An improved dynamic model of tuning fork probe for scanning probe microscopy.

This paper presents a two coupled oscillators model to describe the dynamics of a tuning fork with a probe attached. The two coupled oscillators are unbalanced only in their effective masses and the damping ratios. By applying a frequency domain system identification approach in experimental investigation of various probe attachment cases, a good accuracy of the model is demonstrated. The effectiveness of the model is further demonstrated in quantitative analysis of the noise performance and the sensitivity of force sensing with a tuning fork probe. Compared with existing models, the proposed model can more accurately characterize the dynamics of a tuning fork probe.

Dynamics of the pituitary-adrenal ensemble in hypocretin-deficient narcoleptic humans: blunted basal adrenocorticotropin release and evidence for normal time-keeping by the master pacemaker.

Narcolepsy is a sleep disorder caused by disruption of hypocretin (orexin) neurotransmission. It has been suggested that anomalous timing by the biological clock contributes to the symptomatology. Hypocretins stimulate the pituitary-adrenal (PA) axis in rodents. We explored whether hypocretin deficiency disrupts circadian timing and blunts PA hormone release. We deconvolved 24-h plasma profiles of ACTH and cortisol, and determined their circadian rhythm by cosinor analysis in seven hypocretin-deficient narcoleptic males and seven matched controls. Basal and total ACTH production were blunted in narcoleptics [310 +/- 86 vs. 760 +/-160 ng/liter.24 h (P = 0.02) and 920 +/- 147 vs. 1460 +/- 220 ng/liter.24 h (P = 0.04), respectively], whereas pulsatile release did not differ between groups. In contrast, basal, pulsatile and total cortisol secretion were similar in both groups. The cross-approximate entropy of the joint ACTH/cortisol time series was higher in narcoleptics (1.26 +/- 0.07 vs. 1.07 +/- 0.04; P = 0.04), reflecting reduced secretory process regularity. The acrophases of both ACTH and cortisol occurred at similar clock times (approximately 0830 h) in patients and controls, which supports the idea that the master pacemaker is intact in narcolepsy. The reduced (basal) ACTH secretion and the diminished secretory process regularity of the ACTH/cortisol ensemble conjointly suggest that hypocretin deficiency induces changes in the interplay between PA hormones.

Reduction of plasma leptin levels and loss of its circadian rhythmicity in hypocretin (orexin)-deficient narcoleptic humans.

Recent observations have implicated hypocretin deficiency in the pathogenesis of narcolepsy. Hypocretin neurotransmission also affects energy balance, and narcoleptic patients tend to become obese. Because hypocretins appear to have important neuroendocrine effects, we hypothesized that the neuroendocrine systems that regulate energy balance might be distinctly set in narcolepsy. As leptin is a pivotal part of these systems, we explored the 24-h plasma leptin (20-min sampling interval) concentration profile in six narcoleptic males and six normal controls, matched for age, sex, body mass index, waist/hip ratio, and fat mass. We thus demonstrated a reduction of the mean 24-h leptin concentration in narcoleptics to 52% of that in controls (5.9 microg/liter in narcolepsy vs. 11.4 microg/liter in controls; P < 0.05). Further, a nocturnal acrophase (clock time of the highest concentration), which is typical of normal leptin secretion, was observed in controls (mean, 2335 h; 95% confidence interval, 2105-0205 h), but not in narcoleptic patients. The mechanisms that potentially disturb the circadian rhythm of leptin levels in hypocretin-deficient narcoleptic humans include anomalies of the sleep-wake cycle and/or disruption of the circadian distribution of autonomic activity. As leptin deficiency clearly leads to morbid obesity in experimental animals and humans, we infer that the observed reduction of plasma leptin levels may predispose narcoleptic humans to weight gain.

Clinical outcome after standardized versus dosimetric radioiodine treatment of hyperthyroidism: an equivalence study.

The aim of this study was to investigate the equivalence in outcome of standardized versus uptake-adjusted dosing of radioactive iodine (131I) for hyperthyroidism. We performed a 1-year follow-up study of two patient cohorts: 326 patients referred for 131I treatment of hyperthyroidism in Graves' disease (GD; n=216) or toxic multinodular goitre (TMG; n=110) in the period June 1995 to January 1998. Of these patients 128 were treated according to a standardized regimen, based on palpated thyroid volume and diagnosis, and 198 with a 131I uptake-adjusted dosimetric method. The incidence of hypothyroidism, euthyroidism or recurrence of disease was recorded. In Graves' disease hypothyroid outcome in the standardized versus adjusted method was 40.7% vs 44.6% (95% CI difference, -17.4 to +9.5%); it was 67.4% vs 70.8% (95% CI difference -15.9 to +9.3%) for all non-euthyroid outcomes. In TMG, due to wide confidence interval ranges a conclusion of equivalence could be made only for recurrence of hyperthyroidism (mean -3.2%, 95% CI, -13.8 to +7.5%). A simplified dosage method for 131I treatment of hyperthyroidism, which omits 131I uptake adjustment, may improve procedure efficiency and patient convenience, and leads to an equivalent outcome in GD and probable equivalent outcome in TMG.

The spectrum of chronic mature T-cell disorders: a report of four cases.

We describe four patients with a mature T-cell disorder. These four specific entities belong to a group formerly called "T-cell chronic lymphocytic leukaemia" (T-CLL). Nowadays we understand that these chronic T-cell lymphoproliferative disorders consist of four different entities. They stand out as well-described and separate disorders on the basis of their clinical, immunophenotypic and cytogenetic properties. Unfortunately, the majority of patients have a bad response to chemotherapy. The purine analogs may offer a better prognosis for some patients.

Pulsatile LH release is diminished, whereas FSH secretion is normal, in hypocretin-deficient narcoleptic men.

Hypocretin (orexin) peptides are involved in the regulation of energy balance and pituitary hormone release. Narcolepsy is a sleep disorder characterized by disruption of hypocretin neurotransmission. Pituitary LH secretion is diminished in hypocretin-deficient animal models, and intracerebroventricular administration of hypocretin-1 activates the hypothalamo-pituitary-gonadal axis in rats. We evaluated whether hypocretin deficiency affects gonadotropin release in humans. To this end, we deconvolved 24-h serum concentrations of LH and FSH in seven hypocretin-deficient narcoleptic males (N) and seven controls (C) matched for age, body mass index, and sex. Basal plasma concentrations of testosterone, estradiol, and sex hormone-binding globulin were similar in both groups. Mean 24-h LH concentration was significantly lower in narcolepsy patients [3.0 +/- 0.4 (N) vs. 4.2 +/- 0.3 (C) U/l, P = 0.01], which was primarily due to a reduction of pulsatile LH secretion [23.5 +/- 1.6 (N) vs. 34.3 +/- 4.9 (C) U.l(-1).24 h(-1), P = 0.02]. The orderliness of LH and FSH secretion, quantitated by the approximate entropy statistic, was greater in patients than in controls. In contrast, all other features of FSH release were similar in narcoleptic and control groups. Also, LH and FSH secretions in response to intravenous administration of 100 microg of GnRH were similar in patients and controls. These data indicate that endogenous hypocretins are involved in the regulation of the hypothalamo-pituitary-gonadal axis activity in humans. In particular, reduced LH release in the face of normal pituitary responsivity to GnRH stimulation in narcoleptic men suggests that hypocretins promote endogenous GnRH secretion.

Myocardial creatine kinase-MB concentration in normal and explanted human hearts and released from hearts of patients with acute myocardial infarction.

Using an enzyme immunoassay of creatine kinase (CK)-MB concentration commercially available for diagnosis of acute myocardial infarction (AMI), we studied CK-MB concentrations in myocardium of subjects who died from noncardiac causes and in cardiac explants of patients with either coronary heart disease or cardiomyopathy who underwent cardiac transplantation. Secondly, CK-MB concentrations were measured in serial plasma samples of 93 patients with AMI. By calculation of cumulatively released amounts of CK-MB and cumulatively released activities of CK, aspartate aminotransferase (AST) and alpha-hydroxybutyrate dehydrogenase (HBDH), we obtained values of the proportions in which these quantities were released from the myocardium. Taking a myocardial HBDH activity of 152 U/g as a reference value, the released activities of CK and AST, and the released mass of CK-MB per gram of myocardium were calculated. These values were compared to the corresponding quantities in myocardium of normal hearts and in explanted myocardium. Normal hearts differ from explanted myocardium and from "infarcted" hearts with respect to CK-MB concentration, but not with respect to CK, AST and HBDH activities. The wide range of CK-MB concentrations in normal hearts (1-515 micrograms/g) suggests variable expression of the CK-MB gene. The presence of CK-MB is not confined to cardiac tissue. CK-MB concentration in 12 samples of human skeletal muscle equalled 27 +/- 1 micrograms/g (2.1 +/- 0.5% of total CK activity). In conclusion, the mean concentration of CK-MB in normal hearts is low (139 micrograms/g) with a high variation coefficient (127%), but is high (369 micrograms/g) with a small variation coefficient (31%) in explanted hearts.(ABSTRACT TRUNCATED AT 250 WORDS)