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Biomedical subjects

M Dan

Publications and source records attributed to M Dan.

At least 19 recordsLinked to original sources

Gastric microbiota in elderly patients fed via nasogastric tubes for prolonged periods.

Aspiration of oropharyngeal contents is a constant threat for elderly patients fed via a nasogastric tube (NGT). Colonization of the oropharynx of these patients by pathological flora and the development of biofilms on the feeding tube has been documented recently. In addition, the presence of the NGT may interfere with the gastro-oesophageal sphincter, leading to gastro-oesophageal reflux. Thus, the passage of pathogenic bacteria in both directions is facilitated. The purpose of this study was to explore the microbiota of the gastric juice and the oropharynx in NGT-fed elderly patients. Samples of gastric juice were drawn after an overnight fast, and microbial cultures and direct pH measurement were performed. Concomitant cultures were obtained from the oropharynx. Overall, 107 gastric and oropharyngeal cultures were obtained from 52 subjects. Pathogenic flora (Gram-negative bacteria or Staphylococcus aureus) were isolated from 74% of stomach samples and from 69% of oropharynx samples. Proteus spp. (26%) and Escherichia coli (22%) were the most common isolates in the gastric juice, and Proteus spp. (24%) and Pseudomonas spp. (21%) were the most common isolates in the oropharynx. Similarity in the composition of the oropharynx and gastric flora was observed in most cases. The gastric pH was relatively high (4.57 +/- 0.65 at 3 h after feeding and 4.2 +/- 0.9 at 12 h after feeding) and was highly correlated with the isolation of pathogenic bacteria (r = 0.58, P < 0.01). These results support the view that in addition to the oropharynx, the stomach of NGT-fed elderly patients constitutes a reservoir of pathogens that could be associated with the risk of aspiration pneumonia. The cause of the high gastric pH and its relation to pathogenic bacteria warrants further study.

Aged↗

Candida colonization of the vagina in elderly residents of a long-term-care hospital.

The present study was conducted in order to determine the prevalence of vaginal colonization by Candida spp in elderly residents of a long-term-care hospital and to examine the determinants of vaginal candidiasis. Vaginal swabs for Gram stain and culture were obtained from 106 bedridden residents of a long-term-care hospital (study group; mean age, 83+/-7 years) and a control group of 50 similarly aged women admitted to an acute-care hospital for non-genital problems (mean age, 81+/-8 years). The characteristics of patients who tested positive for Candida spp were compared with those who tested negative. Candida spp were isolated from 34 (32%) patients in the study group and from four (8%) control patients (p=0.001). In the study group, Candida glabrata was by far the most common species isolated (51.2%). The warm and moist environment in the perineal area created by diaper use in incontinent individuals, together with decubitus ulcers and immobilization, which are common in elderly patients receiving long-term care, might be responsible for the high occurrence of vaginal colonization with Candida in these women.

Aged↗

A genetically engineered attenuated coxsackievirus B3 strain protects mice against lethal infection.

Coxsackievirus B3 (CVB3) is a common human pathogen that is endemic throughout the world. There is currently no vaccine available, although the virus is known to be highly lethal to newborns and has been associated with heart disease and pancreatitis in older children and adults. Previously, we showed that the virulence of CVB3 is reduced by a lysine-to-arginine substitution in the capsid protein VP2 (K2168R) or a glutamic acid-to-glycine substitution in VP3 (E3060G). In this report, we show that the double mutant virus CVB3(KR/EG) displays additional attenuation, particularly for the pancreas, in A/J mice. In addition, two other attenuating mutations have been identified in the capsid protein VP1. When either the aspartic acid residue D1155 was replaced with glutamic acid or the proline residue P1126 was replaced with methionine, the resulting mutant also possessed an attenuated phenotype. Moreover, when either of these mutations was incorporated into CVB3(KR/EG), the resulting triple mutant viruses, CVB3(KR/EG/DE) and CVB3(KR/EG/PM), were completely noncardiovirulent and caused only small foci of damage to the pancreas, even at a high dose. Both triple mutants were found to be immunogenic, and a single injection of young A/J mice with either was found to protect them from a subsequent lethal challenge with wild-type CVB3. These findings indicate that the triple mutants could be exploited for the development of a live attenuated vaccine against CVB3.

Animals↗

Cranberry juice and urinary tract infection.

Cranberries have long been the focus of interest for their beneficial effects in preventing urinary tract infections (UTIs). Cranberries contain 2 compounds with antiadherence properties that prevent fimbriated Escherichia coli from adhering to uroepithelial cells in the urinary tract. Approximately 1 dozen clinical trials have been performed testing the effects of cranberries on the urinary tract. However, these trials suffer from a number of limitations. Most importantly, the trials have used a wide variety of cranberry products, such as cranberry juice concentrate, cranberry juice cocktail, and cranberry capsules, and they have used different dosing regimens. Further research is required to clarify unanswered questions regarding the role of cranberries in protecting against UTI in general and in women with anatomical abnormalities in particular.

Bacterial Adhesion↗

Concentrations of moxifloxacin in serum and synovial fluid, and ex vivo bactericidal activity against arthritis-causing pathogens.

Three doses of moxifloxacin 400 mg qd were administered orally to 20 candidates for knee arthroscopy (mean age, 71.2 years). The procedure was scheduled at four different points of time after the last dose: 2, 6, 12, and 24 h. Five patients were studied at each point of time. Drug levels were determined by the bioassay method. Bactericidal activity against four bacterial pathogens (two strains of each) was studied on serum and synovial fluid samples obtained during arthroscopy using the NCCLS guidelines. Mean (+/-S.D.) peak serum and synovial fluid concentrations were 3.46 +/- 0.78 mg/L and 3.42 +/- 0.51 mg/L, respectively. Levels above 1.0 mg/L were detected as long as 24 h. The peak bactericidal titers were (in serum and synovial fluid, respectively) 1:18.3 and 1:32 against Staphylococcus aureus, 1:18.3 and 1:22.6 against Streptococcus pyogenes, 1:45.2 and 1:64.0 against Klebsiella pneumoniae, and 1:2.3 and 1:1.7 against Pseudomonas aeruginosa. Bactericidal titers >1:2 were documented against the first three pathogens up to 24 h after dosing. On the basis of its pharmacokinetic and pharmacodynamic characteristics, moxifloxacin seems to be an excellent candidate for the treatment of joint infections, except those caused by P. aeruginosa.

Administration, Oral↗

Attenuating mutations in coxsackievirus B3 map to a conformational epitope that comprises the puff region of VP2 and the knob of VP3.

Ten antibody escape mutants of coxsackievirus B3 (CVB3) were used to identify nucleotide substitutions that determine viral virulence for the heart and pancreas. The P1 region, encoding the structural genes of each mutant, was sequenced to identify mutations associated with the lack of neutralization. Eight mutants were found to have a lysine-to arginine mutation in the puff region of VP2, while two had a glutamate-to-glycine substitution in the knob of VP3. Two mutants, EM1 and EM10, representing each of these mutations, were further analyzed, initially by determining their entire sequence. In addition to the mutations in P1, EM1 was found to have two mutations in the 3D polymerase, while EM10 had a mutation in stem-loop II of the 5' nontranslated region (5'NTR). The pathogenesis of the mutants relative to that of CVB3 strain RK [CVB3(RK)] then was examined in A/J mice. Both mutants were found to be less cardiotropic than the parental strain, with a 40-fold (EM1) or a 100- to 1,000-fold (EM10) reduction in viral titers in the heart relative to the titers of CVB3(RK). The mutations in VP2, VP3, and the 5'NTR were introduced independently into the RK infectious clone, and the phenotypes of the progeny viruses were determined. The results substantiated that the VP2 and VP3 mutations reduced cardiovirulence, while the 5'NTR mutation in EM10 was associated with a more virulent phenotype when expressed on its own. Stereographic imaging of the two mutations in the capsomer showed that they lie in close proximity on either side of a narrow cleft between the puff and the knob, forming a conformational epitope that is part of the putative binding site for coreceptor DAF.

Animals↗

First clinical trial for a new CRRT machine: the Prismaflex.

A new CRRT machine has been designed to fulfill the expectations of nephrologists and intensivists operating in the common ground of critical care nephrology. The new equipment is called "Prismaflex" (Gambro-Dasco, Mirandola, Modena) and it is the natural evolution of the Prisma machine that has been utilized worldwide for CRRT in the last decade. We performed a preliminary "alfa trial" to establish usability, flexibility and realiability of the new device. Accuracy was also tested by recording various operational parameters during different intermittent and continuous renal replacement modalities. Forty-one runs were conducted on 13 patients and the difference between delivered and prescribed parameters was always lower than 2%. We concluded that the new Prismaflex is a well designed new machine for CRRT and can be safely and effectively utilized in the critical care nephrology setting.

Acute Kidney Injury↗

[Cranberry juice and urinary tract infection].

Cranberries have long been the focus of interest for their beneficial effects in preventing urinary tract infections (UTIs). Cranberries contain two compounds with anti-adherence properties, which prevent fimbriated E. coli from adhering to uroepithelial cells in the urinary tract. Approximately a dozen clinical trials have been performed testing the effects of cranberries on the urinary tract. However, these trials have a number of apparent limitations. Most importantly, the trials have used a wide variety of cranberry products, such as cranberry juice concentrate, juice cocktail, and cranberry capsules, and have employed different dosing regimens. Further research is required to clarify unanswered questions regarding the role of cranberries in protecting against UTI in general and in women with anatomical abnormalities in particular.

Beverages↗

Continuous renal replacement technology: from adaptive devices to flexible multipurpose machines.

OBJECTIVE: To review the evolution of technologies in the development of renal replacement therapies. DATA SOURCES: Articles and published reviews on renal replacement therapies. SUMMARY OF REVIEW: Continuous arterio-venous haemofiltration (CAVH) was the first continuous renal replacement technique capable of overcoming the traditional haemodialysis-related side effects, making possible the treatment of critically ill patients safely and with less physiological instability. The evolution of technology and the progress experienced in intensive care units (ICUs) has made it possible to start renal replacement therapy programs in the absence of a chronic dialysis facility or a trained nephrological team. Initial limitations and draw-backs of CAVH, stimulated the ICU staff to explore new avenues for better therapy. Extracorporeal therapies are today a routine experience in the ICUs: continuous renal replacement therapies are a broadly accepted treatment for acute renal failure. Furthermore, alternative indications for extracorporeal blood circulation (e.g. sepsis, liver failure, congestive heart failure, drug intoxications, hyperthermia, immuno-mediated syndromes) are becoming more and more popular. The ideal machine has yet to be completed, but progress has occurred and has opened a new era for critical care nephrology and the further expansion of blood purification technology in the ICU. CONCLUSIONS: Technical advances in renal replacement therapies have increased their functionality (i.e. used in hepatic failure, sepsis, cardiac failure and immuno-mediated syndromes), are easier to operate and have less side-effects compared with their standard extracorporeal counterparts. Further improvements may see them become a routine part in the management of the critically ill patient.

Journal Article↗

Optic neuritis complicating west nile virus meningitis in a young adult.

A case of West Nile virus (WNV) infection with meningitis and optic neuritis in a 28-year-old man is presented. The patient had a number of unusual clinical and laboratory findings that broadened the differential diagnosis. The emergence of WNV infection in southern Europe and North America calls for increased awareness of physicians to this clinical entity.

Adult↗

When the ICU patient refuses vital supports.

The aim of this paper is to discuss the problem of caring for ICU patients who request forgoing of intensive supports; in particular, evaluating their competence and building effective relationships among the patients themselves, their relatives and the health care team. The histories of 2 adult competent ICU patients 2 asked that vital intervention be forgone are presented, together with the discussion of problems posed by such a request and of possible solutions which respect patients' autonomy and bystanders needs. These patients were hospitalized in an Italian general 14 bed ICU. The patients' request were weighted against their prognosis and their view of life, in order to evaluate their reliability. Also the refusal of either treatment or outcome was evaluated, in order to effectively safeguard the patients' interests. The request of one patient was satisfied and he was allowed to die, after all the involved people had understood and accepted the final decision. The second patient, who was somehow forced to undergo intensive treatment, is alive and satisfied with having been cured. In Italy too, autonomy is an increasingly applied principle in end-of-life decisions in ICUs. It is usually tempered by a consideration about the patients' best interest as perceived by involved bystanders.

Cardiopulmonary Resuscitation↗

Increasing incidence of gonorrhea in Israel associated with countrywide dissemination of a ciprofloxacin-resistant strain.

The annual incidence of gonorrhea in Israel has sharply increased during the past 2 years. At the end of 1999, high-level ciprofloxacin-resistant strains of Neisseria gonorrhoeae (MIC90, > or =32 mcg/ml) also exhibiting decreased susceptibility to penicillin and tetracycline were isolated for the first time in southern Israel, as well as in other regions of the country. The incidence of male gonococcal urethritis in the south increased in a 1.5-year period from 3/100,000 to 12/100,000 ( P<0.05) in correlation with increased isolation of ciprofloxacin-resistant organisms. A marked increase in the incidence of gonorrhea was also encountered in Jerusalem, where ciprofloxacin resistance affected 54.5% of the isolates in 2000. Pulsed-field gel electrophoresis typing of gonococci from different areas of Israel indicated that all of the ciprofloxacin-resistant isolates belonged to identical or related strains. Since fluoroquinolone-resistant gonococci may emerge and disseminate extensively over a short period of time, continuous surveillance of antibiotic susceptibility among gonococcal isolates should be performed to guide empiric therapy.

Adult↗

Empiric use of trimethoprim-sulfamethoxazole (TMP-SMX) in the treatment of women with uncomplicated urinary tract infections, in a geographical area with a high prevalence of TMP-SMX-resistant uropathogens.

This study evaluated whether trimethoprim-sulfamethoxazole (TMP-SMX) is effective for treatment of uncomplicated urinary tract infections (UTIs) due to TMP-SMX-resistant (TMP-SMX-R) pathogens. Healthy nonpregnant premenopausal women with symptomatic lower UTI were assessed for the presence of pyuria and bacteriuria; if either was present, a urine sample was cultured and TMP-SMX was prescribed. Clinical and microbiologic cure was assessed at days 5-9 and 28-42 after cessation of therapy. For 71%, of patients, cultures grew TMP-SMX-susceptible (TMP-SMX-S) microorganisms, and for 29%, cultures grew TMP-SMX-R organisms. Escherichia coli remained the predominant bacteria in both groups of cultures. At visit 2, microbiological cure had been achieved in 86% of the patients in the TMP-SMX-S group and 42% of those in the TMP-SMX-R group. Similar differences were found at visit 3 by clinical evaluation. Treatment with TMP-SMX of uncomplicated UTI caused by TMP-SMX-R microorganisms results in microbiologic and clinical failure. In high-resistance areas, TMP-SMX should not be the empiric drug of choice for uncomplicated UTI.

Adult↗

High rate of vaginal infections caused by non-C. albicans Candida species among asymptomatic women.

A prospective observational study of patients attending a gynecological clinic and those referred to a clinic for genitourinary infections was undertaken with the purpose of evaluating the relative prevalence of non-C. albicans Candida species among Candida isolates from the vagina in different clinical settings in an area with high occurrence of vulvovaginal candidiasis. The rate of non-C. albicans Candida species was 44.5% among asymptomatic women, 19.4% among those with sporadic vaginitis and 21% among patients with chronic vaginal symptoms (p < 0.001 for asymptomatic vs. pooled symptomatic women). No increase in the rate of non-C. albicans Candida was observed during a period of 4 years (1995-1998) despite a 1.57-fold increase in the sales of azole antifungal agents. Unlike some previous reports we could not document an association of non-C. albicans Candida species with chronic vaginal symptoms or increased use of azole antifungal agents. The significantly higher rate of these yeasts in asymptomatic women is in accord with the known tendency of non-C. albicans Candida species to cause mild symptoms.

Antifungal Agents↗

Effects of different doses in continuous veno-venous haemofiltration on outcomes of acute renal failure: a prospective randomised trial.

BACKGROUND: Continuous veno-venous haemofiltration is increasingly used to treat acute renal failure in critically ill patients, but a clear definition of an adequate treatment dose has not been established. We undertook a prospective randomised study of the impact of different ultrafiltration doses in continuous renal replacement therapy on survival. METHODS: We enrolled 425 patients, with a mean age of 61 years, in intensive care who had acute renal failure. Patients were randomly assigned ultrafiltration at 20 ml/h-1/kg(-1) (group 1, n = 146), 35 ml/h(-1)/kg(-1) (group 2, n = 139), or 45 ml/h(-1)/ kg(-1) (group 3, n = 140). The primary endpoint was survival at 15 days after stopping haemofiltration. We also assessed recovery of renal function and frequency of complications during treatment. Analysis was by intention to treat. RESULTS: Survival in group 1 was significantly lower than in groups 2 (p = 0.0007) and 3 (p = 0.0013). Survival in groups 2 and 3 did not differ significantly (p = 0.87). Adjustment for possible confounding factors did not change the pattern of differences among the groups. Survivors in all groups had lower concentrations of blood urea nitrogen before continuous haemofiltration was started than non-survivors. 95%, 92% and 90% of survivors in groups 1, 2 and 3, respectively, had full recovery of renal function. The frequency of complications was similarly low in all groups. INTERPRETATION: Mortality among these critically ill patients was high, but increase in the rate of ultrafiltration improved survival significantly We recommend that ultrafiltration should be prescribed according to patient's bodyweight and should reach at least 35 ml/h(-1)/kg(-1).

APACHE↗

Assessment of adequacy of ICU admission.

BACKGROUND: Direct costs of critical care are increasing more than in other health care sectors. Tools are needed to evaluate adequacy of ICU admission in order to have a proper allocation of ICU resources. OBJECTIVE: evaluation of different ways used to assess adequacy of ICU admission. METHODS STUDY TYPE: 12 months prospective descriptive study. SETTING: 24 Intensive Care beds of a 1000 beds tertiary hospital in Italy. PATIENTS: 2314 patients admitted to Cardiac Surgery, General and Postoperative Intensive Care Units. INTERVENTIONS: all patients admitted to the ICUs were studied. Information was collected for the patients' age, source of admission, diagnoses, surgical status, reason for admission, SAPS II score, NEMS daily score, LOS, ICU outcome. The number of available beds (ventilated or not) and nurse working hours were obtained. RESULTS: 2373 patients were admitted to the ICs, with an overall readmission rate of 2.5%, and a total amount of 8084 NEMS record. The mean Work Utilization Ratio was significantly different between the three IC and between working and weekend days in PACU and CSU. The 49.7% of the NEMS points is scored by the SAPS II 43-78 patients, corresponding to the 29.2% of >24 h admissions. The level of care provided and the trend of each admission was derived from NEMS score according to Iapichino. The proportion of HT records in each IC was 88.3% in ICU, 73.1% in PACU and 91.2% in CSU; the outcome (dead/discharged) was significantly different between LT and HT. CONCLUSIONS: Despite the difficulties imposed by he rigid nurses' work organization in Italy, a daily data collection about level of care, severity of illness, workload utilization could provide, together with standard administrative indexes, the necessary framework to assess and to improve adequacy of ICU admission.

Humans↗

Principles, protocols and patients: the practical management of a limit in ICU.

The definition and management of a limit is a common but sometimes extremely complex problem in the Intensive Care Unit (ICU). Guidelines and consensus documents have been published in order to help clinicians. Yet, many controversial issues are brought into question. Legal rules are sometimes vague and derive more from the interpretation of various and unrelated principles (which vary from country to country) than from a clear ad hoc law. In this sense, the practical management of a limit in ICU is usually run by a dual normativity: an external one, which derives from the cultural, moral and legal values of the society, and an internal one, which depends on the particular clinical and human situation, namely the values of everybody involved in (the patient, his/her relatives, the health staff) and the relationships among these people. The considerable freedom left for the decision by an open communication is a great and favourable potential which must be used in the interest of the patient's and of his/her family.

Clinical Protocols↗