Impaired responses of plasma catecholamines to exercise in diabetic patients with abnormal heart rate reactions to tilt

The plasma catecholamine response to a standardized bicycle exercise test was evaluated in 24 insulin-dependent diabetic (IDDM) patients in whom the heart rate reactions to deep breathing (E/I ratio) and to tilt, the immediate acceleration and the transient deceleration (acceleration and brake indices), had been assessed as tests of autonomic neuropathy. Patients with an abnormal acceleration index (n = 8) showed, compared with non-diabetic (n = 18) controls who had participated in previous studies, an impaired increment in noradrenaline during exercise (80% of maximal working capacity) (MWC) (12.38 +/- 1.46 nmol l-1 vs. 18.74 +/- 1.45 nmol l-1; P less than 0.01) and adrenaline (50% of MWC: 0.25 +/- 0.04 nmol l-1 vs. 0.54 +/- 0.08 nmol l-1; P less than 0.05). Similarly, patients with an isolated abnormal brake index (n = 6), i.e. with a normal acceleration index and a normal E/I ratio, showed compared with controls an impaired increment in noradrenaline (9.53 +/- 1.66 nmol l-1 vs. 18.74 +/- 1.45 nmol l-1; P less than 0.01) and adrenaline (1.41 +/- 0.22 nmol l-1 vs. 2.92 +/- 0.51 nmol l-1; P less than 0.05) during 80% of MWC. IDDM patients with abnormal heart rate reactions to tilt, an abnormal acceleration index or an abnormal brake index show impaired catecholamine responses to exercise, which can be demonstrated also in patients without signs of parasympathetic neuropathy.     

Autonomic and peripheral nerve function in early diabetic neuropathy. Possible influence of a novel aldose reductase inhibitor on autonomic function

Autonomic and peripheral nerve functions as well as the possible short-term effect of a novel aldose reductase inhibitor (ARI) on neuropathy were evaluated in 30 male type I diabetics (age 25-44 years, mean 34; duration of diabetes 10-20 years, mean 34) with neurographic signs of peripheral neuropathy (PN). Autonomic neuropathy (AN) was established by the heart rate reactions to deep breathing (E/I ratio = vagal function) and to tilt (acceleration index = sympathetic and vagal functions; the brake index = vagal function). Twenty-nine patients, 13 with AN, completed the study. Among neurographic variables, only sural nerve function tests correlated with autonomic functions. Patients with AN showed significantly lower mean sensory action potential amplitudes (SAPA) sural, indicating axonal losses, than patients without AN (3.58 +/- 0.79 microV v. 7.34 +/- 1.12 microV; p less than 0.01). PN as measured by neurography did not improve during ARI treatment. On the other hand, vagal function (brake indices) improved (p less than 0.05) during ARI in AN patients.     

Autonomic nerve function tests. Reference values in healthy subjects

Autonomic nerve function was evaluated by deep breathing (E/I heart rate ratio) and tilt table tests (acceleration index, brake index, and blood pressures) in 56 healthy subjects in order to find reference values. The results showed that the E/I ratio, the acceleration index and the brake index fell with increasing age. There was no influence of age on the systolic and the diastolic blood pressure reactions to tilt. Age-related reference values are needed in the evaluation of autonomic neuropathy indices.     

Autonomic neuropathy in type I diabetes: influence of duration and other diabetic complications

To evaluate the influence of duration on the development of autonomic neuropathy (AN) a group of type I diabetic patients (n = 58) who had been diagnosed between the ages of 15 and 25 years was investigated. The duration of diabetes varied from 2 months to 30 years (mean 13 years). AN tests included a deep breathing test (E/I ratio) and an orthostatic test on tilt table (acceleration and brake indices) and the results were corrected for age. A clear correlation between AN test and duration of diabetes was shown only for the E/I ratio (r = -0.44, p less than 0.001). On the other hand, deteriorations in the brake index were unrelated to the duration of diabetes and occurred early; 35% of the patients with a duration of 10 years or less showed an abnormal brake index. Autonomic test deviations were related to other diabetic complications. The E/I ratio and the acceleration index were especially low in patients with retinopathy as well as in patients with symptoms of AN if combined with peripheral neuropathy (PN). The brake index was low in patients with symptoms of AN independent of PN.     

Insulin-like growth factors in pygmies. The role of puberty in determining final stature

We measured the serum concentrations of insulin-like growth factors (IGF) I and II and testosterone in pygmy children, adolescents, and adults, as well as in controls, to determine more precisely the role of these factors in controlling growth. We had previously shown that growth hormone levels were normal in pygmies. Prepubertal pygmy children and controls did not differ in linear growth or in serum concentrations of IGF I and II. In pygmy adolescent boys, the mean (+/- SEM) serum concentration of IGF I was only one third that in control adolescents, who were similar to the pygmies in age and Tanner stage of development (154 +/- 22 vs. 435 +/- 37 ng per milliliter; P less than 0.01). A similar difference in IGF I concentration was observed in girls (278 +/- 18 vs. 570 +/- 25 ng per milliliter; P less than 0.01). IGF II and testosterone levels were normal in all groups. There was a significant difference in growth between controls and pygmies only during puberty. There was a marked acceleration of growth in the controls during adolescence, but such an acceleration was absent or blunted in the pygmies. These findings suggest that the short stature of adult pygmies is due primarily to a failure of growth to accelerate during puberty. We postulate that IGF I is the principal factor responsible for normal pubertal growth and that testosterone does not accelerate growth appreciably in the absence of an increase in the level of IGF I.     

Involvement of central nervous system in patients with diabetes mellitus detected by evoked potentials

Somatosensory (SSEPs) and brainstem auditory evoked potentials (BAEPs) were recorded for 44 patients with diabetes mellitus (age, 63.0 +/- 9.3 years, mean +/- SD) and 20 age-matched healthy controls (age, 67.3 +/- 9.1 years) to elucidate the involvement of the central nervous system (CNS) in diabetes mellitus. Furthermore, relationships between SSEP or BAEP and clinical variables such as autonomic nervous function, peripheral nerve conduction velocity, duration of diabetes, metabolic control (fasting blood sugar level, HbA1 and HbA1c levels) and therapeutic method, were studied. The central conduction time (CCT), which represents the peak latency between N13 and N20, in patients with diabetes mellitus was significantly longer than that of the healthy controls (p less than 0.005). Likewise, diabetic patients showed significant prolongation of interpeak latency between waves I and V (I-V IPL) compared to the healthy controls (p less than 0.005). Significant correlations between CCT and motor conduction velocity of median nerve (p less than 0.05) were observed although the correlation between CCT and sensory nerve conduction velocity was not found to be significant (p less than 0.1). Furthermore, I-V IPL was significantly correlated with the duration of illness (p less than 0.05). There were no significant correlations between CCT or I-V IPL and autonomic nervous dysfunction as determined by orthostatic hypotension and the coefficient variation of the R-R interval or metabolic control or therapeutic method. From the present results, it would appear that there is CNS involvement even in diabetic patients not manifesting overt CNS signs and symptoms and that it is correlated somewhat with impairment of the peripheral nervous system and duration of illness.     

A comparison of childhood and adult type I diabetes mellitus

The incidence rate of insulin-dependent (Type I) diabetes mellitus is bimodal: one peak occurs close to puberty, and the other in the fifth decade. To evaluate possible differences in these forms of the disease, we examined the clinical, biochemical, autoimmune, and genetic features of 82 children and adolescents (1.3 to 18.2 years old) and 44 adults (20.0 to 55.8 years old) when they presented with Type I diabetes. The mean (+/- SEM) duration of symptoms before diagnosis was longer in the adults (7.5 +/- 1.0 vs. 3.9 +/- 0.4 weeks; P less than 0.001), and their serum C-peptide concentrations at diagnosis were higher (0.29 +/- 0.03 vs. 0.17 +/- 0.01 nmol per liter; P less than 0.001), suggesting that they had more residual beta-cell function. There were no significant differences between the two groups in sex ratio, blood glucose levels, hemoglobin A1 values, degree of metabolic decompensation, or frequency of Type I diabetes in first-degree relatives. Thirty-four of 80 children tested (42.5 percent) were positive for insulin autoantibodies, as compared with only 1 of 26 adults (3.8 percent; P less than 0.001). However, the frequencies of islet-cell autoantibodies were similar in the adults and children (conventional autoantibodies, both 81 percent; complement-fixing autoantibodies, 46.2 percent and 60 percent). More children than adults were heterozygous for both HLA-Dw3/4 antigens (26.6 percent vs. 9.8 percent; P less than 0.05) and HLA-DR3/4 antigens (36.6 percent vs. 12.5 percent; P less than 0.05). We conclude that Type I diabetes that begins in adulthood is characterized by a longer symptomatic period before diagnosis, better preservation of residual beta-cell function, and lower frequencies of insulin autoantibodies and HLA-D3/D4 heterozygosity than Type I diabetes that begins in childhood or adolescence.     

Autonomic regulation after exercise evidenced by spectral analysis of heart rate variability in asthmatic children.

BACKGROUND: Bronchial asthma is associated with abnormal autonomic nervous function in childhood. Exercise is one of the most common precipitating factors of acute asthmatic crises although the exact mechanism of autonomic regulation in asthmatic children after exercise is unclear. OBJECTIVE: The aim of this study was to investigate the features of autonomic regulation after exercise in asthmatic and control children. METHODS: Pulmonary function tests and heart rate variability spectral analysis were performed in 15 asthmatic children and 7 control children (age 6 to 15 years) during and after an exercise challenge. RESULTS: The maximum % fall of forced expiratory volume in 1 second (FEV1) was significantly greater (P < .01) in asthmatic subjects (9.1 +/- 5.1%) than in normal control subjects (1.0 +/- 2.5%). The high frequency band (HF) amplitude, an index of cardiac vagal tone, 5 minutes after exercise was significantly higher (P < .05) in the asthmatic subjects (14.4 +/- 7.9 msec) than in control subjects (5.9 +/- 2.6 msec). Furthermore, the difference in the HF amplitude between the control group and the exercise-induced asthma group was significant both 5 minutes (P < .01) and 10 minutes (P < .05) after challenge. There was a significant correlation (P = .565, P = .0165) between HF amplitude 5 minutes after exercise and the magnitude of the decrease in FEV1. On the other hand, no significant difference was observed in the low frequency band amplitude between the controls and the asthmatic subjects. The ratio of low frequency to high frequency power, which is suggested to correlate with cardiac sympathetic activity, did not differ between the two groups. CONCLUSION: These findings suggest that autonomic nervous activities, particularly vagal response after exercise, in asthmatic children is different from that in control children.     

Lack of tocopherol in peripheral nerves of vitamin E-deficient patients with peripheral neuropathy

Vitamin E deficiency is often associated with symptoms of a peripheral neuropathy. To evaluate whether vitamin E deficiency affects the vitamin E content of the peripheral nervous system, we measured the alpha-tocopherol content in biopsy specimens of sural nerve and adipose tissue from 5 patients with symptomatic vitamin E deficiency (2 with homozygous hypobetalipoproteinemia and 3 with familial isolated vitamin E deficiency) and 34 control patients with neurologic diseases without vitamin E deficiency. A significant reduction in tissue tocopherol content was present in the vitamin E-deficient patients, as compared with the controls, both in sural nerves (1.8 +/- 1.2 vs. 20 +/- 16 ng per microgram of cholesterol [P less than 0.001], or 7.7 +/- 5.4 vs. 64 +/- 44 ng per milligram of wet weight [P less than 0.01]) and in adipose tissue (46 +/- 43 vs. 222 +/- 111 ng per milligram of triglyceride [P less than 0.001]). Levels of tocopherol in adipose tissue were significantly correlated (P less than 0.001) with levels in peripheral nerves. The low tocopherol content of the nerves preceded histologic degeneration in three vitamin E-deficient patients, suggesting that the nerve injury resulted from the low nerve tocopherol content.     

Plasma prorenin activity and complications in children with insulin-dependent diabetes mellitus

BACKGROUND. Renin, secreted into the blood by the juxtaglomerular cells of the kidneys, is derived from a larger precursor, prorenin. Plasma prorenin activity is increased in patients with insulin-dependent (Type I) diabetes mellitus who have microvascular complications of their disease. We undertook this study to determine prospectively whether rising prorenin activity can predict the development of complications in young patients with Type I diabetes. METHODS AND RESULTS. Plasma prorenin was measured in 135 children and adolescents with Type I diabetes. The mean (+/- SE) plasma prorenin activity among the 32 patients over the age of 10 years who had had uncomplicated diabetes for 0.1 to 5 years was 8.43 +/- 0.58 ng of angiotensin I per liter.second, as compared with 7.06 +/- 0.32 in 37 control subjects of the same age (P less than 0.05). In the 9 patients older than 10 who had retinopathy or overt albuminuria, the mean plasma prorenin activity was 13.09 +/- 1.43 ng of angiotensin I per liter.second (P less than 0.0001). In 34 patients 10 years old or older with uncomplicated diabetes, 3 to 13 measurements of plasma prorenin activity were taken during a follow-up period of 6 to 39 months. Urinary albumin was determined at each visit, and the patients had regular retinal examinations. Only 1 of the 20 patients who had consistently normal plasma prorenin values had overt albuminuria (ratio of urinary albumin to creatinine, greater than 0.017) or retinopathy, whereas one or both of these complications appeared in 8 of the 14 who had at least one high prorenin value. The plasma prorenin value was significantly higher in these eight patients at least 18 months before a complication was found. CONCLUSIONS. Increased plasma prorenin activity identifies a group of young patients with diabetes who are at high risk for retinopathy or nephropathy.     

Impaired insulin action in puberty. A contributing factor to poor glycemic control in adolescents with diabetes

Patients with insulin-dependent diabetes mellitus often have poor metabolic control during puberty. To determine whether puberty is associated with decreased insulin-stimulated glucose metabolism, we compared the results of euglycemic insulin-clamp studies in adults and prepubertal and pubertal children with and without insulin-dependent diabetes. In nondiabetic pubertal children, insulin-stimulated glucose metabolism (201 +/- 12 mg per square meter of body surface area per minute) was sharply reduced, as compared with that of prepubertal children and adults (316 +/- 34 and 290 +/- 21 mg per square meter, respectively; P less than 0.01), despite comparable hyperinsulinemia (insulin levels of 80 to 90 microU per milliliter). Similarly, the response to insulin was 25 to 30 percent lower in the diabetic pubertal children than in the diabetic prepubertal children (P less than 0.05) and adults (P = 0.07). At each stage of development, the stimulating effect of insulin on glucose metabolism was decreased by 33 to 42 percent in the children with diabetes (P less than 0.01). In all the groups of children studied, the response to insulin was inversely correlated with mean 24-hour levels of growth hormone (r = -0.52, P = 0.01). Among the diabetic children, the glycosylated hemoglobin levels were substantially higher in the pubertal children than in the prepubertal children (P less than 0.02), although the daily insulin doses tended to be higher. These data suggest that insulin resistance occurs during puberty in both normal children and children with diabetes. The combined adverse effects of puberty and diabetes on insulin action may help explain why control of glycemia is so difficult to achieve in adolescent patients.     

Psychological stress and metabolic control in patients with type I diabetes mellitus

Acute psychological stress is believed to cause disturbances of metabolic control in patients with Type I diabetes. To examine the validity of this assumption, we subjected nine healthy persons (mean [+/- SEM] blood glucose level, 74 +/- 2 mg per deciliter), nine patients with Type I diabetes who had normoglycemia (130 +/- 10 mg per deciliter), and nine diabetic patients with hyperglycemia (444 +/- 17 mg per deciliter) to two acute psychological stresses: mental arithmetic and public speaking. Subjects in the three groups were matched for age, weight, sex, and socioeconomic status. For all subjects, the mean increase in heart rate was 20 beats per minute while they were doing mental arithmetic and 25 beats per minute while they were speaking publicly (P less than 0.001). In all three groups, systolic and diastolic pressure rose markedly, the plasma epinephrine level increased by 50 to 150 pg per milliliter, and the norepinephrine level by 100 to 200 pg per milliliter under both stress conditions (P less than 0.001). The plasma cortisol level rose significantly after public speaking in all groups. Neither stress induced changes in circulating levels of glucose, ketones, free fatty acids, glucagon, or growth hormone. Thus, sudden, short-lived psychological stimuli causing marked cardiovascular responses and moderate elevations in plasma concentrations of catecholamines and cortisol are unlikely to disturb metabolic control in patients with Type I diabetes.     

Evaluation of asymptomatic central neuropathy in type I diabetes mellitus

OBJECTIVES: Diabetic neuropathy is recognized as the most common clinical picture of nervous system disorders caused by diabetes mellitus (DM). Although peripheral and autonomic nervous system involvements are frequently encountered, there exists a few data about the incidence of central diabetic neuropathies. Central nervous system degeneration is a well known pathology in diabetic patients in the long term. It is possible to reveal central nervous system involvement at the early stages by using evoked potentials (EP). The aim of this study is to evaluate the auditory, visual and sensorial abnormalities in type I diabetic patients, who also have normal nerve conduction studies, with somatosensory, brainstem auditory and visual EP studies (SEP, VEP BAEP); to determine the frequency of these abnormalities and to investigate the relationship between other variables such as age, gender, duration of the diabetes and degree of the metabolic control. PATIENTS AND METHODS: A total of 36 asymptomatic type I DM children, ages ranging between 6-17 (mean age 11 +/- 3.24) taking insulin treatments were included in this study. Control group was made up of healthy children. EPs were evaluated and comparisons were made between the two groups. RESULTS: In a large group of diabetic children (47.2%), independent from parameters such as age, gender, glycemic control degree, auditory and visual deficits, retinopathy, joint movement limitation; but dependent on the peripheral SEP pathologies and disease duration there were central electrophysiological disturbances. In 13 (36.1%) of the patients SEP pathologies; in 9 (25%) of the patients VEP pathologies and in 14 (38.9%) of the patients BAEP pathologies were detected. Conclusion: Besides independent from peripheral pathologies, central nervous system involvement could also be observed in diabetic children. EP changes can be detected in asymptomatic patients that would be a predictor of future symptoms.     

Increased growth after long-term oral 1alpha,25-vitamin D3 in childhood renal osteodystrophy.

We evaluated oral 1,25-vitamin D3 for as long as 26 months in six prepubescent children with renal osteodystrophy previously treated with vitamin D2. Therapy was given at 14 to 41 ng per kilogram per day to correct hypocalcemia and reverse bone disease. Serum levels of 1,25-vitamin D3 were initially reduced at 15 +/- 5 pg per milliliter (mean +/- S.E.M.) and after treatment rose to 54 +/- 13. Serum calcium rose from 7.5 +/- 1.6 mg per deciliter (mean +/- S.D.) to 9.8 +/- 0.6 after one month (P less than 0.02). Alkaline phosphatase activity fell from 536 +/- 298 to 208 +/- 91 IU per liter after 12 months (P less than 0.05). Serum immunoreactive parathyroid levels fell from 900 +/- 562 microliter eq per milliliter 411 +/- 377. Healing of rickets and subperiosteal erosions was found. Remineralization of bone was demonstrated by the photon absorption technic. In four patients growth velocity, evaluated for 12 months before and after therapy, increased from 2.6 +/- 0.8 to 8.0 +/- 3.2 cm per year. Growth velocity per year increased from less than third percentile in each to the 10th to 97th percentile after therapy. Height increment ranged from 27 to 113 per cent of that expected for change in chronologic age and 40 to 114 per cent expected for change in bone age after therapy. This trial demonstrates that oral 1,25-vitamin D3 can reverse renal bone disease and increase growth in uremic children.     

Serum resistance in Escherichia coli strains causing acute pyelonephritis and bacteraemia.

The capacity of Escherichia coli to resist the bactericidal action of serum was examined in 367 clinical isolates obtained from children with acute pyelonephritis (n = 57), adults with acute pyelonephritis (n = 55), non-diabetic patients with bacteraemia (n = 101), diabetic patients with bacteraemia (n = 65) and from the faecal flora of healthy controls (n = 89). The incidence of serum-resistant E. coli strains was significantly higher in pyelonephritogenic strains from children and adults (93% and 82%) as compared to faecal control strains (57%, p less than 0.001 and p less than 0.005 respectively). Strains causing bacteraemia in non-diabetic and diabetic patients were more often serum resistant (72% and 80%) as compared to control strains (p less than 0.05 and p less than 0.001 respectively). The frequency of serum-sensitive strains was similar in diabetic patients with decreased renal function or proteinuria compared to those with normal renal function. There were no significant correlations between serum resistance of E. coli and expression of P fimbriae, type I fimbriae or mannose-resistant haemagglutination, cell surface hydrophobic properties, production of aerobactin, haemolysin or cytotoxic necrotizing factor in 53 pyelonephritogenic strains from adult patients.     

The influence of type-1 diabetes mellitus on dentition and oral health in children and adolescents

PURPOSE: The present study is to investigate the effects of type 1 diabetes mellitus on dentition and oral health for children and adolescents. MATERIALS AND METHODS: The investigation was carried out on 100 subjects. The first group consisted of 50 subjects with type 1 diabetes mellitus (21 females, 29 males), age 9+/-0.14 years; In the second group, there were 50 healthy subjects who did not suffer from any systemic disease (25 females, 25 males), age 9+/-0.11 years. The subjects were evaluated and divided into two groups of 5-9 years old, and 10-14 years old. The dentition of all participants was examined. Besides, the DFS/dfs index, oral hygiene conditions were evaluated, as well as the plaque index (PI), gingival index (GI) and calculus index (CI). The data obtained from each group were compared statistically. RESULTS: When compared to the non-diabetic group, we observed that dental development was accelerated until the age of 10 in the diabetic group, and there was a delay after the age of 10. The edentulous interval was longer in the group with type 1 diabetes mellitus. This was accompanied by a high ratio of gingival inflammation. Gingival inflammation was 69.7% in the group of 5-9 year-old, and 83.7% in the group of 10-14 year-old with type 1 diabetes mellitus. Though there was a greater loss of teeth in the group with type 1 diabetes mellitus, there were more caries in the control group. The PI, GI and CI values showed an increase with aging in favor of the group with type 1 diabetes mellitus. There was statistically significant difference in PI, GI and CI between the control and type 1 diabetes mellitus groups for 10-14 year-old patients (p<0.001). CONCLUSION: The findings we obtained showed that type 1 diabetes mellitus plays an important part in the dentition and oral health of children and adolescents.     

Left ventricular responses to experimental aortic coarctation in growing puppies.

The haemodynamic status of 8 coarctated and 7 sham-operated beagle puppies was studied by a catheterization technique at rest and during isoproterenol and volume loading at the ages of 7 (I) and 9 (II) months (5 and 7 months after the experimental coarctation). Proximal aortic systolic and pulse pressures were constantly higher in the coarctation group than in the control group (P less than 0.05), and the systolic pressure gradient across the coarctation was always significantly higher in the coarctation group [I at rest mean 45 +/- 5 (SD) vs 5 +/- 4 mmHg, P less than 0.001, and after I isoproterenol infusion 56 +/- 9 vs 10 +/- 6 mmHg, P less than 0.001, and after I dextran infusion 58 +/- 10 vs 8 +/- 7 mmHg, P less than 0.001]. The time constant of exponential isovolumic left ventricular pressure fall after the isoproterenol tests was longer in the coarctation group (I 28 +/- 8 ms and II, 30 +/- 4 ms) than in the control group (I, 21 +/- 2, P less than 0.05 and II, 19 +/- 3 ms, P less than 0.005), indicating impaired relaxation. The tension time index during the volume loading tests increased in the coarctation dogs (I, 4150 +/- 660 and II, 4080 +/- 810 mmHg s min-1) to higher levels than in the control group (I, 3550 +/- 220, II, 2540 +/- 1140 mmHg s min-1, P less than 0.05 both). Cardiac output, left ventricular end diastolic pressure, inotropic parameters and heart rate were similar in both groups during the infusions.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of AS-4370 on gastric motility in patients with diabetic autonomic neuropathy]

Delayed gastric emptying in diabetic patients occurs with progress of automatic neuropathy as one late complication. Delayed emptying is deeply correlated with poor glycemic control, due to imbalance between nutrients absorption and effect of exogenous insulin. AS-4370 is a newly developed prokinetic agent which has been reported to selectively activate motility of the upper gastrointestinal tract through enhancing acetylcholine release from nerve terminals within the enteric mural plexus. In this study, we evaluated the effect of AS-4370 on gastric motility in diabetic patients with autonomic neuropathy. Eight diabetic patients with autonomic neuropathy (3 males and 5 females) with mean age of 56 years old (range 29-66) participated to this study after giving written informed consent. Gastric motility was evaluated by gastric emptying and electrogastrography. Gastric emptying study was done using 99mTc-Tin colloid labeled omelet meal served with 2 slices of toast and 200 ml of milk. Electrogastrography was recorded from epigastric skin surface, for 30 minutes before and after meal each. AS-4370, 7.5 mg tid, was given for four weeks after basal recording of gastric motility studies. Following the 4-week treatment with AS-4370, gastric motility studies were repeated. For the motility studies after medication, drug was given 30 minutes before test meal. Gastric retention rate at 150 minutes in all patients were over 45% of upper limit of normal range in basal study with mean value of 69 +/- 5%, which decreased significantly to 52 +/- 5%, with AS-4370 treatment (p < 0.01). Gastric emptying speed, another parameter for gastric emptying also improved with medication.(ABSTRACT TRUNCATED AT 250 WORDS)     

Spot urine albumin to creatinine ratio and serum cystatin C are effective for detection of diabetic nephropathy in childhood diabetic patients

Spot urinary albumin to creatinine ratio (ACR) measurement has been suggested as a surrogate to 24-hr urine collection for the assessment of microalbuminuria, and cystatin C (cysC) is known as an advantageous marker for renal function. The aim of this study was to evaluate the clinical values of spot urinary ACR and serum cysC for the assessment of diabetic nephropathy instead of 24-hr urine microalbumin in children and adolescents with diabetes. A total of 113 children and adolescents (age 12-19 yr, M:F = 47:66) with type 1 or 2 diabetes were enrolled. We evaluated the validity of spot urine ACR and serum cysC, and then compared them to 24-hr urine microalbumin and creatinine clearance. Spot urine ACR was correlated with 24-hr urine albumin excretion (R(2) = 0.828, P = 0.001) and creatinine clearance (R(2) = 0.249, P = 0.017). The ROC curve analysis of serum cysC demonstrated higher diagnostic accuracy than that of serum creatinine (AUC 0.732 vs 0.615). Both the measurements of spot urine ACR and serum cysC might better predict the presence of diabetic nephropathy than 24-hr urine microalbumin in childhood diabetic patients.     

Age-dependency of left ventricular filling dynamics and relaxation as assessed by pulsed Doppler echocardiography

Left ventricular diastolic function was assessed from transmitral flow velocity curves as measured by Doppler echocardiography in healthy individuals aged 21-69 years, each decade comprising 12 subjects. By ageing, progressive changes in the various filling parameters were observed. When comparing the youngest and oldest age groups, the ratio between peak velocities in early and late diastole decreased from 2.0 +/- 0.3 to 1.2 +/- 0.3 (P less than 0.001). The filling fraction of first third of diastole decreased from 54 +/- 5% to 45 +/- 4% (P less than 0.001). Isovolumic relaxation time increased from 61 +/- 11 ms to 77 +/- 12 ms (P less than 0.01). Correlation coefficients of velocity ratio, filling fraction and isovolumic relaxation time vs. age were r = -0.71 (P less than 0.001), r = -0.56 (P less than 0.001) and r = 0.44 (P less than 0.001), respectively. When isovolumic relaxation time and age were used together in multivariate regression analysis, only age was an independent predictor of velocity ratio and filling fraction. Stroke volume, peak velocity in left ventricular outflow tract, heart rate and systolic blood pressure were similar in all age groups. Thus, velocity ratio and filling fraction indicated a relative filling shift towards late diastole by ageing and were more sensitive than systolic parameters in reflecting age-related changes in cardiac function. The changes could be explained neither by delayed relaxation nor by change in systolic parameters. When using Doppler echocardiography for evaluation of left ventricular filling, age-matching of reference groups is necessary.