Long-term outcome of a prospective randomized trial of conversion from cyclosporine to azathioprine treatment one year after renal transplantation

BACKGROUND: Since the introduction of cyclosporine (CsA), 1-year renal allograft survival has improved, but concern persists about the long-term adverse effects of CsA, especially with respect to renal function and blood pressure. This randomized controlled trial was set up to establish whether withdrawal of CsA would alter long-term outcome. METHODS: Adult patients who, at 1 year after renal transplantation, had a stable serum creatinine of less than 300 micromol/L and who had not had acute rejection within the last 6 months were eligible for entry. Patients were randomized either to continue on CsA (n=114) or to stop CsA and start azathioprine (Aza, n=102). All patients remained on prednisolone. Median follow-up was 93 months after transplantation (range: 52-133 months). RESULTS: There was no significant difference in actuarial 10-year patient or graft survival (Kaplan-Meier), despite an increased incidence of acute rejection within the first few months after conversion. Median serum creatinine was lower in the Aza group (Aza: 119 micromol/L; CsA. 153 micromol/L at 5 years after randomization, P=0.0002). The requirement for antihypertensive treatment was also reduced after conversion to Aza; 75% of patients required antihypertensive treatment at the start of the study, decreasing to 55% from 1 year after randomization in the Aza group and increasing to >80% in the CsA group (55% (Aza) and 84% (CsA) at 5 years after randomization, P<0.005). CONCLUSIONS: Conversion from CsA to Aza at 1 year after renal transplantation results in improvement in both blood pressure control and renal allograft function, and is not associated with significant adverse effects on long-term patient or graft survival.     

Glycopeptide antibiotic resistance genes in glycopeptide-producing organisms

The mechanism of high-level resistance to vancomycin in enterococci consists of the synthesis of peptidoglycan terminating in D-alanyl-D-lactate instead of the usual D-alanyl-D-alanine. This alternate cell wall biosynthesis pathway is ensured by the collective actions of three enzymes: VanH, VanA, and VanX. The origin of this resistance mechanism is unknown. We have cloned three genes encoding homologs of VanH, VanA, and VanX from two organisms which produce glycopeptide antibiotics: the A47934 producer Streptomyces toyocaensis NRRL 15009 and the vancomycin producer Amycolatopsis orientalis C329.2. The predicted amino acid sequences are highly similar to those found in VRE: 54 to 61% identity for VanH, 59 to 63% identity for VanA, and 61 to 64% identity for VanX. Furthermore, the orientations of the genes, vanH, vanA, and vanX, are identical to the orientations found in vancomycin-resistant enterococci. Southern analysis of total DNA from other glycopeptide-producing organisms, A. orientalis 18098 (chloro-eremomycin producer), A. orientalis subsp. lurida (ristocetin producer), and Amycolatopsis coloradensis subsp. labeda (teicoplanin and avoparcin producer), with a probe derived from the vanH, vanA, and vanX cluster from A. orientalis C329.2 revealed cross-hybridizing DNA in all strains. In addition, the vanH, vanA, vanX cluster was amplified from all glycopeptide-producing organisms by PCR with degenerate primers complementary to conserved regions in VanH and VanX. Thus, this gene sequence is common to all glycopeptide producers tested. These results suggest that glycopeptide-producing organisms may have been the source of resistance genes in vancomycin-resistant enterococci.     

Interaction between a murine myeloma cell line and bone marrow stromal cells

Intravenous transplantation of an in vitro maintained murine myeloma cell line, 5T33, results in progressive growth in the bone marrow of C57Bl/KaLwRiJ mice. Concurrent with the growth of the tumor in vivo, the bone marrow stromal cells are inhibited, as assayed by their ability to form stromal cell foci and long-term monolayers in vitro. Inhibition of normal mouse marrow stromal cell growth also occurs when 5T33 cells are added to the marrow cells in vitro, and contact between the marrow and 5T33 cells is not necessary to achieve inhibition, indicating secretion of one or more diffusible inhibitory factors.     

栅对准误差对双栅MO SFET 性能影响的分析

对栅MOSFET是一种非常有发展前途的新型器件，它具有跨导高、亚阈值特性优异、短沟道特性好等优点，但是目前自对准的双栅MOSFET的工艺制作相当困难。本文中分析了双栅MOSFET的正、背面栅存在对准误差时，对器件的表态及动态特性的影响，并提出了一种改善这种影响的方法。     

Personality disorders and psychiatric symptoms in psoriasis

Two groups of psoriatic outpatients (ns = 192 and 119) were given, respectively, the Million Clinical Multiaxial Inventory-II and Foulds' Delusions-Symptoms-States Inventory. They were compared with dental (n = 192) and with general surgical (n = 190) patients. The psoriatic group presented clearly higher mean scores and frequencies on most of the personality disorder scales. On Foulds' inventory, psoriatic patients showed higher frequencies of neurotic and psychotic class allocations. A cluster analysis of personality scores provided evidence for 4 different personality clusters of patients with psoriasis: (a) Avoidant, Dependent, Schizoid, and Self-defeating (32.2%), (b) Compulsive, Narcissistic, and Aggressive (30.7%), (c) no personality disorder (18.2%), (d) Borderline, Paranoid, and Schizotypal, etc. (18.8%).     

Cyclosporine A in the treatment of early rheumatoid arthritis. A prospective, randomized 24-month study

OBJECTIVE: To investigate the efficacy, tolerability and safety of cyclosporine A (CSA) in early rheumatoid arthritis (RA) patients. METHODS: Patients with an early diagnosis of RA, a disease duration of less than 3 years, and without prior disease modifying antirheumatic drug (DMARD) treatment were studied. They randomly received oral CSA (3 mg/kg/day) or oral methotrexate (MTX) (0.15 mg/kg/week). In addition, all patients in both groups received oral prednisone (7.5 mg/day). RESULTS: Fifty-two patients were assigned to the CSA group and 51 to the MTX group. After 24 months of treatment, 48 patients from the CSA group and 48 from the MTX group showed significant clinical improvement. This was evaluated by the duration of morning stiffness, grip strength, the total joint count, joint swelling, and joint tenderness and pain, compared to pre-treatment values. The clinical improvement was also associated with a significant decrease in ESR and CRP values in both groups. No significant radiological deterioration was observed in the CSA patients compared to those treated with MTX after 24 months. Four patients from the CSA group dropped out of the study, two because of a synovitis flare, one because of severe hypertrichosis and one because of severe gingival hyperplasia. Three patients from the MTX group withdrew, one because of disease flare-up and two because of gastrointestinal disturbances. CONCLUSION: Early immunointervention in RA patients appears to be crucial to limit the development of joint damage. Cyclosporine A appears to be effective, well tolerated and safe in the long-term treatment of RA and can therefore be used as a first immunomodulatory drug in the armamentarium for the treatment of RA.     

Ki-1 large cell anaplastic lymphoma--a clinicopathological study

Ki-1 large cell anaplastic lymphoma is a recently described variant of malignant lymphoma. A retrospective study of 10 cases of Ki-1 lymphoma was carried out at the Armed Forces Institute of Pathology (AFIP) Rawalpindi to document its clinical and morphological features. The morphological features were evaluated by a study of paraffin embedded sections stained with haematoxylin and eosin stains. Immunohistochemical stains for BER-H2 and leucocyte common antigen (LCA) were performed in all cases. The age of the patients ranged from 2 to 60 years and male to female ratio was 2.3:1. Cervical lymphadenopathy was the most common presentation. Histologically, there was a complete effacement of the lymph node architecture in 8 cases. The Reed-Sternberg like cells were seen in 2 and histiocyte like cells in 7 cases. Immunohistochemically all cases were positive for BER-H2. It is suggested that the possibility of Ki-1 lymphoma should be considered in all cases of lymphoma with pleomorphic morphology.