Centenary of the first radiotherapy treatment of retinoblastoma (Hilgartner, 1903)

One hundred years ago, Hilgartner used external radiotherapy for the first time in the treatment of retinoblastoma. This first case was published in the Texas Medical Journal in 1903. Immediate results were reported to be excellent but the long-term outcome was not known. The first documented cure of retinoblastoma over a long period of time was a case initially treated by Verhoeff (Boston) in 1917, with histopathological findings provided 71 years later by Marcus et al. at the patient's death. Henry Louis Hilgartner was born in 1868 in Baltimore and died in 1937 at the age of 69. His revolutionary treatment developed from the discovery of X-rays in 1895 by Wilhelm Conrad R?ntgen and the parallel discovery of radioactivity by Henri Bequerel and Marie and Pierre Curie. In the sociopolitical context of 1903, Emile Loubet was president of France and this same year saw the Wright brothers' first motorized flight with the first power-driven heavier-than-air machine. The development of radiotherapy in the treatment of retinoblastoma can be divided into three distinct periods: an initial period of trial and error lasting from 1903 to 1928; a second period from 1929 to 1948 covering the introduction of calibrated radon needles up to the advent of external radiotherapy, and a third period, from 1948 to the present day, which can be considered a time of technical improvement and innovation. One hundred years ago, radiotherapy made a triumphant entry on the scene of retinoblastoma management. With our present knowledge of its side effects, we are now trying to remove it.     

Photocoagulation of the retinal feeder vessels of a chorioretinal anastomosis in age-related macular degeneration

The presence of a chorioretinal anastomosis in the setting of age-related macular degeneration is known as a sign of poor prognosis. No treatment has proven to be effective. We describe a 71-year-old female patient presenting with exudative age-related macular degeneration, a chorioretinal anastomosis with two retinal feeder vessels (arteriole and veinule), a serous retinal pigment epithelium detachment, and a suspected early subretinal neovascular membrane. She was treated with ICG-guided laser photocoagulation directed to the hot spot, with treatment-zone enlargement directed to the retinal feeder vessels and followed up for 6 months. Although a second laser treatment for the reperfused subretinal neovascular membrane was needed, the clinical and angiographic end result was beneficial. Visual acuity improved by two lines, the chorioretinal anastomosis was occluded, and the pigment epithelium reattached. Taking into account the low therapeutic success rate described in the literature, we suggest that the specific treatment of the retinal feeder vessels, which to our knowledge has not been described before, may be a valuable treatment option.     

Lack of BRAF mutations in uveal melanoma

RAF proteins are serine/threonine kinases that mediate cellular responses to growth signals by activating the mitogen-activated protein kinase pathway. Mutations in the BRAF gene causing a V599E amino acid substitution that enhance the kinase activity have been described in >60% of cutaneous melanomas and premalignant melanocytic lesions. We have investigated the frequency of BRAF mutations at the expression level in melanomas of the uveal tract. None of the 30 metastases and 10 primary uveal melanomas tested expressed the V599E mutation. In contrast, this mutation was expressed by 65% of cutaneous melanoma samples, confirming previous results. In addition, a double mutation resulting in V599K substitution was detected in two suspect ocular metastases of cutaneous melanoma. Analysis of exon 11, the second common site of BRAF mutations, revealed only wild-type sequences in uveal melanomas. Analysis of tumor lysates showed the presence of phosphorylated mitogen-activated protein kinase, kinase, and mitogen-activated protein kinase in 50% of uveal and 100% of cutaneous melanoma metastases. Taken together, these results suggest that although the common BRAF mutations found in cutaneous melanoma do not play a role in tumorigenesis of uveal tract melanocytes, activation of the RAF/mitogen-activated protein kinase pathway may nevertheless play an important role in uveal melanoma.     

Impact of body mass index on fasting blood glucose concentration among Helicobater pylori carriers

BACKGROUND/AIMS: Despite the fact that Helicobacter pylori (Hp) is regarded as a major gastroduodenal pathogen, it has recently been suggested to be an important factor for non-gastroenterologic conditions such as diabetes mellitus. Accordingly, it seems that Hp infection may have implications in glycemic control and in fasting plasma glucose concentrations. As overnutrition and obesity are directly related to impaired glucose tolerance, the aim of the present study was to determine whether Hp infection leads to alterations in fasting plasma glucose concentrations of Hp carriers and especially in relation to their body mass index. METHODS: Serum was obtained from 224 young, male navy recruits. An enzyme-linked immunosorbent assay to detect Hp-specific IgG serum antibodies as well as gastroscopy along with biopsy was used to identify the infected individuals. Serum levels of glucose, urea, creatinine and uric acid were also determined. Non-fasting subjects and persons with abnormal oral glucose tolerance curve test were excluded. RESULTS: Among Hp-positive individuals, obese persons presented with a significantly lower mean blood glucose level than non-obese persons. Obese Hp-contaminated participants had significantly lower mean fasting blood glucose concentrations as well as a significantly smaller percentage of participants with abnormal elevated blood glucose levels than obese participants negative to Hp infection. CONCLUSIONS: Our data suggest that obesity in combination with Hp infection may induce an enhanced response to insulin leading to reduced fasting blood glucose levels, among Hp-positive obese persons in comparison to Hp-positive lean persons.     

Pathogenesis of endometriosis: the role of defective 'immunosurveillance'.

OBJECTIVE: To analyse the aetiopathogenesis and the role of defective 'immunosurveillance' in endometriosis. METHOD: Review of studies on the pathogenesis of endometriosis, focusing particularly on novel molecules which express adhesive or proteolytic properties. Hypotheses addressing the role of oxidative stress in endometriosis were also reviewed. RESULTS: Endometriosis is a multifactorial disease associated with a general inflammatory response aiming to clear the peritoneal cavity from the ectopic endometriotic cells and tissue. Modern theories suggest that this inflammatory response creates an environment that may promote implantation and proliferation due to defective 'immunosurveillance'. CONCLUSION: The modern interpretation of the theory of reflux menstruation holds that women destined to develop endometriosis have a deficient immune system, which cannot defend against regurgitated endometrial cells. New findings on genetics, immune modulation, and secreted products of endometriotic lesions of affected women have given insight into the pathogenesis of this disorder and may serve as the background for new treatments of endometriosis-associated pain and infertility.     

Idiopathic sclerochoroidal calcification: new observations.

Two cases of idiopathic sclerochoroidal calcification are reported with follow-up of two and ten years. In addition we have reviewed 102 cases of choroidal osteoma, including six misleading case reports which actually described idiopathic sclerochoroidal calcification and not choroidal osteoma. Clinical manifestation and the angiographic features of idiopathic sclerochoroidal calcification are outlined. The differential diagnosis of intraocular deposition of calcium salts is discussed in detail.