (IgA-D) and common variable immunodeficiency (CVID) may represent polar ends of a clinical spectrum reflecting a single underlying genetic defect. This proposal was supported by our finding that individuals with these immunodeficiencies have in common a high incidence of C4A gene deletions and C2 rare gene alleles. Here we present our analysis of the MHC haplotypes of 12 IgA-D and 19 CVID individuals from 21 families and of 79 of their immediate relatives. MHC haplotypes were defined by analyzing polymorphic markers for 11 genes or their products between the HLA-DQB1 and the HLA-A genes. Five of the families investigated contained more than one immunodeficient individual and all of these included both IgA-D and CVID members. Analysis of the data indicated that a small number of MHC haplotypes were shared by the majority of immunodeficient individuals. At least one of two of these haplotypes was present in 24 of the 31 (77%) immunodeficient individuals. No differences in the distribution of these haplotypes were observed between IgA-D and CVID individuals. Detailed analysis of these haplotypes suggests that a susceptibility gene or genes for both immunodeficiencies are located within the class III region of the MHC, possibly between the C4B and C2 genes.

Asunto(s)

Agammaglobulinemia/genética , Deficiencia de IgA , Complejo Mayor de Histocompatibilidad , Secuencia de Bases , Southern Blotting , ADN , Femenino , Haplotipos , Humanos , Masculino , Datos de Secuencia Molecular , Linaje , Polimorfismo de Longitud del Fragmento de Restricción

RESUMEN

IgA deficiency and common variable immunodeficiency are heritable disorders that can occur within the same family. Both immunodeficiencies are characterized by arrests in B-cell differentiation that vary in the extent of the immunoglobulin isotypes involved. A high frequency of major histocompatibility complex supratypes associated with a null allele of the gene encoding the C4A isotype of complement component C4 has been observed in IgA-deficient individuals. In search of a genetic linkage between the two immunodeficiencies, we examined the major histocompatibility complex (MHC) class III genes encoding complement components C2, C4A, and C4B and steroid 21-hydroxylase in addition to the HLA serotypes in individuals with either common variable immunodeficiency or IgA deficiency. Twelve of 19 patients with common variable immunodeficiency (63%, P less than 0.001) and 9 of 16 patients with IgA deficiency (56%, P less than 0.01) had rare C2 alleles and/or C4A and 21-hydroxylase A deletions, whereas these gene features were seen in only 5 of 34 healthy individuals (15%) in the control group. Nine of 11 patients with C4A deletion had an HLA haplotype consistent with the MHC supratype HLA-A1, Cw7, B8, C4AQ0, C4B1, BfS, DR3 previously found to be associated with IgA deficiency. The data support the hypothesis that common variable immunodeficiency and IgA deficiency are related disorders, susceptibility to which is determined by a gene(s) within or near the MHC class III gene region on chromosome 6.

Asunto(s)

Disgammaglobulinemia/genética , Deficiencia de IgA , Síndromes de Inmunodeficiencia/genética , Complejo Mayor de Histocompatibilidad , Polimorfismo Genético , Alelos , Antígenos CD/análisis , Antígenos CD/genética , Linfocitos B/inmunología , Proteínas del Sistema Complemento/genética , Disgammaglobulinemia/complicaciones , Disgammaglobulinemia/inmunología , Femenino , Genes MHC Clase I , Genes MHC Clase II , Humanos , Inmunoglobulina A/genética , Síndromes de Inmunodeficiencia/complicaciones , Síndromes de Inmunodeficiencia/inmunología , Masculino , Polimorfismo de Longitud del Fragmento de Restricción , Receptores de Antígenos de Linfocitos B/análisis , Receptores de Antígenos de Linfocitos B/genética , Valores de Referencia , Linfocitos T/inmunología