Translation invariant (TI) cycle spinning is an effective method for removing artifacts from images. However, for a method using O(n) time, the exact TI cycle spinning by averaging all possible circulant shifts requires O(n(2)) time where n is the number of pixels, and therefore is not feasible in practice. Existing literature has investigated efficient algorithms to calculate TI version of some denoising approaches such as Haar wavelet. Multiscale methods, especially those based on likelihood decomposition, such as penalized likelihood estimator and Bayesian methods, have become popular in image processing because of their effectiveness in denoising images. As far as we know, there is no systematic investigation of the TI calculation corresponding to general multiscale approaches. In this paper, we propose a fast TI (FTI) algorithm and a more general k-TI (k-TI) algorithm allowing TI for the last k scales of the image, which are applicable to general d-dimensional images (d = 2, 3, …) with either Gaussian or Poisson noise. The proposed FTI leads to the exact TI estimation but only requires O(n log2 n) time. The proposed k-TI can achieve almost the same performance as the exact TI estimation, but requires even less time. We achieve this by exploiting the regularity present in the multiscale structure, which is justified theoretically. The proposed FTI and k-TI are generic in that they are applicable on any smoothing techniques based on the multiscale structure. We demonstrate the FTI and k-TI algorithms on some recently proposed state-of-the-art methods for both Poisson and Gaussian noised images. Both simulations and real data application confirm the appealing performance of the proposed algorithms. MATLAB toolboxes are online accessible to reproduce the results and be implemented for general multiscale denoising approaches provided by the users.

A new strain, Candida tropicalis UFMG BX 12-a, was found to produce higher yields of xylitol on poplar wood hemicellulose hydrolysate. The hemicellulose hydrolysate liquor was detoxified using a novel method we developed, involving vacuum evaporation and solvent separation of inhibitors which made the hydrolysate free of toxins while retaining high concentrations of fermentable sugars. The effect of the detoxification method on the fermentation was also reported and compared to well-known methods reported in literature. In this study, the new strain C. tropicalis UFMG BX 12-a was used on the detoxified hydrolysate to produce xylitol. It was also compared to Candida guilliermondii FTI 20037, which has been reported to be one of the best strains for fermentative production of xylitol. To further improve the efficiency of the fermentation process, these strains were immobilized in calcium alginate beads. The yield (0.92 g g-1) and productivity (0.88 g L-1 h-1) obtained by fermenting the wood hydrolysate detoxified by our new detoxification technique using an immobilized new Candida strain were found to be higher than the values reported in literature.

In order to investigate cardiac muscle behavior after inhibition of either sarcoplasmic reticulum (SR) Ca2+ release or SR Ca2+ uptake, 35 papillary muscles of adult Wistar rats were studied after a 60 minutes exposure to ryanodine 10(-7) M (n = 11) or to cyclopiazonic acid (CPA) 10(-5) M (n = 14) and compared with a control group containing the solvent alone (n = 10). We measured the maximum extent of muscle shortening of the preloaded twitch (DLp) and the normalized total force of the fully isometric twitch (FTi). The peak lengthening velocity of the preloaded twitch (VRp) and the normalized negative peak force derivative of the fully isometric twitch (-DFi) tested the lusitropic state. Intrinsic changes in the relaxation phase, independent of the contractile state, i.e., the relaxant effects, were analysed using 1) two ratios; the VRp/DLp ratio of the preloaded twitch and the -DFi/FTi ratio of the fully isometric twitch and 2) the slopes of the VR versus DL and of the -DF versus FT relationship over the whole continuum of load. Ryanodine induced a marked negative inotropic effect associated with a decrease in VRp from 2.7 +/- 0.2 to 1.4 +/- 0.2 Lmax/s (p < 0.001). The VRp/DLp ratio and the slope of the VR versus DL relationship remained unchanged, indicating that ryanodine was devoid of intrinsic relaxant effect under isotonic conditions. At a 10/min stimulation frequency, inhibition of Ca(2+)-uptake function of the SR with CPA had no inotropic effect but decreased VRp from 2.9 +/- 0.1 to 2.2 +/- 0.1 Lmax/s (p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Protein farnesyltransferase (FTase) is an important target in many research fields, more markedly so in cancer investigation since several proteins known to be involved in human cancer development are thought to serve as substrates for FTase and to require farnesylation for proper biological activity. Several FTase inhibitors (FTIs) have advanced into clinical testing. Nevertheless, despite the progress in the field several functional and mechanistic doubts on the FTase catalytic activity have persisted. This work provides some crucial information on this important enzyme by describing the application of molecular dynamics simulations using specifically designed molecular mechanical parameters for a variety of 22 CaaX peptides known to work as natural substrates or inhibitors for this enzyme. The study involves a comparative analysis of several important molecular aspects, at the mechanistic level, of the behavior of substrates and inhibitors at the dynamic level, including the behavior of the enzyme and peptides, as well as their interaction, together with the effect of the solvent. Properties evaluated include the radial distribution function of the water molecules around the catalytically important zinc metal atom and cysteine sulfur of CaaX, the conformations of the substrate and inhibitor and the corresponding RMSF values, critical hydrogen bonds, and several catalytically relevant distances. These results are discussed in light of recent experimental and computational evidence that provides new insights into the activity of this enzyme.

Background/purpose: Metabolic associated fatty liver disease (MAFLD) is the commonest cause of chronic liver disease, which is associated with obesity and diabetes. However, it also occurs in lean individuals especially in Asian populations.

Methods: The participants of Tzu Chi MAFLD cohort (TCMC) including health controls or MAFLD patients were enrolled. MAFLD was defined as fatty liver in imaging without hepatitis B virus, hepatitis C virus infection, drug, alcohol or other known causes of chronic liver disease. Lean MAFLD was defined as MAFLD in lean subjects (BMI < 23 kg/m²).

Results: A total of 880 subjects were included for final analysis. Of 394 MAFLD patients, 65 (16.5%) patients were diagnosed as lean MAFLD. Lean MAFLD patients were elder, higher percentage of female gender, lower ALT, diastolic blood pressure, triglyceride, and waist circumference but higher HDL than non-lean MAFLD patients. Using binary regression analysis, elder age and lower waist circumference were associated with lean MAFLD. Compared with lean healthy controls, lean MAFLD patients had higher BMI, waist circumference, and percentage of hypertension. In body composition, fatty tissue index (FTI), lean tissue index (LTI) ,and total body water (TBW) were lower in lean MAFLD than non-lean MAFLD patients; but they were comparable with lean healthy controls.

Conclusions: The prevalence of lean MAFLD was 16.5% in this study population and it was higher in elder age, especially of female subjects. Lean MAFLD patients had different metabolic profiles compared with lean healthy controls, but different body composition compared with non-lean MAFLD patients.

Keywords: BMI; Bioelectrical impedance analysis; Body composition; Fatty tissue index; Lean; Lean tissue index; MAFLD; Metabolic profiles; Sarcopenic obesity; Waist circumference.

UNASSIGNED

This study describes the use of lesion index (LSI) as a direct measure to assess the adequacy of ablation lesion formation with force-sensing catheters in ablation of paroxysmal atrial fibrillation (PAF). LSI is calculated by the formula:LSI = CF (g) ×Current (mA) ×Time (sec).

UNASSIGNED

Fifty consecutive patients with PAF underwent pulmonary vein (PV) isolation using a catheter dragging technique and targeting different LSI values in different anatomical areas.A force-sensing ablation catheter was used to continuously measure contact force (CF) and guide radiofrequency ablation (RF) lesion formation. Ablation lesions were delivered to achieve an LSI value of 5.0 in posterior locations, 5.5 in anterior locations and 6.0 in the regionbetween the left atrial appendage and left superiorpulmonary vein ridge. Force-time Integral (FTI) was not used to evaluate lesion formation.

UNASSIGNED

A single center, retrospective analysis was performed with 196/198 (99%) PVs acutely isolated. The mean procedure time was 134 ± 34 mins and the mean fluoroscopy time was 7.8 ± 3.2 mins. At a mean follow up of two years, 43/50 (86%) of patients were in normal sinus rhythm with no documented recurrences of atrial fibrillation.

UNASSIGNED

LSI can be used to guide the placement of durable lesion formation with RF ablation using CF catheters in patients with PAF.

Background: Ablation Index (AI), a novel lesion quality marker, includes contact force, time, and power of radiofrequency application, but not regional variation in wall thickness within the wide antral catheter ablation (WACA) circle. This study explored the relationships among AI target value, atrial wall thickness and gap formation within the WACA circle in patients with paroxysmal atrial fibrillation (PAF).

Methods: We evaluated 102 consecutive patients (mean age, 65 ± 9 years) with PAF who underwent AI-guided WACA for ipsilateral pulmonary vein isolation (PVI). Each WACA circle was subdivided into 8 segments, and overall 7143 radiofrequency applications were delivered, including 125 gaps in PVI ablation lines. For each radiofrequency tag within the ablation circle, we collected data on ablation lesion depth surrogates (time of application, delivery power, impedance drop, average contact force, force-time integral [FTI], and AI) and left atrial wall thickness measured by multi detector computer tomography scanning.

Results: The anterior and roof walls were the thickest segments of the ablation circle, in which 85.8% of gaps concentrated, while the posterior and inferior walls were the thinnest. Gap formation was significantly associated with FTI, AI, wall thickness, FTI/wall thickness and AI/wall thickness. AI/wall thickness had the highest predictive value for gap formation, with a cutoff of 195.6 au/mm for effective ablation.

Conclusions: In AI-guided PVI of PAF, AI/wall thickness by normalizing myocardial thickness variation along the WACA circle was a strong predictor of gap formation, with a target of 195.6 au/mm appearing suitable for effective ablation. This article is protected by copyright. All rights reserved.

Keywords: AI; AI/wall thickness; Gap formation; WACA; wall thickness.

BACKGROUND

Lower extremity overuse injuries are detrimental to military readiness. Extremes of arch height and heavy loads carried by military personnel are associated with increased risk for overuse injury. Little is known regarding the impact of load carriage on plantar pressure distributions during gait.

OBJECTIVE

The objective of this study was to determine how load carriage affects plantar pressure distributions during gait in individuals with varying arch types.

METHODS

A cross-sectional, repeated-measures design was used for the study.

METHODS

The study was performed at a research laboratory at Fort Sam Houston, Texas. Service members who were healthy and weighing ≥70 kg were enrolled in the study. The participants (97 men, 18 women; mean age=31.3 years, SD=5.6; mean weight=86.0 kg, SD=11.0) were categorized as having high-, normal-, or low-arched feet on the basis of published cutoff values for the arch height index. Plantar pressure measurements were obtained with the use of an in-shoe pressure measurement system while participants wore combat boots and walked on a treadmill under 3 loaded conditions (uniform, 20-kg load, and 40-kg load). Maximal force (MaxF) and force-time integral (FTI) were assessed with the use of a 9-sector mask to represent regions of the foot. A 3 × 3 repeated-measures analysis of variance was used for analysis across the levels of load and arch type.

RESULTS

A significant interaction existed between arch type and load for MaxF and FTI in the medial midfoot, with greater force in low-arched feet. In the medial forefoot, MaxF and FTI were greatest in high-arched feet across all load conditions. In the great toe region, low-arched and normally arched feet had greater MaxF and FTI. The relative distribution of FTI increased proportionately in all regions of the foot regardless of arch type for all load conditions.

CONCLUSIONS

The influence of fatigue, greater loads, and different walking speeds was not assessed.

CONCLUSIONS

Regardless of arch type, increases in load did not alter the relative distribution of force over the plantar foot during gait. Participants with high-arched feet had greater force in the medial forefoot region, whereas those with normally arched or low-arched feet had greater force in the great toe region, regardless of load. These differences in force distribution may demonstrate different strategies to generate a rigid lever during toe-off.

Background: It has been a long-standing clinical concern that haemodialysis (HD) patients on afternoon shifts (ASs) are more prone to protein-energy wasting (PEW) than those on morning shifts (MSs), as their dialysis scheme and post-dialysis symptoms may interfere with meal intake. We evaluated the effect of time of day of HD on the evolution of body composition changes and PEW surrogates.

Methods: We conducted a retrospective study among 9.963 incident HD patients treated in NephroCare centres (2011-16); data were routinely collected in the European Clinical Database. The course of multi-frequency bioimpedance determined lean and fat tissue indices (LTI and FTI) between patients in MSs/ASs over 2 years were compared with linear mixed models. Secondary PEW indicators were body mass index, albumin, creatinine index and normalized protein catabolic rate. Models included fixed (age, sex, vascular access and diabetes mellitus) and random effects (country and patient).

Results: Mean baseline LTI and FTI were comparable between MSs (LTI: 12.5 ± 2.9 kg/m2 and FTI: 13.7 ± 6.0 kg/m2) and ASs (LTI: 12.4 ± 2.9 kg/m2 and FTI: 13.2 ± 6.1 kg/m2). During follow-up, LTI decreased and FTI increased similarly, with a mean absolute change (baseline to 24 months) of -0.3 kg/m2 for LTI and +1.0 kg/m2 for FTI. The course of these malnutrition indicators did not differ between dialysis shifts (P for interaction ≥0.10). We also did not observe differences between groups for secondary PEW indicators.

Conclusions: This study suggests that a dialysis shift in the morning or in the afternoon does not impact the long-term nutritional status of HD patients. Regardless of time of day of HD, patients progressively lose muscle mass and increase body fat.

Keywords: body composition; dialysis shift; fat tissue index; lean tissue index; protein-energy wasting.

BACKGROUND

The relationship between leptin and insulin sensitivity, sexual steroids and insulin concentrations in women with polycystic ovary syndrome is still controversial. The objective of this study was to assess the relationship between insulin levels, insulin resistance parameters and serum leptin concentrations in healthy and polycystic ovary syndrome women.

METHODS

33 hyperandrogenic polycystic ovary syndrome women (GHA) and 27 healthy women (GS) were included in this study. Leptin, insulin, sex-hormone binding globulin (SHBG), testosterone and estradiol concentrations were determined in a basal sample. Body mass index, waist diameter and waist to hip ratio were recorded. Insulin sensitivity was calculated by means of insulin tolerance test and glycemia/insulinemia ratio.

RESULTS

The leptin concentration was not different between GHA and GS. Insulin levels and free testosterona index (FTI) were higher in GHA than GS (p < 0.01). The glycemia/insulinemia ratio, SHBG levels, and insulin sensitivity were lower in GHA (p < 0.01). In both groups positive correlations between leptin concentration and body mass index (p < 0.01), waist diameter (p < 0.01), insulin levels (p < 0.01) and glycemia/insulinemia ratio (p < 0.01) were observed. Only GHA showed correlation between insulin sensitivity and leptin concentration (p < 0.02). SHBG and leptin levels were not correlated.

CONCLUSIONS

The leptin concentration was not different between GHA and healthy women, although they are metabolically different. This phenomenon could be due to the fact that in hyperandrogenic women the effects of insulin resistance and hyperandrogenemia counteract each other.

BACKGROUND: The metabolic inhibitor rotenone inhibits hepatocellular proliferation and the incidence of liver cancer resulting from exposure to the PPARalpha agonist Wy-14,643, via unknown mechanisms. Since the absence of thyroid hormones diminishes hepatomegaly, an early biomarker for the hepatocarcinogenicity induced by PPARalpha agonists, this study was undertaken to investigate whether rotenone might interference with the ability of Wy-14,643 to alter the animal thyroid status. METHODS: Male B6C3F1 mice were given Wy-14,643 (100 ppm), rotenone (600 ppm) or a mixture of both, in the feed for 7 days. Bromodeoxyuridine (BrDU), marker of cell replication, was delivered through subcutaneously implanted osmotic mini-pumps. At the end of the experiment, sera were collected and corticosterone and thyroid hormone levels were measured by solid-phase radioimmunoassay kits. In addition, liver tissue samples were stained immunohistochemically for BrDU to determine percentages of labeled cells. Further, cell surface area was determined from images generated by a Zeiss Axioplan microscope equipped with a plan Neofluar x40 0.75 na objective. Tracings of individual hepatocyte perimeters were then analyzed and cell-surface areas were calculated using MicroMeasure FL-4000. RESULTS: Wy-14,643 caused a significant increase in liver weights, hepatocyte BrDU labeling index (LI), and hepatocyte surface area. In animals which received both Wy-14,643 and rotenone simultaneously, all of these effects were significantly less pronounced compared with mice that received Wy-14,643 alone. Rotenone alone decreased liver weights, LI and surface area. The Free Thyroid Index (FTI), which provides an accurate reflection of the animal's thyroid status, was 5.0 +/- 0.3 in control mice. In animals exposed to rotenone, these values decreased to 2.0 +/- 0.9, but in animals which received Wy-14,643, levels increased significantly to 7.7 +/- 0.9. FTI values decreased to 3.4 +/- 0.8 in mice receiving both rotenone and Wy-14,643. CONCLUSION: A strong correlation was observed between the animal thyroid status and both, hepatocyte proliferation (r2 = 0.62), and hepatocyte surface area (r2 = 0.83). These results support the hypothesis that the thyroid status of the animal plays a role in PPARalpha-induced hepatocellular proliferation and liver cell enlargement. Both these events are known to contribute to the expression of liver cancer in response to the activation of PPARalpha.

BACKGROUND

The use of integrating viral vectors in Gene therapy clinical trials has pointed out the problem of the deleterous effect of the integration of the ectopic gene to the cellular genome and the safety of this strategy. We proposed here a way to induce the death of gene modified cells upon request by acting on a pro-apoptotic protein cellular localization and on the activation of its apoptotic function.

RESULTS

We constructed an adenoviral vector coding a chimeric p53 protein by fusing p53 sequence with the 21 COOH term amino acids sequence of H-Ras. Indeed, the translation products of Ras genes are cytosolic proteins that become secondarily associated with membranes through a series of post-translational modifications initiated by a CAAX motif present at the C terminus of Ras proteins. The chimeric p53HRCaax protein was farnesylated efficiently in transduced human osteosarcoma p53-/- cell line. The farnesylated form of p53 resided mainly in the cytosol, where it is non-functional. Farnesyl transferase inhibitors (FTIs) specifically inhibited farnesyl isoprenoid lipid modification of proteins. Following treatment of the cells with an FTI, p53HRCaax underwent translocation into the nucleus where it retained transcription factor activity. Shifting p53 into the nucleus resulted in the induction of p21waf1/CIP1 and Bax transcription, cell growth arrest, caspase activation and apoptosis.

CONCLUSIONS

Artificial protein farnesylation impaired the transcriptional activity of p53. This could be prevented by Farnesyl transferase inhibition. These data highlight the fact that the artificial prenylation of proteins provides a novel system for controlling the function of a transactivating factor.

Results are described on the association of decreased serum total thyroxine (T4) and free thyroxine index (FTI) with antiepileptic drug therapy in a group of randomly selected chronically medicated outpatients (n = 291). For monotherapy subgroups (n = 164), the highest incidence (T4, 23.9%; FTI, 25.4%) of below normal values occurred in patients medicated with carbamazepine (CBZ), followed by phenytoin [(PHT) T4, 13.2%; FTI, 7.9%], and phenobarbital [(PB) (T4, 3.4%; FTI, 0%]. No T4 and FTI values below normal were detected in any patients (n = 30) on chronic valproic acid (VPA) monotherapy. For CBZ monotherapy (n = 67), women (n = 37) had a higher frequency of below normal values of T4 (p less than 0.05) and FTI (p less than 0.001) than men (n = 30). Therefore, the order of decreasing T4 and FTI effect was as follows: CBZ (women) greater than CBZ (men) greater than PHT greater than PB greater than VPA. For polytherapy subgroups (n = 127), the highest incidence (T4, 51.9%; FTI, 48.1%) was found in patients medicated with PHT and CBZ, followed by PHT and VPA (T4, 37.0%; FTI, 23.9%), and PHT and PB (T4, 17.2%; FTI, 10.3%). For PHT and CBZ poly-therapy (n = 52), women (n = 21) had a higher frequency of below normal values of T4 (p less than 0.05) and FTI (p less than 0.001) than men (n = 31). The magnitude of the decreasing T4 and FTI effect was greater for polytherapy subgroups (versus monotherapy subgroups) and in order as follows: PHT + CBZ (women) greater than PHT + CB (men) greater than PHT + VPA greater than PHT + PB.(ABSTRACT TRUNCATED AT 250 WORDS)

The clinical usefulness of Enzyme-linked Immunosorbent analysis (ELISA) for the assay of triiodothyronine (T3), thyroxine (T4) and T4 Uptake was studied in groups of clinically defined subjects. The following ranges of values were obtained in the normal control subjects: T3: 1.1-2.9 nmol/1; T4: 61.8-144 nmol/l; T4-Uptake: 0.7-1.34 and Free Thyroxine Index (FTI): 52.8-136. The diagnostic sensitivity of the technique was found to be reasonably good: showing good discrimination between hypothyroid, hyperthyroid and euthyroid subjects. Free thyroxine Index provided the best consistent correlation with the clinical states of the subjects particularly in subjects with altered binding protein levels. Several advantages offered by ELISA technique over radiochemical methods such as freedom from radiation hazards, non-requirement of specialized laboratories with expensive equipment and cheaper reagents with relatively longer shelf lives, make this procedure particularly suitable for use in small laboratories.

OBJECTIVE

We aimed to determine the total body water (TBW) by means of bioimpedance analysis (BIA) and to analyze the association of TBW, graft function, and arterial stiffness by means of pulse-wave velocity (PWV) and echocardiographic measurements in renal transplant (RT) recipients.

METHODS

Eighty-two RT recipients (mean age, 38.7 ± 11.5 y; 58 male) who were using ≥1 antihypertensive treatment were enrolled in the study. Biochemical parameters, 24-hour urinary protein loss, estimated glomerular filtration rate (eGFR), transthoracic echocardiography, bioimpedance analysis according to systolic blood pressure, TBW, lean tissue index (LTI), extracellular water (ECW), intracellular water (ICW), lean tissue mass (LTM), phase angle (Phi50) levels, and renal resistive index (RRI) were evaluated.

RESULTS

TBW and ECW were significantly correlated with systolic blood pressure. Urinary protein loss, pulmonary artery pressure, frequency of overhydration, systolic blood pressure, TBW, LTI, ECW, ICW, LTM, and Phi50 values were significantly higher in patients with estimated glomerular filtration rate (eGFR) 15-49 mL/min but similar in patients with eGFR 50-70 mL/min.

CONCLUSIONS

Hypertensive RT recipients have increased TBW, LTI, ICW, FTI, LTM, and Phi50 values. Graft function is positively correlated with systolic blood pressure and BIA parameters. Therefore, hypertensive RT recipients should be closely followed with the use of BIA for an early diagnosis of loss of graft function.

Of 5008 patients with normal serum thyroxine concentrations (T4 = 4.8-12.2 micrograms/dl) assayed by our laboratory during an 11-mo period, only 41 (0.82%) had an abnormal free thyroxine index (FTI). Narrowing the T4 normal range by 0.5 microgram/dl at both ends to create a discriminatory range of 5.3-11.7 microgram/dl reduced this number to 13 (0.26%). Evaluation of the medical records for 11 of these 13 patients revealed his histories of estrogen and thyroid-hormone administration, individually or in combination, which may have contributed to their divergence form the population. A program for these selective performance of serum Tc uptake (T3U and FTI determinations only on those sera wtih T4 concentrations outside of a discriminatory range is described and evaluated. This initial discrimination is the first step in practical system for selective performance of additional in vitro thyroid function assays to derive maximum diagnostic information from a single patient sample. In our institution of program described is easily adapted to computerization and has resulted in a substantial reduction of reagent costs while providing more efficient utilization of laboratory personnel.

The purpose of this study is to investigate the association of hypothalamic-pituitary axis abnormalities with the free thyroxine index (FTI) in critically ill patients. Fourteen critically ill patients and twenty healthy volunteers were studied using combined anterior pituitary gland testing with CRF, GHRH, TRH, and GnRH. The subjects were grouped as follows: I-healthy volunteers; II-sick/normal FTI; and III-sick/low FTI. Serial measurements of hormones were performed over a two-hour interval and the following parameters were measured: baseline level, response amplitude and time to maximal response. Response velocities and area-under-the-curves (integrated responses) were also computed. Group III had a longer mean ICU duration prior to testing than group II. Urinary cortisol, serum cortisol and serum PRL levels were elevated in groups II and III. However, group III had lower baseline ACTH levels, slower ACTH and TSH response velocities and decreased PRL integrated responses. Cortisol response parameters were similar between groups II and III. There were no differences in LH, FSH or GH response velocities or integrated responses among the 3 groups. These data confirm that critically ill patients develop hyperprolactinemia and hypothalamic-pituitary-adrenal axis activation but when a low FTI exists, a plurality of changes occur reflected by attenuated PRL, TSH and ACTH responses despite unaffected adrenal cortisol output.

OBJECTIVE

The prevalence of abnormal in-vitro thyroid function tests in psychiatric in-patients may be as high as 24%. Thus far, however, there is only limited data addressing the underlying causes of these abnormal test results, i.e. how often they can be attributed to genuine thyroid disease.

METHODS

We conducted an observational study of all in-patients admitted to our institution during 1 calendar year running analyses of total thyroxin (T4), free thyroxin index (FTI) and thyroid-stimulating hormone (TSH). Patients with abnormal test results were classified according to an algorithm which had been established previously.

RESULTS

In 243 of 880 patients with in-vitro thyroid function analysis, at least one concentration of either T4, FTI or TSH was found to be outside the reference range. Work-up according to the algorithm was completed in 848 patients; alterations were classified as representing thyroid dysfunction in 100 (41% of patients with abnormal test results), non-specific findings in 92 (38%), influence of ingested drugs in 18 (7%) and of severe physical disease in 1 (0.4%). As measures of T4 and/or FTI provided no essential information in 854 patients (97% of tested), we found that in most cases the determination of TSH alone was sufficient for demonstrating normal thyroid function.

CONCLUSIONS

In 27.6% of newly admitted patients living in an iodine-deficient area, at least one abnormal result in either T4, FTI or TSH values was found. Genuine thyroid disease was found in slightly less than half the patients with an abnormal value.

CD-1 mice were exposed in utero to one of 14 treatment regimes, several of them being replicated, with close agreement between series. Prenatal exposure to a teratogenic dose at a sensitive time enabled detection of 10 of 14 teratogen regimes by alterations in frequency or severity of a substantial number of the 88 variants in the Skeletal Variant Assay System (SVAS) screen when examined at 60-65 days post natal (DPN). These included 2,4,5-T (245T), Trifluralin (TFL), Maneb (MNB), Decamethrin (DMT), Acetazolamide (ACZM) either at 8 days post-coitus (DPC) or days 9-11 PC, trypan blue (TB), or 5' Bromodeoxyuridine (BUDR) on either 7 DPC, 8 DPC, or 9 DPC. Most of these observations have been reported elsewhere. All of the treatment regimes mentioned above, and another group of treatments, could be detected in the exposed CD-1 cohorts when additional endpoints were employed. One such endpoint was "frequently responding variants." These were: Interfrontals (IF), Parted Frontals (PF), Preoptic Sutures (PS), Foramina Transversaria Imperfecta of the first cervical (C) vertebra (FTI C1), FTI of the axis (C2), Accessory (Acc) Transverse Foramina (TF) of C3-C6, malformations of C3-C7, Fourteen (14) Ribs, Carpal Fusions (Fus), Lumbar Fus, 27-Presacral Vertebrae (PSV), and Sacral Fus. This endpoint revealed significant differences in the initial group of 10, plus Captan (CAPT) and Phenytoin (DPH). Yet another useful endpoint reported here was the existence of high magnitude effects (i.e., dramatic alterations in frequency of occurrence of a variant). These included IF in TB and ACZM; PF in ACZM; PS in BUDR; FTI-C1 in TB and 245T; FTI-C2 in 245T; 14 Ribs in ACZM, BUDR, and TFL; Carpal Fus in TB; 27-PSV in ACZM; Fewer than (<) 30 Caudal Vertebrae (Vert) in 245T, TFL; Caudal Fus in TB, ACZM-D9. Eight treatment regimes in all could be detected by the existence of 3 or more high magnitude effects (245T, MNB, TB, ACZM8, ACZM9-11, phenytoin, and possibly BUDR on days 7 or 8, each seen in one of two series only). Clusters of related variants were affected in 9 of the 14 groups: Frontal (F) bones and C Vert in 245T; F bones in ACZM-D8; Fus in Posterior Vert Column in ACZM-D9-11; C Vert and Fus in Vert and articular skeleton in TB; Thoracic (Th) Vert and rib-cage effects in BUDR.(ABSTRACT TRUNCATED AT 400 WORDS)

OBJECTIVE

To report an association between two autoimmune conditions, Graves' disease and stiff-person (stiff-man) syndrome, and discuss the relevant literature.

METHODS

We present a case of a 52-year-old white woman with stiff-person syndrome who also had Graves' disease, discuss her management, and review the related literature. Pertinent published reports from 1950 through 2004 were researched with use of MEDLINE and PubMed, and cross-references to other articles were reviewed.

RESULTS

A 52-year-old white woman presented with symptoms of hyperthyroidism due to Graves' disease. Laboratory data were as follows: thyrotropin <0.005 m IU/mL, thyroxine 11.1 microg/dL, free thyroxine index (FTI) 10.7, and triiodothyronine 170 ng/dL. Thyroid-stimulating immunoglobulins (TSI) and thyrotropin-binding inhibitory immunoglobulins (TBII) were positive at 1,986% and 82.5 U/L, respectively. The hyperthyroidism was treated with propranolol. She had a long-standing history of musculoskeletal complaints and was ultimately diagnosed with stiff-person syndrome. During her thyroid evaluation, she had severe neurologic deterioration that necessitated hospitalization and treatment with clonazepam, baclofen, intravenous immunoglobulin, and subsequently prednisone and azathioprine for appreciable symptomatic relief. The aggressive immunosuppression had a profound effect on her symptoms of hyperthyroidism, results of thyroid function tests, and thyrotropin receptor antibodies (TRABs). Thyrotropin was 0.52 microIU/mL, thyroxine was 6.9 microg/dL, and FTI was 5.7. The TSI decreased from 1,986% to 248%, and her TBII normalized from 82.5 U/L to <5 U/L. She was clinically and biochemically euthyroid at last follow-up in May 2004.

CONCLUSIONS

This case illustrates the association between TRAB-positive Graves' disease and stiff-person syndrome and the improvement of Graves' disease with immunosuppressive therapy.

OBJECTIVE

To investigate the status of male reproductive health among middle-aged and older men in the urban area of Nanjing.

METHODS

We collected the laboratory results of 884 middle-aged and older men aged 55 - 89 years from the Xuanwu District of Nanjing present for routine physical examinations, including those of blood routine tests, liver and kidney function, blood glucose, blood lipid, and total prostate specific antigen (TPSA), as well as such reproductive hormone indexes as total serum testosterone (TT), free serum testosterone (fT), and sex hormone binding globulin (SHBG). We also obtained the above reproductive hormone indexes from 119 young and middle-aged men aged 20 - 39 years as controls.

RESULTS

Aging-related changes were found in the 50 percentiles of all the reproductive hormones and relevant parameters but those of TT and E2, with gradual increases in LH, FSH and SHBG and decreases in fT, TSI and fTI. Comparison of reproductive hormones and relevant parameters by Mann-Whitney U test did not show any statistically significant differences in the TT level between any two of the five age groups (20 - 39, 55 - 59, 60 - 69, 70 - 79, and>> or = 80 yr) (P>> 0.05) except between the control and>> or = 80 yr groups and the 60 - 69 and>> or = 80 yr groups (P < 0.05), nor in the E2 level between any two groups, nor in the levels of LH and FSH except between the 55 - 59 and 60 - 69 yr groups and the 70 - 79 and>> or = 80 yr groups, and nor in the levels of fT and TSI except between the 55 - 59 and 60 - 69 yr groups. However, there were significant differences in the levels of SHBG and fTI between any two age groups. Spearman correlation analysis revealed that fT, TSI, and fTI were correlated negatively with aging and LH (P < 0.05, I r I>> 0.5) but weakly positively with cholesterol, blood glucose and hemoglobin (P < 0.05, /r/ < 0.5), SHBG and LH positively with aging, SHBG weakly negatively with blood glucose and hemoglobin, LH weakly negatively with hemoglobin, and TT weakly negatively with aging but positively with hemoglobin.

CONCLUSIONS

The levels of serum testosterone, particularly that of fT, declined with aging in middle-aged and older men in the urban area of Nanjing, which may contribute to abnormal lipid metabolism, low hemoglobin and high blood glucose.

Serum thyroxine-binding globulin (TBG) was measured by using a radioimmunoassay method. The within-batch coefficient of variation (CV) of the assay was 5% or less at different TBG concentrations with a between-batch variation of less than 10%. The mean TBG concentration in hypothyroidism (28.5 +/- 6.7 mg/l) was significantly higher, and that in hyperthyroidism (22.3 +/- 3.5 mg/l) was significantly lower, than the euthyroid mean (25.4 +/- 6.9 mg/l). Acutely ill patients suffering from various non-thyroidal illnesses were found to have significantly low mean TBG (13.8 +/- 4.3 mg/l). A group of women in late pregnancy had a higher mean value, as expected. Serum TBG level, however, was ineffective as a thyroid function test because of overlapping concentrations between groups. The derived index T4:TBG ratio was found to be superior to free thyroxine index (FTI) in many cases of acutely ill patients, pregnancy, and hereditary TBG abnormality. The 95% confidence limit for the ratio in euthyroids was 2.3 to 7.1. Serum TBG level with T4:TBG ratio is recommended as a replacement for the T3-uptake test and FTI.