Improvement of Splenomegaly and Pancytopenia by Enzyme Replacement Therapy Against Type 1 Gaucher Disease: A Report of Sibling Cases

Gaucher disease is a genetic lipid storage disease and represents a potentially serious health problem. It arises from a deficiency of glucocerebrosidase activity with secondary accumulation of large quantities of glucocerebroside. Symptoms are usually multisystemic, often debilitating or disabling, and sometimes disfiguring, and they can lead to death. We report objective clinical response's to repeated infusion of human placental and recombinant glucocerebrosidase in 2 patients with type 1 Gaucher disease and increased hemoglobin levels and platelet counts. Splenic volume decreased during the period of enzyme administration. Enzyme replacement therapy has improved the treatment of type 1 Gaucher disease by safely and effectively arresting, decreasing, or normalizing many of its major signs and symptoms. Consideration by physicians must be given to Gaucher disease, and appropriate treatments must be given when confronted with cryptogenic pancytopenia or hepatosplenomegaly.     

Progressive systemic sclerosis associated with primary small cell carcinoma of the stomach

A 64-year-old man with a 5-year history of progressive systemic sclerosis (PSS) was hospitalized because of melena. Radiological and endoscopic examinations showed an ulcerative lesion with sharply demarcated and raised margins in the fornix of the stomach. Tumor markers—serum carcinoembryonic antigen (CEA, 11.3 ng/ml) and neuron-specific enolase (NSE, 38.9 ng/ml) were elevated. Histological examination of endoscopic biopsy specimens (and of necropsy specimens) showed proliferation of atypical small round cells. Immunohistological examination of these cells showed they were positive for epithelial membranous antigen (EMA), and neuron-specific enolase (NSE), but negative for UCHL1, leukocyte common antigen (LCA), anti-leukocyte B-cell (MB1), and antileukocyte T-cell (MT1) antigens. Based on these histological and immunohistological tests, a definite diagnosis of small cell carcinoma of the stomach with PSS was established. Our case is a rare combination of PSS and gastric small cell carcinoma. We also reviewed the literature for the association between PSS and gastric cancer in Japanese patients.     

Pathological findings of bronchiectases caused by Mycobacterium avium intracellulare complex

It has been argued whether bronchiectasis is truly caused by MAC infection or just a predisposed condition in which MAC colonizes. Our present study was designed to evaluate the pathological findings of bronchiectases caused by Mycobacterium avium intracellulare complex (MAC) lung infection and to demonstrate MAC in the lesion of bronchiectases. A retrospective study was performed in nine cases with positive cultures for MAC in whom lung resections were performed. A determination of whether or not MAC caused pulmonary disease was made using the 1997 criteria required by the American Thoracic Society. In addition, MAC were cultured from all nine lung specimens. Pathological findings of bronchiectases were evaluated in these nine patients. Destruction of bronchial cartilage and smooth muscles layer, obstruction of airway by granulomas, and ulceration of bronchial mucosa were frequently observed. Our present study demonstrates that destruction of fundamental bronchial structure due to extensive granuloma formation throughout the airways was likely the main cause of bronchiectases in MAC infection.     

Whole-body periodic acceleration enhances brachial endothelial function.

BACKGROUND: Periodic acceleration in the direction of the spinal axis through repetitive movement increases the shear stress on the vascular endothelium. In the present study it was assessed whether whole-body periodic acceleration with a new device would enhance endothelial function in sedentary adult volunteers. METHODS AND RESULTS: Twenty-six sedentary subjects (44+/-3 years) were randomly assigned to remain sedentary or perform exercise training for 4 weeks, followed by crossover. Periodic acceleration was applied with a horizontal motion platform at 2-3 Hz and approximately +/-2.2 m/s2 for 45 min. Increases in the brachial artery diameter were examined at rest, during reactive hyperemia (flow-mediated dilatation: %FMD) and after sublingual administration of 0.3 mg nitroglycerin (%NTG) using high-resolution ultrasound. All subjects completed the study with no adverse side-effects. There were no significant changes in the resting heart rate or arterial pressure, body weight, or lipid profiles during the study. Although %FMD did not change during the non-training period with periodic acceleration, it significantly increased from 7.3+/-0.4% at baseline to 8.4+/-0.4% after the training period (p<0.05), while %NTG remained unchanged. CONCLUSIONS: Whole-body periodic acceleration with a horizontal motion platform improved vascular endothelial function in sedentary adults. This device might offer an alternative to active exercise for patients whose medical condition limits physical activity.     

C-type natriuretic peptide, a novel antifibrotic and antihypertrophic agent, prevents cardiac remodeling after myocardial infarction

OBJECTIVES: We assessed the hypothesis that in vivo administration of C-type natriuretic peptide (CNP) might attenuate cardiac remodeling after myocardial infarction (MI) through its antifibrotic and antihypertrophic action. BACKGROUND: Recently, we have shown that CNP has more potent antifibrotic and antihypertrophic effects than atrial natriuretic peptide (ANP) in cultured cardiac fibroblasts and cardiomyocytes. METHODS: Experimental MI was induced by coronary ligation in male Sprague-Dawley rats; CNP at 0.1 mug/kg/min (n = 34) or vehicle (n = 35) was intravenously infused by osmotic mini-pump starting four days after MI. Sham-operated rats (n = 34) served as controls. After two weeks of infusion, the effects of CNP on cardiac remodeling were evaluated by echocardiograpic, hemodynamic, histopathologic, and gene analysis. RESULTS: C-type natriuretic peptide markedly attenuated the left ventricular (LV) enlargement caused by MI (LV end-diastolic dimension, sham: 6.7 +/- 0.1 mm; MI+vehicle; 8.3 +/- 0.1 mm; MI+CNP: 7.7 +/- 0.1 mm, p < 0.01) without affecting arterial pressure. Moreover, there was a substantial decrease in LV end-diastolic pressure, and increases in dP/dt(max), dP/dt(min), and cardiac output in CNP-treated MI rats compared with vehicle-treated MI rats. Importantly, CNP infusion markedly attenuated an increase in morphometrical collagen volume fraction in the noninfarct region (sham: 3.1 +/- 0.2%; MI+vehicle: 5.7 +/- 0.5%; MI+CNP: 3.9 +/- 0.3%, p < 0.01). In addition, CNP significantly reduced an increase in cross-sectional area of the cardiomyocytes. These effects of CNP were accompanied by suppression of MI-induced increases in collagen I, collagen III, ANP, and beta-myosin heavy chain messenger ribonucleic acid levels in the noninfarct region. CONCLUSIONS: These data suggest that CNP may be useful as a novel antiremodeling agent.     

Effects of prolactin and growth hormone on proliferation and survival of cultured trout leucocytes

The in vitro effects of prolactin (PRL) and growth hormone (GH) on the proliferation and survival of leucocytes isolated from the blood of the rainbow trout (Oncorhynchus mykiss) were examined, with special reference to the immunosuppression by cortisol. Both PRL and GH induced a mitogenic effect in trout leucocytes. Contrary, the frequencies of annexin V-positive apoptotic cells and propidium iodide-positive dead cells were decreased by the administration of PRL, but were uninfluenced by GH. Administration of cortisol suppressed the mitotic activity and induced cell death of leucocytes. PRL inhibited the decrease in mitosis and the increase in cell death due to cortisol. GH significantly assisted recovery of cortisol-suppressed mitosis but did not influence the survival of leucocytes. These results suggest that PRL and GH are involved in the maintenance of specific immune functions in fish through a prevention of immunosuppression by cortisol.     

A case of mediastinal teratoma with elevated serum tumor marker levels]

A 27-year-old man complaining of cough was admitted to our hospital because of a giant mediastinal tumor on the chest radiograph. Chest CT and MRI revealed a giant polycystic mediastinal tumor. Chest radiographs on admission showed left pleural effusion due to perforation of the cyst. Laboratory data showed high serum and pleural fluid concentrations of CA 125, CA 19-9, SLX and others. The mediastinal mass was resected and diagnosed pathologically as a mature teratoma. It is reported that patients with mediastinal teratomas often have pleural fluid as a result of self-digestion by pancreatic enzymes, and some mediastinal teratomas have high serum tumor marker levels. We suspected that the high serum tumor marker levels in our case were caused by the high concentrations of tumor markers in the pleural fluid. We suggest that serum tumor marker levels may be useful in the preoperative differential diagnosis of anterior mediastinal cystic tumors.     

Effects of diacylglycerol administration on serum triacylglycerol in a patient homozygous for complete lipoprotein lipase deletion

We investigated postprandial and long-term effects of dietary diacylglycerol (DAG) on serum triacylglycerol (TAG) levels in a 34-year-old man homozygous for complete lipoprotein lipase deletion (LPL deletion). In study 1, Three different oils (DAG, TAG, or medium-chain fatty acid TAG [MCT]) were ingested to examine differences in the postprandial serum TAG response. Postprandial serum TAG levels after DAG oil ingestion were lower than those after TAG oil ingestion and similar to those after MCT oil ingestion. In study 2, the patient was allowed to ingest ordinary cooking oil for 2 months and then DAG oil (containing 80% DAG; target, 20 g/d) for the next 3 months. During the test period, serum TAG levels were measured and dietary evaluations were performed every month. The patient was provided with dietary instruction and consultation at each clinical visit. Serum TAG levels were 1939 to 2525 mg/dL when he used ordinary cooking oil, 1926 to 1173 mg/dL when he used ordinary cooking oil together with DAG oil, and 749 mg/dL when he used DAG oil alone. The TAG intake decreased from 86.9 to 43.0 g and the DAG intake increased from 0.9 to 12.4 g during the study period. Subsequently, 45 g DAG oil (equivalent to 36 g DAG) per day was consumed, and the serum TAG level increased to 2195 mg/dL. Although there was a positive correlation between the TAG intake and serum TAG levels during the period of DAG oil use (P < .01, y = 33.7x - 583.1), there was no such correlation between DAG oil intake and serum TAG levels. These results suggested that substitution of 12.0 g/d DAG (equivalent to 15 g DAG oil) for TAG oil had the same effect as reducing TAG oil consumption for controlling the serum TAG levels in an LPL-depleted patient with hypertriglyceridemia. In conclusion, the results of study 1 and study 2 demonstrate that DAG oil might be replaced by MCT oil as cooking oil for those with LPL deletion.     

Refractory hepatic hydrothorax treated with transjugular intrahepatic portosystemic shunt

A 66-year-old cirrhotic woman was referred to our hospital for evaluation of refractory pleural effusion and dyspnea. Massive right sided-pleural effusion but no ascites was detected. She had been treated with diuretics and albumin, repeated thoracenteses, and pleural drainage with an intercostal catheter, all of which had failed to relieve her symptoms. The diagnosis of hepatic hydrothorax without ascites was made by injection of technetium-99m-sulfur colloid into the peritoneal cavity. A transjugular intrahepatic portosystemic shunt was placed and successfully reduced the pleural effusion, resulting in complete relief of her symptoms. The patient has been free of symptoms for 18 months after the procedure. (Received Jan. 19, 1998; accepted June 24, 1998)