Robust rigid registration of retinal angiograms through optimization

Retinal fundus photographs are employed as standard diagnostic tools in ophthalmology. Serial photographs of the flow of fluorescein and indocyanine green (ICG) dye are used to determine the areas of the retinal lesions. For objective measurements of features, the registration of the images is a necessity. In this paper, we employ optimization techniques for registration with the help of 2-parameter translational motion model of retinal angiograms, based on non-linear pre-processing (Wiener filtering and morphological gradient) and computation of the similarity criteria for the alignment of the two gradient images for any given rigid transformation. The optimization methods are effectively employed to minimize the similarity criterion.

The presence of noise, the variations in the background and the temporal variation of the fluorescence level pose serious problems in obtaining a robust registration of the retinal images. Moreover, local search strategies are not robust in the case of ICG angiograms, even if one uses a multiresolution approach.

The present work makes a systematic comparison of different optimization techniques, namely the minimization method derived from the optical flow formulation, the Nelder-Mead local search and the HCIAC ant colony metaheuristic, each optimizing a similarity criterion for the gradient images. The impact of the resolution and median filtering of gradient image is studied and the robustness of the approaches is tested through experimental studies, performed on macular fluorescein and ICG angiographies.

Our proposed optimization techniques have shown interesting results especially for high resolution difficult registration problems. Moreover, this approach seems promising for affine (6-parameter motion model) or elastical registrations.     

Complement component C5a predicts restenosis after superficial femoral artery balloon angioplasty.

PURPOSE: To investigate whether balloon angioplasty of the superficial femoral artery (SFA) increases serum levels of C5a and whether C5a predicts risk of restenosis. METHODS: C5a antigen was measured at baseline and 8 hours after intervention in 131 consecutive patients (76 women; median age 72 years) with intermittent claudication who underwent successful primary SFA balloon angioplasty. Patients were followed for a median 10 months [interquartile range (IQR) 6 to 14] for the occurrence of >50% restenosis by duplex ultrasound. RESULTS: Median C5a levels increased significantly from 39.7 ng/mL (IQR 27.8 to 55.0) at baseline to 53.8 ng/mL (IQR 35.6 to 85.1, p<0.001) 8 hours post intervention. During the follow-up period, 70 (53%) patients developed restenosis. Increasing levels of C5a (quartiles) at baseline were significantly associated with an increased risk for restenosis (p=0.0092). Adjusted hazard ratios (95% confidence intervals) for restenosis with increasing quartiles of baseline serum C5a levels were 1.24 (0.60 to 2.58), 1.93 (0.95 to 3.93), and 2.08 (1.02 to 4.21), respectively, compared to the lowest quartile. This effect was independent of nonspecific inflammation as reflected by plasma levels of C-reactive protein. CONCLUSION: Inflammatory mechanisms play a major role in the development of restenosis after angioplasty. The complement component C5a exerts strong chemotactic and proinflammatory effects. Enhanced complement activation prior to PTA, as measured by higher levels of C5a, was significantly associated with restenosis after SFA balloon angioplasty. Pathways of complement inhibition thus may be worth investigating with respect to improving patency rates.     

The palmar radiocarpal ligaments: A study of adult and fetal human wrist joints

The palmar radiocarpal ligaments were studied with use of fifty-four dissected adult cadaver wrists and serial sections on twenty-three wrists from fetuses ranging in size from 23 to 230 millimeters crown-rump length. Three palmar radiocarpal ligaments were clearly identified: the radioscaphocapitate, long radiolunate, and short radiolunate ligaments. The radioscaphocapitate ligament originates from the radial styloid process and inserts into the radial aspect of the waist of the scaphoid, hemicircumferentially around the distal pole of the scaphoid and interdigitates with fibers from the palmar aspect of the triangular fibrocartilage complex just palmar to the head of the capitate, with only a minor insertion distally into the body of the capitate. The long radiolunate ligament originates just ulnar to the radioscaphocapitate ligament, being separated from it throughout its course by the interligamentous sulcus. The long radiolunate supports, but is separate from, the palmar aspect of the scapholunate interosseous ligament, and inserts into the radial half of the palmar surface of the lunate. The short radiolunate ligament, previously not described, originates just palmar to the lunate facet of the distal radius articular surface and inserts as a flat sheet of fibers into the proximal margin of the palmar surface of the lunate. Each ligament is intracapsular, enveloped within a continuous superficial fibrous stratum and deep synovial stratum.     

Treatment of osteoporosis in men

Osteoporosis in men is recognised worldwide as an important and increasing public health problem. The causes are more heterogeneous than those in women. About 50% are diagnosed as secondary cases. In some secondary forms of osteoporosis the specific diagnosis results in additional therapeutic options (e.g. androgen therapy in proven hypogonadism). The basic therapy for osteoporosis in men is no different to that in postmenopausal women, namely recommendations for counteracting modifiable risk factors, especially with regard to diet, physical exercise, and calcium and vitamin D supplementation. Concerning specific drug medications, however, even today there is still a therapeutic dilemma in male osteoporosis. While older substances (e.g. calcitonin, fluoride, alfacalcidol) are approved for both sexes, all newer medications have primarily been approved for the treatment of postmenopausal osteoporosis. Health authorities request studies in purely male populations. For new drugs, fracture data are necessary while for new substances within a class (e.g. bisphosphonates), at the very least consistent effects on bone mineral density (BMD) and bone turnover markers are requested. Due to these regulatory rules, ibandronate, teriparatide and strontium ranelate are not approved in the European Union. Some years ago, alendronate was the first bisphosphonate that was approved for the treatment of men with osteoporosis, based on consistent results from two independent male studies using a daily 10 mg dosage. Very recently risedronate was approved by the FDA and EMEA. A randomised, placebo-controlled multicentre trial of 285 male patients showed, after 2 years, a 5.8% increase in lumbar spine BMD in the risedronate 35 mg once weekly group vs 1.2% in the placebo group. In a prospective controlled study on 316 men with primary or secondary osteoporosis we found, after 12 months, a lumbar spine BMD of +4.7% vs +1.0% in controls. The number of patients with one or more new vertebral fractures was 8 in the risedronate group and 20 in the placebo group (a fracture reduction of 60%). Furthermore, we found a significantly smaller decrease in height and a steeper decrease in back pain in the risedronate group. Risedronate is the first oral bisphosphonate available for men with the more comfortable once weekly dosage.     

Hematopoietic turnover index in reactive and neoplastic bone marrow lesions: quantification by apoptosis and PCNA labeling

 In order to determine the dynamics of hematopoietic cell turnover, proliferative activity and incidence of apoptosis (programmed cell death) were evaluated in bone marrow trephine biopsies. Selection of patients (20 in each group) included in addition to a control group, idiopathic thrombocytopenia (ITP), reactive thrombocytosis (TH), secondary polycythemia-smokers' polyglobuly (PG), primary (essential-hemorrhagic) thrombocythemia (PTH), polycythemia vera (PV), and finally acute myeloid leukemia (AML). Apoptosis was demonstrated by the in situ end-labeling technique (ISEL) and proliferative activity by applying the monoclonal antibody PC10 raised against proliferating cell nuclear antigen (PCNA). To assess dynamic features of hematopoiesis, an index was calculated consisting of the ratio between PCNA-positive nuclei and the apoptotic cell fraction. This factor was termed the hematopoietic turnover index (HTI). Morphometric analysis revealed that the HTI was significantly increased in AML and PV. According to cell culture studies both disorders are characterized by either a prevalent proliferation of the myeloid or erythroid cell mass. On the other hand, PG, PTH, and TH showed no relevant enhancement of this index in comparison to the control specimen. In vitro experiment results are in keeping with the finding that PG and PTH are not associated with a significant expansion of the erythroid lineage (CFU-E). Similar to ITP and TH, in PTH megakaryocyte proliferation (CFU-MEG) is the predominant feature of cell turnover. Differences between PTH and TH are in line with the reduced in vitro formation of CFU-MEG in the latter disorder. In conclusion, our in situ study on turnover rates of the bone marrow in various neoplastic and reactive lesions extends previous experimental data on hematopoietic cell kinetics. Received: 10 March 1997 / Accepted: 18 May 1997     

A human amphotropic retrovirus receptor is a second member of the gibbon ape leukemia virus receptor family.

Retrovirus infection is initiated by binding of the viral envelope glycoprotein to a cell-surface receptor. The envelope proteins of type C retroviruses of mammals demonstrate similarities in structural organization and protein sequence. These similarities suggest the possibility that retroviruses from different interference groups might use related proteins as receptors, despite the absence of any relationship between retrovirus receptors isolated to date. To investigate this possibility, we have identified a human cDNA clone encoding a protein closely related to the receptor for gibbon ape leukemia virus and have found that it functions as the receptor for the amphotropic group of murine retroviruses. Expression of this protein (GLVR-2) is likely to be a requirement for infection of human cells by amphotropic retroviral vectors for purposes of gene therapy.