[Pulmonary Nocardia otitidis-caviarum infection in a patient with Cushing's disease].

While Nocardial infections are being diagnosed with increasing frequency, infection with Nocardia otitidiscaviarum remains relatively uncommon. We report a case of pulmonary Nocardia otitidis-caviarum infection in a 35-year-old man with Cushing's disease. This work describes the first case of nocardiosis in Japan caused by Nocardia otitidis-caviarum in Cushing's disease. The patient was admitted to our department because of edema. A diagnosis of Cushing's disease was made on the basis of elevated serum levels of cortisol and adrenocorticotropic hormone (ACTH) and pituitary adenoma was found in a cranial CT scan. One month after admission, chest radiographs showed a large bilateral mass on the lung fields. Nocardia otitidis-caviarum was isolated from the sputum. The patient responded poorly to intravenous PAPM/BP, but later improved after treatment with trimethoprim-sulfamethoxazole, but he died of heart failure and respiratory failure after the initiation of this therapy. This case demonstrated that nocardiosis must be considered in differential diagnosis as an opportunistic infection.

The anti-dementia drug nefiracetam facilitates hippocampal synaptic transmission by functionally targeting presynaptic nicotinic ACh receptors.

Nefiracetam, a pyrrolidone derivative developed as an anti-dementia drug, persistently potentiated currents through neuronal nicotinic acetylcholine (ACh) receptors (alpha7, alpha4beta2) expressed in Xenopus oocytes, and the potentiation was blocked by either the selective protein kinase C (PKC) inhibitors, GF109203X and staurosporine, or co-expressed active PKC inhibitor peptide. In primary cultures of rat hippocampal neurons, nefiracetam increased the rate of nicotine-sensitive miniature excitatory postsynaptic currents, without affecting the amplitude, and the increase was inhibited by GF109203X. In addition, the drug caused a marked increase in the glutamate release from electrically stimulated guinea pig hippocampal slices, and the effect was abolished by the nicotinic ACh receptor antagonists, alpha-bungarotoxin and mecamylamine. Nefiracetam induced a long-lasting facilitation of synaptic transmission in both the CA1 area and the dentate gyrus of rat hippocampal slices, and the facilitation was inhibited by alpha-bungarotoxin and mecamylamine. Such facilitatory action was still found in the hippocampus with selective cholinergic denervation. The results of the present study, thus, suggest that nefiracetam enhances activity of nicotinic ACh receptors by interacting with a PKC pathway, thereby increasing glutamate release from presynaptic terminals, and then leading to a sustained facilitation of hippocampal neurotransmission. This may represent a cellular mechanism underlying the cognition-enhancing action of nefiracetam. The results also provide the possibility that nefiracetam could be developed as a promising therapeutic drug for senile dementia or Alzheimer's disease.

Prevalence of cervical lesions in rheumatoid arthritis: cross-sectional study on 263 patients.

Abstract Spinal lesions in upper and sublaxilar cervical vertebrae were studied radiologically in 263 patients (25 men and 238 women) with rheumatoid arthritis (RA). Their average age was 58.9 years, and their disease duration was ranged from 6 months to 24 years (mean 13 years). Functional lateral views of the cervical spine were made. Atlantaxial subluxation (AAS) and vertical subluxation (VS) were evaluated as upper cervical lesions. Subaxilar subluxation (SAS) and endplate erosion were evaluated as subaxilar cervical lesions. One hundred and seventy-eight (67.7%) of the patients had a cervical lesion. Upper and subaxilar cervical abnormalities were recognized in 136 (51.7%) and 113 (43.0%) patients, respectively. There was no linkage between upper and subaxilar cervical lesions. While the prevalence of these lesions increased with time, the frequency was found to be over 50% within only 5 years from onset in patients with mutilating deformity. This prevalence tended to be associated with disease activity.

Anterior floating method for cervical myelopathy caused by ossification of the posterior longitudinal ligament.

Ossification of the posterior longitudinal ligament lessens the sagittal diameter of the cervical canal and compresses the spinal cord anteriorly, and may produce severe disabling myelopathy. The anterior floating method is one of the anterior decompression and reconstructions used in the treatment of cervical myelopathy caused by ossification of the posterior longitudinal ligament. This procedure consists of subtotal resection of vertebral bodies and discs, with slight thinning and release of the ossified ligament using air instrumentation. This is followed by reconstruction of the cervical spine using autogenous strut bone graft accompanied by postoperative application of a halo vest. This method is indicated for patients who present with moderate or severe myelopathies, and especially in those where the canal narrowing ratio exceeds 60%. This radical procedure causes decompression of the spinal cord and restores its function by enlarging the neural canal with anterior migration of the ossified ligament. The procedure minimizes the extent of surgical invasions and avoids damage to the neural tissue, because it does not require the removal of the ossification of the posterior longitudinal ligament. It also stops postoperative regrowth of the ossification. The operative results with long term followup indicate a 71% average recovery rate based on the criteria established by the Japan Orthopedic Association.

Development of an instrument to measure postmortem lividity and its preliminary application to estimate the time since death.

A degree of postmortem lividity was related to a subcutaneous hemoglobin concentration, which can be measured by using light absorption. On the basis of this theory, the authors have developed an instrument utilizing a light to measure the degree of postmortem lividity. By using 42 corpses whose postmortem intervals were known, the authors examined the relationship between the actual postmortem intervals and the measurements, and found that there was significant correlation between them.

Effects of tolbutamide on cultured heart cells of mice.

To investigate the direct effects of tolbutamide on the myocardium, we studied the ultrastructure, direct effects of tolbutamide on the myocardium, we studied the ultrastructure, beating rhythm, cytotoxicity determining the 51Cr release from damaged cells and the 45Ca activity in the cultured heart cells of mice. After 48 h of cultivation, tolbutamide was added to give a final concentration of 0.37, 0.93, 1.85, and 3.7 nM. The addition of high dose of tolbutamide (greater than 1 mM) to the culture medium produced irregular beating after 1 min and cessation of beating after 20 h. The cultured heart cells incubated with control solution or low concentrations of tolbutamide (less than 1 mM) showed little change in the beating rhythm and frequency. Cytotoxicity of tolbutamide on the cultured heart cells was observed only in high concentrations (greater than 1 mM): the 51Cr release index was 23% at 1.85 mM and 40% at 3.7 mM. On electron microscopy, the heart cells cultured with high concentration of tolbutamide (greater than 1 mM) showed electron-dense bodies in the mitochondria and shortened Z-Z intervals. However, these ultrastructural alterations were not observed in the cultured heart cells incubated with low concentration of tolbutamide (less than 1 mM). The 45Ca activity of cultured heart cells, after the incubation for 24 h in medium containing 45Ca, was significantly increased only with high concentrations of tolbutamide (greater than 1 mM). We conclude that tolbutamide in dose of less than 1 mM had no cytotoxicity and had little effect on the beating rhythm, ultrastructure and intracellular calcium concentration of the cultured heart cells of mice.