Keratoconus: an inflammatory disorder?

Keratoconus has been classically defined as a progressive, non-inflammatory condition, which produces a thinning and steepening of the cornea. Its pathophysiological mechanisms have been investigated for a long time. Both genetic and environmental factors have been associated with the disease. Recent studies have shown a significant role of proteolytic enzymes, cytokines, and free radicals; therefore, although keratoconus does not meet all the classic criteria for an inflammatory disease, the lack of inflammation has been questioned. The majority of studies in the tears of patients with keratoconus have found increased levels of interleukin-6 (IL-6), tumor necrosis factor-α(TNF-α), and matrix metalloproteinase (MMP)-9. Eye rubbing, a proven risk factor for keratoconus, has been also shown recently to increase the tear levels of MMP-13, IL-6, and TNF-α. In the tear fluid of patients with ocular rosacea, IL-1α and MMP-9 have been reported to be significantly elevated, and cases of inferior corneal thinning, resembling keratoconus, have been reported. We performed a literature review of published biochemical changes in keratoconus that would support that this could be, at least in part, an inflammatory condition.     

Mass-casualty, terrorist bombings: epidemiological outcomes, resource utilization, and time course of emergency needs (Part I)

INTRODUCTION: This article characterizes the epidemiological outcomes, resource utilization, and time course of emergency needs in mass-casualty, terrorist bombings producing 30 or more casualties. METHODS: Eligible bombings were identified using a MEDLINE search of articles published between 1996 and October 2002 and a manual search of published references. Mortality, injury frequency, injury severity, emergency department (ED) utilization, hospital admission, and time interval data were abstracted and relevant rates were determined for each bombing. Median values for the rates and the inter-quartile ranges (IQR) were determined for bombing subgroups associated with: (1) vehicle delivery; (2) terrorist suicide; (3) confined-space setting; (4) open-air setting; (5) structural collapse sequela; and (6) structural fire sequela. RESULTS: Inclusion criteria were met by 44 mass-casualty, terrorist bombings reported in 61 articles. Median values for the immediate mortality rates and IQRs were: vehicle-delivery, 4% (1-25%); terrorist-suicide, 19% (7-44%); confined-space 4% (1-11%); open-air, 1% (0-5%); structural-collapse, 18% (5-26%); structural fire 17% (1-17%); and overall, 3% (1-14%). A biphasic pattern of mortality and unique patterns of injury frequency were noted in all subgroups. Median values for the hospital admission rates and IQRs were: vehicle-delivery, 19% (14-50%); terrorist-suicide, 58% (38-77%); confined-space, 52% (36-71%); open-air, 13% (11-27%); structural-collapse, 41% (23-74%); structural-fire, 34% (25-44%); and overall, 34% (14-53%). The shortest reported time interval from detonation to the arrival of the first patient at an ED was five minutes. The shortest reported time interval from detonation to the arrival of the last patient at an ED was 15 minutes. The longest reported time interval from detonation to extrication of a live victim from a structural collapse was 36 hours. CONCLUSION: Epidemiological outcomes and resource utilization in mass-casualty, terrorist bombings vary with the characteristics of the event.     

Levels of IL-32 in Serum,Induced Sputum Supernatant,and Bronchial Lavage Fluid of Patients with Chronic Obstructive Pulmonary Disease

Interleukin-32 (IL-32) is a newly described cytokine which is expected to have an important role in autoimmune disorders. It was shown that chronic obstructive pulmonary disease (COPD) has a component of autoimmunity, though the role of IL-32 in its pathogenesis is not known. The aim of this study was to estimate IL-32 concentrations in serum, induced sputum (IS) supernatant and bronchoalveolar lavage (BAL) fluid from patients with COPD, and to compare asthma patients with and healthy subjects. Outpatients with COPD (63.7 ± 8.4 years, n = 51), asthma (58.3 ± 12.4 years, n = 31), and healthy subjects (59.8 ± 8.2 years, n = 9) were studied. The levels of IL-32 in serum, BAL fluid, and IS supernatant samples were analyzed by ELISA. Concentrations of IL-32 were higher in all the studied materials from patients with COPD (BAL 22.46 ± 2.48 pg/ml, IS 19.66 ± 1.69 pg/ml, serum 26.77 ± 2.56 pg/ml) in comparison with patients with asthma (BAL 6.25 ± 1.08 pg/ml, IS 5.82 ± 1.15 pg/ml, serum 6.09 ± 1.16 pg/ml, p < 0.05 respectively) as well as healthy subjects (BAL 4.21 ± 1.13 pg/ml, IS 3.59 ± 0.66 pg/ml, serum 4.63 ± 1.03 pg/ml, p < 0.05 respectively). Moreover, the level of IL-32 was higher in COPD smokers than in COPD ex-smokers in investigated respiratory tissue compartments and serum, and correlated with smoking history. Increased level of IL-32 in serum, IS supernatant, and BAL fluid from patients with COPD in comparison with asthma patients and healthy subjects suggest that IL-32 may play an important role in the pathogenesis of COPD, which depends on the smoking history.     

Children and adolescents with follicular lymphoma have an excellent prognosis with either limited chemotherapy or with a “watch and wait” strategy after complete resection

Data on clinical features and outcome in pediatric follicular lymphoma (pFL) are scarce. The aim of this retrospective study including 13 EICNHL and/or i-BFM study group members was to assess clinical characteristics and course in a series of 63 pFL patients. pFL was found to be associated with male gender (3:1), older age (72 % ≥10 years old), low serum LDH levels (<500 U/l in 75 %), grade 3 histology (in 88 %), and limited disease (87 % stage I/II disease), mostly involving the peripheral lymph nodes. Forty-four out of sixty-three patients received any polychemotherapy and 1/63 rituximab only, while 17/63 underwent a “watch and wait” strategy. Of 36 stage I patients, 30 had complete resections. Only one patient relapsed; 2-year event-free survival and overall survival were 94?±?5 and 100 %, respectively, after a median follow-up of 2.2 years. Conclusively, treatment outcome in pFL seems to be excellent with risk-adapted chemotherapy or after complete resection and an observational strategy only.     

Microsatellite instability analysis in hereditary non-polyposis colon cancer using the Bethesda consensus panel of microsatellite markers in the absence of proband normal tissue

Background  

Hereditary non-polyposis colon cancer (HNPCC) is an autosomal dominant syndrome predisposing to the early development of various cancers including those of colon, rectum, endometrium, ovarium, small bowel, stomach and urinary tract. HNPCC is caused by germline mutations in the DNA mismatch repair genes, mostly hMSH2 or hMLH1.     

Association of PTPN22 C1858T and CTLA-4 A49G polymorphisms with type 1 diabetes in Croatians

In this case–control study the association between the PTPN22 1858T and CTLA-4 49G gene variants and T1D in Croatian population was examined. We found that distribution of PTPN22 C1858T and CTLA-4 A49G genotypes between T1D patient (n = 102) and control (n = 193) groups differ significantly (p < 0.0001 and p = 0.012, respectively). Moreover, although the risk alleles of both SNPs are distributed more frequently in patients, the significant difference is observed only for PTPN22 1858T allele (p < 0.0001). This is therefore the first evidence that analyzed gene variants contribute to T1D pathogenesis in Croatian population.     

Long-term effects of beclomethasone dipropionate on prednisone dosage in the corticosteroid-dependent asthmatic

The average prednisone dosage of 54 corticosteroid-dependent asthmatics was computed for one year prior to initiation of beclomethasone dipropionate. This was compared to the average prednisone dosage after nine months on the beclomethasone with progressive tapering of prednisone to either dose compatible with control of asthma or discontinuation. Beclomethasone was found clinically useful in the great majority of these patients because it permitted a significant decrease in dosage of prednisone, a change from daily to alternate-day prednisone, or discontinuation of prednisone after cautious tapering. The first two advantages were most evident in those asthmatics who initially required higher doses of oral steroids while the latter was evident in those requiring lower doses. Those patients whose prednisone dosage does not appear to be beneficially affected by the use of beclomethasone should be suspect as to adherence to proper medical dosage schedule.