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Introduction: Parkinson's disease (PD) is a disorder characterized by motor symptoms, such as rigidity, akinesia, and resting tremor, as well as non-motor symptoms, including psychiatric manifestations and autonomic failure. The prevalence of PD increases with age, and the condition is more common in men than in women. Conversely, polypharmacy has emerged as a paramount medical concern, especially among older patients, correlating with medicines' adverse effects, interactions between medicines, frequent admissions to the hospital, and a high risk of morbidity and mortality. Case description: We encountered an older male patient with idiopathic PD and mild renal dysfunction. Originally prescribed 14 types of medicines, including anti-PD drugs, the patient developed delirium and epileptic seizures during hospitalization. After reducing the number of medications, including amantadine, the symptoms significantly improved. This clinical course suggests that polypharmacy, in addition to PD itself, poses a significant risk of delirium and epileptic seizures, even in patients with mild renal dysfunction. Conclusion: This report is indicative of the risk of polypharmacy and highlights the importance of citing drug interactions for a correct diagnosis in patients presenting with complex symptoms.
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Aneurisma da Aorta Torácica , Polimialgia Reumática , Trombose , Humanos , Polimialgia Reumática/complicações , Polimialgia Reumática/diagnóstico , Aneurisma da Aorta Torácica/complicações , Aneurisma da Aorta Torácica/diagnóstico , Trombose/complicações , Trombose/diagnóstico por imagem , Trombose/etiologia , Trombose/diagnóstico , Feminino , Idoso , Masculino , Idoso de 80 Anos ou mais , Tomografia Computadorizada por Raios XRESUMO
Non-typhoidal Salmonella (NTS) rarely causes bacteremia and subsequent focal infections as an extraintestinal complication, even in immunocompetent adults. A 25-year-old man was hospitalized for several days with difficulty moving due to fever, acute buttock pain, and shivering. He had no recent or current respiratory symptoms and no clear gastrointestinal symptoms. Physical examination revealed mild redness around the left buttock and difficulty raising the left lower extremity due to pain, in addition to which blood tests showed high levels of inflammatory markers. His clinical course and laboratory findings suggested sepsis, and magnetic resonance imaging revealed a high-intensity area in the left piriformis muscle on diffusion-weighted imaging; therefore, acute piriformis pyomyositis was strongly suggested. Cephazolin was started upon hospitalization; however, blood and stool cultures proved positive for NTS, and the antibiotics were changed to ceftriaxone. Follow-up MRI showed a signal in the left piriformis muscle and newly developed left pyogenic sacroiliitis. On the 25th hospital day, a colonoscopy was performed to identify the portal of entry for bacteremia, which revealed a longitudinal ulcer in the sigmoid colon in the healing process. His buttock pain gradually improved, and the antibiotics were switched to oral levofloxacin, which enabled him to continue treatment in an outpatient setting. Finally, the patient completed seven weeks of antimicrobial therapy and returned to daily life without leaving any residual disability. Invasive NTS infection due to bacteremia is rare among immunocompetent adults. Piriformis pyomyositis and subsequent pyogenic sacroiliitis should be added to the differential diagnosis of acute febrile buttock pain. In the case of NTS bacteremia, the entry site must be identified for source control. Additionally, the background of the host, especially in such an immunocompetent case, needs to be clarified; therefore, the patient should be closely examined.
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The effectiveness of ischemic postconditioning (iPoC) in patients with ST-elevation myocardial infarction (STEMI) without ischemic preconditioning has not been determined. Therefore, we investigated the impact of iPoC and its potential mechanism related to heat shock protein 72 (HSP72) induction on myocardial salvage in patients with STEMI without prodromal angina (PA).We retrospectively analyzed data from 102 patients with STEMI with successful reperfusion among 323 consecutive patients with acute coronary syndrome. Among these, 55 patients with iPoC (iPoC (+) ) underwent 4 cycles of 60-second inflation and 30-second deflation of the angioplasty balloon. Both the iPoC (+) and iPoC (-) groups were divided into 2 further subgroups: patients with PA (PA (+) ) and those without (PA (-) ). We analyzed HSP72 levels in neutrophils, which were measured until 48 hours after reperfusion. I-123 ß-methyl-p-iodophenyl-pentadecanoic acid (BMIPP) scintigraphy was performed within a week of reperfusion therapy. In 64% of patients, thallium-201 (TL) scintigraphy was performed 6-8 months after STEMI onset.Using BMIPP and TL, in the PA (-) subgroups, the iPoC (+) group had a significantly greater myocardial salvage ratio than the iPoC (-) group. iPoC was identified as an independent predictor of the myocardial salvage ratio. The HSP72 increase ratio was significantly elevated in the iPoC (+) PA (-) group. Importantly, the myocardial salvage effect in patients without PA was significantly correlated with the HSP72 increase ratio, which was greater in patients with iPoC.These results suggest the potential impact of iPoC via HSP72 induction on myocardial salvage; however, the effects may be limited to patients with STEMI without PA.
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Proteínas de Choque Térmico HSP72 , Pós-Condicionamento Isquêmico , Infarto do Miocárdio com Supradesnível do Segmento ST , Humanos , Masculino , Feminino , Proteínas de Choque Térmico HSP72/metabolismo , Estudos Retrospectivos , Idoso , Pessoa de Meia-Idade , Infarto do Miocárdio com Supradesnível do Segmento ST/terapia , Pós-Condicionamento Isquêmico/métodos , Angina Pectoris/terapia , Sintomas Prodrômicos , Intervenção Coronária Percutânea/métodos , Neutrófilos/metabolismoRESUMO
Thrombocytopenia, anasarca, myelofibrosis, renal dysfunction, and organomegaly (TAFRO) syndrome is a rare condition with diverse clinical and pathological characteristics related to multi-organ damage. We report a case of TAFRO syndrome complicated by immune thrombocytopenia with prolonged fever and thrombocytopenia for several weeks. A 61-year-old man was transferred with sepsis caused by Enterococcus faecalis, and developed disseminated intravascular coagulation. Antibiotics treatment was initiated: however, low-grade fever and thrombocytopenia persisted despite the adequate antimicrobial treatment. Systemic edema, pleural effusion, and ascites had developed before hospitalization, and renal and liver function had deteriorated, resulting in progressive multi-organ damage. Prednisolone 40 mg/day was initiated based on the assumption of a condition in which excessive production of inflammatory cytokines would lead to systemic deterioration and fatal organ damage. Subsequently, the fever resolved, and renal function began to normalize. However, thrombocytopenia did not show much recovery trend after Helicobacter pylori eradication therapy and initiation of thrombopoietin receptor agonists. Bone marrow biopsy results showed normal bone marrow with no malignant findings. Alternatively, significant clinical signs met the diagnostic criteria for TAFRO syndrome, and a renal biopsy revealed thrombotic microangiopathy, which is also reasonable for renal involvement in TAFRO syndrome. The use of cyclosporine remarkably corrected the thrombocytopenia. We considered this a case of TAFRO syndrome that developed after sepsis with disseminated intravascular coagulation and performed the differential diagnosis of prolonged thrombocytopenia and excluded it. Although TAFRO syndrome is a unique disease concept, diagnostic criteria may consist of nonspecific elements such as generalized edema, thrombocytopenia, persistent fever, and elevated inflammatory response, and there are many differential conditions to exclude, requiring caution in diagnosing TAFRO syndrome.
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Coagulação Intravascular Disseminada , Sepse , Microangiopatias Trombóticas , Masculino , Humanos , Lactente , Coagulação Intravascular Disseminada/diagnóstico , Coagulação Intravascular Disseminada/etiologia , Febre/tratamento farmacológico , Edema/diagnóstico , Edema/etiologia , Edema/tratamento farmacológicoRESUMO
The interaction of the ß-coronavirus severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) nucleocapsid (N) protein with genomic RNA is initiated by specific RNA regions and subsequently induces the formation of a continuous polymer with characteristic structural units for viral formation. We hypothesized that oligomeric RNAs, whose sequences are absent in the 29.9-kb genome sequence of SARS-CoV-2, might affect RNA-N protein interactions. We identified two such hexameric RNAs, In-1 (CCGGCG) and G6 (GGGGGG), and investigated their effects on the small filamentous/droplet-like structures (< a few µm) of N protein-genomic RNA formed by liquid-liquid phase separation. The small N protein structures were sequence-specifically enhanced by In-1, whereas G6 caused them to coalesce into large droplets. Moreover, we found that a guanosine 12-mer (G12, GGGGGGGGGGGG) expelled preexisting genomic RNA from the small N protein structures. The presence of G12 with the genomic RNA suppressed the formation of the small N protein structures, and alternatively apparently altered phase separation to induce the formation of large droplets with unclear phase boundaries. We showed that the N-terminal RNA-binding domain is required for the stability of the small N protein structures. Our results suggest that G12 may be a strong inhibitor of the RNA-N protein interaction.
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COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/genética , Proteínas do Nucleocapsídeo/química , Proteínas do Nucleocapsídeo/genética , Proteínas do Nucleocapsídeo/metabolismo , RNA Viral/genética , RNA Viral/química , RNA Viral/metabolismo , Ligação ProteicaRESUMO
Objective: Pneumonia is a disease with high morbidity and mortality among older individuals in Japan. In practice, most older patients with pneumonia are not required ventilatory management and are not necessarily in critical respiratory condition. However, prolonged hospitalization itself is considered to be a serious problem even in these patients with non-critical pneumonia and have negative and critical consequences such as disuse syndrome in older patients. Therefore, it is essential to examine the factors involved in redundant hospital stays for older hospitalized patients with non-severe pneumonia, many of whom are discharged alive. Method: We examined hospitalized patients diagnosed with pneumonia who were 65 years and older in our facility between February 2017 and March 2020. A longer length of stay (LOS) was defined in cases in which exceeded the 80th percentile of the hospitalization period for all patients was exceeded, and all other cases with a shorter hospitalization were defined as a shorter LOS. In a multivariate logistic regression model, factors determining longer LOSs were analyzed using significant variables in univariate analysis and clinically relevant variables which could interfere with renal function, including fasting period, time to start rehabilitation, estimated glomerular filtration rate (eGFR), the Quick Sequential Organ Failure Assessment (qSOFA) score of 2 or higher, bed-ridden state. Results: We analyzed 104 eligible participants, and the median age was 86 (interquartile range, 82-91) years. Overall, 31 patients (30.7%) were bed-ridden, and 37 patients (35.6%) were nursing-home residents. Patients with a Clinical Frailty Scale score of 4 or higher, considered clinically frail, accounted for 93.2% of all patients. In multivariate analysis, for a decrease of 5 ml/min/1.73m2 in eGFR, the adjusted odds ratios for longer LOSs were 1.22 (95% confidence interval, 1.04-1.44) after adjusting for confounders. Conclusion: Reduced renal function at admission has a significant impact on prolonged hospital stay among older patients with non-severe pneumonia. Thoughtful consideration should be given to the frail older pneumonia patients with reduced renal function or with chronic kidney disease as a comorbidity at the time of hospitalization to prevent the progression of geriatric syndrome associated with prolonged hospitalization.
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Behçet's disease is an inflammatory disease which manifests itself as various symptoms, such as uveitis, oral and genital aphthae, erythema nodosa, gastro-intestinal ulcerations and encephalopathy. Among the manifestations, renal dysfunction is reported in some percentage of the patients with this disorder. We experienced a middle-aged male with Behçet's disease who showed an extremely high level of urinary ß2-microglulin, which is one of the markers of renal dysfunction, despite normal serum creatinine levels. The patient was on non-steroidal anti-inflammatory drug (NSAID) therapy for 7 weeks, and this could have affected his renal dysfunction. The present report suggests that renal injury should not be underestimated in patients with Behçet's disease, especially in patients using NSAIDs.
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Síndrome de Behçet , Preparações Farmacêuticas , Anti-Inflamatórios não Esteroides/efeitos adversos , Síndrome de Behçet/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
A male 15-year-old promising gymnast suffered palpitations, which emerged only after landing a round-off back somersault. The performance induced an attack of regular narrow QRS complex tachycardia that was highly reproducible. Not a single element of the performance, but a whole sequence of round-off back somersault was required to induce the attack. An electrophysiologic study revealed an intra-nodal dual pathway causing atrioventricular nodal reentrant tachycardia (AVNRT). A complication of a tiny atrial septal defect (ASD) was incidentally detected, thus we initially suspected a causal relation of ASD as the platypnea-orthodeoxia syndrome. However, it was denied as the major mechanism of attack because of a very faint shunt flow and no-induction of hypoxemia during a round-off back somersault. The major triggering mechanisms of a whole sequence of round-off back somersaults were speculated to be related to transient atrial overload and autonomic imbalance induced by a swift postural-axial change together with an intense Valsalva maneuver with the maximal level of breath holding. The AVNRT attack was successfully treated by radiofrequency catheter ablation and has never recurred even by a whole sequence of round-off back somersaults. Currently he is a healthy and active gymnast with no symptoms.
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Fabry disease (FD) is an X-linked disorder of the sphingolipid metabolism, caused by deficiency or decreased activity of α-galactosidase A. We report a rare case of Fabry nephropathy (FN) in a 21-year-old Japanese female patient presenting with only urinary mulberry bodies; she was treated with pharmacological chaperone therapy (PCT) after renal biopsy. The patient underwent a detailed examination because her mother was diagnosed with FD in the Division of Community Medicine of our hospital. She did not have renal dysfunction or proteinuria, and only mulberry bodies were detected in the urine. The activity of α-galactosidase A was low, and genetic analysis revealed the R301Q mutation. A percutaneous renal biopsy was performed, and the findings revealed enlargement and vacuolation of glomerular podocytes by light microscopy, and myelin and zebra bodies were detected in podocytes by electron microscopy. She was diagnosed with FN by renal biopsy and gene analysis. PCT was selected as the treatment to prevent cardiac events and renal dysfunction. The present case suggests that renal biopsy may be necessary even for young women with only mulberry bodies for the diagnosis of FN. It could be useful to evaluate the effect of treatment using the counts of mulberry bodies in the urine. In addition, due to its oral administration, PCT may be suitable for patients who are unable to visit the hospital frequently.
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BACKGROUND: There is limited information about the respiratory function of ever-smokers without lung disorders. We sought to assess the effects of smoking habits on respiratory function in subjects without lung disorders. METHODS: Subjects were recruited from among patients without any evidence of respiratory disorders who visited rural primary care clinics. Each participant was asked to answer a questionnaire that included questions smoking history. Their forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) were measured. RESULTS: We analyzed 802 subjects (364 men and 438 women). The means of the lambda-mu-sigma method derived z-score of FEV1 (zFEV1) both in current-smokers and ex-smokers were lower than that in never-smokers. The mean zFEV1 in the ever-smokers with more than 30 pack-years of smoking history were lower than that in the ever-smokers with less smoking history. Univariate analysis showed that there were significant negative correlations between pack-years and zFEV1 both in the ex-smokers and current-smokers. There was no significant correlation between the duration of smoking cessation and zFEV1 in the ex-smokers. CONCLUSIONS: Our data suggests that respiratory function in healthy ever-smokers is decreased based on smoking habits in a dose-dependent manner. Even after a long period of smoking cessation, the decreased respiratory function seems to be maintained in ex-smokers.
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Voluntários Saudáveis , Pulmão/fisiopatologia , Fumar/efeitos adversos , Adulto , Idoso , Análise de Variância , Feminino , Volume Expiratório Forçado , Humanos , Masculino , Pessoa de Meia-Idade , Abandono do Hábito de Fumar , Inquéritos e Questionários , Fatores de Tempo , Capacidade VitalRESUMO
BACKGROUND: Combination antihypertensive therapy with an angiotensin receptor blocker (ARB) and a calcium channel blocker (CCB) or diuretics is common. This subanalysis investigated blood pressure (BP) variability in patients receiving ARB-based combination therapy. METHODS: In a prospective, randomized, open-label trial, hypertensive outpatients (≥65 years) who did not achieve their target BP with ARB monotherapy switched to losartan 50 mg/hydrochlorothiazide 12.5 mg (ARB + D) or ARB plus amlodipine 5 mg (ARB + C) for 12 months. Clinic BP and heart rate (HR), measured every 3 months, visit-to-visit variability and seasonal variation were evaluated. RESULTS: No significant between-group differences in average, maximum, or minimum systolic or diastolic BP, or HR, were found. Visit-to-visit BP variability (systolic) was significantly higher in the ARB + D group than in the ARB + C group. When each group was subdivided into two seasonal groups (summer and winter), no significant between-group differences in BP were found. Multivariate regression analyses showed a tendency toward negative correlation between outdoor temperature and urinary albumin:creatinine ratio and estimated glomerular filtration rate at 12 months in the ARB + D group. CONCLUSION: Combination therapy with an ARB plus a CCB may be preferable to that with an ARB plus diuretics for decreasing BP variability. As for seasonal variability, both treatments can be used safely regardless of season.
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Anti-Hipertensivos/administração & dosagem , Pressão Sanguínea/fisiologia , Hipertensão/fisiopatologia , Estações do Ano , Idoso , Anlodipino/administração & dosagem , Pressão Sanguínea/efeitos dos fármacos , Quimioterapia Combinada , Feminino , Humanos , Hidroclorotiazida/administração & dosagem , Hipertensão/tratamento farmacológico , Losartan/administração & dosagem , Masculino , Estudos Prospectivos , Resultado do TratamentoRESUMO
Conifer and broadleaf trees emit volatile organic compounds in the summer. The major components of these emissions are volatile monoterpenes. Using solid phase microextraction fiber as the adsorbant, monoterpenes were successfully detected and identified in forest air samples. Gas chromatography/mass chromatogram of monoterpenes in the atmosphere of a conifer forest and that of serum from subjects who were walking in a forest were found to be similar each other. The amounts of α-pinene in the subjects became several folds higher after forest walking. The results indicate that monoterpenes in the atmosphere of conifer forests are transferred to and accumulate in subjects by inhalation while they are exposed to this type of environment.
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BACKGROUND: Angiotensin II (AII) plays a central role in vascular remodeling via oxidative stress. However, the interaction between AII and reduced glutathione (GSH) redox status in cardiovascular remodeling remains unknown. METHODS: In vivo: The cuff-induced vascular injury model was applied to Sprague Dawley rats. Then we administered saline or a GSH inhibitor, buthionine sulfoximine (BSO, 30 mmol/L in drinking water) for a week, subsequently administered 4 more weeks by osmotic pump with saline or AII (200 ng/kg/minute) to the rats. In vitro: Incorporation of bromodeoxyuridine (BrdU) was measured to determine DNA synthesis in cultured rat vascular smooth muscle cells (VSMCs). RESULTS: BSO reduced whole blood GSH levels. Systolic blood pressure was increased up to 215 ± 4 mmHg by AII at 4 weeks (p<0.01), which was not affected by BSO. Superoxide production in vascular wall was increased by AII and BSO alone, and was markedly enhanced by AII+BSO. The left ventricular weight to body weight ratio was significantly increased in AII and AII+BSO as compared to controls (2.52 ± 0.08, 2.50 ± 0.09 and 2.10 ± 0.07 mg/g respectively, p<0.05). Surprisingly, the co-treatment of BSO totally abolished these morphological changes. Although the vascular circumferential wall stress was well compensated in AII, significantly increased in AII+BSO. The anti-single-stranded DNA staining revealed increasing apoptotic cells in the neointima of injured arteries in BSO groups. BrdU incorporation in cultured VSMCs with AII was increased dose-dependently. Furthermore it was totally abolished by BSO and was reversed by GSH monoethyl ester. CONCLUSIONS: We demonstrated that a vast oxidative stress in impaired GSH redox system totally abolished AII-induced vascular, not cardiac remodeling via enhancement of apoptosis in the neointima and suppression of cell growth in the media. The drastic suppression of remodeling may result in fragile vasculature intolerable to mechanical stress by AII.
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Angiotensina II/metabolismo , Glutationa/metabolismo , Estresse Oxidativo , Remodelação Vascular/genética , Animais , Aorta/efeitos dos fármacos , Aorta/metabolismo , Aorta/patologia , Apoptose/efeitos dos fármacos , Pressão Sanguínea , Butionina Sulfoximina/administração & dosagem , Glutationa/antagonistas & inibidores , Humanos , Músculo Liso Vascular/efeitos dos fármacos , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/patologia , Ratos , Superóxidos/metabolismoRESUMO
BACKGROUND: It remains unclear whether administration of ARB with reactive oxygen species (ROS) scavenging effects improves the prognosis of patients undergoing PCI. OBJECTIVES: This study investigated whether the pre-intervention antioxidant effect of angiotensin receptor blocker (ARB) affects long-term outcomes in patients after successful percutaneous coronary intervention (PCI) without early adverse events. METHODS: Fifty-two patients who underwent elective PCI were randomly assigned for treatment with or without ARB, which was administered within 48 hours before PCI. ROS levels in mononuclear cells (MNCs) and serum superoxide dismutase (SOD) activity were measured pre-PCI and 6 months post-PCI. After exclusion of unexpected early adverse events during angiographic follow-up period, the long-term outcome (major adverse cerebro-cardiovascular event; MACCE) was assessed in eligible patients. RESULTS: Forty-three patients (non-ARB n = 22, ARB n = 21) were followed up in this study. During angiographic follow-up period, ROS formation in MNCs was significantly increased in the non-ARB group (from 29.4 [21.6-35.2] to 37.2 [30.7-45.1] arbitrary units; p = 0.031) compared to that in the ARB group. Meanwhile, SOD activity was significantly impaired in the non-ARB group alone (from 24.0 ± 17.0 to 16.3 ± 13.8%, p = 0.004). During the follow-up period (median, 63.3 months), MACCEs were observed in 6 patients. The cumulative event ratio of MACCE was significantly higher in the non-ARB group than in the ARB group (p = 0.018). CONCLUSIONS: Concomitant administration of ARB effectively reduced ROS production of PCI patients during angiographic follow-up period. Initial ROS inhibition following ARB administration may contribute to improvement of worse outcomes in patients who have undergone successful PCI.
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OBJECTIVE: Combination therapy with angiotensin receptor blockers (ARBs) and calcium channel blockers or diuretics is common for hypertensive patients. This study aimed to determine which combination is better for elderly hypertensive patients. METHODS: In this prospective, randomized, open-label trial, hypertensive outpatients aged at least 65 years who had not achieved their target blood pressure (BP) with standard ARB dosages were randomly assigned to receive either a fixed-dose combination of losartan (50âmg) and hydrochlorothiazide (12.5âmg) (ARB+D; nâ=â72) or a combination of amlodipine (5âmg) and the typical dosage of ARBs (ARB+C; nâ=â68) to evaluate the change in the BP, laboratory values and cognitive function. RESULTS: At 3 months, the SBP/DBP was found to have significantly decreased from 156/83â±â15/11âmmHg to 139/76â±â14/10âmmHg in the ARB+D group and 155/83â±â11/10âmmHg to 132/72â±â14/10âmmHg in the ARB+C group. The BP reduction efficacy was greater in the ARB+C group than in the ARB+D group. At 6 months, the SBP/DBP reached the same level in both groups. At 12 months, the urine albumin/creatinine ratio was significantly decreased from the geometric mean of 17.1 to 9.6âmg/g in the ARB+D group, whereas it was increased from 19.8 to 23.7âmg/g in the ARB+C group. Conversely, the estimated glomerular filtration rate tended to show a decrease in the ARB+D group. There was no significant difference in mini-mental state examination after 1 year. CONCLUSION: ARB+amlodipine (5âmg) yielded a greater BP reduction, whereas ARB+HCTZ (12.5âmg) resulted in a greater reduction in the albuminuria, suggesting that each combination therapy is advantageous in a different manner for elderly hypertensive patients.