Visual performance in the rhesus monkey after exposure to blue light.

Rhesus monkeys trained to perform a visual task (Landolt ring discrimination) were exposed for 1000 sec to known amounts of 441 nm light by means of a 2500 W xenon lamp with narrow bandpass filter. Radiant exposures to the macula of 30 J/cm² did not impair vision, but 60 J/cm² produced a transient loss of 20/20 vision which lasted from 20 to 30 days. A radiant exposure of 90 J/cm² produced a permanent loss of 20/20 vision. These results, in addition to explaining solar retinitis and eclipse blindness, correlate well with the retinal photopathology of the short wavelength photochemical lesion.     

Future directions

In this final paper, we summarise briefly the principal conclusions to emerge from the conference. We also review possible future directions in the light of the contributions of different authors and discussions at the conference. The paper argues that changes in the Swedish health services are both inevitable and desirable. The challenge is to maintain the strengths of the existing system while tackling widely acknowledged weaknesses. It is not yet clear what will emerge from the process of reform but the probable outcome is a period of innovation and experimentation leading to greater diversity in service provision. We argue that diversity is most likely to develop within the context of a continuing commitment to equity and comprehensiveness in the delivery of health care.     

Detection of bilateral and symmetrical anomalies in technetium-99m-HMPAO brain SPECT studies.

The detection of bilateral and symmetrical regional cerebral blood flow (rCBF) abnormalities requires knowledge of the antero-posterior rCBF distribution in normal subjects of all age groups. These data are very difficult to obtain in children for ethical reasons and in older subjects because of the necessity of recruiting a large number of healthy volunteers from each age group. Therefore, to obtain normal values of antero-posterior rCBF distribution, we have retrospectively selected a group of patients with a low probability of having cerebral lesions, whose 99mTc-HMPAO brain SPECT studies were analyzed semiquantitatively. Cerebellum/mean cerebral cortex index when compared to young adults was higher in the neonatal period, slightly lower between 2 mo and 15 yr, and more or less identical after 15 yr. Cortico/occipital indexes exhibit considerable changes during the first year of life due to important differences in maturation timing of cerebral cortical areas. After 1 yr, all cerebral cortical areas approximately displayed a parallel evolution. A slight increase in fronto/occipital and temporo/occipital indexes was, however, still observed during childhood, while in elderly subjects there was a trend towards a decrease in all cortico/occipital indexes (particularly in prefrontal and motor areas). Changes that occurred after 1 yr were, however, usually smaller than interindividual variation. Despite the large range of "normal" values, the antero-posterior analysis could be useful in various neurologic disorders, because it allows detection of symmetrical rCBF anomalies undiagnosed by the right-left analysis.     

Work loads of a sample of general surgeons in N.S.W.

The work loads of 34 general surgeons in New South Wales during a six week period in 1977 have been determined. Data was obtained on the number of elective, emergency and supervised procedures, and of elective and emergency first consultations. The operative work loads were assessed by a simple grading system, and also by the "hernia-equivalent" method which relates the work involved in a given operation to that for an adult unilateral inguinal herniorrhaphy. The latter is arbitrarily given a score of one. The hernia-equivalent scores for academics, country and city surgeons were similar. The mean hernia-equivalent rating for the 2,321 operations assessed was 1.1; thus, the "typical" operation was equivalent to a herniorrhaphy. The mean number of operations per week was 11.4, or 12.6 hernia-equivalents. Assuming a 48-week working year, these figures represent an annual work load of 547 operations, or 605 hernia-equivalents. Comparison of these results with those obtained in the U.S.A. (the "SOSSUS" report) indicates that these work loads are almost three times those found for board-certified general surgeons in the U.S.A.     

Role of prosaposin in the male reproductive system: effect of prosaposin inactivation on the testis, epididymis, prostate, and seminal vesicles

SGP-1/prosaposin can be secreted or targeted to the lysosomes where it is processed into smaller saposins (A, B, C, and D) required for the hydrolysis of glycosphingolipids. The deficiency of saposins B and C results in variant forms of metachromatic leukodystrophy and Gaucher's disease, respectively, which are characterized by lysosomal storage of undegraded glycosphingolipids. In the nervous system, prosaposin presents trophic activity. A mouse model was recently developed by creating a null allele in embryonic stem cells through gene targeting to investigate the phenotypic diversity of prosaposin mutations and the involvement of this protein in lysosomal storage diseases, and for the development of therapeutic approaches. Mice homozygous mutants die at the age of 35-40 days and neurological disorders contribute to the early demise of the mutant mice. The male reproductive organs in homozygous mutants show several abnormalities, such as a decrease in testis size with reduced spermiogenesis and an involution of the prostate, seminal vesicles, and epididymis. In these animals, the blood levels of testosterone remain normal. In the prostate of homozygous mutants, only the basal epithelial cells appear to be present, while the secretory cells are absent. These findings suggest that prosaposin may be involved in the development and maintenance of the male reproductive organs, as well as, in cellular differentiation.     

Health risks of counterfeit pharmaceuticals.

Pharmaceutical products are not exempt from the practice of counterfeiting. In recent years, many reports have become available demonstrating the presence of fake medicines on the market. Several studies have demonstrated that they are quite often of bad quality. It is estimated that 5% of all world trade in branded goods is counterfeit, leading to huge financial losses for the pharmaceutical industry. But much more important, from a public health point of view, is that history has shown that such products may lead to a great health risk. The essence of counterfeit products and the reason they are so dangerous is the complete absence of quality control, since they are often indistinguishable from the genuine product. The existence of counterfeit drugs has long been ignored both by the pharmaceutical industry and by drug regulatory authorities. At present initiatives are being taken, nationally and internationally, to curb counterfeiting. It is now realised that a strong regulatory agency is essential, but the initiatives can only be successful if all parties concerned actively co-operate.     

Characterization of gastrin-induced proangiogenic effects in vivo in orthotopic U373 experimental human glioblastomas and in vitro in human umbilical vein endothelial cells.

PURPOSE: This study aims to investigate the role of gastrin-17 (G17) on angiogenesis features in gliomas both in vitro and in vivo. EXPERIMENTAL DESIGN: The influences of G17 and G17 receptor antagonists were characterized in vitro in terms of angiogenesis on human umbilical vein endothelial cell (HUVEC) tubulogenesis processes on Matrigel and in vivo with respect to U373 orthotopic glioma xenografts. The influence of phosphatidylinositol 3'-kinase, protein kinase C, and nuclear factor-kappaB inhibitors was characterized in vitro on G17-mediated HUVEC tubulogenesis. G17-mediated release of interleukin (IL)-8 from HUVECs and G17-induced modifications in nuclear factor-kappaB DNA binding activity were characterized by means of specific enzyme-linked immunosorbent assays. The influence of G17 on E- and P-selectin expression was determined by means of computer-assisted microscopy, whereas the influence of E- and P-selectin on HUVEC migration was approached by means of antisense oligonucleotides. The chemotactic influence of G17 and IL-8 on HUVEC migration was characterized by means of computer-assisted videomicroscopy with Dunn chambers. RESULTS: Messenger RNAs for cholecystokinin (CCK)A, CCKB, and CCKC receptors were present in HUVECs and microvessels dissected from a human glioblastoma. Whereas G17 significantly increased the levels of angiogenesis in vivo in the U373 experimental glioma model and in vitro in the HUVECs, the CCKB receptor antagonist L365,260 significantly counteracted the G17-mediated proangiogenic effects. G17 chemoattracted HUVECs, whereas IL-8 failed to do so. IL-8 receptor alpha (CXCR1) and IL-8 receptor beta (CXCR2) mRNAs were not detected in these endothelial cells. Gastrin significantly (but only transiently) decreased the level of expression of E-selectin, but not P-selectin, whereas IL-8 increased the expression of E-selectin. Specific antisense oligonucleotides against E- and P-selectin significantly decreased HUVEC tubulogenesis processes in vitro on Matrigel. CONCLUSIONS: The present study shows that gastrin has marked proangiogenic effects in vivo on experimental gliomas and in vitro on HUVECs. This effect depends in part on the level of E-selectin activation, but not on IL-8 expression/release by HUVECs.