Nationwide paediatric cohort study of a protective association between allergy and complicated appendicitis.

BACKGROUND: In a nationwide cohort the potentially protective association between allergy and complicated appendicitis was analysed, and the influence of seasonal antigens, antihistamine treatment, and timing of allergy onset assessed. METHODS: Some 1 112 571 children born between 2000 and 2010 were followed from birth until the end of 2014. A cross-sectional analysis of appendicitis cases, with comparison of allergic versus non-allergic children for absolute risk and odds of complicated appendicitis was first undertaken. This was followed by a longitudinal analysis of children with allergy and matched controls who had never had an allergy, for incidence rate and hazard of subsequent complicated or simple appendicitis. RESULTS: Of all children, 20.4 per cent developed allergy and 0.6 per cent had appendicitis during follow-up. Among children with appendicitis, complicated appendicitis was more common among non-allergic children (18.9 per cent, 948 of 5016) than allergic children (12.8 per cent, 173 of 1351) (P < 0.001), and allergic children had a lower adjusted odds of complicated appendicitis (adjusted odds ratio (OR) 0.80, 95 per cent c.i. 0.67 to 0.96; P = 0.021 ). The risk of complicated appendicitis among children with manifest allergy was reduced by one-third in the longitudinal analysis (incidence rate 0.13 versus 0.20 per 1000 person-years; hazard ratio (HR) 0.68, 95 per cent c.i. 0.58 to 0.81; P < 0.001), whereas the risk of simple appendicitis remained unchanged (incidence rate 0.91 versus 0.91; HR 1.00, 0.94 to 1.07; P = 0.932 ). Seasonal antigen exposure was a protective factor (adjusted OR 0.82, 0.71 to 0.94; P = 0.004) and ongoing antihistamine medication a risk factor (adjusted OR 2.28, 1.21 to 4.28; P = 0.012). CONCLUSION: Children with allergy have a lower risk of complicated appendicitis, but the same overall risk of simple appendicitis. Seasonal antigen exposure reduced, and antihistamine treatment increased, the risk of complicated disease.

Nationwide study of appendicitis in children.

BACKGROUND: Paediatric surgical care is increasingly being centralized away from low-volume centres, and prehospital delay is considered a risk factor for more complicated appendicitis. The aim of this study was to determine the incidence of paediatric appendicitis in Sweden, and to assess whether distance to the hospital was a risk factor for complicated disease. METHODS: A nationwide cohort study of all paediatric appendicitis cases in Sweden, 2001-2014, was undertaken, including incidence of disease in different population strata, with trends over time. The risk of complicated disease was determined by regression methods, with travel time as the primary exposure and individual-level socioeconomic determinants as independent variables. RESULTS: Some 38 939 children with appendicitis were identified. Of these, 16·8 per cent had complicated disease, and the estimated risk of paediatric appendicitis by age 18 years was 2·5 per cent. Travel time to the treating hospital was not associated with complicated disease (adjusted odds ratio (OR) 1·00 (95 per cent c.i. 0·96 to 1·05) per 30-min increase; P = 0·934). Level of education (P = 0·177) and family income (P = 0·120) were not independently associated with increased risk of complicated disease. Parental unemployment (adjusted OR 1·17, 95 per cent c.i. 1·05 to 1·32; P = 0·006) and having parents born outside Sweden (1 parent born in Sweden: adjusted OR 1·12, 1·01 to 1·25; both parents born outside Sweden: adjusted OR 1·32, 1·18 to 1·47; P < 0·001) were associated with an increased risk of complicated appendicitis. CONCLUSION: Every sixth child diagnosed with appendicitis in Sweden has a more complicated course of disease. Geographical distance to the surgical facility was not a risk factor for complicated appendicitis.

ANTECEDENTES: La atención quirúrgica pediátrica está cada vez más centralizada lejos de los centros de bajo volumen, y el retraso pre-hospitalario se considera un factor de riesgo para las apendicitis más complicadas. El objetivo de este estudio fue determinar la incidencia de apendicitis pediátrica en Suecia y evaluar si la distancia al hospital era un factor de riesgo para una enfermedad complicada. MÉTODOS: Se analizó un estudio de cohortes a nivel nacional que incluyó todos los casos de apendicitis pediátrica en Suecia durante el periodo 2001-2014, incluida la incidencia de la enfermedad en diferentes estratos de la población y las tendencias a lo largo del tiempo. El riesgo de enfermedad complicada se determinó mediante métodos de regresión, con el tiempo de viaje como exposición primaria y los determinantes socioeconómicos a nivel individual como variables independientes. RESULTADOS: Se identificaron 38.939 casos de apendicitis pediátrica. De estos, el 17% eran complicados y el riesgo estimado de apendicitis pediátrica a los 18 años era del 2,5%. El tiempo de viaje al hospital de tratamiento no se asoció con una enfermedad complicada (razón de oportunidades, odds ratio OR ajustada 1,00 (i.c. del 95%: 0,96 a 1,05) por aumentos de 30 minutos, P = 0,93). El nivel de educación (P = 0,18) y los ingresos familiares (P = 0,120) no se asociaron de forma independiente con un aumento del riesgo de enfermedad complicada. El desempleo de los padres (OR ajustada 1,17 (1,05 a 1,32), P = 0,006) y tener padres nacidos fuera de Suecia se asociaron con un mayor riesgo de apendicitis complicada (P < 0,001; un progenitor nacido en Suecia: OR ajustada 1,12 (1,01 a 1,25), ambos progenitores nacidos fuera de Suecia: OR ajustada 1,32 (1,18 a 1,47)). CONCLUSIÓN: Uno de cada seis niños diagnosticados de apendicitis en Suecia sufre un curso de enfermedad más complicado. La distancia geográfica al hospital donde se llevó a cabo la cirugía no fue un factor de riesgo para la apendicitis complicada.

Penicillium expansum strain isolated from indoor building material was able to grow on gypsum board and emitted guttation droplets containing chaetoglobosins and communesins A, B and D.

AIMS: Emission of toxic metabolites in guttation droplets of common indoor fungi is not well documented. The aims of this study were (i) to compare mycotoxins in biomass and guttation droplets from indoor fungi from a building following health complaints among occupants, (ii) to identify the most toxic strain and to test if mycotoxins in guttation liquids migrated trough air and (iii) to test if toxigenic Penicillium expansum strains grew on gypsum board. METHODS AND RESULTS: Biomass suspensions and guttation droplets from individual fungal colonies representing Aspergillus, Chaetomium, Penicillium, Stachybotrys and Paecilomyces were screened toxic to mammalian cells. The most toxic strain, RcP61 (CBS 145620), was identified as Pen. expansum Link by sequence analysis of the ITS region and a calmodulin gene fragment, and confirmed by the Westerdijk Institute based on ITS and beta-tubulin sequences. The strain was isolated from a cork liner, was able to grow on gypsum board and to produce toxic substances in biomass extracts and guttation droplets inhibiting proliferation of somatic cells (PK-15, MNA, FL) in up to 20 000-fold dilutions. Toxic compounds in biomass extracts and/or guttation droplets were determined by HPLC and LC-MS. Strain RcP61 produced communesins A, B and D, and chaetoglobosins in guttation droplets (the liquid emitted from them) and biomass extracts. The toxins of the guttation droplets migrated c. 1 cm through air and condensed on a cool surface. CONCLUSIONS: The mycotoxin-containing guttation liquids emitted by Pen. expansum grown on laboratory medium exhibited airborne migration and were >100 times more toxic in bioassays than guttation droplets produced by indoor isolates of the genera Aspergillus, Chaetomium, Stachybotrys and Paecilomyces. SIGNIFICANCE AND IMPACT OF THE STUDY: Toxic exudates produced by Pen. expansum containing communesins A, B and D, and chaetoglobosins were transferable by air. This may represent a novel mechanism of mycotoxin dispersal in indoor environment.

Mothers with gestational diabetes are more likely to give birth to children who experience early weight problems.

AIM: We tracked the body mass index (BMI) of children born to mothers with or without gestational diabetes mellitus (GDM) or type 1 diabetes from birth to 12 years of age and examined the trends in both diseases. METHODS: Antenatal and postnatal health survey data were collected from 6909 Finnish children born at six time points between 1974 and 2004. We compared the BMI trajectory between the offspring of mothers with and without GDM or type 1 diabetes, and the association between GDM and overweight offspring was analysed. RESULTS: The prevalence of GDM and type 1 diabetes increased markedly over the study period. The BMI trajectory in the GDM or type 1 diabetes offspring differed significantly from the nondiabetic offspring. The timing of adiposity rebound occurred significantly earlier in the GDM (4.8 years) and type 1 diabetes (4.4 years) groups than the nondiabetic group (5.5 years). GDM offspring were more likely to be overweight at five, seven and 12 years of age (24.6%, 28.1%, 29.4%) than nondiabetic offspring (15.6%, 18.3%, 18.1%). CONCLUSION: Children born to mothers with GDM were significantly more likely to be overweight at an early age than those born to nondiabetic mothers.

Mug handle affordance and automatic response inhibition: behavioural and electrophysiological evidence.

Behavioural evidence has shown that the perception of an object's handle automatically activates the corresponding action representation. The activation appears to be inhibited if the object is a task-irrelevant prime mug that is presented very briefly prior to responding to the target arrow. The present study uses an electrophysiological indicator of automatic response priming, the lateralized readiness potential (LRP), to investigate the mechanisms of this inhibition effect. We presumed that this effect would reflect motor self-inhibition processes. The self-inhibition explanation of the effect would assume that the effect reflects activation-followed-by-inhibition observed rapidly after the offset of the prime at the primary motor cortex. However, the results showed that the effect is not associated with modulation of the early LRP deflections. In contrast, the inhibition manifested itself in the later LRP deflections that we assume to be linked to interference in the processing of response-related aspects of the target. We propose that the LRP pattern is similar to what would be predicted from the negative priming explanation of the effect. The study sheds light on understanding inhibition mechanisms associated with automatically activated affordance representations.

Carotid intima-media thickness after pediatric renal or liver transplantation at high-resolution B-mode ultrasonography.

In a previous study, we observed a higher incidence of dyslipidemia in pediatric renal recipients compared with liver recipients. In the present study, we measured common carotid artery intima-media thickness (IMT) in 13 pediatric renal recipients, 9 liver recipients, and 26 control individuals with median age of 11.4, 10.8, and 12.0 years, respectively. The patients were studied from 0.2 to 10.8 years after renal transplantation (RTx) or liver transplantation (LTx). An experienced radiologist (T.K.) blinded to the status of the children measured the IMT using a high-resolution B-mode ultrasonography method. In patients who underwent RTx or LTx, serum fasting lipid profile, estimates of renal and liver function, and glucose metabolism were determined. Children undergoing RTx or LTx more often had hypertension compared with the control individuals (P = .004). Before transplantation, dyslipidemia was greater in patients undergoing RTx compared with those undergoing LTx (P < .05). Children who underwent RTx, compared with those who underwent LTx or control individuals, had thicker mean IMT at the 6 sites measured (mean [SD], 0.57 [0.07], 0.51 [0.05], and 0.53 [0.06] mm, respectively; P = .02]. As a result of linear regression in renal recipients, variability of glomerular filtration rate (<60 mL/min/1.73 m(2) vs normal) accounted for 43.3% of variability of the mean of maximal IMT (B = 8.9; SE = 3.1; P = .01). Variability of pre-RTx serum triglyceride concentration (B = 1.6; SE = 0.6; P = .03) and actual triglyceride concentration (B = 10.3; SE = 2.2; P = .002) accounted for 82.2% of variability of maximal IMT. Our findings support previous data on the importance of maintenance of good graft function with sufficient but not overly efficient immunosuppression after transplantation in prevention of future cardiovascular disease.

Bone mass and structure in adolescents with type 1 diabetes compared to healthy peers.

SUMMARY: We measured bone mass and structure using pQCT and DXA in adolescents with Type 1 diabetes and compared the results with those of healthy peers. Our results showed that diabetes is associated with reduced bone mass and smaller bones. The diabetes-associated deficits seemed to concern male adolescents more than females. INTRODUCTION: The aim of this study was to compare bone mass and structure between adolescents with type 1 diabetes and their healthy peers. METHODS: Peripheral quantitative computed tomography (pQCT) at radius and tibia, and dual-energy X-ray absorptiometry (DXA) at lumbar spine and proximal femur were performed for 48 adolescents, 26 girls and 22 boys, with type 1 diabetes, and for healthy peers matched for age, sex, body height and weight, and pubertal maturity. RESULTS: Diabetes was associated with reduced bone mineral content (BMC) and smaller bone cross-sectional size. Diabetic boys seemed to be more affected than diabetic girls. Among the boys, the mean deficit in BMC of all measured skeletal sites was more than 10%, while among the girls it was less than 5%. CONCLUSION: In conclusion, type 1 diabetes is associated with reduced BMC and appears to affect bone cross-sectional size and cortical rigidity. The diabetes-related skeletal deficits seemed to concern male adolescents more than females. Whether diabetes-related deficits would contribute to an increased risk of fractures in adulthood or later in life remains to be confirmed.

Gene expression of pulmonary cytokines after sevoflurane or thiopentone anaesthesia in pigs.

BACKGROUND: Volatile anaesthetics have diverse inflammatory effects on the lungs. They increase gene expression of some pro-inflammatory cytokines in alveolar macrophages whereas in alveolar type II cells they seem to decrease secretion and gene expression of pro-inflammatory cytokines. We have previously detected increased leukotriene C4, nitrate and nitrite concentrations in bronchoalveolar lavage fluid after sevoflurane anaesthesia. In the current study, we measured gene expression of inflammatory cytokines in the lung tissue and plasma concentrations of cytokines in pigs after thiopentone or sevoflurane anaesthesia. METHODS: Sixteen pigs were randomly selected to receive either a continuous thiopentone infusion (control group, n = 8) or sevoflurane (n = 8) at 4.0% inspiratory concentration (1.5 MAC) in air for 6 h. Tissue samples were collected at the end of the study for measurement of gene expression of inflammatory cytokines. Blood samples were collected during anaesthesia for measurement of plasma cytokine concentrations. RESULTS: Compared with thiopentone anaesthesia, lower gene expression of tumour necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) in lung tissue was observed after sevoflurane anaesthesia. Of measured cytokines IL-1beta, TNF-alpha, IL-6, IL-8 and IL-10 only plasma concentrations of IL-6 could be measured during the study without a difference between the groups. CONCLUSION: Lower gene expression of TNF-alpha and IL-1beta was found in the intact porcine lung tissue after sevoflurane anaesthesia compared with thiopentone anaesthesia. Clinical significance of this finding is unknown.

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.

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.

Pulmonary inflammatory mediators after sevoflurane and thiopentone anaesthesia in pigs.

BACKGROUND: Volatile anaesthetics have been shown to affect the release of pulmonary inflammatory mediators and exacerbate pulmonary injury after experimental aspiration. Thus, in theory, volatile anaesthetics may worsen inflammatory pulmonary injury and disease. We have previously described that no significant changes in alveolar ultrastructure are seen after sevoflurane anaesthesia. However, this does not exclude any possible physiological alterations. The aim of our study was to evaluate pulmonary inflammatory mediators in bronchoalveolar lavage (BAL) after sevoflurane and thiopentone anaesthesia in pigs with intact lungs. METHODS: Sixteen pigs were randomly selected to receive either a continuous thiopentone infusion (control group, n = 8) or sevoflurane (n = 8) at 4.0% inspiratory concentration (1.5 MAC) in air for 6 h. Bronchoalveolar lavage samples were collected at the end of the study to determine pulmonary inflammatory markers. RESULTS: Compared with thiopentone anaesthesia, significant increases in BAL leukotriene C4 (LTC4), NO3-, and NO2- levels were observed after sevoflurane anaesthesia. In addition, there was a significant decrease in total blood leukocyte count in sevoflurane-treated animals. CONCLUSION: We conclude that sevoflurane increases pulmonary LTC4, NO3-, and NO2- production in pigs, indicating an inflammatory response.

Investigation of the mechanisms of therapy-related hypoglycaemia in children with acute lymphoblastic leukaemia.

AIM: To determine the mechanisms of fasting hypoglycaemia occurring during maintenance therapy (MT) for childhood acute lymphoblastic leukaemia (ALL). METHODS: Thirty-five children and adolescents with ALL, aged 2.4-17.4 y, were fasted for up to 16 h during MT. Nineteen of the children developed hypoglycaemia after 11 to 16 h of fasting. Blood samples for determination of metabolic changes were taken on completion of fasting. Nineteen patients underwent a glucagon stimulation test after 4 to 16 h of fasting during MT. Erythrocyte concentrations of the metabolites of methotrexate (E-MTX) and 6-mercaptopurine (E-TGN) were measured at the time of fasting. Fifteen out of 19 patients who became hypoglycaemic were re-studied 3 to 4 mo after cessation of therapy. RESULTS: In the hypoglycaemia group, plasma levels of gluconeogenic amino acids alanine and glutamine were lower (medians 117 vs 190 micromol L(-1), p = 0.009, and medians 396 vs 448 micromol L(-1), p = 0.031, respectively) than in the normoglycaemia group. Serum levels of free carnitine were lower (medians 20.3 vs 29.8 micromol L(-1), p = 0.027), free fatty acids higher (medians 3.09 vs 1.23 mmol L(-1), p < 0.001) and marked dicarboxylic aciduria was more common in the patients with hypoglycaemia (in 14/16 vs in 2/14, p < 0.001). Impaired responses to glucagon stimulation occurred in 36% (4/11) in the hypoglycaemia group and in 12.5% (1/8) in the normoglycaemia group (p = 0.243). No significant differences were detected in E-MTX and E-TGN between the groups. Most of the metabolic abnormalities returned to normal after cessation of chemotherapy. CONCLUSIONS: Low levels of gluconeogenic amino acids, especially of alanine, are associated with hypoglycaemia. Reduced hepatic glycogen stores may also be involved in the aetiology.

Ectopic beats in heart rate variability analysis: effects of editing on time and frequency domain measures.

BACKGROUND: Various methods can be used to edit biological and technical artefacts in heart rate variability (HRV), but there is relatively little information on the effects of such editing methods on HRV. METHODS: The effects of editing on HRV analysis were studied using R-R interval data of 10 healthy subjects and 10 patients with a previous myocardial infarction (MI). R-R interval tachograms of verified sinus beats were analyzed from short-term ( approximately 5 min) and long-term ( approximately 24 hours) recordings by eliminating different amounts of real R-R intervals. Three editing methods were applied to these segments: (1) interpolation of degree zero, (2) interpolation of degree one, and (3) deletion without replacement. RESULTS: In time domain analysis of short-term data, the standard deviation of normal-to-normal intervals (SDANN) was least affected by editing, and 30%-50% of the data could be edited by all the three methods without a significant error (< 5%). In the frequency domain analysis, the method of editing resulted in remarkably different changes and errors for both the high-frequency (HF) and the low-frequency (LF) spectral components. The editing methods also yielded in different results in healthy subjects and AMI patients. In 24-hour HRV analysis, up to 50% could be edited by all methods without an error larger than 5% in the analysis of the standard deviation of normal to normal intervals (SDNN). Both interpolation methods also performed well in the editing of the long-term power spectral components for 24-hour data, but with the deletion method, only 5% of the data could be edited without a significant error. CONCLUSIONS: The amount and type of editing R-R interval data have remarkably different effects on various HRV indices. There is no universal method for editing ectopic beats that could be used in both the time-domain and the frequency-domain analysis of HRV.

Fasting hypoglycemia is common during maintenance therapy for childhood acute lymphoblastic leukemia.

Nineteen of 35 children (54%) with acute lymphoblastic leukemia receiving maintenance therapy consisting of daily oral 6-mercaptopurine and weekly oral methotrexate developed hypoglycemia (blood glucose level <2.7 mmol/L [50 mg/dL] or <2.9 mmol/L [54 mg/dL] with symptoms) during 16 hours of overnight fasting. In 15 of 15 re-studied children, fasting tolerance had improved, and in 67% (10/15), it had become normal a few months after cessation of therapy.

Hereditary tyrosinaemia type I: from basics to progress in treatment.

Hereditary tyrosinaemia type I is the most common of the diseases caused by defects in tyrosine metabolism. The underlying genetic defect is a mutation in the gene for fumarylacetate hydrolase (FAH), and more than 30 different mutations in this gene have been identified. The main clinical consequences of this defect include hepatic involvement, with a high risk for liver cancer, and renal tubular dysfunction. Restriction of phenylalanine and tyrosine from the diet along with supportive measures can ameliorate the symptoms, but cure has so far been possible only with liver transplantation. Recent discovery of a pharmacological treatment with a peroral inhibitor of tyrosine catabolic pathway, 2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione (NTBC), offers a new promising tool for the treatment of patients with hereditary tyrosinaemia type I. Mouse models of FAH deficiency have been successfully used in experimental gene therapy, and these studies indicate that future management of tyrosinaemia with a gene therapeutic approach may become feasible.

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.

The effects of glycopyrrolate on oral mucous host defenses in healthy volunteers.

UNLABELLED: We studied the effects of glycopyrrolate on oral mucous host defenses. Single IV doses of glycopyrrolate (4 microg/kg) or placebo were administered to 12 healthy volunteers in a randomized, double-blinded, cross-over study. Salivary flow rates and the concentrations/activities of total protein, amylase, and nonimmunologic (lysozyme, lactoferrin, myeloperoxidase, total salivary peroxidase, and thiocyanate) and immunologic (total immunoglobulin A, immunoglobulin G, and immunoglobulin M) mucous host defense factors were determined for paraffin-stimulated whole saliva before and 1, 3, 6, 12, 24, and 48 h after drug administration. Glycopyrrolate serum concentrations were determined before and 2, 4, 6, 10, 15, and 30 min and 1, 2, 3, 6, 12, and 24 h after IV drug injection. Salivary flow rates were decreased significantly for 12 h after glycopyrrolate injection, compared with saline injection. The concentrations of immunologic and nonimmunologic defense factors were increased in the glycopyrrolate group, and differences between the groups were found for all factors (P < 0.05-0.001) except lysozyme and total salivary peroxidase. In contrast, because of the reduced flow rate, the output of all defense factors into the saliva was decreased after glycopyrrolate injection, compared with saline injection. Glycopyrrolate thus decreases the output of salivary host defense factors into the oral cavity. IMPLICATIONS: Glycopyrrolate induces long-lasting hyposalivation and decreases the secretion of salivary immunologic and nonimmunologic defense factors in healthy volunteers.