The FBN1 (R2726W) mutation is not fully penetrant.

The R2726W mutation in the fibrillin 1 (FBN1, Marfan syndrome) gene segregates with isolated skeletal features of Marfan syndrome and/or high stature. Here we report a family in which two out of four individuals, an 18-year-old son and his mother, a 41-year-old woman, had the R2726W mutation of FBN1. Both family members carrying the mutation were of average height. The son had a Marfan-like phenotype, but his mother did not. The FBN1 R2776W mutation, which is associated with skeletal features of Marfan syndrome, appears incompletely penetrant. Consequently, genetic counselling in the presence of this mutation is difficult.

Treatment of allergy to heterologous monocomponent insulin with human semisynthetic insulin. Long-term study.

Eight type II (non-insulin-dependent) diabetic subjects (7 women, 1 man, aged 42-61 yr), initially treated with oral hypoglycemic agents and intermittently treated with conventional insulins, were identified as developing allergic reactions to porcine and mixed-species monocomponent insulin. Allergy was systemic (urticaria and nonthrombocytopenic purpura) and local delayed in two subjects and local immediate or biphasic in six subjects. Lipoatrophy was present in two subjects. After treatment with human semisynthetic insulin (Monotard HM and Actrapid HM), systemic allergy disappeared. Local allergy disappeared in five subjects and was reduced in three subjects. No lipoatrophy occurred in new injection areas. The clinical results were accompanied by a significant decrease in serum insulin-specific IgE after 6, 12, 18, 24, 30, and 36 mo. Insulin-specific IgG showed an evident decrease in five of eight patients, but the difference in mean values was not significant after 6, 18, 24, 30, and 36 mo. With one exception, intradermal skin tests were positive to human, bovine, and porcine insulin before and after human insulin treatment.

[Diabetic foot: practical management of an old recurrent problem]. / Piede diabetico: gestione pratica di un vetusto problema ricorrente.

A simplified approach to the management of major lesions of the diabetic foot is presented. Two nosological types, the angiopathic foot and the neuropathic foot, are proposed, on the basis of diagnostic, therapeutic, prognostic and preventive criteria. A ten years personal experience is discussed.

[HLA typing and insulin antibody production in insulin-dependent diabetics]. / Tipizzazione HLA e produzione di anticorpi anti-insulina nel diabetico insulina-dipendente.

The literature of the past ten years shows that the introduction of highly purified heterologous and, lastly, homologous insulins has notably lowered the production of IgG and IgE specific insulin antibodies, but has not succeeded in completely eliminating clinical manifestations of the immune or hyper-immune response to insulin therapy. In particular, insulin allergy with or without lipodystrophy is still seen. Among the factors of insulin immunogenicity, there is a possible genetic control of the immune response in type I diabetes: determining HLA halloantigens (A, B, C, D) might identify specific immune response genes (Ir genes). Initial researches, performed until now almost exclusively upon diabetics treated with conventional heterologous insulin, seem to indicate a positive relationship between haplotype HLA - B15 - DR4 and an elevated immune response, whereas haplotypes HLA - B8 - DR3 and HLA - B18 - DR3 might protect against the formation of anti-insulin antibodies. Antigens D/DR3 and D/DR4 are known to be primitively associated to susceptibility for type I diabetes, whereas antigens B8, B15, B18 are secondarily associated to the rise in frequency of DR3 and DR4 for the "linkage disequilibrium" existing between alleles of B and D loci. The results of HLA typing are presented in 2 groups of insulin-dependent diabetics (ID) followed from an immunological viewpoint during therapy with monocomponent heterologous insulin for over 5 years. The first group is composed of 50 patients with low IgG anti-insulin antibody titers (less than 1 mU/ml, Christiansen: low responders); the second group is made up of 23 patients with high IgG anti-insulin antibody titers (greater than 2.5 mU/ml, Christiansen: high responders) and includes 5 subjects with insulin allergy (associated or not with insulin lipoatrophy) and high levels of insulin specific IgE antibodies. A study of the frequencies of various HLA-B antigens in both groups of patients, in regard to a control group of piemontese population, in relation to the intensity of association (relative risk) and to the statistical importance of frequencies, shows only a possible protective effect of the HLA-B18 phenotype (linkage disequilibrium with HLA - DR3) towards the production of anti-insulin antibodies and hyperimmune clinical manifestations, such as allergy. Reliable conclusions are not possible between low and high responders for the other phenotypes (HLA - B7, B8, B15) commonly implicated. HLA-B12 was noted in 3 of 5 patients with allergy, in 2 cases associated with B8.(ABSTRACT TRUNCATED AT 400 WORDS)

[Education of the diabetic patient: 10-year experience at the Karen Bruni Center]. / L'educazione del diabetico: dieci anni di esperienza al centro KB.

On the basis of a ten year experience, new behavioural and philosophical approaches to the education of insulin-dependent diabetic patients are proposed by the Karen Bruni Diabetes Center of Turin. Conceptual and methodological revisions of conventional programs should be tried out. Practical difficulties are still restricting an integrated educational treatment of the diabetic persons.

[The HLA system and insulin-dependent diabetes mellitus. A review and personal studies]. / Sistema HLA e diabete insulina-dipendente. Rassegna e indagini personali.

Present knowledge regarding the HLA system and the association between HLA antigens and insulin-dependent type 1 diabetes mellitus (IDDM) is reviewed. The heterogeneity of diabetes, immunogenetically speaking, is emphasized. Results are reported for HLA typing in 18 cases of known IDDM recently diagnosed and observed at the Karen Bruni Diabetes Center in approximately one year (1981-82). The frequency of HLA antigens B7, B8 (in linkage disequilibrium with DR3), B15 (in linkage disequilibrium with DR4) and B18 was examined in comparison with a Piemontese control group. The X2 method was used for calculating the relative risk and statistic importance of the intensity of association. IDDM susceptibility in association with HLA-B18 was confirmed and resulted significantly higher in our cases in respect to controls. Correlations without, however, reliable importance, have also been found between HLA-B8 and B15. IDDM protection by HLA-B7 was not confirmed. Diabetes began during the winter, from October to February, in 10 out of 18 cases, and some were positively related to a previous respiratory viral infection. Previous virus infection was found in three B7-positive cases. The more frequent arousal of diabetic symptoms during the winter in subjects positive for HLA-B8 and B18 was confirmed in 7 out of 8 cases. This work demonstrates the current practicability of HLA typing of recently diagnosed insulin-dependent diabetic in a Diabetes Center. This element helps to a more correct classification--on a subclinical basis--of initial cases of type 1 and 2 diabetes and can be used for possible problems during the course of insulin therapy.

[Home self-monitoring of blood glucose with a new reflectance photometer]. / Autocontrollo domiciliare della glicemia con un nuovo fotoreflettometro.

The accuracy of a new reflectance photometer, RapidGluco Italamec, intended for home blood glucose monitoring was compared with that of two other reflectometers, Glucocheck Medistron and Glucometer Ames, all using Dextrostix strips, and a routine laboratory method (Glucose Analyzer Beckman). Venous blood sugar values from 300 randomly selected patients attending our Clinic, obtained with each of the reflectometers (RapidGluco, Glucocheck, Glucometer), correlated significantly with those obtained with the Glucose Analyzer (r = 0.95, 0.99, 0.90; y = 1.06x + 3.29; y = 1.04x + 0.26; y = 0.87x + 34.8). The reflectometer - Dextrostix system proved accurate and convenient for practical purposes with all three instruments. Attention may be drawn to the lower cost of the RapidGluco. Prospective studies are needed to evaluate the reliability of the system when used by patients themselves, the advantages of reflectometers over visual readings of the strips, and their improvement of diabetic control.

[Principles, means and evaluation of a programme for diabetes education (author's transl)]. / Principi, mezzi e verifica di un programma di informazione per i diabetici.

A programme of patient information and education, as a primary tool of diabetes treatment, has been developed during the past 5 years, aiming to an effective self-management of diabetes. The programme is patient-oriented, with an essential psychological approach, based on a realistic language and following the concepts of a simple "diabetes philosophy". The diabetes is considered as an human condition, not necessarily a disease. Two phases are proposed. The first, termed "basic information", essentially consists of: 1) an individual checklist of 20 main-items to be gradually completed, with sharing of responsibilities between professionals and diabetics, according to the Etzwiler's contract concept; 2) a set of six original slide-tapes (Bell a. Howell and Reflex projectors) and video-tape films (Fairchild), with personal comments; 3) the red booklet "Condizione diabete" published in 1978 by the Karen Bruni Diabetes Centre. The second phase of the programme, termed "advanced information", is intended for a continuous up-to-dating of diabetological knowledge. The means used are: 1) periodical information meetings with discussion on various existential problems of diabetics; 2) a quarterly magazine "Centro KB", in which new techniques and investigations (such as C peptide and insulin antibody determination) are explained or local events are commented. The effectiveness of the programme has been evaluated through a questionnaire given to 305 subjects attending both the diabetes ward (in-patients and out-patients) and the diabetes clinic (out-patients only). The questionnaire asks 20 specific questions, of the multiple choice type, about day-to-day care complications, natural history of the diabetes, and so on. The percentage of total correct responses, as well as of correct responses to 3 key questions (hypoglycaemia, hyperglycaemia, complicating infections) has been analyzed on a computer PDP 11/23 (FORTRAN) in relation to demographic and diabetological variables. The educational level appears to be positively correlated with attendance to the ward (initial hospitalization) in comparison to the out-patients clinic, young age and insulin-dependence, and schooling. No relationship was found between level of information and metabolic control, as assessed by HbA1C. Following conclusions are drawn: 1) the complete programme of patient education is particularly valuable for young insulin dependent (ID) diabetics, who really need and properly use the information; 2) to the adult-old, non insulin-dependent diabetics (NID) a limited information programme seems to be more suitable; 3) a separation between ID and NID diabetics has to be considered when planning a future information programme; 4) permanent hard personal engagement by the diabetologist, and continuous review and criticism of information means and techniques, are requested if the tasks of a really patient-oriented teaching have to be attained.