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Biomedical subjects

J D Malley

Publications and source records attributed to J D Malley.

27 records · Page 2Linked to original sources

Telephone triage by primary care physicians.

To determine if experienced primary care physicians are more likely to reach correct decisions on the telephone than their less experienced colleagues, we asked 31 first-year and 29 third-year residents, 21 faculty, and 36 private practitioners in pediatrics and family practice to evaluate three pediatric patients via a telephone interview with a simulated mother and to decide whether each patient needed to be seen that evening. Compared with first-year residents, the third-year residents, faculty and private practitioners decided less frequently to see children who were not severely ill (P less than .05) or injured (P less than .01); however, less than half obtained histories considered adequate to rule out potential serious illnesses. Faculty did better than either residents or private practitioners in managing a severely dehydrated child; 100% of the faculty, but less than 60% of the residents or private practitioners, chose to see the patient promptly (P less than .001). More than one third of all residents and private practitioners reached inappropriate management decisions despite obtaining information that should have altered their decisions. In these simulations, experience in private practice was not associated with improved telephone management of very sick children. Faculty physicians appeared to be better able to identify severely ill children without inappropriately evaluating those who were less ill. In all three simulations, attainment of the correct decision appeared to be determined not by the number or type of questions asked, but rather by the physician's interpretation of the information collected.

Acute Disease↗

Variation of hepatic fibrosis and granuloma size among mouse strains infected with Schistosoma mansoni.

To investigate the relation between the size of circumoval granulomas and hepatic fibrosis, a variety of mouse strains infected with Schistosoma mansoni were examined and the number of eggs in the tissues, the fibrotic responses to the eggs, and the volume of the granulomas were determined. Marked differences in granuloma volume and in hepatic fibrosis were found between mouse strains, and those strains with the largest granulomas also showed the most hepatic fibrosis. On the other hand no significant correlation between granuloma size and hepatic fibrosis was found in the progeny of the F2 generation and backcrosses between F1 mice and the parental strains when crosses were made between Nmri mice (high granuloma volume and high fibrosis) and C57BL/6 mice (low granuloma volume and low fibrosis). Hepatic fibrosis per egg decreased with increasing infection intensity while granuloma volume was unaffected, indicating that fibrosis and granuloma size are at least in part modulated by different factors. The number of eggs found in the tissues per worm pair and the proportion of eggs in the liver also decreased as infection intensity increased. Some influence of the major histocompatibility complex on both granuloma size and fibrosis was found. Congenic mice on the C57BL/10 and C3H/HeSn backgrounds showed larger granulomas in H-2b than in H-2k mice, but no such correlation was found in comparing C57BL/6 mice with B6.H-2k mice. Less hepatic fibrosis was found in B10.M (H-2f), B10.SM (H-2v), and B10.RIII (H-2r) animals than in C57BL/10 mice. The regulation of granuloma size and of hepatic fibrosis is clearly complex and involves genes both outside of and within the major histocompatibility complex.

Animals↗

Treatment of precocious puberty in the McCune-Albright syndrome with the aromatase inhibitor testolactone.

The McCune-Albright syndrome is characterized by café au lait spots, fibrous dysplasia of bones, and sexual precocity. Girls with precocious puberty due to this syndrome have episodic increases in serum estrogen levels together with the formation of large ovarian cysts. The serum gonadotropin levels are typically suppressed, and the precocious puberty has not responded to treatment with long-acting analogues of luteinizing hormone-releasing hormone (LHRH). Encouraged by our initial success in a pilot study of one patient, we have now treated five girls with the McCune-Albright syndrome with the aromatase inhibitor testolactone, which blocks the synthesis of estrogens. Testolactone decreased the levels of circulating estradiol (P less than 0.05) and the ovarian volume (P less than 0.05), and there was a return to pretreatment levels after testolactone was stopped. During treatment, the peak responses of luteinizing hormone and follicle-stimulating hormone to stimulation by LHRH rose above suppressed pretreatment levels--significantly above pretreatment levels for follicle-stimulating hormone (P less than 0.02)--and then returned to pretreatment levels after testolactone was discontinued. Growth rates fell in three patients during treatment but could not be assessed in the other two because of bone deformities. The mean rate of bone maturation decreased and menses stopped in three of the four girls who were menstruating regularly. We conclude that testolactone is an effective treatment of precocious puberty in the McCune-Albright syndrome.

Aromatase Inhibitors↗

Evolution and structure of the fibrinogen genes. Random insertion of introns or selective loss?

Chromosomal linkage as well as sequence homologies provide unequivocal evidence that the genes for the alpha, beta and gamma chains of fibrinogen arose by successive duplication of a single ancestral gene. Yet, when the three fibrinogen chains are aligned by amino acid homology, the positions of intervening sequences coincide at only two positions for all three chains. While one additional intron occurs at a homologous site in the beta and gamma chains, none of the positions of the remaining 11 introns in the three genes is shared. This arrangement of introns in the three fibrinogen genes suggests that either introns were selectively lost, implying that there is essential information in the retained introns, or the common introns were present in the ancestral fibrinogen gene and introns have been randomly inserted since the triplication of the original gene. The more likely possibility of selective loss of introns implies that the ancestral gene, as it existed about one billion years ago, must have been composed of numerous small exons.

Amino Acid Sequence↗

Job satisfaction of staff registered nurses in primary and team nursing delivery systems.

Job satisfaction for nurses in team and primary nursing delivery systems as measured by a human needs questionnaire was studied. Staff-level registered nurses from 27 units in a large research hospital completed a 22-item questionnaire. Each item measured present and desired job satisfaction and the importance of the item to the respondent. Data from 115 primary-system nurses and 65 team-system nurses were analyzed by Kruskal-Wallis tests of significance and chi-square contingency tables. Overall, primary-system nurses reported greater job satisfaction than team-system nurses. The primary system offered more opportunity for accountability and fulfilling higher level needs. Neither system provided sufficient opportunities for self fulfillment, decision-making, or independent judgment. The identified weakness of the primary system was the unmet need for supervision. Of all the nurses in this study, 75% were dissatisfied with the prestige accorded to them.

Adult↗

Central venous pressure or pulmonary capillary wedge pressure as the determinant of fluid replacement in aortic surgery.

Both central venous pressure (CVP) and pulmonary capillary wedge pressure (PCWP) have been used as guides to fluid replacement in patients undergoing abdominal aortic surgery. To test the hypothesis that changes in PCWP (deltaPCWP) may be reliably estimated from changes in CVP (deltaCVP), 55 patients had simultaneous measurements (302 paired observations) of CVP and PCWP, as well as of cardiac output, before and during operation. The correlation between deltaCVP and deltaPCWP was high (r = 0.716, P less than 0.001). The estimated slope for the linear regression was 0.88. The standard error of the estimate was +/- 3.75 torr, making the prediction of deltaPCWP from deltaCVP accurate only to within 7.5 torr. There were five patients who each had a low and failing CVP accompanied by a stable cardiac output and a rising PCWP; for them, a decision to administer fluid based on the CVP might have resulted in pulmonary edema. Although deltaCVP accurately predicted direction and magnitude of deltaPCWP in the majority of patients (90%), there was a small group in whom there was no substitute for direct measurement of PCWP.

Adult↗

Size and shape analysis of schistomsome egg-counts in Egyptian autopsy data.

We study egg-counts from a series of Egyptian autopsy cases with active schistosomiasis at death (Kamel, Cheever, Elwi, Mosimann and Danner 1977). The data are unique, and enable us to study the proportional distribution of eggs among various organs in relation to infection intensity for two species of schistosome worms. We develop a model for the distribution of eggs in three organs of the mesenteric circulation. Under a lognormal distribution assumption, several exact statistical procedures are presented and used to examine model consistency as well as isometry with respect to geometric means. Mesenteric egg counts for both Schistosoma mansoni and S. haematobium behave consistently with the model, and show little or no departure from isometry in cases without Symmers' fibrosis of the liver. We show that cases with Symmers' fibrosis have relatively more S. mansoni eggs in the small, as opposed to large, intestine. In the genito-urinary organs we show that the proportion of S. haematobium eggs in the bladder is high for low-intensity infections. This is consistent with the conclusion of Smith, Elwi, Kamel and Lichtenberg (1975), based on egg/gram data, that such infections may be initiated in the bladder. The correspondingly high proportion of eggs in the ureters with high-intensity infections indicates that increased intensity may have a disproportionately large pathologic effect on the infected individual.

Autopsy↗

Recovery of reproductive function in rats treated with the aromatase inhibitor fadrozole.

The aromatase inhibitor, fadrozole hydrochloride (CGS 16949A), was developed for the treatment of breast cancer, and has not been available for pediatric use because of the lack of information about potential reproductive toxicology. To determine the effect of fadrozole on subsequent fertility and reproductive performance in rats, peripubertal male and female Sprague-Dawley rats (10/group) were given fadrozole by oral gavage once a day for 60 consecutive days (age 21 through 80 d) at a dose of 0, 1200, or 6000 micrograms/kg/d (dose range in women with breast cancer: 60 to 240 micrograms/kg/d). Following a 30-d recovery period (days 81 through 111 of age), cohabitation with untreated rats of the opposite sex was accomplished for 30 d or until positive evidence of mating was obtained (daily vaginal smears). The nonfadrozole-treated males used for cohabitation were proven fertile breeders; the females were virgin with proven 4-d estrous cycles. The duration of pregnancy, number, sex, condition, and body weight of pups were determined. Pregnant rats were weighed on gestational days 7, 14, and 20. There was a profound decrease in the number of estrous cycles at both dose levels of fadrozole compared to the control (P < 0.001). During the 30-d recovery period, estrous cycles were reestablished within a few days in the treated rats and the number and length of estrous cycles were not statistically different between fadrozole-treated and control rats. The gestational body weights of fadrozole-treated and untreated females did not differ significantly. There were no statistically significant differences in the number of matings/number of pairings, gestational length, mean live pups/litter, % pups born alive/litter, and % male pups/litter in the three groups (vehicle-, low-, and high-dose fadrozole-treated females, cohabited with untreated males and fadrozole-treated males, cohabited with untreated females). Thus, young male and female rats treated for 60 d with large doses of fadrozole had no detectable adverse effect on subsequent reproductive function.

Administration, Oral↗