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Expression of major cold shock proteins and genes by Yersinia enterocolitica in synthetic medium and foods.

Yersinia enterocolitica is a psychrotrophic foodborne pathogen that has been implicated in outbreaks of foodborne illness involving cold-stored foods, especially milk and pork. A major mechanism bacteria use to adapt to cold is expression of cold shock proteins. The objective of this research was to study the expression of major cold shock proteins of Y. enterocolitica in Luria-Bertani (LB) broth, milk, and pork following a temperature downshift from 30 to 4 degrees C. Y. enterocolitica was inoculated into 10 ml of LB broth, sterile skim milk, or pork, and the samples were stored at 4 degrees C (cold shock) or 30 degrees C (control) for 0, 4, 8, 12, and 24 h. At each sampling time, total protein and total RNA were extracted from Y. enterocolitica harvested from LB broth, milk, and pork and subjected to two-dimensional gel electrophoresis and dot blot analysis. Two major cold shock proteins (CspA1 and CspA2) of approximately 7 kDa and their genes were expressed by Y. enterocolitica following cold shock. However, the CspA1 and CspA2 proteins were not expressed by Y. enterocolitica at 30 degrees C. Y. enterocolitica CspA1 and CspA2 were observed as early as 2 h of cold shock in cultures from LB broth and milk and at 8 h of cold shock in cultures from pork.

Animals↗

Effects of prenatal ethanol exposure on hypothalamic-pituitary-adrenal responses to chronic cold stress in rats.

Animals prenatally exposed to ethanol typically exhibit hypothalamic-pituitary-adrenal (HPA) hyperresponsiveness to stressors. In contrast to previous studies that have investigated effects of prenatal ethanol exposure on HPA responses to acute or intermittent stressors, our study investigated HPA responses to a chronic continuous stressor, cold stress (4 degrees C for 0, 1, or 3 days). We tested the hypothesis that prenatal ethanol exposure would result in increased plasma corticosterone (CORT) and adrenocorticotropin (ACTH) responses and increased peptide [corticotropin-releasing factor and vasopressin] mRNA levels in the paraventricular nucleus (PVN) of the hypothalamus compared to that in control animals. In addition, CORT and ACTH responses were measured after exposure to an acute stressor (i.p. isotonic saline injection), superimposed during chronic cold exposure, to examine possible sensitization of the HPA response to the acute stress. Thus, blood samples were collected at the end of each of the three periods of cold exposure, either before (0 min) or 15 min after acute stress. The subjects were adult male and female Sprague-Dawley rat offspring from prenatal ethanol (E), pair-fed (PF), and ad libitum-fed control (C) treatment groups. Exposure to cold stress resulted in significant body weight loss in E males at 1 day and in both males and females of all prenatal treatment groups by 3 days of cold stress. Males in all prenatal groups also exhibited significant increases in adrenal weight:body weight ratios. Cold stress alone (0 min condition) increased CORT levels in E males and overall ACTH levels in E males and females compared to controls. ACTH levels were also higher overall in E compared to control males after acute stress (15 min condition). Sensitization of the CORT response to acute stress was observed in males but not females across all prenatal treatment groups. Corticotropin-releasing factor and vasopressin mRNA levels in the PVN were not significantly affected by prenatal treatment or chronic cold stress in either males or females. In contrast, both males and females displayed increases in PVN thyrotropin-releasing hormone (TRH) mRNA levels after cold stress. These data support and extend previous work demonstrating differential effects of prenatal ethanol exposure on HPA responsiveness of male and female offspring, and suggest that E males may be more vulnerable to the effects of chronic cold stress than E females.

Adrenocorticotropic Hormone↗

[Changes in blood constituents induced by noradrenaline infusion and acute cold exposure in rats treated chronically with noradrenaline and thyroxine (author's transl)].

Rats were treated with noradrenaline (NA), thyroxine (T4), NA plus T4, and NA plus ACTH for 28 days, and changes in rectal temperature and blood concentrations of nonesterified fatty acids (NEFA), sugar, and lactate were observed following NA infusion and acute cold exposure. Results obtained were compared with those found in cold-acclimated rats. NA infusion caused a marked elevation of the rectal temperature in cold-acclimated rats and NA plus T4-treated ones. No significant changes were observed in plasma NEFA level following NA infusion in cold-acclimated and NA-treated rats. Treatment with T4 tended to augment the lipolytic action of NA. Treatment with NA plus ACTH showed similar effect of augmented lipolysis. Changes in blood sugar level induced by NA infusion were small in cold-acclimated and NA plus T4 groups. Changes in blood lactate level were not significant in NA plus ACTH group. After acute cold exposure plasma NEFA level was low in cold-acclimated rats and high in NA plus T4-treated rats. Blood sugar level was slightly higher in cold-acclimated and NA plus T4-treated rats than in the other groups. Plasma lactate level showed relatively high values in T4 and NA plus T4 groups. It was thus suggested that metabolic patterns in cold-acclimated rats and in NA plus T4- as well as NA-treated rats were somewhat alike, but not always the same.

Acclimatization↗

[Cold-induced urticaria].

Cold urticaria is characterized by the development of urticaria, usually superficial and/or angioedematous reaction after cold contact. It was found predominantly in young women. The diagnosis is based on the history and ice cube test. Patients with a negative ice cube test may have represented systemic cold urticaria (atypical acquired cold urticaria) induced by general body cooling. The pathogenesis is poorly understood. Cold urticaria can be classified into acquired and familial disorders, with an autosomal dominant inheritance. Idiopathic cold urticaria is most common type but the research of a cryopathy is necessary. Therapy is often difficult. It is essential that the patient be warned of the dangers of swimming in cold water because systemic hypotension can occur. H1 antihistamines can be used for treatment of cold urticaria but the clinical responses are highly variable. The combination with an H2 antagonists is more effective. Doxepin may be useful in the treatment. Leukotriene receptor antagonists may be a novel, promising drug entity. In patients who do not respond to previous treatments, induction of cold tolerance may be tried.

Acetates↗

[Physiologic basis of human adaptation to cold].

Intermittent exposures to cold (15 head out immersions into 14 degrees C water, for 1 h, within 3 weeks) induce physiological changes leading to the restriction of heat loss from the body, due to hypothermia and vasoconstriction. These adaptational changes may save more than 25% of energy during 1 hour cold test. Insulative adaptation due to increased amount of the subcutaneous fat is less prominent. Winter swimmers show similar mechanisms of cold adaptationn as humans adapted by intermittent cold exposures in the laboratory. Additionally, winter swimmers exert a greater capacity of nonshivering thermogenesis than nonadapted controls. Thus, adaptation of humans to cold involves hypothermic, metabolic and insulative mechanisms. Time courses of development of individual mechanisms of adaptation differ. Intermittent local cold exposures (20 immersions of legs into 12 degrees C water, for 45 min, within 4 weeks lower sympathetic tone and induce redistribution of cardiac output, in order to ensure preferential warming of central parts of the body. Basal metabolism and cold induced thermogenesis are increased, but the threshold for induction of cold thermogenesis is not influenced. In contrast to changes induced by repeated whole body immersions, these changes may not ensure greater resistance to the cold stress.

Adaptation, Physiological↗

Nicotine effects on thermoregulatory responses of men and women during acute cold exposure.

INTRODUCTION: Due to the impact of nicotine (NIC) on the physiological processes involved in temperature regulation during cold exposure, it is conceivable that NIC may affect the body's thermoregulatory abilities during a cold stress. Thus, the purpose of this study was to examine the effects of NIC on thermoregulatory responses during acute cold exposure. METHODS: There were six men and six women between the ages of 18 and 25 yr who participated in this study. All subjects were active, apparently healthy smokers. Each subject performed two cold air trials consisting of a 30-min baseline period (BASE) and a 120-min exposure to 10 degrees C air. One cold air trial was performed following a NIC dosing using a 21-mg transdermal patch while the other trial was performed after a placebo (PL) treatment. RESULTS: During the cold air trials, there were no differences in rectal temperature (Tre) or mean skin temperature (Tsk) between the PL and NIC treatments in either sex (p > 0.05). However, in men, heat production (M) was 12% lower (p < or = 0.05) and tissue insulation was 17% higher (p < or = 0.05) during the NIC treatment compared with the PL treatment, while these responses in women were unaffected. In both men and women, finger skin vascular conductance (SVCfin), expressed as a percentage of the BASE value, was higher during the NIC treatment compared with the PL treatment during the cold air trials (p < or = 0.05). Lastly, throughout the cold air trials, there was no difference in thermal sensation between the PL and NIC treatments (p > 0.05). DISCUSSION: In conclusion, although NIC administration resulted in sex-specific alterations in M and tissue insulation during cold exposure, the response in Tre was unaffected.

Adult↗

[Questionnaire survey of the relationship between the common cold and acute asthma exacerbation].

Using questionnaires for 281 healthy subjects and 139 asthmatic patients in 5 medical institutes, we investigated the relationship between the common cold and acute asthma. The frequency of the common cold, duration to recovery and absences from work were slightly higher in asthmatics than healthy subjects. Acute asthma occurred in a few days following common cold and subsided at the end of or after the common cold. Evaluation of the types of common cold revealed that the cold, which causes upper respiratory symptoms, frequently induced acute asthma. Bronchodilators seemed to be less effective for cold-induced asthma. Collectively, these results suggested that the common cold induces acute asthma not through virus-induced direct inflammatory responses but through indirect immunological responses. Through these questionnaires, we realized that it is important to prevent the common cold, a trigger of asthma attacks. As the guidelines of asthma therapy recommended, the use of corticosteroid must be considered when acute asthma attacks occur.

Acute Disease↗

Acclimation to intermittent hypobaric hypoxia modifies responses to cold at sea level.

INTRODUCTION: Residence at high altitude modifies thremoregulatory responses to cold stress upon return to lower altitude. These changes are difficult to explain since several stresses related to high altitude may interact, including hypoxia, cold, solar radiation, and physical exertion. We hypothesized that adaptation to hypoxia without cold exposure would produce at least part of the observed changes. METHODS: Five men underwent acclimation to intermittent hypoxia (AIH) in a hypobaric chamber (8 h daily for 4 d, and 6 h on the last day, 4500 to 6000 m) at 24 degrees C. Cold stress responses were tested during a whole-body standard cold air test (1 degrees C, 2 h at rest at sea level) both before and after AIH. RESULTS: Increased reticulocyte counts and percentages confirmed acclimation to hypoxia after AIH. Changes in thermoregulation during the cold test included lower mean skin temperature after 60-80 min (18.8 +/- 0.7 degrees C vs. 19.4 +/- 0.7 degrees C); higher mean metabolic heat production (127 +/- 8 W x m(-2) vs. 118 +/- 6 W x m(-2)); and lower heat debt (7.7 +/- 1.3 kJ x kg(-1) vs. 10.3 +/- 1.2 kJ x kg(-1)), without significant change in rectal temperature. Time to onset for continuous shivering decreased after AIH (12 +/- 5 min vs. 21 +/- 6.3 min), and shivering activity occurred at higher mean skin but not rectal temperatures. CONCLUSION: AIH in comfortable ambient temperature leads to a normothermic-insulative-metabolic general cold adaptation. We conclude that AIH modifies the thermoregulatory responses to cold at sea level without cold exposure leading to a cross-adaptation.

Acclimatization↗

Evidence for adrenal medulla involvement in cold adaptation of preoptic-lesioned rats.

The cold-adaptation process was examined in preoptic-lesioned (PO, 18 rats) and adrenaldemedullated-preoptic-lesioned rats (ADPO, 16 rats). PO rats and ADPO female Wistar rats were cold acclimatized to 5 degrees C for 2 operated and then treated exactly like the lesioned rats. Lesions in the PO region caused a decrease in the ability to maintain normal body temperature in a cold environment (5 degrees C for 2 h). Their colonic temperature fell even by the end of the 2nd h of cold exposure (-1.1 degrees C for PO rats and -1.25 degrees C for ADPO rats, P less than 0.01). However, after 2 weeks of cold acclimation the PO rats, but not the ADPO rats were able to thermoregulate in the cold and showed a normal increase in interscapular brown adipose tissue weight (79%, P less than 0.01). These data suggest that the PO is not an essential link for cold adaptation when a mild cold-adaptation method is used. Furthermore, the data show that increased adrenal medullary activity is required for the cold adaptation process in PO rats.

Adaptation, Physiological↗

Cold sensitivity of the hand in arterial occlusive disease.

Digital blood pressure was measured using photoplethysmography in patients with cold sensitivity of the hand. In 19 patients with Buerger's disease, or arteriosclerosis obliterans (arterial occlusion group), 90 of 91 fingers with cold sensitivity showed significantly low pressures. In 17 patients with typical Raynaud's phenomena due either to primary Raynaud's disease or secondary to collagen disease (Raynaud's group), decreased digital pressure was noted in only five of 123 fingers with cold sensitivity. Blood pressure measurements in the fingers after local cooling of the hand showed a more severe response to cold in the Raynaud group than in the arterial occlusion group. These results indicate that the pathophysiologic mechanism for cold sensitivity in arterial occlusive disease is different from that in Raynaud's disease. In the arterial occlusion group impaired circulation due to occlusions in the digital arteries or more proximal arteries is a necessary precondition for cold sensitivity, and an increased sympathetic response to cold is of less importance as an etiologic factor. Thus a patient with cold sensitivity of the hand and normal digital blood pressure should not be considered to have arterial occlusive disease as the underlying cause of cold sensitivity.

Adult↗

[Nutrient utilization during cold exposure and adaptation].

BACKGROUND: Repeated exposure to cold leads to a decline in the intensity of physiological defence reactions. In the complex of adaptational responses metabolic, thermogenic and insulation reactions predominate. The objective of the present investigation was to provide evidence of the predominating type of response of sportsmen exposed repeatedly to cold in an aqueous environment and to elucidate metabolic processes which serve to meet the energy demands of a certain type of adaptation to cold. METHODS AND RESULTS: The examination was made in a group of volunteers (men, mean age 21.0 +/- 1.8 years, height 1.80 +/- 0.04 m, body weight 77.0 +/- 3.1 kg, body fat 13.2 +/- 1.7%, anaerobic capacity expressed as maximum oxygen consumption 4.5 +/- 0.43 l.min-1). The cold acclimation programme involved immersion of the body into water 14 +/- 1 degree C 3 times a week for 1 month. During cold exposure the median body temperature before the acclimation programme dropped by 3.9 degrees C, after the acclimation programme by 4.1 degrees C. The total metabolic turnover after the programme declined by a 0.23 multiple of the metabolism at rest, at the end of the programme merely by a multiple of 0.07. During immersion the oxygen consumption doubled regardless of the stage of adaptation and an insignificant rise of non-esterified fatty acids occurred before the onset of the programme as well as after its termination. After the first exposure to cold a significant drop of the blood sugar was observed, while after the acclimation programme it increased insignificantly. The serum level of the thyroid stimulating hormone and triiodothyronine were affected only insignificantly by exposure to cold, the thyroxine level only at the borderline of significance before the onset of the acclimation programme. CONCLUSIONS: From values of the blood sugar level, respiratory quotient RQ, the non-esterified fatty acid level and body temperature at the periphery we may conclude that there is a restriction of the carbohydrate component as regards meeting energy demands of cold exposure before adaptation and a mixed type of meeting energy demands after termination of the cold acclimation programme.

Adaptation, Physiological↗

Antibiotics and upper respiratory infection: do some folks think there is a cure for the common cold.

BACKGROUND: Symptomatic treatment is the only recommended therapy for the uncomplicated "common cold." The purpose of this study was to examine the use of antibiotics and other prescription medications for the common cold in a Medicaid population seen in ambulatory care settings. METHODS: A cross-sectional sample of Kentucky Medicaid claims from July 1, 1993, through June 30, 1994, was analyzed. Subjects were patients seen in an ambulatory setting for the common cold, defined as acute nasopharyngitis. A total of 1439 individuals were seen for 2171 separate outpatient and emergency department encounters for the common cold. Outpatient visits accounted for 99% (2144) of the encounters. RESULTS: Patients in 35% (752) of the encounters did not fill a prescription for medication, 6% (129) filled a prescription for an antihistamine or other symptomatic medication, and 60% (1290) filled a prescription for an antibiotic for the common cold. Nineteen different antibiotics, 54% of which were amoxicillin, were prescribed for the common cold. Less than 2% of the encounters had a secondary diagnosis of either acute sinusitis or otitis media. These encounters were not more likely than the total sample to receive antibiotics. Adults were more likely than children to receive an antibiotic (P<.001), and urban physicians were more likely than rural physicians to prescribe antibiotics (P=.02). A conservative estimate of the annual cost of antibiotic prescribing for the common cold in the United States was $37.5 million. CONCLUSIONS: A majority of persons receiving medical care for the common cold are given prescriptions for an unnecessary antibiotic. Unchecked, this practice may lead to greater antibiotic resistance and unnecessary use of health care resources. Future research should focus on the ability to institute behavioral changes for treatment of the common cold in both closed systems (eg, managed care) and open systems (eg, general community of physicians).

Adolescent↗

Significance of cold intolerance in upper extremity disorders.

After upper extremity injury, pain on exposure to cold (cold sensitivity) is a significant problem. This cross-sectional observational study (1) assesses the incidence and prevalence of cold intolerance, (2) evaluates the relationship between functional status and degree of cold intolerance, and (3) correlates health-related quality of life (HRQL) with symptoms of cold intolerance. Patients in a tertiary care center completed questionnaires to document (1) cold sensitivity, (2) upper extremity pain, symptoms, and function, and (3) HRQL. Cold sensitivity was found to be associated with more functional limitations, greater pain, and reduced HRQL. As the severity of cold intolerance increased, functional limitations and pain increased and HRQL decreased. Cold intolerance has a profound effect on HRQL.

Activities of Daily Living↗

The effect of trigeminal neurotomy on the alteration of local cerebral blood flow of normotensive and hypertensive rats in acute cold stress.

The cold season is reported to have the highest incidence of stroke in a year. Cold is usually detected by cold receptors in the face. The present studies were designed to test whether the trigeminal nerve plays a role in the regulation of local cerebral blood flow (LCBF) in animals exposed to a cold environment. Since hypertension affects the incidence of strokes, both Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) were used. Each species was divided into four groups: trigeminal neurotomy (TNx) or control group at room temperature (20 degrees C) or cold environment (5 degrees C), respectively. LCBF in 14 brain structures was measured using the [14C] iodoantipyrine technique and tissue dissecting methods. Our results show that TNx did not alter physiological parameters and LCBFs in WKY and SHR kept either at 20 degrees C or at 5 degrees C for 30 min. However, a transient exposure (30 minutes) to cold caused concomitantly a significant decrease in core body temperature of both WKY and SHR groups (p<0.05, Student's paired t-test) and a significant decrease in LCBFs at the temporal cortex (TC), hypothalamus (HYP) and midbrain (MID) of WKY and TC of SHR (P<0.05, MANOVA). TNx did not alter LCBFs significantly following transient cold exposure in WKY and SHR. Our findings indicate that in the cold environment, the lowered LCBFs in some areas of the brain may relate to the decreased metabolic rate caused by decreased body temperature, and may partly contribute to the higher prevalence of stroke in winter. Our findings also suggest that trigeminal nerve do not exert tonic control of LCBFs and the cold afferents in trigeminal nerve are not important in modulation of the LCBFs.

Animals↗

Superficial heat or cold for low back pain.

BACKGROUND: Heat and cold are commonly utilised in the treatment of low-back pain by both health care professionals and people with low-back pain. OBJECTIVES: To assess the effects of superficial heat and cold therapy for low-back pain in adults. SEARCH STRATEGY: We searched the Cochrane Back Review Group Specialised register, the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 3, 2005), MEDLINE (1966 to October 2005), EMBASE (1980 to October 2005) and other relevant databases. SELECTION CRITERIA: We included randomised controlled trials and non-randomised controlled trials that examined superficial heat or cold therapies in people with low-back pain. DATA COLLECTION AND ANALYSIS: Two authors independently assessed methodological quality and extracted data, using the criteria recommended by the Cochrane Back Review Group. MAIN RESULTS: Nine trials involving 1117 participants were included. In two trials of 258 participants with a mix of acute and sub-acute low-back pain, heat wrap therapy significantly reduced pain after five days (weighted mean difference (WMD) 1.06, 95% confidence interval (CI) 0.68 to 1.45, scale range 0 to 5) compared to oral placebo. One trial of 90 participants with acute low-back pain found that a heated blanket significantly decreased acute low-back pain immediately after application (WMD -32.20, 95%CI -38.69 to -25.71, scale range 0 to 100). One trial of 100 participants with a mix of acute and sub-acute low-back pain examined the additional effects of adding exercise to heat wrap, and found that it reduced pain after seven days. There is insufficient evidence to evaluate the effects of cold for low-back pain, and conflicting evidence for any differences between heat and cold for low-back pain. AUTHORS' CONCLUSIONS: The evidence base to support the common practice of superficial heat and cold for low back pain is limited and there is a need for future higher-quality randomised controlled trials. There is moderate evidence in a small number of trials that heat wrap therapy provides a small short-term reduction in pain and disability in a population with a mix of acute and sub-acute low-back pain, and that the addition of exercise further reduces pain and improves function. The evidence for the application of cold treatment to low-back pain is even more limited, with only three poor quality studies located. No conclusions can be drawn about the use of cold for low-back pain. There is conflicting evidence to determine the differences between heat and cold for low-back pain.

Adult↗

Cold storage sensitizes rat femoral artery to an endotoxin-induced decrease in endothelium-dependent relaxation.

Cold-stored arteries, tissues or organs are transferred in vascular, reconstructive and transplantation surgery. The function of transferred vessels and tissues diminishes when infection complicates transplantation, thereby contributing to morbidity. To evaluate the mechanisms involved, the effects of cold storage on basal vascular reactivity and the sensitivity to the vascular effects of endotoxin were tested in isolated rat femoral artery segments. A crossover design was followed, so that prior to cold storage 4 vessels were incubated for 2 h at 37 degrees C with endotoxin (Escherichia coli 0127:B8, 50 microg mL(-1)) in Krebs solution and 4 with Krebs solution only, while, after cold storage, segments from the former vessels were incubated with Krebs solution only and segments from the latter with endotoxin in Krebs solution. Vascular reactivity was tested in a wire myograph by the addition of depolarizing 125 mM KCl or norepinephrine (NE) as well as the endothelium-dependent vasodilator acetylcholine (ACh) and endothelium-independent vasodilator sodium nitroprusside (SNP). Cold storage did not affect vascular reactivity in the absence of endotoxin. Endotoxin decreased maximum response to NE prior to storage and sensitivity to SNP prior to and after cold storage. After cold storage, endotoxin decreased relaxation to ACh and increased vasoconstriction in response to KCl and NE (P < 0.05). We conclude that cold storage does not alter endothelial and smooth muscle function but sensitizes rat femoral artery to an endotoxin-induced decrease in endothelium-dependent relaxation and thereby to an increase in vasoconstrictor responses, whereas endotoxin alone only decreases receptor-dependent vasoconstrictor responses and sensitivity to NO donors. This may explain in part the detrimental effect of infection on function of cold-stored arterial grafts and tissue/organ transfers.

Acetylcholine↗

Predictive factors from cold knife conization for residual cervical intraepithelial neoplasia in subsequent hysterectomy.

OBJECTIVE: The optimal management of cervical intraepithelial neoplasia after cold knife conization remains controversial. Reliable predictors of residual dysplasia in the cervix after cold knife conization have not been consistently identified. This study was initiated to examine the accuracy of the traditional factors used to predict residual dysplasia in hysterectomy specimens after cold knife conization. STUDY DESIGN: A retrospective 10-year chart review identified a cohort of 1272 patients who underwent cold knife conization, of whom 311 had a subsequent hysterectomy within 1 year of conization. Residual disease was defined as cervical intraepithelial neoplasia or cancer in the hysterectomy specimen. All cone specimens were completely submitted for pathologic examination, and the following factors were analyzed for their predictive value: degree of dysplasia, margin involvement, endocervical gland involvement, and status of the endocervical curettage. The predictive value of age, race, gravidity, parity, socioeconomic status, cigarette smoking, and marital status were also examined. The chi 2 test, t test, and logistic regression were used for statistical analysis. RESULTS: Dysplasia or cancer were identified in 1066 (84%) of the 1272 patients who underwent cold knife conization. Of the 311 patients having a subsequent hysterectomy, 106 (34%) had residual disease in their hysterectomy specimen. By multivariate analysis only increasing age and degree of dysplasia were predictive of residual disease. The odds ratio of residual disease in the hysterectomy specimen for a 25-year-old woman was 2.7 (95% confidence interval 1.6 to 4.4) compared with a 40-year-old woman whose odds ratio was 4.9 (95% confidence interval 2.2 to 10.8). The presence of dysplasia in the cold knife conization specimen conferred an odds ratio of 12.1 (95% confidence interval 2.7 to 54.5) of identifying residual disease. Dysplasia involving the ectocervical margin, endocervical margin, and endocervical glands was not predictive of disease in the hysterectomy specimens. Endocervical curettage was not performed in 44% of the patients, preventing reliable statistical evaluation. Further analysis indicated that residual disease was found in 32% of the hysterectomy specimens with negative margins, in 31% with no endocervical gland involvement, and in 23% with a negative endocervical curettage sample. CONCLUSIONS: The presence or absence of dysplasia in the cold knife conization ectocervical margin, endocervical margin, and endocervical glands was not predictive of residual dysplasia in post-cold knife conization hysterectomy specimens. Increasing age and severity of disease in the cone specimen were the only factors that accurately predicted residual dysplasia. The traditional factors used to justify hysterectomy after cold knife conization may not be valid on the basis of these results.

Adolescent↗

Augmentation of transgene expression in cold-preserved organs using vascular endothelial growth factor receptor-mediated adenoviral vector combined with hyperbaric oxygen.

Adenovirus-mediated gene transfer has been widely used in gene therapy for congenital metabolic, cardiovascular, and malignant diseases. It has been reported that a gene transfer technique into transplanted organs may suppress rejection reactions and inhibit preservation injury. However, the magnitude of transgene expression in organs preserved at a cold temperature remains to be determined. In this study, we compared the transgene expression using vascular endothelial growth factor receptor (VEGFR)-mediated adenoviral vector at cold versus warm temperatures alone and combined with hyperbaric oxygen in cold-preserved organs. The transgene expression by porcine endothelial cells transduced with adenoviral vector was significantly higher after a 24 hour-incubation at warm temperature than after a 1 hour-incubation with warm or cold temperature. Moreover, the transgene expression of after a 1-hour incubation at cold temperature was significantly lower than a 1-hour incubation at warm temperature. The VEGFR-mediated adenoviral vector augmented transgene expression during a 1-hour incubation at cold temperature compared to the control vector. A/J skin graft survival in C3H mice was significantly prolonged compared to control or standard vector with CTLA4Ig cDNA using VEGFR-mediated adenoviral vector with CTLA4Ig cDNA in a 1-hour cold preservation. Furthermore, combined use of VEGFR-mediated adenoviral vector with CTLA4Ig cDNA plus FK506 showed an augmented effect on graft prolongation. It is concluded that adenovirus-mediated gene transfer in 1-hour cold-preserved organ is difficult compared to that in the warm condition. However, VEGFR-mediated gene transfer can augment the transgene expression in 1-hour cold-preserved organs, followed by the effective suppression of rejection reactions in allogeneic transplantation.

Abatacept↗