Neuropeptide Y and leptin in patients with obstructive sleep apnea syndrome: role of obesity

Neuropeptide Y (NPY) and leptin are two peptides involved in the regulation of body weight, energy balance, and sympathetic tone. This study investigates the independent role of apneas and obesity on NPY and leptin plasma levels in patients with obstructive sleep apnea syndrome (OSAS). To this end we compared their values in 23 obese (body mass index > 30 kg/m2) and 24 nonobese (body mass index < 27 kg/m2) patients with OSAS, and in 19 obese and 18 nonobese control subjects without OSAS. Patients who used continuous positive airway pressure for more than 4 hours/night were reexamined 3 and 12 months later. We found that NPY levels were increased (p < 0.01) in patients with OSAS independently of obesity. Leptin levels were also increased in OSAS but this was mostly associated to obesity. Continuous positive airway pressure treatment reduced NPY levels in all patients and leptin levels only in nonobese patients (p < 0.01). We concluded that NPY and leptin plasma levels are increased in patients with OSAS. Yet, whereas the former appear independent of obesity, the latter are mostly associated with obesity.     

A second-look TUR in T1 transitional cell carcinoma: why?

T1 transitional cell cancer of the urinary bladder is associated with a significant risk of tumor progression when transurethral resection (TUR) is the only treatment. Additional intravesical immunotherapy can reduce this risk; however, long-term results of more than 15 years of follow-up indicate that almost half of the patients may lose their bladder or even die due to recurrent tumor. The alternative to TUR is cystectomy at either the initial presentation or time of first recurrence. However, although the results of this treatment strategy are encouraging, an unknown percentage of patients will lose their bladder and go on to experience all possible complications of urinary diversion unnecessarily. The central issue of conservative treatment but also the indication for cystectomy is the quality of TUR. From the present literature, it is evident that a 'textbook TUR' cannot be performed on every patient, i.e. macroscopical clearance of the bladder from tumor, separate thorough resection of the tumor base and separate biopsies of the borders of the resection area. Moreover, even in cases of a so-called 'correct TUR', a significant percentage of residual tumor is left behind and will be the source of local recurrence or progression. In addition, TUR specimens may be difficult to diagnose accurately, especially in respect to grade and stage. Recent publications demonstrate that the routinely performed second TUR detects residual tumors of similar or higher stage in a significant percentage of patients. The clinical implications of these findings can be considerable as the absence or presence of tumor may determine whether patients undergo conservative or aggressive treatment. Moreover, results of retrospective studies support this suggestion. Currently, there is no standard appropriate treatment of T1 tumors. However, we strongly recommend that future studies on the conservative treatment of T1 tumors include a second TUR within 2 to 4 weeks after the first one.     

Invasive disease caused by Haemophilus influenzae: the sensitivity of statutory reporting

PURPOSE: The objective of the study was to investigate the sensitivity of the statutory reporting of Haemophilus influenzae invasive disease (HIID) during the period between 1996 and 1997 in Catalonia, Spain. METHODS: The incidence of HIID reported passively by clinicians was compared with the cases detected by a system of microbiological surveillance. In all cases isolated, the age of the patient, the clinical form and the serotype were investigated. RESULTS: Sixty-six cases were passively reported and 111 were detected by microbiological surveillance. Overall sensitivity of reporting was 59.5% (95% CI, 50.7-69.1), with differences being observed according to the variables studied. The highest values were obtained in children under 5 years (87.8%; 95% CI, 73.7-95.9), in cases with meningitis and/or sepsis (64.3%; 95% CI, 50.4-76.6) and in serotype b (73.0%; 95% CI, 60.3-83.4). In the logistical regression analysis, only age under 5 years was associated with greater reporting (OR= 9.8; 95% CI, 2.5-37.8). CONCLUSIONS: Reported morbidity in children under 5 years is a good estimate of the true incidence of HIID in Catalonia (underreporting was 12.2%), but not for those above this age in whom the underreporting was 57.2%.     

Bacteriophages and diffusion of beta-lactamase genes

We evaluated the presence of various Beta-lactamase genes within the bacteriophages in sewage. Results showed the occurrence of phage particles carrying sequences of bla(OXA-2), bla(PSE-1) or bla(PSE-4) and bla(PSE)-type genes. Phages may contribute to the spread of some Beta-lactamase genes.     

Immunoglobulin therapy to control lung damage in patients with common variable immunodeficiency

BACKGROUND: Lung damage progression is the most frequent condition in patients with common variable immunodeficiency (CVID). Appropriate immunoglobulin dose adjustments and follow-up guidelines to evaluate this have not been well established. Objective: To assess the evolution of lung damage once stable residual serum levels of IgG over 600 mg/dl had been achieved. METHODS: A prospective study was conducted in 24 adult patients consecutively diagnosed with CVID, with no previous intravenous immunoglobulin (IVIG) treatment. IVIG dose, total serum IgG level, bacterial infection rate, pulmonary function tests (PFTs) and high resolution computed tomography (HRCT) of the thorax were monitored over 2 years. Moreover, outcome data were determined by measurement of chronic pulmonary disease (CPD). RESULTS: IVIG dose variability (205-372 mg/kg/21 days) to obtain the required serum IgG levels was determined. Patients with CPD needed higher doses than those without CPD (p=0.045). A significant reduction in severe and mild infections/patient-year was observed during treatment. Overall, there were no changes in PFTs and HRCT scores in patients without CPD, but both improved in patients with CPD. An increase of over 15% in overall HRCT score was detected in two patients without evidence of impairment in either clinical status or PFT values. CONCLUSIONS: Residual levels of total IgG over 600 mg/dl may help prevent progression of lung damage in patients with CVID. Levels of IgG, clinical manifestations and PFTs seem sufficient for routine follow-up. HRCT examination of the thorax, at least biennially, may help to identify patients in whom lung injury is progressing even though they may remain symptom-free and with stable PFTs.     

Regulation of Nogo and Nogo receptor during the development of the entorhino-hippocampal pathway and after adult hippocampal lesions

Axonal regeneration in the adult CNS is limited by the presence of several inhibitory proteins associated with myelin. Nogo-A, a myelin-associated inhibitor, is responsible for axonal outgrowth inhibition in vivo and in vitro. Here we study the onset and maturation of Nogo-A and Nogo receptor in the entorhino-hippocampal formation of developing and adult mice. We also provide evidence that Nogo-A does not inhibit embryonic hippocampal neurons, in contrast to other cell types such as cerebellar granule cells. Our results also show that Nogo and Nogo receptor mRNA are expressed in the adult by both principal and local-circuit hippocampal neurons, and that after lesion, Nogo-A is also transiently expressed by a subset of reactive astrocytes. Furthermore, we analyzed their regulation after kainic acid (KA) treatment and in response to the transection of the entorhino-hippocampal connection. We found that Nogo-A and Nogo receptor are differentially regulated after kainic acid or perforant pathway lesions. Lastly, we show that the regenerative potential of lesioned entorhino-hippocampal organotypic slice co-cultures is increased after blockage of Nogo-A with two IN-1 blocking antibodies. In conclusion, our results show that Nogo and its receptor might play key roles during development of hippocampal connections and that they are implicated in neuronal plasticity in the adult.     

Evaluation of the impact of the heat wave in the summer of 2003 on mortality

The effect of the elevated temperatures experimented in Europe during the summer 2003 on mortality was observed in several countries. This study, carried out in Spain, describes the mortality between the 1st June and the 31st August and evaluates the effect of the heat wave on mortality. Observed deaths were obtained from official vital Registers of the capital city of the 50 provinces. Deaths from 107 randomly selected rural villages were also obtained from the same source. Observed deaths were compared with expected estimated applying a Poisson regression model to historical mortality series adjusting for the upwards trend and seasonality observed. Meteorological information was provided by the National Institute of Meteorology. Spain experienced three heat waves. Total excess deaths associated was 8% (43,212 observed compared with 40,046 expected). Excess deaths were only observed among 65 years old and over (15%). The increased mortality was also observed in rural villages. This phenomenon is becoming an emerging public health problem because of its increasing attributable risk because of the aging of Spanish population. Alert and response systems based on monitoring of climate related risks, emergency rooms activity and mortality and the strengthening of social and health services response capacity should be considered.     

The WHO/ISUP 1998 and WHO 1999 systems for malignancy grading of bladder cancer. Scientific foundation and translation to one another and previous systems

Recently, two new classification systems for grading of urothelial neoplasms have been published. The objective of both was to avoid the overdiagnosis of cancer and to create better criteria for the grades. The WHO/ISUP classification of 1998 distinguishes papilloma, papillary urothelial neoplasm of low malignant potential (PUNLMP), low and high grade carcinomas, whereas the WHO 1999 system subdivides the high grade into grades II and III, and is otherwise identical. This note summarizes studies supporting the rationale of the two new systems, describes pattern recognition criteria for the grades, and highlights the homology between them.     

Effect of inhibition of Na(+)/Ca(2+) exchanger at the time of myocardial reperfusion on hypercontracture and cell death

OBJECTIVE: There is recent evidence that Ca(2+) influx via reverse mode Na(+)/Ca(2+) exchange (NCX) at the time of reperfusion can contribute to cardiomyocyte hypercontracture. However, forward NCX is essential for normalization of [Ca(2+)](i) during reperfusion, and its inhibition may be detrimental. This study investigates the effect of NCX inhibition with KB-R7943 at the time of reperfusion on cell viability. METHODS: The effect of several concentrations of KB-R7943 added at reperfusion was studied in Fura-2 loaded quiescent cardiomyocytes submitted to 40 min of simulated ischemia (NaCN 2 mM, pH 6.4), and in rat hearts submitted to 60 min of ischemia. [Ca(2+)](i) and cell length were monitored in myocytes, and functional recovery and LDH release in isolated hearts. From these experiments an optimal concentration of KB-R7943 was identified and tested in pigs submitted to 48 min of coronary occlusion and 2 h of reperfusion. RESULTS: In myocytes, KB-R7943 at concentrations up to 15 microM reduced [Ca(2+)](i) rise and the probability of hypercontracture during re-energization (P<0.01). Nevertheless, in rat hearts, the effects of KB-R7943 applied during reperfusion after 60 min of ischemia depended on concentration and timing of administration. During the first 5 min of reperfusion, KB-R7943 (0.3-30 microM) induced a dose-dependent reduction in LDH release (half-response concentration 0.29 microM). Beyond 6 min of re-flow, KB-R7943 had no effect on LDH release, except at concentrations > or = 15 microM, which increased LDH. KB-R7943 at 5 microM given during the first 10 min of reflow reduced contractile dysfunction (P=0.011), LDH release (P=0.019) and contraction band necrosis (P=0.014) during reperfusion. Intracoronary administration of this concentration during the first 10 min of reperfusion reduced infarct size by 34% (P=0.033) in pigs submitted to 48 min of coronary occlusion. CONCLUSIONS: These results are consistent with the hypothesis that during initial reperfusion NCX activity results in net reverse mode operation contributing to Ca(2+) overload, hypercontracture and cell death, and that NCX inhibition during this phase is beneficial. Beyond this phase, NCX inhibition may impair forward mode-dependent Ca(2+) extrusion and be detrimental. These findings may help in the design of therapeutic strategies against lethal reperfusion injury, with NCX as the target.