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Biomedical subjects

C Hunter

Publications and source records attributed to C Hunter.

At least 37 records · Page 2Linked to original sources
PubMed1999

A novel sublingual apomorphine treatment for patients with fluctuating Parkinson's disease.

We tested a novel preparation of a sublingual apomorphine hydrochloride tablet (APO) in 10 patients with advanced Parkinson's disease complicated by motor fluctuations. After a dose titration, patients took either 40 mg APO three times per day alternating with levodopa doses (eight patients) or six doses of 20 mg APO taken concurrently with levodopa doses (two patients) for 3 months. Assessments included timed tapping and ambulation tests, Unified Parkinson's Disease Rating Scale (UPDRS), and patient diaries. Tapping speed while taking only APO (12 hours after stopping levodopa) was faster than while taking only levodopa (p <0.05). The daily levodopa dose decreased by 32.1% (p <0.01), yet the total "on" time increased from 73.5% +/- 10.2% to 81.5% +/- 7.5% of the day (p <0.01) after starting APO. "On" UPDRS part II scores (p <0.05) and "on" UPDRS part III (motor examination) scores (p <0.05) also improved. Adverse events such as nausea, orthostatic hypotension, and disagreeable taste did not limit the dose of APO in any case. The short-term benefit and tolerability demonstrated in this study warrant further study of this new APO preparation.

Administration, Sublingual↗
PubMed1999

Who gets what treatment for obesity? A survey of GPs in Scotland.

OBJECTIVE: To describe the types and delivery of obesity treatment currently favoured by General Practitioners (GPs) working in Scotland. DESIGN: Representative cross-sectional survey using a postal questionnaire which included case stories as stimuli for questions about the GPs' nutrition guidance to overweight female patients. SUBJECTS: A systematic sample of 1400 general practitioners (GPs) from a total of 3593 GPs working in Scotland in 1997. RESULTS: From 1363 eligible GPs, 609 returned the full questionnaire and a further 132 took part in a telephone mini-interview. Net response was 54.4% (741/1363). Almost half of the GPs (45.6%) reported that they had read the recent national clinical guideline for integrating obesity prevention with weight management (SIGN 1996). The majority of GPs (89.6%) agreed that nutrition has an important role to play in the management of disease and 82.4% agreed that they can offer healthy eating advice to patients. However, only 34.8% of GPs believed that they had been successful in treating overweight patients. Routinely used treatments involve either a dietitian, practice nurse and/or a commercial slimming group and realistic weight loss was considered one criteria of successful treatment by some GPs. Age, year qualified and location of practice were found to have little influence over variations in GP treatment while weak associations between gender of GP and treatment were found. CONCLUSIONS: The readership of the clinical guidelines in Scotland has been moderate so far although a multidisciplinary approach to obesity treatment is recognised. Further investigations of any relationships between nutrition education-obesity treatment are needed.

Adult↗
PubMed1998

Bifurcations of periodic orbits in axisymmetric scalefree potentials.

We study orbits in potentials with central cusps, emphasizing the spheroidal equidensity (SED) potentials generated by mass distributions with spheroidal equidensity surfaces. The most prominent bifurcations are those related to 1:1 and 4:3 resonances between radial motions and motions perpendicular to the central plane. We find that 1:1 resonances can cause the thin tube orbit, as well as the equatorial plane orbit, to become unstable. We concentrate on period-tripling bifurcations because they appear to be the least understood. We study them via a class of analytic maps. This study suggests that stable period-three orbits generally arise de novo in stable and unstable pairs via a turning-point bifurcation, and not through a bifurcation from the thin tube at a 120 degree rotation angle. The stable period-three orbits typically have only a short span of existence before becoming unstable to a period-doubling instability through a supercritical pitchfork bifurcation.

Journal Article↗
PubMed1997

Alterations of GABAA receptor subunit mRNA levels in the aging Fischer 344 rat inferior colliculus.

The inhibitory neurotransmitter, gamma-aminobutyric acid (GABA) is critically involved in shaping neuronal responses to simple and complex acoustic stimuli in the central auditory structure, the inferior colliculus (IC). Studies in rat and human suggest that age-related changes in markers for GABA neurotransmission occur in the IC. In particular, these changes include findings indicative of an age-related increase in the efficacy/potency of GABA to inhibit ligand binding at the GABAA receptor picrotoxin site in the Fischer (F344) rat IC. Such changes in GABAA receptor modulation suggest the potential for an alteration in GABAA receptor subunit composition in the old rat IC. To test this idea, the present study used in situ hybridization to quantify age-related changes in GABAA receptor subunit mRNA levels in the three major subdivisions of the IC in the F344 rat: dorsal cortex (DCIC), external cortex (ECIC), and the central nucleus (CIC). In support of earlier findings of an age-related change in GABAA receptor modulation, the present study found: (1) GABAA receptor subunit mRNA levels were significantly altered in the IC of old rats, and (2) age-related changes in subunit levels appeared to be regionally selective and subunit specific. A highly significant increase in the level of the gamma 1 subunit mRNA was observed with little change in the levels of the alpha 1, beta 2, and gamma 2 subunit mRNAs. A nonstatistically significant increase in alpha 2 subunit mRNA was also observed. This observed increase in alpha 2 subunit mRNA could be important since previous expression studies have shown that the alpha 2 and gamma 1 subunits coassemble and are incorporated into GABAA receptors which appear to be more sensitive to GABA. If the observed changes in subunit mRNA levels with age correlate well with enhanced GABAA receptor function in the IC of old rats, this, in turn, may represent a compensatory mechanism in response to presynaptic GABAergic changes.

Aging↗
PubMed1997

Amniotic fluid interleukin-10 (IL-10) concentrations during pregnancy and with labor.

To determine if amniotic fluid interleukin-10 (IL-10) concentrations are elevated in women with labor, either at term or preterm, and in the setting of infection-associated preterm labor, amniotic fluid samples were collected from women: (1) at term, not in labor (n = 42); at term, in labor (n = 56), preterm contractions, undelivered within 1 week (n = 22), and preterm labor, delivered within 1 week (n = 31). IL-10 concentrations were assayed in each sample via ELISA (Pharmingen, San Diego, CA). In a subsequent analysis, 8 women with preterm labor associated with chorioamnionitis were matched for gestational age with women experiencing preterm contractions (undelivered within 7 days) and preterm labor (delivered within 7 days) and amniotic fluid IL-10 concentrations compared. Approximately 40-70% of amniotic fluid samples obtained from women in each group had detectable IL-10. However, there were no significant differences in amniotic fluid IL-10 concentrations among the patients. While 1 of 8 patients with chorioamnionitis had amniotic fluid IL-10 concentrations greater than 300 pg/ml, there were no statistically significant differences among the matched samples. Amniotic fluid IL-10 concentrations were not elevated in women with term labor, preterm labor, or chorioamnionitis. This finding contrasts with the elevated concentrations of pro-inflammatory cytokines and chemokines such as interleukin-1, tumor necrosis factor-alpha, IL-6, IL-8, MIP-1 alpha, and GRO alpha reported in previous studies. Because we did not detect elevations of the key anti-inflammatory cytokine IL-10 in amniotic fluid of women with infection-associated preterm labor, we suggest that anti-inflammatory processes in this setting may be attenuated.

Adult↗
PubMed1997

Aggressiveness of colon carcinoma in blacks and whites. National Cancer Institute Black/White Cancer Survival Study Group.

Black patients with colon cancer in the Black/White Cancer Survival Study were found to have a poorer survival than white patients. More advanced-stage disease at diagnosis was the primary determinant, accounting for 60% of the excess mortality. After adjusting for stage, factors such as poverty, other socioeconomic conditions, and treatment did not further explain the remaining survival deficit. This study examined the aggressiveness of colon tumors in blacks and whites to explore its role in the racial survival differences. Tumor characteristics of 703 cases of newly diagnosed invasive colon adenocarcinoma were centrally evaluated by a gastrointestinal pathologist, blinded in regard to the age, race, and sex of the patients. Blacks were less likely to have poorly differentiated (grade 3) tumors [odds ratio (OR), 0.44; 95% confidence interval, 0.22-0.88] and lymphoid reaction (OR, 0.49; 95% confidence interval, 0.26-0.90) when compared with whites. These black/white (B/W) differences remained statistically significant after adjusting for age, sex, metropolitan area, summary stage, socioeconomic status, body mass index, and health care access and utilization. In addition, blacks were less likely to have high-grade (grade 3) nuclear atypia, mitotic activity, and tubule formation, although these ORs did not reach a statistical significance level of 0.05. Similar B/W differences were observed for patients with advanced disease but not with early stage. Comparison by anatomical subsite showed that blacks had statistically significantly better differentiated tumors for cancers of the proximal and transverse colon but not for the distal. No racial differences were found for blood vessel and lymphatic invasion, necrosis, fibrosis, and mucinous type of histology. The findings, therefore, are the opposite of those hypothesized. After adjusting for stage, more aggressive tumor characteristics do not explain the adverse survival differential in blacks. This suggests that there may be racial differences in environmental exposure, and that the intensity and mode of delivery of carcinogen insult as well as host susceptibility may differ by race and anatomical subsite. Future studies should explore the B/W differences in tumor biology using molecular markers that precede the conventional histological parameters evaluated here.

Adult↗
PubMed1996

Elevations of amniotic fluid macrophage inflammatory protein-1 alpha concentrations in women during term and preterm labor.

OBJECTIVE: To determine whether elevated concentrations of macrophage inflammatory protein-1 alpha (MIP-1 alpha) in amniotic fluid (AF) are related to term and preterm labor. METHODS: Amniotic fluid was obtained from women from five different clinical situations: 1) term cesarean delivery, no labor (n = 29); 2) normal term labor, no infection (n = 36); 3) preterm labor, delivery more than 1 week from sampling, no infection (n = 19); 4) preterm labor, delivery within 1 week from sampling, no infection (n = 18); and 5) preterm chorioamnionitis (n = 8). Amniotic fluid was collected aseptically at the time of amniocentesis, amniotomy, or hysterotomy. Concentrations of MIP-1 alpha were determined by enzyme-linked immunosorbent assay. Statistical analysis was by Wilcoxon rank-sum test, Kruskal-Wallis test, and unpaired t test. RESULTS: Women in normal term labor had significant elevations of AF MIP-1 alpha concentrations when compared with women at term undergoing repeat cesarean delivery (P < .001). In women with term gestation, AF MIP-1 alpha correlated well with cervical dilation (r2 = 0.479, P < .001). In women with preterm labor who later delivered within 1 week of presentation, AF MIP-1 alpha concentrations were higher than those from women who did not deliver within 1 week. Women who presented with clinically evident chorioamnionitis had the highest concentrations of AF MIP-1 alpha (P = .001). CONCLUSION: Women in labor have significantly elevated AF concentrations of MIP-1 alpha, particularly if labor is associated with intrauterine infection. We suggest that MIP-1 alpha is involved in the physiology of normal labor and in the pathogenesis of infection-associated preterm labor.

Amniotic Fluid↗
PubMed1996

Elevations of serum interleukin-12 concentrations in women with severe pre-eclampsia and HELLP syndrome.

The objective is to test the hypothesis that serum IL-12 concentrations would be elevated in women with severe pre-eclampsia and HELLP syndrome. The Methods used were as follows: Serum was obtained from women admitted to our Labor and Delivery unit diagnosed with severe pre-eclampsia or HELLP syndrome and normal control patients. IL-12 concentrations in these samples were determined by the use of two different and specific enzyme-linked immunosorbent assays for the p40 subunit and the intact p75 dimer. It was found that serum IL-12 (p40 subunit) concentrations were elevated in women with both severe pre-eclampsia (p = 0.011) or HELLP syndrome (= 0.004). Similar findings were noted for these patients when matched with control patients for maternal age, gestational age, and parity. Eleven women had elevations of serum IL-12 p75 dimer, and 10 of these 11 patients had severe pre-eclampsia or HELLP syndrome. In conclusion, we found that women with severe pre-eclampsia and HELLP syndrome commonly have detectable concentrations of the IL-12 p40 monomer and were more likely than normal control women to have detectable serum IL-12 p75 dimer. While the exact role of IL-12 in hypertensive disease during pregnancy is unclear, our data support the hypothesis that the regulation of IL-12 production and metabolism is abnormal in women with pre-eclampsia and HELLP syndrome, perhaps contributing to the immunologic alterations characteristic of these disorders.

Adult↗
PubMed1996

Value of fetal fibronectin as a predictor of preterm delivery for a low-risk population.

OBJECTIVE: We examined clinical value of cervical fetal fibronectin detection by a quantitative enzyme-linked immunosorbent assay as a predictor of preterm delivery in a population (n = 111) of middle-class pregnant women considered to be at low risk for preterm delivery. STUDY DESIGN: In this prospective study, fetal fibronectin samples from cervicovaginal secretions were obtained biweekly from 24 to 34 weeks' gestation. RESULTS: Twenty-two (20%) patients had at least one positive fetal fibronectin test result. Eleven women (10%) were delivered spontaneously at < 37 weeks; seven of these had at least one positive fetal fibronectin test result (positive predictive value = 31.8%, sensitivity = 63.6). An additional three women were delivered prematurely because of other obstetric indications, and all had negative fetal fibronectin test results. The remaining 15 patients with at least one positive fetal fibronectin test result were delivered at term (> or = 37 weeks). Of the seven women with positive fetal fibronectin results who were delivered prematurely, five were delivered within 2 weeks of obtaining a positive result. However, there were no obvious clinical discriminators between true-positive and false-positive fetal fibronectin results. Eighty-nine women tested negative, and 85 of these women were delivered at term (specificity = 82.0%). The negative predictive value of fetal fibronectin as a predictor of term delivery in this low-risk population is 96.6%, with odds ratio = 8.8 (95% confidence interval 1.9 to 40.3), relative risk = 6.9 (95% confidence interval 1.8 to 26.6), and Fisher Exact Test p = 0.007. CONCLUSIONS: Although negative biweekly fetal fibronectin determinations for prediction of preterm delivery in this low-risk obstetric population correlate well with the absence of preterm delivery, they are of limited clinical value for the prediction of preterm birth.

Adult↗
PubMed1996

Elevation of amniotic fluid interleukin-4 concentrations in women with preterm labor and chorioamnionitis.

Preterm labor associated with intrauterine infection is characterized by increased amniotic fluid concentrations of various proinflammatory cytokines, including interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), IL-6, IL-8, and macrophage inflammatory protein-1alpha (MIP-1alpha). The purpose of this study was to determine if preterm labor in women with clinically evident chorioamnionitis is marked by elevations of the anti-inflammatory cytokine interleukin-4 (IL-4) and the T cell growth factor IL-2. Amniotic fluid samples were obtained from (1) women at term, not in labor (n = 10); (2) women at term, in labor (n = 10); (3) women with preterm contractions but undelivered within 1 week of amniotic fluid collection (n = 10); (4) women with preterm labor and delivery without clinically evident chorioamnionitis (n = 10); (5) women with preterm labor associated with chorioamnionitis (n = 8); and (6) women with preterm labor and delivery without infection matched with patients with chorioamnionitis (n = 8). Amniotic fluid concentrations of IL-4 and IL-2 were determined for each sample with a specific and sensitive enzyme-linked immunoassay. We found that women with infection-associated preterm labor and delivery had significantly higher concentrations of IL-4 when compared to appropriately matched controls (p < 0.05). Additionally, women with preterm labor and delivery not associated with infection had higher amniotic fluid IL-4 concentrations than women with preterm contractions but no labor (p < 0.05). Women with term labor had rare modest elevations of amniotic fluid IL-4. No IL-2 was detected in any sample. Our data indicate that amniotic fluid IL-4 is elevated in women with preterm labor and delivery, particularly in association with chorioamnionitis. We suggest that IL-4, although previously considered an anti-inflammatory agent, may have a paradoxical proinflammatory role in the pathogenesis of infection-associated preterm labor.

Adult↗
PubMed1996

Significant decrease in parathyroid hormone-related protein concentrations in amniotic fluid with labour at term but not preterm.

It has been determined whether amniotic fluid concentrations of parathyroid hormone-related protein (PTHrP) change with labour. An evaluation of which cells from intrauterine tissues might produce PTHrP has also been conducted. Amniotic fluid was obtained by amniocentesis from women: (1) at term, not in labour; (2) in normal term labour; (3) in preterm labour, undelivered within one week; (4) in preterm labour, delivered within one week; (5) in preterm labour associated with clinical chorioamnionitis; and (6) who were gestation-matched controls for chorioamnionitis patients-women in this group were similar to those in Group 4 but were different patients. Amnion, chorion, and decidual cells were grown by standard techniques and incubated with interleukin-1 beta (IL-1 beta). PTHrP was assayed in duplicate samples of amniotic fluid or tissue culture media using an immunoradiometric assay. There was a significant reduction in amniotic fluid concentrations of PTHrP during labour at term. Preterm labour was not associated with significant changes in amniotic fluid concentrations of PTHrP although a trend for reduced concentrations was observed. Amnion and chorion produced measurable quantities of PTHrP and rates of production were increased by treatment with IL-1 beta. Decidual cells did not produce detectable amounts of PTHrP. Hence, labour at term is associated with a decrease in amniotic fluid PTHrP concentrations that may reflect reduced amnion production, which in turn may play a permissive or active role in the mechanism(s) of parturition. These data support the view that the mechanisms that control term and preterm labour may be regulated differently.

Amniocentesis↗
PubMed1995

Cognitive function, thyroid status and postpartum depression.

Impairment of cognitive function can occur with thyroid disorder and also with depression. Since depression occurs in conjunction with postpartum autoimmune thyroiditis, the question arises as to whether any impairment of cognitive function in postpartum women is related to change in thyroid status or to depressed mood. A total of 242 women (110 thyroid antibody-positive and 132 antibody-negative) were assessed at 8, 12, 20 and 28 weeks postpartum in the outpatients of a district general hospital. Thyroid antibody levels (antimicrosomal and antithyroglobulin) were monitored at monthly intervals, together with plasma T3, T4 and thyroid-stimulating hormone. The main outcome measures were Research Diagnostic Criteria for depression, the 17-item Hamilton Depression Rating Scale and the Edinburgh Postnatal Depression Scale, together with reaction time and digit span. Subjects with postnatal depression showed detectable cognitive impairment independent of thyroid antibody status and actual thyroid dysfunction.

Antibodies↗
PubMed1995

Expression of Drosophila lamin C is developmentally regulated: analogies with vertebrate A-type lamins.

Vertebrate nuclear lamins form a multigene family with developmentally controlled expression. In contrast, invertebrates have long been thought to contain only a single lamin, which in Drosophila is the well-characterized lamin Dm0. Recently, however, a Drosophila cDNA clone (pG-IF) has been identified that codes for an intermediate filament protein which harbors a nuclear localization signal but lacks a carboxy-terminal CAAX motif. Based on these data the putative protein encoded by pG-IF was tentatively called Drosophila lamin C. To address whether the pG-IF encoded protein is expressed and whether it encodes a cytoplasmic intermediate filament protein or a nuclear lamin we raised antibodies against the recombinant pG-IF protein. The antibodies decorate the nuclear envelope in Drosophila Kc tissue culture cells as well as in salivary and accessory glands demonstrating that pG-IF encodes a nuclear lamin (lamin C). Antibody decoration, in situ hybridization, western and northern blotting studies show that lamin C is acquired late in embryogenesis. In contrast, lamin Dm0 is constitutively expressed. Lamin C is first detected in late stage 12 embryos in oenocytes, hindgut and posterior spiracles and subsequently also in other differentiated tissues. In third instar larvae lamins C and Dm0 are coexpressed in all tissues tested. Thus, Drosophila has two lamins: lamin Dm0, containing a CaaX motif, is expressed throughout, while lamin C, lacking a CaaX motif, is expressed only later in development. Expression of Drosophila lamin C is similar to that of vertebrate lamin A (plus C), which loses its CaaX motif during incorporation into the lamina.

Animals↗
PubMed1994

Clinical value of amniotic fluid interleukin-6 determinations in the management of preterm labour.

OBJECTIVE: To ascertain whether the determination of amniotic fluid interleukin-6 (IL-6) concentrations would be a useful clinical test in the management of women with preterm contractions. SETTING: The labour and delivery unit and the Fetal Diagnostic Centre at the University of Utah. SUBJECTS: Pregnant women at various stages of gestation in the third trimester. DESIGN: Amniotic fluid samples were collected from women experiencing one of four clinical scenarios: 1. term pregnancy, not in labour with no evidence of intrauterine infection; 2. normal term labour with no evidence of infection; 3. preterm labour with no evidence of infection and undelivered within one week of sampling; and 4. preterm labour and delivered within seven days of sample collection. Amniotic fluid was obtained by amniocentesis or at the time of amniotomy or hysterotomy. IL-6 in each specimen was determined by a specific rapid ELISA. RESULTS: Amniotic fluid IL-6 levels, given as mean (SEM) in the four groups of women listed were: 1. term pregnancy, not in labour: 20.9 (7.2) pg/ml (n = 60); 2. normal term labour with no infection: 554 (90.7) pg/ml (n = 46); 3. preterm labour with no evidence of infection, undelivered: 47.0 (17.2) pg/ml (n = 35); and 4. preterm labour, delivered: 456.7 (101.7) pg/ml (n = 40). There was no significant difference in the means of amniotic fluid IL-6 for the term labour and preterm labour delivered groups. In general, amniotic fluid IL-6 levels during term labour increased with advancing cervical dilation. There was no correlation of cervical dilation and amniotic fluid IL-6 levels in women having preterm delivery. Receiver-operator curves revealed optimal IL-6 levels for discrimination of labour at term to be 50 pg/ml and for preterm delivery to be 200 pg/ml. CONCLUSIONS: IL-6 can readily be detected in the amniotic fluid of most women who are in active labour, regardless of gestational age. Our data suggest that amniotic fluid IL-6 determinations may be clinically useful in the management of preterm labour.

Adult↗