[Acute polyarthritis during a parvovirus B19 primary infection]. / Polyarthrite aiguë au cours d'une primo-infection à parvovirus B19.

Parvovirus B19 classically causes erythema infectiosum in children, febrile arthralgia or acute erythroblastopenia in adult. The clinical spectrum of adult primary infection is sometimes misleading. We report an observation of an acute rheumatoid-like arthritis following primary parvovirus B19 infection in a 42-year-old woman.

Changes in serum amylase, lipase and leukocyte elastase during diabetic ketoacidosis and poorly controlled diabetes.

Diabetic ketoacidosis (DKA) is frequently associated with pancreatic enzyme abnormalities. In order to determine the main factors that lead to this increase, serum total amylase (TA), pancreatic amylase (PA), lipase (L) and leukocyte elastase (LE), an early predictor of acute pancreatitis, were measured in four groups of patients on admission. Group 1 consisted of 52 patients with DKA (age: 41.9 +/- 19.2 years; blood glucose (Glc): 27.4 +/- 11.5 mmol/L; pH: 7.20 +/- 0.16; plasma bicarbonate: 10.5 +/- 6.2 mmol/L; blood urea nitrogen (BUN): 0.60 +/- 0.44 g/L; HbA(1C): 12.5% +/- 2.8%). Group 2 consisted of 90 patients with poorly controlled non-ketotic diabetes (age: 53.4 +/- 16.0; Glc: 14.3 +/- 0.6; HCO(3)(-): 26.6 +/- 3.2; BUN: 0.38 +/- 0.20; HbA(1C): 11.3 +/- 2.1). Group 3 consisted of 22 patients with well-controlled diabetes (age: 53.7 +/- 12.8; Glc: 10. 1 +/- 5.2; HCO(3)(-): 27.4 +/- 3.8; BUN: 0.36 +/- 0.19; HbA(1C): 6.8 +/- 0.8). Group 4 (controls) comprised 27 non-diabetic patients (age: 46.0 +/- 15.0; Glc: 4.9 +/- 0.5; HCO(3)(-): 28.4 +/- 2.5; BUN: 0.30 +/- 0.16; HbA(1C): 5.2 +/- 0.7) (means +/- SD). Increased enzyme activities were more frequent in group 1 (TA: 30.7; PA: 27.0; L: 36.5; LE: 73%) than in groups 2 (TA: 8.9; PA: 7.1; L: 8.9; LE: 45. 5%), 3 (TA: 13.6; PA: 9.0; L: 18.1; LE: 31.8%) and 4 (TA: 7.0; PA: 3. 0; L: 0.0; LE: 29.6%). Mean serum enzyme activities were significantly different in the 4 groups (ANOVA, P < 0.01) and were higher in group 1 than in groups 2, 3 and 4 (Student's t-test; group 1 vs 2 or 3 or 4: P < 0.001). In groups 1 + 2 + 3 + 4 (all patients), the four enzymes correlated with one another and also with Glc, BUN and HCO(3)(-) (P < 0.001). In group 1, TA correlated negatively with HCO(3)(-) (P < 0.001) and pH (P < 0.05); PA and L correlated positively with Glc and BUN (P < 0.01) and negatively with HCO(3)(-) (respectively, p < 0.01 and 0.05). PA correlated positively with pH (P < 0.01); LE correlated with Glc (P < 0.05) and BUN (P < 0.01). In conclusion, this study suggests that the serum levels of pancreatic enzymes increase with the degree of diabetic disequilibrium, and mainly correlate with metabolic factors such as hyperglycaemia, dehydration and acidosis. Increased pancreatic enzyme activities in patients with DKA, even in combination with abdominal pain, should not be diagnosed as acute pancreatitis; this could be important, particularly for younger clinicians.

[Atrial natriuretic hormone and endocrine functions]. / Hormone natriurétique auriculaire et fonctions endocrines.

The atrial natriuretic hormone (ANP) is a cardiac hormone which gene and receptors are widely present in the body. Its main function is to lower blood pressure and to control electrolyte homeostasis. Its main targets are the kidney and the cardiovascular system but ANP interacts with many other hormones in order to regulate their secretion. The adrenal glands are the first endocrine target. Steroidogenesis, especially mineralocorticoid synthesis, is inhibited by ANP, but glucocorticoid production seems to be depressed too. As ANP synthesis is enhanced by the latter, it suggests a regulatory loop. Moreover ANP inhibits the thyroid synthesis whereas its production is enhanced by thyroid hormone. The hypothalamo-hypophyseal axis is another important target. ANP inhibits ACTH release and arginine vasopressin secretion. Vasopressin enhances ANP synthesis while GH decreases it. Finally the endocrine effects of ANP strengthen the cardiovascular and renal effects of the hormone, antagonizing the salt and water retention due to aldosterone and AVP. Because of a local production, ANP may also act as a paracrine hormone that influences the function of many endocrine systems (ovarian function for instance). In the central nervous system, ANP acts as a neurotransmitter in order to regulate pituitary and vegetative functions. Plasma ANP levels are impaired in several endocrine diseases : the plasma hormone levels increase in hypercortisolism, hyperaldosteronism, thyrotoxicosis and inappropriate antidiuretic hormone secretion; it decreases in hypothyroidism. In case of Addison's disease, ANP may be used to assess the quality of mineralocorticoid treatment, in association with the other biological criteria.

Transient pseudo-hypoaldosteronism following resection of the ileum: normal level of lymphocytic aldosterone receptors outside the acute phase.

Pseudo-hypoaldosteronism (PHA) is due to mineralocorticoid resistance and manifests as hyponatremia and hyperkalemia with increased plasma aldosterone levels. It may be familial or secondary to abnormal renal sodium handling. We report the case of a 54-year-old woman with multifocal cancer of the colon, who developed PHA after subtotal colectomy, ileal resection and jejunostomy. She was treated with 6 g of salt daily to prevent dehydration, which she stopped herself because of reduced fecal losses. One month later she was admitted with signs of acute adrenal failure, i.e. fatigue, severe nausea, blood pressure of 80/60 mmHg, extracellular dehydration, hyponatremia (118 mmol/l); hyperkalemia (7.6 mmol/l), increased blood urea nitrogen (BUN) (200 mg/dl) and creatininemia (2.5 mg/dl), and decreased plasma bicarbonates level (HCO3-: 16 mmol/l; N: 27-30). However, the plasma cortisol was high (66 microg/100 ml at 10:00 h; N: 8-15) and the ACTH was normal (13 pg/ml, N: 10-60); there was a marked increase in plasma renin activity (>37 ng/ml/h; N supine <3), active renin (869 pg/ml; N supine: 1.120), aldosterone (>2000 pg/ml; N supine <150) and plasma AVP (20 pmol/l; N: 0.5-2.5). The plasma ANH level was 38 pmol/l (N supine: 5-25). A urinary steroidogram resulted in highly elevated tetrahydrocortisol (THF: 13.3 mg/24h; N: 1.4+/-0.8) with no increase in tetrahydrocortisone (THE: 3.16 mg/24h; N: 2.7+/-2.0) excretion, and with low THE/THF (0.24; N: 1.87+/-0.36) and alpha THF/THF (0.35; N: 0.92+/-0.42) ratios. The number of mineralocorticoid receptors in mononuclear leukocytes was in the lower normal range for age, while the number of glucocorticoid receptors was reduced. Small-bowel resection in ileostomized patients causes excessive fecal sodium losses and results in chronic sodium depletion with contraction of the plasma volume and severe secondary hyperaldosteronism. Nevertheless, this hyperaldosteronism may be associated with hyponatremia and hyperkalemia suggesting PHA related to the major importance of the colon for the absorption of sodium. In conclusion, this case report emphasizes 1) the possibility of a syndrome of acquired PHA with severe hyperkalemia after resection of the ileum and colon responding to oral salt supplementation; 2) the major increase in AVP and the small increase in ANH; 3) the strong increase in urinary THF with low THE/THF and alpha THF/THF ratios; 4) the normal number of lymphocytic mineralocorticoid receptors outside the acute episode.

Urinary cortisol metabolites in the assessment of peripheral thyroid hormone action: overt and subclinical hypothyroidism.

UNLABELLED: Biological assessment of peripheral thyroid hormone action may be important in subclinical hypothyroidism, where decision-making is often difficult. The impairment of urinary cortisol metabolites in overt hypothyroidism reflects an acquired 11 beta hydroxysteroid dehydrogenase (11 beta OHSD) deficiency, and is assessed in terms of a reduction in the tetrahydrocortisone (THE)/tetrahydrocortisol (THF) ratio or THE/THE + alpha THF ratio; the alpha THF/THF ratio reflects 5 beta reductase activity. The aim of this study was to determine if urinary cortisol metabolite ratios are a good index of peripheral thyroid hormone action in subclinical hypothyroidism. MATERIALS AND METHODS: the THE/THF, THE/THF + alpha THF and alpha THF/THF ratios were measured in 24 h urine samples from 3 groups of subjects: 1) 18 euthyroid subjects; 2) 25 patients with elevated serum TSH and low FT4 levels (overt hypothyroidism); and 3) 25 patients with increased serum TSH and normal FT4 levels (subclinical hypothyroidism. RESULTS: 7/25 overtly and 5/25 subclinically hypothyroid patients had a THE/THF + alpha THF ratio below the mean control value -2 SD, while respectively 20/25 and 11/25 patients had a THE/THF ratio below the mean control value -2 SD. The mean THE/THF + alpha THF, THE/THF and alpha THF/THF ratios were significantly different among the 3 groups (ANOVA) and were lower in the overtly hypothyroid group than in the other two groups (Fisher's test); daily urine sodium output was also significantly different between the three groups and lower in the overtly and subclinically hypothyroid groups than in the control group (Fisher's test). FT3 and FT4 both correlated with THE/THF + alpha THF in the overtly hypothyroid patients (r = 0.43; p < 0.05 and r = 0.40; p < 0.05, respectively). In the subclinically hypothyroid patients, TSH correlated with THE/THF + alpha THF (r = 0.44; p < 0.05) and THE/THF (r = 0.43; p < 0.05). FT3, FT4 and TSH levels correlated with THE/THF + alpha THF (p < 0.001), THE/THF (p < 0.001), alpha THF/THF (p < 0.001) and daily natriuresis (p < 0.05) in the whole population (patients + controls). In conclusion, urinary cortisol metabolites, although impaired in overt hypothyroidism, are not an accurate index of peripheral thyroid hormone deficiency in subclinical hypothyroidism. We also identified an increase in the alpha THF/THF ratio in overt hypothyroidism, which may be related to 5 beta reductase disturbances.

A new culture method for human pancreatic islets using a biopore membrane insert.

The availability of highly purified human islets has increased with the progressive improvement of isolation methods. This has provided opportunities to perform various in vitro studies on human islets. However, when islets are maintained in culture, the overgrowth of fibroblasts results in a reduced islet purity and often has an adverse effect on islet function. To reduce fibroblast growth and to maintain normal islet function, we have investigated a new three-dimensional culture technique using a noncoated transparent Biopore membrane insert (Millicell CM, Millipore). Islets were isolated from seven human pancreata and cultured for 2 months using this membrane insert. At various time intervals, the functional viability of islets was assessed by measurements of insulin released into the culture medium, static incubation assays of basal and stimulated insulin release, islet insulin contents, and insulin biosynthesis. Results were compared to those of islets cultured in hydrophobic plastic petri dishes, our standard procedure. We found that the non-coated membrane does not allow islet attachment to the surface and prevents fibroblast growth, so that islets maintain a three-dimensional structure and remain in a free-floating form. Islets cultured in a membrane insert showed a function similar to or better than that of islets cultured in plastic petri dishes.

Immunohistochemical and ultrastructural study of adult porcine endocrine pancreas during the different steps of islet isolation.

Treatment of diabetes mellitus by transplantation of isolated pancreatic islets could constitute an alternative to human pancreas allograft. Before transplantation, porcine islets are submitted to a procedure of isolation and purification. The quality of islets through these different steps may be assessed by morphological and functional studies. The aim of this work was the histological characterization of the four main cell types of porcine adult endocrine islets during the different steps of the isolation procedure using immunohistochemistry (IHC) applied in light (LM) and electron microscopy (EM). In fresh pancreas, islets were various sizes and shapes in LM. The number was not found different between the different portions of the pancreas. In IHC, insulin (Ins)-secreting cells accounted for the majority of the islet cells, while glucagon(Glu)-somatostatin (Som)- and polypeptide(PP)-immunoreactive cells, in decreasing number, were found in the mantle around the core of Ins-cells. In EM, B-cells contained poly-hedric granules with a dense central core and clear halo. Glu granules were spherical and very dense. D-cells and PP-cells were characterized by numerous granules, rather spherical and of inequal density for Som and more ellipsoidal for PP granules. After purification in Euroficoll, in EM, the four cellular types remained recognizable, but underwent vacuolization, mitochondrial swelling, and enlargement of intercellular spaces. After 3 days of culture on plastic dishes, as on Biopore membranes in a Millicell insert, microvilli appeared and vacuolization increased in EM. At the seventh day of culture, in EM, most of the cells were lysed in contrast to LM where at the same time, the four cell types were clearly identified by IHC but only in collagen matrix. Important discrepancies were noticed between LM and EM. This fact emphasizes the complementarity of morphological and functional studies in assessment of the quality of an islet isolation.

[Congenital diabetes insipidus. Recent advances in molecular genetics]. / Diabètes insipides congénitaux. Acquisitions récentes en génétique moléculaire.

Hereditary diabetes insipidus can occur in two forms: the first, referred to as central diabetes insipidus, is responsive to vasopressin whereas the second, termed nephrogenic diabetes insipidus, is resistant to treatment. Recent advances in molecular genetics have contributed to elucidate the pathogenesis of these affections. Familial central diabetes insipidus depicts two unsimilar illnesses. The first, characterized by an autosomal dominant transmission, is of delayed onset and worsens progressively all through life. It is related to a heterozygous mutation of the vasopressin precursor gene mainly involving either the sequence encoding for the signal peptide or the one encoding for neurophysin II, the hormone carrier protein. Mutations described to date are responsible for impairment of vasopressin precursor transportation and processing. Therefore mutant protein accumulates in the posterior pituitary which is involved in the persistant bright spot seen on magnetic resonance imaging. The second illness or Wolfram syndrome, autosomal recessive, associates obligatory features: insulin-dependant diabetes, bilateral optic atrophy and more inconstantly: diabetes insipidus, deafness, genito-urinary and neuropsychiatric disturbances. The cause of this syndrome, still unknown, may involve mitochondrial ADN mutations. Familial nephrogenic diabetes insipidus, of neonatal onset, are mainly X-linked and associated to mutations in the V2 receptor gene. About 60 mutations have been described until now. Some rare cases, transmission of which is autosomal recessive, result from homozygous mutations of aquaporin 2 gene, a water channel involved in the water reabsorption in the renal collecting duct. Other mutations will be probably discovered in future. In conclusion, familial diabetes insipidus constitutes an interesting pathogenic model because it may be explained by impairment of vasopressin gene precursor as well as by abnormalities of renal receptor or post receptor mechanisms of the hormone.

[Thyreotropic adenoma: review of the literature. Apropos of 2 cases]. / Les adénomes thyréotropes: revue de la littérature. A propos de deux cas.

TSH-secreting adenoma is a rare entity; a series of 69 cases has been collected by Faglia in 1989 and 78 new cases were published from 1987 to 1994. We report two new cases which have been explored by octreotide scintigraphy before treatment with the SRIH analogue. An in vitro SRIH receptor study was also performed in the first patient. This patient, a young man, suffered from hyperthyroidism with enhanced FT3 and FT4 concentrations without decreased TSH values. Plasma alpha subunit level was slightly increased. He had a pituitary tumor, positive in Octreoscan but responded partially to treatment by SRIH analogue. The tumor was in part surgically removed and the SRIH receptors revealed a homogeneous density; their number was equal to those of GH-secreting tumor but their affinity was lower. The second patient, an elderly woman was not surgically treated because the octreotide treatment dramatically improved both tumor volume and thyroid hormone or alpha subunit levels. The tumor, associated to a probable meningioma, was also positive in Octreoscan and was characterized by a highly increased alpha subunit plasma level. These results are discussed by comparison with those of the literature.

[Gonadotropi adenoma linking labeled somatostatin analogs. Lack of relationship with therapeutic effect]. / Adénome gonadotrope fixant un analogue de la somatostatine marquée. Absence de corrélation avec l'efficacité thérapeutique.

Somatotropin- and thyrotropin-secreting adenomas are well known for positive uptake of radio-labeled octreotide in vivo, this fact is not so well assessed for gonadotropin-secreting adenomas (GSA). We report one case of positive somatostatin receptor scintigraphy in a woman suffering from histologically proven GSA. This 63 year old patient has been suffering for two years of akinetic syndrome when the outcome of diplopia led to the discovery of a large hypophyseal tumor spreading till V3 floor and in left cavernous sinus by resonance magnetic imaging (RMI). Clinical examination showed anterior hypopituitarism and bitemporal hemianopsia. Biologically, blood gonadotropins were decreased more on LH (0.6 UI/l, N > 15) than on FSH (10 UI/l; N > 20). A lack of response of gonadotropins to LHRH with low blood estradiol concentration (< 10 pg/ml) was noticed. Basal blood measurement of alpha subunit was at 0.17 microgram/l (N = 0.10-1.6) and increased at 0.39 microgram/l after stimulation by LHRH. Although in low range of normal values, other hypophyseal hormones were normal except prolactinemia (45 mg/L; N < 20), however stimulated by TRH and related to dopaminergic deconnection; Indium 111 labeled octreotide scintigraphy showed an over uptake of the tumor. Three month treatment by octreotide (100 micrograms x 3/day subcutaneously) did not allow to decrease significantly FSH concentration or to reduce the tumoral mass. Incomplete removal of the tumor was performed by transphenoidal route. Immunohistochemical analysis revealed positive immunostaining for alpha subunit and FSH beta on numerous cells while the labeling was slightly less strong for LH beta. These data evoked a GSA. This case record depicts the possibility of detection of GSA by somatostatin receptor imaging. However a positive result does not preclude of somatostatin analog therapeutic efficiency.

[Diabetes insipidus revealing pituitary metastasis of bronchial carcinoma]. / Diabète insipide révélateur d'une métastase hypophysaire d'un carcinome bronchique.

Pituitary metastasis are rare but represent an important differential diagnosis of intrasellar tumorous syndromes. We report one case of intrasellar metastasis of a bronchial adenocarcinoma in a 50 year old woman. Clinical syndrome associated a tumorous syndrome (cephalalgia, bitemporal hemianopsia) and an anterior and posterior hypopituitarism biologically proven. A large intra and suprasellar mass which compressed the optic chiasma and highly enhanced after gadolinium injection was found by nuclear magnetic resonance imaging. The surgical biopsy displayed a pituitary metastasis of a right inferior lobar bronchial adenocarcinoma with bone secondary localizations. Cerebral radiotherapy and corticotherapy allowed recovery of visual loss but did not prevent rapid death. The clinical and radiological features which may evoke an intrasellar metastasis were: the tumorous syndrome associated with or revealed by diabetes insipidus, loss of spontaneous hypersignal of the neurohypophysis in nuclear magnetic resonance imaging, bulking pituitary stalk, bilobar character of the mass which is in favour of rapid cell proliferation, postero-superior extension, lowering of the V3 floor and very strong and homogeneous signal after gadolinium injection.

Ultraviolet light irradiation reduces human islet immunogenicity without altering islet function.

Allograft rejection is the major cause for failure in clinical islet transplantation for diabetic patients. A reduction of donor islet immunogenicity is potentially a useful approach for altering recipient's immune responses. Studies in animal models have shown the immunomodulatory properties of ultraviolet (UV)-B light that are beneficial for allograft survival. However, there is a narrow window between the doses required for immunomodulation and those toxic to beta-cells. In addition, this window varies between one species to another. Our study was designed to determine, in vitro, the UV-B dose for human islets that effectively reduces immunogenicity and maintains islet viability and normal function. Islets were isolated from donor pancreas by collagenase digestion and density gradient centrifugation on Euro-Ficoll. Static incubation and perifusion tests were used to measure glucose-stimulated insulin release. Viability was also assessed by histology and function of UV-irradiated islets transplanted under the renal capsule of athymic mice. The immunogenicity of UV-treated islets was determined in vitro with mixed islet lymphocyte culture using healthy human peripheral blood lymphocytes as responders. At a dose of 300 J/m2, both functional assays detected no impairment of insulin release. At 500 J/m2, a slight decrease of stimulated insulin release was observed only in the perifusion system. At the levels of 600 and 900 J/m2, a clear alteration was observed in both basal and stimulated insulin release. Islets irradiated at 300 J/m2 and transplanted into athymic mice stained strongly for insulin and responded to high glucose challenge in in vivo perfusion performed at two weeks.(ABSTRACT TRUNCATED AT 250 WORDS)

Human islet isolation in 104 consecutive cases. Factors affecting isolation success.

One of the major steps toward successful islet transplantation for the treatment of type diabetes is to obtain islets of sufficient number and viability. Using a standardized method of isolating islets, the goal of this study was to analyze the factors influencing the outcome of islet isolation. A total of 104 cadaveric human pancreata were processed for islets by the same team. Data from the islet-processing charts were reviewed retrospectively. The two endpoints were the recovery of islets, viable after 2 days of culture (group V = viable, group NV = nonviable) and the islet yield. Viable islets were recovered in 61% of cases (n = 63). Minimal blood glucose recorded during hospitalization was very significantly lower in group V (124 +/- 5 vs. 148 +/- 9, P = 0.01). Lack of significant medical history in the donor was associated with better viability as compared with various donor predispositions (chi-2 4.21, P = 0.04). Cold ischemia time (8.1 +/- 0.5 hr in group V vs. 9.8 +/- 0.9 hr in group NV, P = 0.07) and collagenase lot (5 lots tested, chi-2 13.1, P = 0.01) also affected the recovery of viable islets. Hospital time was shorter in group V (65.3 +/- 6.8 vs. 80.9 +/- 17.9 hr, P = 0.35). Multivariate logistic regression analyses of viable islet recovery identified minimal blood glucose (P = 0.03) and collagenase lot (P = 0.06) as the most significant risk factors. However, the best multivariate predictive model--which includes blood glucose, collagenase lot, donor age and surgical procurement team--correctly predicted 66.2% of cases only. Multivariate analysis of final islet yield designed hospitalization length, cardiorespiratory arrest, surgical procurement team, and collagenase lot as the best predictors. These data obtained in a large series of pancreata emphasized several donor and technical factors that should target the attention of islet transplant researchers in order to improve islet yield and viability.