The prevalence of priapism in children and adolescents with sickle cell disease in Brazil

To evaluate priapism rates in individuals <18 years of age with sickle cell disease (SCD) at a referral center. An evaluation was made of 599 consecutive male patients with SCD, separated according to type of hemoglobinopathy (HbSS, HbSC and HbS-β-thalassemia). Age at first episode and number of episodes were recorded. Cases of sickle cell trait were excluded. Mean age was similar in all groups. Overall, priapism occurred in 3.6 % of patients (5.6 % of those with HbSS and 1.1 % of those with HbSC; P = 0.01). In HbSS patients, the prevalence rate of priapism was from 3.5 (CI 95 % 0.94-13.4) when compared with patients with HbSC. No patient with β-thalassemia had priapism. Mean follow-up was 39.7 months (range 1-202 months). Since 91 % of patients with priapism had HbSS, this group was evaluated separately, revealing a rate of priapism of 1.6 % in patients <10 years and 8.3 % in those ≥ 10 years of age (P = 0.002). Regarding priapism in HbSS patients ≥ 10 years (8.3 %) when compared with patients <10 years (1.6 %), the prevalence rate was from 3.3 (CI 95 % 1.1-9.5). Duration of follow-up was not correlated with priapism (P = 0.774). Forty-seven patients were lost to follow-up. Telephone contact was successful with 14/22 patients with priapism, 50 % of whom had required hospital treatment. Most episodes (86 %) occurred at night, always during sleep. Medical interventions were required in 13 cases as follows: intravenous hydration (n = 4), corpora cavernosa puncture and drainage (n = 7) and corpus cavernosum-corpus spongiosum shunts (n = 2). The prevalence of priapism in children <18 years of age with SCD was 3.6 %, lower than previously reported. Prevalence was higher in HbSS patients, increasing in patients >10 years of age. Most episodes occurred at night and half of the patients required some form of urological procedure.     

A Nonlinear Model of Cardiac Autonomic Control in Obstructive Sleep Apnea Syndrome

Using the Volterra–Wiener approach, we employed a minimal model to quantitatively characterize the linear and nonlinear effects of respiration (RCC) and arterial blood pressure (ABR) on heart rate variability (HRV) in normal controls and subjects with moderate-to-severe obstructive sleep apnea syndrome (OSAS). Respiration, R–R interval (RRI), blood pressure (BP) and other polysomnographic variables were recorded in eight normal controls and nine OSAS subjects in wakefulness, Stage 2 and rapid eye-movement sleep. To increase respiratory and cardiovascular variability, a preprogrammed ventilator delivered randomly timed inspiratory pressures that were superimposed on a baseline continuous positive airway pressure. Except for lower resting RRI in OSAS subjects, summary statistical measures of RRI and BP and their variabilities were similar in controls and OSAS. In contrast, RCC and ABR gains were significantly lower in OSAS. Nonlinear ABR gain and the interaction between respiration and blood pressure in modulating RRI were substantially reduced in OSAS. ABR gain increased during sleep in controls but remained unchanged in OSAS. These findings suggest that normotensive OSAS subjects have impaired daytime parasympathetic and sympathetic function. Nonlinear minimal modeling of HRV provides a useful, insightful, and comprehensive approach for the detection and assessment of abnormal autonomic function in OSAS. Supported by NIH Grants HL-58725, EB-001978, and M01 RR-43     

Acute stimulation of aromatization in Leydig cells by human chorionic gonadotropin in vitro.

Aromatization of testosterone in Leydig cells purified from mature rat testes was assessed. Leydig cells incubated for 4 hr with increasing concentrations of [3H]testosterone. At saturating concentrations of testosterone, human chorionic gonadotropin (hCG) acutely stimulated aromatization. This stimulation was first observed at 1 hr, an 8-fold increase being found during a 4-hr incubation. The maximal amount of estradiol produced at saturating concentrations of testosterone and hCG was 1.8 ng per 10(6) cells. These results demonstrate that purified Leydig cells have a high capacity for aromatization and that hCG can acutely stimulate aromatization independently of stimulating testosterone synthesis in vitro.     

Mechanical ventilation modulates Toll-like receptor signaling pathway in a sepsis-induced lung injury model

Background  

Experimental and clinical studies on sepsis have demonstrated activation of the innate immune response following the initial host–bacterial interaction. In addition, mechanical ventilation (MV) can induce a pulmonary inflammatory response. How these two responses interact when present simultaneously remains to be elucidated. We hypothesized that MV modulates innate host response during sepsis by influencing Toll-like receptor (TLR) signaling.     

Origin of renal cell carcinomas

Cancer is a heritable disorder of somatic cells: environment and heredity are both important in the carcinogenic process. The primal force is the “two hits” of Knudson’s hypothesis, which has proved true for many tumours, including renal cell carcinoma. Knudson et al. [1, 2] recognised that familial forms of cancer might hold the key to the identification of important regulatory elements known as tumour-suppressor genes. Their observations (i.e., that retinoblastoma tend to be multifocal in familial cases and unifocal in sporadic presentation) led them to propose a two-hit theory of carcinogenesis. Furthermore, Knudson postulated that patients with the familial form of the cancer would be born with one mutant allele and that all cells in that organ or tissue would be at risk, accounting for early onset and the multifocal nature of the disease. In contrast, sporadic tumours would develop only if a mutation occurred in both alleles within the same cell, and, as each event would be expected to occur with low frequency, most tumours would develop late in life and in a unifocal manner [3, 4]. The kidney is affected in a variety of inherited cancer syndromes. For most of them, both the oncogene/tumour-suppressor gene involved and the respective germline mutations have been identified. Each of the inherited syndromes predisposes to distinct types of renal carcinoma. Families with hereditary predisposition to cancer continue to provide a unique opportunity for the identification and characterisation of genes involved in carcinogenesis. A surprising number of genetic syndromes predispose to the development of renal cell carcinoma, and genes associated with five of these syndromes have been already identified: VHL, MET, FH, BHD and HRPT2. Few cancers have as many different types of genetic predisposition as renal cancer, although to date only a small proportion of renal cell cancers can be explained by genetic predisposition. Supported by an unrestricted educational grant from Pfizer.     

Long-term treatment with insulin induces apoptosis in brown adipocytes: role of oxidative stress

Trying to define the precise role played by insulin regulating the survival of brown adipocytes, we have used rat fetal brown adipocytes maintained in primary culture. The effect of insulin on apoptosis and the mechanisms involved were assessed. Different from the known effects of insulin as a survival factor, we have found that long-term treatment (72 h) with insulin induces apoptosis in rat fetal brown adipocytes. This process is dependent on the phosphatidylinositol 3-kinase/mammalian target of rapamycin/p70 S6 kinase pathway. Short-term treatment with the conditioned medium from brown adipocytes treated with insulin for 72 h mimicked the apoptotic effect of insulin. During the process, caspase 8 activation, Bid cleavage, cytochrome c release, and activation of caspases 9 and 3 are sequentially produced. Treatment with the caspase inhibitor, benzyloxycarbonyl-Val-Ala-Asp (Z-VAD), prevents activation of this apoptotic cascade. The antioxidants, ascorbic acid and superoxide dismutase, also impair this process of apoptosis. Moreover, generation of reactive oxygen species (ROS), probably through reduced nicotinamide adenine dinucleotide phosphate oxidases, and a late decrease in reduced glutathione content are produced. According to this, antioxidants prevent caspase 8 activation and Bid cleavage, suggesting that ROS production is an important event mediating this process of apoptosis. However, the participation of uncoupling protein-1, -2, and -3 regulating ROS is unclear because their levels remain unchanged upon insulin treatment for 72 h. Our data suggest that the prolonged hyperinsulinemia might cause insulin resistance through the loss of brown adipose tissue.     

The superficial midline cervical cleft

Given the anatomy and the histology of the 4 cases of children with a midline cervical cleft presented in this work, and after reviewing the specific literature, an etiologic relationship between: this congenital malformation and the subcutaneous midline cervical bronchogenic cyst can be established. The presence of pseudostratified ciliated columnar epithelium in both entities and their anatomic relationship are determinant. The anatomic differences with the thyroglossal duct cyst indicated that their embryological origins were different, in spite of the presence of ciliated epithelium. In a 6 months old infant, the extirpation of the lesion without practicing a Z-plasty was carried out due to the small size of the malformation with good result after 3 months.