Yoshihiro Matsukawa

Suicide in Patients with Systemic Lupus Erythematosus: A Clinical Analysis of Seven Suicidal Patients

Despite many suicidal cases in patients with systemic lupus erythematosus (SLE), literature on this subject is lacking. To elucidate and prevent this phenomenon, we re-evaluated the clinical records of seven suicidal patients with SLE. Six patients had photosensitivity and insomnia. At the time of the suicide attempt, hypocomplementemia was observed in five of six patients. Diffuse slowing on electroencephalograms were observed in four of five patients. One patient successfully committed suicide while on no therapy while five patients made their attempts under the tapering courses of steroids. Five patients manifested psychoses whereas two patients displayed no psychotic findings. All patients attempted suicide shortly after admission (mean time 20 days). The subsequent courses of the survivors who received more medication were favorable. Therefore, it appears that disease activity was not fully controlled in these patients. Furthermore, signs of an imminent suicide attempt were missed in some cases. Psychosis, insomnia, history of photosensitivity, an incompletely controlled disease state, receiving tapering steroid dose, diffuse slowings on electroencephalograms and the presence of hypocomplementemia appeared to be risks for attempting suicide in SLE. We would recommend that such patients be under psychiatric care for at least 2 months to prevent suicide. When the patient is still psychotic or unstable, further medical care will be required.

Central effect of melatonin against stress-induced gastric ulcers in rats

WE investigated the role of melatonin in the induction of gastric lesions induced by water immersion restraint stress or centrally administered thyrotropin-releasing hormone (TRH). Melatonin (0.1–1 ng) injected intracisternally (i.c.) 30 min prior to stress dose-dependently inhibited the induction of gastric lesions by water immersion restraint stress, while 100 μg/kg, i.p. failed to protect the gastric mucosa. Preadministration of melatonin (1 ng, i.c.) significantly reduced (83%) the severity of gastric lesions induced by a TRH analogue (500 ng, i.c.). Serum melatonin concentrations 30 min after administration of 1 ng melatonin i.c. did not differ from those of rats receiving i.c. vehicle. These results suggest that melatonin plays a protective, anti-stress, role in the gastric mucosa via a mechanism involving the central nervous system.

Antiproteinuric Effect of Angiotensinconverting Enzyme Inhibitors and an Angiotensin II Receptor Blocker in Patients with Lupus Nephritis

Although the effects of angiotensin II receptor blockers (ARBs) on non-diabetic glomerulonephritis have been reported, studies of their effects on collagenvascular diseases, particularly lupus nephritis, are limited. In this retrospective, observational study, systemic lupus erythematosus (SLE) patients (n = 7) with lupus nephritis and uncontrolled proteinuria were treated with an angiotensin-converting enzyme inhibitor followed by the ARB losartan (25–50 mg/day). Urinary protein excretion and renal function were evaluated. After 12 months of losartan, mean urinary protein excretion decreased significantly by 84.8%. Mean systolic and diastolic blood pressures also decreased significantly during the 12 months of losartan treatment, although not in normotensive patients. Complement 4, total complement activity and anti-dsDNA antibody levels, which are indices of SLE activity, and serum creatinine levels, which is an index of renal function, showed no change in response to losartan treatment. A more extensive evaluation of the effects of ARBs in patients with lupus nephritis and poorly controlled proteinuria is required.

Alterations of Quantitative EEG and Mini-Mental State Examination in Interferon-α-Treated Hepatitis C

We have recently observed a diffuse slowing of brain waves using serial quantitative electroencephalographic (qEEG) examinations in interferon (IFN)-α-treated chronic hepatitis C patients. However, it remains unclear how this alteration could be assessed. We evaluated the correlation between the qEEG changes and three tests of mental status, including the Mini-Mental State Examination (MMSE), in such patients. This is the first study to undertake a clinical evaluation of the adverse effects on brain function due to IFN. We undertook blind, prospective and serial qEEG examinations on 56 chronic hepatitis C patients at three independent hospitals. IFN-α was administered intramuscularly at a dose of 9 × 106 IU daily for the first 4 weeks and then 3 times/week for the next 20 weeks. Serial EEGs were obtained before, at 2 and 4 weeks of treatment, and after the IFN-α treatment. The absolute power values of each frequency band in each patient at different stages of treatment were recorded by qEEG. Each patient was assessed by the MMSE, Hamilton Rating Scale for Depression (HSD), and Hamilton Rating Scale for Anxiety (HSA). We statistically evaluated the correlations between the changes in power values and alterations of scores on the mental status tests during IFN-α treatment. The decreased scores observed on the MMSE ranged from 2 to 5 points at both 2 and 4 weeks of IFN-α treatment. There were no significant differences in age distribution for each decreased score on the MMSE. As the alteration in MMSE score during IFN treatment increased, the alteration in absolute power values for the slow waves during IFN treatment increased significantly, while that for the alpha 2 and fast waves during treatment decreased significantly. However, the changes in the HDS and HSA revealed no significant correlations. The alteration of the qEEG was reversible after the treatment. MMSE scores represent one screening method for the clinical assessment of IFN-α-induced alterations of brain function.

Antithymocyte Globulin for a Patient with Systemic Lupus Erythematosus Complicated by Severe Pancytopenia

The clinical use of antithymocyte globulin is rarely reported in patients with rheumatic diseases. We describe the use of this agent in a patient with systemic lupus erythematosus who concomitantly developed severe pancytopenia. High-dose methylprednisolone therapy had been unsuccessful in controlling either the disease exacerbation or the pancytopenia. Antithymocyte globulin and cyclosporin A were therefore administered to achieve immunosuppression. The exacerbation of disease activity was gradually lessened, except for persistent thrombocytopenia and anaemia. Severe and persistent immunosuppression, however, led to a fatal brain abscess. The combined use of both antithymocyte globulin and cyclosporin A induced potent immunosuppression, and should be confined to selected patients with systemic lupus erythematosus, and administered under detailed monitoring.

Helicobacter pylori eradication reduces platelet count in patients without idiopathic thrombocytopenic purpura.

Discrepant outcomes of Helicobacter pylori eradication in patients with idiopathic thrombocytopenic purpura have been reported. Here patients with dyspepsia and no other complications underwent gastroendoscopic examination and evaluation for Helicobacter pylori infection. Helicobacter pylori-infected patients with gastritis and gastric ulcer received eradication therapy: lansoprazole (60 mg/day), clarithromycin (400 mg/day), and amoxicillin (1500 mg/day) for 1 week. Lansoprazole 30 mg/day was administrated additional 7 weeks. Peripheral platelets were counted before treatment, 8 weeks after initiation of therapy, and at follow-up periods. Platelet counts in patients with both gastritis and gastric ulcer were evaluated with reference to the presence of Helicobacter pylori infection. Eighty-seven patients with gastritis and 35 of those with gastric ulcer underwent successful eradication therapy. Peripheral platelet counts in patients with gastritis decreased from 235+/−55 to 228+/−58 (103/µL) (p = 0.0337), and those with gastric ulcer decreased from 248+/−60 to 232+/−48 (103/µL) (p = 0.020) 8 weeks after initiation of therapy. Non-eradicated patients did not show such a tendency. Helicobacter pylori eradication reduced peripheral platelet counts in patients with gastritis and gastric ulcer. Amelioration of thrombocytopenia by eradicating Helicobacter pylori appears to involve mechanisms specific to idiopathic thrombocytopenic purpura.

Efficacy of Lansoprazole against Peptic Ulcers Induced by Nonsteroidal Anti-Inflammatory Drugs: Endoscopic Evaluation of Ulcer Healing

Beyond the obvious step of limiting use of non-steroidal anti-inflammatory drugs (NSAIDs), the treatment of ulcers induced by NSAIDs remains controversial. We evaluated the efficacy of the proton-pump inhibitor lansoprazole on NSAID-induced ulcers. Ulcers were endoscopically diagnosed in 47 NSAID users. These patients received 30 mg/day lansoprazole, orally, for 6 or 8 weeks (6 weeks for duodenal ulcers and 8 weeks for other ulcers). Ulcer healing was assessed using an established classification system. The presence of immunoglobulin G antibody against Helicobacter pylori was also evaluated. The antibody was present in the sera of 51% of patients (24/47). Most of the ulcers reached scarring stages S1 (healing) or S2 (good healing), and the S2 healing rate was 35%. Two H. pylori seropositive patients did not reach these stages; their ulcers were improved by H. pylori eradication therapy, followed, in one case, by medication with misoprostol. Lansoprazole seemed to be useful for most patients with NSAID-induced ulcers, but a few needed additional treatments.

Interstitial pneumonitis possibly due to mitoxantrone

A 41-year-old patient with chronic myelogenous leukemia in the accelerated phase was treated with mitoxantrone. She developed pyrexia 7 days after receiving the third administration of mitoxantrone. After 3 more days, she experienced dry cough and dyspnea. Bilateral fine crackles were audible, but no signs of heart failure were found. A chest X-ray film revealed diffuse reticulogranular infiltrates bilaterally. An increase in the prednisolone dosage led to an improvement. Specimens of the bronchoalveolar lavage revealed an increase in CD4-/CD8- lymphocytes. The peripheral lymphocytes also expressed neither CD4 nor CD8. Specimens of a transbronchial lung biopsy disclosed thickening of the alveolar wall with infiltration of lymphoid cells.

Increased soluble IL-2 receptor in serum of patients with systemic lupus erythematosus.

SummaryWe estimated the concentration of soluble IL-2R (sIL-2R) in the serum of patients with systemic lupus erythematosus (SLE) and examined the relationship between the serum levels of sIL-2R and clinical features or laboratory data. We found that elevated levels of sIL-2R were present in the serum of SLE patients with discoid rash, and sIL-2R concentrations were correlated with the soluble CD4 and soluble CD8 concentrations but not with classical serological marker, anti-DNA antibody or complement titer.

Long term changes in platelet counts after H. pylori eradication in non-ITP patients

Helicobacter pylori eradication is becoming a first-line therapy against idiopathic thrombocytopenic purpura (ITP) and its long term efficacy has already been reported. In contrast, eradication therapy reduced peripheral platelets in non-ITP patients 8 weeks later. To confirm the long term efficacy of Helicobacter eradication on platelet counts in non-ITP patients, we evaluated changes in peripheral platelet counts in endoscopically diagnosed patients with Helicobacter infection. Endoscopically diagnosed patients with Helicobacter infection received eradication therapy using amoxicillin (1500 mg/day), clarithromycin (400 mg/day) and lansoprazole (60 mg/day). The changes in platelet counts after Helicobacter eradication were serially evaluated for as long as 3 years or more. In total, 294 patients were enrolled: 243 patients successfully received eradication therapy and 51 were unsuccessfully treated. As a whole, peripheral platelet counts significantly decreased after Helicobacter eradication, being reduced by more than 1.0 × 109/l by 5–6 months, 1 year, 2 years and 3 years or more (from 24.2+/−5.6 to 23.1+/−5.0, 23.0+/−5.0, 22.1+/−4.5, 22.4+/−5.6, and 21.6+/−5.3 × 109/l: p = <0.0001, <0.0001, 0.0001, 0.0052, and <0.0001, respectively). Helicobacter pylori eradication finally reduced peripheral platelet counts around 2.0 × 109/l in non-ITP patients. There was a definite difference in platelet regulation by Helicobacter pylori between ITP and non-ITP patients. These bivalent effects, upregulation and downregulation, on the peripheral platelet induced by Helicibacter pylori infection appeared to originate from quite different mechanisms.