Effects of heterozygosity for the E180 splice mutation causing growth hormone receptor deficiency in Ecuador on IGF-I, IGFBP-3, and stature.

CONTEXT & OBJECTIVE: The Ecuadorian GH receptor deficiency (GHRD)/Laron syndrome population is the only large cohort with a single GHR mutation (E180 splice), permitting identification of numerous carrier and noncarrier first-degree relatives, to ascertain effects of heterozygosity on GH-dependent IGF-I and IGFBP-3 concentrations and on growth. DESIGN: First-degree relatives (n=212) of GHRD patients had specimens taken for IGF-I, IGFBP-3, and GHR genotyping. Normal statured (n=40) and short statured (n=40) unrelated controls had measurement of IGF-I, IGFBP-3, and stature. RESULTS: There were no significant differences between heterozygous and homozygous normal relatives in IGF-I or IGFBP-3 standard deviation scores (SDS). Heterozygous relatives had lower mean height SDS than did homozygous normals, but with extensive overlap between genotype groups in both child and adult relatives. Height SDS in general did not relate to IGF-I or IGFBP-3 concentrations. CONCLUSIONS: GH-dependent IGF-I and IGFBP-3 secretion is not affected by heterozygosity for the E180 splice mutation that causes GHRD/Laron syndrome in the Ecuadorian population. Heterozygosity is associated with reduction in mean statural SDS, but this is not sufficient to be clinically important and not mediated through measurable differences in circulating IGF-I or IGFBP-3 related to genotype.     

Free insulin-like growth factor-I and cognitive function in older persons living in community.

CONTEXT: Increasing evidences from experimental and human studies suggest that the activity of the growth hormone (GH/insulin-like growth factor-I) axis may contribute to the age-related cognitive decline and poor cognition in late life. OBJECTIVE: The aim of the present study was to evaluate the relationship of total serum free IGF-I and its binding protein-3 with cognitive performance in older persons aged 80 years or older. DESIGN: Data are from baseline evaluation of the ilSIRENTE study (n=353). Cognitive performance was evaluated using five items enclosed in the Minimum Data Set for Home Care assessment form: short-term memory, procedural memory, cognitive skills in daily decision making, verbal expression, comprehension. Free insulin-like growth factor-I (free IGF-I) and IGF-binding protein-3 (IGFBP-3) in blood were measured. Analysis of covariance (ANCOVA) was used to examine the relationship between cognitive impairment and the serum free IGF-I and IGFBP-3 concentrations, after adjustment for potential confounding variables. RESULTS: After adjustment for potential confounders, which included age, gender, education, cerebrovascular disease, ischemic heart disease, congestive heart failure, hypertension, diabetes, depression, Parkinson diseases, thyroid diseases, smoking status, alcohol abuse, body mass index, and number of medications, individuals with verbal expression problems (n=20) and individuals with comprehension problems (n=24) had a significantly lower serum levels of readily dissociable IGF-I than participants without cognitive impairments. The serum IGFBP-3 presented the same behavior of free IGF-I. CONCLUSION: The present study suggests that among old-old subjects living in the community lower levels of total serum free IGF-I and IGFBP-3 are associated with impairment of cognitive performance. This finding suggests that the GH/IGF-I axis may play an important role in the age-related decline of cognitive performance.     

Hemoglobin adducts of benzo[a]pyrene diolepoxide in newspaper vendors: association with traffic exhaust

Benzo[a]pyrene diol epoxide adducts with hemoglobin (Hb) weremeasured to detect human exposure to environmental benzo[a]pyrenefrom traffic exhaust. Benzo[a]pyrene tetrahydrotetrols (BPTs)released from Hb after acid hydrolysis were quantitated by gaschromatography-mass spectrometry after immunoaffinity chromatography.Fifty three newspaper vendors were enrolled. The median adductconcentration was 0.3 fmol BPTs/mg Hb in high density traffic-exposedvendors and     

Changes in Neutrophil Oxidative Potential in Patients Undergoing Cardiopulmonary Bypass with Polypropylene Hollow Fiber Oxygenators

Neutrophil oxidative metabolism, C3d and beta 2 microglobulin levels, were assessed in nine consecutive patients undergoing cardiopulmonary bypass surgery with polypropylene hollow fiber oxygenators for open cardiac operations. Generation of oxygen free radicals by neutrophils was measured as luminol-enhanced chemiluminescence after stimulation with opsonized Zymosan and phorbol myristate acetate. A significant increase in light emission was detected by using both of the chemiluminescence stimulators. Moreover, a remarkable and significant increase in C3d levels was found already at 10 min. Conversely minimal changes in levels of beta 2 microglobulin were detected during cardiopulmonary bypass surgery. These data suggest that the impact of the patient blood with the foreign surface of cardiopulmonary bypass results in activation of phagocyte cells with increased potential in oxygen consumption. These effects could be partially complement-mediated.     

Self-expanding mesh stent for endoscopic palliation of rectal obstructing tumors: a preliminary report

Summary The endoscopic insertion of self-expanding mesh stents in four patients affected by obstructing rectal malignant tumors is reported. The preliminary experience shows that, in the short term, normal defecation was achieved, with no complications. Longer follow-up is necessary to evaluate the duration and the quality of the palliative effect.     

Analysis of risk factors for tumor recurrence after liver transplantation for hepatocellular carcinoma: key role of immunosuppression.

To confirm recent observations about the relationship between immunosuppression and the recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT), we retrospectively analyzed 70 consecutive HCC patients who underwent LT and received cyclosporine (CsA)-based immunosuppression. CsA trough blood levels, measured with the same technique (fluorescence polarization immunoassay), were analyzed at different time points after transplantation. The exposure to the drug was calculated with the trapezoidal rule in each patient. CsA was associated with steroids in 26 patients and steroids and azathioprine in 44 patients. HCC recurred in 7 patients (10.0%). Different immunosuppressive schedules (CsA and steroids vs. CsA, steroids, and azathioprine) or the cumulative dosage of steroids and azathioprine did not influence HCC recurrence that was associated instead with CsA exposure (278.3 +/- 86.4 ng/mL in recurrent vs. 169.9 +/- 33.3 in tumor-free patients; P < 0.001); CsA exposure above 189.6 ng/mL was related to HCC recurrence at the receiver operating characteristic analysis (ROC). The relationship between CsA exposure; various clinical (sex, age, viral- vs. non-viral-related cirrhosis, preoperative vs. incidental diagnosis of HCC, alpha-fetoprotein [AFP] blood level), pathologic (pathologic tumor staging [pT] stage, presence of Milan criteria), and histologic (grading, presence of microvascular tumor invasion) parameters; and tumor recurrence were assessed. AFP (P = 0.032), microvascular tumor invasion (P = 0.044), and CsA exposure (P < 0.001) influenced recurrence-free survival at the univariate analysis; CsA exposure was the only independent prognostic determinant at multivariate analysis (P < 0.001). High CsA exposure favors tumor recurrence; CsA blood levels should be kept to the effective minimum in HCC patients. In the presence of pathologic and histologic risk factors, specific immunosuppressive protocols should be considered.     

Current controversies in oral lichen planus: report of an international consensus meeting. Part 1. Viral infections and etiopathogenesis.

Despite recent advances in understanding the immunopathogenesis of oral lichen planus (LP), the initial triggers of lesion formation and the essential pathogenic pathways are unknown. It is therefore not surprising that the clinical management of oral LP poses considerable difficulties to the dermatologist and the oral physician. A consensus meeting was held in France in March 2003 to discuss the most controversial aspects of oral LP. Part 1 of the meeting report focuses on (1) the relationship between oral LP and viral infection with special emphasis on hepatitis C virus (HCV), and (2) oral LP pathogenesis, in particular the immune mechanisms resulting in lymphocyte infiltration and keratinocyte apoptosis. Part 2 focuses on patient management and therapeutic approaches and includes discussion on malignant transformation of oral LP.     

The scientific roots of José A. Campos-Ortega, a German neurobiologist born in Spain.

In this review article, we shall focus our attention on the initial steps in the research career of José A. Campos-Ortega and the studies he undertook. Particular emphasis will be placed on how these early experiences shaped his personality and his future scientific contributions.