Biomedical subjects

M Caprio

Publications and source records attributed to M Caprio.

17 recordsLinked to original sources

PubMed2007

Rationale for the administration of acellular pertussis vaccine to parents of infants in the neonatal intensive care unit.

Pertussis infections in the United States are increasing as a consequence of waning immunity and increased surveillance. Those most at-risk of mortality include infants less than 6 months of age and premature infants. The 2006 immunization schedule emphasizes an adolescent pertussis booster at 12 years of age. However, of concern is the current generation of parents and grandparents who will still be un-immunized and therefore, available vectors of pertussis to vulnerable neonates. Given the proximity of parents to medical care in the Neonatal Intensive Care Unit (NICU), and the potential for severe disease in their children, NICU personnel should consider administration of acellular pertussis vaccine to parents of hospitalized infants.

Adult↗

PubMed2006

Community outreach with weekly delivery of anti-retroviral drugs compared to cognitive-behavioural health care team-based approach to improve adherence among indigent women newly starting HAART.

Sustained virological suppression requires adherence to >95% of doses of therapy. Overall there is paucity of data on adherence interventions among women and post-intervention outcomes. In this pilot study, we evaluated a novel strategy of weekly delivery of medications (Directly Delivered Therapy: DDT) for six months using an outreach worker (ORW), among ARV naïve indigent women starting HAART and compared the 'during intervention' and 'post-intervention' outcomes to the health care team (a nurse educator, a case worker, a pharmacist and social worker/drug addictions counsellor) based approach termed Adherence Coordination Services (ACS) and the Standard of Care (SoC) historical referent group. The baseline characteristics of the three groups were comparable. The proportion of women who achieved sustained virologic suppression in 4-8 month period for DDT; ACS and SoC groups were 86% (18/21); 54% (6/11); and 36% (8/22) (P<0.004); and in the 10-14 month period were 80% (12/15); 54% (6/11) and 45%(10/22) (P=0.036 for DDT vs. SoC). Retention rate in the DDT was 87%, and 92% of 307 ORW visits were kept, and post-intervention satisfaction was high. Short-term weekly delivery of medications using a community based liaison is a feasible, acceptable and a cost-effective strategy for improving both short-term and perhaps long-term adherence among women initiating their first HAART regimen.

Adult↗

PubMed2005

The epidemiology of partialandrogen deficiency in aging men (PADAM).

The quest for eternal youth has been prevalent in civilised societies in many cultures for many centuries. Preventing or deferring the disabilities and morbidities associated with aging through judicious pharmacotherapy has become a particularly relevant healthcare target with the rapid and relentless global demographic shift towards an increasingly elderly population in the 21th century. Aging men commonly loose muscle, become frail, have impaired sexual and cognitive functions, low mood, develop osteopenia and/or osteoporosis with increased risk for fractures and gain visceral fat which predisposes to diabetes, dyslipidaemia, and ischemic heart disease. These alterations in body function are reminiscent of states of androgen deficiency in younger patients. Indeed, aging is associated with a progressive age-related but variable decline in sex hormones. This condition has been named partial androgen deficiency in aging men (PADAM) and consists in a gradual decline in sex hormone levels over years resulting in physical and psychological changes as depression, impotence, decreased sex drive, loss of muscle tone or strength and lethargy. In this review we have tried to give a real identity to PADAM and quantify its entitiy, using the power of the epidemiology.

Aged↗

PubMed2004

Inactivating mutations of the mineralocorticoid receptor in Type I pseudohypoaldosteronism.

Type I pseudohypoaldosteronism (PHA1) is a rare form of mineralocorticoid resistance characterized by neonatal renal salt wasting and failure to thrive. Typical biochemical features include high levels of plasma aldosterone and renin, hyponatremia and hyperkalemia. Different mutations of the human mineralocorticoid receptor (hMR) gene have been identified in subjects affected by the autosomal dominant or sporadic form of the disease. Our laboratory has investigated a large number of subjects with familial and sporadic PHA1. Several different mutations have been detected, which are localized in different coding exons of the hMR gene. These mutations either create truncated proteins, either affect specific amino acids involved in receptor function. In this paper, we review hMR mutations described to date in PHA1 and their functional characterization. We discuss the absence of mutations in some kindreds and the role of precise phenotypic and biological examination of patients to allow for identification of other genes potentially involved in the disease.

Aldosterone↗

PubMed2003

Pathology of erection.

Erectile dysfunction (ED) is defined as the inability to achieve and maintain a penile erection which is adequate for satisfactory sexual intercourse. It is a significant male health problem affecting approximately 150 million men worldwide. This value is expected to more than double by the year 2025. The incidence of ED increases sharply with age since it is a common cross-cultural denominator, affecting 19 to 64% of men aged 40 to 80 years, both in developing and industrialized countries. Epidemiological studies may underestimate the true dimensions of the problem because of the embarrassment or stigma that is associated with ED. Men with ED may experience diminished self-image and self-esteem, anxiety and fears of rejection, and even depression as psychogenic factors. Pathologic conditions which are commonly encountered in the ageing male (diabetes, hypertension, atherosclerosis, cardiovascular disease, etc) as well as chronic diseases (arthritis, renal and hepatic failure, pulmonary disease) represent a frequent cause of organic ED and are often treated with medications that can interfere with sexual function at central and/or peripheral level. In addition, incorrect lifestyle--i.e. obesity, cigarette smoking, alcohol or drug abuse--may all contribute to the onset of ED. Finally, trauma or surgery affecting either the nervous system or interfering with the blood supply to the penis are associated with increased incidence of ED.

Disease↗

PubMed2003

Non-invasive vascular imaging for erectile dysfunction.

In the era of orally active agents the clinical context of the diagnosis and treatment of erectile dysfunction (ED) has radically changed. There is a general trend oriented towards choosing invasive diagnostic testing and surgical treatment solutions. Along this view, penile pharmacotesting (PPT) may represent an inexpensive and easy diagnostic procedure to be performed in the office setting. However, this procedure provides no direct vascular imaging, has a high percentage of false diagnoses and its accuracy for subsequent treatment decisions remains quite limited. Hence, home testing with orally active agents may provide better information for the patient's goals. In the diagnostic work-up of ED, the combination of PPT plus colour-duplex Doppler ultrasonography (CDDU) has gained more credit because of a higher diagnostic accuracy than PPT alone, so that it should be always performed when possible. It represents an accurate mean to predict cavernous artery inflow and venous leakage when compared to more invasive diagnostic techniques; in fact it allows the measurement of the resistive index when maximal response to vasodilator challenge has occurred. In conclusion, we recommend CDDU to all ED patients with a significant risk of cardiovascular disease, as well as in the presence of penile plaques whereas a frequent involvement of neuro-anatomical structures occurs. Other vascular testing--i.e. natural penile tumescence, cavernosometry/graphy, angiography are reserved to selected patients in whom CDDU alone has provided inconsistent information.

Erectile Dysfunction↗

PubMed2003

Dynamic testing in the evaluation of male gonadal function.

The maturation and physiologic functions of male sexual apparatus are under the control of the hypothalamic-pituitary-gonadal (HPG) axis. The determination of gonadotropins and testosterone as secretory products of pituitary and gonads, respectively, represents the first step in the evaluation of male sexual function and the diagnosis of disorders in male reproductive axis. However, there are several clinical situations that require a dynamic evaluation of this system and the measurement of basal gonadotropins and testosterone must be combined with specific dynamic tests. These mainly consist in GnRH stimulation, which evaluates the endocrine reserve capacity of the pituitary, and human chorionic gonadotropin (hCG) stimulation, which is used in the assessment of Leydig cells activity. The paper illustrates the technical aspects, the normal/pathological responses and the role of these two tests in assessing the male HPG axis in respect to different clinical diagnostic queries.

Adolescent↗

PubMed2001

The TEL/PDGFbetaR fusion in chronic myelomonocytic leukemia signals through STAT5-dependent and STAT5-independent pathways.

The TEL/PDGFbetaR gene, which encodes a fusion protein containing the ETS-family member TEL fused to the protein-tyrosine kinase domain of the platelet-derived growth factor receptor-beta (PDGFbetaR), confers interleukin 3 (IL-3)-independent growth on Ba/F3 hematopoietic cells. TEL/PDGFbetaR mutants have been generated that contain tyrosine-to-phenylalanine (Tyr-->Phe) substitutions at phosphorylation sites present in the native PDGFbetaR to assess the role of these sites in cell transformation by TEL/PDGFbetaR. Similar to previous findings in a murine bone marrow transplantation model, full transformation of Ba/F3 cells to IL-3-independent survival and proliferation required the TEL/PDGFbetaR juxtamembrane and carboxy terminal phosphorylation sites. In contrast to previous reports concerning comparable mutants in the native PDGFbetaR, each of the TEL/PDGFbetaR mutants is fully active as a protein-tyrosine kinase. Expression of the TEL/PDGFbetaR fusion protein causes hyperphosphorylation and activation of signal transducer and activator of transcription (STAT5), and this activation of STAT5 requires the juxtamembrane Tyr579 and Tyr581 in the TEL/PDGFbetaR fusion. Hyperphosphosphorylation of phospholipase Cgamma (PLCgamma) and the p85 subunit of phosphatidylinositol 3-kinase (PI3K) requires the carboxy terminal tyrosine residues of TEL/PDGFbetaR. Thus, full transformation of Ba/F3 cells by TEL/PDGFbetaR requires engagement of PI3K and PLCgamma and activation of STAT5. Taken together with the growth properties of cells transformed by the TEL/PDGFbetaR variants, these findings indicate that a minimal combination of these signaling intermediates contributes to hematopoietic transformation by the wild-type TEL/PDGFbetaR fusion. (Blood. 2001;98:3390-3397)

Animals↗

PubMed2001

Leptin in reproduction.

In mammals, the function of the reproductive system is dependent on the availability of energy in the environment. It is well established that acute modifications of energy balance modulate the hypothalamic-pituitary-gonadal axis. In several species, fasting and caloric restriction have been shown to cause the suppression of pulsatile luteinizing hormone secretion, via an inhibition of the gonadotropin-releasing hormone pulse generator. Such a mechanism probably prevents energy being wasted for reproduction. By contrast, excessive energy storage and obesity interfere with the correct regulation of the reproductive axis. The identification of leptin and leptin receptors, along with studies performed in animal models of leptin deficiency and resistance, has focused attention on the role of this molecule in reproduction, and disclosed new aspects of the relationship between energy stores, adipose tissue and reproductive function. Here, we discuss the central and peripheral effects of leptin on reproductive tissues, and try to fit a complex reality into a simplified model. In particular, the roles of leptin in reproduction at different anatomical levels and in various clinical and experimental settings are discussed.

Animals↗

PubMed2000

Androgens and penile erection: evidence for a direct relationship between free testosterone and cavernous vasodilation in men with erectile dysfunction.

OBJECTIVE: Androgens are essential in the maintenance of nitric oxide-mediated erectile activity in the rat. The objective of the present study was to investigate the role of androgens in regulating trabecular smooth muscle relaxation in the corpus cavernosum in response to vasoactive challenge in men with erectile dysfunction (ED). DESIGN: Retrospective, double-blind correlation analyses. PATIENTS: Fifty-two impotent patients without confounding risk factors for ED were obtained from a total of 250 undergoing diagnostic evaluation. MEASUREMENTS: All patients had dynamic colour duplex ultrasound (D-CDU) and hormonal evaluation for LH, total and free testosterone, SHBG and oestradiol. RESULTS: Based upon D-CDU results patients were diagnosed as having arteriogenic (AR, n = 18; mean age 51) or corporeal venocclusive (CVO, n = 13; mean age 49) ED; in other patients (n = 21, mean age 43) a diagnosis of psychogenic (P)-ED was made by comprehensive psychogenic testing and confirmed by normal D-CDU results. AR and CVO patients had altered compliance of cavernous arteries recorded by D-CDU [20-25% lower resistive index (RI) than patients with psychogenic ED], and lower free testosterone (FT) levels than psychogenic patients [42.3 +/-3.5 SE and 49.3+/-5.2 vs. 75.2+/-7.6 pmol/l, respectively; P<0.01]. More important, in all patients there was a strong direct correlation between resistive index values and FT levels (r = 0.47, P = 0.002); the relationship was maintained also when adjusted for age, SHBG and oestradiol (r = 0.37, P = 0.02). CONCLUSIONS: These results indicate that in men with erectile dysfunction low free testosterone may correlate independently of age with the impaired relaxation of cavernous endothelial and corporeal smooth muscle cells to a vasoactive challenge. These findings give clinical support to the experimental knowledge of the importance of androgens in regulating smooth muscle function in the penis.

Cross-Sectional Studies↗

PubMed2000

Leptin and aging: correlation with endocrine changes in male and female healthy adult populations of different body weights.

Aging is associated with changes in plasma levels of several hormones. There are conflicting reports on whether circulating leptin levels change during aging, the possible explanation for which is that alterations in adiposity and body mass index (BMI) also occur. In this study we measured plasma leptin and other hormonal parameters known to influence leptin in 150 men and 320 women of a wide age (18-77 yr) and BMI (18.5-61.1 kg/m2) range. Subjects of each gender were separated into 2 groups of similar BMI, i.e. nonobese (BMI, <30) and obese (BMI, >30), and treated separately. Statistical analysis was performed, treating each group of subjects as a whole population or divided into age groups (<30, 30-50, and >50 yr). BMI-adjusted leptin levels were progressively lower with increasing age in women, with a consistent fall after menopause (-21%; P < 0.001); in men, leptin levels also tended to be lower in subjects more than 50 yr of age, but the reduction was not significant. Multiple linear regression analysis, performed on subjects treated either as a whole population or divided into obese and nonobese, showed that in both genders BMI and age were independent contributors of leptin levels, and there was an inverse relationship between leptin and age in both obese (standardized coefficient beta = -0.25 in women and -0.23 in men; P < 0.01) and nonobese (-0.22 in women and -0.20 in men; P < 0.05) subjects. The correlation of leptin and age with plasma levels of sex and thyroid hormones, GH, insulin-like growth factor I, PRL, and insulin was also evaluated. The variables that correlated with leptin were included in a multiple regression model that included BMI and age. Testosterone in men (-0.43 in nonobese and -0.19 in obese; P < 0.05) and estradiol in women (0.22 in nonobese and 0.24 in obese; P < 0.05) were important contributors to leptin levels; also, dehydroepiandrosterone sulfate in obese women (-0.16) and sex hormone-binding globulin in obese subjects of both genders (0.15 in women and 0.19 in men) were significant determinants in the model. However, none of the hormonal parameters abolished the negative correlation between leptin and age or the gender difference in leptin levels. In conclusion, our data show that in adult humans of different body weight, serum leptin gradually declines during aging; leptin reduction is higher in women than in men, but it is independent from BMI and other age-related endocrine changes.

Adolescent↗

PubMed1999

Expression of functional leptin receptors in rodent Leydig cells.

Several studies indicate that the size of body fat stores and the circulating levels of the adipocyte-derived hormone leptin are able to influence the activity of the hypothalamic-pituitary-gonadal axis. The leptin-hypothalamic-pituitary-gonadal interactions have been mainly studied at the level of the central nervous system. In this study, we investigated the possibility that leptin may have direct effects on the rodent Leydig cell function. To probe this hypothesis, we first analyzed the expression of leptin receptors (OB-R) in rodent Leydig cells in culture. RT-PCR studies showed that rat Leydig cells express both the long (OB-Rb) and short isoform (OB-Ra) of leptin receptor, whereas MLTC-1 cells (a murine Leydig tumor cell line) express only the long isoform. Short-term (30-90 min) incubation of rat Leydig cells with increasing concentrations ofleptin (2-500 ng/ml) led to a significant and dose-dependent inhibition of human (h)CG-stimulated testosterone (T) production (approximately 60% reduction, IC50 = 20 ng/ml) but no change in basal androgen release. Also, leptin (150 ng/ml) amplified hCG-induced intracellular cAMP formation (1- to 2-fold) without modifying basal cAMP levels. Subsequent experiments showed that leptin inhibited 8Br-cAMP-stimulated T production, indicating that leptin's effect is exerted beyond cAMP. The inhibitory effect of leptin on hCG-induced T secretion was accompanied by a significant reduction of androstenedione and a concomitant rise of the precursor metabolites pregnenolone, progesterone, and 17-OH-progesterone, conceivable with a leptin-induced lesion of 17,20 lyase activity. Separate experiments performed with the MLTC-1 cells (not expressing cytochrome P450-17alpha) showed that leptin, though amplifying hCG-stimulated cAMP production, did not modify hCG-stimulated pregnenolone and progesterone release. These results further indicate that leptin action on steroidogenesis occurs downstream of progesterone synthesis. Northern Blot experiments showed no acute effect of leptin on cytochrome P450-17alpha messenger RNA accumulation in rat Leydig cells in basal and hCG-stimulated conditions, excluding that the rapid changes observed were caused by messenger RNA degradation. In conclusion, these findings, for the first time, show that leptin has direct, receptor-mediated actions on rodent Leydig cells in culture, at concentrations within the range of obese men.

8-Bromo Cyclic Adenosine Monophosphate↗

PubMed1999

Leptin and androgens in male obesity: evidence for leptin contribution to reduced androgen levels.

Leptin circulates in plasma at concentrations that parallel the amount of fat reserves. In obese males, androgen levels decline in proportion to the degree of obesity. Recently, we have shown that in rodent Leydig cells leptin inhibits hCG-stimulated testosterone (T) production via a functional leptin receptor isoform; others have found that leptin inhibits basal and hCG-induced T secretion by testis from adult rats. In this study, we further investigated the relationship linking leptin and androgens in men. Basal and hCG-stimulated leptin and sex hormone levels were studied in a large group of men ranging from normal weight to very obese (body mass index, 21.8-55.7). Initial cross-sectional studies showed that circulating leptin and fat mass (FM) were inversely related with total and free T (r = -0.51 and r = -0.38, P < 0.01 and P < 0.05, respectively). Multiple regression analysis indicated that the correlation between leptin or FM and T was not lost after controlling for SHBG and/or LH and/or estradiol (E2) levels and that leptin was the best hormonal predictor of the lower androgen levels in obesity. Dynamic studies showed that in obese men the area under the curve of T and free T to LH/hCG stimulation (5000 IU i.m.) was 30-40% lower than in controls and inversely correlated with leptin levels (r = -0.45 and r = -0.40, P < 0.01 and P < 0.05, respectively). Also, LH/hCG-stimulation caused higher increases in 17-OH-progesterone to T ratio in obese men than in controls, whereas no differences were observed between groups either in stimulated E2 levels or in the E2/T ratio. In all subjects, the percentage increases from baseline in the 17-OH-progesterone to T ratio were directly correlated with leptin levels or FM (r = 0.40 and r = 0.45, P < 0.01), but not with E2 or other hormonal variables. In conclusion, our studies, together with previous in vitro findings, indicate that excess of circulating leptin may be an important contributor to the development of reduced androgens in male obesity.

17-alpha-Hydroxyprogesterone↗

PubMed1998

[Pharmacology of male sexual dysfunction].

The understanding of pharmacology of impotence has shown a steady improvement over the last 15 years which has resulted in a better appreciation of the neurovascular mechanisms of the erectile process especially at the level of the corpora cavernosa; however, central mechanisms which control libido and erection are not yet completely elucidated. Frequent diseases most commonly encountered in elderly patients--i.e. diabetes, hypertension, atherosclerosis, depression, etc--represent a frequent cause of erectile dysfunction (ED) and are treated with medications that can interfere with sexual functioning at the central and/or peripheral level. Antidepressants, including the tricyclics and the monoamine oxidase inhibitors, have been implicated in ED, decreased libido, and impaired ejaculation. Most antihypertensives have been associated with some erectile impairment, but diuretics seem to have little effect on erectile function. The calcium channel blockers and ACE inhibitors are associated with a low incidence of ED. Sympatholytic antihypertensives seldom cause importence but can cause retrograde ejaculation because of the relaxation of the smooth muscles in the prostatic urethra and bladder neck. The most commonly prescription drugs that can affect sexual function are briefly discussed and an integrated pharmacological approach to the patient with drug-induced ED is proposed.

Androgens↗

PubMed1996

Anxiety-induced failure in erectile response to intracorporeal prostaglandin-E1 in non-organic male impotence: a new diagnostic approach.

Intracavernous injection (ICI) of prostaglandin-E1 (PGE1) is used widely as the first diagnostic test in the study of erectile dysfunction. However, a lack of full erection after a maximal dose is frequent. As well as vascular incompetence, this may be due to stress-induced changes, related to the ICI procedure. The aim of this study was to investigate the influence of emotional disturbances on erectile response to ICI in impotent patients. Initially, 24 young men with non-organic impotence (age 34.6 +/- 1.5 years; mean +/- SEM) were selected and randomized single-blind to pharmacoerection with PGE1 alone (20 micrograms/mL) or a mixture (cocktail) containing 20 micrograms PGE1 plus an alpha-adrenergic receptor blocker, phentolamine (Phe, 0.5 mg/mL). Additional studies were also performed double-blind on 10 men with non-organic impotence (age 37.6 +/- 1.2 years) utilizing higher PGE1 dosages for ICI (25 micrograms/mL alone or in combination with Phe, 0.5 mg/mL). After a 7-day interval, all subjects were crossed-over to receive the alternative treatment. The presence of emotional disturbances was assessed in all patients by the administration of rapid tests (Stai-X1 and Stai-X1r for state-anxiety before and after ICI, respectively; Stai-X2 for trait-anxiety; Zung-test for depression) at the first and at the remaining (Stai-X1 and Stai-X1r) ICI sessions. ICI with 20 and 25 micrograms/mL PGE1 led to a comparable percentage of patients who reported a valid-for-intromission (VFI) erection (63 and 60%, respectively). In contrast, use of the cocktails significantly increased the percentage of subjects with a VFI (87 and 90% of the total number of patients tested, respectively; p < 0.05). Moreover, a strong inverse correlation between state-anxiety scores (Stai-X1) and the erectile response to ICI with 20 and 25 micrograms PGE1 was found (r = -0.69, p < 0.001); such a correlation was not present in patients who underwent ICI with the cocktails. Two cases of prolonged erection occurred (one after 20 micrograms PGE1 and the other after 20 micrograms PGE1 plus Phe) which were reversed promptly by the intracavernous injection of metharaminol. It is concluded that the lack of a full erectile response after ICI with PGE1 can be related to the presence of a high 'state-anxiety' in the patients. In such patients, a VFI erectile response can be induced by the administration of a cocktail test-dose.

Adrenergic alpha-Antagonists↗

PubMed1996

[Azoospermia and genetic mutations: implications for the methods of in vitro fertilization].

Much evidence suggests the fundamental role of the Y chromosome during spermatogenesis. Especially, a gene on the long arm (localized in a portion of the chromosome called Yq11), the AZF (azoospermic factor), is necessary for the achievement and the maintenance of the spermatogenetic process. In fact mutations and deletions in this part of the chromosome inevitably cause severe oligozoospermia or azoospermia. Furthermore other genes on the short arm seem to have a role during spermatogenesis: they are called ZFY (zink finger Y, which encodes a DNA binding protein) and TSPY (expressed in the spermatids nuclei); but the function of these genes is still uncertain, since at this moment no deletions or mutations have been found at this level. Further genes only recently cloned include the CREM (cAMP-responsive element modulator), whose mutation causes azoospermia with a spermatidic arrest in the mouse, and the complex c-kit/Steel-factor. The latter is essential for spermatogonial proliferation and differentiation, so that an alteration at this level can determine spermatogonial arrest or the absence of germinal cells with the presence of Sertoli cells only (Sertoli cells only syndrome). In contrast with AZF, both the CREM gene and c-kit/Steel-factor genes are autosomal (chromosome 10 for the CREM, 4 for c-kit, 1 for Steel-factor, respectively). Several genes may be involved in the spermatogenetic process, but their role, excepting for AZF, is still unclear.

Animals↗

PubMedDate not supplied

Demonstration of communication between alveolus and interstitium in persistent interstitial pulmonary emphysema: case report.

Persistent interstitial pulmonary emphysema (PIPE) is an uncommon complication of premature infants suffering from hyaline membrane disease who have been treated with mechanical ventilation. The presumed mechanism for the development of the disease is via a break in the bronchioalveolar system that allows air to escape into the interstitium. We report a case of a 9-week-old child who developed the localized form of the disease and underwent a lobectomy. Immunohistochemical stains helped to demonstrate the communication between the airway system and interstitium. This report strengthens the theory that the disease develops from airway rupture at the alveolar level.

Cysts↗