Biomedical subjects
Publications and source records attributed to K J Ryan.
Reported is a maternal death associated with bilateral postpartum vulvar edema. Data are reviewed for this patient and four other patients who were previously reported to have had a syndrome of unilateral postpartum vulvar edema associated with maternal death. Overall, an 80% mortality rate has been observed.
The effects of nicotine, cotinine and anabasine on rat adrenal steroidogenesis were examined by spectral and enzymatic techniques. The addition of nicotine, cotinine or anabasine to preparations of rat adrenal mitochondria produced type II cytochrome P-450 difference spectra. The addition of nicotine or anabasine, but not cotinine, to rat adrenal microsomes yielded type II cytochrome P-450 difference spectra. Nicotine and anabasine competitively inhibited rat adrenal mitochondrial 11 beta-hydroxylase and microsomal 21-hydroxylase. Cotinine competitively inhibited mitochondrial 11 beta-hydroxylase, but did not inhibit microsomal 21-hydroxylase. The apparent enzymatic inhibition constants for cotinine, nicotine, anabasine and metyrapone inhibition of the mitochondrial 11 beta-hydroxylase were 32, 96, 120 and 74 microM respectively. These studies suggest that components of cigarette smoke may alter patterns of adrenal steroidogenesis.
We studied the utility of Gram-stained smears and semiquantitative cultures of endotracheal aspirates (ETAs) in diagnosing pneumonia in intubated patients in a pediatric intensive care unit. The chest radiographs of 35 intubated patients were independently reviewed by a pediatric radiologist and classified into probable, possible and unlikely pneumonias. Concomitant bacteriologic and radiographic information was available in 15 episodes of probable and 13 of possible pneumonia. These findings were compared with the ETAs obtained during the study from patients with no radiographic evidence of pneumonia (N = 21). There was a good correlation between ETA findings and radiographic evidence of pneumonia when ETAs were obtained within 60 minutes of initial intubation. Only a growth of greater than or equal to 3+ of a pathogen was associated with probable pneumonia when ETAs were obtained more than 60 minutes from initial intubation. There was a poor correlation between the microbiologic findings from ETAs and the results of blood cultures and postmortem examinations. Moreover 5 of 10 pairs of ETAs obtained within 18 hours of each other demonstrated discordant results. The ETAs from patients with indwelling endotracheal tubes correlated poorly with radiographic findings and are of questionable value in diagnosing the presence of pneumonia or its etiology in this group. They must be cautiously interpreted in critically ill patients.
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In a study of serum levels of endogenous tumour necrosis factor (TNF) in healthy people and patients with neoplastic or infectious disease, only patients with kala-azar (visceral leishmaniasis) and malaria were found to have a strikingly increased frequency of raised TNF levels (66.6% and 70.0%, respectively). 7.9% of samples from both healthy subjects and patients with neoplastic disease contained measurable TNF. The discovery of elevated TNF levels in the sera of patients with parasitic diseases suggests that this cytokine may play a part in host defences against parasitic infections.
Experiments were designed to identify the neural cell type(s) responsible for the aromatization and 5 alpha-reduction of androgens in the rat hypothalamus. Primary cultures of fetal rat hypothalamic cells, which had enhanced neuronal morphology, were treated at various times after plating with kainic acid (KA), a neurotoxic agent which selectively destroys neuronal cells. Neuronal morphology was disrupted in a time (0-6 days)- and dose (10(-4)-10(-2) M)-dependent fashion after KA treatment, with no apparent change in the appearance of the flattened, underlying non-neuronal cells. KA treatment for 4 days decreased aromatization by 94% in a dose-dependent fashion (10(-4)-10(-2) M KA), while 5 alpha-reduction declined by no more than 25%. A 6-day time course with 10(-3) M KA showed a dramatic decline in aromatization and no alteration in 5 alpha-reduction. In control experiments, substance P, a neuronal peptide, declined after KA treatment while the activity of glutamine synthetase, a glial enzyme, did not change. We conclude from these results that aromatase is localized primarily to neuronal cells in the hypothalamus while 5 alpha-reductase is confined primarily to non-neuronal cells.
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Hyperplasia of testicular Leydig cells and ovarian theca-lutein cells is a common histologic finding in infants of diabetic mothers. The functional correlates of this histologic finding were investigated by measurement of the beta-subunit of human chorionic gonadotropin, testosterone, dihydrotestosterone, androstenedione, estradiol, and estrone in the amniotic fluid compartment of gestations with male and female fetuses in diabetic mothers (N = 34) and control women (N = 34) at term. When compared with those of control subjects, gestations of diabetic mothers had significantly higher amniotic fluid concentrations of the beta-subunit of human chorionic gonadotropin. Gestations with either male or female fetuses in diabetic mothers had significantly higher amniotic fluid testosterone and dihydrotestosterone levels when compared with those of their respective gender controls. In gestations with male fetuses in diabetic mothers there was a significant positive correlation between the beta-subunit of human chorionic gonadotropin and testosterone. There was no significant difference in amniotic fluid androstenedione, estradiol, or estrone levels between the gestations of diabetic mothers and those of control women. These results suggest that the testicular Leydig cell and ovarian theca-lutein cell hyperplasia seen in infants of diabetic mothers is due, in part, to elevated levels of human chorionic gonadotropin and is associated with elevated testosterone and dihydrotestosterone concentrations in the amniotic fluid.
Epidemiologic studies suggest that women who smoke have lower endogenous estrogen than nonsmokers. To explore the possible link between cigarette smoking and decreased endogenous estrogens, we have examined the effects of constituents of tobacco on estrogen production in human choriocarcinoma cells and term placental microsomes. In choriocarcinoma cell cultures, nicotine, cotinine (a major metabolite of nicotine), and anabasine (a minor component of cigarette tobacco) all inhibited androstenedione conversion to estrogen in a dose-dependent fashion. Removal of nicotine, cotinine, and anabasine from the culture medium resulted in the complete reversal of the inhibition of aromatase. In the choriocarcinoma cell cultures, a supraphysiologic concentration of androstenedione (73 microM) in the culture medium blocked the inhibition of aromatase caused by nicotine, cotinine, and anabasine. In preparations of term placental microsomes, nicotine, cotinine, and anabasine inhibited the conversion of testosterone to estrogen. Kinetic analysis demonstrated the inhibition to be competitive with respect to the substrate. These findings suggest that some nicotinic alkaloids directly inhibit aromatase. This mechanism may explain, in part, the decreased estrogen observed in women who smoke.
The effects of insulin and insulin-like growth factors (IGFs) on ovarian androgen production were examined in ovarian stroma obtained from four women with hyperandrogenism and three women without hyperandrogenism. In incubations of stroma obtained from all four hyperandrogenic patients, insulin alone (500 ng/ml) significantly stimulated androstenedione and testosterone release. LH alone (25 ng/ml) significantly stimulated androstenedione release in incubations of stroma obtained from three of the four hyperandrogenic patients and testosterone release in incubations of stroma obtained from one of the four hyperandrogenic patients. In stromal incubations from three of the four hyperandrogenic patients, insulin alone (500 ng/ml) resulted in a significantly greater release of androstenedione and testosterone than did LH alone (25 ng/ml). Dihydrotestosterone was released in measurable quantities in incubations of stromal tissue obtained from three of the four hyperandrogenic women. In all three instances in which dihydrotestosterone was detectable, insulin alone (500 ng/ml), but not LH alone (25 ng/ml), significantly stimulated dihydrostestosterone release. Incubations of stroma obtained from three nonhyperandrogenic, normally cycling women demonstrated low levels of androstenedione release and negligible testosterone and dihydrotestosterone release. Insulin alone (500 ng/ml) and LH alone (25 ng/ml) produced no significant increase in androstenedione release. Insulin (500 ng/ml) plus LH (25 ng/ml) significantly stimulated androstenedione accumulation in stroma obtained from two of the nonhyperandrogenic women. One insulin dose-response experiment was performed using stromal tissue obtained from a hyperandrogenic woman. In this experiment, insulin, at a dose of 50 ng/ml, was as effective as insulin at a dose of 500 ng/ml in stimulating androstenedione and testosterone release. In addition to insulin, IGF-I/somatomedin C (50 ng/ml) stimulated androstenedione and testosterone release. Relaxin (1 microgram/ml) and multiplication-stimulating activity (50 ng/ml) did not stimulate androstenedione and testosterone release. These studies suggest that human ovarian stroma may be a target tissue for insulin and IGF-I, and that hyperinsulinemia may be an important factor contributing to ovarian hyperandrogenism.
Sixteen episodes of fungemia due to Coccidioides immitis were identified in 15 patients over a 7-year period at 2 hospital associated with the University of Arizona in Tucson. Fourteen of the 15 patients were male and 13 had an underlying condition, including malignancy in 6 and AIDS in 3. Ten of the patients were receiving corticosteroids at the time of fungemia. TP antibodies were present in 5 of 9 episodes and some titer of CF antibody was present in 7 of 11 instances. None of the 10 patients tested had a positive 1:100 coccidioidin skin test. In 11 of 15 episodes, a miliary chest roentgenographic pattern was apparent at the time of fungemia. Eleven of the 16 episodes ended in death within 1 month of the positive blood culture. Fungemic patients were compared to patients with culture-proven coccidioidomycosis without fungemia and differed from them significantly in 3 respects. First, fungemic patients were more likely to have a diffuse miliary pattern on chest radiograph. Second, all fungemic patients had, by definition, disseminated coccidioidomycosis and this was more likely among fungemic patients than among non-fungemic patients. Finally, fungemic patients were more likely to die within 1 month of the positive culture for C. immitis. Fungemia occurred in greater than 30% of patients with culture-proven coccidioidomycosis who had a blood culture performed. These results suggest that coccidioidal fungemia is a marker for a severe, acute form of disseminated coccidioidomycosis associated with a high mortality.
Recent epidemiologic studies suggest that women smokers have lower endogenous estrogen levels than nonsmokers. The effects of aqueous extracts of cigarette smoke on aromatase were evaluated in cultures of human granulosa cells. Aqueous extracts of cigarette smoke inhibited the conversion of androstenedione (delta 4A) to estradiol in a dose-dependent manner. Dialysis experiments demonstrated that 90% of the inhibitory activity of aqueous extracts of cigarette smoke was in the less than 1000 mol wt fraction. Removal of the aqueous extract of cigarette smoke from the culture medium resulted in a complete reversal of the inhibition of delta 4A aromatization. Addition of supraphysiologic concentrations of delta 4A (73 microM) to the culture medium blocked the smoke-induced inhibition of aromatization. Two low-molecular-weight components of cigarette smoke, nicotine and anabasine, inhibited granulosa cell aromatase in a dose-dependent manner. These studies suggest that constituents of cigarette smoke inhibit a major steroidogenic pathway.
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Rapid microbiologic testing is of value to the clinician only to the extent that these results are reported in an equally rapid fashion. This paper discusses an approach where both manual and automated results are transmitted via a laboratory computer system as soon as they are generated in the laboratory. For the Vitek AutoMicrobic System, on-line interfaces have been developed; this system operates in a manner similar to instruments in clinical chemistry or hematology laboratories. Systems for on-line editing of bacterial identification and antimicrobial susceptibility data are also discussed. It is concluded that computer systems capable of accomplishing instantaneous transfer of traditional and rapid microbiologic results are available and such systems are operating in some clinical microbiology laboratories.
Legionella maceachernii, previously isolated only from the environment, was shown to be a cause of fatal pneumonia in an immunocompromised patient.
Leydig cell hyperplasia is a common histological finding in male infants of diabetic mothers. The functional correlates of this histological finding were investigated by measuring beta hCG, testosterone, androstenedione, dihydrotestosterone, and progesterone in mixed cord serum of male and female infants of diabetic mothers (n = 40) and normal mothers (n = 40) at term. Male and female infants of diabetic mothers had significantly higher cord serum beta hCG levels than male and female controls. Male infants of diabetic mothers had significantly higher cord serum testosterone concentrations than male controls, female controls, and female infants of diabetic mothers. Cord serum testosterone concentrations were similar in female infants of diabetic mothers and female controls. In the male infants of diabetic mothers, there was a significant positive correlation between beta hCG and testosterone (r = 0.64; P less than 0.01). There was no significant correlation between beta hCG and testosterone in the male controls (r = -0.15; P = NS). There was no significant difference in cord serum dihydrotestosterone in any group tested. Cord serum progesterone was significantly higher in the males than in the females. Cord serum androstenedione was lower in the infants of diabetic mothers than in the controls. This study suggests that the Leydig cell hyperplasia found in male infants of diabetic mothers is due, in part, to elevated concentrations of hCG and is accompanied by elevated testosterone concentrations in the fetal compartment.
Interview and record review data from 12,023 singleton deliveries were analyzed to determine the relationships between neonatal hyperbilirubinemia (10 mg/dL or greater) and maternal characteristics. Confounding variables were controlled by multiple logistic regression analysis. There was a statistically significant positive relationship between hyperbilirubinemia and low birth weight, Oriental race, premature rupture of membranes, breast-feeding, neonatal infection, use of the "pill" at time of conception, instrumental delivery, and history of first trimester bleeding. Maternal smoking and black race were negatively related to hyperbilirubinemia and statistically significant. In this study, other previously suspected etiologic factors such as epidural anesthesia, parity, use of oxytocin in labor, and white race were not associated with hyperbilirubinemia.
To evaluate the risk of spontaneous abortion among former intrauterine contraceptive device (IUD) users, we compared the contraceptive history of 328 women with a spontaneous abortion up to 28 weeks' gestation with that of 1715 women having a term delivery. A similar percentage of case and comparison subjects reported prior IUD use as well as IUD use within the year before pregnancy. However, IUD use lasting more than 12 months was associated with a 1.5-fold increase in the crude risk of spontaneous abortion up to 28 weeks' gestation (p less than 0.05), a 1.8-fold increased risk of first-trimester spontaneous abortion, and a 1.7-fold increased risk of incomplete abortion (p less than 0.01). The results were not altered by control of individual confounding factors. When confounding factors were controlled simultaneously in a multiple logistic regression analysis, the relative risks were 1.4, 1.7 and 1.6, respectively; however, they were no longer statistically significant. The results suggest that prolonged IUD use may be associated with a modest increase in risk of subsequent spontaneous abortion.