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Biomedical subjects

R Castello

Publications and source records attributed to R Castello.

At least 37 records · Page 2Linked to original sources
PubMed1996

Early changes in plasma glucagon and growth hormone response to oral glucose in experimental hyperthyroidism.

The mechanisms underlying deterioration of glucose tolerance associated with hyperthyroidism are not completely understood. Increases in glucagon and growth hormone (GH) secretion have been previously found in hyperthyroid subjects, and could play a crucial role in this phenomenon. However, studies have not yet established the time sequence of changes in plasma glucose on the one hand and glucagon and GH on the other. To assess the early effects of thyroid hormone excess on glucose tolerance and plasma concentrations of the main glucoregulatory hormones, 12 nondiabetic euthyroid subjects underwent an oral glucose tolerance test (OGTT) before and after triiodothyronine ([T3] 120 micrograms/d) was administered for 10 days. Plasma levels of glucose, insulin, glucagon, and GH were determined at fasting and after the glucose load. T3 administration caused a marked increase in serum T3 (8.8 +/- 0.6 v 2.0 +/- 0.1 nmol/L), with clinical and biochemical signs of thyrotoxicosis. During the treatment, plasma glucose significantly increased both at fasting and after the glucose load (basal, 5.3 +/- 0.1 v 4.9 +/- 0.2 mmol/L, P < .05; area under the curve [AUC] for OGTT, 7.7 +/- 0.3 v 6.7 +/- 0.4 mmol/L min, P < .01) without any change in plasma insulin levels. After T3 administration, plasma glucagon levels were lower than at baseline (basal, 92 +/- 7 v 148 +/- 35 ng/L; AUC, 74 +/- 6 v 98 +/- 16 ng/L.min, P < .05), showing an appropriate reduction by the increased glucose levels. Conversely, plasma GH showed impaired suppression by hyperglycemia (AUC, 1.2 +/- 0.3 v 0.7 +/- 0.2 microgram/L.min, P < .05). In conclusion, thyroid hormone excess rapidly impairs glucose tolerance. Altered secretion of GH is an early event in thyrotoxicosis accompanying the onset of hyperglycemia, whereas plasma glucagon is appropriately suppressed by the increased plasma glucose levels. Thus, GH but not glucagon may contribute to the early hyperglycemic effect of thyrotoxicosis.

Administration, Oral↗
PubMed1996

Insulin infusion amplifies 17 alpha-hydroxycorticosteroid intermediates response to adrenocorticotropin in hyperandrogenic women: apparent relative impairment of 17,20-lyase activity.

Recent data suggest that insulin is a modulator of ovarian and adrenal steroidogenesis and that, in the ovary of hyperandrogenic women, hyperinsulinemia might cause dysregulation of cytochrome P450c17 alpha activity. To further assess in vivo the effects of insulin on adrenal steroidogenesis, ACTH stimulation was carried out in 21 hyperandrogenic women during a 3-h hyperinsulinemic (80 mU/m2-min) euglycemic clamp. In all of these women the procedure was repeated during saline infusion as n control. In nonamenorrheic patients, the tests were performed in the early follicular phase of two different menstrual cycles. Serum cortisol, progesterone, 17-hydroxypregnenolone (17-OHJPREG). 17-hydroxyprogesterone (17-OHP), dehydroepiandrosterone (DHEA), and androstenedione (A) were measured after 2 h of insulin or saline infusion (zero time) and, subsequently, 30 and 60 min after an iv bolus of 0.25 mg ACTH-(1-24). At zero time, no difference was found in the serum steroid concentrations between the two protocols. ACTH-stimulated serum 17-OHPREG and, to a lesser extent, 17-OHP were significantly higher during insulin than during saline infusion (peaks, 60.6 +/- 9.0 vs. 40.7 +/- 7.9 and 7.7 +/- 7.7 vs. 6.6 +/- 0.6 nmol/L; P < 0.005 and P < 0.01, respectively). Serum DHEA was also slightly higher during hyperinsulinemia, although only after 30 min (54.5 +/- 3.0 vs. 48.2 +/- 4.2 nmol/L; P < 0.05). No statistically significant difference in the cortisol, progesterone, or androstenedione response to ACTH was found between the two protocols. ACTH-stimulated 17-OHPREG/DHEA and 17-OHP/A molar ratios, indexes of apparent 17,20-lyase activity, were significantly higher during the clamp studies than during saline infusion (by ANOVA, F = 12.8; P < 0.001 and F = 6.7; P < 0.005, respectively), suggesting an impaired enzyme activity. These in vivo data support the hypothesis that insulin potentiates ACTH-stimulated steroidogenesis. This effect of insulin seems to be associated with a relative impairment of 17,20-lyase activity.

17-Hydroxycorticosteroids↗
PubMed1996

The insulin resistance in women with hyperandrogenism is partially reversed by antiandrogen treatment: evidence that androgens impair insulin action in women.

To assess whether androgen excess per se might impair insulin action, insulin sensitivity was measured by a two-step (20 and 80 mU/m2.min) hyperinsulinemic euglycemic clamp combined with indirect calorimetry and tracer glucose infusion in 43 women (13 obese and 30 nonobese) with normal glucose tolerance and clinical evidence of increased androgen action (hirsutism and/or polycystic ovary syndrome) as well as 12 age- and body mass index-matched healthy controls. Hyperandrogenic women were studied basally and after 3-4 months of antiandrogen treatment with 3 different drugs: spironolactone (n = 23), flutamide (n = 10), or the GnRH agonist buserelin (n = 10). Six women given spironolactone were also reexamined after 1 yr of therapy. At baseline, insulin-mediated glucose uptake was lower in hyperandrogenic women than in controls (by ANOVA, F = 14.3; P < 0.001). Insulin resistance was observed in both ovarian and nonovarian hyperandrogenism, as distinguished by acute GnRH agonist testing. After antiandrogen therapy, insulin action on glucose metabolism significantly increased for both the patients as a whole (F = 7.4; P < 0.01) and each treatment group separately. However, insulin action remained lower than in controls and showed no further improvement in patients reevaluated after I yr of treatment. Increases in both oxidative and nonoxidative glucose metabolism accounted for the improvement in substrate disposal induced by antiandrogen drugs. The increase in the effectiveness of insulin was greater in the lean subjects, whereas the change was small and not statistically significant in the obese women. Response to treatment was more pronounced in women with nonovarian hyperandrogenism, particularly at the low insulin infusion rate. Endogenous glucose production in hyperandrogenic patients was similar to that in healthy women and was unaffected by therapy. In conclusion, antiandrogen treatment partially reversed the peripheral insulin resistance associated with hyperandrogenism regardless of which antiandrogen was used. These data strongly suggest that in women, androgen excess per se contributes to impairment of insulin action.

Adult↗
PubMed1996

Power spectral analysis of heart rate in hyperthyroidism.

The aim of the present study was to evaluate the impact of hyperthyroidism on the cardiovascular system by separately analyzing the sympathetic and parasympathetic influences on heart rate. Heart rate variability was evaluated by autoregressive power spectral analysis. This method allows a reliable quantification of the low frequency (LF) and high frequency (HF) components of the heart rate power spectral density; these are considered to be under mainly sympathetic and pure parasympathetic control, respectively. In 10 newly diagnosed untreated hyperthyroid patients with Graves' disease, we analyzed power spectral density of heart rate cyclic variations at rest, while lying, and while standing. In addition, heart rate variations during deep breathing, lying and standing, and Valsalva's maneuver were analyzed. The results were compared to those obtained from 10 age-, sex-, and body mass index-matched control subjects. In 8 hyperthyroid patients, the same evaluation was repeated after the induction of stable euthyroidism by methimazole. Heart rate power spectral analysis showed a sharp reduction of HF components in hyperthyroid subjects compared to controls [lying, 13.3 +/- 4.1 vs. 32.0 +/- 5.6 normalized units (NU; P < 0.01); standing, 6.0 +/- 2.7 vs. 15.0 +/- 4.0 NU (P < 0.01); mean +/- SEM]. On the other hand components were comparable in the 2 groups (lying, 64.0 +/- 6.9 vs. 62.0 +/- 6.5 NU; standing, 77.0 +/- 6.5 vs. 78.0 +/- 5.4 NU). Hence, the LF/HF ratio, which is considered an index of sympathovagal balance, was increased in hyperthyroid subjects while both lying (11.3 +/- 4.5 vs. 3.5 +/- 1.1; P < 0.05) and standing (54.0 +/- 12.6 vs. 9.8 +/- 2.6; P < 0.02). This parameter was positively correlated with both T3 (r = 0.61; P < 0.05) and free T4 (r = 0.63; P < 0.05) serum levels. Among traditional cardiovascular autonomic tests, the reflex response of heart rate during lying to standing was significantly lower in hyperthyroid patients than in controls (1.12 +/- 0.03 vs. 1.31 +/- 0.04; P < 0.002). No statistically significant difference in reflex responses between the two groups was found in deep breathing or Valsalva's maneuver. In the 8 patients reexamined after methimazole treatment, we observed complete normalization of altered cardiovascular parameters, with slight predominance of the vagal component compared with controls. These results suggest that thyroid hormone excess may determine reduced parasympathetic activity and, thus, a relative hypersympathetic tone.

Adolescent↗
PubMed1995

Genetic screening to identify the gene carrier in Italian and German kindreds affected by multiple endocrine neoplasia type 1 (MEN 1) syndrome.

Multiple endocrine neoplasia type 1 (MEN 1) is an autosomal dominantly inherited disorder characterized by parathyroid hyperplasia, anterior pituitary adenomas and neoplasms of the endocrine cells of the gastroenteric tract. It has been established that also other tissues exhibit excessive proliferation associated to the MEN 1 syndrome: carcinoids (bronchial and intestinal), lipomas (visceral and cutaneous), thyroid adenomas and goiter, and adrenal gland cortex adenomas. The men 1 gene has been mapped by genetic studies to the long arm of human chromosome 11, region q12-13. Genetic analysis of families and tumoral deletion mapping made possible to narrow the men 1 region to a 5 cM interval on chromosome 11q12-13. Thirteen marker complexes (17 DNA probes) were found to be linked to the men 1 gene and they span a 14% meiotic recombination with the men 1 locus in the middle. We report a genetic study on 103 subjects from 7 collected MEN 1-kindreds, six Italian and one German, including 30 affected individuals. By linkage analysis to 9 DNA markers (10 DNA probes) of the chromosome region where the men 1 gene maps (11q12-13), we identified 10 mutant gene carriers. The predicted MEN 1 diagnosis was clinically confirmed for 2 of these identified carriers. A predictive accuracy of this genetic test can reach up to 99.5% when it is possible to exclude meiotic crossing-over between the analyzed DNA markers and the disease locus.

Adult↗
PubMed1995

Quantitation of aortic regurgitation by Doppler echocardiography: a practical approach.

Aortic regurgitation is most frequently assessed noninvasively by Doppler echocardiography by use of continuous wave and Doppler color flow mapping. To compare both Doppler methods, 161 patients who had undergone cardiac catheterization and complete echocardiographic studies were studied. The continuous wave parameters analyzed included the slope of the diastolic deceleration and the pressure half-time of the regurgitant jet. From color flow Doppler, conventional parameters such as JH and its ratio to LVOH, JASA and its ratio to LVOA, and the regurgitant JA and its ratio to the LVA were obtained. The JH/LVOH was the color flow parameter that best correlated with angiography (r = 0.91). A ratio of < or = 25% was used to predict mild aortic regurgitation with 96% accuracy. A ratio of > or = 40% was also used to predict severe aortic regurgitation (3 to 4+) with 96% accuracy. Absolute JH at the origin of the regurgitant jet was the second best color flow parameter that correlated with angiography (r = 0.89). When continuous wave-derived slope was used, a significant overlap among different degrees of aortic regurgitation was observed. Predictive accuracy for mild aortic regurgitation was 70% by using a slope < 2 m/sec2 and 86% for severe aortic regurgitation when using a slope > 3 m/sec2. In conclusion, color flow Doppler appears to be superior to continuous wave Doppler in the assessment of aortic regurgitation. The JH/LVOH appears to be the best color parameter for quantifying aortic regurgitation. The measurement of the absolute JH at its origin appears to be the simplest and most practical method for assessing the degree of aortic regurgitation.

Adult↗
PubMed1995

Differential characterization of blood flow, velocity, and vascular resistance between proximal and distal normal epicardial human coronary arteries: analysis by intracoronary Doppler spectral flow velocity.

To characterize coronary blood flow velocity parameters and to determine the relation among velocity, volumetric flow, and vascular resistance in awake human beings, we performed paired proximal and distal velocity measurements in 28 angiographically normal coronary arteries. Mean velocity, peak velocity, diastolic-to-systolic velocity ratio, and diameter and cross-sectional area of proximal and distal arteries were determined and coronary flow and vascular resistance computed. Mean velocity and coronary vasodilator reserve were similar for all three native arteries and were preserved from proximal to distal segments. Volumetric flow decreased from proximal to distal segments. The demonstrated inverse and curvilinear (polynomial) relation between volumetric flow and vascular resistance agrees with theoretical and animal models of coronary physiologic characteristics and suggests a nadir of coronary vascular resistance below which coronary flow no longer increases.

Adult↗
PubMed1995

Relation between pulmonary venous flow and pulmonary wedge pressure: influence of cardiac output.

Multiple factors affect the systolic and diastolic components of pulmonary venous flow. It has been suggested that left ventricular function might influence the effects of filling pressures on indexes of pulmonary venous flow. The present study was designed to evaluate the effect of the pulmonary wedge pressures, left ventricular function, and cardiac output on the pulmonary vein flow pattern. Forty-five patients undergoing cardiac surgery were included in this study. Pulmonary venous flow and mitral flow variables were obtained by transesophageal echocardiography with hemodynamic variables obtained simultaneously. In the total group, there was no consistent relation between the pulmonary venous flow or the mitral flow parameters and the capillary wedge pressures. When patients were grouped according to normal (> 2.2 L/min/m2) or low (< 2.2 L/min/m2) cardiac index, a significant and positive relation was found between the systolic component of the pulmonary venous flow and the pulmonary wedge pressure in patients with normal cardiac index (r = 0.69; p = 0.003). Conversely, in patients with low cardiac index there was also a significant although negative correlation between the systolic velocity integral and the pulmonary wedge pressure (r = -0.58; p < 0.001). In conclusion, the systolic component of the pulmonary venous flow correlates closely and significantly with the capillary wedge pressures. The direction of this relation depends to a large extent on the total cardiac output and to a lesser extent on the left ventricular systolic function as assessed by the ejection fraction.

Adult↗
PubMed1995

Flutamide in the treatment of hirsutism: long-term clinical effects, endocrine changes, and androgen receptor behavior.

OBJECTIVE: To investigate the long-term effects of treatment with low doses of flutamide on clinical and hormonal parameters, as well as on the androgen receptor status, in hirsute women. DESIGN: Eighteen hirsute patients with regular menses were studied basally and during treatment with 125 mg flutamide, three times per day for 12 months. Barrier or intrauterine contraception was used during the study in sexually active women. Safety parameters were assessed throughout the study. Hirsutism, graded by the modified Ferriman-Gallwey score, and hormonal parameters were evaluated basally and at 4-month intervals during treatment. Gonadotropin-releasing hormone and ACTH stimulation tests were performed before and after 3 to 4 months of therapy. In addition, the concentration of androgen receptors in mononuclear leukocytes was measured, in both the follicular and luteal phases of the menstrual cycle, basally and after 4 months of flutamide treatment. RESULTS: Flutamide was well tolerated in all women, with the noticeable exception of one patient who presented increased serum transaminase after 8 months of therapy. Hirsutism markedly improved in all women during the treatment (Ferriman-Gallwey score after 1 year: 4.1 +/- 0.5 versus 14.1 +/- 0.9). A reduction of serum androgens was found, whereas no change was observed in either basal or GnRH-stimulated gonadotropins or in the cortisol and 17 alpha-hydroxyprogesterone response to ACTH. Cycles remained ovulatory. Before treatment, the number of androgen receptors was higher in the luteal than in the follicular phase. This rhythmic differentiation disappeared after the patients had been given the antiandrogen drug. CONCLUSIONS: Flutamide is effective in the treatment of hirsutism but requires constant surveillance of liver function. Androgen receptor blockade might be potentiated by a reduction of serum androgens. Flutamide affects androgen receptor behavior during the menstrual cycle. The meaning of this finding remains to be elucidated.

Acne Vulgaris↗
PubMed1994

Glucose counterregulatory response to acute hypoglycemia in hyperthyroid human subjects.

To evaluate the impact of hyperthyroidism on the counterregulatory response to hypoglycemia, eight hyperthyroid and eight sex-, age-, and body mass index-matched healthy women were given an iv insulin bolus (0.1 U/kg BW), and blood was drawn from 0-120 min for glucose, epinephrine, norepinephrine, glucagon, GH, ACTH, and cortisol measurements. In the basal state plasma glucose, GH, and cortisol levels were similar in the two groups, whereas plasma glucagon and ACTH were increased (135 +/- 17 vs. 80 +/- 10 ng/L and 6.4 +/- 1.5 vs. 2.6 +/- 0.4 pmol/L, respectively; both P < 0.025), and plasma catecholamines were reduced [epinephrine, 142 +/- 25 vs. 371 +/- 71 pmol/L (P < 0.025); norepinephrine, 0.41 +/- 0.07 vs. 1.41 +/- 0.12 nmol/L (P < 0.001)] in hyperthyroid patients. After insulin injection, plasma glucose similarly declined in the two groups (nadir, 1.5 +/- 0.2 vs. 1.6 +/- 0.2 mmol/L). Conversely, recovery from hypoglycemia was significantly faster in the hyperthyroid patients. In this respect, it is noteworthy that the plasma glucagon response had remarkably increased in the latter (peak, 444 +/- 56 vs. 198 +/- 17 ng/L; P < 0.005). On the other hand, the epinephrine responses were similar in the two groups, whereas norepinephrine levels remained consistently lower (peak, 0.97 +/- 0.20 vs. 2.61 +/- 0.24 nmol/L; P < 0.001), and the GH increase was severely impaired (peak, 10.6 +/- 1.9 vs. 29.6 +/- 6.2 micrograms/L; P < 0.01) in hyperthyroid patients. Plasma ACTH remained slightly higher in hyperthyroid subjects, but there were no substantial differences in the cortisol response between the two groups. In conclusion, hyperthyroidism affects plasma levels of several counterregulatory hormones, either in the fasting state or after insulin-induced hypoglycemia, with increased efficiency of plasma glucose recovery from hypoglycemia.

Acute Disease↗
PubMed1994

Clinical and hormonal effects of the 5 alpha-reductase inhibitor finasteride in idiopathic hirsutism.

Hyperactivity of 5 alpha-reductase in the skin is considered a major mechanism of excessive hair growth in hirsute women with normal levels of serum androgens (idiopathic hirsutism). Preventing the conversion of testosterone to dihydrotestosterone by inhibiting 5 alpha-reductase activity could thus be the most rational and effective treatment in this condition. The present study evaluated the effects of the oral administration of finasteride (5 mg once daily) for 6 months in 17 young women with idiopathic hirsutism, 5 of whom were also given an oral contraceptive. The degree of hirsutism (graded by a modified Ferriman-Gallwey score), serum sex hormone levels, and serum and urinary 5 alpha-metabolism steroid profiles were determined basally and periodically during the treatment period. The modified Ferriman-Gallwey score showed a remarkable reduction after 6 months of finasteride treatment (5.9 +/- 0.6 vs. 11.7 +/- 1.3; P < 0.01). Serum 5 alpha-dihydrotestosterone and 3 alpha-androstanediol glucuronide levels were decreased, and urinary C19 and C21 5 beta/5 alpha metabolite ratios were increased compared with pretreatment values. No significant adverse effect was reported. In women treated with finasteride and oral contraceptive, clinical efficacy was slightly more pronounced. In conclusion, the 5 alpha-reductase inhibitor finasteride is well tolerated and seems to be a useful tool in the treatment of idiopathic hirsutism.

Adult↗
PubMed1993

Usefulness of transesophageal echocardiography in unexplained cerebral ischemia.

Two-hundred seventy consecutive patients with "unexplained cerebral ischemia" were studied with transesophageal echocardiography to determine the value of this test in identifying potential cardiac sources of cerebral embolism. The findings of this group were compared with those of 772 consecutive patients undergoing transesophageal echocardiographic evaluation for indications other than cerebral ischemia. This study also examined this group of patients with unexplained cerebral ischemia to determine differences in relation to underlying cardiac rhythm and patient age. Intracardiac thrombus, atrial septal aneurysm, patent foramen ovale, spontaneous left atrial contrast and protruding debris in the thoracic aorta were found more often in patients with unexplained cerebral ischemia. Wall motion abnormalities of the left ventricle, as well as mild to moderate valvular lesions including mitral valve prolapse, were found to be similar in both groups. Spontaneous left atrial contrast, as well as mild to moderate valvular abnormalities, were found more often in patients with atrial fibrillation (22% of the group with unexplained cerebral ischemia). However, the presence of intracardiac thrombus was no more frequent in patients with atrial fibrillation than in those with normal sinus rhythm. Patients aged > 50 years were found to have atrial fibrillation and larger left atrial size more often than their younger cohorts, as well as a greater incidence of valvular abnormalities and left ventricular wall motion abnormalities. Mitral valve prolapse was seen more frequently in the younger cohort of patients.

Adolescent↗
PubMed1993

Analysis of coronary blood flow velocity dynamics in angiographically normal and stenosed arteries before and after endolumen enlargement by angioplasty.

OBJECTIVES: This study was designed to assess whether the spectral waveform of coronary velocity on Doppler study is characteristically altered in the presence of significant stenosis with normalization of the spectral waveform after relief of endolumen obstruction. BACKGROUND: Although coronary flow reserve determinations have provided physiologic information complementary to the angiographic percent diameter narrowing, flow velocity measurements have been limited to proximal arteries with inconsistent results after angioplasty. A 12-MHz Doppler guide wire permits flow velocity determination in the proximal and distal coronary artery with fast Fourier spectral analysis. METHODS: With the Doppler guide wire, proximal arterial flow velocity and flow reserve measurements in 17 angiographically normal arteries were compared with measurements in 29 significantly stenosed arteries. Proximal and distal flow velocity measurements were also obtained before and after angioplasty of the 29 abnormal arteries. Velocity spectrum was digitized to compute peak diastolic velocity, peak systolic velocity, mean velocity, diastolic/systolic velocity ratio and first third and first half flow fraction. RESULTS: Compared with proximal stenosed arteries, proximal normal arteries had significantly higher peak diastolic velocity (64 +/- 26 cm/s vs. 41 +/- 26 cm/s) and higher coronary vasodilator reserve (2.3 +/- 0.8 vs. 1.6 +/- 0.7). Normal arteries had higher flows in the first third and first half of the coronary cycle (46 +/- 3% vs. 39 +/- 7% and 65 +/- 2% vs. 56 +/- 10%, respectively). Before angioplasty, coronary velocity variables were significantly lower distal than proximal to the stenosis. After angioplasty, there was a greater mean increase in distal velocities (200% vs. 90% for the proximal arteries) that resulted in near equalization of proximal and distal mean velocity and a significant reduction in proximal/distal mean velocity ratio (2.4 +/- 1.7 vs. 1.2 +/- 0.4). CONCLUSIONS: Before angioplasty, abnormal coronary flow velocity dynamics are more marked distal than proximal to the stenosis. Greater increase in coronary flow velocities in the distal circulation after relief of endolumen obstruction results in a significant reduction in the proximal/distal flow velocity ratio. Thus, normalization of Doppler-derived flow velocity variables with marked reduction of the proximal/distal flow velocity ratios parallels angiographic success and may prove useful as an additional end point measurement in interventional cases with questionable angiographic findings.

Angioplasty, Balloon, Coronary↗
PubMed1993

Intranasal meperidine titration for postoperative pain relief.

A prospective, randomized, double-blind study investigating the efficacy of intranasal meperidine as compared with intravenous (i.v.) administration for postoperative pain relief is described. The study was limited to the initial titration of pain relief during a 2-h period immediately after surgery. Sixty women having undergone a hysterectomy were studied. Initially and when complaining of a pain intensity > or = 40 on the 101-point numerical rating scale (NRS), 30 patients received 6 sprays (27 mg) meperidine intranasally and simultaneously 6 mL NaCl 0.9% i.v. (nasal group); another 30 patients received 6 sprays of NaCl 0.9% intranasally and 6 mL of a diluted meperidine solution (27 mg) i.v. (intravenous group). Patients already having a pain reduction < 40 on the 101-point NRS, received half of the above dose. Meperidine was repeated every 5 min until the patients were pain free or refused further analgesic. Before the onset of meperidine titration and at 5- to 10-min intervals for 2 h thereafter, pain was evaluated with a 101-point NRS and a verbal rating scale. Within 20 and 35 min the pain scores evaluated by the NRS and verbal rating scale decreased in the intravenous and nasal group to a median of zero. The total dose of meperidine was 76.5 mg (range, 40.5-135.0) in the intravenous group and 104.4 mg (range, 27-135.0) in the nasal group (P < 0.05). One patient in each group showed a brief decrease in arterial hemoglobin oxygen saturation to < 90%. No patient complained of pain or burning in the nose.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Intranasal↗
PubMed1993

Distribution of VLA integrins in solid tumors. Emergence of tumor-type-related expression. Patterns in carcinomas and sarcomas.

Integrins form a family of membrane-spanning cell-surface proteins that promote cell-cell or cell-matrix adhesion and integrate the pericellular matrix to the cytoskeleton. Integrins are believed to be involved in the differentiation of tissues during development. They are involved in the relationship of tumor cells to the matrix and may on the other hand reflect the differentiation status of cells. In this study, we evaluated immunohistochemically the distribution of VLA integrins (alpha 1 to alpha 6 chains of beta 1 integrins) in a representative selection of normal tissues and 110 solid tumors. In simple epithelia, VLA2 and VLA3 were usually uniformly present in epithelial cells, whereas in ductal and stratified epithelia they were seen predominantly in the basal/myoepithelial cells. VLA6 was seen in the basal aspect of epithelia in a polar manner. In carcinomas, VLA2 and VLA3 were variably expressed, showing either basal distribution in cellular islands or generalized widespread distribution or rarely being absent. VLA2 and VLA3 were also seen in epithelial components of epitheliomesenchymal tumors. VLA1 and VLA5 were widely distributed in benign and malignant mesenchymal tumors and in the desmoplastic stroma of carcinomas. They were usually not seen in epithelia, except that VLA1 was present in myoepithelia of the breast and VLA5 occasionally in poorly differentiated carcinoma cells. Mesenchymal cell/tumor types had characteristic patterns of VLA integrins; for example, smooth muscle and its benign tumors showed VLA1, 3, and 5, whereas schwannomas showed VLA1, 2, 3 and 6. Endothelial cells and angiosarcomas showed multiple VLA-types: VLA1, 2, 3, 5, and 6 in a similar manner. In malignant schwannomas and leiomyosarcomas, moderate to extensive reduction of expression of VLA2, 3, and 6 and of VLA3 and 5, respectively, occurred. The results show that VLA (beta 1) integrins show characteristic cell lineage-dependent distribution patterns in solid tumors and are a potentially useful tool in tumor typing.

Carcinoma↗
PubMed1993

Homozygotes for the autosomal dominant neoplasia syndrome (MEN1).

Families in which both parents are heterozygotes for the same autosomal dominant neoplasia syndrome are extremely unusual. Recently, we had the unique opportunity to evaluate three symptomatic siblings from the union between two unrelated individuals affected by multiple endocrine neoplasia type 1 (MEN1). When the three siblings and their parents and relatives were genotyped for 12 markers tightly linked to the MEN1 locus, at 11q13, two of the siblings were found to be homozygotes, and one a heterozygote, for MEN1. With regard to the MEN1 syndrome, no phenotypic differences were observed between the two homozygotes and the heterozygotes. However, the two homozygotes showed unexplained infertility, which was not the case for any of the heterozygotes. Thus, MEN1 appears to be a disease with complete dominance, and the presence of two MEN1 alleles with mutations of the type that occur constitutionally may be insufficient for tumor development.

Adrenal Cortex Neoplasms↗