Metastatic melanoma to the ovary in pregnancy: A case report.

Metastatic melanoma to the ovary is an uncommon presentation. We report a case of metastatic melanoma to the ovary that presented as a growing left adnexal mass during pregnancy and was thought to be benign by imaging and frozen section pathology. Here we discuss the challenges in radiologic and pathologic diagnosis, as well as considerations for the mother and newborn.

Chloroquine for the treatment of uncomplicated malaria in Guyana.

At a public hospital in Georgetown, Guyana, 44 patients seeking treatment for symptomatic, slide-confirmed malaria were given standard chloroquine (CQ) therapy and followed for 28 days. The patients apparently had pure infections with Plasmodium falciparum (14), P. vivax (13) or P. malariae (one), or mixed infections either of P. falciparum and P. vivax (17) or of P. falciparum, P. malariae and P. vivax (two). Each received supervised treatment with 10 mg CQ base/kg on each of days 0 and 1, and 5 mg/kg on day 2. On the day of enrollment (day 0), the patients complained of fever (100%), headache (100%), malaise (94%), myalgia (79%), nausea (67%), vertigo (49%) and vomiting (33%). Many (39%) were ill enough to confine themselves to bed. On day 4, fewer of the subjects complained of fever (15%), headache (15%), malaise (6%), myalgia (21%), nausea (6%), vertigo (24%) or vomiting (0%) despite the relatively high (>48%) risk of therapeutic failure. The cumulative incidence of parasitological failure against P. falciparum was 15% at day 4, 33% at day 7 and 48% at day 14. All of the P. vivax and P. malariae infections cleared before day 4 and none recurred by day 7. Two infections with P. vivax recurred later (on day 14 or 28) but in the presence of less than adequate, whole-blood concentrations of CQ plus desethyl-chloroquine (i.e. <100 ng/ml). Taken together, the results indicate a high risk of therapeutic failure of CQ against P. falciparum but also indicate that resistance to CQ in P. vivax occurs infrequently in Guyana.

Seminal fluid causes temporarily reduced egg hatch in previously mated females.

In Drosophila, male accessory gland fluid (seminal fluid) has multiple effects on the female's reproductive efficiency. Here, we show the effect of seminal fluid on rate of egg hatch immediately following mating. Singly mated females were remated to two classes of sterile males, one with seminal fluid and one without seminal fluid. Transfer of seminal fluid results in a strong reduction in egg hatch shortly after the mating. Also, it is shown that remating with normal males causes an immediate reduction of egg hatch followed by recovery to normal egg hatch. In all cases, unhatched eggs contained no sperm. These results are consistent with a role for seminal fluid in sperm competition, mediated by incapacitation or inefficient use of resident sperm.

Female x male interactions in Drosophila sperm competition.

In several organisms, the success of a male's sperm in multiply inseminated females depends on the male's genotype. In Drosophila, the female also plays a role in determining which sperm are successful. Pairwise tests among six isogenic lines of Drosophila melanogaster were performed to determine whether there is a genotype-specific interaction in the success of sperm. The success of a particular male's sperm was found to depend on the genotype of the female with which he mates, providing evidence for an interaction with profound evolutionary consequences.

Polymorphism in genes that influence sperm displacement.

Paternity of offspring of multiply inseminated females is in many organisms highly skewed, with an advantage generally going to the male that most recently mated. Variation in sperm competitive ability can result in strong natural selection, and one expects that a gene that offers an advantage in sperm displacement would, all else being equal, be rapidly fixed, leaving low equilibrium levels of variability in sperm competition. However, empirical studies have demonstrated genetic variation in sperm displacement, begging the question of how this variation can be maintained. Here we develop a population genetic model to find conditions that maintain polymorphism in alleles that influence sperm displacement. We consider a one-locus model in which allelic variants have pleiotropic effects on fecundity and mating ability in addition to sperm displacement. This model can admit more than one stable polymorphism, and we find conditions for protected polymorphism. Induced overdominance is not necessary for stable polymorphism. These results have direct bearing on the observed variation in the ability of resident sperm to defend against displacement.

Stress and coping in families with deaf children.

More than 90% of deaf children are born to hearing parents who experience stress, not only in respose to the initial diagnosis, but also in adapting to the unique needs of their deaf child. This article is a selective literature review summarizing information from three fields in order to broaden our understanding of family adaptation to deafness. Discussion includes (1) psychology's model of individual stress and coping (2) family science's model of family stress management, and (3) literature on family adjustment to disability. The last part of the article traces the development of professionals' understanding of the reciprocal influences between deaf children and their families and describes recent research indicating that the impact of deafness on families is complex and variable. The final conclusion is that adoption of a family stress and coping paradigm would inform discussion of current issues in deafness, such as cochlear implants and bilingualism/biculturalism.

Variation in sperm displacement and its association with accessory gland protein loci in Drosophila melanogaster.

Genes that influence mating and/or fertilization success may be targets for strong natural selection. If females remate frequently relative to the duration of sperm storage and rate of sperm use, sperm displacement may be an important component of male reproductive success. Although it has long been known that mutant laboratory stocks of Drosophila differ in sperm displacement, the magnitude of the naturally occurring genetic variation in this character has not been systematically quantified. Here we report the results of a screen for variation in sperm displacement among 152 lines of Drosophilia melanogaster that were made homozygous for second and/or third chromosomes recovered from natural populations. Sperm displacement was assayed by scoring the progeny of cn;bw females that had been mated sequentially to cn;bw and tested males in either order. Highly significant differences were seen in both the ability to displace sperm that is resident in the female's reproductive tract and in the ability to resist displacement by subsequent sperm. Most lines exhibited nearly complete displacement, having nearly all progeny sired by the second male, but several lines had as few as half the progeny fathered by the second male. Lines that were identified in the screen for naturally occurring variation in sperm displacement were also characterized for single-strand conformation polymorphisms (SSCP) at seven accessory gland protein (Acp) genes, Glucose dehydrogenase (Gld), and Esterase-6 (Est-6). Acp genes encode proteins that are in some cases known to be transmitted to the female in the seminal fluid and are likely candidates for genes that might mediate the phenomenon of sperm displacement. Significant associations were found between particular Acp alleles at four different loci (Acp26Aa/Ab, Acp29B, Acp36DE and Acp53E) and the ability of males to resist displacement by subsequent sperm. There was no correlation between the ability to displace resident sperm and the ability to resist being displaced by subsequent sperm. This lack of correlation, and the association of Acp alleles with resisting subsequent sperm only, suggests that different mechanisms mediate the two components of sperm displacement.

Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry of paclitaxel and related taxanes.

Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry has been demonstrated for the analysis of Taxus brevifolia extracts. The detection limit for the taxanes contained therein is estimated at 1 pmol using the matrix 4-nitroaniline at a matrix-to-analyte molar ratio of 100:1. Acquisition and calibration of the mass spectral data requires less than 5 min. The [M+H]+, [M+Na]+, and [M+K]+ ions provide mol wt confirmation and structurally significant fragment ions indicative of the various substituent groups located on the diterpene skeleton are formed.

F statistics in Drosophila buzzatii: selection, population size and inbreeding.

Drosophila buzzatii is confined to reproducing in a well defined patchy environment consisting of rotting cactus cladodes which are ephemeral, permitting at most three generations. Flies emerging from such rots were used to estimate the additive genetic variance within rots and the genetic variance between rots for body size and also were electrophoresed to determine their genotypes at six polymorphic loci. F statistics were estimated from body size and allozyme data. The FST derived from body size was significantly larger than the allozyme FST. It is proposed this is due to selective differentiation of body size. The allozyme FST is used to estimate effective population size: 10 < N < 50. It is suggested that the regularly observed positive FIS's could be due to partial sib mating, S. If so, the estimated lower bound is S = 0.258. Experiments are identified which could support or contradict these interpretations.

C-peptide and the classification of diabetes mellitus patients in the Early Treatment Diabetic Retinopathy Study. Report number 6. The ETDRS Research Group.

The Early Treatment Diabetic Retinopathy Study (ETDRS), conducted at 22 clinical centers during the period 1980 to 1989, collected baseline data on C-peptide levels after ingestion of Sustacal in 582 patients with diabetes mellitus, prior to enrollment in the trial. Data on several clinical factors associated with diabetes were also collected from all 3711 enrolled patients. C-peptide data were used to develop sets of clinical criteria for the classification of ETDRS patients and to compare and contrast definitions of type of diabetes used in previous studies. The distribution of C-peptide levels was strikingly bimodal, suggesting a division of study participants into two groups--those with levels at 80 pmol/L or less and those with more than 80 pmol/L of C-peptide after Sustacal ingestion. Constellations of clinical characteristics that could serve as proxies for C-peptide level were ascertained. The result was two sets of clinically developed definitions for type of diabetes in the ETDRS. According to the more restrictive set of definitions, three groups were identified, compared to two groups using the "broad" set of definitions. Discriminant analysis was also used to classify ETDRS patients, yielding similar results. A comparison of definitions of type of diabetes used in the ETDRS and in previous studies revealed that even in the absence of C-peptide data, clinically derived definitions provided good discrimination between type I and type II diabetes.

Pathogenic factors in the development of type I and type II diabetes mellitus: 1990.

The pathogenesis of IDDM and NIDDM indicates a distinct difference between these diseases. Viral illness is implicated in IDDM, linked with evidence for an immune deficiency. NIDDM is not linked to viral illness or autoimmunity but is highly influenced by the inheritance of a defect in insulin production.

Is there selection on RFLP differences in mitochondrial DNA?

Experimental populations of Drosophila simulans were established for the purpose of detecting the presence or absence of selection on a restriction fragment length polymorphism in mitochondrial DNA (mtDNA). It was then discovered that the founding strains differed with respect to the Rickettsia-mediated incompatibility system in this species, which is maternally transmitted together with the mtDNA differences. A population model was constructed using the known fitness effects of the incompatibility system, with the result that the population trajectories can be completely explained by the effects of the microorganism with no need to invoke selection on mtDNA. The strong conclusion is that in this case we can rule out the strong selection proposed by MacRae and Anderson to explain the "dramatic mtDNA changes" in their Drosophila pseudoobscura populations. The population theory used for the experiments is discussed in the context of natural populations. Estimated parameters include the possibility that with two populations, one with the organism and one without it, there may be no bias as to which will invade the other, which in turn suggests no global tendency for the infection to spread or decline.

Synthesis of an attached autosome, C(3)RM, in Drosophila pseudoobscura.

Drosophila pseudoobscura has three acrocentric autosomes. In the experiments reported, homologous arms of the third chromosome were attached to the same centromere. This is a 'reversed metacentric compound' third chromosome, denoted by C(3)RM. This compound chromosome is relatively fertile in within-strain crosses (ca. 50% egg hatch) but sterile when outcrossed to a normal karyotype. When constructing translocations for this experiment, the behavior of the Y-autosome translocations suggested that this species can tolerate more Y chromosome deficiency while retaining fertility than can Drosophila melanogaster. Finally, there were no Robertsonian exchanges observed among the 96 autosome-autosome translocations analyzed cytologically.

Laboratory estimates of heritabilities and genetic correlations in nature.

A lower bound on heritability in a natural environment can be determined from the regression of offspring raised in the laboratory on parents raised in nature. An estimate of additive genetic variance in the laboratory is also required. The estimated lower bounds on heritabilities can sometimes be used to demonstrate a significant genetic correlation between two traits in nature, if their genetic and phenotypic correlations in nature have the same sign, and if sample sizes are large, and heritabilities and phenotypic and genetic correlations are high.

Ecological aspects of the heritability of body size in Drosophila buzzatii.

The heritability of thorax length in the cactophilic Drosophila buzzatii was determined for flies from each of 10 rotting cactus cladodes. For each rot, emerging flies were used as parents of progeny reared in the laboratory. The methods used were full sib analysis with the parents mated assortatively and also offspring-parent regression. From this, heritabilities were measured for the laboratory environment and for the natural environment of the rotting cladode. For the laboratory environment, h2 = 0.3770 +/- 0.0203 and for the natural environment h2 = 0.0936 +/- 0.0087 within rots and h2 = 0.0595 +/- 0.0123 for a population drawn randomly from different rots. Because of the possibility of genotype-environment interaction between the laboratory and rot environments, the methods of B. Riska, T. Prout and M. Turelli were used to show it is possible that there is no such interaction, but if there is, the above natural heritabilities are approximate lower bounds. These results are related to the general problem of determining heritabilities in nature where it is impractical to measure both parents and progeny in nature. Determining heritability not only in nature but in relation to subdivision into ephemeral patches (cladodes in this case) has an important bearing on natural selection response and to general theories of stabilizing selection proposed to explain the existence of genetic variation. Attempts were made to detect selection by using the size of emerging adults as an indicator of various levels of larval stress. No selection was detected, but the power to do so was very weak. Differences between progeny means from different rots indicated some genetic differences between rots which can be adequately explained by small numbers of founders. This suggests a random fine scale subdivision amounting to FST = 0.1483 +/- 0.0462.

Restoration of mutationally suppressed characters in Drosophila melanogaster.

We examined three strains of Drosophila melanogaster made wingless for periods of up to 40 years by homozygosity for the recessive mutant, vestigial. The intent was to quantify the degeneration of genes for wing structure and function that were not expressed during these periods. No increase in abnormality of wing morphology or use was found in the oldest strains despite up to 1000 generations of winglessness. We propose that these genes have remained intact because of important pleiotropic effects not connected with wing formation.

Gene flow and the geographical distribution of a molecular polymorphism in Drosophila pseudoobscura.

This paper discusses the relation between the geographical distribution of an enzyme polymorphism and population structure in Drosophila pseudoobscura. California populations of this species living in very different montane and lowland habitats separated by several kilometers are similar to each other in the frequency of an esterase allele. Previous estimates suggest that gene flow is too limited to account for this homogeneity of genetic structure, so that it must reflect some balancing force of natural selection. We slow, however, that dispersal over unfavorable habitats is much greater than earlier supposed. Isolated populations of D. pseudoobscura separated by 15 km from other populations are subject to large amounts of immigration. This is shown by changes in the seasonal abundance of this species and in the annual pattern of lethal alleles in such populations. The genetic structure of an experimentally perturbed isolated population in an oasis returned to normal within a single year, suggesting that such populations are ephemeral and that the oasis is subject to annual recolonization by distant migrants. Direct assessment of marked flies shows that they can move at least 10 10 km in 24 hours over a desert. Such extensive gene flow may help explain the distribution of the esterase allele, and is relevant to the high level of molecular polymorphism and its general lack of geographic differentiation throughout the range of D. pseudoobscura.

Patient recruitment techniques in clinical trials.

Recruitment is never easy, but insurmountable difficulties may arise if this problem is not addressed during the planning phase. Preparation for recruitment must then be started long before the study actually begins. These preparations include building local interest in the participating hospital, visiting local hospitals and medical groups, and informing the general public when feasible. As active recruitment begins, access to the study must be kept open and logistical problems must be solved on a daily basis. Frequent reassessment may demonstrate a failure to maintain goals. Innovative methods for reviving the campaign must then be put in place. Above all, share all successful recruitment methods with others in the study.