Pseudophakic bullous keratopathy

We reviewed the records of all patients with pseudophakic bullous keratopathy (271 eyes, 251 patients) seen during a six-month period to determine predisposing factors, associated problems, current management, and visual outcome. Pseudophakic bullous keratopathy was associated most frequently with anterior chamber intraocular lenses in general (155 of 271), and with Leiske style lenses in particular (100 of 271). It was associated with a visual acuity of 20/200 or less in 206 eyes and a visual acuity of counting fingers or less in 129 of the eyes at the initial examination. Penetrating keratoplasties had been performed in 189 of the eyes. After penetrating keratoplasty, 108 of 189 of the eyes had a visual acuity of 20/200 or less (mean follow-up, 15 months). Visual acuity improved with longer follow-up, and among patients with a minimum follow-up of two years, 23 of 36 eyes had a visual acuity of 20/100 or better. Most grafts were clear (145 of 189). Pseudophakic bullous keratopathy was associated with marked visual loss, which was permanent despite clear grafts in 29 of 92 eyes followed-up for one year or longer.     

FK506 in combination with methotrexate for the prevention of graft- versus-host disease after marrow transplantation from matched unrelated donors

The safety and potential efficacy of FK506 in combination with a short course of methotrexate (MTX) for the prevention of acute graft-versus- host disease (GVHD) after marrow transplantation from HLA-matched unrelated donors was evaluated in a single-arm Phase II study conducted at two centers. Forty-three patients, 15 to 54 (median 41) years of age, were transplanted for hematologic malignancies. Thirty-seven of 43 evaluable patients had evidence of sustained marrow engraftment. Five patients died before day 17 after transplantation. The median time to an absolute neutrophil count of > 0.5 x 10(5)/L was 21 (range, 14 to 30) days. Nephrotoxicity (serum creatinine concentration > 2 mg/dL or doubling of baseline) occurred in 32 patients (74% cumulative incidence during the first 100 days after transplant). Other adverse effects included hypertension (n = 27), hyperglycemia (n = 27), neurotoxicity (n = 9) and thrombotic thrombocytopenic purpura (n = 2). Severe veno- occlusive disease of the liver occurred in 9 (21%) of the 43 patients. Eighteen patients (42%) developed grades II to IV acute GVHD and five (12%) developed grades III to IV acute GVHD. Twelve of 25 evaluable patients developed extensive chronic GVHD within 1 year of marrow transplantation resulting in an estimate of the probability of developing this complication of 48%. The cumulative incidence of transplant-related mortality during the first 100 days was 37%. Kaplan- Meier estimates of disease-free survival at 2 years for good-risk, poor- risk, and all patients were 65%, 4%, and 32%, respectively. FK506 in combination with a short course of MTX appears active in preventing acute GVHD after marrow transplantation from unrelated donors. Further studies comparing the combination of FK506 and MTX with cyclosporine and MTX for the prevention of acute GVHD are warranted.     

Postoperative opiate analgesia requirements of smokers and nonsmokers

BACKGROUND: Smoking cigarettes and other forms of nicotine administration appear to blunt the perception of pain. Abrupt discontinuation of nicotine in nicotine-dependent patients appears to increase the perception of pain. The clinical importance of nicotine's effect on pain perception is not fully understood. OBJECTIVE: To determine whether smokers who abruptly discontinue smoking as a result of being hospitalized for coronary artery bypass graft (CABG) require more postoperative opiate analgesics than nonsmokers. METHODS: A retrospective review of patients who underwent a CABG was performed. Smokers (n = 20) were compared with nonsmokers (n = 69) with regard to opiate analgesic use during the first 48 hours postoperatively. The use of nonopiate sedatives was also compared between the groups. RESULTS: When normalized for weight and body mass index, smokers required 23% and 33%, respectively, more opiate analgesics than did nonsmokers (p = 0.027 and 0.023, respectively). The percentage of patients who received benzodiazepines postoperatively was similar in the 2 groups. CONCLUSIONS: In this study, smokers deprived of nicotine required a greater amount of opiates in the first 48 hours after CABG than did nonsmokers. Healthcare providers need to be aware of the potential for increased narcotic requirements among nicotine-deprived smokers. Further study is needed to determine whether nicotine replacement lessens the requirement for postoperative analgesics in smokers.     

Development and characterization of monoclonal antiplatelet autoantibodies from autoimmune thrombocytopenic purpura-prone (NZW x BXSB)F1 mice

Male (NZW x BXSB)F1 (W/BF1) mice develop systemic autoimmunity involving autoantibodies, progressive thrombocytopenia, lupus nephritis, and degenerative coronary vascular disease with myocardial infarction. Platelet-associated IgG (PAIgG) on the platelet surface mediates platelet destruction by the reticuloendothelial system in the autoimmune thrombocytopenic purpura (ATP) of W/BF1 mice. Because the epitopes targeted in ATP by PAIgG have not been identifiable using serum from thrombocytopenic W/BF1 mice, we developed seven hybridomas secreting antiplatelet monoclonal antibodies (MoAbs) using splenocytes of thrombocytopenic W/BF1 mice. Epitopes recognized by three MoAbs were similar to those recognized by PAIgG, because eluted IgG from platelets of thrombocytopenic W/BF1 mice inhibited platelet binding by MoAbs in competitive micro-enzyme-linked immunosorbent assay. Hybridoma cells or purified Ig from the ascites of two clones (2A12 and 6A6), when injected into nude mice produced acute thrombocytopenia, elevated the levels of PAIgG, purpura, and megakaryocytosis. MoAbs of two clones also reacted with single-stranded DNA or double-stranded DNA, and one of these clones (4-13) bound to cardiolipin (CL) but was nonpathogenic in nude mice, suggesting that anti-CL and antiplatelet autoantibodies can be distinct. On immunoblotting analysis, antiplatelet MoAbs frequently bound a 100-Kd platelet protein. These MoAbs contribute to an understanding of the etiopathogenesis of ATP and the several antigens and autoantibodies involved.     

Marrow transplantation with or without donor buffy coat cells for 65 transfused aplastic anemia patients

Sixty-five multiply transfused patients with severe aplastic anemia were given cyclophosphamide followed by grafts anemia were given cyclophosphamide followed by grafts from HLA-identical siblings. The effect of the administration of viable donor buffy coat cells following the marrow inoculum was evaluated with regard to graft rejection and survival. Results in 43 patients so treated are presented along with those in 22 concurrent patients given marrow alone. Most patients given buffy coat had positive in vitro tests of sensitization indicating a high risk for graft rejection, while all but one of the patients given marrow alone had negative tests. Thirty of the 43 (70%) patients given marrow and buffy coat are alive between 10 and 61 mo (median 36) after grafting; 4 died after graft rejection and 6 with acute or chronic graft-versus-host disease (GVHD). Eleven of the 22 (50%) patients given marrow alone are alive between 29 and 65 mo (median 52); 7 died after graft rejection and 3 with GVHD. The addition of buffy coat cell infusions to the marrow inoculum reduced the risk of rejection and increased survival in the currently reported transfused patients when compared to patients grafted before 1976. However, there was an increased risk of chronic GVHD. Recipients of marrow from female donors survived slightly better (73%) than recipients of male marrow (58%).     

A defective Vkappa A2 allele in Navajos which may play a role in increased susceptibility to haemophilus influenzae type b disease.

The antibody response to H. influenzae type b (Hib) is pauciclonal, and is dominated by antibodies using the VkappaA2 gene. Navajos have a 5-10-fold increased incidence of Hib disease compared with control populations. We hypothesized that a polymorphism in one of the genes in this oligoclonal response may lead to increased disease susceptibility. Since the predominant A2+ anti-Hib antibodies have high avidity for Hib and can be unmutated, the A2 Vkappa gene was analyzed. Over half of the Navajos studied, but only one control individual, had a new allele of A2, termed A2b, with three changes from the published A2 germline sequence. One of the changes was in the recombination signal sequence, suggesting that the A2b allele might not undergo V-J rearrangement very frequently. This possibility was confirmed by analyzing the relative frequency of non-productive A2 rearrangements in A2a/b heterozygous Navajos. Many fewer A2b rearrangements were observed, showing that the A2b allele is defective in its ability to undergo rearrangement. The prevalence of this allele in Navajos may play a role in their increased susceptibility to invasive Hib disease. If so, it would underscore the importance of the germline Ig repertoire for protective antibody responses to pathogenic bacteria in unimmunized children.     

Intra-articular Chlamydial Antigen and Inflammatory Arthritis

Joint material from 133 patients with well-characterized inflammatoryarthritis, including individuals likely to have suffered reactivearthiritis, was studied. The majority of patients were alsoexamined for the presence of genital tract infection with Chlamydiatrachomatis. Fluorescein-conjugated monoclonal antibodies demonstratedthe presence of C. trachomatis antigen in synovial fluid celldeposits or synovial sections from inflamed knee joints of sevenpatients with reactive arthritis. The significance of thesefindings is discussed, as is the low rate of detection of chlamydialantigen in either the genital tract or the joint from patientsin this study. We emphasize the need for further work aimedat identifying the relevant immunogenic chlamydial antigensresponsible for the initiation of reactive arthritis.