No One Saw This Coming: Endoparasitic Mites Behind the Eyes of a Double-Crested Cormorant.

We found hundreds of mites behind the eyes of a Double-crested Cormorant, Phalacrocorax auritus (Suliformes: Phalacrocoracidae). The mites were Neottialges evansi (Acari: Hypoderatidae), representing the first report of this parasite in P. auritus from western North America. Deutonymphs of N. evansi are endoparasites, typically reported infecting fat deposits over the pectoral muscles, axillary areas, and vent of cormorants. Here mites infected only orbital tissues, a new infection site for hypoderatid mites. We suggest a lack of reports of this infection site could be explained by limited scrutiny of orbits, and deutonymphs mites infecting orbits may be more common than expected.

The influence of geographical location, host maturity and sex on intestinal helminth communities of the double-crested cormorant Phalacrocorax auritus from the eastern United States.

Here the intestinal helminth infracommunities of 218 double-crested cormorants (Phalacrocorax auritus) from 11 locations in Alabama, Minnesota, Mississippi and Vermont are documented. Trematode infections were present in 98% of hosts; 65% of cormorants carried cestode infections, 4% were infected with acanthocephalans and 66% had nematode intestinal parasites. Parasite infracommunities of hosts collected on wintering grounds had higher richness and diversity than did birds collected on breeding grounds. Differences in parasite richness and diversity between male and female P. auritus were also detected, but not between immature and mature bird hosts. Parasite intensity did not differ by sex, maturity, or between breeding and wintering season. The most common parasite was Drepanocephalus auritus (spathans), which is recognized as a disease agent that negatively impacts the catfish aquaculture industry in the US. Echinochasmus sp. in double-crested cormorants is documented for the first time in the United States. We suggest that the differences observed among parasite infracommunities could be associated with the foraging distances travelled by P. auritus during breeding and wintering seasons, which is limited by allocation of parental care during the breeding season.

Pre-treatment protoporphyrin IX concentration in actinic keratosis lesions may be a predictive biomarker of response to aminolevulinic-acid based photodynamic therapy.

BACKGROUND: Although aminolevulinic acid (ALA)-induced protoporphyrin IX (PpIX) photodynamic therapy (PDT) is an effective FDA-approved therapy for actinic keratosis (AK), a substantial fraction of patients (up to 25%) do not respond to treatment. This study examined the feasibility of using pre-treatment measurements of PpIX concentration in AK lesions to predict response of ALA-PpIX PDT. METHODS: A non-invasive fiber-optic fluorescence spectroscopy system was used to measure PpIX concentration in patients undergoing standard-of-care ALA-PDT for AK. All patients provided assessments of pain at the time of treatment (n=70), and a subset reported pain and erythema 48-76 h after treatment (n=13). RESULTS: PpIX concentration was significantly higher in lesions of patients reporting high levels of pain (VAS score ≥5) immediately after treatment vs. patients reporting pain scores below VAS=5 (p<0.022) (n=70). However, pain was not an exclusive indicator of PpIX concentration as many patients with low PpIX concentration reported high pain. In a subpopulation of patients surveyed in the days after treatment (n=13), PpIX concentration measured on the day of treatment was uncorrelated with pain-reported immediately after treatment (r=0.17, p<0.57), but positive correlations were found between PpIX concentration and patient-reported pain (r=0.55, p<0.051) and erythema (r=0.58, p<0.039) in the 48-72 h following treatment. CONCLUSIONS: These data suggest that in vivo optical measurements of PpIX concentration acquired before light delivery may be an objective predictor of response to ALA-PpIX PDT. Identification of non-responding patients on the day of treatment could facilitate the use of interventions that may improve outcomes.

Comparison of once-daily and twice-daily dosing of 0.75% metronidazole gel in the treatment of bacterial vaginosis.

BACKGROUND AND OBJECTIVES: Bacterial vaginosis is the most common cause of vaginal symptoms in women and has potential complications. Efforts to improve treatment of this disease process are warranted. GOAL OF THIS STUDY: The goal of this study was to compare the safety and efficacy of once-daily intravaginal administration of 0.75% metronidazole gel for 5 days to the established twice-daily regimen in the treatment of bacterial vaginosis. STUDY DESIGN: Nonpregnant women with bacterial vaginosis diagnosed by accepted clinical criteria at 14 geographically diverse general gynecology clinics were enrolled in this prospective, randomized, investigator-blind, parallel study. They were treated with either once-daily or twice-daily 0.75% metronidazole gel 5 g intravaginally for 5 days and were reevaluated at 7 to 12 days and 28 to 35 days after completing treatment. Efficacy was determined by clinical criteria. Adverse drug reactions were monitored. RESULTS: Of the 514 evaluable women enrolled, bacterial vaginosis was cured at the first return visit among evaluable patients in 153 of 199 (77%) of those who received the once-daily and in 157 of 196 (80%) of those who received the twice-daily administration. Bacterial vaginosis was cured among evaluable patients at the final visit in 104 of 180 (58%) of those who received once-daily and 109 of 178 (61%) of those who received the twice-daily regimen. Intent-to-treat analysis showed cure at 1 month in 118 of 207 (57%) of those treated once daily and 129 of 209 (62%) of those treated twice daily. Side effects were mild, and none caused treatment discontinuation. CONCLUSIONS: Once-daily dosing of 0.75% metronidazole gel 5 g for 5 days yields efficacy, safety, and tolerance equivalent to the currently used twice-daily dosing in the treatment of bacterial vaginosis, adding another competitive choice to the available therapeutic options for this condition.

Induction of luteolysis by luteinizing hormone-releasing factor (LRF) agonist: sensitivity, reproducibility, and reversibility.

The reproducibility, reversibility, and the maximal effectiveness of the luteolytic action of [D-Trp6,Pro9NEt]-LRF (luteinizing hormone-releasing factor) (LRF-agonist) were evaluated during 43 treatment cycles in 15 normal women. LRF-Ag (50 microgram) administration subcutaneously on 1 or 2 days at varying times during the luteal phase of consecutive cycles was made. Successful luteolysis was achieved in 26 of 27 cycles (96%) in which LRF-Ag was administered between 5 and 8 days after the luteinizing hormone (LH) peak. However, LRF-Ag treatment failed to induce luteolysis in 10 of 13 cycles (77%) when treatment began within 5 days of the LH peak. The luteal phase of posttreatment cycles was functionally unaffected by prior LRF-Ag treatment. The present study has thus demonstrated the reproducibility and reversibility of LRF-Ag as a potent luteolytic agent, although its action is dependent upon the timing of administration with a window of maximal effectiveness on days 5 to 8 of the luteal phase.

Luteal phase defects induced by an agonist of luteinizing hormone-releasing factor: a model for fertility control.

Subcutaneous injection of 50 micrograms of a luteinizing hormone-releasing factor agonist (LRF agonist) for three successive days at the time of menstruation in normal cycling women induces a shortened luteal phase with suboptimal concentrations of circulating estradiol and progesterone. This luteal phase defect follows a reduced concentration of follicle-stimulating hormone during the follicular phase and a resulting inadequate follicular maturation. Since a short luteal phase is associated with an endometrium not conductive to implantation, administration of the LRF agonist at the onset of menstrual cycle may prove to be a practical and novel approach to fertility control.

Chorionic gonadotropin prevents LRF-agonist-induced luteolysis in the human.

The effects of exogenous and endogenous hCG on the luteolytic action of LRF-agonist, [D-Trp6, Pro9NEt]-LRF (LRF-Ag), were evaluated. In sequential studies, 4 normal cycling women treated with LRF-Ag (50 microgram S.C.) on two consecutive days had premature decline of circulating levels of progesterone (P) and estradiol (E2) with a shortened (p < 0.05) luteal phase (11.5 +/- 1.2 days) when compared to the control cycle (15 +/- 0.7 days). When intramuscular hCG was added to the LRF-Ag treatment in doses of 100 IU or 5000 IU daily for 7 days, the luteal function was prolonged (19 +/- 1.2 days, p < 0.05) with significant (p < 0.001) elevation of P and E2 levels compared with the control cycle. Four women with early pregnancy, requesting therapeutic abortion, were given LRF-Ag (50 microgram or 500 microgram S.C.) on 2 consecutive days. None of the 4 women aborted and there was no change in the levels of beta hCG, P or E2 over the course of a week. These results indicate that both exogenous or endogenous hCG can overcome the luteolytic effect of LRF-Ag within the dose and duration used. The possibility that a more prolonged administration of a larger dose of LRF-Ag may negate the luteotropic effect of hCG remains to be explored.

Evidence for increased dopaminergic and opioid activity in patients with hypothalamic hypogonadotropic amenorrhea.

PIP: The functional activity of endogenous opioids and dopamine (DA) was assessed by analyzing gonadotropin and prolactin responses to DA receptor antagonist (metoclopramide) and the opioid receptor antagonist (naloxone) in selected patients with hypothalamic hypogonadotropic amenorrhea and in normal cycling women. 8 amenorrheic and 9 normal women during the low estrogen (early follicular) phase of menstrual cycle were studied. Simultaneous blood sampling and agent infusion was performed via 2 indwelling catheters after an overnight fast. Those receiving metoclopramide (10 mg intravenous bolus) and those receiving naloxone (1.6 mg/h for 4 hours) had blood samples withdrawn at various intervals. The 8 amenorrheic patients weighed significantly less (P .01) and had significantly lower mean basal serum luteinizing hormone (LH) (P .0001) and prolactin (P .01) than normal women. Metoclopramide administered to normal women induced no significant changes in pituitary gonadotropin levels. In contrast, 4 of 8 hypogonadotropic amenorrhea patients responded to metoclopramide with a significant mean net change of LH (P .05); a concomitant rise in follicle stimulating hormone (FSH) was also seen but was not statistically significant. The other 4 showed no response, as in normal women. Prolactin response to metoclopramide was reduced uniformly in all 8 patients, independent of LH responders or nonresponders. Naloxone in normal women showed no response. However, a clear increment of mean LH in response to naloxone was observed in the same 4 hypogonadotropic amenorrhea patients who also responded to metoclopramide. Mean LH nearly doubled; FSH levels showed no significant changes. Those other 4 patients who had no response to metoclopramide also had no response to naloxone. The 4 LH nonresponders with significantly (P .01) lower mean basal prolactin levels compared with normal women showed greater than l00% increase in prolactin levels by Hour 3 of naloxone infusion; in contrast, the LH responders showed no changes in prolactin levels in response to naloxone infusion.^ieng

Evidence for an increased opioid inhibition of luteinizing hormone secretion in hyperprolactinemic patients with pituitary microadenoma.

The inhibiting role of endogenous opioid peptides on gonadotropin secretion was evaluated by the infusion of an opioid receptor antagonist, naloxone (1.6 mg/h for 4 h), in 10 hyperprolactinemic patients with pituitary microadenoma (prolactinoma) and 5 normal women during the early follicular phase of the cycle. In normal women, naloxone infusion induced no significant changes in any of the three pituitary hormones measured. Six prolactinoma patients with low normal levels of basal LH [10.0 +/- 1.0 mIU/ml +/- SE)] responded to naloxone infusion with an increment of circulating LH in the form of an amplified pulsatile pattern of release, which lasted for at least 2 h after the infusion. The other 4 patients with prepubertal levels of LH (4.9 +/- 0.8 mIU/ml) exhibited no LH response to naloxone. There were no significant changes in FSH or PRL levels in either group of patients. These findings suggest that an increased endogenous opioid inhibition of LH release occurs in patients with PRL-producing microadenoma.

Gonadotropin-estradiol responses to a superactive luteinizing hormone-releasing hormone agonist in women.

After the sc administration of 1, 10, and 50 micrograms of the LRF agonist [D-Trp6,Pro9,NEt]LRF, dose-dependent increments in circulating levels of LH, FSH, and estradiol were observed which were 2- to 3-fold greater in the late than in the early follicular phase. The 10-microgram dose of LFR agonist appears to induce a maximal acute gonadotropin-estradiol response. Both 10- and 50-microgram doses of the agonist elicited gonadotropin increments which were several times greater than that seen during the midcycle surge. The only difference between the two doses was the more sustained action on gonadotropin release of the latter. It is estimated that this superactive LRF agonist is approximately 140 times more potent than the decapeptide LRF. These observations provide information useful in the application of this LRF agonist for clinical studies.

Activation of pituitary gonadotropic function by an agonist of luteinizing hormone-releasing factor in the puerperium.

To test the hypothesis that long-term deprivation of endogenous luteinizing hormone-releasing factor (LRF) during the course of pregnancy may account for the lack of gonadotropin in the puerperium, six normal postpartum women were treated with the potent and long-acting LRF agonist (D-Trp6, Pro9-NEt)-LRF. A 50 microgram dose of LRF agonist was administered subcutaneously every 48 hours for four doses, with the first dose given on the first day post partum. Prior to treatment, each subject was tested with two pulses of LRF (10 micrograms at 2 hour intervals) and again at the end of LRF agonist treatment on day 10 post partum. Pulses of LRF induced no significant elevation of follicle-stimulating hormone (FSH) levels on day 1 post partum. During treatment, a significant (P less than 0.005) increase in basal FSH levels occurred after the second dose of LRF agonist administration. Following treatment, pulses of LRF elicited a remarkable gonadotropin release with a relatively greater percent rise for FSH than for human chorionic gonadotropin-luteinizing hormone. Our data indicate that the lack of gonadotropin activity during the first 3 weeks post partum is, at least in part, related to insufficiency of endogenous LRF secretion and that resumption of gonadotropin secretion can be functionally activated by treatment with the appropriate dose and intervals of an LRF agonist.

Effects of a superactive luteinizing hormone-releasing factor agonist on gonadotropin and ovarian function during the menstrual cycle.

The effect of a potent luteinizing hormone-releasing factor (LRF) agonist (D-Trp6, Pro9 NEt)-LRF on pituitary gonadotropin release and its concomitant ovarian response was examined in normal women during the early follicular (EFP), late follicular (LFP), and midluteal (MLP) phases. A single subcutaneous injection of 50 micrograms of LRF agonist in subjects during the EFP caused prompt release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) to levels comparable to those found during spontaneous midcycle gonadotropin surges, while in LFP subjects gonadotropin levels rose 1 1/2 to 2 times above the levels of midcycle surges. The LH/FSH release in the MLP was almost identical to that found in the EFP. The ovarian response as measured by increasing estradiol levels followed a similar pattern during the 48 hours after injection in all three phases of the cycle. The inappropriate gonadotropin surge induced by LRF agonist in EFP subjects resulted in prolonged follicular phases and anovulation. Three of four subjects in the LFP showed evidence of ovulation in response to the same dose of LRF agonist. The pharmacodynamics of gonadotropin-ovarian responses to this potent LRF agonist reported here should provide an important reference for systemic investigation and rational clinical application.

PIP: A potent luteinizing hormone-releasing factor (LRF) agonist (D-Trp6-Pro9 NEt)-LRF was studied to determine its effect on pituitary gonadotropin release, and its concomitant ovarian response was examined in normal women during the early follicular (EFP), late follicular (LFP), and midluteal phases (MLP). 16 normal, healthy women volunteered for this study where a single subcutaneous dose of 50 mcg of LRF agonist was injected during the EFP, LFP, and MLP. During the EFP, an injection caused prompt release of luteinizing hormone (LH) and follicle stimulating hormone (FSH) to levels comparable to those of the spontaneous midcycle gonadotropin surge. In LFP subjects, gonadotropin levels rose 1.5-2 times above the midcycle surge level. The LH/FSH release in MLP was almost identical to that found in the EFP. Ovarian response, as measured by increasing estradiol levels, followed a similar pattern during the 48 hours after injection in all 3 phases of the cycle. Prolonged follicular phases and anovulation were the result of the gonadotropin surge induced by LRF agonist in EFP. 3/4 subjects in the LFP showed evidence of ovulation in response to the same dose of agonist. This study demonstrates that this LRF agonist is a potent agonist of LRF in human subjects, and is approximately 144 times more potent than the decapeptide LRF.

Effects of maternal smoking on circulating catecholamine levels and fetal heart rates.

Eight pregnant chronic cigarette smokers were studied after 34 weeks of gestation to determine the effects of acute cigarette (two nonfilter cigarettes) inhalation on maternal neuroendocrine and cardiovascular changes and on the fetus. Cigarette smoking was found to induce rapid (within 2 1/2 minutes) elevations in maternal plasma norepinephrine and epinephrine levels and this was associated with a rise in maternal pulse and blood pressure. These changes are followed, with a 5 minute lag time, by a significant increase in fetal heart rate. A relatively slow but sustained increase in maternal carboxyhemoglobin (HbCO) concentration occurred. The time course of this increase in HbCO did not seem to be responsible for the acute changes in fetal heart rate. Maternal cortisol levels also showed a slow but sustained elevation. Our present findings, together with data obtained from animal models, suggest that cigarette smoking during pregnancy induces fetal hypoxia through two independent but additive pathways: (1) An acute effect is caused by nicotine activation of adrenergic discharge, resulting in vasoconstriction, a decreased uterine perfusion, and a consequent transient fetal tachycardia, and (2) a delayed but prolonged increase in HbCO may cause a sustained reduction of fetal oxygenation.