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A Waller

Publications and source records attributed to A Waller.

At least 19 recordsLinked to original sources
PubMed2001

Validation of flow cytometric competitive binding protocols and characterization of fluorescently labeled ligands.

BACKGROUND: Fluorescently labeled ligands and flow cytometric methods allow quantification of receptor-ligand binding. Such methods require calibration of the fluorescence of bound ligands. Moreover, binding of unlabeled ligands can be calculated based on their abilities to compete with a labeled ligand. In this study, calibration parameters were determined for six fluorescently labeled N-formyl peptides that bind to receptors on neutrophils. Two of these ligands were then used to develop and validate competitive binding protocols for determining binding constants of unlabeled ligands. METHODS: Spectrofluorometric and flow cytometric methods for converting relative flow cytometric intensities to number of bound ligand/cell were extended to include peptides labeled with fluorescein, Bodipy, and tetramethylrhodamine. The validity of flow cytometric competitive binding protocols was tested using two ligands with different fluorescent properties that allowed determination of rate constants both directly and competitively for one ligand, CHO-NLFNYK-tetramethylrhodamine. RESULTS: Calibration parameters were determined for six fluorescently-labeled N-formyl peptides. Equilibrium dissociation constants for these ligands varied over two orders of magnitude and depended upon the peptide sequence and the molecular structure of the fluorescent tag. Kinetic rate constants for CHO-NLFNYK-tetramethylrhodamine determined directly or in competition with CHO-NLFNYK-fluorescein were statistically identical. CONCLUSIONS: Combination of spectrofluorometric and flow cytometric methods allows convenient calculation of calibration parameters for a series of fluorescent ligands that bind to the same receptor site. Competitive binding protocols have been independently validated.

Binding, Competitive↗
PubMed2000

Selection of controls in injury case-control studies.

PURPOSE: To assist in elucidating principles underlying the design of injury case-control studies.APPROACH: We begin by defining "event" as the sequence of circumstances that place a person at risk of injury (e.g. bicycle crash) and "injury given the event" as the resultant physical damage (e.g. head injury in bicycle crash). We then identify two broad classes of research question: 1) Studies of risk factors for the event, and, 2) Studies of risk factors for injury given the event. The study base for the first type of research question is all persons at risk of the event, while the study base for the second type is all persons who experience the event, and are therefore at risk of injury. It follows that in studies of risk factors for injury given the event, the controls should be a sample of all persons who experience the event. For example, in a study of bicycle helmets and head injuries, a suitable case group would be cyclists treated for head injury following a bicycle crash. The appropriate control group is drawn from the base population of all cyclists who crashed, including those who had no injuries. The control group may be restricted to cyclists who crashed and sought treatment for non-head injury under the assumption that the exposure distribution (prevalence of cycle helmet use) in the crash/no injury group is identical to the exposure distribution in the crash/non-head injury group.CONCLUSIONS: It is over ten years since innovative researchers in Seattle first applied the case-control design to the problem of bicycle crashes. Since then, successive bicycle injury studies at other centers have largely failed to extend and refine the Seattle methodology. A more critical approach to the design of case-control studies is required if we are to continue to advance the field of injury epidemiology.

Journal Article↗
PubMed2000

Author reply

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Journal Article↗
PubMed2000

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.

Aged↗
PubMed2000

Identification and characterization of a rat macrophage inflammatory protein-1alpha receptor.

A macrophage inflammatory protein-1alpha (MIP-1alpha) receptor has been cloned from rat (Rattus norvegicus) genomic DNA by PCR using oligonucleotides based on the mouse CCR1 DNA sequence and expressed in HEK293 cells to enable its characterization. The receptor was cloned three times in independent experiments to generate a consensus sequence. The rat ccrl receptor amino acid sequence is 92% identical to mouse and 80% identical to human CCR1. A consensus clone was transfected into HEK293 cells using the expression vector pIRES, and stable receptor expressing cell lines were isolated. In competitive receptor binding assays using iodinated human MIP-1alpha, rat ccrl binds hMIP-1alpha, hMIP-1beta, and hMCP-3, but not hRANTES or human interleukin-8 (hIL-8). We have been unable to demonstrate calcium mobilization by rat ccrl in HEK293 cells using human chemokines as ligands. Therefore, we have adopted lowercase nomenclature for the receptor until signaling is observed. This receptor and cell line may be of use in the preclinical development of CCR1 antagonists.

Amino Acid Sequence↗
PubMed2000

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.

Aged↗
PubMed1999

High dose morphine use in the hospice setting. A database survey of patient characteristics and effect on life expectancy.

BACKGROUND: Pain control is one of the most important goals of end-of-life care, and the use of opioids for this purpose is extremely common in hospice settings. However, it is unknown how many of the patients require high dose morphine (HDM, >299 mg/day of oral morphine equivalent), what the characteristics of these patients are, and whether the use of HDM might affect their survival. METHODS: The authors retrospectively studied the medical records of all 651 inpatients hospitalized at their center between January 1996 and December 1997. Information was collected regarding demographic parameters, medical diagnosis, pain mechanism, morphine dosage, use of rescue doses in addition to regular doses, use of coanalgesics and adjuvant treatments, and survival time in the hospice setting as associated with morphine dosage. RESULTS: The authors identified 453 patients (69.58%) who received morphine for pain relief, of whom 55 (12.14%) needed more than 299 mg/day. Morphine dosage was negatively associated with age (r = -0.35, P = 0.01). Male patients and nonwhite patients required slightly higher dosages than others. Primary breast and genitourinary cancers, as well as metastases to bone and spinal diseases, were associated with higher morphine dosages. Statistical analysis indicated a positive correlation between the log maximum of morphine dosage and the total number of rescue dosages (r = 0.307, P = 0.025). The median survival of patients on HDM was 15.6 days and did not differ from the survival of patients taking a lower dosage. CONCLUSIONS: A fairly strong correlation exists between morphine dosage and some clinicodemographic data. No significant dose-limiting adverse effects were observed, suggesting a high clinical safety profile. High morphine dosage does not affect patient survival. Awareness of the dosage factors will improve our ability to treat and predict probable HDM dosage, thus shortening the period until pain relief is reached.

Aged↗
PubMed1998

Threshold and graded response behavior in human neutrophils: effect of varying G-protein or ligand concentrations.

Observing the qualitative characteristics of response behavior as key variables in the signal transduction cascade are changed can provide insight into the fundamental roles of these interactions in producing cellular responses. Using flow cytometric assays and pertussis toxin (PT) treatment of human neutrophils, we have shown that actin polymerization stimulated with the chemoattractants N-formyl-Met-Leu-Phe, leukotriene B4, and interleukin-8 exhibits threshold behavior in terms of G-protein number. Partial PT treatment resulted in both responding and nonresponding populations of cells upon stimulation. As PT treatment was increased, the responding population of cells continued to respond maximally, while the number of cells responding decreased. We also showed that N-formyl peptide-stimulated oxidant production exhibits threshold behavior in terms of G-protein number, and the threshold for oxidant production is significantly greater than that for actin polymerization. The threshold behavior observed with PT treatment contrasted with the graded response behavior seen when cells were stimulated with different doses of ligand. For actin polymerization, only one population of cells was observed at submaximal ligand concentrations, and as ligand concentration was decreased the whole population responded submaximally. For oxidant production, as ligand concentration was decreased there were two populations of cells, but the responding cells responded submaximally. A mathematical model incorporating receptor/ligand binding and G-protein activation was developed to account for these differences in response behavior. Our results predict that an early signal transduction event in addition to, and not initiated by G-protein activation, is necessary to account for actin polymerization and oxidant production in neutrophils.

Actins↗
PubMed1998

Second primary cancer of the larynx in patients with lung cancer.

Synchronous or metachronous second primary malignancies of the lung are sometimes encountered in patients with laryngeal cancer while the occurrence of a laryngeal second primary following cancer of the lung is rare. A two-armed study was conducted. A prospective arm in which the larynges of 56 terminal lung cancer patients were examined, and a retrospective arm incorporating both a chart study of 126 terminal head and neck cancer patients (HNCP) and a computerized search of all hospital records of patients with laryngeal and lung cancers. No laryngeal malignancy was found in the lung cancer patients' group and no antedating pulmonary malignancy was recorded in the terminal HNCP. The computerized search of 1778 lung cancer patients and 213 laryngeal cancer patients also failed to demonstrate cases where the former preceded the latter. In conclusion. No second primary of the larynx was found in lung cancer patients. These results compare with reports of large databases where cancer of the larynx was found in a negligible percentage of lung cancer survivors and theories explaining this are discussed.

Aged↗
PubMed1997

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.

Head and Neck Neoplasms↗
PubMed1997

Distant metastases in terminal head and neck cancer patients.

With improved control of cancer above the clavicles, distant metastases (DM) are frequently more seen and are becoming a more common cause of morbidity and mortality. The present study defined the incidence of distant metastases in a cohort of terminal head and neck cancer patients (HNCP) and compared it to current reported data. The incidence of distant metastases in relation to the primary tumour was evaluated and their impact on survival was assessed. A retrospective survey of patient charts was made, based on the hospice database and original referring hospital charts. Data of 59 patients admitted to the hospice were evaluated. The incidence and location of locoregional and distant disease were studied and effects on survival analyzed. The overall survival from diagnosis to demise was 42.7 months. Thyroid cancer was seen in 20.3 per cent of cases and squamous cell cancer was seen in 59.3 per cent. Distant metastases were found in 83 per cent and 48.6 per cent of patients respectively. Laryngeal cancer patients had a 54.5 per cent incidence of distant metastases. Locoregional disease was seen in 47 per cent of cases and 35.7 per cent of them had distant metastases while a 64.3 per cent incidence of distant metastases was found in cases without locoregional disease. Mean survival was 47.3 months with distant metastases vs 36.5 months without metastases. The difference was not statistically significant. The incidence of distant metastases in squamous cell cancer in terminal HNCP was 48.6 per cent. This is the highest reported incidence of metastases in a clinical series. Patients without locoregional disease had almost a two-fold incidence of metastases. Survival was not affected by metastases in this series.

Aged↗
PubMed1997

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.

Adult↗
PubMed1997

Towards a narrative-based augmentative communication system.

Augmentative communication systems enable non-speaking people to communicate using letters, words, phrases and sentences. Few systems provide support for longer lengths of text despite the fact that most day-to-day conversation is characterised by 'story telling'. This paper discusses the need for communication systems to facilitate this type of interaction, whilst allowing for other modes of communication. A case history detailing the use of a prototype system with an adult with dysphasia illustrates that providing augmentative communication should not be restricted to expression of 'needs and wants', but should enable the non-speaking individual to share past experience and future hopes.

Aphasia↗
PubMed1995

[Corticosteroids in terminal cancer].

Corticosteroids are frequently prescribed in terminal cancer. They were prescribed in more than 50% of 100 consecutive patients of our hospice for palliation of anorexia, weakness, symptoms of cerebral metastases and of hypercalcemia, and other problems. There was objective and/or subjective improvement in most, though usually of short duration. If there is no improvement after a few days, corticosteroids should be discontinued.

Adrenal Cortex Hormones↗
PubMed1995

Care of the terminal head and neck cancer patient in the hospice setting.

The ratio of incidence to mortality is somewhat less than 3:1 for head and neck cancer, and the 5-year relative survival rate is 50%. Despite the high mortality rate, few reports have focused on patients with terminal head and neck cancer. A growing number of these patients end their lives in a hospice facility. A retrospective analysis was undertaken of 67 patients with terminal head and neck cancer who were admitted to the Tel Hashomer Hospice between 1988 and 1992. Patient data were reviewed and analyzed, and the particular characteristics of this population were defined. This study found that terminal head and neck cancer patients seem to receive better support in a hospice than in a general hospital or some family settings.

Aged↗