Differential analysis of serum and urine S100 proteins in juvenile-onset systemic lupus erythematosus (jSLE).

Up to 80% of juvenile-onset systemic lupus erythematosus (jSLE) patients develop lupus nephritis (LN) that affects treatment and prognosis. Easily accessible biomarkers do not exist to reliably diagnose LN, leaving kidney biopsies as the gold-standard. Calcium-binding S100 proteins are expressed by innate immune cells and epithelia and may act as biomarkers in systemic inflammatory conditions. We quantified S100 proteins in the serum and urine of jSLE patients, matched healthy and inflammatory (IgA vasculitis) controls. Serum S100A8/A9, and serum and urine S100A12 are increased in jSLE patients when compared to controls. Furthermore, serum S100A8/A9, and serum and urine S100A12 are increased in jSLE patients with active as compared to patients with inactive/no LN. No differences in S100A4 levels were seen between groups. This study demonstrates potential promise for S100A8/A9 and S100A12 as biomarkers for jSLE and active LN. Findings require to be confirmed and tested prospectively in independent and larger multi-ethnic cohorts.

Decreased interferon-ß induced STAT-4 activation in immune cells and clinical outcome in multiple sclerosis.

OBJECTIVES: Interferon-ß (IFN-ß) is used in the treatment of multiple sclerosis (MS). IFN-ß activation of signal transduction and activation of transcription (STAT)-4 is linked to its immunomodulatory effects. Previous studies suggest a type I IFN deficit in immune cells of patients MS, but data on interferon-α/ß receptor (IFNAR) expression and the relationship with treatment response are conflicting. Here, we compare IFN-ß-mediated STAT4 activation in immune cells of untreated patients with MS and controls. MATERIALS AND METHODS: Peripheral blood mononuclear cells from 27 untreated patients with relapsing MS, obtained before the initiation of IFN-ß treatment, and 12 matched controls were treated in vitro with IFN-ß. Total and phosphorylated STAT4 (pSTAT4) and IFNAR were measured by flow cytometry and quantitative PCR. The patients were followed up for 5 years. RESULTS: pSTAT4 induction by IFN-ß was lower in patients with MS than in controls, as was expression of IFNAR. pSTAT4 expression did not correlate with the clinical outcome at 5 years, measured by EDSS change. There was a negative correlation between the baseline IFNAR1 mRNA levels and relapse rate. CONCLUSIONS: The results suggest decreased IFN-ß responsiveness in patients with MS, associated with reduced STAT4 activation and reduced IFNAR expression. This reduced responsiveness does not appear to affect the long-term clinical outcome of IFN-ß treatment.

Increased expression of low density granulocytes in juvenile-onset systemic lupus erythematosus patients correlates with disease activity.

Neutrophils are implicated in a wide range of non-infectious inflammatory conditions. A subset of neutrophils in the peripheral circulation of systemic lupus erythematosus (SLE) patients has been described and termed low density granulocytes (LDGs). This study investigates the expression of LDG in juvenile-onset SLE (JSLE) patients compared to controls, and any correlations with disease activity.Neutrophils and LDGs were isolated from JSLE (n = 13) and paediatric non-inflammatory control patients (n = 12). Cell populations were assessed and compared using flow cytometry and morphological analysis. Standard clinical data, which included disease activity markers/scores, were collected for each patient.Significantly increased LDG expression (%mean ± SEM, range) was observed in JSLE patients (10.4 ± 3.26, 3.41-36.3) compared to controls (2.4 ± 0.44, 0.36-5.27; p = 0.005). A statistically significant positive correlation was observed between LDG expression and the British Isles Lupus Activity Group (correlation coefficient 0.685; p = 0.010) and SLE Disease Activity Index (correlation coefficient 0.567; p = 0.043) and the biomarker of dsDNA-antibodies (correlation coefficient 0.590; p = 0.043).Here we observe increased expression in LDGs in JSLE patients, which correlate with dsDNA antibody concentration and scores of disease activity. These correlations indicate that the increased LDG expression observed in this study may have a potential role in the pathogenesis of JSLE, and may be a useful biomarker.

Increased concentration of plasma TNFR1 and TNFR2 in paediatric lupus nephritis.

BACKGROUND: Juvenile-onset systemic lupus erythematous (JSLE) is a debilitating condition that frequently involves the kidneys (lupus nephritis; LN). Tumour necrosis factor alpha (TNF-α), an important pro-inflammatory cytokine, is expressed locally in the kidney and correlates with LN disease activity. The aim of this study was to ascertain whether soluble receptors for TNF-α (sTNFR1/sTNFR2) are significantly increased in children with LN. METHODS: Plasma samples were collected from JSLE patients at routine review. Concentrations of sTNFR1 and sTNFR2 were measured (median; interquartile range, IQR) using enzyme-linked immunosorbent assay (ELISA) in 25 JSLE patients (seven LN) and 20 healthy controls (HCs). RESULTS: sTNFR2 concentration was significantly increased in JSLE (5149 pg/dl, 3413-8561) compared to HCs (3858 pg/dl, 2254-5165; p = 0.049). sTNFR1 concentration was significantly increased in active LN (n = 7, 1765 pg/dl, IQR 1133-4167) compared to inactive LN (n = 18, 1104 pg/dl, 886-1272; p = 0.018). There was a non-significant increase in sTNFR2 concentration in active LN (9829 pg/dl, 3298-21271) compared to inactive LN (4595 pg/dl, 3345-6993; p = 0.146). sTNFR1 concentration correlated moderately with sTNFR2 (r = 0.66, p < 0.001). sTNFR2 demonstrated strong positive correlations with ESR (r = 0.941, p < 0.01) and anti-dsDNA antibodies (r = 0.998, p = 0.041). Both receptors also positively correlated with creatinine (TNFR1 r = 0.81, p < 0.001; TNFR2 r = 0.50, p = 0.015) and urinary albumin creatinine ratio (TNFR1 r = 0.64, p < 0.01; TNFR2 r = 0.63, p < 0.01). CONCLUSIONS: These data indicate that sTNFR1 and sTNFR2 concentrations are elevated in LN and may reflect renal activity. These results provide basis for further investigation into the pathological pathways underlying LN.

Acute Hypotensive Response to Continuous and Accumulated Isocaloric Aerobic Bouts.

Evidence indicates that chronic reductions in blood pressure (BP) due to aerobic exercise depend on the ability to induce post-exercise hypotension (PEH) after each training bout. The purpose of this study was to investigate PEH after isocaloric bouts of continuous and accumulated running. 10 healthy pre-hypertensive men (aged 27.6±3.5 years) performed the following bouts of exercise: a) A continuous bout (CONT) expending a total of 400 kcal; and b) An accumulated bout split into 2×200 kcal (INTER1 and INTER2) to total 400 kcal at 75% of oxygen uptake reserve. BP, mean arterial pressure (MAP) and heart rate variability were monitored 10 min before and 60 min after control and all exercise conditions. The decrease in MAP over time after continuous (400 kcal) and accumulated (2×200 kcal) bouts of exercise was more pronounced than during control (mean diff between 1.6 and 5.4 mmHg, P≤0.01), although the magnitude of change was similar between continuous and accumulated bouts (mean diff=0.1 mmHg, P=0.79). Concomitant to the PEH, sympathovagal balance was inversely related to changes in MAP after isocaloric bouts performed continuously and cumulatively (r=- 0.72 and-0.85, P=0.019 and 0.002, respectively). In conclusion, BP decreased to similar levels after continuous and accumulated acute aerobic exercise matched for total energy expenditure. Our findings also indicate that the recovery pattern of cardiac autonomic activity may have an important role in eliciting PEH.

Utility of a Non-Exercise VO2max Prediction Model for Designing Ramp Test Protocols.

This study investigated the validity of determining the final work rates of cycling and walking ramp-incremented maximal cardiopulmonary exercise tests (CPETs) using a non-exercise model to predict maximal oxygen uptake VO2max and the American College of Sports Medicine ACSM's metabolic equations. The validity of using this methodology to elicit the recommended test duration of between 8 and 12 min was then evaluated. First, 83 subjects visited the laboratory once to perform a cycling (n=49) or walking (n=34) CPET to investigate the validity of the methodology. Second, 25 subjects (cycling group: n=13; walking group: n=12) performed a CPET on 2 separate days to test the reliability of CPET outcomes. Observed VO2max was 1.0 ml·kg(-1)·min(-1) lower than predicted in the cycling CPET (P=0.001) and 1.4 ml·kg(-1)·min(-1) lower in the walking CPET (P=0.001). Only one of the 133 conducted CPETs was outside the test duration range of 8-12 min. Test-retest reliability was high for all CPET outcomes, with intraclass correlation coefficients of 0.90 to 0.99. In conclusion, the non-exercise model is a valid and reliable method for establishing the final work rate of cycling and walking CPETs for eliciting test durations of between 8 and 12 min.

Effects of different half-time strategies on second half soccer-specific speed, power and dynamic strength.

This study compared the effects of whole body vibration (WBV) and a field-based re-warm-up during half-time (HT) on subsequent physical performance measures during a simulated soccer game. Ten semi-professional male soccer players performed 90-min fixed-intensity soccer simulations (SAFT(90)), using a multi-directional course. During the HT period players either remained seated (CON), or performed intermittent agility exercise (IAE), or WBV. At regular intervals during SAFT(90), vastus lateralis temperature (T(m)) was recorded, and players also performed maximal counter-movement jumps (CMJ), 10-m sprints, and knee flexion and extension contractions. At the start of the second half, sprint and CMJ performance and eccentric hamstring peak torque were significantly reduced compared with the end of the first half in CON (P≤0.05). There was no significant change in these parameters over the HT period in the WBV and IAE interventions (P>0.05). The decrease in T(m) over the HT period was significantly greater for CON and WBV compared with IAE (P≤0.01). A passive HT interval reduced sprint, jump and dynamic strength performance. Alternatively, IAE and WBV at HT attenuated these performance decrements, with limited performance differences between interventions.

Urinary monocyte chemoattractant protein 1 and alpha 1 acid glycoprotein as biomarkers of renal disease activity in juvenile-onset systemic lupus erythematosus.

A higher proportion of patients with juvenile-onset systemic lupus erythematosus (JSLE) will have renal involvement compared with adult-onset disease, some progressing to renal failure in adulthood. Histological examination is the gold standard for diagnosing lupus nephritis (LN), but its invasive nature limits routine use. Using cross-sectional cohort analysis, we aimed to determine whether urinary concentrations of monocyte chemoattractant protein-1 (MCP1), alpha-1-acid glycoprotein (AGP) and interferon-inducible protein 10 (IP10) are biomarkers of active LN. Sixty JSLE patients recruited to the UK JSLE Cohort Study were categorized according to the British Isles Lupus Assessment Group (BILAG) activity index. Patients with active renal JSLE (n = 8; renal BILAG score A, B) had significantly higher urinary MCP1 concentrations than patients with inactive renal disease (n = 52; renal BILAG score C, D, E; 582 pg/mg creatinine [Cr], 207 pg/mg Cr; p = 0.018) or healthy controls (n = 23; 117 pg/mg Cr; p = 0.005). Urinary AGP concentration was significantly elevated in patients with active renal disease compared with inactive renal disease (1517 ng/mg Cr, 485 ng/mg Cr; p = 0.027) or healthy controls (313 ng/mg Cr; p = 0.013). Urinary IP10 concentration was not significantly different between groups, but did strongly correlate with uMCP and uAGP levels (rho = 0.38, p = 0.009; rho = 0.33, p = 0.021). Urinary MCP1 and AGP are biomarkers of LN, providing insight into its pathophysiology. Longitudinal studies are warranted.

Patients' views of physical activity whilst living with and beyond head and neck cancer.

Exercise is an important component of recovery following cancer. Head and neck cancer (HNC) patients typically report low levels of engagement in exercise initiatives. The aim of this study was to give insight into HNC patients' reflections on how and why they would be interested in participating in an exercise programme. A stratified sample of 51 patients based on age, gender and initial interest in an exercise programme was selected from 430 postal survey respondents. Twenty-five took part in a semi-structured telephone interview. There was responder bias with females, younger patients, and those already participating in or interested in an exercise programme being over-represented. The responders in this study highlighted issues related to physical activity levels, perceived ability to meet physical activity guidelines for cancer survivors, perceived exercise benefits, perceived exercise barriers, and advice to others diagnosed with cancer. The findings support the premise of personalized interventions tailored towards the specific needs of the patient, supported by patient peers to emphasize the benefits and help motivate patients to take part. In order to promote engagement in exercise there needs to be collaborative, culturally sensitive and individualized approaches, in order to address the specific barriers experienced by HNC patients.

Cellular localization of nuclear antigen during neutrophil apoptosis: mechanism for autoantigen exposure?

Juvenile-onset systemic lupus erythematosus (JSLE) is a multisystem autoimmune disease characterized by hyperactive B-cells producing auto-antibodies directed against nuclear antigens. A potential source of these antigenic components is apoptotic cells. We have previously demonstrated increased dysregulated neutrophil apoptosis in JSLE patients. Here we investigate autoantigen expression on JSLE neutrophils during apoptosis. Neutrophils from non-inflammatory controls and JSLE patients were incubated with JSLE and control serum. Apoptosis and dsDNA expression was measured using flow cytometry and confocal microscopy. Increased neutrophil apoptosis and dsDNA expression was observed in JSLE and control neutrophils incubated with JSLE serum. During neutrophil apoptosis nuclear material was exposed on the cell surface rather than within the cell as seen with viable neutrophils. The increased neutrophil apoptosis induced by JSLE compared with control serum resulted in increased surface expression of nuclear antigens. This may provide an additional mechanism leading to the generation of autoantibodies in JSLE.

Differential expression of factors involved in the intrinsic and extrinsic apoptotic pathways in juvenile systemic lupus erythematosus.

Dysregulated neutrophil apoptosis may result in the development of autoimmune disease by contributing to nuclear autoantigen exposure, leading to autoantibody generation and a breakdown in immune tolerance. It has previously been shown that neutrophil apoptosis is increased in juvenile-onset systemic lupus erythematosus (JSLE). This study aims to investigate the pathways involved in JSLE serum-induced apoptosis. Caspases 3, 7-9, IAP1/2, XIAP and FADD mRNA levels and TRAIL R2, BID/tBID, caspase 8 and 9 protein expression were measured in neutrophils from JSLE patients (n = 14) and controls (n = 10). The mRNA levels of caspases 7-9 were significantly higher in JSLE neutrophils than in controls, whereas the mRNA levels of IAP1, IAP2 and XIAP were decreased (p < 0.05). A decrease in neutrophil apoptosis induced by JSLE serum was observed in the presence of caspase 8 and 9 inhibitors (p < 0.05), and the activity of caspases 8 and 9 increased over time. tBID protein expression increased following incubation with JSLE serum. These data focus specifically on the expression and activity of the main caspases in the intrinsic and extrinsic apoptotic pathways. Increased expression of factors involved in the downstream signalling of the extrinsic apoptotic pathway indicates a prominent involvement of this pathway in JSLE serum-induced apoptosis.

The effects of low and high glycemic index 24-h recovery diets on cycling time trial performance.

AIM: The present study investigated the effects of high and low glycemic index (GI) 24 h recovery meals on the physiological responses and subsequent athletic performance, following a glycogen depleting protocol. METHODS: Ten well trained cyclists (age, 33.6±7.4y, height, 175.3±7.6 cm, weight 74.5±8.2 kg, and VO(2max), 60.5±6.0 ml∙kg(-1)∙min(-1)) participated in two trials in a randomized cross- over design. On day 1, subjects performed a glycogen depleting protocol after which they then consumed either high or low GI recovery diets over the next 24 h, which provided 8 g.kgBW(-1) of carbohydrate. On day 2, the subjects returned to the laboratory, 2- 3 h postprandial, to perform a 40 km time trial (TT) on the Velotron cyclePro© ergometer. RESULTS: No difference was observed in TT performance times between the high GI (93. 5±9.29 min) trial and the low GI (90.7±11.1 min) trial (t=1.1; P=0.35). Additionally, no differences in carbohydrate (F=1.1, P=0.37) fat (F=1.1, P=0.40) oxidation or blood glucose concentration (F=0.9, P=0.5) was observed. DISCUSSION: The results of the present study suggest that the ingestion of a high GI carbohydrate 24 h recovery diet following glycogen depleting exercise, has no greater effect on endurance performance than consuming a low GI carbohydrate 24 h recovery diet. It may be concluded from these results that, provided enough carbohydrate is consumed during a 24 h recovery period, there is no difference in subsequent endurance performance.

Metabolic alkalosis, recovery and sprint performance.

Pre-exercise alkalosis and an active recovery improve the physiological state of recovery through slightly different mechanisms (e. g. directly increasing extracellular bicarbonate (HCO3 (-)) vs. increasing blood flow), and combining the two conditions may provide even greater influence on blood acid-base recovery from high-intensity exercise. Nine subjects completed four trials (Placebo Active ( PLAC A), sodium bicarbonate (NaHCO3) Active ( BICARB A), Placebo Passive ( PLAC P) and NaHCO3 Passive ( BICARB P)), each consisting of three, 30-s maximal efforts with a three min recovery between each effort. Pre-exercisealkalosis was evident in both NaHCO3 conditions, as pH and HCO3 (-) were significantly higher than both Placebo conditions (pH: 7.46 ± 0.04 vs. 7.39 ± 0.02; HCO3 (-): 28.8 ± 1.9 vs. 23.2 ± 1.4 mmol·L (-1); p<0.001). In terms of performance, significant interactions were observed for average speed (p<0.05), with higher speeds evident in the BICARB A condition (3.9 ± 0.3 vs. 3.7 ± 0.4 m·s (-1)). Total distance covered was different (p=0.05), with post hoc differences evident between the BICARB A and PLAC P conditions (368 ± 33 vs. 364 ± 35 m). These data suggest that successive 30-s high intensity performance may be improved when coupled with NaHCO3 supplementation.

Influence of cardiopulmonary exercise testing protocol and resting VO(2) assessment on %HR(max), %HRR, %VO(2max) and %VO(2)R relationships.

The findings of previous studies investigating the strength of the relationships between the percentages of maximal heart rate (%HR(max)), heart rate reserve (%HRR), maximal oxygen uptake (%VO(2max)), and oxygen uptake reserve (%VO(2)R) have been equivocal. This inconsistency between studies could largely be due to differences in methodology. The purpose of this study was therefore to determine whether different VO(2max) test protocols and resting VO(2) assessment influence the relationships between the %HR(max), %HRR, %VO(2max), and %VO(2)R. Thirty-three young men performed maximal treadmill protocols (ramp, Bruce) to assess HR(max) and VO(2max). Resting VO(2) was assessed as follows: a) resting VO(2standard), using strict criteria (24 h exercise abstention, alcohol, soft drinks, or caffeine; 8 h fasting; 30 min assessment); b) resting VO(2sitting) and; c) resting VO(2standing) (both 5 min before exercise testing). The %HRR was closer to %VO(2max) than to %VO(2)R, especially in the ramp protocol (p<0.001). In the Bruce protocol, relationships were closer to the identity line, and there was no significant difference between %HRR and %VO(2max), or %VO(2)R. The VO(2max) was significantly higher in the ramp protocol compared to the Bruce protocol (p<0.001). In both protocols resting VO(2) assessment produced no significant difference in the intercepts and slopes of the %HRR-%VO(2)R relationships obtained from individual regression models. The %VO(2)R calculated using resting VO(2standard) was closer to %HRR compared to VO(2sitting) and VO(2standing). The premise that %HRR is more strongly related to %VO(2)R than to %VO(2max) was not confirmed. Methodological differences should be considered when interpreting previous studies investigating %HR(max), %HRR, %VO(2max), and %VO(2)R relationships.

Emergence of the verification phase procedure for confirming 'true' VO(2max).

Traditional (.)VO(2max) criteria are typically based on attainment of a (.)VO2 plateau, and threshold values for the respiratory exchange ratio, heart rate and blood lactate concentration. Despite long-standing criticisms directed at these criteria, their use remains widespread. This article discusses an alternative procedure, termed the verification phase, for confirming the attainment of true (.)VO(2max). Following a continuous incremental exercise test to the limit of tolerance and appropriate recovery period, the verification phase is performed and is characterized by a supramaximal square wave exercise bout. Consistent peak (.)VO2 values in the incremental and verification phases, confirms that a true (.)VO(2max) has been attained. Six recent studies investigated the utility of the verification phase for evaluating true (.)VO(2max). These studies consistently found small insignificant mean differences between the maximal (.)VO2 attained in the incremental and verification phases. However, this group mean approach does not identify individual subjects who may not have attained a true (.)VO(2max). Notably, only one of the six studies reported a criterion threshold to verify the (.)VO(2max) of individual subjects. Further research is required to investigate the utility of different verification phase procedures and to establish a suitable verification criterion threshold for confirming true VO(2max).

Release of VCAM-1 associated endothelial microparticles following simulated SCUBA dives.

Microparticles (MP) are shed into the circulation from endothelium following activation or apoptosis. Vascular cell adhesion molecule-1 (VCAM-1) is expressed on endothelial cells following activation and here we report quantification of VCAM-1 positive microparticles (VCAM + MP) following simulated SCUBA dives, breathing either air or oxygen. VCAM + MP were quantified pre-dive (09:00 and 13:00) and post-dive (+1, +3 and +15 h) on both air and oxygen dives and compared with control samples taken from the same subjects. VCAM + MP followed a similar trend in all experiments, however both dives caused a change in endothelial state, as measured by VCAM + MP. A significant increase in VCAM + MP was observed 1 h post-air dive relative to the control (p = 0.013), which was not observed after the oxygen dive (p = 0.095). Oxidative stress (TBARS) was correlated with VCAM + MP. Data presented highlights the potential of MP as a biological marker of both endothelial state and decompression illness.

The effects of caffeine ingestion on time trial cycling performance.

AIM: The purpose of this work was to determine the effects of caffeine ingestion on cycling time trial (TT) performance in well trained male subjects. METHODS: Eight males, with the following physical characteristics (Mean +/- SD) age 30.2+/-10.1 years, height 180.3+/-7.1 cm, mass 70.4+/-5.1 kg, VO2max 63.6+/-4.4 mL.kg(-1).min(-1) undertook three 1 h TT performances on a VelotronPro cycle ergometer, in a double blind, random fashion. The trials were Control (C), Placebo (Pl) and Caffeine (CAF). The CAF and Pl were given 60 min prior to exercise in a dose of 6 mg.kg(-1) body mass. Prior to ingestion, 60 min post ingestion, and at the end of the TT, subjects gave 10 mL of venous blood which was analysed for lactate, glucose, and free fatty acids. Expired air was collected throughout each test by indirect calorimetry. RESULTS: The cyclists rode significantly further in CAF trial (28.11+/-1.32 km) than they did in the C (26.69+/-1.5 km, P < 0.03) or Pl (27.0+/-1.5 km, P < 0.03) trials. No significant differences were seen between C and Pl trials (P > 0.88). No differences between C and Pl were seen in heart rate data throughout the TT (p > 0.05). The free fatty acid (FFA) concentrations were significantly higher in the CAF trials both post ingestion (P < 0.005) and post exercise (P < 0.0001) than either C or Pl trials. CONCLUSION: We concluded that performance was improved possibly based upon a greater reliance on fat metabolism, as indicated by increased FFA and a lower respiratory exchange ratio (RER).

Follicle-stimulating hormone is secreted more irregularly than luteinizing hormone in both humans and sheep.

Recently introduced statistical tools capable of discerning differences between the pattern of luteinizing hormone (LH) secretion and that of follicle-stimulating hormone (FSH) could be valuable in understanding ovulation and menopause, and ultimately in making diagnostic decisions and treating infertility and polycystic ovary syndrome. We assessed the validity and scope of the hypothesis that FSH is secreted more irregularly than LH in ewes and fertile women. We compared secretory irregularity of LH to that of FSH in both ovariectomized ewes (n = 7) and women of proven fertility (n = 5) during the follicular and luteal phases of their reproductive cycles. In each sheep, time series from both hypophyseal portal blood (HPB) and peripheral blood were evaluated in 72 samples obtained every 5 min; in each human, both luteal and follicular periods were studied in 192 samples obtained every 7.5 min. To quantify serial irregularity, we used approximate entropy (ApEn), a scale- and model-independent statistic. FSH secretion was consistently more irregular than that of LH in each subject. For sheep HPB, ApEn(FSH) = 1.415+/-0.097 was larger than ApEn(LH) = 0. 822+/-0.213, P < 0.0001 (mean+/-SD, paired t test). This difference persisted peripherally: ApEn(FSHper) = 1.431+/-0.101 > ApEn(LHper) = 1.252+/-0.086, P = 0.024. In women, ApEn(FSH) = 1.467+/-0.217 > ApEn(LH) = 0.923+/- 0.305, P < 0.0001. ApEn(FSH) > ApEn(LH) in 100% of women (peripheral) and sheep HPB. Secretion during the follicular phase was more irregular than during the luteal phase for both FSH and LH (P < 0.01). LH mean level secretion showed a wake/sleep difference in women, P < 0.005, with higher values awake. The consistency and statistical significance of these findings suggest that this LH/FSH difference may be broadly based within higher mammals. Ranges of normative and abnormal regularity values of LH, FSH, and their difference can be used in a number of settings, both (currently) research and (potentially ultimately) clinical milieus.

Dose-response relationship of luteinizing hormone to luteinizing hormone--releasing hormone in man.

In previous clinical studies with highly purified porcine luteinizing hormone-releasing hormone (LH-RH), administration of the somewhat arbitrarily chosen doses of 700-1500 mug resulted in increased serum levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH). The present study determined the minimum effective dose as well as the relationship of the response of serum LH and FSH to the dose of LH-RH administered. Three normal men received i.v. injections of 1.1-810 mug of LH-RH. A dose of 10 mug of LH-RH caused a statistically significant elevation in serum LH. 30 mug of LH-RH significantly increased serum FSH levels. A highly significant linear trend was observed in the log dose-response curve. The results indicate that both LH and FSH release occurs in man with doses of LH-RH much lower than previously used and that a linear log dose-response relationship can be obtained.

Actual versus perceived risk of cervical cancer among college women smokers.

UNLABELLED: Cervical cancer is a well-established smoking-related illness, but many at-risk women are unaware of this link. OBJECTIVE: The authors designed this study to (1) investigate the relationship of smoking behavior with the history of abnormal Pap test results, sexual history, and perceived risk of cervical cancer and (2) determine whether self-classified smoking status (and hence perceived risk) corresponds with actual smoking behavior in a college student population. PARTICIPANTS AND METHOD SUMMARY: College women students (N = 135) completed a survey assessing smoking history, health history, sexual risk behavior, and risk awareness. RESULTS: Relative to those who had not smoked in the past month, current smokers (n = 36, or 27% of the total sample) perceived themselves to be at higher risk for developing cervical cancer, but did not demonstrate increased awareness of specific cervical cancer risk factors, including smoking. Twenty-eight percent (10 of 36) of past-month smokers did not define themselves as current smokers. CONCLUSION: The authors conclude that anti-smoking and health-related messages targeting smokers may misfire for individuals who do not define themselves as smokers but are nonetheless at risk for smoking-related consequences and escalating use.