Search PubMed⌕ Search

Biomedical subjects

N Bornfeld

Publications and source records attributed to N Bornfeld.

At least 19 recordsLinked to original sources

High-dose chemotherapy with autologous stem cell rescue in children with retinoblastoma.

Children with metastatic retinoblastoma are considered to have a poor prognosis after conventional chemotherapy. We used high-dose chemotherapy (HDC) with peripheral hematopoietic stem cell transplantation in such patients in an attempt to improve their survival. Four patients with bone marrow metastases and one child with extraorbital disease were treated with HDC after achieving complete remission by enucleation and conventional chemotherapy. The child with extraorbital tumor was the only one to receive local irradiation. The conditioning regimen included thiotepa (900 mg/m(2)), etoposide (40 mg/kg) and carboplatin (1.5 g/m(2)) in four patients, and BCNU (300 mg/m(2)), cyclophosphamide (6.8 g/m(2)) and etoposide (1.6 g/m(2)) in one child. Hematologic recovery occurred without delay in all patients. The main toxicities were diarrhea, mucositis and infectious complications. No toxic deaths or any major late toxicities were observed. The child treated with the BCNU regimen developed a meningeal relapse 10 months after HDC, which was partially resected and treated with conventional chemotherapy, but not with radiotherapy. He is in complete remission (CR) 105 months off treatment. The other patients are in CCR for 107, 57, 9 and 8 months after HDC. HDC with thiotepa, etoposide and carboplatin may represent a curative option for children with extrabulbar or disseminated retinoblastoma responsive to chemotherapy. It may control occult CNS disease. The necessity to irradiate these children and the curative potential of this strategy for patients with bulky CNS disease remain to be determined.

Antineoplastic Combined Chemotherapy Protocols↗

[Blocking nociceptive afferents by retrobulbar bupivacaine does not decrease nausea and vomiting after propofol-remifentanil anaesthesia].

UNLABELLED: To test whether prophylactic neural blockade of noziceptive afferents or antiemetics diminutes postoperative nausea and vomiting (PONV) we studied in a randomised, prospective, and ouble-blind fashion 102 patients receiving implantation of an episcleral radioactive applicator for treatment of ocular malignant melanoma during remifentanil-propofol-anaesthesia. METHODS: 15 minutes prior to induction Dolasetron 12.5 mg (n = 18) or 50 mg (n = 20), Ondansetron 8 mg (n = 18), Droperidol 20 microg/kg (n = 23) or NaCl 0.9 % (n = 22) were randomly injected i.v. Furthermore, 4-8 ml Mepivacain 2 %/Bupivacain 0.5 % (n = 52) or saline (n = 50) were injected into the retrobulbar space after anaesthetic induction. Piritramid (0.1 mg/kg) was given for postoperative analgesia 30 minutes before end of surgery. Metamizol (1 g i.v.) and Dolasetron (12.5 mg i.v.) were provided on request as "rescue" medications. Variables were assessed by standardised questioning (NRS; yes/no) before and 1, 6, and 24 hours after surgery. STATISTICS: Chi(2)-, Mann-Whitney-U-, Kruskal-Wallis-test and logistic regression analysis, p < 0.05. RESULTS: Although retrobulbar anaesthesia decreased ocular pain (p = 0.013) and total postoperative complaints (p = 0.017) the incidence of PONV was not diminished. Droperidol was the only antiemetic to decrease PONV significantly (p = 0.001). CONCLUSIONS: Although prophylactic blockade of nozizeptive afferents by retrobulbar anesthesia decreased ocular pain and postoperative complaints, it failed to decrease the incidence of PONV. Thus, PONV after ocular surgery under propofol-remifentanil anaesthesia is not attenuated by preoperative blockade of noziceptive afferents. In patients undergoing total intravenous anaesthesia with propofol-remifentanil, droperidol prevented PONV more effectively than the used serotonin receptor antagonists.

Aged↗

Photodynamic therapy using verteporfin in circumscribed choroidal haemangioma.

AIM: To investigate the safety and efficacy of photodynamic therapy with verteporfin in patients with choroidal haemangioma. METHODS: A non-randomised, prospective clinical investigation of 19 patients with symptomatic circumscribed choroidal haemangioma was performed. Unsuccessful pretreatment (external beam irradiation, laser photocoagulation) was performed in four patients. Patients were included when (1) subretinal exudation involving the fovea, (2) a decrease in visual function, and (3) additional symptoms (for example, metamorphopsia) were present. Photodynamic therapy (PDT) was performed with verteporfin at a concentration of 6 mg/m(2) body surface area and a light dose of 100 J/cm(2) at 692 nm. RESULTS: The mean follow up time was 10.6 months (2-24 months). The mean number of treatment sessions was 2.15 (range 1-5). Visual acuity improved by at least one line in 73.3%, by at least two lines in 42.1%, was stable in 21.1%, and decreased by one line in 5.2% of the patients. Exudation was completely resolved in 94.8% of the cases. Regression of tumour height was documented in all 19 tumours. Patients receiving any pretreatment before PDT, a visual acuity of 0.1 and less, a history of more than 30 months, and no significant response after the first PDT session, did not show any significant improvement. Cox regression analysis revealed that the number of PDT treatment sessions was inversely associated with the improvement in visual acuity of at least two lines. No recurrences and no local or systemic side effects were observed during the follow up time. CONCLUSION: PDT using verteporfin is a safe and effective therapy for the treatment of symptomatic choroidal haemangioma even in tumours located beneath the fovea.

Adult↗

Thermochemotherapy in hereditary retinoblastoma.

BACKGROUND/AIM: The combination of chemotherapy and transpupillary thermotherapy, thermochemotherapy (TCT) has become an established part of the treatment plan in advanced retinoblastoma. The aim of this study was to identify safe indications, the complications as well as the limitations of this new treatment for retinoblastoma. METHODS: Tumour response and side effects of TCT with an indirect laser ophthalmoscope (spot size about 400 micro m) in 55 tumours of 26 children with bilateral retinoblastoma were analysed. Using the Reese-Ellsworth classification system, nine of 35 eyes were classified as type I, 13 eyes as type II, 10 eyes as type III, and three eyes as type V. The mean age of the children was 0.74 (SD 0.61) years. The mean tumour height was 3.5 (2.3) mm with a mean diameter of 6.1 (4.1) mm. Treatment parameters were 4.3 (1.6) (median 5) thermochemotherapy sessions with a mean energy of 539 (211) mW and a mean duration of 13.5 (5.6) minutes. Chemotherapy courses (vincristine, etoposide, and carboplatin) were repeated every 3 weeks. The mean follow up period was 1.25 (0.6) years. RESULTS: Local recurrence occurred in 21 tumours (38%), with a mean onset of 3.2 (2.9) months after TCT. The risk of tumour recurrence was correlated with tumour height. The recurrence rate was 17% for tumours with a height less than 2 mm, 37% for tumours with a height between 2 and 4 mm, and 63% for larger retinoblastomas. Multivariate analysis identified fish flesh regression after TCT (p = 0.0007) as the most important risk factor for tumour recurrence besides tumour height (p = 0.001) and the necessity of increased laser power during TCT sessions (p = 0.018). Complications during therapy included transient corneal opacification in two eyes (6%), focal iris atrophy (three eyes, 8.5%), peripheral lens opacity (two eyes, 6%), circumscribed transient retinal detachment (one eye, 3%) and diffuse choroidal atrophy (one eye, 3%). CONCLUSION: TCT using an indirect laser ophthalmoscope with a spot size of about 400 micro m was efficient for retinoblastoma with a tumour height less than 4 mm. In larger tumours, the recurrence rate was unacceptably high. Fish flesh regression after TCT correlates with a higher rate of local tumour recurrence. Treatment related complications occurred in less than 9% of the treated eyes.

Antineoplastic Combined Chemotherapy Protocols↗

High resolution magnetic resonance imaging of retinoblastoma.

BACKGROUND/AIMS: Diagnosis of retinoblastoma is mainly based on indirect ophthalmoscopy, but additional imaging techniques are indispensable for the staging of the disease. A new high resolution magnetic resonance imaging (MRI) technique for the examination of the eye was evaluated. A new surface coil with a diameter of 5 cm allows a field of view of 60 mm with an in-plane resolution of 0.8 mm. We compared preoperative MRI scans with the histology after enucleation in 21 cases of retinoblastoma. Parameters studied were appearance of retinoblastoma, choroidal and scleral infiltration, extraocular extension, optic nerve infiltration, and vitreous seeding. RESULTS: All retinoblastomas could be visualised as hypointense to vitreous on T2 weighted images and slightly hyperintense to vitreous on plain T1 weighted images with a moderate enhancement after contrast application. Histology revealed seven cases with infiltration of the optic disc or optic nerve. Preoperative MRI scans depict juxtapapillary tumour masses, but it was impossible to differentiate between a juxtapapillary retinoblastoma, a prelaminar infiltration of the optic disc, or a just postlaminar optic nerve infiltration. In five of 14 cases with a proved tumour infiltration of the choroid, MRI scans showed an inhomogeneous contrast enhancement of the choroid in enhanced T1 weighted sequences beneath the retinoblastoma. Whether this sign is specific for a choroidal infiltration or is just an artefact remains unclear. High resolution MRI scans did not allow the exclusion of this form of intraocular tumour extension. All nine cases with proved vitreous seeding were not detected by MRI scans. None of these cases showed scleral infiltration or orbital tumour extension. Therefore, it is not possible to judge the rank of this technique in detecting orbital tumour growth. CONCLUSION: The new MRI technique is of limited value in visualisation of prelaminar or postlaminar infiltration of the optic nerve. Advanced choroidal infiltration might be visualised by contrast enhanced T1 weighted MRI scans, but the available spatial resolution did not allow the exclusion this critical form of tumour growth by MRI scans. Nevertheless, high resolution MRI with the new surface coil has superior contrast and spatial resolution compared to computed tomograph (CT) or other available imaging techniques. MRI cannot replace CT in detecting tumour calcification but with increasing experience with this new technique it should be possible to renounce CT scans in the majority of cases of retinoblastoma.

Child↗

Monitoring retinal function in neovascular maculopathy using multifocal electroretinography - early and long-term correlation with clinical findings.

PURPOSE: To objectively investigate and longitudinally monitor retinal function in patients with choroidal neovascularization (CNV) due to exudative age-related macular degeneration (AMD) and myopia using multifocal electroretinography (mfERG). METHODS: Patients with classic and occult subfoveal CNV secondary either to AMD or to myopia were enrolled in the study. The mfERGs were performed at the beginning of the study and every 3 months subsequently during a follow-up period of 15 months. In addition, standardized visual acuity testing, ophthalmologic examinations, color fundus photographs and fluorescein angiography were performed. The mfERG records were derived with the VERIS-System (Electro-Diagnostic Imaging, San Mateo, Calif., USA); 103 locations within the central 50 degrees in diameter were stimulated concurrently by means of the m-sequence technique. Fixation stability was monitored throughout the recording session with an infrared eye monitoring system (VERIS Refractor/Camera unit). The first-order response component was extracted for each stimulated retinal location. The response densities of the first-order kernel were evaluated as a function of eccentricity from the center (ring 1) to the periphery of the stimulated area (ring 6). The results were compared to those derived from age-matched normal control groups. For each patient mfERG responses measured on follow-up visits were compared to each other to evaluate and monitor changes in retinal function. These changes were tested for correlation with those observed in other clinical and electroretinographic findings. Statistical analysis was performed using the Pearson coefficient. RESULTS: Subfoveal neovascular maculopathy was associated with a reduction in response density most prominent within the central 5 degrees over the area affected by CNV detected either at the beginning of the study or at the follow-up recordings. During the follow-up period patients 1 and 4 showed stabilization or a slight increase in response densities over the neovascular lesion-complex and a corresponding stabilization or slight increase in visual acuity accompanied by a decrease in the activity of the neovascular lesion as determined by fluorescein angiography. Patient 2 revealed an increase in response density correlating with an increase in visual acuity and decrease in lesion size. In the contralateral eye of this patient the response density dropped in the area of new subfoveal CNV. In patient 3 continuous progression of the disease was documented by fluorescein angiography and visual acuity. It correlated well with a continuous decrease in retinal response densities during the follow-up. CONCLUSIONS: Objective monitoring of retinal function and correlation with morphological and psychophysical findings was at least in part possible in patients suffering from AMD and myopia. In all of four patients whose subfoveal CNV was documented by fluorescein angiography. Response densities were reduced particularly in the central 5 degrees and in visual acuity. The mfERG data showed a moderate to high statistical correlation with visual function as measured by visual acuity. On the other hand, the greatest linear dimension of the lesion size showed only a weak to moderate statistical correlation with both the response densities of the mfERG and the visual acuity. We conclude that the size of the CNV complex does not represent an accurate measure of retinal function in neovascular maculopathy. The good correlation of the mfERG data with visual acuity suggests that it may serve for objective assessment of retinal function, of the areas overlying the CNV. It shows potential as a valuable tool for longitudinal monitoring of AMD patients.

Aged↗

[Endoscopic resection of malignant melanomas of the uvea after preoperative stereotactic single dose convergence irradiation with the Leksell gamma knife].

In cases of large volume and highly prominent melanomas of the uvea, it is rare for conventional methods of radiation therapy to enable salvage of the globe or even residual functionality of the affected eye. Complications due to the massive amount of accumulated necrotic tissue often necessitate subsequent enucleation of the blinded eye. Tumor-destroying, single-dose convergence irradiation (radiosurgery) of such tumors applied shortly before endoresection can represent a possible therapeutic alternative in these types of cases.

Adult↗

Partial deletions of the long and short arm of chromosome 3 point to two tumor suppressor genes in uveal melanoma.

Uveal melanoma is the most common form of primary eye cancer. Monosomy 3, which is an unusual finding in tumors but is present in approximately 50% of uveal melanomas, is significantly correlated with metastatic disease. To obtain positional information on putative tumor suppressor genes on this chromosome, we have investigated tumors from 333 patients by comparative genomic hybridization, microsatellite analysis, or conventional karyotype analysis. A partial deletion of the long arm was found in eight tumors, and the smallest region of deletion overlap (SRO) spans 3q24-q26. We found six tumors with a partial deletion of the short arm and were able to define a second SRO of about 2.5 Mb in 3p25. This SRO does not overlap with the VHL gene. Our finding suggests a role for two tumor suppressor genes in metastasizing uveal melanoma and may explain the loss of an entire chromosome 3 in these tumors.

Chromosome Deletion↗

Expression of Fas and Fas ligand in uveal melanoma: biological implication and prognostic value.

The interaction between Fas and Fas ligand is one possible immune escape mechanism used by tumour cells. In the present study, melanoma tissue from 103 patients who underwent enucleation for malignant uveal melanoma (iris melanomas excluded) was stained by immunohistochemistry with monoclonal antibodies specific for Fas, Fas ligand, CD3, CD8, and CD68. Histological and clinical data for these tumours were assessed. Both Fas and Fas ligand were detected in uveal melanomas. Cells of the monocyte/macrophage lineage rather than T-cells were the predominant group of tumour-infiltrating cells. The metastasis-free 5-year survival rates in the univariate analyses were considerably lower in patients with tumours that lacked Fas ligand expression (< 35% of the tumour cells), in the presence of more than 50 CD8-positive cells in 20 high-power fields and in the presence of more than 100 CD3-positive cells in 20 high-power fields. Fas and Fas ligand expression was associated with scleral infiltration. After adjustment for scleral infiltration, the predictive value of both Fas and Fas ligand expression was markedly decreased. In addition, the CD3- and CD8-positive cell count was positively associated with the histological cell type. Cox proportional hazards models showed that the presence of CD3- and CD8-positive cells was not an independent prognostic factor after adjusting for histological cell type. This preliminary observation deserves further investigation, which may shed more light on the immune escape mechanisms of this tumour and thus enable novel therapeutic strategies. The clinical relevance of this observation is limited, as more predictive parameters have been described for uveal melanoma.

Adolescent↗

[Iodine-125 brachytherapy and trans-scleral tumor resection in large uveal melanomas].

BACKGROUND: The treatment of large uveal melanomas is always a challenge to the ophthalmic oncologist due to the expected long-term complications. The purpose of this study was to compare 125Iodine plaque brachytherapy with transscleral resection of large uveal melanomas in terms of preserving visual function and avoiding secondary enucleation. PATIENTS AND METHODS: A total of 135 patients with similar tumor features were selected from a group of 211 patients with uveal melanomas where the tumor height was greater than 7.5 mm. Of these patients 87 were treated by 125Iodine brachytherapy and 48 patients by transscleral tumor resection. The mean follow-up time was 26 months. RESULTS: After transscleral resection 58% of the patients and after 125Iodine-brachytherapy 15% of the patients retained a visual acuity of > or = 0.1 after a follow-up of 28 months. Following iodine-brachytherapy there was a sixfold higher rate of secondary glaucoma. No difference was found with respect to the eye retention and mortality rate. CONCLUSION: Patients with large melanomas eligible for transscleral local resection have a better visual function than those treated by 125Iodine brachytherapy.

Adult↗

[Clinical findings in autosomal recessive syndrome of blue cone hypersensitivity].

BACKGROUND: Intrafamilial variability of the syndrome of night blindness, maculopathy, and enhanced S-cone hypersensitivity was examined. PATIENTS AND METHODS: Siblings with a history of night blindness and reduced visual acuity were examined clinically, psychophysically, electroretinographically (ERG), and electro-oculographically (EOG). RESULTS: The siblings had had night blindness since early childhood and reduced visual acuity since the age of 20 years. Ophthalmoscopy showed degenerative, pigmented changes and subretinal spots, while one sibling had cystic lesions in the fovea. Scotopic ERG showed no rod-driven responses, while large, slow waveforms were detected in response to bright flashes. Photopic ERG induced responses similar in time, amplitude, and configuration to those of the dark-adapted ERG. The b-wave configuration was unchanged in response to chromatic stimuli. However, photopic ERG was more sensitive to blue and white than to red stimuli. The light peak on EOG was reduced. CONCLUSIONS: The enhanced S-cone sensitivity syndrome was expressed to a different degree of severity and probably inherited in an autosomal recessive mode. These unusual ERG findings may be due to a depressed rod system and an increased number of S-cone photoreceptors, postreceptoral circuits, and S-cone sensitive ganglion cells.

Adult↗

Scleral buckling versus primary vitrectomy in rhegmatogenous retinal detachment (SPR Study): design issues and implications. SPR Study report no. 1.

BACKGROUND: In patients with more complex rhegmatogenous retinal detachments (RRD) not complicated by proliferative vitreoretinopathy (PVR), the most appropriate operating method is controversial, and different surgeons use different techniques. The Scleral Buckling Versus Primary Vitrectomy in Rhegmatogenous Retinal Detachments Study (SPR Study) is designed to compare primary vitrectomy and scleral buckling techniques in these patients. METHODS: The SPR Study is a multicentre, randomised, controlled clinical trial stratified by lens status. Patients with RRD which is not complicated by PVR grade B or C and which cannot be treated with a single meridional sponge are randomised to either scleral buckling or pars plana vitrectomy as first surgical intervention. Four hundred consecutive patients are to be recruited per subtrial (phakic and aphakic/pseudophakic patients), and followed up for 1 year. The primary endpoint (functional outcome) is the change in visual acuity. Secondary endpoints (anatomical outcome) include postoperative PVR, retinal reattachment and the number of reoperations necessary to achieve retinal reattachment. Twenty-seven institutions (49 surgeons) in six European countries have been recruited for participation in the study. CONCLUSION: The SPR Study is the first randomised prospective clinical trial to compare scleral buckling and primary vitrectomy in patients with RRD. The results of this study should enable vitreoretinal surgeons to improve the surgical therapy of patients with the more complicated manifestations of RRD.

Humans↗

[Corneoretinal dystrophy (Bietti)-- Long-term course of one patient over a period of 30 years, and interindividual variability of clinical and electrophysiological findings in two patients].

BACKGROUND: A tapetoretinal dystrophy with crystalline deposits of the retina and limbal cornea was described by Bietti in 1937. To date, only a few cases with long-term follow up have been reported. PATIENTS AND METHODS: Two patients are presented including the clinical findings, fluorescein angiography, electrophysiology [electroretinography (ERG); electrooculography (EOG), multifocal electroretinography (MERG)], adaptometry, and transmission electron microscopy (TEM) of peripheral blood lymphocytes. The clinical findings were at least in part documented over a period of 30 years. RESULTS: The most striking features were deposits in the retina and cornea associated with crystalloid lysosomal inclusions in peripheral lymphocytes, and choroidal atrophy especially in advanced stages of the disease. The light rise (EOG), rod- and cone-driven responses (ERG), the responses of the MERG and visual fields were affected progressively during the course. These advanced changes of the retinal pigment epithelium and choriocapillaris were observed in the 2(nd) decade already. CONCLUSIONS: The findings of deposits in the cornea, retina and lymphocytes may help to differentiate BCD from other chorioretinal dystrophies. The results confirm a variable course in clinical expression of BCD between individuals.

Adult↗

The possible role of radiofrequency radiation in the development of uveal melanoma.

There are few epidemiologic studies dealing with electromagnetic radiation and uveal melanoma. The majority of these studies are exploratory and are based on job and industry titles only. We conducted a hospital-based and population-based case-control study of uveal melanoma and occupational exposures to different sources of electromagnetic radiation, including radiofrequency radiation. We then pooled these results. We interviewed a total of 118 female and male cases with uveal melanoma and 475 controls matching on sex, age, and study regions. Exposure to radiofrequency-transmitting devices was rated as (a) no radiofrequency radiation exposure, (b) possible exposure to mobile phones, or (c) probable/certain exposure to mobile phones. Exposures were rated independently by two of the authors who did not know case or control status. We used conditional logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (95% CIs). We found an elevated risk for exposure to radiofrequency-transmitting devices (exposure to radio sets, OR = 3.0, 95% CI = 1.4-6.3; probable/certain exposure to mobile phones, OR = 4.2, 95% CI = 1.2-14.5). Other sources of electromagnetic radiation such as high-voltage lines, electrical machines, complex electrical environments, visual display terminals, or radar units were not associated with uveal melanoma. This is the first study describing an association between radiofrequency radiation exposure and uveal melanoma. Several methodologic limitations prevent our results from providing clear evidence on the hypothesized association.

Adolescent↗

The prognostic value of cyclin D1, p53, and MDM2 protein expression in uveal melanoma.

Malignant uveal melanoma is the commonest primary intraocular tumour in adults. It metastasizes frequently and 50% of patients die within 10 years of diagnosis. The expression of cyclin D1, p53, and MDM2 in uveal melanoma and their relationship to metastasis-free 5-year survival was determined, in order to investigate whether these proteins help to distinguish those patients with a favourable prognosis from those with a poorer one. Ninety-six eyes enucleated for uveal melanomas were immunohistochemically analysed for the protein expression of cyclin D1 and related cell-cycle markers, p53 and MDM2. The evaluation of the specimens was undertaken by two independent pathologists without knowledge of the outcome. Statistical analysis of clinical, morphological, and immunohistological features was performed. A 'favourable outcome' was defined as survival of at least 5 years after diagnosis, without metastases (n=57). An 'unfavourable outcome' was defined as death from metastases within the first 5 years after diagnosis of uveal melanoma (n=39). Cyclin D1 positivity (>15% positive tumour cells) as well as p53 positivity (>15% positive tumour cells) was associated with an unfavourable outcome (for cyclin D1: odds ratio=4. 2, 95% confidence interval 1.5-11.8, p=0.006; for p53: odds ratio=3. 2, 95% confidence interval 1.1-9.3, p=0.03). In addition, cyclin D1 positivity was associated with the presence of extraocular extension of the tumour (p=0.01), with the mixed or epithelioid cell type (p=0. 02), and with the tumour cell MIB-1 positivity (p=0.0001). MDM2 immunoreactivity of the tumour cells showed a potential correlation with clinical outcome (odds ratio=2.1, 95% confidence interval 0.8-5. 8, p=0.13). Multiple logistic regression models showed that cyclin D1 positivity is an independent prognostic factor after control for other prognostic markers. The expression of cyclin D1 in uveal melanoma is associated with a more aggressive course and histologically unfavourable disease. This could serve as a further independent prognostic factor in uveal melanoma.

Adolescent↗