Evaluation of CHIP (iproplatin) in recurrent pediatric malignant solid tumors

CHIP (325 mg/M²), a second generation cisplatin derivative, was administered intravenously every 3 weeks to 85 pediatric patients with recurrent sarcomas (19), osteosarcomas (20), neuroblastoma (23), germ cell tumors (10), and other malignant tumors (7). Thirty-eight of them had been previously exposed to cisplatin. Partial remissions were only observed in 3 of 23 (13% SE=7%) patients having neuroblastoma. Severe thrombocytopenia (65%) and neutropenia (35%) were the dose limiting factors.     

Bilateral acute confluent disseminated choroiditis in Borrelia burgdorferi infection

Two patients with bilateral extensive confluent choroidal lesions, exudative retinal detachments, positive lyme serology and a typical history are documented: A 32-year-old woman presented 14 days after a "flu-like" illness with bilateral acute extensive choroidal lesions and exudative retinal detachments (OD from 5 to 8:30 o'clock, OS from 5 to 8 o'clock, both including the macula) accompanied by a mild lymphocytic meningitis. The laboratory work-up revealed increased serum and CSF titers of antibodies against Borrelia burgdorferi (Lyme immunofluorescent test (IFT) and Lyme-IgM IFT) which declined after a 14-day treatment with doxycycline (200 mg/d), CSF titers non-detectable (serum IgG: from 1:640 to 1:320, serum IgM: from 1:40 to 1:20). A distinct improvement with visual acuity increasing from OD 0.2/OS 0.3 p to OD/OS 0.8 p was observed after seven days of treatment. A 40-year-old man with a 14-day history of tick-bite developed the same, though more severe ocular findings and a lymphocytic meningitis. The serological work-up revealed increased antibody titers against Borrelia burgdorferi (ELISA); the IgM titer was normal. After a 10-day treatment with penicillin, antibody titers against the spirochete decreased slightly and the patient's neurologic and ophthalmologic status improved dramatically. Five weeks after admission visual acuity was OD/OS 0.5 (compared to OD/OS 0.1) and has remained at 0.8 p (OD/OS) since the ninth week after onset. The clinical course of the disease and the decreasing lyme serology strongly suggest an infection with Borrelia burgdorferi. The authors propose thorough laboratory work-ups including tests for Lyme disease in selected patients with diffuse choroidal lesions.     

Frequency of portrayal of foramen transversarium of the second cervical vertebra on rotational panoramic radiographs

OBJECTIVES: To determine the prevalence of portrayal of the foramen transversarium of the second cervical vertebra on rotational panoramic radiographs. METHODS: A stratified random sample of 1600 diagnostic-quality rotational panoramic radiographs were retrospectively reviewed. Approximately 100 radiographs each for males and females were reviewed for each of the decades of life up to age 69 and for subjects 70 or older. RESULTS: The foramen was portrayed 29.3% of all radiographs, 35% of females and 22.6% of males. However, when considering only those radiographs in which cervical vertebrae were visible, the foramen was more frequently portrayed in males than in females. Portrayal of the foramen did not differ substantially among age groups. CONCLUSIONS: The foramen transversarium is found sufficiently often on rotational panoramic radiographs that this structure should be identifiable by clinicians who use these images.     

Ocular changes in mucopolysaccharidosis IV A (Morquio A syndrome) and long-term results of perforating keratoplasty

BACKGROUND: The mucopolysaccharidoses (MPS) are an inhomogeneous group of disorders of errors in the carbohydrate metabolism with severe ocular involvement (corneal opacification, retinal degeneration, optic atrophy). PATIENT PRESENTATION: We report on a boy aged 12 years, with Morquio A (MPS IV A) syndrome. Ocular findings: progressive pseudoexophthalmus due to shallow orbits, increasing corneal stromal clouding, intermittent dissociated manifest nystagmus of the left eye, nyctalopia. Visual acuity OD cc = 0.16, OS cc = 0.05. Electrophysiology: changes suggesting a symptomatic tapetoretinal degeneration and optic atrophy. TREATMENT AND COURSE OF DISEASE: OS: perforating keratoplasty. Postoperative improvement of visual acuity to 0.25 for nearly a year, followed by progressive reopacification of the corneal graft. Both eyes: progressive signs of tapetoretinal degeneration and optic atrophy. Visual acuity now reduced to OD 0.05, OS 0.1. CONCLUSIONS: Success of a keratoplasty is limited by (1) reopacification of the cornea, (2) visual impairment due to (a) retinal degeneration and (b) optic atrophy. The indication for perforating keratoplasty has to be thought about very carefully in these multimorbid patients. In our patient, beside progressive visual impairment there is a progressive deafness which dominates his social and school life. Attending school is severely complicated by the double handicap. Perforating keratoplasty enabled the boy to attend a school for physically handicapped without a special low-vision care for another year. Progressive visual loss without further treatment options now renders optical and electronic low-vision aids necessary. Although the time of improved visual acuity lasted less than a year, we think patients with a life expectancy of less than 20 years should have every possible improvement of their situation - even if it does not last permanently. We therefore propose perforating keratoplasty in spite of insufficient long-term results.     

Initial clinical experiences with the Dresden 3D display in conjunction with the Heidelberg Retina Tomograph (HRT)]

BACKGROUND: For years the Heidelberg Retina Tomograph has been an established method to diagnose early glaucomatous damages at the optic nerve head. The major difficulty consists in defining the outlayer of the optic nerve head in a 2-dimensional reflective or topographic picture. A 3-dimensional presentation of the ocular fundus could ease the defining very much. The Dresden 3D-display tested provides a true 3-dimensional presentation of the HRT-values measured. METHODS: For the study 5 groups of prediagnosed follow-up examinations were formed, which in their course showed various progression. The examination firstly was carried out by manual defining of the papilla contour on the Dresden 3D-display and secondly by the new automatic contour-finding of the 3D-software. RESULTS: Through the 3-dimensional presentation a more correct position of the contour can be found when drawn manually. As a result some diagnoses of the 2-dimensional HRT-pictures had to be revised. The results proved considerable differences between the automatic outlayer-finding and the probably real position of the papilla borders. CONCLUSION: The 3-dimensional presentation of the HRT-pictures represents an subjective improvement regarding the accuracy of manual contour definition. In particular, the fact that it is feasible to make the pictures rotate around the axes offers completely new insights to the morphology of the disc.     

Importance of the orbital collateral circulation for the origin of ischemic ophthalmopathy in stenotic diseases of the internal carotid artery

Ischemic ophthalmopathy is the leading ocular symptom of occlusive processes of the internal carotid artery. It can be preceded by embolic symptoms as amaurosis fugax or occlusion of a branch or the main stem of the central retinal artery. Both, ophthalmologists and neurologists, should be familiar with these disturbances as they can involve important diagnostic and therapeutic consequences. Five out of six patients with an angiographically demonstrated extracranial occlusion of one internal carotid artery and a retrograde collateral circulation to the intracranial space via the external carotid and the ophthalmic arteries showed an ischemic ophthalmopathy of the ipsilateral eye. This high coincidence supports the notion that an ischemic ophthalmopathy may not be the result of the occlusive process of the internal carotid artery per se, but may be caused by ocular "steal mechanisms" due to the retrograde orbital collateral circulation.     

Adenine nucleotide levels in preserved and ischemically injured canine kidneys

This study explored the relationship between adenine nucleotide levels in canine renal cortex and renal function following: (a) graded periods of warm ischemia; (b) 48 hours' flush cooling with electrolyte solutions and ice storage; and (c) continuous hypothermic perfusion. Exposure to normothermic ischemia resulted in a rapid (within 15 minutes) degradation of ATP to ADP and AMP as well as a slow decline in total adenine nucleotide (TAN) to levels which were proportional to the duration of the ischemic injury. No functional impairment was evident after 15 minutes' ischemia, but with longer times, both the extent of decline in TAN and the degree of recovery following restoration of blood flow could be used to predict the quality of renal function.The relationship between TAN levels and function was of less predictive value following cold storage or continuous perfusion. The efficacy of intracellular flush solutions could not be attributed solely to conservation of TAN, nor did the well-maintained TAN levels during continuous perfusion necessarily lead to significantly better 48-hour storage than flush cooling with C2 solution.

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Résumé Cette étude faite chez le chien examine la corrélation entre la fonction rénale et le taux d'adénine nucléotide dans le cortex rénal suite à: 1) différentes périodes d'ischémic chaude; 2) entreposage sur glace pendant 48 heures apres flushing avec des solutions électrolytiques; 3) hypotermie par perfusion continuelle. L'ischémie chaude a produit une dégradation rapide de l'ATD en ADP et AMP (en moins de 15 minutes) et une diminution progressive de la quantité totale d'adénine nucléotide (TAN) proportioneile à la durée de la période ischémique. La fonction rénale n'a pas été affectée par des périodes d'ischémie de 15 minutes ou moins. Suite à des périodes ischémiques plus longues cependant, la chutte des taux de TAN et leur niveau de rétablissement après réouverture de la circulation sanguine ont permis de prédire la qualité de la fonction rénale. Après storage au froid ou perfusion continue, la relation entre les taux de TAN et la fonction rénale est disparue. Le flushing à l'aide des solutions de type intracellulaire, malgré sa faible capacité à conserver les taux de TAN s'est avéré une méthode d'entreposage aussi efficace que la perfusion continuelle, laquelle a maintenu des taux normaux de TAN.

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Supported by Veterans Administration Research Grant 1519-01.     

Reactivation of codogenic endogenous retroviral (ERV) envelope genes in human endometrial carcinoma and prestages: Emergence of new molecular targets

Endometrial carcinoma (EnCa) is the most common invasive gynaecologic carcinoma. Over 85% of EnCa are classified as endometrioid, expressing steroid hormone receptors and mostly involving pathological prestages. Human endogenous retroviruses (ERV) are chromosomally integrated genes, account for about 8% of the human genome and are implicated in the etiology of carcinomas. The majority of ERV envelope (env) coding genes are either not present or not consistently represented between common gene expression microarrays. The aim of this study was to analyse the absolute gene expression of all known 21 ERV env genes including 19 codogenic and two env genes with premature stop codons in EnCa, endometrium as well as in hyperplasia and polyps. For EnCa seven env genes had high expression with >200 mol/ng cDNA (e.g. envH1-3, Syncytin-1, envT), two middle >50 mol/ng cDNA (envFc2, erv-3) and 12 low <50 mol/ng cDNA (e.g. Syncytin-2, envV2). Regarding tumor parameters, Syncytin-1 and Syncytin-2 were significantly over-expressed in advanced stage pT2 compared to pT1b. In less differentiated EnCa Syncytin-1, erv-3, envT and envFc2 were significantly over-expressed. Syncytin-1, Syncytin-2 and erv-3 were specific to glandular epithelial cells of polyps, hyperplasia and EnCa using immunohistochemistry. An analysis of 10 patient-matched EnCa with endometrium revealed that the ERV-W 5'' long terminal repeat regulating Syncytin-1 was hypomethylated, including the ERE and CRE overlapping MeCP2 sites. Functional analyses showed that 10 env genes were regulated by methylation in EnCa using the RL95-2 cell line. In conclusion, over-expressed env genes could serve as indicators for pathological pre-stages and EnCa.