Platelet adhesion to collagen types I through VIII under conditions of stasis and flow is mediated by GPIa/IIa (alpha 2 beta 1-integrin)

Platelet adhesion to fibrillar collagens (types I, II, III, and V) and nonfibrillar collagens (types IV, VI, VII, and VIII) was investigated in the presence of physiologic concentrations of divalent cations under conditions of stasis and flow. Under static conditions, platelet adhesion was observed to collagen types I through VII but not to type VIII. Under flow conditions, platelet adhesion to collagen types I, II, III, and IV was almost independent of shear rates above 300/s. Collagen type V was nonadhesive. Platelet adhesion to collagen type VI was shear rate-dependent and optimal at a rate of 300/s. Collagen types VII and VIII showed minor reactivity and supported platelet adhesion only between shear rates 100 to 1,000/s. Monoclonal antibody (MoAb) 176D7, directed against platelet membrane glycoprotein Ia (GPIa; very late antigen [VLA]-alpha 2 subunit), completely inhibited platelet adhesion to all collagens tested, under conditions of both stasis and flow. Platelet adhesion to collagen type III at shear rate 1,600/s was only inhibited for 85%. The concentration of antibody required for complete inhibition of platelet adhesion was dependent on the shear rate and the reactivity of the collagen. An MoAb directed against GPIIa (VLA-beta subunit) partially inhibited platelet adhesion to collagen. These results show that GPIa-IIa is a major and universal platelet receptor for eight unique types of collagen.     

The immotile cilia syndrome: radiological manifestations

The immotile cilia syndrome (ICS) is an uncommon disorder characterized by specific and genetically determined defects of cilia that cause upper and lower respiratory disease. We reviewed the radiographic patterns in 30 patients who had ICS (15 females, 15 males) and ranged in age from newborn to 26 years. Except for two neonates, sinusitis and otitis were present in all patients. Chest radiographic abnormalities, universally present, included bronchial wall thickening, hyper-inflation, segmental atelectasis or consolidation, and segmental bronchiectasis. Situs inversus, present in 50% (7 females, 8 males), was not an essential part of this disorder. Radiologically, the disease progresses from bronchial wall thickening with or without hyperinflation, to increasing hyperinflation plus parenchymal changes including segmental atelectasis, consolidation, and bronchiectasis. There is also a predilection for anatomic middle lobe abnormalities. The radiological appearance and clinical state have similarities to cystic fibrosis, although they are less severe and less progressive. ICS should be considered in the differential diagnosis of slowly progressive chronic lung disease, sinusitis, and otitis.     

Quantity and distribution of plaque in orthodontic patients treated with molar bands

Objective

The placement of orthodontic bands usually increases plaque accumulation due to numerous mechanical retention sites. The purpose of this investigation was to evaluate the amount and distribution pattern of biofilm in the oral (palatal and lingual) and interproximal regions surrounding orthodontic bands.

Materials and Methods

We evaluated the formation of biofilm on 32 orthodontic bands which had been placed intraorally for 6?C37?months. Two parameters were measured: the percentage of surface covered by biofilm (quantity) and the biofilm distribution pattern of accumulation. We measured these two parameters in four regions of interest: the mesial and distal interproximal regions, as well as the mesial and distal regions of the oral attachment.

Results

The quantity of biofilm formation was similar in all four regions of interest, ranging from 13.3% to 16.8%. In contrast to biofilm quantity, distribution patterns differed in the four regions. In the mesial and distal interproximal regions it appeared as extensive insular areas in 87.5% and 71.9%, respectively, whereas it appeared more often supragingival and linear in nature in regions adjacent to the oral attachment, i.e. in 65.6% and 68.8%, respectively.

Conclusion

Our results indicate that firstly, oral hygiene in the palatal and lingual regions of orthodontic bands seems as difficult as it is in the interproximal areas, thus requiring thorough hygiene in both areas. Secondly, orthodontic patients with a history of periodontal disease require special attention regarding the use of orthodontic bands.     

First Report of Dramatic Tumor Responses with Ramucirumab and Paclitaxel After Progression on Pembrolizumab in Two Cases of Metastatic Gastroesophageal Adenocarcinoma

Checkpoint inhibitors targeted at programmed cell death‐1 receptor (PD‐1) and its ligand (PD‐L1) can result in significant benefit to a small proportion of patients with cancer, including those with tumors of the stomach and gastroesophageal junction. These drugs are now approved for several solid tumors, including the recent accelerated approval of pembrolizumab for gastroesophageal adenocarcinomas in the third‐line setting and beyond based on the KEYNOTE‐059 phase II trial. Data are lacking on the efficacy of chemotherapy after progression on PD‐1 blockade in metastatic gastroesophageal adenocarcinoma. This report describes the exceptional response of two patients who received ramucirumab plus paclitaxel after progressive disease on pembrolizumab. This early clinical observation suggests that the sequence of administration of PD‐1 blockade and chemotherapy may be important in this disease.