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The influence of warning signal timing and cognitive preparation on the aversiveness of cold-pressor pain.

This study examined the role of prior warning time, cognitive preparation and self-efficacy in the reaction to cold-pressor pain that has a substantial stimulus duration and leaves a residual effect. Forty-eight, paid, male subjects were randomly assigned to one of 3 cognitive preparation groups: (1) Training group, provided with a self-instructional booklet of pain control techniques, (2) Citizenship group, to control for reading a booklet, and (3) Control group with no advanced preparation. Warning times used on a within-subjects basis were 0, 30, and 180 sec prior to immersion of their arms in cold water. Results indicated that overall, the 180 sec warning time yielded the lowest pain ratings. Warning time had no effect on duration in water for subjects who underwent training, but the 30 sec and 180 sec warning time yielded longer duration in water, for subjects in the other groups. The Training group preparation was effective in raising perceived self-efficacy for coping with pain which, in turn, was found to be correlated with pain tolerance. Perceived self-efficacy was also found to have an effect on heart rate with high scorers yielding a lower reaction upon immersion into the cold water compared to the low scorers. The results point to the need to consider the effect of the stimulus characteristics and the centrality of perceived self-efficacy when preparing a subject prior to pain stimulation.

Adult↗

Treatment of cold urticaria.

BACKGROUND: The etiology of cold contact urticaria is unknown and the therapy is therefore usually rather disappointing. METHODS: This study reports therapeutic data on 42 patients with cold urticaria treated with a combination of terbutaline (3 x 5 mg a week, later 3 x 2.5 mg) and aminophylline-containing drugs (3 x 150 mg). RESULTS: Complete remission of the urticarial response was achieved in 37 of the 42 patients. CONCLUSIONS: The therapy was tolerated relatively well and the results are promising.

Adolescent↗

Tolerance of chick embryos to low temperatures in reference to the heart rate.

Ten-day-old embryos were exposed to 28, 18 and 8 degrees C environments and their electrocardiograms (ECG) monitored. Embryos in 28 and 18 degrees C environments maintained a constant heart rate averaging 97 and 25 beats/min, respectively, followed by arrhythmias and cardiac arrest at 101 and 59 hr. Embryos in an 8 degrees C environment went into cardiac arrest after 2-4 hr, but recovered 20 hr later upon rewarming to 38 degrees C. Six to 20-day-old embryos exposed to 8 degrees C were examined for tolerance time after cardiac arrest. The younger the embryo the longer its tolerance to prolonged cardiac arrest.

Acclimatization↗

Transcriptional profiling of sunflower plants growing under low temperatures reveals an extensive down-regulation of gene expression associated with chilling sensitivity.

Being able to sow early to maximize the growing season and to escape drought stress has increased the importance of low-temperature tolerance in sunflower. Yet knowledge about the molecular basis of sunflower response to low temperature is still lacking. To address this issue, nylon microarrays containing >8000 putative unigenes were developed and used. Early- and late-flowering genotypes were sown at 15 degrees C and grown until the two-leaf stage when they were subjected to 7 degrees C until the four-leaf stage. The transcriptional profiles of low temperature-grown plants (15 degrees C and 7 degrees C) were compared with those grown under standard conditions (25 degrees C). Two-step ANOVA normalization and analysis models were used to identify the differentially expressed genes. A total of 108 cDNA clones having a P-value <10(-3) were found to be differentially expressed between the low temperature-grown plants (15 degrees C and 7 degrees C) and their corresponding two-leaf- and four-leaf-stage controls across the two genotypes. About 90% of these genes were down-regulated. This includes genes potentially involved in the metabolism of carbohydrate and energy, protein synthesis, signal transduction, and transport function. Comparing gene expression profiles at 15 degrees C and 7 degrees C revealed that only four genes can be considered as differentially expressed, in both genotypes, suggesting that similar genetic programmes underlie the response of sunflower plants to these temperature regimes. The analysis also revealed that early- and late-flowering genotypes respond similarly to low-temperature tolerance as justified by the low number of genes showing a significant genotype x treatment interaction effect. It seems likely that the down-regulation and/or non-induction of genes having a critical role in low-temperature tolerance may be responsible for the sensitivity of sunflower plants to low-temperature tolerance. The results reported provide an initial characterization of the transcriptome activity of sunflower, as a chilling-sensitive plant under suboptimal temperatures, and could be of importance to reveal the potential differences between chilling-sensitive and chilling-tolerant species.

Acclimatization↗

Bundle sheath proteins are more sensitive to oxidative damage than those of the mesophyll in maize leaves exposed to paraquat or low temperatures.

In maize leaves growth at low temperatures causes decreases in maximum catalytic activities of photosynthetic enzymes and reduced amounts of proteins, rather than effects on regulation or co-ordination of the photosynthetic processes. To test the hypothesis that differential localization of antioxidants between the different types of photosynthetic cell in maize leaves is a major determinant of the extreme sensitivity of maize leaves to chilling damage, oxidative damage to proteins, induced by incubation of maize leaves with paraquat, has been measured and compared with the effects incurred by growth at low temperatures. While the increase in protein carbonyl groups caused by paraquat treatment was much greater than that caused by low temperature growth conditions, most carbonyl groups were detected on bundle sheath proteins in both stress conditions. With one or two exceptions proteins located in the mesophyll tissues were free of protein carbonyl groups in both situations. Paraquat treatment caused a complete loss of the psaA gene products, modified the photosystem II reaction centre polypeptide, D1, and increased the number of peptides arising from breakdown of ribulose 1,5-bisphosphate carboxylase oxygenase (Rubisco). In contrast, growth at 15 degrees C increased the abundance (but not number) of Rubisco breakdown products and decreased that of the psaB gene product while the psaA gene product and PEP carboxylase were largely unaffected. Since bundle sheath proteins are more susceptible to oxidative damage than those located in the mesophyll cells, strategies for achieving a more balanced system of antioxidant defence may be effective in improving chilling tolerance in maize.

Adaptation, Physiological↗

Intranasal interferon (rIFN-alpha A, Ro 22-8181) for contact prophylaxis against common cold: a randomized, double-blind and placebo-controlled field study.

The prophylactic efficacy of low-dose intranasal recombinant leucocyte interferon alpha (rIFN-alpha A, Ro 22-8181) was investigated under field conditions in 147 families (n = 587 participants), randomized to receive placebo or rIFN-alpha A intranasally in daily doses of 1.5 or 0.3 X 10(6) IU. Treatment was started within 2 days after the appearance of an index case in the household and was continued for 5 days. Clinical data of the index case and of all members of the household were recorded for 10 days. In index cases and all ill contact persons nasal washes were collected for rhinovirus isolation and immunochemical detection of other respiratory viruses. The local tolerance of the intranasal rIFN-alpha A was excellent. Both doses of rIFN-alpha A failed to exert therapeutic effects on established common cold or to prevent the spread of common cold within families. Prophylactic treatment with 1.5 X 10(6) IU did however shorten the duration of the cold (median of 2 days vs. 4 in the placebo group, P = 0.01) and reduced the severity of any ensuing common cold (median total score of 10.5 vs. 30, P less than 0.001). No correlation was found between viral etiology (55% rhinoviruses vs. 13% other respiratory viruses, n = 122 nasal washes) and prophylactic efficacy or clinical severity.

Administration, Intranasal↗

Responses to freezing exposure of hatchling turtles Trachemys scripta elegans: factors influencing the development of freeze tolerance by reptiles.

Hatchling red-eared turtles Trachemys (= Pseudemys) scripta elegans (Wied) from a Louisiana population display a significant ability to withstand the freezing of extracellular body fluids. All animals survived at least 2 h of freezing at -2.5 or -4 degrees C. At -2.5 degrees C, survival declined to 50% after 6 h of freezing and no animals recovered after 24 h or longer, when mean ice content reached 54.7 +/- 1.4% of total body water. At -4 degrees C, all turtles recovered from 4 h of freezing exposure with a mean ice content of 49.6 +/- 2.4%, but survival dropped sharply thereafter with no animals recovering after 8 h, when ice content had reached 64.5 +/- 0.7%. Survival times were substantially shorter and percentage ice values greater than comparable values for hatchling painted turtles (Chrysemys picta (Schneider)) from northern populations subjected to identical freezing exposures. The ability to synthesize cryoprotectants in response to freezing was poorly developed in T. s. elegans; maximal accumulation of glucose was only 3.2 mumol g-1 wet mass in liver. Lactate content increased two- to threefold in oxygen-sensitive organs (heart and brain) during freezing, but levels of lactate and other putative cryoprotectants were unchanged in other organs. Total free amino acid content rose significantly in liver, muscle and blood during freezing; increased taurine concentration was primarily responsible for the changes in liver and blood. The capacity for freezing survival by T. s. elegans hatchlings from southern populations would be of limited use for hibernation in a cold climate, but the metabolic responses to freezing displayed by these animals might be enhanced by northern populations to increase their freeze tolerance.

Acclimatization↗

Safety of zinc gluconate glycine (Cold-Eeze) in a geriatric population: a randomized, placebo-controlled, double-blind trial.

Zinc gluconate glycine lozenges are an over-the-counter homeopathic remedy that significantly reduced the duration and severity of common colds in adults in 2 independent clinical trials. To evaluate the safety of zinc gluconate glycine lozenges in elderly individuals with 1 or more health conditions, with or without a cold. This randomized, double-blind, placebo-controlled, parallel-group trial enrolled men and women between 60 and 91 years of age, who self-administered 1 zinc gluconate glycine or placebo lozenge every 3 to 4 hours for 6 days. One or more of the following conditions was present in the study population: arthritis, cancer, depression, heart disease, hypertension, lung disease, osteoporosis, prostate disease, and stroke. Assessments were performed at baseline and at 7 (+/-1 day) and 14 days. The safety evaluation considered physical examinations, clinical laboratory tests, vital signs, adverse events, and concomitant medications. Of 75 persons enrolled, 66 completed the study. Safety assessments demonstrated no clinically significant differences between treatment groups. Four participants taking zinc tablets and 3 participants taking placebo tablets reported mild adverse events. Of those participants taking zinc tablets, 6 adverse events were possibly related to the study product and 2 adverse events were probably related to the study product. Of those participants taking placebo tablets, 3 adverse events were reported that were possibly related to the study product. No serious or clinically significant adverse events were noted. Zinc gluconate glycine lozenges are safe and well tolerated by a geriatric population and are suitable for prophylactic or therapeutic use to reduce the duration or severity of the common cold.

Aged↗

Respiratory adjustments of the unanaesthetized chicken, Gallus domesticus, to elevated metabolism elicited by 2,4-dinitrophenol or cold exposure.

The effects of pharmacologically elevated metabolism on ventilation, gaseous exchange and blood gases were studied in spontaneously breathing unanaesthetized decerebrate chickens using 2,4-dinitrophenol (DNP) injected intravenously in successive single doses of 2.5-5.0 mg/kg. These responses were compared with the cardiorespiratory adjustments to elevated metabolism evoked by shivering in conscious birds. Oxygen consumption increased with cumulative amounts of DNP, reaching 275 +/- 30% of control values at the maximum tolerated dose of 10-15 mg/kg. Increases in ventilation matched the changes in oxygen consumption via increases in both breathing frequency and tidal volume. Arterial blood gases and pH remained unchanged. Exposure to cold (Ta = 2 +/- 2 degrees C) caused oxygen consumption to increase to 185 +/- 21% of control values. Respiratory and cardiovascular adjustments were similar to those evoked by DNP and were comparable to those produced by low intensity treadmill exercise (cf. Gleeson and Brackenbury, 1984).

2,4-Dinitrophenol↗

Yttrium-90-ibritumomab tiuxetan radioimmunotherapy: a new treatment approach for B-cell non-Hodgkin's lymphoma.

This article will review the clinical development of ibritumomab tiuxetan, a yttrium-90-conjugated monoclonal antibody to CD20, for patients with relapsed B-cell non-Hodgkin's lymphomas. Ibritumomab is the murine parent anti-CD20 antibody that was engineered to make the human chimeric antibody rituximab. Tiuxetan is an MX-DTPA chelator that is linked to ibritumomab to form ibritumomab tiuxetan. Since yttrium-90 ((90)Y) is a pure beta emitter and cannot be used for patient imaging, indium-111 ((111)In) is chelated to ibritumomab tiuxetan for tumor and normal organ imaging in clinical practice and for dosimetry in clinical trials. (90)Y-ibritumomab tiuxetan is the form used for therapy. This review discusses the clinical trials that have demonstrated the efficacy of ibritumomab tiuxetan and summarizes the safety data in patients with relapsed B-cell non-Hodgkin's lymphomas. Two phase I trials of (90)Y-ibritumomab tiuxetan were conducted to establish the toxicity profile and the maximum tolerated single dose that could be administered to outpatients without the use of stem cells or prophylactic growth factors. In the first trial, cold ibritumomab was used prior to ibritumomab tiuxetan; the second trial used the human chimeric antibody rituximab. The phase I trials determined that in patients with a platelet count of greater than or equal to 150 x 10(9)/l, a schedule of intravenous rituximab 250 mg/m(2) on days 1 and 8, and 0.4 mCi/ kg of intravenous (90)Y-ibritumomab tiuxetan on day 8 was safe and efficacious and did not require stem cells. A dose of 0.3 mCi/kg was recommended for patients with a baseline platelet count of 100,000- 149,000 x 10(6)/l. Adverse events were primarily hematologic, and nonhematologic adverse events were primarily due to rituximab. There was no normal organ toxicity. The overall response rate was 67% for all patients and 82% in patients with low-grade non-Hodgkin's lymphomas. A subsequent phase III trial randomized 143 eligible patients to either rituximab or ibritumomab tiuxetan. The aim was to demonstrate that the addition of the yttrium-90 radioisotope to the antibody provided additional efficacy over the unconjugated ("cold") rituximab alone. The results of this study showed an overall response rate of 80% with (90)Y-ibritumomab tiuxetan versus 56% for rituximab (p = 0.002). An additional trial enrolled 54 patients who were nonresponsive or refractory to rituximab and treated the patients with a single dose of 0.4 mCi/kg (90)Y-ibritumomab tiuxetan. An overall response rate of 74% was found in these rituximab-refractory patients. These data provide further evidence of the added value of the yttrium-90. Finally, a fifth trial treated 30 patients with mild thrombocytopenia using 0.3 mCi/kg (90)Y-ibritumomab tiuxetan and found an overall response rate of 83%. (90)Y-ibritumomab tiuxetan radioimmunotherapy is a new treatment modality for patients with relapsed B-cell non-Hodgkin's lymphoma. The advantages of this therapy are that it utilizes targeted radiation in a single-dose, outpatient schedule that is well tolerated and accepted by the patient. Future trials will build on these results and determine at what point in the disease course this modality can best be utilized to maximize the benefits to the patient.

Antibodies, Monoclonal↗

Mycosporine-glutamicol-glucoside: a natural UV-absorbing secondary metabolite of rock-inhabiting microcolonial fungi.

Microcolonial ascomycetes are known to inhabit bare rock surfaces in cold and hot deserts and thus are habitually exposed to high levels of solar radiation. Several of these stress-tolerant fungal isolates, cultivated in the laboratory under daylight illumination, were studied for the presence of effective UV-radiation protection substances. Liquid chromatography/mass spectrometry (LC/MS) and liquid chromatography/tandem mass spectrometry (LC/MS/MS) analyses allowed for efficient separation and structure clarification of two mycosporines. It was demonstrated that both mycosporine-glutamicol-glucoside and mycosporine-glutaminol-glucoside are natural and constitutive secondary metabolites of microcolonial fungi. The function and relation of these substances in the fungal cell are discussed.

Ascomycota↗

Aortic reconstruction in kidney transplant recipients.

Renal transplantation has increased the longevity of patients with uremia. An increasing number undergo aortic reconstruction, which exposes the transplanted kidney to ischemic injury. To evaluate the risk for renal failure, loss of the transplant, and methods of renal protection, we reviewed our experience. Clinical data were reviewed for 10 consecutive patients (7 men, 3 women; mean age 52.7 years [range 32 to 75 years]) with a transplanted kidney who underwent aortic reconstruction between 1977 and 1994 at our institution. Mean interval between renal transplantation and aortic reconstruction was 5.9 years (range 1 month to 12.7 years). Seven patients required emergency repair because of dissection (2 patients), aneurysm rupture (4 patients), or symptomatic aneurysm (1 patient); three underwent elective repair. Reasons for reconstruction included aortic dissection (2 patients), aneurysm of the descending thoracic (2 patients), thoracoabdominal (1 patient), or abdominal aorta (3 patients), and aortoiliac occlusive disease (2 patients). Patients with thoracic or thoracoabdominal reconstructions underwent repair with atriofemoral, aortofemoral, or femorofemoral shunt placement or bypass. Of the five abdominal aortic reconstructions, the kidney was protected with aortofemoral shunt placement in one patient and cold renal perfusion in three. In two of them, topical cooling of the kidney also was used. One patient with acute aortic dissection died at 39 days as a result of respiratory failure. Loss of the recently transplanted kidney was caused by acute rejection. One patient had a transient increase in serum creatinine concentration. Eight no worsening of renal function, and none of the nine survivors lost the transplanted kidney. We concluded that aortic reconstruction can be safely performed in kidney transplant recipients. Patients in whom thoracic or thoracoabdominal aortic reconstruction was required were protected with an atriofemoral or aortofemoral bypass or shunt. Patients undergoing abdominal aortic reconstruction did well when cold renal perfusion with or without local cooling of the transplant was used for renal protection. Transplanted kidneys appeared to tolerate ischemic injury similarly to native kidneys.

Adult↗

Oral mucosal blood flow following dry ice stimulation in humans.

The aim of the current pilot study was to establish a procedure that would allow the investigation of microcirculatory changes in the oral cavity. The authors studied the effects of painful stimulation using dry ice (CO2). To investigate potential regional differences in the change of blood flow, recordings were made for the tongue and at the mucosa of the hard palate, lip, and oral vestibule. The authors investigated 26 patients divided into groups of younger subjects (10 men, 3 women; age range 21-31 y) and older patients (2 men, 11 women; age range 54-74 y). Mucosal blood flow (mBF) was obtained at the hard palate, at the tip of the tongue, on the midline of the oral vestibule, and at the lip. Measurements were made during rest and for 2 minutes after application of dry ice for a 10-second duration, using a pencil-shaped apparatus. Blood pressure, heart rate, cutaneous blood flow, transcutaneous partial pressure of carbon dioxiode (PCO2) and partial pressure of oxygen (PO2) were recorded. Mucosal blood flow increased at all sites in response to application of dry ice (p <0.001), with peak flow at 0.5 minute to 1.5 minutes after onset of stimulation. During the 1.5 minutes to 2 minutes, blood flow decreased at all measurement sites with a tendency to return to baseline. Heart rate, blood pressure, pCO2, PO2, and cutaneous blood flow did not show significant changes. Overall, responses in older patients showed more variance when compared with younger patients. Stimulation by dry ice appears to be an effective, noninvasive, and tolerable means to investigate mucosal blood flow at different mucosal sites. Preliminary data indicate different levels of responsiveness to painful cold stimulation at different sites on the oral and perioral mucosa; particularly, mucosal blood flow response at the tongue was least pronounced. Therefore, assessment of stimulated mucosal blood flow appears to be a promising tool to investigate the pathophysiology of a number of neurologic symptoms, eg, the burning mouth syndrome.

Adult↗

Autonomic and behavioral thermoregulation in the golden hamster during subchronic administration of clorgyline.

Chronic administration of clorgyline, a type-A monoamine oxidase inhibitor, leads to a decrease in peritoneal (i.e., core) temperature of golden hamsters. To better understand the mechanisms of clorgyline's thermoregulatory effects, autonomic and behavioral thermoregulatory effectors were measured in Syrian hamsters following chronic infusion of clorgyline via a minipump (2 mg/kg/day). Metabolic rate, evaporative water loss, motor activity, and core temperature were measured after 60 min of exposure to ambient temperatures (Ta) of 5, 20, 30, and 35 degrees C. Behavioral thermoregulatory responses were assessed by measuring selected Ta and motor activity of the same animals in a temperature gradient over the course of 23 h. Metabolic rate and motor activity were significantly elevated in clorgyline-treated hamsters exposed to a Ta of 5 degrees C. There were no effects of clorgyline on evaporative water loss. In the temperature gradient the mean selected Ta of clorgyline-treated hamsters was nearly equal to that of the saline-treated hamsters, 30.7 and 31.2 degrees C, respectively. On the other hand, the mode of selected Ta in the clorgyline group was 2.8 degrees C higher than that of the saline group. Motor activity in the gradient was significantly elevated and food consumption was depressed by clorgyline treatment. Overall, these findings indicate that chronic clorgyline treatment in the golden hamster results in novel autonomic and behavioral modification; it stimulates metabolic thermogenesis during cold exposure, but appears to increase the behavioral zone of thermoneutrality. This latter effect may mean an improvement in heat tolerance, suggesting that this drug might assist in the adaptation to warm temperatures.

Animals↗

The use of arterial allografts for vascular reconstruction in patients receiving immunosuppression for organ transplantation.

PURPOSE: This study was undertaken to assess the biologic behavior of arterial allografts used for vascular reconstruction in patients undergoing immunosuppression therapy because of a previously transplanted organ. METHODS: Thirteen patients with a transplanted kidney and receiving azathioprine, cyclosporine, and prednisone therapy, received 16 ABO-compatible arterial allografts to treat vascular complications of the kidney transplantation, popliteal aneurysms, and chronic or critical ischemia of the lower extremities. One aortoiliac, one iliorenal, two iliofemoral, three femorofemoral, one femoroperoneal, and eight femoropopliteal grafts were used in this particular group of patients. The arteries were retrieved from a donor whose diagnosis was cerebral death and, after careful preliminary studies, were stored cold, with use of liquid nitroxide vapor. RESULTS: The patients were monitored up to 45 months, mean 20 months. Graft tolerance was good, there were no signs or symptoms of acute rejection, and there was no perturbation of the immunologic tolerance of the transplanted kidney. During the follow-up period, two grafts occluded. On the basis of the histologic studies, it was not possible to relate the occlusion to rejection. CONCLUSIONS: This clinical study, undertaken for the first time in human beings, seems to confirm that immunosuppression modifies host tolerance to arterial allografts, improving their biologic behavior, a fact that was already documented in animal experimentation.

Adult↗

Donor-specific unresponsiveness induced by intraportal grafting and FK506 in rat islet allografts: importance of low temperature culture and transplant site on induction and maintenance.

Previously we demonstrated prolongation of islet allograft survival in rat by administration of FK506 to the recipients. The purpose of the present study was to determine whether specific immune unresponsiveness had been induced and to determine the effects of low temperature culture of donor islets as well as the transplant site on the induction of immune unresponsiveness. At 90 days after transplantation, normoglycemic recipients bearing functional intrahepatic grafts were made diabetic again with streptozotocin (STZ) and donor specific or third party islets were transplanted either into the liver or beneath the kidney capsule. When fresh islets were used as donors in initial transplantation in conjunction with FK506, intrahepatic re-transplants of fresh islets from the donor-specific strain in the absence of FK506 maintained normoglycemia for more than 60 days, while third party transplants (n = 3) were rejected within 1 wk. In contrast to intrahepatic regrafts, all the renal subcapsular regrafts from the donor-specific strain (n = 3) were rejected with mean survival time of 12.7 +/- 6.4 days. When cultured (24 degrees C, 7 days) islets were used for initial transplantation in conjunction with FK506, re-transplants of fresh or cultured islets from the donor specific strain beneath the kidney capsule maintained normoglycemic in 3 out of 6 or all (n = 4) of the recipients, respectively. Cultured third party regrafts beneath the kidney capsule (n = 2) were rejected at 9 days.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗