Aliskiren, a novel oral renin inhibitor, provides dose-dependent efficacy and placebo-like tolerability in Japanese patients with hypertension.

Aliskiren is a novel orally active renin inhibitor for the treatment of hypertension. This study evaluated the antihypertensive efficacy, safety and tolerability of aliskiren in Japanese patients with hypertension. Forty hundred and fifty-five Japanese men and women with a mean sitting diastolic blood pressure of 95-110 mmHg were randomized to receive once-daily double-blind treatment for 8 weeks with aliskiren 75, 150 or 300 mg or placebo. Aliskiren produced significant, dose-dependent reductions in mean sitting diastolic blood pressure (p<0.0005 vs. placebo for each dose) and mean sitting systolic blood pressure (p<0.001 vs. placebo for each dose). The placebo-corrected reductions in mean sitting systolic/diastolic blood pressure were 5.7/4.0, 5.9/4.5 and 11.2/7.5 mmHg in the aliskiren 75, 150 and 300 mg groups, respectively. After 8 weeks' treatment, 27.8%, 47.8%, 48.2% and 63.7% of patients in the placebo and aliskiren 75, 150 and 300 mg groups, respectively, achieved a successful treatment response (diastolic blood pressure <90 mmHg and/or reduced by > or =10 mmHg from baseline; p<0.005 vs. placebo for each dose). Aliskiren treatment was well tolerated, with the incidence of adverse events reported in the active treatment groups (53-55%) being similar to that in the placebo group (50%). This study, which is the first to assess the antihypertensive efficacy and safety of aliskiren in Japanese patients with hypertension, demonstrates that the once-daily oral renin inhibitor aliskiren provides significant, dose-dependent reductions in blood pressure with placebo-like tolerability.     

Clinico-pathological comparative study between brainstem encephalitis of Iizuka type and neuro-Beh?et's disease

We experienced one necropsy case of brainstem encephalitis of Iizuka type (BSE) and one necropsy case of the brain-stem syndrome (BSS) of typical neuro-Beh?et's disease, and compared them clinically and neuropathologically. Clinically both of these cases showed chronic progressive mental disturbance, pseudobulbar paresis, spastic tetraparesis, cerebrospinal fluid pleocytosis, increased protein, and brainstem atrophy observed by X-CT. Neuropathologically, irregular, boundary-indistinct demyelinating lesions and obsolete softening lesions were sporadically found, associated with perivascular lymphocytic infiltration and gliosis centering on the brainstem. In this way, both cases were similar in many points except for the presence or absence of cutaneo-muco-ocular signs specific for Beh?et's disease. Also BSE and BSS reports in the literature showed that both diseases were similar not only in clinical findings consisting of mental disturbance and brainstem signs but also in neuropathological findings with similar topographical distribution of the same histopathological changes, including the variations and diversity of these characteristics. Especially of much interest is their similarity in characteristic mental disturbance. In discriminating BSE from multiple sclerosis and other diseases with exclusive involvement of the brainstem, it is important to understand their clinical characteristics. The characteristic mental disturbance includes damage to memory and sentiment, a change in personality, and lowering in spontaneity, but calculation ability and orientation are comparatively preserved. Of course the similarity in clinical and neuropathological findings does not necessarily mean the identical etiopathogenesis. However, it is possible to consider that neuro-Beh?et's disease (syndrome) may form a wide spectrum with BSE and typical neuro-Beh?et's disease at the both ends, regarding the time and spatial diversity of the appearance of cutaneo-muco-ocular signs.     

Juvenile-onset dystonia with bilateral atrophy of the basal ganglia on MRI]

A 40-year-old man was hospitalized for tremor of the right upper limb, gait disturbance and dysarthria. His course of development had been normal until the age of 14, when difficulties in speaking and walking, and tremor of the upper limb became evident following an episode of fever. His symptoms have been gradually worsening for the past 25 years. His elder sister showed similar clinical symptoms and progressive course of illness. The patient showed no indication of mental retardation. Neurological examination showed dysarthria, slow dyskinetic movement of the tongue, dystonic posture of the left hand, tremor of irregular frequency of the right upper limb, diminished tendon reflex, positive Romberg's sign, diminished vibratory and position sense in the lower limbs and pyramidal signs. Cystometry indicated defective voiding of the bladder. Magnetic resonance imaging of the brain showed bilateral atrophy of the putamina, globus pallidus, caudate nuclei and substantia nigra. MRI showed similar findings in her sister. By electrophysiological and pathological examination, disorders of other systems were evident, such as upper motor neurons, and sensory tract. GM1 and GM2 gangliosidosis appeared the most likely diagnosis, but were ruled out on the basis of the result of lysozomal enzyme assay and rectal biopsy. The present patient's condition may possibly be the result of an unknown metabolic disorder, or a new disease entity affecting various components of the nervous system.     

Malignant schwannoma of acoustic nerve: a case report

During a routine physical examination in 1976, a 54-year-old man was noted to suffer from hearing difficulty and continuing tinnitus of his right ear. He had, however, no further consultations for the next five years, although the symptom persisted and gradually worsened. In May 1981, he experienced complete hearing loss in his right ear. A computed tomography disclosed no abnormalities, and other laboratory tests were unremarkable. In September 1981, the patient began to complain of paresthesia of the right angle of the mouth and tongue, right-sided facial paralysis, and walking difficulty. A repeated computed tomography showed a tumor at the right cerebellopontine angle region. A clinical diagnosis of acoustic schwannoma was made. The first operation was performed in December 1981. Complete removal of the tumor was impossible because of its unexpected, unusual hardness. The pathologic diagnosis was a malignant mesenchymal tumor, compatible with a malignant nerve sheath tumor of the acoustic nerve. A second operation was performed in January 1982, but the rapid postoperative regrowth of the tumor necessitated a third operation in March 1982. The patient died in the next month. Family histories did not show any evidence of von Recklinghausen's disease, and neither did the patient have any clinical stigmata of this disease.     

Two cases of psychotic state following normal-dose benzodiazepine withdrawal

We report two cases of severe withdrawal symptoms after abrupt discontinuation of a long-term normal-dose benzodiazepines (BZD) administration. Case 1, a 61-year-old man, suffered from delirium on the 7th day after abrupt discontinuation of nitrazepam, 10 mg/day. Case 2, a 49-year-old woman, suffered from auditory hallucination on the 4th day and visual cognitive disorder on the 5th day after abrupt discontinuation of nitrazepam, 5 mg/day, and triazolam, 0.5 mg/day. A withdrawal syndrome after discontinuation of normal-dose BZD is uncommon, and a psychotic withdrawal reaction is even more uncommon. We show how a continuous administration of BZD for a period of longer than 6 months and the presence of severe insomnia are risk factors predictive of a psychotic reaction. We also explain the predictive method used to determine the onset time of such a severe state. In the case of a psychotic state, we recommend intravenous diazepam injection. To prevent withdrawal reaction, we also recommend a gradual reduction after administration of normal-dose BZD.     

A case of bilateral blepharospasm responsive to edrophonium]

A case of bilateral blepharospasm who registered the efficacy of edrophonium was reported. The case is a 49-year-old female. She had been in good health until January, 1991 when she complained of difficulty in opening her eyes while driving. Thereafter the condition progressed to such a degree that she was unable to experience a comfortable life. Her blinking rate did not changed. The symptoms were triggered by stress or some physical action, such as walking or driving. They were attenuated by taking a bath, sleep or sedation. The severity of the symptoms varied during the day and from day to day. Neurological examination revealed bilateral spasms of the orbicular oculi muscles, and occasionally of the orbicular oris muscles, sternocleidmastoid muscles and the perinasal regions. Neither orolingual dyskinesia nor other involuntary movements were detected. Surface electromyography (EMG) disclosed tonic discharges mainly from the orbicular oculi muscles. The abnormal spasm disappeared with the injection of edrophonium chloride. The test for the serum antiacetylcholine receptor antibody was negative and a repetitive stimulation EMG showed no waning phenomenon. No thymoma or thymus abnormalities were detected by pneumomediastinography. A needle EMG revealed neurogenic change in the distal portion of the limbs. A single fiber EMG showed elongation of the jitter value and the blocking phenomenon. Although distigmine bromide was ineffective against the spasm, pyridostigmine bromide and the local injection of botulinum toxin were very effective.(ABSTRACT TRUNCATED AT 250 WORDS)     

Immunohistochemical characterization of cellular infiltrates in squamous cell carcinoma and Bowen's disease occurring in one patient.

We investigated populations of the infiltrating cells in Bowen's disease (BD) and squamous cell carcinoma (SCC), both of which arose in the same patient, using the Avidin-Biotin-peroxidase complex method with eight monoclonal antibodies. T lymphocytes were most predominant among infiltrating cells; NK cells, B cells, and monocytes were rarely seen in either BD or SCC. Analysis of subsets of the infiltrating T lymphocytes revealed that the number of suppressor/cytotoxic (s/c) T cells was twice that of helper/inducer (h/i) T cells in BD, while the number of s/c T cells was lower than that of h/i T cells in SCC. The immunohistochemical results in the present case differed from those of predominant infiltration of h/i T cells and of s/c T cells in three other reports of BD and SCC. These results suggest that the population of the cellular infiltrates may be modulated by the nature of tumors and by the immuno-competent state of the hosts.     

Histopathological studies on experimental marine toxin poisoning--4. Pathogenesis of experimental maitotoxin poisoning

Repeated injections of 45 ng/kg of maitotoxin into the peritoneal cavities of male ICR mice resulted in marked atrophy of lymphoid tissues, a reduction of lymphocytes in the circulating blood, reduced immunoglobulin M in serum, and an increase of calcium content in the adrenal glands. A single injection of 200 ng/kg of maitotoxin induced a marked increase in total calcium content of the adrenal glands as well as in plasma cortisol concentration (about seven times control) within 1 hr. In contrast, mice pretreated with CoCl2, a calcium channel inhibitor, and/or adrenalectomized mice, showed no discernible changes in the lymphoid tissues after repeated injections of maitotoxin. It is thus suggested that maitotoxin first stimulates calcium influx in the adrenal glands, which then causes the release of cortisol into the blood. The excess amount of cortisol in serum produces acute involution of the thymus and other lymphoid tissues.     

Clinical evaluation of antithrombin III concentrate (BI 6.013) for disseminated intravascular coagulation in obstetrics. Well-controlled multicenter trial

Antithrombin III (AT III) is known to be the most important inhibitor of serine protease in the coagulation system. In the presence of heparin, AT III is converted from its progressive activity state to an immediate activity state. In disseminated intravascular coagulation (DIC) in the field of obstetrics, the treatment has to be initiated very early. Heparin treatment, on the other hand, is critical since frequently postpartal or postoperative wound bleeding is present. We, therefore, established diagnostic criteria for the early diagnosis of DIC and investigated the clinical efficacy of a therapy with AT III in a well-controlled comparative study versus the injectable synthetic protease inhibitor FOY. The results of the trial showed that the AT III group (92%; n = 24) was significantly (p less than 0.001) superior in clinical efficacy to the FOY group (60%; n = 15). No side effects whatsoever were observed after treatment with AT III concentrate (Behring Institute). From these results, it could be concluded that a single therapy with AT III concentrate can sufficiently control the symptoms of DIC in the field of obstetrics without the risk of increased bleeding.