Biomedical subjects

A Lang

Publications and source records attributed to A Lang.

At least 19 recordsLinked to original sources

PubMed2006

Movement disorders in patients taking anticonvulsants.

BACKGROUND: A wide variety of movement disorders may occur as a consequence of the administration of antiepileptic drugs (AEDs). Although it has been suggested that the risk of parkinsonism is 10-fold higher in those taking valproate as compared with other AEDs, there have been no large, systematic trials assessing this. AIM: To establish more precisely the prevalence of and risk factors for developing parkinsonism associated with valproate use,and to assess the occurrence of movement disorders with the newer AEDs. METHODS: Patients with epilepsy were recruited from the Toronto Western Hospital Epilepsy Clinic (University of Toronto, Toronto, Ontario, Canada). Each patient was examined by a movement disorder specialist who was blinded to the treatment status of the patient. RESULTS: 201 patients were included. Postural tremor was the most common movement disorder (45%), followed by parkinsonism (4.5%). The odds of having parkinsonism were 5 times higher with valproate than with other AEDs. No single factor predicted the presence of parkinsonism; however, many (5/9) of the patients concurrently used other drugs or had comorbidities that could have caused or exacerbated parkinsonism. None of the newer AEDs were clearly associated with the presence of movement disorders; however, the numbers were too small to make a formal analysis. CONCLUSION: Although the risk of parkinsonism with valproate is higher than with other AEDs, it is lower than originally reported. The cases available were not enough to accurately comment on the prevalence of movement disorders with the newer AEDs.

Adult↗

PubMed2006

Measuring quality of life in PSP: the PSP-QoL.

OBJECTIVE: To develop a new patient-reported outcome measure for progressive supranuclear palsy (PSP) and to test its psychometric properties. METHODS: First, the authors generated a pool of potential scale items from in-depth patient interviews. Second, the authors administered these items, in the form of a questionnaire, to a sample of people with PSP and traditional psychometric methods were used to develop a rating scale satisfying standard criteria for reliability and validity. Third, the authors examined the psychometric properties of the rating scale in a second sample. RESULTS: In stage 1, a pool of 87 items was generated from 27 patient interviews. In stage 2, a scale with two subscales (physical, 22 items; mental, 23 items), satisfying standard criteria for reliability and validity, was developed from the response data of 225 patients with PSP. In stage 3, the scale was examined in 188 people with PSP. Missing data were low, scores in both subscales were evenly distributed, floor and ceiling effects were small. Reliability was high (Cronbach's alpha 0.93, 0.95; test-retest 0.95, 0.92). Validity was supported by the interscale intercorrelation (0.60), factor analysis, and the magnitude and pattern of correlations with four other rating scales, disease severity, and disease duration. The psychometric properties of the new scale were similar in the United Kingdom and North America, and in clinic- and community-based samples studied. CONCLUSIONS: The Progressive Supranuclear Palsy Quality of Life scale (PSP-QoL) may be a helpful patient-reported scale for clinical trials and studies in PSP.

Aged↗

PubMed2006

Medium-term follow-up data after sentinel node biopsy alone for breast cancer.

AIMS: In patients with early breast cancer sentinel node biopsy (SNB) proved to be an accurate procedure for axillary staging with significantly reduced morbidity. Medium- and long-term observational studies are needed to establish, whether SNB alone is able to prevent locoregional recurrence without impairing long-term survival. METHODS: 298 patients with invasive breast cancer were subjected to SNB in a prospective audit. Lymphatic mapping was performed with blue dye and radiocolloids. 180 patients had SNB alone (group 1), while 118 subsequently underwent axillary dissection (AD; group 2). In ten patients AD was omitted despite the tumor burden in the SN. Clinical follow-up studies were performed at regular intervals. The mean follow-up time was 47months in group 1 (range 7-90) and 46months in group two (range 1-87months). RESULTS: Sentinel nodes were identified in 286 out of 298 patients (96%). One patient in group 1 developed axillary and simultaneous supraclavicular lymph node recurrence. After AD regional relapses have so far not been observed. One ipsilateral local recurrence was detected in each group. Five patients in group 1 and 15 patients in group 2 developed distant metastases. Three out of six and eight out of nine patients, respectively, died of their advanced disease. All patients with SN tumor infiltration not subjected to AD are alive and well. CONCLUSIONS: Axillary recurrence is rare after sentinel node biopsy alone. Its rate is comparable to that after AD, even in patients with SN micrometastases. These conclusions are confirmed by reports in the literature.

Adult↗

PubMed2005

Risk factors regarding the need for a second operation in patients with Crohn's disease.

BACKGROUND/AIMS: The majority of Crohn's disease patients undergo surgery. However, the factors that predict post-operative recurrence remain controversial. The aim of the present study was to shed light on the potential predictors of such recurrence. METHODS: 86 patients who underwent operative procedures for Crohn's disease were retrospectively studied. Recurrence was defined as the need for a second operation. Life table and multivariate analysis were performed to find the predictors of recurrence. RESULTS: In 26/86 (30%) of the patients, post-operative recurrence was diagnosed within a mean of 42 months of the follow-up. Logistic regression analysis revealed that smoking (OR 3.69, 95% CI 2.06-11.52) and perforating disease (OR 4.09, 95% CI 1.31-12.65) were associated with a risk of recurrence. However, survival analysis showed that only perforating disease was associated with an early post-operative recurrence (log-rank test, p < 0.001). Neither resected surgical specimen characteristics, nor the duration and the location of the disease were found to predict the need for a second operation. CONCLUSION: The risk for Crohn's disease patients who undergo surgery is related to the presence of perforating disease and smoking, which predict the need for a second operation. The former is associated with an even earlier recurrence.

Adult↗

PubMed2005

Impact of ACTH during oestrus on the ultrastructure of the spermatozoa and their environment in the tubal reservoir of the postovulatory sow.

This study investigated whether injections of synthetic ACTH (simulating short-term stress) in sows during standing oestrus have a negative effect on spermatozoa and the local intraluminal environment in the utero-tubal junction (UTJ) and isthmus. Seven of the 14 sows were given ACTH through a jugular catheter every 2 h from the onset of standing oestrus until the sow ovulated (ACTH-group), while the other seven sows were given NaCl solution (C-group). All sows were artificially inseminated before ovulation. Six hours after ovulation (detected with transrectal ultrasonography) the sows were anaesthetised, the right oviduct was fixed in toto by vascular perfusion with glutaraldehyde, and the UTJ and specimens from the isthmus were prepared for scanning electron microscopy (SEM). SEM revealed that a seemingly viable population of spermatozoa remained in the UTJ 6 h after ovulation. A majority of sows in the ACTH-group had moderately to exaggerated amounts of mucus in the intraluminal environment of the sperm reservoir. In conclusion, stress simulated by exogenous ACTH in sows may alter the intraluminal environment of the sperm reservoir.

Adrenocorticotropic Hormone↗

PubMed2005

Transition from initiation to promoter proximal pausing requires the CTD of RNA polymerase II.

The C-terminal domain (CTD) of mammalian RNA polymerase II consists of 52 repeats of the consensus hepta-peptide YSPTSPS, and links transcription to the processing of pre-mRNA. Although Pol II with a CTD shortened to five repeats (Pol II Delta5) is transcriptionally inactive on chromatin templates, it is not clear whether CTD is required for promoter recognition in vivo. Here, we demonstrate that in the context of chromatin, Pol II Delta5 can bind to the c-myc promoter with the same efficiency as wild type Pol II. However, Pol II Delta5 does not form a stable initiation complex, and does not transcribe promoter proximal sequences. Fluorescence recovery after photobleaching (FRAP) experiments with cells expressing enhanced green fluorescent protein (EGFP)-tagged Delta5 or wildtype Pol II revealed a single, highly mobile Pol II Delta5 fraction whereas wildtype Pol II yielded less mobile fractions. These data suggest that CTD is not required for promoter recognition, but rather for subsequent formation of a stable initiation complex and isomerization to an elongation competent complex.

Binding Sites↗

PubMed2005

Impact of ACTH administration on the oviductal sperm reservoir in sows: the local endocrine environment and distribution of spermatozoa.

The objective of the study was to investigate if short-term stress in sows (simulated by injections of synthetic adrenocorticotrophic hormone (ACTH)) during standing oestrus had a negative effect on the local environment in the utero-tubal junction (UTJ) and isthmus and the distribution of spermatozoa in these segments. Fourteen sows were monitored for ovulation using ultrasonography in two consecutive oestruses. The sows were fitted with jugular catheters and, from onset of the second oestrus, blood samples were collected every second hour. In the 2nd oestrus, seven sows were given ACTH every second hour, from the onset of standing oestrus until the sow ovulated (ACTH-group), whereas the other seven sows remained as controls (C-group) and were given NaCl solution. The sows were artificially inseminated 16-18 h before expected ovulation. Six hours after ovulation the sows were anaesthetised, and blood samples were repeatedly taken from veins draining the uterus and the UTJ-isthmus, respectively. This oviduct was thereafter removed and divided in four adjacent sections consisting of: (i) the UTJ, (ii) the first, and (iii) the second isthmus segment prior to (iv), the ampullary-isthmic junction (AIJ) and the ampulla. The three first-mentioned segments were flushed to retrieve spermatozoa, whereas the last one was flushed to collect oocytes/ova. The number of spermatozoa attached to the zona pellucida was counted. The concentrations of cortisol in jugular blood of the ACTH-group sows during the time of ACTH-injections were significantly higher than of the C-group sows (p<0.05), as were the levels of progesterone (p<0.001). Progesterone and cortisol concentrations measured in the blood samples draining the UTJ-isthmic region 6 h after ovulation did not significantly differ between the groups, but the C-group displayed significantly higher concentrations of progesterone in the UTJ-isthmic region compared with the levels measured in parallel samples taken of jugular blood (p<0.01). The C-group, but not the ACTH-group, also displayed a significant elevation in progesterone concentration 6h after ovulation compared with the basal levels before ovulation (p<0.01). Numbers of retrieved spermatozoa were not significantly different between the C-group and the ACTH-group. However, there was a tendency for a larger number of spermatozoa among sows in the ACTH-group, especially in the isthmic segment adjacent to the AIJ. In conclusion, simulated stress induced by injections of ACTH during standing oestrus results in elevated concentrations of progesterone before ovulation and may interfere with the rise of progesterone after ovulation. However, ACTH-injections appeared to augment transport of spermatozoa through the female genital tract of pigs.

Adrenocorticotropic Hormone↗

PubMed2005

Factors regulating ovarian function in pigs.

The hormonal interactions of the hypothalamic-pituitary-ovarian-uterine axis are accountable for a normal reproduction in female pigs. It is of importance to have knowledge of estrous symptoms and hormonal profiles around ovulation. The introduction of the transrectal ultrasonography in sows has given us the possibility to study ovarian activity in conscious animals and relate the timing of estrus to ovulation. Combining this technique with measuring of several hormones like luteinizing hormone (LH), follicle-stimulating hormone (FSH), inhibin, estradiol, progesterone, insulin-like growth hormone I (IGF-I), prostaglandin F2alpha (PGF2alpha) metabolite, oxytocin, facilitate our knowledge about the sequence of ovarian events. Evidence suggests that activation of the hypothalamic-pituitary-adrenal axis may hamper the normal gonadotropin secretion and in consequence, the ovarian function. The metabolic status during lactation, weaning of piglets and social stress might affect onset of ovarian activity and the related estrous behavior. The role of seminal plasma, artificial insemination and presence of the boar might also be included as factors regulating the temporal kinetics of ovulation, corpus luteum development, uterine function and steroid production in the ovary. Studies using a simulated stress by means of adrenocorticotrophic hormone (ACTH) administration or food deprivation are tools in understanding how the ovary is susceptible to impairment. The intention of this paper is to review current knowledge concerning the endocrine aspects of normal and stress-influenced ovarian function in pigs.

Animals↗

PubMed2004

[Calculation of the incidence of primary care visits due to acute respiratory infections].

Data collected by the German influenza sentinel of the Working Group on Influenza (AGI) do not allow calculation of the incidence of primary care visits due to acute respiratory infections (ARI). Because patients do not have to register with a particular general practitioner, the population covered by primary care physicians is unknown. Until now the incidence of primary care visits due to ARI is estimated indirectly by extrapolating the sentinel sample of physicians to the total number of primary care physicians caring for the total population. However, distortions of the estimated incidence occur in weeks with public holidays (particularly around Christmas and New Year) and when many physicians close their practice simultaneously because of vacation. We have attempted to quantify the shortage of medical services and established thresholds to correct for situations where service by medical providers is extraordinarily reduced. The suggested method avoids distortions to a large extent and makes interpretation of data during those critical periods possible. A second subject of the paper is the validation of the estimated ARI incidence in primary care practices by comparing the data to other sources such as sick leave statistics of health insurance as well as ICD-based data from a primary care network. We found that the estimated ARI incidence in primary care practices was in line with data from other sources and appears plausible.

Acute Disease↗

PubMed2004

Risk factors for mortality in patients undergoing percutaneous endoscopic gastrostomy.

BACKGROUND AND STUDY AIMS: Percutaneous endoscopic gastrostomy (PEG) is a method used for feeding patients who are unable to eat. High early mortality rates among hospitalized patients have been reported. The aim of this study was to shed light on the risk factors for early mortality after PEG tube insertion. PATIENTS AND METHODS: Outpatients from nursing homes and hospitalized patients who underwent PEG between July 1995 and July 2001 were compared. Survival analysis was used to assess mortality after PEG. In a logistic regression analysis, mortality within 30 days among hospitalized patients was chosen as the outcome variable and the predictor variables were demographic characteristics, co-morbid conditions, and indication for PEG. RESULTS: A total of 502 PEG tubes were inserted in 419 hospitalized and 83 nursing-home patients. The prevalence of co-morbid conditions was similar in the two groups. Both the 30- and 60-day mortality rates were around six times higher in the hospitalized patient group than in the nursing-home patient group (30-day mortality rate 8 % vs. 1.2 %, P = 0.034; 60-day mortality rate 12 % vs. 2.4 %, P = 0.016). Risk factors for 30-day mortality among hospitalized patients were: serum albumin < 3 g/dl (odds ratio 2.82, 95 % CI 1.34 - 5.96), chronic obstructive pulmonary disease (odds ratio 2.79, 95 % CI 1.26 - 6.14), and diabetes mellitus (odds ratio 2.44, 95 % CI 1.20 - 4.97). CONCLUSIONS: Compared with nursing-home patients, hospitalized patients are at higher risk for early mortality after PEG. The presence of diabetes, chronic obstructive pulmonary disease, and a low serum albumin level each increase the 30-day mortality risk among hospitalized patients threefold.

Aged↗

PubMed2004

Unique TCRDV1-positive lymphocytes that infiltrate colonic neoplasia originate from a selected cell population present in the intestinal mucosa and the peripheral blood.

TCRDV1-positive lymphocytes, which infiltrate colon carcinomas, were recently shown to be cytolytic for tumour cells. However, the immune compartment from which these cells originate is unknown. The aim of the present studies was to determine the origin of TCRDV1-positive cells in colonic neoplasia. Biopsies were obtained from normal colon, polyps or carcinomas, concurrently with a sample from the peripheral blood. RNA was extracted and a TCRDV1-specific reverse transcriptase-polymerase chain reaction (RT-PCR) was performed. Amplification products were analysed by a CDR3 display and sequence analysis. In five out of six patients, the TCRDV1 CDR3 display of the whole cell population within the neoplastic tissue was distinct from that in the normal mucosa and the peripheral blood. The nucleotide sequences of CDR3 domains from the three compartments were distinct as well. In one patient, a pattern similar to the CDR3 display was detected in neoplastic and normal intestinal tissues. However, using junction-specific RT-PCR of CDR3 sequences derived from the neoplastic cells, such sequences could be detected in all three compartments. These findings suggest that in contrast to the current paradigm, a unique TCRDV1 cell population circulates in the peripheral blood and normal intestinal tissue and infiltrates colon neoplasia rather than being restricted to a single compartment as previously thought.

Carcinoma↗

PubMed2004

Temozolomide and interferon alpha 2b in metastatic melanoma stage IV.

BACKGROUND: A multicentre, centrally randomized, open-labelled study with temozolomide and interferon (IFN)-alpha 2b was carried out to study the therapeutic effect in patients with metastatic melanoma stage IV. OBJECTIVES: The response rate, efficacy, side-effects, reasons for discontinuation of therapy and survival rate of 47 patients treated with temozolomide in combination with two different dosing regimens of IFN-alpha 2b were documented. PATIENTS/METHODS: Twenty-nine male and 18 female patients (mean age 57.6 years, range 34-74) were centrally randomized to two different arms: 20 patients received a treatment schedule with temozolomide 150 mg m(-2) on days 1-5 orally every 28 days in combination with IFN-alpha 2b 10 MIU m(-2) every other day and 27 patients received temozolomide 150 mg m(-2) on days 1-5 every 28 days in combination with IFN-alpha 2b in a fixed dose of 10 MIU every other day. RESULTS: We observed an overall response rate of 27.6% comprising five complete remissions (10.6%: one patient group A, four patients group B), in two of these five patients at the last follow-up in the study (4.3%, both in group B); and eight partial remissions (17%: six patients in group A, two patients in group B), in three of these eight patients at the last follow-up in the study (6.4%, two patients in group A, one patient in group B). Three patients showed stable disease (6.4%: one patient in group A, two patients in group B). Mean survival was 14.5 months [95% confidence interval (CI) 10-19] with no significant differences between treatment groups. However, there was a significant correlation with response after three cycles (log rank test, P < 0.03). Within the 32 patients who completed at least three cycles of therapy, seven patients (three in group A and four in group B) with a partial or complete response showed a significantly better mean survival of 30.6 months (95% CI 19.1-42) compared with 25 patients who did not respond (13.7 months 95% CI 9.2-18.3). In total, patients with at least one complete remission showed the longest survival (37.1 months 95% CI 26.3-47.9), followed by patients with at least one partial response (17.4 95% CI 10.9-23.9). Major side-effects of the treatment were nausea, vomiting, headache, leucopenia, thrombopenia, elevation of liver function parameters and neurological symptoms. In five patients, the side-effects led to a discontinuation of treatment: neurological symptoms (two patients), sepsis (one patient), brain haemorrhage (one patient) and exanthema (one patient). There were no treatment-related deaths. CONCLUSIONS: The combination of temozolomide and IFN-alpha 2b can easily be administered and shows tolerable toxicity. When an objective response occurs after three cycles, it indicates a significant survival advantage.

Adult↗

PubMed2004

Food allergy as a risk factor for nutritional rickets.

The case of a 14-month-old boy with vitamin D deficiency rickets as a result of unsupervised dietary manipulation in the context of cow's milk allergy is presented. Adequate supervision by a qualified dietician, coupled with appropriate supplementation, is essential if nutritional compromise is to be avoided in children with food allergy.

Alkaline Phosphatase↗

PubMed2004

Influence of CRH and ACTH administration on endocrine profile and ovulation in sows.

Grouping of sows is a stressful event until the ranking is established. The purpose of this study was to simulate stress by repeated administration of porcine corticotropin releasing hormone (CRH) and adrenocorticotropic hormone (ACTH)/tetracosactide and to study its influence on endocrine profile and ovulation. Four multiparous sows were used and blood was collected every 2 h from the onset of pro-oestrus until 12 h after ovulation. The first oestrus after weaning was used to check ovulation and acclimate the sows to their environment. The second oestrus after weaning was used as control. At their third oestrus CRH (0.6 microg/kg) and at their fourth oestrus ACTH (5 microg/kg) were given every 4 h from onset of oestrus until ovulation. The total 'area under the curve' of cortisol was twofold larger in two of four sows during the CRH treatment period, and two- to fourfold larger (p < or = 0.05) during the ACTH treatment period, compared with the corresponding control period. In three sows, there was no clear effect of either CRH or ACTH on the levels of oestradiol 17beta, luteinizing hormone (LH) or on the timing of ovulation. One sow was different in all hormonal patterns and also in the timing of ovulation. In all four sows, ACTH treatment lowered the baseline level of prostaglandin F(2 alpha)-metabolite. Therefore, we conclude that stage of the oestrous cycle seems to be of importance when investigating the influence of exogenous administration of CRH/ACTH on hormonal pattern and ovulation time in the sow.

Adrenocorticotropic Hormone↗

PubMed2003

Parkin-proven disease: common founders but divergent phenotypes.

OBJECTIVE: To compare and contrast clinical and genetic findings in six probands with parkinsonism with a parkin exon 3 438- to 477-bp deletion (Ex3Delta40) to search for evidence of a common founder. METHOD: Clinical review, parkin gene sequencing, dosage studies, and high-resolution genotype/haplotype analysis were performed. RESULTS: All subjects had two or more signs consistent with a diagnosis of possible or probable PD with age at onset younger than 45 years (mean +/- SD 29.3 +/- 10.2 years, range 16 to 42 years). Affected individuals were either homozygotes, compound heterozygotes, or Ex3Delta40 carriers with one normal parkin allele. Haplotype analysis revealed both Ex3Delta40 and Ex7 924 C-->T (R275W) mutations originated from common founders, the former most probably of Irish descent. Although three cases had Ex7 924 C-->T (R275W) and Ex3Delta40 mutations, their clinical presentation and mode of inheritance were variable. CONCLUSION: Parkin mutations on common parkin haplotypes provide testable hypotheses of parkin function in genetically defined parkinsonism.

Adult↗

PubMed2003

A randomized study comparing interferon (IFN alpha) plus low-dose cytarabine and interferon plus hydroxyurea (HU) in early chronic-phase chronic myeloid leukemia (CML).

This multicenter randomized phase III study was designed to compare the efficacy and toxicity of IFN alpha-2c (3.5 MU/d) in combination with either araC (10 mg/m(2) d1-10) or hydroxyurea (HU: 25 mg/kg per day) in newly diagnosed CML patients. A total of 114 patients were randomized. Following a median observation period of 36 (range 1-73) months the major cytogenetic response rates were 25 and 27% and the 4-year survival probabilities 62.5 and 63% for the araC and HU group, respectively. While the overall toxicity profile was comparable between both groups, patients in the HU arm exhibited a slightly higher degree of WHO grades 3 and 4 non-hematological toxicities.

Adult↗

PubMed2002

Advanced training model for beating heart coronary artery surgery: the Zurich heart-trainer.

OBJECTIVE: Coronary artery surgery with beating heart technique is gaining increasing popularity. However, it is a challenging technique even for well-trained cardiac surgeons. Thus, a training model for beating heart surgery was developed to increase safety and accuracy of this procedure. METHODS: The model consists of differentially hardened polyurethane resembling mechanical properties of the human heart. The covering used in this model is a 1:1 replica of the human thoracic wall with optionally embedded skeletal structures. Sternotomy, lateral thoracotomy or trocar placement is possible to access the lungs, the pericardium and the heart with adjacent vessels. Disposable artificial coronaries variable in size, wall quality or wall thickness are embedded in the synthetic myocardium. Two-layer vessels, which can simulate dissection, are available. Bypass conduits utilize the same material. Coronaries/bypasses as well as part of the ascending aorta are water-tight and can be rinsed with saline. Lungs can be inflated. A purpose-built pump induces heart movement with adjustable or randomized stroke volume, heart rate and arrhythmia induction. RESULTS: The model was tested in a recent 'Wet-Lab' course attended by 30 surgeons. All conventional instruments and stabilizers with standard techniques can be used. Training with beating or non-beating heart was possible. Time needed for an anastomosis was similar to clinical experience. Each artificial tissue showed its individual nature-like qualities. Various degrees of difficulty can be selected, according to stroke volume, heart rate, arrhythmia, vessel size and vessel quality. The model can be quickly and easily set up and is fully reusable. CONCLUSIONS: The similarity to human tissue and the easy set-up make this completely artificial model an ideal teaching tool to increase the confidence of cardiac surgeons dealing with beating heart and minimally invasive surgery.

Cardiac Surgical Procedures↗

PubMed2002

Lidocaine inhibits secretion of IL-8 and IL-1beta and stimulates secretion of IL-1 receptor antagonist by epithelial cells.

Lidocaine and related local anaesthetics have been shown to be effective in the treatment of ulcerative colitis (UC). However, the mechanisms underlying their therapeutic effect are poorly defined. Intestinal epithelial cells play an important role in the mucosal inflammatory response that leads to tissue damage in UC via the secretion of pro-inflammatory cytokines and chemokines. The aim of this study was to evaluate the direct immunoregulatory effect of lidocaine on pro-inflammatory cytokine and chemokine secretion from intestinal epithelial cells. HT-29 and Caco-2 cell lines were used as a model system and treated with lidocaine and related drugs. The expression of IL-8, IL-1beta and the IL-1 receptor antagonist (RA) were assessed by ELISA and quantification of mRNA. In further experiments, the effect of lidocaine on the secretion of IL-8 from freshly isolated epithelial cells stimulated with TNFalpha was tested. Lidocaine, in therapeutic concentrations, inhibited the spontaneous and TNFalpha-stimulated secretion of IL-8 and IL-1beta from HT-29 and Caco-2 cell lines in a dose-dependent manner. Similarly, suppression of IL-8 secretion was noted in the freshly isolated epithelial cells. Other local anaesthetics, bupivacaine and amethocaine, had comparable effects. Lidocaine stimulated the secretion of the anti-inflammatory molecule IL-1 RA. Both the inhibitory and the stimulatory effects of lidocaine involved regulation of transcription. The results imply that the therapeutic effect of lidocaine may be mediated, at least in part, by its direct effects on epithelial cells to inhibit the secretion of proinflammatory molecules on one hand while triggering the secretion of anti-inflammatory mediators on the other.

Adenocarcinoma↗