Induced-Charge Capacitive Deionization: The Electrokinetic Response of a Porous Particle to an External Electric Field.

We demonstrate the phenomenon of induced-charge capacitive deionization that occurs around a porous and conducting particle immersed in an electrolyte, under the action of an external electric field. The external electric field induces an electric dipole in the porous particle, leading to its capacitive charging by both cations and anions at opposite poles. This regime is characterized by a long charging time, which results in significant changes in salt concentration in the electrically neutral bulk, on the scale of the particle. We qualitatively demonstrate the effect of advection on the spatiotemporal concentration field, which, through diffusiophoresis, may introduce corrections to the electrophoretic mobility of such particles.

Delivery of minimally dispersed liquid interfaces for sequential surface chemistry.

We present a method for sequential delivery of reagents to a reaction site with minimal dispersion of their interfaces. Using segmented flow to encapsulate the reagents as droplets, the dispersion between reagent plugs remains confined in a limited volume, while being transmitted to the reaction surface. In close proximity to the target surface, we use a passive array of microstructures for removal of the oil phase such that the original reagent sequence is reconstructed, and only the aqueous phase reaches the reaction surface. We provide a detailed analysis of the conditions under which the method can be applied and demonstrate maintaining a transition time of 560 ms between reagents transported to a reaction site over a distance of 60 cm. We implemented the method using a vertical microfluidic probe on an open surface, allowing contact-free interaction with biological samples, and demonstrated two examples of assays implemented using the method: measurements of receptor-ligand reaction kinetics and of the fluorescence response of immobilized GFP to local variations in pH. We believe that the method can be useful for studying the dynamic response of cells and proteins to various stimuli, as well as for highly automated multi-step assays.

Rapid detection of urinary tract infections using isotachophoresis and molecular beacons.

We present a novel assay for rapid detection and identification of bacterial urinary tract infections using isotachophoresis (ITP) and molecular beacons. We applied on-chip ITP to extract and focus 16S rRNA directly from bacterial lysate and used molecular beacons to achieve detection of bacteria specific sequences. We demonstrated detection of E. coli in bacteria cultures as well as in patient urine samples in the clinically relevant range 1E6-1E8 cfu/mL. For bacterial cultures we further demonstrate quantification in this range. The assay requires minimal sample preparation (a single centrifugation and dilution), and can be completed, from beginning of lysing to detection, in under 15 min. We believe that the principles presented here can be used for design of other rapid diagnostics or detection methods for pathogenic diseases.

Miniaturized system for isotachophoresis assays.

We present an inexpensive hand-held device (240 g) that implements microchip isotachophoresis (ITP) with laser induced fluorescence (LIF) detection. This self-contained instrument integrates the functionality required for high voltage generation onto a microelectronic chip, includes LIF detection and is powered by a universal serial bus (USB) link connected to a laptop computer. Using this device we demonstrate focusing and detection of a fluorescent species with a limit of detection of 100 pM. We show that the response of the detector is linear with the initial analyte concentration, making this device suitable for quantitative analysis. We also demonstrate the use of our simulation tools for design and prediction of ITP assays, and validate these results with a demonstration of multiplexed indirect detection of (unlabeled) analytes performed using the device. We find good agreement between simulations and experimental results. Using a label-free isotachaphoresis assay implemented in the hand-held device we detect two explosives and an endocrine disruptor spiked in river water, with no prior sample processing.

Fluorescent carrier ampholytes assay for portable, label-free detection of chemical toxins in tap water.

We present a novel method for fluorescence-based indirect detection of analytes and demonstrate its use for label-free detection of chemical toxins in a hand-held device. We fluorescently label a mixture of low-concentration carrier ampholytes and introduce it into an isotachophoresis (ITP) separation. The carrier ampholytes provide a large number of fluorescent species with a wide range of closely spaced effective electrophoretic mobilities. Analytes focus under ITP and displace subsets of these carrier ampholytes. The analytes are detected indirectly and quantified by analyzing the gaps in the fluorescent ampholyte signal. The large number (on the order of 1000) of carrier ampholytes enables detection of a wide range of analytes, requiring little a priori knowledge of their electrophoretic properties. We discuss the principles of the technique and demonstrate its use in the detection of various analytes using a standard microscope system. We then present the integration of the technique into a self-contained hand-held device and demonstrate detection of chemical toxins (2-nitrophenol and 2,4,6-trichlorophenol) in tap water, with no sample preparation steps.

Method for analyte identification using isotachophoresis and a fluorescent carrier ampholyte assay.

We present a novel method for identification of unlabeled analytes using fluorescent carrier ampholytes and isotachophoresis (ITP). The method is based on previous work where we showed that the ITP displacement of carrier ampholytes can be used for detection of unlabeled (nonfluorescent) analytes. We here propose a signal analysis method based on integration of the associated fluorescent signal. We define a normalized signal integral which is equivalent to an accurate measure of the amount of carrier ampholytes which are focused between the leading electrolyte and the analyte. We show that this parameter can be related directly to analyte effective mobility. Using several well characterized analytes, we construct calibration curves relating effective mobility and carrier ampholyte displacement at two different leading electrolyte (LE) buffers. On the basis of these calibration curves, we demonstrate the extraction of fully ionized mobility and dissociation constant of 2-nitrophenol and 2,4,6-trichlorophenol from ITP experiments with fluorescent carrier ampholytes. This extraction is based on no a priori assumptions or knowledge of these two toxic chemicals. This technique allows simultaneous identification of multiple analytes by their physiochemical properties in a few minutes and with no sample preparation.

A multicentre international study of sedation for uncontrolled symptoms in terminally ill patients.

The issue of symptom management at the end of life and the need to use sedation has become a controversial topic. This debate has been intensified by the suggestion that sedation may correlate with 'slow euthanasia'. The need to have more facts and less anecdote was a motivating factor in this multicentre study. Four palliative care programmes in Israel, South Africa, and Spain agreed to participate. The target population was palliative care patients in an inpatient setting. Information was collected on demographics, major symptom distress, and intent and need to use sedatives in the last week of life. Further data on level of consciousness, adequacy of symptom control, and opioids and psychotropic agents used during the final week of life was recorded. As the final week of life can be difficult to predict, treating physicians were asked to complete the data at the time of death. The data available for analysis included 100 patients each from Israel and Madrid, 94 patients from Durban, and 93 patients from Cape Town. More than 90% of patients required medical management for pain, dyspnoea, delirium and/or nausea in the final week of life. The intent to sedate varied from 15% to 36%, with delirium being the most common problem requiring sedation. There were variations in the need to sedate patients for dyspnoea, and existential and family distress. Midazolam was the most common medication prescribed to achieve sedation. The diversity in symptom distress, intent to sedate and use of sedatives, provides further knowledge in characterizing and describing the use of deliberate pharmacological sedation for problematic symptoms at the end of life. The international nature of the patient population studied enhances our understanding of potential differences in definition of symptom issues, variation of clinical practice, and cultural and psychosocial influences.

Salivary flow and its relation with oral symptoms in terminally ill patients.

BACKGROUND: Patients with terminal malignant disease commonly report hyposalivation or xerostomia. This leads to "dry mouth," fungal infection, and mucosal abnormalities. To the authors' knowledge oral symptomatology and findings have not been correlated previously with accurate salivary flow measurements. METHODS: Measurement of stimulated parotid salivary flow rate and clinical recording of oral symptoms within 24 hours from the time of hospital admission were obtained in 48 terminally ill cancer patients. Subjective reporting of symptoms by patients, parotid salivary flow rate, clinical recording of dental status, presence of candidiasis, angular cheilitis, and dryness of the floor of the mouth were obtained. RESULTS: A clinical diagnosis of oral candidiasis was made tentatively in 94% of patients, and 50% of the patients were found to have angular cheilitis. Thirty-one of 45 evaluable patients (68%) reported a sensation of oral dryness. Sixteen of the 48 patients (33%) had no saliva at the floor of the mouth. Analysis of individual salivary flow rates was stratified into 3 levels of secretion: 0, < 0.2, and > or= 0.2 mL/minute. Symptoms were found to correlate with salivary flow rates. CONCLUSIONS: In the current study, symptoms were found to be most severe in the patients with xerostomia followed by those patients with hyposalivation. Treatment should be directed individually to each group of patients using either salivary substitutes or stimulants. The rate of incidence of oral pathologic findings may be higher than formerly recognized.

Pain experienced by patients with terminal head and neck carcinoma.

BACKGROUND: Pain is one of the most feared consequences of cancer and is experienced by up to 80% of patients with head and neck carcinoma (HNC). Pain in terminal HNC patients is common and often defined as severe. This study evaluated the effectiveness of the World Health Organization (WHO) analgesic ladder in the treatment of a cohort of terminal HNC patients. METHODS: The authors prospectively evaluated 62 consecutive terminal HNC patients admitted to the Chaim Sheba Medical Center Tel Hashomer Hospice or the general hospital. Data pertaining to tumor origin, spread, treatment, and results were defined. Pain was assessed with the McGill Pain Questionnaire, using a 10-point visual analogue scale (VAS) and a body map. Pain was diagnosed according to cause and type. Treatment was selected according to the guidelines provided in the WHO analgesic ladder. RESULTS: Only 10 patients suffered from pain that was not locoregional. The results of the VAS score were available in the first reading in all patients with pain (n = 48), with a mean of 4.7 (standard deviation [SD] +/- 2.0). A mean second VAS score obtained 72 hours after the first was 1.9 (SD +/- 1.1). The difference between the two scores was statistically significant (P < 0.001). A third score was available for only 6 patients, with a mean of 1.6. Only 2 patients did not experience improvement of pain after 72 hours of treatment; both of these patients had bony involvement with tumor. Thirty-one patients (65%) were diagnosed with pain of nociceptive origin; these patients were categorized as having actual nociceptive pain (22), nociceptive nerve pain (6), or referred pain to the ear (3). Nonnociceptive pain of neuropathic origin was noted for only 6 patients (12.5%). Pain that could not be well defined but was responsive to opioid analgesic treatment was noted for 11 patients. A different form of non-cancer-related pain was noted for only one patient. CONCLUSIONS: Patients were treated for pain according to the WHO analgesic ladder. They received adequate narcotic analgesics and supportive measures that allowed significant reduction of pain in nearly all cases, with acceptable side effects.

Home and inpatient hospice care of terminal head and neck cancer patients.

The objective is to evaluate and compare data on a cohort of terminal head and neck cancer (HNC) patients from both home and hospital-based hospice programs and to define the particular problems and needs of those patients. The setting was a tertiary academic referral centre in Tel Hashomer, Israel. We carried out a retrospective survey of patient charts based on hospice databases and death certificates of the hospital tumor registry. Charts of 102 HNC patients admitted to the hospice between 1988 and 1994 and 24 charts of HNC patients cared for by the home hospice program between 1990 and 1994 were studied. Pain, airway problems, and dysphagia were the common problems reported. A comparison of the two programs showed home hospice patients to be younger and with lower pain levels, less weight loss, and less oral candidiasis. There were fewer oral cavity tumor patients in the home hospice group. The incidence of distant metastases was in 50% range in both groups. Judging by chart entries relating to pain, airway care, and food intake, treatment protocols were effective in both programs in the alleviation of pain and other symptoms. Both programs appeared to provide adequate care for terminal HNC patients. The main difference in care between the two groups stemmed from the decisions of referring physicians and not from a predetermined level of care. The incidence of distant metastases was higher than that reported in earlier clinical series.

Effect of acute changes in the PaCO2 on acid-base parameters in normal dogs and dogs with metabolic acidosis or alkalosis.

There is a linear relationship between the PaCO2 and blood hydrogen ion concentration in normal dogs, but for theoretical reasons to be discussed, we questioned whether this relationship would apply in animals with metabolic acidosis or alkalosis. To study this in more detail, animals were divided into three groups: normal, metabolically acidotic, and metabolically alkalotic. Following anesthesia and bilateral ureteral ligation, dogs were intubated and ventilated to produce acute steady state PaCO2 values corresponding to the range observed during disease states. Changes in the volume and electrolyte composition of the gastrointestinal fluid and urine as well as the concentration and distribution of lactate were evaluated in all experiments. We observed the previously described linear relationship between the PaCO2 and blood hydrogen ion concentration in normal dogs, but the slope of the regression line differed significantly from those of dogs with metabolic acidosis and metabolic alkalosis. On the other hand, there was a consistent relationship between the ratio of the PaCO2 values, but not the absolute PaCO2, and the change in the plasma bicarbonate concentration over a wide range of PaCO2 values in all groups of dogs. The chemical basis for these observations will be discussed.

Elevation of the blood lactate concentration by alkali therapy without requiring additional lactic acid accumulation: theoretical considerations.

A patient presented with lactic acidosis and severe acidemia; sodium bicarbonate was administered to titrate the very large hydrogen ion load. Coincident with this therapy, the blood lactate concentration rose from 21 to 27 mmole/L. In order to evaluate whether this rise in lactate could have occurred without requiring additional net lactic acid production, the effect of the hydrogen ion concentration on lactate distribution was evaluated. Data obtained from animal studies support the established hypothesis that lactate is distributed like other weak organic acids at steady-state; hence, alkalemia should favor a shift of lactate from the intracellular fluid (ICF) to the extracellular fluid (ECF). The authors calculated that the blood lactate concentration could rise by 50% without requiring net lactic acid accumulation when the severe acidemia was corrected by alkali therapy. Thus, an increase in lactate concentration of the magnitude observed during alkali therapy need not indicate a worsening of the metabolic picture in lactic acidosis.