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Biomedical subjects

A C Moll

Publications and source records attributed to A C Moll.

At least 19 recordsLinked to original sources
PubMed2006

Stage of presentation and visual outcome of patients screened for familial retinoblastoma: nationwide registration in the Netherlands.

BACKGROUND: In the Netherlands a comprehensive programme for screening just after birth for familial retinoblastoma is taking place. In this report the stage of the disease at the time of detection, by way of screening, and the long term visual outcome in these patients was evaluated. METHODS: A nationwide, retrospective study. From January 1992-July 2004, patients at risk for familial retinoblastoma were screened 1-2 weeks after birth, and investigated for laterality, Reese-Ellsworth classification/International Classification of Retinoblastoma, macular involvement, age of primary retinoblastoma, initial therapy, and visual outcome. RESULTS: 17 patients were diagnosed with familial retinoblastoma. 88.3% developed bilateral, 11.7% unilateral retinoblastoma. Of the 34 eyes, 56% were R-E group I, 16% were group II A-B, 16% were group III A-B, 9% were group IV, 3% were group V. Using the International Classification of Retinoblastoma, 72% were group A, 19% were group B, 6% were group C, 3% were group E. The visual outcome revealed 73.5% of eyes with 20/20-20/40, 26.5% eyes with < or = 20/100-no light perception; 5.9% of eyes were enucleated, all other eyes were treated with local or conservative treatment methods. Of all eyes, 59% had extramacular retinoblastoma, 98% of patients had at least one eye with extramacular retinoblastoma. CONCLUSION: Most familial retinoblastoma patients present as a R-E group I or group A when screened within 2 weeks after birth. Nearly 90% of patients had a long term visual acuity of 20/20-20/40. Despite the common occurrence of macula involvement, bilateral macula involvement was infrequent, and since most eyes were salvaged, good vision was obtained in the majority of patients.

Age of Onset↗
PubMed2006

Evaluation of cross-sectional and longitudinal construct validity of two vision-related quality of life questionnaires: the LVQOL and VCM1.

The Low Vision Quality of Life (LVQOL) questionnaire and the Vision-related Quality of Life Core Measure (VCM1) are two of the many vision-related quality of life (QOL) questionnaires that have been developed in recent years. Although psychometric properties of the LVQOL and VCM1 compare well with other vision-related QOL questionnaires, construct and longitudinal validity have not been assessed (adequately). The purpose of this study was to examine the cross-sectional and longitudinal construct validity of these questionnaires by testing specific pre-specified hypotheses about the relations of these questionnaires with other measures. The percentage of hypotheses regarding the cross-sectional construct validity that were refuted for the LVQOL was 22% for the basic aspects of vision subscale, 50% for the mobility subscale, 39% for the adjustment subscale and 17% for the reading and fine work subscale. For the VCM1 this percentage was 57%. For the longitudinal construct validity the percentage of hypotheses that were refuted ranged from 33 to 75% for the LVQOL subscales and was 50% for the VCM1. In conclusion, cross-sectional construct validity was satisfactory for the LVQOL subscales, but seemed poor for the VCM1. In addition, the longitudinal validity of these scales was poor to moderate.

Aged↗
PubMed2005

Inflammation and endothelial dysfunction are associated with retinopathy: the Hoorn Study.

AIMS/HYPOTHESIS: The exact pathogenesis of retinopathy in diabetic and non-diabetic individuals is incompletely understood, but may involve chronic low-grade inflammation and dysfunction of the vascular endothelium. The aim of this study was to investigate the association of inflammation and endothelial dysfunction with prevalent retinopathy in individuals with and without type 2 diabetes. METHODS: As part of a population-based cohort study, 625 individuals aged 50-74 years, stratified according to age, sex and glucose tolerance status, underwent an extensive physical examination. Retinopathy was assessed by an ophthalmological examination, including funduscopy and two-field 45 degrees fundus photography with mydriasis in both eyes. Levels of C-reactive protein (CRP), soluble intercellular adhesion molecule-1 (sICAM-1), von Willebrand factor, and soluble vascular adhesion molecule-1 (sVCAM-1) were assessed, together with the urinary albumin : creatinine ratio, and the results were combined to obtain summarising z scores for inflammation and endothelial dysfunction. RESULTS: The prevalence of retinopathy was positively associated with tertiles of CRP and sICAM-1. When compared with the lowest tertile, the highest tertile of the inflammatory z score was associated with retinopathy in all subjects (odds ratio [OR]=2.2, 95% CI 1.2-4.1, adjusted for age, sex and glucose tolerance status). The highest tertile of the endothelial dysfunction z score was associated with retinopathy among diabetic individuals (OR=4.4, 95% CI 1.2-15.9, adjusted for age and sex) but not in non-diabetic individuals. Additional adjustment for other risk factors, such as systolic and diastolic blood pressure, BMI, total cholesterol and triglycerides, or mutual adjustment of the inflammatory and endothelial dysfunction z scores did not change the results. CONCLUSIONS/INTERPRETATION: In this study, inflammatory activity and endothelial dysfunction were associated with retinopathy, which suggests their involvement in the pathogenesis of retinopathy.

Aged↗
PubMed2004

Fluorine-18 fluorodeoxyglucose positron emission tomography (PET) to detect vital retinoblastoma in the eye: preliminary experience.

BACKGROUND/AIMS: To report our first experience with FDG-PET in the detection of vital retinoblastoma. METHODS: Four newly diagnosed retinoblastoma patients, two treated retinoblastoma patients, and four control patients were enrolled in this pilot study. F18-FDG uptake was assessed in the light of clinical and histopathological features. RESULTS: PET discriminated between new patients and controls, although tumor uptake varied widely. PET added no useful information with regard to possible vital tissue in tumor scars in the eye of the two treated retinoblastoma patients. Moreover, PET findings did not correlate with clinical or histopathological features. CONCLUSION: Based on this small pilot study, F18-PET shows little promise in the detection of retinoblastoma. More research on other radiofarmacons is recommended.

Child, Preschool↗
PubMed2003

Comparative genomic hybridisation divides retinoblastomas into a high and a low level chromosomal instability group.

BACKGROUND: Retinoblastoma is the most common intraocular malignancy in childhood and is responsible for approximately 1% of all deaths caused by childhood cancer. AIMS/METHODS: Comparative genomic hybridisation was performed on 13 consecutive, histologically confirmed retinoblastomas to analyse patterns of chromosomal changes and correlate these to clinicopathological variables. Six cases were hereditary and seven cases were sporadic. RESULTS: In 11 of the 13 tumours chromosomal abnormalities were detected, most frequently gains. Frequent chromosomal gains concerned 6p (46%), 1q (38%), 2p, 9q (30%), 5p, 7q, 10q, 17q, and 20q (23%). Frequent losses occurred at Xq (46%), 13q14, 16q, and 4q (23%). High level copy number gains were found at 5p15 and 6p11-12. A loss at 13q14 occurred in three cases only. Relatively few events occurred in the hereditary cases (27) compared with the non-hereditary cases (70 events). The number of chromosomal aberrations in these 13 retinoblastomas showed a bimodal distribution. Seven tumours showed less than four chromosomal aberrations, falling into a low level chromosomal instability (CIN) group, and six tumours showed at least eight aberrations, falling into a high level CIN group. In the low level CIN group the mean age was half that seen in the high level CIN group, there were less male patients, and there were more hereditary and bilateral cases. Microsatellite instability was not detected in either of the two groups. CONCLUSION: Despite the complex pattern of genetic changes in retinoblastomas, certain chromosomal regions appear to be affected preferentially. On the basis of the number of genetic events, retinoblastomas can be divided in low and a high level chromosomal instability groups, which have striking differences in clinical presentation.

Age Factors↗
PubMed2001

Histopathologic features of retinoblastoma and its relation with in vitro drug resistance measured by means of the MTT assay.

BACKGROUND: Retinoblastoma is frequently treated with chemotherapy to facilitate intraocular therapy, as well as to diminish or delay radiotherapy in invasive disease. It is also used more extensively in patients with dissemination to the central nervous system and/or the bone marrow. Once the disease has spread, the prognosis is poor. Radiotherapy is effective in ocular retinoblastoma, but is associated with facial deformation and a higher chance for second primary tumors in the irradiation field. These sequelae emphasize the need to determine more effective chemotherapy schedules and local treatment. The aim of this study is to investigate the relation between in vitro drug resistance for ten cytostatic drugs and histopathologic features in primary retinoblastoma. MATERIALS AND METHODS. Forty-four fresh samples of primary retinoblastoma were tested for in vitro drug resistance using the 3-[4,5-dimethylthiazol-2yl]-2,5-diphenyl tetrazolium bromide (MTT) assay. The histopathologic features for differentiation, invasion and intra-ocular extension, necrosis, mitosis, and apoptosis were scored. RESULTS: The differentiation of the tumors revealed 24 poorly differentiated, 14 intermediately differentiated, and 6 well differentiated tumors. Tumor infiltration showed 3 minimal and 3 massive choroideal invasions, as well as 21 prelaminary and 2 postlaminary optic nerve invasions. The tumor was unifocal in 16 eyes and multifocal in 28 eyes, with extensive retinal involvement in 10 eyes and tumor seeding in 21 eyes. The MTT assay was successful in 82% of the samples after enzymatic handling of the tumor cells was omitted. Undifferentiated tumors were more sensitive to carboplatin (p = 0.034) and doxorubicin (p = 0.025), thiotepa (p = 0.051) and ifosfamide (p = 0.075) in comparison to differentiated tumors. Type of retinal involvement, invasion, focality, and seeding did not show a relationship with drug resistance. Calcified tumors were more resistant to actinomycin D and ifosfamide and more sensitive to vincristine; conversely, apoptotic tumors were more sensitive to ifosfamide and more resistant to vincristine (p = 0.027). Necrotic tumors were more sensitive to actinomycin D (p = 0.004), and mitotic tumors were more sensitive to idarubicin (p = 0.026). In 90% of the tumors extreme drug resistance to cytarabin was present. CONCLUSIONS: In retinoblastoma many histopathologic features are related to in vitro drug resistance. Undifferentiated tumors are more sensitive to several cytostatic drugs. Calcification and apoptosis show an inverse relation with in vitro drug resistance to ifosfamide and vincristine. Extreme drug resistance to cytarabin is observed; this drug should not be used in retinoblastoma treatment.

Antineoplastic Agents↗
PubMed2001

[Intraocular retinoblastoma: new therapeutic options].

Retinoblastoma is the most frequently occurring primary intraocular malignant tumour in children (12-15 new patients per year in the Netherlands). It occurs in one or two eyes. Bilateral retinoblastoma, which occurs in 40% of the cases, is always hereditary; unilateral retinoblastoma, which is found in 60% of cases, is hereditary in 10% of these cases. The presenting symptoms are: leucocoria, strabismus or a red, painful eye. Early detection of retinoblastoma is important for the chance of survival, the visual prognosis and preservation of the eye. The choice of treatment is based on the risk of metastases, the diameter and the location of the tumour, the age of the patient, the heredity and the visual prognosis. Nowadays, treatment more often consists of a combination of techniques. Enucleation is carried out when a large tumour fills over half of the globe; often this is the only possible treatment. Small tumours (diameter and thickness < 2 mm) in the centre of the retina can be treated with laser therapy and those in the peripheral retina by cryotherapy. Small to medium-sized tumours (< 8 mm diameter) can be treated with thermochemotherapy: systemic chemotherapy and laser hyperthermia, if necessary with adjuvant laser therapy or brachytherapy. Medium-sized tumours (< 8 mm thick) can be treated with just brachytherapy, sometimes preceded by chemoreduction.

Antineoplastic Agents↗
PubMed2001

[From gene to disease; retinoblastoma and the RB1 gene].

Retinoblastoma is caused by mutations in the RB1 gene. The penetrance is 95%, as in approximately 5% of the mutation carriers, no second somatic mutation occurs in one of their retina cells during embryonic development. Molecular diagnosis is performed by a complete scanning of the RB1 coding sequence which includes flanking intronic sequences. Approximately 85% of pathogenic mutations can be identified.

Child↗
PubMed2001

Second primary tumors in hereditary retinoblastoma: a register-based study, 1945-1997: is there an age effect on radiation-related risk?

OBJECTIVE: The aim of this study is to evaluate the influence of age at external beam irradiation (EBRT) on the occurrence of second primary tumors (SPTs) inside and outside the irradiation field in hereditary retinoblastoma patients. DESIGN: Cross-sectional study. PARTICIPANTS: The study included 263 hereditary retinoblastoma patients born in The Netherlands between 1945 and 1997. METHODS: A national register-based follow-up cohort study was performed on hereditary retinoblastoma patients. Information on therapy, age at irradiation, and location of SPT was obtained from the register. The Kaplan-Meier method calculated cumulative incidences of SPT in three subgroups: irradiation before (early EBRT) and after 12 months of age (late EBRT), and no irradiation. The Mantel-Cox method determined the statistical significance of differences between the cumulative incidence curves. MAIN OUTCOME MEASURES: Development of SPT inside and outside a precisely defined irradiation field in relation to age at irradiation. Our definition excluded pineoblastoma as SPT, because they constitute part of a trilateral retinoblastoma; in addition, they lie outside the field of irradiation. RESULTS: The cumulative incidence of SPT at the age of 25 years was 22% (95% confidence intervals 13%-34%) in the early EBRT group, 3% (0%-14%) in the late EBRT group, and 5% (1%-16%) in the nonirradiated group (Mantel-Cox overall: P = 0.001; between early and late EBRT, P = 0.04). However, in early irradiated patients, the incidence of SPTs inside and outside the irradiation field was similar (11%), and the difference between early and late EBRT in incidence of SPT inside the field of irradiation was less prominent than overall (11% vs. 3%: P = 0.37). Sensitivity analysis showed the results depended on the way SPT, irradiation field, and, especially, pineoblastomas are defined. CONCLUSIONS: Hereditary retinoblastoma confers an increased risk for the development of SPT, especially in patients treated with EBRT before the age of 12 months. However, the presence of similar numbers of SPTs inside and outside the irradiation field suggests that irradiation is not the cause. In other words, this study does not show an age effect on radiation-related risk. Rather, early EBRT is probably a marker for other risk factors of SPT.

Adolescent↗
PubMed2000

At what age could screening for familial retinoblastoma be stopped? A register based study 1945-98.

AIM: To evaluate until what age children in families with retinoblastoma should be screened. METHODS: A register based cohort (n= 685) study of Dutch retinoblastoma patients (1945-1998). The records of all familial hereditary retinoblastoma patients from 1945 were reviewed and the age at diagnosis and either they were screened from birth determined. RESULTS: 75 patients had the familial hereditary form of retinoblastoma. The mean age at diagnosis in patients with fundus screening (n=50) from birth on was 4.9 months (median 1.9 months; range 1 day to 48 months). Thus, 4 years was the latest onset of familial retinoblastoma properly evaluated from birth. This mean age was significantly different (p<0.0001) from the mean age at diagnosis in patients without fundus screening (n=25) from birth (mean 17.2 months; median 10.0 months; range 1.5-63.0 months). CONCLUSIONS: Ophthalmological screening of children and sibs at risk for familial hereditary retinoblastoma is recommended until the age of 4 years in order to detect retinoblastoma as early as possible.

Age Factors↗
PubMed1998

Distribution of tumors in the retina in hereditary retinoblastoma patients.

We have compared the location of the ocular tumors in hereditary retinoblastoma in relation to the age of the patients at time of diagnosis. Eighty fundus drawings were analyzed from 59 hereditary patients containing I 59 tumors. At the time of diagnosis, indirect ophthalmoscopy was performed under general anaesthesia in all patients and standard drawings of the retina were made depicting the number and relative location of all tumors. The distance between the center of the tumor and the center of the macula was measured and plotted against the age of the patients at time of diagnosis. The results show that the distance between the center of the tumor and the center of the macula at time of diagnosis increases with age during the first seven months after birth.

Child, Preschool↗
PubMed1997

Second primary tumours in hereditary- and nonhereditary retinoblastoma patients treated with megavoltage external beam irradiation.

The purpose of this retrospective study is to investigate the influence of 45 Gy megavoltage external beam radiotherapy on the occurrence of second primary tumours in hereditary- and non-hereditary retinoblastoma patients. Eighty-seven hereditary and 19 non-hereditary patients were irradiated for retinoblastoma. The follow-up of the hereditary patients ranged from 4-23 years (mean 12.4 years), of the non-hereditary patients from 6-23 years (mean 12 years). In the hereditary group 4 patients developed a second primary tumour (2 rhabdomyosarcoma, 1 osteosarcoma, 1 malignant histiocytoma), and 5 patients developed a pineoblastoma. Three second primary tumours were situated inside the radiation field. The latency period ranged from 1.5 to 18 years (mean 4.8 years). None of the non-hereditary patients developed a second primary tumour. The actuarially calculated probability of being free from second primary tumours was 96.9% at 10 years and 89.4% at 20 years (pineoblastoma excluded). The survival was 91.2% at 10 years and 84.2% at 20 years (pineoblastoma excluded). From this study it is suggested that external beam irradiation has a potentiating effect in patients, with the genetic predispopsition for retinoblastoma and who are more susceptible to second primary malignancies.

Adolescent↗