There are many different glomerular disorders, including glomerulonephritis, diabetic nephropathy, and hypertensive nephrosclerosis. However, once glomerular damage reaches a certain threshold, the progression of renal disease is consistent and irreversible. Recent studies emphasized the crucial role of tubulointerstitial injury as a mediator of progression of kidney disease. One common mechanism that leads to renal failure via tubulo-interstitial injury is massive proteinuria. Accumulating evidence suggests critical effects of filtered macromolecules on tubular cells, including lysosomal rupture, energy depletion, and tubular injury directly induced by specific components such as complement components. Another common mechanism is chronic hypoxia in the tubulointerstitium. Tubulointerstitial damage results in the loss of peritubular capillaries, impairing blood flow delivery. Interstitial fibrosis also impairs oxygen diffusion and supply to tubular cells. This induces chronic hypoxia in this compartment, rendering a vicious cycle. Development of novel therapeutic approaches against these final common pathways will enable us to target any types of renal disease.
Worldwide energetic efforts have provided several clues for the management of Alzheimer’s disease and related dementias in elderly people, although the history of dementia treatment is not long. Various pharmacological or non-pharmacological treatments are carried out in daily medical practice, but evidence for the validity of these treatments is limited. In United States and Europe, several pharmacological and a few non-pharmacological treatments have been proven effective and a few drugs are approved by various governments and used in practice. In contrast, only one acetylcholinesterase inhibitor, donepezil has been proven effective and used for patients with mild or moderate Alzheimer’s disease in Japan. Anti-hypertensive or anti-platelet therapy has been shown to reduce the incidence or recurrence of stroke, probably preventing vascular dementia. Effectiveness of drugs and types of care awaits to be validated in the light of scientific procedures.
Objective The optimal duration of immunosuppressive therapy and the timing of treatment for treating membranous nephropathy (MN) have yet to be established. We examined outcomes of a short course of cyclophosphamide alternating with prednisolone for MN patients with nephrotic syndrome. Methods and Patients Cyclophosphamide (2 mg/kg/day for 8 weeks) combined with prednisolone (1 mg/kg every 48 hours for 8 weeks, then tapering off for 1 year) was prescribed for 28 MN patients (12 men and 16 women; mean age 52.4±2.25 years SEM). We first evaluated the response rates to this combined therapy, then compared the clinical characteristics of those who achieved remission (group A) with those who did not (group B) within 6 months of the start of treatment. Results The incidences of complete and partial remission increased with the follow-up period; 32 and 21% by 6 months, 54 and 29% by 12 months, and 79 and 11% by 24 months, respectively. Serum IgG (906±100.8 versus 562±66.1 mg/day; p<0.01) was significantly higher in group A, and the selectivity index (CIgG/Calbumin 0.16±0.015 versus 0.30±0.040; p<0.01), significantly lower. Nephrotic syndrome persisted in 3 group B patients (23%), who finally had impaired renal function. Conclusion MN patients with nephrotic syndrome responded favorably to a short course of cyclophosphamide combined with prednisolone. The serum IgG level and selectivity index may serve as markers of early response to this treatment.
Objective To adapt the Nottingham Health Profile (NHP) for Japanese and to describe the results of the assessment of its psychometric properties. Methods Assessments included test-retest reliability over approximately a 2-week interval, internal consistency and construct validity in 133 patients with COPD. Results The distribution of scores indicated that most of the NHP sections exhibited a floor effect, although this is greatly reduced with the NHP-Distress scale. The test-retest reliability was above 0.8 for all sections when patients reporting any change in their health status rating were excluded. Cronbach’s alpha coefficients reflected the number of items contained in each section. The internal consistency of the emotional reactions section at one timepoint and the physical mobility section at both timepoints were lower than expected to be higher. All sections except the pain section could be used to distinguish patients who reported their health status to be good or fair from those who rated it to be poor or very poor. Conclusion The adaptation of the NHP for Japanese was successful. Most sections showed reasonable test-retest reliability, indicating that they produced acceptable levels of random measurement error. The internal consistency of the sections was confirmed, although the alpha values of the emotional reactions and physical mobility sections were lower than might be expected for scales of their length. Different sections of the Japanese NHP were shown to have known group validity.
Objective Non-herpetic acute limbic encephalitis (non-herpetic ALE) is regarded as a new subgroup of limbic encephalitis. In the present study, clinical findings and cerebrospinal fluid (CSF) cytokines in patients with non-herpetic ALE were investigated. Patients and Methods For adult inpatients in our hospital and related hospitals from 1996 to 2001, non-herpetic ALE was examined according to the criteria described in this study. Six patients were diagnosed as having non-herpetic ALE, and their clinical data and magnetic resonance imaging (MRI) were analyzed. In the CSF samples of the 6 patients with non-herpetic ALE and 6 patients with herpes simplex encephalitis (HSE), the concentrations of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and interferon (IFN)-γ were determined using sandwich-type enzyme-linked immunosorbent assay (ELISA) kits. Results The six patients with non-herpetic ALE showed all the acute encephalitis features, such as fever, altered consciousness, seizures, memory impairment, and mild CSF pleocytosis. MRI demonstrated selective abnormal signals in the limbic system, including the bilateral hippocampi and amygdalae. The levels of CSF IL-6 and IFN-γ in patients with non-herpetic ALE were significantly lower than those in patients with HSE (p<0.05 and p<0.01, respectively). The levels of both TNF-α and IL-1β were below the detection limits in both groups. Conclusion Six patients were newly diagnosed as having non-herpetic ALE in this study. These patients revealed both acute limbic encephalitis and MRI abnormalities in the bilateral hippocampi and amygdalae. The levels of IL-6 and IFN-γ in the CSF of patients with non-herpetic ALE were significantly lower than those of patients with HSE, possibly reflecting an immunological process in this type of ALE rather than direct viral infection.
Objective To address the presence of post-Q fever fatigue syndrome (post-QFS) in Japan, and to evaluate the efficacy of minocycline for this condition. Patients and Methods In 20 Coxiella burnetii (C. burnetii) seropositive patients with persistent nonspecific symptoms including general fatigue, low-grade fever, myalgia and arthralgia, changes in subjective symptoms, C. burnetii antibody titers and C. burnetii DNA were evaluated after antibiotic treatment. Results After treatment mainly with minocycline (100 mg/day for 3 months), the clinical picture improved in all 20 patients as evidenced by decreases in body temperature (13/17), general fatigue (20/20) and headache (9/12). The mean performance status (PS) score improved from 5.0 to 1.8 (p<0.01). All 7 who had been positive for C. burnetii DNA, became negative together with an improvement in subjective symptoms. Indirect immunofluorescence tests demonstrated 6 of the 20 patients to be positive for C. burnetii IgM antibody to phase II antigen (1:32), and 18 to be positive for IgG antibody (1:128, 1:256). Antibody titers of both IgM (6/6, 1:16) and IgG (18/18, 1:16) decreased markedly after treatment. Conclusion These results of an open label study in Japan suggest that minocycline administration is useful for improving chronic nonspecific symptoms considered to be post-Q fever fatigue syndrome caused by C. burnetii infection.
Hypertrophic obstructive cardiomyopathy (HOCM), which shows left ventricular outflow pressure gradient (LVPG), is often complicated with mitral regurgitation (MR). We examined a 62-year-old Japanese female with HOCM and MR. Ultrasound echocardiography showed severe MR, asymmetrical septal hypertrophy, systolic anterior movement of the mitral valve anterior leaflet, and left ventricular outflow stenosis. Her LVPG, measured using continuous wave Doppler recording, was 118 mmHg. During heart catheterization, the aortic pressure and left ventricular pressure were simultaneously measured. An intravenous injection of 70 mg cibenzoline decreased the LVPG from 110 mmHg to 16 mmHg. Left ventriculography was performed immediately after the injection and did not show MR. This clearly demonstrates that cibenzoline decreases LVPG in patients with HOCM and also improves the MR that arises from LVPG.
A 90-year-old woman with hypertension developed metabolic alkalosis and myoclonus. Her medications included diltiazem hydrochloride, benidipine hydrochloride, kallidinogenase, procaterol hydrochloride, sennoside, dihydrocodeine phosphate, and KM powder® antacid that contained 354 mg of licorice and 900 mg of sodium bicarbonate per 3.9 g of powder. Endocrinological studies showed slightly reduced plasma renin activity and normal plasma aldosterone concentration. A provisional diagnosis of licorice-induced metabolic alkalosis was established and the patient was successfully treated after correction of serum pH and cessation of the medications. Licorice-induced metabolic alkalosis must be considered in the differential diagnosis of myoclonus.
Elevated parathyroid hormone (PTH) levels and hyperphosphatemia are thought to be associated with the development of calciphylaxis. We report a patient on hemodialysis who developed proximal calciphylaxis with consistently low PTH levels after parathyroidectomy. A 31-year-old man was admitted to our hospital because of abdominal skin ulcerations. Calciphylaxis spread to the penis, and simultaneous progressive lung calcification was evident on chest X-ray, suggestive of pulmonary calciphylaxis on 99mTc-methylene disphosphonate scintigraphy. The patient died of respiratory failure despite intensive treatment including hyperbaric oxygen therapy. This is the first report of a patient on hemodialysis who developed calciphylaxis involving the penis after parathyroidectomy.
We report a case of pulmonary hyalinizing granuloma (PHG) with laryngeal and subcutaneous involvement. A 43-year-old man was admitted to our hospital for assessment of hoarseness. Cervical and chest computed tomography, respectively, revealed a laryngeal tumor and two pulmonary masses. Specimens obtained from the pulmonary masses were compatible with PHG. The histopathology of biopsy specimens from both the laryngeal tumor and a subcutaneous tumor resembled that of the resected lung masses. Although there is no established treatment for PHG, the laryngeal tumor was diminished and all other lesions disappeared with glucocorticoid treatment.
We report a case of acute promyelocytic leukemia (APL) with drug-induced hypersensitivity syndrome associated with Epstein-Barr virus (EBV) infection. A 33-year-old woman was admitted because of APL. After complete remission was obtained with the use of all-trans retinoic acid (ATRA), intensive chemotherapy was administered. She developed high grade fever and severe systemic erythematous eruptions followed by cervical lymphoadenopathy, hepatosplenomegaly, hepatitis and hypotension in a state of myelosuppression during consolidation chemotherapy. Systemic corticosteroids alleviated the symptoms. Since an anti-EB VCA IgM antibody titer was continuously positive, persistent infection of EBV was suspected. In this case, EBV infection may have contributed to the development of drug-induced hypersensitivity syndrome.
Juvenile muscular atrophy of the distal upper extremity (Hirayama disease) is a benign and non-progressive motor neuron disease. Application of a cervical collar is believed to prevent progression of symptoms in the early stages, but there is no effective therapy for the advanced disease. We found that tendon transfer improved the activities of daily living (ADL) of a patient with advanced Hirayama disease. An operative reconstruction can be valuable, even in patients with Hirayama disease who have developed impaired ADL due to extensive intrinsic hand muscle atrophy.