A case of small cell carcinoma of the lung associated with paraneoplastic cerebellar degeneration and Lambert-Eaton myasthenic syndrome]

A 51-year-old male who showed severe ataxia, dysarthria, bilateral blepharoptosis, diplopia and nystagmus with the subacute onset was reported. The chest roentgenogram and CT scan revealed mass lesions at the hilus of the left lung. The tumor markers, NSE and ProGRP, were elevated; 12.8 ng/ml (< or = 10) and 140.7 pg/ml (< or = 46), respectively. The biopsy was performed surgically and the small cell carcinoma of the lung was confirmed pathologically. His cerebellar symptoms were considered to be caused by the paraneoplastc cerebellar degeneration. However, the blepharoptosis was peculiar. The electrophysiological studies were carried out The muscle strength test of the right APB muscle was 5. But the supramaximum stimulation of the right median nerve evoked only 2.0 mV of CMAP of the right APB muscle. The repetitive stimulation tests of the same nerve showed that 3 Hz stimulation resulted in 42% waning but 20 Hz stimulation evoked no waxing. The post-exercise test of the right APB muscle showed 73% increase of the CMAP. These findings indicated that he also suffered from Lambert-Eaton myasthenic syndrome. The titer of the antibody against the P/Q type voltage-gated calcium channel (VGCC) was remarkably elevated, 1,920 pM. None of the following antibodies were detected ; they included antibodies against acetylcholine receptor, Hu, Yo, Ri, Ma-2, CRMP-5, amphiphysin and glutamic acid dehydrogenase. The small cell carcinoma was treated with the combination of irinotecan hydrochloride and cisplatin, leading to the reduction of the mass lesions and the tumor markers. His cerebellar symptoms improved slightly but his blepharoptosis was unchanged. The titer of antibody against the P/Q type VGCC reduced remarkably to 451.8 pM. We reviewed reported cases associated with paraneoplastic cerebellar degeneration and Lambert-Eaton myasthenic syndrome and discussed the relation between the paraneoplastic syndromes and autoantibodies.     

Blood pressure response to erythropoietin injection in hemodialysis and predialysis patients.

Recombinant human erythropoietin (rHuEPO) has been reported to induce hypertension. We investigated the effect of a single injection of rHuEPO on blood pressure in patients receiving hemodialysis (HD) and in patients with predialysis chronic renal failure (CRF). Forty-one patients receiving HD and 36 patients with predialysis CRF received an intravenous injection of rHuEPO, and blood pressure and plasma endothelin-1 were measured before and 30 min after the injection. Mean blood pressure was increased significantly in HD patients, but not in CRF patients (HD: 103+/-5 to 105+/-6 mmHg, p<0.05; CRF: 103+/-4 to 103+/-6, NS). The percentage of patients with increased mean blood pressure of more than 10 mmHg after rHuEPO injection was significantly larger in the HD than in the CRF group (27.0% vs. 5.5%, p<0.01). A positive correlation was found between changes in endothelin-1 level and mean blood pressure in the HD (r=0.43, p<0.01) but not in predialysis chronic renal failure. In conclusion, a single injection of rHuEPO increased blood pressure with a positive correlation with endothelin-1 release in hemodialysis patients, but not in predialysis chronic renal failure patients.     

Repeat operations in the management of clival chordomas: palliative surgery.

Some chordomas have a very poor prognosis because of their aggressive growth nature, but the efficacy of repeat operations for these cases has not been well documented. This report concerns 3 patients with aggressive chordoma of the clivus, who underwent operations 6 to 12 times over a period of 8 to 17 years because of symptomatic regrowth. Overall mean interval between repeat operations was 18 months with a range from 5 to 57 months and survival times were 9 to19 years after the first surgery. Main symptoms before each operation were diplopia and visual disturbance. Repeat palliative operations by intentional extradural debulking of the tumour to decompress offending neural structures, as well as maximal removal of the tumour, using appropriate skull base approaches, can mitigate progressive symptoms, and may result in better quality and some prolongation of life, although our patients gradually deteriorated neurologically throughout the clinical course.     

A New Serum Tumor Marker, CAM 123-6, Highly Specific to Pulmonary Adenocarcinoma

KL-6, a circulating mucin-like glycoprotein, is a pulmonary adenocarcinoma-associated antigen and is also regarded as an indicator of disease activity of interstitial pneumonitis. KL-6 has extensive heterogeneous antigenic determinants and consists of multiple heterogeneous antigen molecules. We have searched for circulating KL-6-associated glycoproteins with superior diagnostic value to KL-6 as a tumor marker for pulmonary adenocarcinoma. A new murine monoclonal antibody EH-123 reacting with an asialosugar chain on KL-6 was established. A new KL-6-associated molecule detected by a bimonoclonal bideterminant sandwich assay using the EH-123 antibody as a catcher and horseradish peroxidase-labeled KL-6 as a tracer was designated as CAM 123-6. In 59% (22 of 37) of patients with pulmonary adenocarcinoma, serum levels of CAM 123-6 were abnormally elevated and the positive rate increased with the progression of clinical stage. Elevated levels were not detected in normal individuals or in patients with benign lung diseases, other histologic types of lung cancer, gastric cancer, colon cancer or breast cancer. CAM 123-6 was more specific to pulmonary adenocarcinoma than carcinoembryonic antigen (CEA), but the sensitivity of CAM 123-6 for pulmonary adenocarcinoma was similar to that of CEA. CAM 123-6 is a promising candidate as a serum tumor marker for pulmonary adenocarcinoma.     

Glutaminase and glutamine synthetase activities in human cirrhotic liver and hepatocellular carcinoma.

Glutamine synthetase and glutaminase activities in human cirrhotic liver tissues and hepatocellular carcinomas were determined for comparison with normal liver tissues. In hepatocellular carcinoma, glutamine synthetase activity was approximately one-third of that in normal liver, whereas no detectable change in the enzyme activity was observed in cirrhotic liver. Phosphate-dependent and phosphate-independent glutaminase activities were increased approximately 20-fold and 6-fold, respectively, both in the carcinoma and cirrhotic liver compared with those from normal liver, Oxypolarographic tests showed that the rate of glutamine oxidation in the tumor and cirrhotic liver mitochondria was about 5-fold higher than that in the liver mitochondria. The rate of glutamate oxidation in the liver mitochondria was comparable to that in the cirrhotic liver and tumor mitochondria. Glutamine oxidation was inhibited by prior incubation of the mitochondria with 6-diazo-5-oxo-L-norleucine, which inhibited mitochondrial glutaminase. These results indicate that the product of glutamine hydrolysis, glutamate, is catabolized in the tumor and cirrhotic liver mitochondria to supply ATP. In the liver and cirrhotic liver mitochondria, glutamate was oxidized via the routes of transamination and deamination. On the other hand, glutamate oxidation was initiated preferentially via a transamination pathway in the tumor mitochondria.     

Synthesis, pharmacological activity and biopharmaceutical characteristics of alpha,2-dimethyl-5H-[1]benzopyrano[2,3-b]pyridine-7-acetates

The pro-drugs of alpha,2-dimethyl-5H-[1]benzopyrano[2,3-b]pyridine-7-acetic acid(I) with a potent anti-inflammatory activity were synthesized in order to reduce its gastrointestinal side effects. Various esters synthesized were evaluated for their anti-inflammatory activity and ulcerogenicity. Among the compounds maintaining a potent activity of I, N,N-dimethylcarbamoylmethyl alpha,2-dimethyl-5H-[1]benzopyrano[2,3-b]pyridine-7-acetate (II-18) showed excellent biopharmaceutical characteristics. The ulcerogenic effect of II-18 on the rat gastric mucosa was about 3 times less than that of I. It was suggested that II-18 may be an useful biolabile pro-drug for I among the compounds tested.