Clinical impact of 99mTc-HDP SPECT/CT imaging as standard workup for foot and ankle osteoarthritis.

Objective: The primary aim of this study was to assess to what extent 99mTc-HDP Single photon emission computed tomography/computed tomography (SPECT/CT) will lead to change of diagnosis and treatment, in patients with suspected foot and ankle osteoarthritis (OA). Secondary aim was to assess the intraobserver variability. Methods: Retrospectively 107 patients, with suspected foot and/or ankle OA of which a SPECT/CT was made, were included for analysis. All the clinical and radiological data were randomized and blinded before being scored by one experienced orthopaedic surgeon. Firstly, based on the clinical data and conventional radiographs, a diagnosis and treatment plan was scored. Secondly, the observer accessed the SPECT/CT and could change the diagnosis and treatment plan. Additionally, the intraobserver reliability was determined by data of 18 patients that were added in twofold to the dataset, without awareness of the observer and by calculating the κ values. Results: The diagnosis changed in 53% (57/107) and treatment plans changed in 26% (28/107) of the patients. Intraobserver reliability for the conventional workup was k = 0.54 (moderate strength of agreement), compared to k = 0.66 (substantial strength of agreement) when SPECT/CT data were added. Conclusions: This study describes the influence of SPECT/CT on diagnosis and treatment plans in patients with suspected symptomatic OA. Also, it shows SPECT/CT leads to a higher intraobserver variability. We believe SPECT/CT has a promising role in the workup for foot and ankle OA. Advances in knowledge: In addition to what was found in complex foot and ankle cases, this study shows that in patients with non-complex foot and ankle problems, SPECT/CT has a substantial influence on the diagnosis (and subsequent treatment plan).

How does hip osteoarthritis differ from knee osteoarthritis?

Hip and knee osteoarthritis (OA) are leading causes of global disability. Most research to date has focused on the knee, with results often extrapolated to the hip, and this extends to treatment recommendations in clinical guidelines. Extrapolating results from research on knee OA may limit our understanding of disease characteristics specific to hip OA, thereby constraining development and implementation of effective treatments. This review highlights differences between hip and knee OA with respect to prevalence, prognosis, epigenetics, pathophysiology, anatomical and biomechanical factors, clinical presentation, pain and non-surgical treatment recommendations and management.

Course and predictors of upper leg muscle strength over 48 months in subjects with knee osteoarthritis: Data from the osteoarthritis initiative.

Objectives: Weakness of upper leg muscles has a negative impact on future disease and functional status in subjects with knee osteoarthritis (OA). The aims of the present study were to (i) describe the course of muscle strength over 48 months and (ii) identify baseline predictors for a decline in upper leg muscle strength over time in subjects with knee OA. Methods: Data were obtained from the Osteoarthritis Initiative (OAI) database, a multicenter, observational study of knee OA. Upper leg muscle strength (in N/kg) was measured at baseline, 24 and 48 months. Potential baseline predictors included demographics, OA-specific and health and lifestyle related factors. Linear mixed model analyses were performed. Results: A total of 1390 subjects with knee osteoarthritis were included. A statistically significant decline of muscle strength was found between baseline and 24 months (B = -0.186, 95%CI [-0.358,-0.014], p = 0.03), but not between other time points (24-48 months p = 0.89, and baseline and 48 months p = 0.058). Predictors of a decline in muscle strength over time included demographic predictors (older age, being female, higher body mass index (BMI)), one lifestyle predictor (lower dietary protein intake) and one OA-specific predictor (radiographic severity). Conclusions: Muscle strength declined over time in subjects with knee OA. The identified predictors may help clinicians to select and treat subjects with knee OA at risk of a decline in muscle strength.

Dietary protein intake and upper leg muscle strength in subjects with knee osteoarthritis: data from the osteoarthritis initiative.

The aims of this study were (1) to describe dietary protein intake, and (2) to evaluate the association between dietary protein intake and upper leg muscle strength in subjects with knee osteoarthritis (OA). Baseline data from the OA was used, in a cross-sectional study. All subjects were diagnosed with symptomatic and radiographic knee OA. Daily dietary protein intake was measured with the Block Brief 2000 food frequency questionnaire (g/kg body weight). The sum of knee flexion and extension strength of the index knee (N/kg bodyweight) was assessed with the Good Strength chair test. Linear regression analysis was used to test the association between dietary protein intake and muscle strength, adjusting for relevant confounders. Data from 1316 subjects (mean age 61.4 ± SD 9.1 years, 57.0% female) were used. The mean daily protein intake was 0.72 ± SD 0.30 g/kg bodyweight, and 65.1% of the subjects had a protein intake lower than the recommended daily allowance of 0.8 g/kg bodyweight. The mean muscle strength was 5.4 ± SD 2.1 N/kg bodyweight. Lower protein intake was significantly associated with lower muscle strength (B = 0.583, 95% CI 0.230-0.936, p = 0.001). The majority of the subjects with knee OA had a dietary protein intake lower than the recommended daily allowance. Lower protein intake was associated with lower upper leg muscle strength. Longitudinal observational and interventional studies are needed to establish whether dietary protein intake has a causal effect on muscle strength in subjects with knee OA.

Comparison of MRI, CT and bone scintigraphy for suspected scaphoid fractures.

PURPOSE: The best diagnostic modality for confirmation of the diagnosis of a scaphoid fracture that is not visible on the initial radiograph (occult scaphoid fracture) is still subject of debate. The aim of this study was to compare the accuracy of magnetic resonance imaging (MRI), computed tomography (CT) and bone scintigraphy (BS) for the diagnosis of these occult scaphoid fractures. PATIENTS AND METHODS: In a study period of 12 months, 33 consecutive patients with a clinically suspected scaphoid fracture without a fracture on the scaphoid radiographs were evaluated with MRI, CT and BS. In case of a discrepancy between the diagnostic modalities, the final diagnosis was based on standardised follow-up with clinical examination and a repeated radiograph. RESULTS: Three of the 33 patients had a scaphoid fracture. MRI missed one scaphoid fracture and did not over-diagnose. CT missed two scaphoid fractures and did not over-diagnose. BS missed no scaphoid fractures and over-diagnosed one scaphoid fracture in a patient with a fracture of the trapezium. CONCLUSION: This study shows that neither MRI, nor CT and BS are 100 % accurate in diagnosing occult scaphoid fractures. MRI and CT miss fractures, and BS tends to over-diagnose. The specific advantages and limitations of each diagnostic modality should be familiar to the treating physicians and taken into consideration during the diagnostic process.

MRI as a reference standard for suspected scaphoid fractures.

OBJECTIVES: Some have suggested that MRI might be the best reference standard for a true fracture among patients with suspected scaphoid fractures. The primary aim of this study was to determine the rate of false-positive diagnosis of an acute scaphoid fracture in a cohort of healthy volunteers. METHODS: In a prospective study, 33 healthy volunteers were recruited and both wrists of each were scanned, except for 2 volunteers for whom only one wrist was scanned. To simulate the usual clinical context the 64 scans of healthy volunteers were mixed with 60 MRI scans of clinically suspected scaphoid fractures but normal scaphoid radiographs. These 124 MRI scans were blinded and randomly ordered. Five radiologists evaluated the MRI scans independently for the presence or absence of a scaphoid fracture and other injuries according to a standard protocol. RESULTS: To answer the primary question, only the diagnoses from the 64 scans of healthy volunteers were used. The radiologists diagnosed a total of 13 scaphoid fractures; therefore, specificity for diagnosis of scaphoid fracture was 96% (95% confidence interval: range 94-98%). The 5 observers had a moderate interobserver agreement regarding diagnosis of scaphoid fracture in healthy volunteers (multirater κ=0.44; p<0.001). CONCLUSIONS: The specificity of MRI for scaphoid fractures is high (96%), but false-positives do occur. Radiologists have only moderate agreement when interpreting MRI scans from healthy volunteers. MRI is not an adequate reference standard for true fractures among patients with suspected scaphoid fractures.

Concentration and size distribution of particles in abstracted groundwater.

Particle number concentrations have been counted and particle size distributions calculated in groundwater derived by abstraction wells. Both concentration and size distribution are governed by the discharge rate: the higher this rate the higher the concentration and the higher the proportion of larger particles. However, the particle concentration in groundwater derived from abstraction wells, with high groundwater flow velocities, is much lower than in groundwater from monitor wells, with minimal flow velocities. This inconsistency points to exhaustion of the particle supply in the aquifer around wells due to groundwater abstraction for many years. The particle size distribution can be described with the help of a power law or Pareto distribution. Comparing the measured particle size distribution with the Pareto distribution shows that particles with a diameter >7 microm are under-represented. As the particle size distribution is dependent on the flow velocity, so is the value of the "Pareto" slope beta.

Diode laser hair removal around ileo-colo ostomys is safe, effective and beneficial: a pilot study.

BACKGROUND AND OBJECTIVE: Hair removal around an ileo-colo ostomy can cause a number of problems. We compared laser hair removal with mechanical shaving around the ostomy. METHOD: Eleven patients were selected with hairy skin around the ostomy for therapy with an AlGaAs diode laser at 800 nm. Three to four treatments were given with an interval of 6 weeks. RESULTS: Ten patients completed laser therapy. The average hair reduction was 60% based on visual inspection. Shaving frequency reduced from once a week to once every 6 weeks. CONCLUSIONS: Laser hair removal likely becomes the preferred method in ostomy patients.

Pendra goes Dutch: lessons for the CE mark in Europe.

The development of a truly non-invasive continuous glucose sensor is an elusive goal. We describe the rise and fall of the Pendra device. In 2000 the company Pendragon Medical introduced a truly non-invasive continuous glucose-monitoring device. This system was supposed to work through so-called impedance spectroscopy. Pendra was Conformité Européenne (CE) approved in May 2003. For a short time the Pendra was available on the Dutch direct-to-consumer market. A post-marketing reliability study was performed in six type 1 diabetes patients. Mean absolute difference between Pendra glucose values and values obtained through self-monitoring of blood glucose was 52%; the Pearson's correlation coefficient was 35.1%; and a Clarke error grid showed 4.3% of the Pendra readings in the potentially dangerous zone E. We argue that the CE certification process for continuous glucose sensors should be made more transparent, and that a consensus on specific requirements for continuous glucose sensors is needed to prevent patient exposure to potentially dangerous situations.

[Dumping syndrome in a child with an incorrectly positioned gastrostomy catheter]. / Dumpingsyndroom bij een kind met een verkeerd gelegen gastrostomiekatheter.

A 13-month-old girl experienced an epileptic fit due to hypoglycaemia. She was born with a posterolateral diaphragm defect and at the age of 1.5 months had undergone a Nissen fundoplication with which a gastrostomy was also performed. The tip of the gastrostomy catheter was found to be lying in the bulbus duodeni. Once this had been pulled back, the patient made a good recovery. Dumping syndrome is usually the result of a quicker gastric emptying time or a smaller gastric capacity, and in children it is mostly due to a Nissen fundoplication. In patients fed by tube who exhibit symptoms of dumping syndrome, the position of the feeding tube must be checked before other diagnostic or therapeutic steps are undertaken.

Muting of androgen negative feedback unveils impoverished gonadotropin-releasing hormone/luteinizing hormone secretory reactivity in healthy older men.

Plasma bioavailable testosterone concentrations decline in healthy older men without a uniformly commensurate rise in serum LH concentrations, which disparity is consistent with a hypothesis of relative hypogonadotropism. Likewise, preserved gonadotrope responsiveness to exogenous GnRH stimulation, despite an attenuated amplitude of endogenous LH pulses, points to reduced hypothalamic GnRH feedforward signaling in aging males. To appraise GnRH/LH secretory reserve more directly in older men, we have compared daily LH secretion, driven by profound short-term blockade of androgen biosynthesis by oral ketoconazole administration, in nine young (ages, 18-32 yr) and seven older (ages, 60-73 yr) volunteers. The ability to unleash endogenous GnRH-driven LH secretion in response to acute testosterone withdrawal was quantitated by sampling blood every 10 min, for 24 h, followed by high-precision immunoradiometric assay. The resultant serum LH concentration profiles were analyzed by: 1) model-free discrete peak detection (Cluster) analysis; 2) the approximate entropy statistic to quantitate pattern regularity; and 3) 24-h rhythmic (cosinor) analysis. At baseline, mean and integrated (24-h) serum LH concentrations were similar in both age cohorts. However, Cluster analysis established an elevated LH peak frequency [18 +/- 0.86 (older) vs. 13 +/- 1.3 pulses/24 h (young), P = 0.0028] and a reduced incremental LH pulse area [37 +/- 6.9 (older) vs. 106 +/- 20 (young) IU/L x min, P = 0.016] in older men. Approximate entropy calculations also revealed more irregular LH release patterns in older men before intervention (P = 0.00089). Feedback stress, achieved by ketoconazole-induced androgen deprivation, unmasked further neuroregulatory defects in older volunteers, who failed to equivalently increase the: 1) mean (24-h) serum LH concentration [i.e. to 5.0 +/- 0.99 (older men) vs. 9.0 +/- 1.1 (young) IU/L, P = 0.000071]; 2) maximal LH peak height (to 6.1 +/- 1.1 vs. 10.4 +/- 1.2 IU/L, P = 0.00043); 3) incremental LH pulse area (to 41 +/- 8.8 vs. 87 +/- 20 IU/L x min, P = 0.016); 4) interpeak nadir serum LH concentration (to 4.0 +/- 0.77 vs. 7.9 +/- 1.0 IU/L, P < 10(-6)); 5) the quantitable irregularity of LH release (P = 0.00089); and 6) the mesor of 24-h rhythmic LH secretion (P = 0.000062). In summary, experimental imposition of a novel hypoandrogenemic open-loop feedback stressor, for 48 h, to heighten hypothalamic GnRH feedforward drive, unveils impoverished augmentation of LH pulse mass, impaired orderliness of LH release, and diminished 24-h rhythmic LH secretion in older men. The foregoing trilogy of neuroregulatory defects identifies unequivocally attenuated hypothalamo-pituitary reactivity to muting of androgen negative feedback in the aging male.

[A child without edema in spite of albumin deficiency]. / Een kind zonder albumine en toch geen oedeem.

During extended investigation of a newborn girl with recurrent respiratory tract infection a continuous elevated blood sedimentation rate was noted together with a normal level of C reactive protein. This abnormality could be explained by analbuminaemia, causing a change in concentration of several other proteins such as transferrin. It was striking that this girl without albumin showed no signs of oedema. This lack of oedema could be explained by a decrease of oncotic pressure in the interstitium. Analbuminaemia is an autosomal recessive disorder. At follow-up the girl was still without complaints after 6 years.

Stereoselectivity at the beta2-adrenoceptor on macrophages is a major determinant of the anti-inflammatory effects of beta2-agonists.

Previous research has shown that beta-adrenoceptor (beta-AR) agonists have potent anti-inflammatory capabilities, e.g. represented by suppression of release of the proinflammatory cytokines. Aim of this research was to determine whether the effects of beta-agonists on LPS-induced TNFalpha and IL-10 release are influenced by their different stereochemistry. In addition, the role of the beta-AR subtypes was studied. The effect of two stereoisomers of the selective beta2-AR agonist TA2005 [(R,R)- and (S,S)-] on the LPS-induced TNFalpha and IL-10 release by U937 macrophages was compared. The (R,R)-stereoisomer was 277 times more potent in inhibiting the TNFalpha release than the (S,S)-form. The (R,R)-stereoisomer also appeared to be more potent in increasing the IL-10 release. In radioligand binding studies the affinity of (R,R)-TA2005 for the beta-adrenoceptor was 755 times higher than the (S,S)-TA2005 stereoisomer. In addition, the elevation of intracellular cAMP in U937 cells appeared to be stereoselective: (R,R)-TA2005 was more potent in elevating intracellular cAMP. The effect of both stereoisomers on the LPS-induced TNFalpha release could almost completely be antagonized by preincubation with the selective beta2-AR-antagonist ICI-118551. Further evidence that the effect of the beta-agonists is mediated via the beta2-adrenoceptor subtype exclusively was acquired by incubation of U937 cells with selective beta1- and beta3-agonists. None of these receptor subtype agonists showed significant suppressive effect on TNFalpha release. This study provides additional proof that the anti-inflammatory effects of beta2-agonists are mediated via the beta2-adrenoceptor and indicates that these effects are highly dependent on the stereoselectivity of the ligand.

Modulation of AT1 receptor-mediated contraction of rat uterine artery by AT2 receptors.

The aim of this study was to characterize the angiotensin II receptors in isolated uterine arteries from non pregnant and pregnant rats, since it has been reported from binding studies that ovine uterine arteries contain AT2 receptors. Uterine arterial segments were obtained from virgin, non-pregnant and late pregnant (18-21 days) Sprague-Dawley rats and mounted in small vessel myographs. Concentration-response curves were constructed to angiotensin II (1 nM-10 microM) in the absence and presence of various angiotensin II receptor subtype selective compounds. These included losartan (AT1 antagonist; 1, 10 and 100 nM), PD 123319 (AT2 antagonist; 1 microM) and CGP 42112 (AT2 agonist; 1 microM). Responses to angiotensin II were measured as increases in force (mN) and expressed as a per cent of the response to a K+ depolarizing solution. Losartan (1, 10 and 100 nM) caused significant concentration-dependent rightward shifts of the angiotensin II concentration-response curve in uterine arteries from non-pregnant and pregnant rats. The pA2 values calculated from these data were 9.8 and 9.2, respectively, although the slope of the Schild plot in the non-pregnant group was less than unity. PD 123319 (1 microM) caused significant 6- and 3 fold leftward shifts of the angiotensin II concentration-response curve in uterine arteries from non-pregnant and pregnant rats, respectively. In vessels from pregnant rats, PD 123319 also significantly increased the maximum response to angiotensin II. CGP 42112 (1 microM) attenuated the response to angiotensin II of uterine arteries from non-pregnant rats. This was reflected by a 14 fold rightward shift of the angiotensin II concentration-response curve and a decrease in the maximum response. In uterine arteries from pregnant rats, CGP 42112 (1 microM) caused a 3 fold rightward shift of the angiotensin II concentration-response curve, but had no effect on the maximum response. PD 123319 (1 microM) and CGP 42112 (1 microM) had no effect on the concentration-response curves to phenylephrine (PE) of uterine arteries from non-pregnant or pregnant rats. In addition, CGP 42112 (1 nM-1 mM) had no vasodilator effect on tissues precontracted with phenylephrine. These results suggest that the contractile responses of the rat uterine artery are mediated by the AT1 receptor. Furthermore, in this vascular preparation, the AT2 receptor appears to inhibit the response mediated by the AT1 receptor, although, this is not uniform between the non-pregnant and pregnant states.

Disparate serum free testosterone concentrations and degrees of hypothalamo-pituitary-luteinizing hormone suppression are achieved by continuous versus pulsatile intravenous androgen replacement in men: a clinical experimental model of ketoconazole-induced reversible hypoandrogenemia with controlled testosterone add-back.

To investigate the neuroendocrine mechanisms underlying the negative feedback actions of testosterone on both the pulsatile mode of LH release and the entropy or disorderliness of the LH release process, we blocked testicular androgen biosynthesis using oral high dose ketoconazole treatment with concomitant low dose glucocorticoid replacement for 48 h in six healthy young men. Volunteers were then infused iv with saline or a total of 8.0 mg testosterone base over the second 24 h via either a continuous or a pulsatile (90-min boluses) delivery pattern. Discrete peak detection (Cluster analysis) was applied to obtain a model-independent estimate of the frequency of serum LH concentration peaks, maximal and incremental LH peak amplitudes, peak area, and interpeak nadir serum LH concentrations. Approximate entropy was used to quantify the relative orderliness/disorderliness of the LH release process over 24 h. Ketoconazole treatment markedly lowered 24-h mean serum total and free testosterone concentrations (by 17- and 9-fold respectively), and significantly increased LH pulse frequency, maximal LH peak height, and interpeak nadir serum LH concentrations. Continuous iv testosterone add-back increased 24-h pooled serum free testosterone concentrations 3-fold more and concomitantly reduced mean (24-h) serum LH concentrations by at least 2-fold more than pulsatile delivery of the same total daily amount of androgen. Both modes of testosterone infusion suppressed pulsatile LH release, but the effects were distinguishable; namely, treatment with continuous vs. intermittent androgen add-back, respectively, decreased LH pulse frequency and incremental LH pulse amplitude. Ketoconazole treatment alone also significantly increased approximate entropy values, indicating greater disorderliness of LH release during androgen removal. Approximate entropy/orderliness was restored to baseline by continuous, but not pulsatile, iv testosterone replacement. In conclusion, the present novel testosterone add-back clinical experimental paradigm indicates that 1) remarkably different 24-h mean serum free testosterone concentrations can result from continuous vs. pulsatile testosterone delivery into the bloodstream; 2) androgen negative feedback can exert frequency- as well as amplitude-dependent suppression of pulsatile LH release; and 3) testosterone is required to maintain an orderly 24-h LH release process in young men.

Neuroendocrine mechanisms by which selective Leydig cell castration unleashes increased pulsatile LH release.

A novel pharmacological model of acute reversible Leydig cell "castration" induced by a steroidogenic enzyme inhibitor, ketoconazole, achieves marked hypoandrogenemia in healthy men with an attendant 2.5-fold increase in 24-h mean serum luteinizing hormone (LH) concentrations. Mechanistically, the unleashing of amplified pulsatile LH release can be accounted for by any of three distinct models of deconvolution-estimated gonadotropin secretion, all of which are marked by a nearly twofold acceleration in LH secretory burst frequency. In addition, the models variously also predict concomitant prolongation of the endogenous LH half-life, an augmented LH secretory burst mass and duration, and/or the emergence of significant basal LH secretion. The nyctohemeral (cosinor analysis) rhythmicity of serum LH concentrations is not disturbed when androgenic negative-feedback signaling is withdrawn abruptly, but the apparent process randomness of LH release increases, as quantified by higher approximate entropy values. Thus we conclude that an intact (closed loop) androgen-mediated negative-feedback network in the adult human male is required to sustain low-frequency pulsatile LH release in a quantifiably orderly manner.

Contrasts in the gonadotropin-releasing hormone dose-response relationships for luteinizing hormone, follicle-stimulating hormone and alpha-subunit release in young versus older men: appraisal with high-specificity immunoradiometric assay and deconvolution analysis.

The secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) is regulated by gonadotropin-releasing hormone (GnRH). As men age, mean serum concentrations of immunoreactive gonadotropic hormones tend to increase, while serum testosterone concentrations tend to decline. To evaluate age-related changes in gonadotroph cell function, we have assessed the dose-dependent secretory responses of immunoreactive LH, FSH and alpha-subunit to saline versus five doses of GnRH in older and young men. Ten older men, mean age 66 years (range 61-78), and nine young men, mean age 26 years (range 22-30), received iv bolus injections of GnRH (range 10-100 micrograms) in randomized order every 2 h, except that the 100-microgram dose was always given last. Blood samples for immunoradiometric assays of serum LH, FSH and alpha-subunit concentrations were obtained every 10 min for a total of 12 h, which included a 2-h preinjection baseline. Deconvolution analysis was performed to estimate gonadotropin and alpha-subunit secretory burst mass, amplitude and duration, as well as endogenous LH, FSH and alpha-subunit half-lives. The mean (+/- SEM) baseline 2-h serum FSH (IU/I) concentration was higher in older than younger men (5.9 +/- 0.8 vs 3.8 +/- 0.5, p < 0.05). The mean 2-h serum LH concentrations after GnRH were significantly higher than corresponding values in young men at GnRH doses of 25, 50 and 75 micrograms, and in the case of FSH at GnRH doses of 10 and 25 micrograms. Non-linear curve-fitting of these dose-response relationships revealed that the calculated maximal mean 2-h serum LH concentration response (IU/l) was higher in older than young men following GnRH stimulation: 15.4 (13.5-16.2) vs 10.8 (8.7-12.1) (95% confidence interval). The maximal mean 2-h serum FSH concentration response (IU/l) was also significantly higher in older men: 11.9 (10.2-13.1) versus 8.6 (7.2-9.6). Maximal alpha-subunit responses (microgram/l) were similarly increased in the older cohort: 1.16 (0.99-1.25) vs 0.83 (0.71-0.91). The incremental LH (p < 0.05) and FSH (p < 0.01) secretory burst mass from 10 to 25 micrograms GnRH was significantly greater in older than younger men. The LH and FSH half-lives and second component alpha-subunit half-lives were similar in older and young men. In addition, secretory burst durations were invariant of age. In contrast, by non-linear curve-fitting, the calculated mass of LH secreted was higher in older men at 13.5 (11.8-15) vs 10.6 (9.2-11.7) IU/l of distribution volume (p < 0.05) for the maximal absolute mass and 11.3 (9.5-12.7) vs 7.4 (6.0-8.4) IU/l (p < 0.05) for the maximal incremental mass of LH secreted after GnRH. The estimated maximal mass of FSH secreted after GnRH also was higher in older men: 4.6 (3.4-5.5) vs 3.2 (2.9-3.4) IU/l (p < 0.01). Finally, calculated maximal GnRH-stimulated alpha-subunit secretory burst mass was statistically greater in older individuals: 2.3 (1.8-2.5) vs 1.6 (1.4-1.8) micrograms/l. In contrast, half-maximally effective GnRH doses were not different in the two age groups. We conclude that older men show significantly increased maximal and incremental gonadotropin release due to amplified secretory burst mass in response to escalating doses of GnRH with no evident differences in LH, FSH, or alpha-subunit half-lives or secretory burst durations. Increased gonadotroph responsiveness may be due to diminished gonadal hormone negative feedback or primary alterations in the hypothalamo-pituitary unit with aging.

The dentin abrasivity potential of a new electric toothbrush.

PURPOSE: To evaluate the safety of the new Braun Oral-B Ultra Plaque Remover (D9) electric toothbrush, by measuring its abrasivity to dentin and comparing it with the abrasivity of a standard ADA reference toothbrush. MATERIALS AND METHODS: Dentin abrasion was measured by a radiotracer technique, using a modification of the ADA recommended methodology. A V-8 cross-brushing machine, set to make 1,500 strokes, was used for the standard reference ADA toothbrush. Because the electric toothbrush would not fit on the V-8 machine, the brushing procedure was modified so the D9 was suspended from a ring stand in a shaker bath set to give 44 strokes/minute. Both toothbrushes were tested with a slurry of 25 g of Crest dentifrice in 40 ml of water. After both toothbrushes had been tested for 8.5 minutes, samples of the slurry were put in a scintillation counter and mean net counts per minute (cpm) per gram of slurry were calculated. RESULTS: The mean relative dentin abrasion (RDA) of the Braun Oral-B Ultra Plaque Remover (D9) brush was found to be low (16) and was markedly less than that of the ADA reference brush (100).