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Biomedical subjects

G Lombardi

Publications and source records attributed to G Lombardi.

At least 91 records · Page 5Linked to original sources
PubMed2002

Longitudinal study of vasopressin-cell antibodies and of hypothalamic-pituitary region on magnetic resonance imaging in patients with autoimmune and idiopathic complete central diabetes insipidus.

Diagnosis of autoimmune central diabetes insipidus (CDI) is based on the presence of autoantibodies to AVP-secreting cells (AVPcAb) or the coexistence of other autoimmune polyendocrine syndromes; moreover, it can be also suggested by the presence of lymphocytic infundibulo-neurohypophysitis, evidenced by biopsy of pituitary stalk and/or by pituitary stalk thickening on magnetic resonance imaging (MRI). However, so far, in clinical CDI patients with lymphocytic infundibulo-neurohypophysitis, AVPcAb have not been investigated and in those with or without autoimmune polyendocrine syndromes (APS), longitudinal studies on the behavior of AVPcAb alone, or of both AVPcAb and hypothalamic pituitary imaging on MRI are lacking. Aim of this work was to investigate in these patients the occurrence of AVPcAb (by indirect immunofluorescence) and of pituitary stalk thickening (by MRI) and their longitudinal changes during a follow-up period. We studied 22 patients, aged 29-53, with APS and complete CDI, grouped as follows: 10 with recent onset (< or =1.5 yr) of CDI (group 1a) and 12 with CDI of long-term duration (> or = 7 yr) (group 1b); moreover, a group of 13 patients with apparent idiopathic CDI of recent onset (<1.5 yr) were studied. They were divided, on the basis of the detection of AVPcAb as follows: 5 AVPcAb positive patients (aged 19-26) classified as isolated autoimmune CDI (group 2) and 8 AVPcAb negative patients (aged 21-26), classified as true idiopathic CDI (group 3). All patients were evaluated yearly, along 5 yr, for AVPcAb and for hypothalamic-pituitary region imaging. At study entry, 8/10 (80%) of patients in group 1a and 7/12 (58.3%) in group 1b were positive for AVPcAb and persisted positive subsequently, during all the follow-up period, even if at lower titers. All patients in group 2 were positive and all those in group 3 were negative for AVPcAb and persisted positive and negative, respectively, for all the follow-up study. Among the AVPcAb-positive patients, only 5 in group 1a and 2 in group 2 showed also pituitary stalk thickening at the first observations, which however spontaneously disappeared subsequently indicating a possible lymphocytic infundibulo-neurohypophysitis. All patients in the studied groups showed loss of the hyperintense signal of the neurohypophysis on MRI at entry and during all the follow-up period. Results of this longitudinal study suggest: 1) AVPcAb, frequently present at high titers in recent phases of CDI, persist subsequently, even if at lower titers, several years after the onset of disease. 2) The occurrence of a lymphocytic infundibulo-neurohypophysitis suggested by the pituitary stalk thickening on MRI only in patients positive for AVPcAb confirms a further autoimmune variant of CDI also in these cases. 3) The longitudinal behavior of patients in group 3 suggests that the absence of AVPcAb at the onset of clinical idiopathic CDI is able to exclude a subsequent appearance of these antibodies and consequently an autoimmune involvement in CDI of these patients. Instead the finding of AVPcAb in several patients with only CDI, thought at first clinical observation as idiopathic, indicates that the prevalence of autoimmune CDI must be considered much higher than that so far reported.

Adult↗
PubMed2002

Increased intima-media thickness of the carotid artery wall, normal blood pressure profile and normal left ventricular mass in subjects with primary hyperparathyroidism.

OBJECTIVE: Despite the increasing evidence that primary hyperparathyroidism (PHPT) contributes to greater risk of cardiovascular morbidity and mortality, its exact role in the development of cardiovascular changes and its clinical significance are still controversial. Given the multiple influence of PHPT on the cardiovascular system, this study aimed to assess the effects of PHPT on blood pressure profile, and on features of the heart and arterial vessels in normotensive symptomless patients. DESIGN: Twenty patients (8 males and 12 females) with a median age of 51.5 years (range 44 to 65 years) were evaluated and the results were compared with those of 20 controls matched for age, gender and body mass index. Patients' parathyroid hormone levels ranged from 172 to 454 pg/ml and Ca levels ranged from 11.4 to 13.5 mg/dl. Fasting levels of glucose, insulin, total and high density lipoprotein cholesterol and triglycerides were within the normal range in all subjects recruited. METHODS: Twenty-four-hour blood pressure profile, left ventricle (LV) dimension and carotid artery anatomy were investigated, the latter two by ultrasonography. RESULTS: No difference was found between the patients and controls in blood pressure profile, when the following parameters were considered: supine systolic/diastolic pressure, average 24-h systolic, diastolic and mean arterial pressure, day-time mean arterial pressure and fall in nocturnal blood pressure (-17% and -18% respectively). Heart rate and all parameters of LV mass were similar in patients and controls. The only alteration found in patients was in significantly greater carotid intimal-medial thickness (IMT) (P<0.001). Atherosclerotic plaques were more frequent in patients than in controls, with a difference reaching a trend (40% vs 10%, chi(2)=4.8; P=0.091). Considering that the carotid IMT is considered to be a marker of systemic atherosclerosis, our finding suggests early atherosclerotic changes in PHPT. No correlation was found between the severity and cardiovascular manifestation of PHPT. CONCLUSIONS: Vascular changes may occur due to a combination of structural and functional impairments in PHPT patients, likely as a result of altered calcium metabolism and impaired equilibrium of other factors regulating vascular function. Both extent and duration of PHPT can play a relative role in the development of cardiovascular complications. Considering that PHPT is now recognized as a quite common and often symptomless endocrine disorder, the evidence of cardiovascular manifestation in normotensive patients, found by this morphological study, suggests a possible implication for the management of such patients. In this light, screening for abnormalities in cardiovascular system function should be recommended in all PHPT subjects.

Adult↗
PubMed2002

Epidemiology of bloodstream infections and time to detection of positive blood cultures: an evaluation of the automated BacT/Alert and BACTEC 9240 systems.

Data of 3,097 blood culture sets processed with the BacT/Alert system in 1997 were compared to those of 3,158 blood culture sets processed with BACTEC 9240 in 1999. Agents responsible for bloodstream infections (BSI) were detected in 15.9% and 20.0% of blood cultures in 1997 and 1999, respectively. The incidence of BSI was 9.3 (1997) vs. 11.3 (1999) per 1,000 admissions. In both years, S. aureus was the most frequent isolate, followed by E. coli. Overall, the mean detection time (MDT) obtained with the BACTEC 9240 was significantly shorter than that of the BacT/Alert. Significant MDT differences were found for all organisms, except for Enterobacteriaceae (12.7 vs. 10.6 h). With both systems, over 95% positive samples were detected within 3 days, indicating that a 4-day incubation protocol may disclose most BSI agents. Thus, the added speed of the BACTEC 9240 allowed a particularly fast clinical management of septic patients.

Automation↗
PubMed2002

Identification and antimicrobial susceptibility testing of clinical isolates of nonfermenting gram-negative bacteria by the Phoenix Automated Microbiology System.

The Phoenix Automated Microbiology System (Becton Dickinson, Sparks, MD) was evaluated for its ability to identify nonfermenting gram-negative pathogens and measure their drug susceptibility. Isolates producing rare extended-spectrum beta-lactamases (PER-1, IMP-2, VIM-1, and VIM-2) were included in the study. Species identification was compared to that given by the ATB System (bio-Mérieux, Marcy l'Etoile, France), whereas susceptibility results were compared to those produced by a reference broth microdilution test (panels manufactured by Pasco Laboratories, Becton Dickinson). The Phoenix system consistently identified all isolates of Pseudomonas aeruginosa (n = 55) and Stenotrophomonas maltophilia (n = 28), while in other cases species agreement was obtained for 47/53 isolates (Acinetobacter baumannii, 29/31; Pseudomonas putida, 10/11; Burkholderia cepacia, 6/7; and Pseudomonas fluorescens, 2/4). Overall, the Phoenix and ATB systems gave equal results in 130/136 cases (95.6%). For two isolates, consistent identification was obtained at the genus level, thus bringing the cumulative agreement to 97.1%. MIC values (interpreted according to NCCLS guidelines) gave essential and categorical agreement in 94.2% and 93.1% of cases, respectively. Minor and major errors were 5.1% and 5.2%, respectively. No very major errors were produced. The mean time to results (TTR) for the Phoenix system was 14.8 +/- 1.6 h (mean +/- SD), with the shortest TTR being observedfor A. baumannii (13.0 +/- 1.8 h) and the longest one for P. aeruginosa (15.6 +/- 1.2 h). In conclusion, the Phoenix system performed rapidly and correctly in the identification of clinical isolates of important opportunistic pathogens and in measuring their susceptibility to antipseudomonal drugs.

Automation↗
PubMed2001

Human CD4(+)CD25(+) cells: a naturally occurring population of regulatory T cells.

Despite thymic deletion of cells with specificity for self-antigens, autoreactive T cells are readily detectable in the normal T-cell repertoire. In recent years, a population of CD4(+) T cells that constitutively express the interleukin-2 receptor-alpha chain, CD25, has been shown to play a pivotal role in the maintenance of self-tolerance in rodent models. This study investigated whether such a regulatory population exists in humans. A population of CD4(+)CD25(+) T cells, taken from the peripheral blood of healthy individuals and phenotypically distinct from recently activated CD4(+) T cells, was characterized. These cells were hyporesponsive to conventional T-cell stimuli and capable of suppressing the responses of CD4(+)CD25(-) T cells in vitro. Addition of exogenous interleukin-2 abrogated the hyporesponsiveness and suppressive effects of CD4(+)CD25(+) cells. Suppression required cell-to-cell contact but did not appear to be via the inhibition of antigen-presenting cells. In addition, there were marked changes in the expression of Notch pathway molecules and their downstream signaling products at the transcriptional level, specifically in CD4(+)CD25(+) cells, suggesting that this family of molecules plays a role in the regulatory function of CD4(+)CD25(+) cells. Cells with similar phenotype and function were detected in umbilical venous blood from healthy newborn infants. These results suggest that CD4(+)CD25(+) cells represent a population of regulatory T cells that arise during fetal life. Comparison with rodent CD4(+)CD25(+) cells suggests that this population may play a key role in the prevention of autoimmune diseases in humans.

Adult↗
PubMed2001

Estrogens and health in males.

Estrogen receptor concentrations are higher in the male reproductive tract than in other organs. Brain structure, neuronal organization and behavioral sex differences result from brain conversion of testosterone into estradiol within the brain. Estrogens modulate hormonal secretion at pituitary level and immune function at thymus level. Estrogens promote vasodilatatory and protective effects on the cardiovascular system by acting on the vascular smooth muscle and endothelium. Adult men with mutations in genes for estrogen receptor or aromatase are affected by osteopenia and tall stature, open epiphysis, which is corrected by estrogen treatment. Over the past few years there has seen a decline in sperm concentration, which has been attributed to exposure of fetal testes to estrogens. Many substances have estrogen-like properties and inhibit the action of estradiol or testosterone action. In conclusion, estrogens play a pivotal role in men also. In particular, taking in account their prevalent origin from testosterone aromatization at tissue and peripheral levels the presence and the distribution of the two receptors (ERalpha and ERbeta) are responsible for different responses in physiological and pathological conditions.

Adult↗
PubMed2001

T-cell anergy and peripheral T-cell tolerance.

The discovery that T-cell recognition of antigen can have distinct outcomes has advanced understanding of peripheral T-cell tolerance, and opened up new possibilities in immunotherapy. Anergy is one such outcome, and results from partial T-cell activation. This can arise either due to subtle alteration of the antigen, leading to a lower-affinity cognate interaction, or due to a lack of adequate co-stimulation. The signalling defects in anergic T cells are partially defined, and suggest that T-cell receptor (TCR) proximal, as well as downstream defects negatively regulate the anergic T cell's ability to be activated. Most importantly, the use of TCR-transgenic mice has provided compelling evidence that anergy is an in vivo phenomenon, and not merely an in vitro artefact. These findings raise the question as to whether anergic T cells have any biological function. Studies in rodents and in man suggest that anergic T cells acquire regulatory properties; the regulatory effects of anergic T cells require cell to cell contact, and appear to be mediated by inhibition of antigen-presenting cell immunogenicity. Close similarities exist between anergic T cells, and the recently defined CD4+ CD25+ population of spontaneously arising regulatory cells that serve to inhibit autoimmunity in mice. Taken together, these findings suggest that a spectrum of regulatory T cells exists. At one end of the spectrum are cells, such as anergic and CD4+ CD25+ T cells, which regulate via cell-to-cell contact. At the other end of the spectrum are cells which secrete antiinflammatory cytokines such as interleukin 10 and transforming growth factor-beta. The challenge is to devise strategies that reliably induce T-cell anergy in vivo, as a means of inhibiting immunity to allo- and autoantigens.

Animals↗
PubMed2001

Fast determination of phenols in contaminated soils.

An extraction method for the determination of phenols in contaminated soils, based on the application of solid-phase microextraction (SPME) coupled with GC-flame ionization detection analysis, was developed and tested. This method was developed using a natural soil spiked with phenol to a concentration level typical of an acute contamination event that can occur in an industrial site. The effects of the extraction parameters (pH, extraction time and salt concentration) on the extraction efficiency were studied and the method was then applied to determine the pollutant concentration at the beginning and during the biological treatment of a soil, contaminated with phenol and 3-chlorophenol, respectively. The SPME results were validated by comparison with those obtained with an US Environmental Protection Agency certified extraction method. The SPME method was also successfully applied to the determination of the adsorption behavior of 3-chlorophenol on a natural clay soil and was shown to be suitable for different matrices and phenolic compounds. Application of SPME technique results in a sharp reduction of the extraction times with negligible solvent consumption.

Chromatography, Gas↗
PubMed2001

HLA-DP allele-specific T cell responses to beryllium account for DP-associated susceptibility to chronic beryllium disease.

Occupational exposure to small molecules, such as metals, is frequently associated with hypersensitivity reactions. Chronic beryllium (Be) disease (CBD) is a multisystem granulomatous disease that primarily affects the lung, and occurs in approximately 3% of individuals exposed to this element. Immunogenetic studies have demonstrated a strong association between CBD and possession of alleles of HLA-DP containing glutamic acid (Glu) at position 69 in the HLA-DP beta-chain. T cell clones were raised from three patients with CBD in whom exposure occurred 10 and 30 years previously. Of 25 Be-specific clones that were obtained, all were restricted by HLA-DP alleles with Glu at DP beta69. Furthermore, the proliferative responses of the clones were absolutely dependent upon DP beta Glu(69) in that a single amino acid substitution at this position abolished the response. As befits a disease whose pathogenesis involves a delayed type hypersensitivity response, the large majority of Be-specific clones secreted IFN-gamma (Th1) and little or no IL-4 (Th2) cytokines. This study provides insights into the molecular basis of DP2-associated susceptibility to CBD.

Alleles↗
PubMed2001

Amino acid substitutions in the putative MHC class II "dimer of dimers" interface inhibit CD4+ T cell activation.

Activation of T lymphocytes is dependent on multiple ligand-receptor interactions. The possibility that TCR dimerization contributes to T cell triggering was raised by the crystallographic analysis of MHC class II molecules. The MHC class II molecules associated as double dimers, and in such a way that two TCR (and two CD4 molecules) could bind simultaneously. Several subsequent studies have lent support to this concept, although the role of TCR cross-linking in T cell activation remains unclear. Using DRA cDNAs modified to encode two different C-terminal tags, no evidence of constitutive double dimer formation was obtained following immunoprecipitation and Western blotting from cells transiently transfected with wild-type DRB and tagged DRA constructs, together with invariant chain and HLA-DM. To determine whether MHC class II molecules contribute actively to TCR-dependent dimerization and consequent T cell activation, panels of HLA-DR1beta and H2-E(k) cDNAs were generated with mutations in the sequences encoding the interface regions of the MHC class II double dimer. Stable DAP.3 transfectants expressing these cDNAs were generated and characterized biochemically and functionally. Substitutions in either interface region I or III did not affect T cell activation, whereas combinations of amino acid substitutions in both regions led to substantial inhibition of proliferation or IL-2 secretion by human and murine T cells. Because the amino acid-substituted molecules were serologically indistinguishable from wild type, bound antigenic peptide with equal efficiency, and induced Ag-dependent CD25 expression indicating TCR recognition, the reduced ability of the mutants to induce full T cell activation is most likely the result of impaired double dimer formation. These data suggest that MHC class II molecules, due to their structural properties, actively contribute to TCR cross-linking.

Amino Acid Substitution↗
PubMed2001

Turner's syndrome mosaicism 45X/47XXX: an interesting natural history.

Mosaicism 45X/47XXX is a sporadic form of ovarian dysgenesis. Many of the cases previously described were characterized by a variable phenotype expression. We here report the case of a 33-yr-old woman with recent secondary amenorrhea, weight loss and breast regression. Her menarche had occurred at the age of 11 yr and 6 months and her menstrual cycles had been regular until the age of 28; then, oligomenorrhea and hypertricosis developed. A pelvic ultrasound showed enlarged polycystic-like ovaries and normal uterus. She was treated with ethynil-estradiol and cyproterone acetate for one year. At the age of 31 yr, she underwent a pelvic ultrasound--which revealed normal volume of the ovaries--and hormonal assays including FSH (69 UI/l), LH (113 UI/l), 17beta-estradiol (88 pg/ml), plasma androgens and cortisol levels within normal ranges. No organ-specific autoantibodies toward ovaries, steroid-producing cells or adrenals were found. At the age of 33 yr, there was ultrasound evidence of streak-like ovaries. The patient's height was 145 cm and her weight 45 kg. She had normal female external genitalia, abnormal upper-to-lower body segment ratio, webbed neck, low posterior hair line, cubitus valgus, short and asymmetrical 4th metacarpi, hallux with lateral deviation and moderate scoliosis. No increase in ovarian steroids were found after GnRH-analogue triptorelin (0,1 mg sc) administration. The karyotype analysis on peripheral blood lymphocytes showed a mosaic 45X (90% cells) and 47XXX (10% cells). Diagnostic pelviscopy confirmed streak gonads. Chronic lymphocytic thyroiditis was diagnosed but no cardiovascular or kidney abnormalities were found. A neuro-psychological evaluation revealed emotional and social immaturity, disorders in motorial coordination, visual-spatial organization, as well as reading difficulties and impaired complex phrase construction. The presence of several somatic features of Turner's syndrome, neuro-psychological disorders and an interesting natural history probably depended on the quantitative proportion of 45X to 47XXX cell-lines in different tissues and organs. Estrogen and progestin replacement therapy led to weight gain, re-appearance of secondary sexual characteristics and a mild improvement in mental equilibrium.

Adult↗
PubMed2001

Beryllium binding to HLA-DP molecule carrying the marker of susceptibility to berylliosis glutamate beta 69.

Berylliosis is a chronic granulomatous disorder caused by inhalation of Be dusts that is driven by the accumulation of Be-specific CD4+ Th1-cells at disease sites. Susceptibility to berylliosis has been associated with the supratypic variant of HLA-DP gene coding for glutamate at position beta69 (HLA-DPbetaGlu69). The aim of this study was to test the hypothesis that the HLA-DPbetaGlu69 residue plays a role in the interaction with Be. To this end, soluble HLA-DP2 molecule (carrying betaGlu69) and its mutated form carrying lysine at position beta69 (HLA-DP2Lys69) were produced in Drosophila melanogaster and then used in a Be binding assays. BeSO4 (1-1000 microM) was used to compete for the binding of the biotinilated invariant chain-derived peptide CLIP (50 microM). BeSO4 was capable of compete out biotin-CLIP binding from the HLA-DP2 (IC50%: 4.5 microM of BeSO4 at pH 5.0 and 5.5 microM of BeSO4 at pH 7.5), but not from the HLA-DP2Lys69 molecule (IC50%: 480 microM of BeSO4 at pH 5.0 and 220 microM of BeSO4 at pH 7.5). Moreover, the binding of NFLD.M60, a MoAb recognizing an epitope in the HLA-DP peptide binding region, to the HLA-DP2, but not to the HLA-DP2Lys69 soluble molecules was inhibited BeSO4. NFLD.M60 binding to HLA-DP2, but not to HLA-DP2Lys69 stably transfected murine cells was also inhibited by Be both at pH 5.0 and at pH 7.5. The data indicate a direct interaction of Be with the HLA-DPGlu69 molecule, in the absence of antigen processing.

Amino Acid Sequence↗
PubMed2001

Properties of multidrug-resistant, ESBL-producing Proteus mirabilis isolates and possible role of beta-lactam/beta-lactamase inhibitor combinations.

At our institution, isolation rates of clinical strains of ESBL-producing Proteus mirabilis increased to 8.8% of all P. mirabilis isolates during the period 1997-1999. To evaluate the susceptibility of ESBL-producing P. mirabilis strains against commonly used drugs, we studied 50 non-duplicated isolates selected on the basis of synergy between clavulanate and beta-lactams (ceftazidime, aztreonam, cefotaxime, and ceftriaxone). The presence of ESBL-coding genes was confirmed by colony hybridization with bla(TEM-1) and bla(SHV-1) probes. Minimum inhibitory concentrations of several antimicrobial agents for each isolate were obtained using the Etest method. All strains were encoding for TEM-derived enzymes. Gene sequencing showed that at least three different genes (TEM-15, TEM-20, and TEM-52) were present. These enzymes have not been previously reported in P. mirabilis. Isolates were characterized by: (a) reduced susceptibility or resistance to third- and fourth-generation cephalosporins (MIC > or = 2 mg/l), (b) resistance to piperacillin that was abolished by tazobactam (MIC > or = 256 vs. < or = 2 mg/l, respectively), (c) multiple antibiotic resistance that included gentamicin, fluoroquinolones and co-trimoxazole. Therapeutic failure and lack of eradication of ESBL-positive P. mirabilis by third-generation cephalosporins has been repeatedly observed both at our Institution and elsewhere. Piperacillin-tazobactam, as well as amikacin and meropenem appear to be important therapeutic options for infections due to multidrug-resistant, ESBL-producing P. mirabilis isolates.

Anti-Bacterial Agents↗
PubMed2001

High prevalence of reflux symptoms in duodenal ulcer patients who develop gastro-oesophageal reflux disease after curing Helicobacter pylori infection.

BACKGROUND: Gastro-oesophageal reflux disease may develop following eradication of Helicobacter pylori. However gastro-oesophageal reflux disease could be preexistent and misdiagnosed since patients often misinterpret gastro-oesophageal reflux disease symptoms or focus their attention on abdominal symptoms. A questionnaire for analysis of gastro-oesophageal reflux disease symptoms has not been used until now. METHODS: A total of 70 patients with duodenal ulcer and Helicobacter pylori gastritis, without oesophagitis and/or typical gastro-oesophageal reflux disease symptoms were studied. All patients received a questionnaire with 5 items focused on abdominal symptoms and 5 on gastro-oesophageal reflux disease symptoms. The two symptom scores were calculated separately. After Helicobacter pylori treatment, follow-up consisted of clinical controls every 3 months for 1 year. Patients were asked to describe their complaints and to answer the questionnaire. If gastro-oesophageal reflux disease symptoms recurred endoscopy was performed. RESULTS: At interview, all patients reported a significant improvement in their abdominal symptoms after eradication; however 23 patients (32.8%: group A) reported the occurrence of gastro-oesophageal reflux disease symptoms, and 5 of them developed oesophagitis; gastrooesophageal reflux disease symptoms did not appear in the remaining 47 patients (group B). Basal gastro-oesophageal reflux disease score was significantly higher in group A than in group B (1.9+/-1.5 vs 0.9+/-0.9, p<0.005), while the abdominal symptoms score was not different. Following eradication, the score for abdominal symptoms decreased significantly (4.2+/-1.5 vs 1+/-0.8, p<0.0001) in the two groups; conversely, the total gastro-oesophageal reflux disease score remained unchanged, improving in 2 patients in group A and 11 in B, and worsening in 5 in group A and in 1 in B. Presence of hiatus hernia and male sex significantly correlated with the development of reflux symptoms. CONCLUSIONS: Patients who present with gastro-oesophageal reflux disease after Helicobacter pylori eradication are likely to already be affected by gastro-oesophageal reflux disease.

Adult↗
PubMed2001

Uncommon clinical course of multiple osteochondromatosis in a patient with a long-term history of Cushing's disease.

Cushing's disease (CD), the chronic endogenous hypercortisolism derived from an ACTH-secreting pituitary adenoma, and multiple osteochondromatosis (MO), a congenital mesoderm dyschondroplasia, represent two distinct rare neoplastic diseases. Clinical appearance of MO usually occurs during the first-second decade of life. In fact, the growth of osteochondromas parallels the patient's growth, then becoming quiescent after the closure of the epiphyses and the achievement of final stature. Here we describe an uncommon case of a patient with a long-term history of childhood-onset CD, who surprisingly developed MO during the third decade of life, after the remission of CD. Indeed, a female patient had been followed for CD from the age of 12 to the age of 24 years, when CD definitively remitted. At the age of 26 the patient complained progressively worsening backache and pain at level of hips and feet. Standard radiography of skeleton showed multiple bone dysmorphisms at level of the four limbs, spine and pelvis consistent with multiple osteochondromas and exostoses. A diagnosis of MO was performed. Total body bone scintigraphy with 99mTc-MDP revealed an increased uptake of the radioligand, suggesting an increased metabolic turnover in correspondence of the majority of the osteochondromas. However, the negativity of the majority of the lesions at 99mTc-DMSA scintigraphy and the histological diagnosis of benign osteochondroma of the only positive lesion at 99mTc-DMSA evidenced that the high metabolic activity of the osteochondromas was not due to malignant transformation. However, the activity of the lesions was highly surprising considering that they usually become quiescent after the achievement of the final stature. In last analysis, the uncommon characteristics of MO and, particularly, its occurrence after stable remission of hypercortisolism, suggests a possible role of glucocorticoids in influencing the clinical course of the skeletal disease. The inhibitory effect of hypercortisolism on bone growth and maturation could explain the block in the proliferation of skeletal lesions during the developmental age, where CD was in the active phase, and the opposite effect of stimulation of the ostochondromas growth during stable normalization of cortisol secretion, after CD remission.

Adrenocorticotropic Hormone↗
PubMed2001

Cardiovascular complications in acromegaly: methods of assessment.

Cardiac involvement is common in acromegaly. Evidence for cardiac hypertrophy, dilation and diastolic filling abnormalities has been widely reported in literature. Generally, ventricular hypertrophy is revealed by echocardiography but early data referred increased cardiac size by standard X-ray. Besides, echocardiography investigates cardiac function and value disease. There are new technologic advances in ultrasonic imaging. Pulsed Tissue Doppler is a new non-invasive ultrasound tool which extends Doppler applications beyond the analysis of intra-cardiac flow velocities until the quantitative assessment of the regional myocardial left ventricular wall motion, measuring directly velocities and time intervals of myocardium. The radionuclide techniques permit to study better the cardiac performance. In fact, diastolic as well as systolic function can be assessed at rest and at peak exercise by equilibrium radionuclide angiography. This method has a main advantage of providing direct evaluation of ventricular function, being operator independent. Coronary artery disease has been poorly studied mainly because of the necessity to perform invasive procedures. Only a few cases have been reported with heart failure study by coronarography and having alterations of perfusion which ameliorated after somatostatin analog treatment. More recently, a few data have been presented using perfusional scintigraphy in acromegaly, even if coronary artery disease does not seem very frequent in acromegaly. Doppler analysis of carotid arteries can be also performed to investigate atherosclerosis: however, patients with active acromegaly have endothelial dysfunction more than clear-cut atherosclerotic plaques. In conclusion, careful assessments of cardiac function, morphology and activity need in patients with acromegaly.

Acromegaly↗