Usefulness of Serum Pepsinogens in Helicobacter pylori Chronic Gastritis: Relationship With Inflammation, Activity, and Density of the Bacterium

We sought to study the relationship between serum pepsinogens and different histopathologic features of Helicobacter pylori-related chronic gastritis. One hundred forty-nine consecutive dyspeptic patients underwent endoscopy with biopsies; serum pepsinogens I and II were measured by immunoassay. Serum levels of pepsinogens (sPG) were significantly correlated with H. pylori density both of the corpus (sPGI: r = 0.32, P < .001; sPGII: r = 0.56, P < .001) and antrum (sPGI: r = 0.41, P < .001; sPGII: r = 0.43, P < .001) as well as with chronic inflammation (sPGI: r = 0.26, P < .001; sPGII: r = 0.49, P < .001) and activity (sPGI: r = 0.38, P < .001; sPGII: r = 0.50, P < .001) in the antrum. Only sPGII was correlated with chronic inflammation (r = 0.44, P < .001) and activity (r = 0.40, P < .001) in the corpus. SPGI was inversely correlated with atrophy (r = –0.33, P < .001) and intestinal metaplasia (r = –0.37, P < .001) in the corpus. sPGII levels could be considered as markers of gastric inflammation all over in the stomach. sPGI levels are inversely related to atrophic body gastritis.     

Influence of Race on Inpatient Treatment Intensity at the End of Life

OBJECTIVE To examine inpatient intensive care unit (ICU) and intensive procedure use by race among Medicare decedents, using utilization among survivors for comparison. DESIGN Retrospective observational analysis of inpatient claims using multivariable hierarchical logistic regression. SETTING United States, 1989–1999. PARTICIPANTS Hospitalized Medicare fee-for-service decedents (n = 976,220) and survivors (n = 845,306) aged 65 years or older. MEASUREMENTS AND MAIN RESULTS Admission to the ICU and use of one or more intensive procedures over 12 months, and, for inpatient decedents, during the terminal admission. Black decedents with one or more hospitalization in the last 12 months of life were slightly more likely than nonblacks to be admitted to the ICU during the last 12 months (49.3% vs. 47.4%, p <.0001) and the terminal hospitalization (41.9% vs. 40.6%, p < 0.0001), but these differences disappeared or attenuated in multivariable hierarchical logistic regressions (last 12 months adjusted odds ratio (AOR) 1.0 [0.99–1.03], p = .36; terminal hospitalization AOR 1.03 [1.0–1.06], p = .01). Black decedents were more likely to undergo an intensive procedure during the last 12 months (49.6% vs. 42.8%, p < .0001) and the terminal hospitalization (37.7% vs, 31.1%, p < .0001), a difference that persisted with adjustment (last 12 months AOR 1.1 [1.08–1.14], p < .0001; terminal hospitalization AOR 1.23 [1.20–1.26], p < .0001). Patterns of differences in inpatient treatment intensity by race were reversed among survivors: blacks had lower rates of ICU admission (31.2% vs. 32.4%, p < .0001; AOR 0.93 [0.91–0.95], p < .0001) and intensive procedure use (36.6% vs. 44.2%; AOR 0.72 [0.70–0.73], p <.0001). These differences were driven by greater use by blacks of life-sustaining treatments that predominate among decedents but lesser use of cardiovascular and orthopedic procedures that predominate among survivors. A hospital’s black census was a strong predictor of inpatient end-of-life treatment intensity. CONCLUSIONS Black decedents were treated more intensively during hospitalization than nonblack decedents, whereas black survivors were treated less intensively. These differences are strongly associated with a hospital’s black census. The causes and consequences of these hospital-level differences in intensity deserve further study.     

Professional Characteristics and Job Satisfaction Among SGIM Members: A Comparison of Part-time and Full-time Physician Members

BACKGROUND  As more physicians work part-time (PT), the faculty, institutions, and organizations that represent them should understand the factors that motivate and satisfy these physicians. OBJECTIVE  Compare factors associated with job satisfaction among PT and full-time (FT) academic physicians. DESIGN  Cross-sectional survey. PARTICIPANTS  Members of the Society of General Internal Medicine (SGIM), a national, academic Internal Medicine organization. RESULTS  Fifty percent (1,396 of 2,772) of SGIM members responded, 11% work PT. Compared to FT, PT physicians were more often female (85% vs 38%, p < .001), clinicians (Cs) or clinician–educators (CEs) (84% vs 56%, p < .001), and of a lower rank (77% vs 61%, p = .001). Job satisfaction was similar between PT and FT Cs and CEs. For PT Cs and CEs, record of publication (11% vs 21%, p = .04) and local and national recognition (24% vs 36%, p = .03) were less important to overall job satisfaction compared to FT Cs and CEs. In multivariate analysis, academic rank (odds ratio [OR] = 7.18, 95%CI = 1.40–36.50) was associated with higher satisfaction among PT Cs and CEs. CONCLUSIONS  PT and FT C and CE SGIM members report similar satisfaction, but different factors contribute to satisfaction. Knowing what motivates and satisfies PT physicians may allow medical centers to retain faculty and create positions to help them to fulfill their potential. Portions of this paper were presented at the 2006 Society of General Internal Medicine national meeting, Los Angeles, CA, USA.     

Primary Care Visit Length,Quality, and Satisfaction for Standardized Patients with Depression

BACKGROUND The contribution of physician and organizational factors to visit length, quality, and satisfaction remains uncertain, in part, because of confounding by patient presentation. OBJECTIVE To determine associations among visit length, quality, and satisfaction when patient presentation is controlled. DESIGN A factorial experiment using standardized patients to make primary care visits presenting with either major depression or adjustment disorder, and a musculoskeletal complaint. PARTICIPANTS One hundred fifty-two primary care physicians, each seeing 2 standardized patients. MEASUREMENTS Visit length was determined from surreptitiously obtained audiorecordings. Other key measures were derived from physician and standardized patient report. RESULTS Mean visit length for 294 completed encounters was 22.3 minutes (range = 5.8–72.2, SD = 9.4). Key factors associated with visit length were: physician style (ρ = 0.68 and 0.54 after multivariate adjustment), nonprofessional experience with depression (11% longer, 95% CI = 0–23%), practicing within an HMO (26% shorter, 95% CI = 61–90%), and greater practice volume (those working >9 half-day clinic sessions/week had 15% shorter visits than those working fewer than 6, 95% CI = 0–27%, and those seeing >12 patients/half-day had 27% shorter visits than those seeing <10 patients/half-day, 95% CI = 13–39%). Suicidal inquiry (a process-based quality-of-care measure for depression) was not associated with adjusted visit length. Satisfaction was linearly associated with visit length but not with suicide inquiry or follow-up interval. CONCLUSIONS Despite experimental control for clinical presentation, wide variation in visit length persists, largely reflecting individual physician styles. Visit length is a significant determinant of standardized patient satisfaction.     

A Ten-Month Program in Curriculum Development for Medical Educators: 16 Years of Experience

BACKGROUND Despite increased demand for new curricula in medical education, most academic medical centers have few faculty with training in curriculum development. OBJECTIVE To describe and evaluate a longitudinal mentored faculty development program in curriculum development. DESIGN A 10-month curriculum development program operating one half-day per week of each academic year from 1987 through 2003. The program was designed to provide participants with the knowledge, attitudes, skills, and experience to design, implement, evaluate, and disseminate curricula in medical education using a 6-step model. PARTICIPANTS One-hundred thirty-eight faculty and fellows from Johns Hopkins and other institutions and 63 matched nonparticipants. MEASUREMENTS Pre- and post-surveys from participants and nonparticipants assessed skills in curriculum development, implementation, and evaluation, as well as enjoyment in curriculum development and evaluation. Participants rated program quality, educational methods, and facilitation in a post-program survey. RESULTS Sixty-four curricula were produced addressing gaps in undergraduate, graduate, or postgraduate medical education. At least 54 curricula (84%) were implemented. Participant self-reported skills in curricular development, implementation, and evaluation improved from baseline (p < .0001), whereas no improvement occurred in the comparison group. In multivariable analyses, participants rated their skills and enjoyment at the end of the program significantly higher than nonparticipants (all p < .05). Eighty percent of participants felt that they would use the 6-step model again, and 80% would recommend the program highly to others. CONCLUSIONS This model for training in curriculum development has long-term sustainability and is associated with participant satisfaction, improvement in self-rated skills, and implementation of curricula on important topics.     

Lipoprotein receptor associated protein (LRPAP1) insertion/deletion polymorphism: association with gallbladder cancer susceptibility

Background Low-density lipoprotein receptor-related protein associated protein (LRPAP1) insertion/deletion polymorphism influences cholesterol homeostasis and may confer risk for gallstone disease and gallbladder carcinoma (GBC) incidence usually parallels with the prevalence of cholelithiosis. Aim We aimed to examine the role of LRPAP1 polymorphism in susceptibility to GBC. Methods Present case control study included 129 proven GBC patients, 183 gallstone patients, and 208 healthy controls. Genotyping was done by polymerase chain reaction–restriction fragment length polymorphism method. Results The D allele of LRPAP1 was significantly higher in GBC patients as compared to gallstone patients (p = 0.013; OR = 1.6, 95% CI = 1.1–2.4). However, II genotype and I allele was associated with reduced risk of GBC as compared to gallstone patients (p = 0.002; OR = 0.1, 95% CI = 0.1–0.6; p = 0.013; OR = 0.6, 95% CI = 0.4–0.8) The increased risk due to D allele was limited to female GBC patients (p = 0.021; OR = 1.8, 95% CI = 1.1–3.0). However, reduced risk due to II genotype and I allele was observed which was also confined to female GBC patients (p = 0.005; OR = 0.1, 95% CI = 0.1–0.6; p = 0.021; OR = 0.5, 95% CI = 0.3–0.8). On comparing GBC patients having gallstone with gallstone patients, high risk was observed in the GBC patients having gallstone due to the presence of D allele (p = 0.032; OR = 1.7, 95% CI = 1.0–2.8). However, low risk was observed because of I allele in GBC patients with gallstone in comparison to gallstone patients (p = 0.032, OR = 0.6, 95% CI = 0.4–0.9). Conclusion It appears that ‘D’ allele may modulate the susceptibility of GBC, and the risk is independent to genetic risk of gallstone.     

Haemoglobin levels are associated with bone mineral density in the elderly: a population-based study

Hypoxemia has been associated with low bone mineral density (BMD) in animal and human models. We assessed the association of haemoglobin levels with ultrasound-derived (UD) T score, Z score and the stiffness index in all 358 subjects aged 75+ living in Tuscania (Italy). Also, we searched for the haemoglobin cutoff levels that might best identify participants with osteoporosis. In the multivariable linear regression analysis, haemoglobin levels were associated among participants with the UD T score [β = 0.13; 95% confidence interval (CI) = 0.01–0.25; p = 0.030], Z score (β = 0.11; 95% CI = 0.01–0.22; p = 0.045) and stiffness index (β = 1.87; 95% CI = 0.51–3.21; p = 0.007) after adjusting for potential confounders. Haemoglobin levels <140 g/L in men and <130 g/L in women best predicted osteoporosis in linear discriminant analysis. Haemoglobin is independently associated with all UD-BMD parameters. Haemoglobin levels <140 g/L in men and 130 g/L in women might be adopted in clinical practice to identify older subjects in whom screening for osteoporosis might yield higher effectiveness.     

Association of IL-18 gene polymorphism (?137C) with arthritis manifestations in SLE: combined effect with IFN gamma gene polymorphism (+874A)

We analyzed the association between single nucleotide polymorphisms in IL-12 and IL-18 genes in disease susceptibility and severity of SLE in Thais. A weak association was observed between A allele of the IL-12 gene at the 3′ untranslated region in SLE patients with proteinuria (OR = 1.89, 95% CI = 1.05–3.40, P = 0.02, Pc = 0.06). In addition, we found a significant association between C allele of IL-18 (−137) with arthritis (OR = 6.88, 95% CI = 1.54–42.93, P = 0.003, Pc = 0.009). The presence of one C allele (C/C+C/G) was associated with significant OR of 8.72 (95% CI = 1.83–56.71, P = 0.001, Pc = 0.003). Interestingly, we found the combined effect between the G/C genotype of IL-18 (−137) and the A/A genotype of IFNG (+874) gene causing susceptibility of arthritis in SLE patients (OR = 13.22, 95% CI = 1.56–291.66, P = 0.004).     

Risk factors for infection and treatment outcome of extended-spectrum β-lactamase-producing <Emphasis Type="Italic">Escherichia coli</Emphasis> and <Emphasis Type="Italic">Klebsiella pneumoniae</Emphasis> bacteremia in patients with hematologic malignancy

This study was performed to evaluate the impact of extended-spectrum β-lactamase (ESBL)-producing bacteremia on outcome in patients with hematologic malignancy. We collected and analyzed data on 156 hematologic malignancy patients with Escherichia coli or Klebsiella pneumoniae bacteremia from the database of nationwide surveillance studies for bacteremia. Thirty-seven of the 156 patients (23.7%) harbored ESBL-producing bacteremia. No significant differences in underlying diseases were found in either group. The multivariate analysis showed that significant factors associated with ESBL-producing bacteremia were ICU care (OR = 7.03, 95% CI = 1.79–27.6) and nosocomial acquisition (OR = 5.66, 95% CI = 1.60–20.23). There was an association between prior receipt of cephalosporins and ESBL-producing bacteremia, although this association was not statistically significant (OR = 2.27, 95% CI = 0.99–5.23). The overall 30-day mortality rate of the study population was 20.4% (29/142), and the 30-day mortality rate for the ESBL group was significantly higher than that for the non-ESBL group (44.8% vs. 14.2%, P < 0.001). Multivariate analysis showed that ESBL-producing bacteremia was the most important risk factor associated with 30-day mortality (OR, 5.64; 95% CI, 1.91–16.67), along with ICU care (OR = 4.35, 95% CI = 1.16–16.26) and higher Pitt bacteremia score (per 1-point increment) (OR = 1.50, 95% CI = 1.18–1.92). In conclusion, ESBL-producing bacteremia was the most important risk factor associated with 30-day mortality in patients with hematologic malignancy, along with ICU care and higher Pitt bacteremia score. Our data suggest that determining the optimal empiric antimicrobial therapy in patients with hematologic malignancy is now becoming a challenge for clinicians in the era of multidrug-resistant Gram-negative bacilli.     

A systematic review and meta-analysis of rituximab-based immunochemotherapy for subtypes of diffuse large B cell lymphoma

Addition of rituximab to chemotherapy (R-chemo) has been shown to improve overall survival (OS) in patients with diffuse large B cell lymphoma (DLBCL). Germinal center B cell-like (GCB) subtype of DLBCL has a significantly better clinical outcome than those with non-germinal center B cell-like (non-GCB) subtype. Further research is needed to confirm this difference between those two subtypes treated with R-chemo. We searched for randomized controlled trials that compared R-chemo with identical chemotherapy alone in patients with newly diagnosed or relapsed DLBCL. A random versus fixed effects model was selected according to heterogeneity. Six eligible trials involving 748 adult patients were included in this meta-analysis. Fixed-effects analysis showed OS to be superior for the GCB patients treated with R-chemo (relative risk (RR) = 1.16, 95% confidence interval (CI) = 1.03–1.31, P = 0.02). Superiority was also observed for the GCB subtype under R-chemo with respect to disease control (RR = 1.16, 95% CI = 0.99–1.36) and overall response (RR = 1.19, 95% CI = 0.99–1.99). Both subtypes showed an increased OS (RR = 1.30, 95% CI = 1.11–1.51; RR = 1.89, 95% CI = 1.52–2.35, respectively) and disease control rate (RR = 1.27, 95% CI = 1.05–1.54, P = 0.01; RR = 2.21, 95% CI = 1.68–2.90, respectively) following R-chemo. Therefore, treated with R-chemo, GCB patients still has a significantly better clinical outcome than those with non-GCB subtype.     

Psychometric evaluation of the Moroccan version of the Bath Ankylosing Spondylitis Functional Index (BASFI) and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) for use in patients with ankylosing spondylitis

The objectives of this study are to translate, adapt in the Moroccan cultural context, and validate in patients with ankylosing spondylitis (AS) the Bath Ankylosing Spondylitis Functional Index (BASFI) and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). The cross-cultural adaptation of the BASFI and BASDAI was obtained in accordance with the guidelines for translation of the health status measures. Eighty-five patients with AS were included in the study. The test–retest reliability and the internal consistency were analyzed, and both questionnaires were assessed for external construct validity. Structural validity was analyzed with correlation matrix. Twenty-four-hour test–retest reliability was good: BASFI intraclass correlation coefficient (ICC) = 0.96 (confidence interval (CI) at 95%, 0.93–0.97), BASDAI ICC = 0.93 (CI at 95%, 0.90–0.95). Cronbach’s alpha was 0.90 for the BASFI and 0.86 for BASDAI. The construct validity of the instruments was evaluated. The BASFI showed a strong validity when correlating its results with Schober’s test (r = −0.56), occipital wall distance (r = 0.46), chest expansion (r = −0.46), BASDAI (r = 0.54), Bath Ankylosing Spondylitis Metrology Index (r = 0.70), Bath Ankylosing Spondylitis Global Score (BAS-G; r = 0.58), Bath Ankylosing Spondylitis Radiology Index (r = 0.61), and the radiological changes in sacroiliac joints (r = 0.54). A good correlation was observed between the BASDAI and the spinal pain (r = 0.53), the number of nocturnal awakenings (r = 0.57), the morning stiffness (r = 0.65), the enthesic index (r = 0.47), the BAS-G (r = 0.53), the BASFI (r = 0.54), and the erythrocyte sedimentation rate (r = 0.41; for all p < 0.001). The correlation matrix showed an intermediate correlation between items. The Moroccan version of the BASFI and the BASDAI showed adequate reliability and validity. These instruments can be used in the clinical evaluation of Moroccan and Arabic-speaking patients with AS.     

Brazilian-Portuguese version of the Health Assessment Questionnaire for Spondyloarthropathies (HAQ-S) in patients with ankylosing spondylitis: a translation,cross-cultural adaptation,and validation

To translate and cross-culturally adapt to the Brazilian-Portuguese language (BP), five items were added to Health Assessment Questionnaire (HAQ) to validate the resulting HAQ-S BP version for ankylosing spondylitis (AS). The items were translated into BP following translation and back-translation. To assess validity, 25 patients were evaluated using the HAQ, Bath AS Functional Index (BASFI), Bath AS Disease Activity Index (BASDAI), Bath AS Metrology Index (BASMI), and laboratory variables (erythrocyte sedimentation rate, C-reactive protein). One question required modification to adapt culturally to Brazilian conditions. The test–retest and interobserver correlation coefficients were 0.990 (p < 0.05) and 0.993 (p < 0.05), respectively. HAQ-S BP correlated to BASFI (r = 0.574; p < 0.05) and to HAQ (r = 0.963; p < 0.05), but not to BASDAI (r = 0.282), BASMI (r = 0.194), and laboratory variable. Individually, the fifth item referring to driving correlated highly to neck rotation (r = 0.900; p < 0.05), while the HAQ-S BP correlated to the neck rotation component (r = 0.303), but did not reach statistical significance. The HAQ-S BP version demonstrated adequate reproducibility, internal consistency and validity, confirming its utility in the research of AS in Brazil.     

VEGF gene polymorphisms and susceptibility to colorectal cancer disease in Italian population

Background  The vascular endothelial growth factor (VEGF) is an endothelial cell-specific mitogen involved in the process of angiogenesis, a crucial phase in tumor growth and metastasis. We carried out a case–control study to evaluate whether polymorphisms of VEGF gene modulate the risk of developing colorectal cancer disease (CCD). Materials and methods  We evaluated VEGF −2578A/C, −460T/C, and +405C/G genotypes obtained from a series of 302 CCD patients and 115 controls from the Italian population using polymerase chain reaction restriction fragment length polymorphism assay. Results  Strong linkage disequilibrium (LD) was detected between −2578A/C and −460T/C (D′ = 0.97; CI = 0.93–1) and between −2578A/C and +405C/G (D′ = 0.97; CI = 0.98–1) in the case group. Complete LD was detected between −2578A/C and +405C/G and between −460T/C and +405C/G (D′ = 1; CI = 0.84–1; CI = 0.82–1, respectively) in the control group. A reduced risk for the disease was associated with −2578C/A and −2578C/C (odds ratio (OR) = 0.34, CI = 0.162–0.676 and OR = 0.38, CI = 0.181–0.775, respectively). A direct association was found for carriers of the VEGF −460C/C polymorphism (OR = 3.55; CI = 1.659–8.469). We identified a protective haplotype −2578A, −460T, and +405G (OR = 0.04; CI = 0.009–0.19) and two different high-risk haplotypes −2578A, −460C, and +405G (OR = 1.90; CI = 1.31–2.27) and −2578C, −460C, and +405C (OR = 9.62; CI = 1.3–70.87). Conclusions  The present study suggests that the VEGF gene polymorphisms may play a role in the development of colorectal cancer. Paolo Maltese and Emanuele Canestrari contributed equally to the study.     

Quantitative analysis of vascularization in the finger joints in patients with rheumatoid arthritis using three-dimensional volumetric ultrasonography with power Doppler

This study aimed to compare the intraobserver and interobserver reliability of three-dimensional (3D) and two-dimensional (2D) power Doppler ultrasonography (PDUS) and to assess the relationship between 3D PDUS and clinical parameters in patients with rheumatoid arthritis (RA). Bilateral second/third metacarpophalangeal joints and second/third proximal interphalangeal joints in 33 patients were examined by both 2D and 3D PDUS. Each joint was given a separate 2D PDUS subjective score (range, 0–3) in a standard manner. The 2D PDUS index is the sum of the scores of all eight joints assessed. 3D PDUS voxel signals were quantitatively analyzed by using computerized voxel counts. Intraobserver reliability was high for both examinations (2D PDUS: ICC = 0.957, 95% confidence interval = 0.818–0.999; 3D PDUS: ICC = 0.998, 95% confidence interval = 0.998–1.000). Interobserver reliability was also high (2D PDUS: ICC = 0.993, 95% confidence interval = 0.806–0.988; 3D PDUS: ICC = 0.999, 95% confidence interval = 0.999–1.000). A significant correlation was found between the 2D PDUS index and 3D PDUS voxel count (r = 0.795; p < 0.001). The 3D PDUS voxel count showed significant correlation with 28 joints Disease Activity Score (DAS28)-erythrocyte sedimentation rate (r = 0.448, p < 0.01) and DAS28-C-reactive protein (r = 0.383, p < 0.05). Our study indicates that the measurement of 3D PDUS may be a valuable tool for predicting disease activity.     

Accelerated atrophy of lower leg and foot muscles—a follow-up study of long-term diabetic polyneuropathy using magnetic resonance imaging (MRI)

Aims/hypothesis  The aim of the study was to determine the loss of muscle volume in the lower leg and foot in long-term diabetic patients in relation to the presence of neuropathy. Methods  We re-examined 26 type 1 diabetic patients who had participated in magnetic resonance imaging (MRI) studies on muscle volume in the lower leg and foot 9 to 12 years earlier. Re-examination involved MRI, isokinetic dynamometry, clinical examination, electrophysiological studies and quantitative sensory examinations. Results  Annual loss of muscle volume of ankle dorsal and plantar flexors was 4.5 (5.5–3.9)% (median [range]) and 5.0 (7.0–4.2)% in neuropathic patients, 1.9 (3.2–1.0)% and 1.8 (2.6–1.3)% in non-neuropathic patients, and 1.7 (2.8–0.8)% and 1.8 (2.4–0.8)% in controls, respectively (p < 0.01). Annual change of volume and strength correlated for ankle dorsal flexors (r _s = 0.73, p < 0.01) and for ankle plantar flexors (r _s = 0.63, p < 0.05) in diabetic patients. In addition, annual change of muscle volume for dorsal and plantar flexors was related to the combined score of all measures of neuropathy (r _s = −0.68, p < 0.02 and r _s = −0.73, p < 0.01, respectively). Foot muscle volume declined annually by 3.0 (3.4–1.0)% in neuropathic patients and by 1.1 (4.0–0.2)% in non-neuropathic patients, both values being significantly different from controls (0.2 [−2.5 to 2.4]%). Loss of foot muscle volume was related to severity of neuropathy assessed at clinical evaluation (r _s = −0.6, p < 0.05). Conclusions/interpretation  Muscular atrophy in long-term diabetic neuropathy occurs early in the feet, progresses steadily in the lower legs, relates to severity of neuropathy and leads to weakness at the ankle. An erratum to this article can be found at     

High prevalence of low plasma thiamine concentration in diabetes linked to a marker of vascular disease

Aims/hypothesis To assess thiamine status by analysis of plasma, erythrocytes and urine in type 1 and type 2 diabetic patients and links to markers of vascular dysfunction. Methods Diabetic patients (26 type 1 and 48 type 2) with and without microalbuminuria and 20 normal healthy control volunteers were recruited. Erythrocyte activity of transketolase, the concentrations of thiamine and related phosphorylated metabolites in plasma, erythrocytes and urine, and markers of metabolic control and vascular dysfunction were determined. Results Plasma thiamine concentration was decreased 76% in type 1 diabetic patients and 75% in type 2 diabetic patients: normal volunteers 64.1 (95% CI 58.5–69.7) nmol/l, type 1 diabetes 15.3 (95% CI 11.5–19.1) nmol/l, p < 0.001, and type 2 diabetes 16.3 (95% CI 13.0–9.6) nmol/l, p < 0.001. Renal clearance of thiamine was increased 24-fold in type 1 diabetic patients and 16-fold in type 2 diabetic patients. Plasma thiamine concentration correlated negatively with renal clearance of thiamine (r = −0.531, p < 0.001) and fractional excretion of thiamine (r = −0.616, p < 0.001). Erythrocyte transketolase activity correlated negatively with urinary albumin excretion (r = −0.232, p < 0.05). Thiamine transporter protein contents of erythrocyte membranes of type 1 and type 2 diabetic patients were increased. Plasma thiamine concentration and urinary excretion of thiamine correlated negatively with soluble vascular adhesion molecule-1 (r = −0.246, p < 0.05, and −0.311, p < 0.01, respectively). Conclusions/interpretation Low plasma thiamine concentration is prevalent in patients with type 1 and type 2 diabetes, associated with increased thiamine clearance. The conventional assessment of thiamine status was masked by increased thiamine transporter content of erythrocytes.     

Pregnancy plasma glucose levels exceeding the American Diabetes Association thresholds,but below the National Diabetes Data Group thresholds for gestational diabetes mellitus,are related to the risk of neonatal macrosomia,hypoglycaemia and hyperbilirubinaemia

Aims/hypothesis Gestational diabetes mellitus (GDM) is a risk factor for perinatal complications. In several countries, the criteria for the diagnosis of GDM have been in flux, the American Diabetes Association (ADA) thresholds recommended in 2000 being lower than those of the National Diabetes Data Group (NDDG) that have been in use since 1979. We sought to determine the extent to which infants of women meeting only the ADA criteria for GDM are at increased risk of neonatal complications. Materials and methods In a multiethnic cohort of 45,245 women who did not meet the NDDG criteria and were not treated for GDM, we conducted nested case–control studies of three complications of GDM that occurred in their infants: macrosomia (birthweight >4,500 g, n = 494); hypoglycaemia (plasma glucose <2.2 mmo/l, n = 488); and hyperbilirubinaemia (serum bilirubin ≥342 μmol/l (20 mg/dl), n = 578). We compared prenatal glucose levels of the mothers of these infants and mothers of 884 control infants. Results Women with GDM by ADA criteria only (two or more glucose values exceeding the threshold) had an increased risk of having an infant with macrosomia (odds ratio OR = 3.40, 95% CI = 1.55–7.43), hypoglycaemia (OR = 2.61, 95% CI = 0.99–6.92) or hyperbilirubinaemia (OR = 2.22, 95% CI = 0.98–5.04). Glucose levels 1 h after the 100-g glucose challenge that exceeded the ADA threshold were particularly strongly associated with each complication. Conclusions/interpretation These results lend support to the ADA recommendations and highlight the importance of the 1-h glucose measurement in a diagnostic test for GDM.     

Circulating nitric oxide (NO), asymmetric dimethylarginine (ADMA), homocysteine,and oxidative status in obstructive sleep apnea–hypopnea syndrome (OSAHS)

Obstructive sleep apnea–hypopnea syndrome (OSAHS) with episodic hypoxia–reoxygenation is associated with increased cardiovascular morbidity and mortality. Therefore, increased homocysteine, asymmetric dimethylarginine (ADMA), oxidative status, and decreased nitric oxide levels have been implicated as possible mechanisms for development of cardiovascular diseases. We aimed to investigate changes in the levels of these substances in patients with OSAHS in comparison with nonapneic controls. Thirty-four OSAHS patients and 15 healthy controls were included in this study. In the blood samples, oxidative status and nitric oxide levels were measured with spectrophotometric methods. Plasma ADMA and homocysteine levels were determined by using high-performance liquid chromatography with fluorescence detection. Nitric oxide levels were significantly low in OSAHS patients (p < 0.05) and correlated with mean SaO₂ (r = 0.513, p < 0.002) and lowest SaO₂ (r = 0.363, p < 0.03). Oxidative status, ADMA, and homocysteine levels were higher in OSAHS patients, but difference did not reach statistical significance. After dividing patients into moderate (AHI = 5–29) and severe (AHI ≥ 30) OSAHS groups, significantly increased homocysteine levels were observed in the severe OSAHS group (p < 0.05). Nitric oxide levels negatively correlated with oxidative status in total OSAHS patients (r = −0.415, p < 0.02) and also in severe OSAHS group (r = −0.641, p < 0.007). Hyperhomocysteinemia and diminished NO production may be causal factors in endothelial dysfunction seen in OSAHS and may explain the association between OSAHS and cardiovascular diseases. These modifiable factors should be monitored in patients suspected of having OSAHS.     

Hypoxemia and obesity modulate plasma C-reactive protein and interleukin-6 levels in sleep-disordered breathing

C-reactive protein (CRP) and interleukin-6 (IL-6) are pro-inflammatory proteins and important risk factors for atherosclerosis. Plasma CRP levels in snoring children may or may not be elevated. Since obesity is prevalent among snoring children and is associated with elevated CRP levels, we aimed to investigate the relative contributions of sleep-disordered breathing (SDB) and obesity to the inflammatory processes in snoring children in this prospective study. Two hundred forty-four children (mean age 8.9 ± 3.4 years) underwent polysomnographic evaluation. CRP was measured the following morning, and plasma IL-6 levels from 111 randomly selected children were also examined. Plasma CRP and IL-6 levels were elevated in children with SDB. Log plasma CRP levels were higher in the moderate-severe SDB group (apnea/hypopnea index, AHI ≥ 5) compared to the mild SDB group (AHI ≥ 1 and <5; p < 0.0001) or the control group (AHI < 1; p = 0.0001). Log plasma CRP levels correlated with AHI, arousal index, relative BMI, and SpO₂ nadir (r = 0.30, p < 0.0001; r = 0.21, p = 0.002; r = 0.39, p < 0.0001, r = −0.36, p < 0.0001, respectively). Log plasma CRP levels were lower in children with SpO₂ nadir ≥90 (p < 0.0001). Sub-analysis of the 116 non-obese children in the cohort revealed similar findings. Log plasma IL-6 levels were increased in children with moderate–severe SDB compared to controls (p = 0.03) and correlated with AHI (r = 0.28, p = 0.003) and SpO₂ nadir (r = −0.24, p = 0.02). Children with SDB display significant severity-dependent increases in plasma CRP and IL-6 levels independent of obesity.     

Tryptophan degradation and neopterin levels in treated rheumatoid arthritis patients

Increased kynurenine/tryptophan—reflects trytophan degradation—and neopterin levels have been regarded as a biochemical marker of cell-mediated immune response and inflammation. This study was designed to evaluate the usefulness of tryptophan degradation and neopterin levels in active rheumatoid arthritis patients under therapy. In this case–control study, kynurenine and tryptophan levels were determined by HPLC; neopterin and tumor necrosis factor-α levels were measured with ELISA in 32 active rheumatoid arthritis patients and 20 healthy controls. Although mean values of tryptophan, kynurenine, ratio of kynurenine to tryptophan, neopterin, and tumor necrosis factor-α levels did not show statistically significant differences between patient and control groups, neopterin levels correlated positively with kynurenine (r = 0.582, p < 0.02), kynurenine/tryptophan (r = 0.486, p < 0.05), erythrocyte sedimentation rate (r = 0.472, p < 0.05) and RF (r = 0.478, p < 0.05) in the rheumatoid arthritis group. CRP levels of the patient group correlated with kynurenine levels (r = 0.524, p < 0.03). Determination of tryptophan degradation and neopterin levels in chronic inflammatory disease may provide a better understanding of progression of the disease.