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Biomedical subjects

C McArdle

Publications and source records attributed to C McArdle.

At least 19 recordsLinked to original sources

Pituitary adenylate cyclase activating peptide-38 (PACAP-38), PACAP-27, and PACAP related peptide (PRP) in the rat median eminence and pituitary.

Pituitary adenylate cyclase activating peptide (PACAP) is a member of the vasoactive intestinal peptide-like peptide family. It is found in the hypothalamus, where the PACAP precursor is processed to form PACAP-38, the C-terminal truncated PACAP-27 and PACAP related peptide (PRP). Both PACAPs are potent stimulators of anterior pituitary adenylate cyclase activity, but the physiologically relevant anatomical sources of PACAP and possible importance of PRP in this regard are poorly understood. Using immunocytochemistry with epitope-specific antisera, we now show that PACAP38-, PACAP27- and PRP-positive nerve fibres are all present in the rat median eminence. The major immunoreactive species present was PACAP38. Numerous PACAP38-immunoreactive nerve fibres were observed in the internal layer and a few were present in the posterior pituitary lobe. The external layer of the median eminence contained a few PACAP-38-immunoreactive fibres and PACAP-38-positive nerve terminals were rarely seen in the perivascular portal spaces. Surprisingly, delicate PACAP-38-positive nerve fibres were identified in the anterior pituitary lobe intermingled between the pituitary cells although none of the secretory pituitary cells contained immunoreactive PACAP38, PACAP27 or PRP and preproPACAP mRNA was not detected in the gland by Northern blotting or in situ hybridization. PACAP-27- and PRP-immunoreactive nerve fibres and terminals were found in the same locations as PACAP-38 although generally in lower numbers. Specific radioimmunoassays and HPLC revealed that PACAP-38 accounts for the vast majority of the adenohypophyseal PACAP-immunoreactivity, whereas PACAP-27 and PRP were found in low to undetectable concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Removal of retained intrauterine contraceptive devices in pregnancy.

Using real-time ultrasound and clinical expertise gained from chorionic villus sampling, we describe a technique for ultrasound-guided intrauterine device removal in those cases in which the string is not visible. Utilizing a stone clamp for intrauterine manipulation, we were easily able to extract the device without interrupting the pregnancy. We concur with recent recommendations advocating all intrauterine devices can be removed if pregnancy termination is declined.

Adult

Detection of mRNA for ribosomal phosphoprotein P2 in normal colon and colonic tumours by in situ hybridization.

We have localized the mRNA for the ribosomal phosphoprotein P2, a putative metastasis-related sequence, in normal colon and colonic carcinomas by in situ hybridization, using an oligonucleotide probe end-labelled with digoxigenin. The mRNA was identified in normal colonic epithelial cells, the intensity of the signal being greater in cells at the base of the crypts compared with those on the surface. A strong positive signal was also seen in plasma cells, in fibroblasts in granulation tissue, in ganglion cells, and in hepatocytes. A positive signal was identified in all 16 primary colonic tumours studied and in 7 hepatic metastases. In contrast to previous studies based on Northern blot analysis, we were unable to demonstrate increased expression in metastases as compared with primary tumours, nor could we demonstrate any increased expression in primary tumours which were associated with distant metastases.

Adenocarcinoma

Forearm blood flow response to posture change in the very old: non-invasive measurement by venous occlusion plethysmography.

Little is known about the peripheral vascular response to posture change in very elderly people who are vulnerable to the development of orthostatic hypotension. This is due, in part, to the risks of currently utilized invasive vascular monitoring techniques in the elderly population. We studied the forearm vascular response to active standing in 18 healthy young, 10 healthy old, and 19 impaired elderly subjects, using the non-invasive technique of venous occlusion plethysmography. In six subjects this technique was compared to duplex doppler ultrasonography for the measurement of postural changes in forearm blood flow. Forearm blood flow changes determined by venous occlusion plethysmography were 11% larger than doppler measurements, but the two methods strongly correlated (r = 0.90, P less than .001). Mean forearm vascular resistance increased to a significantly greater extent at 1 minute of standing in young subjects than in both groups of old, although the response was quite variable in all groups. Two healthy elderly (20%) and eight impaired elderly (40%) subjects had unexpected forearm vasodilatation at 1 minute of standing. By 3 minutes, forearm vascular resistance had increased by similar amounts in all three groups of subjects. Five impaired elderly and no healthy young or healthy old subjects had orthostatic hypotension, defined as greater than or equal to 10 mm Hg decline in mean arterial blood pressure at 1 or 3 minutes of standing. Forearm vascular resistance changes did not correlate with blood pressure response to standing. Thus, forearm vascular response to 1 minute of active standing is attenuated in many elderly subjects. This abnormality may impair adaptation to orthostatic stress in advanced age.

Adult

Evaluation of high performance liquid chromatography (HPLC), enzyme linked immunosorbent assay (ELISA) and particle concentration fluorescence immunoassay (PCFIA) methods for the screening, quantitation and pharmacokinetic study of furosemide in horses.

Equine plasma and urine samples were analyzed by using a high-performance liquid chromatography (HPLC), enzyme-linked immunosorbent assay (ELISA) and particle concentration fluorescence assay (PCFIA). Although ELISA and PCFIA were rapid, simple and sensitive for the screening of furosemide, they did not give reproducible quantitative results. The HPLC method, which required relatively longer analysis time, provided simple and reproducible quantitative analysis of furosemide in plasma and urine. The performance of the three methods was compared for the quantitation of furosemide in plasma obtained from thoroughbred mares dosed intravenously with furosemide (500 micrograms/kg (n = 7) and 1.0 mg/kg (n = 5)). Although the plasma furosemide profiles determined by ELISA, PCFIA and HPLC were similar, ELISA and PCFIA methods exhibited considerable variation in values. At high furosemide concentrations, the PCFIA method gave better quantitative values than ELISA. However, at trace furosemide concentrations the PCFIA method gave false positive values which were not confirmed by HPLC or ELISA. The pharmacokinetic values obtained from the HPLC data and the pharmacokinetic values obtained previously from the gas chromatographic data were comparable. The data obtained by ELISA and PCFIA were not suitable for the pharmacokinetic calculations.

Animals

Simultaneous analysis of furosemide and bumetanide in horse plasma using high performance liquid chromatography.

A high performance liquid chromatographic method is described for the simultaneous determination of furosemide and bumetanide in horse plasma. The C8 (3 microns) reversed phase column (4.8 x 150 mm) provided clear separation of furosemide and bumetanide with other components present in the horse plasma. The detection limit for both the drugs was 10 ng/mL. Both drugs were stable in plasma (at natural or acidic pH) for up to 24 h. The method is sufficiently sensitive to detect furosemide levels in plasma obtained from horses receiving a therapeutic dose of furosemide.

Animals

MR angiography and dynamic flow evaluation of the portal venous system.

We studied the value of MR angiographic techniques in imaging the portal venous system. Projection angiograms were created by postprocessing a series of two-dimensional, flow-compensated gradient-echo images. Flow velocity was determined by a bolus-tracking method with radiofrequency tagging and multiple data readout periods. Each image was acquired during a breath-hold. MR angiography was applied to six normal subjects and four patients with abnormal hemodynamics in the portal venous system. Flow velocity determined by MR was correlated with the results of duplex sonography. The main portal vein and intrahepatic branches were shown in all cases. Portosystemic collaterals were identified in all patients with portal hypertension. In normal subjects, peak flow velocities (17.9 +/- 2.8 cm/sec) on MR correlated well with values determined by duplex sonography (17.5 +/- 2.2 cm/sec) (r = .846, p less than .04). Reversed portal blood flow was shown in two patients. One patient with portal vein thrombosis had no evidence of flow by MR angiography. Our results indicate that MR angiography can provide a three-dimensional display of normal and abnormal vascular anatomy as well as functional information in the portal venous system.

Blood Flow Velocity

In vitro fertilization: sonographic perspective.

The applications of sonography were evaluated in 220 patients undergoing 354 in vitro fertilization cycles. A baseline sonogram demonstrated adnexal abnormalities in 10.7% of cycles. Serial sonograms were beneficial in monitoring follicular development. Oocyte harvest was canceled in 18.4% of cycles owing to inadequate follicle growth progression, as demonstrated by ultrasound. An additional 9% of cycles were canceled owing to the development of a single lead follicle. Six percent of cycles were accompanied by a spontaneous rise in serum luteinizing hormone values, necessitating sonographic correlation to exclude ovulation.

Female

Sonographic biophysical profile in the postdate pregnancy.

One hundred thirty-one postdate pregnancies were evaluated by the sonographic biophysical profile. Results of prenatal testing were compared to neonatal condition. Predictive values were calculated in order to determine whether this testing scheme could be used to detect the fetus at risk for neonatal distress. The results of this study show that a normal biophysical profile score is highly predictive of normal outcome, but an abnormal test has only a 14% predictive value of poor neonatal outcome.

Female

Comparison of intermediate-dose purified urinary follicle-stimulating hormone with and without human chorionic gonadotropin for ovulation induction in polycystic ovarian disease.

Urinary FSH is capable of inducing ovulation in PCOD. The duration of treatment can be reduced by administering an intermediate dose. However, it appears that prospective monitoring with E2 assays and ultrasound, combined with hCG, is required to optimize outcome and minimize complications. Studies comparing urinary FSH with similar doses of hMG with and without hCG are needed to determine the most effective form of gonadotropin therapy in PCOD.

Chorionic Gonadotropin

Ovulation induction in polycystic ovary syndrome with urinary follicle-stimulating hormone or human menopausal gonadotropin.

In patients with polycystic ovarian disease (PCOD) ovulation was induced with a combination of human menopausal gonadotropin (hMG) and human chorionic gonadotropin (hCG) or with urinary follicle-stimulating hormone (uFSH; Metrodin, Serono Laboratories, Inc., Randolph, MA) alone. hMG/hCG and uFSH resulted in comparable rates of ovulation and conception in patients with PCOD. The incidence of hyperstimulation and the potential for multiple births appeared lower with uFSH. The fact that endogenous ovulation did not occur in hMG patients who had hCG withheld or in 3 of the 11 uFSH patients who had preovulatory levels of estradiol and follicles greater than 15 mm may imply that these similarly derived gonadotropins in some instances block endogenous ovulation.

Androstenedione

Events surrounding the initiation of puberty with long term subcutaneous pulsatile gonadotropin-releasing hormone in a female patient with Kallman's syndrome.

An 18-yr-old woman with primary amenorrhea, anosmia, and total lack of secondary sexual development was treated for 230 days using sc pulsatile GnRH. GnRH testing with 100 micrograms, sc, initially revealed a peak FSH to LH ratio greater than 1. After 28 days of treatment, this ratio had reversed. A dosage of 20 micrograms/2 h for 200 days resulted in a LH to FSH ratio greater than 2. Widening the interval to 20 micrograms/3 h significantly lowered LH, but not FSH, levels. Increasing the frequency to 20 micrograms/90 min again increased the LH to FSH ratio. Twenty-four-hour testing revealed a sleep-entrained PRL rise both during and after GnRH therapy, but no sleep-entrained rise in LH. Ultrasound monitoring revealed cyclic changes in ovarian diameter at 30- to 60-day intervals that coincided with cyclic increases in LH and estradiol. The uterine fundus doubled in length between days 50 and 110 of treatment. The patient progressed from Tanner pubic hair and breast stage I to stage II during treatment, which was terminated due to an allergic reaction to GnRH. This study provides the first report of hormonal and ultrasound events surrounding puberty induction with GnRH in the female. We conclude widening the interval of GnRH administration can reduce LH levels while maintaining FSH levels, cyclic changes in ovarian diameter, LH, and estradiol occur before menarche, and although pulsatile GnRH provides a fascinating model for the study of puberty in the female, the chronicity of therapy needed and its potential for allergic reaction make this method of inducing puberty suboptimal.

Adolescent