Utility of exhaled nitric oxide as a noninvasive biomarker of lung inflammation in a disease model.

There is a great deal of interest in developing less invasive markers for monitoring airway inflammation and the effect of possible novel anti-inflammatory therapies that may take time to impact on disease pathology. Exhaled nitric oxide (eNO) has been shown to be a reproducible, noninvasive indicator of the inflammatory status of the airway in the clinic. The aim of the present study was to determine the usefulness of measuring eNO as a marker of the anti-inflammatory impact of glucocorticoid and an inhibitor of kappaB kinase-2 (IKK-2) inhibitor 2-[(aminocarbonyl)amino]-5-(4-fluorophenyl)-3-thiophenecarboxamide (TPCA-1), in a pre-clinical model of airway inflammation. Rats were given vehicle, budesonide or TPCA-1 prior to exposure to lipopolysaccharide, previously shown to induce an increase in eNO and airway neutrophilia/eosinophilia. Comparison of the effect of the two compounds on inflammatory components demonstrated a significant correlation between the impact on eNO and inflammatory cell burden in the airway. The current study demonstrates the usefulness of profiling potential disease-modifying therapies on exhaled nitric oxide levels and the way in which an effect on this noninvasive biomarker relates to effects on pathological parameters such as lung cellularity. Information from studies such as the current one would suggest that the measurement of exhaled nitric oxide has potential for monitoring inflammatory status in lung tissue.     

Radioiodine therapy of Graves' hyperthyroidism in patients without pre-existing ophthalmopathy: can glucocorticoids prevent the development of new ophthalmopathy?

BACKGROUND: Radioiodine therapy (RIT) combined with glucocorticoids is an effective therapy for Graves' disease, but it is debatable whether glucocorticoids should be applied in patients without Graves' ophthalmopathy (GO). METHODS: The effect of 0.4 - 0.5 mg prednisone every second day over a period of 5 weeks after RIT was monitored over a follow-up period of at least 12 months after RIT. A questionnaire was sent to 186 consecutive patients without GO concerning eye symptoms after RIT. 148 patients (80 %) answered. If eye symptoms had occurred after RIT, additional clinical examination was carried out at our outpatient clinic. The primary endpoint was the absence or onset of GO within the first year after RIT. RESULTS: Within 12 months after RIT the examination confirmed GO in 5 out of 148 patients (3.4 %). In all cases the symptoms were transient. No adverse reaction to the use of prednisone after RIT was noted. CONCLUSIONS: The risk of new GO in the first year after RIT was low and the clinical course of GO was mild when RIT was combined with a low-dose glucocorticoid regimen. Preventive administration of glucocorticoids can therefore be recommended in patients with Graves' disease even without evident GO.     

Maximal inspiratory and expiratory pressure measurement in tracheotomised patients.

The present study compared four different sites and conditions for the measurement of maximal inspiratory pressure (MIP) and maximal expiratory pressure (MEP) in 38 spontaneous breathing tracheotomised patients. Of the patients, 28 had chronic obstructive pulmonary disease (COPD). The four different conditions were: 1) through a cuff inflated cannula (condition A); 2) through the mouth with a deflated cannula (condition B); 3) through the mouth with a phonetic uncuffed cannula (condition C); and 4) through the mouth after stoma closure (condition D). Five trials in each condition were performed using a standardised method. The measurement of both MIP and MEP differed significantly depending on the condition of measurement. MIP taken in condition A was significantly higher when compared with conditions B, C and D. MEP in condition A was significantly higher when compared with condition B and D. In condition A the highest frequency of the best measurement of MIP and MEP was observed at the fourth and fifth effort, respectively. The same results were obtained after the selection of only COPD patients. In conclusion, respiratory muscle assessment differs significantly depending on measurement condition. Measurement through inflated cannula tracheotomy yields higher values of both maximal inspiratory and maximal expiratory pressure.     

Role of tumour necrosis factor-alpha receptor p75 in cigarette smoke-induced pulmonary inflammation and emphysema.

Chronic obstructive pulmonary disease (COPD) is characterised by a local pulmonary inflammatory response to respiratory pollutants and by systemic inflammation. Tumour necrosis factor (TNF)-alpha has been implicated in systemic effects of COPD and operates by binding the p55 (R1) and p75 (R2) TNF-alpha receptors. To investigate the contribution of each TNF-alpha receptor in the pathogenesis of COPD, the present study examined the effects of chronic air or cigarette smoke (CS) exposure in TNF-alpha R1 knockout (KO) mice, TNF-alpha R2 KO mice and wild type (WT) mice. CS was found to significantly increase the protein levels of soluble TNF-alpha R1 (by four-fold) and TNF-alpha R2 (by 10-fold) in the bronchoalveolar lavage of WT mice. After 3 months, CS induced a prominent pulmonary inflammatory cell influx in WT and TNF-alpha R1 KO mice. In TNF-alpha R2 KO mice, CS-induced pulmonary inflammation was clearly attenuated. After 6 months, no emphysema was observed in CS-exposed TNF-alpha R2 KO mice in contrast to WT and TNF-alpha R1 KO mice. CS-exposed WT and TNF-alpha R1 KO mice failed to gain weight, whereas the body mass of TNF-alpha R2 KO mice was not affected. These current findings suggest that both tumour necrosis factor-alpha receptors contribute to the pathogenesis of chronic obstructive pulmonary disease, but tumour necrosis factor-alpha receptor-2 is the most active receptor in the development of inflammation, emphysema and systemic weight loss in this murine model of chronic obstructive pulmonary disease.     

Characteristics and outcome of patients with active pulmonary tuberculosis requiring intensive care.

Severe tuberculosis (TB) requiring intensive care unit (ICU) care is rare but commonly known to be of markedly bad prognosis. The present study aimed to describe this condition and to determine the mortality rate and risk factors associated with mortality. Patients with confirmed TB admitted to ICU between 1990 and 2001 were retrospectively identified and enrolled. Clinical, radiological and bacteriological data at admission and during hospital stay were recorded. A multivariate analysis was performed to identify the predictive factors for mortality. A total of 58 TB patients (12 females, mean age 48 yrs) admitted to ICU were included. Mean Acute Physiology and Chronic Health Evaluation (APACHE) II score at admission was 13.1+/-5.6 and 22 of 58 (37.9%) patients required mechanical ventilation. The in-hospital mortality was 15 of 58 (25.9%); 13 (22.4%) patients died in the ICU. The mean survival of patients who died was 53.6 days (range 1-229), with 50% of the patients dying within the first 32 days. The factors independently associated with mortality were: acute renal failure, need for mechanical ventilation, chronic pancreatitis, sepsis, acute respiratory distress syndrome, and nosocomial pneumonia. These data indicate a high mortality of patients with tuberculosis requiring intensive care unit care and identifies new independently associated risk factors.     

The first 1000 cases of Italian Endovenous-laser Working Group (IEWG). Rationale, and long-term outcomes for the 1999-2003 period.

AIM: The innovations for disease management need to be thoroughly evaluated so that their benefits and potential downsides can be compared with the already existing approaches. Endovascular laser (EVL) treatment for varicose veins offers today several advantages over surgical standard stripping. The Italian Endovenous-laser Working Group (IEWG) is a homogeneous group of surgeons and phlebologists who have been using EVL since 1999 and has undertaken to examine EVL in a multicenter study starting from a well defined rationale, with the benefit of a single protocol to use. METHODS: In a cooperative, multicenter, clinical study, 1076 limbs in 1050 patients, mean age of 54.5 years, 241 males and 809 females affected by chronic venous insufficiency (CVI) were considered eligible for surgery and stratified by CEAP classification in a four-year period (January 1999 December 2003). Inclusion criteria were insufficiency of the great and/or small saphenous vein at various levels, beyond those accessory saphenous trunks with incompetence in the saphenofemoral junction. In all cases truncular reflux apparead up on duplex scan examination, with or without associated varicosities. All the patients underwent a surgery on the basis of the clinical assessment. All the centres involved performed treatment in conformity with the Food and Drug Administration (FDA) validated procedure, using an endo-laser venous system kit with a 810-980 nm diode. Duplex scan was performed in all patients after 36 months with very few lost to follow-up cases. RESULTS: In the immediate postoperative period the results have been impressive, with a very effective closure of incompetent great saphenous vein and the other treated varicose veins (the early occlusion rate has been 99%). Major complications have not been detected: in particular, no deep venous thrombosis (DVT) evaluated duplex ultrasound. The patients' acceptability and satisfaction regarding the procedure, have been measured by means of a questionnaire on the quality of life, and the result was 96.7%. After 36 months, the total occusion rate of saphenous trunks has been 97%. CONCLUSIONS: The first important Italian experience with EVL based on preoperative, perioperative and postoperative duplex control and which is also based on the patients' satisfaction at mid/long-term has indicated some advantages over the standard treatment with the stripping method. In terms of reduced postoperative pain, shorter sick leave, a faster resumption of the normal activities, and, in particular, the total absence of DVT, we can conclude that EVL is a good solution for all patients with anatomic and hemodinamic patterns for saphenous vein surgery.     

Effects of poor glucose handling on arterial stiffness and left ventricular mass in normal children.

AIM: Cardiovascular risk factors can be present in children and young adults. We previously found abnormal microvascular function in children who had glucose intolerance and insulin resistance. The aim of the present study was to investigate whether they also have abnormalities in left ventricular mass (LVM) and arterial stiffness. METHODS: We measured heart dimensions and LVM using echocardiography, and arterial stiffness using pulse wave analysis in 23 children with good glucose handling (postfeeding glucose: 3.9 to 5 mmol/L) and 21 with poor glucose handling (7.7 to 11.4 mmol/L). RESULTS: The time to pulse reflection was slightly shorter in the poorer glucose handlers (mean+/-SD: 143+/-10 vs 153+/-20 ms, P=0.04), suggestive of increased arterial stiffness. Also in this group, there were significant relationships between intraventricular septal thickness, blood pressure and body mass index, but not in the normal glucose handlers. CONCLUSIONS: We have found that normal children who are in the lowest quintile of glucose tolerance in comparison with their peers are exhibiting the first signs of arterial stiffening. In addition, we have seen the beginnings of a relationship between blood pressure, body mass index and left ventricular enlargement in this group. While these changes may not yet be clinically significant, their emergence might be further evidence of early predisposition to cardiovascular disease.     

Evaluation of a strict protocol approach in managing women with severe disease due to abortion.

AIM: To evaluate whether the introduction of a strict protocol approach based on the systemic evaluation of critically ill pregnant women with complications of abortion affected outcome. SETTING: Indigent South Africans managed in the regional and tertiary hospitals of the Pretoria Academic Complex. METHOD: Since 1997 a standard definition of severe acute maternal morbidity (SAMM) has been used in the Pretoria Academic Complex. All cases of SAMM and maternal deaths were entered on the Maternal Morbidity and Mortality Audit System programme. A comparison of outcome of severely ill women who had complications of abortion was made between 1997-1998 (original protocol) and 2002-2004 (strict protocol). OUTCOME MEASURES: The mortality index and prevalence of organ system failure or dysfunction. RESULTS: In 1997-1998 there were 43 women with SAMM who survived and a further 10 maternal deaths due to complications of abortion, compared with 107 women with SAMM and 7 maternal deaths during 2002-2004. The mortality index declined from 18.9% in 1997-1998 to 6.1% in 2002-2004 (p = 0.02, odds ratio 0.28, 95% confidence limits 0.10 - 0.79). Significantly more women had hypovolaemic shock in 2002-2004 compared with 1997-1998 (54.4% v. 35.8%, p = 0.04), but fewer women had immune system failure including septic shock (18.4% v. 47.2%, p = 0.0002) and metabolic dysfunction (0 v. 5.7%, p = 0.03) and there was a trend to less renal failure (10.5% v. 22.6%, p = 0.06) and cardiac failure (4.4% v. 13.2%, p = 0.08). CONCLUSION: The strict protocol approach based on systemic evaluation in managing critically ill pregnant women with complications of abortion, coupled with an intensive, regular feedback mechanism, has been associated with a reduction in the mortality index.