Beneficial Immune Effects of Myeloid-Related Proteins in Kidney Transplant Rejection.

Acute rejection is a risk factor for inferior long-term kidney transplant survival. Although T cell immunity is considered the main effector in clinical acute rejection, the role of myeloid cells is less clear. Expression of S100 calcium-binding protein A8 (S100A8) and S100A9 was evaluated in 303 biopsies before and after transplantation from 190 patients. In two independent cohorts of patients with acute rejection (n = 98 and n = 11; mostly cellular rejections), high expression of S100 calcium-binding protein A8 (S100A8) and A9 (S100A9) was related to improved graft outcome. Mechanisms of action of the S100 molecules were investigated. In the graft and peripheral blood cells, S100A8 and S100A9 expression correlated with myeloid-derived suppressor markers. In line with this finding, recombinant S100A8 and S100A9 proteins inhibited maturation and the allogeneic T cell stimulatory capacity of dendritic cells. S100A9 enhanced the production of reactive oxygen species by macrophages, which suppressed T cell activity at low concentrations in the form of hydrogen peroxide. Intragraft S100A8 and S100A9 expression linked to reduced expression of T cell immunity and tissue injury markers and higher expression of immune regulatory molecules. This study sheds new light on the importance of myeloid cell subsets in directing the outcome of T cell-mediated acute rejection.

[Compartment syndrome caused by rhabdomyolysis in the context of pychogenic polydipsia]. / Kompartmentsyndrom nach Rhabdomyolyse im Rahmen einer psychogenen Polydipsie.

Psychogenic polydipsia leading to severe hyponatremia is well documented in the literature. This electrolyte disorder can result in encephalopathy, cerebral edema and epileptic seizures. Another rare effect is rhabdomyolysis with all its well known complications (e.g. renal failure, hyperkalemia and cardiac arrhythmia) and even resulting in compartment syndrome due to severe muscle edema. We present the case of a patient with severe hyponatremia caused by psychogenic polydipsia leading to rhabdomyolysis and compartment syndrome.

[Patient consent for the TraumaRegistry DGU based on the GDPR-A challenge for the hospitals: status quo and solution strategies]. / Patienteneinwilligungen für das TraumaRegister DGU® aufgrund der EU-Datenschutz-Grundverordnung (EU-DSGVO) ­ Eine Herausforderung für die Kliniken: Status quo und Lösungsstrategien.

According to the General Data Protection Regulation (GDPR 05/2018), anonymized data sets with a sufficiently high data density are classified as traceable and require a declaration of consent if they are evaluated centrally for research or quality control purposes. Quality assurance and further increases in the quality of care are, however, only possible with a nearly complete survey of seriously injured persons in the sense of health services research. The more than 600 German clinics that take part in the TraumaRegistry DGU® try to obtain the declarations of consent from this special patient population. The study clinic evaluated the rate of consent and the reasons for rejection or failure to obtain consent over a 12-month period. While using a resource-intensive workflow especially for patient education and obtaining the consent, a patient consent rate of 64.5% and an error rate of 35.5% were recorded. Of the 276 potential TraumaRegistry DGU® data records 98 could not be entered and were therefore neither available for quality control nor for multiple trauma research. In order to guarantee the quality control and the further improvement of the quality of care, an approximate total recording of the patient population is necessary; however, this cannot be achieved by requiring a declaration of consent. We therefore advocate creating the possibility of collecting the TraumaRegistry data set without consent, as this ultimately represents a standard data set, comparable to the Hospital Remuneration Act (§21-KHEntgG) data set but pseudonymised.

A systematic review and meta-analysis of 30-day readmission rates following burns.

INTRODUCTION: Unplanned hospital readmissions in surgical areas account for high costs and have become an area of focus for health care providers and insurance companies. The aim of this systematic review is to identify the rate and common reasons for unplanned 30-day readmission following burns. METHODS: This study was performed following the PRISMA guidelines. Pubmed, Web of Science and CENTRAL databases were searched for publications without date or language restrictions. Extracted outcomes included 30-day readmission rate and reasons for readmission. Pooled 30-day readmission rate was estimated from weighted individual study estimates using random-effect models. Pooled estimates for risk factors are reported as odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: A total of eight studies were included into qualitative analysis and six (four adults, two children) into quantitative analysis. The overall readmission rate was 7.4% (95% CI 4.1-10.7) in adults and 2.7% (95% CI 2.2-3.2) in children. Based on two studies in 112,312 adult burn patients, burn size greater than 20% total body surface area (TBSA) was not a significant predictor of readmission rate (OR 1.75, 95% CI 0.64-4.75; NS). The most common reasons were infection/sepsis, wound healing complications, and pain in both adults and children. DISCUSSION: Unplanned readmissions following burns are generally low and appear more common in adults than in pediatric patients. However, only few studies are reporting on 30-day readmission rates following burns. Evidence is limited to support a significant association between greater burn size and higher readmission rates. Since cost effectiveness and utilized hospital capacity are becoming an area of focus for improvement in health care, future studies should assess the risk factors of unplanned readmission following burns. Follow-up assessments and outpatient resources, even if not underlined by this data, could reduce readmission rates. SYSTEMATIC REVIEW REGISTRATION: PROSPERO: CRD42019117649.

[Wnt signaling in cutaneous wound healing]. / Wnt-Signalwege bei kutaner Wundheilung.

Human skin is an efficient barrier that protects the organism from noxious substances. Wounds destroy this barrier. Wound healing is a phased physiological regeneration of the destroyed tissue that ideally leads to occlusion of a wound, in particular by regeneration of connective tissue and capillaries. The Wnt signaling pathway is a highly conserved signal transduction cascade across the animal kingdom that controls basic cellular interactions in multicellular organisms. Accordingly, through the Wnt signaling path many processes, e. g. as the balance between proliferation and differentiation or apoptosis, coordinated. Wnt signaling is activated by a wound and participates in each subsequent phase of the healing process, beginning with inflammatory control and programmed cell death, to the mobilization of stem cells within the wound. Endogenous Wnt signaling is an attractive therapeutic approach to assist in the repair of skin wounds, as the complex mechanisms of the Wnt signaling pathway have become increasingly understood over the years. This review summarizes current data to clarify the role of Wnt signaling in the wound healing process of the skin.

The use of the LARS system in the treatment of AC joint instability - Long-term results after a mean of 7.4 years.

BACKGROUND: The acromioclavicular (AC) joint is of great importance for shoulder stability and one of the most frequently injured regions of the shoulder. HYPOTHESIS: AC joint reconstruction with the ligament augmentation & reconstruction system (LARS™) leads to a good-to-excellent outcome at long-term follow-up. PATIENTS AND METHODS: This study was performed as a retrospective single-centre data analysis of a level-I trauma centre. All patients treated operatively for an acute AC dislocation with the LARS™ between 2003 and 2013 were included. RESULTS: The study group consisted of three female (6%) and 44 male patients (94%) with an average age of 37 years and a minimum follow-up of two years. The overall mean clinical outcomes at latest follow-up were: Constant 93, DASH 2.64, ASES 96, SST 97, UCLA 34 and VAS 0.4-representing a good-to-excellent outcome in all patients. Overall, 45 patients (96%) reported to be very satisfied with the achieved result at latest follow-up. In five patients, (11%) complications occurred during the follow-up period, requiring surgical revision in four of the five patients (80%). CONCLUSION: AC joint reconstruction with the LARS™ achieves good-to-excellent clinical and functional outcomes at long-term follow-up with a surgical revision rate of 8.5%. LEVEL OF EVIDENCE: Retrospective follow-up study, case series, level IV.

Depressive symptoms, impaired glucose metabolism, high visceral fat, and high systolic blood pressure in a subgroup of women with recent gestational diabetes.

Women with gestational diabetes (GDM) are a high risk group for early type 2 diabetes (T2D). Depression is a risk factor for T2D in the general population. We investigated in women after a recent pregnancy with GDM and without a clinical diagnosis of depression, whether mild to moderate depressive symptoms associate with pathologic glucose metabolism. In a cross-sectional analysis, we examined 173 women, 9 ± 3 months after delivery with several psychopathological assessments, 5-point oral glucose tolerance test with insulin, anthropometrics, and laboratory chemistry. In a subgroup of 101 women, abdominal visceral fat was quantified by magnetic resonance imaging (MRI). A total of 22 women (13%) showed mild to moderate depressive symptoms, and the proportion of women with pathologic glucose metabolism (impaired fasting glucose, impaired glucose tolerance, or T2D) was higher in this group than in the women without depressive symptoms (59.1% vs. 33.1%, p = 0.018). Women with depressive symptoms also had higher body mass index (BMI), systolic blood pressure, plasma leptin, plasma resistin, and abdominal visceral fat volume. Pathologic glucose metabolism (OR = 2.594, 95% CI: 1.021-6.592), systolic blood pressure (OR = 1.076, 95% CI: 1.027-1.128), and abdominal visceral fat volume (OR = 2.491, 95% CI: 1.142-5.433) remained, even after adjustment for BMI, associated with the presence of depressive symptoms. Taken together, we found depressive symptoms at a level not generally diagnosed in clinical practice in a subgroup of women with recent GDM. This subgroup also showed an unfavorable metabolic profile. Mild to moderate depressive symptoms may therefore help to identify this special subgroup.

Role of epinephrine-mediated beta-adrenergic mechanisms in hypoglycemic glucose counterregulation and posthypoglycemic hyperglycemia in insulin-dependent diabetes mellitus.

Initially euglycemic (overnight insulin-infused) patients with insulin-dependent diabetes mellitus (IDDM), compared with nondiabetic controls, exhibit similar, but somewhat delayed plasma glucose nadirs, delayed glucose recovery from hypoglycemia, and posthypoglycemic hyperglycemia after the rapid intravenous injection of 0.075 U/kg of regular insulin. These abnormalities are associated with and potentially attributable to markedly diminished glucagon secretory responses, partially reduced epinephrine secretory responses and delayed clearance of injected insulin in the diabetic patients. Because glucagon normally plays a primary role in hypoglycemic glucose counterregulation and enhanced epinephrine secretion largely compensates for glucagon deficiency, we hypothesized that patients with IDDM, who exhibit diminished glucagon secretory responses to hypoglycemia, would be more dependent upon epinephrine to promote glucose recovery from hypoglycemia than are nondiabetic persons. To test this hypothesis, glucose counterregulation during beta-adrenergic blockade with propranolol was compared with that during saline infusion in both nondiabetic controls and in patients with IDDM. Glucose counterregulation was unaffected by beta-adrenergic blockade in controls. In contrast, glucose recovery from hypoglycemia was significantly impaired during beta-adrenergic blockade in diabetic patients. This finding confirms the hypothesis that such patients are more dependent upon epinephrine-mediated beta-adrenergic mechanisms to promote glucose recovery from hypoglycemia and indicates that the measured deficiency of glucagon secretion is functionally important in patients with IDDM. Further, in the time frame of these studies, posthypoglycemic hyperglycemia was prevented by beta-adrenergic blockade in these patients. There was considerable heterogeneity among the diabetic patients with respect to the degree to which beta-adrenergic blockade limited the posthypoglycemic rise in plasma glucose. This rise was directly related to the degree of residual glucagon secretion and inversely related to plasma-free insulin concentrations.THUS, WE CONCLUDE: (a) that patients with IDDM are, to varying degrees, dependent upon epinephrine-mediated beta-adrenergic mechanisms to promote glucose recovery from hypoglycemia and that the degree of this dependence upon epinephrine is an inverse function of the residual capacity to secrete glucagon in response to hypoglycemia in individual patients; (b) that sympathoadrenal activation, coupled with the inability to secrete insulin, plays an important role in the pathogenesis of posthypoglycemic hyperglycemia in patients with IDDM.

[Osteosynthesis of displaced fractures of the greater tuberosity with the Bamberg plate]. / Osteosynthese dislozierter Tuberculum-majus-Frakturen mit der Bamberger Platte.

OBJECTIVE: Internal fixation of displaced fractures of the greater tuberosity allowing functional aftercare. INDICATIONS: Displaced fractures of the greater tuberosity >5 mm. Displaced fractures of the greater tuberosity >3 mm in athletes or overhead workers. Multiply fragmented fractures of the greater tuberosity. CONTRAINDICATIONS: Displaced 3­ or 4­part fractures of the proximal humerus. Nondisplaced fractures of the greater tuberosity. SURGICAL TECHNIQUE: Exposure of the fracture of the greater tuberosity by an anterolateral approach. Open reduction and temporary retention with a Kirschner wire or a "Kugelspieß" or reinforcement of the supraspinatus tendon and distal retention. Bending and positioning of the Bamberg plate and fixation by conventional or locking screws. Optional fixation of the rotator cuff to the plate. Exact monitoring of the implant position using the image intensifier to avoid inadequate distalization of the greater tuberosity. POSTOPERATIVE MANAGEMENT: Arm sling (e. g. Gilchrist) for 2 weeks. Start passive assisted exercise on postoperative day 1. Movement allowed up to the pain threshold. Physiotherapeutic treatment to prevent adhesions and capsular shrinking. RESULTS: In all, 10 patients with displaced fractures of the greater tuberosity underwent osteosynthesis using the Bamberg plate. After a follow-up of at least 6 months, a Constant-Murley score of 94.2  points (range 91-98 points) was achieved. The patients' average age was 45.6 years (range 29-68 years).

Studies on lung surfactant replacement in respiratory distress syndrome. Rapid film formation from binary mixed liposomes.

Binary mixed liposomes were prepared from dipalmitoylphosphatidylcholine (DPPC) and a minor compound, e.g., egg phosphatidylglycerol (PG) at a ratio of 9:1. Using different preparative techniques, large unilamellar vesicles (LUV), small unilamellar vesicles (SUV) or multilamellar vesicles (MLV) were obtained and were studied with an electron microscope for morphology, with a Wilhelmy balance for spreading and surface tension lowering potential, and in the surfactant-depleted isolated rat lung for their ability to restore expiratory lung capacity. Only the simultaneous investigation of phospholipids by negative staining and thin sectioning allows unequivocal classification of liposomes. The surface-active structures prepared with the technique of Bangham et al. (Bangham, A.D., Hill, M.W. and Miller, N.G.A. (1974) in Methods in Membrane Biology (Korn, E., ed.), Vol. 1, pp. 1-68, Plenum Press, New York) at room temperature are LUV. LUV containing DPPC:PG at a ratio of 9:1 rapidly spread to a film with high surface tension lowering potential. Within 5 min after injection into the subphase they rise to the surface and form a film at the air/liquid interface able to lower the surface tension to less than 1 mN/m at compression. SUV of the same chemical composition, however, are immediately surface-active only when spread directly onto the surface. MLV exhibit poor surface activity. LUV or pure DPPC, applied onto the surface, are weakly surface active within 5 min. DPPC vesicles injected into the subphase at 37 degrees C do not adsorb to any film with surface tension lowering potential in this time. The minor compounds PE, PI, PS, PA, lysoPC enable DPPC to form surface-active films after application on saline at 37 degrees C. Removal of surfactant decreases the expiratory lung capacity of the isolated rat lung from 49.7 to 12.4% at 4 cmH2O. After substitution with natural surfactant, the expiratory lung capacity is twice that of the washed lung (25.9%), but the original distensibility of the native lung is not restituted. The effect of LUV containing DPPC:PG at a ratio of 9:1 is also remarkable (21.2%).

Isolation from rat adipocytes of a chemical mediator for insulin activation of pyruvate dehydrogenase.

Insulin treatment of adipocytes increased the amount or activity of a low molecular weight, acid-stable material which, when isolated from intact adipocytes by heat extraction and subsequent Sephadex G25 chromatography, yielded a single active fraction that stimulated mitochondrial pyruvate dehydrogenase by activating the phosphatase and not by altering the kinase activity. Phosphatase activation was demonstrated by the ability of the active material to increase pyruvate dehydrogenase activity in the absence of ATP and by the ability of NaF, a phosphatase inhibitor, to this stimulation. Involvement of the kinase in this activation mechanism was eliminated by the fact that, in the presence of ATP, (1) NaF completely blocked the stimulation of pyruvate dehydrogenase by the active fraction, and (2) the stimulation of pyruvate dehydrogenase by dichloroacetic acid, a kinase inhibitor, was additive to the stimulation caused by the active fraction. This active fraction may contain an intracellular chemical mediator or second messenger for insulin.

Calcium ions and the structure of muscle actin filament. An X-ray diffraction study.

In order to investigate the effects of Ca(2+)-binding to troponin on the conformation of the muscle thin filament (consisting of actin, tropomyosin and troponin) in the absence of actomyosin interaction, two series of X-ray diffraction experiments were undertaken. Firstly, the small angle X-ray scattering from filaments in solution indicate the tropomyosin strands are centred at about 3.5 nm from the filament axis and this distance is calcium independent. Secondly, X-ray fibre diffraction patterns from the filaments orientated in glass capillaries were studied. The X-ray intensity of the 2nd actin layer-line increased in a highly co-operative manner at a concentration of free calcium ions [Ca2+] of 10(-6.8) M, which is the range in which muscle contraction is physiologically regulated. However, this intensity increase accounted for some 30% of the total increase observed in diffraction patterns from muscle on activation, suggesting that the Ca(2+)-binding alters the state of the thin filament, which then undergoes further changes upon interaction with myosin.

X-ray diffraction studies on oriented gels of vertebrate smooth muscle thin filaments.

The ATPase activity of acto-myosin subfragment 1 (S1) at low ratios of S1 to actin in the presence of tropomyosin is dependent on the tropomyosin source and ionic conditions. Whereas skeletal muscle tropomyosin causes a 60% inhibitory effect at all ionic strengths, the effect of smooth muscle tropomyosin was found to be dependent on the ionic strength. At low ionic strength (20 mM) smooth muscle tropomyosin inhibits the ATPase activity by 60%, while at high ionic strength (120 mM) it potentiates the ATPase activity three- to five-fold. Therefore, the difference in the effect of smooth muscle and skeletal muscle tropomyosin on the acto-S1 ATPase activity was due to a greater fraction of the tropomyosin-actin complex being turned on in the absence of S1 with smooth muscle tropomyosin than with skeletal muscle tropomyosin. Using well-oriented gels of actin and of reconstituted specimens from vertebrate smooth muscle thin filament proteins suitable for X-ray diffraction, we localized the position of tropomyosin on actin under different levels of acto-S1 ATPase activity. By analysing the equatorial X-ray pattern of the oriented specimens in combination with solution scattering experiments, we conclude that tropomyosin is located at a binding radius of about 3.5 nm on the f-actin helix under all conditions studied. Furthermore, we find no evidence that the azimuthal position of tropomyosin is different for smooth muscle tropomyosin at various ionic strengths, or vertebrate tropomyosin, since the second actin layer-line intensity (at 17.9 nm axial and 4.3 nm radial spacing), which was shown in skeletal muscle to be a sensitive measure of this parameter, remains strong and unchanged. Differences in the ATPase activity are not necessarily correlated with different positions of tropomyosin on f-actin. The same conclusion is drawn from our observations that, although the regulatory protein caldesmon inhibits the ATPase activity in native and reconstituted vertebrate smooth muscle thin filaments at a molar ratio of actin/tropomyosin/caldesmon of 28:7:1, the second actin layer-line remains strong. Only adding caldesmon in excess reduces the intensity of the second actin layer-line, from which the binding radius of caldesmon can be estimated to be about 4 nm. The lack of predominant meridional reflections in oriented specimens, with caldesmon present, suggests that caldesmon does not project away from the thin filament as troponin molecules in vertebrate striated muscle in agreement with electron micrographs of smooth muscle thin filaments. In freshly prepared native smooth muscle thin filaments we observed a Ca(2+)-sensitive reversible bundling effect.(ABSTRACT TRUNCATED AT 400 WORDS)

Refinement of the F-actin model against X-ray fiber diffraction data by the use of a directed mutation algorithm.

The F-actin model has been refined by a Directed Mutation Algorithm, a reiterative procedure which combines a Monte-Carlo method of selecting subdomains to be refined at each cycle with a non-linear least-squares routine to get the best fit for the particular selected domains. The G-actin crystal structure was used as a starting model. The experimental data were obtained by X-ray fiber diffraction patterns from oriented F-actin gels. After 250 cycles we were able to obtain an almost perfect fit of the calculated diffraction pattern to the experimental diffraction pattern as well as a reasonable stereochemistry including intermolecular interactions of the actin monomers with an r.m.s. shift in the C alpha-positions of 3.2 A from the crystal coordinates. The stereochemistry of the intersubunit packing was calculated by molecular dynamics using the program X-PLOR. In addition, the binding site of phalloidin, a cyclic heptapeptide from the mushroom Amanita phalloides, could be determined. Furthermore, we were able to determine differences in the structures of F-actin with and without phalloidin. The method proved itself robust and showed a high degree of convergence.

Methods of preparing well-orientated sols of f-actin containing filaments suitable for X-ray diffraction.

In this paper we describe methods of preparing orientated f-actin and reconstituting thin filaments that are suitable for X-ray diffraction that allow us to analyse the structure of f-actin to at least 15 A resolution (1 A = 0.1 nm). We described problems that occur during the process of orientation and ways of solving them.

An atomic model of the unregulated thin filament obtained by X-ray fiber diffraction on oriented actin-tropomyosin gels.

We present a model of the actin-tropomyosin complex in which the radial and azimuthal position of tropomyosin was adjusted to fit the X-ray fiber diffraction patterns from oriented actin-tropomyosin gels at a resolution of 1/8 A-1. We used the recently published atomic F-actin model for the calculations. The atomic model of tropomyosin was obtained by model-building a coiled coiled-coil structure from the tropomyosin sequence. The resulting atomic model is strongly preferred and shows strong electrostatic interactions between charged side-chains of tropomyosin residues and actin residues in subdomain 3 and subdomain 4. Furthermore, calculations of enthalpies based upon electrostatic interactions indicate that there is a favored rotational position of the tropomyosin core at the calculated azimuthal and radial position given by the X-ray refinement. Rotations of the tropomyosin strand out of this position turn strongly attractive electrostatic interactions into repulsive forces. The resulting binding radius of 39 A and the determined azimuthal position of tropomyosin are in good agreement with electron microscopy reconstructions and neutron diffraction experiments. Furthermore, the calculated position of tropomyosin would still partly block the rigor interaction of myosin cross-bridges with actin, whereas it very likely allows undisturbed binding of the cross-bridges in a weak binding state.

Hyperkalemia and hyperglycemic increments in plasma potassium in diabetes mellitus.

The frequency of persistent or intermittent hyperkalemia in patients with diabetes is unknown. In 405 predominantly insulin-treated patients, major hyperkalemia was not common (< 5.0 mEq/L in 2.5%). In ten insulin-treated patients sampled hourly from 8 AM through 8 PM, major intermittent hyperkalemia was not detected (< 4.8 mEq/L in all samples). However, mean plasma potassium values paralleled mean glucose values; these variables were significantly correlated in seven of ten patients. In contrast, there were no relationships between plasma potassium and plasma free insulin, glucagon, epinephrine, or norepinephrine values. We conclude that (1) hyperkalemia--fasting or intermittent--does not occur commonly in patients with diabetes, and (2) hyperglycemia, but not insulin or epinephrine lack or glucagon excess, appears to be a direct determinant of plasma potassium but is not a sufficiently potent determinant to commonly produce clinically important hyperkalemia in insulin-treated diabetic patients.

Hypoglycemia due to serum-complexed insulin in a patient with diabetes mellitus.

A 28-year-old woman with insulin-dependent diabetes mellitus presented with a "hyperlabile" state of hyperglycemia and ketoacidosis alternating with hypoglycemia. Measurements of total and free insulin levels suggested that the clinical syndrome may have been due to antibody binding of insulin. Equilibrium analysis of insulin binding to the patient's serum demonstrated two classes of anti-insulin activities. The first class was of high affinity (dissociation constant approximately equal to 10(-9) M) and low capacity (150 microU/ml). At low total serum insulin concentrations, most of the circulating insulin was bound to the high-affinity binding activity, and the patient presented with hyperglycemia or ketosis. The second class of insulin binding activity had a lower affinity (dissociation constant approximately equal to 5 X 10(-7) M). The insulin that was bound to this low-affinity serum substance still maintained biologic activity in vivo. Isophane insulin (NPH) had a markedly prolonged serum half-life, which resulted in delayed hypoglycemia. Serum insulin complexes--that is, bound insulin--may not be "inactive" but may contribute to total insulin action. A determination of insulin activity, not only free insulin levels, may help explain hypoglycemia in selected patients with diabetes mellitus.

Oral propranolol and metoprolol both impair glucose recovery from insulin-induced hypoglycemia in insulin-dependent diabetes mellitus.

To the extent that they have deficient glucagon secretory responses to plasma glucose decrements, as they commonly do, patients with insulin-dependent diabetes mellitus (IDDM) are dependent on epinephrine-mediated beta-adrenergic mechanisms to promote recovery from hypoglycemia. Thus, they are at increased risk for prolonged hypoglycemia if treated with a nonselective beta-adrenergic antagonist such as propranolol. If the hyperglycemic actions of epinephrine are mediated through beta 2-adrenergic mechanisms, therapeutic efficacy (e.g., for hypertension or ischemic heart disease) could be accomplished without increased risk of hypoglycemia by selective beta 1-adrenergic blockade in such patients. However, oral administration of the relatively selective beta 1-adrenergic antagonist metoprolol (100 mg) and of the nonselective beta-adrenergic antagonist propranolol (80 mg) both impaired recovery from insulin-induced hypoglycemia in patients with IDDM. Thus, at a dose of 100 mg, oral metoprolol is not safer than oral propranolol with respect to recovery from hypoglycemia in patients with IDDM.