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Biomedical subjects

F A Gries

Publications and source records attributed to F A Gries.

At least 37 records · Page 2Linked to original sources
PubMed1996

PTCA: periprocedural platelet activation. Part II of the Duesseldorf PTCA platelet study (DPPS)

BACKGROUND: Percutaneous transluminal coronary angioplasty (PTCA) with its various manipulations could create a dangerous, sudden haemostatic response. This study was performed to investigate PTCA-induced periprocedural changes in platelet activation and its consequences. METHODS: Twenty-five consecutive patients admitted for elective PTCA were preclassified as having or not having circulating activated platelets. Blood samples were taken for platelet activation marker analysis before, six times during and 2 h after PTCA. Intravascular platelet activation was analysed by flow cytometry to measure activation-dependent surface markers thrombospondin, P-selectin (CD62) and lysosomal GP53 (CD63). RESULTS: PTCA was associated with a significant reduction of peripheral platelet count. The initiation of the PTCA procedure led to a significant loss of more than 50% of the degranulated, activated platelets. After PTCA, the number of degranulated, activated platelets uniformly increased. CONCLUSIONS: We conclude that PTCA can induce consumption, particularly of preactivated platelets, and lead to sustained platelet activation after the procedure. This might explain why preactivated patients are at increased risk of suffering periprocedural ischaemic events and why increased thrombogenicity favours acute flow disruption and the progression of coronary stenosis at the lesion site.

Angioplasty, Balloon, Coronary↗
PubMed1995

[Arachnoid cyst as the differential diagnosis of ischemic optic neuropathy in type-II diabetes].

HISTORY AND CLINICAL FINDINGS: A 71-year-old woman, a diabetic (type IIb) for 27 years, developed bilateral hemianopsia over a period of about 2 years. A few weeks before hospital admission the defect in her visual fields increased more rapidly and double vision occurred intermittently. The hemianopsia was demonstrated by finger perimetry. There was no evidence of heart failure or peripheral vascular disease. Muscle reflexes were normal, but there was a decrease in vibratory sensation in both feet. The cause of the visual disturbance was at first thought to be an ischaemic optic neuropathy. INVESTIGATIONS: Biochemical tests showed an HbA1 of 12.8%, blood sugar levels were between 230 and 359 mg/dl, and there was increased intravascular platelet activation. Ophthalmological examination confirmed bitemporal hemianopsia and early retinopathy. Magnetic resonance imaging of the skull revealed an intra- and suprasellar cystic space-occupying lesion extending to the right optic chiasma. These findings, taken together, indicated an arachnoidal cyst. TREATMENT AND COURSE: After the diabetic metabolic state had been normalized with insulin treatment (average of 30 IU of an intermediary insulin) and dietary measures, the cyst was evacuated stereotactically. The hemianopsia quickly improved markedly and the patient was discharged 4 days after the operation with her vision nearly fully restored.

Aged↗
PubMed1995

Insulitis and islet-cell antibody formation in rats with experimentally reduced beta-cell mass.

We studied the effect of severe reduction of beta-cell mass by 90% pancreatectomy on the immune tolerance to the endocrine pancreas. Four months after subtotal pancreatectomy all LEW.Han rats had developed mononuclear infiltration of islets and 9 of 14 rats were positive for islet-cell antibodies. Electron microscopy revealed lymphocytic invasion of endocrine tissue, lysis of beta cells and phagocytotic macrophages. None of these changes were seen 2 weeks after 90% pancreatectomy or 4 months after 10% pancreatectomy. Weekly substitution of islet antigens in the form of a homogenate of 100 islets into 90% pancreatectomized LEW.Han rats almost completely prevented the development of insulitis and autoantibodies. The dependence of insulitis on T cells was shown when 90% pancreatectomy in LEW.rnu rats (i.e., the congenic athymic nude strain), did not result in islet infiltration. The exocrine tissue remained normal in all experimental groups. During the observation period insulitis was not associated with overt diabetes but was accompanied by substantial enlargement of islets and of beta-cell mass, as shown by morphometry. Suppression of islet inflammation by injection of islet antigens abolished beta-cell regeneration, despite continuing metabolic stress in rats with 90% pancreatectomy. The findings indicate induction of islet autoimmunity in response to 90% but not to 10% pancreatectomy. We conclude that severe reduction of the islet-antigen mass allows the development of T-cell-dependent islet autoimmunity which indicates a loss of immune tolerance. In addition, the data suggest the existence of islet-antigen autoreactive immune cells in rats not genetically predisposed to autoimmune diabetes. Finally, we conclude that selective beta-cell regeneration occurs in association with insulitis.

Animals↗
PubMed1995

Treatment of symptomatic diabetic peripheral neuropathy with the anti-oxidant alpha-lipoic acid. A 3-week multicentre randomized controlled trial (ALADIN Study).

Anti-oxidant treatment has been shown to prevent nerve dysfunction in experimental diabetes mellitus, thus providing a rationale of potential therapeutic value for diabetic patients. The effects of the anti-oxidant alpha-lipoic acid (thioctic acid) were studied in a 3-week multicentre, randomized, double-blind placebo-controlled trial (Alpha-Lipoic Acid in Diabetic Neuropathy; ALADIN) in 328 non-insulin-dependent diabetic patients with symptomatic peripheral neuropathy who were randomly assigned to treatment with intravenous infusion of alpha-lipoic acid using three doses (1200, 600, or 100 mg ALA) or placebo (PLAC). Neuropathic symptoms (pain, burning, paraesthesiae, and numbness) were scored at baseline and at each visit (days 2-5, 8-12, and 15-19) prior to infusion. In addition, the Hamburg Pain Adjective List, a multidimensional specific pain questionnaire, and the Neuropathy Symptom and Disability Scores were assessed at baseline and day 19. According to the protocol 260 (65/63/66/66) patients completed the study. The total symptom score in the feet decreased from baseline to day 19 by -4.5 +/- 3.7 (-58.6%) points (mean +/- SD) in ALA 1200, -5.0 +/- 4.1 (-63.5%) points in ALA 600, -3.3 +/- 2.8 (-43.2%) points in ALA 100, and -2.6 +/- 3.2 (-38.4%) points in PLAC (ALA 1200 vs PLAC: p = 0.003; ALA 600 vs PLAC: p < 0.001). The response rates after 19 days, defined as an improvement in the total symptom score of at least 30%, were 70.8% in ALA 1200, 82.5% in ALA 600, 65.2% in ALA 100, and 57.6% in PLAC (ALA 600 vs PLAC; p = 0.002). The total scale of the Pain Adjective List was significantly reduced in ALA 1200 and ALA 600 as compared with PLAC after 19 days (both p < 0.01). The rates of adverse events were 32.6% in ALA 1200, 18.2% in ALA 600, 13.6% in ALA 100, and 20.7% in PLAC. These findings substantiate that intravenous treatment with alpha-lipoic acid using a dose of 600 mg/day over 3 weeks is superior to placebo in reducing symptoms of diabetic peripheral neuropathy, without causing significant adverse reactions.

Adolescent↗
PubMed1995

Autoantibodies to the islet antigen ICA69 occur in IDDM and in rheumatoid arthritis.

Islet cell antigen (ICA) 69 is a newly-recognized islet cell antigen to which autoantibodies have been observed in prediabetic relatives of patients with insulin-dependent-diabetes mellitus (IDDM). Here we extend the earlier analysis of ICA69 antibodies to patients with recent-onset IDDM and to patients with other immune-mediated diseases. ICA69 antibodies were determined by Western blot using an affinity purified recombinant fusion protein of ICA69 and maltose binding protein. ICA69 antibody quantities were determined as titres using a titration curve of a standard serum as reference. Mean logarithmic ICA69 antibody titres were 3.4 (+/- 1.4) in 99 patients with acute IDDM compared to 2.8 (+/- 0.9) in 49 healthy blood donors (p < 0.001). A higher mean ICA69 antibody titre of 4.1 (+/- 0.8) was observed in 16 patients with rheumatoid arthritis in comparison to acute IDDM (p < 0.01) and healthy control subjects (p < 0.001). The percentage of sera with ICA69 antibody titres above the 2 SD level of normal subjects was 21% in IDDM, 31% in rheumatoid arthritis and 6% in healthy blood donors. None of the patients with autoimmune thyroid disease (n = 20), inflammatory bowel disease (n = 9) or multiple sclerosis (n = 7) had elevated ICA69 antibodies. In IDDM, presence of ICA69 antibodies persisted and the titre remained the same over 18 months of follow-up. The relationship of ICA69 antibodies to islet cell antibodies (ICA) or insulin autoantibodies (IAA) was tested. The production of ICA69 antibodies was not associated in diabetic patients with the presence of any of the two other autoantibodies.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1995

Alternative therapeutic principles in the prevention of microvascular and neuropathic complications.

Since the prevention of chronic diabetic complications by near normal metabolic control is not always achievable, alternative therapeutic principles have been developed. The specific intervention at metabolic abnormalities which seem to play a key role in the pathogenesis of complications has been shown to prevent the development of microangiopathy and neuropathy in experimental diabetes, e.g. inhibition of non-enzymatic glycation by aminoguanidine, inhibition of polyol pathway activity by aldose reductase inhibitors, prevention of hypoxia and oxidative stress by vasodilators and radical scavengers such as alpha-lipoic acid. Some of these drugs should soon be available for common clinical use.

Aldehyde Reductase↗
PubMed1995

Insulinkinetic and -dynamic in diabetic patients under insulin pump therapy after injections of human insulin or the insulin analogue (B28Asp).

In this double blind randomized study we compared the insulinkinetic, insulindynamic and the frequency of hypoglycemic events after s.c. injection of human insulin and the insulin analogue (B28Asp). Fourteen c-peptide negative patients treated with continuous subcutaneous insulin infusion (CSII) were included in the study. Their mean age was 42.9 (range 26-60 yrs), duration of diabetes 18.5 (5-29) and mean duration of CSII 6.3 yrs (3-10). Serum free insulin (FIRI) was determined from 8:00 to 11:00 h, and blood glucose from 7:00 to midnight. Maximum FIRI values were obtained after 45 min for (B28Asp) and after 90 min for Actrapid HM. Maximum blood glucose increase (Tmax) was obtained 60 min after injection of (B28Asp) and 90 min after Actrapid HM. The AUCBC was greater after administration of Actrapid HM compared to (B28Asp) (p < or = 0.05). A total number of 16 hypoglycemias (BG < or = 3.3 mmol.l-1) were registered. 8 episodes were induced equally by (B28Asp) and by Actrapid HM. We conclude that in insulin dependent diabetic patients the insulin analogue (B28Asp) showed a faster absorption and less hyperinsulinemia than Actrapid HM after s.c. administration. The corresponding BG-values were higher after s.c. administration of Actrapid HM compared to (B28Asp). These findings in patients support the concept of a more physiological effect of rapid acting insulin analogues than of regular insulin.

Adult↗
PubMed1995

Exposure of adhesion molecules on activated platelets in patients with newly diagnosed IDDM is not normalized by near-normoglycemia.

It has been suggested that platelet hyperactivity contributes to the early evolution of diabetic vascular disease per se. This study directly evaluates the level of intravascular platelet activation in newly diagnosed IDDM patients before and after tight metabolic control. Platelet activation was determined by the Duesseldorf-III flow cytometry assay in 21 recent-onset hyperglycemic IDDM patients before insulin, after 3 days of treatment with intravenous insulin, and after 14 and 60 days of intensified conventional insulin therapy. The intravasal platelet activation status was quantified by the percentage of platelets exposing the activation-dependent molecules CD62 (P-selectin), thrombospondin (TSP), and CD63 (GP53) as well as the activated fibrinogen receptor (GPIIB/IIIA). Fifty matched normal subjects served as control subjects. Fourteen patients completed the 60-day study design. After initial recompensation, near-normoglycemic control was achieved after 14 days (fasting blood glucose, 117.0 +/- 19.0 mg/dl), and the HbA1 concentration was 7.6 +/- 1.2% after 60 days. CD62+ (4.0 +/- 4.5%), TSP+ (2.0 +/- 1.8%), CD63+ (11.0 +/- 7.0%), and activated-GPIIB/IIIA+ (7.6 +/- 7.7%) platelet levels were initially 5, 3.3, 5.7, and 2.8 times higher than the mean level of normal. There was no correlation with any of the nearly normalized metabolic parameters. Thus, more activated platelets circulate in newly diagnosed IDDM patients, which supports the assumption of a prethrombotic condition even in disease stages without apparent vascular damage.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Endothelin-1 inhibits the adipose differentiation of cultured human adipocyte precursor cells.

We studied the effect of endothelin-1 (ET-1) on the differentiation of adipocyte precursor cells obtained from human adipose tissue and cultured in a serum-free hormone-supplemented medium. ET-1 was found to inhibit in a dose-dependent manner the accumulation of lipid droplets and the expression of glycerol-3-phosphate dehydrogenase (GPDH), a marker of adipose differentiation. The half-maximal inhibitory effect was observed in the range of 8.5 x 10(-10) mol/L. Full inhibition required the continuous exposure of the cells to ET-1. The prevention of adipose conversion was not associated with a stimulation of mitogenesis. The presence of staurosporine, an inhibitor of the protein kinase C signaling pathway, completely prevented the inhibitory effect of ET-1 on adipose differentiation. Addition of ET-1 to newly developed fat cells also caused a suppression of GPDH activity without changing adipocyte morphology. Again, the magnitude of this effect was dependent on the exposure time. These findings suggest that ET-1 is a potent modulator of fat cell formation in man, which may act through activation of protein kinase C. Because of the close spatial relationship between fat cell precursors and blood vessels, ET-1 may exert its action in a paracrine manner.

Adipocytes↗
PubMed1994

Cerebral glucose metabolism in type 1 diabetic patients.

To evaluate whether cerebral glucose metabolism is impaired in diabetes the [18F]-2-deoxy-2-fluoro-D-glucose method and positron emission tomography were used to determine the regional cerebral metabolic rate of glucose in 12 healthy subjects, 8 newly diagnosed Type 1 diabetic patients 6 Type 1 diabetic subjects without peripheral neuropathy, and 7 Type 1 diabetic patients with symptomatic peripheral neuropathy, all of whom were men. In addition, multimodal evoked potentials were assessed. Cerebral glucose consumption was significantly reduced in the group with neuropathy as compared with the newly diagnosed diabetic patients and the healthy subjects (26.9 +/- 1.0 vs 33.9 +/- 1.9 and 32.5 +/- 1.1 mumol 100 g-1 min-1; p < 0.05), while in the patients without neuropathy it was 30.2 +/- 2.5 mumol 100 g-1 min-1 (NS vs the remaining groups). There were no significant differences between the groups regarding brainstem auditory and visual evoked potentials. No relationship was noted between cerebral glucose metabolism and P300 latency of event-related potentials as an index of cognitive function, but there was an inverse correlation with age (r = -0.42; p < 0.05) and duration of diabetes (r = -0.67; p < 0.05). These results suggest that cerebral glucose metabolism is normal at the time of diagnosis of Type 1 diabetes, but may become altered with both increasing duration of diabetes and age in the absence of central conduction deficits or cognitive dysfunction. Diabetic neuropathy may constitute a possible additional correlate of reduced cerebral glucose consumption.

Adult↗
PubMed1994

Noninvasive blood glucose sensors based on near-infrared spectroscopy.

Research into noninvasive devices for self-monitoring of blood glucose is mainly based on near-infrared spectroscopy. Such a device is particularly desirable in the intensive therapy of patients with diabetes mellitus to achieve optimal metabolic control through frequent glucose testing. The state of noninvasive assay technology is presented. Using diffuse reflectance spectra of mucous lip tissue has advantages and drawbacks compared with tissue transmittance experiments. Different approaches have been proposed in the patent literature; however, current technology requires further significant improvements, particularly within the lower normal and hypoglycemic glucose concentration ranges.

Blood Glucose Self-Monitoring↗
PubMed1994

[Lipid metabolism and insulin resistance--clinical aspects and pathobiochemistry].

About 3 decades ago insulin resistance has been described as the pathogenetic factor leading from abnormal fat metabolism to diabetes mellitus. Within the metabolic syndrome insulin resistance is related to the upper body (android) type of obesity, hypertriglyceridaemia, hypertension, and diabetes mellitus ("deadly quartet"). It precedes the development of arterial hypertension and the metabolic disorders. The pathomechanisms leading from obesity and hypertriglyceridaemia to insulin resistance may be described by the glucose fatty acid cycle of Randle et al. According to their metabolic scheme increased supply of fatty acids results in reduced glucose oxidation. Concomittantly hepatic glucose production is increased. On the other hand insulin resistance combined with hyperinsulinaemia may lead to an elevation of VLDL-triglycerides and to a decrease of HDL-cholesterol in blood, thus creating a vicious cycle, in which elevated VLDL-triglycerides reinforce insulin resistance via the glucose fatty acid cycle. Interventions to improve insulin sensitivity and thereby lower plasma insulin should reduce obesity and hypertriglyceridaemia by dietary treatment. They usually improve promptly diabetic metabolism. New developments in pharmacological inhibition of fatty acid oxidation are discussed.

Arteriosclerosis↗
PubMed1994

Prevalence of gastrointestinal symptoms in diabetic patients and non-diabetic subjects.

To determine the frequency of gastrointestinal symptoms in diabetic patients, 190 patients, consecutively referred to the Diabetes Research Institute, reported their gastrointestinal symptoms on a standardized symptom list. One hundred and eighty non-diabetic healthy subjects served as (matched) controls. Finally, 75 patients with Type 1 (insulin-dependent) diabetes mellitus (33 male, 43 female; age 34,1 (18-60) yrs, diabetes duration: 11,1 (0,3-41) yrs) and 68 patients with Type 2 (non-insulin-dependent) diabetes mellitus (31 male, 37 female, age: 61,4 (37-88) yrs, diabetes duration: 10,7 (0,3-40) yrs) were studied and compared with two cohorts of controls of the same size. There were no differences in prevalence of symptoms referrable to the upper and lower GI-tract in type 1 diabetic patients as compared with controls. Among patients with type 2 diabetes the main gastrointestinal complaint was constipation (22,1% vs 10,3%; p < 0.05). Upper gastrointestinal symptoms were also more frequent among Type 2 diabetic subjects (nausea 11,8% vs 2,9%, p < 0.05). There was a tendency for an increased symptom prevalence with higher age in both type 1 and type 2 diabetes. Presence of peripheral neuropathy was associated with a higher symptom prevalence in type 1 diabetes. After stratification, diabetes duration and glycaemic control (HbA1c) did not influence the frequency of symptoms. Thus, gastrointestinal symptoms occur frequently among both diabetic patients and non-diabetic subjects. However, significant differences were found only in type 2 (non-insulin-dependent) diabetes, the commonest symptom being constipation. These findings support the need of a nondiabetic control group in epidemiological studies evaluating symptom prevalence in diabetes mellitus.

Adolescent↗
PubMed1994

Hyperinsulinism in patients with coronary artery disease.

AIM: To assess the clinical impact of hyperinsulinism and major coronary risk factors in patients with angiographically documented or excluded coronary artery disease (CAD), a clinical study was carried out in 268 men admitted for left heart catheterization. METHODS: Fasting immunoreactive insulin (IRI) levels were correlated to all major cardiovascular risk factors and to the presence and degree of CAD. RESULTS: IRI levels were correlated significantly with the degree of CAD (one-vessel disease: mean IRI 9.45 microU/ml +/- 0.43 SEM; two-vessel disease: mean IRI 10.4 microU/ml +/- 0.71 SEM; three-vessel disease: mean IRI 11.88 microU/ml +/- 0.98 SEM) and inversely to the high-density lipoprotein level (P < 0.05). In patients with arterial hypertension, IRI levels were elevated, without a significant difference between those with and those without CAD, whereas the IRI levels of non-hypertensive men with CAD (n = 81; mean IRI 9.85 microU/ml +/- 0.51 SEM) differed significantly (P < 0.05) from those of non-hypertensive men without CAD (n = 59; mean IRI 7.76 microU/ml +/- 0.43 SEM). IRI levels were significantly higher (P < 0.05) in obese patients (n = 65; mean IRI 11.68 microU/ml +/- 0.70 SEM versus n = 203; mean IRI 9.32 microU/ml +/- 0.34 SEM), in patients with elevated triglycerides (n = 58 mean IRI 11.59 microU/ml +/- 0.81 SEM versus n = 210; mean IRI 9.42 microU/ml +/- 0.33 SEM), and in patients with lowered HDL cholesterol (n = 178; mean IRI 11.06 microU/ml +/- 0.63 SEM versus n = 90; mean IRI 9.29 microU/ml +/- 0.34 SEM). Diabetic patients on angiotensin converting enzyme inhibitor therapy (n = 11; mean IRI 7.91 microU/ml +/- 0.91 SEM) had significantly (P < 0.05) lower IRI levels than those not treated with ACE inhibitors (n = 25; mean IRI 12.96 microU/ml +/- 1.47 SEM). IRI levels exceeding 8 microU/ml were associated with a 1.98-fold risk for CAD compared with IRI levels below 8 microU/ml. Stepwise logistic regression showed that insulin was an independent determinant of CAD. CONCLUSION: Knowledge of the fasting insulin level is an important contribution to the identification of patients with, or at risk of, CAD.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1993

Transfer of insulin-dependent diabetes between HLA-identical siblings by bone marrow transplantation.

Insulin-dependent diabetes was observed in a woman, aged 29, 4 years after transplantation of bone marrow from her HLA-identical brother with insulin-dependent diabetes. Both had classic symptoms and insulin dependency from onset. At diagnosis of diabetes the recipient was positive for high-titre islet cell antibodies (ICA) whereas she had been ICA negative before transplantation. Chromosomal analyses verified that all circulating leucocytes were of male donor type. These findings suggest transfer of insulin-dependent diabetes by bone marrow cells and confirm the immune nature of the disease.

Adult↗