Molecular immaturity of the immune receptor genes in a case of acute leukaemia with complete lymphoid lineage switch.
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Acute Disease↗
Biomedical subjects
A Torres
Publications and source records attributed to A Torres.
Use of elastin fibre detection in the diagnosis of ventilator associated pneumonia.
BACKGROUND: Elastin fibre detection could be a simple and reliable marker of ventilator associated pneumonia. To confirm this, a prospective study was undertaken to evaluate the diagnostic yield of elastin fibre detection in the diagnosis of ventilator associated pneumonia. METHODS: Seventy eight mechanically ventilated patients were evaluated by examining endotracheal aspirates for the presence of elastin fibres. All patients were previously treated with antibiotics. Quantitative bacterial cultures of endotracheal aspirates and protected specimen brush samples were also performed. Patients were classified into three diagnostic categories: group 1, definite pneumonia (n = 25); group 2, probable pneumonia (n = 35); and group 3, controls (n = 18). RESULTS: Patients with definite and probable pneumonia were grouped together. The presence of elastin fibres in endotracheal aspirate samples was more frequent in groups 1 and 2, being found in 19 of the 60 patients compared with five of the control group. Although the presence of elastin fibres had a low sensitivity (32%), it was a reasonably specific marker (72%) of pneumonia. This specificity increased to 86% and 81% respectively when only Gram negative bacilli and Pseudomonas aeruginosa pneumonia were considered. Again, calculated sensitivity was 43% and 44% when analysing cases infected by Gram negative bacilli and Ps aeruginosa, respectively. The negative predictive value of the detection of elastin fibres in pneumonia caused by Ps aeruginosa was 81%. Detection was more frequent with infection by Gram negative bacilli (14/19), particularly with Ps aeruginosa (8/14). By contrast, pneumonia due to Gram positive cocci or non-bacterial agents uncommonly resulted in positive elastin fibre preparations (4/19, 21%). When analysing patients with and without chronic obstructive pulmonary disease, the diagnostic value of elastin fibre detection did not change. CONCLUSIONS: Potassium hydroxide preparation of elastin fibres is a rapid and simple specific marker of ventilator associated pneumonia and may be a useful technique to help diagnose pulmonary infections in mechanically ventilated patients, although this assessment is at present limited to patients without adult respiratory distress syndrome.
Adult↗
Prognostic factors influencing the outcome in pneumocystis carinii pneumonia in patients with AIDS.
BACKGROUND: Studies attempting to identify the prognostic factors that influence the outcome of Pneumocystis carinii pneumonia (PCP) in patients with AIDS using a multivariate analysis are few. In order to identify those prognostic factors amenable to medical intervention, univariate and multivariate analyses were performed on 102 patients with AIDS suffering a first episode of PCP. METHODS: One hundred and two consecutive patients with AIDS (51% drug abusers, 45% homosexuals, and 4% with other HIV risk factors) admitted to our institution between 1986 and 1989 whose respiratory infection was diagnosed by bronchoalveolar lavage were studied prospectively. RESULTS: The overall mortality was 28%, rising to 79% in those patients who required mechanical ventilation. According to univariate analysis the following variables were related to a poor prognosis: age > 35 years; risk factor for HIV infection other than drug abuse; and AIDS diagnosis confirmed before 1988; PaO2 < 8 kPa at admission; severe acute respiratory failure on admission (PaO2/FIO2 < 20 kPa); mechanical ventilation; antibiotic therapy for PCP other than trimethoprim-sulphamethoxazole; multiple microbial pulmonary infection; serum lactate dehydrogenase (LDH) > 22.5 mukat/l on admission; serum albumin level < 30 g/l. Multivariate analysis showed that only mechanical ventilation was independently associated with a poor outcome. CONCLUSIONS: The mortality of AIDS patients presenting with a first episode of PCP before 1990 was high (28%). The main prognostic factor associated with poor outcome was the requirement for mechanical ventilation due to severe acute respiratory failure.
AIDS-Related Opportunistic Infections↗
Effect of K+ channel blockade on fatigue in rat diaphragm muscle.
K+ channel blockers increase skeletal muscle force during twitch contractions; the present study determined whether K+ channel blockade also modulates force during longer term and higher frequency stimulation. 4-Aminopyridine (4-AP; 0.3 mM) increased rat diaphragm force during twitch, 5-Hz and 20-Hz but not 100-Hz stimulation, and prolonged isometric contraction but not half-relaxation time. In response to continuous 5-Hz stimulation, the rate of force decline was accelerated by 4-AP so that over time force dropped below that of control muscle strips. In response to intermittent 20-Hz stimulation, 4-AP produced an early force potentiation; the 4-AP-induced force increase was maintained throughout repetitive stimulation despite an accelerated rate of force decline. In response to continuous 100-Hz stimulation, 4-AP did not affect rate of force decline. During 5- and 20-Hz stimulation, there was an interaction between 4-AP and duration of stimulation in prolonging contraction and especially half-relaxation time. Tetraethylammonium (10 mM) augmented diaphragm force less than did 4-AP, did not affect rate of force decline during 5-Hz stimulation, and did not interact with fatigue to prolong isometric twitch kinetics. These data indicate that K+ channel blockade with 4-AP increases diaphragm force at low to intermediate stimulation frequencies, may increase early force potentiation during repetitive contraction, and depending on stimulation pattern either accelerates or has no effect on rate of fatigue.
4-Aminopyridine↗
Re-intubation increases the risk of nosocomial pneumonia in patients needing mechanical ventilation.
In order to confirm that re-intubation can be a risk factor of nosocomial pneumonia in mechanically ventilated patients, a case-control study was performed. Forty consecutive patients needing re-intubation were selected as cases. Each case was paired with a matched control for the previous duration of mechanical ventilation (+/- 2 d). Nineteen (47%) of the cases developed pneumonia after re-intubation compared with 4 (10%) of the controls (odds ratio [OR] = 8.5; 95% confidence interval [CI] 1.7 to 105.9; p = 0.0007). After adjusting for age, sex, and presence of prior bronchoscopy, the conditional logistic regression analysis demonstrated that re-intubation was the only significant factor related to the development of pneumonia (OR: 5.94; 95% CI 1.27 to 22.71; p = 0.023). Sixteen (73%) of the 22 patients lying semirecumbent during the interval between extubation and re-intubation developed nosocomial pneumonia versus three (16%) of the 18 in supine position (p = 0.001). These results indicate that semirecumbency during the period between extubation and re-intubation may play a role in nosocomial pneumonia development in patients who need re-intubation. Total intensive care unit stay (19.4 +/- 10 versus 13.9 +/- 11.9 days, p = 0.0008) and crude mortality (35 versus 20%, p = 0.14) were also higher in re-intubated patients when compared with controls. We conclude that re-intubation is a risk factor for ventilator-associated pneumonia and might be avoided in a substantial number of cases.
Case-Control Studies↗
Semirecumbent position protects from pulmonary aspiration but not completely from gastroesophageal reflux in mechanically ventilated patients.
The aim of this study was to evaluate the effect of two body positions (supine and semirecumbency) on the dynamics of gastroesophageal reflux (GER) in 15 patients requiring mechanical ventilation and having a nasogastric tube in place. Samples of gastric contents, pharyngeal and bronchial secretions, and blood were obtained at baseline and every hour during a period of 5 h after nasogastric tube isotopic instillation of 37 megabecquerels of Tc99m. Radioactivity counting (RAc) was performed using a gamma counter with correction for decay. Irrespective of the body position, all patients showed at 3, 4, and 5 h after the isotope instillation a significant increase in RAc of the oropharyngeal contents (p < 0.05, each), indicating GER. Although RAc values in the pharynx were higher in supine from 1 through 4 h (p < 0.05), at the end of the study (5 h) the values did not differ between each position. Likewise, the slopes of the regression lines of sequential oropharyngeal RAc values were not different between each position (0.39 +/- 0.09 versus 0.45 +/- 0.11, respectively). In contrast, RAc values in bronchial secretions were higher at 5 h in the supine position compared with baseline (p < 0.05) and to semirecumbency (p < 0.01). These results strongly support that GER in mechanically ventilated patients with a nasogastric tube is a feature occurring irrespective of body position. Semirecumbent position does not protect completely from GER and subsequently from oropharyngeal colonization from gastric origin.
Cross Infection↗
Diffuse alveolar hemorrhage in allogeneic bone marrow transplantation. A postmortem study.
To define better the syndrome of diffuse alveolar hemorrhage (DAH), we conducted a postmortem study in 77 patients who died of pulmonary complications, distributed into three groups. Group A included 47 patients with hematologic diseases treated with allogeneic bone marrow transplant (BMT); Group B, 20 patients with hematologic diseases treated with conventional chemotherapy; and Group C, 10 patients without hematologic diseases. The diagnosis of DAH was established when there was blood in at least 30% of the lung tissue evaluated without evidence of infection or any other pathologic change that could account for its presence. The presence of an associated pulmonary complication was considered only when there was normal lung parenchyma between both blood and the specific lesions. Diffuse alveolar hemorrhage was shown in 11 patients in Group A (23%) compared with 1 patient in Group B (5%) (p < 0.05). Of the 11 patients with DAH in Group A, 10 had some associated pulmonary complication: 7 presented with diffuse alveolar damage (DAD), 2 with associated bacterial pneumonia and 1 with invasive aspergillosis, 2 others had an associated cytomegalovirus (CMV) pneumonitis, and the remaining patients had an associated herpes pneumonia. There were no clinical differences between patients with and without DAH. Of 8 patients with confirmed DAH in Group A, who had been submitted to a bronchoscopic examination within 1 wk of death, 4 had normal BAL fluid; by contrast, 7 of 13 patients without DAH had hemorrhagic BAL fluid.(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
Role of bronchoalveolar lavage in the diagnosis of fat embolism syndrome.
Fat embolism syndrome (FES) is a serious clinical disorder occurring in trauma patients. The diagnosis of fat embolism syndrome may be difficult to establish clinically. We therefore wanted to investigate the usefulness of bronchoalveolar lavage (BAL) in the diagnostic evaluation of fat embolism syndrome. We analysed the presence of fat droplets in BAL cells in 32 trauma patients (7 with full diagnostic criteria of fat embolism syndrome, 17 with incomplete diagnostic criteria, and 8 with no diagnostic criteria at the time of bronchoscopy), 9 nontrauma patients with acute respiratory failure and radiographic pulmonary infiltrates, and a control group composed of 10 individuals. An increased percentage of oil red O positive alveolar macrophages (cut-off point > 3%) in BAL was found in 6 out of 7 patients with definite clinical criteria of fat embolism syndrome, and in 6 out of 20 trauma patients without the clinical diagnosis of fat embolism syndrome. In two patients with fat embolism syndrome, sequential BAL showed that the percentage of positive macrophages decreased when the clinical manifestations disappeared. An increased number of BAL macrophages with fat droplets was also observed in two trauma patients without evidence of fat embolism syndrome after long-bone surgical intervention. By contrast, all non-trauma patients had a percentage of positive cells lower than 3%. Our findings suggest that BAL oil red O positive macrophages are frequently observed in trauma patients irrespective of the presence of fat embolism syndrome. Conceivably, a high number of oil red O positive macrophages could reflect clinically silent fat embolization.
Adult↗
Aetiology and prognostic factors of patients with AIDS presenting life-threatening acute respiratory failure.
Respiratory failure is a significant contributor to morbidity and mortality in patients with the acquired immune deficiency syndrome (AIDS). We performed a study to investigate the aetiology, prognostic factors, and short- and long-term outcome of AIDS patients with life-threatening respiratory failure and pulmonary infiltrates. Forty-two AIDS patients (29 of whom required mechanical ventilation), admitted to a Respiratory Intensive Care Unit (ICU) from 1985 to 1992 because of severe respiratory failure (arterial oxygen tension/fractional inspiratory oxygen (Pa,O2/FI,O2) ratio at hospital admission 19 +/- 14 kPa (mean +/- SD)) and diffuse pulmonary infiltrates, were studied for evaluation of the aetiology and outcome. Necropsy studies were performed in 14 out of 23 (61%) patients who died. Pneumocystis carinii was the most common aetiology of pulmonary infiltrates (28 patients (67%)). Overall, 19 patients survived (45%) and 23 (55%) died. A multivariate analysis of prognostic factors influencing the outcome of the whole population showed that the presence of P. carinii pneumonia and the requirement for mechanical ventilation (MV) were the major determinants of outcome for this type of patient. The median survival time after ICU discharge for P. carinii pneumonia patients was lower (49 days) when compared to that of the remaining patients (154 days). Median survival time after ICU discharge for patients needing MV (112 days) did not differ from that observed in patients not requiring artificial ventilatory support (154 days). Although the ICU survival rate in this study was reasonable, 55% for the whole population, and 36% for P. carinii pneumonia patients, the poor outcome after ICU discharge, in particular for P. carinii pneumonia patients, deserves the reassessment of ICU admission criteria for this type of AIDS population.
AIDS-Related Opportunistic Infections↗
Empirical treatment of nonsevere community-acquired pneumonia: still a difficult issue.
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Anti-Bacterial Agents↗
Glucocorticoid stimulation interacts with sympathetic innervation to affect cardiac development in oculo.
The effects of chronic glucocorticoid stimulation and sympathetic innervation on myocardium developing in the absence of hemodynamic load were tested by grafting embryonic rat hearts into the anterior eye chamber (in oculo) of adult host rats. Myocardial grafts in control rats with normal hormonal milieu were compared with grafts in rats with chronic glucocorticoid stimulation (dexamethasone 40 micrograms/d) or glucocorticoid receptor type II blockade (RU 38486, 330 micrograms/d). Unilateral superior cervical ganglionectomy of one eye chamber prevented sympathetic innervation to one graft in each host. Two indices of growth, graft size (projected area) and terminal graft weight, were obtained. Dexamethasone treatment increased both size and weight of sympathetically innervated grafts, whereas RU486 treatment significantly decreased graft weight. Conversely, dexamethasone treatment decreased graft size in denervated eye chambers, whereas RU486 treatment had no effect. No differences in graft beating rate were observed among conditions. Sympathetic innervation modulated the effect of glucocorticoids on developing myocardium, suggesting that growth of sympathetically innervated myocardium is enhanced with glucocorticoid exposure, but growth of noninnervated myocardium (e.g. fetal heart) may be compromised by excessive glucocorticoid exposure.
Animals↗
Molecular heterogeneity in childhood precursor B acute lymphoblastic leukemia with immunoglobulin heavy chain gene in germline configuration.
Four childhood acute leukemias with morphological, cytochemical and immunological characteristics correlating to precursor B lymphocyte and with germline configuration of the immunoglobulin heavy chain joining region were studied for the organization of the C mu segment. Two of the four lymphoblast samples retained the germline configuration of both JH and C mu regions. The other two samples showed delection of the entire JH region resulting in the rearrangement of the C mu region. In contrast to patients with C mu rearrangement, patients with C mu in germline form were not able to achieve complete remission after induction therapy. Study of the C mu region in patients with JH segment in germline configuration could separate subgroups in childhood precursor B acute lymphoblastic leukemia with different prognoses.
Adolescent↗
Bovine somatotropin dose titration in lactating dairy ewes. 1. Milk yield and milk composition.
Seventy-four lactating dairy ewes were injected with recombinant bST (sometribove) in a sustained-release formulation. Ewes received 0, 80, 160, or 240 mg of bST every 14 d from wk 3 to 8 of lactation (part 1) and 0, 80, or 160 mg of bST every 14 d from wk 11 to 23 of lactation (part 2). Sometribove increased milk yield over that of the controls for all treatment groups. The increase was largest for the group that was administered 160 mg of bST: milk yield was 34.1 and 53.2% and 6% FCM was 36.9 and 51.8% for parts 1 and 2 of the study, respectively. Sometribove increased milk fat during part 1 of the study, but decreased milk fat during part 2. Protein contents of milk were decreased throughout the study. For all group, bST increased the yield of milk constituents over that of the controls. When milking frequency was reduced from twice to once daily, the difference in milk yield between control ewes and those treated with bST was maintained. Neither mastitis incidence nor milk SCC were affected by bST treatment. Recombinant bST is efficacious in increasing both actual milk yield and 6% FCM over the dose range of 80 to 240 mg/14 d without adverse effects for lactating ewes.
Animals↗
Markers of ventilator-associated pneumonia.
The diagnosis of ventilator-associated pneumonia (VAP) is difficult for several reasons. Firstly, clinical markers show a large percentage of false-positive and false-negative results. Secondly, microbiological diagnosis based on quantitative cultures of protected specimen brush (PSB), bronchoalveolar lavage (BAL), and endotracheal aspirates also present false-positive and false-negative results. Furthermore, definite results are delayed for 48-72 hours. For all these reasons it would be an advantage to have a biological marker of ventilator-associated pneumonia in clinical practice. Since clinical features of pneumonia in mechanically ventilated patients are neither specific nor sensitive, rapid markers of pneumonia might be of great assistance to the clinician in deciding whether to start an empiric antibiotic regimen. A marker of ventilator-associated pneumonia could be a rapid alternative diagnostic method which permits the definite diagnosis of pneumonia. Accordingly, specific markers of VAP, namely the presence of intracellular microorganisms, the detection of elastin fibres, the antibody-coated bacteria test, the level of endotoxin in bronchoalveolar lavage fluid, the local production of interleukin-8, the levels of lactate dehydrogenase, and decreased surfactant protein A, may be important as they can provide a rapid diagnosis of VAP. Among the markers alluded to above, the search for intracellular bacteria in polymorphonuclear leukocytes or macrophages is the most widely validated technique with an excellent specificity, provided that prior antibiotics are not given. However, this technique has its own limitations; it requires a considerable time effort for the microbiologist, and also compels the performance of BAL, a technique not always harmless to the patient.
Antibody-Coated Bacteria Test, Urinary↗
The role of the gastric reservoir in ventilator-associated pneumonia.
Ventilator-associated pneumonia (VAP) is a common complication of mechanical ventilation with an incidence ranging from 9-70% and averaging around 25%. The pathogenesis of VAP requires abnormal oropharyngeal and gastric colonisation and then aspiration of these contents into the lower airways. Another co-existing mechanism could be direct oropharyngeal or lower airways inoculation of microorganisms through contaminated respiratory therapy equipment. Ventilator-associated pneumonia develops easily if aspiration or inoculation of microorganisms occur in patients with artificial airways and in whom mechanical, cellular and/or humoral defences are altered. Both host factors and treatments may alter pulmonary defence mechanisms; these too may contribute to the development of VAP. An alternative mechanism to explain VAP is bacterial translocation, although this mechanism is still under investigation. Figure 1 illustrates a schema of the pathogenesis of VAP. In this paper we review the possible role of the gastric reservoir in the aetiology of VAP, emphasising the following issues: 1. Risk factors for gastric colonisation 2. Clinical evidence of gastric aspiration to the lower airways in mechanically ventilated patients 3. Clinical evidence and controversies surrounding the role of the gastric reservoir in ventilator-associated pneumonia 4. The role of bacterial translocation as a mechanism for the development of VAP 5. A summary of prophylactic measures.
Bacterial Infections↗
Nonsteroidal human progesterone receptor modulators from the marine alga Cymopolia barbata.
The co-transfection assay is a novel functional assay using cells transiently transfected with plasmids encoding intracellular receptors and corresponding reporter genes. Using this assay, natural product extracts were tested to identify compounds that modulate intracellular receptor activity, measured as changes in reporter gene activity. A crude extract of the marine alga Cymopolia barbata was found to inhibit progesterone-stimulated reporter gene expression in cells transfected with the human progesterone receptor (hPR) and an appropriate reporter construct. Purification of the active constituents of the extract, guided by the co-transfection assay, yielded two diastereomers of cyclocymopol monomethyl ether, possessing opposing pharmacological activities with the hPR. The antagonist (3R)-cyclocymopol monomethyl ether (LG100127) blocked 1 nM progesterone-stimulated reporter gene expression with an IC50 value of 549 +/- 55 nM in the co-transfection assay. The agonist (3S)-cyclocymopol monomethyl ether (LG100128) had efficacy similar to that of progesterone and an EC50 value of 35 +/- 2 nM. Stimulation by progesterone of the hPR in the human breast cancer cell line T-47D results in enhanced expression of alkaline phosphatase; LG100127 blocked alkaline phosphatase expression stimulated either by progesterone or by LG100128, and LG100128 mimicked progesterone in this assay. Both diastereomers displaced [3H]progesterone from baculovirus-expressed hPR. LG100127 and LG100128 each interacted with the human androgen receptor but did not interact with the human glucocorticoid receptor, estrogen receptor, vitamin D receptor, or retinoid receptors. In summary, these in vitro studies describe the first nonsteroidal pharmacophores for the hPR and demonstrate the use of the co-transfection assay in their discovery.
Animals↗
Community-acquired pneumonia in the intensive care unit.
CAP requiring ICU admission is a distinct clinical entity. The mortality rate of pneumonia in this subset of patients has been unchanged in the past several years. Aggressive diagnostic of strategies to establish the causative pathogens of pneumonia rapidly will enable clinicians to adjust antibiotic therapy appropriately. It is hoped that new adjunctive therapeutic options that positively influence host-related factors and bolster pulmonary antibacterial defense will result in reduced morbidity and mortality.
AIDS-Related Opportunistic Infections↗
Caloric rather than protein deficiency predominates in stable chronic haemodialysis patients.
BACKGROUND: The monitoring of energy and protein intake is considered fundamental in uraemic patients. However, in the clinical practice only protein ingestion is indirectly evaluated by the protein catabolic rate. METHODS: In a cross-sectional study we evaluated the relationship between caloric and protein intake of 29 stable chronic haemodialysis patients (18M, 11F, mean age 49 +/- 17 years, 68 +/- 6 months on maintenance haemodialysis), and the validity of protein catabolic rate determination. Normalized protein catabolic rate was obtained according to Sargent's formula, and Watson's equation was used to calculate urea distribution volume. Caloric and protein intake were recorded during a 3-day period, and average daily ingestion of nutrients was calculated using a computerized diet analysis system. RESULTS: A greater reduction of daily energy intake (26.8 +/- 11.9 Kcal/kg bw) than daily protein intake (1.02 +/- 0.4 g/kg bw) was observed. Fifty-nine percent of patients had low protein intake while 86% of patients had lower caloric intake than recommended. An inverse relationship between age and protein (r = -0.65, P < 0.001) or caloric intake (r = -0.67, P < 0.001) was observed. Negative relationships between daily protein (r = -0.60, P < 0.01) and also caloric intake (r = -0.39, P < 0.05) and the ratio between the urea generation rate and the total dietary nitrogen were found, indicating that in patients with low nutrient intake the nitrogen balance tends to be negative. Normalized protein catabolic rate was directly correlated with protein intake (r = 0.77, P < 0.001). A protein catabolic rate cut-off of 1 g/kg bw correctly identified all patients with normal daily protein intake, and 14 of 17 patients with deficient daily protein intake (< 1 g/kg bw). Thus in only 10% of haemodialysis patients an imbalance between both parameters was observed. Moreover, patients with a daily protein intake lower than 1 g/kg bw were older and showed lower BUN and protein catabolic rate values than their counterparts. CONCLUSIONS: Nutritional abnormalities are frequently found, even in apparently clinically stable patients on chronic haemodialysis. Caloric rather than protein undernutrition is the major abnormality of their wasting. Inadequate intake of proteins and calories appears more commonly in older patients, and in association with lower BUN and protein catabolic rate values. Although normalized protein catabolic rate shows a direct correlation with a daily protein intake, the identity line shows that when daily protein intake was lower than 1 g/kg bw, it was overestimated by protein catabolic rate. Conversely, when daily protein intake is higher than 1 g/kg bw it is underestimated by the protein catabolic rate. This relationship should to be considered when interpreting the protein catabolic rate in a clinical setting.
Adolescent↗