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PubMed1998

Prevalence of retinopathy in people with diabetes, impaired glucose tolerance, and normal glucose tolerance.

OBJECTIVE: Recently, an international expert committee published new revised criteria for diagnosing diabetes. According to the new criteria, the 2-h glucose level for diabetes in the oral glucose tolerance test (OGTT) is the same as in the previous World Health Organization criteria, but the cut point for the fasting blood glucose level has been lowered to be equivalent to the 2-h OGTT level. Measurement of the fasting blood glucose level is preferred to the 2-h OGTT glucose level. The ability of the new cut point for fasting blood glucose to discriminate between those at a high and a low risk for retinopathy was tested in a population-based study RESEARCH DESIGN AND METHODS: The population consisted of all the 1,008 subjects (456 men) born in 1935 and living in a Finnish city A screening for type 2 diabetes was carried out in the first phase. All participants who were not on antidiabetic medication were invited for an OGTT in the second phase. A fasting blood glucose value was measured from the diabetic subjects on antidiabetic medication. In addition, measurements of serum cholesterol, HDL cholesterol, and triglycerides were made, and fundus photographs were taken. Altogether, 831 subjects (368 men) (82%) participated and constitute the eligible study population for the present analyses. Fundus photographs were available for 790 subjects (347 men) (95%). RESULTS: There were 28 subjects (3.5%) who had mild retinopathic changes in the fundus photographs. Retinopathic changes were associated with higher fasting blood glucose levels, but not with any of the other background factors. The prevalence of retinopathy was 10.2% (95% CI 4.8-18.5) in subjects with a fasting blood glucose of > or =6.1 mmol/l, while it was 2.6% (1.5-4.0) in those with a lower fasting blood glucose level. In the former group, a majority (seven of nine) of the subjects with retinopathy were previously diagnosed diabetic patients. Some cases of retinopathy were found regardless the level of glycemia, and measurement of the 2-h OGTT glucose levels did not increase information. CONCLUSIONS: The results of this population study give support to the use of fasting blood glucose levels in diagnosing type 2 diabetes. The lower limit of the highest decile of the fasting glucose level was 6.1 mmol/l, and it discriminated subjects at a high risk for retinopathy from those at a low risk. Because of the limited number of subjects with retinopathy in this study, the level of hyperglycemia associated with retinopathy cannot be estimated accurately.

Blood Glucose↗
PubMedDate not supplied

Glucose tolerance and blood lipids in bran-fed patients with impaired glucose tolerance.

Thirty-eight patients (13 men and 25 women) with impaired glucose tolerance, aged 33--70 yr, underwent a dietary program adding 20 g of raw bran to their usual diet without changing their dietary habits. After 1 mo of treatment, the areas under the curves for glucose and insulin were reduced from 26,214 +/- 5618 to 24,529 +/- 5207 g/min (P < 0.001) and from 15,893 +/- 9714 to 12,440 +/- 7377 mU/min (P < 0.001), respectively, cholesterol was reduced from 234 +/- 40 to 212 +/- 29 mg/dl (P < 0.001), and triglycerides were reduced from 108 +/- 56 to 97 +/- 50 mg/dl (P < 0.05). Body weight (initially 128.44% relative body weight) decrease 0.8% (P < 0.02). After the first month, 14 subjects were studied for a further 2 mo. Six patients continued bran feeding, and eight, who stopped bran, were used as controls. Patients who took bran maintained metabolic improvement over the 3-mo treatment period, while those who stopped bran did not.

Adult↗
PubMed1992

Tolerance, cross-tolerance and withdrawal in rats made dependent on diazepam.

Rats were trained to discriminate pentylenetetrazole (PTZ; 20 mg/kg) from midazolam (MDZ; 1 mg/kg) and from saline using a three-lever food-reinforced choice task. Using a cumulative dosing procedure, PTZ substituted for PTZ, and MDZ, chlordiazepoxide and diazepam (DZP) substituted for MDZ, in a dose-dependent manner. The animals were then treated with chronic DZP (20 mg/kg/8 hr for 7 days); 24 hr after the last dose of this regimen, the dose-effect curve of DZP was redetermined. The ED50 for the discrimination of DZP increased 4.8-fold after chronic DZP. In a second group of subjects trained on this discrimination and treated with DZP (20 mg/kg/8 hr for 7 days), the ED50 for the discrimination of MDZ was increased 2.2-fold. After 14 days of recovery, the MDZ dose-effect curve shifted back to the left and was not significantly different from the ED50 value obtained before chronic DZP treatment. When the benzodiazepine antagonist flumazenil was tested in a cumulative manner (1.0-32.0 mg/kg), the animals selected the saline lever. Analogous to the previous chronic dosing regimen, DZP (20 mg/kg/8 hr/7 days) was then administered, and a combination of three tests were then given at 1, 2, 4, 7, 10 and 14 days after the last DZP treatment. On each of these days, a saline test was given first; it was followed by a DZP (2.5 mg/kg) test; which was then followed by a flumazenil (32.0 mg/kg) test. On the 1st day of testing, tolerance was seen to DZP and precipitated withdrawal (PTZ lever selection) was seen with flumazenil.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Glucose tolerance test periodicity as a descriptor of glucose tolerance abnormality.

The periodicity of the standard 100-g glucose tolerance test (GTT) was examined in a prospective study of 194 pregnant patients to determine how well gestational diabetes could be identified. A simplified formula, the GTT periodicity, was used to estimate the time for the GTT curve to return to the fasting level. One hundred one study subjects had all normal glucose values by the National Diabetes Data Group criteria (0-abnormal group), 47 had one value greater than normal (1-abnormal group), and 46 had more than one value abnormal or gestational diabetes. The 0-abnormal patients had a significantly shorter GTT periodicity than did 1-abnormal or gestational diabetic mothers (3.6 versus 4.8 versus 6.6 hours, respectively; P less than .04). Calculating the periodicity for the corresponding insulin excursions yielded significantly increasing values in a graduated fashion for each group (5.2 versus 6.9 versus 9.6 hours, respectively; P less than .05). Examination of the oscillation of the GTT curve about the fasting level allows a physiologic description of normal and abnormal glucose responses in pregnancy. Furthermore, our findings suggest that glucose and insulin periodicities are useful predictors of gestational diabetes in patients with positive screening.

Adult↗
PubMed2005

[Contribution to the study of mechanisms of rejection and tolerance in organ transplantation: minimizing immunosuppression as a strategy for graft tolerance in pediatric liver transplantation]].

Basic concepts in transplantation immunology have been recently revisited. Accordingly, the immune response towards an allograft is not anymore considered as necessarily harmful, but could participate, under certain conditions, to graft acceptation through active mechanisms. This novel paradigm was progressively evaluated in clinical liver transplantation, with the aim to minimize the immunosuppressive regimens and, as a first step, to completely withdraw steroids from the immunoprophylactic regimen. The development of laboratory tests to reproducibly assess the immune reactivity of a recipient towards his/her transplanted organ should allow the identification of operationally tolerant patients, and the elective withdrawal of maintenance immunosuppression in this subgroup.

Child↗
PubMed1990

Use of a specular microscope with pachymeter in ocular tolerance studies of eye drops in the rabbit. Evaluation of ocular tolerance of benzalkonium chloride in aqueous solution 0.01% and 0.1%.

Eye drops, unlike cosmetics or chemicals, only cause minor irritations which often prove difficult to objectively observe and assess. A specular microscope with pachymeter is used to measure corneal thickness, and to examine and photograph corneal endothelium in ocular tolerance studies in the rabbit. Rabbits were instilled 5 times a day for 16 days with BKC aqueous solution, 0.01% or 0.1% and subjected after anaesthesia to 4 corneal inspections (before treatment, 7th and 14th days of treatment, 5th day after treatment). Only the 0.1% concentration provoked an increase in corneal thickness. Thickening progressed during the treatment period (5.3% on day 7, 26% on day 14) and strongly regressed 5 days after treatment stopped (3%). A slit lamp examination revealed very light or light corneal opacities, but the correlation between corneal thickening ratio and opacity was poor (r = 0.62).

Animals↗
PubMed1985

Tolerance and cross-tolerance to the antisecretory effects of enkephalins on the guinea-pig ileal mucosa.

The antisecretory properties of opiates in the guinea-pig ileum have been shown previously to be mediated through interactions with delta-like opiate receptors present in the intestinal mucosa. The present investigation examined the development of tolerance to opioid-induced alterations in intestinal ion transport processes. Osmotic minipumps continuously delivering the prototypic delta-opioid agonist [D-Ala2,D-Leu5]enkephalin (DADLE) (5 micrograms/hr) or the potent mu-opiate agonist fentanyl (10 micrograms/hr) over a 5-day period were implanted s.c. into guinea pigs; control animals did not receive chronic drug infusions. DADLE, DADLE ethylamide and [D-Ala2,D-Met5]enkephalin dose-dependently decreased base-line transepithelial potential difference and short-circuit current in isolated segments of ileal mucosa from untreated control animals, with an order of potency of DADLE greater than [D-Ala2, D-Met5 enkephalin greater than DADLE ethylamide. In tissues from DADLE-infused animals, the antisecretory dose-effect curves of the three enkephalin analogs displayed downward shifts to the right compared to control conditions. In contrast, the potency of DADLE was significantly increased in tissues from animals chronically infused with and rendered physically dependent upon fentanyl. The administration of the opioid antagonists naloxone, diprenorphine or the selective delta-opioid antagonist M 154, 129 produced no significant changes in short-circuit current of mucosal segments from either DADLE- or fentanyl-infused animals. Chronic administration of either DADLE or fentanyl did not significantly alter the effects of nonopioids, bombesin, somatostatin or epinephrine, on ion transport; however, the efficacy but not the potency of neurotensin in increasing short-circuit current was attenuated after chronic DADLE infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1983

[Relation between intravenous glucose tolerance tests and oral glucose tolerance tests in severely obese patients. II].

OGTT (75 g glucose) and IVGTT (25 g glucose) were compared in 20 extra-obese patients, both glycaemia and insulin levels being calculated. In only 2 out of 7 cases was the glucose intolerance revealed by OGTT confirmed by IGVTT and IVGTT was never able to identify the excessive insulin output revealed by OGTT. It can therefore be confirmed that in the extra-obese even more than in normal patients, IVGTT and OGTT investigate different functions of glucose tolerance and acute insulin output.

Administration, Oral↗
PubMed1978

Immunologic tolerance in the chicken. I. Isolation of two suppressive fractions from serum of chickens tolerant to bovine serum albumin.

Serum from 14-day-old chickens rendered tolerant at hatching with 1250 mg bovine serum albumin (BSA)/KBW was found to suppress an adoptive secondary response to BSA and an in vitro response to sheep red blood cells (SRBC). Chromatographic separation resulted in three fractions: I, II, and III. The suppressive activity was found to be contained in fraction I (m.w. greater than 1 X 10(6)) and fraction III (m.w. less than 2.5 X 10(4)). Analysis of fraction I by affinity chromatographic techniques revealed that it was composed of soluble BSA-antibody complexes and their removal removed the suppressive activity. Analysis of peak III revealed that the suppressive activity could only be removed by BSA and anti-Line 3 antiserum columns.

Animals↗
PubMed1981

[Glycosylated hemoglobins and the oral glucose tolerance test in evaluation of glucose tolerance].

We performed OGTT and glycosylated hemoglobin (HbA1) determinations in 62 subjects. In those with IGT we noticed significantly increased average levels of HbA1 in comparison to normal or borderline ones, but 65.3% of the subjects with abnormal OGTT according to Fajans and Conn's criteria and 83.3% of those scored as borderline, had normal HbA1. This latter group showed a positive significant correlation with sum and peak of plasma glucose concentrations at 60 and 120 min during the test. Our opinion is that the mutual presence of abnormal OGTT and of increased HbA1 levels allows a reliable diagnosis of IGT, and the presence of normal HbA1 must induce us to suspect a false IGT diagnosis. 18 normal subjects showed, moreover, a remarkable HbA1 increase 30 days after the glucose load, with a return to basal levels after 40 days, while in 8 subjects with IGT, HbA1 remained constantly unmodified after 30 and 40 days. This is probably a consequence of a difference in daily glycemic profile between individuals with normal glucose tolerance and others with a reduced one.

Adult↗
PubMed1994

Oral tolerance: a biologically relevant pathway to generate peripheral tolerance against external and self antigens.

OT is a relevant biological pathway for generating peripheral tolerance against both self and external antigens with minimal side effects (fig. 3). This route might, therefore, contain promising potential for the treatment of autoimmune and allergic diseases in the human (fig. 3). Thus, oral administration of autoantigens suppresses experimental autoimmune diseases (EAE, EAU, AA, collagen-induced arthritis, NOD diabetes) in a disease- and antigen-specific manner, and oral administration of alloantigens has led to increase of allograft survival. OT might be important in treatment of immune complex diseases and food allergies. OT is mediated by T lymphocytes using at least two nonmutually exclusive mechanisms: suppression and anergy. Suppression can be adoptively transferred by CD8+ T lymphocytes which act by releasing TGF-beta and IL-4 following antigen-specific triggering. Antigen-driven tissue-directed suppression occurs following oral administration of an antigen from the target organ, even if it is not the disease-inducing antigen (bystander suppression). Thus, synthetic peptides can induce OT, and tolerogenic epitopes of antigen may be different from the autoreactive epitope. Due to the promising results in animal models, OT is being tested in clinical trials in multiple sclerosis, rheumatoid arthritis and uveitis [193, 194].

Administration, Oral↗
PubMed2001

Tolerability of hormone therapies for breast cancer: how informative are documented symptom profiles in medical notes for 'well-tolerated' treatments?

Hormonal therapies for cancer are often viewed as a gentler option than many other cancer treatments, but is low toxicity an accurate perception of patients' experiences? Side effects tend to be described as minimal or well tolerated, yet published symptoms from hormonal therapy vary considerably in their descriptions and frequencies. Previous research has highlighted under-reporting of side effects by clinical staff so as part of a wider study examining tamoxifen and goserelin treatment as adjuvant therapy for breast cancer, treatment-related symptoms documented in medical notes were compared with those that patients reported during a research interview. There was a significant difference in the frequency of many side effects reported by the two methods in this study. Sixty four out of 72 (89%) women who had received adjuvant tamoxifen or goserelin had side effects recorded in their medical notes, compared with 74/75 (99%) reporting side effects at interview. We compared the published frequencies of commonly reported symptoms with those found ourselves. The discrepancies between patient-reported and clinician-recorded (usually from clinical trial data) symptom profiles were similar to those found in our study. Without accurate comprehensive side effect profiles for hormone therapies, prospective patients cannot make informed judgements on proposed treatments.

Adult↗
PubMed2005

Dendritic cell subset ratio in tolerant, weaning and non-tolerant liver recipients is not affected by extent of immunosuppression.

Dendritic cell (DC) subsets regulate alloimmune responses and may play a role in transplant tolerance. We extend an analysis of circulating precursors (p) of CD11c(+) CD123(-/lo) (IL-3Ralpha(-/lo)) (pDC1) and CD11c(-) CD123(hi) (pDC2) DC subsets in primary cadaveric liver allograft recipients. Additionally, we examine DC subset levels in relation to the nature and extent of immunosuppressive therapy. The data consolidate the finding that the pDC2/pDC1 subset ratio is significantly higher in patients on minimal calcineurin inhibitor monotherapy undergoing successful weaning (n = 36) and in those off all anti-rejection therapy (n = 18) compared with patients on maintenance immunosuppression (n = 21). No relationship was found between the incidence of either pDC subset or the pDC subset ratio and time post-transplant or time off immunosuppression in any group. There was also no correlation between the pDC subset ratio and either prednisone or tacrolimus dose or tacrolimus trough blood level. No evidence was found that combination of these drugs influenced the incidence of pDC2 relative to pDC1. Thus, a greater prevalence of pDC2 in stable liver recipients on low dose anti-rejection therapy or in those off immunosuppression, compared with that in patients on maintenance immunosuppression, does not reflect a differential effect of anti-rejection drugs on pDC subsets.

Adolescent↗
PubMed1989

[A study in the Ivory Coast (1985-1987) of the efficacy and tolerance of ivermectin (Mectizan) in human onchocerciasis. III. The tolerance and efficacy of a single oral dose of 150 mcg/kg in children].

One hundred and three male and female children of 6 to 14 years old with onchocerciasis, having or not ocular involvement and a mean skin microfilariae level of 36.1 mf/mg, received, in October 1986, a single oral dose of 150 mcg/kg ivermectin and controlled at day 4, 3 months, 6 months and 12 months post treatment. After the last control they were retreated with the same dose. The skin microfilariae count fell down to 94% of the initial level at day 4 and to 99% at 3 months. At 6 months the microfilariae count was 2% of the initial level and 5% at 12 months. The percentage of patients having microfilariae in the anterior chamber of the eye which was 33% before treatment fell down to 6% at 12 months. The percentage of patients having microfilariae in the cornea was 39% before treatment and 18% at 12 months. In the cornea and anterior chamber there was a very reduced number of microfilariae still present. 65% of the children had lesions of keratitis before treatment and 34% two months later. Adverse effects (fever, headache, pruritus, oedemas, myalgias, arthralgias) occurred in 64% of children after the first treatment and 50% after the second. They were of weak or moderate intensity and receded rapidly after administration of aspirin and/or anti-histaminic. The administration of ivermectin is an efficient and well tolerated drug in children above 5 years old.

Administration, Oral↗
PubMed1981

Antihypertensive effect and tolerability of two fixed combination of metoprolol and hydrochlorothiazide followed by a long-term tolerance study with one combination.

After a run-in period with metoprolol 100 mg b.i.d. 55 patients with essential hypertension grade WHO I and II were randomly allocated to a fixed combination of metoprolol 100 mg and hydrochlorothiazide 12.5 mg (group A) or 25 mg (group B) b.i.d for 12 weeks. Every fourth week blood pressure, heart rate and side effects were registered. After 12 weeks there was a significant fall in supine blood pressure from 172/105 mm Hg to 148/92 in group A and from 170/104 mm Hg to 152/96 in group B. Serum potassium fell significantly (from 4.4 to 4.0 mmol/l) in group B only. 4 patients had values between 3.5 and 3.2 mmol/l. Serum uric acid was unchanged in both groups. Side effects were few and mild to moderate in both groups but there was a tendency to more side effects in group B. After 6 months' follow-up, 51 patients on treatment with low dose combination showed no further change in blood pressure. 27 patients took part in an extended follow-up study to 15 months and 13 patients to 18 months. During the whole follow-up study there was no further change in blood pressure, laboratory values or side effects. The study has confirmed that a low dose of hydrochlorothiazide is as effective as a high dose when combined with metoprolol. Because of few side effects and good tolerability during long treatment we find that the low dose combination can be recommended in treatment of milk to moderate essential hypertension.

Adolescent↗