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PubMed2003

Comparison of blood-ethanol concentration in deaths attributed to acute alcohol poisoning and chronic alcoholism.

Ethanol concentrations were measured in femoral venous blood in deaths attributed to acute alcohol poisoning (N = 693) or chronic alcoholism (N = 825), according to the forensic pathology report. Among acute alcohol poisonings were 529 men (76%) with mean age 53 years and 164 women (24%) with mean age 53 years. In the chronic alcoholism deaths were 705 men (85%) with mean age 55 years and 120 women (15%) with mean age 57 years. The blood-ethanol concentrations were not related to the person's age (r = -0.17 in acute poisonings and r = -0.09 in chronic alcoholism). The distribution of blood-ethanol concentrations in acute poisoning cases agreed with a normal or Gaussian curve with mean, median, standard deviation, coefficient of variation, and spread of 0.36 g/100 mL, 0.36 g/100 mL, 0.086 g/100 mL, 24% and 0.074 to 0.68 g/100 mL, respectively. The corresponding concentrations of ethanol in chronic alcoholism deaths were not normally distributed and showed a mode between 0.01 and 0.05 g/100 mL and mean, median, and spread of 0.172 g/100 mL, 0.150 g/100 mL, and 0.01 to 0.56 g/100 mL, respectively. The 5th and 95th percentiles for blood-ethanol concentration in acute poisoning deaths were 0.22 and 0.50 g/100 mL, respectively. However, these values are probably conservative estimates of the highest blood-ethanol concentrations before death owing to metabolism of ethanol until the time of death. In 98 chronic alcoholism deaths (12%) there was an elevated concentration of acetone in the blood (>0.01 g/100 mL), and 50 of these (6%) also had elevated isopropanol (>0.01 g/100 mL). This compares with 28 cases (4%) with elevated blood-acetone in the acute poisoning deaths and 22 (3%) with elevated blood-isopropanol. We offer various explanations for the differences in blood-ethanol and blood-acetone in acute poisoning and alcoholism deaths such as chronic tolerance, alcohol-related organ and tissue damage (cirrhosis, pancreatitis), positional asphyxia or suffocation by inhalation of vomit, exposure to cold coupled with alcohol-induced hypothermia, as well as various metabolic disturbances such as hypoglycemia and ketoacidosis.

2-Propanol↗
PubMed1986

Self-esteem, types of attributional style and sensation and distress pain ratings in males.

This descriptive study focused on self-esteem and types of attributional style, and their relationship to sensation and distress pain ratings. Negative correlations were hypothesized between self-esteem and each pain rating, between positive internal type of attributional style and each pain rating, and between negative external type of attributional style and each pain rating. One hundred and nine healthy, non-institutionalized males, aged 21-50 years, participated in this study. The Tennessee Self-Concept Scale and revised Attributional Style Questionnaire were administered prior to the cold pressor test, a safe, short duration cold water hand immersion procedure for pain induction. Sensation and distress pain ratings were measured using visual analogue scales, and a pain history was obtained. The predicted relationship between self-esteem and distress pain ratings was supported. All other correlations were not statistically significant. A pain history question, asking subjects to rate their pain tolerance as compared with other people, was significantly related to both pain ratings, the correlations being negative.

Adult↗
PubMed1990

Scalp cooling by cold air for the prevention of chemotherapy-induced alopecia.

A new system is described for cooling the scalp with cold air in order to prevent chemotherapy-induced alopecia. Compressed air was cooled by means of a vortex tube built into a hair-drier cap. This system reduced the blood flow in the scalp to 35%, the surface temperature to 14.2 degrees C and the intradermal temperature at hair follicle level to 29.2 degrees C. The low temperature could be kept constant for at least one hour of cooling. By means of comparison, with cryogel packs the lowest epidermal temperature attained was 17.9 degrees C; moreover, once this was reached after 10 min, it rapidly rose again to 20.6 degrees C after 40 min. Forty-eight patients receiving cytostatic treatment for breast cancer were subjected to scalp cooling with the cold air system, starting 15 min before chemotherapy and lasting for 90 min. With the system set at an air temperature of -12 degrees C, the treatment was well tolerated. Of the 13 patients treated with 40 mg/m2 doxorubicin in combination with other cytostatics, 6 had hair loss less than WHO grade 3, in contrast to 1 of 4 patients given cryogel packs. However, patients treated with epirubicin at 75 mg/m2 all showed grade 3 hair loss in spite of air cooling. In view of the possibility of achieving and maintaining low scalp temperatures, the cold air system is to be preferred to cryogel packs. Whether better clinical results may be obtained with cooling for longer periods and/or to lower temperatures remains to be determined.

Alopecia↗
PubMed2006

Environmental stress response in wine lactic acid bacteria: beyond Bacillus subtilis.

Lactic acid bacteria (LAB) constitute a heterogeneous group of bacteria that are traditionally used to produce fermented foods. The industrialization of food transformations has increased the economical importance of LAB, as they play a crucial role in the development of the organoleptic and hygienic quality of fermented products. However, the strains selected for industrial purposes, should tolerate adverse conditions encountered in industrial processes, either during starter handling and storage (freeze-drying, freezing, or spray-drying) or during food processing in which abiotic stresses such as heat, cold, acidity, and high concentration of NaCl or ethanol are common. Wine LAB have to deal with several stresses including an acidic pH, a high alcoholic content, non optimal growth temperatures, and growth-inhibitory compounds such as fatty acids and tannins, originated from yeast and bacteria metabolism. Wine LAB have developed several mechanisms to escape or to tolerate wine conditions. They carry out a malolactic fermentation in this stressful environment. In addition to the regulation of the expression of specific genes, bacteria have evolved adaptive networks to face the challenges of a changing environment and to survive under conditions of stress. The so called Global Regulatory Systems control the simultaneous expression of a large number of genes in response to a variety of environmental stress factors. CIRCE sequences able to bind the HrcA repressor, sigma(B) dependent promoters and CtsR regulatory elements have been observed in several genes identified from wine LAB. Improved knowledge of regulators and a better understanding of LAB stress responses could constitute a basis of comparison with the well known model microorganisms, Escherichia coli and Bacillus subtilis. Moreover, it can provide an important insight into improving current industrial starter strains.

Bacillus subtilis↗
PubMed1992

Mechanisms of adaptation to cold.

The animal model used the most frequently for understanding the mechanisms of adaptation to cold in humans has been the rat. It has been established that rats kept in the cold for a few weeks stop shivering while preserving a normal internal temperature because of an enhanced thermogenic capacity of the brown adipose tissue (BAT) mediated by the sympathetic nervous system. Studies on groups of humans exposed to cold have shown that shivering is also attenuated but without compensatory increased in heat production possibly because of non-significant contribution of the BAT. However when humans and laboratory animals are exposed repeatedly to short severe cold evidence for adaptation has been described. This adaptation is not metabolic; instead it is related to the phenomenon of habituation. When exposed to a novel stress such as cold, the alarm reaction is initiated as evidenced by the activation of the sympathetic nervous system which opposes the stressing situation. However with time, when it is realized that the normal functioning of the body is not endangered the responses are attenuated and enhanced tolerance is observed. This type of adaptation was observed in Eskimos, fishermen, outdoor workers, etc.

Adaptation, Physiological↗
PubMed2005

Gender, interpersonal transactions, and the perception of pain: an experimental analysis.

UNLABELLED: Two experiments assessed how interpersonal transactions influence responses to cold pressor pain in women versus men. In Experiment 1, 91 young adults (57 women, 34 men) were randomly assigned to either a no transaction (NT) condition in which they coped alone with the cold pressor test or a transaction opportunity (TO) condition in which they also had the option of interacting with an empathetic, reflecting experimenter. Compared to men, women had lower pain tolerance and reported more pain and catastrophizing, although there were no gender differences in support seeking or other ways of coping. Within the TO condition, women were no more likely than men to initiate a transaction, but female speakers were more pain-focused than male speakers, and speaking with the empathetic interaction partner had generally negative effects on pain perception and coping. In Experiment 2, 126 young adults (76 women, 50 men) were randomly assigned to NT, TO, or experimenter-directed (1) Distraction (DT), (2) Reinterpretation (RT), or (3) Encouragement (ET) conditions. Although men had similar levels of pain tolerance across the 5 transaction conditions, women in NT and TO conditions exhibited reduced tolerance compared with those in the DT, RT, and ET conditions. Pain tolerance times among women in DT, RT, and ET conditions were equal to or exceeded those of men in these conditions. Together, findings suggest the nature of interpersonal transactions exerts a greater influence on women's responses to noxious stimulation than those of men. PERSPECTIVE: This study adds to literature indicating that women exhibit reduced tolerance for experimentally induced pain compared with men. These results suggest that the nature of interpersonal transactions also affects women's responses to noxious stimulation, more than those of men.

Adolescent↗
PubMed1998

The effects of the alpha2-adrenergic agonist, dexmedetomidine, in the spinal nerve ligation model of neuropathic pain in rats.

UNLABELLED: Peripheral nerve injury may lead to neuropathic pain. Alpha2-adrenergic agonists acting in the descending inhibitory tracts of the spinal cord are effective in acute nociceptive, inflammatory, and, possibly, neuropathic pain. We studied the prevention and treatment of neuropathy with the selective alpha2-adrenergic agonist dexmedetomidine in male Sprague-Dawley rats with unilateral peripheral mononeuropathy resulting from tight ligation of the L5 and L6 spinal nerves. Rats with ligation injury developed mechanical and cold allodynia, but not heat hyperalgesia. Dexmedetomidine (120 microg/kg subcutaneously [S.C.] 30 min before the injury) did not attenuate mechanical or cold allodynia. Dexmedetomidine infusions (60 microg/d for 7 days after the injury, or 30 microg/d for 7 days started 14 days after the injury) did not attenuate mechanical or cold allodynia in the ipsilateral paw, but they increased mechanical allodynia during the latter treatment in the paw contralateral to the injury. Atipamezole (1 mg/kg S.C.) induced mechanical and cold allodynia in rats that had not developed allodynia in 14 days after the injury. In conclusion, although alpha2-adrenergic mechanisms are recognized as important in the development of neuropathic pain-like symptoms in this animal model, we found no favorable effect from systemic treatment with dexmedetomidine at tolerable doses. IMPLICATIONS: We studied the prevention and treatment of nerve injury-induced pain with the alpha2-adrenergic agonist dexmedetomidine in an animal model. At tolerable doses, systemic dexmedetomidine neither prevented nor attenuated neuropathic pain behavior.

Adrenergic alpha-Agonists↗
PubMedDate not supplied

African Americans show alterations in endogenous pain regulatory mechanisms and reduced pain tolerance to experimental pain procedures.

OBJECTIVES: To examine ethnic differences in pain sensitivity and relationship of pain tolerance to blood pressure and neuroendocrine factors. METHODS: Fifty-one African Americans (24 men, 27 women) and 55 people from other ethnic groups (primarily Caucasian; 26 men, 29 women) were tested twice for pain sensitivity to tourniquet ischemia, thermal heat, and cold pressor tests, once following mental stress and once following rest control. Resting and stress-induced blood pressure (BP), plasma norepinephrine (NE), and cortisol were assessed. RESULTS: In response to all three pain tests, African Americans had lower pain tolerance relative to Caucasian/Others after both rest and stress. Only the non-African American group showed the expected inverse relationship between BP and pain sensitivity. African Americans had lower cortisol concentrations at rest and stress and showed blunted NE and systolic BP responses to stress. Only in Caucasians/Others was the relationship seen between higher stress-induced BP, cortisol, and NE levels and greater pain tolerance. CONCLUSIONS: The results suggest that there are alterations in endogenous pain regulatory mechanisms involving BP, cortisol, and NE in African Americans. Such dysregulation may contribute to the greater rate of clinical pain symptoms they experience. It is hypothesized that greater chronic stress in African Americans may be a contributing factor to the alterations in pain regulation.

Adolescent↗
PubMed2004

Molecular and physiological analysis of the role of osmolyte transporters BetL, Gbu, and OpuC in growth of Listeria monocytogenes at low temperatures.

Listeria monocytogenes is a ubiquitous food-borne pathogen found widely distributed in nature as well as an undesirable contaminant in a variety of fresh and processed foods. This ubiquity can be at least partly explained by the ability of the organism to grow at high osmolarity and reduced temperatures, a consequence of its ability to accumulate osmo- and cryoprotective compounds termed osmolytes. Single and multiple deletions of the known osmolyte transporters BetL, Gbu, and OpuC significantly reduce growth at low temperatures. During growth in brain heart infusion broth at 7 degrees C, Gbu and OpuC had a more pronounced role in cryoprotection than did BetL. However, upon the addition of betaine to defined medium, the hierarchy of transporter importance shifted to Gbu > BetL > OpuC. Upon the addition of carnitine, only OpuC appeared to play a role in cryoprotection. Measurements of the accumulated osmolytes showed that betaine is preferred over carnitine, while in the absence of a functional Gbu, carnitine was accumulated to higher levels than betaine was at 7 degrees C. Transcriptional analysis of the genes encoding BetL, Gbu, and OpuC revealed that each transporter is induced to different degrees upon cold shock of L. monocytogenes LO28. Additionally, despite being transcriptionally up-regulated upon cold shock, a putative fourth osmolyte transporter, OpuB (identified by bioinformatic analysis and encoded by lmo1421 and lmo1422), showed no significant contribution to listerial chill tolerance. Growth of the quadruple mutant LO28deltaBCGB (deltabetL deltaopuC deltagbu deltaopuB) was comparable to the that of the triple mutant LO28deltaBCGsoe (deltabetL deltaopuC deltagbu) at low temperatures. Here, we conclude that betaine and carnitine transport upon low-temperature exposure is mediated via three osmolyte transporters, BetL, Gbu, and OpuC.

ATP-Binding Cassette Transporters↗
PubMed2000

Gabapentin enhances the analgesic effect of morphine in healthy volunteers.

UNLABELLED: The most effective group of drugs for the treatment of severe pain is opioid analgesics. Their use, however, is limited by decreased effects in neuropathic and chronic pain as a result of increased pain and development of tolerance. Gabapentin (GBP) is effective in both experimental models of chronic pain and clinical studies of neuropathic pain. Therefore, we investigated, in a randomized, placebo-controlled, double-blinded study, the pharmacodynamic and pharmacokinetic interaction of GBP and morphine in 12 healthy male volunteers. Morphine (60 mg, controlled release) or placebo was administered at 8:00 AM, and GBP (600 mg) or placebo was administered at 10:00 AM, thus comparing the analgesic effect of placebo + GBP (600 mg) with placebo + placebo and morphine (60 mg) + GBP in comparison to morphine plus placebo by using the cold pressor test. The duration and intensity of the side effects were assessed by using visual analog scales. The analgesic effect was evaluated by the change in the area under the curve (h x %; 0% baseline before Medication 1) of pain tolerance. Placebo + GBP (18.9% x h, 95% confidence interval [CI]: -2.5 to 40.3) did not present any significant analgesic effect compared with placebo + placebo (4.7% x h, 95% CI: -16.7 to 26.1). A significant increase in pain tolerance was observed comparing the combination of morphine and GBP (75.5% x h, 95% CI: 54.0-96.9) with morphine + placebo (40.6% x h, 95% CI: 19. 2-62.0). The observed adverse events after placebo + GBP were not significantly different compared with placebo + placebo. Morphine + placebo led to the expected opioid-mediated side effects. They were significantly more pronounced compared with placebo + placebo but did not differ significantly compared with the combination of morphine + GBP. Concerning the pharmacokinetic variables of morphine and its glucuronides, no significant difference between morphine + placebo and morphine + GBP was observed, whereas the area under the curve of GBP (43.9 +/- 5.3 vs 63.4 +/- 16.2 microg. h(-1). mL(-1), P < 0.05) significantly increased, and apparent oral clearance (230.8 +/- 29.4 mL/min vs 178 +/- 97.9 mL/min, P = 0.06) and apparent renal clearance (86.9 +/- 20.6 vs 73.0 +/- 24.2 mL/min, P = 0.067) of GBP decreased when morphine was administered concomitantly. These results suggest two different sites for the pharmacokinetic interaction-one at the level of absorption and the other at the level of elimination. Our study reveals both a pharmacodynamic and pharmacokinetic interaction between morphine and GBP, leading to an increased analgesic effect of morphine + GBP. These results and the good tolerability of GBP should favor clinical trials investigating the clinical relevance of the combination of morphine and GBP for treating severe pain. IMPLICATIONS: In a randomized, placebo-controlled, double-blinded trial with 12 healthy volunteers, we studied the interaction of morphine and gabapentin using the cold pressor test. The anticonvulsant gabapentin enhanced the acute analgesic effect of morphine. Furthermore, the plasma concentration of gabapentin was increased when morphine was administered concomitantly. Therefore, the well tolerated combination of gabapentin and morphine may improve pain therapy, especially in pain states, like chronic and neuropathic pain, which respond poorly to opioids.

Acetates↗
PubMed2001

Cold acclimation-induced WAP27 localized in endoplasmic reticulum in cortical parenchyma cells of mulberry tree was homologous to group 3 late-embryogenesis abundant proteins.

We have shown that two 27-kD proteins, designated as WAP27A and WAP27B, were abundantly accumulated in endoplasmic reticulum-enriched fractions isolated from cortical parenchyma cells of mulberry tree (Morus bombycis Koidz.) during winter (N. Ukaji, C. Kuwabara, D. Takezawa, K. Arakawa, S. Yoshida, S. Fujikawa [1999] Plant Physiol 120: 480--489). In the present study, cDNA clones encoding WAP27A and WAP27B were isolated and characterized. The deduced amino acid sequences of WAP27A and WAP27B cDNAs had 12 repeats of an 11-mer amino acid motif that was the common feature of group 3 late-embryogenesis-abundant proteins. Under field conditions, transcripts of WAP27 genes were initially detected in mid-October, reached maximum level from mid-November to mid-December, and then gradually decreased. The transcript levels of WAP27 genes in cortical parenchyma cells harvested in October was drastically induced by cold treatment within a few days, whereas those in cortical parenchyma cells harvested in August were low even by cold treatment for 3 weeks. Immunocytochemical analysis by electron microscopy confirmed that WAP27 was localized specifically in vesicular-form ER and also localized in dehydration-induced multiplex lamellae-form ER. The role of WAP27 in the ER is discussed in relation to acquisition of freezing tolerance of cortical parenchyma cells in mulberry tree during winter.

Acclimatization↗
PubMed1985

Tolerance of one-month intranasal interferon.

Under double-blind conditions, groups of volunteers (68 in total) were allocated at random to take intranasal solutions of placebo or one of three doses of highly purified leucocyte interferon by intranasal spray twice a day for 28 days. The highest dose would have been expected to protect against experimental colds. Treatment was discontinued because of upper respiratory symptoms as often in each of the interferon groups as in the placebo group. However, it was possible to distinguish clinically between "colds" on placebo and low-dose interferon and "reactions to treatment" on high-dose interferon. The features of the reactions to treatment were a protracted build-up of local symptoms and minor epistaxis. None of the volunteers on the high-dose interferon were thought to have a definite cold, but viruses were isolated from four out of six volunteers on low-dose interferon who had definite colds. Previous experiments had also shown this dose to be insufficient to protect against experimental rhinovirus challenge. The dose of interferon that appeared to protect against virus infection caused significant unwanted effects. It is essential to find interferon preparations with less inflammatory activity before interferon can be considered for use as a long-term prophylactic against the common cold.

Administration, Intranasal↗
PubMed1999

Dehydrins in cold-acclimated apices of birch (Betula pubescens ehrh. ): production, localization and potential role in rescuing enzyme function during dehydration

Dehydrins accumulate in various plant tissues during dehydration. Their physiological role is not well understood, but it is commonly assumed that they assist cells in tolerating dehydration. Since in perennials the ability of the shoot apex to withstand dehydration is pivotal for survival through winter, we investigated if and how dehydrins may be involved. A first step in assessing such a role is the identification of their subcellular location. We therefore mapped the location of dehydrin homologues, abscisic acid-responsive (RAB 16-like) polypeptides, in the apex of birch (Betula pubescens Ehrh.). In non-cold-acclimated plants a single low-abundant RAB 16-member (a 33-kDa polypeptide) was produced, and localized in the cytoplasm only. During cold acclimation two additional members were produced (24 and 30 kDa) and accumulated in nuclei, storage protein bodies and starch-rich amyloplasts. Western blots of proteins isolated from purified starch granules and from protein bodies revealed the presence of the 24-kDa dehydrin. Since starch and protein reserves are gradually consumed during winter, serving cell maintenance, starch- and protein-degrading enzymes must remain locally active. We therefore investigated the hypothesis that dehydrins might create local pools of water in otherwise dehydrated cells, thereby maintaining enzyme function. In agreement with our hypothesis, enzyme assays showed that under conditions of low water activity a partially purified dehydrin fraction was able to improve the activity of alpha-amylase (EC 3.2.1.1.) relative to fractions from which dehydrin was removed by immunoprecipitation. The results confirm the general belief that dehydrins serve desiccation tolerance, and suggest that a major function is to rescue the metabolic processes that are required for survival and re-growth.

Journal Article↗
PubMed2000

The role of inorganic phosphate in the development of freezing tolerance and the acclimatization of photosynthesis to low temperature is revealed by the pho mutants of Arabidopsis thaliana.

Low temperature inhibits sucrose synthesis, leading to a phosphate-limitation of photosynthesis. We have used the Arabidopsis pho1-2 and pho2-1 mutants with decreased and increased shoot phosphate, respectively, to investigate whether low phosphate triggers cold acclimatization of photosynthetic carbon metabolism. Wild-type Arabidopsis, pho1-2 and pho2-1 were grown at 23 degrees C and transferred to 5 degrees C to investigate acclimatization in pre-existing leaves and in new leaves developing at 5 degrees C. The development of frost tolerance and the accumulation of proline and sugars was unaltered or improved in pho1-2, and impaired in pho2-1. Sucrose phosphate synthase and cytoplasmic fructose-1,6-bisphosphatase activity and protein increase after transfer to 5 degrees C. This increase was accentuated in pho1-2 and attenuated in pho2-1. RBCS and LHCB2 transcript levels decrease in pre-formed wild-type leaves after transfer to 5 degrees C and recover in new leaves that develop at 5 degrees C. The initial decrease was attenuated in pho1-2, and accentuated in pho2-1, where the recovery in new leaves was also suppressed. Rubisco activity increased in wild-type leaves that developed at 5 degrees C. This increase was accentuated in pho1-2 and absent in pho2-1. NADP-glyceraldehyde-3-phosphate dehydrogenase, plastidic fructose-1,6-bisphosphatase and aldolase activity increase relative to phosphoglycerate kinase, transketolase and phosphoribulokinase in wild-type leaves at 5 degrees C. This shift was accentuated in pho1-2 and reversed in pho2-1. Transcript levels for COR genes increase transiently 1 day after transfer to 5 degrees C but were very low in leaves that developed at 5 degrees C in wild-type Arabidopsis, pho1-2 and pho2-1. We conclude that low phosphate plays an important role in triggering cold acclimatization of leaves, leading in particular to an increase of Rubisco expression, changes in other Calvin cycle enzymes to minimize sequestration of phosphate in metabolites, and increased expression of sucrose biosynthesis enzymes.

Acclimatization↗
PubMed1987

Action of centrally mediated autonomic stimulation on human upper gastrointestinal transit: a comparative study of two stimuli.

Two well established experimental stressors, hand immersion in cold water, and mental stimulation with dichotomous listening, were applied to 37 normal subjects after the ingestion of a standard meal. Orocaecal transit was measured by serial exhaled breath hydrogen sampling. Cold water significantly delayed transit compared with warm water control (warm water 71.8 +/- 3.6 mins v cold water 93.2 +/- 5.7 mins p less than 0.01), with significant rises in blood pressure pulse rate perceived discomfort and plasma catecholamines. In contrast mental stimulation was unaccompanied by any change in transit (control; 67.4 +/- 4.7 v test 64.3 +/- 5.3 mins p greater than 0.1) despite a significant rise in pulse rate, skin conductance and plasma catecholamines. Repeated cold water immersion studies in eight individuals produced consistent orocaecal transit and autonomic responses, whereas mental stimulation showed reduced autonomic responses on repeat testing, suggesting that tolerance to the stimulus had occurred. The results of these studies show stimulus specific gastrointestinal response patterns to autonomic stimuli, and appear to have important implications for the design of future studies of human gastrointestinal autonomic physiology and for the investigation of patients with stress related gut dysfunction.

Acoustic Stimulation↗
PubMed1997

Pulmonary responses during cold induced acute pain.

Cold induced acute pain is associated with many autonomic responses of the cardiovascular system, skin conductance and pupil size. However, there are few reports suggesting changes in pulmonary function. Hence present study reports preliminary data on this. Acute pain was induced in 30 non-smoker males, 30-50 yrs of age by immersing hand in cold water and their respiratory rate (RR), tidal volume (TV), inspiratory and expiratory reserve volumes (IRV, ERV) and respective capacities, vital capacity (VC), force vital capacity (FVC), FEV1%, peak flow and flow rates at 75%, 50% and 25% of expired volume (V75,50,25) were measured. Acute pain parameters like pain threshold, tolerance and sensitivity were also recorded. Besides these, heart rate, blood pressure (systolic and diastolic), skin temperature of forehead and opposite palm were also measured. Comparisons were made between values recorded before, during and after cold induced pain. An increase in RR, RV, IC, EC, FVC, FVC%, FEV1 was observed during cold induced pain reflecting an acute state of sympathetic dominance. Positive correlations between heart rate and respiratory rate, and other respiratory with pain parameters were seen during period of induction of acute pain. Hence the study indicates that alterations in pulmonary profile form a part of multidimensional responses observed during cold induced acute pain.

Acute Disease↗
PubMed2001

Methadone maintenance patients are cross-tolerant to the antinociceptive effects of morphine.

We have previously shown that methadone maintenance patients are hyperalgesic. Very little is known about the antinociceptive effects of additional opioids in these patients. This study (1) compared the intensity and duration of antinociceptive responses, at two pseudo-steady-state plasma morphine concentrations (C(SS1) and C(SS2)), between four patients on stable, once daily, doses of methadone and four matched control subjects; and (2) determined, in methadone patients, whether the antinociceptive effects of morphine are affected by changes in plasma R(-)-methadone concentration that occur during an inter-dosing interval. Two types of nociceptive stimuli were used: (1) a cold pressor test (CP), (2) electrical stimulation (ES). Morphine was administered intravenously to achieve the two consecutive plasma concentrations. Blood samples were collected, concurrently with nociceptive responses, to determine plasma morphine concentrations. Methadone patients achieved mean C(SS1) and C(SS2) of 16 and 55 ng/ml respectively; those of controls were 11 and 33 ng/ml. Methadone patients were hyperalgesic to pain induced by CP but not ES. Despite significantly greater plasma morphine concentrations, methadone patients experienced minimal antinociception in comparison with controls. Furthermore in methadone patients, the antinociception ceased when the infusion ended. In comparison, the duration of effect in control subjects was 3 h. The fluctuations that occurred in plasma R(-)-methadone concentration during an inter-dosing interval had little effect on patients' responses to morphine. Our findings suggest that methadone patients are cross-tolerant to the antinociceptive effects of morphine, and conventional doses of morphine are likely to be ineffective in managing episodes of acute pain amongst this patient group. Further research is needed to determine whether other drugs are more effective than morphine in managing acute pain in this patient population.

Acute Disease↗