An autopsy case of Degos disease with neurological symptoms--neuropathological observations and increased platelet aggregation]

We reported clinical and neuropathological observations of a 41-year-old man with Degos disease. He first noted painless skin lesions over the upper extremities in January, 1982. Three years later he was diagnosed as Degos disease by skin biopsy, and treatment with aspirin was started. In September, 1985, he complained of paresthesia on his right arm, followed by a series of new neurological manifestations suggesting multifocal spinal cord lesions. On October 28, examination of admission showed papules with central umblication over the whole body except the head, face, palms, soles and scrotum. Neurological examination revealed no weakness, diminished right biceps reflex, exaggerated patellar reflexes and Achilles reflexes, left extensor plantar reflex, hypesthesia and hypalgesia to the level of Th8, mild left spastic gait, and retention of urine. In November, he had paraparesis, loss of vibration sense of lower extremities, hypesthesia and hypalgesia to the level of TH4, and weakness of right upper extremity. In December, he showed tetraplegia, left-sided facial palsy, and hypesthesia and hypalgesia to the level of C5. In January, 1986, he showed right facial palsy, left facial hypesthesia, pseudobulbar palsy. In February, he had bilateral abducens nerve palsy and hiccups. On February 18, he died of intracranial hemorrhages. He had episodic abdominal pain several times during admission. His condition deteriorated progressively in four months after the first manifestation of neurological symptoms, despite the therapy with heparin, urokinase, ticlopidine, dipyridamole, and prednisolone. Laboratory studies showed gradual increase of CSF proteins (from 156 mg/dl to 602 mg/dl) and extremely increased platelet aggregation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Delayed sternal closure after cardiac surgery]

Following cardiac surgery, approximation of sternum will produce systemic hypotension or elevation of left atrial and central venous pressures. A new criteria for delayed sternal closure is proposed. Sternal closure has to be delayed when mean left atrial or central venous pressures increased over 2 mmHg at the tentative closure. In seven cases (3.5%) of consecutive 201 patients was delayed the sternal closure under the above mentioned state, all survived and received the successful closure later. One of them died of congestive heart failure four months after the operation and one died of the rupture of the ascending aortic pseudoaneurysm eleven months after the initial operation. Microbiological examination of the mediastinal and pericardial contents obtained at the final sternal closure were negative in all cases. Comparing the total cardiopulmonary bypass time, ventricular fibrillation time, and myocardial ischemic time between in the secondary closure group and in the primary closure group, the total bypass time and the ventricular fibrillation time of the former were significantly longer than the latter, but the ischemic time revealed no difference. In conclusions, persistent elevation of left atrial or central venous pressures after cardiac surgery at the tentative sternal closure seems the reliable predictor for the delayed closure of the sternum. Careful post-operative management prevents serious mediastinal infection. Delayed sternal closure is preferable procedure for the patient with brittle hemodynamics after open heart surgery.     

The clinical significance of eosinophils in urine]

The clinical significance of eosinophils in urine was examined. Eosinophils were found in 9 out of 10 cases of interstitial cystitis, and there were more than 50 eosinophils in 50 fields in 6 of these cases. Although the number of eosinophils almost correlated with the number of leucocytes, the relationship between eosinophils and leucocytes in interstitial cystitis was different in acute and chronic cystitis. Since urinary eosinophils could be observed in cases of interstitial cystitis in which leucocytes were as low as 3 to 10 per field and the number of eosinophils was not decreased by chemotherapy, the urinary eosinophils in interstitial cystitis may be of allergic significance and reflect eosinophilic infiltration into the bladder wall.     

An Autopsied Case of Interferon Encephalopathy

Abstract: A 78-year-old male with renal carcinoma was treated with a high dose infusion of interferon-alpha (IFN-alpha) for eight months. The patient had evidence of organlc brain syndrome such 88 : dysfunction of memory, slowing of behavior, and development of mental confusion that appeared eight months after the treatment. MRI at the time of mental confusion revealed difise white matter lesions. Neuropathologic findings were compatible to Binswanger's disease and Senile Dementia of Alzheimer Type (SDAT), Preexisting neurologic abnormalities including intracerebral arteriosclerosis and cerebral atrophy may increase susceptibility to unacceptably severe IFN neurotoxicity.     

Neuropathology of progressive multifocal leukoencephalopathy]

Progressive multifocal leukoencephalopathy (PML) is caused by opportunistic infection of JC virus which belongs to Papovavirus, and presents with progressive demyelinating lesion in the central nervous system. PML was originally reported as a rare complication of hematologic disorders, but later greatly increased in number in association with acquired immunodeficeincy syndrome (AIDS). Original neuropathological features of PML consist of demyelination lacking inflammatory reaction or necrosis, accompanying oligodendroglial nuclear inclusions in the periphery of demyelination. The lesion is preferentially localized to gray-white junction of the cerebral hemisphere and manifests as characteristic demyelinating lesion, called scallopping. Detection of JC virus is essential for the final diagnosis of PML and is achieved via immunohistochemical detection of JC virus with antibodies raised against their components, ultrastructural demonstration of virions characteristic of JC virus, or detection with in-situ hybridization of the genome of JC virus. JC virus can replicate only in oligodendroglial cells, but astrocytes are frequently infected by the virus. The resume of immunological function through therapeutic intervention develops new pathology in PML, exhibiting severe inflammatory reaction with edema and necrosis. This new pathological feature is called immune reconstruction syndrome and clinically presents with severe progression in symptoms of the central nervous system. Nevertheless, treatment of PML is directed for the elimination of the viruses by host immune system. The modification of the above immune reconstruction syndrome is essential for successful outcome of such therapeutic trial.     

Mucosal interleukin-1β production and acid secretion in enlarged fold gastritis

Background : We have previously shown that eradication of Helicobacter pylori increases acid secretion in H. pylori -associated enlarged fold gastritis.
Aim : To investigate whether locally produced interleukin-1β is possibly involved in the inhibition of acid secretion in H. pylori gastritis.
Methods : IL-1β release from the gastric body mucosa was determined by short-term culture of biopsy specimens in 13 patients with enlarged fold gastritis (all H. pylori -positive), five H. pylori -positive and 10 H. pylori -negative patients without enlarged folds. The acid-inhibitory effect of locally produced IL-1β was examined by [¹⁴C]-aminopyrine uptake assay using isolated rabbit gastric glands.
Results : IL-1β release was significantly greater in patients with enlarged fold gastritis, significantly correlated with both basal and tetragastrin-stimulated acid outputs in the H. pylori -positive patients ( r  = −0.591 and r  = −0.641, respectively; P  < 0.01), and significantly decreased with concomitant increases in acid secretions after eradication of H. pylori . [¹⁴C]-aminopyrine uptake was inhibited by IL-1β in a dose-dependent manner.
Conclusions : Increased production of IL-1β caused by H. pylori infection is possibly involved in the inhibition of acid secretion in enlarged fold gastritis.     

A clinical trial of low dose methotrexate therapy in patients with rheumatoid arthritis]

The efficacy and safety of MTX in active RA were evaluated based on patient medical records. The study population consisted of 460 patients with active RA who had received no prior MTX therapy and started it at our hospital between August 1998 and December 2003 (80 men and 380 women with a mean age of 59.3 years). After 24 weeks of MTX therapy, 61.3% of patients showed a 20% improvement, and 30.4% achieved a 50% improvement according to the ACR criteria. The cumulative rate of patients who continued MTX therapy for 48 weeks was 0.567. During the observation period, 260 patients (56.5%) experienced 304 adverse reactions. 52 patients (11.3%) discontinued treatment because of adverse reactions, and 10 patients (2.2%) died. The adverse reactions that occurred in at least 1% of patients were: abnormal hepatic function (31.7%), infection (6.1%), gastrointestinal symptoms (5.0%), stomatitis (3.9%), hematological abnormalities (3.5%), fracture (3.5%), malignant tumor (2.6%), interstitial pneumonia (2.0%), cerebrovascular or cardiovascular disorder (2.0%), headache (1.7%), eruption (1.3%), and alopecia (1.1%). Adverse reactions were more common in the elderly and patients with advanced stage disease. This study reaffirms the therapeutic benefit of MTX, but suggests that careful monitoring is of great importance.     

Distribution characteristics of immunosuppressants FK506 and cyclosporin A in the blood compartment

Using two representative immunosuppressants, FK506 (FK) and cyclosporin A (CyA), of which the mechanism of pharmacological action is the same although there is a great difference in the pharmacological intensity, the distribution characteristics were studied in both in vivo and in vitro experiments using rat, dog, and human blood. Blood samples were fractionated by means of sedimentation in Ficoll-Paque®, and the drug contents in the diluted plasma fraction, erythrocyte fraction, and lymphocyte fraction were measured by an HPLC method. FK distributes to the lymphocyte fraction to a level about three times greater than that of CyA, while CyA distributes to the erythrocyte fraction to a level ten times that of FK. The distribution pattern of these fractions was independent of the drug concentration and species after correcting the drug concentration in each fraction with the blood drug concentration. The uptakes of FK and CyA in the isolated lymphocytes obtained from the rat spleen and human peripheral blood were also studied. The amount of FK taken up by the spleen lymphocytes is five times greater than that of CyA. In the case of the uptake study using human peripheral blood lymphocytes, the concentration of FK in the lymphocyte is 100-fold higher than that of CyA. This difference in the lymphocyte level between the two immunosuppressants is thought to be one of the reasons why FK is more potent than CyA, a difference of about 100-fold in the in vitro pharmacological study and about tenfold in the in vivo organ transplantation experiments.