Biomedical subjects
Publications and source records attributed to E A Murphy.
After a report of clinical effectiveness, four adult patients with monilethrix were treated with griseofulvin for six months at an orally administered dose of 500 mg (microsize) per day. No objective or subjective improvement was observed.
The advantages and disadvantages of evolutionary fitness (probability that a single mutant line will not become extinct) and genetic fitness (mean fecundity) are compared. For deterministic processes the two are equivalent, but for stochastic branching processes they may be totally unrelated except that an absolute genetic fitness of unity or less implies an evolutionary fitness of zero. To know the variance as well as the mean family size does not in general uniquely determine the evolutionary fitness. Except where genetic fitness is close to unity, the impact of selection is shown to be rapid for the binomial, Poisson, negative binomial, and truncated negative binomial distributions. Evolutionary fitness, though somewhat cumbersome, has greater relevance to evolution, genetic counseling, and voluntary population control; but genetic fitness which is much easier to handle is the more appropriate measure where a large number of mutants is involved. Some empirical data on the transmission of various types of characters from parent to child are analyzed to allow comparison of genetic fitness, Crow's index, and a Malthusian parameter, with evolutionary fitness. There is a fair, but far from perfect, agreement among them. Multiple correlation of evolutionary fitness with mean and variance of family size taken jointly suggests a much more satisfactory approximation. It thus appears that, at the least, the population geneticist cannot afford to ignore the variance (which is not adequately represented in Crow's index). These relationships, based on two sets of data only may be accidental and should be invoked with caution. It seems more than likely that other aspects of the distribution of family size (eg, even higher moments) may contain relevant information in certain cases.
The effect of parental longevity on the length of survival of offspring has been examined according to selected demographic and environmental characteristics. The present study is based on 7,103 progeny, 20 years old or older. They were the sons and daughters of 1,766 men or women, 90 or more years old, who were alive in 1922-1930 at the time of ascertainment. The age at death of the other parent of the offspring is the basis of classification used in this analysis. A positive relationship was found between age at death of the non-proband parent and the age at death of the offspring. This relationship existed regardless of similarities or differences in the characteristics analyzed.
Explore the source record for details and available documents.
Neuronal ceroid-lipofuscinosis is characterized by pigmentary degeneration of the retina, psychomotor degeneration, epilepsy and intracellular deposition of ceroidlipofuscin. Recent reports have suggested that deficiency of peroxidase is the basic genetic defect. However, deficiency of myeloperoxidase could be demonstrated in some but not all patients; this deficiency was noted only when p-phenylenediamine (PPD) was used as hydrogen donor and could not be confirmed with guaiacol. We found that horseradish peroxidase (HR-P) oxidized PPD in the absence of added H2O2. The oxidative product of PPD showed the same absorption spectrum as the peroxidative product. The oxidation of PPD by HR-P was not inhibited by catalase or superoxide dismutase. In addition, catalase oxidized PPD in the presence of H2O2. Soluble and granular fractions obtained from human polymorphonuclear leukocytes (PMN) also oxidized PPD in the absence of H2O2. Addition of H2O2 inhibited the oxidation of PPD in some cell fractions. This inhibition could be partially eliminated by dialysis of the cell fractions. Thus, PPD is not a suitable hydrogen donor for the study of peroxidase. This may explain the variable results obtained by the previous investigators. In contrast, guaiacol did not show these undesirable characteristics. The PMN peroxidase (measured with guaiacol), catalase, beta-glucuronidase, acid and alkaline phosphatases were studied in individuals from three families with juvenile neuronal ceroid-lipofuscinosis. Family 1: an affected boy and healthy parents; all showed normal enzyme activities in both soluble and granular fractions. Family 2: two affected sisters, one healthy sib and mother, and Family 3: one affected boy; all showed reduced peroxidase activities in the granular fractions. Other enzymes were normal. The role of peroxidase deficiency in the pathogenesis of neuronal ceroid-lipofuscinosis is not clear. The basic defect of this syndrome remains uncertain.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Blood from a woman with unexplained erythrocytosis had increased oxygen affinity, but no abnormality could be detected by electrophoresis or chromatography of her hemolysate. Separation of the tryptic peptides of her beta chains disclosed two half-sized peaks in the regions of beta T-11. The faster of these was abnormal, with the structure beta 101 Glu replaced by Asp. The new hemoglobin was called "Potomac." Three of the proband's four surviving siblings and both of her children were carriers. Differences in the ratio of carrier: normal children born to male of female carriers of 23 other high-affinity hemoglobins were not significant. The high proportion of carriers in this kindred was probably due to chance alone, and not because high maternal oxygen affinity interfered with oxygen transport to fetuses with normal hemoglobin.
An experiment was performed in which 13 scientists experienced in analyzing data on platelet survival were sent blind duplicate sets of ten platelet survival curves and requested to fit the "best" straight line through the data by eye and determine its point of intersection with the time axis. The duplicate sets labeled "control" and "aspirin" respectively were artificial data generated from evaluation for various times of a gamma curve of order five and adding random independent normal (Gaussian) errors having a standard deviation of 0.03. The results were analyzed to examine inter- and intra-observer variance, reproducibility and bias. The range of means of estimated survival was 8.68 days to 11.59 days and in the control data showed about 63 times as much variance among observers as that due to random error of measurement alone. The "aspirin" data showed similar results. Correlation coefficients within observers for the pairs of estimates varied from -0.307 to +0.920. Three observers showed strong systematic differences between the duplicate readings. These results provide clear evidence of the need for formal, rather than graphical, analysis of the data.
Explore the source record for details and available documents.
The significance of chromosomal markers in linkage and assignment has been pointed out. The usefulness of linkage in disease prevention is discussed with the limitations of this approach.
In families with one of the Mendelian hereditary polyposes, one can predict the proportion of patients at risk and thus obtain a denominator against which colonoscopy, barium enema, and fecal occult blood can be validated. Colonoscopy is more sensitive than barium enema. There were 42 positive colonoscopies, 12 positive barium enemas, both being positive in 10 of these. There were 141 negative enemas, 133 negative colonscopies, and 118 negative for both. Occult blood was positive in 30% of patients with polyposis, five to seven times more frequently than in those without evident polyposis. Colonoscopy detected polyposis in 30% of the progeny of affected people. The shortfall, compared with the 50% expected under the Mendelian hypothesis, is readily explained by removal of affected cases from the study by surgery or death from cancer.
In order to evaluate indium-111 (111In) as a "physiological" platelet label, rabbit platelets were labeled in vitro with 111In-8-hydroxyquinoline. The in vivo behavior of 111In labeled platelets was then compared with that of chromium-51 51Cr) labeled platelets in the rabbit. Several important features were evident. First, unlike 51Cr, reasonable platelet labeling efficiency could be achieved with 111In, even when the platelets were suspended in small amounts of autologous plasma. Second, the initial recovery of platelets at 20 minutes after infusion was significantly higher for the 111In labeled platelets than for 51Cr labeled platelets, providing the platelets were suspended and "washed" in plasma. Third, the mean survival time of 111In labeled platelets, as estimated using four different mathematical models, was comparable with that of 51Cr platelets. Finally, the high photon yield of gamma emitting 111In, unlike 51Cr, permits quantitative gamma camera imaging of the in vivo distribution of labeled platelets. Thus, this nuclide possesses advantages as a platelet label that will foster statistically more accurate kinetic research as well as quantitative in vivo distribution studies in humans.
The relationship of sensitivity and specificity to disease frequency is considered in quantitative detail for typical screening situations. It is shown by illustrative examples that most screening procedures applied unselectively to total populations will yield a vast abundance of false positive results. The important role of prior probability in interpreting diagnostic test results is spelled out and applied to paradigms for screening.
Explore the source record for details and available documents.
A matrix method to calculate conditional likelihoods in a pedigree and use them to determine recurrence risks for unilocal disorders in genetic risks is presented in this paper. Different matrices are assigned to individual members of the pedigree and combined into matrix expressions. The method is explained for X-linked recessive conditions and autosomal dominant conditions with incomplete penetrance.
Like general medicine, clinical genetics has responsibilities to research, to dissemination and to service. Each exists at three broad levels. The elemental comprises acquisition of fact and development of technics. At the intermediate level coherence becomes a major concern: the discernment of relations among facts; the incorporation of data into ideas and insights; organization of clinical findings into a diagnosis; and the development of the rational management. The sophisticated level calls for theories and cosmologies at the scientific level, and cultivation of scholarship and of clinical wisdom. All nine compartments should be mutually correcting. If any of them is neglected or isolated from the rest, the whole will be impoverished-the student will suffocate in disconnected, empirical facts; fanciful theories will be spun from tenuous evidence; well established theory will be neglected by the practitioner; the best-intentioned schemes will have disastrous long-term consequences.