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Biomedical subjects

C Binder

Publications and source records attributed to C Binder.

At least 37 records · Page 2Linked to original sources
PubMed1990

[Immunosuppression with cyclosporin induces clinical remission and improved beta cell function in patients with newly diagnosed insulin-dependent diabetes. A national and international multicenter study].

A prospective, randomized, double-blind, placebo-controlled international multicenter trial including 188 newly diagnosed insulin-dependent diabetic (IDDM) patients was undertaken with the aim of investigating whether immunosuppression for one year with ciklosporin (Cs) could induce and maintain clinical remission and improvement of beta-cell function. The relative odds for non-insulin-requiring remission at one year were increased approximately five times in the Cs-treated group. After three months Cs-treated patients achieved more than a doubling of beta-cell function compared to baseline than did placebo-treated patients, and the Cs-treated group maintained this improvement in beta-cell function for 12 months, whereas the placebo-group lost beta-cell function during the same period. Short duration of disease (less than or equal to six weeks of symptoms, less than or equal to two weeks of insulin treatment) was associated positively with remission, as was an elevated proinsulin/C-peptide ratio, especially in patients with the tissue-type HLA-DR 3,4; 4,X and X,X. Cs-treatment inhibited the formation of antibodies against insulin and islet cell components, but islet cell antibody status at entry was not predictive of remission. Cs-treatment caused a reversible decrement of kidney function as measured with serum creatinine and the calculated creatinine clearance, but studies of renal physiology and kidney biopsies performed on a limited subset of patients indicated that Cs treatment in IDDM patients for one year induced a slight chronic nephropathy in some of these.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1990

Monitoring of blood glucose concentration in subjects with hypoglycaemic symptoms during everyday life.

OBJECTIVE: To study the persistence of hypoglycaemic symptoms, changes in blood glucose concentrations, and the relation between reported symptoms and measured blood glucose values in functional hypoglycaemia. DESIGN: Re-evaluation of symptoms in patients admitted consecutively with suspected hypoglycaemia followed by a case-control study. SETTING: The Steno Memorial Hospital in Gentofte, Denmark, which specialises in the diagnosis and treatment of and research on endocrine disorders, including hypoglycaemia. PATIENTS: 21 Subjects admitted consecutively with hypoglycaemic symptoms that were relieved by eating in whom insulinoma and other organic disorders presenting with hypoglycaemia had been ruled out. Twelve of these subjects with persistent symptoms entered the case-control study, as did a matched control group. INTERVENTIONS: Four days of monitoring blood glucose concentrations at home, six daily samples being taken in fixed relation to meals by the finger prick method. Extra samples were taken when symptoms occurred. MAIN OUTCOME MEASURES: Blood glucose concentration, glycated haemoglobin concentration, and within subject variation in measured values. RESULTS: After one to three years of observation 19 of the 21 subjects still had symptoms. Six out of 12 subjects experienced hypoglycaemic symptoms during the controlled study. Blood glucose concentration ranged from 3.7 mmol/l to 7.5 mmol/l during these episodes. Changes in blood glucose concentration, mean blood glucose concentrations at each time point, within subject variation in the measured values, and glycated haemoglobin concentration were not significantly different in all patients compared with the control subjects and in patients with symptoms during the study compared with controls. CONCLUSION: Hypoglycaemic symptoms during everyday life in apparently healthy subjects are persistent but are not related to chemical hypoglycaemia.

Adult↗
PubMed1990

Proinsulin and C-peptide at onset and during 12 months cyclosporin treatment of type 1 (insulin-dependent) diabetes mellitus.

An increased proinsulin to C-peptide molar ratio at the onset of Type 1 (insulin-dependent) diabetes mellitus has been suggested. We studied fasting proinsulin levels and proinsulin/C-peptide ratios in the newly diagnosed diabetic subjects participating in the Canadian/European placebo controlled cyclosporin study at entry, during the one year treatment period and six months of follow-up. Available entry data from 176 out of the 188 allocated patients were compared to 60 age and weight matched control subjects. Fasting proinsulin was significantly elevated in male patients compared to male control subjects (p less than 0.01), whereas the levels only tended to be elevated in female patients. The proinsulin/C-peptide ratio was three to fourfold elevated in the diabetic groups of both sexes, (p less than 0.001). Further, proinsulin and C-peptide were studied in 83 cyclosporin and 86 placebo-treated subjects during the trial and follow-up. An additional increase of proinsulin/C-peptide ratio was observed during the first three months of placebo treatment. It remained constantly high for nine months and then declined to entry level. This pattern was not seen in the cyclosporin-treated group, where the ratio was unchanged during the 12 months trial and follow-up. The effect of cyclosporin on the induction of non-insulin requiring remission was unrelated to fasting and glucagon stimulated C-peptide levels at entry, whereas 64% of the cyclosporin-treated against 28% of the placebo-treated subjects (p less than 0.01) went into remission if the proinsulin/C-peptide ratio at entry was above 0.024.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Effects of dexamethasone on glucose-induced insulin and proinsulin release in low and high insulin responders.

We compared the effects of dexamethasone-induced insulin resistance on B-cell secretory performance in 12 low insulin responders (LIR) and in eight high insulin responders (HIR). A hyperglycemic clamp (120 minutes) was performed before and after the subjects had ingested dexamethasone 3 mg x 2 for 2 1/2 days. Fasting levels of blood glucose increased from 4.60 +/- 0.13 to 5.74 +/- 0.23 mmol/L after dexamethasone in LIR and from 4.37 +/- 0.18 to 5.26 +/- 0.13 mmol/L in HIR. Dexamethasone treatment increased fasting levels of total immunoreactive insulin (IRI), C-peptide, and proinsulin, as well as the proinsulin to IRI ratio to a similar degree in LIR and HIR. The amount of glucose infused to uphold hyperglycemia during the clamp decreased by 54% after dexamethasone in LIR and by 46% in HIR. Mean level of stimulated IRI during the clamp increased after dexamethasone by 43% in LIR and by 53% in HIR. Mean level of stimulated C-peptide increased by 11% (not significant) in LIR and by 24% in HIR. Mean level of stimulated proinsulin increased by 86% in LIR and by 93% in HIR. The effects of dexamethasone on insulin secretion varied among individuals, since steroid treatment failed to affect IRI responses to glucose in two LIR and two HIR. The magnitude of dexamethasone effects on secretion was not correlated to pre-dexamethasone insulin sensitivity as assessed by a somatostatin-insulin-glucose infusion test (SIGIT) or by M/I (glucose infused/insulin level) ratios of the control clamp.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

The relationship between symptomatic and biochemical hypoglycaemia in insulin-dependent diabetic patients.

The relationship between symptomatic (subjective feelings) and biochemical (blood glucose concentration less than 3 mmol l-1) hypoglycaemia was studied in 66 randomly selected insulin-dependent diabetic out-patients under normal conditions of daily life with conventional insulin injection regimens. The patients (a) collected 7-point diurnal blood glucose profiles at home on three consecutive days and then once weekly for 3 weeks, (b) indicated whether they felt hypoglycaemic at sampling times, and (c) collected extra samples if they felt hypoglycaemic at any time during the study period. The weekly frequencies of symptomatic and biochemical hypoglycaemia were 0.99 and 1.75 per patient, respectively. Biochemical hypoglycaemia was present in 29% of the symptomatic episodes, and symptomatic hypoglycaemia accompanied 16% of the biochemical episodes. Symptomatic hypoglycaemia was experienced at a median blood glucose concentration of 3.4 mmol l-1 (range 1.4-14.9 mmol l-1). Fifty per cent of both symptomatic and biochemical episodes occurred before lunch, while the remainder were evenly distributed throughout the day. The occurrence of biochemical hypoglycaemia, but not of symptomatic hypoglycaemia, was inversely correlated with HbA1c and median blood glucose concentration. Thus symptomatic hypoglycaemia is an unreliable indicator of biochemical hypoglycaemia and of the degree of glycaemic control. Blood glucose measurements are a prerequisite for the diagnosis of hypoglycaemia.

Adult↗
PubMed1990

Acute actions of sulfonylurea drugs during long-term treatment of NIDDM.

The acute effect of sulfonylurea drugs during long-term treatment was evaluated in two separate studies. In the first study, the levels of plasma glucose, insulin, and C-peptide were measured after intake of 10 mg glyburide alone or together with a standardized mixed meal in 10 non-insulin-dependent diabetes mellitus (NIDDM) patients treated with 10-20 mg glyburide/day for greater than 2 yr. There was no acute effect of glyburide on the insulin and C-peptide responses to the meal or during continued fasting, indicating the absence of an acute insulinotropic action of glyburide during chronic treatment. The glucose increase after the meal was also unchanged, but a significant glucose reduction was found after glyburide intake during continued fasting, suggesting a sustained acute extrapancreatic (hepatic) effect. In the second study, the diurnal glycemic excursions in 8 NIDDM patients chronically and continuously (24 h/day) exposed to glipizide (2.5-7.5 mg 3 times/day) were similar when the drug was taken 30 min before each of the three main meals and when taken immediately before the meals. It is concluded that there is no acute insulinotropic action of sulfonylurea drugs during chronic continuous exposure, whereas an acute extrapancreatic action may prevail. During such exposure, there seems to be no clinical benefit in taking a sulfonylurea 30 min before rather than at the start of a meal.

Aged↗
PubMed1989

[Hypoglycemic effects of equimolar quantities of semisynthetic human and porcine insulin in insulin-dependent diabetic patients].

In some diabetic patients, transition from porcine insulin (PI) to human insulin (HI) has resulted in alterations or non-appearance of the usual hypoglycaemic symptoms. The authors have, therefore, undertaken a double-blind cross-over trial with induction of hypoglycaemia with semisynthetic HI and PI administered in equimolar quantities to eight insulin-dependent men. Prior to induction of hypoglycaemia, the blood glucose (BG) was stabilized at approximately 6 mmol/l. At the time 0, the BG was 5.9 (5.4-7.1) mmol/l and 6.2 (4.8-7.1) mmol/l (NS), BS-nadir was 2.1 (1.3-2.9) mmol/l and 2.1 (1.3-2.8) mmol/l PI versus HI. At the time -15 minutes and at BG-nadir, assessment of symptoms and neuropsychological testing were performed. The total symptom scorings were identical for the two types of insulin, the maximum intraindividual difference was +1 on a scale from 0 to 3. Cognitive function was reduced significantly in hypoglycaemia with no differences for the types of insulin. The conclusion is that, in insulin-dependent diabetic patients, no differences in hypoglycaemic effects were observed between PI and HI after intravenous administration of equimolar quantities.

Adult↗
PubMed1989

Glucocorticoid receptors in monocytes in type 1 diabetes mellitus.

Glucocorticoid receptor binding characteristics were investigated in 8 males with poorly controlled Type 1 diabetes mellitus and 14 healthy males. The cell type studied was monocytes, and a method for correction for heterogeneity in glucocorticoid binding in a mononuclear leucocyte population was introduced. The number of receptors and the dissociation constant KD were, respectively, 13,699 and 2.93 X 10(-8) mol/l for the control group and 15,788 and 2.75 X 10(-8) mol/l for diabetics (p greater than 0.05). In diabetics, KD correlated negatively with blood glucose (r = 0.762, p less than 0.05) indicating an increased sensitivity to cortisol at high blood glucose levels. In 6 of the diabetics and 7 of the control group, a simultaneous insulin receptor study was carried out. However, glucocorticoid receptor binding characteristics did not correlate with insulin receptor binding characteristics or with HbA1c. In conclusion, no major abnormalities in glucocorticoid receptor binding characteristics could be demonstrated in Type 1 diabetes mellitus.

Adult↗
PubMed1989

Modeling absorption kinetics of subcutaneous injected soluble insulin.

Absorption of subcutaneously injected soluble insulin deviates markedly from simple first-order kinetics and depends both on the volume and concentration of the injected solution. This paper presents a model of the absorption process in which insulin is presumed to be present in subcutis in a low molecular weight form, a high molecular weight form, and an immobile form where the molecules are bound to the tissue. The model describes how diffusion and absorption gradually reduce the insulin concentrations in the subcutaneous depot and thereby shift the balance between the three forms in accordance with usual laws of chemical kinetics. By presuming that primarily low molecular weight insulin penetrates the capillary walls, the model can account for experimentally observed variations in the absorption rate over a wide range of volumes and of concentrations. The model is used to determine the effective diffusion constant D for insulin in subcutis, the absorption rate constant B for low molecular weight insulin, the equilibrium constant Q between high and low molecular weight insulin, the binding capacity C for insulin in the tissue, and the average life time T for insulin in its bound state. Typical values for a bolus injection in the thigh of fasting type I diabetic patients are D = 0.9 x 10(-4) cm2/min, B = 1.3 X 10(-2)/min, and Q = 0.13 (ml/IU)2. Binding of insulin in the tissue is significant only at small concentrations. The binding capacity is of the order of C = 0.05 IU/cm3 with a typical average life time in the bound state of T = 80.0 min. Combined with a simplified model for distribution and degradation of insulin in the body, the absorption model is used to simulate variations in plasma free insulin concentrations with different delivery schedules, i.e., bolus injection and dosage by means of an infusion pump. The simulations show that a pump repetition frequency of 1-2 per hr is sufficient to secure an almost constant plasma insulin concentration.

Absorption↗
PubMed1989

Plasma zinc concentrations during the first 2 years after diagnosis of insulin-dependent diabetes mellitus: a prospective study.

Studies of zinc status in insulin-dependent diabetes mellitus (IDDM) have shown contradictory results. Zinc is essential for many enzymes involved in the human metabolism and may play a role in the biosynthesis and storage of insulin in the B-cell. We therefore prospectively followed 26 patients (14 males and 12 females) with newly diagnosed IDDM in order to determine the plasma zinc variation at the time of diagnosis and after 1, 3, 6, 12 and 24 months. Seventy-two healthy persons (36 males and 36 females) served as controls. Only minor differences in plasma zinc were demonstrated during the first 2 years of IDDM. A sex difference was found in healthy controls but only after 24 months in the diabetics. Quantitative changes of the B-cell function, development of insulin antibodies, age, body weight and serum albumin did not correlate with the course of plasma zinc.

Adolescent↗
PubMed1989

Clinical manifestations of respiratory tract infections due to respiratory syncytial virus and rhinoviruses in hospitalized children.

From September 1984 to May 1986, nasopharyngeal secretions were obtained from 519 children with some form of respiratory tract infection. The nasal secretions were screened for respiratory syncytial virus (RSV), rhinoviruses, adenoviruses, parainfluenza virus types 1, 2, 3, influenza virus types A and B, and enteroviruses by tissue culture virus isolation technique and/or enzyme-linked immunosorbent assay. A uniform questionnaire gave information about age, sex, individual signs and symptoms, findings of the physical examination and clinical diagnosis of the patients. RSV was detected in 119 (23%) specimens and was thus the most frequent causative agent of respiratory infections. After RSV, rhinoviruses were the most frequently recovered pathogens accounting for 60 (12%) cases of acute respiratory disease. A comparison of the individual signs and symptoms, the findings of the physical examination and the clinical diagnosis of RSV and rhinovirus infected children revealed that there was no characteristic clinical pattern associated with either of the two viral respiratory pathogens. According to our results, rhinovirus infections were a major cause of lower respiratory tract infections in hospitalized children less than or equal to 3 years old.

Child, Preschool↗
PubMed1989

Elevated proinsulin in healthy siblings of IDDM patients independent of HLA identity.

Based on the recent demonstration of elevated serum proinsulin levels in cystic fibrosis patients with impaired glucose tolerance, it was hypothesized that proinsulin could be an indicator of altered beta-cell function. We therefore analyzed fasting proinsulin levels in 99 siblings of insulin-dependent diabetes mellitus (IDDM) patients, most of them discordant for diabetes for greater than 6 yr. The results from this group were compared with the results from 41 healthy age- and sex-matched control subjects with no family history of diabetes. Median (range) fasting proinsulin in siblings was 8.9 pM (1.7-58 pM) vs. 3.8 pM (less than 1.2-28 pM) in control subjects (P less than .00001). There was no difference between the groups in fasting blood glucose concentrations. Both groups had fasting insulin concentrations within the normal range with a tendency toward lower values in the siblings: 108 pM (60-237 pM) vs. 118 pM (71-175 pM) (P = .07). The 99 siblings were subdivided into groups according to HLA sharing with their diabetic proband. The concentration of proinsulin, insulin, and blood glucose among the groups of 33 HLA-identical, 40 HLA-haploidentical, and 26 nonidentical siblings did not differ significantly. The fasting proinsulin level did not correlate with fasting levels of insulin, blood glucose, age, or body weight. We conclude that fasting proinsulin is elevated in healthy siblings of IDDM patients, whereas fasting insulin is normal or slightly decreased independent of HLA identity with their diabetic sibling. Elevated proinsulin levels could represent a family trait, perhaps mirroring a beta-cell more vulnerable to destruction, or it could reflect previous beta-cell damage that does not lead to IDDM.

Adolescent↗
PubMed1989

Hypoglycemia in IDDM.

Hypoglycemia causes substantial morbidity and some mortality in insulin-dependent diabetes mellitus (IDDM). It is often the limiting factor in attempts to achieve euglycemia. The prevention or correction of hypoglycemia normally involves both dissipation of insulin and activation of glucose counterregulatory systems. Among the latter, glucagon plays a primary role initially, whereas epinephrine is not critical, although it becomes critical when glucagon is deficient. Growth hormone and cortisol play demonstrable roles in recovery from prolonged hypoglycemia. Glucose autoregulation may be involved in defense against severe hypoglycemia. With respect to pathophysiology, counterregulatory systems are involved in at least five clinical glucoregulatory syndromes. Defective glucose counterregulation is associated with, and best attributed to, combined deficiencies of the glucagon and epinephrine responses to plasma glucose decrements. Almost assuredly in concert with hypoglycemia unawareness, it results in a markedly increased frequency of severe hypoglycemia, at least during intensive therapy of IDDM. Defined as a night to morning increase in plasma glucose concentration, the dawn phenomenon is thought to result from dissipation of insulin plus the effects of nocturnal growth hormone secretion. Despite a sound rationale, the clinical relevance of the Somogyi phenomenon has been recently questioned. The clinical impression of altered glycemic thresholds for symptoms, i.e., patients with poorly controlled IDDM suffer symptoms of hypoglycemia at relatively high plasma glucose levels, whereas those with very well-controlled IDDM often tolerate subnormal glucose levels, has received experimental support. Clearly, hypoglycemia in IDDM is a problem that needs to be solved. Numerous issues need to be addressed through both basic and clinical research.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Glucose↗
PubMed1988

Glycaemic threshold for changes in electroencephalograms during hypoglycaemia in patients with insulin dependent diabetes.

The relation between blood glucose concentration, the symptoms and signs of hypoglycaemia, and electroencephalographic changes in diabetic patients is not known. The effect of hypoglycaemia on brain function was studied in 13 patients with insulin dependent diabetes. During a gradual fall in blood glucose concentration induced by a bolus injection of insulin followed by an intravenous infusion of insulin, during 60 minutes of biochemical hypoglycaemia, and after restoration of normoglycaemia with intravenous glucose electroencephalograms were evaluated continuously by period-amplitude analysis; blood samples were taken every 10 minutes throughout. No changes were seen in electroencephalograms when the blood glucose concentration was above 3 mmol/l. At a median blood glucose concentration of 2.0 (95% confidence interval 1.7 to 2.3) mmol/l alpha activity decreased abruptly in the electroencephalograms concomitant with an increase in theta activity, reflecting neuronal dysfunction in the cortex. When the blood glucose concentration was further lowered changes were observed in the electroencephalograms indicating that deeper brain structures were affected. A normal electroencephalogram was re-established at a blood glucose concentration of 2.0 (1.8 to 2.1) mmol/l. There was no significant correlation between the blood glucose concentration at the onset of changes in the electroencephalograms and age, duration of diabetes, insulin dose, haemoglobin A1c concentration, initial blood glucose concentration, rate of fall in blood glucose concentration, and appearance of symptoms and signs of hypoglycaemia. Changes in electroencephalograms during hypoglycaemia appear and disappear at such a narrow range of blood glucose concentrations that the term threshold blood glucose concentration for the onset of such changes seems justified.

Adult↗
PubMed1988

Contribution of rhinoviruses to respiratory viral infections in childhood: a prospective study in a mainly hospitalized infant population.

A prospective study was carried out to investigate the contribution of rhinoviruses to respiratory viral infections in children and to investigate the influence of age, passive smoking, and educational level of the head of the family on the clinical course of viral respiratory disease. Nasopharyngeal aspirates from 519 infants (90.8% inpatients, 9.2% outpatients) were screened for the presence of rhinoviruses, respiratory syncytial virus (RSV), adenoviruses, parainfluenza virus types 1, 2, 3, influenza virus types A and B, and enteroviruses by tissue culture isolation procedure, enzyme-linked immunosorbent assay, and/or indirect immunofluorescence method. The total detection rate was 42.4%. The rate decreased with increasing age. Higher detection rates were observed in specimens from children suffering from a more severe respiratory disease, and the highest rate of virus-positive specimens was found in those aged 0-6 months. Second to RSV (23.1%), rhinoviruses were the most frequently recovered pathogens found in 11.8% of children with acute respiratory tract infections (RTI). In the age group 0-6 months the majority of severe respiratory illnesses was due to RSV. In infants aged 6 months to 1 year a decrease in the number of severe illnesses caused by RSV and an increase in the number of children suffering from a more severe RTI caused by rhinoviruses was found. With the possible exception of one group of children infected with rhinoviruses, a negative effect of passive smoking on the incidence and severity of viral RTI could not be established. A beneficial effect of breast feeding on the severity of viral RTI could not be definitely demonstrated.

Austria↗
PubMed1988

Insulin autoantibodies are associated with islet cell antibodies; their relation to insulin antibodies and B-cell function in diabetic children.

Blood was drawn from 74 children, 3-16 years old, at diagnosis of Type 1 (insulin-dependent) diabetes and before the first insulin injection. Insulin autoantibodies were detected with a polyethylen-glycol-method in 27/74 (36.4%) and with an immuno-electrophoretic method in 6/74 (8.1%). Islet cell cytoplasmic antibodies detected by indirect immuno-fluorescence were found in 49/74 patients (66.2%), who included as many as 23 of the 27 patients with insulin autoantibodies determined with the polyethylen-glycol-method (p less than 0.01). The proportion of insulin autoantibody-positive patients who developed insulin antibodies during the first 9 months of insulin treatment was not significantly greater (51.8%) than that of insulin autoantibody-negative patients (44.6%), but patients with both islet cell antibodies and insulin autoantibodies at diagnosis produced more insulin antibodies during the first 9 months (p less than 0.05). There was no difference in fasting or meal stimulated serum C-peptide after 3, 9 or 18 months as related to occurrence of insulin autoantibodies and/or islet cell antibodies. The correlation between insulin autoantibodies and islet cell antibodies indicates that both types of autoantibodies reflect the same immunological process, although the lack of correlation to C-peptide may indicate that they play a minor causal role. In addition, the results show that patients with an active autoimmune process evidently tend to produce more insulin antibodies during the first months of insulin treatment, but the islet cell antibodies and insulin autoantibodies-positive patients had at least as good residual B-cell function as patients without autoantibodies at diagnosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Autoantibodies↗
PubMed1988

Incidence of nocturnal hypoglycaemia in insulin-dependent diabetic patients on intensive therapy.

The frequency of nocturnal hypoglycaemia, i.e. blood glucose concentration (BG) less than 3.0 mmol/l, was evaluated in consecutively selected insulin-dependent patients on multiple insulin injections (MII), n = 23, or continuous subcutaneous insulin infusions (CSII), n = 25. Blood was sampled hourly from 23.00 to 07.00. Seven patients (30%) on MII had at least one BG less than 3.0 mmol/l during the night. Eleven patients (44%) on CSII had hypoglycaemia (NS). The total number of BGs less than 3.0 mmol/l was higher on CSII, 42 of 225, versus 16 of 207 on MII (p less than 0.025). The duration of hypoglycaemia was 2 hours (range 1-6) on MII and 4 hours (range 1-7) on CSII with a maximal prevalence at 4 hours and between 5 and 7 hours, respectively (p = less than 0.05). The frequency of nocturnal hypoglycaemia is high in patients on intensified insulin regimens. Nocturnal hypoglycaemia occurs later in the night and is of longer duration on CSII than on MII. HbA1c, BG before bedtime and in the morning might be useful in the evaluation of nocturnal hypoglycaemia.

Adult↗