Effect of Induction Therapy Protocols on Transplant Outcomes in Crossmatch Positive Renal Allograft Recipients Desensitized with IVIG

Here we retrospectively examine the efficacy of two antibody induction regimens using Zenapax or Thymoglobulin in patients with positive complement-dependent cytotoxicity crossmatches (CDC-CMXs) desensitized with IVIG (intravenous immunoglobulin). Between January 1999 and March 2005, 97 patients with (+) CDC-CMXs received kidney transplants (43 deceased donors/54 living donors). All patients received at least 2 g/kg IVIG (maximum four doses) until an acceptable CMX was obtained. Patients were divided into two groups: 1. IVIG + Zenapax (n = 58), 2. IVIG + Thymoglobulin (n = 39). A total of 94% of patients in Group 1 and 84% in G2 have at least 2 years of follow up. Patient and graft survival was 96%/84% in Group 1 and 100%/90% in Group 2, p = NS. The number and severity of AR episodes were similar (36% Group 1 vs. 31% Group 2, p = NS) as was the incidence of C4d (+) antibody-mediated rejection (AMR) (Banff Grade II/III) (22% Group 1 vs. 21% Group 2). Mean serum creatinines (SCrs) at 24 months were similar (Group 1: 1.4 +/- 0.7 vs. G2: 1.5 +/- 0.7 mg/dL). Induction therapy with Zenapax or Thymoglobulin results in excellent patient, graft survival and graft function at 2 years. There was no increased risk of viral infections or malignancies with either agent. Neither agent was effective in reducing the incidence of AMR.     

Preoperative care of infants with nephroblastoma. The International Society of Pediatric Oncology 6 experience.

The International Society of Pediatric Oncology (SIOP) recommends preoperative treatment in the management of eligible patients with Wilms' tumor. Until 1980, children younger than 12 months of age (infants) at diagnosis had been excluded from the SIOP trials. SIOP 6, conducted from 1980 to 1987, was the first SIOP study to include infants older than 6 months of age. This retrospective analysis of 145 infants registered to SIOP 6 demonstrates that in infants older than 6 months and having favorable histology (FH), a two-drug preoperative chemotherapy (CT) regimen of 4 weeks significantly ameliorated stage distribution as determined at delayed surgery but did not affect a good outcome. However, the CT dose utilized in SIOP 6 resulted in an unacceptable toxicity in this age group, and SIOP 9, the new SIOP study of Wilms' tumor, recommends a reduced dose of CT in infants. Preoperative CT is not recommended in infants younger than 6 months of age. Specifically, the high incidence (29%) of mesoblastic nephroma in this age group does not justify such an approach. Histopathologic diagnosis should be obtained in these patients before any treatment.     

Intravenous Gammaglobulin (IVIG): A Novel Approach to Improve Transplant Rates and Outcomes in Highly HLA-Sensitized Patients

Intravenous immunoglobulin (IVIG) products are derived from pooled human plasma and have been used for the treatment of primary immunodeficiency disorders for more than 24 years. Shortly after their introduction, IVIG products were also found to be effective in the treatment of autoimmune and inflammatory disorders. Over the past 2 decades, the list of diseases where IVIG has a demonstrable beneficial effect has grown rapidly. These include Kawasaki disease, Guillain-Barre syndrome, myasthenia gravis, dermatomyositis and demyelinating polyneuropathy. Recently, we have described a beneficial effect on the reduction of anti-HLA antibodies with subsequent improvement in transplantation of highly HLA-sensitized patients as well as a potent anti-inflammatory effect that is beneficial in the treatment of antibody-mediated rejection (AMR). These advancements have enabled transplantation of patients previously considered untransplantable. These studies and relevant mechanism(s) of action will be discussed here.     

Use of immobilized lysozyme in the treatment of suppurative wounds of the soft tissues

The use for local treatment in 45 patients with abscesses and phlegmons of lysozyme immobilized in polymethylsiloxane contributed to acceleration in wound cleaning of necrotic masses, active granulation and epithelization, reduction in duration of patients' treatment by 3-5 days.     

Thoracic outlet syndrome: a comprehensive evaluation

Using various modalities, 480 patients were evaluated for thoracic outlet compression syndrome. Of this group, 300 patients were eventually diagnosed as having thoracic outlet syndrome after extensive evaluation. Ninety of these patients underwent a total of 103 operative procedures for thoracic outlet decompression. Nerve conduction velocities and directional Doppler studies were the most useful adjuncts in making the diagnosis. Surgical therapy after proper selection yielded an 80.6 per cent long-term "good" operative result and an additional 6.9 per cent long-term "fair" operative result in follow-up to 12 years.     

Characterization of two unusual clinically significant Francisella strains.

We have isolated two phenotypically distinct nonfastidious Francisella strains (Fx1 and Fx2) from the blood of compromised patients with pneumonia and compared them with eight other Francisella strains, including Francisella tularensis biovar tularensis, F. tularensis biovar novicida, and F. philomiragia. Our isolates grew well on sheep blood agar, chocolate agar, modified Thayer-Martin agar, and Trypticase soy agar. Fx1 and Fx2 were determined to be within the Francisella genus by cellular fatty acid analysis and by the utilization of glucose, production of H2S and catalase, and lack of motility, oxidase, nitrate reductase, and gelatinase. They were additionally shown to belong to the species F. tularensis by sequencing of two variable regions comprising approximately 500 nucleotides of the 16S rRNA gene. Also, RNA probe hybridization confirmed their belonging to the species F. tularensis. However, the new strains, which are not identical, are distinguished from other F. tularensis strains by growth characteristics, repetitive extragenic palindromic PCR fragment pattern, and some biochemical tests. Key biochemical differences included the findings that Fx1 was positive for beta-galactosidase and arabinose hydrolysis and that both strains were citrulline ureidase positive and glycerol negative. Commercial F. tularensis antiserum agglutinated stock F. tularensis strains but not Fx1, Fx2, F. tularensis biovar novicida, or F. philomiragia; serum from either patient failed to agglutinate or only weakly agglutinated commercial antigen but showed agglutination when tested against each patient's respective isolate. Fx1 and Fx2 produced beta-lactamase. Because of their good growth, negative serology, and biochemical profile, the organisms could be misidentified in the clinical laboratory if standard strategies or commercial identification systems are used.     

The breast-feeding dilemma and its impact on HIV-infected women and their children

The rate of HIV transmission via breast-feeding ranges from 14% to 26%, depending on the timing of maternal infection. In settings where infant mortality rates from infectious diseases and malnutrition are low and relatively safe alternatives to breast-feeding are available, HIV-infected mothers should be advised not to breast-feed. Where breast-feeding by HIV-infected mothers and bottle-feeding both present serious risks of mortality, changing the conditions in which families live so that safe feeding alternatives become available must be a top priority. At the same time, these mothers need information about the relative risks and benefits of breast-feeding, early weaning, wet-nursing, and formula feeding. This article reviews the available research data and discusses critical gaps in current knowledge.