Towards a new ICIDH

In 1995 a special issue of Disability and Rehabilitation was published on the use of the International Classification of Impairments, Disabilities and Handicaps (ICIDH) which was issued by WHO in 1980. Since 1995 a lot of energy has been spent by WHO and other organizations aiming at the development of a new and improved ICIDH. In 1997, a draft ICIDH-2 (Beta-1 version) was circulated by WHO in order to be tested in the field. This paper informs the reader about the content of the draft ICIDH, the revision process planning and some Dutch comments relating to the actual draft.     

New approach to dextran derivatives containing primary amino functions

Dextran derivatives containing primary amino functions were prepared by reacting 4-nitrophenyl carbonate-substituted dextran with the mono-protected diamine N-tritylenediamine (7) . Acidic treatment of the resulting dextran N-[2-(N-trityl)aminoethyl]carbamate (8) yields dextran N-(2-aminoethyl)carbamate (5a) . Alternatively, aminodextran derivatives were prepared by adding 4-nitrophenyl carbonate-substituted dextran to a large excess of a diamine or a triamine.     

Ruptured aneurysms of the aorta. Analysis of a series of 75 cases

Rupture of an abdominal aorta aneurysm was treated in 75 patients between 1969 and 1984. Global mortality was 70%, and factors influencing mortality, and its causes, are analyzed in this series. The presence and course of hemorrhagic shock is the essential prognostic factor, as well as the type of rupture. Mortality as a function of the groups varied between 27 and 90%. Causes of early mortality were directly related to collapse and its severity, other types of fatal complication being related to the patients general condition. Prognosis is improved by early diagnosis and rapidity of operative treatment. This series represents, in fact, only 36% of the total aneurysms operated upon during the same period, and a preventive surgical attitude is the only means of improving overall prognosis.     

Carrier and hapten functions in immune deviation. III. Possible antigenic competition between hapten and carrier determinants at the macrophage level

The effects of the intravenous injection of DNP-Ficoll on delayed hypersensitivity reactions to bovine gamma globulins (BGG) and anaphylactic reactions to the hapten induced by immunization with DNP-BGG in Freund's adjuvant were studied in guinea pigs. Animals treated with DNP-Ficoll exhibited stronger delayed hypersensitivity to BGG and lower anaphylactic reactions to the hapten than control animals treated with saline, Ficoll alone or with an unrelated protein antigen. These results could be explained by antigen competition between hapten and carrier determinants occurring at the macrophage level.     

Transgenic hepatocarcinogenesis in the rat.

Although transgenic hepatocarcinogenesis has been accomplished in the mouse with a number of genetic constructs targeting the oncogene to expression primarily in the liver, no example of this process has yet been developed in the rat. Because our understanding of the multistage nature of hepatocarcinogenesis is most advanced in the rat, we have developed a strain of transgenic rats carrying the promoter-enhancer sequences of the mouse albumin gene linked 5' to the simian virus-40 T antigen gene. A line of transgenic rats bearing this transgene has been developed from a single founder female. Five to six copies of the transgene, possibly in tandem, occur within the genome of the transgenic animals, which are maintained by heterozygous matings. Livers of transgenic animals are histologically normal after weaning; at 2 months of age, small foci of vacuolated cells appear in this organ. By 4 months of age, all animals exhibit focal lesions and nodules consisting primarily of small basophilic cells, many of which exhibit considerable cytoplasmic vacuolization. Mating of animals each bearing the transgene results in rats with a demyelinating condition that develops acutely in pregnant females and more chronically in males. Ultrastructural studies of these cells indicate that the vacuoles contain substantial amounts of glycogen, with the cells resembling hepatoblasts. Malignant neoplasms with both a glandular and a hepatoblastoma/hepatocellular carcinoma pattern arise from the nodules. Enzyme and immunohistochemical studies of all lesions reveal many similarities in gene expression to comparable lesions in rats subjected to chemically induced hepatocarcinogenesis, with certain exceptions. The placental form of glutathione-S-transferase is absent from all lesions in the transgenic animal, as is the expression of connexin 32. A significant number of lesions express serum albumin, and many, but not all, exhibit the T antigen. Lesions expressing the T antigen also contain stainable amounts of the p53 gene product; by contrast, normal hepatocytes express only very low levels of the T antigen within their nuclei and no demonstrable p53. All of the animals develop hepatic lesions, and approximately one-third also develop adenomas and carcinomas derived from the islet cells of the pancreas. Although there are differences in the morphology, biology, and genetic expression in early and late hepatic lesions in this strain of transgenic rat, many similarities also occur, making this a potential model system with which to study the interactions of environmental factors with a genetic program for hepatocarcinogenesis.     

Recurrent abnormal follicular maturation and ovarian stimulation for in-vitro fertilization

A total of 1078 cycles were stimulated for in-vitro fertilization between 1 January 1986 and 31 July 1987. One-hundred-and-ninety-six cycles had to be cancelled because of an abnormal ovarian response (18.2%). The majority of these cancellations were due to the phenomenon of follicular atresia (45%) or the absence of follicular growth (30%). Bad responder patients who had undergone cancellation during at least two successive cycles, when compared with normal responder patients, were somewhat older and had more frequent periovarian adhesions and ovulatory defects. The use of a GnRH agonist allowed correction of a certain number of ovarian response inadequacies, but follicular atresia and absence of folliculogenesis remained frequent phenomena.     

A comparison of pattern and multifocal electroretinography in the evaluation of age-related macular degeneration and its treatment with photodynamic therapy

This study compares pattern electroretinography (PERG) and multifocal electroretinography (mfERG) measures in 13 patients with predominantly classic choroidal neovascularisation (CNV) associated with age-related macular degeneration (ARMD, 9/13 unilateral, 4/13 bilateral), assesses the usefulness of each test in monitoring disease progression, and identifies electrophysiological predictors of outcome following treatment with photodynamic therapy (PDT). PERG and mfERGs were recorded at presentation, 2 weeks post-treatment, and at 3 monthly intervals for 2 years. The PERG was detectable in 8/13 patients with unilateral disease; the mfERG was detectable in 12/13 patients. P50 and N95 amplitudes increased in 6/8 patients and mfERG p1 increased in 7/13 patients at 2 years. PERG amplitudes correlated strongly with mfERG amplitudes in patients with unilateral disease. PERG P50 and mfERG p1 amplitude correlated with visual acuity at 2 years (R = 0.68, R = 0.82, respectively). The largest PERG P50 and mfERG p1 amplitude difference between treated and fellow eyes of all the groups on initial visit was associated with a poor visual outcome (P50 64% difference; p1 29% difference) whereas those with the smallest P50 and p1 amplitude difference was associated with improved vision at 2 years (P50 30% difference; p1 21% difference). The PERG and mfERG provide an objective measure of central retinal function in the progression of ARMD. A detectable PERG on presentation was the single best indicator of improved function and visual acuity at 2 years. The mfERG demonstrated disease progression from central retina into the paramacular regions over 2 years. Patients with poor visual outcomes had the largest inter-ocular amplitude difference on presentation, suggesting that such patients may have a worse prognosis following treatment.In part presented at ARVO 2004 (Fort Lauderdale, USA) and ISCEV 2004 (Peurto Rico, USA).     

Profiling the humoral immune response in colon cancer patients: diagnostic antigens from Streptococcus bovis

The human bowel contains a large and dynamic bacterial population that is not only essential for intestinal health, but also critical for the development of diseases such as cancer. In this respect, the Gram-positive bacterium Streptococcus bovis has been associated with colon cancer for many years. To investigate the clinical importance of this association, an immunocapture mass spectrometry assay was developed that can generate infection-related protein profiles. The composition of these profiles is governed by the capture of specific antigens by serum antibodies from colon cancer patients. This assay showed that S. bovis antigen profiles could distinguish 11 out of 12 colon cancer patients from 8 control subjects, whereas antigen profiles derived from the gut bacterium Escherichia coli were not diagnostic for colon cancer. Moreover, S. bovis antigen profiles were also detected in polyp patients, indicating that infection with this bacterium does occur early during carcinogenesis. Highly accurate tandem mass spectrometry was used to identify one of the diagnostic antigens as a surface-exposed heparin-binding protein, which might be involved in attachment of S. bovis to tumor cells. Together, these findings corroborate the hypothesis that colonic lesions provide a specific niche for S. bovis, resulting in tumor-associated "silent" infections. These infections, however, only become apparent in colon cancer patients with a compromised immune system (bacteremia) or coincidental cardiac valve lesions (endocarditis). This makes profiling of the humoral immune response against "silent" S. bovis infections a promising diagnostic tool for the early detection of human colon cancer, which is crucial for the effective treatment of this disease.