A Pure Life: The Microbial Ecology of High Purity Industrial Waters.

The microbial ecology of various natural environments has been an active area of research since the earlier part of the twentieth century. Remote and sometimes extreme environments such as the deep ocean and the deep terrestrial subsurface have revealed a remarkable array of microorganisms. The majority of these environments are nutrient limited, and microorganisms-principally, bacteria-have developed a number of survival strategies that enable their survival and, in some cases, replication. While planktonic microorganisms exist in oligotrophic environments, the predominant mode of survival and growth is associated with biofilms. There are a number of similarities between the physicochemistry of industrial water systems and some natural aquatic ecosystems, and these similarities extend to the microbial populations and the survival mechanisms that are employed. The "starvation-survival" mechanisms, including biofilm formation, may be associated with deleterious effects on industrial water systems. These effects include heat transfer inhibition, microbially influenced corrosion, and contamination of various products manufactured in a wide array of industries. Biological fouling of industrial water systems has significant direct and indirect (through antimicrobial chemical applications) impacts on engineered materials and on the etiology of some waterborne diseases. This review provides an overview of the microbial ecology of purified waters and discusses the impacts of biological activity on industrial systems.

Erythropoiesis-stimulating agents significantly delay the onset of a regular transfusion need in nontransfused patients with lower-risk myelodysplastic syndrome.

BACKGROUND: The EUMDS registry is an unique prospective, longitudinal observational registry enrolling newly diagnosed patients with lower-risk myelodysplastic syndrome (MDS) from 17 European countries from both university hospitals and smaller regional hospitals. OBJECTIVE: The aim of this study was to describe the usage and clinical impact of erythropoiesis-stimulating agents (ESAs) in 1696 patients enrolled between 2008 and 2014. METHODS: The effects of ESAs on outcomes were assessed using proportional hazards models weighting observations by propensity to receive ESA treatment within a subset of anaemic patients with or without a regular transfusion need. RESULTS: ESA treatment (median duration of 27.5 months, range 0-77 months) was administered to 773 patients (45.6%). Outcomes were assessed in 897 patients (484 ESA treated and 413 untreated). ESA treatment was associated with a nonsignificant survival benefit (HR 0.82, 95% CI: 0.65-1.04, P = 0.09); this benefit was larger amongst patients without prior transfusions (P = 0.07). Amongst 539 patients for whom response to ESA treatment could be defined, median time to first post-ESA treatment transfusion was 6.1 months (IQR: 4.3-15.9 months) in those transfused before ESA treatment compared to 23.3 months (IQR: 7.0-47.8 months) in patients without prior transfusions (HR 2.4, 95% CI: 1.7-3.3, P < 0.0001). Responding patients had a better prognosis in terms of a lower risk of death (HR 0.65, 95% CI: 0.45-0.893, P = 0.018), whereas there was no significant effect on the risk of progression to acute myeloid leukaemia (HR 0.71, 95% CI: 0.39-1.29, P = 0.27). CONCLUSION: Appropriate use of ESAs can significantly delay the onset of a regular transfusion need in patients with lower-risk MDS.

Nursing home structure and association with agitation and use of psychotropic drugs in nursing home residents in three countries: Norway, Austria and England.

BACKGROUND: Understanding the underlying mechanisms and risk factors leading to agitation is crucial to reduce the severity of agitation and increase quality of life. International comparative studies offer special advantages in elucidating environmental risk factors by providing a wider diversity of environmental exposures such as nursing home structures, health care systems and genetic diversity. METHODS: Baseline data for three different intervention studies in Austria (n = 38), England (n = 302) and Norway (n = 163) were combined posthoc. Patients were grouped according to their dementia severity using the global deterioration scale (GDS), functional assessment staging (FAST) and clinical dementia rating (CDR) scales. For the measurement of agitation, the Cohen-Mansfield Agitation Inventory (CMAI) was used. Data analysis was performed using one-way ANOVA, multivariate and linear regression analysis. RESULTS: CMAI scores were available for 503 subjects with dementia. There were significant differences between the nursing home residents in the three countries regarding age, gender and dementia severity (all p values < 0.001). In the multivariate analyses, the level of agitation differed with higher mean scores in the Austrian (mean (SD) score 51.9(21.8)) compared to UK (43.3(16.1)) and Norwegian (41.6(13.2)) nursing homes (p = 0.002). Similarly, the use of psychotropic drugs differed significantly, with a higher proportion of neuroleptics in UK (48%, p < 0.001) and Austrian (52.6%; p = 0.001) compared to Norwegian (19%) nursing homes. CONCLUSION: We found differences in agitation and antipsychotic drug use which are likely related to structural and cultural differences in nursing homes in three European countries. These findings suggest that structural changes can improve quality of care and quality of life for nursing home residents.

[Out-of-hospital resuscitation in Israel 2000].

The aim of the study was to evaluate the impact of pre-hospital cardio-pulmonary resuscitation, performed by mobile intensive cardiac care units of Magen David Adom (MDA) teams in the framework of a national survey conducted in the period February and March 2000. During the survey, MDA performed 539 resuscitations, 485 of which were performed by mobile intensive care units of MDA, and they constitute the study population of the present analysis. The average age of the patients was 70.5 years, and 68% were men. The mean response time of the mobile intensive care units was 10.3 minutes. In 14% of the cases, a bystander initiated basic cardiac life support before the arrival of the MDA team. Upon arrival of the resuscitation team, 242 patients (50%) had asystole, 19% ventricular tachycardia (VT)/ventricular fibrillation (VF), 13% pulseless electrical activity (PEA), and 18% had other severe arrhythmias. One hundred and ninety-nine patients (41%) were transferred alive to the hospital after successful resuscitation. Hospital summaries were obtained for 148 of these patients. The cause of cardiac arrest was cardiac in 64% of the cases and 48% of the patients who reached the hospital had a previous history of heart disease. Fifty-three patients (11%) were discharged alive from the hospital. Patients discharged alive were younger, more promptly resuscitated, 78% had a cardiac cause of death and 38% of them were in ventricular tachycardia/fibrillation when first seen by the resuscitation team. The rate of successful resuscitation to discharge in the sub-group with VT/VF was 21%, and only 4% for patients in asystole, which is in line with other studies. However, the rate of initiation of resuscitation by bystanders is low in Israel. These data may help the medical staff and the health policy providers in Israel.

Biological characterization of a novel biodegradable antimicrobial polymer synthesized with fluoroquinolones.

Biomaterial-related infections continue to represent a significant challenge to the medical community. Several approaches have been utilized to incorporate antimicrobial agents at the surface of implant devices in attempts to delay or eliminate the formation of biofilms. To date, most of these strategies have focused on drug conjugation or diffusion-limited systems for the delivery of such pharmaceutical agents. More recently, work has been presented on the feasibility of incorporating drugs into the backbone of polymers as a main-chain monomer. When sequenced into the backbone of the polymer with other monomers that are hydrolytically sensitive to enzyme-catalyzed breakdown, it is thought that drugs may be able to be selectively released. Specifically, degradable polyurethanes have been synthesized with fluoroquinolone antibiotics and have shown an ability to kill bacteria when released following degradation of the polymer chains by the macrophage-derived enzyme cholesterol esterase. However, specificity of the cleavage sites in the polymer was difficult to control. Since cholesterol esterase has specificity for hydrophobic moieties, it is desirable to alter the formulation of the polyurethanes to incorporate long hydrophobic monomers immediately adjacent to the ciprofloxacin molecule. Hence, the current study focuses on evaluating the enzyme-catalyzed degradation of a degradable polyurethane synthesized with 1,12 diisocyanatododecane as a substitute for 1,6 diisocyanatohexane, which was used in previous work. Validation of specific ciprofloxacin release and the generation of antimicrobial are shown. A preliminary cell study to assess the cytotoxicity of this biodegradable antibiotic polymer shows that the material has no observable effects on cell proliferation or cell membrane structure.

Erythropoietin induces tumor regression and antitumor immune responses in murine myeloma models.

Recombinant human erythropoietin (rHuEpo) has been used successfully in the treatment of cancer-related anemia. Clinical observations with several patients with multiple-myeloma treated with rHuEpo has shown, in addition to the improved quality of life, a longer survival than expected, considering the poor prognostic features of these patients. Based on these observations, we evaluated the potential biological effects of rHuEpo on the course of tumor progression by using murine myeloma models (MOPC-315-IgAlambda(2) and 5T33 MM-IgG(2b)). Here we report that daily treatment of MOPC-315 tumor-bearing mice with rHuEpo for several weeks induced complete tumor regression in 30-60% of mice. All regressors that were rechallenged with tumor cells rejected tumor growth, and this resistance was tumor specific. The Epo-triggered therapeutic effect was shown to be attributed to a T cell-mediated mechanism. Serum Ig analysis indicated a reduction in MOPC-315 lambda light chain in regressor mice. Intradermal inoculation of 5T33 MM tumor cells followed by Epo treatment induced tumor regression in 60% of mice. The common clinical manifestation of myeloma bone disease in patients with multiple-myeloma was established in these myeloma models. Epo administration to these tumor-bearing mice markedly prolonged their survival and reduced mortality. Therefore, erythropoietin seems to act as an antitumor therapeutic agent in addition to its red blood cell-stimulating activity.

Recombinant human erythropoietin reduces allogeneic blood transfusion requirements in patients undergoing major orthopedic surgery.

Blood loss is a significant problem encountered in patients undergoing total joint arthroplasty, and is considered to be one of the factors affecting the outcome of the operation. Traditionally these patients have been treated with blood transfusions. The introduction of recombinant human erythropoietin (rHuEpo) into clinical practice enabled assessment of its effectiveness to decrease the allogeneic blood transfusion requirement (BTR), thus avoiding or minimizing transfusion-related complications. Fifteen patients undergoing total hip replacement (THR, 10 patients) and total knee replacement (TKR, 5 patients) in our institute (from January-April 1997), were studied. After signing an informed consent they received daily s.c. rHuEpo (100 IU/kg for those with hemoglobin (Hb) > 13 g/dl, 300 IU/kg for Hb < 13) during the 10 days prior to surgery and the 4 days following the operation. Allogeneic red blood cell (RBC) transfusions were given as needed. Hb levels were measured on days -10, 0, +1.3 and 7 of the procedure and the BTR was recorded. The results were compared with those of previous patients operated on from January-December 1996. Patients who were eligible for the study but refused to participate served as controls. The mean Hb level in the study group prior to rHuEpo administration (day -10) was 13.41 g/dl, similar to those of the control group (13.47 g/dl on day 0). However, the mean Hb levels in the rHuEpo treated patients on days 0, 1, 3 and 7 were 14.37, 11.09, 10.99, and 11.2 g/dl, respectively. This way compared with the levels of 13.47 (p = 0.016), 9.88 (p = 0.024), 9.60 (p = 0.004) and 9.97 g/dl (p = 0.007) in the control patients. The difference between the rHuEpo treated patients and the control patients was more significant among the THR patients than among the TKR patients. Of the 10 rHuEpo-treated THR patients, only a single patient required one allogeneic blood unit, as compared with 23 units transfused to the 30 control patients. None of the rHuEpo-treated TKR patients required blood transfusion as opposed to 4 units needed by the 11 control patients. In total, only one allogeneic blood unit was required by the study group which way calculated to an average consumption of 0.066 blood unit per person, compared with 27 blood units used by the 41 controls, i.e. 0.66 blood units per person (p < 0.001). In the patients treated, rHuEpo was very well tolerated with no adverse effects.

Oral contraceptives can cause falsely low vitamin B(12) levels.

Serum vitamin B(12) radioimmunoassays may give falsely low results in patients with folate deficiency, multiple myeloma, megadose of vitamin C and following radioisotope organ scan. We evaluated 10 consecutive healthy women on oral contraceptives (OC) who had falsely low vitamin B(12) levels, as reflected by normal urine methylmalonic acid and plasma homocysteine. After 1-month cessation of OCs, vitamin B(12) returned to the normal range in all women. Transcobalamin I (TCI) blood level was decreased in 60% of patients. OCs may cause temporary low vitamin B(12) blood levels of no clinical significance that can be associated with low TCI levels

Report of an international working group to standardize response criteria for myelodysplastic syndromes.

Standardized criteria for assessing response are essential to ensure comparability among clinical trials for patients with myelodysplastic syndromes (MDS). An international working group of experienced clinicians involved in the management of patients with MDS reviewed currently used response definitions and developed a uniform set of guidelines for future clinical trials in MDS. The MDS differ from many other hematologic malignancies in their chronicity and the morbidity and mortality caused by chronic cytopenias, often without disease progression to acute myeloid leukemia. Whereas response rates may be an important endpoint for phase 2 studies of new agents and may assist regulatory agencies in their evaluation and approval processes, an important goal of clinical trials in MDS should be to prolong patient survival. Therefore, these response criteria reflected 2 sets of goals in MDS: altering the natural history of the disease and alleviating disease-related complications with improved quality of life. It is anticipated that the recommendations presented will require modification as more is learned about the molecular biology and genetics of these disorders. Until then, it is hoped these guidelines will serve to improve communication among investigators and to ensure comparability among clinical trials. (Blood. 2000;96:3671-3674)

The incidence of pseudothrombocytopenia in automatic blood analyzers.

UNLABELLED: The aim of the present work was to undertake an assessment of the incidence of pseudothrombocytopenia (PTCP) in patients referred for evaluation of thrombocytopenia in an outpatient hematology clinic. METHODS: Prospective assessment of 60 consecutive cases with platelet count < 100 x 10(9)/l in a hematology clinic during a 2-year period. RESULTS: PTCP was the second most common cause for low platelet count, with an incidence of 17%. Platelet count of patients with PTCP at presentation was 42 +/- 22 x 10(9)/l, and when re-analyzed on fresh samples, 208 +/- 39 x 10(9)/l. The relatively high prevalence of pseudothrombocytopenia in our series was due to a lack of microscopic inspection of the blood smear in the primary care laboratories and considerable delay in sample processing. CONCLUSIONS: PTCP should be considered in the assessment of low platelet count. While decreasing the transfer time of blood specimens may decrease PTCP incidence, microscopic inspection of the blood smear may avoid erroneous diagnosis of thrombocytopenia.

Severe amyloidosis with mild multiple myeloma--an unusual course.

Amyloidosis may be primary or myeloma-associated. Skeletal lesions and the percentage of bone marrow plasma cells (<10% in primary, >20% in myeloma) account for the major differences between the two varieties. In the literature there are rare cases of primary amyloidosis presenting without myeloma and followed by development of myelomatous manifestations. Usually, the primary disease (i.e. the myeloma) is advanced, when amyloidosis is diagnosed. We describe a patient who had presented with a severe and progressive systemic amyloidosis and was diagnosed later to have a mild light chain myeloma. Aggressive treatment with melphalan, prednisone and colchicine resulted in a temporary partial remission, followed by a rapid downhill course, and the patient's death. The point of relatively mild myeloma following a rapidly progressive course of advanced amyloidosis is emphasized. Awareness of the possibility of such a combination may lead to early diagnosis, a more aggressive or novel therapeutic approach and, possibly, to a better prognosis.

Localized drug delivery using crosslinked gelatin gels containing liposomes: factors influencing liposome stability and drug release.

We describe a drug-delivery vehicle that combines the sustained release properties of liposomes with the structural advantages of crosslinked gelatin gels that can be implanted directly or coated onto medical devices. Liposome inclusion in gelatin gels does not compromise thermal stability nor does it interfere with the resiliency of gels to tensile force. However, electron spin resonance analysis of sequestered DPPC liposomes revealed a slight depression (ca. 1.0 degrees C) of the gel-to-fluid phase transition relative to liposomes in suspension. The level of liposome release from gels was determined by liposome concentration, liposome size, and the presence of poly(ethylene oxide) chains in the gel matrix or in the liposome membrane. Both neutral and charged liposomes displayed relatively high affinities for poly(ethylene glycol)gelatin gels, with only 10-15% release of initially sequestered liposomes while liposomes in which poly(ethylene glycol) was included within the membrane were not as well retained (approximately 65% release). The in vitro efflux of ciprofloxacin from liposomal gels immersed in serum was nearly complete after 24 h compared to 38% release of liposomal chlorhexidine after 6 days. The serum-induced destabilization of liposomal ciprofloxacin depended on the accessibility of serum components to gels as partly immersed gels retained approximately 50% of their load of drug after 24 h. In vivo experiments using a catheterized rabbit model of urinary tract infection revealed the absence of viable Escherichia coli on coated catheter surfaces in seven out of nine cases while all untreated catheter surfaces examined (n = 7) were contaminated.

Synthesis and characterization of a novel biodegradable antimicrobial polymer.

Bacterial infection is a frequent complication associated with the use of medical devices. In an effort to address this problem, antibacterial agents have been incorporated or applied directly onto the surfaces of numerous types of medical devices. This study assessed the feasibility of using a novel biodegradable polymer to release antibiotic drugs in response to inflammatory related enzymes. A model drug polymer was synthesized using 1,6-hexane diisocyanate (HDI), polycaprolactone diol (PCL), and a fluoroquinolone antibiotic, ciprofloxacin. Polymers were characterized by size-exclusion chromatography (SEC), and elemental analysis. Biodegradation studies were carried out by incubating the polymers with solutions of cholesterol esterase (CE) or phosphate buffer (pH 7.0) for 30 days at 37 degrees C. The degradation was assessed by high-performance liquid chromatography (HPLC), mass spectrometry (MS) and 14C radiolabel release. Subsequently, the activity of the released antibiotic was assessed against a clinical isolate of Pseudomonas aeruginosa. HPLC analysis showed the release of multiple degradation products which were identified, by tandem MS, to include ciprofloxacin and derivatives of ciprofloxacin. The microbiological assessment showed that the released ciprofloxacin possessed antimicrobial activity; 1 microg/ml was measured after 10 days. The results of this study suggest that these novel bioresponsive antimicrobial polymers or similar analogs show promise for use in the control of medical device associated infections.

Splenic lymphoma presenting as warm autoimmune hemolytic anemia associated with pure red cell aplasia.

BACKGROUND AND OBJECTIVE: Warm autoimmune hemolytic anemia (AIHA) is a condition in which peripheral red blood cell (RBC) destruction is induced by the presence of an autoantibody. Pure red cell aplasia (PRCA) represents an isolated process of decreased erythropoiesis. The combination of both is quite rare, with a very poor prognosis. We describe a patient with isolated splenic lymphoma whose presentation was a combination of AIHA and PRCA. The patient was resistant to all treatment. MATERIALS AND METHODS: Erythroid colony assays were performed, in order to compare the effect of the patient's serum on colonies with that of a normal control. RESULTS: The patient's serum significantly suppressed normal erythroid colony growth. A red cell eluate revealed the presence of a warm autoantibody. CONCLUSIONS: The patient's serum contained warm autoantibody responsible for peripheral RBC destruction and a humoral factor, perhaps the warm autoantibody, which suppressed bone marrow erythropoiesis. Establishing an early diagnosis, and treatment of the underlying disease might result in a better prognosis.