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1.
J Addict Med ; 16(6): 725-729, 2022.
Article in English | MEDLINE | ID: mdl-35675152

ABSTRACT

OBJECTIVE: To measure trends for the emergence of opioid withdrawal (OW) and leaving against medical advice (AMA) among hospitalized patients. METHOD: Retrospective time-series of hospitalized patients with OW, defined by a Clinical Opioid Withdrawal score >8, using electronic health record data at a tertiary health system and of patients with a discharge status of AMA from January 1, 2017 to December 31, 2020. RESULTS: The average number of monthly hospitalizations with OW showed a year-to-year increment of 15% in 2018, 21% in 2019, and 34% from 2019 to 2020, whereas the total monthly hospitalizations remained stable. The segmented regression analysis showed that the upward trend in hospitalizations with OW became significant after January 2019 (slope: 1.14, 95% confidence interval [CI]: 0.70, 1.57). After August 2019, Fentanyl was added to the hospital urine drug testing panel and was identified in most OW patients. The monthly proportion of patients who left AMA was significantly higher among the OW patients than among all other admitted patients. There was a significant increase of 0.39 (95% CI: 0.29-0.49, P < 0.001) per month in %AMA among patients with OW. The estimated difference in %AMA among OW patients versus all other patients was 7.25 (95% CI: 5.12-9.38) in January 2017, and 16.92 (95% CI: 14.60-19.24) in December 2020. CONCLUSIONS: The number of hospitalized patients either presenting with or developing OW increased between 2017 and 2020 with a significant rise occurring after January 2019. The percentage of patients who left AMA among those who developed OW steadily worsened during the entire study period.


Subject(s)
Patient Discharge , Substance Withdrawal Syndrome , Humans , Retrospective Studies , Analgesics, Opioid/adverse effects , Substance Withdrawal Syndrome/epidemiology , Narcotics
3.
Antimicrob Resist Infect Control ; 9(1): 65, 2020 05 14.
Article in English | MEDLINE | ID: mdl-32410673

ABSTRACT

BACKGROUND: Healthcare-associated infections are the most frequent adverse events in healthcare worldwide, with limited available evidence suggesting highest burden in resource-limited settings. Recent Ebola epidemics emphasize the disastrous impact that spread of infectious agents within healthcare facilities can have, accentuating the need for improvement of infection control practices. Hand hygiene (HH) measures are considered to be the most effective tool to prevent healthcare-associated infections. However, HH knowledge and compliance are low, especially in vulnerable settings such as Guinea. The aim of PASQUALE (Partnership to Improve Patient Safety and Quality of Care) was to assess knowledge and compliance with HH and improve HH by incorporating the WHO HH Strategy within the Faranah Regional Hospital (FRH), Guinea. METHODS: In a participatory approach, a team of FRH staff and leadership was invited to identify priorities of the hospital prior to the start of PASQUALE. The local hygiene committee was empowered to increase its activities and take ownership of the HH improvement strategy. A baseline assessment of knowledge, perception and compliance was performed months before the intervention. The main intervention consisted of local alcohol-based-hand-rub (ABHR) production, with final product efficacy testing, in conjunction with a training adapted to the needs identified in the baseline assessment. A follow-up assessment was conducted directly after the training. Effectiveness of the intervention was assessed via uncontrolled before-and-after comparison. RESULTS: Baseline knowledge score (13.0/25) showed a significant increase to 19.0/25 in follow-up. Baseline-Compliance was 23.7% and increased significantly to 71.5% in follow-up. Compliance rose significantly across all professional groups except for midwifes and in all indications for HH, with the largest in the indication "Before aseptic tasks". The increase in compliance was associated with the intervention and remained significant after adjusting for confounders. The local pharmacy successfully supplies the entire hospital. The local supply resulted in a ten-fold increase of monthly hospital disinfectant consumption. CONCLUSION: The WHO HH strategy is an adaptable and effective method to improve HH knowledge and compliance in a resource-limited setting. Local production is a feasible method for providing self-sufficient supply of ABHR to regional hospitals like the FRH. Participatory approaches like hygiene committee ownership builds confidence of sustainability.


Subject(s)
Cross Infection/prevention & control , Hand Hygiene/organization & administration , Personnel, Hospital/education , Guideline Adherence/statistics & numerical data , Guinea , Health Knowledge, Attitudes, Practice , Humans , Practice Guidelines as Topic , World Health Organization
5.
Transplant Proc ; 50(2): 683-684, 2018 Mar.
Article in English | MEDLINE | ID: mdl-29579888

ABSTRACT

Infections in transplanted patients are still an important cause of morbidity and mortality. Among them, fungal infections with pathogens have become increasingly more prevalent in the last decade. We report the clinical course and management of disseminated Scedosporium apiospermum infection in a kidney transplant recipient, with microbiological isolation of the fungus in cerebrospinal fluid culture. S apiospermum is a fungus that is distributed worldwide and can be grown from soil samples or stagnant water. Disseminated infection is the most frequent form of infection, with cerebral involvement in most cases, which leads to a very high mortality (around 75%). Post-transplant renal infections require a thorough evaluation. Specifically, a high suspicion index is necessary, considering Scedosporium infection among the differential diagnosis of invasive fungal diseases in renal transplantation patients. It is essential to confirm the microbiological diagnosis for an adequate diagnosis and treatment.


Subject(s)
Immunocompromised Host , Kidney Transplantation/adverse effects , Mycoses/immunology , Postoperative Complications/immunology , Aged , Antifungal Agents/therapeutic use , Fatal Outcome , Humans , Male , Mycoses/diagnosis , Mycoses/drug therapy , Postoperative Complications/diagnosis , Postoperative Complications/microbiology , Scedosporium , Transplant Recipients
6.
Nutr Hosp ; 23(3): 268-76, 2008.
Article in Spanish | MEDLINE | ID: mdl-18560704

ABSTRACT

Hemodialysis patients present an increase in plasma homocysteine (Hcy) due to methylation impairment caused by uremia and the deficiency of the co-factors needed (vitamin B, folic acid). This correlates with a more common development of premature vascular disease. There is no consensus on the therapy, with a poor response to oral administration of conventional doses of folic acid. In this work, we assessed the response of hyperhomocysteinemia in 73 regular hemodialysis patients after the administration of 50 mg of parenteral folinic acid for 18 months. Plasma homocysteine of the patients at the time of the study beginning presented mean values of 22.67 (micromol/L). During the first year of supplementation the mean value was kept at 20 micromol/L. From the first year to the end of the 18-months observation period the mean homocysteine levels were 19.58 micromol/L. Although we found a clear trend towards a decrease in plasma homocysteine levels during the treatment period, there were no significant differences. Homocysteine levels did not come back to normal in none of the patients treated.


Subject(s)
Hyperhomocysteinemia/drug therapy , Leucovorin/therapeutic use , Renal Dialysis , Drug Resistance , Female , Humans , Male , Middle Aged , Renal Insufficiency/therapy
7.
Nutr. hosp ; 23(3): 268-276, mayo-jun. 2008. ilus, tab
Article in Es | IBECS | ID: ibc-68170

ABSTRACT

Los pacientes en hemodiálisis presentan un aumento de homocisteína plasmática (Hcy), debido a la alteración en la metilación causada por la uremia y déficit de los cofactores necesarios (vitamina B, ácido fólico). Esto se correlaciona con un mayor desarrollo de la enfermedad vascular prematura. El tratamiento, no está consensuado, siendo escasa la respuesta a la administración oral de dosis convencionales de ácido fólico. En este trabajo valoramos la respuesta de la hiperhomocisteinemia de 73 pacientes en programa de hemodiálisis periódica tras la administración de 50 mg de ácido folínico parenteral durante 18 meses. La homocisteína plasmática de los pacientes en el momento de inicio del estudio presentaba unos valores medios de 22,67 (μmol/l). Durante el primer año de suplementación mantuvieron el valor medio de 20μmol/l. A partir del primer año de tratamiento, y hasta finalizar los 18 meses de observación, los niveles medios de homocisteína fueron de 19,58 μmol/l. Aunque con el tiempo de tratamiento encontramos una clara tendencia al descenso de sus valores plasmáticos, no existieron diferencias estadísticamente significativas. Los valores de homocisteína no se normalizaron en ninguno de los pacientes tratados (AU)


Hemodialysis patients present an increase in plasma homocysteine (Hcy) due to methylation impairment caused by uremia and the deficiency of the co-factors needed (vitamin B, folic acid). This correlates with a more common development of premature vascular disease. There is no consensus on the therapy, with a poor response to oral administration of conventional doses of folic acid. In this work, we assessed the response of hyperhomocysteinemia in 73 regular hemodialysis patients after the administration of 50 mg of parenteral folinic acid for 18 months. Plasma homocysteine of the patients at the time of the study beginning presented mean values of 22.67 (μmol/L). During the first year of supplementation the mean value was kept at 20μmol/L. From the first year to the end of the 18-months observation period the mean homocysteine levels were 19.58μmol/L. Although we found a clear trend towards a decrease in plasma homocysteine levels during the treatment period, there were no significant differences. Homocysteine levels did not come back to normal in none of the patients treated (AU)


Subject(s)
Humans , Male , Female , Adult , Hyperhomocysteinemia/diet therapy , Folic Acid/therapeutic use , Renal Dialysis/methods , Renal Insufficiency, Chronic/therapy
8.
Nutr Hosp ; 23(2): 119-25, 2008.
Article in Spanish | MEDLINE | ID: mdl-18449447

ABSTRACT

Current high survival in hemodialysis patients (52% at 5 years) have made the chronic manifestations to emerge such as the high hyponutrition prevalence of these patients, as well as the importance of the nutritional status in their morbimortality. The reason for protein-caloric hyponutrition is multifactorial, although chronic inflammatory conditions associated to the dialysis technique are becoming more and more relevant. The variations in several nutritional biochemical parameters (total proteins, plasma albumin, transferrin, and total cholesterol) have been assessed in 73 hemodialysis patients for one year. The mean age of the patients was 53.3 +/- 18.69 years (43 males and 30 females). The average on hemodialysis program was 43 +/- 33 months, with a mean session duration of 246 +/- 24 minutes, and mean hemodialysis dose administered of 1.37 +/- 0.27 (KT/V) (second generation Daurgidas). A decrease in all the biochemical parameters assessed has been observed, with statistically significant differences: total proteins (p < 0.001), albumin (p < 0.00001), total cholesterol (p < 0.05), and transferrin (p < 0.01). The evolution of the nutritional biochemical parameters assessed showed an important nutritional deterioration of the patients remaining stable with the therapy.


Subject(s)
Kidney Failure, Chronic/therapy , Nutritional Status , Renal Dialysis , Aged , Biomarkers/blood , Female , Follow-Up Studies , Humans , Kidney Failure, Chronic/blood , Male , Middle Aged , Time Factors
9.
Nutr. hosp ; 23(2): 119-125, mar.-abr. 2008. ilus, tab
Article in Es | IBECS | ID: ibc-68149

ABSTRACT

La elevada supervivencia actual del paciente en hemodiálisis (52% hasta 5 años), ha hecho que se pongan de manifiesto complicaciones crónicas como la elevada prevalencia de malnutrición en los enfermos, así como la importancia de la situación nutricional en la morbi-mortalidad que presentan. La causa de desnutrición proteico-calórica es multifactorial, aunque procesos de inflamación crónica asociada a la técnica de diálisis cobran cada vez más relevancia. Se han evaluado las variaciones de distintos parámetros bioquímicos nutricionales (proteínas totales, albúmina plasmática, transferrina y colesterol total) de 73 pacientes en hemodiálisis durante un año de seguimiento. La edad media de los pacientes era de 53,3 ± 18,69 años, con 43 varones y 30 mujeres. El tiempo en programa de hemodiálisis ha sido de 43 ± 33 meses, con una duración media de la sesión de 246± 24 minutos y dosis media de hemodiálisis administrada de 1,37 ± 0,27 (KT/V) (Daurgidas 2ª generación). Se ha observado un descenso en todos los parámetros bioquímicos evaluados, con diferencias estadísticamente significativas: Proteínas totales (p < 0,001), albúmina (p < 0,00001), colesterol total (p < 0,05) y transferrina (p < 0,01). La evolución de los parámetros bioquímicos nutricionales evaluados mostró un importante deterioro nutricional de los pacientes estables con el tratamiento (AU)


Current high survival in hemodialysis patients (52% at 5 years) have made the chronic manifestations to emerge such as the high hyponutrition prevalence of these patients, as well as the importance of the nutritional status in their morbimortality. The reason for protein-caloric hyponutrition is multifactorial, although chronic inflammatory conditions associated to the dialysis technique are becoming more and more relevant. The variations in several nutritional biochemical parameters (total proteins, plasma albumin, transferrin, and total cholesterol) have been assessed in 73 hemodialysis patients for one year. The mean age of the patients was 53.3 ± 18.69 years (43 males and 30 females). The average on hemodialysis program was 43 ± 33 months, with a mean session duration of 246 ± 24 minutes, and mean hemodialysis dose administered of 1.37 ± 0.27 (KT/V) (second generation Daurgidas). A decrease in all the biochemical parameters assessed has been observed, with statistically significant differences: total proteins (p < 0.001), albumin (p < 0.00001), total cholesterol (p < 0.05), and transferrin (p < 0.01). The evolution of the nutritional biochemical parameters assessed showed an important nutritional deterioration of the patients remaining stable with the therapy (AU)


Subject(s)
Humans , Renal Insufficiency, Chronic/physiopathology , Renal Dialysis/adverse effects , Protein-Energy Malnutrition/epidemiology , Renal Insufficiency, Chronic/therapy , Inflammation/physiopathology , Biomarkers/analysis , Serum Albumin/analysis , Blood Proteins/analysis , Cholesterol/analysis
10.
Biol Trace Elem Res ; 113(3): 209-22, 2006 Dec.
Article in English | MEDLINE | ID: mdl-17194922

ABSTRACT

A 6-mo longitudinal study of 48 hemodialysis patients (HPs) with chronic renal failure was performed. Three blood samplings were done. Samples of whole blood from each patient were collected during hemodialysis sessions after passing through the artificial kidney. Zinc and copper levels were measured by atomic absorption spectrometry. Additionally, 36 biochemical indexes were evaluated during the study. Fifty-two healthy matched controls were also considered. Mean serum zinc and copper concentrations in HPs were significantly decreased (Zn) and increased (Cu), when compared with healthy controls (p < 0.01). Zinc concentrations found in the first and second blood samplings from patients were significantly lower than those measured for the third sampling (p < 0.01). The etiology of chronic renal failure influenced the statistically serum Zn levels of patients (p < 0.05). Serum copper levels of HPs were significantly diminished by the existence of secondary associated diseases (p < 0.01). Uric acid and parathyroid hormone, and total-cholesterol and glutamic-pyruvic-transaminase levels were significantly (p < 0.05) and linearly related with serum zinc and copper concentrations, respectively. From all of indexes, creatinine, direct bilirubin, magnesium, calcium, parathyroid hormone, transferrin, and albumin were statistically modified along the longitudinal study (p < 0.05). Transferrin serum levels were significantly diminished in the third blood sampling, indicating the tendency toward anemia in the patients. This result is reinforced by low levels of biochemical and hematological indexes related with iron body staus.


Subject(s)
Copper/blood , Renal Dialysis , Zinc/blood , Aged , Case-Control Studies , Female , Humans , Kidneys, Artificial , Longitudinal Studies , Male , Middle Aged , Spectrophotometry , Spectrophotometry, Atomic , Trace Elements/blood
11.
Actas dermo-sifiliogr. (Ed. impr.) ; 97(8): 525-528, oct. 2006. ilus
Article in Es | IBECS | ID: ibc-049009

ABSTRACT

El angiosarcoma que se desarrolla sobre una extremidad con linfedema crónico se denomina síndrome de Stewart-Treves. Éste aparece típicamente como una complicación de un linfedema de larga evolución localizado en el brazo, tras mastectomía y/o radioterapia por un cáncer de mama. Existen casos de síndrome de Stewart-Treves sobre linfedema crónico en la extremidad superior contralateral al cáncer de mama tratado y sobre linfedema crónico de pierna. Presentamos dos casos de este síndrome. El primero corresponde a un típico síndrome de Stewart-Treves en una mujer de 83 años, que fue diagnosticada de angiosarcoma en el territorio de un linfedema crónico secundario a mastectomía y radioterapia por un cáncer de mama. El segundo caso es mucho más raro, ya que se trata de un caso de angiosarcoma difuso de pierna, en un hombre de 42 años e historia de linfedema. La naturaleza agresiva de este síndrome precisa de su conocimiento e investigación de tratamientos para prevenirlo


Angiosarcoma that develops on a limb with chronic lymphedema is called Stewart-Treves syndrome. This typically appears as a complication of a long course lymphedema located on the arm, after mastectomy and/or radiotherapy due to breast cancer. There are cases of Stewart-Treves syndrome in chronic lymphedema in the upper limb contralateral to the breast treated for cancer and in chronic lymphedema of the leg. We present two cases of this syndrome. The first corresponds to a typical syndrome of Stewart-Treves in an 83-year-old woman who was diagnosed of angiosarcoma in a chronic lymphedema territory secondary to mastectomy and radiotherapy due to breast cancer. The second case is much rarer, since it is a case of diffuse angiosarcoma of the leg in a 42-year-old man with a history of lymphedema. Due to the aggressive nature of this syndrome, knowledge and research on its treatment are necessary


Subject(s)
Male , Female , Adult , Aged , Humans , Hemangiosarcoma/diagnosis , Hemangiosarcoma/therapy , Lymphedema/diagnosis , Tomography, Emission-Computed/methods , Ifosfamide/therapeutic use , Doxorubicin/therapeutic use , Immunohistochemistry/methods , Biopsy/methods , Drug Therapy, Combination , Chemotherapy, Adjuvant/methods , Hyperostosis Frontalis Interna/complications , Mastectomy/adverse effects , Hemangiosarcoma/complications , Lymphedema/complications , Lipoma/complications , Radiotherapy/adverse effects , Chemotherapy, Adjuvant/trends , Chemotherapy, Adjuvant
12.
Nutr Hosp ; 21(2): 155-62, 2006.
Article in Spanish | MEDLINE | ID: mdl-16734067

ABSTRACT

Chronic renal failure is commonly related to hyponutrition, affecting approximately on third of patients with advanced renal failure. We carried out a longitudinal study to assess nutritional evolution of 73 patients on a regular hemodialysis program, assessing changes in the anthropometrical parameter body mass index (BMI) and its correspondence to biochemical nutritional parameters such as total protein (TP) levels and serum albumin (Alb). Every three months plasma TP and albumin levels were collected and BMI was calculated by the standard formula: post-dialysis weight in kg/height in m2. For classifying by BMI categories, overweight and low weight were defined according to the WHO Expert Committee. Studied patients had a mean age of 53 years, 43 were male and 30 were female patients. BMI in women was lower than that in men (p < 0.001), as well as TP (p < 0.001) and Alb (p < 0.001) levels. Mean BMI was 29.3 kg/m2. Three point two percent of the determinations showed low weight, 12.16% overweight, and 83.97% normal BMI. TP were normal in 90.76% and decreased in 9.24%. Alb was normal in 82.2% and low in 17.78%. After the follow-up time (21.6 months, minimum 18 months, maximum 53 months), the Kruskal-Wallis test did not show a statistically significant change for BMI but it did show a change for the biochemical parameters albumin and total proteins (p < 0.05): nutritional impairment in CRF patients is manifested on biochemical parameters (TP and Alb) with no reflection on anthropometrical data.


Subject(s)
Body Mass Index , Adult , Female , Humans , Kidney Failure, Chronic/therapy , Longitudinal Studies , Male , Middle Aged , Renal Dialysis/methods , Serum Albumin/analysis
13.
Nutr. hosp ; 21(2): 155-162, mar.-abr. 2006. ilus, tab, graf
Article in Es | IBECS | ID: ibc-046464

ABSTRACT

La insuficiencia renal crónica está relacionada frecuentemente con la malnutrición, afectando aproximadamente a un tercio de los pacientes con enfermedad renal avanzada. Realizamos un estudio longitudinal de la evolución nutricional de 73 pacientes en programa de hemodiálisis periódica, valorando las modificaciones del parámetro antropométrico de índice de masa corporal (IMC) y su correspondencia con parámetros nutricionales bioquímicos como son proteínas totales (PT) y albúmina sérica (Alb). Trimestralmente se recogieron los niveles plasmáticos de PT y Alb, y se evaluó su IMC calculado por la fórmula Standard: peso postdiálisis en Kg / altura m2. Para la clasificación en grupos según el IMC, sobrepeso y bajo peso fueron definidos según los valores del Comité de Expertos de la OMS. Los pacientes estudiados presentan una edad media de 53 años, 43 eran varones y 30 mujeres. El IMC de las mujeres fue inferior al de los varones (p<0,001), así como los niveles de PT (p<0,001) y Alb (p<0,001). El IMC medio es de 29,3 Kg/m2. El 3,2% de las determinaciones mostraban bajo peso, 12,16% sobrepeso y el 83,97 % un IMC normal. Las PT eran normales en el 90,76% y disminuidas en el 9,24%, la Alb normal en el 82,2% y baja en el 17,78%. Tras el tiempo de seguimiento (21,6 meses, con mínimo de 18 meses y máximo de 53) el Test de Kruskal-Wallis no mostró variación estadísticamente significativa en IMC y sí en los parámetros bioquímicos albúmina y proteínas totales (p<0,05): el deterioro nutricional de los pacientes con IRC en programa de diálisis se manifiesta en los parámetros bioquímicos (PT y Alb) sin que se refleje en los datos antropométricos (AU)


Chronic renal failure is commonly related to hyponutrition, affecting approximately on third of patients with advanced renal failure. We carried out a longitudinal study to assess nutritional evolution of 73 patients on a regular hemodialysis program, assessing changes in the anthropometrical parameter body mass index (BMI) and its correspondence to biochemical nutritional parameters such as total protein (TP) levels and serum albumin (Alb). Every three months plasma TP and albumin levels were collected and BMI was calculated by the standard formula: post-dialysis weight in kg/height in m2. For classifying by BMI categories, overweight and low weight were defined according to the WHO Expert Committee. Studied patients had a mean age of 53 years,43 were male and 30 were female patients. BMI in women was lower than that in men (p < 0.001), as well as TP (p < 0.001) and Alb (p < 0.001) levels. Mean BMI was 29.3 kg/m2. Three point two percent of the determinations showed low weight, 12.16% overweight, and 83.97% normal BMI. TP were normal in 90.76% and decreased in 9.24%. Alb was normal in 82.2% and low in 17.78%. After the follow-up time (21.6 months, minimum 18 months, maximum 53 months), the Kruskal-Wallis test did not show a statistically significant change for BMI but it did show a change for the biochemical parameters albumin and total proteins (p < 0.05): nutritional impairment in CRF patients is manifested on biochemical parameters (TP and Alb) with no reflection on anthropometrical data (AU)


Subject(s)
Adult , Middle Aged , Humans , Body Mass Index , Renal Insufficiency, Chronic/therapy , Longitudinal Studies , Renal Dialysis/methods , Serum Albumin
14.
Actas dermo-sifiliogr. (Ed. impr.) ; 97(2): 118-121, mar. 2006. ilus
Article in Es | IBECS | ID: ibc-043558

ABSTRACT

Las reticulohistiocitosis constituyen un grupo heterogéneo de enfermedades que tienen su origen en la acumulación de células de estirpe histiocitaria en diferentes tejidos y fundamentalmente en la piel. Se han descrito tres formas clínicas principales (multicéntrica, solitaria, cutánea difusa) que presentan idénticas características histológicas, ultraestructurales e inmunohistoquímicas. Presentamos un caso de reticulohistiocitosis cutánea difusa que constituye el patrón clínico menos común dentro del espectro de esta enfermedad


The reticulohistiocytoses make up a heterogeneous group of diseases whose origin lies in an accumulation of cells of histiocytic lineage in different tissues and primarily in the skin. Three main clinical forms have been described (multicentric, solitary, diffuse cutaneous), which present with identical histological, ultrastructural and immunohistochemical characteristics. We present a case of diffuse cutaneous reticulohistiocytosis, which is the least common clinical pattern in the spectrum of this disease


Subject(s)
Male , Middle Aged , Humans , Histiocytosis/complications , Histiocytosis/diagnosis , Histiocytosis/therapy , Immunohistochemistry/methods , Biopsy/methods , Tomography, Emission-Computed/methods , Histiocytes/cytology , Histiocytes/pathology , Histiocytes , Skin Diseases/complications , Skin Diseases/diagnosis , Skin Diseases/therapy , Endoplasmic Reticulum/pathology , Endoplasmic Reticulum
16.
Toxicol Sci ; 75(2): 355-67, 2003 Oct.
Article in English | MEDLINE | ID: mdl-12883091

ABSTRACT

In a previous study of prevalidation, a standard operating procedure (SOP) for two independent in vitro tests (human and mouse) had been developed, to evaluate the potential hematotoxicity of xenobiotics from their direct and the adverse effects on granulocyte-macrophages (CFU-GM). A predictive model to calculate the human maximum tolerated dose (MTD) was set up, by adjusting a mouse-derived MTD for the differential interspecies sensitivity. In this paper, we describe an international blind trial designed to apply this model to the clinical neutropenia, by testing 20 drugs, including 14 antineoplastics (Cytosar-U, 5-Fluorouracil, Myleran, Thioguanine, Fludarabine, Bleomycin, Methotrexate, Gemcitabine, Carmustine, Etoposide, Teniposide, Cytoxan, Taxol, Adriamycin); two antivirals (Retrovir, Zovirax,); three drugs for other therapeutic indications (Cyclosporin, Thorazine, Indocin); and one pesticide (Lindane). The results confirmed that the SOP developed generates reproducible IC90 values with both human and murine GM-CFU. For 10 drugs (Adriamycin, Bleomycin, Etoposide, Fludarabine, 5-Fluorouracil, Myleran, Taxol, Teniposide, Thioguanine, and Thorazine), IC90 values were found within the range of the actual drug doses tested (defined as the actual IC90). For the other 10 drugs (Carmustine, Cyclosporin, Cytosar-U, Cytoxan, Gemcitabine, Indocin, Lindane, Methotrexate, Retrovir, and Zovirax) extrapolation on the regression curve out of the range of the actual doses tested was required to derive IC90 values (extrapolated IC90). The model correctly predicted the human MTD for 10 drugs out of 10 that had "actual IC90 values" and 7 drugs out of 10 for those having only an extrapolated IC90. Two of the incorrect predictions (Gemcitabine and Zovirax) were within 6-fold of the correct MTD, instead of the 4-fold range required by the model, whereas the prediction with Cytosar-U was approximately 10-fold in error. A possible explanation for the failure in the prediction of these three drugs, which are pyrimidine analogs, is discussed. We concluded that our model correctly predicted the human MTD for 20 drugs out of 23, since the other three drugs (Topotecan, PZA, and Flavopiridol) were tested in the prevalidation study. The high percentage of predicitivity (87%), as well as the reproducibility of the SOP testing, confirm that the model can be considered scientifically validated in this study, suggesting promising applications to other areas of research in developing validated hematotoxicological in vitro methods.


Subject(s)
Bone Marrow Cells/drug effects , Colony-Forming Units Assay , Maximum Tolerated Dose , Neutropenia/chemically induced , Predictive Value of Tests , Xenobiotics/toxicity , Acute Disease , Animals , Bone Marrow Cells/pathology , Cells, Cultured , Dose-Response Relationship, Drug , Europe , Fetal Blood/cytology , Humans , International Cooperation , Male , Mice , Mice, Inbred C57BL , Neutropenia/pathology , Reproducibility of Results , Single-Blind Method , United States , Xenobiotics/classification
17.
Scand J Gastroenterol ; 38(12): 1228-34, 2003 Dec.
Article in English | MEDLINE | ID: mdl-14750642

ABSTRACT

BACKGROUND: The VacA cytotoxin produced by Helicobacter pylori is considered an important co-factor in the pathogenesis of chronic gastritis, peptic ulcer and gastric carcinoma. The toxin remains partly bound on the bacterial surface, but a certain amount is secreted and can bind receptors on gastric epithelium. The vacuolizing activity of this toxin is related to alteration of endo-lysosomic function and pore formation into plasmatic membrane. METHODS: We investigated the 'in vitro' effect of filtrates obtained from two broth cultures of H. pylori with different genotype (vacA+ and vacA-) as verified by PCR. The effect was studied on three cell lines of epithelial origin: HeLa cells (reference strain for testing vacuolization), human transformed keratinocytes HaCaT, human gastric carcinoma cells HGC-27, and on a murine leukaemia WEHI-3B. The filtrate concentrations capable of giving vacuolization (NRU test), antiproliferative and cytotoxic effects (MTT test) were determined. The modulating effect of filtrates on drug toxicity was investigated on HeLa and HGC-27 cells by testing topoisomerase inhibitors (Ciprofloxacin and Camptothecin) and non-steroidal anti-inflammatory molecules (Aspirin and Indomethacin). RESULTS: Our results confirm that vacuolizing activity is present only in VacA+ filtrate and that HaCaT and HeLa cells show a similar sensitivity, whereas gastric HGC-27 cells appear significantly resistant to VacA+ activity. Although VacA filtrate does not produce vacuolisation, it affects the cell proliferation and is cytotoxic to the four cell lines. Both the VacA+ and VacA- filtrates (at non-cytotoxic concentrations) produce a decrease in drug toxicity with the unique exception of Ciprofloxacin to gastric HGC-27 cells, which in the presence of VacA+ and VacA- produces a significant increase in toxicity. CONCLUSIONS: These data suggest that products from H. pylori (other than those that have antiproliferative and toxic activity) may modulate the sensitivity of cells to drugs 'in vitro'. If this also occurs 'in vivo', we can assume that H. pylori products interfere with drug activity on gastric tissue and also with other factors (such as cytokines) with a role in the genesis of diseases in which Helicobacters are potentially involved.


Subject(s)
Bacterial Proteins/pharmacology , Bacterial Toxins/pharmacology , Cytotoxins/pharmacology , Helicobacter pylori , Stomach Neoplasms/ultrastructure , Vacuoles/drug effects , Animals , Anti-Inflammatory Agents, Non-Steroidal/toxicity , Cell Division/drug effects , Cell Line , Cell Line, Tumor/drug effects , Cell Survival/drug effects , Colony-Forming Units Assay , Dose-Response Relationship, Drug , Epithelial Cells/drug effects , Epithelial Cells/physiology , Epithelial Cells/ultrastructure , HeLa Cells , Humans , Stomach Neoplasms/pathology , Topoisomerase I Inhibitors
18.
Int Microbiol ; 5(2): 87-90, 2002 Jun.
Article in English | MEDLINE | ID: mdl-12180785

ABSTRACT

The microbiota of the lower female genital tract was evaluated from vaginal swabs obtained from 623 healthy pregnant women at gestation periods of 35-40 weeks. Isolated and identified microorganisms were expressed as percentages of total samples. As expected, lactobacilli made up the dominant vaginal microbiota (70%). Enterobacteriaceae, mainly Escherichia coli, Klebsiella spp. and Proteus, were present in 38% of the samples, which might reflect the possible contamination of vaginal tract with rectal microorganisms. Candida albicans was present in 10% of healthy pregnant woman assayed. Streptoccocci (Streptococcus sp. and Enterococcus faecalis with 3% and 4%, respectively) and other gram-positive cocci (Staphylococcus sp., 5%), along with other microorgansisms such as Gardnerella vaginalis (5%) and Pseudomonas aeruginosa (2%) may represent a potential infection risk. Streptococcus agalactiae (group B streptococci beta-hemolytic, GBS) was detected in 7% of the samples. GBS infection is a leading cause of neonatal morbidity and mortality in the developed world. Furthermore, GBS was often co-isolated with C. albicans (54.5%) in the samples. A complete and detailed evaluation of the vaginal biota swab, with particular attention to the presence of potential pathogens such as GBS, is a preventive strategy that can provide useful information to obstetricians and gynecologist in managing the last days of pregnancy and delivery.


Subject(s)
Candida/isolation & purification , Streptococcal Infections/microbiology , Streptococcus agalactiae/isolation & purification , Vagina/microbiology , Adult , Female , Humans , Mass Screening/methods , Pregnancy , Prevalence , Streptococcal Infections/diagnosis , Vaginosis, Bacterial/microbiology
19.
Int. microbiol ; 5(2): 87-90, jun. 2002. tab
Article in English | IBECS | ID: ibc-14847

ABSTRACT

The microbiota of the lower female genital tract was evaluated from vaginal swabs obtained from 623 healthy pregnant women at gestation periods of 35-40 weeks. Isolated and identified microorganisms were expressed as percentages of total samples. As expected, lactobacilli made up the dominant vaginal microbiota (70%). Enterobacteriaceae, mainly Escherichia coli, Klebsiella spp. and Proteus, were present in 38% of the samples, which might reflect the possible contamination of vaginal tract with rectal microorganisms. Candida albicans was present in 10% of healthy pregnant woman assayed. Streptoccocci (Streptococcus sp. and Enterococcus faecalis with 3% and 4%, respectively) and other gram-positive cocci (Staphylococcus sp., 5%), along with other microorgansisms such as Gardnerella vaginalis (5%) and Pseudomonas aeruginosa (2%) may represent a potential infection risk. Streptococcus agalactiae (group B streptococci beta-hemolytic, GBS) was detected in 7% of the samples. GBS infection is a leading cause of neonatal morbidity and mortality in the developed world. Furthermore, GBS was often co-isolated with C. albicans (54.5%) in the samples. A complete and detailed evaluation of the vaginal biota swab, with particular attention to the presence of potential pathogens such as GBS, is a preventive strategy that can provide useful information to obstetricians and gynecologist in managing the last days of pregnancy and delivery (AU)


Se evaluó la microbiota del tracto genital inferior femenino a partir de raspados vaginales obtenidos de 623 mujeres embarazadas en períodos de gestación de 35-40 semanas. Las cantitades de microorganismos aislados e identificados se expresan en porcentaje sobre la muestra total. Como se esperaba, los lactobacilos constituían la mayor parte de la microbiota vaginal (70 por ciento). En el 38 por ciento de las muestras se encontraron enterobacteriáceas, principalmente Escherichia coli, Klebsiella spp. y Proteus spp., lo cual refleja una posible contaminación del tracto vaginal con microorganismos rectales. Candida albicans estaba presente en el 10 por ciento de las mujeres sanas de la muestra. Los estreptococos (Streptococcus sp. y Enterococcus faecalis con un 3 por ciento y un 4 por ciento, respectivamente), junto con otros microorganismos tales como Gardnerella vaginalis (5 por ciento) y Pseudomonas aeruginosa (2 por ciento) representan un riesgo potencial de infección. Se detectó Streptococcus agalactiae (estreptococo del grupo B b-hemolítico, GBS) en el 7 por ciento de las muestras. La infección por GBS es una de las causas principales de morbidez neonatal y de mortalidad en el mundo desarrollado. Además, GBS suele ser co-aislado con C. albicans (54.5 por ciento) en las muestras. La evaluación e identificación de toda la biota en el raspado vaginal, con especial atención a patógenos como GBS, es una estrategia de prevención que proporciona información útil a los obstétricos y ginecólogos para controlar los últimos días del embarazo y el parto (AU)


Subject(s)
Pregnancy , Adult , Female , Humans , Streptococcal Infections , Streptococcus agalactiae , Vagina/microbiology , Candida/isolation & purification , Prevalence , Vaginosis, Bacterial , Mass Screening/methods
20.
Arch Environ Health ; 50(3): 247-51, 1995.
Article in English | MEDLINE | ID: mdl-7618959

ABSTRACT

Internal noise levels were measured in a 232-point grid that encompassed the main building of a major University Hospital in Valencia, Spain. Most noise equivalent sound levels that were obtained exceeded 55 dBA, and in some instances these sound levels were very high. Hospital workers' subjective responses to noise were evaluated with a self-answered questionnaire. A total of 295 workers volunteered to participate. Their answers revealed that the most important noise sources were located primarily inside the hospital. Noise levels were perceived to be sufficiently high to interfere with their work, and noise levels were also thought to affect patients' comfort and recovery. Most subjects thought it feasible to reduce noise levels in the hospital, and some preventive measures were proposed.


Subject(s)
Hospitals, Urban , Noise , Adolescent , Adult , Aged , Attitude of Health Personnel , Female , Humans , Male , Medical Staff, Hospital , Middle Aged , Noise, Occupational , Nursing Staff, Hospital , Spain , Surveys and Questionnaires
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