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Biomedical subjects

R Cozzi

Publications and source records attributed to R Cozzi.

At least 19 recordsLinked to original sources
PubMed2005

A multi-biomarker analysis of DNA damage in automobile painters.

The genotoxic effects associated with automobile painting were analyzed using a panel of biomarkers. Chromosomal aberrations (CAs), sister chromatid exchange (SCE), and micronuclei were evaluated in 25 car painters (12 smokers, 13 nonsmokers) working in different automobile paint-shops in Italy and in 37 control subjects. The controls were healthy blood donors (14 smokers, 23 non-smokers) that were matched with the experimental population for gender and age. Air samples were analyzed regularly at the work places, and elevated concentrations of benzene and toluene were detected consistently. The exposed group had higher frequencies of CAs (both chromosome- and chromatid-type), micronuclei, and SCE (P < 0.5 - P < 0.001). Furthermore, exposed and control subjects were also genotyped for GSTM1 and GSTT1 polymorphism. No significant associations were detected between the biomarker responses and either the GSTM1 or GSTT1 genotype of the subjects, but the small sample size does not allow definite conclusions on the relationship between the genetic polymorphism and the biomarkers. The results indicate that automobile painters have increased levels of clastogenic and possible aneugenic damage and that smoking may be a confounding factor for the responses.

Adult↗
PubMed2004

Treatment of acromegaly with SS analogues: should GH and IGF-I target levels be lowered to assert a tight control of the disease?

BACKGROUND: in acromegaly, the criteria for the cure of the disease after neurosurgery have become tighter and tighter. In contrast, the evaluation of control of disease activity during medical treatment is based upon the normalisation of IGF-I levels and epidemiological criteria, i.e. lessening GH (assessed by RIA) to levels reported to normalise increased mortality. The aim of this study was to evaluate GH and IGF-I suppression during prolonged SS analogues (SA) treatment. The concordance between "safe" GH and normalised IGF-I levels during SA was also assessed, according to gender and gonadal status. DESIGN: multicentre, retrospective. Patients. GH/IGF-I levels were evaluated in 207 acromegalic patients (132 females, aged 20-85 yr) during a prolonged treatment (longer than 12 months) with individually tailored doses of depot SA( lanreotide or octreotide-LAR in 97 and 110 patients, respectively). Final IGF-I levels were transformed in z-scores using data collected in a large cohort of normal subjects of 3 different age groups (20-40 yr old, 41-60 yr old, 61-80 yr old, n=160, 148, 115, respectively), that allowed to set up quartiles of normality (I = 3rd-25th percentile, II = 26th-50th, III = 51th-75th, IV = 76th-97th). RESULTS: fifty-nine and 19.3% of patients achieved GH levels <2.5 and <1 microg/l, respectively. IGF-I were normalised (z-score between 2 and -2) in 58.4% of patients. The distribution of normal IGF-I values among quartiles was uneven: 7%, 19%, 25%, and 49% of values were distributed in the I, II, III, and IV quartile, respectively. The concordance between GH and IGF-I values was poor: 28.4% of patients attaining GH values <2.5 microg/l had still pathological IGF-I (even 12.5% of those with GH <1 microg/l), and 39.3% of those with GH levels still above the "safe" limit had "nor IGF-I. Although proportions of IGF-I normalisation were not different between males and females, the regression line obtained between GH and IGF-I z-score showed the same slope but with a significantly lower intercept in regularly cycling women than in males and in postmenopausal females. Thus for any GH value, cycling females had lower IGF-I than menopausal women and males, and their IGF-I normalisation could be achieved by higher GH values. By ROC analysis, the achievement of normal IGF-I was predicted by the GH value of 1.8 microg/l in males and 2.4 microg/l in females. CONCLUSIONS: in acromegalic patients on SA treatment, GH and IGF-I levels are often not concordant. In addition to age, sex is to be taken into account in the evaluation of hormonal targets. A better refinement of GH and IGF-I targets to be reached while on treatment with SA is warranted.

Acromegaly↗
PubMed2004

Effects of the selective estrogen receptor modulator LY117018 on growth hormone secretion: In vitro studies.

Sex steroids play an important role in modulating pulsatile growth hormone (GH) release, acting at both hypothalamic and pituitary level in both humans and experimental animals. Selective estrogen receptor modulators (SERMs) act as either estrogen receptor agonists or antagonists in a tissue-selective manner. In postmenopausal women, serum GH levels correlate positively with endogenous estradiol levels and insulin-like grwoth factor-I (IGF-I) is positively related to bone mineral density (BMD) at the spine and hip. The aim of the present study was to evaluate, for the first time, the direct effect of LY117018, an analog of raloxifene, on GH secretion from both human and rodent pituitary cells in vitro. Our results demonstrated that pharmacological concentrations of the raloxifene analog LY117018 can stimulate GH secretion through a direct action on the pituitary. LY117018 also showed an estrogen-like activity, inducing the proliferation of rat pituitary GH-secreting adenomatous cells (GH1).

Adenoma↗
PubMed2003

Estroprogestinic pill normalizes IGF-I levels in acromegalic women.

In some acromegalic patients medical treatment does not succeed in normalizing GH/IGF-I values. Data showing IGF-I suppression in acromegaly by estrogen and by tamoxifen use prompted us to reevaluate the effects of estroprogestins (EP) supplementation on GH/IGF-I levels in acromegalic women resistant or only partially sensitive to medical treatment. Eight active acromegalic women (30-52 yr, 4 with regular menses) entered a prospective open pilot study. Three of them, resistant to medical treatment, were off therapy; the remaining five, partially sensitive, maintained it at the maximally effective dosages throughout the study. Patients were treated with a triphasic pill (ethynil-estradiol 30-40-30 microg/day and desogestrel 50-70-100 mg/day) for 13 +/- 7 months. IGF-I levels fell from 512 (median, interquartile 436-657) microg/l to 282 (244-526) microg/l (p=0.0414); the decrease was observed in 6 patients (75%), and normal values were reached in 4 (50%). GH levels did not change [basal 7.6 (6.2-8.6) microg/l, final 7.6 (6.5-8.3) microg/l]. Effectiveness of treatment was not dependent on concomitant anti-GH treatment or gonadal status. In all patients IGF-I levels re-increased after EP withdrawal. This pilot study shows a marked IGF-I lowering effect of pill in acromegalic women, and warrants a prospective randomized study in patients resistant or partially sensitive to other medical treatments.

Acromegaly↗
PubMed2003

The Comet assay for the detection of DNA damage in Mus spretus from Doñana National Park.

Doñana Park (Spain), a protected area in Europe, was affected by an environmental disaster in April 1998 that caused the spreading of acidic water and mud full of toxic metals from the Aznalcollar pyrite mine. In order to assess the contamination in the area and to monitor the possible biological effects of the toxic spill, a series of coordinated studies was performed utilizing several animal species living in that area. We performed genotoxicity monitoring using the Comet assay on peripheral blood leukocytes of the Algerian mouse (Mus spretus), a nonprotected rodent suitable as a bioindicator. The mice were sampled in different areas 6 months after the ecological disaster and again 1 year later. Our results showed that in 1998 all the areas examined were contaminated, as determined by an increase in the Comet assay parameters in the analyzed animals, whereas a significant decrease in the values of these parameters was observed in the 1999 samples, which were collected in a riverside area subject to tide flows. Thus, the Comet assay has proven to be an interesting and sensitive tool in studies of environmental genotoxicity.

Accidents↗
PubMed2001

GH/IGF-I normalization and tumor shrinkage during long-term treatment of acromegaly by lanreotide.

New depot somatostatin analogs such as lanreotide-slow release (LAN) represent a significant improvement in the medical treatment of acromegaly. Seventy-three consecutive acromegalic patients, treated by LAN, were evaluated in a retrospective monocentric study. Sixteen were excluded from further evaluation due to combined treatment with dopamine agonist drugs, early LAN withdrawal for persistence of headache, or gastrointestinal side-effects. Fifty-seven patients (aged 20-82 years, 16 males) were thus evaluated. Thirty-two patients had been previously treated by neurosurgery (Tx) and/or radiotherapy (Rx). After washout, LAN (30 mg) was administered im at 10-14-day intervals. Time intervals between injections were then individually tailored to normalize IGF-I levels. LAN was administered for 12 (6-36) [median (range)] months. GH and IGF-I levels decreased from 13 (7-20) [median (interquartile)] microg/l to 3.2 (1.7-6.2) microg/l (p<0.0001) and from 780 (596-1000) microg/l to 264 (180-530) microg/l (p<0.000001), respectively. Seven patients were resistant to treatment. Among the 50 sensitive patients, GH levels fell below 2.5 microg/l in 52% (and below 1 microg/l in 18%), IGF-I levels normalized in 72% and both results were obtained in 46%. IGF-I values normalized in 87% of patients treated every 14 days, in 100% every 21-28 days, in 69% every 10 days and in 22% every 7 days. No different control of GH/IGF-I hypersecretion was evidenced between patients previously treated or not by Tx and/or Rx. Patients with the lowest basal hormonal levels and those over 55 years showed greater responsiveness (both p<0.05). The maintenance of LAN schedule up to 18 months determined a further suppression (p=0.04 for IGF-I). A reduction of tumor size was shown in 60% of evaluated patients (6/10). HbA1c slightly increased in 42% of patients and gallstones were observed in 16%. LAN is a very effective tool in the treatment of acromegaly: its chronic administration normalizes GH/IGF-I levels in most patients, shrinks the tumor in a high percentage of patients and seems to control hormonal hypersecretion as primary treatment as well as neurosurgery.

Acromegaly↗
PubMed2001

Differential inhibition of growth hormone secretion by analogs selective for somatostatin receptor subtypes 2 and 5 in human growth-hormone-secreting adenoma cells in vitro.

Somatostatin (SRIH), a cyclic tetradecapeptide hormone originally isolated from mammalian hypothalamus, is a potent suppressor of pituitary growth hormone (GH) secretion. SRIH acts through a family of G-protein-coupled membrane receptors containing seven transmembrane domains. Five genes encoding distinct SRIH receptor (SSTR) subtypes have so far been cloned in human and other species and termed SSTR1-5. In human somatotrophe pituitary adenomas GH secretion is controlled by both SSTR2 and SSTR5. However, in clinical practice only somatostatin analogs selective for SSTR2 (octreotide and lanreotide) are available. This may explain why clinical and in vitro responses to these analogs in acromegaly are only partial. In this study, we investigated the inhibitory effect of two new SRIH analogs with high selectivity for SSTR2 (NC-4-28B) and SSTR5 (BIM-23268) and compared it to that of native somatostatin (SRIH-14) on a large number of GH-secreting adenomas obtained by transphenoidal neurosurgery. Tissues from 16 adenomas were enzymatically dispersed and plated in 24-well dishes at 50,000 cells/well. After 3 days, groups of three wells were incubated for 4 h with medium alone, SRIH-14 or analogs NC-4-28B or BIM-23268, at the concentrations of 0.01, 0.1 and 1 microM. Our results show that 9 out of 16 adenomas were responsive (GH suppression: 20-40% vs. control, p < 0.05) to SRIH. In this group only 4 adenomas showed similar responses to both selective analogs, with 2 nonresponders (expression of other SRIH receptor subtypes) and 2 responders (concomitant expression of SSTR2 and SSTR5) to both analogs. GH release was selectively inhibited by NC-4-28B in 3 adenomas and by BIM-23268 in the remaining 2 adenomas, suggesting predominant expression of SSTR2 and SSTR5, respectively. SRIH failed to inhibit GH release in 7 adenomas (43%). Interestingly, in that group a better inhibitory effect was obtained with BIM-23268 (5 out of 7 adenomas) than with NC-4-28B, suggesting expression of a few SSTR5 receptors only, or of both SSTR2 and SSTR5, respectively. We conclude that the availability of somatostatin analogs selective for SSTR5 will enhance the treatment potency and spectrum in acromegaly.

Adenoma↗
PubMed2001

Failure of radiotherapy in acromegaly.

BACKGROUND: Recent data has raised skepticism regarding the long-term effectiveness of radiotherapy (RxT) in acromegaly and its role as an ancillary tool to neurosurgery (Tx). PATIENTS: We evaluated 72 acromegalic patients previously submitted to RxT. Data were discarded in 23 patients, who were lost to follow-up, operated on after RxT or irradiated with techniques different from external conventional fractionated RxT. Among the remaining 49 (five with mixed GH-prolactin adenoma), 34 were irradiated after surgical failure and 15 as primary treatment. A second cycle of RxT was administered in two. RESULTS: (i) GH/IGF-I. After a median follow-up of 14 years (range 3-41), normal age-matched IGF-I levels were reached in eight patients (16%) after 10 years, and GH levels <2.5 microg/l in six (12%) after 9 years. The rate of persistently pathological hormonal levels was still 90% at 25 years. All patients with GH/IGF-I normalization had undergone irradiation without any antisecretory drug. Neither basal GH nor tumor size affected the outcome of RxT. In three patients (6%) a relapse/worsening occurred. (ii) Tumor size. Tumor shrank after 8.5 years in 24 patients (49%), in nine of whom during GH-suppressive treatment. Tumor shrinkage was not predictive of hormonal normalization. (iii) Side-effects. Hypopituitarism was diagnosed in four patients (selective in three and global in one) and GH deficiency in one. Three patients had neurological side-effects and meningioma was shown in two patients. CONCLUSION: RxT is unable to cure acromegaly, because it seldom achieves hormonal normalization even after a very prolonged follow-up. Concomitant antisecretory treatment seems to counteract its effects. RxT can still play a role in those patients with large tumor remnants, because of its capacity to shrink tumor size.

Acromegaly↗
PubMed2000

Evaluation of genotoxic and cytotoxic properties of pesticides employed in Italian agricultural practices.

In a program coordinated by the Italian Ministry of Works, we tested in vitro four pesticides widely employed in a developed agricultural region of central Italy. The four commercial agents were chosen on the basis of their diffusion in agricultural practice, knowledge of their active principle(s), and scant availability of data concerning their toxic and genotoxic activity. The agents were Cirtoxin, Decis, Tramat Combi (TC), and Lasso Micromix (LM). All substances were tested in three in vitro systems: Chinese hamster ovary (CHO) cells, a metabolically competent hamster cell line (Chinese hamster epithelial liver; CHEL), and root tips of Vicia faba (VF). The cytotoxic and genotoxic end points challenged were micronuclei and root tip length (RTL) in VF and mitotic index (MI), proliferation index (PI), cell survival (CS), cell growth (CG), cell cycle length (CCL), sister chromatid exchanges, chromosomal aberrations, and single-cell gel electrophoresis, or comet assay, in CHEL and CHO cells. Tested doses ranged from the field dose up to 200x the field dose to take into account accumulation effects. On the whole, tested agents appear to induce genotoxic damage only at subtoxic or toxic doses, indicating a low clastogenic risk. MI, PI, CS, CG, RTL, and CCL appear to be the less sensitive end points, showing no effects in the presence of a clear positive response in some or all of the other tests. Using cytogenetic tests, we obtained positive results for TC and LM treatments in CHO but not in CHEL cells. These data could be accounted for by postulating a detoxifying activity exerted by this cell line. However, cytogenetic end points appear to be more sensitive than those referring to cytotoxicity.

Agriculture↗
PubMed2000

From macroprolactinoma to concomitant ACTH-PRL hypersecretion with Cushing's disease.

Multiple pituitary hormone hypersecretions have been already described, but the combination of PRL and ACTH excess is rare. This report deals with a 42-yr-old woman affected by macroprolactinoma (PRL 12,720 microg/l, huge tumor with extrasellar extension at imaging). After one year on dopaminergic treatment causing PRL normalization and tumor shrinkage, she developed hypercortisolism (UFC 1,000 microg/24 h, ACTH 200 ng/l). Cushing's disease was diagnosed. After neurosurgery (at immunocytochemistry mixed ACTH-PRL adenoma was shown) hypercortisolism remitted, whereas pathological hyperprolactinemia with tumor remnant in cavernous sinus persisted and hypopituitarism developed. The patient reported seems atypical for the following reasons: 1) the concomitant PRL and ACTH hypersecretions; 2) the clinical presentation with hypercortisolism following hyperprolactinemia; 3) the surgical cure of hypercortisolism with persisting hyperprolactinemia.

Adrenocorticotropic Hormone↗
PubMed2000

Lanreotide 60 mg, a longer-acting somatostatin analog: tumor shrinkage and hormonal normalization in acromegaly.

BACKGROUND: Somatostatin analogues are nowadays the milestone in the medical treatment of acromegaly. We evaluated the effects of a new 60 mg longer-acting formulation of lanreotide (LAN60) on GH/IGF-I levels and tumor size. PATIENTS: Twenty-one acromegalics entered a prospective monocentric open study. Eight were consecutive "de novo" patients (group I). Thirteen patients sensitive to SA (GH levels < 2.5 [mgr]g/l and/or IGF-I normalization on chronic LAN 30 mg (LAN30) treatment) were switched to LAN60 (group II). PROTOCOL: LAN60 was administered IM for 6 cycles at 28 day intervals. In group I when GH/IGF-I remained pathological, the intervals were shortened to 21 days for the last three cycles. CONTROLS: GH/IGF-I at the end of the 1st, 3rd and 6th cycle; MRI at the end of the study in all patients in group I bearing an adenoma. RESULTS: Group I. GH (p = 0.00638, below 2.5 [mgr]g/l in two patients) and IGF-I (p = 0.0289, normalized in 5) significantly decreased. In one of two patients shortening the LAN60 schedule was more effective in suppressing GH/IGF-I. Group II. No change in GH and IGF-I levels was observed with the administration of LAN60, instead of LAN30. On LAN60 GH remained below 2.5 [mgr]g/l in 8/10 patients and IGF-I normal in 11/11 patients that had attained those values on LAN30. Tumor markedly shrank (23% to 64% vs basal), from 1400 (664-1680) mm3 to 520 (500-960) mm3 (median, interquartile, p = 0.0218) in all the 5 evaluable patients. CONCLUSION: LAN60 is a very effective and longer-lasting formulation for the treatment of acromegaly. A closer administration schedule might achieve greater efficacy. Its effectiveness in shrinking tumor opens new perspectives in the therapy of acromegaly.

Acromegaly↗
PubMed1999

Phyllanthus orbicularis aqueous extract: cytotoxic, genotoxic, and antimutagenic effects in the CHO cell line.

The present work evaluates the cytotoxic, genotoxic, and antimutagenic effects of Phyllanthus orbicularis (plant of genus Phyllantus) aqueous extract in Chinese hamster ovary (CHO) cells. P. orbicularis aqueous extracts are used in Cuban traditional medicine for their antiviral activity against Hepatitis B virus and A and B flu virus. The cytotoxicity of the extract was tested by means of colony-forming ability and growth-inhibition assays as well as by measuring the mitotic index. Apoptosis induction and cell-cycle kinetics were analyzed by cytofluorimetric methods. Chromosome aberration assays were performed to study the genotoxic and antimutagenic activity of the extract. Results show that doses of up to 100 microg/ml of the extract did not induce any cytotoxic effects. Cell survival and mitotic index decreased significantly at doses higher than 100 microg/ml as a function of dose as well as of treatment time. Moreover, continuous treatments of up to 18 h induced the appearance of a significant number of apoptotic cells. Following a 3-h exposure to a dose of 750 microg/ml, cells accumulated significantly in G(2)-M phase and remained blocked in G(1-) and G(2)-M phases after several posttreatments in fresh growth medium. The aqueous extract alone did not induce chromosome aberrations but, in combined treatment with H(2)O(2), significantly reduced H(2)O(2)-induced chromosome aberrations. Flow cytometric analysis of DCFH intracellular oxidation showed that the extract decreased the oxidizing power of H(2)O(2.) This ability could possibly explain the extract's antigenotoxic activity. Absence of cytotoxicity at the lower tested doses and the antimutagenic properties of the extract stimulate the interest in studying possible new pharmaceutical uses of P. orbicularis.

Animals↗
PubMed1999

DNA strand methylation and sister chromatid exchanges in mammalian cells in vitro.

Among other targets, DNA demethylating agents are known to affect the sister chromatid exchange (SCE) frequency in mammalian cells in vitro. The SCE increase appears to be maintained for many (10-16) cell cycles after the end of the pulse in a given cell population, unlike SCEs induced by DNA damaging agents. Yet, epigenetic changes (such as demethylation) would not be expected to affect SCE at all. In the present report we challenge the working hypothesis of a relation between SCEs and demethylation by comparing SCE induction during different rounds of replication when the parental strands were normally methylated or demethylated. Azacytidine (AZA), ethionine (ETH), mitomycin-C (MMC), UV-irradiation (UV) and hydrogen peroxide (H(2)O(2)) were tested for SCE induction in a Chinese hamster ovary cell line after a single pulse, one or two cell cycles before fixation. Whereas MMC, UV and H(2)O(2) induce SCE in both protocols, AZA and ETH show an effect on SCEs only if administered two cycles before fixation. Because two cell cycles are needed in order to achieve demethylation of the parental DNA strand, the data reported here support our working hypothesis that demethylation in the parental DNA strand, at the level of the replication fork (i.e., the region where SCEs are formed), is responsible for an increase in mistaken ligations of processed damage, eventually yielding an increase in SCEs.

Animals↗
PubMed1999

Inhibitory action of melatonin on H2O2- and cyclophosphamide-induced DNA damage.

Melatonin, the pineal gland hormone known for its ability to modulate circadian rhythm, has recently been studied in its several functions. It is believed to inhibit cancer growth, to stimulate the immune system and to act as an antioxidant. In particular, this latter activity is ascribed to two different mechanisms: stimulation of radical detoxifying enzymes and scavenging of free radicals. We used this compound in mammalian cells in vitro to investigate its mechanism of action in modulating DNA damage. Cytogenetic and cytofluorimetric analyses were performed. We show that melatonin is able to modulate chromosome damage (chromosomal aberrations and sister chromatid exchanges) induced by cyclophosphamide. Conversely, its involvement in modulating oxidative processes, thereby reducing DNA damage, is less clear. In particular, melatonin is able to decrease H2O2-induced chromosomal aberrations but not sister chromatid exchanges and has been found to induce oxygen species in a cytofluorimetric test (DCFH assay).

Animals↗
PubMed1999

Neurosurgery restores late GH rise after glucose-induced suppression in cured acromegalics.

OBJECTIVE AND DESIGN: A decrease of GH levels below 2 microg/l after an oral glucose tolerance test (OGTT) is still currently accepted as the gold standard for assessing cure in surgically treated acromegaly. Whether glucose-induced suppression of GH is accompanied by a restoration of normal GH late rebound has not yet been evaluated in this disease. In order to assess the restoration of normal GH regulation after removal of a pituitary adenoma, we have evaluated GH changes after an OGTT in a series of selected acromegalic patients (transsphenoidal surgery and lack of pituitary failure). METHODS: Twenty-nine patients (13 male, 16 female, age range 27-70 years) entered the study. Their neuroradiological imaging before neurosurgery showed microadenoma in 7, intrasellar macroadenoma in 8 and macroadenoma with extrasellar extension in 14. Plasma GH levels were assayed up to 300 min after glucose administration (75 g p.o.) and IGF-I on basal samples. RESULTS: Basal GH levels were below 5 microg/l in 20 patients and below 2 microg/l in 5 of these. Normal age-adjusted IGF-I levels were observed in 12 patients. GH values were suppressed below 2 microg/l during an OGTT in 13 patients, and below 1 microg/l in 7 of these. In 9 patients out of these 13, a marked rise in GH levels occurred after nadir. Baseline and nadir GH values of these 9 patients were not different from the corresponding values of the other 4 patients without OGTT-induced late GH peaks. CONCLUSIONS: GH rebound after GH nadir occurs in acromegalic patients considered as cured on the basis of OGTT-induced GH suppression and/or IGF-I normalization. The restoration of this physiological response could be regarded as a marker of recovered/preserved integrity of the hypothalamic-pituitary axis. Even though the reason for this GH rebound has not yet been elucidated (GHRH discharge?/end of somatostatin inhibition?), the lack of late GH peak in the patients regarded as cured by the usual criteria could be due to injury to the pituitary stalk caused by the adenoma or by surgical manipulation.

Acromegaly↗
PubMed1999

A comparison between octreotide-LAR and lanreotide-SR in the chronic treatment of acromegaly.

BACKGROUND: At present long-acting somatostatin analogs represent the first-line medical treatment of acromegaly. These drugs produce stable suppression of GH in most sensitive patients and IGF-I normalization in many; they also increase the compliance of acromegalic patients. The recent availability of octreotide (OC)-LAR, a somatostatin analog to be administered at 28-day intervals, has prompted us to compare, in the same group of patients, its effects and those of another somatostatin analog already available, lanreotide-SR (LSR, to be administered at 14-day intervals). PATIENTS: Twelve somatostatin analog-sensitive acromegalic patients with active disease were enrolled in a prospective open sequential study after giving their informed consent. After chronic treatment with LSR (6-24 months), the patients were changed to treatment with OC-LAR, without wash-out. LSR had been administered at individually tailored dosages (30 mg i.m. at 7-21-day intervals, median 10 days - every 7 days in seven patients, 10 days in two patients, 14 days in two patients and 21 days in one patient) according to GH and IGF-I responses. Disease stability was obtained, as shown by maximal GH/IGF-I suppression without any significant hormonal change between the last two control measurements. OC-LAR was administered i.m. at 28-day intervals six times at the dosage of 20 mg for the first three times and 10 or 30 mg for the last three times (according to individual GH/IGF-I responses). GH (mean of three, hourly samples) and IGF-I concentrations were evaluated on the same day as each administration of the drug, before its injection. RESULTS: GH and IGF-I values were significantly decreased by LSR treatment. GH decreased from 41.6 +/- 14.6 microg/l (mean +/- s.e.) to 7.2 +/- 1.5 microg/l (P < 0.02), whereas IGF-I values declined from 959 +/- 95 microg/l to 460 +/- 61 microg/l (P < 0.00001), expressed as absolute values, and from 287 +/- 30% to 137 +/- 19% expressed as percentage of the upper limit of normal range (% ULNR). At the end of the last cycle, OC-LAR treatment achieved a significant further suppression both in GH (to 5.1 +/- 1.1 microg/l, P < 0.05 compared with LSR) and in IGF-I concentrations (to 374 +/- 60 microg/l, P<0.05 compared with LSR, and to 112 +/- 19% as % ULNR). LSR decreased GH concentrations to less than 2.5 microg/l in one patient and normalized IGF-I concentrations in four patients. OC-LAR decreased GH concentrations to less than 2.5 microg/l in four patients and normalized or near-normalized IGF-I concentrations (i.e. to < 110% ULNR) in eight patients. CONCLUSIONS: These preliminary results show that the once-monthly OC-LAR administration schedule proved more efficacious than LSR given every 7-21 days, in a greater number of acromegalic patients.

Acromegaly↗
PubMed1998

Scintigraphic imaging of pituitary adenomas: an in vivo evaluation of somatostatin receptors.

UNLABELLED: We have performed pituitary scintigraphy with the somatostatin (SS) analog pentetreotidean by (111In-P) in patients with GH-secreting adenoma or with "clinically non functioning" adenoma (NFA) to evaluate the presence and the functionality of SS receptors (SS-R). 111In-P pituitary accumulation was expressed as Activity Ratio (AR): the ratio between the uptake of radioactivity by the adenoma and that of the normal brain tissue. In subjects without pituitary disease, AR ranged from 1.6 to 2.2 and a value lower than 2.2 was thus arbitrarily considered as normal. In 15 out of the 17 patients with GH-secreting adenoma, an accumulation of the radioligand was shown. Median AR was 3.8 (range 1-6.9; in 14 AR were greater that 2.2) and ARs were directly correlated (r = 0.54; p < 0.05) with the suppressibility of plasma GH levels by octreotide (OC) acute administration. In two patients who repeated scintigraphy during chronic OC treatment, AR values were reduced. In all the 22 patients with NFA an accumulation of 111In-P at the pituitary level was observed and median AR was 3.0 (range 1.5-20; in 14 greater that 2.2). In vitro autoradiography of surgical specimens in 6 NFA patients revealed SS-R in 4 cases with high scintigraphic AR and negative results in two cases with low AR. Scintiscan was repeated during chronic OC treatment in 5 patients with high score: AR decreased in one patient, increased in three, and did not change in the other patient. No changes in tumor size were shown in any of these patients. A total of 8 patients (3 GH secreting and 5 NFA) had "normal" AR values. CONCLUSIONS: In acromegaly scintigraphy with 111In-P visualizes functioning pituitary SS-R coupled to intracellular events that control hormonal hypersecretion and tumor growth. In contrast, in spite of the positivity of 111In-P imaging in most patients with NFA, their receptors might have a defect in the coupling-transduction process, as they are not inhibited by OC treatment and no tumor shrinkage is observed.

Adenoma↗