Diffuse alveolar haemorrhage (DAH) is a serious complication of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). A literature review was performed to ascertain the diagnostic features, treatment, and outcome of this rare but serious condition. Haemoptysis and dyspnoea are common but non-specific features. Chest radiography is usually abnormal, and high-resolution computerised tomographic scanning is more sensitive. Increased uptake of inhaled carbon monoxide and reduced clearance of C15O on lung function testing is suggestive of intra-alveolar blood. Fiberoptic bronchoscopy and bronchoalveolar lavage are useful when a super-added infection is suspected. Concurrent renal disease is common and contributes to the morbidity and mortality. Treatment should be individualised, and it is based on glucocorticoid and cyclophosphamide induction with azathioprine maintenance. The role of plasmapheresis is unclear, and is currently being evaluated. Patients are at risk of disease and treatment-related long-term complications. Ongoing research into the most efficacious therapeutic regimens associated with the least side effects is especially important.
Objective The calcineurin inhibitor tacrolimus has been shown to be safe and effective as salvage therapy for steroid-refractory ulcerative colitis (UC). Since differences in the onset of action between various agents are thought to influence the achievement and maintenance of disease remission, top-down or accelerated step-up therapy with tacrolimus may be useful. However, the efficacy of tacrolimus in moderate to severe UC patients not receiving concomitant steroids remains unknown. Methods Ten patients (11 attacks) with active, moderate to severe UC were treated with oral tacrolimus at a dose of 0.1 mg/kg body weight daily. The dosages were adapted to maintain trough whole-blood levels of 10 to 15 ng/mL to induce remission and 5 to 10 ng/mL to maintain remission. Lichtiger scores, the incidence of adverse effects (serum creatinine and glucose) and long-term outcomes were assessed. Results At four weeks after the initiation of tacrolimus therapy, clinical remissions were observed for eight attacks (72.7%) and clinical responses were demonstrated for three attacks. At 12 weeks after the initiation of tacrolimus treatment, clinical remissions were achieved for nine attacks (90%). After a mean follow-up of 10.4 months, clinical remissions were maintained for eight of 11 attacks. During the tacrolimus treatment, the serum creatinine and glucose levels were not significantly elevated. Conclusion Oral tacrolimus is a safe and effective therapy for the treatment of moderate to severe UC in patients not receiving concomitant treatment with systemic steroids. Although further studies are required to establish the efficacy and safety of oral tacrolimus therapy in patients with UC, oral tacrolimus may represent a top-down or accelerated step-up treatment option for patients with moderate to severe UC.
Objective Brachial-ankle pulse wave velocity (baPWV) is a measure of arterial stiffness. However, precisely how aging, hypertension and other factors influence this in progressively stiffening large arteries, especially in older adults, remains uncertain. We examined changes in arterial stiffness in a population of active older Japanese adults using a five-year follow-up cohort study. Methods Comprehensive geriatric assessments were performed in socially active adults over the age of 70 years at The Life Planning Center Clinic in Tokyo. Clinically acceptable baPWV measurements at baseline and at the end of the study were obtained in 257 individuals (115 men, baseline mean age of 78±4 years; 142 women, baseline mean age of 77±4 years) classified into four groups based on the use of antihypertensive interventions at the end of the study: Group 1 (112 normotensives), Group 2 (49 hypertensives without medication use), Group 3 (39 hypertensives with medication use initiated during the follow-up period) and Group 4 (57 hypertensives receiving medications throughout the follow-up period). Results During the follow-up period, Group 1 exhibited no changes in blood pressure with increases in baPWV. Group 2 exhibited increases in blood pressure and baPWV. Both Groups 3 and 4 exhibited decreases in blood pressure without any changes in baPWV. Other factors such as age, gender and the hemoglobin level could also have influenced baPWV. Conclusion Arterial stiffness increases with aging; however, antihypertensive medications were found to provide protective effects against the development of arterial stiffness during a five-year follow-up period. Other factors that modify baPWV were also identified.
Objective Premature graying or whitening of the hair may possibly represent premature atherosclerotic changes as a surrogate marker of different host responses to cardiovascular risk factors (CVRFs). This study was undertaken to test whether carotid artery intima-media thickness (CIMT) as a validated surrogate marker of the severity and extent of coronary artery disease (CAD) is higher in subjects with prominent signs of hair whitening, independent of chronological age and other CVRFs. Methods The current study was conducted in young and middle-aged patients (<55 years age) without a history of cardiovascular disease. Two hundred and two eligible patients consecutively admitted to our outpatient clinic for CVRF management were included. A gray/white-hair scale was used to determine the percentage of hair whitening. Results In the groups determined according to the degree of hair whitening, age (p<0.001), waist circumference (p=0.011), the presence of hypertension (p=0.003), the uric acid levels (p=0.008), the C - reactive protein levels (p=0.002) and CIMT (p<0.001) were significantly different. When we performed multivariate analyses to determine the independent predictors of CIMT and hair whitening, CIMT was found to be related to age, waist circumference, the levels of uric acid, bilirubin and gamma-glutamyl transpeptidase, the presence of a family history of CAD and hair whitening, while hair whitening was found to be related to age, hypertension, the bilirubin level and CIMT. Conclusion Our findings suggest that premature hair whitening intensity is independently related to CIMT. In cumulative assessments of CVRFs on the human body, the presence of premature hair whitening may be useful in identifying individuals with an increased risk of cardiovascular disease.
Objective The associations between atrial fibrillation (AF) or complete right bundle branch block (RBBB) and other laboratory tests have not been examined sufficiently in healthy populations. Methods These associations were examined with multivariable logistic regression analyses using data from 6,381 apparently healthy subjects including 46 subjects with AF and 100 subjects with RBBB. Results The mean age, body mass index (BMI), hemoglobin, the prevalence of male sex and a history of coronary heart disease (CHD) were significantly higher in subjects with AF or RBBB than without. The odds ratio (OR) (95% confidence interval (CI)) of AF was 1.62 (1.28-2.05) p<0.0001 for each 1 g/dL increment of hemoglobin and 1.07 (0.36-3.21) p=0.90 and 4.32 (1.29-14.43) p=0.017, respectively for the second and the third tertiles of hemoglobin compared with the first tertile after adjusting for sex, age, BMI, CHD, and other confounding covariates. The OR (95% CI) of RBBB was 1.53 (1.32-1.77) p<0.0001 for each 1 g/dL increment of hemoglobin and 2.53 (1.06-6.00) p=0.036, 3.10 (1.12-8.61) p=0.030, and 4.03 (0.91-17.82) p=0.066, respectively, for the second, third, and fourth quartiles of hemoglobin compared with the first quartile after adjusting for sex, age, BMI, CHD, and other confounding covariates. Conclusion An increased blood levels of hemoglobin was independently associated with AF and RBBB after adjusting for sex, age, BMI, CHD, and other confounding covariates in apparently healthy subjects.
Objective The prognosis of patients with hypertensive emergencies has recently improved dramatically owing to the development of effective antihypertensive therapy. We examined the histological and clinical features of patients with hypertensive emergency-related nephropathy. Methods Twelve patients (11 men and one woman) were diagnosed as having hypertensive emergencies with acute renal failure according to the Joint National Committee-7 classification of blood pressure for adults and underwent renal biopsies at our hospital between 1995 and 2008. These patients were enrolled in this retrospective study. Results The age of the subjects was 40.1±9.8 years. At presentation, the mean systolic/diastolic blood pressure was 232±32/146±12 mmHg and none of the patients were being treated with antihypertensive drugs, although 10 patients had histories of hypertension. The mean serum creatinine level was 6.1±4.7 mg/dL. All 12 patients showed left ventricular hypertrophy on echocardiography. On light microscopy of the renal biopsy specimens, all 12 patients showed onion skin patterns of the arterioles; however, no fibrinoid necrosis of the small arteries was found. Electron microscopy revealed electron-lucent widening of the subendothelial zone of the glomerular capillary walls in seven patients. One of the 12 patients did not respond to medical therapy and required regular dialysis. The other 11 patients responded to treatment. Conclusion An onion skin pattern of the arterioles is the most frequent histological finding in patients with hypertensive emergency-related nephropathy. Long-standing hypertension might contribute to this arteriolar change, since left ventricular hypertrophy was also seen in these patients. With strict control of hypertension using antihypertensive medications, the prognosis of patients with hypertensive emergency-related nephropathy can be improved.
Objective Acute promyelocytic leukemia (APL) is characterized by the proliferation of blasts with distinct morphology and promyelocytic leukemia-retinoic acid receptor alpha (PML-RARA) transcripts. Although the treatment outcome is dramatically improved by all-trans retinoic acid (ATRA), life-threatening bleeding from enhanced fibrinolytic-type disseminated intravascular coagulation (DIC) remains a serious clinical problem, and a standard treatment has not been established. However, recent reports indicate that recombinant human soluble thrombomodulin (rTM) is effective against DIC. Methods To elucidate the clinical characteristics and outcomes of DIC resulting from APL, we retrospectively analyzed 10 patients with DIC resulting from APL at our institution over a six year period. Of the 10 patients, four were treated with serine protease inhibitors (SPI) and six were treated with rTM. The diagnosis of DIC was based on the diagnostic criteria of the Japanese Ministry of Health and Welfare. In addition to treating APL with ATRA, rTM was administered for six consecutive days. Results The DIC was resolved within seven days after initiating treatment in 25.0% (1/4) of the patients in the SPI group and 66.6% (4/6) of the patients in the rTM group. Although the rTM group consisted of patients with life-threatening bleeding who required RCC transfusion, a prompt resolution rate and reduced DIC score without progression of bleeding was achieved in this group. All patients were alive after the 28-day observation period. Conclusion Based on the present findings, rTM administration may be an effective, safe, and feasible therapeutic modality, producing a rapid resolution without progression of hemorrahage.
Objective The feasibility and efficacy of high-dose melphalan (HD-MEL) followed by autologous hematopoietic stem cell transplantation (auto-SCT) in elderly patients with multiple myeloma (MM) are discussed. Methods We retrospectively analyzed and compared the results of 25 elderly patients (aged 65-76 years, elderly group) and 63 control patients (aged 51-64 years, control group). Many patients received a vincristine and doxorubicin combined with dexamethasone (VAD) regimen (elderly group: 92%, control group: 78%) with autologous peripheral blood stem cells being harvested after the administration of chemotherapy with high-dose cyclophosphamide (elderly group: 72%, control group: 87%). Ten elderly patients received MEL at a dose of 100-120 mg/m2, while 15 patients received MEL at a dose of 180-200 mg/m2. Results Treatment-related deaths occurred in one elderly patient and two younger patients due to infections. The rate of achieving complete response (CR) or very good partial response (VGPR) was 60% in the elderly group and 83% in the control group. Progression-free survival from auto-SCT in the elderly group was similar to that observed in the control group (median 17.1 vs. 20.8 months, p=0.26), with the median overall survival (OS) from auto-SCT being 40.8 months in the former and 72.5 months in the latter group (p=0.07). When calculated from the beginning of induction treatment, the median OS of the elderly group was 47.0 months and the 3-year OS rate was 81%. Conclusion The current study provides evidence for the efficacy of auto-SCT in elderly MM patients. A prospective study of auto-SCT in elderly patients using strict eligibility criteria is required to evaluate the prolongation of survival in the era of novel agents.
A 65-year-old man was referred to our hospital due to an acute onset of dyspnea and persistent fever. Echocardiography revealed an ejection fraction (EF) of 25% with diffuse severe left ventricular (LV) dysfunction. 18F-fluorodeoxy glucose-positron emission tomography imaging showed significantly increased uptake by the LV and right ventricular walls, indicating active inflammation. The histologic findings of the endomyocardial biopsy specimens indicated the presence of epithelioid cell granuloma. The final diagnosis was thus cardiac sarcoidosis with acute inflammation. Five-months after the initiation of steroid therapy, echocardiography showed an EF of 50%. This is a rare case in which acute inflammation led to acute heart failure mimicking acute myocarditis.
A man in his late seventies was suffering from right-sided pleural effusion and worsening leg edema. He was diagnosed with a rare case of secondary protein-losing enteropathy caused by constrictive pericarditis (CP) using technetium 99m-labeled human serum albumin abdominal scintigraphy and comprehensive Doppler echocardiography. We herein report the importance of evaluating a low cardiac output in addition to established Doppler echocardiographic findings for making a diagnosis of CP coexistent with protein-losing enteropathy.
Calcium antagonists, nicorandil and long-acting nitrates are highly effective for preventing coronary spasm. The withdrawal of coronary vasodilators, especially calcium antagonists, is risky in cases of vasospastic angina. We herein present a case of cardiopulmonary arrest that occurred due to coronary spasm triggered by the discontinuation of coronary vasodilators during the peri-operative period of gastrectomy. Vasospastic angina patients who are not able to take oral coronary vasodilators in the peri-operative period should be maintained on a parenteral vasodilator until they are able to take them orally. Physicians should also be aware of the possible development of nitrate tolerance in patients on prolonged nitrate therapy.
11β hydroxylase deficiency (OHD) is one of the main causes of congenital adrenal hyperplasia. There have been only a few reported cases of nonclassic 11β OHD, a milder form of the disease. It is difficult to detect occult nonclassic 11β OHD because patients present with no or mild symptoms. We herein present a case of thyrotoxic periodic paralysis (TPP) with Graves' disease leading to the discovery of a hidden nonclassic 11β OHD. In this case, increased levels of thyroid hormone seem to have induced symptoms of occult nonclassic 11β OHD and aggravated TPP.
Glucocorticoid-induced hyperglycemia is common in patients with or without known diabetes mellitus. Exenatide, a glucagon-like peptide-1 receptor agonist, improves glycemic control without causing weight gain or hypoglycemia and is currently widely used in patients with type 2 diabetes mellitus. We herein report four cases of patients with type 2 diabetes with worsened glycemic control due to glucocorticoids who were successfully treated with exenatide administration.
A 32-year-old male with CATCH22 syndrome presented with a high fever and productive cough after taking drugs for acute bronchitis, including L-carbocisteine. Chest radiography revealed ground-glass opacities in the bilateral lung fields. He had a history of similar pneumonia. Under the assumption of drug-induced pneumonia, or bacterial or viral pneumonia, all drugs including L-carbocisteine were discontinued, and antibiotics were started. A drug-induced lymphocyte stimulation test was positive only for L-carbocisteine. The only drug in common between this and the previous episode of pneumonia was L-carbocisteine. We thus concluded that this was a definite case of L-carbocisteine-induced pneumonia in a patient with CATCH22 syndrome.
Bacillus cereus (B. cereus) is a Gram-positive rod that is widely distributed in the environment and can be a cause of food poisoning. We herein present a case of B. cereus necrotizing pneumonia in a patient with nephrotic syndrome under corticosteroid treatment after developing transient gastroenteritis symptoms. B. cereus was isolated from bronchial lavage fluid and transbronchial biopsy specimens. A multiplex polymerase chain reaction analysis of the toxin genes revealed a strain possessing enterotoxicity. The patient recovered after one week of intravenous meropenem followed by a combination of oral moxifloxacin and clindamycin. B. cereus is a pathogen that causes necrotizing pneumonia in immunocompromised hosts.
Investigations completed in a 77-year-old ex-smoker presenting with weight loss showed raised CA 19-9 levels. The findings of chest radiograph, abdominal computed tomography (CT) and gastrointestinal endoscopic examinations were all normal. On follow-up, the patient developed left upper lobe collapse on chest radiograph with increasing CA 19-9 levels. Chest CT findings suggested the presence of a left upper lobe tumour. The results of a biopsy of the left upper lobe nodule seen on bronchoscopy suggested a diagnosis of amyloidosis; however, this was not the only diagnosis. The left upper lobe mass comprised a neuroendocrine tumour with amyloid deposition just beneath the bronchial epithelium and focally between the nests of the tumour cells. We report and discuss this uncommon association and presentation.
Posterior reversible encephalopathy syndrome (PRES) is a known but extremely rare side effect of bortezomib therapy. An unusual case of PRES possibly caused by bortezomib during induction treatment in a patient with multiple myeloma is reported. The patient experienced neither hypertensive crisis nor uremic encephalopathy at the onset of PRES, which are both well-known etiologies of PRES. The patient's PRES-related symptoms resolved completely after discontinuation of bortezomib and administration of a bulk dose of corticosteroids. The importance of early recognition of this potential neurological complication must be emphasized because this new drug is being increasingly prescribed.
We herein report the case of a 75-year-old woman with a paradoxical cerebral air embolism (CAE). She developed a bilateral visual disturbance at the time of needle puncture during a computed tomography (CT)-guided percutaneous needle lung biopsy in the face down position. The air density within the descending aorta on chest CT suggested the presence of a cerebral air embolism. Brain MRI demonstrated increased signal intensity in the bilateral occipital lobes on diffusion-weighted images. Usually, CAE occurs predominantly in the right hemisphere for anatomical reasons. The face down position and the anatomical features of the right subclavian artery, which diverges backward from the brachiocephalic artery, might explain such a unique distribution of CAE in this patient.
The case of a Japanese sialidosis type I patient with a novel NEU1 gene mutation is described. The patient developed an unsteady gait at age 14 and was referred to our hospital at age 16. On admission, subnormal intelligence, dysarthria, myoclonus, intentional tremors, limb and gait ataxia, hyperreflexia and macular cherry-red spots were observed. An enzymological analysis revealed a primary deficiency of neuraminidase. An NEU1 gene analysis identified two heterozygous missense mutations: p.P80L and p.D135N. The p.D135N mutation is a novel mutation that is considered to be associated with the mild clinical phenotype of sialidosis. Serial brain MRI showed diffuse brain atrophy progressing rapidly over the 41-month observation period.
Crohn's disease (CD) is a chronic inflammatory disorder of the gastrointestinal tract that is frequently accompanied by systemic complications. Neuropathologies have not been well investigated as extraintestinal manifestations of CD. We herein report the case of a 36-year-old man with CD who presented with progressive weakness and numbness. A neurological examination and the results of a nerve conduction study and a sural nerve biopsy led to a diagnosis of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Plasma exchanges were initially effective; however, the effects gradually declined starting 10 days after the plasma exchange (PE). These results suggest that humoral factors may play an important role in CIDP associated with CD.
We herein report the case of a 77-year-old man admitted for an acute cutaneous infection and persistent fever. A physical examination revealed systemic small blisters and scrotal swelling. He was suspected of having complications from chickenpox or bullous impetigo as the initial diagnosis. Nocardia was detected on an aspiration biopsy of the small blisters and the surgically removed testis at a later date. Testicular nocardiosis is a rare condition; however, we should consider nocardiosis in the differential diagnosis because delay in providing treatment may worsen a patient's general condition.
A 76-year-old woman on hemodialysis (HD) presented with pain and swelling in the left wrist and forearm. The osteomyelitis occurred in the part of the ulna adjacent to the arteriovenous fistula. Mycobacterium tuberculosis was identified in pus obtained from the left forearm, leading to a diagnosis of tuberculous osteomyelitis. The patient was treated with anti-tuberculous drugs and her symptoms improved. In this study, we report a case of tuberculous osteomyelitis occurring in the ulna, which is not the usual site of predilection for tuberculosis infection. As HD patients exhibit a high frequency of extrapulmonary tuberculosis, tuberculous osteomyelitis should be considered in the differential diagnosis of infectious osteomyelitis. In addition, it may be useful to perform stab cultures at an early stage in order to diagnose tuberculous osteomyelitis.
An emphysematous liver abscess is a fatal condition that often occurs in patients with uncontrolled diabetes mellitus. I herein describe two cases of Klebsiella pneumoniae-induced emphysematous liver abscesses complicated by septic pulmonary emboli in patients with poorly controlled diabetes mellitus. Both patients showed hemoglobin A1c levels of more than 10% and did not present with any abdominal symptoms on admission. However, they were diagnosed and successfully treated with percutaneous transhepatic abscess drainage and antibiotics. This fatal disease should be taken into consideration in patients with uncontrolled diabetes mellitus who suffer from prolonged fevers and uncharacteristic general malaise.
The case of a 66-year-old woman with untreated diabetes mellitus who was admitted to our hospital with a fever, hypotension and an altered mental status is herein reported. Computed tomography revealed bilateral emphysematous pyelonephritis along with a splenic abscess. Blood and urine cultures grew Escherichia coli. Treatment with systemic antibiotics combined with the insertion of percutaneous and renoureteral catheters was successful. The patient was discharged and completed treatment without developing any subsequent complications.
Necrolytic migratory erythema is an obligatory paraneoplastic syndrome. Here we describe a patient with a neuroendocrine tumor of probably pancreatic origin. She developed the typical skin lesions under chemotherapy with temozolomide and capecitabine.