Biomedical subjects
G Tolis
Publications and source records attributed to G Tolis.
Coronary artery bypass grafting in severe left ventricular dysfunction: excellent survival with improved ejection fraction and functional state.
OBJECTIVES: The present study evaluated our experience with coronary artery bypass grafting in patients with severe left ventricular dysfunction. BACKGROUND: Despite the ominous prognosis of advanced ischemic cardiomyopathy, coronary artery bypass grafting in this setting remains controversial because of concerns over operative risk and lack of functional or survival benefit. METHODS: We analyzed the data of 83 consecutive patients (69 men, 14 women, aged 42 to 83 years [mean 66.8]) with a left ventricular ejection fraction < or = 30% who underwent isolated coronary artery bypass grafting (without aneurysmectomy, valve replacement or other open heart procedures) performed by one surgeon during a 6-year period. The ejection fraction ranged from 10% to 30% (mean 24.6%). Preoperatively, 49% of patients had angina, 52% had congestive heart failure (17% with pulmonary edema) and 30% manifested significant ventricular arrhythmia. The mean number of grafts was 2.7/patient. The internal mammary artery was used in 82% of grafts to the left anterior descending coronary artery. The intraaortic balloon pump was required therapeutically (for angina or pump failure) in 19% of patients and was prophylactically placed preoperatively in another 43% of patients. RESULTS: The hospital mortality rate was 8.4% (7 of 83). The mortality rate was 3.3% (2 of 61) in those patients who did not require admission to an intensive care unit immediately before operation. Canadian Cardiovascular Society angina class improved postoperatively by 1.9 categories and New York Heart Association congestive heart failure class by 1 category. Left ventricular ejection fraction (assessed postoperatively in 68 of 76 hospital survivors) improved from 24.6% preoperatively to 33.2% postoperatively (36% increase) (p < 0.001). At 1 and 3 years, respectively, all-cause survival was 87% and 80% and freedom from cardiac death was 89.8% and 84.5%. CONCLUSIONS: In patients with coronary artery disease and advanced ventricular dysfunction: 1) coronary artery bypass grafting can be performed relatively safely, 2) good medium-term survival is attained, 3) improvement in left ventricular function can be documented objectively after bypass grafting, 4) quality of life is improved (as reflected by improvement in anginal and congestive heart failure status), and 5) the internal mammary artery can safely be used as a conduit. The use of coronary artery bypass grafting is encouraged for this group of patients and may provide a viable alternative to transplantation in selected patients.
Therapeutic use of gonadotropin-releasing hormone agonists in polycystic ovarian syndrome.
Polycystic ovarian syndrome is a heterogeneous disorder characterized by abnormal function of the hypothalamic-pituitary-gonadal axis, excessive production of androgens, aberrant intermediary metabolism, and structural changes in ovarian morphology. Long-term administration of the GnRH agonistic analogues brings about pituitary gonadotroph down-regulation after an initial period of stimulation of FSH/LH release. The resulting decrease in LH output and ovarian androgen production exerts beneficial effects on the clinical and biochemical parameters of the PCO syndrome. Ovarian volume and stroma usually decrease, but the results of treatment are not permanent, since relapse of the syndrome is usually observed a few months after cessation of the agonist. There are no serious side effects, and a small decrease in bone mineral content is recovered after discontinuation of the treatment. Possible indications for this regime include patients with very large ovaries and resistant hyperandrogenemia. On the other hand, the use of GnRH agonists in the preparation of PCOS patients for ovulation induction is already established.
Pharmacokinetic study and effects on growth hormone secretion in healthy volunteers of the new somatostatin analogue BIM 23014.
We have studied the pharmacokinetics and the effects of BIM 23,014 (BIM), a new, long-acting octapeptide somatostatin analogue, on basal and stimulated GH secretion in normal men. BIM 250 micrograms sc significantly reduced a GHRH-induced increase in plasma GH. The continuous sc administration of BIM for 24 h dramatically blunted spontaneous GH secretion; 2000 and 3000 micrograms daily reduced GH secretion to a greater extent than 1000 micrograms daily. During these experiments a significant negative correlation (r - 0.66) was found between plasma GH and BIM levels. Acute sc administration of 1000 micrograms BIM significantly reduced the rise in plasma GH observed in the second part of the oral glucose tolerance test. Plasma BIM levels peaked around 30 min, and the elimination half life was 90 min. Plasma BIM levels were below 1 ng/ml 6 h after the injection of 1000 micrograms BIM, and at that time GH started to rise again. We conclude that BIM 23,014 250 to 1000 micrograms sc is able to reduce the plasma GH response to GHRH or to the fall in glucose following an oral glucose tolerance test; a constant infusion of BIM, in doses 1000 micrograms daily, dramatically suppresses spontaneous GH secretion; 2000 micrograms/day by chronic subcutaneous infusion was the most effective dose of BIM in the suppression of GH secretion, and was associated only with minor adverse effects.
Treatment of polycystic ovarian disease during adolescence with ethinylestradiol/cyproterone acetate versus a D-Tr-6-LHRH analog.
OBJECTIVE: This study was undertaken to compare the clinical and endocrinological results of two kinds of treatment on adolescents with polycystic ovarian disease (PCOD). METHOD: Forty-five adolescents with PCOD were randomly allocated into two groups, treated either with ethinylestradiol (EE)/cyproterone acetate (group A) or the GnRH analog D-Tr-6-LHRH (group B). RESULT: No significant changes were detected on the body mass index and waist-hip circumference. A significant improvement of hirsutism was noticed in both groups of patients. A normal menstrual period was recorded in group A adolescents while all group B patients became amenorrheic. A favorable decrease of ovarian volume was detected in both groups. LH/FSH ratio and delta 4-androstenedione serum levels were found significantly reduced in both groups in comparison to pre-treatment levels. The comparison between the two groups, after 6 months, showed significantly lower values of LH/FSH ratio in group B cases. CONCLUSION: Both forms of treatment are safe and effective to a various degree for the management of PCOD adolescents.
The corticotrophin releasing factor test: a valuable and rapid procedure for the differential diagnosis of hirsutism.
Plasma concentrations of adrenocorticotrophic hormone, cortisol, 17-hydroxyprogesterone, testosterone, delta 4-androstenedione and dehydroepiandrosterone sulphate were determined in 10 regularly menstruating hirsute women 0, 15, 30, 60, 90 and 120 min after intravenous injection of 100 micrograms corticotrophin releasing factor. The baseline concentrations of adrenocorticotrophic hormone, cortisol, progesterone and dehydroepiandrosterone sulphate were within the normal range, whereas the mean delta 4-androstenedione and testosterone concentrations were mildly elevated. The administration of corticotrophin releasing factor induced a rapid and significant increase in plasma concentrations of adrenocorticotrophic hormone, cortisol, 17-hydroxyprogesterone and delta 4-androstenedione after 60 min, whereas dehydroepiandrosterone sulphate and testosterone concentrations were not significantly elevated. These findings suggest that the corticotrophin releasing factor test can readily be used as an out-patient procedure to exclude adrenal hirsutism.
Endocrine abnormalities in thalassemia.
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Is androgen substitution necessary in hypogonadal patients when they are treated with chemotherapy for malignant diseases?
A patient with hypogonadotropic hypogonadism owing to endogenous gonadotropin releasing hormone deficiency, who developed Hodgkin's disease is described. Chemotherapy administration caused prolonged and life-threatening myelosuppression; androgen substitution seemed to reverse bone marrow function and to maintain normal peripheral blood counts. Whether or not androgens are a necessary substitution in hypogonadal patients suffering from cancer and undergoing chemotherapy is discussed.
Enhancement of renal function by a long-acting somatostatin analogue in patients with decompensated cirrhosis.
The effect of the long-acting somatostatin analogue SMS 201-995 on renal function was investigated in nine cirrhotic patients with ascites, low urine output, low serum sodium, and normal serum creatinine. SMS 201-995, infused at 40 micrograms/h for 2 h, produced a significant increase in urine volume, a significant decrease in urine osmolality, and a significant increase in creatinine clearance. These changes, although less pronounced, persisted 24 h after the infusion of the analogue. No significant changes in free water clearance, urinary sodium excretion or serum sodium were noted. The effects of SMS 201-995 might be attributed to an improvement of renal haemodynamics through inhibition of vasoconstrictor systems acting in cirrhosis. It is concluded that SMS 201-995 may have a role in the treatment of the renal abnormalities complicating liver disease.
Long-term management of acromegaly with sandostatin.
The present report illustrates the effectiveness of a long-acting somatostatin analog, SMS 201-995 (Sandostatin), in the chronic treatment of acromegaly. Daily doses of 50-300 micrograms were administered subcutaneously to 37 patients. Gradual dose increments induced a progressive GH decrease accompanied by a parallel reduction in plasma somatomedin C concentrations. There was a concomitant amelioration of clinical signs and symptoms throughout the investigational period. No escape phenomenon or tachyphylaxis was observed. It is concluded that chronic therapy with SMS 201-995 represents a promising medical alternative for the treatment of active acromegaly.
Pituitary somatotropic and corticotropic function in patients with beta-thalassemia on iron chelation therapy.
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Objective response and disease outcome in 59 patients with stage D2 prostatic cancer treated with either Buserelin or orchiectomy. Disease aggressivity and its association with response and outcome.
A comparative study was done in 59 recently diagnosed Stage D2 prostatic cancer patients treated with either long-term GnRH-A (Buserelin) (N = 42) or with orchiectomy (N = 17) and followed up for three years. The suppressed limits of plasma testosterone and estradiol levels after eight-week follow-up as well as the objective clinical response and disease outcome were found to be similar with either treatment. Hot flushes and loss of libido were noticed in both groups throughout the follow-up period; however, there were no other side effects. Analysis of Stage D2 patients based on their time of death enables us to identify nonhormonal variables which, in the form of an aggressiveness score, correlated well with both clinical response and disease outcome. These data confirm that (1) Buserelin is an effective and safe alternative to orchiectomy in advanced prostatic cancer, and (2) in clinical studies a multifactor aggressiveness score is useful for analyzing clinical efficacy data. Prospective application of that score may enable predictability of patient response and influence patient management.
Therapy of acromegaly with SMS 201-995: long-term studies.
Fourteen acromegalic patients, half of whom had been unsuccessfully treated with surgery, radiotherapy, or bromocriptine, were given the somatostatin analogue SMS 201-995 parenterally as the sole therapeutic regimen after a single administration had demonstrated suppression of serum growth hormone (GH). An impressive and sustained clinical improvement was documented in all patients, including those in whom bromocriptine had failed; most marked was the decrease in soft tissue swelling and headache and an improved performance status. GH levels decreased each time SMS 201-995 was injected but returned to basal levels within 8 h in most of the patients. With chronic therapy, 24-h mean levels were significantly suppressed, and the GH stimulability of thyrotrophin-releasing hormone and growth-hormone-releasing hormone (pl-44) was markedly reduced. Discontinuation of SMS 201-995 therapy was associated with a return of symptoms and abnormal GH dynamics. The efficacy and safety of chronically administered SMS 201-995 in active acromegaly opens new horizons for its treatment.
Therapeutic efficacy of a somatostatin analogue (SMS 201-995) in active acromegaly.
Twelve patients with active acromegaly, six of whom had not responded to previous combined surgery, radiotherapy, and bromocriptine administration, were treated with an octapeptide long-acting somatostatin analogue, SMS 201-995, given subcutaneously for up to 1 year. Growth hormone (GH) levels decreased by 50% to 90% after a single 25-micrograms SMS 201-995 injection in all patients, including two who were resistant to bromocriptine therapy. After GH values reached a nadir, they returned to preinjection values over a 12-hour period and no rebound was seen. Assessment of the GH-lowering effect of the drug at weekly intervals for the first 6 weeks and monthly thereafter disclosed no tachyphylaxis. Gradual increase of the dose from 50 to 150 micrograms daily led to a significant increase in clinical improvement. Shrinkage of the size of the pituitary tumor was documented in three of nine evaluated cases. Abdominal cramps of a transient nature not associated with diarrhea were noted in two patients but there were no other side effects. Hematological and biochemical blood and urine tests, including serum thyroxine and cortisol levels, did not reveal any abnormality during chronic treatment. This study demonstrates the safety and efficacy of SMS 201-995 in the short-term treatment of acromegaly.
Long-term follow-up of patients with advanced prostatic carcinoma treated with either buserelin (HOE 766) or orchiectomy: classification of variables associated with disease outcome.
We compared the clinical efficacy and safety of Buserelin treatment versus orchiectomy in 29 patients with newly diagnosed advanced prostatic cancer. There was no significant difference between the two treatment modalities in 1) reduction of plasma testosterone to below 100 ng/dl after 8 weeks, 2) objective clinical response rates in patients with stage D2 carcinoma, 3) induction of complete remission in patients with stages C and D1 carcinoma, or 4) relapse rates and death rates in patients with stage D2 carcinoma. After scoring stage D2 disease according to our aggressiveness analysis system, we found that patients with less aggressive neoplasms displayed a qualitatively better response and more prolonged remission. These data and the absence of estrogenic effects confirm Buserelin as a favorable alternative to orchiectomy in the treatment of prostatic cancer. Additionally, the study demonstrates the importance of considering the heterogeneity of the aggressiveness of stage D2 disease in assessing the benefits of clinical trials in prostatic carcinoma.
Advanced prostatic adenocarcinoma: biological aspects and effects of androgen deprivation achieved by castration or agonistic analogues of LHRH.
Twenty-nine patients with advanced prostatic adenocarcinoma were evaluated clinically, biochemically and radiologically and randomly assigned either to orchiectomy or to medical treatment. The latter consisted of the chronic administration of an LHRH agonistic analogue by parenteral and/or intranasal routes. Plasma testosterone levels fell to castrate values and remained so for as long as the follow-up lasted (24 months); estrogen levels fell as well. No change in basal cortisol, thyroxine or prolactin levels was noticed. A decrease in prostate size and improvement in prostatism occurred in all. Bone pain and radiology conventionally or by isotopic scanning, did not parallel the improvement seen in the primary disease locus. Similarly, the changes in alkaline phosphatase were minimal when compared to that of prostatic acid phosphatase. Both enzymes increased prior to or concurrently with relapse of the disease. The longest remission and survival was seen in patients with low enzyme levels, non diffuse bone metastases and high degree of tumor differentiation. Chronic use of agonistic analogues of LHRH induces effective castration in men with prostatic carcinoma and can replace orchiectomy or estrogen administration. The quantitative analysis of androgen receptors (AR) in subcellular fractions of tumor cells; the use of techniques to enhance the number of AR in the cytosol; and the determination of the type II/I regulatory subunit of protein kinase may be used to identify hormone independent clones and spare patients of unnecessary procedures.
Sheehan's syndrome: in vivo diagnosis with the use of computerized axial tomography and pituitary provocative testing.
Postpartum amenorrhea associated with other symptoms and signs of hypopituitarism, such as inability to lactate, weakness, easy fatigability, sexual-hair loss, and clinical evidence of hypothyroidism, were found in two female patients with the antecedent of postpartum hemorrhage. The baseline values of the gonadal, thyroid, and glucocorticoid hormones were all consistently lower than normal. The serum levels of the pituitary hormones were low, and the responses to standard stimulatory tests were either insignificant or blunted. Plane skull films and conventional sella tomography did not reveal any abnormality in the sella turcica. CAT identified hypodensity in the area of the hypophysis with preservation of the pituitary stalk. The combination of the failure of provocative stimuli to affect anterior pituitary hormone release with the radiologic picture compatible with pituitary infarction readily makes the diagnosis of Sheehan's syndrome in vivo and should be used in patients where this syndrome is suspected.
Pregnancy in hyperprolactinemic women.
Pregnancy achieved in women who receive treatment to correct the secretory dysfunction of nontumoral HPRL or microprolactinomas requires close prenatal care, but generally its course does not vary from normal. When a macroprolactinoma is present, consequences of pregnancy are insignificant, provided the tumor has been previously treated or bromocriptine is given continuously during the pregnancy. On those rare occasions when symptoms of tumor growth appear during pregnancy, bromocriptine and dexamethasone effectively control such manifestations. Breast-feeding of the infant can be allowed, and a second pregnancy within a short term is not contraindicated. When a new pregnancy is not desired, nonhormonal contraceptive methods are advised. Patients with nontumoral HPRL and microadenomas require periodic checkups. Macroadenomas may be surgically excised, but longterm bromocriptine treatment also achieves good results and is highly recommended.