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Biomedical subjects

E Vilardell

Publications and source records attributed to E Vilardell.

At least 37 records · Page 2Linked to original sources

Symptomatic and hormonal hypoglycaemic responses to human and porcine insulin in patients with type I diabetes mellitus.

In recent years there has been great concern that human insulin (HI) may induce fewer hypoglycaemic warning symptoms than porcine insulin (PI). We addressed this issue in eight patients aged 25.6 +/- 3.3 (SEM) years with Type I (insulin-dependent) diabetes mellitus of 15.1 +/- 3.7 years duration who complained that hypoglycaemia unawareness had appeared after transferring from PI to HI. Acute induction of hypoglycaemia was induced on two occasions with semisynthetic HI and purified PI under double-blind conditions. Blood glucose was first clamped for 2 h at 4.4-6.7 mmol l-1 with an intravenous infusion of HI or PI at 50 mU kg-1 h-1 and 20% glucose at a variable rate. Thereafter, insulin infusion alone was maintained for 100 minutes. Heart rate, arterial pressure, reflex times, autonomic and neuroglycopenic signs and symptoms were assessed every 10 min. Arterialized venous blood samples were taken to measure blood glucose every 10 min and catecholamines, insulin, glucagon, growth hormone, and cortisol every 20 min. Autonomic symptoms first appeared at a plasma glucose level of 2.92 +/- 0.21 mmol l-1 with HI vs 2.92 +/- 0.48 mmol l-1 with PI (NS). There were no significant differences between the two studies concerning any of the above mentioned clinical parameters or the counterregulatory hormone responses. A differential effect of insulin species on the ability to perceive hypoglycaemia in patients who ascribed diminished perception of hypoglycaemia to the use of HI was thus not observed.

Adult↗

Primary localized cutaneous amyloidosis and familial medullary thyroid carcinoma.

We have studied a family with an autosomal dominant inheritance of primary localized cutaneous amyloidosis (PLCA) and familial medullary thyroid carcinoma (MTC). Ten family members were screened for multiple endocrine neoplasia (MEN) 2; five were found to have MTC and two had C-cell hyperplasia. None had evidence of phaeochromocytoma or parathyroid abnormalities. Five of these seven patients presented characteristic interscapular hyperpigmented lesions, showing dermal amyloid deposits in two of the four patients in which a biopsy was performed. The data are analysed in the light of two recent reports of MEN 2A associated with identical lesions. We conclude that PLCA should be sought in MTC patients, even if no other endocrinopathies are present. This may be informative of the familial character of MTC in index cases and also of the tumour gene status in family members who are being screened.

Adult↗

Natural history of islet cell antibodies during the clinical period of type 1 diabetes. High titres at diagnosis are associated with longer persistence.

The natural history of islet cell antibodies (ICA), using standardized Juvenile Diabetes Foundation (JDF) units, was studied for two years in 64 type 1 (insulin dependent) diabetic patients, aged 7-45 years prospectively from clinical onset. While ICA were present among 44/64 (68.8%) of the newly diagnosed patients, only 9.3% remained positive at 24 months. The only factor which showed significant predictive value for ICA survival was high initial JDF ICA titres: Maximal persistence of ICA was observed in patients with 80 JDF units at diagnosis (100% at 12 and 24 month). This persistence was lower in patients with 40 JDF units at diagnosis (77% at 12 month, 40% at 24 month) and the lowest for patients with 5 JDF at diagnosis (14% at 12 month, 0% at 15 month). 14/20 (70%) of patients negative for the ICA test at diagnosis became positive during follow-up, but always with a low titre (5-10 JDF units) and for a short period (3-6 months). It is concluded that initial titre is the most important variable in predicting the maintenance of ICA during the first two years of clinical type 1 diabetes.

Adolescent↗

Acute water intoxication after intranasal desmopressin in a patient with primary polydispsia.

Only a few cases of severe acute water intoxication (AWI) due to intranasal desmopressin have been reported, none of which occurred in patients with primary polydipsia. We describe a case of AWI with semicoma and convulsions, due to intranasal desmopressin, in a 32-year-old patient with dipsogenic diabetes insipidus. Previous reported cases of AWI due to desmopressin are discussed. The importance of ruling out primary polydipsia when this drug is used, not only for central diabetes insipidus but also for other current indications such as classic hemophilia, is stressed.

Administration, Intranasal↗

Evaluation of clinical and hormonal effects in hirsute women treated with ketoconazole.

Seven hirsute women were treated with 200 mg/12 h po of ketoconazole during 6 months. We evaluated clinical and hormonal effects during this period. Ketoconazole treatment decreased testosterone, androstenedione and dehydroepiandrosterone sulfate, while 17-alfahydroxyprogesterone increased. This finding suggests a steroidogenic blockade at the level of C17-20 lyase. We did not observe changes in LH, SHBG and cortisol values. In spite of this findings after 6 months treatment, hirsutism remained unmodified. We conclude that ketoconazole inhibits androgen synthesis in hirsute women, but the use of this drug as an alternative and effective treatment of hirsutism warrants further evaluation.

17-alpha-Hydroxyprogesterone↗

Effects of thromboxane synthesis inhibitor triflusal on renal hemodynamics in microalbuminuric diabetic patients.

Triflusal (2-acetoxy-4-trifluormethylbenzoic acid) is a platelet-antiaggregant drug that selectively inhibits thromboxane synthesis with little effect on prostacyclin production. In this study, we evaluated the effect of 5-day administration of 900 mg/day triflusal on glomerular filtration rate (GFR), renal plasma flow (RPF), urinary albumin excretion (UAE), thromboxane B2 (TXB2), 6-ketoprostaglandin F1 alpha (PGF1 alpha), and PGE2 in nine normotensive insulin-dependent diabetic patients with UAE between 30 and 103 micrograms/min. Plasma TXB2 and plasma renin activity (PRA) were also determined. After administration of triflusal, we observed a reduction in microalbuminuria (59 +/- 25 vs. 33 +/- 22 micrograms/min, P less than 0.01), an increase in RPF (648 +/- 119 vs. 722 +/- 134 ml.min-1 x 1.73 m-2, P less than 0.01), and a reduction in filtration fraction (0.24 +/- 0.04 vs. 0.20 +/- 0.03, P less than 0.01). Triflusal produced a significant reduction in both plasma TXB2 (130 +/- 39 vs. 52 +/- 32 pg/ml, P less than 0.02) and urine TXB2 (523 +/- 249 vs. 312 +/- 11 pg/min, P less than 0.02), without changes in PRA and UAE of 6-keto-PGF1 alpha and PGE2. Metabolic control and arterial blood pressure did not change during the study. These results suggest that platelet-antiaggregant therapy can reduce microalbuminuria in diabetic patients. This effect could be mediated by a reduction in the transglomerular hydraulic pressure through a vasodilation of efferent arterioles secondary to renal thromboxane synthesis inhibition.

6-Ketoprostaglandin F1 alpha↗

[Evaluation of the treatment of Cushing's syndrome using ketoconazole].

The effectiveness of ketoconazole for the therapy of Cushing's syndrome, both of adrenal and pituitary origin, was retrospectively evaluated. To this end, the clinical and hormonal results in 5 patients were assessed. There were 4 females and one male, with ages ranging between 17 and 64 years. Three of them, who had Cushing's disease, received sustained treatment with ketoconazole when other therapeutic measures had failed. The two remaining patients (one with Cushing's disease and the other with adrenal adenoma) were treated with this drug in the preoperative period to alleviate the deterioration in the clinical condition caused by hypercortisolism. The clinical evolution of the patients is described, as well as the plasma adrenocorticotropin (ACTH) and the free cortisol in 24 hour urine in the subsequent controls. In view of the study results, we feel that ketoconazole is an effective treatment for the long term control of Cushing's syndrome. In addition, it may be also useful as preoperative therapy in those patients severely deteriorated by the sustained hypercortisolism.

Adolescent↗

[Cushing's disease in a patient with primary empty sella turcica].

Primary empty sella is a neuroanatomical condition which is more common in middle aged obese multiparous females with long-standing hypertension. Usually there are no symptoms, but occasionally nonspecific headache may be present. Hormone studies are commonly normal in these patients, although several functional hypothalamic and pituitary abnormalities have been reported. We report a 64-year-old female with primary empty sella in whom Cushing's disease was diagnosed. The association of both disorders is exceptional.

Cushing Syndrome↗

Late-onset hypocalcemia appearing years after thyroid surgery.

We revised four cases of hypocalcemia diagnosed yr after thyroid surgery, including 1 man and 3 women, operated 5-23 yr before the onset of symptoms, which ranged from mild paresthesia to convulsive seizures. Total serum calcium levels ranged from 1.1 to 2.05 mmol/l, and PTH levels were low in the 3 cases in which they were measured. Hypoparathyroidism appearing as late-onset hypocalcemia after extense thyroid surgery is a poorly understood condition, perhaps not as unfrequent as it is considered.

Adult↗

The effect of hypoglycemic sulfonylureas on human red blood cell transglutaminase activity.

We have examined the effect of glipizide, a hypoglycemic sulfonylurea, upon transglutaminase activity in human red blood cells. In a first series of experiments the in vitro effect of the drug was assessed. The results obtained showed that glipizide inhibits transglutaminase activity in human red blood cells. In a second approach, glipizide was administered orally to six type 2 diabetic patients during 3 months, in order to evaluate the long-term effect upon transglutaminase activity. Again, glipizide induced a significant decrease in the enzyme activity in blood red cells (P less than 0.01). We suggest that treatment of type 2 diabetes mellitus with hypoglycemic sulfonylureas could improve insulin effects by inhibiting cellular transglutaminase activity.

Calcium↗

A case with persistent nephrogenic diabetes insipidus following parathyroidectomy for hyperparathyroidism.

A 25-year-old woman with persistent nephrogenic diabetes insipidus (NDI) following parathyroidectomy for primary hyperparathyroidism is described. NDI is a well recognized complication of primary hyperparathyroidism, generally imputed to hypercalcemia, and promptly reversible after correcting it. In our case, the impaired concentrating ability of the renal tubule was irreversible after the removal of the parathyroid adenoma and the correction of the hypercalcemia, presumptively due to the morphological irreversible changes in the kidney. In addition, hypercalciuria persisted and was the cause of a compensatory hyperparathyroidism. Treatment with thiazide diuretic was effective to decrease relative hypercalciuria, thus reversing the compensatory hyperparathyroidism.

Adenoma↗

Presence of insulin autoantibodies at clinical diagnosis of diabetes mellitus type I predicts loss of beta cell function.

Recently the spontaneous development of insulin autoantibodies (IAA) has been detected in patients at diagnosis of Type I diabetes mellitus before the beginning of insulin treatment. The present study was undertaken to investigate if the presence of IAA at clinical onset of IDDM may act as a new marker of the beta cell function. The results obtained showed that IAA were present in 44% of newly diagnosed diabetic patients before therapy. Patients without IAA displayed a higher C-peptide secretion than those with IAA, at six months (12.11 +/- 5.08 versus 5.88 +/- 3.25 ng/ml/10 min.)(X +/- SD) and at twelve months (10.45 +/- 3.05 versus 4.90 +/- 5.25 ng/ml/10 min)(X +/- SD) of the follow up period. HbA1 levels, and insulin requirements were similar in both groups (IAA+ and IAA-). We conclude that the presence of insulin autoantibodies at clinical diagnosis, before initiating insulin treatment, may well predict the loss of the beta cell function.

Adolescent↗

[Effect of tolbutamide on the activity of transglutaminase].

Five obese patients were studied during 7 days, 750 mg of tolbutamide, per os, was given. Blood samples were drawn at basal state and at 3, 5, 7 days during the treatment and 6 days after it. The values of transglutaminase activity (that in the basal state were similar to that in the controls) decreased significantly at the seventh day of treatment (72.3%). This decrease was transient and rapidly returned to the basal values when the drug was suspended. The results suggest that sulfonylureas exert in part their hypoglucemic effect by modificating the insulin receptor binding through the inhibition of transglutaminase activity.

Adult↗

Erythromelalgia associated with acute diabetic neuropathy: an unusual condition.

Erythromelalgia is a syndrome characterized by erythema, burning pain and increased skin temperature of the affected extremities. It can be either primary (idiopathic) or secondary, but both forms require a critical temperature between 32-36 degrees C to provoke the crisis. Among the secondary forms, its association with diabetes mellitus is infrequent and its significance is little known. The histological studies have been fundamentally performed in patients with this syndrome affected by thrombocythemia; vascular thrombosis and fibromuscular intimal arteriolar proliferation were the prominent findings not corroborated in patients with the primary form. We studied one patient with acute diabetic neuropathy who developed erythromelalgia. We noted the absence of histopathological lesions, suggesting a disorder in vascular motility regulation favored by the severe neuropathy, without being able to discount a possible immunomediated mechanism. We describe the favourable evolution of the patient after treatment with aspirin and methysergide.

Acute Disease↗

Diagnosis of lung carcinoid with cutaneous hyperpigmentation eight years after bilateral adrenalectomy.

A 26-yr-old male was submitted to bilateral adrenalectomy in 1977 for Cushing's syndrome. Some months later he developed intense skin hyperpigmentation together with increased ACTH levels (149 to 4000 ng/l). The sellar region was always normal in X-ray studies. In April 1985, when the patient complained of chest pain, a chest x-ray showed a polycyclic mass in the upper left lobe of the lung. ACTH ranged from 20,000 to 100,000 ng/l, with no response to CRF or cyproheptadine administration. Urinary 5-OH-indolacetic acid was negative. Thoracotomy was performed in July 1985 with resection of two intrapulmonary masses. Histologic study demonstrated a carcinoid tumor, with positive neuron-specific enolase and ACTH immunochemical stain. ACTH concentration in tumoral tissue was 91 pg/g tissue. After surgery ACTH fell dramatically to 37 ng/l, and has remained at this level since then, associated with resolution of the skin hyperpigmentation.

Adrenalectomy↗

Acute effect of glibenclamide upon red cell transglutaminase activity in diabetic patients.

The acute effect of glibenclamide, a hypoglycemic sulfonylurea, upon transglutaminase activity was investigated in 6 type II diabetic patients by perfusing 1 mg glibenclamide during 1 h. Blood samples were drawn 0, 10, 20, 30, 60 min during and 30 and 60 min after perfusion to determine insulin, glucose and transglutaminase activity. No significant modifications in plasma insulin, plasma glucose and transglutaminase activity in red cells was induced by glibenclamide perfusion. Nevertheless, glibenclamide induced a significant decrease (p less than 0.005) in transglutaminase activity after 20 min of perfusion (629.83 +/- 53.08 and 521.18 +/- 43.92, mean +/- SE, at 0 and 20 min). No correlation was observed between glucose or insulin plasma levels and transglutaminase activity.

Adult↗