A morphologic study of Vietnam veterans.

The possibility that service in Vietnam has had an adverse effect on Vietnam veterans and is the cause of some of their current illnesses has been a controversial issue in the post-Vietnam period. Addressing this problem, a pathology study has been carried out at the Armed Forces Institute of Pathology (AFIP). Pathologic diagnoses found in Vietnam veterans have been compared with a control group of contemporary veterans without Vietnam service. This has revealed no statistically significant or unexplained differences in their demographic, anatomic, or morphologic findings. The essential similarity of their disease profiles to date fails to suggest the presence of any unique environmental factor that might have acted on the Vietnam group.

Cost-effective uroflowmetry in men.

A simple method of timed urine flow measurement performed at home by the patient is compared to instrumental measurements of peak flow rate. The timed method correlates well with the peak flow rate. Timed uroflowmetry is free, can be done in the privacy of the home and provides multiple measurements. This is a valid technique to document a weak stream and is a useful screening test for patients with lower urinary tract obstruction.

Levels of adenylate deaminase, adenylate kinase, and creatine kinase in frozen human muscle biopsy specimens relative to type 1/type 2 fiber distribution: evidence for a carrier state of myoadenylate deaminase deficiency.

Myoadenylate deaminase deficiency is believed to reflect a genetic deficiency of skeletal muscle, but its pattern of inheritance has not been established. We examined, histochemically and by quantitative biochemical assay, muscle biopsy specimens from 3 putative carriers of this disorder. Adenylate kinase and creatine kinase were assayed in parallel with adenylate deaminase in order to establish enzyme activity ratios and the variation of each enzyme with fiber-type distribution. Control tissue consisted of 34 biopsy specimens without notable abnormalities from 30 patients, and included 4 specimen pairs with disparate fiber-type contributions. By linear regression analysis, adenylate deaminase level averaged 2.8-fold higher, and adenylate kinase 4.5-fold higher, in type 2 than in type 1 fibers, whereas creatine kinase level did not differ. The slopes of the regression lines resulting from analysis of the four specimen pairs from individual patients agreed well with the overall regression line in each plot. The 3 putative carriers had adenylate deaminase levels 2.5 to 5.7 times lower than the mean control value for their fiber-type distribution, but at least 20 times higher than their enzyme-deficient kinfolk. This finding indicates that a carrier state does exist, and that the deficiency state reflects an autosomal recessive inheritance pattern. Three additional biopsy specimens were excluded from evaluation when preliminary analysis showed elevated adenylate kinase/adenylate deaminase ratios that were outliers at the 1% level. This result suggests a carrier incidence of 10% in the muscle biopsy specimen population, which would markedly bias population estimates if undetected.

Modifications of Callender's classification of uveal melanoma at the Armed Forces Institute of Pathology.

One hundred well-documented cases of uveal melanoma accessioned at the Armed Forces Institute of Pathology before 1970 were reviewed and reclassified to identify changes made in the Callender classification. We compared the new classification with the original classification to determine the effect of the changes on the prediction of outcome for the patient after enucleation. Staff pathologists had originally classified 52 of the 100 cases as spindle-cell type melanoma. Only 31 of the 100 cases were reclassified as spindle-cell types (two spindle-cell nevi and 29 spindle-cell melanomas). Tumors classified as mixed-cell type were further subdivided into groups based on the percentage and size of the epithelioid cells. Tumors formerly classified as spindle-cell type that contained small or rare epithelioid cells were reclassified as mixed-cell type. This improved the prediction of outcome for the patient. We found that nucleolar size and pleomorphism are important variables that should be considered in the classification of uveal melanomas.

Uveal melanoma: location, size, cell type, and enucleation as risk factors in metastasis.

In this series of 3,432 cases of malignant melanoma of the choroid and ciliary body, mortality from metastasis 15 years after enucleation was 46 per cent. This mortality was at least ten times greater than has been observed with tumors of the iris, probably owing to the greater size and more malignant cytology of choroidal and ciliary body tumors. In 56 per cent of the 3,432 cases, the melanomas were composed of a mixture of spindle and epithelioid cells. The 15-year mortality of patients with melanomas of mixed cell type was three times that of patients with tumors of pure spindle cell type. In 30 per cent of the cases in this series, the melanomas of the choroid and ciliary body were larger than 15 mm in diameter. Size was highly correlated with mortality. The distribution of deaths following enucleation in the 3,432 cases was a log-normal function of time from enucleation. This indicated that metastasis occurred in these fatal cases close to the time of enucleation. The authors were also able to infer that many years were usually required for these uveal melanomas to grow from small (7 to 10 mm in diameter) to large (greater than 15 mm in diameter). These observations are consistent with the hypothesis that dissemination of tumor cells at the time of enucleation has been a major cause of metastasis with small and medium-sized uveal melanomas.

Preliminary use of linear discriminant function to predict success or failure of kidney transplant.

Adenylate kinase (AK) activity appears in serum or in urine as a result of tissue destruction. The serum and urine AK activity are normally very low (as previously reported). These studies were carried out to determine the usefulness of measuring the appearance of urinary AK activity in the detection of renal transplant crisis. Serum creatinine determinations, the results of nuclear medicine studies and other clinical evidence, were compared with urinary AK activity during renal transplant crises. As a result of these studies, a model is proposed which assesses the reliability of predictors of success or failure of kidney transplants by step-wise discriminant function analysis using adenylate kinase and creatinine clearance measurements of urine to separate patients into two groups based on whether the kidney transplant was removed or retained postoperatively. The effectiveness of the predictors used in the analyses changed with respect to their importance during nonhomogeneous time intervals of analysis.

Inferred natural history of uveal melanoma.

We have observed that the fatality rate of patients with posterior uveal melanomas rapidly increased from a very low rate prior to enucleation to a maximum of 8% per year during the second year after enucleation. These data suggest to us that events related to enucleation have a deleterious effect on survival, and we have postulated that these events are either the iatrogenic dissemination of tumor cells or an adverse effect on the immune-defense system, or both. Others have proposed that the relationship between enucleation and increased mortality is only happenstance. They would attribute the onset of symptoms to the rapid growth of the malignant tumor and thus claim that this brings the patient to enucleation soon after the tumor becomes malignant. We have studied 2105 cases on file in the REgistry of Ophthalmic Pathology and have found that enucleation was not always performed shortly after the onset of visual disturbance. In one third of the cases, enucleation was delayed until onset oment was not obtained until the tumor measured larger than 15 mm in diameter. Using Zelen's method to infer the natural history of uveal melanoma, we found that the mean time it took for a small tumor (less than 10 mm in diameter) to become a large tumor (greater than 15 mm) was approximately 7 years. The average age of patients treated for medium-sized tumors was 5 years less than that of patients treated for larger tumors. This is interpreted as evidence of an average delay of 5 years in the treatment of large melanomas. If this delay is taken into consideration, then the patients treated with medium-sized tumors had a worse survival during the first 7 years than did patients whose treatment was delayed until the tumor became large. After the seventh year, however, the survival was better. These findings support our hypothesis that the postoperative increase in mortality during the first several years, particularly among patients with tumors of medium size, was related to enucleation.

Statistical analysis of follow-up data concerning uveal melanomas, and the influence of enucleation.

Reappraisal of follow-up data obtained on patients whose uveal melanomas were treated by enucleation before 1955 has led to the conclusion that the operation may have had an adverse effect, accelerating dissemination and a lethal outcome, especially among patients whose tumors were large and/or contained epitheloid cells. The temporal relationship of tumor deaths to enucleation is demonstrable regardless of whether calculations represent "death density" or "hazard" functions. Use of an inferred natural history model suggests that uveal melanomas are slowly growing neoplasms. An average of seven to eight years is required for small tumors to become large and an additional period of four years before metastatic diseases might be anticipated. The eye is exceptionally vulnerable to great fluctuations in tissue pressure that may account for iatrogenic spread of tumor cells during a variety of manipulations before and during enucleation. Research to prevent dissemination by improved management is indicated.

Variability of dry mass as a fundamental biological property demonstrated for the case of Vaccinia virions.

The dry mass of individual vaccinia virions, as an example of a presumably uniform biological population, prepared in different lost at the Institute for Tropical Hygiene in Hamburg, was tested for variability by quantitative electron microscopy. A value of 5.26 X 10(-15) g for the median weight of the particle was calculated from 7,300 determinations. By assessing the variability of polystyrene latex spheres, which were used as mass standards, we demonstrated that the variability of dry mass of vaccinia virions is fivefold greater than the variability (standard) introduced by the method for determining mass. It was concluded that while genetic control in a presumably homozygous virion is strict with respect to quality, quantity of viral components (other than DNA) varies in fashion that can be aptly described by a log-normal distribution. It is recognized that this observation is empirically supported by the paradigm that any composite biological entity is subject to quantitative variability, the more so the heavier the individual representatives of a species are. In addition, the effects that extractions and staining have on the dry mass of vaccinia are reported, as well as is the median for the dry mass of other strains of pox viruses.

Correlation of choice reaction time performance with biorhythmic criticality and cycle phase.

The biorhythm theory correlates behavior to physical, emotional, and intellectual cycles. It states that an individual's behavior is influenced by these three cycles which begin at the moment of birth and operate thereafter simultaneously. The theory is commonly tested when the occurrence of accidents is compared to the phase of the biorhythm cycles. If the theory is true, more accidents would occur on a critical day than would be expected by a random distribution. A second method to test the theory is used in this paper, where actual performance of a laboratory task is correlated with the phases of the cycle. Performance was measured in a choice reaction time (CRT) task with each task composed of 400 light flashes. The methods and results are presented and discussed. The conclusion reached from analyses of the data was that performance in the CRT task was no influenced by biorhythms.

Does enucleation of the eye containing a malignant melanoma prevent or accelerate the dissemination of tumour cells.

A reappraisal of survival data on patients with uveal melanomas has led us to these impressions: (a) that the mortality rate before enucleation is low, estimated at 1% per year; (b) that the mortality rate rises abruptly following enucleation, reaching a peak of about 8% during the second year after enucleation; and (c) that approximately two-thirds of the fatalities could be attributed to the dissemination of tumour emboli at the time of enucleation. From these impressions we believe the following conclusions are warranted: (a) enucleation as it has been performed in the past may have for many patients an adverse rather than a beneficial effect with respect to the development of metastatic disease from malignant melanoma of the choroid and ciliary body. (b) A long-term follow-up study of untreated patients with melanomas of the choroid and ciliary body is indicated. (c) New techniques for enucleation designed to prevent the dissemination of tumour cells must be developed and tested to enable the ophthalmic surgeon to remove safely the tumour-containing eye that has developed such complications as uncontrollable glaucoma, panophthalmitis, or proptosis from extraocular extension.

Uveal melanomas: correlation of cytologic features with prognosis.

Forty uveal melanomas were examined, half of which had proved fatal. Twenty cells were selected from each tumor, and six cytologic features were measured on each of these cells. It was found that the cells selected from fatal tumors had longer nuclei, more nucleoli, and greater nuclear pleomorphism than those selected from nonfatal tumors. Also, cells from melanomas classified as mixed cell type by the Callender classification had wider nuclei and longer nucleoli than those from tumors classified as spindle B cell type. Since the former cell type is associated with a worse prognosis, these features would probably assist in assigning prognosis to a large group of randomly selected malanomas. Thus, five nuclear characteristics (long nuclei, wide nuclei, long nucleoli, multiple nucleoli, and nuclear pleomorphism) should prove useful for predicting death from the dissemination of uveal melanoma.

Prognostic factors in small malignant melanomas of choroid and ciliary body.

Two hundre seventeen small malignant melanomas, each with a volume less than 1,400/cu mm, were studied to determine what factors were useful in predicting metastasis. Using a single-factor approach with 16 risk factors, we found seven that correlated well with outcome. These were cell type, pigmentation, size (largest dimension), scleral extension, mitotic activity, location of anterior margin of the tumor, and optic nerve extension. Using a linear discriminant function, the four best factors in combination were cell type, largest dimension, scleral extension, and mitotic activity. Four variables (largest diameter, location of anterior margin, mitotic activity, and optic nerve invasion) that might be correlated with clinical observations were found to be less accurate in separating fatal and nonfatal cases than cell type alone.