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Diagnostic circumstances and clinical forms of type 1 diabetes. In its classic form, type 1 diabetes is the prototype of insulindependent diabetes. But ketoacidosis can occur outside of type 1 diabetes, so ketoacdosis does not necessarily mean definitive insulin therapy. Conversely, type 1 diabetes may initially be mistaken for type 2 diabetes. This is often associated with insulin delay after months of wandering and poor blood glucose control. New forms of diabetes have appeared, such as fulminant diabetes, specific to individuals from South Asia and the Far East, but also iatrogenic forms associated with new immunomodulatory treatments that revolutionize the management of certain cancers. This review presents the clinic and differential diagnosis of type 1 diabetes including these new forms of diabetes.Circonstances diagnostiques et formes cliniques du diabète de type 1. Dans sa forme classique, le diabète de type 1 est le prototype du diabète insulinodépendant. Mais l’acidocétose peut s’observer en dehors du diabète de type 1, elle ne signifie donc pas forcément insulinothérapie définitive. À l’inverse, le diabète de type 1 peut être pris initialement pour un diabète de type 2 ; cela est souvent associé à un retard à la mise à l’insuline après des mois d’errance et de mauvais contrôle des glycémies. De nouvelles formes de diabète sont apparues, comme le diabète fulminant, spécifique des individus originaires de l’Asie du Sud et de l’Extrême-Orient, mais aussi des formes iatrogènes associés aux nouveaux traitements immunomodulateurs qui révolutionnent la prise en charge de certains cancers. Ce texte présente le tableau clinique et le diagnostic différentiel du diabète de type 1 en incluant ces nouvelles formes de diabète.

Summary: Interleukin-1 receptor antagonist (IL-1Ra) is elevated in the circulation during obesity and type 2 diabetes (T2D) but is decreased in islets from patients with T2D. The protective role of local IL-1Ra was investigated in pancreatic islet β cell (βIL-1Ra)-specific versus myeloid-cell (myeloIL-1Ra)-specific IL-1Ra knockout (KO) mice. Deletion of IL-1Ra in β cells, but not in myeloid cells, resulted in diminished islet IL-1Ra expression. Myeloid cells were not the main source of circulating IL-1Ra in obesity. βIL-1Ra KO mice had impaired insulin secretion, reduced β cell proliferation, and decreased expression of islet proliferation genes, along with impaired glucose tolerance. The key cell-cycle regulator E2F1 partly reversed IL-1β-mediated inhibition of potassium channel Kir6.2 expression and rescued impaired insulin secretion in IL-1Ra knockout islets. Our findings provide evidence for the importance of β cell-derived IL-1Ra for the local defense of β cells to maintain normal function and proliferation.

The distribution of specific radiolabeled biological compounds in tumor tissues can be imaged by positron emission tomography (PET). The substance used is fluorodeoxyglucose, labeled with the positron emitter fluorine-18. This substance is partly trapped in tumor cells with increased glucose metabolism. This noninvasive imaging technique allows to assess quantitatively and in three dimensions the extent of metastatic disease in ENT cancer. The case presented illustrates the important value we foresee for this new imaging modality in the presurgical staging of cervical metastatic disease of ENT tumors. Sensitivity and specificity of the PET-FDG imaging technique for the loco-regional staging of ENT cancer are, according to preliminary results of an ongoing, prospective clinical study, very high.

In a double-blind parallel study, 20 elderly hypertensive subjects (mean age 85 years) were treated either by nicardipine or by nifedipine in slow-release form for 7 days. Blood pressure was measured by ambulatory, non-invasive daytime monitoring. Efficacy of both drugs was similar on the seventh day of treatment. However, the hypotensive effect induced by nifedipine was maximal on the first day of treatment, in contrast to the progressive effect induced by nicardipine. In 2 cases, marked hypotension was observed after the first tablet of nifedipine.

In a double-blind parallel study, 20 elderly hypertensive subjects (mean age 85 years) were treated either by nicardipine or by nifedipine in slow-release form for 7 days. Blood pressure was measured by ambulatory, non-invasive daytime monitoring. Efficacy of both drugs was similar on the seventh day of treatment. However, the hypotensive effect induced by nifedipine was maximal on the first day of treatment, in contrast to the progressive effect induced by nicardipine. In 2 cases, marked hypotension was observed after the first tablet of nifedipine.

43 potroom workers (aluminium industry) with fluorosis have been compared with 18 foundry workers of the same age, but who had never been exposed to fluorides. Clinical examination revealed a higher incidence of articular pain and limitation of motion in the exposed group. The diagnosis of fluorosis is not only clinical but calls for other investigations such as urinary fluoride determination, bone radiology and, above all, bone biopsy for fluoride determination, histology and microradiography.

The analgesic properties of 89Sr were investigated in 17 patients with multiple painful bone metastases. 89Sr is a radioisotope, the metabolism of which in the body is comparable to that of calcium. It is a pure beta emitter and its half-life is 51 days. When injected intravenously it is captured by bone, especially at locations where the turnover is increased. Each patient received 1--2 mCi of 89Sr. Bone scans and hematological investigations were performed before, and 2 months after, treatment. No significant changes were found. Shealy's method was used to assess pain, initially twice a week and then at more prolonged intervals. One patient suffering from multiple myeloma showed a spectacular improvement and 6 others responded favourably. Improvement generally occurred within 3--7 days, but was sometimes delayed for up to 3 weeks. Relief lasted for up to several months. Five patients had an increase of pain during the 24 hours immediately after treatment. An average of 28% of the administered radioactive dose was found in the urine collections during the first 48 hours. Although the treatment was not successful in every case, the use of 89Sr as a long acting analgesic in multiple bone metastases should be considered more frequently, especially as there are no side effects.

57Co-bleomycin scanning dates from the early 1970s, when the first results were presented by Renault et al. Since then there have been numerous publications concerning the high sensitivity of this type of study in the detection of pulmonary or cerebral neoplasms. In the region below the diaphragm, however, sensitivity was poor due to hyperactivity of the kidney, liver and bladder. To eliminate this problem the authors have used single photon emission computerized tomography (SPECT), and their department is currently investigating the sensitivity of this technique for the detection of neoplasms. Two typical cases are described which illustrate the value of this method in the detection of cancer.

Dichloromethylene diphosphonate (Clodronate) has powerful activity against osteoclasts. We studied its effects on calcium balance in patients with malignant osteolytic lesions. Ten normocalcemic patients with advanced metastatic bone disease or myeloma were evaluated in a baseline 20-day calcium balance and kinetic study. They were then randomized to a clodronate or placebo regimen, treated intravenously for two weeks and orally for a month, and finally re-evaluated in another 20-day balance and kinetic study, conducted while they were still receiving treatment. The results show that both calcium balance and calcium absorption increased from base line in the clodronate group and that these changes were significantly different from those in the placebo group. There was a marginal decrease in bone resorption in the clodronate group and no change in bone accretion. Our results suggest that clodronate may be a useful adjuvant in managing metastatic bone disease.

The weighing of the human body under water is an application of Archimedes' law. Fat being lighter than water or than the structures of lean body mass, body fat can be measured by determining the specific gravity of the human body; that is, by underwater weighing. Body fat has been determined in an "ideal" sample of 14 men and 23 women, all aged 20 years. Testing against a reference measure of body fat makes it possible to test the validity of some anthropometric measurements and of some indices of obesity. These indices offer no advantages over anthropometric measurements.

The authors have investigated the assumption that alcohol increases iron absorption. Using the whole body counter technique, they show that iron absorption is lowered significantly by addition to the test dose of either normal or dealcoholized whisky, but that there is no difference between these two latter groups. Wine has a similar effect. The use of ethanol added to a test meal demonstrates that it is organic iron, and not the inorganic form, whose absorption is diminished by alcohol.

Echocardiography and radionuclide angiography are presently the two first choices non-invasive methods for the diagnosis of pericardial effusion. To evaluate the sensitivity and specificity of these methods, a prospective study of 43 consecutive patients was undertaken. Confirmation by tap or autopsy was obtained in 10 cases; for the remainers, strict clinical signs were requested. The results of both methods were classified in a quantitative manner. Our data confirms the greater sensitivity and specificity of echocardiography compared with radionuclide angiocardiography, when small amounts of effusion are present. However, the correlation between the two methods is satisfactory when a greater amount of fluid is present.

Stenoses of the left anterior descending coronary artery of varying severity (15-73% of internal diameter, 20-95% of internal surface) were created in 25 open-chest pigs. The regional distribution of myocardial blood flow perfusion was studied by the radioactive microspheres technique at rest and during reactive hyperemia. Reactive hyperemic responses to 10 sec occlusions were used to produce maximal flow increases and to judge the physiological significance of the narrowings in the subendocardial and subepicardial layers in calculating coronary flow reserves. Measurements of coronary reserve are sensitive indices of functional impairment even when resting flow is unimpaired. At 75% stenosis the subendocardial coronary reserve is completely abolished and the zone perfused by the stenosed artery is unable to increase its flow when needed if the experimental conditions do not change. Any further increase in oxygen demand will provoke electrical and metabolic disorders. For abolition of the subepicardial coronary reserve a 94% stenosis is required.

An evaluation is presented of (1) the overall sensitivity and specificity of 201Tl myocardial scintigraphy in 230 patients with suspected coronary artery disease and (2) the effects of the number and location of the diseased vessels, and the presence of previous infarction, on regional sensitivity in 151 patients. Overall sensitivity was 91% (80%, 95%, 97%) in patients with 1, 2 or 3 vessels respectively. Overall specificity was 81% or 89% if 7 patients with infarction and normal coronaries were excluded. In 80% of patients with one diseased vessel, in 41% of patients with 2 diseased vessels, and in only 24% with 3 diseased vessels were all lesions detected. 201Tl scintigraphy detected 52% of circumflex lesions as compared to 75% of right coronary and 74% of left anterior descending lesions. Of the 151 patients with proven coronary disease, 75 had a previous infarction. Overall and regional 201Tl sensitivity were greater (but not significantly) in this subgroup as compared to patients without myocardial infarction.

Phase analysis and ejection fraction (EF) of the left ventricle were obtained by radionuclide angiography in 53 patients at rest, during submaximal exercise and 3-8 minutes after exercise. The standard deviation of the peak of the histogram of phases (SDP) was used as an index of the synchronicity of regional contraction. The material comprised 13 sportsmen and 40 patients who underwent coronarography, 12 of whom had normal coronaries and 28 significant lesions. EF, while comparable in the three groups at rest, increased significantly on effort in normals and did not change in patients with coronary disease. At rest SDP was higher in coronary patients than in normals (p less than 0.01), and during exercise, it increased, but decreased in normals (p less than 0.01). After exercise, mean EF decreased in comparison with exercise in normals (p less than 0.01), while the opposite was the case in coronary patients. Normals had lower SDP values in the post-exercise period than at rest; on the other hand, SDP of coronary patients was significantly higher in the post-exercise period than at rest (p less than 0.001). Phase analysis during, and particularly after, exercise was found to be superior to EF in detecting ischemic left-ventricular dysfunction, and should be used in conjunction with EF to evaluate patients suspect for coronary disease.

99mTc-diethyl-HIDA selective captation by hepatocytes and rapid excretion into bile provides a scintigraphic imaging of liver, biliary system and gall bladder. Substance blood clearance and liver half-life measurements add quantitative information on liver function. Normal, cirrhotic and jaundiced patients with extrahepatic obstruction were studied and each group showed significant characteristics. Through non-invasive biliary system visualization and liver function evaluation, hepatobiliary scintigraphy has its place as a complementary investigation in hepatology.

In the 111-indium-leukocyte scan method described by M. L. THAKUR et al. in 1977 for the diagnosis of abdominal abscesses the whole leukocyte fraction from a blood sample is labeled and injected into patients. We propose a modification in which purified granulocytes are used. The results of 43 granulocyte scans show that this modification does not diminish the sensitivity of the method. Furthermore, it allows the detection of abscesses in a shorter time (2-4 hours after injection) and with 111-indium doses (200 muCi) at least 3 times lower than in the original method. Increased specificity can also be expected.

A multidisciplinary study on the prolonged treatment of involution osteoporosis with fluoride was performed on a homogeneous population of 31 women aged 51 to 75 years (mean 64 years). The selection criteria were the following: significant backache, vertebral compression fractures on X-rays, bone biopsy evidence of osteoporosis, and absence of other risk factors after a complete workup. The patients were treated for a period of 3 to 6 years (mean 4 years) with daily doses of 30 mg (10 mg 3 times) fluorides ion associated during the last 3 years with 500 mg calcium twice daily, 750 mg phosphate and 1000 units vitamin D daily. The study demonstrated a favourable effect of the treatment on the backache and that it was well tolerated in the majority of cases, the side effects being intermittent osteo-articular pains of the lower extremities due to the fluoride in 9 patients, and gastric intolerance to the phosphate in 7. X-ray follow-up showed slowing of the vertebral compressions after the first year of treatment, but no effect on fractures of the extremities. There was no evidence of alterations in parameters of mineral and bone metabolism, and in endocrine, hepatic, renal or hematological assays. Histomorphometric and biophysical examination of biopsies indicated that, although there was no significant increase in the quantity of mineralized bone under the treatment, there was a very significant improvement in the crystallinity of the mineral substance, thus enhancing the quality of the bone tissue and its resistance to pressure. This study is the first in which a catamnesis of the patients was undertaken, 28 of them having received a clinical and radiological examination 2 years after the end of therapy: a favourable evolution was observed in most of the cases, both in those patients treated for a period of 3 years and in those whose treatment had lasted for a longer period.

The influence of chronic alcohol ingestion and artificially induced folic acid deficiency on iron absorption has been measured in rabbits by whole body counter. Results show that chronic alcohol ingestion does not modify iron absorption. Folic acid deficiency increases iron absorption by two probable mechanisms: first by increased plasma iron turnover (PIT), which parallels ineffective erythropoiesis, and second by a probable direct effect on the intestinal mucous membranes. This second mechanism appears to be independent of PIT: concomitant deficiency of folic acid and alcohol ingestion produces an increase in iron absorption without modification of PIT. Experience with drugs inhibiting protein synthesis suggests that this increase may be mediated by decreased protein synthesis.