Expression of the preoptic regulatory factor-1 and ?2 genes in rat testis

Hormone-responsive peptides play a vital role in development and regulation of testicular function. The preoptic regulatory factors, porf-1 and porf-2, were originally discovered in the rat brain, but are also expressed in the rat and human testis. In the brain expression is age-related, hormone-responsive, region-specific, and gender-related, suggesting that porf-1 and porf-2 are involved in gender-specific brain development and function. Tissue-specific porf-1 and porf-2 mRNAs are also found in the testis and hypophysectomy may alter testicular porf-2 expression. It was thus of interest to further examine porf-1 and porf-2 expression in the testis to evaluate their potential as hormone-responsive peptides that regulate testicular development and function. Testicular expression of both porf-1 and −2 was analyzed as a function of maturational stage, aging and hypophysectomy by the solution hybridization/nuclease protection assay, and cellular location determined byin situ hybridization histochemistry. Expression was quantitatively compared in normal male rats at 15,30, and 60 d (n=4) and at 2, 6, 12, and 24 mo of age (n=5). During development porf-1 is expressed at a constant level at 15, 30, and 60 d, then declines significantly with advancing age; levels at 24 mo are only 20% of those seen at 2 mo (p<0.05). In contrast, porf-2 expression is highest at 15 d of age and steadily declines at 30 and 60 d, plateaus in the mature adult (6 and 12 mo), then exhibits an additional significant decline in the aged 24 mo animals (6 vs 24 mo,p<0.05). Hypophysectomy of young adult rats at day 42 results in increased testicular expression 12 d later of both porf-1 (p<0.05) and porf-2 (p<0.005) compared to intact 54-d-old rats (n=5).In situ hybridization histochemistry confirms that both porf-1 and porf-2 are expressed in the mature testis at 60 d of age. Porf-2 mRNA is localized to immature germ cells including spermatogonia and primary spermatocytes. Porf-1 mRNA is associated with mature sperm and at low levels in the Sertoli cell cytoplasm surrounding spermatocytes. These data suggest that porf-2 is a pituitary hormone-responsive factor in the developing testis and that both porf-1 and porf-2 have cell-type specific functions in the germ cell compartment of the mature testis.     

Noninvasive versus invasive microbial investigation in ventilator-associated pneumonia: evaluation of outcome

Noninvasive and invasive diagnostic techniques have been shown to achieve comparable performances in the evaluation of suspected ventilator-associated pneumonia (VAP). We studied the impact of both approaches on outcome in a prospective, open, and randomized study in three intensive care units (ICUs) of a 1,000-bed tertiary care university hospital. Patients with suspected VAP were randomly assigned to noninvasive (Group 1) versus invasive (Group 2) investigation (tracheobronchial aspirates [TBAS] versus bronchoscopically retrieved protected specimen brush [PSB] and bronchoalveolar lavage [BAL]. Samples were cultured quantitatively, and BAL fluid (BALF) was examined for intracellular organisms (ICO) additionally. Initial empiric antimicrobial treatment was administered following the guidelines of the American Thoracic Society (ATS) and adjusted according to culture results (and ICO counts in Group 2). Outcome variables included length of ICU stay and mechanical ventilation as well as mortality. Overall, 76 patients (39 noninvasive, 37 invasive) were investigated. VAP was microbiologically confirmed in 23 of 39 (59%) and 23 of 37 (62%) (p = 0.78). There were no differences with regard to the frequencies of community-acquired and potentially drug-resistant microorganisms (PDRM). Antimicrobial treatment was changed in seven patients (18%) of Group 1 and 10 patients (27%) of Group 2 because of etiologic findings (including five of 17 with ICO = 2% (p = not significant [NS]). Length of ICU stay and mechanical ventilation were also not significantly different in both groups. Crude 30-d mortality was 31 of 76 (41%), and 18 of 39 (46%) in Group 1 and 14 of 37 (38%) in Group 2 (p = 0.46). Adjusted mortality was 16% versus 11% (p = 0.53), and mortality of microbiologically confirmed pneumonia 10 of 23 (44%) in both groups (p = 1.0). We conclude that the outcome of VAP was not influenced by the techniques used for microbial investigation.     

Spur cell anaemia and acute haemolysis in patients with hyperreactive malarious splenomegaly. Experience in an isolated Yanomamo population of Venezuela

A prospective study, aimed to investigate the aetiology of an unusual clustering of cases of severe acute haemolytic anaemia affecting a high percentage of the adult population, was carried out in two isolated Yanomamo communities of the Upper Orinoco basin in Venezuela. Twenty-six patients with active or recent episodes of severe haemolysis were evaluated. All of them exhibited massive liver and spleen enlargement and fulfilled the diagnostic criteria of the hyperreactive malarious splenomegaly (HMS) syndrome. In four cases with advanced non-alcohol-related chronic liver disease, hypersplenism, severe haemolytic anaemia and acanthocytosis, the characteristic clinical and laboratory findings of spur cell anaemia were documented. Chronic infection by the HBV and HCV was present in three of them. However, in most of the 22 additional HMS cases, the acute haemolytic condition appeared associated with the occurrence of a cold agglutinin-mediated autoimmune response. The clustering of a significant number of cases of severe acute haemolysis in HMS patients from this small isolated aboriginal community is most unusual, and represents a serious complicating factor for a population already beleaguered by a high prevalence of malaria due to multiresistant strains of Plasmodium falciparum. Moreover, the coexistence of HMS and severe chronic HBV or HCV infection may further aggravate the course of the haemolytic disorder, because of the occurrence of spur cell anaemia.     

Comparison of the new acceleration spectrum analysis with other time- and frequency-domain analyses of the signal-averaged electrocardiogram

Aim To compare four analysis techniques of the signal-averaged-electrocardiogram,including time-domain, spectral temporal mapping, spectral turbulenceanalysis and the new acceleration spectrum analysis. Methods and Results We studied 634 subjects (77 with bundle branch block) dividedinto three groups. Group 1 comprised 117 post-myocardial infarctionpatients tested for inducibility of sustained ventricular tachycardia,and which was induced in 54 of them. Group 2 comprised 407 consecutiveacute myocardial infarction survivors, followed for 1 year;29 of them had suffered major arrhythmic events: 15 were casesof sustained ventricular tachycardia, three resuscitated ventricularfibrillation and 11 sudden cardiac death. Group 3 comprised110 control subjects. The different analysis techniques werecompared by their likelihood ratio for the prediction of ventriculartachycardia inducibility (Group 1) or major arrhythmic events(Group 2). The likelihood ratios of spectral-turbulence-analysis,acceleration spectrum analysis, spectral temporal mapping andtime-domain were 8·0, 3·3, 1·7, 1·3in Group 1, and 3·8, 2·1, 1·5, 2·6,in Group 2, while the corresponding false-positive rates inGroup 3 (control) were 0·9%, 10·0%, 4·5%,and 3·6%, respectively. Conclusion Spectral turbulence analysis was the most accurate techniquefor the prediction of either ventricular tachycardia inducibilityor major arrhythmic events after myocardial infarction. It alsoshowed the highest specificity among control subjects.     

Studies on the pathogenesis of the dawn phenomenon in insulin-dependent diabetic patients

To assess the role of hormonal factors in the pathogenesis of the dawn phenomenon, nocturnal (9:00 PM to 9 AM) concentrations of blood glucose, free insulin, and counterregulatory hormones were determined in eight insulin-dependent diabetic patients under feedback-controlled and continuous insulin infusions after previous blood glucose normalization. Under feedback control, mean insulin requirements, necessary for maintenance of euglycemia rose significantly in the early morning (11:00 PM to 3 AM: 8.4 +/- 1.4; 5 AM to 9 AM: 12.6 +/- 1.5 mU/kg/h; P less than 0.01). Mean free-insulin concentrations did not increase simultaneously. Correspondingly, mean insulin-clearance rates under continuous insulin infusion were higher in the morning (11:00 AM to 3 AM: 359 +/- 58; 5 AM to 9 AM: 459 +/- 72 mL/min/m2; P less than 0.05). Increases of insulin clearance rates were most marked (greater than 15%) in patients whose blood glucose rose during continuous insulin administration. Glucagon and norepinephrine concentrations were stable throughout both parts of the study. Cortisol and growth hormone exhibited the known nocturnal rhythms. Epinephrine levels were at the lower limit of detection at night and rose to normal basal concentrations at 9:00 AM. We conclude that increases of insulin clearance rates may be an important factor for the development of the dawn phenomenon while the role of most counter-regulatory hormones is still uncertain.