Failure and efficacy of insulin therapy in insulin dependent (type I) diabetic patients

Summary In order to determine the degree of metabolic control (HbA_1c [normal<5.8%], mean blood glucose [MBG], glucosuria and lipids) and the prevalence of late diabetic complications in insulin-dependent diabetic patients treated by conventional insulin therapy both patients of a diabetes center (DC: n=130; age 37.1±1.4 years) and a rural area (RA: n=73; age 38.4±2.4 years) were examined within their local setting. Eighty such insulin-dependent diabetic patients were also taught a technique of near normal glycemic insulin substitution (NIS), which separates basal from prandial insulin replacement and instructs the patients to immediately correct self-controlled (3.8±0.1/day) aberrant blood glucose values. None of the groups on conventional insulin therapy was able to achieve satisfactory metabolic control or to avoid late diabetic complications, but rural patients were even worse off (BG 240±10 mg/dl; HbA_1c 8.7±0.2% [normal: 3/73=4%]) than those of the DC (MBG 191±5 mg/dl; HbA_1c 7.1±0.2% [normal: 27/130=21%]), while the prevalence of late diabetic complications was almost identical (RA/DC: neuropathy 22%/25%; retinopathy 41%/38%; macroangiopathy 15%/13%; but proteinuria 14%/5.4%). Metabolic control was improved by NIS with twice daily injections of basal (long acting) and separately of prandial (regular) insulin (total: 4.8±0.1 injections/day; MBG 130±2 mg/dl; HbA_1c 5.8±0.1% [normal: 41/80=51%]. We conclude (1) that conventional insulin therapy just prevents metabolic catastrophe but in more than 79% of insulin-dependent diabetic patients lacks the ability to provide good metabolic control, while (2) NIS, a more physiological form of insulin therapy, improves this deplorable situation 5- to 12.4-fold. Presented in part at the 20th Annual Meeting of the European Association for the Study of Diabetes, London, England, September 12–15, 1984. Supported in part by a grant (#01/0086) of the?sterreichische Forschungsgemeinschaft, and by Novo-Austria. The study was made possible by the generous cooperation of the following general practitioners: Drs I. Avancini, U. Brandl, H. Dabringer, P. Erhart, G. Freerk, F. Geiger, W. Günther, W. J?ger, A. K?hle, R. Lanner, K. Lhotta, F. Menhart, J. Mühlburger, G. Offer, M. Pesendorfer, F. Pistoja, R. Reiger, W. Reiter, K. Schartner, H.J. Somavilla, K. Somavilla, C. Steiger, H. Stocker, J. Tummer, H. Trojer. R. Unterweger, and G. Weg.     

Bacterial antigen-induced release of white cell- and platelet-derived bioactive substances in vitro

Summary Objectives. Poor prognosis after resection of primary colorectal cancer may be related to the combination of perioperative blood transfusion and subsequent development of infectious complications. Various white cell- and platelet-derived cancer-growth substances may be involved in this process. Therefore, we studied the in vitro release of substances from white cells and platelets stimulated by bacterial antigens and supernatants from stored red-cell components. Methods. Eight units of whole blood (WB) and 8 U of buffy-coat-depleted red-cell (SAGM) blood were donated by healthy blood donors. Subsequently, one-half of each unit was leucocyte-depleted by filtration, and all 32 half-units were stored under standard conditions for 35 d. Just after storage, and on d 7, 21, and 35 during storage, aliquots of the supernatants were removed from the units and frozen at −80°C. WB from other healthy donors was stimulated for 2 h with sodium chloride (controls), with Escherichia coli (E. coli) lipopolysaccharide (LPS) alone, or with LPS plus supernatants from the WB units (diluted 1:10), or from the SAGM units (diluted 1:20) stored for 0, 7, 21, or 35 d, respectively. Similar assays were performed using Staphylococcus aureus-derived protein A as a stimulatory antigen. The concentration of eosinophil cationic protein (ECP), myeloperoxidase (MPO), histamine (HIS), and plasminogen-activator inhibitor-1 (PAI-1) were determined in supernatants from the stored blood and in assay supernatants by using enzyme-linked immunosorbent assay (ELISA) and radioimmunoassay (RIA) methods. Results. The extracellular concentration of ECP, MPO, and HIS increased significantly in a storage-time-dependent manner in nonfiltered WB and SAGM blood, and the increase was abrogated by prestorage leukofiltration. Similarly, PAI-1 increased significantly in nonfiltered WB, and the increase was abrogated by prestorage leukofiltration. The supernatant concentrations of the four substances were significantly increased in LPS-stimulated (0.5-4 fold) and in protein A-stimulated (0.5-13.5-fold) assays compared with controls. The addition of supernatants from stored nonfiltered WB or SAGM blood significantly increased the assay supernatant of ECP, MPO, HIS, and PAI-1 concentrations storage--time-dependently in LPS-stimulated assays. Prestorage leukofiltration abrogated the additional effect of supernatants from stored blood. Similar results were observed for ECP and HIS through the addition of supernatants from stored blood to protein A-stimulated assays. Protein A stimulation did not lead to increased PAI-1 release in assays diluted by supernatants from stored blood. However, the MPO concentrations were significantly (p=0.004), and independent of storage time and leukofiltration, increased in protein A-stimulated assays diluted by supernatants from stored blood compared with sodium chloride dilution. Conclusion. Extracellular ECP, MPO, HIS, and PAI-1 accumulate during storage of nonfiltered red-cell components, but the accumulation can be prevented by prestorage leukofiltration. In addition, bacterial antigens appear to induce significant release of the substances from white cells and platelets. Addition of supernatants from stored, nonfiltered WB and SAGM blood may increase the substance levels in a storage-time-dependent manner, and prestorage leukofiltration may prevent further increase by supernatants, except for MPO.     

Persistence of Chlamydia pneumoniae in degenerative aortic valve stenosis indicated by heat shock protein 60 homologues

BACKGROUND AND AIMS OF THE STUDY: Based on the concept of chronic persistent infections with Chlamydia pneumoniae among variable stressors for aortic valve degeneration, the study aim was to assess the presence of chlamydial heat shock protein (cHSP) 60 and its human homologue (hHSP60) in diseased valvular tissue. METHODS: Surgical specimens of high-grade stenosed, native (n = 33) and bioprosthetic (n = 10) aortic valves were examined immunohistochemically for the localization of cHSP60, hHSP60 and macrophages (CD68), supplemented by polymerase chain reaction (PCR) and electron microscopy to prove microbial presence. RESULTS: Degenerated valves showed specific immunostaining of cHSP60 in 27 cases (65%), of hHSP60 in 26 (63%), and of CD68 in 36 (84%). Both HSP60 homologues were predominantly detected in valvular fibrosa, consistently co-localized with macrophages and, quantitatively, showed a strong correlation (r = 0.81, p < 0.001). Presence of C. pneumoniae was demonstrated by PCR in a subset of 11 of 18 valves (61%). Microbial persistence was confirmed by ultrastructural analysis. Degenerated prosthetic valves revealed markedly higher macrophage infiltration and cHSP60 signaling compared with degenerated native valves (each p < 0.05). CONCLUSION: Beyond detection of C. pneumoniae, the present data on co-localization and valvular predilection sites (fibrosa) of both HSP60 homologues indicate the presence of chronic persistent C. pneumoniae infection as well as regional stressor effects, and suggest their involvement in native and prosthetic valve degeneration.     

Marked disproportionality in bone size and mineral,and distinct abnormalities in bone markers and calcitropic hormones in adult turner syndrome: a cross-sectional study

Most women with Turner syndrome (TS) have no gonadal activity and thus lack estrogen. Bone mineral density (BMD) is often reduced, leading to an increased risk of osteoporosis and fractures. However, growth retardation with reduced final height and other endocrine disturbances may compromise interpretation of skeletal measurements. The aim of the present study was to explore skeletal findings, bone metabolism, and calcium homeostasis in TS. Sixty women with TS (age, 37 +/- 9 yr) and 181 normal age-matched female controls were studied. Bone area (A; square centimeters), bone mineral content (BMC; grams), area-adjusted BMD (aBMD; grams/square centimeter), and volumetric BMD (vBMD; grams/cubic centimeter) were measured at lumbar spine, femoral neck, and forearm using dual energy x-ray absorptiometry. Twenty-eight percent had osteopenia, and 23% had osteoporosis, according to World Health Organization criteria. At the lumbar spine, A, BMC, aBMD, and vBMD were reduced by 18, 27, 11, and 6%, respectively; at the femoral neck, A, BMC, and aBMD were reduced by 2, 10, and 8%, respectively, whereas the 9% reduction in vBMD was insignificant (P = 0.07); and in the forearm, A, BMC, and aBMD were reduced by 53, 55, and 9%, respectively. Bone markers indicated an enhanced bone resorption (21 and 23% increase in C-terminal and N-terminal cross-linking telopeptides of type I collagen/creatinine, respectively) with unchanged (osteocalcin, procollagen I N-terminal propeptide) or reduced (54% reduction in bone alkaline phosphatase) bone formation. Plasma levels of calcium and 25-hydroxyvitamin D (26%) were reduced, and PTH levels increased (74%) in TS. IGF-I (30%), IGF binding protein 3 (18%), testosterone (50%), and SHBG (40%) were reduced in TS. In summary, A, BMC, and aBMD were found to be universally reduced in TS, whereas vBMD was slightly reduced in the spine. Increased resorption of bone was present, with normal or blunted bone formation, suggesting uncoupling or imbalance in bone remodeling. Skeletal changes may be induced by chromosome abnormalities or by secondary endocrine or metabolic changes related to a relative estrogen deficiency, testosterone deficiency, reduced IGF-I, low vitamin D status, and secondary hyperparathyroidism.     

A randomized trial of coronary stenting versus balloon angioplasty as a rescue intervention after failed thrombolysis in patients with acute myocardial infarction

OBJECTIVES: This study was conducted to assess whether coronary stenting produces better results compared with balloon angioplasty in patients with acute myocardial infarction (AMI) after failed thrombolysis. BACKGROUND: Little evidence exists on the value of rescue mechanical reperfusion after failed thrombolysis. METHODS: This open-label, randomized study enrolled 181 patients with AMI referred for failed thrombolysis performed within the previous 24 h. The patients had to have a Thrombolysis In Myocardial Infarction (TIMI) flow grade of 相似文献   

Combination Therapy of Active HBsAg Vaccination and Interferon-α in Interferon-α Nonresponders with Chronic Hepatitis B

Treatment with interferon- leads to cessation of viral replication in 30–40% of patients with chronic hepatitis B. Preliminary data suggest that therapeutic vaccination in patients with chronic HBV infection may be beneficial. The present trial was conducted to assess the efficacy of combination therapy of interferon- with HBsAg vaccination in patients who previously failed to respond to interferon- alone. Eighteen patients positive for HBsAg and HBeAg were included. Mean ALT was 81 ± 23 units/liter and 7 (39%) patients had HBV-DNA levels >2000 pg/ml. Patients received 5 million IU interferon- 2b (Intron A) thrice weekly for six months and recombinant HBsAg (Gen H-B-Vax) at the beginning and 4 and 12 weeks after initiation of interferon therapy. No serious side effects were seen during the trial period. Loss of HBeAg was seen in 39% (7/18), HBV DNA was undetectable in 50% (9/18), and ALT was normal in 56% 10/18) of patients six months after completion of therapy. Simultaneous administration of interferon- and HBsAg vaccination in patients previously not responding to interferon alone appears to be safe, well-tolerated, and it achieved response rates similar to or even higher than interferon in treatment naive patients. This combination therapy seems to offer a new and promising approach for patients with chronic hepatitis B virus infection.     

Neurohormones as markers of right- and left-sided cardiac dimensions and function in patients with untreated chronic heart failure

BACKGROUND: It is now well accepted that neuroendocrine activation is of pathophysiological and prognostic importance in patients with chronic heart failure (CHF). We hypothesized that the different neuroendocrine factors reflect different aspects of the cardiac dysfunction in CHF patients and that neuroendocrine profiling could be of value. In order to study this, we investigated the relationship between hormones and cardiac dimensions and function of both the right and left ventricle. METHODS: Twenty-three patients with newly diagnosed, untreated CHF were included. Right (RVEF) and left ventricular ejection fractions (LVEF) and volumes were measured by means of first-pass and equilibrium radionuclide ventriculography. RESULTS: LVEF was 0.29 (range: 0.11-0.55). Two-thirds of the patients had dilated left ventricles with volumes above upper reference limit. Right ventricular ejection fraction was normal in all subjects as well as right ventricular volumes. Likewise, on average, the lung transit time (LTT) was normal. Brain natriuretic peptide (BNP) significantly correlated with LVEF, left ventricular end-diastolic volume index (LVEDVI) and left ventricular end-systolic volume index (LVESVI). Adrenaline correlated significantly with both right ventricular end-diastolic volume index and right ventricular end-systolic volume index. Lung transit time correlated with atrial natriuretic peptide (ANP) and BNP (only ANP in multivariate analysis). CONCLUSIONS: (1) BNP reflects the LVEF as well as diastolic and systolic dimensions; (2) adrenaline reflects the right ventricular systolic and diastolic dimensions; and (3) ANP reflects the lung transit time. We conclude that "neuroendocrine profiling" may potentially be of diagnostic and therapeutic use.