Fasting C-peptide and Related Parameters Characterizing Insulin Secretory Capacity for Correctly Classifying Diabetes Type and for Predicting Insulin Requirement in Patients with Type 2 Diabetes.

BACKGROUND/AIMS: C-peptide allows estimation of insulin secretion even in the presence of insulin treatment. C-peptide may be suitable for the differential diagnosis of type 1 and type 2 diabetes, and, within type 2 diabetes, of insulin-requiring vs. non-insulin-requiring patients. Relating C-peptide concentrations to ambient glucose levels might improve its diagnostic potential. PATIENTS/METHODS: The diagnostic value (a) fasting C-peptide, (b) C-peptide/glucose ratios, and (c) the HOMA-ßC-peptide-index for predicting a diagnosis of type 1 (vs. type 2) diabetes were assessed. SETTING: Specialised hospital for the care of diabetic patients (inpatient treatment). 303 patients with type 1 diabetes and 841 patients with type 2 diabetes. MAIN OUTCOME MEASURE: Odds ratios and 95% confidence intervals for a clinical diagnosis of type 1 diabetes or for insulin treatment by deciles of (a) fasting C-peptide, (b) C-peptide/glucose ratios, and (c) HOMA-ßC-peptide-index. RESULTS: Low C-peptide concentrations were associated with a high odds ratio for type 1 diabetes and vice versa (p<0.0001). Concentrations of 0.13-0.36 nmol/l did not discriminate. C-peptide/glucose ratios or HOMA-ßC-Peptide did not perform better. The ability of all 3 parameters to predict the necessity for insulin treatment within the population of type 2-diabetic patients was low. CONCLUSIONS: Fasting C-peptide and derived parameters help to differentiate type 1 from type 2 diabetes, but there is a range of C-peptide concentrations that does not help discriminate. Relating C-peptide to glucose did not improve diagnostic accuracy. C-peptide does not help predicting a need for insulin treatment in patients with type 2 diabetes.

Anti-inflammatory drugs reduce age-related decreases in brain volume in cognitively normal older adults.

Previous studies have indicated a decreased risk for developing Alzheimer's disease in anti-inflammatory (AI) drug users. Yet few studies have determined whether AI drug use provides a protective effect against normal age-related changes in the brains of older adults. Regional volume changes in gray and white matter were assessed cross-sectionally using optimized voxel-based morphometry in 36 females taking AI drugs as arthritis or pain medication and 36 age- and education-matched female controls. Although mean gray and white matter volume differences between AI drug users and the non-AI group were small, AI drug use interacted with age, such that the non-AI group showed significantly greater age-related volume changes in regions of both gray and white matter compared to the AI drug users. These regions included the superior and medial frontal gyri, middle and inferior temporal gyri, fusiform and parahippocampal gyri, and occipital gray matter as well as temporal, parietal, and midbrain white matter. The results are consistent with the notion that AI drugs provide protection against age-related changes in brain volume. It is possible that inflammation plays a role in volume decreases associated with normal aging, and that suppressing the inflammatory response moderates this decrease.

Beta-trace protein as sensitive marker for CSF rhinorhea and CSF otorhea.

OBJECTIVE: Beta-trace protein concentrations in cerebrospinal fluid (CSF), serum and nasal secretions are investigated with a new quantitative, immunonephelometric assay. RESULTS: The mean beta-trace concentration of normal lumbar CSF (18.4 mg/l) and normal serum (0.59 mg/l), from n = 132 control patients, were 10% higher than reported earlier for smaller control groups. The reference range of beta-trace protein in nasal secretions is very low (median: 0.016 mg/l, range <0.003-0.12 mg/l, for n = 29 controls). Clinically confirmed cases of CSF rhinorhea (n = 20) showed beta-trace concentrations between 0.36 and 53.6 mg/l, with a median of 2.4 mg/l. We propose a cut-off value of 0.35 mg/l above which a CSF contamination in the secretion is plausible. A clinically confirmed CSF otorhea had a value of 1.75 mg/l. CONCLUSION: This new beta-trace protein assay offers a fast, sensitive and reliable routine method to detect a CSF rhinorhea or otorhea.

Intrinsic properties of muscle satellite cells are changed in response to long-term selection of mice for different growth traits.

Satellite cell cultures were derived from mice selected long-term over 70 generations for body weight (DU-6, growth), carcass protein amount (DU-6P, protein) and an index combining body weight and endurance treadmill performance (DU-6+LB, growth + fitness) at 42 days of age and from an unselected control line (DU-Ks). They were grown under identical environmental conditions to examine intrinsic cellular differences in proliferation, protein metabolism and responsiveness to growth factors. Growth kinetics (DNA and protein amounts) were determined over a 12-day period. During exponential growth, all growth-selected cultures grew faster than the control culture: (DU-6+LB=DU-6P)>DU-6>DU-Ks. The differences in DNA and protein levels were maintained until day 8. DU-Ks cultures reached similar levels as the growth (DU-6) and protein (DU-6P) cultures in terms of DNA at day 12 of cultivation. Thus, the cultures from the growth and protein lines, but not from the growth + fitness line, exhibited larger protein:DNA ratios (cell size) than the control cultures. Cell cultures from the selected lines were more responsive to serum and epidermal growth factor in terms of [(3)H] thymidine incorporation into DNA, whereas no stimulation by insulin or insulin-like growth factor-I was detectable in cultures from selected lines or controls. During differentiation, protein metabolism in cultures from selected lines was characterised by higher rates of protein synthesis (PS) and degradation (PD), as measured by [(3)H] phenylalanine incorporation or release, respectively, than in control cells. The ratios of the relative differences from the control in PS and PD were only >1.0 in the growth and protein lines. In conclusion, long-term selection for growth therefore modifies the intrinsic capability of satellite cells for proliferation and protein metabolism, with changes being dependent on the selection trait.

Relevance of variants in serum antiproteinases for the course of chronic pancreatitis.

BACKGROUND: Mutations of the pancreatic serine protease inhibitor, Kazal type 1 (SPINK1), the cationic trypsinogen (PRSS1) and the cystic fibrosis transmembrane conductance regulator (CFTR) were reported to be genetic risk factors of chronic pancreatitis (CP). The aim of this study was to determine the role of genetic variants of the main serum antiproteinases alpha-1-antitrypsin (AAT) and alpha-2-macroglobulin (A2M) for the course of chronic pancreatitis. METHODS: 124 patients with non-alcoholic chronic pancreatitis (with PRSS1 or SPINK1 mutations or idiopathic pancreatitis) and 64 healthy controls were investigated for the AAT mutations PiS and PiZ, and the PiM determining variants R101H, V213A, E376D. In 101 subjects, the 'bait region' of A2M was sequenced. A pentanucleotide deletion in the bait region of A2M was analysed in 147 chronic pancreatitis (CP) patients and 87 controls. RESULTS: The lowest prevalences of V213A and E376D were found in PRSS1 patients, whereas an increased rate of these mutations was present in the SPINK1 group, and the highest prevalence was found in patients with idiopathic pancreatitis. The prevalence of PiM variants was higher in patients with early onset CP than in late onset (P < 0.05 for E376D). The coding region of the bait region of A2M was of wild type in all investigated subjects. The A2M pentanucleotide deletion showed a homogenous distribution in patients and controls. CONCLUSIONS: Our study suggests a moderating, but not predominant, role of AAT variants in the course of chronic non-alcoholic pancreatitis.

Human stoned B interacts with AP-2 and synaptotagmin and facilitates clathrin-coated vesicle uncoating.

Synaptic vesicle biogenesis involves the recycling of synaptic vesicle components by clathrin-mediated endocytosis from the presynaptic membrane. stoned B, a protein encoded by the stoned locus in Drosophila melanogaster has been shown to regulate vesicle recycling by interacting with synaptotagmin. We report here the identification and characterization of a human homolog of stoned B (hStnB). Human stoned B is a brain-specific protein which co-enriches with other endocytic proteins such as AP-2 in a crude synaptic vesicle fraction and at nerve terminals. A domain with homology to the medium chain of adaptor complexes binds directly to both AP-2 and synaptotagmin and competes with AP-2 for the same binding site within synaptotagmin. Finally we show that the mu 2 homology domain of hStnB stimulates the uncoating of both clathrin and AP-2 adaptors from clathrin-coated vesicles. We hypothesize that hStnB regulates synaptic vesicle recycling by facilitating vesicle uncoating.

Apoptotic signaling during initiation of detachment-induced apoptosis ("anoikis") of primary human intestinal epithelial cells.

Apoptosis after the loss of cell anchorage--"anoikis"--plays an important role in the life cycle of adherent cells. Furthermore, loss of anchorage dependency is believed to be a critical step in metastatic transformation. The aim of this study was to further characterize the sequence of intracellular events during anoikis in a nontransformed population of human intestinal epithelial cells (IECs). Purified human IECs were kept in suspension to induce anoikis in over 90% of IECs within 3 h. Two initiator caspases, caspase-2 and -9, are activated within 15 min, followed by the hierarchical activation of downstream caspases within 1 h. The activation of the caspase FLICE (caspase-8) does not contribute to the initiation of anoikis, and massive release of cytochrome c from mitochondria cannot be detected before 60 min, indicating that cytochrome c release does not play a role during initiation of anoikis. This study delineates the signaling cascade during anoikis of nontransformed cells. Future studies may identify alterations of this cascade in neoplastic cells, thereby possibly gaining insight into carcinogenesis and metastatic transformation.

Single-dose pharmacokinetics of repaglinide in subjects with chronic liver disease.

Repaglinide is a novel insulin secretagogue developed in response to the need for a fast-acting, oral prandial glucose regulator for the treatment of type 2 (non-insulin-dependent) diabetes mellitus. Repaglinide is metabolized mainly in the liver; its pharmacokinetics may therefore be altered by hepatic dysfunction. This open, parallel-group study compared the pharmacokinetics and tolerability of a single 4 mg dose of repaglinide in healthy subjects (n = 12) and patients with chronic liver disease (CLD) (n = 12). Values for AUC and Cmax were significantly higher in CLD patients compared with healthy subjects, and the MRT was prolonged in CLD patients. Values for tmax did not differ between the groups, but t1/2 was significantly prolonged in CLD patients compared with previously determined values in healthy subjects. AUC was inversely correlated with caffeine clearance in CLD patients but not in healthy subjects. Blood glucose profiles were similar in both groups. Adverse events (principally hypoglycemia) were similar in the two groups; none was serious. Repaglinide clearance is significantly reduced in patients with hepatic impairment; the agent should be used with caution in this group.

Prevalence and determinants of house dust mite allergen in East German homes.

BACKGROUND: In 1990/91, allergic sensitization to house dust mites (HDM) and other allergens was more prevalent in children from West Germany than from East Germany. OBJECTIVE: To test the hypothesis that low indoor exposure to HDM allergen in East Germany has contributed to this difference. METHODS: HDM allergen concentrations were determined in 634 East German dwellings shortly after the German reunification. RESULTS: HDM group I allergen (Der p 1 + Der f 1) levels in mattresses (median 2.16, geometric mean 2.07, maximum 278.9 microg/g dust) and carpets (median 0.41, geometric mean 0.48, maximum 96.3 microg/g dust) were within the range of levels determined in West Germany in other studies. One particular East German type of dwelling (light concrete buildings) was associated with lower mite allergen exposure, but only a minority of the population lived there. Coal heating, installed in the majority of dwellings before 1989, was associated with higher allergen exposure. Higher relative humidity (RH) was a main risk factor for higher Der p 1 exposure (odds ratio [OR] for exposure to > 0.05 microg/g dust on carpets: 1.4 [95% confidence interval (CI) 1.2-1.8] for + 10% RH) but not for higher Der f 1 exposure. Higher temperature was associated with a lower risk for elevated Der p 1 levels (> 0.05 microg/g dust on carpets): OR 0.6 (95% CI 0.5-0.8) for + 2 degrees C. CONCLUSION: Mite allergen exposure is not lower in East Germany than in West Germany. The data does not support the hypothesis, that low HDM allergen exposure in East Germany is a cause for the lower prevalence of HDM sensitization in East German children.

[Amalgam separators: nearly half are defective! The results of a survey]. / Séparateurs d'amalgame: près de la moitié sont défectueux! Résultats d'enquête.

By means of a questionnaire sent to 1615 dentist practices in 9 Lander of the former West Germany, a survey has been organized of the efficiency of amalgam separators, which had been made compulsory on 1 January 1990. Only 51% seems to be operating without any defaults. The frequency and the nature of the defaults, as well as the cost-price of the repairs have been analysed per type of separator. Separator noise and vibrations are due to the construction. Erroneous sensor signals are contributed to insufficient sealing. Sometimes there is the sensor sensitivity to foaming blood. In order to keep the maintenance related defects to a minimum, the manufacturers have tightened the maintenance instructions up to an unrealistic level. The dentists wonder whether the reliability of these expensive tools (worth an average of 75,000 BF) cannot be improved. More in particular, they demand more reliable electronic sensors, and the rotor as receptacle is only found satisfactory in limited practice circumstances. There is a demand for polyvalent, more reliable amalgam separators.

[Environmental problems in dentistry]. / Milieuproblemen in de tandartspraktijk.

The materials used to treat dental patients endanger the environment. The most important polluting materials are the heavy metals, in particular mercury. The sulphides are of lesser importance and the other chemically active and infected materials are almost harmless. The gathering and discharging of most of these materials, preferably by own initiative, does not pose any problems. The removal of amalgam from the sewage however, requires a specific apparatus.

[Technology and progress in the use of information systems in the dental office]. / Technologie und Fortschritt von Informationssystemen in der zahnärztlichen Praxis.

The numerous DP systems used in dental offices are designed for administrative work. Data storage and management is limited to accountancy applications, and the advantages of the flow of information are restricted to operational purposes. Data of medical use are available only to a moderate extent. It should be possible, however, to use these information systems for processing purely medical data, for the structured input of comprehensive diagnostic information, and to have these data available for specific decisions. The use of a "decision-supporting system" has been tested in the documentation of dental diagnostic findings.

Unreliability of oxygen tension-based indices in reflecting intrapulmonary shunting in critically ill patients.

Measurement of intrapulmonary shunting (Qsp/Qt), a widely used method for monitoring disturbances of pulmonary oxygen transfer in critically ill patients, involves calculation of arterial and mixed venous oxygen contents. In circumstances where mixed venous blood samples are not readily available, oxygen tension-based indices such as the alveolar to arterial oxygen tension differences (P[A-a]O2), arterial oxygen tension to alveolar oxygen tension ratio (PaO2/PAO2), PaO2 to FIO2 ratio (PaO2/FIO2) and respiratory index (RI) are widely utilized to reflect Qsp/Qt. Oxygen content-based indices such as the estimated shunt are not as widely utilized as the oxygen tension indices. In 75 critically ill patients in whom a pulmonary artery catheter was being utilized to augment clinical care, comparisons were made between Qsp/Qt and P(A-a)O2, PaO2/PAO2, PaO2/FIO2, RI, and estimated shunt to determine which index best reflected Qsp/Qt. Correlations between Qsp/Qt and estimated shunt were good (r = .94) and poor for the P(A-a)O2 (r = .62), PaO2/PAO2 (r = .72), PaO2/FIO2 (r = .71), and RI (r = .74). We conclude that there are no real substitutes for venous oxygen contents in critically ill patients. When pulmonary artery blood is not available for analysis, oxygen tension-based indices are unreliable reflectors of Qsp/Qt while the estimated shunt, an oxygen content-based index, provides a more reliable reflection of Qsp/Qt.