Developing preference-based measures for diabetes: DHP-3D and DHP-5D.

AIMS: The aim of this study was to develop two diabetes-specific preference-based measures [the Diabetes Health Profile-3 Dimension (DHP-3D) and the Diabetes Health Profile-5 Dimension (DHP-5D)] for use in the calculation of Quality Adjusted Life Years, a key outcome in economic evaluation. These measures were based on the non-preference-based instrument the Diabetes Health Profile. METHODS: For DHP-3D, psychometric and Rasch analyses were used to develop a health state classification system based on the Diabetes Health Profile-18 (DHP-18). The DHP-5D added two dimensions to the DHP-3D to extend the range of impacts measured. Each classification system was valued by 150 general public respondents in the United Kingdom using Time Trade Off (TTO). Multivariate regression was used to estimate utility value sets. The matched dimensions across each measure were compared using z-score tests. RESULTS: The DHP-3D included three dimensions defined as mood, eating and social limitations, and the DHP-5D added dimensions defined as hypoglycaemic attacks and vitality. For both, the random effects generalized least squares regression model produced consistent value sets, with the DHP-3D and DHP-5D ranging from 0.983 (best state) to 0.717 (worst state), and 0.979 to 0.618 respectively. The addition of the two extra dimensions leads to significant differences for the more severe levels of each matched dimension. CONCLUSIONS: We have developed two diabetes-specific preference-based measures that, subject to psychometric assessment, can be used to provide condition-specific utility values to complement generic utilities from more widely validated measures such as the EuroQol-5 Dimension.

Developing a questionnaire to determine the impact of self-management in diabetes: giving people with diabetes a voice.

BACKGROUND: The prevalence of diabetes mellitus (DM) is increasing dramatically, placing considerable financial burden on the healthcare budget of each country. Patient self-management is crucial for the control of blood glucose, which largely determines the chances of developing diabetes-related complications. Self-management interventions vary widely, and a method is required for assessing the impact of self-management. This paper describes the development of a questionnaire intended for use to measure the impact of self-management in diabetes. METHODS: An iterative development process was undertaken to identify the attributes of self-management using 5 steps. First, a literature review was undertaken to identify and understand themes relating to self-management of DM to inform a topic guide. Second, the topic guide was further refined following consultation with a Patient and Public Involvement group. Third, the topic guide was used to inform semi-structured interviews with patients with Type 1 DM (T1DM) and Type 2 DM (T2DM) to identify how self-management of DM affects individuals. Fourth, the research team considered potential attributes alongside health attributes from an existing measure (Diabetes Health Profile, DHP) to produce an instrument reflecting both health and self-management outcomes simultaneously. Finally, a draft instrument was tested in a focus group to determine the wording and acceptability. RESULTS: Semi-structured interviews were carried out with 32 patients with T1DM and T2DM. Eight potential attributes were identified: fear/worry/anxiety, guilt, stress, stigma, hassle, control, freedom, and feeling supported. Four of these self-management attributes were selected with four health attributes (mood, worry about hypos (hypoglycaemic episodes), vitality and social limitations) to produce the Health and Self-Management in Diabetes (HASMIDv1) questionnaire. CONCLUSIONS: HASMIDv1 is a short questionnaire that contains eight items each with four response levels to measure the impact of self-management in diabetes for both T1DM and T2DM. The measure was developed using a mixed-methods approach that involved semi-structured interviews with people with diabetes. The measure has high face validity. Ongoing research is being undertaken to assess the validity of this questionnaire for measuring the impact of self-management interventions in economic evaluation.

Treatment of facial erythema in patients with rosacea with topical brimonidine tartrate: correlation of patient satisfaction with standard clinical endpoints of improvement of facial erythema.

BACKGROUND: Once-daily brimonidine tartrate (BT) 0.5% gel was shown to provide significantly greater efficacy vs. vehicle for the treatment of facial erythema in patients with rosacea. OBJECTIVES: To demonstrate that patient satisfaction with overall appearance is correlated with reduction in facial erythema, as measured by clinician and patient assessments. METHODS: Data from two identical phase III, multicentre, randomized, controlled trials of moderate facial erythema of rosacea (study A: n = 260; study B: n = 293) with topical BT 0.5% compared to vehicle gel once-daily for 4 weeks were analysed. Correlations of Patient's Assessment of Appearance (PAA) with Clinician's Erythema Assessment (CEA) and Patient's Self-Assessment (PSA) of erythema were evaluated by calculation of gamma statistics. RESULTS: PAA correlated with CEA post-application on Days 1, 15 and 29 for the intent-to-treat population and provided a median gamma value of 0.57 (min = 0.28, max = 0.61). PAA and PSA was also highly correlated post-application on Days 1, 15 and 29; with a median gamma value of 0.87 (min = 0.66, max = 0.89). Subjects who achieved a clinically meaningful improvement in both CEA and PSA scales were more likely to report satisfaction with the overall appearance of their skin (P < 0.001). CONCLUSIONS: Both one- and two-grade improvements in facial erythema assessed by subjects (PSA) and clinicians (CEA) correlate well with PAA, a patient-centered representation of meaningful change.

Bringing the patient's perspectives forward in drug development and health-care evaluation.

INTRODUCTION: For many years, psychologists and other social scientists have been pushing for the individual patient's perspective - priorities, needs, feelings, and functioning - to be incorporated into drug development. This is usually achieved through the use of patient-reported outcome measures (PROMs) in clinical trials. AREAS COVERED: This paper discusses some key issues in the use of PROM data as the sole method of generating information about the patient's perspective and outlines the relevance of narrative evidence to enhance understanding and interpretation of PROM data. EXPERT OPINION: The development and use of PROMs situates them at the vertex of two very different trends in medicine: patient-centered care and standardization. Indeed, the application of PROMs - which pull in the direction of standardization - results in a narrow conception of evidence by overriding the subjectivity of individual experiences, beliefs, and judgments. Without additional context, PROM data cannot easily support individual patient-level care. When collected systematically and with an interpretive phenomenological approach, narrative data can contain valuable information about the patient experience that numerical ratings from PRO measures do not capture.

Diabetes and Covid-19: Diabetes research funding and support during the pandemic.

AIMS: Between late 2020 and early 2022, EURADIA undertook a survey of organisations and individuals supporting or working in the field of diabetes research with the aim of understanding better the impact of the Covid-19 pandemic on funding for diabetes research in Europe. METHODS: Information was collected via online survey augmented in some cases by face-to-face interviews. RESULTS: Findings were mixed but the majority of those responding suggested a moderate impact of the pandemic on diabetes research activity. Many respondents reported a reduction in funding during the pandemic and many of those involved in clinical research experienced a reduction in research clinicians' availability for diabetes research as they were redeployed to Covid-19 patient care. It was frequently reported that the impact might not be fully appreciated until several years after the end of the pandemic. CONCLUSIONS: This preliminary survey suggests there may be a significant impact of the pandemic on all aspects of diabetes research and that a more detailed follow-up on the impact of the pandemic on funding of diabetes research should be carried out in the future.

Once-daily topical brimonidine tartrate gel 0·5% is a novel treatment for moderate to severe facial erythema of rosacea: results of two multicentre, randomized and vehicle-controlled studies.

BACKGROUND: Erythema of rosacea is thought to result from abnormal cutaneous vasomotor activity. Brimonidine tartrate (BT) is a highly selective α(2) -adrenergic receptor agonist with vasoconstrictive activity. OBJECTIVE: To determine the optimal concentration and dose regimen of topical BT gel for the treatment of erythema of rosacea and to evaluate its efficacy and safety. METHODS: In study A, 122 subjects were randomized to receive a single application of BT 0·07%, 0·18%, 0·5% or vehicle. In study B (4-week treatment and 4-week follow-up), 269 subjects were randomized to receive BT 0·5% once daily, BT 0·18% once daily, vehicle once daily, BT 0·18% twice daily or vehicle twice daily. Evaluations included Clinician's Erythema Assessment (CEA), Patient's Self-Assessment (PSA), Chroma Meter measurements and adverse events. RESULTS: In study A, a single application of topical BT gel reduced facial erythema in a dose-dependent fashion. A significant difference between BT 0·5% and vehicle in Chroma Meter redness value was observed from 30min to 12h after application. In study B, BT 0·5% once daily had a statistically superior success profile (defined as a two-grade improvement on both CEA and PSA over 12h) compared with vehicle once daily on days 1, 15 and 29 (all P<0·001). No tachyphylaxis, rebound of erythema or aggravation of other disease signs (telangiectasia, inflammatory lesions) was observed. All regimens were safe and well tolerated with similarly low incidence of adverse events. CONCLUSIONS: Once-daily BT gel 0·5% is well tolerated and provides significantly greater efficacy than vehicle gel for the treatment of moderate to severe erythema of rosacea.

A longitudinal study of predictors of research-defined carpal tunnel syndrome in industrial workers: findings at 17 years.

In 1984, we initiated a prospective study of factors associated with research-defined carpal tunnel syndrome (CTS) in 471 industrial workers. Medical history, lifestyle factors and job tasks were assessed by questionnaire and CTS case status was based on both symptoms and electrophysiologic findings. Participants were re-examined in 1989, 1994 to 1995 and 2001 to 2002. This study reports both baseline and aggregated risk factors associated with increased risk of CTS by 2001 to 2002 for 166 participants successfully re-examined after 17 years. In analyses of baseline risk factors, fewer repetitive tasks at work, female gender and greater relative weight were associated with any occurrence of CTS during follow-up. In analyses of aggregate risk factor scores through 1994 to 1995, only greater relative weight and female gender were associated with CTS in 2001 to 2002. Although obesity and gender are consistent predictors of CTS, workplace demands appear to bear an uncertain relationship to CTS. These findings are also discussed in relation to the possible differences between research-defined CTS and medically referred CTS.

Effect of computer-based learning on diabetes knowledge and control.

Two interactive computer-based systems have been evaluated: a teaching program with text and animated graphics and a multiple-choice knowledge-assessment program (KAP) with optional prescriptive feedback. One hundred seventy-four routine-attending insulin-dependent diabetes mellitus (IDDM) and non-insulin-dependent diabetes mellitus (NIDDM) patients were allocated to active and control groups to determine the effect of these programs on knowledge and control after a 4- to 6-mo follow-up period. Interactive computer teaching (ICT) resulted in a significant knowledge increment in both IDDM and NIDDM patients (P less than .05), together with a mean fall of 0.8 and 0.7%, respectively, in HbA1c (P less than .05 and P greater than .1), but no changes were observed in respective control groups. The KAP with feedback also produced a significant knowledge increment in both IDDM and NIDDM patients (P less than .05), of similar magnitude to the ICT program, and a mean fall in HbA1c of 1.2 and 1.3%, respectively (P less than .05), with no changes in the corresponding control groups. Even when KAP was used without prescriptive feedback, smaller but significant mean falls in HbA1c of 0.7 and 0.8% (P less than .05) were seen in IDDM and NIDDM patients, respectively, suggesting a motivational effect resulting from program participation.(ABSTRACT TRUNCATED AT 250 WORDS)

Intermediate and long-term outcomes following simple decompression of the ulnar nerve at the elbow.

INTRODUCTION: There is currently little consensus regarding the appropriate surgical approach to treatment of cubital tunnel syndrome (CubTS), and few studies have reported long-term follow-up of patients who have received surgical treatment for ulnar nerve compression at the elbow. METHOD: Seventy-four patients with a total of 102 cases of CubTS treated with simple decompression of the ulnar nerve were examined 1.0-12.4 years postoperatively. Ulnar nerve conduction studies (slowest conducting 5 cm segment of ulnar nerve motor fibers measured at the elbow) were performed both pre- and postoperatively. The primary clinical outcome was percentage relief of symptoms, divided into "excellent" outcome group or less (> or = 90% improvement or < 90% improvement). RESULTS: Ulnar nerve conduction improved pre- to postoperatively, but clinical improvement was not related to changes in velocity. Women reported greater clinical improvement than men, and weight gain in men (but not women) predicted less improvement. Relief of cubital tunnel symptoms was greatest for those arms receiving carpal tunnel release surgery simultaneous or subsequent to cubital tunnel release. DISCUSSION: Simple decompression may offer excellent intermediate and long-term relief of symptoms associated with CubTS. Although improvement in ulnar motor nerve conduction velocity occurs following treatment of CubTS, it may not be a consistent marker of perceived symptom relief. Finally, these findings suggest that less complete relief of symptoms following ulnar nerve decompression may be related to unrecognized carpal tunnel syndrome or weight gain.

Sex- and age-specific differences in relaxin family peptide receptor expression within the hippocampus and amygdala in rats.

Relaxin is an essential pregnancy-related hormone with broad peripheral effects mediated by activation of relaxin-like family peptide 1 receptors (RXFP1). More recent studies suggest an additional role for relaxin as a neuropeptide, with RXFP1 receptors expressed in numerous brain regions. Neurons in an area of the brainstem known as the nucleus incertus (NI) produce relaxin 3 (RLN3), the most recently identified neuropeptide in the relaxin family. RLN3 has been shown to activate both RXFP1 and relaxin-like family peptide receptor 3 (RXFP3) receptor subtypes. Studies suggest wide-ranging neuromodulatory effects of both RXFP1 and RXFP3 activation, although to date the majority of studies have been conducted in young males. In the current study, we examined potential sex- and age-related changes in RLN3 gene expression in the NI as well as RXFP1 and RXFP3 gene expression in the dorsal hippocampus (HI), ventral hippocampus (vHI) and amygdala (AMYG) using young adult (9-12weeks) and middle-aged (9-12months) male and female rats. In addition, regional changes in RXFP1 and RXFP3 protein expression were examined in the CA1, CA2/CA3 and dentate gyrus (DG) as well as within basolateral (BLA), central (CeA), and medial (MeA) amygdaloid nuclei. In the NI, RLN3 showed an age-related decrease in males. In the HI, only the RXFP3 receptor showed an age-related change in gene expression, however, both receptor subtypes showed age-related changes in protein expression that were region specific. Additionally, while gene and protein expression of both receptors increased with age in AMYG, these effects were both region- and sex-specific. Finally, overall males displayed a greater number of cells that express the RXFP3 protein in all of the amygdaloid nuclei examined. Cognitive and emotional processes regulated by activity within the HI and AMYG are modulated by both sex and age. The vast majority of studies exploring the influence of sex on age-related changes in the HI and AMYG have focused on sex hormones, with few studies examining the role of neuropeptides. The current findings suggest that changes in relaxin family peptides may contribute to the significant sex differences observed in these brain regions as a function of aging.

Insulin-like growth factor binding protein-3 in breast cyst fluid: relationships with insulin-like growth factors I and II and transforming growth factor-beta 1 and 2.

Women who have palpable breast cysts with intracystic Na/K > 3 may have a lower risk of developing breast cancer than those with intracystic Na/K < 3. In this study significantly higher concentrations of insulin-like growth factor-binding protein-3 (IGFBP-3), insulin-like growth factors I and II (IGF-I, IGF-II) and transforming growth factor-beta 2 (TGF-beta2) were found in the Na/K > 3 sub-group. No difference was found in transforming-growth factor-beta 1 (TGF-beta1) levels between the two sub-groups of breast cysts. A positive correlation was obtained for IGFBP-3 and TGF-beta1 in the Na/ K > 3 sub-group consistent with reports that TGF-beta1 may regulate the production of IGFBP-3. Equimolar amounts of total IGFs and IGFBP-3 in breast cyst fluid imply that most, if not all, of these IGFs are protein-bound. The significantly higher concentrations of TGF-beta2 in the Na/K > 3 sub-group may partly explain the lower risk of breast cancer in this group of women.

The effects of recombinant human IGF-I administration on concentrations of acid labile subunit, IGF binding protein-3, IGF-I, IGF-II and proteolysis of IGF binding protein-3 in adolescents with insulin-dependent diabetes mellitus.

The long term therapeutic potential of recombinant human (rh) IGF-I administration in insulin-dependent diabetes mellitus (IDDM) may be determined by changes in the IGF binding proteins (IGFBPs) and thus the bioavailability of IGF-I. We have therefore studied the effects of a single subcutaneous dose of rhIGF-I (40 micrograms/kg at 1800 h), when compared with an untreated control night, in 17 subjects with IDDM, on serum concentrations of IGF-I, IGF-II, IGFBP-3, acid labile subunit (ALS), and IGFBP-3 proteolysis. Mean (+/- S.E.M.) IGF-I levels increased from 242 +/- 30 ng/ml to 399 +/- 26 ng/ml (P = 0.01) after rhIGF-I whereas IGF-II levels declined from 600 +/- 45 ng/ml to 533 +/- 30 ng/ml. There was a small overnight reduction in baseline ALS levels from 48 +/- 2.8 to 44.5 +/- 3.2 micrograms/ml (P = 0.04) after rhIGF-I administration. An early fall in IGFBP-3 concentrations on the control night was not seen after rhIGF-I and overall mean levels were increased (5.2 +/- 0.2 micrograms/ml vs 4.9 +/- 0.2 micrograms/ml, P = 0.04, on the control night). On the baseline night, IGFBP-3 levels correlated with the sum of IGF-I and IGF-II (r = 0.73, P = 0.02) and with levels of the ALS (r = 0.7, P = 0.002). However after rhIGF-I, the sum of IGF-I and IGF-II no longer correlated with IGFBP-3, whereas the relationship with ALS was maintained. Immunoblot studies in six subjects indicated that 60%-70% of the IGFBP-3 was detected as a low molecular weight fragment at 1900 h on both study nights, but the amount of fragment declined to approximately 50% at 0100 h and 45% at 0700 h. In conclusion, despite a slight but significant fall in ALS, IGFBP-3 levels rise after rhIGF-I administration in IDDM. This cannot be explained by alterations in IGFBP-3 proteolysis, and may relate to the relative stability of ALS/IGFBP-3 when complexed principally with IGF-I rather than IGF-II.

Examination of factors that influence the expansion of the fragile X mutation in a sample of conceptuses from known carrier females.

The Collaborative Prospective Fragile X Study was established to collect information on the pregnancy outcome of women known to be carriers of the fragile X syndrome. The prospective design of this study allows collection of ascertainment-free data and, thereby, avoids biases caused by sampling problems encountered in retrospective family studies. The results of 337 submitted cases are summarized. These data show that the segregation of the fragile X mutation is normal and the sex ratio of conceptuses is as expected for a prenatal sample. There is no excess of dizygotic twinning among the pre- or full mutation carrier females. Data are limited at this time but provide a suggestion that the risk of expansion to the full mutation may be correlated with maternal age and to the parental origin of premutation of carrier women. More data are needed to confirm these suggested trends. The prospective data base provides a valuable resource to continue to examine factors in an unbiased fashion.

Survey of the fragile X syndrome and the fragile X E syndrome in a special education needs population.

To begin to understand the population dynamics of the fragile X (FRAXA) mutation and to learn more about the fragile X E (FRAXE) syndrome, we have initiated a surve of children in special needs education programs in the public school system. With respect to the FRAXA syndrome, we found approximately 1/1,000 full mutations among males. No large alleles at the FRAXE locus were observed among 462 individuals. The allele distributions at the two loci among Caucasians and among African Americans were examined as well as the level of heterozygosity. We found a significant difference in the FRAXA allele distribution among the two ethnic groups; the major difference was due to the lack of smaller alleles among the African Americans. No difference was found for the FRAXE allele distribution among the two groups. The level of heterozygosity was less than predicted by the allele distribution at both loci. This is probably due to unidentified large alleles among females with a test result of a single band. Alternatively, this excess may indicate that the population is not at equilibrium.

Resolution of recalcitrant molluscum contagiosum virus lesions in human immunodeficiency virus-infected patients treated with cidofovir.

BACKGROUND: Molluscum contagiosum virus (MCV) causes cutaneous skin growths that mainly affect children, sexually active adults, and immunocompromised individuals. Lesions of MCV in patients infected with human immunodeficiency virus can be large and numerous, and response to available treatments is often unsatisfactory. OBSERVATIONS: We describe 3 men infected with human immunodeficiency virus who presented with extensive MCV lesions that were not responsive to various treatments. Patient 1 demonstrated dramatic clearing of his MCV lesions when intravenous cidofovir therapy was started for his treatment-resistant bilateral CMV retinitis and because of cidofovir's possible activity against MCV. In case 2, cidofovir was compounded as a 3% cream in a combination vehicle (Dermovan) for extensive facial involvement, and complete resolution of MCV was seen after 1 month of therapy. In case 3, intravenous cidofovir therapy was started both for CMV retinitis and in an attempt to clear 90% facial MCV involvement; after 1 month of treatment, all clinical evidence of MCV had resolved. All 3 patients remain clear of recurrence. CONCLUSIONS: Cidofovir, a nucleotide analog of deoxycytidine monophosphate, appears to have contributed to clearing of advanced MCV lesions in these 3 patients, thus providing suggestive evidence of clinical activity against MCV. Controlled trials of cidofovir therapy for MCV in persons infected with human immunodeficiency virus are warranted.

Antibodies to glutamate, aspartate and glycyl-D-aspartate reversibly suppress stimulus-evoked, extracellularly recorded responses in slices of rat neocortex.

Polyclonal antibodies raised against glutamate, aspartate and the dipeptide, glycyl-D-aspartate were dissolved in artificial cerebrospinal fluid (aCSF) and administered at concentrations as low as 0.05% to slices of prefrontal cortex maintained in vitro. These antisera caused a reversible attenuation of evoked field potentials and/or single-unit activity recorded extracellularly following the delivery of shocks to the underlying white matter, or to cortical layer IV. To the best of our knowledge, this result provides the first demonstration using electrophysiological recording of the use of a transmitter-specific antibody as a blocker of synaptic transmission in living slices of the central nervous system (CNS). The results lend support to the suggestion that glutamate, aspartate, and a molecule related closely to glycyl-D-aspartate, are involved in synaptic transmission at major pathways within prefrontal cortex.

Copper transfer from Rhus vernicifera laccase.

Tree laccase, a multi-copper oxidase, has been studied as a copper donor in conjunction with the demetalated forms of three blue copper proteins. Copper transfer could be observed under reducing conditions in the absence of air. Only about 10% of the total copper in laccase could be transferred regardless of the amount of acceptor present in solution, hence, the laccase is heterogeneous as isolated. Potential sources of the heterogeneity are considered. After transfer, laccase could be partially resolved into copper-deficient and nearly holoprotein fractions that would not donate copper when recombined with acceptor protein. EPR results in conjunction with thiol titrations indicate that there is no net loss of type 1 copper from laccase but that there is loss of type 2 copper as well as a small amount of type 3 copper. Very little transfer is observed when type 2-depleted laccase is used as the donor. Finally, the implications that these results could have in the elucidation of possibly more physiologically relevant processes are briefly summarized.

Developing outcome measures for ambulatory care--an application to asthma and diabetes.

Increasing emphasis is now being placed on the assessment of patient outcomes, both in evaluating medical interventions and in quality assurance initiatives. Clinicians, purchasers, managers and researchers need outcome measures that are valid, reliable and responsive. This paper describes the theory and practice underlying the development of outcome measures for two chronic conditions, asthma and diabetes, for application in ambulatory settings. Existing generic and condition-specific health status and health-related quality-of-life measures were administered to almost 1300 patients. The psychometric properties of these measures were examined to identify those that were of adequate validity and reliability in these population groups. Step-wise regression procedures were then used to identify a core set of scales that best predicted patients' general health perceptions, which could be used in measuring general health outcomes for each of these groups. These core sets consist of up to 40 items, spanning physical function, energy and vitality, emotional well-being and condition-specific aspects of health such as symptom control. Further analysis is being carried out to assess the responsiveness to change of these core item sets.

Alterations in the insulin-like growth factor system during the menstrual cycle in normal women.

OBJECTIVES: To evaluate the effects of endogenous estrogens and progestins on the IGF-system during the normal menstrual cycle in healthy premenopausal women not using contraceptive drugs. METHODS: Nine women had fasting blood samples obtained at 2-3 days intervals during a 5 week study period. Plasma levels of IGF-I, IGF-II, IGFBP-I, IGFBP-3, estradiol and progesterone were measured by radioimmunoassay (RIA) in each sample. IGFBP-3 was also evaluated by Western ligand blot (WLB) and immunoblot. Any differences between the menstrual phase (defined as day 1-5), follicular and luteal phases (separation based on plasma estradiol and progesterone values) were evaluated by the Friedman test. RESULTS: A small but significant difference in plasma levels of IGF-I (P < 0.01) and IGFBP-d (P < 0.05) measured by RIA between the three phases were seen with the highest levels found during the follicular phase. No change in plasma levels of IGFBP-1 and IGF-II was found and immunoblots did not reveal any alteration in the ratio of fragmented to intact IGFBP-3 during the menstrual cycle. A positive correlation between plasma levels of IGF-I and estradiol was seen in 8 out of 9 patients (P = 0.012). CONCLUSIONS: The finding of a slight but significant higher level of plasma IGF-I in the follicular and luteal phases compared with the menstrual phase suggests plasma estradiol may influence the level of this growth factor. This hypothesis is further supported by the finding of a correlation between plasma levels of IGF-I and estradiol but not progesterone in individual patients at different times during the menstrual cycle.

SCH 23390: D-1 modulation of oral dyskinesias induced in snakes by Xenopus skin mucus.

The granular gland skin secretion of Xenopus laevis induces seven involuntary oral dyskinesias and climbing behavior in the water snake Nerodia sipedon. In a previous study the D-2 receptor antagonist, haloperidol (HAL), selectively potentiated mucus-induced yawning and chewing but attenuated fixed gaping; other oral behaviors were unaffected; HAL alone induced no dyskinesias and failed to modify mucus-induced decreases in tongue flicking, cage climbing and activity. As skin compounds have neuroleptic properties known to induce human and animal dyskinesias, we hypothesized that D-1 receptor antagonism may modulate the four of seven mucus-induced dyskinesias and the climbing not altered by HAL. We found that, like HAL, SCH 23390 (SCH) potentiated mucus-induced yawning, attenuated fixed gaping and had no effect on climbing. Unlike HAL's potentiation of chewing, SCH attenuated chewing and potentiated writhing tongue movements. SCH alone, like skin mucus, attenuated tongue flicking and activity but, given with mucus, SCH increased tongue flicking and activity to control levels. Compared to the HAL study, results suggest that mucus-induced yawning and fixed gaping are similarly modulated by both HAL and SCH, while these drugs have opposite effects on writhing tongue and chewing. SCH given alone or with frog mucus had unique effects on activity and normal tongue flicking.