Long waiting time before tooth extraction may increase delayed wound healing in elderly Japanese.

In osteoporosis patients receiving antiresorptive medications, stopping the drug and delaying tooth extraction has been suggested to reduce the risk of osteonecrosis of the jaw (ONJ). However, postponing tooth extraction for ≥ 2 months was associated with an increased risk of delayed wound healing beyond 8 weeks after extraction, a risk factor for developing ONJ. INTRODUCTION: A long waiting time before tooth extraction could result from concern about a potential increased risk of osteonecrosis of the jaw (ONJ) in osteoporosis patients. We clarified whether a long waiting time before tooth extraction during the past year may be associated with an increased risk of delayed wound healing beyond 8 weeks after tooth extraction, which may be a risk factor of ONJ. METHODS: Of 5639 patients aged ≥ 60 years who visited our 20 clinics or hospitals and answered a structured questionnaire, 426 patients (151 men, 275 women) aged 60-96 years comprised the final participants in this study. Self-reported kyphosis was used as a surrogate marker of vertebral fractures. Stepwise logistic regression analysis, adjusted for covariates, was used to calculate the odds ratio (OR) and the 95% confidence interval (CI) for the presence of delayed wound healing longer than 8 weeks after tooth extraction during the past year based on the duration before extraction. RESULTS: Subjects who had waited > 2 months for tooth extraction had a significantly higher risk of delayed wound healing compared with those whose tooth was extracted within 1 month (OR = 7.23; 95% CI = 2.19-23.85, p = 0.001) regardless if antiresorptive medications for osteoporosis were used. The presence of self-reported kyphosis was significantly associated with an increased risk of delayed wound healing (OR = 5.08; 95% CI = 1.11-23.32, p = 0.036). CONCLUSIONS: A long waiting time before tooth extraction may be a risk factor for delayed wound healing beyond 8 weeks after extraction in patients aged ≥ 60 years.

Acquired Downregulation of Donor-Specific Antibody Production After ABO-Incompatible Kidney Transplantation.

The mechanism of long-term B cell immunity against donor blood group antigens in recipients who undergo ABO-incompatible (ABOi) living-donor kidney transplantation (LKTx) is unknown. To address this question, we evaluated serial anti-A and anti-B antibody titers in 50 adult recipients. Donor-specific antibody titers remained low (≤1:4) in 42 recipients (84%). However, antibodies against nondonor blood group antigens were continuously produced in recipients with blood type O. We stimulated recipients' peripheral blood mononuclear cells in vitro to investigate whether B cells produced antibodies against donor blood group antigens in the absence of graft adsorption in vivo. Antibodies in cell culture supernatant were measured using specific enzyme-linked immunosorbent assays (ELISAs). Thirty-five healthy volunteers and 57 recipients who underwent ABO-compatible LKTx served as controls. Antibody production in vitro against donor blood group antigens by cells from ABOi LKTx patients was lower than in the control groups. Immunoglobulin deposits were undetectable in biopsies of grafts of eight recipients with low antibody titers (≤1:4) after ABOi LKTx. One patient with blood type A1 who received a second ABOi LKTx from a type B donor did not produce B-specific antibodies. These findings suggest diminished donor-specific antibody production function in the setting of adult ABOi LKTx.

Significant improvement of bone mineral density and bone turnover markers by denosumab therapy in bisphosphonate-unresponsive patients.

Bone mineral density (BMD) sometimes cannot be improved by long-term bisphosphonate (BP) therapy in osteoporosis (OP). This study showed that lumbar as well as hip BMD significantly increased after denosumab treatment in patients not responsive to BPs. Thus, denosumab may be a strong OP treatment option for BP-unresponsive patients. INTRODUCTION: BMD sometimes cannot be improved by long-term BP therapy. METHODS: We administered denosumab to osteoporotic patients with a poor response to BPs who had been taking them for 2 years or longer. Ninety-eight women with BP-poor responsive OP were enrolled in this study. Mean (standard deviation [SD]) age was 71.2 (6.9) years and mean (SD) duration of BP treatment was 59.9 (34.3) months. We distinguished BP responders from non-responders based on changes in BMD values at denosumab commencement (baseline) from 2 years beforehand. RESULTS: There were no significant differences in age, duration of BP use, bone turnover markers, or BMD at baseline between the groups. Prior to denosumab, BMD had increased significantly in responders and decreased significantly in non-responders. Bone turnover markers had decreased significantly at 4 months of denosumab treatment (P < 0.001) and lumbar and hip BMD were significantly increased at 1 year of therapy in both groups (P < 0.001). Simple correlation coefficients were -0.337 for lumbar and -0.339 for hip BMD changes (both P = 0.001) before and after denosumab treatment. Both at the lumbar spine and hips, decreased BMD before denosumab therapy was significantly associated with an increase in BMD at 1 year of treatment (spine, t value = -3.502, P = 0.001, R = 0.113; hip, t value = -3.526, P = 0.001, R = 0.115). CONCLUSIONS: These results suggest that denosumab may be a strong OP treatment option for BP-unresponsive patients.

Establishment of transgenic silkworms expressing GAL4 specifically in the haemocyte oenocytoid cells.

Insect haemocytes play significant roles in innate immunity. The silkworm, a lepidopteran species, is often selected as the model for studies into the functions of haemocytes in immunity; however, our understanding of the role of haemocytes remains limited because the lack of haemocyte promoters for transgene expression makes genetic manipulations difficult. In the present study, we aimed to establish transgenic silkworm strains expressing GAL4 in their haemocytes. First, we identified three genes with strong expression in haemocytes, namely, lp44, Haemocyte Protease 1 (HP1) and hemocytin. Transgenic silkworms expressing GAL4 under the control of the putative promoters of these genes were then established and expression was examined. Although GAL4 expression was not detected in haemocytes of HP1-GAL4 or hemocytin-GAL4 strains, lp44-GAL4 exhibited a high level of GAL4 expression, particularly in oenocytoids. GAL4 expression was also detected in the midgut but in no other tissues, indicating that GAL4 expression in this strain is mostly oenocytoid-specific. Thus, we have identified a promoter that enables oenocytoid expression of genes of interest. Additionally, the lp44-GAL4 strain could also be used for other types of research, such as the functional analysis of genes in oenocytoids, which would facilitate advances in our understanding of insect immunity.

Increased visceral adiposity is associated with coronary artery calcification in male patients with chronic kidney disease.

BACKGROUND/OBJECTIVE: Recent epidemiological data have shown that abdominal fat accumulation is associated with increased risk of cardiovascular events in patients with chronic kidney disease (CKD). This study aimed to investigate the association between visceral adiposity and coronary artery calcification (CAC) in CKD patients. SUBJECTS/METHODS: Cross-sectional study with 65 nondialyzed CKD male patients (59 ± 9 years, CKD stages 3 and 4). Abdominal fat compartments were assessed by computed tomography (CT) at L4-L5 level. Visceral to subcutaneous (V/S) fat ratio was calculated. Visceral obesity was defined as a V/S fat ratio greater than the median value of the sample study (>0.55). CAC was detected by multi-slice CT. CAC scores were calculated with the Agatston method. RESULTS: CAC was present (calcium score >10 AU) in 66% of patients. In the group with visceral obesity, the CAC score was significantly higher. This group had lower adiponectin and higher leptin levels compared to patients without visceral obesity. In the whole sample, higher V/S fat ratio was associated with CAC score, independently of age, body mass index, diabetes, ionized calcium, smoking or renal function. CONCLUSION: Our results show an association between visceral obesity and CAC in CKD patients, suggesting a deleterious effect of visceral fat in these patients. Increased visceral adiposity might enhance cardiovascular risk in this particular population.

Visceral obesity assessed by computed tomography predicts cardiovascular events in chronic kidney disease patients.

BACKGROUND AND AIM: Cardiovascular disease is the leading cause of death among patients with chronic kidney disease (CKD). Although there is emerging evidence that excess visceral fat is associated with a cluster of cardiometabolic abnormalities in these patients, the impact of visceral obesity evaluated by a gold-standard method on future outcomes has not been studied. We aimed to investigate whether visceral obesity assessed by computed tomography was able to predict cardiovascular events in CKD patients. METHODS AND RESULTS: We studied 113 nondialyzed CKD patients [60% men; 31% diabetics; age 55.3 ± 11.3 years; body mass index (BMI) 27.2 ± 5.3 kg/m(2); estimated glomerular filtration rate (GFR) 33.7 ± 13.6 ml/min/1.73 m(2)]. Visceral and subcutaneous abdominal fat were assessed by computed tomography at L4-L5. Visceral to subcutaneous fat ratio >0.55 (highest tertile cut-off) was defined as visceral obesity. Cardiovascular events including acute myocardial infarction, angina, arrhythmia, uncontrolled blood pressure, stroke and cardiac failure were recorded during 24 months. Cardiovascular events were 3-fold higher in patients with visceral obesity than in those without visceral obesity. The Kaplan-Meier analysis indicated that patients with visceral obesity had shorter cardiovascular event-free time than those without visceral obesity (P = 0.021). In the univariate Cox analysis, visceral obesity was associated with higher risk of cardiovascular events (hazard ratio = 3.4; 95% confidence interval = 1.1-10.5; P = 0.03). The prognostic power of visceral obesity for cardiovascular events remained significant after adjustments for sex, age, diabetes, previous cardiovascular disease, smoking, sedentary lifestyle, BMI, GFR, hypertension, dyslipidemia and inflammation. CONCLUSION: Visceral obesity assessed by computed tomography was a predictor of cardiovascular events in CKD patients.

Five-body cluster structure of the double-Λ hypernucleus (ΛΛ)(11)Be.

Energy levels of the double Λ hypernucleus (ΛΛ)(11)Be are calculated within the framework of a ααnΛΛ five-body model. Interactions between constituent particles are determined so as to reproduce reasonably the observed low-energy properties of the αα, ααn nuclei and the existing data for Λ-binding energies of the αΛ, ααΛ, αnΛ, and ααnΛ systems. An effective ΛΛ interaction is constructed so as to reproduce, within the αΛΛ three-body model, the B(ΛΛ) of (ΛΛ)(6)He, which was extracted from the emulsion experiment, the NAGARA event. With no adjustable parameters for the ααnΛΛ system, B(ΛΛ) of the ground and bound excited states of (ΛΛ)(11)Be are calculated with the Gaussian expansion method. The Hida event, recently observed at KEK-E373 experiment, is interpreted as an observation of the ground state of the (ΛΛ)(11)Be.

Carpal tunnel pressure measurement during two-portal endoscopic carpal tunnel release.

BACKGROUND: Although there remain concerns of median nerve damage during endoscopic carpal tunnel release for carpal tunnel syndrome, carpal tunnel pressure variations during Chow's two-portal technique have not been well investigated. METHODS: We performed a modified two-portal endoscopic carpal tunnel release on 30 patients by inserting a catheter pressure transducer into the carpal tunnel for continuous pressure measurement during the procedure. Grip and pinch strengths, Semmes-Weinstein monofilament test, and nerve conduction studies were examined preoperatively and at postoperative 1, 3, and 6 months. Numbness and the Disabilities of the Arm, Shoulder and Hand score were also evaluated pre and postoperatively. FINDINGS: Subjective symptoms and nerve conduction study findings improved uneventfully. The pressure was always observed to be maximum pressure immediately before the cannula was withdrawn from the exit portal, and carpal tunnel pressure >300 mm Hg was recorded in most of the patients. INTERPRETATION: A transient increase in the carpal tunnel pressure occurred in all the patients; however, it did not correlate with their clinical outcome or with increased risk of peri-operative complications. Since time-pressure threshold of the median nerve during endoscopic carpal tunnel release is still unknown, our results did not guarantee its safety.

Nutritional status and body composition after 6 months of patients switching from continuous ambulatorial peritoneal dialysis to automated peritoneal dialysis

Our objective was to determine if automated peritoneal dialysis (APD) leads to changes in nutritional parameters of patients treated by continuous ambulatory peritoneal dialysis (CAPD). Twenty-six patients (15 males; 50.5 ± 14.3 years) were evaluated during CAPD while training for APD and after 3 and 6 months of APD. Body fat was assessed by the sum of skinfold thickness and the other body compartments were assessed by bioelectrical impedance. During the 6-month follow-up, 12 patients gained more than 1 kg (GW group), 8 patients lost more than 1 kg (LW group), and 6 patients maintained body weight (MW group). Except for length on dialysis that was longer for the LW group compared with the GW group, no other differences were found between the groups at baseline. After 6 months on APD, the LW group had a reduction in body fat (24.5 ± 7.7 vs 22.1 ± 7.3 kg; P = 0.01), body cell mass (22.6 ± 6.2 vs 21.6 ± 5.8 kg, P = 0.02) and phase angle (5.4 ± 0.9 vs 5.1 ± 0.8 degrees, P = 0.004). In the GW group, body fat (25 ± 7.6 vs 27.2 ± 7.6 kg, P = 0.001) and body cell mass (20.1 ± 3.9 vs 20.8 ± 4.0 kg, P = 0.05) were increased. In the present study, different patterns of change in body composition were found. The length of previous dialysis treatment seems to be the most important factor in determining these nutritional modifications.

Nutritional status and body composition after 6 months of patients switching from continuous ambulatorial peritoneal dialysis to automated peritoneal dialysis.

Our objective was to determine if automated peritoneal dialysis (APD) leads to changes in nutritional parameters of patients treated by continuous ambulatory peritoneal dialysis (CAPD). Twenty-six patients (15 males; 50.5 +/- 14.3 years) were evaluated during CAPD while training for APD and after 3 and 6 months of APD. Body fat was assessed by the sum of skinfold thickness and the other body compartments were assessed by bioelectrical impedance. During the 6-month follow-up, 12 patients gained more than 1 kg (GW group), 8 patients lost more than 1 kg (LW group), and 6 patients maintained body weight (MW group). Except for length on dialysis that was longer for the LW group compared with the GW group, no other differences were found between the groups at baseline. After 6 months on APD, the LW group had a reduction in body fat (24.5 +/- 7.7 vs 22.1 +/- 7.3 kg; P = 0.01), body cell mass (22.6 +/- 6.2 vs 21.6 +/- 5.8 kg, P = 0.02) and phase angle (5.4 +/- 0.9 vs 5.1 +/- 0.8 degrees, P = 0.004). In the GW group, body fat (25 +/- 7.6 vs 27.2 +/- 7.6 kg, P = 0.001) and body cell mass (20.1 +/- 3.9 vs 20.8 +/- 4.0 kg, P = 0.05) were increased. In the present study, different patterns of change in body composition were found. The length of previous dialysis treatment seems to be the most important factor in determining these nutritional modifications.

Intraflagellar transport complex in Leishmania spp. In silico genome-wide screening and annotation of gene function.

Flagella are constructed and maintained through the highly conserved process of intraflagellar transport (IFT), which is a rapid movement of particles along the axonemal microtubules of cilia/flagella. Particles that are transported by IFT are composed of several protein subunits comprising two complexes (A and B), which are conserved among green algae, nematodes, and vertebrates. To determine whether or not homologues to members of the IFT complex proteins are conserved in Leishmania spp, we scanned genomes, transcriptomes and proteomes of Leishmania species in a search for putative IFT factors, which were then identified in silico, compared, cataloged, and characterized. Since a large proportion of newly identified genes in L. major remain unclassified, with many of these being potentially Leishmania- (or kinetoplastid-) specific, there is a need for detailed analyses of homologs/orthologs that could help us understand the functional assignment of these gene products. We used a combination of integrated bioinformatics tools in a pathogenomics approach to contribute to the annotation of Leishmania genomes, particularly regarding flagellar genes and their roles in pathogenesis. This resulted in the formal in silico identification of eight of these homologs in Leishmania (IFT subunits, 20, 27, 46, 52, 57, 88, 140, and 172), along with others (IFTs 71, 74/72, and 81), as well as sequence comparisons and structural predictions. IFT, an important flagellar pathway in Leishmania, begins to be revealed through screening of trypanosomatid genomes; this information could also be used to better understand fundamental processes in Leishmania, such as motility and pathogenesis.

Characterization of core promoter elements for ecdysone receptor isoforms of the silkworm, Bombyx mori.

Two ecdysone receptor (EcR) isoforms, EcR-A and EcR-B1, are expressed in a tissue- and stage-specific manner, although the details of their transcription mechanisms are unknown. We determined the transcription start sites of EcR-A and EcR-B1 isoforms of Bombyx mori and found that both core promoter regions consist of initiator (Inr) and downstream promoter elements (DPE) but not TATA boxes. Promoter truncation analysis performed using the luciferase reporter assays and BmN cells showed that, in both isoforms, the regions -296 to -74 for BmEcR-B1, -104 to -61 for BmEcR-A and downstream regions of +1 are essential for basal transcriptional activity. Mutation experiments revealed that both DPE and its 5'-flanking CGCGCG sequence are crucial but DPE of BmEcR-B1 is not important for BmEcR-A transcription. These results indicate that the basal promoter activities differ between the two BmEcR isoforms.

Resting energy expenditure and its determinants in hemodialysis patients.

OBJECTIVE: Chronic kidney disease is associated with several metabolic disturbances that can affect energy metabolism. As resting energy expenditure (REE) is scarcely investigated in patients on hemodialysis (HD) therapy, we aimed to evaluate the REE and its determinants in HD patients. DESIGN: Cross-sectional study. SETTING: Dialysis Unit of the Nephrology Division, Federal University of São Paulo, Brazil. SUBJECTS: The study included 55 patients (28 male, 41.4+/-12.6 years old) undergoing HD therapy thrice weekly for at least 2 months, and 55 healthy individuals pair matched for age and gender. Subjects underwent fasting blood tests, as well as nutritional assessment, and the REE was assessed by indirect calorimetry. RESULTS: REE of HD patients was similar to that of pair-matched controls (1379+/-272 and 1440+/-259 kcal/day, respectively), even when adjusted for fat-free mass (P=0.24). REE of HD patients correlated positively with fat-free mass (r=0.74; P<0.001) and body mass index (r=0.37; P<0.01), and negatively with dialysis adequacy (r=-0.46; P<0.001). No significant univariate correlation was found between REE and age, dialysis vintage, serum creatinine, urea, albumin, bicarbonate, parathyroid hormone (PTH) or high-sensitivity C-reactive protein (CRP). In the multiple linear regression analysis, using REE as dependent variable, the final model showed that besides the well-recognized determinants of REE such as fat-free mass and age, PTH and CRP were the independent determinants of REE in HD patients (R (2)=0.64). CONCLUSIONS: In this study, the REE of HD patients was similar to that of healthy individuals, even with the positive effect of secondary hyperparathyroidism and inflammation on REE of these patients.

Intraflagellar transport complex in Leishmania spp. In silico genome-wide screening and annotation of gene function

Flagella are constructed and maintained through the highly conserved process of intraflagellar transport (IFT), which is a rapid movement of particles along the axonemal microtubules of cilia/flagella. Particles that are transported by IFT are composed of several protein subunits comprising two complexes (A and B), which are conserved among green algae, nematodes, and vertebrates. To determine whether or not homologues to members of the IFT complex proteins are conserved in Leishmania spp, we scanned genomes, transcriptomes and proteomes of Leishmania species in a search for putative IFT factors, which were then identified in silico, compared, cataloged, and characterized. Since a large proportion of newly identified genes in L. major remain unclassified, with many of these being potentially Leishmania- (or kinetoplastid-) specific, there is a need for detailed analyses of homologs/orthologs that could help us understand the functional assignment of these gene products. We used a combination of integrated bioinformatics tools in a pathogenomics approach to contribute to the annotation of Leishmania genomes, particularly regarding flagellar genes and their roles in pathogenesis. This resulted in the formal in silico identification of eight of these homologs in Leishmania (IFT subunits, 20, 27, 46, 52, 57, 88, 140, and 172), along with others (IFTs 71, 74/72, and 81), as well as sequence comparisons and structural predictions. IFT, an important flagellar pathway in Leishmania, begins to be revealed through screening of trypanosomatid genomes; this information could also be used to better understand fundamental processes in Leishmania, such as motility and pathogenesis.

Molecular genetic cascades for external genitalia formation: an emerging organogenesis program.

External genitalia are anatomical structures located at the posterior embryonic region as part of several urogenital/reproductive organs. The embryonic anlage of the external genitalia, the genital tubercle (GT) develops as a bud-shaped structure with an initial urethral plate and later urethra. Embryonic external genitalia are considered to be one of the appendages. Recent experiments suggest that essential regulatory genes possess similar functions for the outgrowth regulation of the GT and limb appendages. The transient embryonic epithelia located in the distal GT are called the distal urethral epithelium (DUE) regulating, at least in part, the (distal) GT development. This review covers the available data about early patterning of GT and discusses the molecular developmental similarities and points of divergence between the different appendages. Development of the male and female external genitalia is also reviewed.

A phase I/II trial of irinotecan-cisplatin combined with an anti-late-diarrhoeal programme to evaluate the safety and antitumour response of this combination therapy in patients with advanced non-small-cell lung cancer.

We conducted a phase I/II study in patients with advanced non-small-cell lung cancer (NSCLC) to increase the therapeutic index of the cisplatin-irinotecan combination by institution of an anti-late-diarrhoeal program (ADP). A total of 77 chemotherapy-naive patients with advanced NSCLC were enrolled. The cisplatin dose was fixed at 60 mg m(-2) (Day 1). Irinotecan was escalated in 5 mg m(-2) increments, starting from 60 mg m(-2) (Days 1 and 8). ADP consisted of oral sodium bicarbonate, magnesium oxide, basic water, and ursodeoxycholic acid, and was administered orally for 4 days with each dose of irinotecan. In the phase I portion, irinotecan pharmacokinetics was also examined. After the recommended dose of irinotecan with ADP was determined, a phase II study was conducted to evaluate the response. Maximum tolerated dose was reached at an irinotecan dose of 80 mg m(-2) (Grade 4 diarrhoea and neutropenia). Pharmacokinetic studies show that the maximum concentration and the area under the curve of both irinotecan and SN38 (active metabolite of irinotecan) tend to increase in the dose-dependent manner of irinotecan. The phase II portion of the study included 48 patients, who were treated with 75 mg m(-2) of irinotecan. Grade 3/4 toxicities included neutropenia in 65%, leucopenia in 33%, and late diarrhoea in 6% of the patients. During this treatment, PS did not change in 65% of patients. At the end of the chemotherapy, PS did not decline in 90% of patients. In the phase II portion, a response occurred in 63% (95% confidential interval (CI), 47-76%) of patients. Median time to progression was 19 weeks (95% CI, 15-22 weeks), and median survival was 52 weeks (95% CI, 39-64 weeks). This regimen of irinotecan and cisplatin with ADP resulted in promising efficacy with acceptable toxicity for patients with advanced NSCLC. This regimen is a candidate for the experimental arm towards future phase III studies.

Protein and energy depletion in chronic hemodialysis patients: clinical applicability of diagnostic tools.

Protein and energy depletion states are common and associated with increased morbidity and mortality in chronic hemodialysis (CHD) patients. Therefore, proper use of diagnostic tools to assess depleted states in CHD patients is critical. Assessment of protein and energy status can be done by an array of methodologies that include simple estimates of the visceral and somatic pools of protein to more refined techniques to measure protein and energy balance. The nutritional and metabolic derangements in the CHD population are highly complex and can be confounded by multiple comorbidities and fluid shifts between body compartments. Therefore, assessment of protein and energy status in CHD patients requires a wide range of methodologies that not only identify depleted states but also monitor nutrition therapy and predict clinical outcome. Most important, these methods require cautious and individualized interpretation in order to minimize the interference of comorbid conditions frequently observed in the CHD population. Currently, there is not a single method that can be considered the gold standard for assessment of protein and energy status in CHD patients. Therefore, a combination of methods is recommended. In this review, we describe available methods to assess protein and energy status, with special considerations pertaining to CHD patients.

Quantitative MRI of the wrist and nerve conduction studies in patients with idiopathic carpal tunnel syndrome.

OBJECTIVE: To correlate morphological findings of idiopathic carpal tunnel syndrome (CTS) with the function of the median nerve. METHODS: In this study, 105 wrists of 105 women patients with idiopathic CTS, and 36 wrists of 36 female volunteers were subjected to nerve conduction studies and MRI. Cross sectional area, signal intensity ratio, and the flattening ratio of the median nerve, carpal tunnel area, flexor tendon area, synovial area, and intersynovial space, and the palmar bowing of the transverse carpal ligament (TCL) were quantified by MRI and correlated with the severity of the disease determined by nerve conduction studies. RESULTS: Cross sectional areas of the median nerve, flexor tendons, and carpal tunnel, and the palmar bowing of the TCL of the CTS groups were greater than in the control group, but differences were not detected among the CTS groups for the area of the flexor tendons and the carpal tunnel. Enlargement, flattening, and high signal intensity of the median nerve at the distal radioulnar joint level were more significant in the advanced than in the earlier stages of the disease. Increase in palmar bowing of the TCL was less prominent in the most advanced group. Linear correlation between the area of the carpal tunnel and palmar bowing of the TCL was noted. CONCLUSION: Severity of the disease could be judged by evaluating not only longitudinal changes of signal intensity and configuration of the median nerve, but also palmar bowing of the TCL. Increased palmar bowing of the TCL was found to be associated with an increase in the area of the carpal tunnel.