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Biomedical subjects

D Ziegler

Publications and source records attributed to D Ziegler.

At least 73 records · Page 4Linked to original sources

Effects of previous glycaemic control on the onset and magnitude of cognitive dysfunction during hypoglycaemia in type 1 (insulin-dependent) diabetic patients.

To determine whether the degree of previous glycaemic control may modify cognitive responses to hypoglycaemia, the glycaemic thresholds for, and magnitude of cognitive dysfunction as assessed by P300 event-related potentials as well as subjective and hormonal responses during hypoglycaemia were evaluated. Hypoglycaemia was induced by intravenous insulin infusion in 18 Type 1 (insulin-dependent) diabetic patients, 7 of whom were strictly controlled (HbA1c: 6.3 +/- 0.3%; mean +/- SEM; Group 1) and 11 of whom were poorly controlled (HbA1c: 9.1 +/- 0.4%; Group 2). Within 60 min, mean blood glucose declined from 5.6 and 5.7 mmol/l (baseline) to a nadir of 1.6 and 1.8 mmol/l followed by an increase to 5.6 and 4.3 mmol/l after 120 min in Group 1 and 2, respectively. There was no significant difference between the groups in regard to P300 latency at baseline, but between 50 and 70 min a significant prolongation of this component was noted in Group 2 as compared with Group 1 at blood glucose levels between 1.6 and 2.3 mmol/l (p less than 0.05). The glycaemic thresholds at which a significant increase of P300 latency over baseline was first noted were 1.6 +/- 0.2 mmol/l in Group 1 and 3.5 +/- 0.2 mmol/l in Group 2 (p less than 0.05). The glucose thresholds at which this prolongation was no longer demonstrable were 1.9 +/- 0.1 mmol/l in Group 1 and 3.8 +/- 1.4 mmol/l in Group 2, respectively (p less than 0.05). The glycaemic threshold at which the P300 amplitude was first significantly reduced was 2.2 mmol/l in Group 2, whereas no such reduction was observed in Group 1.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Septicemia in 980 patients at a university hospital in Berlin: prospective studies during 4 selected years between 1979 and 1989.

A total of 980 episodes of clinically and bacteriologically proven septicemia were included in four prospective 1-year studies at a 1,300-bed university hospital in Berlin between 1979 and 1989. The incidence was 8.1 per 1,000 admissions. The percentage of patients with severe underlying diseases increased significantly from 67% to 95% over the decade. Septicemia due to gram-positive bacteria decreased from 47.3% in 1979 to 43.7% in 1986 and increased again to 51.2% in 1989. Septicemia due to gram-negative organisms decreased constantly from 45.0% in 1979 to 39.8% in 1989. The most frequently isolated species were Escherichia coli (26.4%), Staphylococcus aureus (18.9%), coagulase-negative staphylococci (10.2%), enterococci (7.7%), viridans streptococci (6.4%), Klebsiella species (5.5%), and pneumococci (5.0%). The overall mortality rate decreased significantly from 33.6% in 1979 to 20.8% in 1989. Mortality for episodes of septicemia due to gram-positive bacteria (25.5%) was higher than that for septicemia due to gram-negative bacteria (18.3%). Mortality rates associated with polymicrobic and fungal septicemia were higher than the overall mortality rate.

Bacteremia↗

Assessment of cardiovascular autonomic function: age-related normal ranges and reproducibility of spectral analysis, vector analysis, and standard tests of heart rate variation and blood pressure responses.

To establish normal ranges for assessment of autonomic dysfunction, a battery of cardiovascular reflex tests was performed in 120 healthy subjects aged 15-67 years using a computer-based technique. Tests of heart rate variation (HRV) included 8 measures at rest: coefficient of variation (CV), root mean squared successive difference (RMSSD), spectral analysis of HRV in the low frequency, mid frequency, and high frequency bands in the supine and standing postures; 5 measures during deep breathing: CVb, RMSSDb, Expiration-Inspiration (E-I) difference, E/I ratio, and mean circular resultant of vector analysis; Valsalva ratio, and max/min 30:15 ratio. In addition, the change in systolic and diastolic blood pressure in response to standing and the diastolic blood pressure response to sustained handgrip were determined. The results of all measures, the blood pressure tests excepted, declined significantly with increasing age (r = -0.16 to -0.59; p less than 0.05). Moreover, RMSSD, RMSSDb, and E-I difference decreased considerably with increasing heart rate (r = -0.37 to -0.52; p less than 0.001). The longest and shortest R-R intervals in response to standing were distributed within beats 21-39 and 6-24, respectively. All tests were independent of sex. Log transformation was used to define the age-related lower limits of normal at the 2.3 centile for all tests of HRV, except for the E/I, Valsalva, and max/min 30:15 ratios. The results of these tests had to be analysed using a log(y-1) transformation. The intra-individual reproducibility determined on two consecutive days in 20 healthy subjects and 21 diabetic patients indicated that there were no major differences between the two groups regarding the day-to-day variation of test results, which was highest for the Valsalva ratio. We conclude that: (1) all indices of spectral and vector analyses of HRV are age-dependent and have the advantage of being independent of heart rate; (2) RMSSD, E-I difference, and the 30:15 ratio as it was used previously are not suitable for evaluation of autonomic dysfunction in diabetes; (3) log(y-1) transformation is required to determine age-dependent normal ranges and reproducibility for the three ratios.

Adolescent↗

Prevalence of cardiovascular autonomic dysfunction assessed by spectral analysis, vector analysis, and standard tests of heart rate variation and blood pressure responses at various stages of diabetic neuropathy.

To establish a test battery for the detection and characterization of cardiovascular autonomic neuropathy (CADN) and to evaluate its prevalence, a number of autonomic function tests based on spectral analysis, vector analysis, and standard tests of heart rate variation and blood pressure responses were performed in 261 diabetic patients aged 11-76 years with various stages of peripheral neuropathy. The percentages of abnormal results in the individual tests based on heart rate variation were 6-31% in 115 patients without peripheral neuropathy, 16-45% in 61 patients with subclinical neuropathy, 22-59% in 73 patients with symptomatic peripheral neuropathy, and 67-100% in 12 patients with the latter in conjunction with autonomic symptoms (p < 0.05). The most frequently abnormal indices, each representing a different physiological basis, were the coefficient of variation, low-frequency and mid-frequency power spectrum at rest, mean circular resultant, postural change in systolic blood pressure, and, in particular, the max/min 30:15 ratio and Valsalva ratio. CADN, defined as the presence of > or = 3 abnormalities among these seven parameters was detected in none of 120 control subjects, 13.0% of the patients without peripheral neuropathy, 34.4% of those with subclinical neuropathy, 49.3% of those with symptomatic peripheral neuropathy, and in 100% of the subjects with the latter and concomitant autonomic symptoms (p < 0.05). The overall prevalence of CADN in 103 patients completing all parameters was 46.6%. The corresponding rate of CADN defined as > or = 2 abnormalities among the five tests included in an optimized version of the battery proposed by Ewing and Clarke was 38.8%.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Prevalence of cardiovascular autonomic dysfunction assessed by spectral analysis and standard tests of heart-rate variation in newly diagnosed IDDM patients.

OBJECTIVE: To determine the prevalence of cardiovascular autonomic nerve dysfunction in patients with newly diagnosed insulin-dependent diabetes mellitus (IDDM) compared with healthy nondiabetic subjects. RESEARCH DESIGN AND METHODS: A battery of cardiovascular reflex tests was performed in 130 newly diagnosed IDDM patients aged 12-40 yr at mean blood glucose levels of 7.2 mM after insulin had been administered for 3-39 days. Age-dependent lower limits of normal of these tests were defined at the 2.3 percentile in 120 nondiabetic subjects. Tests of heart-rate variation (HRV) included the coefficient of variation (C.V.) and the low-frequency (LF), midfrequency (MF), and high-frequency (HF) bands of spectral analysis at rest, HRV during deep breathing (C.V., expiratory-inspiratory ratio, and mean circular resultant), Valsalva ratio, and maximum/minimum 30:15 ratio. In addition, spectral analysis on standing, the change in systolic blood pressure to standing, and diastolic blood pressure response to sustained handgrip were determined in 50 patients. RESULTS: A significantly higher percentage of abnormal test responses in the diabetic group compared with the control group was noted for power spectrum in the LF band (7.3 vs. 0.8%, P less than 0.05) and MF band (10.6 vs. 0%, P less than 0.001) at rest and HF band on standing (10.0 vs. 0.9%, P less than 0.05), maximum/minimum 30:15 ratio (25.4 vs. 5.0%, P less than 0.001), and Valsalva ratio (17.5 vs. 4.2%, P less than 0.001). There were no significant differences between both groups in regard to the remaining parameters. Ten (7.7%) diabetic patients but none of the nondiabetic subjects had cardiovascular autonomic neuropathy defined by the strict criterion of abnormal results in more than three of six tests (P less than 0.001). In addition, 12 (9.2%) patients but only 2 (1.7%) control subjects had abnormal results in two of six tests (P less than 0.01). CONCLUSIONS: Cardiovascular autonomic nerve dysfunction is relatively common in newly diagnosed IDDM patients after correction of the initial metabolic imbalance. A combination of tests based on spectral and conventional analysis of HRV appears suitable for detection of early abnormalities in autonomic function in diabetes.

Adolescent↗

Age- and sex-specific incidence rates of migraine with and without visual aura.

Age- and sex-specific incidence rates for the onset of migraine headache with and without preceding visual aura were estimated from a population-based telephone interview survey conducted between March 1986 and June 1987 of 10,169 randomly selected residents of Washington County, Maryland, between the ages of 12 and 29 years. A total of 392 males and 1,018 females were identified as having a history of migraine. Of these, 27% of male cases and 28% of female cases were defined as having migraine with visual aura. Among both males and females, the incidence rate for migraine with visual aura appears to have peaked as much as 3-5 years earlier than the age peak for migraine without aura. For males, the age-specific incidence for migraine with visual aura appears to have peaked on or before 5 years of age at 6.6/1,000 person-years, or possibly higher. In contrast, the highest incidence for migraine without aura occurred between 10 and 11 years of age at 10.1/1,000 person-years. New cases of migraine were uncommon among males in their late 20s. The initial onset of migraine headache begins at a later age among females than among males. For females, the highest incidence of migraine with aura occurred between 12 and 13 years of age at 14.1/1,000 person-years; the highest incidence for migraine without aura occurred between 14 and 17 years of age at 18.9/1,000 person-years. In contrast to males, new onset of migraine was relatively common among females in their late 20s.

Adolescent↗

Glucose counterregulation in type 1 diabetic patients with decreased symptoms of hypoglycemia after insulin pump treatment.

We were interested in studying whether impaired hypoglycemic awareness after intensified insulin treatment with insulin pumps is associated with impaired glucose counterregulation. Glucose counterregulatory hormones were measured in 7 type I diabetic patients with altered symptoms after 6 months of continuous subcutaneous insulin infusion (CSII) (group 1) and in 9 patients with unchanged symptoms of hypoglycemia under CSII (group 2). The groups did not differ in diabetic control, duration of diabetes, or prevalence of neuropathy. Counterregulatory hormone response to an insulin-induced episode of hypoglycemia was measured before (first test) and after 6 months (second test) of CSII. Glucose nadirs and glucose recovery were similar in both groups and both tests. The mean plasma glucagon values demonstrate a lack of glucagon response in both groups and both tests. Growth hormone and cortisol increased in both groups and both tests without any difference between the groups or first and second tests. Epinephrine response was similar in both tests of group 2 (first test: 50 +/- 5 to 416 +/- 73; second test; 45 +/- 5 to 456 pg/ml), while in group 1 the response was not increased significantly in the second test [first test: 32 +/- 6 to 346 +/- 63; second test: 44 +/- 7 to 575 +/- 91 pg/ml; areas under curve (AUC) 11,977 and 16,345 pg x ml-1 x 90 min-1 (p = 0.36)].(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

The natural history of somatosensory and autonomic nerve dysfunction in relation to glycaemic control during the first 5 years after diagnosis of type 1 (insulin-dependent) diabetes mellitus.

The natural evolution of neural dysfunction was studied prospectively over 5 years following diagnosis of Type 1 (insulin-dependent) diabetes in 32 patients aged 12-36 years. Motor and sensory nerve conduction velocities, heart rate variation at rest and during deep breathing, and pupillary function were measured at diagnosis and after 3, 12, 24, 48, and 60 months. Thermal and vibration sensation thresholds were determined after 24, 48, and 60 months of diabetes. Mean HbA1 levels of months 3-60 within the normal range of less than 8.3% (7.3 +/- 0.2%) were observed in 13 patients (Group 1), while a mean HbA1 of months 3-60 greater than or equal to 8.3% (10.0 +/- 0.3%) was found in 19 patients (Group 2). Mean nerve conduction was significantly diminished in Group 2 as compared with Group 1 in at least 4 out of 6 nerves tested during months 12-60 (p less than 0.05). Both tests of heart rate variation were significantly impaired in Group 2 as compared with Group 1 after 24 and 60 months (p less than 0.05), but no differences in pupillary function were observed between the groups. Thermal discrimination but not vibration perception thresholds on the foot were significantly higher in Group 2 than in Group 1 at 40 and 60 months (p less than 0.05). Abnormalities in nerve conduction, thermal discrimination, and heart rate variation, but not vibration perception threshold and the pupillary function tests were significantly more frequent in Group 2 than in Group 1 at 60 months (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

One-year treatment with the aldose reductase inhibitor, ponalrestat, in diabetic neuropathy.

A double blind placebo controlled trial was performed to evaluate the effects of the aldose reductase inhibitor, ponalrestat, on symptomatic diabetic neuropathy. After a 4-week placebo run-in phase, 60 patients were 2:1 randomized to receive either 600 mg ponalrestat or placebo once daily over 12 months. Forty-six patients, 30 of whom were treated with ponalrestat and 16 with placebo, completed the study. Motor and sensory nerve conduction, thermal and vibration sensation thresholds, heart rate variation at rest, E/I ratio, pupillary dilation velocity and pupillary reflex latency were determined at baseline and after 6 and 12 months. Neuropathic symptom scores were assessed every 3 months. Among the fifteen nerve function parameters studied, only trends in favour of ponalrestat were noted for heart rate variation and E/I ratio after 6 months (P = 0.06), but no significant differences between the groups could be demonstrated during the study. No adverse reactions were observed. It is concluded that one-year treatment with ponalrestat has no beneficial effects on symptoms or electrophysiological parameters in diabetic neuropathy.

Aldehyde Reductase↗

Changes in brainstem auditory evoked potentials during insulin-induced hypoglycaemia in type 1 diabetic patients.

To determine whether the central and peripheral auditory pathways are disturbed during hypoglycaemia, brainstem auditory evoked potentials were measured in 16 Type 1 diabetic patients aged 17-55 years during intravenous insulin infusion. Within 60 min mean blood glucose declined from 5.0 mmol l-1 to a nadir at 1.7 mmol l-1 followed by an increase to 2.8 mmol l-1 30 min after the insulin infusion had been discontinued. The latency of wave I of brainstem auditory evoked potentials remained unchanged during hypoglycaemia. However, latencies of waves III and V and interpeak latencies I-III, III-V, and I-V were significantly prolonged at average blood glucose levels of 1.7 or 2.1 mmol l-1 when compared with baseline: III 3.96 +/- 0.03 (+/- SE) vs 4.01 +/- 0.04 ms; V 5.69 +/- 0.07 vs 5.81 +/- 0.07 ms; I-III 2.30 +/- 0.05 vs 2.37 +/- 0.05 ms; III-V 1.73 +/- 0.06 vs 1.83 +/- 0.07 ms; and I-V 4.01 +/- 0.05 vs 4.14 +/- 0.06 ms (all p less than 0.05). When blood glucose was allowed to increase to 2.8 mmol l-1, these conduction delays were no longer demonstrable. The depression of the brainstem was approximately paralleled by the activation of counter-regulatory hormones and development of hypoglycaemic symptoms. We conclude that hypoglycaemia results in a rapidly reversible delay of the transmission time in the brainstem but not in the auditory nerve. The dysfunction in the brainstem suggests that not only cortical centres are involved in response to hypoglycaemia in Type 1 diabetic patients.

Adult↗

Elevated platelet activation in type I diabetics with chronic complications under long-term near-normoglycemic control.

A prethrombotic state with altered, hyperactive platelets may contribute to the development of diabetic late complications. Whether increased platelet 'in vivo' activation can be reduced by tight metabolic control is controversial. We studied plasma markers of platelet activation in 64 long-term, microangiopathic type I diabetics after at least 18 months of intensive treatment for near-normoglycemia. Both platelet factor 4 and beta-thromboglobulin proved to be significantly (p less than or equal to 0.05) elevated in comparison with healthy controls: 15.8 (sdf 2)/77.6 (sdf 1.9) vs. 8.9 (sdf 1.6)/45.1 (sdf 2) ng/ml (sdf = standard deviation factor). We found no significant correlations with any metabolic parameter (actual blood glucose, mean blood glucose, HbA1, triglycerides, cholesterol) or with the duration of intensive treatment. It is therefore concluded, that platelet 'in vivo' activation takes place in type I diabetics even after long-term near-normoglycemic control. This deviation could be regarded as indicator of an additional risk for the development of vascular complications.

Adolescent↗

An epidemiologic study of headache among adolescents and young adults.

Despite extensive description of headache among patients in specialty clinics and general practices in the United States, there have been few community-wide investigations. In a population-based telephone interview study of 10,169 Washington County, Maryland, residents who were 12 through 29 years old, 57.1% of males and 76.5% of females reported that their most recent headache occurred within the previous 4 weeks. Four or more headaches in the preceding month were reported by 6.1% of males and 14.0% of females. The average duration of the subjects' most recent headache was 5.9 hours for males and 8.2 hours for females; 7.9% and 13.9%, respectively, missed part of a day or more of school or work because of that headache. Within the month before interview, 3.0% of males and 7.4% of females had suffered from a migraine headache. Consultations with a physician, by specialty, for headache-related problems are described by sex and age of subjects, as is the use of specific prescription and nonprescription medications.

Absenteeism↗

DNA excision-repair ability of embryonic fibroblasts measured by UDS and thymine dimer excorporation in four inbred mice strains.

Differences in the excision-repair capability of embryonic fibroblasts of four inbred strains of mice following various degrees of UV irradiation were assessed. Two methods of determination were used: (1) the incorporation of 3H-thymidine during unscheduled DNA synthesis (UDS) as measured by an autoradiographic technique; (2) the rate of excision of thymine dimers (TT) in the acid-insoluble fraction of the cellular DNA as determined by a dimerspecific radioimmuno-assay. Based on UDS, the repair rates of the four strains could be ranked in decreasing order as follows: DBA/2 (DB); C57BL/6J (B6); AKR/N (AK); CBA/J (CB). The calculated rate for DBA/2 (DB) is approximately twice that of CBA/J (CB). The determination of the TT excision rate indicates that 72 h after irradiation a maximum of 50% of the original UV-induced dimers in the DB strain could be repaired. In the three remaining strains the relatively reduced repair rates of 15% - 40% did not differ significantly.

Animals↗

The natural course of peripheral and autonomic neural function during the first two years after diagnosis of type 1 diabetes.

Motor and sensory nerve conduction velocities (MNCV, SNCV), beat-to-beat variation (BBV) at rest, speed of pupillary dilation (SPD), and pupillary latency time (PLT) were measured in 32 patients aged 12-36 years after 19 +/- 2 (mean +/- SEM) days and again after 3, 12, and 24 months of insulin treatment. Moreover, BBV under deep respiration was determined after 12 and 24 months, and thermal discrimination thresholds (TDT) as well as pain and vibration perception thresholds (PPT; VPT) were evaluated after 24 months. Mean HbA1 levels during months 3-24 within the normal range (7.2 +/- 0.2%; mean +/- SEM) were observed in 20 patients (group 1), while in 12 patients (group 2) mean HbA1 of months 3-24 was elevated (10.1 +/- 0.4%). There were no significant differences between both groups with regard to the nerve function tests at baseline and after 3 months. After 12 months mean median MNCV and median, ulnar, and sural SNCV were significantly lower in group 2 than in group 1 (p less than 0.05). After 24 months mean median MNCV, peroneal MNCV, median SNCV, and sural SNCV as well as both BBV tests and PLT were significantly impaired in group 2 as compared to group 1 (p less than 0.05). In addition, mean malleolar VPT and PPT to heat and cold stimuli on the thenar and the foot were significantly elevated in group 2 as compared to group 1 (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Effects of one year of near-normoglycemia on peripheral nerve function in type 1 (insulin-dependent) diabetic patients.

Ninety poorly controlled C-peptide negative type 1 (insulin-dependent) diabetic patients with chronic complications were allocated to intensified insulin treatment with either continuous subcutaneous insulin infusion or multiple insulin injections; 83 were studied over 1 year (seven patients dropped out of the study). Peripheral nerve function was assessed by clinical examination, malleolar vibration perception threshold, and motor and sensory nerve conduction velocities (MNCV; SNCV) in the median, ulnar, peroneal, and sural nerves. In order to assess the effect of metabolic control on peripheral nerve function, the results in patients with normal mean HbA1 levels during months 3-12 of the study less than 8.6% (tight control (tc); n = 50) were compared with those with abnormal mean HbA1 greater than or equal to 8.6% (poor control (pc); n = 33). Mean blood glucose was significantly higher in pc than in tc at months 2-9 and 11 (P less than 0.05). In pc median and ulnar SNCV were significantly lower at 6 and 12 months, and ulnar and peroneal MNCV at 12 months than in tc (P less than 0.05). No significant differences between the groups were observed for median MNCV, sural SNCV, and vibration sensation. Further analysis revealed that in well-controlled patients who showed abnormal peripheral nerve tests at baseline, median, and ulnar MNCV and SNCV but not peroneal MNCV, sural SNCV, and vibration sensation were significantly improved after 12 months as compared with poorly controlled patients with initially abnormal tests (P less than 0.05). There were no differences in nerve function between well- and poorly-controlled patients who had normal nerve tests at baseline.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗