A patient with lambda type light-chain disease associated with Crow-Fukase syndrome and autoimmune thrombocytopenia]

A 67-year-old woman, who presented polyneuropathy, pleural effusion, ascites and sclerosing changes in the ribs, was admitted to our hospital on June 17, 1987. On admission, cerebrospinal examination showed a marked protein-cell dissociation and a delay in nerve conduction velocity. Bence-Jones protein was detected in urine, and the immunohistochemical study of biopsied bone marrow of the rib revealed lambda-chain positive plasmacytoma. Serum immunoelectrophoresis, however, showed no monoclonal gamma-globulinemia. From the findings described above, she was diagnosed as having Crow-Fukase syndrome associated with lambda-type light chain disease. Even with a therapy by prednisolone, platelet counts progressively declined to 10,000/ml3. Bone marrow aspiration showed normal number of megakaryocytes. Since platelet-associated IgG was increased to 452 ng/1.0 x 10(8) plt, a diagnosis of autoimmune thrombocytopenia was considered. Melphalan and cyclophosphamide to plasmacytoma resulted in a marked improvement of platelets. In addition, the level of platelet-associated IgG returned to normal range. Polyneuropathy, however, didn't respond to those therapies. It was suggested that both Crow-Fukase syndrome and thrombocytopenia were closely concerned with plasmacytoma but developed in a different manner.     

Effects of iodine-enriched egg (IE-egg) on nasal allergy: basic and clinical investigations

The effect of iodine-enriched egg (IE-egg) on nasal allergy was investigated using an experimental allergic model. In addition, the effect of IE-egg was investigated using patients with yearly nasal allergy. IE-egg could suppress the leakage of pontamine sky blue dye in the experimental allergic model. beta-Glucuronidase activity in the perfusate was suppressed with the ingestion of IE-egg. The symptoms of the patients with yearly nasal allergy were mitigated by the ingestion of IE-egg. beta-Glucuronidase activity in the pituita of nasal allergic patients tended to be decreased.     

Pharmacokinetics of clarithromycin granule and tablet in children

It has been known that clarithromycin (TE-031, A-56268), a new macrolide antibiotic (ML), achieves higher concentrations in blood, is better excreted into urine and is better distributed into various tissues than conventional MLs. We investigated the pharmacokinetics of TE-031 in children upon oral administration of the drug in the following method. TE-031 granular preparation with a potency of 100 mg/g was given to 6 boys (5 years 4 months-14 years 0 month) with dose levels of 5 mg/kg and 10 mg/kg for each 3 boys. A tablet preparation with each tablet containing 50 mg of TE-031 was administered to 4 boys and 2 girls (8 years 5 months-11 years 6 months) with dose level of 2 tablets (i.e., 100 mg) and 3 tablets (i.e., 150 mg) for each 3 children. All administrations were done at 30 minutes before meal. Then, to conduct a cross-over test, the granule preparation was given orally to the 3 children mentioned above who was given 2 tablets and the 1 of 3 cases that were given 3 tablets at the same dose levels (100 mg and 150 mg) respectively. A bioassay was used to determine concentrations in blood of active antibiotic compounds and an high performance liquid chromatography (HPLC) was used to determine unchanged TE-031 and its main metabolite, M-5. Urinary concentrations of active antibiotic compounds were also determined by the bioassay and the HPLC was used to determine concentrations and proportions of unchanged TE-031 and its metabolites, M-1, M-4, M-5, M-6 and M-7 to figure out the urinary recovery rate in the first 6 hours. The results of these experiments are summarized as follows. 1. As was mentioned above, TE-031 was administered orally to 2 groups of children at dose levels of 5 mg/kg and 10 mg/kg, respectively. Mean serum levels of total active antibiotic compounds reached their maximum in 1 and 2 hours for the 5 mg/kg and the 10 mg/kg dosage groups, respectively, at 1.28 and 3.62 micrograms/ml, respectively. Mean half lives of serum concentrations in the 2 groups were quite similar, with values of at 2.1 and 2.0 hours, respectively. Mean serum concentrations of unchanged TE-031 determined by the HPLC method reached their peaks in 1 hour after administration in either of the 5 and 10 mg/kg dosage groups at peak levels of 0.65 micrograms/ml and 2.67 micrograms/ml, respectively. Thus, dose-response relationships were observed with TE-031 and M-5.(ABSTRACT TRUNCATED AT 400 WORDS)     

alpha 2-macroglobulin stimulation of protein tyrosine phosphorylation in macrophages via the mannose receptor for Fc gamma receptor-mediated phagocytosis activation.

Macrophage phagocytic activity has previously been shown to be increased by binding of modified alpha 2-macroglobulin (alpha 2M) with mannose residues at termini of sugar chains to mannose receptors on macrophages, with a subsequent increase in the number of Fc gamma receptors at the cell surface. In the present study, an examination was made of the association of protein tyrosine kinase with the increase in number of Fc gamma receptors following binding of modified alpha 2M to mannose receptors. The phagocytosis of IgG-opsonized sheep red blood cells through the action of the Fc gamma receptor by modified alpha 2M was inhibited by mannose and herbimycin A and slightly so by genistein. The mannose receptor would thus appear to be associated with tyrosine kinase activity. By Western blotting, tyrosine phosphorylated proteins with molecular weights of 32000, 34000, 36000, 65000, 85000 and 110000 appeared or increased upon treating macrophages with modified alpha 2M. The degree of tyrosine phosphorylated proteins was the same for control macrophages following incubation in the presence of mannose and herbimycin A. Genistein treatment affected only tyrosine phosphorylated proteins of 65000 and 110000. The binding of modified alpha 2M to mannose receptors was demonstrated by the inducement of tyrosine kinase activation that was sensitive to herbimycin A, followed by an increase in Fc gamma receptors and consequently greater phagocytosis.     

Preparation of Asialofetuin-Labeled Liposomes with Encapsulated Human Interferon-γ and Their Uptake by Isolated Rat Hepatocytes

The selective delivery of human recombinant interferon (IFN)- to isolated rat hepatocytes was studied with asialofetuin (AF)-labeled liposomes. AF-liposomes containing buffer solution were initially prepared by the detergent removal method, and IFN- was subsequently encapsulated by the freeze-thawing method without loss of activity. Virtually no free [³²P]IFN- was internalized into isolated rat hepatocytes, whereas AF-liposomes containing [³²P]IFN- were taken up to a significant degree. Liposomal binding to the hepatocytes (estimated at 4°C) was one-fifth of the uptake (estimated at 37°C). Since the uptake was inhibited by the addition of free AF, AF-liposomes may be taken up by the action of galactose-binding protein on the hepatocytic cell surface. The liposome preparation method reported in this paper provides a useful means for the encapsulation of unstable macromolecules into AF-liposomes. AF-liposomes were found effectively to carry IFN- into hepatocytes in vitro.     

Clinical studies on cefprozil granules in pediatric skin soft tissues infections]

Cefprozil (CFPZ), a newly developed cephalosporin in fine granular form, was administered to pediatric patients with skin and soft tissue infections. MICs were determined for 6 drugs including CFPZ, cephalexin (CEX), cefaclor (CCL), ampicillin (ABPC), methicillin (DMPPC), cloxacillin (MCIPC) against 53 clinical isolates of Staphylococcus aureus from these patients. An inoculum size of 10(6) CFU/ml was used in the MIC-determinations. CFPZ was given to 73 patients with ages ranging from 6 months to 10 years and 8 months and 71 cases were evaluable for clinical effects as follows; impetigo (65), Staphylococcal scalded skin syndrome (1), furuncle (1), subcutaneous abscess (3), and periproctal abscess (1). To study clinical efficacy, bacteriological effects and safety of this drug, a mean dose of 8.4 mg/kg with 3-4 daily dosages (57 cases of t.i.d. and 14 cases of q.i.d.) was administered for an average of 6 days. The results obtained are summarized as follows. 1. With regard to the 53 isolates of S. aureus, MICs of CFPZ against 52 strains (98.1%) ranged from 0.78 to 3.13 micrograms/ml. 45 strains (84.9%) were inhibited at 0.78 micrograms/ml. MIC90 of CFPZ was 1.56 micrograms/ml, but MIC against 1 strain of Methicillin-resistant S. aureus (MRSA) was 100 micrograms/ml. The MIC90 of CEX and CCL were 6.25 micrograms/ml and MIC of CEX and CCL against 1 MRSA strain were 200 and 100 micrograms/ml, respectively. The MIC90 of ABPC, DMPPC and MCIPC were 6.25, 3.13 and 0.39 micrograms/ml, respectively. CFPZ showed the second highest activity after MCIPC against S. aureus. 2. CFPZ showed very good clinical responses and clinical effects in 71 patients all of whom judged by doctors in charge as having "good" or better responses. 3. For impetigo patients, the evaluable cases by score 3, 5 and 7 days after administration of the drug were 52, 39 and 20 patients, respectively. The efficacy rates on these days were 90.4, 100 and 100%, respectively. The efficacy rate at a daily dose of 30.1-45.0 mg/kg on day 3 was 17.2% higher than that at 22.5-30.0 mg/kg, and the "excellent" response rate of 30.1-45.0 mg/kg group was 45.3% greater. Because of these results, it is expected that good clinical effects can be obtained at a daily dose of 22.5-30.0 mg/kg of CFPZ, but better responses can be expected at 30.1-45.0 mg/kg in 3-4 divided doses given for 5 days. 4. Bacteriological effects of CFPZ were determined against 60 strains of S. aureus.(ABSTRACT TRUNCATED AT 400 WORDS)     

Implications of arterial anatomy in patients with cancer of the periampullary region

BACKGROUND/AIMS: Preoperative information on arterial anatomy in the peripancreatic and hepatic areas is valuable to any surgeon performing pancreatoduodenectomy. METHODOLOGY: Between 1994 and 1998, 49 patients with periampullary cancer (31 distal bile duct and 18 ampullary tumors) underwent visceral angiography and radical pancreatoduodenectomy with lymphadenectomy. Surgically "significant" arterial variations and their effects on operative management and results were examined retrospectively. RESULTS: Arterial variations were found in 18 patients (37%); 15 (31%) were "significant" and 3 (6%) were "nonsignificant." All 15 patients with "significant" variants required specific type of various preservations of the hepatic arterial system. Intraoperative blood loss, transfused blood units, and operation time were greater in patients with "significant" variations than in patients without (P<0.05). Histopathologic diagnosis, tumor staging, morbidity, and mortality did not differ between the 2 groups. The 5-year survival was 33% for patients with "significant" variations and 63% for patients without (P<0.05). CONCLUSIONS: Information on arterial anatomy in the peripancreatic and hepatic areas is necessary for preoperative evaluation in patients requiring radical pancreatoduodenectomy. Presence of "significant" arterial variations may be considered as one of the negative prognostic factors in patients with periampullary cancer.     

Postoperative complications of repeat hepatectomy for liver metastasis from colorectal carcinoma

BACKGROUND/AIMS: When a repeat hepatectomy is possible, it is the most effective treatment modality for recurrent colorectal liver metastasis. The aim of this study was to evaluate the surgical risks of repeat hepatectomy for liver metastasis from colorectal carcinoma. METHODOLOGY: Between 1986 and 1996, 60 patients with hepatic metastasis from colorectal carcinoma underwent surgery in the Department of Surgery I, Oita Medical University. Ten of them underwent a repeat hepatectomy. The cases of these 10 patients were studied retrospectively; in particular, postoperative complications and intraoperative blood loss were compared between the initial and second operation. RESULTS: During the second surgery, recurrence was detected adjacent to the hepatic stump in 9 of the 10 patients. During the initial surgery, 6 underwent non-anatomic resections, and 4 had anatomic resection, including 1 extended lobectomy, 1 lobectomy, and 2 segmentectomies. For the second surgery, 3 had anatomic resections, including 2 lobectomies, and 1 segmentectomy, and 7 underwent non-anatomic resections. There were no mortalities during the initial or second operation. There was no morbidity following the initial surgeries and 7 postoperative complications (intraabdominal abscess, 4 cases; biloma, 3 cases) following the second surgeries. Mean blood loss during the second operation (1044 mL) was significantly greater than during the initial operation (561 mL). CONCLUSIONS: The present results show that repeat hepatectomy for recurrent liver metastasis from colorectal carcinoma resulted in significantly greater intraoperative blood loss and postoperative complications than those of the initial surgeries. The blood loss and complications in the second operation, the one for the recurrence, were directly associated with the fact that the recurrence was so close to the hepatic stump. Since the resection line in the second surgery was adjacent to the hepatic hilus, resection of the lesion caused much more injury to the main bile duct and main portal vein than that caused by the.