Prolonged paradoxical reaction requiring over 5 years of corticosteroid administration in a patient with severe tuberculous meningitis.

Tuberculous meningitis (TBM) is a rare disease in low-incidence countries like Japan, where general physicians have fewer experience with TBM. Despite its proper treatment and early improvement of the condition, TBM often causes paradoxical reactions (PRs), which can lead to severe complications such as stroke. As PRs in the brain are difficult to detect without regular neuroimaging surveillance and have a later onset than in other organs, delayed treatment can be fatal. We report a case of a 54-year-old, human immunodeficiency virus (HIV)-negative man who presented with TBM and miliary tuberculosis (TB) in an unconscious state. Standard anti-tuberculous therapy with adjunctive systemic high-dose dexamethasone brought rapid clinical and microbiological improvement, which allowed the dexamethasone to be tapered. However, he developed cerebral infarction with left hemiplegia due to a TBM-related PR five months after admission. Therefore, the initial high-dose dexamethasone was again added to the anti-tuberculous drugs, achieving the significant effects on the PR-related lesions. Anti-tuberculous drugs had been administered for 3 years and the dexamethasone was carefully tapered. Nevertheless, enlargement of PR-related lesions in the brain recurred 5 years later. Accordingly, the dose of corticosteroid was again increased, resulting in resolving the lesions. It is important to note that severe TBM may cause prolonged PRs, which require a long-term neuroimaging follow-up and anti-inflammatory drugs for the successful management of the TBM-related PR.

The challenge of differentiating tuberculous meningitis from bacterial meningitis.

Tuberculous meningitis (TBM) is a rare but important differential diagnosis in patients with impaired consciousness. Here, we describe a case of TBM in an 83-year-old Japanese woman who presented to a local hospital with fever and decreased consciousness of 20 days' duration (from day -40). She was started on treatment for bacterial meningitis due to an increased cerebrospinal fluid cell count, but her condition did not improve. She was transferred to a second hospital on suspicion for cholecystitis, then to a university hospital when consciousness did not improve and finally to us at a fourth hospital. On day -2, diffuse granulation was seen in both lung fields on chest computed tomography, sputum Mycobacterium test was positive and adenosine deaminase was elevated in spinal fluid. We diagnosed TBM secondary to miliary tuberculosis and started treatment with steroids and anti-tuberculous drugs (day 0). However, her level of consciousness did not improve and she died at a sanatorium on day 178. Delayed treatment of TBM has a prognostic impact and should be kept in mind as a differential diagnosis for impaired consciousness.

Progressive plasterer's pneumoconiosis complicated by fibrotic interstitial pneumonia: a case report.

BACKGROUND: Although the prevalence of pneumoconiosis has been decreasing due to improvements in working conditions and regular health examinations, occupational hygiene measures are still being established. Plasterers encounter a number of hazardous materials that may be inhaled in the absence of sufficient protection. CASE PRESENTATION: A 64-year-old man who plastered without any dust protection for more than 40 years was referred to our hospital with suspected interstitial pneumonia. Mixed dust pneumoconiosis and an unusual interstitial pneumonia (UIP) pattern with fibroblastic foci were diagnosed by video-assisted thoracoscopic surgery, and an elemental analysis detected elements included in plaster work materials. Despite the cessation of plaster work and administration of nintedanib, the patient developed advanced respiratory failure. CONCLUSION: Plasterers are at an increased risk of pneumoconiosis and may have a poor prognosis when complicated by the UIP pattern. Thorough dust protection and careful monitoring are needed.

[IMPACT OF COEXISTING NONTUBERCULOUS MYCOBACTERIA DURING THE TREATMENT OF PULMONARY TUBERCULOSIS].

BACKGROUND: Nontuberculous mycobacteria (NTM) are often detected in patients undergoing treatment for pulmonary tuberculosis. This clinical status is thought to represent NTM disease, contamination, or colonization, but discriminating between these three conditions is difficult. PURPOSE: We examined the clinical characteristics and pathogenicity of coexisting NTM among patients with pulmonary tuberculosis, as well as its impact on clinical practice. PATIENTS AND METHODS: The subjects comprised 59 patients with pulmonary tuberculosis treated at the National Hospital Organization Utsunomiya National Hospital between January and December 2013. Patients in whom NTM was detected in one or more cultures were defined as the NTM group (19 patients), and they were compared to the non-NTM group (40 patients). Antiglycopeptidolipid (anti-GPL) core antibody titers were investigated in 18 patients from the NTM group. RESULT: We observed no significant difference in patient characteristics (age, sex, complications, history of pulmonary tuberculosis, lung disease, chest imaging findings, degree of smear positivity on admission) between the two groups. Mean duration of hospitalization was markedly longer for the NTM group, excluding those with coexisting NTM after discharge (98.8 ± 7.9 days), than for the non-NTM group (58.3 ± 3.5 days; p < 0.001). No anti-GPL core antibodies were detected in any of the 18 patients from the NTM group, including 13 patients who fulfilled the ATS/IDSA criteria. CONCLUSION: Coexisting NTM observed during treatment for tuberculosis likely results from colonization or contamination and usually has low pathogenicity. However, this finding is related to prolonged hospitalization.

[A case of drug-induced hypersensitivity syndrome caused by levofloxacin used for treating pulmonary tuberculosis].

The patient was a 27-year-old man with pulmonary tuberculosis, who was initially treated with isoniazid, rifampicin, ethambutol, and pyrazinamide. However, because of hepatic dysfunction and visual impairment, the four-drug therapy was switched to a three-drug regimen with isoniazid, rifampicin, and levofloxacin. At 9 weeks after the initiation of levofloxacin, the patient developed cervical lymphadenopathy, fever, systemic erythema, and hepatic dysfunction. He was diagnosed with drug-induced hypersensitivity syndrome (DIHS) based on positive results in the human herpesvirus (HHV)-6 DNA test, an indicator of HHV-6 reactivation. The symptoms improved after withdrawal of the antituberculosis drugs and initiation of steroid administration. However, considering the risk of relapse of DIHS, the tuberculosis treatment, which was initially planned for 9 months, was stopped at 7 months. Neither DIHS nor tuberculosis recurred.

Effects of new calcium channel blocker, azelnidipine, and amlodipine on baroreflex sensitivity and ambulatory blood pressure.

The effect of dihydropyridine calcium channel blocker (CCB) on baroreflex sensitivity (BRS) is not well described. We studied the effect of a new CCB, azelnidipine, compared with amlodipine, on BRS and ambulatory blood pressure (BP) in newly diagnosed untreated hypertension. This study was a prospective, randomized, and open-label study. We randomized patients to either azelnidipine or amlodipine treatment. Azelnidipine 8 to 16 mg (average 14.5 mg) and amlodipine 2.5 to 7.5 mg (average 4.9 mg) were used to lower the clinical BP <140/90 mm Hg. BRS, evaluated by the spontaneous and the Valsalva methods, and clinical and ambulatory BP were evaluated at baseline and after 13 weeks of each treatment. A total of 47 patients (age 53.1 +/- 10.8 years, 51% male), 26 in the azelnidipine group and 21 in the amlodipine group, completed the study. For baseline and after therapy respectively, both Valsalva-BRS (4.8 +/- 1.7 vs. 8.4 +/- 3.1 msec/mm Hg, P = 0.001) and spontaneous-BRS (5.5 +/- 2.5 vs. 8.2 +/- 5.6 msec/mm Hg, P = 0.019) were increased by azelnidipine, but amlodipine did not change them. Clinical and awake BPs were similarly reduced by each drug therapy. In conclusion, BRS was increased by azelnidipine therapy, but not by amlodipine therapy. This differential effect may be important in cardiovascular risk reduction.

Comparison of the effects of pioglitazone and metformin on insulin resistance and hormonal markers in patients with impaired glucose tolerance and early diabetes.

Impaired glucose tolerance (IGT) is associated with cardiovascular risk factors, but the effects of pioglitazone and metformin on IGT are not well described. We tested the hypothesis that each drug would exhibit antiatherogenic and anti-inflammatory effects in subjects with IGT and early diabetes. The study design was a prospective, randomized, open label, cross-over study. Blood tests, including a 75-g oral glucose tolerance test (OGTT), were performed at baseline and after each treatment. Pioglitazone 15 mg/day or metformin 500-750 mg/day was given for 3 months. Biochemical markers to assess insulin resistance as well as lipid, inflammatory, neurohumoral, and hemostatic factors were included. Twenty-five subjects (17 male, 8 female; age [mean+/-SD]: 61+/-9 years; 84% hypertensive) completed the protocol. Of 25 subjects, 14 were diagnosed as IGT and 11 as diabetes with 75-g OGTT. Pioglitazone significantly reduced fasting glucose (p<0.05), and homeostasis model assessment of insulin resistance (HOMA-IR) (p<0.05) and metformin (p<0.01) reduced cholesterol. Both drugs significantly reduced aldosterone (both p<0.05) and von Willebrand factor (vWF) (both p<0.05). Plasma adiponectin was increased only by pioglitazone (p<0.001). Neither drug affected BP levels. In conclusion, pioglitazone was superior to metformin for the improvement of insulin resistance and adiponectin, and both drugs were equally effective in reducing vWF and aldosterone in subjects with IGT and early diabetes. Early intervention with pioglitazone or metformin therapy may reduce the incidence of future cardiovascular disease in subjects with impaired glucose tolerance or early diabetes.

A case of vertebral artery dissection associated with morning blood pressure surge.

We report a case of a middle-aged man who suffered a cerebral infarction resulting from dissection of a vertebral artery associated with morning blood pressure surge. A 56-year-old man was transferred to our hospital with dizziness and vomiting in the early morning on a cold day in winter. He reported that he had been standing in front of the sink after bathing when he suddenly felt dizzy and fell down. He did not lose consciousness, and by the time he reached the hospital by ambulance, his dizziness had subsided, but he complained of severe headache and vomited 3 times. On admission, he was alert, and there were no neurological or radiological abnormalities (CT, MR angiography) in the brain. However, infarction in the left cerebellar hemisphere was detected by brain MRI on the 5th day of hospitalization. String sign of the left vertebral artery was noted by angiography, confirming the diagnosis of dissection of the left vertebral artery. Ambulatory blood pressure monitoring was performed after discharge. Although the mean 24-h blood pressure was in the normal range, a marked morning blood pressure rise was observed. We speculated that the acute rise of blood pressure in the early morning might have contributed to the dissection of the vertebral artery.