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Biomedical subjects

M Salo

Publications and source records attributed to M Salo.

At least 19 recordsLinked to original sources

Effects of anaesthesia using endotracheal intubation or the laryngeal mask airway, or spinal anaesthesia, on oral mucosal host defences during minor surgery.

BACKGROUND: Oral mucosal host defences are altered after anaesthesia and surgery. The effects of endotracheal intubation (ET) and the use of the laryngeal mask airway (LMA) on oral mucosal host defences after minor surgery were compared. METHODS: Immunological (immunoglobulin A (IgA), IgG and IgM) and non-immunological (myeloperoxidase, total peroxidase, thiocyanate) oral host defence factors, and amylase and protein concentrations, were measured from saliva pre-operatively and on the first post-operative day in 60 ASA I-II patients undergoing minor surgery. The patients underwent general anaesthesia using oral ET or LMA. Spinal anaesthesia (S) was used as control. Serum IgG, IgM and IgA concentrations were determined. RESULTS: Protein-related salivary secretion of amylase and salivary concentration of IgM showed the only statistically significant overall differences between the groups. By contrast, changes were observed within the ET group in the salivary flow rate, protein concentration, amylase activity and immunological host defence factors. Some changes were also observed in the LMA group, but none in the S group. Most non-immunological test values did not change within any of the groups. CONCLUSIONS: ET and LMA induced similar oral mucosal host defence responses. There were, however, observations in this study that indicated a stronger response during ET than when LMA was used.

Adult↗

Effects of post-operative pain treatment using non-steroidal anti-inflammatory analgesics, opioids or epidural blockade on systemic and local immune responses in children.

BACKGROUND: Many studies have been carried out on the effects of anaesthetic drugs and methods on the immune response, but pain and its relief also affect the immune response. We measured systemic immune responses in the blood circulation and local responses in the surgical wound when non-steroidal anti-inflammatory analgesics (NSAIDs), opioids or epidural blockade was used in the peri-operative treatment of pain. METHODS: Responses were measured in 51 children, aged from 2 to 12 years and undergoing major surgery under balanced anaesthesia. Bolus doses of diclofenac intravenously (i.v.) and rectally (NSAID group), continuous i.v. infusion of oxycodone (opioid group) or continuous epidural infusion of bupivacaine + fentanyl (epidural group) were used peri-operatively for pain relief. RESULTS: The only difference related to the analgesic method was shorter duration of post-operative leucocytosis and lower phytohaemagglutinin (PHA)-induced lymphocyte proliferative responses in peripheral blood in the opioid group than in the NSAID or epidural groups. By contrast, time-related alterations were seen overall in leucocyte and differential counts, lymphocyte and their subset counts, lymphocyte proliferative responses, and in serum cortisol, C-reactive protein, plasma interleukin-6 and group II phospholipase A2 concentrations and in the appearance of different cell types in the wound. CONCLUSIONS: Post-operative pain treatments using diclofenac (NSAID), oxycodone (opioid) and epidural blockade have basically similar effects on systemic and local immune responses with only slight, probably clinically unimportant differences in children undergoing surgery under general anaesthesia.

Analgesia, Epidural↗

Local and systemic immune response to surgery under balanced anaesthesia in children.

We studied perioperative changes in the immune response and compared changes in the peripheral blood with those in the wound in 20 boys (0.5-3 years) during elective inguinal surgery under balanced anaesthesia. Blood samples were drawn before premedication, immediately, and 4 or 24 h after anaesthesia. Cells from the wound were harvested with the Cellstick device, removed from the wound 4 (n=10) or 24 h (n=10) after anaesthesia. We found decreased lymphocyte counts in the peripheral blood, increased percentages of activated T lymphocytes and B lymphocytes, and decreased percentages of total T lymphocytes, T helper cells and T cytotoxic cells. The percentages of T helper cells and B lymphocytes were lower in the wound than in blood. Mitogen-induced lymphocyte proliferative responses decreased. This study demonstrates perioperative changes in the immune response in children and, as a new finding, that immune effector cells in the blood and in the wound are in a dynamic balance.

Analysis of Variance↗

Immune response in infants undergoing application of cast: comparison of halothane and balanced anesthesia.

PURPOSE: To study the immunological effects of two types of anesthesia on the immune response in infants during a minimally stressful surgical procedure. METHODS: The effects of inhalational halothane (halothane + N2O + O2, spontaneous breathing, n = 12) and conventional balanced anesthesia (thiopental + N2O + O2 + fentanyl + vecuronium, mechanical ventilation, n = 12) on immune function were measured in a crossover study in 12 infants undergoing application of casts to the lower extremity or hip joint. Leukocyte and differential counts, lymphocyte subpopulations, spontaneous lymphocyte proliferative responses as well as responses to phytohemagglutinin (PHA), concavalin A (ConA) and pokeweed mitogen (PWM), and serum cortisol concentration were measured before, immediately after and four hours after the end of anesthesia. RESULTS: Halothane anesthesia was associated with a higher percentage of T helper cells than conventional balanced anesthesia [47.1+/-1.8 (SEM)%, 48.1+/-2.3% and 50.7+/-1.9% before, immediately and four hours after anesthesia vs. 45.7+/-1.7%, 44.0+/-2.3% and 45.1+/-1.9%, respectively, by groups, P<0.05]. Leukocyte count and the percentages of activated T cells, natural killer cells and B cells showed similar alterations in both groups, and no alterations were observed in the percentages of T lymphocytes or T cytotoxic cells. Lymphocyte transformation response to PWM was decreased four hours after anesthesia in the halothane but not in the balanced anesthesia group. CONCLUSION: Anesthesia of short duration during minimal surgical stress alters lymphocyte subpopulations and lymphoproliferative responses in infants and, furthermore, halothane anesthesia and balanced anesthesia have different effects.

Anesthesia↗

Immune response after laparoscopic and conventional Nissen fundoplication.

OBJECTIVE: To compare the changes in the immune responses of patients undergoing laparoscopic or conventional Nissen fundoplication. DESIGN: Prospective randomised clinical study. SETTING: University hospital, Finland. SUBJECTS: 20 patients undergoing Nissen fundoplication for symptomatic erosive oesophagitis. INTERVENTION: Laparoscopic Nissen fundoplication (n = 10) or conventional open Nissen fundoplication (n = 10). MAIN OUTCOME MEASURES: Leucocyte and differential counts; percentages of lymphocyte subpopulations (CD3, CD4, CD8, CD16 and CD20 positive lymphocytes); and monocytes (CD 14); phytohemagglutinin, concanavalin A and pokeweed mitogen-induced and unstimulated proliferation of separated lymphocytes; plasma interleukin-6 (IL-6), serum C-reactive protein (CRP), albumin, and cortisol concentrations; and group II phospholipase A2 (PLA2) activity. RESULTS: Laparoscopic fundoplication was associated with less tissue damage (IL-6, and CRP concentrations) than the conventional open operation. However, although there were pronounced changes in immune responses over time, there were no differences between the groups. CONCLUSION: Laparoscopic fundoplication seemed to cause less tissue damage than the conventional open operation, but this difference was not reflected in patients' immune responses.

Esophagitis↗

Distribution of glial cell line-derived neurotrophic factor mRNA in human colon suggests roles for muscularis mucosae in innervation.

BACKGROUND/PURPOSE: Glial cell line-derived neurotrophic factor (GDNF) is a ligand for the receptor complex of GDNF family receptor alphas (GFRalphas) and Ret receptor tyrosine kinase, the product of a known Hirschsprung's disease gene. The aim of this study was to analyze the mRNA distribution of these genes in the developing human intestine to understand their roles in enteric innervation. METHODS: Cryosections of fetal and newborn stomach, ileum, and colon were hybridized in situ with S35-labeled cRNA probes to GDNF, Ret, GFRalpha-1 or GFRalpha-2. GDNF mRNA levels in fetal ileum and colon were compared by reverse transcription-polymerase chain reaction (PCR). RESULTS: GDNF mRNA expression was abundant in the muscularis mucosae of both fetal and newborn colon but was found neither in the neural plexuses nor in other regions of the intestine. Accordingly, by reverse transcription-PCR, GDNF mRNA level was many times higher in colon than ileum. Ret, GFRalpha-1 and GFRalpha-2 mRNA were expressed in the ganglionic cells of both myenteric and submucosal plexuses throughout the intestine. CONCLUSIONS: The highly restricted distribution of GNDF mRNA suggests an important role for muscularis mucosae in the development of human enteric nervous system. Ret, GFRalpha-1, and GFRalpha-2 most likely act as GDNF receptors in colon but may have alternative ligands in other enteric segments.

Colon↗

Mucosal host defence response to hysterectomy assessed by saliva analyses: a comparison of propofol and isoflurane anaesthesia.

We compared the effects of propofol-based (n = 15) and isoflurane-based anaesthesia (n = 15) on mucous host defences by measuring the salivary flow and the concentrations/activities of salivary total protein and amylase, and of salivary immunological (IgA, IgG and IgM) and nonimmunoglobulin defence factors (lysozyme, myeloperoxidase, total salivary peroxidase and thiocyanate) in patients undergoing elective abdominal hysterectomy. The saliva samples were collected pre-operatively and on the first and fourth postoperative days. The concentrations of salivary protein and amylase as well as those of immunological and nonimmunological defence factors were significantly increased on the first postoperative day. The secretion rate of total protein, amylase, lysozyme, total peroxidase, thiocyanate and IgG, however, decreased owing to a marked decrease in the salivary flow, but no alterations were found in secretion rate of myeloperoxidase, IgA and IgM. The changes were similar in both groups. These findings show that nonimmunological oral mucous host defences are altered after major surgery, but immunoglobulin responses are better maintained. Both types of anaesthesia induce marked short-term hyposalivation.

Adult↗

Common mutations in autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy patients of different origins.

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED; OMIM *240300, also called APS 1,) is a rare autosomal recessive disorder that is more frequent in certain isolated populations. It is generally characterized by two of the three major clinical symptoms that may be present, Addison's disease and/or hypoparathyroidism and/or chronic mucocutaneous candidiasis. Patients may also have a number of other clinical symptoms including chronic gastritis, gonadal failure, and rarely, autoimmune thyroid disease and insulin-dependent diabetes mellitus. We and others have recently identified the gene for APECED, which we termed AIRE (for autoimmune regulator). AIRE is expressed in thymus, lymph nodes, and fetal liver and encodes a protein containing motifs suggestive of a transcriptional regulator, including two zinc finger motifs (PHD finger), a proline-rich region, and three LXXLL motifs. Six mutations, in cluding R257X, the predominant Finnish APECED allele, have been defined. R257X was also observed in non-Finnish APECED patients occurring on different chromosomal haplotypes suggesting different mutational origins. Here we present mutation analyses in an extended series of patients, mainly of Northern Italian origin. We have detected 12 polymorphisms, including one amino acid substitution, and two additional mutations, R203X and X546C, in addition to the previously described mutations, R257X, 1096-1097insCCTG, and a 13-bp deletion (1094-1106del). R257X was also the common mutation in the Northern Italian patients (10 of 18 alleles), and 1094-1106del accounted for 5 of 18 Northern Italian alleles. Both R257X and 1094-1106del were both observed in patients of four different geo-ethnic origins, and both were associated with multiple different haplotypes using closely flanking polymorphic markers showing likely multiple mutation events (six and four, respectively). The identification of common AIRE mutations in different APECED patient groups will facilitate its genetic diagnosis. In addition, the polymorphisms presented provide the tools for investigation of the involvement of AIRE in other autoimmune diseases, particularly those affecting the endocrine system.

Female↗

Hirschsprung's disease genes and the development of the enteric nervous system.

Hirschsprung's disease or aganglionic megacolon causes chronic, congenital obstipation at an incidence of 1 per 5000 live births. Two approaches have been vital to the present understanding of the pathogenesis and genetic background of the disease: disease linkage analyses and mouse models of aganglionic megacolon. Because the increasing number of transgenic or natural mouse strains with congenital megacolon has led to mutation screening in Hirschsprung's disease patients, almost every second patient could now receive a genetic explanation for his/her disease. The known disease genes include tyrosine kinase receptor Ret, endothelin receptor B and its ligand endothelin 3. In addition, mutations have been found in the gene encoding the glial cell line-derived neurotrophic factor, the ligand for Ret, but these may only have a modifier effect. The mouse models have also provided insight into the developmental mechanisms of the normal intestinal innervation. We combine here the present clinical data on the gene mutations in Hirschsprung's disease with the experimental molecular biology data, and formulate a hypothesis on the pathogenesis of this multigenic-multifactorial disease.

Animals↗

Enhanced spontaneous antibody response after coronary artery bypass surgery.

PURPOSE: Cells spontaneously secreting immunoglobulins can be seen in the blood one week after open-heart surgery. The purpose of this study was to measure the antibody specificities of activated cells. METHODS: Immune responses were studied preoperatively and on the seventh postoperative day in 18 patients undergoing elective coronary artery bypass surgery. The number of cells secreting adenovirus, measles, rubella and tetanus antigen specific antibodies spontaneously and induced by pokeweed mitogen PWM (ASCs) as well as the total number of cells secreting IgG, IgM and IgA (ISCs) were studied using an enzyme-linked immunospot (ELISPOT) assay. Spontaneous as well as phytohaemagglutinin (PHA)- and pokeweed mitogen (PWM)-induced lymphocyte proliferation was also measured. RESULTS: The number of cells spontaneously secreting IgG, IgM and IgA antibodies was increased on the seventh day after coronary bypass surgery, against adenovirus, measles, rubella and tetanus as well as the total number of cells secreting immunoglobulins IgG, IgM and IgA (P < 0.05/0.001). By contrast, only slight fluctuation was seen in the numbers of cells secreting antibodies after PWM stimulation. Spontaneous lymphocyte proliferation was also increased, PHA proliferative responses were depressed and PWM responses were not changed on the seventh postoperative day compared with preoperative values. CONCLUSION: Coronary artery bypass surgery caused marked polyclonal B cell activation demonstrated by an increase of cells producing spontaneously antibodies against virus antigens and tetanus toxoid. This activation could not be intensified by PWM stimulation.

Adult↗

Neural network modeling for estimation of the aqueous solubility of structurally related drugs.

The ability of neural network models to predict aqueous solubility within series of structurally related drugs was evaluated. Three sets of compounds representing different drug classes (28 steroids, 31 barbituric acid derivatives, and 24 heterocyclic reverse transcriptase inhibitors) were studied. Topological descriptors (connectivity indices, kappa indices, and electrotopological state indices) were used to link the structures of compounds with their aqueous solubility. Separate models were built for each class of drugs using back-propagation neural networks with one hidden layer and five topological indices as input parameters. The effect of network size and training time on the prediction ability of the network was studied by the leave-one-out (LOO) procedure. In all three compound groups a neural network structure of 5-3-1 was optimal. To avoid chance effects, artificial neural network (ANN) ensembles (i.e.; averaging neural network predictions over several independent networks) were used. The cross-validated squared correlation coefficient (Q2) for 10 averaged predictions was 0.796 in the case of the steroid set. The corresponding standard error of prediction (SDEP) was 0.288 log units. For the barbiturates, Q2 and SDEP were 0.856 and 0.383, respectively, and for the RT inhibitors, these parameters were 0.721 and 0.401, respectively. The results indicate that neural networks can produce useful models of the aqueous solubility of a congeneric set of compounds, even with simple structural parameters.

Drug Design↗

Effects of propofol emulsion and thiopentone on T helper cell type-1/type-2 balance in vitro.

We have earlier found increased percentages of T helper cells (CD4-positive lymphocytes) in the blood circulation after propofol infusion anaesthesia. Cytokines interferon-gamma (IFN gamma) and interleukin-4 (IL-4) are important in the differentiation of T helper cells into subtypes T helper type-1 (Th1) and type-2 (Th2). To study the effects of propofol emulsion, its solvent Intralipid and thiopentone on Th1/Th2 balance, measurements of IFN gamma and IL-4 production by mononuclear leucocytes were carried out in vitro. As IL-2 has a central role in immune responses to surgery, its production was also measured. Concanavalin A-stimulated mononuclear cells were cultured in the presence of propofol emulsion at 3.5 or 10 micrograms.ml-1, Intralipid 35 or 100 micrograms.ml-1, or thiopentone 3 micrograms.ml-1. Cytokine production was measured from the conditioned media of mononuclear cell cultures. Decreased IFN gamma (p < 0.001) and IL-4 concentrations (p < 0.01) were found in the presence of thiopentone, but IL-2 production was unaffected. By contrast, propofol emulsion or Intralipid had no effects on IFN gamma, IL-2 or IL-4 concentrations. Propofol 10 micrograms.ml-1 increased the IFN gamma/IL-4 ratio from the control value median 243 (162-562) (25th-75th percentile) to 363 (195-1028) (p < 0.01), but thiopentone decreased it to 145 (60-214) (p < 0.01). These findings show that propofol and thiopentone have different effects in vitro on Th1/Th2 balance and suggest that they have different modulating effects on the immune response.

Anesthetics, Intravenous↗

Effects of open heart surgery on oral mucous host defence systems.

BACKGROUND: The immune response is affected by anaesthesia and surgery. This study was carried out on the effects of open heart surgery on the oral mucous host defence system, which is part of the common mucosal immune system. METHODS: Amylase, nonimmunological (lysozyme, myeloperoxidase, hypothiocyanite and thiocyanate) and immunological (IgA, IgG, and IgM) mucous host defence factors as well as oral bacterial flora were determined in the saliva of 18 patients undergoing open heart surgery preoperatively and on the 2nd, 3rd, and 7th postoperative days. To assess the specificity of the changes, the salivary flow rate and total protein content were also determined. RESULTS: Stimulated salivary flow decreased from 1.8 (1.3-2.2) ml/min (median; 25th and 75th quartiles) to 0.4 (0.3-0.5) ml/min by the 2nd postoperative day and to 0.4 (0.2-1.0) ml/min by the 3rd postoperative day (P < 0.001). Amylase, lysozyme, myeloperoxidase, total salivary peroxidase and thiocyanate levels increased, whereas hypothiocyanite levels decreased postoperatively (p < 0.01-0.001). Their total secretion rate, however, was reduced (P < 0.05-0.001) owing to the lowered salivary flow rate. IgG and IgM concentrations were raised on the 2nd, 3rd and 7th postoperative days (P < 0.05-0.001), and IgA concentrations on the 2nd postoperative day (P < 0.05). The total secretion of IgG and IgM as well as their salivary concentrations in relation to total protein concentrations also increased. The number of salivary anaerobically growing bacteria decreased postoperatively (P < 0.01), but the number of salivary streptococci remained unaffected. CONCLUSIONS: Open heart surgery decreases the salivary secretion of nonimmunological host defence factors and increases the salivary secretion of IgA, IgG and IgM.

Adult↗

Structure-retention relationships of steroid hormones in reversed-phase liquid chromatography and micellar electrokinetic capillary chromatography.

Quantitative structure-retention relationship (QSRR) studies are useful in retention prediction, finding the relevant structural descriptors for analytes and estimating the relative biological activities of a series of analytes. Most of the studies have been conducted by RP-HPLC and a few by micellar electrokinetic capillary chromatography (MECC). The aim of this work was to find structural parameters and characteristics related to the RP retention and electrophoretic migration of steroids in order to predict the retention/migration of steroid hormones on the basis of their molecular structure. Retention data were obtained with an ODS column using a mobile phases aqueous methanol-acetonitrile (mobile phase A) and methanol-tetrahydrofuran (mobile phase B). MECC was conducted with a sodium dodecyl sulfate (SDS)-borate system and with a mixed micellar solution of SDS and sodium cholate. Several topological indices, such as the connectivity indices, chi, were used as structural parameters. Steric factors seem to have a great effect on the retention of steroid hormones, especially with the MeCN-containing mobile phase. Retention in mobile phase B could be predicted more accurately. Topological indices can be used in the modelling and prediction of the retention/migration of steroid hormones when the solutes form a congeneric series and stereochemical properties do not govern the separation process.

Chromatography↗

Propofol infusion anaesthesia and the immune response in elderly patients undergoing ophthalmic surgery.

In our earlier studies, propofol infusion anaesthesia increased the percentage of T helper cells in middle-aged surgical patients undergoing minor or major surgery. In the present study we compared the effects of total intravenous propofol anaesthesia and combined isoflurane anaesthesia on the immune response to ophthalmic surgery in elderly patients. Twenty patients (median age 75 years, ASA 2-3) were randomly allocated to receive total intravenous propofol anaesthesia (median total dose of propofol 710 mg) or combined isoflurane anaesthesia (median end-expiratory concentration of isoflurane 0.45 vol %). The following were measured pre-operatively, at the end of operation and on the first postoperative morning: leucocyte and differential counts: percentages of lymphocyte subpopulations (CD3, CD4, CD8, CD20, CD16) and monocytes (CD14); phytohaemagglutinin-, concanavalin A- and pokeweed mitogen-induced and unstimulated lymphocyte proliferative responses: polyclonal immunoglobulin synthesis as well as serum cortisol concentrations. The immune response to ophthalmic surgery was basically similar in both anaesthetic groups. The percentage of T helper cells in the blood circulation increased in the propofol group (p < 0.05) but not in the isoflurane group. The difference in the time-response profile for T helper cell percentages between the groups was also statistically significant (p < 0.01).

Aged↗