Disorders of perfusion of the anterior segment of the eye

Background: We have investigated the vascular perfusion of a wide variety of conditions of the anterior segment using fluorescein angiography.
Methods: The conditions were classified and findings reported according to the system set out below. Patients underwent full ocular examination. Fluorescein angiography of the anterior segment was carried out when indicated to investigate iris atrophy and neovascularisation. Specular microscopy of the corneal endothelium was used to detect changes in this tissue.
Results: The hypoperfusion was variable in degree and accompanied by varying degrees of iris hypoplasia and atrophy with neovascularisation. The degree of neovascularisation depended upon its rapidity of development, the pre-existing state of vascular perfusion and the underlying pathological condition.
Conclusions: Hypoperfusion with resultant ischaemia and neovascularisation is common in conditions of the anterior segment. An understanding of the changes is valuable in treating many conditions affecting the anterior segment. The changes observed may also occur elsewhere in the physical system and may be a significant part of the ageing process, either as scattered, disparate processes or as part of a general disease process.     

The results of combined cataract extraction and trabeculectomy using separate incisions

A method of combined cataract extraction with posterior chamber intraocular lens and trabeculectomy using separate incisions was tested in 44 operations on 38 patients. The mean preoperative intraocular pressure (IOP) of 28.1 ± 11.7 (range 12 to 56) mmHg on maximum medication was lowered to 13.9 ± 3.4 (9 to 23) mmHg at one year, with half the eyes still requiring topical medication. The IOP was 40 mmHg or more preoperatively in eight eyes and 20 mmHg or more in only two patients at one year. There were no rises in IOP above 20 mmHg in the early postoperative period (days 1 and 2). Visual acuity was 6/9 or better in 27 and 6/12 in three eyes. There was an expulsive haemorrhage in one case, rupture of the posterior capsule in two eyes and a choroidal detachment in one eye, but no flat anterior chambers. The two-incision method allowed placement of an intraocular lens with good postoperative pressure control.     

Molecular characteristics of two esophageal carcinosarcomas: a hint for theclonality of carcinomatic and sarcomatic tumor components

AIM To study the clonality of the esophageal carcinosarcoma by using molecular approaches.METHODS Two esophageal carcinosarcomas were included in the study. Tumor area from dysplasticlesion, squamout cell carcinoma, basaloid cell carcinoma and spindle cell elements were microdissectedseparately. Each element was analyzed with 14 microsatellite markers and direct sequenced for p53 gene andras gene mutation.RESULTS Both tumors displayed a typical histologic feature of carcinosarcoma. Both cases showed thedivergent differentiation by immunohistochemistry study. In case 1 the identical LOH at p53 and hMLH1 lociwas detected. The heterogenous LOH was detected only in carcinosarcoma at RB1 and BRCA1 loci, whilethe LOH at ACTC locus was seen only in sarcoma. The same mutation of the splice site of exon 6-intron 6displayed in the two tumor elements. In case 2, a coordinate LOH at RB locus was demonstrated in threetypes of tumor elements: sqamous carcinoma, basaloid carcinoma and spindle cell element. A heterogenousLOH was seen only in spindle cells at TAP1 locus. No mutation in exon 5-8 of p53 gene has been found incase 2. No mutation of K-ras gene was found.CONCLUSION Although the different differentiation, the two elements of esophageal carcinosarcoma mayhave a single clonality. The p53 gene mutation occurred before the two differentiation directions switched.The distinct molecular genotype can be determined through molecular biological analysis. The microsatelliteprofiling can serve as an approach to find out which genetic alteration occurs before or after thedifferentiation is determines.     

Recruitment and screening policies and procedures used to establish a paid donor oocyte registry

We have reviewed the demographic characteristics of, and report abnormalities noted in, the de-novo growth and development of a paid oocyte donation programme. The personal profiles of all prospective oocyte donors were reviewed. Acceptance or rejection of candidates was based upon screening the results of medical, genetic and psychological testing. A total of 603 candidates initially responded to our advertisement. From this pool, 313 individuals were considered suitable and contacted by telephone. Following further conversation, 176 women were scheduled an entry interview. On completion of the formal screening process, 17.6% (n = 31) of those actually interviewed were denied entry. Thus, from the initial interested parties, only 23% of women wishing to participate in oocyte donation were considered suitable candidates. Given the high attrition rate, we concluded that the need for rigorous and thorough medical, psychological and genetic testing is mandatory for the establishment of a donor registry. Furthermore, professional counselling of prospective donors with respect to the results of tests and the implications of test results with respect to their future medical and reproductive health, are important parts of providing comprehensive care.      

Etoposide causes illegitimate V(D)J recombination in human lymphoid leukemic cells

Etoposide is one of the most widely used antineoplastics. Unfortunately, the same treatment schedules associated with impressive efficacy are associated with an increased risk of secondary acute myeloid leukemia (AML), which has prompted its withdrawal from some treatment regimens, thereby potentially compromising efficacy against the original tumor. Because etoposide-associated AML is characterized by site-specific illegitimate DNA recombination, we studied whether etoposide could directly cause site-specific deletions of exons 2 and 3 in the hprt gene. Human lymphoid CCRF-CEM cells were treated with etoposide for 4 hours, and DNA was isolated after subculturing. The deletion of exons 2 and 3 from hprt was assayed by a quantitative polymerase chain reaction (PCR) method. In the absence of etoposide treatment, the frequency of deletions of exons 2 and 3 was very low (5.05 x 10(-8)). After exposure to 10 mumol/ L etoposide, the frequency of the exon 2 + 3 deletion was increased immediately after and at 24 hours after etoposide treatment (65 to 89 x 10(-8)) and increased to higher levels (128 to 173 x 10(-8)) after 2 and 6 days of subculture (P < .001 overall). The frequency of the exon 2 + 3 deletion assessed at 6 days of subculture after 4 hours of 0, 0.25, 1, 2.5, 5, and 10 mumol/L etoposide treatment increased with etoposide concentration, ie, 5.05 x 10(-8), 89.2 x 10(-8), 108 x 10(-8), 142 x 10(-8), 163 x 10(-8), and 173 x 10(-8), respectively (P < .0001). Sequencing of a subset of amplified products confirmed the presence of DNA sequences at the breakpoints consistent with V(D)J recombination. By contrast, exon 2 + 3 deletions after etoposide treatment in the myeloid cell lines KG-1A and K562 showed no evidence of V(D)J recombinase in their genesis. We conclude that etoposide can induce the illegitimate site-specific action of V(D)J recombinase on an unnatural DNA substrate after a single treatment in human lymphoid cells.