Biomedical subjects
C Coffin
Publications and source records attributed to C Coffin.
Aberrant adrenal sensitivity to multiple ligands in unilateral incidentaloma with subclinical autonomous cortisol hypersecretion: a prospective clinical study.
BACKGROUND: Incidentally discovered adrenal tumours are frequently associated with subclinical autonomous cortisol hypersecretion of unknown origin. Aberrant hormone receptors have been observed in case reports of overt Cushing's syndrome. The question arises as to whether such receptors may be present in the functioning adrenal incidentaloma, which is common and might be a subclinical stage of Cushing's syndrome. PATIENTS AND METHODS: Twenty-one consecutive patients with a unilateral incidentaloma, the biochemical features of subclinical cortisol hypersecretion and/or the scintigraphic features of an autonomously functioning adrenal adenoma were investigated for plasma cortisol responses to various stimuli: upright posture, meal, combined hypothalamic-hormones, the vasopressin analogue terlipressin, glucagon, angiotensin II, the serotonin 5-HT4 agonist cisapride, and ACTH. Six normal controls were similarly investigated. All subjects were studied during 8 mg per day dexamethasone in order to avoid any ACTH-dependent variation of plasma cortisol. RESULTS: The most constant responses in adrenal incidentalomas were observed after stimulation by terlipressin (18/20 patients, 28-415% cortisol increase) and cisapride (17/21 patients, 25-364% cortisol increase). Eighteen out of 21 patients responded to several stimuli (cortisol increase >or= 25%), and all responded to at least one stimulus other than ACTH, while such responses were absent in the controls. Plasma ACTH remained suppressed in all subjects throughout the study. CONCLUSIONS: Aberrant membrane receptors detected by in vivo stimulation tests appear to be common in autonomously functioning unilateral adrenocortical adenomas. These receptors may be involved in the modulation of cortisol secretion in adrenal incidentaloma, with potential therapeutic consequences for the control of subclinical cortisol hypersecretion.
Association between chronic urticaria and thyroid autoimmunity: a prospective study involving 99 patients.
BACKGROUND: The association between chronic urticaria and thyroid autoimmunity has been a subject of debate. However, this link was suggested in studies searching thyroid microsomal antibodies (TMA), which are less sensitive and less specific than anti-thyroperoxidase antibodies, moreover these studies did not measure anti-TSH receptor antibodies, nor did they use a control group. As a consequence, the results of these studies are difficult to interpret. OBJECTIVE: The aim of this study was to determine whether chronic urticaria is statistically associated with thyroid autoimmunity. METHODS: In a prospective case-control study, we compared the frequency of thyroid autoantibodies in 45 patients with chronic urticaria and in 30 healthy adult volunteers; we also compared the frequency of chronic urticaria in 32 patients with thyroid diseases with thyroid autoantibodies and in 22 patients with thyroid diseases without thyroid autoantibodies. Thyroid autoantibodies and thyroid hormones were measured in all the subjects; antinuclear antibodies, rheumatoid factors, complement, IgE were assessed and routine laboratory tests were done in patients with chronic urticaria. Fisher's exact statistics were used to test our hypothesis. RESULTS: The frequency of thyroid autoantibodies was significantly higher in patients with chronic urticaria than in healthy controls (26.7%/3.3%; p < 0.01). All the patients with thyroid autoantibodies had thyroid hormone concentrations within the normal limits. The frequency of chronic urticaria was not significantly different (12.5%/9.1%; p = 0.7) in patients with thyroid diseases with or without thyroid antibodies. The rest of the biological investigations revealed only 1 patient with connective tissue disease. CONCLUSION: This study shows a significant association between chronic urticaria and thyroid autoimmunity, and that tests to detect thyroid autoantibodies are relevant in patients with chronic urticaria, whereas extensive laboratory tests are not.
[Bone mineral density and biological markers of bone repair in patients with adrenal incidentaloma: effect of subclinical hypercortisolism].
PURPOSE: Some adrenal incidentalomas produce cortisol in mild excess ('subclinical' Cushing's adenomas) and can potentially induce osteopenia. Their diagnosis is usually based on exclusive tumour uptake on adrenal scintigraphy using 131I-6 beta-methyl-iodo-19-norcholesterol and on inadequate cortisol response to dexamethasone (DXM) suppression tests. The aims of the present study were to evaluate bone mineral density (BMD) and metabolic markers of bone turnover in patients with incidentalomas and to test the effect of mild hypercortisolism on bone parameters. METHODS: Thirty-five patients (13 men, 22 postmenopausal women, 49-76 years) with unilateral incidentaloma were studied. BMD was measured by dual X-ray absorptiometry. Two biochemical markers of bone formation, serum osteocalcin (BGP) and bone alkaline phosphatase (bALP), and two markers of bone resorption, urinary free deoxypyridinoline (D-Pyr) and urinary carboxy-telopeptide of bone type 1 collagen (CTX), were measured by radioimmunoassay. D-Pyr and CTX were corrected for creatinine excretion. RESULTS: Median values of lumbar and femoral T-score were -1.125 and -0.920, respectively, whereas corresponding Z-score values where normal (0.105 and 0.120, respectively). Thirty-nine percent of patients had low serum BGP values and 3% had low bALP values; 16% showed elevated D-Pyr/creatinine values and 23% increased CTX/creatinine values. Patients both with suppression of the contralateral adrenal on scintigraphy and with an inadequate cortisol response to 1 mg DXM (> 50 nmol/L) (n = 14) presented a lower femoral T-score (P < 0.02) and, to a lesser extent, a lower femoral Z-score (P = 0.11) than other patients (n = 21). The proportion of increased values of CTX/creatinine (42% versus 11%, P = 0.08) also tended to be higher in the first than in the second group of patients. These two groups of patients were similar in terms of age, but tumour size was larger (P < 0.04) and plasma ACTH value was lower (P < 0.02) in patients with scintigraphic and endocrine abnormalities. CONCLUSION: Subclinical hypercortisolism defined on the basis of scintigraphic and hormonal criteria seems to contribute to bone loss in patients with adrenal incidentaloma. As other possible side effects of mild hypercortisolism, these findings have to be taken into account in the therapeutic management of these patients.
Solitary fibrous tumor of the orbit in a child.
PURPOSE: Solitary fibrous tumor is a rare spindle-cell tumor that usually is seen in the pleura. The orbit is one of the most common extrapleural sites. It is frequently misdiagnosed as hemangiopericytoma and is seen in older patients. We present the youngest case of this tumor, which was apparent in family photographs by age 10 and removed at age 15. The first reported echography findings are presented. METHODS: Case report and literature review. RESULTS: Solitary fibrous tumor was diagnosed by microscopy and immunohistochemical study that showed cells reactive with vimentin and CD34. CONCLUSIONS: Solitary fibrous tumor of the orbit has been diagnosed with increasing frequency in recent years as the result of improved methods of pathologic examination. It is important to be aware of this tumor and recognize that it must be included in the differential diagnosis of highly vascular spindle-cell tumors even in young children.
Urinary nandrolone metabolites of endogenous origin in man: a confirmation by output regulation under human chorionic gonadotropin stimulation.
19-Nortestosterone (nandrolone) is an anabolic steroid compound widely used as a doping agent by athletes. The analysis of its urinary metabolites, 19-norandrosterone (NA) and 19-noretiocholanolone (NE) glucuronides, allows the detection of surreptitious administration of nandrolone in sport. A threshold concentration at 2 microgram/L urinary nandrolone metabolites is advocated by the International Olympic Committee for the detection of doping, but some controversy concerning the validity of this threshold arose from the demonstration of endogenous production of nandrolone in mammals, including humans. The regulation of human nandrolone production and its contribution in vivo to the process of aromatization remain unknown. In the present study 10 healthy men were successively submitted to insulinic stress and gonadal stimulation by hCG administration. Urinary NA and NE concentrations were quantified by gas chromatography-mass spectrometry. NA was detected in basal urine samples from all subjects, with a mean urinary excretion rate (UER) of 3.17 +/- 0.35 ng/h, whereas NE was detected in 4 of 10 (UER range, 0.8-4.7 ng/h). Insulinic hypoglycemia did not significantly modify mean NA UER despite random intraindividual variations between timed urine collections. After hCG administration, NA UER increased by 250% (P < 0.01) and estradiol (E(2)) UER by 260% (P < 0.001). The maximum NA concentration obtained after stimulation was 0.43 microgram/L. NA UER, plasma E(2), and E(2)/T ratio peaked on day 1 after hCG administration, whereas plasma T peaked later on day 3. NA UER correlated with plasma E(2) (r = 0.61; P < 0.001) and E(2)/T (r = 0.51; P < 0.001), but not with plasma T. In conclusion, insulinic stress did not significantly alter nandrolone metabolism, whereas the effect of hCG was a stimulation of NA excretion in all subjects, which constitutes strong support for the endogenous origin of low basal NA excretion. The comparative kinetics of NA UER, plasma E(2), and E(2)/T ratio suggest a contribution of the aromatase process to nandrolone biosynthesis in man.
Elevated plasma level of lipotropin revealing an occult carcinoid tumor with normal plasma adrenocorticotropin.
The increases in the level of plasma lipotropin (LPH) and in the LPH/ACTH ratio are considered diagnostic tools in ectopic ACTH syndrome. However, plasma ACTH is also elevated in this syndrome. We report a case of a small carcinoid tumor with an increase in both ACTH and LPH in plasma before surgery. Eight months after the tumoral resection, plasma LPH alone was increased again, whereas plasma ACTH and plasma and urinary cortisol remained normal in this apparently cured patient. This repeated abnormality was the only available feature that allowed successful removal of the occult tumoral residue.
Unexpected MR-T1 enhancement of endocrine liver metastases with mangafodipir.
With the use of available liver magnetic resonance contrast agents, such as mangafodipir (Mn-DPDP), liver metastases do not exhibit enhancement on T1-weighted images. This absence of enhancement is due to the lack of hepatocytes within these tumors. The purpose of this report is to demonstrate an unexpected enhancement on T1-weighted images 30 minutes after injection of mangafodipir, in the case of endocrine liver metastases from a non-hyperfunctioning neuroendocrine pancreatic tumor. Different hypotheses could explain this unexpected enhancement, such as increased arterial tumoral flow or high metabolic activity. Contrary to liver metastases of other origins, Mn-DPDP enhancement can be present in neuroendocrine metastases. J. Magn. Reson. Imaging 1999;10:193-195.
CT detection of an ampullary somatostatinoma in a patient with von Recklinghausen's disease.
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Temporal relationships between hormonal and hemodynamic changes in early human pregnancy.
BACKGROUND: The systemic hemodynamic profile of human pregnancy is characterized by a decrease in mean arterial pressure, a rise in cardiac output and plasma volume in association with an increase in renal plasma flow and glomerular filtration rate. The factors and the time course responsible for the initial hemodynamic changes seen in human pregnancy have not been completely documented. We hypothesize that systemic and renal hemodynamic changes occur early, prior to the presence of the fetal-placental unit. METHODS: Thirteen women were studied prior to and immediately following conception in identical fashion at gestational weeks 6, 8, 10, 12, 24 and 36. Individuals underwent mean arterial pressure, cardiac output, inulin and PAH clearance determinations. RESULTS: Mean arterial pressure decreased by six weeks gestation (mid follicular 81.5 +/- 2.6 vs. six weeks 68.7 +/- 2.0 mm tig, P < 0.001) in association with a significant increase in cardiac output, a decrease in systemic vascular resistance and an increase in plasma volume. Renal plasma flow and glomerular filtration rate increased by six weeks gestation. Plasma renin activity and aldosterone concentration increased significantly by six weeks, whereas norepinephrine levels did not change throughout pregnancy. Atrial natriuretic peptide levels increased later, at 12 weeks gestation. Plasma cGMP levels decreased and cGMP clearance increased by six and eight weeks, respectively. CONCLUSIONS: Peripheral vasodilation occurs early in pregnancy prior to full placentation in association with renal vasodilation and activation of the renin-angiotensin-aldosterone system. Plasma volume expansion occurs early, followed later by increases in ANP concentration, suggesting that ANP increases in response to changes in intravasular volume.
Lack of a nitric-oxide response during the course of Leishmania infantum infection in the golden hamster (Mesocricetus auratus), with or without treatment with liposomal amphotericin B.
Liver and spleen volumes and serum concentrations of nitrate (the end-product of NO in vivo), albumin, gamma-globulin, protein, creatine and urea were measured during the course of progressive infections with Leishmania infantum MON-1 (MHOM/PR/93/CRE29) in 10 Syrian golden hamsters. Each hamster was infected by intraperitoneal injection with 4 x 10(7) promastigotes. Five of the infected animals were treated, with 6 mg liposomal amphotericin B (L-AmB)/kg given by intracardiac injection, on day 107 post-infection (p.i.). Compared with those in the uninfected hamsters used as controls, the liver volumes in the infected animals became significantly enlarged by day 40 p.i. (38% larger than the controls; P < 0.001) whereas significant enlargement of the spleen was first detected on day 72. Each infected animal had detectable serum levels of antileishmanial antibodies on day 72. There were significant elevations in gamma-globulin concentration as early as day 40 (P < 0.05) but significant falls in albumin concentrations were only detected from day 107 (P < 0.001). Nitrate, creatinine and urea concentrations remained unchanged during the course of infection, even after L-AmB treatment. Serum nitrate levels were not enhanced by L. infantum infection nor by the L-AmB treatment which induced a 98.2% decrease in parasite burden. The lack of NO production in visceral leishmaniasis, with or without L-AmB treatment, points to the unresponsiveness of inducible nitric oxide synthase in this rodent model.
[Topographical diagnosis of insulinoma of the pancreas. Value of the test of intra-arterial calcium infusion].
OBJECTIVE: The localization of insulinomas is a central problem, because none of the imaging techniques has proved sufficiently reliable for the diagnosis of tumors smaller than 2 cms. PATIENTS AND METHODS: Calcium stimulation test was performed during selective pancreatic angiogram with calcium gluconate injection in the pancreatic arteries, e.g. gastroduodenal, superior mesenteric and splenic. A simultaneous catheterization of hepatic veins through the femoral vein allowed measurement of insulin level increment after calcium stimulation. RESULTS: In our experience, this test allowed a positive location of an insulinoma in three consecutive patients presenting with organic hypoglycemia, and was useful for surgeons while non-invasive imaging techniques failed to locate the tumor in any of the three patients. DISCUSSION: The calcium stimulation test is a reliable preoperative procedure, particularly when other imaging techniques fail to locate the tumor. However it remains invasive, and our data are still too preliminary to clearly define its place within imaging techniques.
Tumoural portal vein thrombosis. Enhancement with MnDPDP.
PURPOSE: Intrahepatic thrombus is usually associated with either cirrhosis or hepatocellular carcinoma (HCC). Most HCCs enhance after the administration of MnDPDP (Teslascan). Our objective was to analyze the enhancement characteristics of tumour portal vein thrombi. MATERIAL AND METHODS: Thrombi affecting the main or segmental portal veins (17 cases) and the suprahepatic inferior vena cava (1 case) were retrospectively selected from a series of 128 patients studied with MR imaging before and after the administration of MnDPDP. Enhancement was assessed qualitatively and quantitatively. RESULTS: All tumour thrombi enhanced after MnDPDP administration. The enhancement was more conspicuous in the GRE images. On the quantitative evaluation, the portal thrombus enhancement was greater for GRE images than SE images. Portal thrombi enhanced more than the liver and the HCCs. There was a significant difference between the enhancement of the HCCs and the thrombi with both MR imaging techniques. CONCLUSION: The greater enhancement of the tumour thrombus associated with the liver and HCC may suggest that other mechanisms, apart from accumulation of the contrast medium within the hepatocytes inside the thrombi, are involved in thrombus enhancement.
Systemic and renal hemodynamic changes in the luteal phase of the menstrual cycle mimic early pregnancy.
Blood pressure decreases during early pregnancy in association with a decrease in peripheral vascular resistance and increases in renal plasma flow and glomerular filtration rate. These early changes suggest a potential association with corpora lutea function. To determine whether peripheral vasodilation occurs following ovulation, we studied 16 healthy women in the midfollicular and midluteal phases of the menstrual cycle. A significant decrease in mean arterial pressure in the midluteal phase of the cycle (midfollicular of 81.7 +/- 2.0 vs. midluteal of 75.4 +/- 2.3 mmHg, P < 0.005) was found in association with a decrease in systemic vascular resistance and an increase in cardiac output. Renal plasma flow and glomerular filtration rate increased. Plasma renin activity and aldosterone concentration increased significantly in the luteal phase accompanied by a decrease in atrial natriuretic peptide concentration. Serum sodium, chloride, and bicarbonate concentrations and osmolarity also declined significantly in the midluteal phase of the menstrual cycle. Urinary adenosine 3',5'-cyclic monophosphate (cAMP) excretion increased in the luteal compared with the follicular phase, whereas no changes in urinary cGMP or NO2/NO3 excretion were found. Thus peripheral vasodilation occurs in the luteal phase of the normal menstrual cycle in association with an increase in renal plasma flow and filtration. Activation of the renin-angiotensin-aldosterone axis is found in the luteal phase of the menstrual cycle. These changes are accompanied by an increase in urinary cAMP excretion indicating potential vasodilating mediators responsible for the observed hemodynamic changes.
[Contrast media in magnetic resonance imaging of the liver].
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Effect of altitude on uterine artery blood flow during normal pregnancy.
To determine whether uterine blood flow was reduced and indexes of pelvic blood flow distribution altered in normotensive pregnancy at high (3,100 m) compared with low altitude (1,600 m), we measured uterine, common iliac, and external iliac artery blood flow velocities and diameters in women during pregnancy and again postpartum. Pregnancy increased uterine artery diameter, blood flow velocity, and volumetric flow at both altitudes. Uterine artery blood flow velocity was greater (69.0 +/- 2.2 vs. 59.4 +/- 3.0 cm/s; P < 0.005) but diameter was smaller at 3,100 m than at 1,600 m (2.5 +/- 0.3 mm vs. 3.4 +/- 0.2 mm; P < 0.005), resulting in volumetric flow that was one-third lower at week 36 of pregnancy (203 +/- 48 vs. 312 +/- 22 ml/min, respectively; P < 0.01). Pregnancy increased common iliac blood flow velocity and decreased external iliac artery blood flow velocity at both altitudes. The uterine artery received a smaller percent of common iliac flow at 3,100 than at 1,600 m (46 +/- 7 vs. 74 +/- 6%; P < 0.005). Gestational age was similar but birth weight was lower at 3,100 m than at 1,600 m. Among subjects at 1,600 m, variation in uterine blood flow velocity correlated positively with infant birth weight. We concluded that reduced uterine blood flow and altered pelvic blood flow distribution during pregnancy at high altitude likely contributed to the altitude-associated reduction in infant birth weight.
Use of ultrasound to guide radiation boost planning following lumpectomy for carcinoma of the breast.
PURPOSE: To determine if sonographic localization of the breast lumpectomy site is feasible and useful in boost planning. METHODS AND MATERIALS: The operative beds following lumpectomy were localized by ultrasound in 22 patients (15-infiltrating ductal, 7-ductal carcinoma in situ; size: .4-2.0 cm). Twelve patients had two ultrasound examinations on different days for a total of 34 examinations. Twenty-one patients had their course of boost electron therapy planned using ultrasound to guide field placement. While the patient was in the treatment position, the surgical scar was placed at the machine's isocenter. With the electron cone in place, the ultrasound transducer was placed within the cone on top of the surgical scar. The biopsy site was localized and the light field maneuvered so that it's central axis would follow the axis of the transducer, transecting both the scar and biopsy site. RESULTS: The operative bed was highly visible in 26 ultrasound examinations, visible in 7, and subtly visible in 1. Every biopsy site showed some hypoechoic area but most appeared as the mixed hypoechoic pattern. Ultrasound appearances were mixed or mostly hypoechoic (28), anechoic with irregular walls (4), and echoic (hypoechoic compared to parenchyma) (2). In two cases the surgeon placed surgical clips in the operative bed, and in both cases several of these clips could be identified at the margins of the operative bed as hyperechoic foci with shadowing. The mean depth of the operative bed was 21 mm (range 17-36 mm). In 12 patients, two ultrasound examinations were performed on different days, and the mean depth difference between these scans was 2 mm with a range of 0-5 mm. Among patients with two scans we found that both the location and appearance of the operative bed was highly reproducible. CONCLUSION: Ultrasound can successfully be used to localize the biopsy site and facilitate boost field placement in patients treated with lumpectomy and radiation.
Quantitative estimation of human uterine artery blood flow and pelvic blood flow redistribution in pregnancy.
OBJECTIVE: To determine the contributions of uterine artery diameter and mean flow velocity to the increase in volumetric flow during human pregnancy. METHODS: Volunteers (18 pregnant and six not pregnant) were studied using both a commercially available Doppler instrument with imaging ultrasound and an improved Doppler instrument with software that can determine instantaneous true mean blood flow velocity. Diameter and mean flow velocity measurements were combined to yield volumetric flows in the common iliac, external iliac, and uterine arteries during and after pregnancy. RESULTS: Compared with the nonpregnant state, uterine artery diameter doubled by week 21 (from 1.4 +/- 0.1 to 2.8 +/- 0.2 mm; P < .05), did not change between weeks 21 and 30 (2.9 +/- 0.1 mm), and increased between weeks 30 and 36 (to 3.4 +/- 0.2 mm). Uterine artery mean flow velocity rose progressively from nonpregnant values to attain at week 36 a velocity nearly eight times faster (8.4 +/- 2.2 versus 61.4 +/- 3.0 cm/second; P < .05). Unilateral uterine artery blood flow at week 36 was 312 +/- 22 mL/minute. CONCLUSIONS: Compared with nonpregnant values, common iliac artery flow increased and external iliac artery flow decreased during pregnancy, suggesting that redistribution of pelvic flow to favor the uterus contributed to the pregnancy-associated rise in uterus artery flow. Early in pregnancy, the increase in uterine artery blood flow was due in equal parts to changes in uterine artery diameter and mean flow velocity, whereas late in pregnancy, the rise was due mainly to faster mean flow velocity.