Intravenous tissue plasminogen activator for acute ischemic stroke in patients with renal dysfunction.

OBJECTIVE: This study used the Taiwan Stroke Registry data to evaluate the efficacy and safety of intravenous tissue plasminogen activator (tPA) in treating acute ischemic stroke in patients with renal dysfunction. DESIGN: We identified 3525 ischemic stroke patients and classified them into two groups according to the estimated glomerular filtration rate (eGFR) at the emergency department: ≥60, and <60 ml/min/1.73 m2 or on dialysis and by the propensity score from August 2006 to May 2015. The odds ratio of poor functional outcome (modified Rankin Scale ≥2) was calculated for patients with tPA treatment (N = 705), compared to those without tPA treatment (N = 2820), by eGFR levels, at 1, 3 and 6 months after ischemic stroke. We also evaluated the risks of intracerebral hemorrhage, upper gastrointestinal bleeding, mortality, between the two groups by eGFR levels. RESULTS: Among patients with eGFR levels of <60 ml/min/1.73 m2, tPA therapy reduced the odds ratio of poor functional outcome to 0.60 (95% confidence interval = 0.42-0.87) at 6 months after ischemic stroke. The tPA therapy was not associated with increased overall risk of upper gastrointestinal bleeding, but with increased risk of intracerebral hemorrhage. The low eGFR was not a significant risk factor of intracerebral hemorrhage among ischemic stroke patients receiving tPA treatment. CONCLUSIONS: tPA for acute ischemic stroke could improve functional outcomes without increasing the risks of upper gastrointestinal bleeding for patients with or without renal dysfunction. The low eGFR was not a significant risk factor for intracerebral hemorrhage among patients receiving tPA treatment.

Parathyroidectomy slows renal function decline in patients with primary hyperparathyroidism.

PURPOSE: Primary hyperparathyroidism has deleterious effects on health and causes nephrolithiasis and osteoporosis. However, it remains unclear whether parathyroidectomy benefits kidney function among patients with primary hyperparathyroidism. METHODS: In this retrospective study, patients with primary hyperparathyroidism receiving parathyroidectomy in a tertiary medical center between 2003 and 2017 were followed up until December 31 2017, death, or requiring renal replacement therapy. Impact of parathyroidectomy on kidney function was examined using longitudinal estimated glomerular filtration rate (eGFR) change scales: single, average, absolute difference, percent change, annual decline rate, and slope. We applied linear mixed-effect model to determine the effect of parathyroidectomy on kidney function. RESULTS: During study period, 167 patients with primary hyperparathyroidism were identified from 498 parathyroidectomized patients, and finally, 27 patients fulfilled our stringent criteria. Median follow-up duration was 1.50 years (interquartile range 1.05-1.81) before surgery and 2.47 years (1.37-6.43) after surgery. Although parathyroidectomy did not affect amount of proteinuria and distribution of eGFR, parathyroidectomy significantly slowed decline rate of eGFR compared with that before surgery (- 1.67 versus - 2.73 mL/min/1.73 m2/year, p < 0.001). More importantly, parathyroidectomy made more beneficial effects on kidney function in patients with age < 65 years and those without chronic kidney disease or hypertension. CONCLUSIONS: Our study showed that parathyroidectomy slows renal function decline irrespective of age or comorbidities, which offers novel insight into the revision of guidelines for surgical indications in primary hyperparathyroidism. Given small sample size, further large-scale controlled studies are warranted to confirm our findings.

Pre-stroke physical activity is associated with fewer post-stroke complications, lower mortality and a better long-term outcome.

BACKGROUND AND PURPOSE: Physical activity is associated with a reduced incidence of first-time stroke. However, few studies have examined the effect of pre-stroke physical activity on post-stroke complications and clinical outcomes. METHODS: A total of 39 835 cases of stroke registered in the nationwide stroke registry system of Taiwan between 2006 and 2009 were analyzed according to five levels of severity as determined by National Institutes of Health Stroke Scale score upon hospital admission. Pre-stroke physical activity was defined in the Taiwan Stroke Registry as dedicated leisure-time physical activity for at least 30 min/day for 3 days/week for more than 6 months. A Cox model was used to compare complications and outcomes between active and inactive groups. RESULTS: The active and inactive groups were similar in age distribution and stroke type distribution, but the active group had better National Institutes of Health Stroke Scale scores upon admission. The active group also had significantly fewer post-stroke complications. Active patients had lower hospital mortality and better functional outcomes upon discharge as per the modified Rankin Scale. Improved functional status in the active group was significant at 1, 3 and 6 months post-stroke. CONCLUSION: Dedicated leisure-time physical activity for at least 30 min/day, at least three times per week for more than 6 months was associated with decreased stroke severity, fewer post-stroke complications, lower mortality and better outcomes.

Risk and adverse outcomes of fractures in patients with Parkinson's disease: two nationwide studies.

UNLABELLED: The association between Parkinson's disease and fracture was not completely understood. This nationwide study investigated increased risk of fracture in patients with Parkinson's disease. In the nested cohort study, Parkinson's disease was associated with pneumonia, septicemia, stroke, urinary tract infection, and mortality after fracture admission. INTRODUCTION: Falls are a common complication in people with Parkinson's disease (PD). This study evaluated fracture risk and post-fracture outcomes in patients with PD. METHODS: We identified 1,423 adults aged 40 years and older newly diagnosed with PD using the Taiwan National Health Insurance Research Database from 2000 to 2003. Comparison cohort consisted of 5,692 adults without PD randomly selected from the same dataset, frequency matched in age and sex. Followed-up events of fracture from January 1, 2000, until December 31, 2008, were ascertained from medical claims. Adjusted hazard ratios (HR) and 95 % confidence interval (CI) of fracture associated with PD were evaluated. Another nested cohort study of 397,766 hospitalized fracture patients analyzed for adjusted odds ratios (ORs) and 95 % CIs of adverse events after fracture among patients with and without PD between 2004 and 2010. RESULTS: The incidences of fracture for people with and without PD were 39.5 and 23.9 per 1,000 person-years, respectively (p < 0.0001). Compared with control, the adjusted HR of fracture was 2.25 (95 % CI 1.97-2.58) for PD patients. Previous PD was associated with risks of pneumonia (OR 1.44, 95 % CI 1.36-1.52), septicemia (OR 1.41, 95 % CI 1.33-1.49), stroke (OR 1.40, 95 % CI 1.32-1.50), urinary tract infection (OR 1.53, 95 % CI 1.46-1.61), and mortality (OR 1.25, 95 % CI 1.15-1.35) after fracture. CONCLUSIONS: PD was associated with higher risk of fracture. Patients with PD had more complications and mortality after fracture. Fracture prevention and attention to post-fracture adverse events are needed for this susceptible population.

Elevated C-reactive protein level in hemodialysis patients with moderate/severe uremic pruritus: a potential mediator of high overall mortality.

BACKGROUND: Dialysis patients with uremic pruritus have worse outcomes. However, the pathophysiology of the high mortality in these patients remains inconclusive except for links with calcium/phosphate imbalance and sleep disturbance. Whether inflammation, an outcome predictor in dialysis patients, plays a role is unknown. METHODS: This prospective study included 321 chronic hemodialysis (HD) patients (>3 months) for survival analysis. A visual analog scale (VAS) was used to measure the severity of itching, and the patients were divided into four groups: no pruritus (VAS = 0, N = 118), mild (VAS 1-3, N = 76), moderate (VAS 4-7, N = 89) and severe pruritus (VAS 8-10, N = 38). The Pittsburgh Sleep Quality Index (PSQI) was used to define sleep disturbance, while high-sensitive C-reactive protein (hs-CRP) and tumor necrosis factor α (TNF-α) were used to evaluate inflammation. The patients were followed-up for 30 months. RESULTS: Patients with moderate/severe pruritus had higher hs-CRP, but similar TNF-α levels; they also had a worse survival rate (P = 0.0197, log rank test). By stratifying hs-CRP levels, those with higher hs-CRP had worse survival regardless of the severity of uremic pruritus. In a Cox proportional hazard model, hs-CRP levels and moderate/severe uremic pruritus were independent predictors of mortality after adjusting for age, poor sleeper (PSQI > 5), diabetes, albumin, phosphate, hemoglobin and parathyroid hormone levels and (hs-CRP) × (moderate/severe uremic pruritus) (all P < 0.05). CONCLUSION: In moderate/severe pruritic HD patients, those with higher hs-CRP suffer from worse overall mortality. Inflammation may bridge uremic pruritus to high mortality, and elevated hs-CRP predicts a worse outcome in this population.

Marchiafava-Bignami disease with widespread lesions and complete recovery.

MBD is a rare disorder strongly associated with alcoholism. It is characterized pathologically by demyelination and necrosis of the corpus callosum. MBD presents with severe neurologic deficits and significant sequelae developing in most survivors. We report a patient with total clinical recovery. Serial MR imaging demonstrated typical lesions with restricted diffusion in the acute stage and total resolution without atrophy or cystic change.

Progesterone inhibits human endothelial cell proliferation through a p53-dependent pathway.

Previous studies have shown that progesterone inhibits endothelial cell proliferation through a nuclear receptor-mediated mechanism. Here, we further demonstrate that progesterone at physiologic levels (5 - 500 nM) dose- and time-dependently inhibited DNA synthesis of cultured human umbilical vein endothelial cells (HUVEC). The mRNA and protein levels of p21, p27, and p53 in HUVEC were increased by progesterone. The formation of CDK2-p21 and CDK2-p27 were increased and the CDK2 activity was decreased in the progesterone-treated HUVEC. The progesterone-inhibited [3H]thymidine incorporation was completely blocked when the expressions of p21 and p27 were knocked-down together. Transfection of HUVEC with dominant negative p53 cDNA prevented the progesterone-induced increases in p21 and p27 promoter activity and protein level, decreases in thymidine incorporation, and capillary-like tube formation. Matrigel angiogenesis assay in mice demonstrated the antiangiogenic effect of progesterone in vivo. These findings demonstrate for the first time that progesterone inhibited endothelial cell proliferation through a p53-dependent pathway.

Electrolyzed-reduced water reduced hemodialysis-induced erythrocyte impairment in end-stage renal disease patients.

Chronic hemodialysis (HD) patients increase erythrocyte susceptibility to hemolysis and impair cell survival. We explored whether electrolyte-reduced water (ERW) could palliate HD-evoked erythrocyte impairment and anemia. Forty-three patients undergoing chronic HD were enrolled and received ERW administration for 6 month. We evaluated oxidative stress in blood and plasma, erythrocyte methemoglobin (metHb)/ferricyanide reductase activity, plasma metHb, and proinflammatory cytokines in the chronic HD patients without treatment (n=15) or with vitamin C (VC)- (n=15), vitamin E (VE)-coated dialyzer (n=15), or ERW treatment (n=15) during an HD course. The patients showed marked increases (15-fold) in blood reactive oxygen species, mostly H(2)O(2), after HD without any treatment. HD resulted in decreased plasma VC, total antioxidant status, and erythrocyte metHb/ferricyanide reductase activity and increased erythrocyte levels of phosphatidylcholine hydroperoxide (PCOOH) and plasma metHb. Antioxidants treatment significantly palliated single HD course-induced oxidative stress, plasma and RBC PCOOH, and plasma metHb levels, and preserved erythrocyte metHb /ferricyanide reductase activity in an order VC>ERW>VE-coated dialyzer. However, ERW had no side effects of oxalate accumulation easily induced by VC. Six-month ERW treatment increased hematocrit and attenuated proinflammatory cytokines profile in the HD patients. In conclusion, ERW treatment administration is effective in palliating HD-evoked oxidative stress, as indicated by lipid peroxidation, hemolysis, and overexpression of proinflammatory cytokines in HD patients.

Effects of vitamin C infusion and vitamin E-coated membrane on hemodialysis-induced oxidative stress.

Chronic hemodialysis (HD) patients manifest anemia and atherosclerosis with associated oxidative stress. We explored whether intravenous infusion of vitamin C (VC) and/or use of vitamin E (VE)-coated dialysis membrane could palliate HD-evoked oxidative stress. Eighty patients undergoing chronic HD were enrolled and randomly assigned into four groups: HD with intravenous VC (n=20), HD with VE-coated dialyzer (n=20), HD with both (n=20), and HD with neither (n=20). We evaluated oxidative stress in blood and plasma, erythrocyte methemoglobin/ferricyanide reductase (red blood cells (RBC)-MFR) activity, plasma methemoglobin, and pro-inflammatory cytokines in these patients. All patients showed marked increases (14-fold) in blood reactive oxygen species (ROS) after HD. The types of ROS were mostly hydrogen peroxide, and in lesser amounts, O2*- and HOCl. HD resulted in decreased plasma VC, total antioxidant status, and RBC-MFR activity and increased plasma and erythrocyte levels of phosphatidylcholine hydroperoxide (PCOOH) and methemoglobin. Intravenous VC significantly palliated HD-induced oxidative stress, plasma and RBC levels of PCOOH, and plasma methemoglobin levels and preserved RBC-MFR activity. The VE-coated dialyzer effectively prevented RBCs from oxidative stress, although it showed a partial effect on the reduction of total ROS activity in whole blood. In conclusion, intravenous VC plus a VE-coated dialyzer is effective in palliating HD-evoked oxidative stress, as indicated by hemolysis and lipid peroxidation, and by overexpression of proinflammation cytokines in HD patients. Using VE-coated dialyzer per se is, however, effective in reducing lipid peroxidation and oxidative damage to RBCs.

Spontaneous intracerebral hemorrhage in young adults.

Few studies have addressed intracerebral hemorrhage (ICH) in younger adults. We studied spontaneous ICH in adults

Unusual dilatation of Virchow-Robin spaces: case report.

Virchow-Robin spaces normally surround the perforating arteries that enter the brain. These spaces are a well-defined sites where immunological reactions take place and they may have implications in the pathogenesis of a number of neuropathological conditions. We present the case of a 52-year-old woman who had a history of complex partial seizures for 30 years. Her routine neurological examinations and mini-mental tests had normal results. Magnetic resonance images of this patient revealed unusual widening of the Virchow-Robin spaces up to 1.5 cm in diameter along the perforating medullary arteries in the white matter, more so in the left hemisphere. Although it has been concluded that these large spaces are a phenomenon of the normal aging brain and are unrelated to neurological diseases, our patient had had epileptic seizures for 30 years. The large Virchow-Robin spaces of our patient might have been an incidental radiologic finding. Their pathogenesis remains unclear, and their possible clinical relationship to epilepsy deserves further pathological studies.

Osmotic demyelination syndrome with two-phase movement disorders: case report.

Osmotic demyelination syndrome (ODS) is characterized by regions of demyelination throughout the brain, which are most prominent in the pons. This demyelinating disease is associated with electrolyte disturbances and typically occurs in patients who are alcoholic or malnourished. Movement disorders are not frequently recognized in patients with ODS. This report describes a 22-year-old woman with ODS after correction of profound hyponatremia. The main neurologic symptom was two-phase movement disorder. First, she had acute onset dystonia, then the movement disorder transformed to generalized rigidity and tremors in the delayed second phase. Magnetic resonance imaging in the first phase revealed demyelinating lesions in the central pons, bilateral thalami and basal ganglia. In the second phase, the previous myelinolysis had been partially resolved. The clinical course of the two-phase movement disorder did not correlate with the resolving feature of neuroradiologic findings. During the second-phase movement disorder, the patient had a good response to propranolol and trihexyphenidyl.

Differential activation of protein kinase A in various regions of myocardium during sepsis.

Changes in the activities of protein kinase A (PKA) (cAMP-dependent protein kinase) in various regions of rat myocardium during different cardiodynamic phases of sepsis were studied in an attempt to understand the pathophysiology of cardiac dysfunction during sepsis. Sepsis was induced by cecal ligation and puncture (CLP). Experiments were divided into three groups: control, early sepsis, and late sepsis. Early and late sepsis refers to those animals sacrificed at 9 and 18 hr, respectively, after CLP. Cardiac PKA was extracted and partially purified by acid precipitation, ammonium sulfate fractionation, and DEAE-cellulose chromatography. PKA was eluted from DEAE-cellulose column with a linear NaCl gradient. Two types of PKA, Type I (eluted at low ionic strength) and Type II (eluted at high ionic strength), were collected, and their activities were determined based on the rate of incorporation of [gamma-32P]ATP into histone. Under physiological conditions, Type I PKA activities were unevenly distributed (left atrium > right atrium > pacemaker region > left ventricle > right ventricle > ventricular septum) while Type II PKA activities were evenly distributed among different regions of myocardium. During early sepsis, Type I PKA activities remained unchanged while Type II PKA activities were activated by 32 and 70% in right atrium and pacemaker regions, respectively. During late sepsis, Type I PKA activities were stimulated by 228% in ventricular septum while Type II PKA activities were not affected. These data demonstrate that different PKA activities exist in various regions of the myocardium and that PKA activities were preferentially activated in certain areas during the progression of sepsis. Since PKA plays an important role in the regulation of myocardial function and metabolism, the activation of PKA in different regions of myocardial during different stages of sepsis may contribute to the altered cardiac function during the progression of sepsis.

Dissociation between upper and lower neck N13 potentials following paired median nerve stimuli.

Cervical N13 potential in response to the median nerve stimulation can be recorded either from upper (Cv2) or lower (Cv6) neck with almost equal amplitudes and latencies. It has long been debated whether they represent the same or different generator sources. Using a conditioning-test paired stimuli paradigm, we examined the differences of recovery function of Cv2- and Cv6-N13, anterior neck (AN)-P13, and scalp recorded P13/P14 in 6 healthy subjects. All cervical electrodes were referenced to the non-cephalic site. Scalp response was recorded with linked ear reference. The inter-stimulus intervals ranged from 4 to 20 ms with 2 ms increments. Throughout 4 to 18 ms ISI, Cv6-N13, AN-P13 and scalp P13/P14 were suppressed, whereas Cv2-N13 was facilitated. All but scalp P13/P14 returned close to the control at 20 ms ISI. The findings indicate that Cv2-N13, Cv6-N13 and scalp P13/P14 are independent each other and arise from different generator sources. The suppression of Cv6-N13 is consistent with a postsynaptic nature of this potential and may indeed be mediated through dorsal horn interneurons creating a current field orientation in the posterior-anterior direction. The facilitation of Cv2-N13 suggests that this is a presynaptic potential and may travel through the dorsal column with vertical orientation. The longer period of suppression of scalp P13/P14 suggests it to be of polysynaptic origin and to arise at least rostral to the cuneate nucleus.

Familial amyloid polyneuropathy in Taiwan: identification of transthyretin variant (Leu55-->Pro).

We report a family with familial amyloid polyneuropathy (FAP), showing an early-onset and a fatal outcome before age 30. Transthyretin (TTR) gene analysis showed one point mutation (T-->C change) in the second base of codon 55, and the corresponding amino acid substitution of proline (Pro) for leucine (Leu) was confirmed at the protein level. This is the first FAP family of Taiwanese origin demonstrating a causative gene abnormality, and FAP with TTR-Pro55 was considered to be more serious compared with other forms of FAP.

Type I familial amyloid polyneuropathy--report of a family in Taiwan.

We report three cases of histologically verified systemic amyloidosis with polyneuropathy. Common to them were early onset progressive peripheral sensorimotor disturbance starting in the legs and prominent autonomic dysfunctions such as postural hypotension, anhidrosis, and loss of pupillary light reflexes. Other characteristic features included vomiting, alternating diarrhea and constipation, opacities of the vitreous bodies, and congestive heart failure. All these clinical manifestations resemble type I familial amyloid polyneuropathy described by Andrade in 1952 from Portugal. Sural nerve biopsy stained with Congo red showed typical green birefringence under polarized light microscope. Histologically verified familial cases of this form of amyloid polyneuropathy have not been reported from Taiwan before.

Computed tomography, magnetic resonance imaging, and electromyographic studies of tensor veli palatini muscles in patients with nasopharyngeal carcinoma.

One of the factors that induces eustachian tube dysfunction caused by the invasion of nasopharyngeal carcinoma is paralysis of the tensor veli palatini muscle. Electromyography (EMG), computed tomography (CT), and/or magnetic resonance imaging (MRI) were used to study the tensor muscle and the related paratubal structures and parapharyngeal space. This study, from 44 patients with nasopharyngeal carcinoma, showed that 67% of tensor muscles on the side of the symptomatic ear yielded abnormal electromyographic waveforms, which usually indicated a neurogenic disorder. In the majority of the abnormal EMG cases, CT or MRI often revealed that the pharyngobasilar fascia and the tensor muscle were compressed anterolaterally and the upper prestyloid parapharyngeal space was infiltrated. It was found that an abnormal electromyogram of the tensor muscle generally suggested a more advanced T stage and eustachian tube dysfunction. Otitis media with effusion in the stage I cases was usually not caused by paralysis of the tensor muscle. The invasion of some early cancers, especially localized on the torus tubarius, could also cause the effusion.