Gender effect on neuromyelitis optica spectrum disorder with aquaporin4-immunoglobulin G.

BACKGROUND: Neuromyelitis optica spectrum disorder with aquaporin4-immunoglobulin G (NMOSD-AQP4) is an inflammatory disease characterised by a high female predominance. However, the effect of gender in patients with NMOSD-AQP4 has not been fully evaluated. OBJECTIVE: The aim of this study was to determine the effect of gender in clinical manifestations and prognosis of patients with NMOSD-AQP4. METHODS: The demographics, clinical and radiological characteristics, pattern reversal visual evoked potential (VEP) test results, and prognosis of 102 patients (18 males) with NMOSD-AQP4 were assessed. RESULTS: Male patients had a higher age at onset (48.7 vs 41 years, p = 0.037) and less optic neuritis as the onset attack (17% vs 44%, p = 0.026), higher tendency to manifest as isolated myelitis over the follow-up period (67% vs 28%, p = 0.005), fewer optic neuritis attacks per year (0.08 vs 0.27, p < 0.001), and shorter relative P100 latency on VEP testing (97.1% vs 108.3%, p = 0.001). Moreover, male gender was significantly associated with the absence of optic neuritis attacks over the follow-up period independent of their age of onset. CONCLUSION: In NMOSD-AQP4 patients, gender impacts on disease onset age and site of attack. This may be an important clue in identifying NMOSD-AQP4 patients with limited manifestations as well as in predicting their clinical courses.

A multicenter real-life study of the efficacy of an alpha-blocker with or without anticholinergic agent (imidafenacin) treatment in patients with lower urinary tract symptoms/benign prostatic hyperplasia and storage symptoms.

AIMS: To evaluate the efficacy and safety of combination therapy comprising a short-acting anticholinergic, imidafenacin and an alpha-blocker compared with monotherapy with an alpha-blocker only in men with lower urinary tract symptoms (LUTS) and storage symptoms. METHODS: The 12-week, prospective, double-blind, randomised trial enrolled men with LUTS and storage symptom. The inclusion criteria were a total International Prostate Symptom Score (IPSS) ≥12, an IPSS question 4 score ≥2, ≥8 micturitions in 24 hours, and a prostate volume >20 mL. The primary outcome was a change in the micturition number from baseline. Bladder diary variables, Patient Perception of Intensity of Urgency Scale (PPIUS) scores, IPSS and safety were assessed. RESULTS: Of 260 patients screened, 221 completed the study. Patients were randomly assigned to receive an alpha-blocker only (n=111, group 1) or combination therapy comprising an alpha-blocker and an anticholinergic (n=110, group 2) for 12 weeks. Group 1 and 2 showed significant improvement in their 24-hour micturition numbers (-1.87 and -2.08, respectively), nocturia episodes (-0.48 and -0.53, respectively), total IPSS (-9.9 and -8.8, respectively), and PPIUS scores (-0.19 and -0.24, respectively). Micturition number per 24 hours, daytime frequency, urgency, the PPIUS score, the IPSS question 4 score and IPSS QoL score improved significantly in the combination therapy group, but changes in total IPSS, nocturia episodes, and safety outcomes did not differ significantly between the groups. CONCLUSIONS AND CLINICAL IMPLICATIONS: Compared with treatment with an alpha-blocker alone, combination therapy comprising an anticholinergic and an alpha-blocker showed superior efficacy and its safety was similar in patients with LUTS and storage symptoms.

Alterations of Macrophage Migration Inhibitory Factor Expression in the Nervous System of the Rat Cystitis Model.

OBJECTIVE: We evaluated the changes in the migration inhibitory factor (MIF) expression with time in the bladder and spinal cord of a Sprague-Dawley rat cystitis model. METHODS: The bladder created by injecting lipopolysaccharide (LPS) and the lumbosacral spinal cord were removed at 4, 24, and 48 h, and 7 days after the induction of chronic cystitis, and 24 h after the induction of acute cystitis. The MIF expression was estimated using immunohistochemical staining, and the MIF mRNA was quantitatively analyzed using real-time polymerase chain reaction. RESULTS: The MIF expression in the urothelial cell was lowest at 24 h after LPS injection. As the degree of inflammation decreased, the MIF expression in the urothelial cell gradually increased 48 h and 7 days. The quantitative analysis of the MIF mRNA showed that the MIF expression was highest in both the bladder and the lumbosacral spinal cord 24 h after the cystitis became most severe. In chronic cystitis, the MIF mRNA expressions in the bladder and the lumbosacral spinal cord were 2.8 and 2.1 times significantly higher than in the normal control. CONCLUSION: MIF is involved in urinary symptoms and pain in cystitis, and in the mechanism that prolongs the symptoms of chronic cystitis by involving bladder tissue, and the nervous system.

Split-hand phenomenon in amyotrophic lateral sclerosis: A motor unit number index study.

INTRODUCTION: The split-hand phenomenon refers to preferential wasting of the thenar muscles with relative sparing of the hypothenar muscles in amyotrophic lateral sclerosis (ALS). METHODS: We compared the split-hand index (SI) calculated from the compound muscle action potential (CMAP; SICMAP ) with that calculated from the motor unit number index (MUNIX; SIMUNIX ). We performed MUNIX on the abductor policis brevis (APB), first dorsal interosseous (FDI), and abductor digiti minimi (ADM) muscles of 39 ALS patients and 40 age-matched, healthy controls. SI is derived by multiplying the CMAP (or MUNIX) recorded over the APB and FDI and dividing by the CMAP (or MUNIX) recorded over the ADM. RESULTS: Receiver-operating characteristic curve analysis revealed good diagnostic accuracy for both indices, but better performance of SIMUNIX than SICMAP . CONCLUSION: SIMUNIX and SICMAP were useful in differentiating ALS patients from healthy controls. SIMUNIX appears to be a better electrophysiological marker than SICMAP for the split-hand sign of ALS. Muscle Nerve 53: 885-888, 2016.

Motor unit number index (MUNIX) in the orbicularis oculi muscle of healthy subjects.

INTRODUCTION: The motor unit number index (MUNIX) refers to an electrophysiological method that measures the number of motor units in the surface electromyographic interference pattern (SIP) recorded during graded muscle contractions. MUNIX studies of limb muscles have been conducted, but MUNIX studies of bulbo-facial muscles have not been reported. METHODS: We assessed bilateral orbicularis oculi muscles using MUNIX, and the reference values and reproducibility of MUNIX and motor unit size index (MUSIX) were investigated in healthy subjects. RESULTS: In this study, MUNIX was applied successfully to the orbicularis oculi muscles and showed good reproducibility. The correlation coefficients for MUNIX and MUSIX were 0.803 and 0.592, respectively, and the coefficients of variation were 20.9% and 8.5%, respectively. CONCLUSIONS: The MUNIX procedure for the orbicularis oculi muscle would be a useful tool for evaluating bulbar symptoms, especially in amyotrophic lateral sclerosis.

Pattern difference of dissociated hand muscle atrophy in amyotrophic lateral sclerosis and variants.

INTRODUCTION: Split hand is considered to be a specific feature of amyotrophic lateral sclerosis (ALS). METHODS: We evaluated the pattern difference of intrinsic hand muscles of upper limb-onset ALS (UL-ALS), upper limb-onset progressive muscular atrophy (UL-PMA), brachial amyotrophic diplegia (BAD), and Hirayama disease (HD) by measuring objective electrophysiological markers. RESULTS: The abductor digiti minimi (ADM)/abductor pollicis brevis (APB) compound muscle action potential (CMAP) amplitude ratio was significantly higher in UL-ALS than other variants, but a considerable proportion of UL-ALS cases had an amplitude ratio in the range of other variants. Absent APB CMAP and abnormally high ADM/APB CMAP amplitude ratio (≥4) occurred only with UL-ALS. Conversely, an absent ADM CMAP was identified only in UL-PMA and BAD. CONCLUSIONS: The absolute ADM/APB CMAP amplitude ratio was not specific for ALS; however, several findings from simple electrophysiological measurements may help predict prognosis in patients with motor neuron diseases and may be early diagnostic markers for ALS.

Intraoperative electrophysiological monitoring during posterior craniocervical distraction and realignment for congenital craniocervical anomaly.

PURPOSE: Congenital craniocervical segmentation anomaly associated with malalignment of the odontoid process causes progressive spinal cord compression with myelopathy. Recent literatures have reported that ventral decompression could be achieved with posterior craniocervical realignment through posterior instrumented reduction. The purpose of the present study is to show the efficacy of intraoperative electrophysiological monitoring during craniocervical realignment through screws and rod system for congenital craniocervical segmentation anomaly. METHODS: Consecutive ten patients with a congenital craniocervical segmentation anomaly and myelopathy due to a malaligned odontoid process, who underwent posterior craniocervical realignment, were included. Klippel-Feil syndrome (KFS) was combined in four patients. Gait disturbance and motor weakness were the main presentation. Craniocervical realignment was achieved by intraoperative distraction through a rod and screw system. Intraoperative neuromonitoring was performed with transcranial motor-evoked potential (TcMEP) and somatosensory-evoked potential (SSEP). RESULTS: Significant change in TcMEP occurred in two patients with KFS during surgery, but the change was reversed with release of distraction. All patients were awakened without neurological deficit. Motor weakness and gait disturbance were normalized within 6 months in all patients. Postoperative computed tomography scan and/or magnetic resonance imaging showed that the reduction was complete in all patients. CONCLUSIONS: Craniocervical realignment through screws and rod system may be safe and efficacious surgical technique for the treatment of congenital craniocervical anomaly with the help of intraoperative neuromonitoring. However, distraction should be cautiously monitored, especially when Klippel-Feil syndrome is combined.

Characterization of the spectrum of Korean inflammatory demyelinating diseases according to the diagnostic criteria and AQP4-Ab status.

BACKGROUND: The relative frequencies of demyelinating diseases among Korean patients with idiopathic inflammatory demyelinating disease of the central nervous system (IIDD) have not been sufficiently studied. We therefore describe a cohort of 203 patients with IIDD from three centers in Korea whose syndromes were identified precisely according to international clinical criteria and autoantibody to aquaporin 4 (AQP4-Ab) status. METHODS: In total, 260 consecutive patients were screened and 203 were included from three hospitals in Korea. All were tested for AQP4-Ab by using a cell-based assay. Patients who met the criteria for definite neuromyelitis optica (NMO) or had a positive AQP4-Ab test result were defined as the NMO group. Among the others, patients were assessed if they had acute disseminated encephalomyelitis, multiple sclerosis (MS), acute transverse myelitis, optic neuritis, or other demyelinating disease as a clinically isolated syndrome of the brain. RESULTS: Eighteen percent of patients were classified as the NMO group, 2% as acute disseminated encephalomyelitis, 18% as MS, 41% as acute transverse myelitis, 11% as optic neuritis, and 8% as other clinically isolated syndrome of the brain. AQP4-Ab was positive in 18% of patients and the relative frequency of NMO to MS (NMO/MS ratio) was 1.06. The mean duration of follow up in our patients was 64 months. CONCLUSIONS: Among Korean patients with idiopathic inflammatory demyelinating diseases, the incidence of NMO may be similar to that of MS, and the overall positivity of AQP4-Ab could be lower than previously reported. In addition, acute transverse myelitis that is not associated with MS or NMO can be relatively common in these patients. Further population-based studies with AQP4-Ab are needed to determine the exact incidence of NMO and other idiopathic inflammatory demyelinating diseases in Korea.

Diagnostic effectiveness of dynamic colpocystoproctography in women planning for combined surgery with urinary incontinence and pelvic organ prolapse.

OBJECTIVE: To evaluate the advantage of performing the dynamic cystoproctography (DCP) in patients planning for combined surgery due to urinary incontinence and pelvic organ prolapse (POP). MATERIALS AND METHODS: We performed DCP on a total of 113 consecutive women with POP and compared the findings of the physical examination with POP quantification against those of DCP including squeezing, straining and evacuation phases, and analyzed the changes to the rates of surgical planning. For statistical analysis, sensitivity, specificity, and positive predictive value of each test were performed. RESULTS: DCP identified an additional 10 cases of cystocele, 32 cases of rectocele, 2 cases of enterocele, 4 cases of sigmoidocele, and 8 cases of rectal intussusception compared to those cases who were only included for a physical examination. The initial surgical plan was changed in a total of 24 cases (22.1%). The prevalence of bowel symptoms in the group in which the surgical plan changed was higher than in the group with no changes to the surgical plan (p = 0.023). CONCLUSIONS: DCP may be a more sensitive test for diagnosing POP compared to physical examination alone, and it is useful to patients with bowel symptoms by making surgical planning for combined surgery with stress urinary incontinence and POP.

Impact of obesity on the predictive accuracy of prostate-specific antigen density and prostate-specific antigen in native Korean men undergoing prostate biopsy.

OBJECTIVES: To evaluate the impact of obesity on the biopsy detection of prostate cancer. METHODS: We retrospectively reviewed data of 1182 consecutive Korean patients (≥50 years) with serum prostate-specific antigen levels of 3-10 ng/mL who underwent initial extended 12-cores biopsy from September 2009 to March 2013. Patients who took medications that were likely to influence the prostate-specific antigen level were excluded. Receiver operating characteristic curves were plotted for prostate-specific antigen and prostate-specific antigen density predicting cancer status among non-obese and obese men. RESULTS: A total of 1062 patients (mean age 67.1 years) were enrolled in the analysis. A total of 230 men (21.7%) had a positive biopsy. In the overall study sample, the area under the receiver operator characteristic curve of serum prostate-specific antigen for predicting prostate cancer on biopsy were 0.584 and 0.633 for non-obese and obese men, respectively (P = 0.234). However, the area under the curve for prostate-specific antigen density in predicting cancer status showed a significant difference (non-obese 0.696, obese 0.784; P = 0.017). CONCLUSIONS: There seems to be a significant difference in the ability of prostate-specific antigen density to predict biopsy results between non-obese and obese men. Obesity positively influenced the overall ability of prostate-specific antigen density to predict prostate cancer.

Effect of JGK-263 as a new glycogen synthase kinase-3ß inhibitor on extrinsic apoptosis pathway in motor neuronal cells.

Glycogen synthase kinase-3ß (GSK-3ß) has been identified as one of the important pathogenic mechanisms in motor neuronal death. GSK-3ß inhibitor has been investigated as a modulator of apoptosis and has been shown to confer significant protective effects on cell death in neurodegenerative diseases. However, GSK-3ß is known to have paradoxical effects on apoptosis subtypes, i.e., pro-apoptotic in mitochondrial-associated intrinsic apoptosis, but anti-apoptotic in death receptor-related extrinsic apoptosis. In this study, we evaluated the effect of a new GSK-3ß inhibitor (JGK-263) on motor neuron cell survival and apoptosis, by using low to high doses of JGK-263 after 48 h of serum withdrawal, and monitoring changes in extrinsic apoptosis pathway components, including Fas, FasL, cleaved caspase-8, p38α, and the Fas-Daxx interaction. Cell survival peaked after treatment of serum-deprived cells with 50 µM JGK-263. The present study showed that treatment with JGK-263 reduced serum-deprivation-induced motor neuronal apoptosis by inactivating not only the intrinsic, but also the extrinsic apoptosis pathway. These results suggest that JGK-263 has a neuroprotective effect through effective modulation of the extrinsic apoptosis pathway in motor neuron degeneration.

Endocrinopathies in transfusion-associated iron overload.

BACKGROUND: Transfusional iron overload primarily results in reticuloendothelial iron accumulation, which is considered to be less harmful than parenchymal iron accumulation. However, systematic and comprehensive data on endocrine function in transfusion-associated haemochromatosis are limited. METHODS: We examined 25 aplastic anaemia patients (11 men and 14 women) diagnosed with transfusion-associated haemochromatosis at a single institution. Pituitary function was determined with a combined pituitary function test. On a different day, a 75-g oral glucose tolerance test was performed. The bone mineral density (BMD) of the lumbar spine and total hip was assessed with dual-energy X-ray absorptiometry. RESULTS: Twenty-two (88%) of these 25 patients had at least one endocrine abnormality, and 12 had more than one abnormality. The most common pituitary hormonal deficiency involved the pituitary-gonadal axis; 54% of the total subjects had hypogonadotropic hypogonadism. Two patients had an insufficient cortisol response to corticotrophin-releasing hormone stimulation. No patient had a deficiency of growth hormone or thyroid-stimulating hormone. Twelve (48%) had diabetes mellitus, and these patients tended to have higher concentrations of ferritin, alanine aminotransferase and γ-glutamyl transferase. Osteoporosis (T-score <-2·5 SD) was observed in 48% of patients. The reduction in BMD was more pronounced in the lumbar spine than in the total hip. The patients with osteoporosis were accompanied by hypogonadism, which predominantly affected the trabecular bone. CONCLUSIONS: Our observations suggest that endocrinopathies are common in transfusion-associated haemochromatosis.

Utility of aquaporin-4 antibody assay in patients with neuromyelitis optica spectrum disorders.

OBJECTIVE: Our aim was to evaluate the utility of aquaporin-4 antibodies (AQP4-Ab) in patients with neuromyelitis optica spectrum disorders (NMOSD). METHODS: The clinical and radiological characteristics of 78 patients with NMOSD and 22 with multiple sclerosis (MS), who were tested for AQP4-Ab by a cell-based assay, were assessed. RESULTS: The mean time interval between symptom onset and development of optic neuritis and myelitis was 39.9 months in neuromyelitis optica (NMO). About 40% of patients with limited NMO would have fulfilled the diagnostic criteria for MS in the absence of the antibody assay results. In patients with longitudinally extensive transverse myelitis, positive AQP4-Ab assay results were associated with the poor response to acute steroid treatment and asymptomatic visual evoked potential abnormality. Presence of either painful tonic spasm associated with myelitis or severe disability at onset had high specificity and relatively high sensitivity in differentiating NMOSD with AQP4-Ab from MS. CONCLUSIONS: The AQP4-Ab assay can facilitate the early diagnosis of NMO and prevent limited NMO from being misdiagnosed as MS. It can predict the poor response to first-line acute-phase treatment and probably detect the subclinical optic nerve involvement in subgroups of NMOSD. Lastly, it will contribute to the upcoming revision of the current diagnostic criteria for NMO.

Intraoperative neurophysiologic monitoring: basic principles and recent update.

The recent developments of new devices and advances in anesthesiology have greatly improved the utility and accuracy of intraoperative neurophysiological monitoring (IOM). Herein, we review the basic principles of the electrophysiological methods employed under IOM in the operating room. These include motor evoked potentials, somatosensory evoked potentials, electroencephalography, electromyography, brainstem auditory evoked potentials, and visual evoked potentials. Most of these techniques have certain limitations and their utility is still being debated. In this review, we also discuss the optimal stimulation/recording method for each of these modalities during individual surgeries as well as the diverse criteria for alarm signs.

Microbiome in urological diseases: Axis crosstalk and bladder disorders.

Since the identification of the human urinary microbiome, numerous studies have characterized this microbial community and improved our knowledge of its association with urinary diseases. This association between urinary diseases and microbiota is not confined to the urinary microbiota; it is interconnected with the microbiota of other organs. The gastrointestinal, vaginal, kidney, and bladder microbiota all affect urinary diseases because they work with their respective organs to control the growth and operation of the immune, metabolic, and nervous systems through dynamic bidirectional communication along the bladder-centered axis. Therefore, disturbances in the microbial communities may result in the emergence of urinary diseases. In this review, we describe the increasing and intriguing evidence of complicated and critical relationships that may contribute to the development and progression of urinary diseases through disruption of the microbiota in various organs.

The correlation between the expression of ubiquitin-conjugating enzyme 2C and prostate cancer prognosis.

PURPOSE: Ubiquitin-conjugating enzyme E2 C (UBE2C) is known to show a causal relationship with cancer development and advancement. The role of UBE2C is to control the mitotic spindle checkpoint. Excess UBE2C has been identified in patients with advanced prostate cancer. The objective of the present study was to examine positive connections between the expression of UBE2C and prognostic factors for prostate cancer. METHODS: Prostate cancer patients' clinical data were analysed. Tissue microarrays (TMAs) were also performed for human prostate cancer tissues (n = 335) and adjacent non-neoplastic tissues (n = 22). TMA slides were incubated with antibodies against UBE2C. Cores were scored by a pathologist who was blind to cancer results. RESULTS: Of 335 prostate cancer patients, 200 could be assessed for biochemical recurrence, clinical recurrence, and overall survival. Human prostate cancer tissues showed higher expression of UBE2C than adjacent non-neoplastic tissues. High expression level of UBE2C showed a strong positive relationship with a high prostate-specific antigen (PSA), Gleason's score, and pathological stage of prostate cancer. Patients with a higher UBE2C grade demonstrated greater lymphatic engagement of prostate cancer than those with a lower UBE2C grade. CONCLUSION: The expression of UBE2C has positive correlations with several prognostic factors for prostate cancer. Thus, investigating the expression level of UBE2C staining is a promising tool for predicting prostate cancer prognosis.

The Correlations between the Intensity of Histopathological Ubiquitin-Specific Protease 11 Staining and Progression of Prostate Cancer.

BACKGROUND: Ubiquitin-specific protease 11 (USP11), one of the principal phosphatase and tensin homolog (PTEN) deubiquitinases, can reserve PTEN polyubiquitination to maintain PTEN protein integrity and inhibit PI3K/AKT pathway activation. The aim of the current study was to investigate the associations between immunohistochemical USP11 staining intensities and prognostic indicators in individuals with prostate cancer. METHODS: Tissue microarrays (TMAs) were performed for human prostate cancer and normal tissue (control) samples. Data on patient's age, Gleason score, plasma prostate-specific antigen (PSA) titer, disease stage, and presence of seminal vesicles, lymph nodes, and surgical margin involvement were collected. A pathologist who was blinded to the clinical outcome data scored the TMA for USP11 staining intensity as either positive or negative. RESULTS: Cancerous tissues exhibited lower USP11 staining intensity, whereas the neighboring benign peri-tumoral tissues showed higher USP11 staining intensity. The degree of USP11 staining intensity was lower in patients with a higher PSA titer, higher Gleason score, or more advanced disease stage. Patients who showed positive USP11 staining were more likely to have more optimal clinical and biochemical recurrence-free survival statistics. CONCLUSIONS: USP11 staining intensity in patients with prostate cancer is negatively associated with several prognostic factors such as an elevated PSA titer and a high Gleason score. It also reflects both biochemical and clinical recurrence-free survival in such patients. Thus, USP11 staining is a valuable prognostic factor in patients with prostate cancer.

The difference of glucostatic parameters according to the remission of diabetes after Roux-en-Y gastric bypass.

BACKGROUND: Gut hormones play a role in diabetes remission after a Roux-en-Y gastric bypass (RYGB). Our aim was to investigate differences in gut hormone secretion according to diabetes remission after surgery. Second, we aimed to identify differences in insulin secretion and sensitivity according to diabetes remission after RYGB. METHODS: Twenty-two severely obese patients with type 2 diabetes underwent RYGB. A meal tolerance test (MTT) was performed 12 months after RYGB. The secretions of active glucagon-like peptide-1 (active GLP-1), glucose-dependent insulinotropic peptide (GIP), peptide YY, C-peptide and insulin during the MTT test were calculated using total area under the curve values (AUC). Remission was defined as glycated haemoglobin (A(1C)) of <6.5% and a fasting glucose concentration of <126 mg/dL for 1 year or more without active pharmacological therapy. RESULTS: Of the 22 patients, 16 (73%) had diabetes remission (remission group). The secretion CURVES of active GLP-1, GIP and peptide YY were not different between the groups. AUC of insulin and C-peptide were also not different. Homeostasis model assessment estimate of insulin resistance was significantly lower (1.26 ± 1.05 versus 2.37 ± 1.08, p = 0.006), and Matsuda index of insulin sensitivity was significantly higher in the remission group (10.5 ± 6.2 versus 5.8 ± 2.1, p = 0.039). The disposition index (functional reserve of beta cells) was significantly higher in the remission group compared with that in the non-remission group (5.34 ± 2.74 versus 1.83 ± 0.70, p < 0.001). CONCLUSIONS: Remission of diabetes after RYGB is not associated with a difference in gut hormone secretion. Patients remaining diabetic had higher insulin resistance and decreased ß cell functional reserve.

Oral solubilized ursodeoxycholic acid therapy in amyotrophic lateral sclerosis: a randomized cross-over trial.

To evaluate the efficacy and safety of ursodeoxycholic acid (UDCA) with oral solubilized formula in amyotrophic lateral sclerosis (ALS) patients, patients with probable or definite ALS were randomized to receive oral solubilized UDCA (3.5 g/140 mL/day) or placebo for 3 months after a run-in period of 1 month and switched to receive the other treatment for 3 months after a wash-out period of 1 month. The primary outcome was the rate of progression, assessed by the Appel ALS rating scale (AALSRS), and the secondary outcomes were the revised ALS functional rating scale (ALSFRS-R) and forced vital capacity (FVC). Fifty-three patients completed either the first or second period of study with only 16 of 63 enrolled patients given both treatments sequentially. The slope of AALSRS was 1.17 points/month lower while the patients were treated with UDCA than with placebo (95% CI for difference 0.08-2.26, P = 0.037), whereas the slopes of ALSFRS-R and FVC did not show significant differences between treatments. Gastrointestinal adverse events were more common with UDCA (P < 0.05). Oral solubilized UDCA seems to be tolerable in ALS patients, but we could not make firm conclusion regarding its efficacy, particularly due to the high attrition rate in this cross-over trial.

Relationship between vitamin D, parathyroid hormone, and bone mineral density in elderly Koreans.

There is controversy regarding definition of vitamin D inadequacy. We analyzed threshold 25-hydroxyvitamin D (25[OH]D) below which intact parathyroid hormone (iPTH) increases, and examined age- and sex-specific changes of 25(OH)D and iPTH, and association of 25(OH)D and iPTH with bone mineral density (BMD) in elderly Koreans. Anthropometric parameters, serum 25(OH)D and iPTH, lumbar spine and femur BMD by dual-energy radiography absorptiometry (DXA) were measured in 441 men and 598 postmenopausal women. iPTH increased below serum 25(OH) of 36.7 ng/mL in men, but failed to reach plateau in women. Femur neck BMD above and below threshold differed when threshold 25(OH)D concentrations were set at 15-27.5 ng/mL in men, and 12.5-20 ng/mL in postmenopausal women. Vitamin D-inadequate individuals older than 75 yr had higher iPTH than those aged ≤ 65 yr. In winter, age-associated iPTH increase in women was steeper than in summer. In conclusion, vitamin D inadequacy threshold cannot be estimated based on iPTH alone, and but other factors concerning bone health should also be considered. Older people seemingly need higher 25(OH)D levels to offset age-associated hyperparathyroidism. Elderly vitamin D-inadequate women in the winter are most vulnerable to age-associated hyperparathyroidism.