Low-dose thymoglobulin as second-line treatment for steroid-resistant acute GvHD: an analysis of the JSHCT.

A nationwide retrospective study for the clinical outcomes of 99 patients who had received thymoglobulin at a median total dose of 2.5 mg/kg (range, 0.5-18.5 mg/kg) as a second-line treatment for steroid-resistant acute GvHD was conducted. Of the 92 evaluable patients, improvement (complete or partial response) was observed in 55 patients (60%). Multivariate analysis demonstrated that male sex and grade III and IV acute GvHD were associated with a lower improvement rate, whereas thymoglobulin dose (<2.0, 2.0-3.9 and ⩾4.0 mg/kg) was NS. Factors associated with significantly higher nonrelapse mortality included higher patient age (⩾50 years), grade IV acute GvHD, no improvement of GvHD and higher dose of thymoglobulin (hazard ratio, 2.55; 95% confidence interval, 1.34-4.85; P=0.004 for 2.0-3.9 mg/kg group and 1.79; 0.91-3.55; P=0.093 for ⩾4.0 mg/kg group). Higher dose of thymoglobulin was associated with a higher incidence of bacterial infections, CMV antigenemia and any additional infection. Taken together, low-dose thymoglobulin at a median total dose of 2.5 mg/kg provides a comparable response rate to standard-dose thymoglobulin reported previously, and <2.0 mg/kg thymoglobulin is recommended in terms of the balance between efficacy and adverse effects.

[Adrenal gland lymphoma accompanied by renal cell carcinoma].

A 76-year-old man was admitted with right hypochondralgia. Computed tomography revealed tumors measuring 90 mm and 20 mm in the right adrenal gland and kidney, respectively. Under a diagnosis of renal and adrenal cancer, the patient underwent nephro-adrenectomy, which revealed renal cell carcinoma in the kidney and non-Hodgkin's B-cell lymphoma of the diffuse large cell type in the adrenal grand. The patient has been disease-free for ten months after the operation. To our knowledge, this is the first report of coexisting renal cell carcinoma and adrenal lymphoma. The relationship between these two disorders in our patient is discussed.

Successful therapy of pure red cell aplasia secondary to plasma cell dyscrasia with bolus methylprednisolone.

A 65-year-old man, who is a Jehovah's Witness, was admitted to our hospital due to progressive anemia following a four-year history of biclonal gammopathy of no clinical significance. He was diagnosed with pure red cell aplasia (PRCA) associated with plasma cell dyscrasia. Despite a markedly decreased red blood cell count (hematocrit 5.6%), the patient refused transfusion. He was intravenously administered bolus methylprednisolone. Reticulocytosis and recovery from anemia were observed on day 7 after the start of therapy. Secondary PRCA following plasma cell dyscrasia is a rare disorder; the treatments for this rare condition are discussed.

Churg-Strauss Syndrome with pleural involvement.

A 51-year-old Japanese man with Churg-Strauss Syndrome (CSS) diagnosed by pleural biopsy is described. He was hospitalized because of high fever and bilateral knee, elbow and shoulder joint pain. Chest roentgenogram and chest computed tomography (CT) scan revealed bilateral massive pleural effusion. Pleural biopsy revealed eosinophilic infiltration and necrotizing granulomas. He was treated with oral prednisolone and his symptoms improved. This is the first report of CSS diagnosed by pleural biopsy.

The pitfall in evaluating several serological markers of Pneumocystis carinii pneumonia in a neutropenic patient.

We compared the significance of several serum markers to evaluate the activity of Pneumocystis carinii pneumonia (PCP) in an immunocompromised patient. We successively measured KL-6, an amino-terminal propeptide of Type III procollagen (PIIINP), and the cytokeratin 19 fragment (CK19) in the sera of a patient with PCP. Interestingly, PIIINP, KL-6, and CK19 levels in the sera did not increase at the time of onset of PCP during a neutropenic phase. Instead, they markedly increased after the recovery of WBC counts. This case suggests that values of PIIINP, KL-6, and CK19 used for monitoring the activity of PCP might be underestimated in neutropenic patients.

[Angioimmunoblastic T-cell lymphoma presenting with rapidly increasing biclonal gammopathy].

A 59-year-old man was admitted to our hospital with high fever and dysphagia. Physical examination revealed a lingual tumor and swelling of the cervical and inguinal lymph nodes. A lymph node biopsy specimen revealed that the normal nodal architecture had been obliterated by infiltration of small, intermediate, and large pale lymphocytes. Arborous branching of high endothelial venules was also observed. Southern blotting analysis showed rearrangement of the T-cell receptor beta gene. A diagnosis of angioimmunoblastic T-cell lymphoma was made. Serial serum protein fractionation analysis showed rapidly increasing M-protein. Immunofixation electrophoresis indicated specific bands for IgG kappa and IgM lambda, confirming the presence of biclonal gammopathy. Biclonal gammopathy has rarely been reported in patients with angioimmunoblastic T-cell lymphoma. The relationship between the occurrence of biclonal gammopathy and the possible role of HHV-6, HHV-8 and EBV is discussed.

A highly efficient synthesis of cyclaradine and its behaviour towards adenosine deaminase.

(+)-, (-)-, and (+/-)-Cyclaradines were efficiently synthesized from 2-aza-bicyclo[2.2.1]hept-5-en-3-one (ABH). (+)- and (+/-)-Cyclaradines were deaminated by adenosine deaminase whereas (-)-cyclaradine was not hydrolyzed under the same conditions.

Adolescent body image during pregnancy.

This study compares the body perceptions of pregnant teenagers with those of their never-pregnant peers. Forty-three third-trimester pregnant girls were matched by age, race, socioeconomic status, and pubertal development to 43 never-pregnant girls. Subjects were given the Tennessee Self-Concept Scale (TSCS), a self-administered questionnaire consisting of 100 self-descriptive statements which are divided into nine subscales. When compared with never-pregnant girls, the pregnant girls have a higher overall self-esteem, a more positive body image, a surer self-identity, and feel more productive as a family member, but appeared limited in their capacity for self-criticism.

Is repeat pregnancy in adolescents a "planned" affair?

This study assessed whether girls who become pregnant more than once do so for different reasons than girls who are pregnant for the first time. Girls in group 1 (G1) were pregnant for the first time (n = 104, 69%) and those in group 2 (G2) were pregnant for the second time or more (n = 46, 31%). About 60% of the girls in G2 had living children at home, but they were more likely than those in G1 to state that they became pregnant because they wanted a baby (G2 44%, G1 21%; p less than 0.01) and, conversely, girls in G1 were more likely than those in G2 to state that the pregnancy was an accident and "just happened" (G1 61%, G2 37%; p less than 0.01). Many girls who become pregnant more than once appear to do so intentionally.

PIP: The reasons for becoming pregnant reported by teenagers who registered for prenatal care at the University of California San Diego (UCSD) Teen OB Clinic between May 1984 and July 1987 were investigated. 150 consecutive pregnant adolescents 12-19 years old were interviewed by a pediatrician at their first prenatal visit. Group 1 (G1) girls were pregnant for the first time; and group 2 (G2) for a second time or more. Nearly all girls were from the lower socioeconomic classes. Girls in G1 were slightly younger than the girls in G2 (p 0.0002). Only 11% of G1 and only 15% of G2 were married. 55% of G1 compared to 35% of G2 were full-time students (p 0.01). About half of G2 were at home, unemployed, and not in school. At the time of conception about 14% of G1 and 2% of G2 (p 0.01) lived with both parents. 60.6% of G1 stated that the pregnancy was unplanned vs. 37% of G2 (p 0.01). 43.5% of G2 were pregnant because they wanted a baby vs. only about 20% of G1 (p 0.01). About 60% of G2 (27 girls) already had at least one living child at home. About 8% of G1 intended to place the baby for adoption, while none of G2 reported considering adoption (p 0.025). About 41% of G1 and 46% of G2 planned to care for their baby with the father of the baby. 26% of G2 intended to care for their infant alone vs. 7% of G1 (p 0.005). The fathers in both groups were older than the girls by an average of 4-5 years. G2 was further divided into two groups: current planned pregnancy (20 girls; 44%) and current unplanned pregnancy (26 girls; 56%). 14 girls of the planned group (70%) and 13 girls of the unplanned group (50%) already had living children. 4 girls of the planned group and 13 girls of the unplanned group reported a previous induced abortion. Girls in G2 presented for prenatal care at an earlier gestational age (17.1 weeks) than those in G1 (20.4 weeks) (p 0.04).

Antimicrobial activity of dactimicin in vitro compared with that of dibekacin, netilmicin, sisomicin and micronomicin.

Antimicrobial activity of dactimicin, a pseudo-disaccharide aminoglycoside antibiotic, was compared with those of dibekacin, netilmicin, sisomicin and micronomicin using clinical isolates of four Gram-positive and sixteen Gram-negative bacteria. Dactimicin was more active than the reference amino-glycosides against Serratia marcescens, especially gentamicin-resistant Serratia sp., Proteus vulgaris, P. rettgeri and Klebsiella oxytoca, but less active against Pseudomonas aeruginosa and P. mirabilis. Dactimicin was equally active as the references excepting netilmicin against Gram-positive bacteria and some Gram-negative bacteria including Escherichia coli, K. pneumoniae, Morganella morganii, Haemophilus influenzae, Citrobacter freundii, Enterobacter aerogens, E. cloacae, Acinetobacter calcoaceticus and Campylobacter jejunii. Dactimicin was active against resistant strains possessing various aminoglycoside-modifying enzymes including AAC(3)-1, by which dactimicin was acetylated.

[The enzymatic mechanisms of resistance to aminoglycoside antibiotics in methicillin-cephem-resistant Staphylococcus aureus].

We investigated enzymatic mechanisms of resistance to aminoglycoside antibiotics in methicillin-cephem-resistant Staphylococcus aureus (MRSA) by elucidation of the structures of the enzymatic reaction products. According to the MIC data, MRSA, (46 strains) can be classified into 3 groups as follows. 1. Group I (35 strains) was highly resistant to gentamicin (GM) and tobramycin (TOB), and produced 2"-aminoglycosides phosphotransferase (APH (2"]. 2. Group II (8 strains) was sensitive to GM, but was highly resistant to TOB, and produced 4'-aminoglycosides adenylyl-transferase (AAD (4']. 3. Group III (3 strains) was sensitive to GM and TOB, but was highly resistant to kanamycin, and produced 3'-aminoglycosides phosphotransferase (APH (3']-III. Arbekacin (HBK) was the most stable antibiotic to all of the inactivating-enzymes produced by MRSA, and all MRSA were sensitive to HBK.

[Antibacterial activities of arbekacin, a new aminoglycoside antibiotic, against methicillin-cephem-resistant Staphylococcus aureus].

The in vitro and in vivo antibacterial activities of a new aminoglycoside antibiotic, arbekacin (HBK), against methicillin-cephem-resistant Staphylococcus aureus (MRSA) were compared with those of gentamicin (GM), netilmicin (NTL) and amikacin (AMK). The results obtained were summarized as follows: Compared to other aminoglycoside antibiotics, HBK had the highest antibacterial activities against clinically isolated MRSA (46 strains). Therapeutic effects of HBK against experimental systemic infections with MRSA in mice, were superior to those of GM, NTL and AMK. The ED50's of GM, NTL and AMK were more than 2 mg/mouse. Therapeutic effects of HBK against experimental subcutaneous infections with MRSA in mice were also superior to those of GM, NTL and AMK.

In vitro and in vivo antibacterial activities of dactimicin, a novel pseudodisaccharide aminoglycoside, compared with those of other aminoglycoside antibiotics.

When compared with astromicin, amikacin, gentamicin, and sisomicin, dactimicin was similar to astromicin in in vitro activity and was more active than amikacin and gentamicin against the clinical isolates of Serratia marcescens, but less active against Pseudomonas aeruginosa. Dactimicin and astromicin were active against many gentamicin- and amikacin-resistant bacteria expressing aminoglycoside-modifying enzymes, with the exception of aminoglycoside 3-acetyltransferase. However, dactimicin was more resistant than astromicin to inactivation by aminoglycoside 3-acetyltransferase, probably owing to the protective action of the formimidoyl group. The in vivo activity of dactimicin, assessed by the 50% effective doses against systemic infections in mice, was similar or superior to that of astromicin and was superior or inferior to that of amikacin depending on the strains tested.

Cloning of antibiotic-resistance genes in Streptomyces.

Antibiotic-resistance genes were shotgun cloned from antibiotic-producing Streptomyces sp. using pock-forming plasmids (pSF689 and pSF765), as cloning vectors. Streptomyces chartreusis SF1623 and S. lividans 66 were used as host strains. The ribostamycin (RSM) resistance gene was cloned from S. ribosidificus SF733 DNA (on a 2.3 Md PstI fragment) into both S. chartreusis SF1623 and S. lividans 66, using pSF689 as vector. Kanamycin (KM), novobiocin (NB), destomycin (DM) and racemomycin (RM) resistance genes were cloned from S. kanamyceticus M1164, S. spheroides M1469, S. rimofaciens M1470 and S. lavendulae A249 genomic DNA into S. lividans 66, using pSF765 as vector. Furthermore two types of KM resistance determinants derived from S. kanamyceticus M1164 were cloned using S. lividans 66, the pSF689 vector. The RSM resistance gene showed no homology to plasmid pSF733 of S. ribosidificus SF733, but hybridized to PstI or BclI digested total DNA of S. ribosidificus SF733.