Biomedical subjects

P Hougaard

Publications and source records attributed to P Hougaard.

At least 37 records · Page 2Linked to original sources

PubMed1996

Insulin sensitivity index, acute insulin response, and glucose effectiveness in a population-based sample of 380 young healthy Caucasians. Analysis of the impact of gender, body fat, physical fitness, and life-style factors.

BACKGROUND: Insulin sensitivity and insulin secretion are traits that are both genetically and environmentally determined. AIM: The aim of this study was to describe the distribution of the insulin sensitivity index (Si), the acute insulin response, and glucose effectiveness (Sg) in young healthy Caucasians and to estimate the relative impact of anthropometric and environmental determinants on these variables. METHODS: The material included 380 unrelated Caucasian subjects (18-32 yr) with measurement of Si, Sg and insulin secretion during a combined intravenous glucose (0.3 grams/kg body weight) and tolbutamide (3 mg/kg body weight) tolerance test. RESULTS: The distributions of Si and acute insulin response were skewed to the right, whereas the distribution of Sg was Gaussian distributed. Sg was 15% higher in women compared with men (P < 0.001). Waist circumference, body mass index, maximal aerobic capacity, and women's use of oral contraceptives were the most important determinants of Si. Approximately one-third of the variation of Si could be explained by these factors. Compared with individuals in the upper four-fifths of the distribution of Si, subjects with Si in the lowest fifth had higher waist circumference, higher blood pressure, lower VO2max, and lower glucose tolerance and fasting dyslipidemia and dysfibrinolysis. Only 10% of the variation in acute insulin response could be explained by measured determinants. CONCLUSION: Estimates of body fat, maximal aerobic capacity, and women's use of oral contraceptives explain about one-third of the variation in Si in a population-based sample of young healthy Caucasians.

Adolescent↗

PubMed1995

Frailty models for survival data.

A frailty model is a random effects model for time variables, where the random effect (the frailty) has a multiplicative effect on the hazard. It can be used for univariate (independent) failure times, i.e. to describe the influence of unobserved covariates in a proportional hazards model. More interesting, however, is to consider multivariate (dependent) failure times generated as conditionally independent times given the frailty. This approach can be used both for survival times for individuals, like twins or family members, and for repeated events for the same individual. The standard assumption is to use a gamma distribution for the frailty, but this is a restriction that implies that the dependence is most important for late events. More generally, the distribution can be stable, inverse Gaussian, or follow a power variance function exponential family. Theoretically, large differences are seen between the choices. In practice, using the largest model makes it possible to allow for more general dependence structures, without making the formulas too complicated.

Adolescent↗

PubMed1995

Albuminuria and poor glycemic control predict mortality in NIDDM.

The impact of microalbuminuria and macroalbuminuria on mortality was evaluated prospectively in 328 Caucasian patients with non-insulin-dependent diabetes mellitus (NIDDM) followed for 5 years. One hundred ninety-one (109 men and 82 women) patients with normoalbuminuria (albumin excretion rate [AER] < 30 mg/24 h), 86 (50 men and 36 women) patients with microalbuminuria (AER 30-299 mg/24 h), and 51 (43 men and 8 women) patients with macroalbuminuria (AER > or = 300 mg/24 h) < 66 years old at entry were followed from 1987 until death or until 1 January 1993. Mean age at entry was 54 (SD 9) years. In January 1993, 8% of patients with normoalbuminuria, 20% of patients with microalbuminuria, and 35% of patients with macroalbuminuria had died (predominantly from cardiovascular disease) (P < 0.01 [normoalbuminuria versus micro- and macroalbuminuria] and P < 0.05 [microalbuminuria versus macroalbuminuria]). Cox multiple regression analysis revealed significant predictors of all-cause mortality to be preexisting coronary heart disease (relative risk [95% confidence interval]), 2.9 (1.6-5.1); log10AER (factor 10), 1.9 (1.4-2.6); HbA1c level (%), 1.2 (1.0-1.4); and age (years), 1.08 (1.03-1.13). Significant predictors of cardiovascular mortality included preexisting coronary heart disease, 6.1 (2.8-13.5); macroalbuminuria, 2.5 (1.1-5.8); HbA1c level (%), 1.3 (1.1-1.6); and systolic blood pressure (10 mmHg), 1.2 (1.0-1.4). Univariate Cox survival analysis in the normoalbuminuric group revealed that AER above the median of 8 mg/24 h was associated with an increased all-cause mortality risk of 2.7 (0.93-7.69) (P = 0.07).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

PubMed1994

Long-term risk of IDDM in first-degree relatives of patients with IDDM.

Due to a short observation period previous studies may have underestimated prevalence and recurrence risk of IDDM in relatives of IDDM patients. To obtain a more exact life-time risk estimate we identified 310 probands, representative of Danish IDDM patients, characterized by current age more than 50 years, age at onset 40 years or less and diabetes duration of more than 30 years. Family data were obtained from 291 probands. Mean "observation" times (age) (+/- SD) for siblings (n = 553) and offspring (n = 359) were 59.4 +/- 16.1 years and 33.8 +/- 8.8 years, respectively. Of the probands 73 (25.1%) had at least one first-degree relative with IDDM. Seventeen percent had at least one affected sibling. An increase from 10.4% to 22.4% of having first-degree relatives with IDDM among probands with age at onset below 20 years was observed during the period from proband at age 21 years up to 1 September 1992. Among affected siblings 48% of the second cases were affected more than 10 years after the first affected sibling. Using the life-table method cumulative recurrence risks from time of birth were calculated for siblings up to age 30 years of 6.4% and up to age 60 years of 9.6%. For offspring the risk up to age 34 years was 6.3%. In addition, we present a life-table method evaluating the cumulative recurrence risk from time of onset in the proband, as this is the most relevant when giving genetic counselling. In conclusion, the long-term risks of IDDM in siblings and offspring are high compared to that shown in previous reports.

Aged↗

PubMed1994

Relationship between blood pressure and urinary albumin excretion rate in young Danish type 1 diabetic patients: comparison to non-diabetic children. Danish Study Group of Diabetes in Childhood.

In 1989 a nation-wide investigation of blood pressure and urinary albumin excretion rate (AER) was carried out in 506 boys and 441 girls with Type 1 diabetes (approximately 80% of total) treated at 22 paediatric departments. In addition a reference population from 1979 consisting of 663 healthy non-diabetic children (334 boys, 329 girls) served as a control group with respect to blood pressure and body mass index. Microalbuminuria was defined as AER of 20-150 micrograms min-1 in at least two out of three timed overnight urine collections and was diagnosed in 30 adolescents (16 boys, 14 girls). Five patients (3 boys, 2 girls) had overt proteinuria (AER: > 150 micrograms min-1). Age-related percentile charts based on one blood pressure reading were provided for normoalbuminuric diabetic patients and the healthy control group. The study revealed an increase in arterial blood pressure during the period of the pubertal growth spurt for the diabetic and non-diabetic group. The changes were most pronounced for systolic blood pressure. No statistically significant difference was observed in systolic and diastolic blood pressure between normoalbuminuric diabetic children and healthy control children. However, diabetic females aged 15-18 years had significantly higher diastolic blood pressure (75 +/- 1 mmHg, n = 139, mean +/- SE) than healthy control females (72 +/- 1 mmHg, n = 155, p < 0.01), and significantly (p < 0.001) higher body mass index (diabetic females: 22.3 +/- 0.2 kg m-2 vs healthy females: 20.9 +/- 0.2 kg m-2, mean +/- SE.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1994

Heterogeneity models of disease susceptibility, with application to diabetic nephropathy.

It is not, in general, possible to include all relevant risk factors in a model of survival or disease incidence. This heterogeneity must be accounted for in the interpretation, as it can imply otherwise unexpected results. This is illustrated by diabetic nephropathy, a serious complication experienced by some diabetic patients. A mathematical model with varying susceptibility can explain that the incidence increases until 20 years duration of diabetes and later decreases. The hospital-based data cover patients diagnosed during 1933-1972. They are interval censored, because early detection of nephropathy requires chemical analysis of urine samples. The data are consistent with a model where less than half of the patients are susceptible, and for each of these the hazard is increasing. The estimated degree of heterogeneity markedly depends on the assumed model. The dependence on age at onset and calendar time of onset is examined. The highest risk is seen at onset age 13-17 years, and the risk decreases with calendar time. The effect of covariates on the hazard is markedly different for the various models, but this is partly a matter of parametrization, as the disagreement is reduced by a reparametrization inspired by accelerated failure time models.

Adult↗

PubMed1992

Chemical stability of insulin. 2. Formation of higher molecular weight transformation products during storage of pharmaceutical preparations.

Formation of covalent, higher molecular weight transformation (HMWT) products during storage of insulin preparations at 4-45 degrees C was studied by size exclusion chromatography. The main products are covalent insulin dimers (CID), but in protamine-containing preparations the concurrent formation of covalent insulin-protamine (CIP) products takes place. At temperatures greater than or equal to 25 degrees C parallel or consecutive formation of covalent oligo- and polymers can also be observed. Rate of HMWT is only slightly influenced by species of insulin but varies with composition and formulation, and for isophane (NPH) preparations, also with the strength of preparation. Temperature has a pronounced effect on CID, CIP, and, especially, covalent oligo- and polymer formation. The CIDs are apparently formed between molecules within the hexameric unit common for all types of preparations and rate of formation is generally faster in glycerol-containing preparations. Compared with insulin hydrolysis reactions (see the preceding paper), HMWT is one order of magnitude slower, except for NPH preparations.

Chemistry, Pharmaceutical↗

PubMed1991

Prevalence of micro- and macroalbuminuria, arterial hypertension, retinopathy and large vessel disease in European type 2 (non-insulin-dependent) diabetic patients.

The prevalence of micro- and macroalbuminuria was determined in Type 2 (non-insulin-dependent) diabetic patients, less than 76 years of age, attending a diabetic clinic during 1987. All eligible patients (n = 557) were asked to collect a 24-h urine sample for quantitative albumin analysis. Urine collections were obtained in 296 males and 253 females (96%). Normoalbuminuria were defined as urinary albumin excretion less than or equal to 30 mg/24 h (n = 323), microalbuminuria as 31-299 mg/24 h (n = 151), and macroalbuminuria as greater than or equal to 300 mg/24 h (n = 75). The prevalence of macroalbuminuria was significantly higher in males (20%) than in females (6%), while the prevalence of microalbuminuria was almost identical in males (26%) and females (29%). The prevalence of arterial hypertension increased with increased albuminuria, being 48%, 68%, and 85% in patients with normoalbuminuria, microalbuminuria, and macroalbuminuria respectively. Prevalence of proliferative retinopathy rose with increasing albuminuria, being 2%, 5% and 12% in patients with normoalbuminuria, microalbuminuria, and macroalbuminuria respectively. Prevalence of coronary heart disease, based on Minnesota coded electrocardiograms, was more frequent in patients with macroalbuminuria (46%) compared to patients with microalbuminuria (26%) and patients with normoalbuminuria (22%). Foot ulcers were more frequent in micro- and macroalbuminuric patients, being 13% and 25%, respectively, compared to 5% in patients with normoalbuminuria. This cross-sectional study has revealed a high prevalence of microalbuminuria (27%) and macroalbuminuria (14%) in Type 2 diabetic patients. Patients with raised urinary albumin excretion are characterized by obesity, elevated haemoglobin Alc, increased frequency of arterial hypertension, proliferative retinopathy, coronary heart disease and foot ulcers.(ABSTRACT TRUNCATED AT 250 WORDS)

Albuminuria↗

PubMed1991

Receptor binding and tyrosine kinase activation by insulin analogues with extreme affinities studied in human hepatoma HepG2 cells.

The insulin-receptor affinity of five human insulin analogues with one to four amino acid substitutions was measured with human hepatoma cells (HepG2). The binding affinities ranged from 0.05% for AspB25 insulin, 18% for AspB9, GluB27 insulin, 80% for AspB28 insulin, and 327% for AspB10 insulin to 687% for HisA8, HisB4, GluB10, HisB27 insulin relative to human insulin. Binding constants obtained by competition experiments at steady state with [125I]TyrA14-labeled insulin and unlabeled analogues and by kinetic studies with [125I]TyrA14-labeled analogues and insulin gave essentially the same values. The kinetic studies showed that differences in affinity between analogues were due to differences in both dissociation and association rate constants. The affinity for insulinlike growth factor I receptor was low, ranging from less than 0.005% for AspB25 insulin to 0.6% for HisA8, HisB4, GluB10, HisB27 insulin. The potencies of insulin analogues in activation of the tyrosine kinase of solubilized and partially purified insulin receptors from HepG2 cells, measured with the exogenous substrate poly(Glu80-Tyr20), ranked in the same order as the binding affinities, the actual values being somewhat elevated for the high-affinity analogues, however. We conclude that these human insulin analogues are active in insulin-receptor binding and tyrosine kinase stimulation but show wide variation in affinity.

Amino Acids↗

PubMed1990

Type 1 (insulin-dependent) diabetes mellitus diagnosed during pregnancy: a clinical and prognostic study.

The study concerns the clinical outcome and later prognosis (regarding permanent insulin treatment) of patients who develop insulin-dependent diabetes mellitus during pregnancy (which is different from gestational diabetes). Sixty-three such patients (27 +/- 1 (SEM) years old) were delivered at the Copenhagen Centre for Diabetes and Pregnancy during the years 1966-1980. Obstetric complications such as toxaemia were seen in 9.5% of these study patients and the perinatal mortality was 6.3%, both percentages being higher than in the general population (1.1%, p less than 10(-7) and 1.0%, p less than 10(-3), respectively), but similar to those observed in patients with Type 1 diabetes diagnosed before pregnancy. In contrast, the frequency of malformations was 1.6%, the same as in the general population (1.4%), but lower than that seen in patients with long-standing diabetes (8.3%, p less than 0.05). At follow-up examination 8 +/- 1 years after diagnosis all patients were diabetic; 77% were insulin treated, having no or virtually no residual B-cell function, and were clearly Type 1 diabetic patients. After delivery 80% of the patients had a remission period (median 256 days) without insulin treatment. This remission period was absent or shortest in patients with the following characteristics (p less than or equal to 0.03): low age, first parity, not overweight, and high blood glucose level at diagnosis. These prognostic parameters should be considered in obligatory, clinical follow-up plans for such patients.

Adult↗

PubMed1990

Ionization behavior of native and mutant insulins: pK perturbation of B13-Glu in aggregated species.

Upscale titration from pH 2.5 to 11.2 is used as a means for probing solvent accessibility of ionizing groups in zinc-free preparations of native and mutant insulins. Stoichiometry and pK alpha values of ionizing groups in the titration curves are determined by iterative curve fitting. Under denaturing conditions, the titration curve of human insulin is in good agreement with that predicted from the sum of unperturbed titrations of the constituent ionizing groups and yields an apparent isoionic point of 5.3. Under nondenaturing conditions where aggregation and precipitation occur, titrations show that only five out of six carboxylate residues of human insulin ionize in the expected region. Consequently, one carboxylate ionization is masked and the apparent isoionic point located at pH 6.4. Correlation between ionization behavior and patterns of aggregation and solubility is established by titrations of mutant insulins and of dilute native insulin. Titration of an unusually soluble species, B25-Phe----His, shows that precipitation is not responsible for the masked carboxylate ionization of native insulin. Titrations of mutants B13-Glu----Gln and B9-Ser----Asp show that the masked ionization probably originates from monomer-monomer interactions in the insulin dimer. We conclude that the B13-Glu side chain is responsible for the masked carboxylate ionization in aggregated forms of human insulin.

Humans↗

PubMed1990

Equivalent in vivo biological activity of insulin analogues and human insulin despite different in vitro potencies.

In vivo biological potency of two human insulin analogues, AspB9,GluB27 insulin and AspB10 insulin with low and high affinity to the insulin receptor, respectively, was assessed by intravenous infusion of equimolar amounts in pigs, with the euglycemic clamp technique. Human insulin and the low- and high-affinity analogues showed equivalent glucose utilization rates in the steady state (mean +/- SE 14.7 +/- 1.4, 12.7 +/- 1.5, and 12.2 +/- 1.2 mg.kg-1.min-1, respectively; n = 7). The corresponding plasma insulin levels, however, were markedly different (329 +/- 25 and 856 +/- 46 pM, P less than 0.05; 197 +/- 19 pM, P less than 0.05). There was an inverse relationship between the insulin levels and the in vitro activities measured by binding to human hepatoma cells (HepG2; 100, 20, and 308%) or by incorporation of glucose into lipids in mouse free fat cells (100, 31, and 207%). The total amount of glucose infused during and after insulin infusion was equal for the three insulins, whereas glucose utilization as a function of time was somewhat different. By describing the individual plasma concentration courses with an open two-compartment model with elimination from the receptor compartment, the time courses for binding and elimination of the three insulins in the receptor compartment were estimated. The effect seems closely linked to the elimination of insulin from the receptors rather than to the amount of insulin bound to the receptors. In conclusion, the total effect of equimolar amounts of human insulin and the two insulin analogues on glucose utilization is equal regardless of the different receptor affinities of the insulins.

Animals↗

PubMed1989

NovoSol Basal: pharmacokinetics of a novel soluble long acting insulin analogue.

OBJECTIVE: To determine the courses of absorption and the interindividual and intraindividual variations in absorption of iodine-125 labelled Ultratard HM and NovoSol Basal injected subcutaneously. DESIGN: Open randomised crossover study. Each patient was tested during two study periods of five days each, during which he or she received a subcutaneous injection of either 125I-NovoSol Basal or 125I-Ultratard HM on four consecutive days. The aim was to detect a reduction in intraindividual standard deviation by a factor of two with a probability 0.95, taking 0.05 as the level of significance. This required 24 degrees of freedom and led to the choice of four courses in each of eight patients. SETTING: Referrals to the diabetes research centre in Hvidøre, Copenhagen. PATIENTS: Eight insulin dependent (type I) diabetics with low or undetectable C peptide concentrations who were receiving a multiple insulin injection regimen. One patient withdrew immediately after recruitment. INTERVENTIONS: After an overnight fast patients received 96 nmol (16 IU insulin) of either 125I-NovoSol Basal or 125I-Ultratard HM injected subcutaneously into the thigh. To ensure that the insulin entered the subcutaneous fat at the same depth, ultrasonography was performed on each patient before the first injection. A different injection site on the thigh was used each day for four days in order to facilitate monitoring of the disappearance of four different depots in each patient. MAIN OUTCOME MEASURE: Residual activity at the injection site was measured roughly every two hours throughout the day. No radioactivity measurements were performed overnight (10 pm till 8 am). The residual radioactivity after the injection on the first day (upper right thigh) was recorded for five days, that after the injection on the second day (upper left thigh) for four days, after the injection on the third day (lower right thigh) for three days, and after the last injection (lower left thigh) for two days. RESULTS: NovoSol Basal was absorbed according to first order kinetics with a mean t50% of 35.3 (SEM 1.4) hours; Ultratard HM was absorbed after a lag phase and the corresponding t50% was 25.5 (2.5) hours. The intraindividual variations in t50% were significantly smaller with NovoSol Basal than with Ultratard HM (18.4% v 44.5%; p less than 0.001). Interindividual variations, however, were not significantly different (25.2% v 36.9%; p = 0.38). The total variation in t50% was substantially smaller with NovoSol Basal than with Ultratard HM (20.3% v 42.8%). CONCLUSIONS: NovoSol Basal seems to be an appreciable advance over Ultratard HM as a soluble insulin preparation for obtaining reproducible 24 hour insulin concentrations in the blood

Absorption↗

PubMed1988

Prevalence of microalbuminuria, arterial hypertension, retinopathy and neuropathy in patients with insulin dependent diabetes.

Diabetic nephropathy is the main cause of the increased morbidity and mortality in patients with insulin dependent diabetes. The prevalence of microalbuminuria was determined in adults with insulin dependent diabetes of five or more years' duration that had started before the age of 41. All eligible patients (n = 982) attending a diabetes clinic were asked to collect a 24 hour urine sample for analysis of albumin excretion by radioimmunoassay; 957 patients complied. Normoalbuminuria was defined as urinary albumin excretion of less than or equal to 30 mg/24 h (n = 562), microalbuminuria as 31-299 mg/24 h (n = 215), and macroalbuminuria as greater than or equal to 300 mg/24 h (n = 180). The prevalence of microalbuminuria and macroalbuminuria was significantly higher in patients whose diabetes had developed before rather than after the age of 20. The prevalence of arterial hypertension increased with increased albuminuria, being 19%, 30%, and 65% in patients with normoalbuminuria, microalbuminuria, and macroalbuminuria respectively. The prevalence of proliferative retinopathy and blindness rose with increasing albuminuria, being 12% and 1.4%, respectively, in patients with normoalbuminuria, 28% and 5.6% in those with microalbuminuria and 58% and 10.6% in those with macroalbuminuria. An abnormal vibratory perception threshold was more common in patients with microalbuminuria (31%) and macroalbuminuria (50%) than in those with normoalbuminuria (21%). This study found a high prevalence (22%) of microalbuminuria, which is predictive of the later development of diabetic nephropathy. Microalbuminuria is also characterised by an increased prevalence of arterial hypertension, proliferative retinopathy, blindness, and peripheral neuropathy. Thus, urinary excretion of albumin should be monitored routinely in patients with insulin dependent diabetes.

Adult↗

PubMed1988

Soluble, prolonged-acting insulin derivatives. III. Degree of protraction, crystallizability and chemical stability of insulins substituted in positions A21, B13, B23, B27 and B30.

It was previously demonstrated that insulins to which positive charge has been added by substituting B13 glutamic acid with a glutamine residue, B27 threonine with an arginine or lysine residue, and by blocking the C-terminal carboxyl group of the B-chain by amidation, featured a prolonged absorption from the subcutis of rabbits and pigs after injection in solution at acidic pH. The phenomenon is ascribed to a low solubility combined with the readiness by which these analogs crystallize as the injectant is being neutralized in the tissue. However, acid solutions of insulin are chemically unstable as A21 asparagine both deamidates to aspartic acid and takes part in formation of covalent dimers via alpha-amino groups of other molecules. In order to circumvent the instability, substitutions were introduced in position A21, in addition to those in B13, B27 and B30, challenging the fact that A21 asparagine has been conserved in this position throughout the evolution. Biological potency was retained when glycine, serine, threonine, aspartic acid, histidine and arginine were introduced in this position, although to a varying degree. In the crystal structure of insulin a hydrogen bond bridges the alpha-nitrogen of A21 with the backbone carbonyl of B23 glycine. In order to investigate the importance of this hydrogen bond for biological activity a gene for the single-chain precursor B-chain(1-29)-Ala-Ala-Lys-A-chain(1-21) featuring an A21 proline was synthesized. However, this single-chain precursor failed to be properly produced by yeast, pointing to the formation of this hydrogen bond as an essential step in the folding process. The stability of the A21-substituted analogs in acid solutions (pH 3-4) with respect to deamidation and formation of dimers was approximately 5-10 times higher than that of human insulin in neutral solution. The rate of absorption of most insulins is decreased by increasing the Zn2+ concentration of the preparation. However, one analog with A21 glycine showed first-order absorption kinetics in pigs with a half-life of approximately 25 h, independent of the Zn2+ concentration. The day-to-day variation of the absorption of this analog was significantly lower than that of the conventional insulin suspensions, a property that might render such an insulin useful in the attempts to improve glucose control in diabetics by a more predictable delivery of basal insulin.

Absorption↗

PubMed1988

Significance of ventricular ectopic activity in the early recovery phase of acute myocardial infarction.

Holter monitoring of 51 patients on the 4th to 6th day after acute myocardial infarction (AMI) disclosed complex ventricular ectopic beats in 17 (35%), nine of whom (53%) died in the following 26 months. Of the remaining patients with no or only non-complex ectopic beats, five (15%) died. The difference was significant using Gehan's test of censored data (p less than 0.01). Multivariate analysis demonstrated a significant increase of death risk associated with complex ventricular ectopic beats as well as with heart failure (relative risk 3.6 and 5.9, respectively). Age, gender, number of ventricular ectopic beats, cardiac enlargement on X-ray and angina pectoris had no significant effect on mortality. The prevalence of ventricular ectopy was 84% (n = 43) irrespective of age and sex and equal to the finding in the late hospital phase reported by other investigators, and in healthy subjects. Complex ventricular ectopic beats appeared in 35% (n = 17). The prevalence increased significantly with age and was significantly higher in post-infarction patients (38%) than in healthy individuals (8%). The present results indicate that a subgroup containing most of the high-risk patients may be identified early after AMI by detecting complex premature ventricular beats in continuous electrocardiographic recordings.

Adult↗

PubMed1988

Prognostic significance of differential cell counts in non-Hodgkin's lymphomas.

The use of differential counting on H & E stained sections is proposed as a simple means to define low grade malignant and high grade malignant cytologic categories in non-Hodgkin's lymphomas. Differential counts were performed in lymphoma biopsies from 616 cases. In each biopsy we counted 100 lymphoma cells and classified each cell as belonging to a "small", "medium-sized", or "large" cell type. The results indicate the presence of two prognostically distinct cytologic categories: a low grade and a high grade malignant. Lymphomas with less than 10% "large" cells represented low grade malignant cytology. Included in this category were also the, mainly follicular, lymphomas with more then 70% "medium-sized" cells (up to about 25% "large" cells). In addition to the cytologic category, the architectural pattern is of major prognostic importance. We recommend the use of three prognostic categories in non-Hodgkin's lymphomas: I) Favourable architecture + favourable cytology. II) Unfavourable architecture + favourable cytology. III) Unfavourable cytology.

Analysis of Variance↗

PubMed1987

Increased incidence of true type I diabetes acquired during pregnancy.

A longitudinal study was carried out of all patients with newly acquired insulin dependent diabetes during pregnancy (as distinct from non-insulin-dependent gestational diabetes) seen at the Copenhagen Centre for Diabetes and Pregnancy during 1966 to 1980. The series comprised 63 patients with a mean age of 27 (SEM 1) years. At diagnosis the mean fasting blood glucose concentration was 15.6 (1.3) mmol/l and mean maximal insulin dose 49 (3) IU/day. At a prospective follow up examination a mean of 8 (SEM 1) years after diagnosis 46 of 60 patients (77%) were being treated with insulin (35 (2) IU/day) and had a very low mean stimulated plasma C peptide value (0.12 (0.02) nmol/l) suggesting absent or nearly absent beta cell function. The remaining 14 patients (23%), not currently receiving insulin, appeared to be severely glucose intolerant, having a mean fasting blood glucose concentration of 13.4 (1.2) mmol/l. Thus most of these patients developing insulin dependent diabetes during pregnancy had true type I disease. Compared with the age specific incidence of type I diabetes in the background population of women the incidence was at least 70% higher in pregnant than non-pregnant women (p less than 0.001; chi 2 = 11.6; f = 1). This increased incidence occurred in the third trimester when the risk of developing type I diabetes was 3.8 times that of non-pregnant women (p less than 0.000001; chi 2 = 35.6; f = 1). Finally, the risk of developing insulin dependent diabetes during pregnancy was lower when conception occurred in the winter (p less than 0.05; chi 2 = 4.18; f = 1).

Adult↗