Low medical morbidity and mortality after acute courses of electroconvulsive therapy in a population-based sample.

BACKGROUND: To determine event rates for specific medical events and mortality among individuals receiving electroconvulsive therapy (ECT). METHOD: Population-based cohort study using health administrative data of acute ECT treatments delivered in Ontario, Canada, from 2003 to 2011. We measured the following medical event rates, per 10 000 ECT treatments, up to 7 and 30 days post-treatment: stroke, seizure, acute myocardial infarction, arrhythmia, pneumonia, pulmonary embolus, deep vein thrombosis, gastrointestinal bleeding, falls, hip fracture, and mortality. RESULTS: A total of 135 831 ECT treatments were delivered to 8810 unique patients. Overall medical event rates were 9.1 and 16.8 per 10 000 ECT treatments respectively. The most common medical events were falls (2.7 and 5.5 per 10 000 ECT treatments) and pneumonia (1.8 and 3.8 per 10 000 ECT treatments). Fewer than six deaths occurred on the day of an ECT treatment. This corresponded to a mortality rate of less than 0.4 per 10 000 treatments. Deaths within 7 and 30 days of an ECT treatment, excluding deaths due to external causes (e.g., accidental and intentional causes of death), were 1.0 and 2.4 per 10 000 ECT treatments respectively. CONCLUSION: Morbidity and mortality events after ECT treatments were relatively low, supporting ECT as a low-risk medical procedure.

An international study of the quality of national-level guidelines on driving with medical illness.

BACKGROUND: Medical illnesses are associated with a modest increase in crash risk, although many individuals with acute or chronic conditions may remain safe to drive, or pose only temporary risks. Despite the extensive use of national guidelines about driving with medical illness, the quality of these guidelines has not been formally appraised. AIM: To systematically evaluate the quality of selected national guidelines about driving with medical illness. DESIGN: A literature search of bibliographic databases and Internet resources was conducted to identify the guidelines, each of which was formally appraised. METHODS: Eighteen physicians or researchers from Canada, Australia, Ireland, USA and UK appraised nine national guidelines, applying the Appraisal of Guidelines for Research and Evaluation (AGREE II) instrument. RESULTS: Relative strengths were found in AGREE II scores for the domains of scope and purpose, stakeholder involvement and clarity of presentation. However, all guidelines were given low ratings on rigour of development, applicability and documentation of editorial independence. Overall quality ratings ranged from 2.25 to 5.00 out of 7.00, with modifications recommended for 7 of the guidelines. Intra-class coefficients demonstrated fair to excellent appraiser agreement (0.57-0.79). CONCLUSIONS: This study represents the first systematic evaluation of national-level guidelines for determining medical fitness to drive. There is substantive variability in the quality of these guidelines, and rigour of development was a relative weakness. There is a need for rigorous, empirically derived guidance for physicians and licensing authorities when assessing driving in the medically ill.

Reduced GLP-1R expression in gastric glands of patients with type 2 diabetes mellitus.

BACKGROUND: The incretin effect is reduced in type 2 diabetes mellitus (T2DM) patients. Whether the impaired function of the enteropancreatic axis in these patients is due to defective GLP-1 receptor (GLP-1R) expression in extrapancreatic target organs is not known. AIMS AND METHODS: To compare the GLP-1R expression and distribution in gastric mucosa biopsies of patients with (n =22) and without (n =22) T2DM referred for routine esophagogastroduodenoscopies. GLP-1R mRNA levels were estimated by real-time PCR. The intensity of GLP-1R immunostaining, frequency, and types of glandular cells bearing GLP-1R and their glandular distribution in different stomach mucosa regions were evaluated by immunohistochemical morphological semiquantitative and quantitative analysis. RESULTS: Mean mRNA GLP-1R levels were significantly reduced in patients with T2DM compared with nondiabetic patients (P < .02). Immunohistochemical analysis revealed that the reduced GLP-1R expression in T2DM patients was due to a decreased intensity of immunostaining (P < .01). The number of glandular GLP-1R-bearing cells in both body and antrum mucosa was decreased in T2DM patients. Most notably, the frequency of GLP-1R immunoreactive acid-secreting parietal cells was reduced in the neck area of the gastric principal glands of T2DM patients (P < .01). No correlation was found between the reduced GLP-1R expression and clinical parameters including body mass index, age, glycosylated hemoglobin, and disease duration. CONCLUSION: This is the first evidence of reduced GLP-1R expression in gastric glands of T2DM patients. These data demonstrate that the defective function of the incretin axis in T2DM may also result from decreased GLP-1R expression in its extrapancreatic target organs.

Constitutive abnormal expression of RasGRP-1 isoforms and low expression of PARP-1 in patients with systemic lupus erythematosus.

OBJECTIVE: Defective expression of Ras guanil releasing protein-1 (RasGRP-1) and increased apoptosis have been reported in lymphocytes from SLE patients. Whether these aberrations are correlated and linked to disease activity has not been elucidated. METHODS: Expression of normal 90 kDa RasGRP-1, its most prevalent 86 kDa isoform and full PARP-1 116 kDa and its cleavage fragment 84 kDa were determined in whole protein lysates of peripheral blood mononuclear cells (PBMC) in correlation with mitogen activated protein kinase (MAPK) activity and SLE clinical status in a large group of SLE patients during 1 year follow-up. RESULTS: Expression of normal 90 kDa RasGRP-1 was comparable in patients and controls. However, SLE patients demonstrated a constitutively increased 86 kDa/90 kDA ratio (p < 0.01) and decreased full poly (ADP-ribose) polymerase protein-1 (PARP-1) expression (p < 0.002) compared with controls who were disease-independent. A remission in disease activity was associated with decreased RasGRP-1 expression. Expression of 84 kDa PARP-1 cleavage fragment was found in 15% of patients but in none of the controls. In addition, expression of PARP-1 correlated positively with normal 90 kDa RasGRP-1 expression and negatively with the RasGRP-1 86 kDa/90 kDA ratio. CONCLUSIONS: These data suggest that constitutive aberrant expression of PARP-1 and RasGRP-1 ratio may act in concert to impair survival of lymphocytes in SLE patients.

Comparison of modified preadmission glucose-lowering regimen with basal/bolus regimen for glucose control on outcome in general medicine wards.

BACKGROUND: It is undecided whether glucose control as advocated by the professional organisations and the glucose-lowering method by itself affects clinical outcome in patients with diabetes mellitus hospitalised in general medical wards. Our aim was to investigate whether a basal/bolus regimen and a modified prehospitalisation regimen have a different impact on the clinical diabetic patients in general medicine wards. METHODS: Glucose control of patients with diabetes hospitalised in two different wards of internal medicine was achieved according to their wards' policy: a modified preadmission regimen (conventional regime) or a basal/bolus regimen (intensive regime). Death and any adverse event were determined during hospitalisation and within 6 months after discharge to assess clinical outcome. RESULTS: Median fasting and daily glucose levels were similar in the conventional (n = 116) and intensive regime (n = 129) groups: 161 mg/dl (inter-quartile range: 138-201) and 176 mg/dl (152-215) vs. 155 mg/dl (133-208) and 173 mg/dl (146-208) respectively. Clinical outcome was not affected by the treatment modality. In the subgroup of patients hospitalised with infection, the median fasting glucose was significantly lower in the interventional compared with the conventional regime: 141 and 172 mg/dl respectively (p = 0.041). However, tighter control was associated with a significantly higher incidence of adverse events within 6 months after discharge: 48.9% and 21.4% respectively (p = 0.047). CONCLUSION: In general medicine wards, modified prehospital hypoglycaemic regimens and a basal/bolus insulin regimen achieve similar glucose control. The clinical outcome was not affected by the modality of glucose control.

Increased ERK and JNK activities correlate with disease activity in patients with systemic lupus erythematosus.

BACKGROUND: Aberrant signalling along the p21ras/MAP kinase pathway has been demonstrated in systemic lupus erythematosus (SLE). OBJECTIVE: To determine whether expression and activity of the MAP kinases ERK and JNK reflect disease activity in patients with SLE. METHODS: Blood samples of 42 outpatients with SLE were prospectively collected during four consecutive visits. The control group included 20 healthy subjects. Disease activity was assessed using the SLE Disease Activity Index (SLEDAI). Expression of total ERK and JNK kinases and their active forms (pERK and pJNK) was determined in whole protein lysates of peripheral blood mononuclear cells. RESULTS: The mean levels of the active kinases pERK and pJNK were significantly increased in patients with active disease (SLEDAI 4-20) as compared with patients with inactive disease (SLEDAI 0-3), p = 0.04, as well as with healthy controls, p = 0.03 and p = 0.003 for pERK and pJNK, respectively. The percentage of activated forms of ERK and JNK of the total expression of these MAP kinases was also gradually increased, reaching 50% for pERK and >40% for pJNK in patients with SLE with moderate-to-severe disease (SLEDAI 7-20), p = 0.005, p = 0.005 and p = 0.02, p = 0.05 as compared with controls and inactive patients, respectively. A decrease of more than three SLEDAI points was associated with a significant reduction in the expression of both total and activated forms of ERK and JNK, p = 0.03, p = 0.01, respectively. CONCLUSIONS: The results show that ERK and JNK activity reflects disease activity in patients with SLE. These MAP kinases may serve as additional tools for the evaluation of disease activity and management of these patients.

Evidence for aberrant regulation of MAP kinase signal transduction pathway in peripheral blood mononuclear cells in patients with active celiac disease.

BACKGROUND: Aberrant signaling via the p21/mitogen-activated proteins (MAP) kinase pathway has been described in lymphocytes of patients with various autoimmune diseases. There is little published data about the intracellular mediators and signals that regulate expression and activity of transcription factors and their effect on celiac disease induction and progression. AIM: To investigate the possible involvement of MAP kinase pathway in peripheral blood mononuclear cells (PBMC) in celiac disease and its correlation with disease activity. METHODS: Expression of the total and activated forms of two MAP kinases [extracellular response kinase (ERK) and c-Jun amino terminal kinase (JNK)] were studied by Western blots in PBMC of 17 untreated and 19 treated celiac patients, and 17 controls. Seven of these untreated celiac patients were studies before and after 6 months of gluten-free diet. RESULTS: Phosphorylated ERK of active celiac disease patients was significantly lower compared with controls (P < 0.01) and was increased towards normal after 6 month of gluten-free diet (P < 0.01). Phosphorylated JNK was increased significantly in the untreated celiac group (P < 0.01) and normalized towards the control level after 6 months of gluten-free diet (P < 0.04). CONCLUSIONS: Aberrant MAP-kinase pathway activity is associated with active celiac disease (CD). Further studies should examine the potential role of this aberration in pathogenesis of CD.

An open-label study of citalopram for major depression following traumatic brain injury.

Major depression is associated with substantial psychosocial dysfunction and post-concussive symptomatology following traumatic brain injury (TBI). Studies to date of anti-depressant treatment for major depression post-TBI have been limited by small sample size. The goal of the present study is to examine the rates of response and remission associated with citalopram treatment for major depression following traumatic brain injury. Subjects with major depression following mild-to moderate TBI were treated with open-label citalopram with a starting dose of 20 mg/day to a maximum of 50 mg/day for either 6 weeks (n = 54) or 10 weeks (n = 26). The Hamilton Depression Rating Scale (HAMD) was used to assess depression severity. Response was defined by a 50% reduction in HAMD score, and remission was defined by a HAMD score of < or =7. The mean HAMD at baseline and 6 weeks were 23.66 (SD 6.8) and 16.30 (SD 9.3), respectively (t[53] = 7.157, p < 0.0001). The mean HAMD at 10 weeks was 12.96 (SD 7.9) (t[25] = 7.323, p < 0.0001). At 6 weeks, 54 subjects were assessed and 27.7% responded with 24.1% in remission. At 10 weeks, 26 subjects were assessed and 46.2% responded with 26.9% in remission. The response rate in the present sample was substantially lower than previously reported for patients with TBI, but comparable to the results of the largest effectiveness trial of citalopram for general out-patients with major depression in the absence of TBI.

Acute psychotic stress is associated with decreased adiponectin serum levels.

OBJECTIVE: To determine the effect of acute psychotic stress on adipokine secretion in non-diabetic subjects. RESEARCH DESIGN AND METHODS: Adiponectin, leptin, and cortisol serum levels were determined in 39 non-diabetic patients with acute psychotic stress reaction admitted to a psychiatric ward. The clinical global impression (CGI) score was used to evaluate the level of psychotic stress. Insulin sensitivity (IS) was determined by the homeostasis model assessment (HOMA). Patients were re-assessed 2 weeks after admission. During hospitalization patients were treated for variable times with either phenothiazines or thioxanthenes. RESULTS: The mean CGI score decreased significantly with time: 5.3+/-0.8 and 2.6+/-0.8 on admission and after 2 weeks respectively (p<0.001). On admission, the mean adiponectin level was significantly lower in patients compared to normal controls: 15.3+/-8.2 mug/ml and 26+/-12.8 mug/ml, respectively (p=0.02). It increased significantly after 2 weeks to 18.2+/-10 mug/ml (p=0.003). By contrast, the leptin and cortisol levels did not change significantly. No correlation was found between the changes in individual CGI scores and adiponectin levels. However, female patients with the highest stress on admission demonstrated the lowest adiponectin levels and insulin sensitivity: p=0.002 and 0.03 respectively. CONCLUSIONS: These data suggest a link between acute psychotic stress reaction and decreased serum adiponectin levels. Further studies are recommended to determine the strength of this association.

Successful treatment of prolonged agranulocytosis caused by acute parvovirus B19 infection with intravenous immunoglobulins.

A 21-year-old previously healthy male presented with prolonged fever of 3 weeks duration and profound agranulocytosis that did not respond to treatment with granulocyte-stimulating factors. A bone marrow biopsy demonstrated an absence of myeloid lineage. Acute parvovirus B19 infection was diagnosed by the presence of both IgM and IgG anti-parvovirus antibodies. Two days treatment with intravenous immunoglobulins (IVIg) resulted in complete recovery. The role of treatment with immunoglobulins in acute and persistent parvovirus infection is discussed.

Clinical characteristics and diabetes associated autoantibodies in patients with both type 1 diabetes mellitus and asthma.

OBJECTIVE: Type 1 diabetes mellitus (DM1) and asthma are mediated by opposite arms of the cellular immune system, namely T helper (Th)1 and Th2 CD4+ cells, respectively. It is not known whether their coexistence affects their clinical manifestations. METHODS: The number of asthma exacerbations, frequency of hypoglycemic events, HbA1c levels, diabetes associated autoantibody status and diabetes associated late complications were determined in three paired groups of patients (n = 11) matched by gender and age: DM1 and asthma, asthma only, and DM1 only. RESULTS: Patients with both diseases had a higher prevalence of hypoglycemic events per month compared to patients with DM1 only: 5.67 +/- 4.27 vs 1.45 +/- 2.06, respectively (p = 0.008). The co-existence of the two diseases did not modify the remaining clinical and laboratory parameters. CONCLUSION: Patients with both DM1 and asthma have similar clinical characteristics to patients with only one of these diseases apart from a higher rate of hypoglycemic events compared to patients with DM1 without asthma.

Reduction of digital plantar pressure by debridement and silicone orthosis.

The lesser digits are frequent sites of elevated plantar pressure and ulceration in the diabetic foot. We sought to determine whether debridement of callus and the wearing of a custom molded digital orthosis could significantly reduce digital plantar pressure. Fourteen patients with distal digital callus were studied. For each patient, the toe with the highest plantar pressure was selected. A computerized pressure mat was used to record the plantar pressure before and after debridement with and without a moldable silicone digital orthosis. Mean peak plantar digital pressures before treatment were 2.80+/-0.7 kg/cm2 for the entire group. The digital orthosis alone reduced plantar pressure to a mean of 1.95+/-0.65 kg/cm2 p < 0.05. Treatment by debridement similarly reduced pressure to 1.99+/-0.76 kg/cm2 p < 0.05. The most effective reduction of pressure for all patients, as well as the most statistically significant, occurred when both treatments were given, with mean peak plantar pressure falling to 1.28+/-0.61 kg/cm2 p < 0.01. Debridement and custom molded digital orthoses alleviate distal digital plantar pressure. Since elevated plantar pressure increases the risk of neuropathic ulceration, these treatments should be considered in the prophylactic care of appropriate patients.

Enhanced glucose-dependent glucagon-like peptide-1 and insulin secretion in Crohn patients with terminal ileum disease is unrelated to disease activity or ileal resection.

BACKGROUND: Enhanced secretion of glucagon-like peptide-1 (GLP-1) has been reported in patients with Crohn disease (CD). However, the correlation between the enteropancreatic axis and the activity of CD remains unclear. METHODS: Plasma glucose, insulin, GLP-1 levels and insulin sensitivity were determined before and after oral glucose tolerance tests in 13 patients with CD of the terminal ileum, in 13 patients after resection of the terminal ileum and in 7 healthy controls. Basal and stimulated insulin sensitivities were determined using the homeostasis model assessment (HOMA) and the insulin sensitivity index (ISI) methods, respectively. RESULTS: Basal and stimulated glucose levels were comparable in patients and controls. The peak stimulated GLP-1 secretion was significantly higher in the patient group compared to controls: 12.2 +/- 1.24 pM/L and 8.1 +/- 1.72 pM/L, respectively, P=0.03. This was associated with 52% increased overall insulin secretion in the patients' group as compared to controls (P=0.007) and a higher peak insulin response: 63.5 +/- 9.69 mU/L and 41.5 +/- 6.85 mU/L for patients and controls, respectively, P=0.04. Operated patients had similar GLP-1 levels but higher peak and overall insulin secretions compared with those in non-operated patients (P=0.01). Fasting and stimulated insulin sensitivities were reduced only in patients with ileal resection as compared to controls: P=0.01 and P=0.05, respectively. No correlation was found between the CD activity index and GLP-1 or insulin secretion. CONCLUSIONS: CD of the terminal ileum is associated with enhanced glucose-dependent GLP-1 secretion, which is unrelated to disease activity or ileal resection.

Increased expression of tissue factor and receptor for advanced glycation end products in peripheral blood mononuclear cells of patients with type 2 diabetes mellitus with vascular complications.

The aim of the study was to determine the correlation between the expression of tissue factor (TF) and the receptor for advanced glycation end products (RAGEs) and vascular complications in patients with longstanding uncontrolled type 2 diabetes (T2D). TF and RAGE mRNAs as well as TF antigen and activity were investigated in 21 T2D patients with and without vascular complications. mRNA expression was assessed by reverse transcriptase-polymerase chain reaction (RT-PCR) in nonstimulated and advanced glycation end product (AGE) albumin-stimulated peripheral blood mononuclear cells (PBMCs). TF antigen expression was determined by enzyme-linked immunosorbent assay (ELISA) and TF activity by a modified prothrombin time assay. Basal RAGE mRNA expression was 0.2 +/- 0.06 in patients with complications and 0.05 +/- 0.06 patients without complications (P =.004). Stimulation did not cause any further increase in either group. TF mRNA was 0.58 +/- 0.29 in patients with complications and 0.21 +/- 0.18 in patients without complications (P =.003). Stimulation resulted in a nonsignificant increase in both groups. Basal TF activity (U/10(6) PBMCs) was 18.4 +/- 13.2 in patients with complications and 6.96 +/- 5.2 in patients without complications (P =.003). It increased 3-fold in both groups after stimulation (P =.001). TF antigen (pg/10(6) PBMCs) was 33.7 +/- 28.6 in patients with complications, 10.4 +/- 7.8 in patients without complications (P =.02). Stimulation tripled TF antigen in both groups of patients (P =.001). The RAGE/TF axis is up-regulated in T2D patients with vascular complications as compared to patients without complications. This suggests a role for this axis in the pathogenesis of vascular complications in T2D.

Swab cultures accurately identify bacterial pathogens in diabetic foot wounds not involving bone.

AIMS: Current clinical practice assumes swab cultures from wounds are unreliable. However, this assumption is based upon data culled only from wounds in which osteomyelitis and/or gangrene were present. This study aimed to re-evaluate the accuracy of swab cultures vs. deep tissue cultures in diabetic wounds of varying depth and severity. METHODS: A total of 60 infected diabetic foot wounds were cultured. Two specimens were taken from each wound: superficial swab before debridement and deep tissue specimen towards the end of surgical debridement. RESULTS: In 37 wounds (62%), the micro-organisms isolated from the swab specimen and those isolated from the deep tissue specimen were identical. In another 12 wounds (20%), the swab culture contained all micro-organisms isolated from the deep tissue culture, but also contained additional micro-organisms. Analysis according to the depth of the wound, demonstrated that swabs identified all micro-organisms isolated from the deep tissue specimens in 36/40 wounds (90%) that did not extend to bone as opposed to 13/20 wounds (65%) that extended to bone. CONCLUSIONS: Swab cultures are valuable in identifying pathogens in diabetic foot wounds when bone is not involved. When surgical debridement is contraindicated or delayed, swab cultures can be used to select appropriate antibiotic therapy.

Normal p21Ras/MAP kinase pathway expression and function in PBMC from patients with polycystic ovary disease.

Polycystic ovary disease (PCOD) is associated with insulin resistance and increased prevalence of type II diabetes mellitus (T2DM). The p21Ras/MAP kinase is a major intracellular signaling pathway mediating insulin signaling in insulin responsive tissues. The expression, regulation and function of the p21Ras/MAP kinase pathway in PCOD patients were examined. Peripheral blood mononuclear cells (PBMC) were isolated from ten patients with PCOD and ten controls. The expression of p21Ras and its regulatory proteins; hSOS1 and p120GAP were studied. The basal and phytohemaglutinin (PHA) or insulin stimulated phosphorylation of MAP kinase was determined. Expression of p21Ras, and its regulatory proteins hSOS1 and p120GAP were similar in PCOD patients and controls. Basal, PHA and insulin stimulated phosphorylation of MAP kinase, were also comparable in the two groups as well as their PBMC proliferative response. These data indicate that the expression and overall function of the p21Ras/MAP kinase pathway remain intact in non-diabetic patients with PCOD.

Diagnosis of normocalcemic hyperparathyroidism by oral calcium loading test.

We evaluated the oral calcium-loading test (OCLT) in diagnosing normocalcemic primary hyperparathyroidism. Calcium and PTH levels were measured before, 60, 120 and 180 min after oral 1 g of calcium gluconolactate administration in 102 consecutive females with high circulating PTH levels, and 25 controls. Patients were classified as follows: Group A, patients with a parathyroid adenoma identified by two imaging modalities. Sub-Group AO, hyperparathyroid patients [no.=13, mean age 59 yr (SD=10)] evaluated prior to parathyroidectomy. Sub-Group AH, non-operated hypercalcemic patients [no.=29, age 63 yr (SD=11)]. Sub-Group AN, normocalcemic non-operated women [no.=14, age 59 yr (SD=8)]. Group B, normocalcemic individuals [no.=46, age 58 yr (SD=11)] with negative parathyroid imaging. Group C, control patients [no.= 25, age 56 yr (SD=12)]. The concentrations of calcium and PTH overlapped in the normocalcemic groups during the OCLT. Product P, defined as circulating PTH nadir (pg/ml) x peak calcium concentration (mg/dl), better discriminated Sub-Group AN from Group B, AUC=0.98 (95% CI 0.95, 1.00) than did Ratio R, defined as relative PTH decline/relative calcium increment, AUC= 0.86 (95%CI 0.73, 0.99). Assuming normal threshold of Product P and Ratio R at 260 and 17 respectively, the combined parameters diagnose normocalcemic hyperparathyroid patients with 100% sensitivity and 87% specificity.

Lack of correlation between disease activity and decreased stimulated secretion of IL-10 in lymphocytes from patients with celiac disease.

BACKGROUND: Celiac disease (CD) is commonly believed to be a predominantly Th1 disease. However, the exact balance between the Th1 and Th2 arms, as well as the correlation to clinical parameters, remains unclear. The aim was to assess the Th1/Th2 cytokine profile and its correlation to clinical parameters in active and non-active CD patients. METHODS: Peak, total secretion and secretory pattern of the Th1 cytokines (IFN-gamma and IL-2) and Th2 cytokines (IL-4 and IL-10) were determined in resting and stimulated peripheral blood mononuclear cells (PBMC) from 19 CD patients with active and non-active disease and 20 normal controls. RESULTS: Peak and total secretion of IL-10 were significantly reduced in CD patients compared with normal controls. This was due to a persistently flat secretory pattern of IL-10 over time in CD patients. In addition, IFN-gamma/IL-10 and the IL-2/IL-10 ratios of peak and total secretion were higher in patients than in controls. In contrast, peak, total secretion and secretory pattern of IL-2, IFN-gamma and IL-4 were comparable in patients and controls as well as the IL-2/IL-4 and IFN-gamma/IL-4 ratios. No difference in the cytokine secretion or Th1/Th2 ratio was found between active and non-active patients or between pediatric and adult patients. CONCLUSIONS: These data indicate that the Thl/Th2 balance in CD is shifted towards Th1 cytokines because of a down-regulated IL-10 secretion. The aberrant profile of cytokine secretion of these patients is not associated with clinical parameters and suggests an inherent defect in IL-10 secretion in CD.

The relation between adrenal function and the severity of bronchial hyperresponsiveness in children as measured by the methacholine provocation test.

BACKGROUND: There is no satisfactory explanation why some individuals experience severe attacks of asthma, yet others, exposed to similar stimuli, have a milder form of the disease. OBJECTIVE: We tested the hypothesis that children with more severe disease may have relative adrenal insufficiency compared to the children with milder disease. PATIENTS AND METHODS: Sixteen children with chronic asthma aged 8-16 years old were studied. Adrenal function was evaluated by the 24-h excretion of urinary free cortisol (UFC) before and after ACTH stimulation, and by plasma cortisol levels before and 60 min after ACTH administration. The severity of bronchial hyperresponsiveness was evaluated by the methacholine provocation test. RESULTS: Nine children had 20% fall in forced expiratory volume in 1 sec (FEV1) after a provocative concentration (PC20FEV1) of methacholine > or =2.5 mg/ml and were considered as having mild-moderate bronchial hyperresponsiveness (Group A). Seven children had a PC20FEV1 of < or =1.25 mg/ml and were considered as having severe bronchial hyperresponsiveness (Group B). No significant difference was found between the peak plasma cortisol response to ACTH between the two groups (634+/-182 and 586+/-137 nmol/l, respectively). However, there was a significant statistical difference (p <0.01) in the 24-h UFC response to ACTH between the children from Group A (345+/-107 nmol/m2 ) and the children from Group B (161+/-125 nmol/m2). CONCLUSIONS: Based on the low levels of 24-h UFC secretion in severely asthmatic children in our study, we propose the encouragement of provision of a short course of inhaled steroids to be kept at home for the emergency therapy of those children identified as having high-risk asthma.