Predicting the trajectory of will to live in terminally ill patients

Will to live has been shown to vary considerably during the final course of a terminal illness. The goal of this study was to identify illness-related and demographic variables predicting will to live among dying patients. Subjects were 168 patients with cancer who were admitted for palliative care. Will to live was measured twice daily for the duration of hospitalization by using a self-report 100-mm visual analogue scale. Will-to-live data for each patient were summarized into two statistics, intercept and slope, by using simple linear regression analyses. Intercept-slope pairs for all patients were classified into the following five clusters by using spatial and conceptual criteria: patients with sustained high will to live (58%), patients with sustained moderate will to live (11%), patients with sustained low will to live (3%), will-to-live relinquishers (18%), and will-to-live acquirers (10%). Discriminant analyses revealed seven variables that accounted for 69% of the variance in cluster membership: anxiety, shortness of breath, nausea, length of survival from time of admission, having a diagnosis of colon cancer, having no religion, and living with a spouse.     

Release of ATP induced by hypertonic solutions in Xenopus oocytes

ATP mediates intercellular communication. Mechanical stress and changes in cell volume induce ATP release from various cell types, both secretory and non-secretory. In the present study, we stressed Xenopus oocytes with a hypertonic solution enriched in mannitol (300 m m ). We measured simultaneously ATP release and ionic currents from a single oocyte. A decrease in cell volume, the activation of an inward current and ATP release were coincident. We found two components of ATP release: the first was associated with granule or vesicle exocytosis, because it was inhibited by tetanus neurotoxin, and the second was related to the inward current. A single exponential described the correlation between ATP release and the hypertonic-activated current. Gadolinium ions, which block mechanically activated ionic channels, inhibited the ATP release and the inward current but did not affect the decrease in volume. Oocytes expressing CFTR (cystic fibrosis transmembrane regulator) released ATP under hypertonic shock, but ATP release was significantly inhibited in the first component: that related to granule exocytosis. Since the ATP measured is the balance between ATP release and ATP degradation by ecto-enzymes, we measured the nucleoside triphosphate diphosphohydrolase (NTPDase) activity of the oocyte surface during osmotic stress, as the calcium-dependent hydrolysis of ATP, which was inhibited by more than 50 % in hypertonic conditions. The best-characterized membrane protein showing NTPDase activity is CD39. Oocytes injected with an antisense oligonucleotide complementary to CD39 mRNA released less ATP and showed a lower amplitude in the inward current than those oocytes injected with water.     

Early lymphocyte recovery predicts superior survival after autologous hematopoietic stem cell transplantation for patients with primary systemic amyloidosis.

PURPOSE: Absolute lymphocyte count recovery at day 15 (ALC-15) post-autologous stem cell transplantation (ASCT) is a powerful prognostic indicator for survival for multiple hematologic malignancies and metastatic breast cancer. The relationship of ALC-15 with clinical outcomes in primary systemic amyloidosis is unknown. EXPERIMENTAL DESIGN: We evaluated 145 consecutive patients with primary systemic amyloidosis who underwent ASCT at the Mayo Clinic from 1996 to 2003. The ALC-15 threshold was set at 500 cells/microL based on our previous observations. RESULTS: The median patient follow-up was 22 months (range, 3-87 months). Higher hematologic complete response was observed in patients with an ALC-15 > or = 500 cells/microL compared with patients with an ALC-15 < 500 cells/microL (41% versus 21%, P < 0.0008, respectively). The median overall survival and progression-free survival times were significantly better for the 59 patients that achieved an ALC-15 > or = 500 cells/microL compared with 86 patients with ALC-15 < 500 cells/microL (not reached versus 53 months, P < 0.0003 and not reached versus 27 months, P < 0.0001, respectively). Multivariate analysis showed ALC-15 to be an independent prognostic factor for overall survival and progression-free survival. CONCLUSIONS: ALC-15 > or = 500 cells/microL is associated with significantly improved clinical outcomes following ASCT in patients with primary systemic amyloidosis.     

Hypnotic Tactile Anesthesia: Psychophysical and Signal-Detection Analyses

Two experiments that studied the effects of hypnotic suggestions on tactile sensitivity are reported. Experiment 1 found that suggestions for anesthesia, as measured by both traditional psychophysical methods and signal-detection procedures, were linearly related to hypnotizability. Experiment 2 employed the same methodologies in an application of the real-simulator paradigm to examine the effects of suggestions for both anesthesia and hyperesthesia. Significant effects of hypnotic suggestion on both sensitivity and bias were found in the anesthesia condition but not for the hyperesthesia condition. A new bias parameter, C’, indicated that much of the bias found in the initial analyses was artifactual, a function of changes in sensitivity across conditions. There were no behavioral differences between reals and simulators in any of the conditions, though analyses of postexperimental interviews suggested the 2 groups had very different phenomenal experiences.     

Aging disrupts the temporal organization of antioxidant defenses in the heart of male rats and phase shifts circadian rhythms of systolic blood pressure

Biogerontology - Aging is one of the main risk factors for cardiovascular diseases, and oxidative stress is a key element responsible for the development of age-related pathologies. In addition,...     

Prognostic awareness and the terminally ill

The authors rated patients who were in advanced stages of cancer and in their final few weeks of life on their level of awareness of their medical prognosis (N = 200, mean age = 71.0 years). The authors measured prognostic awareness with a semistructured interview, dividing patients into those acknowledging No Awareness, Partial Awareness, and Complete Awareness. The authors also administered a semistructured interview for depressive disorders, along with an assessment of various demographic and social support measures. Nineteen patients (9.5%) denied awareness of both their terminal prognosis and foreshortened life expectancy. Thirty-four patients (17%) were placed in the partial awareness category, with the remaining 147 patients (73.5%) reporting complete awareness. Depression was nearly three times greater among patients who did not acknowledge their prognosis, as compared with those who demonstrated partial or complete acknowledgment (chi2 = 7.094), P = 0.029). In addition to depression, male patients, older patients, and those having "intense social contact" were associated with lower ratings of prognostic awareness. Dying patients differ in respect to their capacity to acknowledge their prognosis. Prognostic disavowal is most likely to arise in patients with underlying psychological distress and emotional turmoil.     

Increased baclofen-stimulated G protein coupling and deactivation in rat brain cortex during development

The number and affinity of GABA(B) receptors (assayed by the specific antagonist [(3)H]CGP54626A) was unchanged when compared in carefully washed cerebrocortical membranes from young (12-day-old) and adult (90-day-old) rats. In contrast, high-affinity GTPase activity, both basal and baclofen-stimulated was significantly higher (by 45% and 56%, respectively) in adult than in young rats. Similar results were obtained by concomitant determination of agonist (baclofen)-stimulated GTP gamma S binding. Under standard conditions, baclofen-stimulated GTPase activity was further considerably enhanced by exogenously added regulator of G protein function, RGS1, but not by RGS16. RGS16 was able to affect agonist-stimulated GTPase activity only in the presence of markedly increase substrate (GTP) concentrations. RGS1 alone slightly increased GTPase activity in adult rats, but neither RGS1 nor RGS16 influenced GTPase activity in membrane preparations isolated from young animals. These findings indicate increasing functional activity of trimeric G protein(s) involved in GABAergic transmission in the developing rat brain cortex and suggest a high potential of RGS1 in regulation of high-affinity GTPase activity.     

Synthesis and antiinflammatory activity of some 2-arylamino-2-thiazoline-4-ones

A mild and efficent method of synthesis of 2-arylamino-2-thiazoline-4-ones was established using 2-carboethoxymethylthio-2-thiazolin-4-one (II) as a key intermediate. Reaction of 2-carboethoxymethylthio-2-thiazolin-4-one with m- or p-aminophenole afforded 2-(3-or4-oxyphenylamino)-2-thiazoline-4-ones (V, XV). Condensation of V, XV with aromatic aldehydes, according to the Knoevenagel, gives respective 5-arylidene derivatives V-XIII, XVI-XXIX, which were obtained alternatively using m- or p-oxyarylthioureas. 5-Carboxymethylderivatives XIV, XXX were synthesized by condensation of arylthioureas and maleic anhydride in acetic acid. Quantum-chemical calculations were made to confirm the possibility of dynamic amino-imino tautomerism of synthesized compounds. Structure and tautomerism of the obtained substances were confirmed by UV, IR, MS and NMR spectra. Biological activity prediction using the computer program PASS C&T has been made. According to these prediction results, some compounds were tested in vivio for their antiinflammatory activity. 5-[2-Chloro-3-(4-nitrophenyl)-2-propenilidene]-2-(3-hydroxyanilino-2-thiazoline-4-one (XII) possess significant antiinflammatory effect in comparison with diclofenac sodium, aspirin, acetaminofen and phenylbutazone.     

LH, FSH and skin temperaure during the menopausal hot flash.

Six postmenopausal women, who were experiencing frequent hot flashes, had an 8 h continuous recording of skin temperature over the dorsum of the finger as an objective index of hot flashes. Frequent blood samples were obtained during the time of the recording for the measurement of serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels. During the 48 h of recording 34 significant temperature elevations were recorded and 32 were associated with a subjective hot flash. 3l pulses of LH release were also observed with 26 occurring simultaneously with the temperature rises. Correlation analysis of simultaneous skin temperature and circulating LH levels showed a significant positive correlation (p less than 0.01). FSH levels showed no consistent relationship with skin temperature. These data suggest that LH or the factors that trigger its pulsatile release are related to the mechanism responsible for the initiation of hot flashes.     

Conditioning in the unattended left ear

Two experiments demonstrated that a conditioned emotional response can both be established and arouse responses without awareness in a dichotic paradigm. Right handed male subjects performed a complex verbal task presented to the right ear, while patterns of musical notes were presented to the left ear. For experimental subjects, one of the patterns was always followed by an aversive noise in the left ear; the noises were presented at random times to control subjects. In Study 1, latency of skin potential response to the noise decreased among experimental subjects relative to control subjects, indicating that the critical tone pattern was acting as a CS. Subject awareness was determined through both recall and recognition procedures, and only unaware subjects were used. Study 2 demonstrated the effect more powerfully by showing conditioned responses among experimental subjects on interpolated CS-alone trials and a lack of reportable awareness among all subjects.