[Role of minimal invasive surgery for primary and secondary hyperparathyroidism]. / Stellenwert der minimal-invasiven Chirurgie beim primären und sekundären Hyperparathyroidismus.

BACKGROUND: The standard surgical approach to treat primary (pHPT) and secondary hyperparathyroidism (sHPT) used to be a cervicotomy with exploration of all four parathyroid glands. This access has been challenged recently by the introduction of minimally invasive techniques in order to achieve superior cosmesic results and to reduce theatre time. We analyzed the advantages and morbidities of these surgical aproaches. PATIENTS AND METHODS: Between 1997 and 2006 a total of 123 patients (109 with pHPT and 14 with sHPT) underwent parathyroidectomy at the ENT Department in Luzern. Ultrasonographic scanning was performed on 74 patients (68%), szintigraphy in 8 patients (7%) and both scanning methods in 27 patients (25%). 103 patients were available for follow-up. The indications for each technique were reviewed and outcome measures included serum Calcium and parathyroid hormone levels. RESULTS: Sensitivity for preoperative ultrasonographic and scintigraphic scanning was 67% and 65% for identification of the correct quadrant and 74% and 71% for identification of the correct side. A bilateral exploration was performed until June 2001 for all patients. Thereafter, a minimally invasive approach was chosen for patients with pHPT, whereas patients with sHPT still require bilateral exploration. Adequate preoperative localization was a prerequisite for a minimally invasive technique. Mean postoperative serum Kalzium levels were within the normal range, independently of the surgical technique and disease. Two patients developed hypercalcemia after an initially successful operation. CONCLUSIONS: Review of the literature confirms the shift from bilateral exploration towards minimally invasive techniques. The incidence of persistent or recurrent disease as well as the rate of complications seems comparable. Operation time for minimally invasive techniques is reduced in the hands of an experienced surgeon. However, proper preoperative localization of the diseased parathyroid gland is not always possible and the expenses of intraoperative parathyroid hormone measures do not lower the overall costs. Considerable experience and a multidisiplinary approach (endocrinologist, surgeon, pathologist) is required to adopt efficient minimally invasive techniques. As for sHPT, bilateral exploration remains the treatment of choice.

The hypothalamic-pituitary-adrenal axis in obese women with different patterns of body fat distribution.

To investigate whether obese subjects with abdominal obesity may be characterized by hyperactivity of the hypothalamic-pituitary-adrenal axis, we examined two groups of obese women with a waist to hip ratio (WHR) lower than 0.80 (n = 13), therefore having peripheral body fat distribution (P-BFD), or a WHR higher than 0.85 (n = 12), thus having abdominal body fat distribution (A-BFD). A group of seven normal weight healthy women served as controls. All subjects underwent the following protocol study that included 1) measurement of daily urinary free cortisol excretion rate; 2) a CRF test (human CRF, 1 microgram/kg BW, as iv bolus), with blood samples taken at regular intervals for ACTH and cortisol determination; and 3) an ACTH test, performed by administering two boli of ACTH (Synacthen, 0.2 microgram/kg BW, iv), at 90-min intervals, with blood samples taken for cortisol determination. Each woman also had a control saline study. Basal levels of both ACTH and cortisol rose significantly after CRF administration in all groups, but this increase was significantly higher in A-BFD than in P-BFD and control women. A significant correlation was found between the incremental area of cortisol and that of ACTH during the CRF test (r = 0.502), but not between these parameters and WHR values. Although the cortisol increase after the ACTH test was higher in A-BFD than in the other groups, these differences were only significant at 60 min during the test and when the analysis for repeated measures was applied. On the contrary, the incremental cortisol area after the ACTH test was not significantly different in the three groups. Moreover, it was not significantly correlated with the incremental cortisol area after CRF test or WHR values. Daily urinary free cortisol excretion rates (per g creatinine), however, were significantly higher in A-BFD than in P-BFD and control women. These results, therefore, suggest that obese women with A-BFD may have hyperactivity of the hypothalamic-pituitary-adrenal axis. This abnormality could be central in origin, due to hypersecretion of CRF or ACTH; alternatively, it could represent an adaptive phenomenon secondary to a state of functional cortisol resistance.

The role of the opioid peptides in the development of hyperinsulinemia in obese women with abdominal body fat distribution.

In this study, we investigated the hypothesis that increased opioid activity may be involved in the development of hyperinsulinemia in women with obesity and abdominal body fat distribution. Two groups of nine obese body (body mass index [BMI], 30 to 40 kg/m2) women with abdominal (A-ob) (waist to hip ratio [WHR] greater than 0.85) or gluteo-femoral (F-ob) (WHR greater than or equal to 0.80) fat distribution were examined and compared with eight normal-weight controls. Basal beta-endorphin levels were higher in the A-ob group than in the other groups. Each woman underwent two oral glucose tolerance tests (OGTT, 75 g glucose). A bolus of naloxone (0.8 mg) followed by a constant infusion of naloxone (0.04 mg/kg/h) or saline was also administered during the glucose challenge in random order, and blood samples for glucose, insulin, and C-peptide were collected at regular times after glucose administration. No difference was observed in basal or stimulated glucose concentrations between the three groups, nor between the saline or naloxone study. However, basal and stimulated insulin levels were significantly higher in obese women (particularly in the A-ob group) than in controls. Naloxone administration, however, did not significantly modify insulin and C-peptide glucose-stimulated concentrations in controls and in the F-ob group, whereas it significantly reduced (by approximately 47%) insulin levels in the A-ob group. Partial correlation coefficients showed a significant negative correlation between percent variation of glucose-stimulated insulin incremental areas during the naloxone study and the WHR in all women considered together (r = .544, P less than .025).(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of obesity and body fat distribution on sex hormones and insulin in men.

To investigate the relationship between body fat distribution, sex hormones, and hyperinsulinemia in male obesity, we examined 52 obese men (body mass index [BMI], 35.0 +/- 6.1, mean +/- SD) and 20 normal-weight controls. Their waist to hip circumference ratio (WHR), which was used as an index of fat distribution, was 0.985 +/- 0.052 and 0.913 +/- 0.061 (P less than .005), respectively. Compared with controls, obese men presented significantly lower levels of total (357 +/- 132 v 498 +/- 142 ng/dL; P less than .005) and free testosterone (14.2 +/- 2.9 v 17.1 +/- 2.6 pg/mL; P less than .05) and sex hormone-binding globulin (SHBG; 41.7 +/- 31.9 v 66.2 +/- 18.6 nmol/L; P less than .001) without any significant difference on the other sex steroid or on gonadotropin concentrations. Fasting and glucose-stimulated insulin and C-peptide levels were significantly higher in obese than in controls, and in obese with the WHR value greater than 0.97 (corresponding to the distribution median) than in those with WHR lower or equal to 0.97. BMI was negatively correlated with testosterone (P less than .005), free testosterone (P less than .01), and SHBG (P less than .001) and positively with fasting (P less than .001) and glucose-stimulated (P less than .005) C-peptide concentrations, whereas no relationship was found between these variables and WHR values. On the contrary, WHR was significantly correlated with fasting and post-glucose insulin levels (P less than .05), but not with those of sex steroids.(ABSTRACT TRUNCATED AT 250 WORDS)

Entomopathogenic nematodes and their interaction with chemical insecticide aiming at the control of banana weevil borer, Cosmopolites Sordidus Germar (Coleoptera: Curculionidae) / Nematoides entomopatogênicos e sua interação com inseticida químico Visando ao controle da broca-da-bananeira cosmopolites sordidus germar (coleoptera: curculionidae)

The banana weevil borer (Cosmopolites sordidus) is the main pest of banana crops, causing significant losses in productivity, being recommended control by chemical insecticides which cause several environmental impacts. On the other hand, entomopathogenic nematodes can be an alternative to the pest control, mainly because of their habits. Thus, this study aimed at evaluating isolated entomopathogenic nematodes under laboratory conditions and also their interaction with a chemical insecticide (carbofuran), aiming at their use for the weevil borer control. Sixteen Sterinernematidae and Heterorhabditidae isolates were evaluated, applied over the banana tree pseudo stem (100 JIs/cm²) and they were compared to one another concerning mortality caused in adults individual of C. sordidus. The most infective isolates were subjected to in vivo multiplication at the host Galleria mellonella and interaction with the insecticide carbofuran, including in this case, viability and infectivity analysis of the entomopathogenic nematodes exposed to the product, as well as the effect of the insecticide on the symbiotic bacteria of the entomopathogenic nematodes. The experiments at this stage were conducted in completely randomized design and the data were subjected to ANOVA, with application of the Tukey test (p 0.05). The most virulent isolates were IBCBn24 and IBCBn40 [...]

A broca-da-bananeira (Cosmopolites sordidus) é a principal praga dos cultivos de banana, acarretando perdas significativas na produtividade da cultura, sendo recomendados inseticidas químicos para seu controle, os quais causam impacto ambiental. Por outro lado, os nematoides entomopatogênicos podem ser uma alternativa para o controle da praga, principalmente devido aos seus hábitos. Assim, este trabalho teve como objetivo avaliar isolados de nematoides entomopatogênicos em condições de laboratório e a interação com inseticida químico (carbofurano), visando a sua utilização no controle da broca. Foram testados 16 isolados das famílias Sterinernematidae e Heterorhabditidae, aplicados sobre pseudocaule de banananeira (100 JIs/cm²) e comparados entre si quanto à mortalidade causada em indivíduos adultos de C. sordidus. Os isolados mais infectivos foram submetidos a experimentos de multiplicação in vivo no hospedeiro Galleria mellonella e de interação com o inseticida carbofurano incluindo, neste caso, análise de viabilidade e infectividade dos nematoides expostos ao produto, bem como o efeito do inseticida sobre as bactérias simbiontes dos nematoides entomopatogênicos. Os experimentos dessa fase foram conduzidos em delineamento inteiramente casualizado, sendo os dados submetidos à ANOVA, com aplicação do teste de Tukey (p 0,05). Os isolados mais virulentos foram o IBCBn24 [...]

Glutamate formyl- and formimino-transferase activities from pig liver.

Formylglutamate:tetrahydrofolate formyltransferase (EC 2.1.2.6) from pig liver is not a separate entity, but represents a reaction catalyzed slowly by the active sites of formiminoglutamate:tetrahydrofolate formiminotransferase (EC 2.1.2.5). The two activities copurify through the stage of crystallization of the formiminotransferase and show very similar responses to heat inactivation and modification with diethylpyrocarbonate. Formylglutamate is a competitive inhibitor against formiminoglutamate, while glutamate is competitive against both the N-substituted glutamate substrates with similar values of Ki. Formyltransferase is a low activity with a Vmax of approximately 0.03% that of the formiminotransferase. All of the formyltransferase activity in liver extracts can be accounted for by the formiminotransferase enzyme.

[Frequency of HFE gene mutations and genotype-phenotype correlations in patients with hereditary hemochromatosis in Switzerland]. / Häufigkeit der HFE-Genmutationen und Genotyp-Phänotyp-Beziehungen bei Patienten mit hereditärer Hämochromatose in der Schweiz.

Hereditary haemochromatosis is one of the most common genetic disorders affecting populations of European ancestry. Isolation of a strong candidate gene, the HFE gene, allows genetic diagnosis in a large number of cases. However, different mutation frequencies have been reported in hereditary haemochromatosis patient populations from various geographic regions. Such data and phenotype-genotype correlations from Swiss patients with hereditary haemochromatosis are lacking. The objective of our study was to determine the frequency of HFE gene mutations in Swiss patients with hereditary haemochromatosis and to describe the clinical phenotype of patients with either a homozygous C282Y mutation or compound heterozygotes. 71 patients with a clinical diagnosis of hereditary haemochromatosis were identified through a questionnaire sent to physicians caring for hereditary haemochromatosis patients. Pertinent clinical data, in particular those reflecting iron body stores, were collected. Genotyping for the C282Y and H63D mutation of the HFE gene was performed. In 90% of the cases a mutation of the HFE gene was found. 86% of the patients were homozygous for the C282Y mutation, 4% were compound heterozygotes for the C282Y and the H63D mutation. Patients with the homozygous C282Y mutation showed a broad phenotypic spectrum that could not be accounted for by age or sex differences only. Our results demonstrate that within the Swiss population genetic testing can also identify the vast majority of patients with hereditary haemochromatosis. However, the diagnosis is not ruled out by a negative genetic test. Furthermore, a broad phenotypic spectrum is associated with the homozygous C282Y mutation in Swiss hereditary haemochromatosis patients. The implications of these findings for planning of widespread genetic screening for hereditary haemochromatosis in the general population are discussed.

Unresponsiveness of hepatic nitrogen metabolism to glucagon infusion in patients with cirrhosis: dependence on liver cell failure.

Glucagon exerts an up-regulatory effect on hepatic nitrogen metabolism in healthy subjects, but its potential role in the presence of liver failure is uncertain. The effects of glucagon on urea synthesis and hepatic nitrogen clearance during alanine infusion were studied in five control subjects and six cirrhotic patients in paired experiments at spontaneous glucagon concentrations and at high physiological glucagon levels (approximately 300 to 500 pmol.L-1) induced by a 7.5-hr continuous glucagon infusion. In all experiments the urea nitrogen synthesis rate increased linearly with increasing alpha-amino-nitrogen concentrations. At spontaneous glucagon concentrations the dynamics of alpha-amino nitrogen to urea nitrogen conversion (functional hepatic nitrogen clearance) were significantly reduced in cirrhosis (23.2 +/- 6.7 L.hr-1 vs. 35.3 +/- 8.0 L.hr-1, p < 0.05) in relation to decreased liver function. Glucagon superinfusion caused a 63% increase in the dynamics of the process in controls (57.7 +/- 11.0 L.hr-1; p vs. spontaneous glucagon, p < 0.01), whereas in cirrhosis it increased on average by only 15% (26.7 +/- 10.7; p = NS). The glucagon-induced change in functional hepatic nitrogen clearance significantly correlated with galactose elimination capacity and antipyrine clearance (r = 0.905 and 0.964, respectively). Glucagon, in high physiological concentrations achieved with glucagon infusion, does not produce significant effects on hepatic nitrogen metabolism in cirrhosis. The reduced sensitivity of the cirrhotic liver to glucagon seems to be dependent on decreased hepatocellular function. These data do not support the role of glucagon as a "catabolic" hormone in cirrhosis.

Effects of chronic administration of ephedrine during very-low-calorie diets on energy expenditure, protein metabolism and hormone levels in obese subjects.

1. We investigated the effects of the chronic administration of a sympathomimetic agent on energy expenditure, protein metabolism and levels of thyroid hormones and catecholamines in 10 obese subjects after a 6-week very-low-calorie-diet programme (1965 kJ, 60 g of protein, 45 g of carbohydrates). L-(-)-Ephedrine hydrochloride (50 mg three times a day by mouth) or placebo were administered during 2-week periods (weeks 2-5 of the VLCD programme) in a randomized, double-blind, cross-over design. Five subjects began with ephedrine and five with placebo. 2. The results were analysed separately in the two groups. No difference was found between them as regards weight loss during the very-low-calorie diet and drug treatments. Conversely, ephedrine therapy induced a significantly lower daily urinary excretion of nitrogen (and, consequently, a better nitrogen balance) with respect to placebo, independently of the drug sequence. Daily urinary levels of 3-methylhistidine during ephedrine and placebo treatments were similar. The fasting resting metabolic rate (oxygen consumption, ml STP/min) fell significantly during the very-low-calorie diet in both groups, but this effect was partially and significantly prevented by administration of ephedrine. Diet therapy significantly reduced 24 h urine levels of vanillylmandelic acid and homovanillic acid, which, however, increased to pretreatment values during ephedrine treatment. No significant effects were shown on 24 h urinary concentrations of adrenaline, noradrenaline and dopamine during the very-low-calorie diet and/or ephedrine treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Relationship between plasma atrial natriuretic factor and opioid peptide levels in healthy subjects and in patients with acute congestive heart failure.

We evaluated plasma atrial natriuretic factor (ANF), beta-endorphin, met-enkephalin, dynorphin and noradrenaline levels in 20 healthy subjects and 20 acute congestive heart failure (CHF) patients. In all acute CHF patients plasma values of these hormones were higher than in healthy subjects. The hormonal pattern differed in patients with the more severe acute CHF (group 1) from patients with less severe acute CHF (group 2) (ANF 53.8 +/- 1.0 vs 34.6 +/- 1.5 pg.ml-1, noradrenaline 563.8 +/- 13.4 vs 202.4 +/- 10.6 pg.ml-1, met-enkephalin 41.0 +/- 3.2 vs 17.0 +/- 1.6 fmol.ml-1, dynorphin 46.8 +/- 3.7 vs 25.2 +/- 2.0 fmol.ml-1, P < 0.01; beta-endorphin 50.6 +/- 5.2 vs 41.8 +/- 4.1 fmol.ml-1,ns). Administration of an opioid antagonist (naloxone, 8 mg i.v.) did not modify ANF or noradrenaline concentration in healthy subjects. In group 1 naloxone administration significantly raised ANF (68.0 +/- 1.4 pg.ml-1), noradrenaline (776.6 +/- 18.7 pg.ml-1), blood pressure and heart rate, whereas in group 2 it significantly decreased ANF values (21.9 +/- 0.5 pg.ml-1) and did not modify the other parameters. Our findings suggest that the opioid system affects ANF release in acute CHF. In patients with severe CHF opioid peptides may attenuate ANF secretion reducing noradrenergic stimulation. On the other hand, when CHF is less severe and the sympathetic activity is moderate, opioid peptides may directly stimulate ANF secretion.

Beta-endorphin response to exogenous corticotrophin-releasing hormone in obese women with different patterns of body fat distribution.

Obese individuals may be characterized by higher than normal basal and stimulated beta-endorphin plasma concentrations, which suggests an increased activity of the opioid system. This study was carried out to investigate whether the regulation of beta-endorphin secretion may be different in different phenotypes of obesity. Twenty-two obese women (body mass index greater than 30 kg/m2) without other endocrine and metabolic abnormalities were investigated. A group of seven normal weight healthy women matched for age served as controls. According to the protocol, obese women included in the study had a waist-to-hip ratio higher than 0.85 (n = 9) or lower than 0.80 (n = 13). The former were defined as having abdominal type and the latter peripheral type body fat distribution. Both groups were matched for body mass index. All women randomly underwent a corticotrophin-releasing hormone test (human CRF, 1 microgram/kg body weight) and a control saline study, with blood samples for beta-endorphin determination taken at regular intervals. Basal beta-endorphin levels were not significantly different between the three groups. No significant variation in the hormone levels occurred during the control study in either group. After CRF injection, however, beta-endorphin rose significantly in all women, but the hormone concentrations were significantly higher in obese women with abdominal fat distribution than in those with peripheral fat distribution and in controls. These results indicate that, among obese women, only those with the abdominal phenotype seem to have increased opioid activity.