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Biomedical subjects

J W Gamel

Publications and source records attributed to J W Gamel.

At least 19 recordsLinked to original sources
PubMed1992

Efficacy of dacarbazine (DTIC) in preventing metastases arising from intraocular melanomas in mice.

At present there are no chemotherapeutic agents that have been proven to be effective in either preventing or retarding the progression of metastases arising from uveal melanomas in human subjects. Dacarbazine (DTIC), the single most effective chemotherapeutic agent in the treatment of cutaneous melanoma, is a potentially useful therapeutic modality for use as an antimetastatic agent in uveal melanoma. However, DTIC has not been evaluated for its ability to impede metastases originating from intraocular melanomas. The present study assessed the antimetastatic efficacy of DTIC in a murine intraocular melanoma model. The results indicate that treatment with DTIC resulted in sharp reductions in the number of spontaneous metastases and a significant prolongation of survival time. Dose-response studies indicated that exceedingly high doses of DTIC were necessary to produce antimetastatic effects even when drug treatment was combined with the calcium channel blocker verapamil. Collectively, the results indicate that DTIC can be an effective adjunctive therapeutic agent when administered at the time of enucleation of the melanoma-containing eye but is ineffectual if administered subsequent to surgery.

Animals↗
PubMed1992

A comparison of prognostic covariates for uveal melanoma.

For 740 selected cases of uveal melanoma from the Armed Forces Institute of Pathology, the following features were determined: the age and sex of the patient, Callender cell type (CT), and largest tumor dimension (LTD). In addition, special morphometric devices were used to measure the standard deviation of nucleolar area (SDNA) and the mean of the largest nucleoli (MLN) from a single routine hematoxylin and eosin-stained section of each tumor. Univariate analysis using the Cox proportional-hazards model revealed that LTD, CT, SDNA, and MLN correlated equally with death from metastatic melanoma (P greater than 10(-6). Age correlated less highly (P less than 0.002), and sex had no relationship to mortality. Multivariate analysis revealed that adding LTD as a prognostic covariate to either CT, SDNA, or MLN yielded a substantial increase in prognostic value. Because MLN can be measured more easily than SDNA and is more reproducible than CT, it can be a useful cytologic index of the malignant potential of uveal melanomas.

Choroid Neoplasms↗
PubMed1991

Immunohistochemical evaluation of uveal melanocytic tumors. Expression of HMB-45, S-100 protein, and neuron-specific enolase.

The authors compared the immunohistochemical reactivity of 13 uveal nevi and 20 uveal melanomas for HMB-45, S-100 protein, and neuron-specific enolase (NSE) in formalin-fixed, paraffin-embedded sections. All 33 of the lesions were positive for HMB-45. The false-negative rates for S-100 protein and NSE were 21% and 18%, respectively. If only strongly positive reactions were considered, more than 50% of the tumors would be interpreted as negative for S-100 protein and NSE. Nevi stained with less intensity than melanomas using all three antibodies. The expression of HMB-45 appeared to be greater in active nevi than in inactive nevi. There was a weak association between S-100 protein reactivity and the ability of the uveal melanomas to metastasize (P = 0.1); however, the standard deviation of nucleolar area was a much better predictor (P = 0.02). These results indicate that pathologists will find HMB-45 to be a useful tool in differentiating uveal melanoma from nonmelanocytic tumors.

Antibodies, Monoclonal↗
PubMed1991

Impact of local tumor relapse on patient survival after cobalt 60 plaque radiotherapy.

The authors investigated the impact of local intraocular tumor relapse on survival in a matched-group comparison study of patients with primary choroidal or ciliary body melanoma managed with cobalt 60 plaque radiotherapy. Sixty-two patients with local relapse were matched with an equal number of relapse-free patients in terms of known clinical prognostic factors for both melanoma-specific mortality (largest linear tumor dimension, location of anterior tumor margin, age) and local tumor relapse (location of posterior tumor margin). The follow-up of every relapse-free patient equaled or exceeded the interval to relapse for each matched patient with local relapse. The estimated 5-year survival (Kaplan-Meier) in the relapse-free patients was 87% (standard error = 4%), while that in the local relapse group was 58% (standard error = 6%). This difference is statistically significant (P less than 0.0001, log rank test). These results support the hypothesis that local tumor relapse after cobalt 60 plaque radiotherapy is an important post-treatment clinical indicator of the tumor's greater malignant potential and the patient's increased risk of melanoma-specific mortality.

Adult↗
PubMed1991

Enlargement of circumscribed choroidal hemangiomas.

The authors describe five patients with circumscribed choroidal hemangiomas. Fundus photography, fluorescein angiography, and ultrasound examinations showed progressive enlargement of these hemangiomas. In all cases, the extent of lesion enlargement was slight: the mean change in tumor size was 1.6 mm x 1.5 mm in basal diameters by 0.9 mm in thickness during a median interval of 52 months (range 33 to 100 months) between initial tumor diagnosis and detection of lesion enlargement. This series of cases demonstrates that circumscribed choroidal hemangiomas can enlarge slightly during long intervals between observations.

Adolescent↗
PubMed1991

Inheritance and regression toward the mean in heterogeneous cell populations.

Traits such as birth size and lifetime can vary widely even among non-mutated progeny of the same cell proliferating in the same environment. On the other hand, population parameters of these traits may remain stable over many generations, and there may be a distinct inheritance of these traits from mother to daughters. We have reconsidered the implication of mother-daughter correlations in light of linear regression analysis. It is proposed that a non-mutant cell whose phenotype deviates from the population mean produces progeny whose rate of regression toward the mean is proportional to 1-r, where r is the mother-daughter correlation coefficient of the trait under study. Theoretical support for this proposition is derived from linear regression analysis. Empirical support is found in pedigree analysis of cell growth constants among NIH3T3 mouse fibroblast cells, where the presence of an activated human ras oncogene is associated with a decreased r and an increased rate at which the growth constants of progeny regress toward the population mean.

Animals↗
PubMed1990

A randomized study of methanol-extraction residue of bacille Calmette-Guerin as postsurgical adjuvant therapy of uveal melanoma.

A randomized controlled clinical trial of methanol-extracted residue of bacille Calmette-Guerin adjuvant treatment of posterior uveal melanoma was undertaken. Of 113 patients, 34 patients received adjuvant immunotherapy and 79 patients received no treatment. No difference in survival was observed between the adjuvant-treated group and the control group of patients. This study found that the size of the tumor was a highly significant risk factor for death caused by metastasis of uveal melanomas. The standard deviation of the nucleolar area of the neoplastic cells was a significant risk factor, even though patients with tumors composed of Callender's spindle-type cells were not included in the study.

Adjuvants, Immunologic↗
PubMed1990

Clinical prognostic factors in patients with posterior uveal malignant melanoma.

The authors evaluated the prognostic value of clinically assessed variables for predicting length of survival until death from metastatic disease in 237 patient with a primary choroidal or ciliary body melanoma. Using multivariate Cox proportional hazards modeling, the authors identified the largest linear basal tumor diameter (mm), estimated by indirect ophthalmoscopy and fundus drawing, the location of the anterior margin of the tumor relative to the ocular equator and ora serrata, and the age of the patient at the time of treatment as the best combination of the clinically assessed variables for predicting survival. For each patient in this group, the authors computed a prognostic index based on the best multivariate Cox model. They showed that patients with low, intermediate, and high values of prognostic index had low, intermediate, and high melanoma-related mortality rates, respectively, during the first 5 to 8 posttreatment years. These results suggest that: (1) clinically assessed variables evaluated according to a standardized protocol are useful for predicting the survival of treated patients with posterior uveal melanoma and (2) ophthalmologists who assess potential clinical prognostic variables consistently may identify subgroups of patients with comparable mortality risk on the basis of noninvasive testing.

Analysis of Variance↗
PubMed1990

Cobalt-60 plaque radiotherapy vs enucleation for posterior uveal melanoma.

We compared the survival of 302 patients with a primary choroidal or ciliary body melanoma treated by cobalt-60 plaque radiotherapy between 1976 and 1982 with the survival of 134 patients treated by enucleation during the same period. Tumor size, location of the anterior margin of the tumor, and patient age at the time of treatment were identified as simultaneous significant clinical variables for predicting melanoma-specific mortality by multivariate Cox proportional hazards modeling. We computed a prognostic index for each patient based on this model and found that patients in the enucleation group had slightly higher values of this index than did patients in the cobalt-60 plaque radiotherapy group. Risk ratios for the treatment effect computed from a Cox model incorporating prognostic index and the treatment variable were found to be approximately equal to 1, both for analysis of melanoma-specific mortality and total mortality. These results indicate that when one controls for differences in prognostic index between the groups, cobalt-60 plaque therapy and enucleation are essentially equivalent in their effect on survival.

Adolescent↗
PubMed1990

Proportion cured and mean log survival time as functions of tumour size.

We obtained maximum likelihood estimates (MLEs) of the proportion cured pi c and mean log survival time mu t for a sample of 4355 patients with intraocular melanoma whose survival times subsequent to treatment were assumed to follow a log-normal distribution. Following stratification by tumour size, MLEs of pi c and mu t derived for each stratum correlate inversely with tumour size. We then expressed pi c and mu t as continuous functions of tumour size and calculated MLEs for the parameters of these functions from the entire sample. This investigation documents for ocular melanoma a significant relationship of tumour size to both cured fraction and mean log survival time.

Humans↗
PubMed1990

Matched group study of preenucleation radiotherapy versus enucleation alone for primary malignant melanoma of the choroid and ciliary body.

We report the results of a nonrandomized, matched group survival study comparing 29 patients with a choroidal or ciliary body melanoma managed by enucleation alone to 29 patients managed by enucleation following external beam ocular irradiation (20 Gy in five fractions over 5-7 days just prior to enucleation). Variables on which the patients in the two groups were matched included age at time of enucleation, largest linear tumor dimension, location of the anterior tumor margin relative to the equator and ora serrata, melanoma cell type, and extrascleral tumor extension. The cumulative 5-year survival in the enucleation alone group was 57.9% (SE = 9.9%), whereas that in the preenucleation radiation therapy group was 63.9% (SE = 12.2%). This difference is not statistically significant (p greater than 0.5, Mantel-Haenszel test). The authors discuss the strengths and limitations of their study and the implications of their results.

Adult↗
PubMed1990

Matched group study of surgical resection versus cobalt-60 plaque radiotherapy for primary choroidal or ciliary body melanoma.

We report the results of a nonrandomized, matched-group, survival and visual preservation study of patients with a choroidal or ciliary body melanoma managed by microsurgical resection of the tumor versus cobalt-60 episcleral plaque radiotherapy. Each treatment group consisted of 30 patients. All patients were matched on a case-by-case basis in terms of tumor size (largest linear tumor dimension), location of the anterior tumor margin relative to the ora serrata, location of the posterior tumor margin relative to the equator, and age at the time of treatment. Although the estimated actuarial 5-year survival probability was slightly greater in the resection group (85.2%) than in the cobalt plaque group (81.8%), this difference was neither clinically impressive nor statistically significant. In contrast, there was a substantially higher rate of early posttreatment severe visual loss in the resection group (P = .0008, Mantel-Haenszel test).

Adult↗
PubMed1989

Clinical parameters predictive of enlargement of melanocytic choroidal lesions.

The authors followed up 197 melanotic choroidal lesions (62 categorised as benign naevi, 76 classified as suspicious naevi, 41 diagnosed as dormant melanomas, and 18 categorised as active melanomas) left untreated after their initial clinical documentation. Thirty-nine of these lesions enlarged during a five-year follow-up interval (cumulative proportion of lesions that enlarged = 26.2% by Kaplan-Meier method). Individual clinical parameters predictive of lesion enlargement (p less than 0.01) included larger size of the lesion, especially lesion thickness, presence of retinal detachment, location of the lesion's posterior margin within 2 disc diameters of the optic disc, presence of symptoms, and presence of orange pigment clumps on the lesion's surface. The best combination of these parameters for prediction of lesion enlargement, as identified by multivariate Cox regression analysis, consisted of thickness of the lesion, retinal detachment, and symptoms. The five-year incidence of lesion enlargement for patients with none of these prognostic parameters was 5.8%, while that for patients with all three unfavourable parameters simultaneously was 90.6%.

Choroid↗
PubMed1988

Interval-by-interval Cox model analysis of 3680 cases of intraocular melanoma shows a decline in the prognostic value of size and cell type over time after tumor excision.

In a selected group of 3680 patients treated by ocular excision for uveal melanoma, 1178 deaths were attributed to this tumor during 20 years following ocular excision. Survival time was divided into intervals containing an equal number of deaths, and coefficients of the Cox statistical model were independently derived for each interval. This analysis revealed a statistically significant decline over time in the prognostic value of largest tumor dimension (LTD) and Callender cell type (CT). Mathematical considerations suggest that the prognostic value of parameters derived from other cancers may also decline with time following excision of the primary tumor.

Follow-Up Studies↗
PubMed1988

A method for determining the optimum transform for covariates of the Cox model with application to 3680 cases of intraocular melanoma.

For most applications of the Cox Model, a simple exponential relationship is assumed between covariates of this model and relative force of mortality (lambda). A method has been developed to examine this relationship in detail for data sets that contain a sufficient number of deaths. This method was applied to 3680 cases of intraocular melanoma with 1178 deaths over 20 years of follow-up, using largest tumor dimension (LTD) as a predictor of tumor-related death. Results indicated that the transform lambda = exp[beta log LTD] provides a closer approximation to observed mortality for this data set than the more traditional lambda = exp [beta LTD]. Additional applications to mathematically generated data sets revealed a close correspondence between lambda estimated by this method and the lambda programmed into each data set.

Epidemiologic Methods↗