Biomedical subjects

M Tzanela

Publications and source records attributed to M Tzanela.

13 recordsLinked to original sources

PubMed2006

Dynamic tests and basal values for defining active acromegaly.

Acromegaly is a rare disease caused by excess secretion of growth hormone (GH), usually from a pituitary somatotrope adenoma. The prevalence of acromegaly is 38-40 cases/1,000,000 subjects, while the annual incidence is 3 new cases/1,000,000 subjects. The increase in morbidity and mortality associated with acromegaly is the result of GH and insulin-like growth factor (IGF)-I oversecretion and the direct mass effect of the pituitary tumor. Once the disease is clinically suspected, laboratory evaluation is mandatory to establish diagnosis. The standard method for the diagnosis of acromegaly has been the measuring of GH nadir (GHn) during an oral glucose tolerance test (OGTT) which in normal individuals is undetectable, while acromegalics failed to suppress GH levels. Determination of IGF-I levels is useful as they correlate with clinical features of acromegaly and with the 24-hour mean GH levels. According to the more recent consensus, a random GH <0.4 microg/l and IGF-I in the age- and gender-matched normal range exclude the diagnosis of acromegaly. If either of these levels are not achieved, an OGTT should be performed, and then GHn <1 microg/l during OGTT excludes acromegaly. The therapeutic goals for acromegaly include the relief of sings and symptoms, the control of the tumor mass, the correction of the biochemical markers to normal levels, and the reduction in morbidity and mortality to the expected rate for the normal population. According to the 2000 consensus criteria, biochemical control of acromegaly is achieved when circulating IGF-I is reduced to an age- and sex-adjusted normal range and GHn during OGTT is <1 microg/l. There is debate in the literature whether GHn or IGF-I levels are more reliable to evaluate treatment of acromegaly. It has been reported that 15% of acromegalics with GHn <1 microg/l after treatment demonstrate abnormal IGF-I levels, while 15% of patients with normal IGF-I fail to suppress GH levels <1 microg/l during the OGTT. Probably, GHn and IGF-I levels represent two different aspects of disease activity in acromegaly. While IGF-I evaluates the secretory function of the somatotropes, GHn provides evidence of the presence or absence of functional autonomy of these cells.

Acromegaly↗

PubMed2005

Diabetes insipidus, secondary hypoadrenalism and hypothyroidism after traumatic brain injury: clinical implications.

Adequate ADH secretion, adrenal and thyroid functions are vital during the acute and post-acute phases of TBI. Deficiencies of these functions as a result of TBI are increasingly recognized. During the acute phase of TBI the incidence of severe DI is 2.9%; the incidence of less severe forms of DI is 21.6-26%. The development of DI seems to correlate with the severity of trauma. In most occasions DI is transient, but persisting DI may develop with an incidence of 6.9-7.5% amongst TBI victims. The assessment of the adequacy of adrenal function during the acute phase of TBI remains a diagnostic challenge. A few studies demonstrated an incidence of hypoadrenalism of 15-16% during the early phase of TBI. It should be noted that early hypoadrenalism may be due to either a structural damage at the level of the hypothalamo-pituitary unit or it may develop in the context of the so-called "relative adrenal insufficiency", a functional abnormality that is currently increasingly recognized during the course of severe illness. Secondary hypoadrenalism during the late phases of TBI appears with an incidence of 7.1-12.7%. The "low-T3 syndrome" compromises the assessment of thyroid function during the acute phase of TBI; the incidence of TSH insufficiency during the recovery phase varies widely between 1-21%. In summary, diabetes insipidus, secondary hypoadrenalism and hypothyroidism may develop in a small albeit significant proportion of patients during the course of TBI. Therefore, assessment of the integrity of ADH secretion, hypothalamic-pituitary adrenal (HPA) axis and thyroid axis is crucial to ensure survival and optimal rehabilitation of TBI patients.

Adrenal Insufficiency↗

PubMed2005

Evaluation of GH reserve in patients with adrenal incidentalomas and biochemical evidence of subclinical autonomous glucocorticoid hypersecretion.

OBJECTIVE: Although it is well established that overt hypercortisolism in patients with active Cushing's syndrome leads to a profound suppression of stimulated GH secretion, the role of subclinical autonomous glucocorticoid hypersecretion (SAGH), currently detected with increasing frequency in patients with adrenal incidentalomas, on GH secretory reserve has received little attention. The aim of the present study was to evaluate whether SAGH in patients presented with adrenal incidentalomas has a negative effect on GH secretory reserve. DESIGN AND PATIENTS: Sixteen patients with overt Cushing's syndrome (CS) and 36 patients with adrenal incidentalomas were investigated. The latter group was further divided in 23 patients who demonstrated an adequate suppression of cortisol levels (of < 70 nmol/l) following the low-dose dexamethasone suppression test (LDDST) and in 13 patients, who failed to suppress (cortisol levels post-LDDST > 70 nmol/l). The former group was defined as normocortisolaemic (NC) and the latter group as representing patients with SAGH. The combined pyridostigmine + GHRH test (PD + GHRH) was used to assess the GH secretory reserve of these patients. RESULTS: Peak GH levels following PD + GHRH administration were significantly lower in CS patients compared to both the NC and SAGH group of patients with adrenal incidentalomas (2.2 +/- 0.7 vs. 18.9 +/- 2.6 and 21.5 +/- 3.6 microg/l, respectively, P < 0.05); no difference was observed in peak GH responses between the NC and SAGH group of patients. A subnormal GH response (defined as GH(max) < 12.8 microg/l) was observed in all 16 patients with CS. However, only seven NC and three SAGH patients failed to respond adequately. Correlation analysis revealed a negative correlation between peak GH response to PD + GHRH and plasma cortisol concentrations in CS patients (R =-0.6, P = 0.012), while in patients with adrenal incidentalomas such a correlation was absent. Contrary to patients with CS in whom body mass index (BMI) was not correlated to peak GH, a significant negative correlation between peak GH response to PD + GHRH and BMI was disclosed in patients with adrenal incidentalomas (R =-0.49, P = 0.003). In these patients, again contrary to CS patients, a significant negative correlation was also found between peak GH post PD + GHRH and age (R = -0.46, P = 0.002). CONCLUSIONS: In conclusion, our results provide evidence that, contrary to patients with overt CS, SAGH does not affect the GH secretory response to provocative stimulation.

Adenoma↗

PubMed1999

Novel concept of antisurvival factor (ASF) therapy produces an objective clinical response in four patients with hormone-refractory prostate cancer: case report.

BACKGROUND: Osteoblasts and osteoblast-derived survival growth factors, such as insulin-like growth factor I (IGF I), inhibit chemotherapy apoptosis of prostate cancer cells, thereby producing cytotoxic drug-resistant tumor growth, in vitro. METHODS: We tested a novel therapeutic approach, referred to as antisurvival factor (AFS) therapy, that aimed at reduction of osteoblast-derived IGFs, using dexamethasone (4 mg per os, qD) and growth hormone (GH)-dependent liver-derived IGFs, using a somatostatin-analog (lanreotide, 30 mg, intramuscularly (i.m.), q14D) in combination with triptorelin (3.75 mg, intramuscularly, q28D) to produce a clinical response in 4 patients with progressing hormone-refractory prostate cancer. RESULTS: The patients given ASF therapy exhibited an excellent improvement of clinical performance and a decline of prostate-specific antigen (PSA) within 2 months of ASF therapy. One of them experienced excellent clinical response (normalization of PSA), two experienced good clinical response (decline of PSA of more than 50%), and one experienced stabilization (decline of PSA of less than 50%). CONCLUSIONS: We conclude that this novel concept of combination therapy, using ASF with hormone ablation, is a promising salvage therapy that should be further assessed with a randomized clinical trial.

Aged↗

PubMed1999

The contribution of vitamin D receptor gene polymorphisms in osteoporosis and familial osteoporosis.

It is well established that genetic factors play a major role in the pathogenesis of osteoporosis. Previous reports have suggested that vitamin D receptor (VDR) gene polymorphisms, particularly the BB, tt and AA genotypes, are associated with low bone mineral density (BMD). If these VDR genotypes are indeed an important determinant of BMD, then a population of related osteoporotic individuals (mother-daughter or sister-sister relationship) should have a high prevalence of the BB, tt or AA VDR genotypes. To test this hypothesis we determined the VDR genotypes in 26 osteoporotic persons (age 44.3 +/- 12.7 years, mean +/- SD) belonging to 12 families. Furthermore, for comparison with existing studies, we applied the VDR genotype analysis in a population of 53 unrelated healthy subjects (age 45.2 +/- 9.8 years, mean +/- SD) and 59 unrelated osteoporotic subjects (age 52.1 +/- 9.0 years, mean +/- SD). The menopausal status of the healthy and osteoporotic populations was pre-, peri- and mostly early postmenopausal. The proportions of the three genotypes, BB, tt and AA, within the 12 osteoporotic families were 15%, 12% and 27%, respectively, whereas the proportions of the other three homozygous genotypes (bb, TT, aa) were 50%, 50% and 23%. The distribution of the BB, tt and AA genotypes in the normal population was 21%, 21% and 36%, respectively (vs bb, TT, aa: 36%, 38%, 21%), whereas in the osteoporotic population it was 24%, 20% and 34% (vs bb, TT, aa: 27%, 34%, 14%). Our data indicate that there is not a statistically significant (p>0.05) difference in the VDR genotype frequencies within osteoporotic families as compared with the same genotypes in the population of unrelated normal or osteoporotic subjects. VDR genotype analysis showed no significant relation between VDR polymorphisms and BMD or Z-score values at the lumbar spine. This study demonstrates the lack of a heritability pattern between the BB, tt and AA genotypes and low BMD.

Adult↗

PubMed1999

Differentiated thyroid cancer: a retrospective analysis of 832 cases from Greece.

OBJECTIVE: To analyse the initial manifestations, pathological findings, therapy, outcome and prognostic factors in patients with papillary and follicular carcinoma. PATIENTS: 832 patients with well differentiated thyroid carcinoma managed in our department during a period of 30 years (1965-1995). Follow-up data were available for 609 patients for a mean of 5.5 years (range 1-38 years), the remainder having been lost to follow-up. RESULTS: The patients were 677 (81%) with papillary and 155 with follicular carcinoma. They were predominantly female (75%), presenting mainly with a single nodule (53%), while at the time of diagnosis 72% had intrathyroidal carcinomas (class I), 17% had nodal metastases (class II), 7% soft tissue invasion (class III) and 4% distant metastases (class IV). Fifty-five percent of the patients had a complete thyroidectomy (36% had a near total or total thyroidectomy and 19% near total or total thyroidectomy plus block dissection), 2.6% received external radiotherapy and 94% had radioactive iodine as part of the treatment of the original disease. Kaplan-Meier survival analysis was used to calculate both cancer related mortality and disease free survival in the patients followed-up. Although mortality (21 cancer-related deaths) was slightly higher for follicular than papillary carcinoma (10% vs. 5% and 16% vs. 10% in 10- and 15-year survival, respectively) the difference was not statistically significant. Extent of disease at diagnosis, male sex, tumour size and age > 60 years affected probability of cancer death. Cox's proportional hazard regression analysis for disease free survival showed that adverse independent prognostic factors were, for papillary carcinoma, male sex, class II or higher, tumour size > 1 cm and age > 60 years, while for follicular, class III or higher, size > 4 cm and age > 40 years. CONCLUSIONS: We conclude that there is a higher prevalence of follicular carcinoma in our country probably due to a moderate degree of iodine deficiency still existing in Greece. Age and extent of disease at diagnosis were important prognostic factors affecting morbidity and mortality, whereas sex, tumour features and histological type were of minor importance. All these prognostic factors and their relative importance should be taken in consideration in the management of this disease.

Adenocarcinoma, Follicular↗

PubMed1997

Recombinant human growth hormone-binding protein fails to enhance the in vivo bioactivity of human growth hormone in normal rats.

GH circulates in the plasma partially bound with a GH-binding protein (GHBP), but the physiological significance of the GHBP and how it affects GH bioactivity in vivo is still unknown. In the present study, we took advantage of the known biological action of exogenous human (h) GH to inhibit endogenous rat (r) pulsatile GH release and examined the effect of combining hGH with recombinant hGHBP on this response in normal rats. Spontaneous 7-h plasma rGH and hGH profiles were obtained from four groups of free-moving adult male rats s.c. administered either: 1) 200 microg hGH alone; 2) a mixture of 200 microg hGH and 200 microg hGHBP preincubated for 30 min before injection; 3) 200 microg hGHBP alone; or 4) Tris buffer (vehicle) alone. Rats administered the vehicle or hGHBP separately exhibited the typical pulsatile pattern of rGH secretion. Injection of hGH alone resulted in a marked (P < 0.01) suppression of spontaneous rGH pulses for approximately 3.5 h after the injection compared with vehicle-injected controls; during the subsequent 3.5- to 7-h period, recovery of spontaneous rGH peaks was evident. Plasma levels of hGH in these animals reached a peak within 1 h after hGH injection and declined to near undetectable levels by the end of the sampling period. In contrast, the disappearance rate of hGH was markedly slower in rats administered the hGH + hGHBP complex; plasma hGH concentrations at 7 h after injection were 14-fold higher than those in animals administered hGH alone, and hGH was still readily detectable up to 24 h after injection. However, despite the markedly higher levels of hGH persisting throughout the sampling period in complex-injected rats, both the time course of hGH-induced inhibition of rGH and the recovery of spontaneous rGH pulses were similar to those of animals administered hGH alone. Moreover, there were no significant modifications of plasma insulin-like growth factor-1 levels for up to 24 h after injection of the hGH + hGHBP complex. Computer simulations revealed that most of the total hGH observed during the 3.5- to 7-h period was circulating in the bound form. These results demonstrate that, despite hGHBP's ability to markedly prolong the bioavailability of hGH, precomplexing hGH with hGHBP failed to enhance hGH's in vivo bioactivity in the inhibition of endogenous pulsatile rGH release. Our findings do not provide support for the concept that the GHBP enhances the bioactivity of GH in vivo, at least over the time course examined here.

Animals↗

PubMed1996

Somatostatin pretreatment enhances growth hormone (GH) responsiveness to GH-releasing hormone: a potential new diagnostic approach to GH deficiency.

Despite the availability of numerous testing procedures to evaluate GH secretion in short children, there is still controversy about the most reliable test in the diagnosis of GH deficiency. We have recently demonstrated that in normal short children, priming with the long-acting somatostatin analog. SMS 201-995 (SMS), significantly potentiates their GH response to subsequent GHRH challenge. In the present study, we used the combined SMS + GHRH test in patients with GH deficiency to validate the hypothesis that this test would better discriminate between normal short children and those with truly diminished GH secretion. We studied 24 children classified into three groups according to their GH peak response to up to four conventional tests: 1) children with normal short stature and normal GH response (NSSA: GH peak > or = 10 micrograms/L, n = 6); 2) children with normal short stature with borderline GH response (NSSB: GH peak > or = 7 micrograms/L but < 10 micrograms/L, n = 4); and 3) GH-deficient children (GHD: GH peak < 7 micrograms/L, n = 14). Two study protocols were performed in all subjects: SMS (1 microgram/kg, sc) was randomly administered or omitted (control test) a 0800 h and GHRH (1 microgram/kg, iv) was given 5 h later. Plasma GH levels were measured every 30 min from 0800 h until 2 h after the GHRH injection. Pretreatment with SMS significantly augmented the GH peak response and the GH area under the GH concentration curve over 2 h after GHRH injection in the NSSA group, compared with control tests, but had no effect in the other two groups. While there was wide overlap of individual peak GH values to both the conventional tests and to the GHRH injection in the control test among the three groups of children, pretreatment with SMS resulted in complete discrimination between GHD and normal short children; the mean GH peak response to GHRH after SMS pretreatment was 8- to 9-fold lower in the GHD subjects (5.2 +/- 0.8 micrograms/L) compared with both the NSSA (44.0 +/- 14.3 micrograms/L; P < 0.01) and NSSB (42.9 +/- 5.0 micrograms/L; P < 0.01) groups and, more importantly, there was no overlap in the individual GH responses between GHD and normal short children. These results demonstrate that the combined SMS + GHRH test clearly discriminates normal short children from those with GHD. In view of its testing economy, safety, and accuracy, this combined test could become the test of choice to establish a diagnosis of GH deficiency in the slowly growing child.

Adolescent↗

PubMed1993

Effect of 131I treatment on the calcitonin response to calcium infusion in hyperthyroid patients.

OBJECTIVE: The objective was to evaluate the effect of 131I treatment for hyperthyroidism on calcitonin secretion by thyroid C-cells. DESIGN: Determination of basal calcitonin levels and calcitonin secretory reserve before and after 131I administration. PATIENTS: Seventeen hyperthyroid patients (15 female, two male) were studied before, and 2 months after 131I treatment, and 12 of these patients were restudied 8 months after 131I treatment. MEASUREMENTS: Calcitonin response was assessed by measuring basal and post calcium infusion calcitonin levels. Basal TSH, T3, and T4 levels were also determined at each study. RESULTS: The rise of plasma calcium resulted in statistically significant increase of plasma calcitonin levels before 131I treatment (10.9 +/- 2.4 pmol/l), while this response was significantly diminished 2 and 8 months after treatment (2.6 +/- 0.7 and 1.6 +/- 0.3 pmol/l, respectively). No correlation was found between the calcitonin response and age or plasma TSH. CONCLUSION: Our results demonstrate that 131I treatment for hyperthyroidism may seriously damage thyroid C-cells and cause calcitonin deficiency.

Adult↗

PubMed1993

Calcium metabolism in diabetes mellitus: effect of improved blood glucose control.

Reduced bone mass occurring with increased frequency in diabetes mellitus has been attributed to poor blood glucose control but the pathogenetic mechanisms remain unknown. To evaluate the role of calcium metabolism, 59 patients with diabetes and normal renal function (22 Type 1, 37 Type 2) were studied. In all patients plasma calcium (Ca), serum phosphate (PO4), serum parathyroid hormone (PTH), and 24-h urinary calcium (uCa) were determined under both poor and improved control (for at least 7 days) as ascertained by four blood glucose determinations daily. Improvement of blood glucose control (p = 0.001) was associated with reduction of uCa both in Type 1 (6.9 +/- 1 vs 4.9 +/- 0.9 mmol day-1, mean +/- SEM, p = 0.02) and in Type 2 patients (4.2 +/- 0.4 vs 3.2 +/- 0.4 mmol day-1, mean +/- SEM, p = 0.002). Considerably more Type 1 patients (10 out of 22) had PTH values below the detection limit (1.5 pmol l-1) during poor than during improved control (2 out of 22). Comparison between the two types of diabetes showed that in Type 1 under poor control, Ca and PTH were lower (p = 0.03), while uCa was higher (p = 0.003), and after improved control, only uCa continued to be higher (p = 0.035). These findings suggest that increased uCa excretion in association with 'functional hypoparathyroidism' (especially in Type 1 diabetes) is observed during poor blood glucose control, and may be one of the factors leading to reduced bone mass in diabetes mellitus.

Adult↗

PubMed1992

PMA-activated neutrophils decrease ectoenzyme activities in rabbit aortic endothelial cells in culture.

We have studied the effects of phorbol 12-myristate 13-acetate (PMA)-activated neutrophils [polymorphonuclear leukocytes (PMN)] on endothelial ectoenzyme [angiotensin-converting enzyme (ACE) and 5'-nucleotidase (NCT)] activities in cultured rabbit aortic endothelial cells (EC) with the use of [3H]benzoyl-Phe-Ala-Pro and 14C-labeled AMP as substrates, respectively, under first-order reaction conditions. PMA (1-1,000 ng/ml) or PMN alone had no effect on ACE activity. When PMA was incubated together with PMN (PMN/EC = 1.25:1 or 2.5 x 10(5) neutrophils/ml) for 4 h in Earle's salts, a PMA dose-dependent decrease in ACE activity was observed. Threshold PMA concentration was 2 ng/ml. At 8 ng PMA/ml, ACE activity was totally abolished, without any evidence of cytotoxicity, as inferred from release of 51Cr from prelabeled EC. The decrease in ACE activity was also dependent on PMN concentration and was detectable at PMN/EC values as low as 1.25:10 (0.25 x 10(5) PMN/ml). Inhibition of ACE occurred as early as 1 h after incubation (PMA 10 ng/ml, PMN/EC = 1.25:1). PMA alone caused a small but significant increase in NCT activity, whereas PMA coincubation with PMN produced a significant decrease in NCT activity (20-29%), which was PMA and PMN concentration independent. PMA increased PMN adherence to endothelial monolayers in a concentration-dependent manner. Pretreating PMN with monoclonal antibody 60.3 (raised against the adhesion glycoprotein CD18) or placing a 2-microns filter between PMN and EC, protected the decrease in ACE activity.(ABSTRACT TRUNCATED AT 250 WORDS)

5'-Nucleotidase↗

PubMedDate not supplied

Leptin alterations in the course of sepsis in humans.

Neuroendocrine response to sepsis may be divided into acute and prolonged phase. As leptin is implicated in the stress response, leptin's profile during both phases, and the possible relationships between leptin and the neuroendocrine response to sepsis were investigated. Thirty adult patients with sepsis in an intensive care unit were studied. Blood samples were collected at the acute and the prolonged phases. In acute sepsis, leptin levels were higher in patients than in controls (10.2 +/- 2.5 vs. 4.1 +/- 1.2 ng/ml, p =0.01) and correlated positively with insulin levels and insulin resistance. A decline in leptin levels was found during prolonged sepsis (from 10.2 +/- 2.5 to 6.2 +/- 1.7 ng/ml, p=0.001), which was not related to survival (p=0.913). At the onset of sepsis, leptin levels increased in correlation with insulin and insulin resistance, possibly indicating a cause-effect relationship. However, the decline in leptin levels during the prolonged phase of sepsis was not related either to survival or to metabolic and hormonal changes.

Adult↗

PubMedDate not supplied

Hemodynamic and metabolic effects of intravenous formyl-methionyl-leucyl-phenylalanine (FMLP) in rabbits.

We have studied the role of neutrophils and the effects of the chemotactic factor FMLP, using normal, neutropenic (after cyclophosphamide treatment) and C5a desArg-treated unanesthetized rabbits. The intravenous administration of FMLP in normal animals induces transient and dose-dependent hypotension, neutropenia and thrombocytopenia, with a maximal response in 3 minutes. When a bolus of 5 x 10(-9) moles FMLP was administered, maximal arterial hypotension (40 +/- 1.1 v.s. 90 +/- 1.1 mmHg in the controls, P < 0.001) accompanied by a significant increase in central venous pressure (0.89 +/- 0.9 v.s. -2.2 +/- 0.7 mmHg in the controls, P < 0.01) and a decrease in systemic vascular resistance (90 +/- 15.6 v.s 187 +/- 16.4 mmHg/L/min, P < 0.005). Plasma pH and bicarbonate were significantly reduced, with a parallel increase in plasma lactate levels. A similar reduction of arterial blood pressure was also noted in neutropenic animals (31 +/- 3% of pretreatment levels respectively). C5a des Arg caused neutropenia similar to that seen after 5 x 10(-9) moles FMLP (120 +/- 60/mm3 and 170 +/- 25/mm3 respectively), but it did not induce hypotension. These data suggest that simple neutrophil activation is not the mechanism of the FMLP-induced hypotension and that this chemotactic factor may interact with other cell types to produce its effects.

Animals↗