Biological resurfacing of the knee: a review of surgical management

Lesions of the articular surfaces of the knee have been managed by various techniques over the last 50 years. Surgical management has involved: excising the damaged area, refashioning the underlying bone to produce a fibrous response, and introducing allograft, autograft and synthetic materials to encourage a repair matrix. The techniques and their pitfalls are reviewed and discussed, and suggestions made as to the direction of future studies for the repair of osteochondral lesions in the painful knee.     

Cell salvage in burn excisional surgery

BackgroundHemostasis during burn surgery is difficult to achieve, and high blood loss commonly occurs. Bleeding control measures are limited, and many patients require allogeneic blood transfusions. Cell salvage is a well-known method used to reduce transfusions. However, its evidence in burns is limited. Therefore, this study aimed to examine the feasibility of cell salvage during burn surgery.Study design and methodsA prospective, observational study was conducted with 16 patients (20 measurements) scheduled for major burn surgery. Blood was recovered by washing saturated gauze pads with heparinized saline, which was then processed using the Cell Saver. Erythrocyte concentrate quality was analyzed by measuring hemoglobin, hematocrit, potassium, and free hemoglobin concentration. Microbial contamination was assessed based on cultures at every step of the process. Differences in blood samples were tested using the Student’s t-test.ResultsThe red blood cell mass recovered was 29 ± 11% of the mass lost. Patients’ preoperative hemoglobin and hematocrit levels were 10.5 ± 1.8 g/dL and 0.33 ± 0.05 L/L, respectively. The erythrocyte concentrate showed hemoglobin and hematocrit levels of 13.2 ± 3.9 g/dL and 0.40 ± 0.11 L/L thus showing a concentration effect. The potassium level was lower in the erythrocyte concentrate (2.5 ± 1.5 vs. 4.1 ± 0.4 mmol/L, p < 0.05). The free hemoglobin level was low (0.16 ± 0.21 μmol/L). All cultures of the erythrocyte concentrate showed bacterial growth compared to 21% of wound cultures.ConclusionRecovering erythrocytes during burn excisional surgery using cell salvage is possible. Despite strict sterile handling, erythrocyte concentrates of all patients showed bacterial contamination. The consequence of this contamination remains unclear and should be investigated in future studies.     

Evaluation of a microplate assay specific for heavy metal toxicity

A rapid, quantitative microbial assay, which is specific for heavy metal toxicity, has been developed. The assay (MetPLATE) is in a 96-well microtitration plate format and is suitable for determining toxicity characteristics such as median inhibitory concentrations. The sensitivity of MetPLATE to heavy metals [Cu, Zn, Cd, Pb, Hg, Cr(III)] was generally higher than Microtox and was of the same order as or better than Daphnia and fish bioassay. MetPLATE was insensitive to organic compounds at concentrations higher than those found in the environment. Six out of 10 industrial wastewaters or process waters surveyed were toxic. Heavy metal analysis of these waters confirmed the presence of heavy metals in the toxic samples. MetPLATE can be run concurrently with other assays for general toxicity to help determine the nature of chemicals causing toxicity.     

Differential cytotoxic T-lymphocyte (CTL) responses in HIV-1 immunised sibling chimpanzees with shared MHC haplotypes

Cell mediated immune responses to HIV-1 and CTL responses in particular differ dramatically in infected individuals. This may largely be influenced by the immunogenetic differences of different individuals such as those encoded by the MHC. These differences may be difficult to dissect due to the immunosuppressive nature of HIV-1 infection itself. In order to reduce the variables associated with effects of the virus, one recombinant viral antigen was chosen from a particular HIV-1 variant (rgp120 of the clinical isolate HIV-1w6.1D). To minimise differences between outbred hosts, we chose two sibling chimpanzees from which the family pedigree and genetic segregation with respect to polymorphic MHC molecules was known. Immunisation induced strong antigen specific antibody and T-helper immune responses. The magnitude and persistence of the humoral and T-helper immune responses were comparable in both chimpanzees. However, CTL responses were only observed in one sibling. These responses were subsequently mapped to several distinct epitopes. The CTL response to the immunodominant epitope was found to be presented in the context of a MHC molecule which was shared by both siblings. The absence of a CTL response in the other sibling is not yet understood, but could not be attributed to MHC alleles that were not shared by these two chimpanzees. These findings suggest that other polymorphic immunoregulatory mechanisms such as those involved in antigen processing and presentation influence host CTL responses to HIV-1.     

HIV-1 vaccine-induced immune responses which correlate with protection from SHIV infection: compiled preclinical efficacy data from trials with ten different HIV-1 vaccine candidates

The specific immune mechanisms necessary and/or sufficient to elicit HIV-vaccine protection remain undefined. Utilising the SHIV rhesus macaque model the immunogenicity as well as the efficacy of ten different HIV-1 vaccine candidates was evaluated. Comparison of the immune responses induced, with the ability of the vaccine to protect from SHIV infection provided a means to determine which type of immune responses were necessary for protection. Vaccine candidates included VLPs, DNA, subunit protein with novel adjuvant formulations, ISCOMs and pox-virus vectors. Protection from SHIV infection was achieved in approximately half of the animals which received a primary intravenous cell-free challenge. The presence of CTL in the absence of other effector responses did not correlate with protection from this route and type of challenge. Virus neutralising antibodies (Nab) appeared to be necessary but alone were insufficient for protection. If Ag-specific IFN-gamma and/or IL-4 as well as lymphoproliferative (LP) responses were found with the lack of a detectable IL-2 response, then protection was not observed. Immunity correlated with the magnitude of Nab responses, beta-chemokines and as well as balanced, qualitative T-helper responses.     

Chemopreventive effects of alpha-santalol on skin tumor development in CD-1 and SENCAR mice.

Studies from our laboratory have indicated skin cancer chemopreventive effectsof sandalwood oil in CD-1 mice. The purpose of this investigation was to study the skin cancer chemopreventive effects of alpha-santalol, a principal component of sandalwood oil in CD-1 and SENCAR mice. alpha-Santalol was isolated from sandalwood oil by distillation under vacuum and characterized by nuclear magnetic resonance and gas chromatography-mass spectrometry. Chemopreventive effects of alpha-santalol were determined during initiation and promotion phase in female CD-1 and SENCAR mice. Carcinogenesis was initiated with 7,12-dimethylbenz(a)anthracene and promoted with 12-O-tetradecanoylphorbol-13-acetate (TPA). The effects of alpha-santalol treatment on TPA-induced epidermal ornithine decarboxylase (ODC) activity and (3)H-thymidine incorporation in epidermal DNA of CD-1 and SENCAR mice were also investigated. alpha-Santalol treatment during promotion phase delayed the papilloma development by 2 weeks in both CD-1 and SENCAR strains of mice. alpha-Santalol treatment during promotion phase significantly (P < 0.05) decreased the papilloma incidence and multiplicity when compared with control and treatment during initiation phase during 20 weeks of promotion in both CD-1 and SENCAR strains of mice. alpha-Santalol treatment resulted in a significant (P < 0.05) inhibition in TPA-induced ODC activity and incorporation of (3)H-thymidine in DNA in the epidermis of both strains of mice. alpha-Santalol significantly prevents papilloma development during promotion phase of 7,12-dimethylbenz(a)anthracene-TPA carcinogenesis protocol in both CD-1 and SENCAR mice, possibly by inhibiting TPA-induced ODC activity and DNA synthesis. alpha-Santalol could be an effective chemopreventive agent for skin cancer. Additional experimental and clinical studies are needed to investigate the chemopreventive effect of alpha-santalol in skin cancer.     

Hypospadias trends in two US surveillance systems

OBJECTIVE: Hypospadias is a common congenital anomaly, the cause of which is unknown. Unexplained increases in the rates of hypospadias occurred in five European countries in the 1970s and 1980s. We examined data from two birth defects surveillance systems in the United States for evidence of similar trends. METHODOLOGY: The Metropolitan Atlanta Congenital Defects Program (MACDP) provided birth prevalence rates from 1968 to 1993. The nationwide Birth Defects Monitoring Program (BDMP) provided rates from 1970 to 1993. MACDP data are population-based and could be categorized by the severity of the hypospadias. BDMP data allowed analysis of rate trends for the four census regions of the United States. RESULTS: Data from both surveillance systems showed an approximate doubling of hypospadias rates in the 1970s and 1980s. MACDP data showed that the rate of severe cases increased while the ratio of mild to severe cases decreased. BDMP data showed that hypospadias rates increased markedly in all four regions of the United States. CONCLUSIONS: The observed increases are unlikely to be attributable to increased sensitivity of the surveillance systems or the identification of more mild cases by physicians over time, because either trend would have increased rather than decreased the ratio of mild to severe cases. If real, these trends represent the largest number of cases and the first report of an increase in hypospadias rates outside of Europe. Additional investigation of a possible increase in hypospadias rates is warranted.     

Analyses of mutation and loss of heterozygosity of coding sequences of the entire transforming growth factor beta type II receptor gene in sporadic human gastric cancer

Mutations in the transforming growth factor beta type II receptor (TGFbetaRII) gene have been detected in several human cancer types exhibiting microsatellite instability. Using intron primers previously reported for examination of the entire coding region of the TGFbetaRII gene, 29 sporadic gastric cancers were screened with non-radioactive single strand conformation polymorphism and subsequent DNA sequencing analysis. Mutations of the TGFbetaRII gene were detected in three out of 29 tumors (10%). Two cases showed deletions in a polyadenine tract in both alleles and was positively associated with replication error. One case had an insertion of GA dinucleotide sequence in one allele. Mutations of the TGFbetaRII gene were restricted to exon 3 and other coding regions were not affected. Loss of heterozygosity was detected by analyzing a polymorphic site in intron 2. Three out of nine (33%) informative cases, which were all of intestinal type and advanced cases, showed loss of heterozygosity but neither TGFbetaRII mutation nor replication error was found in these cases. Immunoreactivity of TGFbetaRII in tumor tissues was reduced to a different extent in the gastric cancer with genetically abnormal transforming growth factor. Although the numbers studied are small, homozygous (A)10 deletion or loss of heterozygosity of TGFbetaRII is involved in tumorigenesis and progression of at least some part of sporadic gastric cancer.