Simple sequential treatment for primary spontaneous pneumothorax: one step closer.
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Humans↗
Biomedical subjects
M T Henry
Publications and source records attributed to M T Henry.
Efficacy of thrombolytic agents in the treatment of pulmonary embolism.
Recent guidelines recommend bolus-dose alteplase for treating massive pulmonary embolism (PE). However, the safest and most effective treatment is as yet unknown. In the present study, a meta-analysis of published studies of alteplase infusion, bolus-dose alteplase and streptokinase was performed. The outcome measures were as follows: objective assessment of thrombolysis; all-cause mortality; deaths due to initial PE, major bleeding episodes and recurrent PE; and morbidity. In total, 26 studies were identified; however, only two comparative studies of alteplase infusion versus either bolus-dose alteplase or streptokinase were found. Meta-analysis revealed no significant difference between the three regimens, but was compromised by a paucity of data. Crude analysis of summated data on thrombolytic efficacy from all studies revealed that alteplase infusion was more effective than bolus-dose alteplase (relative risk (RR): 1.95; 95% confidence interval (CI): 1.19-3.2), whereas streptokinase was more effective than alteplase infusion (RR: 1.27; 95% CI: 1.09-1.47). Alteplase infusion had a lower mortality due to the initial PE than both bolus-dose alteplase and streptokinase (RR: 0.16; 95% CI: 0.05-0.59 and RR: 0.13; 95% CI: 0.04-0.46, respectively). In conclusion, this evidence suggests that the three thrombolytic agents may vary in efficacy. However, large-scale randomised controlled trials are needed to confirm these results.
Fibrinolytic Agents↗
Nontuberculous mycobacteria in non-HIV patients: epidemiology, treatment and response.
Recent international guidelines published in 1997 and 1999 have proposed diagnostic and treatment criteria for disease caused by nontuberculous mycobacteria (NTM). In this paper, the epidemiological data, diagnostic criteria, treatment regimens and outcomes from 117 HIV-negative patients who had a positive culture for NTM between 1995-1999 are reviewed. The authors wished to identify factors associated with improved outcome in these patients. A total of 71 patients were believed to have a clinical disease caused by NTM, as defined by international criteria. A total of 72% patients were found to have had pulmonary disease. There was a rise in infections between 1995-1999, with a peak in infections in 1997. The most striking rise was in Mycobacterium avium intracellulare complex infections (1995: 33% infections; 1996: 36% infections; 1997: 41% infections; 1998: 61% infections; 1999: 57% infections). There was a link between deprivation and number of positive NTM isolates (34.4% isolates occurred in the areas of lowest Carstairs deprivation index versus 20.6% isolates from areas of least deprivation). There was a significant association between appropriate therapy, defined by American Thoracic Society and British Thoracic Society guidelines, and successful outcome (74%) in contrast to those who received inappropriate treatment prior to the publication of these guidelines. Nontuberculous mycobacteria infections remain a significant problem in non-HIV patients. Adherence to published guidelines may improve patient outcomes.
Adult↗
Secretory leukocyte proteinase inhibitor and elafin are resistant to degradation by MMP-8.
The naturally occurring neutrophil elastase inhibitors, alpha1-proteinase inhibitor (alpha1PI), secretory leukocyte proteinase inhibitor (SLPI), and elafin, are potential therapeutic agents in the treatment of neutrophil-mediated lung disease. However alpha1PI has been shown to be susceptible to inactivation by matrix metalloproteinases (MMPs) released by neutrophils, particularly neutrophil collagenase (MMP-8). The aim of this study was to determine if SLPI and elafin are similarly susceptible to degradation by this neutrophil-specific MMP. The effect of MMP-8 on SLPI and elafin was assessed by determining the neutrophil elastase inhibitory capacity (NEIC) and electrophoretic protein profile of both inhibitors following exposure to purified MMP-8. As a positive control, the effect of MMP-8 alpha1PI was assessed in parallel. Although treatment of alpha1PI with MMP-8 resulted in a significant decrease in its NEIC (P = .025), no similar decrease was observed with SLPI or elatin. Electrophoretic analysis confirmed digestion of alpha1PI by MMP-8 but no digestion of either SLPI or elafin was observed. These results demonstrate that SLPI and elafin are resistant to proteolytic inactivation by MMP-8, a property that may enhance their therapeutic application in neutrophil-mediated inflammatory lung disease.
Humans↗
Matrix metalloproteinases and tissue inhibitor of metalloproteinase-1 in sarcoidosis and IPF.
The purpose of this study was to examine the role of interstitial collagenases, members of the family of matrix metalloproteinases, in the development of pulmonary fibrosis. The activity, levels and molecular forms of collagenases (matrix metalloproteinases (MMP)-1, -8 and -13), gelatinase B (MM P-9) and its main endogenous inhibitor, tissue inhibitor of metalloproteinase-1 (TIMP-1) were assessed in bronchoalveolar lavage fluid (BALF) from patients with idiopathic pulmonary fibrosis (IPF) and sarcoidosis patients with varying degrees of pulmonary parenchymal involvement. Collagenase activity was elevated in IPF and group 3 sarcoidosis patients. A positive correlation between BALF collagenase activity and MMP-8 levels was also observed. Western immunoblotting revealed the presence of two isoforms of MMP-8 in patient samples; an 80 kD form representing latent enzyme from polymorphonuclear neutrophils and a 55 kD form representing the fibroblast-type proform. MMP-9 levels were also elevated in both IPF and group 3 sarcoidosis patients, while TIMP-1 levels remained normal, indicating a shift in the balance between the enzyme and inhibitor, favouring MMP-9. Matrix metalloproteinase-8 is the major contributor to the bronchoalveolar lavage fluid collagenase activity in the airways of patients with idiopathic pulmonary fibrosis and sarcoidosis and may initiate collagen destruction and remodelling leading to the development of pulmonary fibrosis.
Aged↗
Sirolimus: another cause of drug-induced interstitial pneumonitis.
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Hemorrhage↗
An alpha1-antitrypsin enhancer polymorphism is a genetic modifier of pulmonary outcome in cystic fibrosis.
Lung disease is the direct cause of death in over 90% of cystic fibrosis (CF) patients. Excess neutrophil elastase is an important determinant of pulmonary disease in CF. alpha1-antitrypsin (AAT), also known as alpha1-proteinase inhibitor (alpha1PI) is a major modulator of elastase activity. We investigated the hypothesis that an enhancer polymorphism in the AAT gene would contribute to pulmonary prognosis in CF. Respiratory function, chest X-ray scores, bacterial colonisation and infective exacerbation were assessed to evaluate pulmonary disease severity in the CF group. Sixteen patients were found to have the 1237A allele, and 108 the more frequent G allele. Contrary to expectation, the patients with the 1237A allele were found to have better indices of pulmonary disease progression than those without, as indicated by less change in X-ray score (1237A: 0.2+/-0.1; 1237G: 1.2+/-0.1; P = 0.002) and fewer infective exacerbations (1237A: 2.8+/-0.6; 1237G: 4.6+/-0.3; P = 0.03) over the preceding 2 years. Also, a higher proportion of the 1237A (25%) than the 1237G (6.5%) were not colonised by Pseudomonas Aeruginosa (P = 0.04). Prospective monitoring of infections for a further 2 years confirmed a lesser propensity to infection in patients with the 1237A allele. These trends were also observed in a tightly matched sub-set of CF genotypes of similar age and sex, thus confirming that these effects were independent of the CF genotype. These results indicate that this AAT enhancer polymorphism is associated with better pulmonary prognosis in CF. Though the number of CF patients with the polymorphism is small, and these data need to be confirmed in larger studies, they suggest that a cautious approach should perhaps be taken to treatment of CF patients with supplemental AAT.
Adolescent↗
Tracheobronchial involvement with Crohn's disease.
We report the case of a young woman with Crohn's disease of the bowel who presented with a purulent tracheobronchitis and life-threatening upper airway obstruction. Fibreoptic bronchoscopy demonstrated severe tracheal and upper bronchial pseudotumours and stenosis. The role of recent discontinuation of corticosteroids, for quiescent inflammatory bowel disease, in the development of endobronchial disease and the dramatic response in airway patency after reintroduction of prednisolone in this rare complication of Crohn's disease are discussed.
Adult↗
Progestogens and Cushing's syndrome.
We report 3 patients where Medroxyprogesterone Acetate (MPA = Provera) and Megestrol Acetate (Megace) in doses used for therapy of breast cancer, caused clinical hypercortisolism and Cushing's syndrome. Studies of the toxicity of Medroxyprogesterone Acetate list the commonest adverse events at 500 mg/day as weight gain, water retention, increased blood pressure, tremor, moon face, sweating, muscle cramps, vaginal bleeding and increased appetite. Glucocorticoid-like effects are seen in up to 30% of patients treated for longer than 6 weeks with mostly large doses of the order of 1500 mg/day but Cushing's syndrome has been reported in patients taking 400 mg/day. Neither the glucocorticoid-like effects or Cushing's syndrome have been previously observed with Megestrol Acetate. In the elderly female population receiving progestogens for neoplastic disease the progestogen itself could be an appreciable cause of morbidity both by causing glucocorticoid-like effects and Cushing's syndrome but also by lack of awareness of the danger of sudden withdrawal of these compounds when the hypothalmic-pituitary-adrenal (HPA) axis is suppressed. The signs and symptoms could be easily overlooked unless appropriate testing for Cushing's syndrome is carried out. While the progestogen may have to be continued indefinitely a dose decrease may be feasible with reduction of morbidity.
Adrenocortical Hyperfunction↗