Introduction: Human neutrophil elastase (HNE) is involved in a variety of serious chronic diseases, especially cardiopulmonary pathologies. For this reason, the regulation of HNE activity represents a promising therapeutic approach, which is evident by the development of a number of new and selective HNE inhibitors, both in the academic and pharmaceutical environments.
Areas covered: The present review analyzes and summarizes the patent literature regarding human neutrophil elastase inhibitors for the treatment of cardiopulmonary diseases over 2014–2018.
Expert opinion: HNE is an interesting and defined target to treat various inflammatory diseases, including a number of cardiopulmonary pathologies. The research in this field is quite active, and a number of HNE inhibitors are currently in various stages of clinical development. In addition, new opportunities for HNE inhibitor development stem from recent studies demonstrating the involvement of HNE in many other inflammatory pathologies, including rheumatoid arthritis, inflammatory bowel disease, skin diseases, and cancer. Furthermore, the development of dual HNE/proteinase 3 inhibitors is being pursued as an innovative approach for the treatment of neutrophilic inflammatory diseases. Thus, these new developments will likely stimulate new and increased interest in this important therapeutic target and for the development of novel and selective HNE inhibitors. 相似文献
Mitotane is often considered the front-line hormonal therapyof adrenocortical carcinoma (ACC). An illustrative case concerningthis issue and the rationale to ponder other alternatives isreported. A 69 year-old woman, diagnosed with ACC was admittedwith hypertensive crisis, supraventricular tachycardia, congestiveheart-failure, diarrhoea and rabdomyolisis. Two years earlier,she had undergone 相似文献
Age is an important parameter for medico-legal cases. Many times doctors are called upon togive opinion about age of a person. For this objective methods of age determination are required. Age of epiphyseal union is an objective important method of age determination. But these ages varies with racial, geographic, climatic and various other factors. These variations have suggested need of separate standards of ossification for separate regions.Present work is undertaken to work out ages of epiphyseal union around wrist joint for Vidarbha region. Study is carried out in total 80 healthy subjects (44 girls and 36 boys) aging from 13 to 23 years &; having length of residence in Vidarbha not less than 10 years. The chronological age upto the day of examination is determined &; A-P view of right wrist joint is taken in each case. These radiographs are studied to determine age of union of epiphyses of lower end of radius &; lower end of ulna. These ages are compared with those reported from various states of India &; also from other countries &; found to vary appreciably. Sexual dimorphism for ages of epiphyseal union is also studied. 相似文献
A case of extensive deep venous thrombosis in a four a day old infant was presented. Unusually this patient was shown to be heterozygous for three thrombophilia genes; Factor V Leiden, prothrombin and antithrombin gene mutations, the latter being novel. Conclusion: There are no randomized controlled trials to guide management in deep venous thrombosis in the newborn but knowledge of the prothrombotic risk factors may help direct treatment. 相似文献
The jararacucu, one of the most dreaded snakes of Brazil, southern Bolivia,
Paraguay and northeastern Argentina, is a heavily-built pit viper which may
grow to a length of 2.2 m. Up to 1000 mg (dry weight) of highly-lethal
venom may be milked from its venom glands on a single occasion. It has
accounted for 0.8% to 10% of series of snake bites in Sao Paulo State,
Brazil. We examined 29 cases of proven jararacucu bites recruited over a
20-year period in two Sao Paulo hospitals. Severe signs of local and
systemic envenoming, (local necrosis, shock, spontaneous systemic bleeding,
renal failure) were seen only in patients bitten by snakes longer than 50
cm; bites by shorter specimens were more likely to cause incoagulable
blood. Fourteen patients developed coagulopathy, six local necrosis
(requiring amputation in one) and five local abscesses. Two became shocked
and four developed renal failure. Three patients, aged 3, 11 and 65 years,
died 18.75, 27.75 and 83 h after being bitten, with respiratory and
circulatory failure despite large doses of specific antivenom and
intensive-care- unit management. In two patients, autopsies revealed acute
renal tubular necrosis, cerebral oedema, haemorrhagic rhabdomyolysis at the
site of the bite and disseminated intravascular coagulation. In one
survivor with chronic renal failure, renal biopsy showed bilateral cortical
necrosis; the patient remains dependent on haemodialysis. Effects of
polyspecific Bothrops antivenom were not impressive, and it has been
suggested that anti-Bothrops and anti-Crotalus antivenoms should be given
in combination.
相似文献
BACKGROUND: The impact of AIDS case list cross-referencing in human immunodeficiency virus look-back was assessed. STUDY DESIGN AND METHODS: Post-1977 blood donations from former donors identified by 11 collaborating health departments as having developed AIDS have been traced at Irwin Memorial Blood Centers since 1983. To assess the changing efficacy of AIDS case list cross-referencing in identifying infected donors and recipients, trends in cases reported through December 1992 were analyzed. RESULTS: Previous donors (n = 638) were identified from 21,917 AIDS case listings, for an overall match rate of 2.9 percent. The rate of detection of previous donors from listings of AIDS cases declined from a peak of 5.3 percent in 1985 to 1.6 percent in 1992. Overall, 86 percent (1824/2122) of donations by persons later reported on AIDS case lists were made prior to January 1983 when risk exclusion measures were initiated. Of the 212 known infected recipients linked to AIDS case list donors, 87 (41%) were previously identified by other look-back approaches. The rate of identification of infected recipients detected exclusively through AIDS case listings declined from a mean of 21 per year from 1984 to 1987 to a mean of 3 per year from 1990 to 1992. No transmissions have been documented from donations prior to 1979. CONCLUSION: These findings demonstrate the declining yield of AIDS case list cross-referencing as a trigger for human immunodeficiency virus look-back. Continued reevaluation of look-back programs is essential so that their various components may be curtailed when justified. 相似文献
The long-term effects of cimetidine on the occurrence of gastricand oesophageal cancer were assessed in a prospective cohortstudy of 9928 patients who had been prescribed cimetidine. Theywere first identified between 1978 and 1980, and cancer registrationsand deaths were identified among them over a period of up to10 years. One hundred and eleven cancers were identified afterthe start of cimetidine treatment: 71 were adenocarcinomas ofthe stomach, 27 were carcinomas of the cardia and/or oesophagus(22 adenocarcinomas, five unknown histology) and the remaining13 tumours were squamous cell cancers of the oesophagus. Onlysix patients presented with early gastric cancers. Over a periodof eight years the ratio of observed to expected (O/E) gastriccancer deaths has fallen from 10.7 (p<0.001) to 1.2 (NS).The O/E ratio of oesophageal cancer deaths also fell over thefirst six years of study, from 5.4 (p<0.01) to 1.4 (NS) butit has risen slightly in years 7 and 8 to 3.7 (p<0.05). Thesefindings do not suggest that there is an increased risk of developingoesophageal or gastric cancer from cimetidine treatment, andare generally consistent with cimetidine being used inadvertentlyto treat the early symptoms of gastric and oesophageal cancer.The slight rise in oesophageal cancer deaths in years 7 and8 was unexpected and will be the subject of further observation. 相似文献
The European Association for the Study of the Liver (EASL) treatment recommendations for hepatitis C no longer discriminate between HIV/hepatitis C virus (HCV)‐coinfected and HCV‐monoinfected patients. However, recent data from Spain are questioning these recommendations on the basis of the findings of higher relapse rates and lower cure rates in HIV/HCV‐infected subjects. The aim of our study was to compare HCV cure rates in monoinfected and coinfected patients from Germany.
Methods
Data acquired from the Deutsches Hepatitis C‐Registry were analysed. A total of 5657 HCV‐monoinfected subjects and 488 HIV/HCV‐coinfected patients were included in the study. Rates of sustained virological response 12 weeks after the scheduled end of therapy (SVR12) were collected in both subgroups and in cirrhotic and noncirrhotic patients.
Results
HIV/HCV‐coinfected patients were more frequently male (84.6% vs. 56.4%, respectively; P <0.001) and younger than HCV‐monoinfected subjects (46.5 ± 9 vs. 53.8 ± 12.5 years, respectively; P < 0.001). The CD4 blood cell count was > 350 cells/μL in 63.1% of HIV‐positive subjects and 88.7% were on antiretroviral therapy. SVR12 rates were 90.3% (5111 of 5657) in our HCV‐monoinfected cohort and 91.2% (445 of 488) in our coinfected patients. Liver cirrhosis was confirmed in 1667 of 5657 (29.5%) monoinfected patients and 84 of 488 (17.2%; P < 0.001) coinfected patients. SVR12 rates did not differ between HCV‐monoinfected and HIV/HCV‐coinfected patients with liver cirrhosis (87.8% vs. 89.3%, respectively; P =0.864). A treatment duration of 8 weeks did not reduce the percentage of patients with SVR12 in either subgroup (93.7% in both groups).
Conclusions
We found high SVR12 rates in monoinfected as well as coinfected individuals. No differences were detected between the two subgroups regardless of whether there was accompanying liver cirrhosis or a shortened treatment duration. 相似文献