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Biomedical subjects

G Tolis

Publications and source records attributed to G Tolis.

At least 19 recordsLinked to original sources

Inferior vena cava and right atrial thrombosis in children with nephroblastoma: diagnostic and therapeutic problems.

BACKGROUND: The neoplastic thrombus in Wilms' tumor rarely can extend in to the inferior vena cava or to the right atrium. The neoplastic thrombus usually is diagnosed concurrently with the tumor, although in some cases the diagnosis of the thrombus may precede the diagnosis of nephroblastoma. METHODS: Among 90 children with Wilms' tumor who were treated in the authors' unit, 4 had extensive tumor thrombosis of the inferior vena cava or the right atrium. One of these patients was found with a life-threatening thrombosis of the inferior vena cava and the right atrium, which was treated surgically; in this case, the diagnosis of nephroblastoma was made postoperatively. As for the 3 remaining patients the diagnosis of neoplastic thrombosis and Wilms' tumor was made simultaneously. RESULTS: In the first case, the patient underwent surgical excision of the thrombus with cardiopulmonary bypass and a short period of hypothermic cardiopulmonary arrest. In the other 3 cases the thrombus resolved with chemotherapy only. CONCLUSIONS: Surgical excision of extensive neoplastic thrombosis is suggested in the case of life-threatening thrombosis even with cardiopulmonary bypass. Chemotherapy is suggested in cases lacking clinical symptoms of thrombosis.

Child↗

Reversible symmetric polyneuropathy with paraplegia after heart transplantation.

BACKGROUND: Neurotoxicity is a well-recognized side effect of cyclosporine therapy in transplant recipients. Cyclosporine can cause a wide range of adverse effects on both the central and peripheral nervous systems. METHODS: We present a case history of symmetric polyneuropathy with flaccid paraplegia, a rare neurological complication of cyclosporine administration. RESULTS: Blood levels of the drug above the therapeutic range accompanied the neurological manifestations. The syndrome subsided fully with dose reduction. Patients' symptoms were attributed to axonal degeneration of the peripheral nerves, according to electromyography findings. CONCLUSIONS: Cyclosporine neurotoxicity should always be considered in patients with neurological complications following transplantation. The case presented in this article illustrates an additional potential mechanism of this adverse effect, namely, axonal degeneration of the peripheral nerves, causing symmetric polyneuropathy.

Cyclosporine↗

Dissociation of ACTH, beta-endorphin and cortisol in graded sepsis.

The function of the hypothalamic-pituitary-adrenal axis as related to the degree of severity of a septic process was assessed by measuring plasma levels of beta-endorphin, ACTH and cortisol. Sixty-one cases of postoperative patients treated at the intensive care unit were classified into four groups according to the severity of infection: Group 1 (control) included patients who did not show any sign of infection, group 2 patients with sepsis, group 3 patients with septic syndrome and group 4 patients with septic shock. Compared to G1 patients' ACTH values (4.16+/-2.6pg/ml), a statistically significant increase in ACTH values in various stages of septicemia (p < 0.005) with a noticeable difference also between G3 (7.11 +/-3.7pg/ml) and G4 (11.5+/-6.6pg/ml) (p<0.05) was found. Differences were also observed in beta-endorphin (with a level of significance between the several groups of p = 0.0001). Also, beta-endorphin values in G4 (40.6+/-30.3 pg/ml) differed significantly from each of G1 (17.5 +/-6.6 pg/ml), G2 (21.1+/-11.3 pg/ml) and G3 (23.5+/-12 pg/ ml) (p<0.05). A progressive hypercortisolemia was obvious, with values of G4 (37.2+/-15.6 microg/dl) differing significantly from those of G1 (18+/-4.6microg/dl) and G2 (24-/+8.4microg/dl) (p<0.05) and of G3 (28.5+/-12.3 microg/dl) from that of G1 (p < 0.05). Interestingly, a dissociation of ACTH, beta-endorphin and cortisol was observed, in that the increased values of beta-endorphin and cortisol, detected in the G3 were not associated with a parallel increase in ACTH. These findings might be interpreted in the sense of an impairment of the stress stimulation of the hypothalamic pituitary adrenal axis. Provided that such a situation can be lethal, our results further confirm the idea that a low-dose, steroid replacement might be beneficial to critical illness.

Adrenocorticotropic Hormone↗

Orexis, anorexia, and thyrotropin-releasing hormone.

The hypothalamus, long known to play a determinant role in food intake and satiety, has recently been shown to exert this homeostatic function via peptidergic neuronal circuits. The major peptide that has been identified as orexigenic, namely neuropeptide Y (NPY), is suppressed by leptin, an adipocyte-derived hormone, in a potential circuit that seems to function as an adipostat. Information regarding energy balance is fed back to the paraventricular nucleus of the hypothalamus where a complex interplay between thyrotropin-releasing hormone (TRH) and corticotrophin-releasing hormone (CRH) determines consequent effects in thermogenesis and stress reactions. Inflammatory mediators that have been implicated in anorexia simultaneously suppress TRH in a dominant way that overcomes the feedback effects of the thyroid hormones. Moreover, endogenous opioids and melanotropic peptides modulate orexigenic and thermogenic effects in a complex, yet poorly understood, way. However, TRH metabolism, which is affected by dietary modifications, seems to be involved in the orexigenic events that take place in the hypothalamus. It is, therefore, evident that TRH is directly involved in the complex hypothalamic networks that establish energy balance by modulation of food intake, satiety, thermogenesis, and other autonomic responses.

Animals↗

The effect of a pure antiandrogen receptor blocker, flutamide, on the lipid profile in the polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is one of the most common endocrinopathies affecting women of reproductive age; it is associated with hyperandrogenism, hyperinsulinemia, and dyslipidemia. This study was designed to assess the long term effects of a pure androgen receptor blocker, flutamide, on the lipid profile in women with PCOS and to examine the possible mechanisms by which androgens may exert their influence. Seventeen women with PCOS (10 obese and 7 lean) were studied. All subjects received a 12-week course of oral flutamide (500 mg/day). The baseline and posttreatment evaluations included lipid profile, androgen levels, insulin sensitivity, and serum catecholamine determinations. The primary outcome was the change in the ratio of low density lipoproteins (LDL) to high density lipoproteins (HDL). Treatment with flutamide was associated with a significant decrease in the LDL/HDL ratio by 23% (P = 0.005), in total cholesterol by 18% (P < 0.0001), in LDL by 13% (P = 0.002), and in triglycerides by 23% (P = 0.002). Flutamide treatment was also associated with a trend toward an increase in HDL (by 14%; P = 0.14). The effects on lipid profile were found regardless of obesity and were not associated with a change in weight. Furthermore, actions of flutamide on lipid metabolism were not associated with significant changes in circulating adrenaline or noradrenaline, glucose metabolism, or insulin sensitivity. This report has demonstrated for the first time that treatment with the pure antiandrogen, flutamide, may improve the lipid profile and that this effect may be due to direct inhibition of androgenic actions.

Adult↗

Sex hormonal preparations and the liver.

The long-term use of oral contraceptives (OCs) may be associated with an increased, though quite small, risk of certain types of liver disease: acute intrahepatic canalicular idiosyncratic cholestasis, benign hepatic tumors (hepatic adenoma, focal nodular hyperplasia, hemangiomas), hepatocellular carcinoma, peliosis hepatis, hepatic vein thrombosis, and portal vein thrombosis. Estrogens have lithogenic properties, as shown by a rise in biliary cholesterol secretion and cholesterol saturation index, yet no substantial increase in the risk of gallstones among estrogen users has been found. Hormone replacement therapy (HRT), given after oophorectomy or menopause, is not associated with clinically significant liver injury. Generally speaking, synthetic sex hormones should not be used in patients with acute and chronic liver disease. A trial of a low-dose estrogen can be instituted under close monitoring for adverse reactions and HRT preparations are not contraindicated in patients with chronic liver disease. Moreover, OCs and HRT can be prescribed quite safely following successful liver transplantation. The incidence of hepatic abnormalities in patients taking androgen hormones is very high. Liver adenomas, cholestasis, peliosis, nodular regenerative hyperplasia and, particularly, hepatocellular carcinoma may complicate long-term use of C17-substituted testosterone and anabolic steroids.

Acute Disease↗

New GH secretagogues and potential usefulness in thalassemia.

Thalassemic patients today undergo intensive transfusion and chelation regimes that offer them prolonged survival and improved quality of life. Nevertheless, they face the consequences of chronic illness and therapies which affect multiple bodily functions. Endocrine derangements involve, among others, the GH-IGF-I axis with consequent impairment of growth. In such cases, GH release, as assessed with stimulation tests, may be normal whereas ultradian GH secretion seems to be subnormal. New GH secretagogues (GHRs) are agents that stimulate pituitary GH release by acting upon different receptors than the endogenous hypothalamic secretagogue, growth hormone-releasing hormone (GHRH). Examples are the growth hormone releasing peptides (GHRPs) GHRP-6, GHRP-1, GHRP-2, Hexarelin and the nonpeptidyl MK-0677. These can be administered by multiple routes, even per os or intranasally, thus obviating the need for injections. Their GH releasing capacity is more pronounced and prolonged than that of GHRH and their use is devoid of serious side effects. The most recently developed GHRs seem to be capable of producing sustained GH release in many cases and can thus be viewed as therapeutic candidates in cases of reduced GH secretion with intact pituitary, as seems to be the case in a group of thalassemic patients.

Growth Disorders↗

Cardiomyopathy due to a pheochromocytoma. A reversible entity.

A 45-year-old male presented with acute pulmonary oedema, chest pain and electrocardiographic manifestations of acute myocardial ischaemia in the setting of hypertension crisis from a hyperfunctioning large left-sided pheochromocytoma. Coronary artery disease was excluded on the basis of thallium stress testing and coronary angiography. The latter revealed a picture consistent with dilated cardiomyopathy. After surgical resection of the tumour, both the hypercatecholaminaemia and the arterial hypertension subsided promptly with gradual improvement of the cardiomyopathy and complete resolution of the congestive heart failure symptoms.

Adrenal Gland Neoplasms↗

Amenorrhea in beta-homozygous thalassemia major.

Hemolytic anemias, and, in particular, beta-homozygous thalassemia, derange all vital organs. A shift of the survival curve to the right has been achieved, thanks to the intensive programs of blood transfusion; iron chelation; infectious control; and, most recently, bone marrow transplantation. Metabolic and endocrine abnormalities do occur, albeit in less severe forms in comparison to available data from 10 to 20 years ago, for example, osteopenia. The most commonly encountered hormonal disorder is the attenuation of gonadal function on a downstream basis, linked to iron deposition in the hypothalamic-pituitary gonadotropin axis. A transition, from low-amplitude endogenous GnRH pulses to apulsatility of LH patterns, precedes the inability of the pituitary gonadotrope to respond to the GnRH decapeptide administered either as an acute bolus injection or in a pulsatile manner for up to 7 days.

Amenorrhea↗

Rapid cooling contracture with cold cardioplegia.

BACKGROUND: Cold cardioplegia can induce rapid cooling contracture. The relations of cardioplegia-induced cooling contracture to myocardial temperature or myocyte calcium are unknown. METHODS: Twelve crystalloid-perfused isovolumic rat hearts received three 2-minute cardioplegic infusions (1 mmol/L calcium) at 4 degrees, 20 degrees, and 37 degrees C in random order, each followed by 10 minutes of beating at 37 degrees C. Finally, warm induction of arrest by a 1-minute cardioplegic infusion at 37 degrees C was followed by a 1-minute infusion at 4 degrees C. Indo-1 was used to measure the intracellular Ca2+ concentration in 6 of these hearts. Additional hearts received hypoxic, glucose-free cardioplegia at 4 degrees or 37 degrees C. RESULTS: After 1 minute of cardioplegia at 4 degrees, 20 degrees, and 37 degrees C, left ventricular developed pressure rose rapidly to 54% +/- 3%, 43% +/- 3%, and 18% +/- 1% of its prearrest value, whereas the intracellular Ca2+ concentration reached 166% +/- 23%, 94% +/- 4%, and 37% +/- 10% of its prearrest transient. Coronary flow was 5.7 +/- 0.2, 8.7 +/- 0.3, and 12.6 +/- 0.6 mL/min, respectively. Warm cardioplegia induction at 37 degrees C reduced left ventricular developed pressure and [Ca2+]i during subsequent 4 degrees C cardioplegia by 16% (p = 0.001) and 34% (p = 0.03), respectively. Adenosine triphosphate and phosphocreatine contents were lower after 4 degrees C than after 37 degrees C hypoxic, glucose-free cardioplegia. CONCLUSIONS: Rapid cooling during cardioplegia increases left ventricular pressure, [Ca2+]i and coronary resistance, and is energy consuming. The absence of rapid cooling contracture may be a benefit of warm heart operations and warm induction of cardioplegic arrest.

Animals↗

Lanreotide in the treatment of patients with thyroid eye disease.

Octreotide, a potent synthetic somatostatin (SM) analogue, was recently evaluated and found to have a beneficial effect in thyroid eye disease (TED), mostly in those patients with a positive Octreoscan-111. Lanreotide (LRT; Somatuline-Ipsen), a new SM long-acting analogue, is more active than natural SM and shows a much longer duration of action. The aim of the present preliminary study was to evaluate the therapeutic effect of LRT in the treatment of TED. Five patients, three males and two females, mean age 50.6 +/- 7.6 S.D. (45-64) years, all with severe symptoms of TED were studied. A similar number of patients, matched for age, sex and severity of ophthalmopathy served as controls. All the patients and controls were investigated with orbital scintigraphy using 111 In DTPA-D-Phe1-octreotide (Octreoscan-111) and selected on the basis of positive octreoscan. The NOSPECS system, as adapted by Donaldson et al. (Journal of Clinical Endocrinology and Metabolism 1973 37 276-285) and a disease activity score, as proposed recently by an International Workshop, have been followed in this study in order to evaluate the response to treatment. The five patients who comprised the treatment group received 0.04 g LRT i.m. once every 2 weeks over a period of 3 months, after which the Octreoscan-111 was repeated. The control patients were given an injection of water i.m., also once every 2 weeks for 3 months, after which they were evaluated clinically. No Octreoscan-111 was performed in the controls. All patients and controls were evaluated by the same physician, who was unaware of the type of treatment used. A decrease in the NOSPECS score and the clinical activity score was regarded as a positive response, while no change or an increase in the NOSPECS score along with no clinical improvement was regarded as a negative response. After 3 months of treatment with LRT, four patients showed a statistically significant improvement in ophthalmopathy in both eyes and one in one eye. Three of the control patients with TED did not show any change, one showed a minor improvement in one eye and no change in the other and one showed deterioration in both eyes. An interesting finding was that orbital Octreoscan-111 activity was absent in all the patients after LRT treatment. In conclusion, these preliminary results show that LRT has a beneficial effect on patients with TED, and that since it has to be given only once every 2 weeks, it is probably superior to any other form of SM treatment. However, as the number of patients was small, further studies are needed to confirm our results.

Adult↗

Combined oral contraceptives and gonadotropin releasing hormone agonistic analogs in polycystic ovary syndrome: clinical and experimental studies.

Polycystic ovary syndrome is a common endocrine disorder, presenting with menstrual irregularities, hirsutism, obesity, infertility and abnormal ovarian morphology. In addition, polycystic ovary syndrome is associated with a self-perpetuating imbalance involving the endocrine system and metabolic pathways, in which carbohydrates, lipids and growth factors are involved. Because of its chronicity, it is considered to be a substantial risk factor for atherogenesis and hormone-dependent neoplasia. The etiology and pathophysiology of the syndrome remain elusive. However, during the last decade, several clues have emerged from human and animal studies that may have significant repercussions in the treatment of polycystic ovary syndrome. Therapeutic maneuvers should be directed towards the dominant abnormalities present in individual patients with polycystic ovary syndrome. Gonadotropin releasing hormone (GnRH) agonists can directly affect the gonadotropin generator and secondary downstream derangements, whereas combined oral contraceptives (COCs) can modify hypothalamic as well as peripheral abnormalities. In view of the fact that GnRH agonistic analogs (GnRH-a) will induce hypoestrogenemia and its sequelae, the add-back strategy of estrogenic supplementation is recommended for preventive reasons and, as it transpires from some studies, for enhancement of GnRH-a effectiveness.

Animals↗

The role of somatostatin agonistic analogs in the treatment of acromegaly.

Acromegaly mainly associated with the presence of a growth hormone (GH)-secreting pituitary tumor causes considerable morbidity and carries a risk of premature mortality. Treatment includes surgery, radiotherapy, and the use of dopaminomimetic drugs and somatostatin agonist analogs (octreotide and lanreotide). The use of long-acting somatostatin analogs is limited to adjuvant therapy following failure of surgery and/or radiotherapy and/or bromocriptine. But it may be considered the drug of choice for childhood acromegaly and for syndrome of plurihormonal pituitary overproduction in association with excess GH-releasing hormone (GHRH) and a McCune/Albright-like syndrome. Octreotide has been administered de novo as primary and/or presurgical preparatory therapy. Octreotide doses of 100 to 1500 micrograms were used in two large series in Europe and the United States, which mainly included acromegalics in whom all other modalities had failed (> 65%). Clinical improvement, which was sustained for over 6 months of follow-up evaluation, was reported for more than 50% to 70% of patients. In evaluable patients with visual-field defects, there was a definite amelioration, even if the tumor mass was not reduced, and there was no worsening during therapy; the same is true for the adenoma mass, which showed a variable reduction (median, 15 to 22%). A reduction of serum GH and insulin-like growth factor-1 (IGF-1) levels was found in more than 90% of patients, with GH serum values < 5 ng/mL and IGF-1 serum values < 2 U/mL recorded in 46% and 49%, respectively. Relapse occurred when treatment stopped. Future developments are expected to improve the clinical usefulness of somatostatin analogs.

Acromegaly↗

Efficacy of chronic therapy with the gonadotrophin releasing hormone agonist decapeptyl in patients with polycystic ovary syndrome.

Our objective was to assess the endocrine and morphological response of polycystic ovary syndrome (PCOS) in patients receiving 6 months of therapy with the long-acting gonadotrophin releasing hormone agonist (GnRH agonist) decapeptyl (3.75 mg monthly injections). Eighteen documented PCOS patients were basally evaluated for hirsutism, gonadotrophin and androgen concentrations and ovarian morphology using trans-vaginal ultrasonography. Measurements were repeated at 3 and 6 months. The results (values as mean +/- SD) showed a significant improvement in hirsutism (Ferriman score 11.0 +/- 5.9 versus 6.6 +/- 2.7, P < 0.01), acne and seborrhoea. A significant post-treatment decrease in gonadotrophins [follicle-stimulating hormone (FSH): 5.8 +/- 1.8 versus 3.8 +/- 1.1 IU/l, P < 0.01; luteinizing hormone (LH): 10.8 +/- 8.3 versus 3.4 +/- 3.3 IU/l, P < 0.01], LH/FSH ratio (1.8 +/- 1.1 versus 0.8 +/- 0.6, P < 0.01) and androgen concentrations (free testosterone: 4.0 +/- 1.9 versus 1.9 +/- 0.7 pg/ml, P < 0.01, delta 4-androstenedione: 3.9 +/- 1.2 versus 1.9 +/- 0.6 ng/ml, P < 0.001) was also found, while oestradiol approximated castration concentrations (68.4 +/- 29.5 versus 29.1 +/- 6.7 pg/ml, P < 0.001). Finally, mean ovarian volume (19.7 +/- 6.2 versus 10.9 +/- 4.6 cm3, P < 0.001), capsule thickness (2.5 +/- 0.8 versus 1.9 +/- 0.7 mm, P < 0.05) and stromal density dropped significantly, as did uterine volume (34.2 +/- 10.5 versus 19.9 +/- 8.9 cm3, P < 0.01). In conclusion, treatment of our PCOS patients for 6 months with the GnRH agonist decapeptyl proved efficient in inducing significant clinical, biochemical and ovarian morphological improvement.

Adolescent↗

Somatostatin analogues suppress the inflammatory reaction in vivo.

Somatostatin (Sms) and its agonist analogues inhibit the secretory activities of endocrine and neural cells. Recent studies have suggested that Sms has significant immunomodulatory properties. In this study, we examine the effects of two Sms octapeptide analogues on the inflammatory reaction in vivo. BIM 23014 (Somatulin) and Sandostatin were administered to male Sprague-Dawley rats subject to carrageenin-induced aseptic inflammation, at doses of 2-10 micrograms/rat, given either systemically or locally. Animals were killed 7 h after the induction of the inflammation, and the inflammatory exudates were aspirated and quantitated in terms of volume and leukocyte concentration. Sms analogues, administered via either route, significantly reduced the volume and the leukocyte concentration of the exudate in a time- and dose-dependent fashion. In corroboration of these, immunohistochemical evaluation of the levels of local inflammatory mediators, such as immunoreactive (Ir) TNF-alpha, Irsubstance P, and Ircorticotropin-releasing hormone, was inhibited significantly by Sms analogue treatment. These findings suggest that Sms analogues have significant antiinflammatory effects in vivo, associated with suppression of proinflammatory cytokines and neuropeptides. Furthermore, these data suggest that Sms agonists may be useful in the control of inflammatory reaction.

Animals↗

The role of insulin in ovarian size in patients with the polycystic ovary syndrome.

The objective of this study was to evaluate whether the degree of suppression of ovarian volume effected by a gonadotropin releasing hormone (GnRH) agonist in patients with polycystic ovary syndrome (PCOS) correlated with basal insulin secretion and insulin secretion provoked by a glucose challenge. Eighteen PCOS patients received the GnRH agonist D-tryptophan-6-LHRH (Decapeptyl, 3.75 mg monthly i.m.) for 6 months and had blood glucose and insulin measured during a 75 g oral glucose tolerance test (OGTT) prior to and at the end of therapy. According to ovarian volume suppression after GnRH agonist therapy, two groups were defined: in group A (n = 10; mean body mass index (BMI) +/- SEM, 25.6 +/- 1.6 kg/m2) ovarian volume regressed from 17.9 +/- 1.6 to 6.7 +/- 0.3 ml (full responders) and in group B (n = 8; mean BMI +/- SEM, 28.1 +/- 2.3 kg/m2) from 21.5 +/- 1.1 to 15.1 +/- 1.0 ml (partial responders). Results showed that GnRH agonist therapy did not affect significantly BMI or fasting levels and area under the curve (AUC) for glucose and insulin in the respective groups. Fasting insulin levels correlated positively with ovarian volume prior to (r = 0.56, p < 0.05) and after 6 months of GnRH agonist therapy (r = 0.80, p < 0.005). The suppressibility of ovarian volume with GnRH agonist therapy correlated negatively with the difference between maximal and basal levels (r = -0.68), the area under the curve (r = -0.62) and maximal levels (r = -0.72) for insulin during the OGTT.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗