R 75251, a new inhibitor of steroid biosynthesis

R 75251, a new imidazole derivative, inhibited the conversion of androgens to estrogens, of progestins to androstenedione and testosterone, and of 11-deoxycorticosterone to corticosterone in human placenta microsomes, subcellular fraction of rat testis, bovine adrenocortical mitochondria, in cultured rat granulosa, testicular and adrenal cells, respectively. In vitro, no effect on cholesterol synthesis and cholesterol side-chain cleavage was found at concentrations up to 10 microM. In rat granulosa cells, no effect on progesterone production was detected. In vitro, no effect on steroid radioligand binding was observed. In male volunteers, a single dose of 300 mg of R 75251 significantly lowered plasma testosterone and estradiol for 24 hours and increased plasma concentration of 17 alpha-hydroxyprogesterone and progesterone. As compared with ketoconazole high dose (600 mg b.i.d), R 75251 (300 mg b.i.d) was at least as efficacious as inhibitor of testosterone synthesis when studied during ACTH stimulation. In contrast to ketoconazole, R 75251 did not significantly affect circulating adrenal androgen levels in male volunteers. Precursors of gluco- and mineralocorticoids such as 11-deoxycortisol and 11-deoxycorticosterone accumulated more than after ketoconazole administration. The data show that the cytochrome P450-dependent aromatase, 17-hydroxylase/17,20-lyase, and 11-hydroxylase are the target enzymes for R 75251.     

Selective unresponsiveness of pancreatic beta-cells to acute sulfonylurea stimulation during sulfonylurea therapy in NIDDM

Patients with non-insulin-dependent diabetes mellitus (NIDDM) who have chronic hyperglycemia lose acute incremental insulin responses to glucose but are able to briskly respond to other beta-cell secretagogues. To investigate whether this is a defect specific for glucose or represents a more general phenomenon, we measured the insulin responses to acute intravenous tolbutamide in 10 obese patients with NIDDM both before and during sulfonylurea therapy with tolazamide. Comparable glycemia was achieved with oral dextrose 2 h before intravenous testing. To assess beta-cell responsiveness to a nonsulfonylurea secretagogue, 1 mg glucagon was administered intravenously during tolazamide therapy. In seven patients, the mean peak insulin increment 5 or 10 min after intravenous tolbutamide was 54 +/- 11 microU/ml when not receiving tolazamide (0.14 +/- 1.3 microU/ml) with tolazamide (P less than .001), even though serum insulin responded rapidly to intravenous glucagon. In four patients tested for reversibility of their refractoriness to intravenous tolbutamide during chronic tolazamide therapy, the mean peak insulin increment 1 wk after discontinuing tolazamide was 79 +/- 22 microU/ml. A relatively rapid development of refractoriness was documented in four patients who were tested only 12 h after beginning tolazamide therapy; the mean peak insulin increments 5-10 min after intravenous tolbutamide were undetectable (-0.5 microU/ml), yet responses to intravenous glucagon were evident. In these NIDDM patients, exposure of pancreatic beta-cells to sustained levels of sulfonylureas induces a reversible state of refractoriness to acute stimulation with sufonylureas but not to another secretagogue.(ABSTRACT TRUNCATED AT 250 WORDS)     

Traumatic aneurysm of the internal carotid artery: a late finding presenting as a mass in the sphenoid sinus.

We describe a case of a traumatic aneurysm of the cavernous portion of the internal carotid artery in a patient who had had craniofacial trauma 12 years before. MR and CT revealed a mass in the sphenoid sinus thought to be unrelated to the patient''s symptoms. Carotid angiography gave the correct diagnosis.     

Food allergy as a cause of rhinitis and/or asthma.

We studied the histories of patients who had visited our Department during the last 5 years, presenting food allergy with exclusively respiratory symptoms (18.5%). We studied the correlation between IgE levels and the histamine release test and the type of food implicated. Seventy-seven percent of patients presented sensitization to one food, and 23% presented polysensitization. We found that foods such as snails and eggs have a strong predilection for the bronchial tree as the shock organ. High total IgE was found in 85.2% of patients. The histamine release test was positive in 66% of cases. We conclude that this is a highly sensitive method for the in vitro diagnosis of food allergy.     

Discoid meniscus in children and adolescents. Our experience in the treatment and follow-up

The purpose of this study was to review the clinical results of partially external meniscectomy performed on 33 arthroscopies in paediatric patients with a minimum follow-up of 24 months. In this retrospective cases series, a partial meniscectomy was performed in all patients. Patients age ranged between 4 and 14 years with an average of 9 years. We used the Watanabe classification for the morphological study of the discoid menisci. Clinical results were determined according to a modified Ikeuchi scale. The results were 25 excellent, two good and one poor. Complications were presented in four patients who developed osteochondritis of the external condyle and external tibial plateau. The arthroscopy is considered a diagnostic and treatment method in symptomatic external discoid meniscus.     

Fate of bone grafts in acetabular roof reconstructions assessed by roentgenography and scintigraphy

Autogeneic bone grafts--26 femoral heads, four femoral and two iliac bone grafts--were used in 32 total hip arthroplasties, mainly on patients with complete dislocation of the hip, to reconstruct deficiencies of the acetabular roof by a standardized procedure. At the follow-up examination after 24 to 101 months (median, 52 months), roentgenography demonstrated lateral resorption of the graft in 20 of 32 hips, but resorption involved bone support of the socket in only three of the hips. Analysis of serial roentgenograms showed that resorption was not a function of time. Complete incorporation of the grafts was observed in 27 hips; partial incorporation was shown in three. Roentgenographically, two grafts were not incorporated. None of three grafts of a cortical nature was incorporated. Graft uptake of radioactive tracer was found by 99mTc-diphosphonate emission scintigraphy in 16 of 21 hips, but did not correlate with progressive bone resorption, nonunion, or loss of bone structure. High quality serial roentgenograms showing good bone detail provided the best information about the integrity of the acetabular roof reconstructions.     

INVASIVE MUCORMYCOSIS WITH GASTRIC INVOLVEMENT IN A PATIENT WITH SEVERE ATHEROMATOUS VASCULAR DISEASE

Gastric mucormycosis involvement is a rare condition that usually occurs in inmunocompromised patients and frequently has a fatal outcome. We report the case of a 73‐year‐old woman admitted to the intensive care unit with severe bleeding after an acute pulmonary disease. Upper endoscopy disclosed wide and deep necrotic ulcers in the body and fundus of the stomach and greenish exudates with the antrum and the duodenum undamaged. Autopsy revealed an invasive mucormycosis and a severe atheromatosis. Several predisposing factors for mucormycosis infection have been reported until now. We postulate that ischemic gastritis could be a predisposing factor for colonization of zygomycete.