Intervención mínima sistematizada en el paciente hospitalizado: una herramienta que hay que conocer para poder utilizarla / Minimum systematized intervention in the hospitalized patient: a tool that must be known in order to use it

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A phase II study of perifosine (D-21226) in patients with previously untreated metastatic or locally advanced soft tissue sarcoma: A National Cancer Institute of Canada Clinical Trials Group trial.

UNLABELLED: BACKGROUND/PATIENTS AND METHODS: 16 adult patients with untreated measurable locally advanced or metastatic inoperable soft tissue sarcoma were treated with oral perifosine, a synthetic alkylphospholipid, believed to inhibit MAP kinase (MAP-K), protein kinase C (PKC), Akt and other regulatory proteins. Perifosine was administered orally in cycles for 21 days out of 28. Loading doses were given day 1 each cycle (900 mg cycle 1, 300 mg cycle 2+) and 150 mg daily was given days 2-21 of each cycle. Cycles were repeated until disease progression, unacceptable toxicity or patient refusal. RESULTS: Seventeen patients were enrolled; 16 and 15 were evaluable for toxicity and response, respectively. A total of 30 cycles of perifosine were administered. Most toxic effects were grade 1 or 2 and commonly included nausea, vomiting, diarrhea, and fatigue (> or =40%). Hematologic toxicity was generally mild. There were no significant biochemical abnormalities due to the drug reported. There were 4 serious adverse events (SAE)-none of which was related to perifosine. No objective responses were seen; 4 patients had stable disease for 1.3 to 8.2 months and the remainder of the patients had progressive disease. CONCLUSIONS: Perifosine when given according to this dosing schedule does not show evidence of activity in a mixed population of adult soft tissue sarcoma patients.

Molecular epidemiology of group B streptococci in Ireland: associations between serotype, invasive status and presence of genes encoding putative virulence factors.

Group B streptococcal isolates (n = 159) from the three Dublin maternity hospitals, were serotyped and analysed for the bac, bca, hylB, pepB, and rib genes. The serotype distribution of the isolates was Ia, 19.5%; Ib, 18.9%; II, 10.7%; III, 29.5%; IV, 1.9%; V, 15.1%; non-typeable, 4.4%. There was a statistically significant association between the serotype and invasive status (carriage or infection) of isolates (P < 0.005), but no significant association between serotype and degree of invasiveness was demonstrated. The presence or absence of each analysed gene was not associated with the invasive status of isolates. Statistically significant associations were revealed between bca and hylB (IS1548) (P = 0.0004) and between bac and bca (P=0.014). The bac, bca, hylB (IS1548) and rib genes and the numbers of tandem repeats in the bca gene showed significant associations with serotype. Almost 50% of serotype III isolates possessed at least one of the bac and bca genes and 55-65% of strains of serotypes Ia, Ib and II possessed the rib gene. Most serotype III isolates had IS1548 in their hylB genes. Serotype Ib was the only serotype in which more than half of the strains contained more tandem repeats in the bca gene than the overall mean for the GBS population studied of 7.4 repeats. These findings indicate that some previously reported associations between putative virulence factors and GBS disease require further study and clarification.

High-percentage lung delivery in children from detergent-treated spacers.

Pressurized metered-dose inhalers attached to spacers are now the most common form of delivery of anti-asthma medication in children. However, no reliable data are available of how much drug reaches the lungs in children of different ages. This information is crucial, as it determines the efficacy of therapy. In this study, we present information on the amount of drug reaching the lungs in children from a pressurized metered-dose inhaler attached to a detergent-coated spacer. We studied 18 asthmatic children inhaling radiolabeled salbutamol through detergent treated spacers to minimize electrostatic charge on the spacer wall. Lung deposition was much higher than expected when using detergent-coated spacers. Mean (SD) lung deposition, expressed as a percentage of the total actuated dose (five actuations), was 16.4% (5.5) in younger children inhaling through a small volume spacer, and 28.2% (6.7) and 41.8% (3. 8) in older children inhaling with different breathing patterns through a large volume spacer. These findings have major implications for dosage regimens for inhaled anti-asthma medication in children. Lower doses may be sufficient for adequate drugs delivered through spacers treated for static to achieve a desired clinical response.

Pulmonary vascular congestion selectively potentiates airway responsiveness in piglets.

The influence of pulmonary vascular congestion on the response of the airways and lung tissue to low doses of inhaled methacholine (MCh) was studied by inflating a balloon catheter in the left atrium of the heart in six piglets, with an additional five piglets serving as control animals. Congestion alone resulted in small increased in baseline airway (Raw) (14.6 +/- 3.7%) and tissue (Rti) resistance (8. 1 +/- 6.5%). Low-dose inhaled MCh (0.3 mg/ml) increased Raw and Rti in the control group by 10.8 +/- 10.3% and 42.2 +/- 29.5%, respectively. The increase in Raw with MCh in the presence of vascular engorgement was significantly greater (67.8 +/- 18.9%) but the increase in Rti (38.1 +/- 13.2%) was similar to that seen in the control group. Morphometric measurements were performed on transverse sections of large and small airways from nine additional piglets (three congested only, three MCh only, and three congestion plus MCh). The thickness of the inner airway wall was similar in all groups. Compared with MCh only piglets, the thickness of the outer airway wall (between the outer border of the smooth muscle and the surrounding lung parenchyma) was increased (p < 0.05) in engorged only and engorged plus MCh piglets. Compared with MCh only and engorgement only, the amount of airway smooth muscle shortening was greater (p < 0.05) in all airway size groups in piglets that underwent engorgement plus MCh challenge. The results of this study demonstrate that pulmonary vascular engorgement, induced by increased left atrial pressure, selectively enhances the airway, but not the parenchymal, response to inhaled MCh. These changes are associated with increased thickness of the outer airway wall in response to vascular congestion, suggesting that uncoupling of the mechanical interdependence between the airway smooth muscle and the lung parenchyma may have occurred. Mechanical uncoupling may reduce the load opposing smooth muscle shortening resulting in increased airway narrowing in response to low doses of inhaled methacholine.

Inhalation therapy in asthma: nebulizer or pressurized metered-dose inhaler with holding chamber? In vivo comparison of lung deposition in children.

OBJECTIVE: To compare lung deposition from a nebulizer and a pressurized metered-dose inhaler (pMDI)/holding chamber to determine their efficiency in aerosol delivery to children. STUDY DESIGN: Children with stable asthma (n = 17) aged 2 to 9 years inhaled in random order radiolabeled salbutamol from a nebulizer and a pMDI through a nonstatic holding chamber. Body and lung deposition of radiolabeled salbutamol was assessed with a gamma camera. RESULTS: Mean (absolute dose) total lung deposition expressed as a percentage of the nebulized dose was 5.4% (108 microg) in younger children (<4 years) and 11.1% (222 microg) in older children (>4 years). Mean (absolute dose) total lung deposition expressed as a percentage of the metered dose was 5.4% (21.6 microg) in younger and 9.6% (38.4 microg) in older children. CONCLUSIONS: For the same age groups we have shown equivalent percentages of total lung deposition of radiolabeled salbutamol aerosolized by either a nebulizer or a pMDI/holding chamber. However, the delivery rate per minute and the total dose of salbutamol deposited were significantly higher for the nebulizer.

Salbutamol delivery from a hydrofluoroalkane pressurized metered-dose inhaler in pediatric ventilator circuits: an in vitro study.

STUDY OBJECTIVES: The aim of our study was to determine the in vitro delivery of salbutamol from a pressurized metered-dose inhaler (pMDI) containing hydrofluoroalkane (HFA) propellant through various delivery devices to four models of a pediatric lung. DESIGN: To determine the effect of electrostatic charge, delivery of salbutamol was initially assessed with a multistage liquid impinger (MSLI) through an inline nonchamber device (Baxter MDI Adapter) and a small (Aerochamber MV) and a large (Nebuhaler) inline chamber device. Following this, the delivery was assessed to four lung models appropriate for a child of 70 kg, 50 kg, 15 kg, and 4 kg, with the same three reduced static devices inserted directly into a pediatric ventilator circuit. MEASUREMENTS AND RESULTS: Reduction of electrostatic charge improved small particle delivery through holding chambers to the MSLI by 12 to 14%. In the ventilator model, the mean delivery was between 1.9% and 5.4% for the nonchamber device, between 14.3% and 27.2% for the small holding chamber, and between 7.2% and 25.7% for the large holding chamber. Delivery was the least efficient in the 4-kg model compared to the 70-kg, 50-kg, and 15-kg models. CONCLUSIONS: Salbutamol from an HFA pMDI is delivered efficiently through inline holding chambers with reduced static in pediatric ventilator settings. A large holding chamber has no advantage over a small holding chamber. In addition, salbutamol delivery is more efficient through a holding chamber than through a nonchamber device.

Atypical mycobacterial pulmonary disease and bronchial obstruction in HIV-negative children.

Atypical mycobacterial infection in HIV-negative children usually presents with cervical lymphadenopathy. We report on 10 children who are HIV-negative and who presented with pulmonary disease, in whom either culture-proven atypical mycobacterium infection (four), positive avian Mantoux test (five), or lack of response to human tuberculosis treatment (one) had been observed. One case was subsequently diagnosed as chronic granulomatous disease and illustrates that children with atypical mycobacterial pulmonary infection should have their immune status fully investigated. Bronchial obstruction was observed in eight cases, and of these, endobronchial disease was found in six children. The diagnosis of atypical mycobacterial disease is difficult, and a negative avian Mantoux test does not exclude the diagnosis. The availability of clarithromycin and rifabutin has offered new therapeutic options in treating atypical mycobacterial pulmonary infection, but management of these cases can be prolonged and difficult.

The elimination half-life of urinary cotinine in children of tobacco-smoking mothers.

Exposure to environmental tobacco smoke (ETS) is strongly associated with childhood morbidity. Cotinine, the major metabolite of nicotine, is a useful marker of tobacco smoke exposure. Cotinine levels in infants are higher than in older children or adults exposed to the same reported quantity of ETS. One hypothesis to explain this difference is that the urinary elimination half-life of cotinine is different between infants and older children. Urine was collected at admission, 12, 24 and 48 h, cotinine levels were subsequently measured and then standardized by correcting for creatinine excretion. Urinary elimination half-life of cotinine was calculated in 31 infants and 23 older children. The median half-life was 28.3 h (range 6.3-258.5 h) in infants, and 27.14 h (range 9.7-99.42 h) in older children. A Mann-Whitney U test showed no significant difference in the median half-life of cotinine between the two age groups (P = 0.18). Multivariate linear regression analysis demonstrated no significant relationship between half-life of cotinine and corrected cotinine level (P = 0.24). Our results support the hypothesis that higher cotinine levels in infants is due to greater exposure, rather than slower metabolism of cotinine.

Haemoptysis in healthy children due to unsuspected foreign body.

Haemoptysis in otherwise healthy children is an uncommon event. Two cases of massive haemoptysis, subsequently requiring lobectomy, are discussed. In each case, foreign vegetable matter was identified despite previously normal bronchoscopy and minimal changes on chest radiograph.

Epidemiology of burns due to domestic flammable agents.

An analysis of the epidemiological factors relating to domestic flammable agents has shown that 17.7 per cent of admissions over a 5-year period were involved in domestic flammable injuries; 87.7 per cent of the patients were male, with 38.9 per cent being young males between 12 and 19 years old. Petrol and diesel accounted for 56.8 per cent of the burns and the average body surface area burned was 17.7 per cent. Most commonly the face, hands and limbs were burned, and the average length of stay was 18.25 days, 69.2 per cent of the burns were due to human error and were thus potentially preventable, 21.2 per cent had predisposing conditions with 8.9 per cent being due to alcohol. It was considered that the strategies to prevent these burns injuries should be aimed particularly at young males.

Pseudoscleroderma and phenylketonuria.

An infant girl with partial phenylketonuria developed pseudoscleroderma. After six years of follow up, both the neurologic and cutaneous conditions improved under a phenylalanine restricted diet. The probable roles of phenylalanine, tryptophan, tyrosine, and their metabolites may cause both conditions through possible transient hypersensitivity of cutaneous and muscular tissues.

Antinuclear antibody determinations in Ro(SSA)-positive, antinuclear antibody--negative lupus and Sjögren's syndrome patients.

Antinuclear antibody determinations were performed on the sera of twenty-eight Ro(SSA)-positive patients, who failed to demonstrate significant antinuclear antibody titers on mouse liver, with the use of various heterologous and homologous substrates. These studies demonstrated the following: (1) The existence of substrate specificity among various tissues and cells employed in the detection of antinuclear antibodies in Ro(SSA)-positive patients. (2) The existence of a significant group of Ro(SSA)-positive lupus patients with prominent cutaneous findings and systemic disease who, despite the employment of a variety of antinuclear substrates, failed to demonstrate significant antinuclear antibody titer.

Cutaneous Endosalpingiosis.

Endosalpingiosis is the aberrant growth of Fallopian tube epithelium outside of its normal location. This phenomenon has long been recognized by gynecologists, since it most often occurs in the pelvic cavity after salpingectomy. We describe a 30-year-old woman with cutaneous columnar ciliated cysts of the umbilicus and adjacent skin that developed shortly after salpingectomy. Evidence is presented that these cysts are cutaneous endosalpingiosis.

A sporotrichoid-like Mycobacterium kansasii infection of the skin treated with minocycline hydrochloride.

A sporotrichoid-like Mycobacterium kansasii infection of the skin is reported. This is the fifth reported case in the English literature of dermatological manifestations of a M. kansasii infection and the first reported case of a response to minocycline hydrochloride therapy.