A protocol for the successful long-term enzyme replacement therapy of scurvy in guinea pigs

Summary Gulonolactone oxidase, a key enzyme in the biosynthesis of ascorbic acid, is missing from guinea pigs and certain other scurvy-prone species. Weekly intraperitoneal injections of glutaraldehyde cross-linked immunoprecipitates of this enzyme have been shown to provide guinea pigs with the capability of synthesizing their own ascorbic acid and of surviving without an exogenous source of this vitamin. This protocol, however, was successful in only a small percentage of the animals tested. The reasons for the limited therapeutic success were investigated. Apparently, the gulonolactone oxidase-treated guinea pigs fed without ascorbic acid were receiving insufficient nutrition. By supplementing these enzyme-treated animals with vitamins A, B, D and E and selenium, we successfully maintained a high proportion of guinea pigs fed without vitamin C.     

Physiological significance of plasma free and conjugated dopamine in healthy volunteers--with special reference to sympathetic nerve activity

In order to elucidate the physiological significance of plasma dopamine, blood pressure, pulse rate (PR), plasma concentrations of free or conjugated dopamine (free or conjugated pDA), noradrenaline (pNA) and adrenaline (pAd) were measured in 9 healthy volunteers. Blood sampling for the measurements was performed at a basal condition maintaining a supine position for 60 minutes, after twenty minutes 60 degrees head-up tilt (tilt) and an intravenous infusion of 1000 ml 0.9% saline for 2 hours. Following tilt, mean values in diastolic and mean blood pressure, PR, pNA and pAd were significantly increased, while free, conjugated and total pDA were decreased. On the other hand, saline infusion yielded significant decreases in hematocrit, pNA, free, conjugated and total pDA, but blood pressure, PR and pAd remained at the same level. Free/conjugated pDA ratio did not change during tilt or saline infusion. The basal value of free, conjugated or total pDA did not significantly correlate with blood pressure, PR, pNA or pAd, respectively. Furthermore, no significant correlations between the changes in pDAs and hemodynamic parameters, pNA or pAd by tilt or saline infusion were observed. From these results, it was suggested that plasma free or conjugated dopamine in physiological conditions may not be released from sympathetic nerve endings or adrenomedullary glands. Further investigations are needed to clarify the physiological significance of plasma dopamine in humans.     

A case of mixed connective tissue disease successfully treated for hemophagocytic syndrome with intermittent intravenous injection of cyclophosphamide]

A 52 year-old woman noticed general fatigue, polyarthralgia, and muscle weakness of lower extremities in October 2001. In December, she felt difficulty in walking due to muscle weakness. In January 2002, she admitted another hospital because of dyspnea on exertion and edema of lower extremities. Laboratory test revealed leukocytopenia, the elevation of creatine kinase and positive anti-U1-RNP antibodies. Her chest computed tomography (CT) showed severe interstitial pneumonia. Cardiac echogram revealed that she had pericardial effusion and pulmonary hypertension. Then she was transferred to Keio University Hospital and she was diagnosed as having mixed connective tissue disease (MCTD) manifestating myositis, interstitial pneumonia, pulmonary hypertension and pericarditis. Prednisolone (PSL) 60mg daily following to methylprednisolone (mPSL) pulse therapy was begun and her symptoms were gradually improved. In middle of February, she complained of high fever over 39.0 degrees C. Bacterial culture tests were negative and laboratory data indicated pancytopenia and a high level of serum ferritin. Bone marrow aspiration revealed hemophagocytosis in bone marrow specimens and she was diagnosed as having hemophagocytic syndrome associated with MCTD. mPSL pulse therapy was not effective and intermittent cyclophosphamide pulse therapy (IV-CY) was performed resulting in improvement of the symptoms. This case suggested the effectiveness of IV-CY therapy in patients with corticosteroid-resistant HPS associated with connective tissue diseases.     

USEFULNESS OF EUS IN PORTAL HYPERTENSION WITH ESOPHAGEAL VARICES

We investigated the relationship between esophageal varices and the collaterals by endoscopy and endoscopic ultrasound (20 MHz ultrasonic miniprobe; UMP). Moreover, we investigated the correlation between the collaterals around the esophagus and recurrence of esophageal varices in patients with portal hypertension who had undergone EIS. The collaterals were divided into two groups: peri‐esophageal collateral veins (peri‐ECVs) and para‐esophageal collateral veins (para‐ECVs). These were scored as mild or severe according to the stage of development. According to endoscopy, the varix form was significantly larger in severe the peri‐ECVs group than in mild the peri‐ECVs group. The prevalence of perforating veins increased according to the varix form. With regard to variceal recurrence, in patients with variceal recurrences, UMP findings included a significantly higher incidence of severe peri‐ECVs, a significantly larger diameter of perforating veins compared with patients without recurrence. In conclusion, the presence of severe peri‐ECVs and large perforating veins in the esophageal wall strongly correlates with occurrence and recurrence of esophageal varices in patients with portal hypertension. An understanding of these UMP abnormalities on the basis of hemodynamics around the esophagus is thought to be important for management of esophageal varices in patients with portal hypertension.     

Preoperative chemotherapy increases cytokine production after lung cancer surgery.

OBJECTIVE: Many phase II trials have shown that preoperative chemotherapy for lung cancer is feasible but associated with postoperative morbidity and mortality. However, little is known about the effect of preoperative chemotherapy on surgical stress and postoperative complications associated with surgical intervention. We evaluated the effect of preoperative chemotherapy on perioperative inflammatory cytokine production as a surgical stress marker. METHODS: The study group comprised 38 patients undergoing anatomical lung resection and mediastinal nodal dissection for clinical stage IB/II non-small cell lung cancer during the period October 2001-December 2003. Nineteen patients received a single cycle of cisplatin (80 mg/m(2)) and docetaxel (60 mg/m(2)) chemotherapy prior to surgery (neoadjuvant group), and 19 patients underwent surgery without any previous chemotherapy (control group). White blood cell and neutrophil counts and serum concentrations of C-reactive protein (CRP), interleukin-6 (IL-6), and granulocyte colony-stimulating factor (GCSF) were determined before surgery and on postoperative days 1 and 3. Postoperative complications were reviewed. Differences were assessed by repeated analysis of variance. RESULTS: Serum concentrations of IL-6 and GCSF rose significantly on postoperative days 1 and 3 in the neoadjuvant group in comparison to concentrations in the control group, but white blood cell count, neutrophil count, and CRP did not differ between the groups. No major complication occurred in either group. CONCLUSIONS: A single cycle of cisplatin and docetaxel chemotherapy followed by surgery can exacerbate overproduction of inflammatory cytokines during the perioperative period in lung cancer patients.     

Aneurysms of the anterior communicating artery and subclavian artery in association with congenital absence of unilateral internal carotid artery]

We encountered a rare case of unilateral internal carotid arterial defect complicated with anterior communicating aneurysm and subclavian artery aneurysm. The patient was a 56-year-old man in whom cerebral angiography and 3D-CTA revealed defects in the right internal carotid artery and the right carotid canal, and an unruptured aneurysm in the anterior communicating artery. In addition, the patient was also found to have an unruptured aneurysm in the right subclavian artery. As both the aneurysms were considered to have a high risk of rupture and such subclavian aneurysms were likely to cause an embolism, radical surgery was performed for each aneurysm. The postoperative course was uneventful, and the patient was discharged without ambulatory limitations. Although the defect in the internal carotid artery is a relatively rare vascular deformity, the incidence of cerebral aneurysm is about 30% in such cases due to the marked hemodynamic stress involved. On the other hand, there have been only two previous case reports of internal carotid arterial defect complicated with a subclavian aneurysm. Moreover, there have been no previous reports of internal carotid arterial defect complicated with both an intracranial aneurysm and a subclavian aneurysm, as observed in the present case. Thus, this case was very rare and is reported here.     

Human parvovirus-induced transient anemia and leukopenia after delivery]

A 30-year-old female at 27 weeks' gestation, was hospitalized on September 24 1990 because of the premature rupture of the amniotic sac. She underwent Caesarean section on the same day with 700 ml blood loss, but no blood transfusion was required. For several days after the operation, her hemoglobin level remained 7.8 g/dl and did not increase significantly in spite of parenteral iron therapy. On the 9th postoperative day, chills and pyrexia developed with leukopenia. Bone-marrow aspiration revealed severe erythroblastopenia with giant proerythroblasts, suggesting recent HPV infection, which was confirmed by the presence of anti-HPV IgM and HPV antigen by ELISA. The hemoglobin level gradually decreased to 6.0 g/dl by the 21st day, then began to increase rapidly. The serum of acute-phase containing HPV antigens inhibited BFU-E and CFU-E but not CFU-GM. The serum of convalescent-phase inhibited neither erythroid colony growth nor myeloid colony growth. These results indicate that the inhibitory effect of HPV in colony assay is highly specific for erythropoiesis and that HPV play a role in transient cessation of erythropoiesis. The reason, however, for leukopenia in HPV infection remained unclear. This case shows that HPV infection may induce severe hematological disorders even in normal person under erythropoietic stress.     

Discrepancy of xenon concentrations between end-tidal and blood collection methods in xenon-enhanced computed tomographic measurement of cerebral blood flow

Summary Using xenon-enhanced computed tomography for the study of cerebral blood flow, simultaneous measurements of end-tidal and arterial blood xenon concentrations using the blood collection method were performed to investigate the validity of substituting the end-tidal for the arterial blood xenon concentration. Simultaneous measurement by both methods was performed 68 times in 27 patients. There was no statistical correlation between the arterial blood accumulation rate constant obtained by arterial blood and end-tidal samples, nor between the arterial blood saturation value obtained by the two methods, even when correction was made for age. In brain tissue, all parameters calculated using the end-tidal concentration were lower than those using arterial blood. We therefore suggest that cerebral blood flow values calculated using end-tidal xenon concentration are useful only for qualitative cerebral blood flow mapping, and not applicable to absolute values of cerebral blood flow.     

Pharmacokinetics of oral alminoprofen (Minalfen) in elderly patients with rheumatoid arthritis and spondylosis deformans]

The pharmacokinetics of oral Alminoprofen, a nonsteroidal anti-inflammatory drug, were studied in five elderly patients with rheumatoid arthritis and spondylosis deformans after 200 mg (three times a day) repeated dose for 5 days. The pharmacokinetic parameters after oral administration of Alminoprofen were analyzed by the one-compartment open model method. The maximum plasma concentrations (Cmax) were 16.1 +/- 2.5 micrograms/ml, after dosing on day 1, 25.2 +/- 1.6 micrograms/ml on day 3 and 21.6 +/- 2.7 micrograms/ml on day 5. The maximum time (Tmax) were about 2 hours after the medication in al cases. The area under the curve in drug concentration in plasma versus time (AUC) were 58.5 +/- 6.3 micrograms hr/ml on day 1, 58.5 +/- 3.1 micrograms hr/ml on day 3 and 58.1 +/- 8.5 micrograms hr/ml on day 5. The biological half-lives (t1/2) were 2.45 +/- 0.35, 2.09 +/- 0.82 and 2.49 +/- 0.63 hours, after dosing on day 1, day 3 and day 5, respectively. The analysis of moment in pharmacokinetics revealed that the mean residence time (MRT) on day 1, day 3 and day 5 observed were 2.31 +/- 0.03, 2.15 +/- 0.09 and 2.15 +/- 0.07 hours, respectively. The variance residence times (VRT) observed were 0.95 +/- 0.05 hour2 on day 1, 0.88 +/- 0.09 hour2 on day 3 and 1.06 +/- 0.07 hour2 on day 5. The ratios of accumulation calculated were 1.16 +/- 0.05 in both the morning medication on day 3 day 5, and it therefore appears that the steady-state equilibrium is established within 3 days after commencement of dosage.(ABSTRACT TRUNCATED AT 250 WORDS)