Core decompression versus nonoperative management for osteonecrosis of the hip

A complete review of the literature disclosed that there were 42 reports of 2025 hips treated by either core decompression (1206 hips) or nonoperative management (819 hips), excluding electrical stimulation, for osteonecrosis of the femoral head. The peer-reviewed published reports included general surveys, prospective studies, and multicenter studies, but excluded case reports. Satisfactory clinical results were reported in 63.5% of hips in 24 studies of core decompression and in 22.7% of hips in 21 studies of nonoperative management. When looking at only precollapse hips, there were 71% versus 34.5% good results, respectively. Recalculation excluding reports by the 4 centers that do the most core decompressions (and report the best results) showed a clinical success rate for core decompression of 53% versus 22.7% for the nonoperatively treated group. Investigators of multiple studies have reported that nonoperative management leads to extremely poor results. Core decompression has been reported to have a notable effect on the natural history and clinical progression in early stages of osteonecrosis of the femoral head. In view of the limitations of this data, further clarification of this effect only can be obtained by large prospective randomized studies.     

Conserved residues are functionally distinct within transketolases of different species

Most of the amino acid residues which interact with thiamine pyrophosphate are highly conserved among enzymes which use this cofactor. The possible roles of several such residues in cofactor binding, catalysis, and/or substrate binding were examined for human transketolase. Mutations in H110 resulted in dramatic reductions to 2% or less of the normal activity. No alterations were found in the K(m)app's for the cofactor or for the donor and acceptor substrates. Alterations in Q428 resulted in a less severe loss of activity and also no changes in the K(m)app's. On the basis of the results, H110, an invariant residue, is proposed to function as a base which abstracts a proton from the protonated 4'-iminopyrimidine ring. The deprotonated 4'-imino moiety is required for generation of the C2-thiazolium carbanion which attacks the donor substrate. Interestingly, the function in the human enzyme of this invariant histidine is distinct from its role in yeast transketolase in which it aids in binding donor substrate and in subsequent catalytic events. Q428 is suggested to play a supportive role by stabilizing and orientating a water molecule which mediates the interaction between the 4'-amino group and H110. In other TPP-utilizing enzymes, the equivalent residue of Q428 is a histidine and is thought to deprotonate the 4'-amino group.     

Red blood cell transfusions for total hip replacement in a regional hospital. A six-year analysis

To evaluate changes in the need for homologous blood and to assess the impact of autologous blood transfusion, red cell transfusions in unilateral total hip replacement surgery, performed electively in the period 1986-1991, were studied in a regional hospital. Transfusion data, perioperative blood loss and post-operative haemoglobin concentration of 495 patients were analysed. From 1986 to 1991, the percentage of patients not transfused with homologous blood increased from 18.5 to 45.5%. After the introduction of an autologous blood transfusion programme in 1987, 116 of 430 patients (27.0%) donated autologous blood. No increase in the percentage of autologous donors was observed during the study. Most common reasons for nonparticipation were the patient's age, doctors' underordering and logistic limitations. 81.9% of autologous donors had total hip replacement surgery without homologous transfusions. Mean blood loss reduced significantly from 1,373 +/- 781 ml in 1986 to 958 +/- 582 ml in 1991 (p < 0.001). Transfusion requirement in the nonautologous patients fell from 2.6 +/- 1.8 units in 1986 to 1.4 +/- 1.4 units per patient in 1989 and increased thereafter to 2.2 +/- 2.1 units in 1991 (p < 0.01) and showed a strong correlation with blood loss (r = 0.58; p < 0.001). No changes in postoperative haemoglobin concentration were observed throughout the study. In conclusion, collection of autologous blood is effective, albeit still underutilized, to reduce homologous blood requirement. The close correlation between blood loss and transfusion requirement accentuates the role of surgical practice in the reduction of homologous transfusions.     

Characterization of a 34-kDa soybean binding protein for the syringolide elicitors

Syringolides are water-soluble, low-molecular-weight elicitors that trigger defense responses in soybean cultivars carrying the Rpg4 disease-resistance gene but not in rpg4 cultivars. 125I-syringolide 1 previously was shown to bind to a soluble protein(s) in extracts from soybean leaves. A 34-kDa protein that accounted for 125I-syringolide 1 binding activity was isolated with a syringolide affinity-gel column. Partial sequences of internal peptides of the 34-kDa protein were identical to P34, a previously described soybean seed allergen. In soybean seeds, P34 is processed from a 46-kDa precursor protein and was shown to have homology with thiol proteases. P34 is a moderately abundant protein in soybean seeds and cotyledons but its level in leaves is low. cDNAs encoding 46-, 34-, and 32-kDa forms of the soybean protein were cloned into the baculovirus vector, pVL1392, and expressed in insect cells. The resulting 32- and 34-kDa proteins, but not the 46-kDa protein, exhibited ligand-specific 125I-syringolide binding activity. These results suggest that P34 may be the receptor that mediates syringolide signaling.     

Developments in the treatment of patients with chronic myeloid leukemia

In the treatment of chronic myelocytic leukaemia (CML) allogeneic bone marrow transplantation (BMT) from a sibling donor is the treatment of choice in patients younger than 50 years; the overall 5-year survival is about 60%. Donor lymphocyte infusion without chemotherapy may serve as an efficacious therapy for recurrence of CML after allogeneic BMT. Application of allogeneic BMT from a matched unrelated donor is increasing, but the outcome is still inferior to that of sibling BMT, largely due to more severe and more frequent complications. Treatment with interferon-alpha has been shown to prolong the overall median survival, but especially in a subgroup of patients (about 15%) who achieve a major cytogenic response. Combination of interferon-alpha and low-dose cytarabine leads to increased survival and a better cytogenic response than interferon-alpha alone. Current investigations are aimed at further improving survival and cytogenic response by using more intensive chemotherapy, such as high-dose cytarabine, followed by interferon-alpha maintenance therapy.     

Nephrologists'' and internal medicine physicians'' expectations of renal dietitians and general clinical dietitians

How well antibodies can protect against disease due to HIV-1 infection remains a pivotal but unresolved issue with important implications for vaccine design and the use of prophylactic antibody to prevent infection after accidental exposure to the virus and to interrupt transmission of virus from mother to child. Strong doubts about the possible utility of antibodies in vivo have been raised because of the relative resistance of primary viruses to antibody neutralization in vitro. Primary viruses are likely to be close to the viruses transmitted during natural infection in humans. Vaccine studies have been of little value in assessing antibody efficacy in vivo because none of the strategies described to date have elicited significant neutralizing antibody responses to primary viruses. Passive immunization studies are similarly hindered by the paucity of reagents able to neutralize primary viruses effectively and a single study has suggested some benefit. Here we describe experiments to explore the ability of passive antibody to protect against primary virus challenge in hu-PBL-SCID mice. In this model, severe combined immunodeficient (SCID) mice are populated with human peripheral blood mononuclear cells (PBMCs) and infected with HIV-1. We find that the potent neutralizing human monoclonal antibody IgG1b12 at high dose is able to completely protect even when given several hours after viral challenge. The results are encouraging for antibody-based postexposure prophylaxis and support the notion that antibody induction could contribute to an effective vaccine.     

Population pharmacokinetics of intravenous amiodarone and comparison with two-stage pharmacokinetic analysis

The disposition of amiodarone, an antiarrhythmic agent was evaluated after a single intravenous infusion (5 mg/kg over 15 minutes) in patients of various ages and with various degrees of renal function and left ventricular function. The plasma concentration-time data were obtained from three clinical studies with similar protocols. The data were analyzed by nonlinear mixed-effects modeling (NONMEM) to estimate the population pharmacokinetic parameters of amiodarone and to determine the significant demographic covariates affecting these parameters. The pharmacokinetic parameters of amiodarone (weight-corrected) also were calculated using two-stage analysis and were compared with the results obtained from the mixed-effects analysis. The population plasma concentration-time profile of amiodarone was best described by a four-compartment model. Demographic covariates (i.e., creatinine clearance and ejection fraction) did not improve the final pharmacostatistical model significantly. The results from the two-stage analysis showed no significant relationship between amiodarone pharmacokinetic parameters and age, gender, renal function, or ejection fraction. The results from one study, however, demonstrated that advanced age (> or = 65 years) resulted in reduced amiodarone clearance coupled with a prolonged elimination half-life. No such correlation was detected with NONMEM analysis, which may be partly attributable to the small number of elderly patients. Overall, the results from NONMEM analysis validated the results obtained from the two-stage analysis.