Human versus porcine insulin gone wrong.
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Animals↗
Biomedical subjects
M Egger
Publications and source records attributed to M Egger.
Risk of severe hypoglycaemia in insulin treated diabetic patients transferred to human insulin: a case control study.
OBJECTIVE: To examine whether transfer from animal insulin to human insulin is associated with an increased risk of severe hypoglycaemia. DESIGN: Matched case-control study of insulin treated diabetic patients admitted to hospital because of hypoglycaemia during 1984-7, the period when human insulin was introduced into treatment. SETTING: Case admissions and control admissions were obtained from eight public hospitals within the Swiss canton of Berne and a second control group comprised members of the Bernese section of the Swiss Diabetes Association. SUBJECTS: 94 patients with insulin treated diabetes with a total of 112 admissions for hypoglycaemia during 1984-7 (case admissions), 182 patients with insulin treated diabetes seen in the same hospitals for reasons other than hypoglycaemia with a total of 225 admissions (control admissions), and 86 insulin treated diabetic patients who were members of the Bernese section of the Swiss Diabetes Association. MAIN OUTCOME MEASURES: Type of insulin used at time of admission, glycaemic control as measured by amount of glycated haemoglobin or glucose concentration; severity of hypoglycaemia. RESULTS: Treatment with human insulin at admission was more common in cases than controls (52/112 (46%) admissions v 77/225 (34%); p = 0.003). 116 out of 129 (90%) of admissions taking human insulin had been transferred from animal insulin, mainly because of non-availability of porcine insulins. The ratio of rate of hypoglycaemia in those taking human insulin to the rate in those taking animal insulin was 2.4 (95% confidence interval 1.3 to 4.4). Other risk factors for hypoglycaemia were a history of hypoglycaemic coma (rate ratio of history to no history 3.8, 2.3 to 6.4) and good glycaemic control (rate ratio of good to poor control 3.9, 1.4 to 7.5). With multivariate analysis the increase in rate ratio associated with use of human insulin rose to 3.0 (1.4 to 6.4). Comparison with the diabetes association controls also showed an increased risk associated with use of human insulin (2.2; 1.1 to 4.8). CONCLUSIONS: Transfer of treatment from animal insulin to human insulin was associated with an increased risk of severe hypoglycaemia. Caution should be exercised when transferring diabetic patients to human insulin. Further studies are required to elucidate why this effect occurs.
Adolescent↗
Influence of human insulin on symptoms and awareness of hypoglycaemia: a randomised double blind crossover trial.
OBJECTIVE: To investigate the apparent increased risk of severe hypoglycaemia associated with use of human insulin by comparing the pattern of symptoms of hypoglycaemia with human insulin and porcine insulin. DESIGN: Randomised controlled double blind crossover trial of treatment with human insulin and porcine insulin, with two treatment periods of six weeks. SETTING: Diabetes outpatient department of a university teaching hospital in Berne, Switzerland. PATIENTS: 44 patients (25 men, 19 women) aged 14 to 60 years, with insulin dependent diabetes mellitus. All patients met the following criteria: receiving treatment with fast acting soluble insulin and long acting protamine insulin; performing multiple daily fingerstick blood glucose self measurements; and had stable glycaemic control with about one mild hypoglycaemic episode a week during the preceding two months. INTERVENTION: Patients were randomised to receive either human or porcine insulin for six weeks and were then changed over to the other type of insulin for a further six weeks. MAIN OUTCOME MEASURE: Questionnaire recording "autonomic" and "neuroglycopenic" symptoms that occurred during hypoglycaemic episodes confirmed by a blood glucose concentration less than or equal to 2.8 mmol/l. RESULTS: Insulin doses and blood glucose, glycated haemoglobin A1c, and fructosamine concentrations were similar during the two treatment periods. 493 questionnaires on hypoglycaemia (234 during treatment with human insulin and 259 during treatment with porcine insulin) were analysed. With human insulin patients were more likely to report lack of concentration (52% v 35%, p = 0.0003) and restlessness (53% v 45%, p = 0.004) and less likely to report hunger (33% v 42%, p = 0.016) than during treatment with porcine insulin. The difference in the pattern of symptoms during the two treatments was similar to that between the 12 patients with a history of recurrent hypoglycaemic coma and the 32 patients without such a history. CONCLUSIONS: The pattern of symptoms associated with human insulin could impair patients' ability to take appropriate steps to avoid severe hypoglycaemia. Caution should be exercised when transferring patients from animal insulin to human insulin, and a large scale randomised trial of the two types of insulin may be justified.
Adolescent↗
[Clinical aspects and epidemiology of cryptosporidiosis in immunocompetent children].
A prospective case-control study was performed in urban and periurban areas of Basel to investigate the epidemiology of Cryptosporidium sp., an intestinal coccidian parasite. 455 children with diarrhoea, who attended paediatric and general practices, participated in the study. Oocysts of the parasite were detected in stool specimens of 21 (4.6%) patients using auramine-fluorescence and modified Ziehl-Neelson staining. Another ten infected people were found during separate investigations of outbreaks in a Kindergarten and in two families. Serial stool stains were performed to determine the period of oocyst shedding. The median duration of diarrhoea was six days and ranged from 1 to 25 days. In contrast, shedding of oocysts of Cryptosporidium sp. lasted for 12.5 days and was significantly longer than the period of diarrhoea (p = 0.02). Compared with control patients suffering from diarrhoea of other origin, respiratory symptoms were significantly (p = 0.02) more frequent in children with cryptosporidiosis (42% vs 13%). In comparison with healthy controls, prior contact with a person suffering from diarrhoea and travel to a Mediterranean country were the most important risk factors for cryptosporidiosis. An illustrative case is described in detail. It is concluded that cryptosporidial infection of the respiratory tract may also occur in immunocompetent children. The possibility of a long period of oocyst shedding is important for the planning of hygiene measures both in individuals and public health.
Adolescent↗
Human insulin and hypoglycaemia unawareness: insights from Pittsburgh?
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Awareness↗
Increasing incidence of hypoglycemic coma in children with IDDM.
OBJECTIVE: To examine the incidence of hypoglycemic coma in children with insulin-dependent diabetes mellitus (IDDM) over 8 yr from 1981 to 1988 and to investigate the importance of residual beta-cell function of HbA1 levels and other variables as risk factors for hypoglycemic coma. RESEARCH DESIGN AND METHODS: The study consisted of 155 children with IDDM aged less than 16 yr at study entry. Mean age at onset of diabetes was 7.9 yr (range 1.1-15.6 yr). We made a prospective assessment of hypoglycemic coma episodes, with a standardized questionnaire, over a total observation time of 816.6 person-yr. Three monthly clinical and laboratory examinations, which included determinations of C-peptide and HbA1 levels, were conducted. We compared children with hypoglycemic coma (cases) with children without hypoglycemic coma (controls) in a case-control analysis matched for diabetes duration. Yearly incidence of hypoglycemic coma, calculated as the number of subjects having an attack in 1 yr divided by the cumulative number of person-years for that year, was measured. Univariate and multivariate odds ratios were calculated from logistic regression. RESULTS: Over the first 4 yr, the average yearly incidence was 4.4/100 person-yr compared with 7.4/100 person-yr during the later 4 yr (P less than 0.0001). This tendency was accompanied by intensification of insulin treatment with an increase in the mean number of daily injections and a decrease in mean HbA1 levels. In the case-control analysis, absent residual beta-cell function was the most important risk factor for hypoglycemic coma (adjusted odds ratio 7.8, 95% confidence intervals 2.0-31.2), followed by near-normal HbA1 levels (adjusted odds ratio 4.5, 95% confidence intervals 1.9-10.5). CONCLUSIONS: In this group of children, improvement of glycemic control apparently led to an increase in the incidence of severe hypoglycemia. In children with recurrent hypoglycemic coma and undetectable C-peptide levels, it may be safer to aim for somewhat less tight glycemic control.
Adolescent↗
Health inequalities and migrant workers in Switzerland.
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Humans↗
Methotrexate in rheumatoid arthritis. Impact on quality of life assessed by traditional standard-item and individualized patient preference health status questionnaires.
In a double-blind, randomized trial of methotrexate vs placebo in rheumatoid arthritis, the effect of treatment on physical, social, and emotional function was measured in two different ways: the same, standard measurements in all patients, and individualized measurements selected by the patients at the start of the trial as representing the functions they most wanted to have improved by treatment. On the standard measurements, methotrexate-treated patients fared better than placebo-treated patients in their physical, social, and emotional function by 11%, 5%, and 6%, respectively, results that, although statistically significant, were small. However, methotrexate-treated patients were 29% better in the individualized measures, a result that was both highly statistically significant and greater than the differences in the standard measurements or in joint counts, grip strength, proximal interphalangeal joint circumference, morning stiffness, or walking time. Because the individualized measurements were as efficient as the best direct joint examination measures, yet reflected functional outcomes of greatest importance to individual patients, they constitute useful measures for such trials.
Adult↗
Immobilized proteins in buffer imaged at molecular resolution by atomic force microscopy.
Samples of supported planar lipid-protein membranes and actin filaments on mica were imaged by atomic force microscopy (AFM). The samples were fully submerged in buffer at room temperature during imaging. Individual proteins bound to the reconstituted membrane were distinguishable; some structural details could be resolved. Also, surface-induced, self-assembling of actin filaments on mica could be observed. Monomeric subunits were imaged on individual actin filaments. The filaments could be manipulated on or removed from the surface by the tip of the AFM. The process of the decoupling of the filamentous network from the surface upon changing the ionic conditions was imaged in real time.
Actins↗
Two-dimensional recognition pattern of lipid-anchored Fab' fragments.
A two-dimensional pattern of oriented antibody fragments was formed at the air-water interface and transferred onto a solid support. The Fab'-fragments of a monoclonal antibody against the hapten dinitrophenyl (DNP) were covalently linked via a hydrophilic spacer to phospholipid vesicles. A monomolecular lipid-protein layer at equilibrium with these vesicles was allowed to form at the air-water interface. The monolayer was separated from the vesicle phase and transferred to a Langmuir-Blodgett trough. By cooling and compressing, the previously homogeneous lipid-protein film was driven into a two-dimensional phase separation resulting in protein-rich domains and a second phase consisting mainly of lipid. This film was transferred onto a solid support in a way that preserved the protein-lipid pattern. The specificity as well as the contrast in the binding activity of the two different separated phases were then quantified using microfluorometry. DNP conjugated to fluorescein-labeled bovine serum albumin (BSA) showed virtually no binding to the lipid regions, but gave a ratio of bound DNP-BSA to Fab'-lipid of greater than 50% in the protein-rich domains proving that the Fab'-moiety retained its biological activity. This demonstrates that the technique presented here is well suited to modify different solid surfaces with a pattern of a given biological function. The optional control of lateral packing and orientation of the components in the monolayer makes it a general tool for the reconstitution of supported lipid-protein membranes and might also open new ways for the two-dimensional crystallization of proteins at membranes.
Antibodies, Monoclonal↗
Symptoms and transmission of intestinal cryptosporidiosis.
Cryptosporidium spp are a cause of diarrhoea in toddlers. Symptoms and routes of transmission were investigated in a prospective case-control study in the city and surroundings of Basel, Switzerland. Twenty one (4.6%) out of 455 children with diarrhoea who attended paediatric and general practices from June to September 1988 were positive for cryptosporidium. The mothers of each case, of two controls with diarrhoea of another origin, and of two healthy controls were interviewed with a standardised questionnaire. In comparison with controls with diarrhoea of another origin, respiratory symptoms were significantly more frequent in children with cryptosporidiosis: eight of 19 (42%) compared with five of 38 (13%). In comparison with healthy controls, preceding contact with a person suffering from diarrhoea was associated with the greatest relative risk for cryptosporidiosis, followed by travel in a Mediterranean country. Transient cryptosporidial infection of the respiratory tract may be common in immunocompetent children. In the area investigated person to person transmission may account for most cases.
Case-Control Studies↗
[Hypoglycemia in children with diabetes treated with human or porcine insulin].
If hypoglycemia unawareness in diabetes is related to human insulin, its use would mean an increased risk of unconscious hypoglycemia. In a prospective study in 59 children treated from onset of diabetes by either human or porcine insulin of equal purity for a mean observation period of more than 3 years, no significant difference in the incidence of hypoglycemic coma was detected: 9/29 (31%) of the children treated by human insulin compared to 8/30 (27%) of those treated by porcine insulin had 1 or more severe hypoglycemic episodes. At the time of the first coma there was no significant difference in age, duration of diabetes, insulin dose, or HbA1 between the groups. Thus, human insulin is not considered to be an additional risk factor for the development of hypoglycemic coma in diabetic children.
Adolescent↗
Adolescent diet and breast cancer in Utah.
A population-based case-control study was conducted to assess the association between breast cancer risk, body mass index (BMI) and adolescent dietary fat and fiber consumption. Data were collected in Utah from white female cases (N = 172) and controls (N = 190) between the ages of 20 and 54 years. Odds ratios (OR) and 95% test-based confidence intervals (CI) were determined by multiple-logistic regression analysis controlling for age, education, age at menarche, and age at first pregnancy. Menopausal status was identified as an effect modifier, therefore, separate analyses were performed for pre and postmenopausal groups. An elevated risk (OR = 2.9 for highest quartile versus lowest, CI = 1.1-8.1) was associated with a larger BMI at age 12 in premenopausal women; a larger adult BMI lowered the odds ratio (OR = 0.4, CI = 0.2-1.0 for highest quartile versus lowest) in premenopausal women; BMI did not alter risk in postmenopausal women. Although not statistically significant, high fat intake consistently lowered the odds ratios below 1.0 in premenopausal women in the upper three quartiles compared to the lowest fat intake referent quartile (OR = 0.7, CI = 0.2-2.1 for highest versus lowest quartile) but was inconsistent in postmenopausal women (OR = 0.7, CI = 0.2-2.7 for highest versus lowest quartile). When fat intake was assessed by its component parts, fat from milk, cheese and yogurt reduced the odds ratios in both premenopausal (OR = 0.4, CI = 0.1-1.1 for highest versus lowest quartile) and postmenopausal women (OR = 0.2, CI = 0.0-0.8). In postmenopausal women, high fiber intake produced elevated odds ratios in all three upper quartiles (OR = 6.6, CI = 1.5-29.6 for highest versus lowest quartile), while fiber from grains resulted in a decreased risk in both premenopausal (OR = 0.2, 95% CI = 0.2-0.7 for highest versus lowest quartile) and postmenopausal women (OR = 0.7, 95% CI = 0.3-2.0). The possibility of biased estimates from low response rates (cases = 60%, controls = 61%), potential recall bias, and some lack of precision in the dietary instrument should be considered. It appears from these analyses that the relation of breast cancer to dietary intake, especially during adolescent years, is not clear, and that risk associated with fat or fiber intake may be affected by the nutrient source.
Adolescent↗
[Mortality in influenza epidemics in Switzerland 1969-1985].
In Switzerland from 1969-1985, 9 out of 11 influenza epidemics were associated with a statistically significant increase in mortality. A total of 12,202 excess deaths from all causes was identified. Expected deaths were forecast for each epidemic period separately for 4 age groups using Fourier and Arima modeling. 75.7% of all-cause excess deaths occurred in age group 70 to 89 and 5.1% in age group 1-59. In the 70-89 years old group the excess mortality risk during influenza epidemics was 271.6 per 100,000, whereas in age group 1-59 it was only 1.7 per 100,000. Only 40% of all excess deaths had been ascribed to acute respiratory conditions. Influenza viruses A H3N2 were the most frequently identified agents. In some instances mortality increased before the morbidity reports of the Swiss practitioners indicated the occurrence of an epidemic. Also, morbidity reporting decreased over successive years. A decrease in mortality following the epidemics was not observed. A more complete vaccination of high risk patients in Switzerland is desirable.
Adolescent↗
Diabetes and hypertension. Blood pressure in clinical diabetic patients and a control population.
Blood pressure was recorded in a group of 514 randomly selected Swiss diabetic patients (267 men and 247 women; 164 early-onset and 350 late-onset diabetics) aged from 35 to 54 years. These patients were compared with a control group from a population survey in Switzerland (877 men and 850 women). Mean systolic pressure (+/- SD) in the diabetic population was 139.3 +/- 21 mm Hg as compared with 125.5 +/- 17 mm Hg among controls. Mean diastolic pressure was 85.4 +/- 12 mm Hg in diabetic subjects as compared with 79.1 +/- 12 mm Hg in controls. The difference was reduced by about 25% after adjustment for body mass, age, and sex; 30.7% of diabetic subjects as compared with 8.2% among controls were hypertensive. Sixty-two percent of the hypertensive diabetic patients and 45% of the hypertensive controls were receiving antihypertensive treatment. In a multivariate analysis, presence of proteinuria and larger body mass had an important influence on systolic and diastolic blood pressures and the risk of hypertension. Diabetes duration had a significant influence only on systolic blood pressure. Efforts are needed in the clinical and research field to limit and clarify the harmful effects of elevated blood pressure in diabetes.
Adult↗
Human platelet electrorotation change induced by activation: inducer specificity and correlation to serotonin release.
Electrorotation of single platelets was compared with [14C]serotonin release, aggregation and electron microscopy. Activation of washed and degranulated platelets was induced by thrombin, arachidonic acid, collagen, adrenaline, platelet activation factor (PAF), ADP and A23187. A strong correlation between electrorotation decrease and serotonin release was found. Electrorotation did not correlate with aggregation. It was concluded that an increase of the specific conductivity of the platelet membrane by three orders of magnitude (approx. 1.0.10(-7) S.m-1 to 1.0.10(-4) S.m-1) upon activation was responsible for the observed decrease of anti-field rotation and the shift of the first characteristic frequency towards higher values. Electrorotation allowed for time-dependent measurements of activation. Characteristic activation times in the order of minutes were found. There was the following sequence of activators classified by increasing activation time constants: A23187 was the fastest followed by thrombin, collagen, PAF, arachidonic acid, adrenaline, and ADP.
Adenosine Diphosphate↗
[Switzerland changes from U-40 to U-100 insulin].
At present over 95% of the insulin used in Switzerland is sold in a concentration of 40 units per ml (U-40 insulin). Only recently a small but increasing amount of more concentrated insulin has been introduced through the use of "pen" injectors which are all designed for U-100 (= 100 units per ml) insulin. Experience in other countries has shown that when different insulin concentrations are available on the market the risk of dosage errors with potentially severe consequences is high. The Swiss Diabetes Association has therefore taken the initiative in standardizing the concentrations available in Switzerland. A change from U-40 and U-100 to exclusively U-100 insulin is planned for the period from October 1988 to March 1989. A survey among 82 Swiss doctors and 243 IDDM patients has shown that about 60% of doctors and patients are in favour of the change while the remaining 40% are either neutral or opposed to it. Advantages, disadvantages and logistic problems of the change to exclusive use of U-100 insulin, and the possibility of pharmacological differences between insulins of different concentrations, are discussed. It is stressed that the change to U-100 must be medically supervised in every patient. An intensive information campaign providing detailed advice for patients, doctors and pharmacists is essential for the prevention of accidents.
Diabetes Mellitus, Type 1↗
Re: Hypoglycaemia (un)awareness: human vs animal insulin.
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Cognition↗