Treatment of severe acute lung allograft rejection with OKT3 and temporary extracorporeal membrane oxygenation bridging.

OBJECTIVES: The use of OKT3 for treatment of advanced high-grade acute rejection episodes eventually can result in cytokine release and consecutive pulmonary edema. Temporary extracorporeal membrane oxygenation (ECMO) bridging can be used to overcome this crucial period before the beneficial effects of OKT3 can be observed. METHODS: We summarize our experience with three patients, who underwent lung transplantation and presented with severe acute rejection episodes. OKT3 had to be initiated due to insufficient response to standard rejection therapy with corticosteroids. Upon initiation of OKT3 treatment, a massive life-threatening deterioration of lung function in spite of heavily invasive respirator treatment was seen and temporary ECMO support was imperative to support graft function. Results of this treatment were retrospectively reviewed. RESULTS: In all cases femoro-femoral veno-arterial ECMO was used for support of the impaired graft and after a period of 4-5 days led to a massive improvement of graft function. In the further course two patients could be discharged from hospital and are still alive 30 and 36 months, respectively, after the described incident. One patient died 4 months later due to liver failure. CONCLUSIONS: We conclude that the use of ECMO support in patients experiencing significant side effects from OKT3 therapy is a useful and effective therapeutic tool to overcome the initial critical period until the lung has sufficiently recovered.     

Influence of caseload and surgical speciality on outcome following surgery for colorectal cancer: a review of evidence Part 2: Long-term outcome

OBJECTIVE: We reviewed recent literature to assess the impact of hospital caseload, surgeon's caseload and education on long-term outcome following colorectal cancer surgery. METHOD: We searched the MEDLINE and Cochrane Library databases for relevant literature starting from 1992. We selected hospital caseload, surgeon's caseload and surgeon's education, type of hospital, and surgeon's experience as variables of interest. Measures of outcome were recurrence-free survival and overall survival, and for rectal cancer frequency of permanent stoma. We reviewed the 34 studies according to tumour location: colonic cancer, rectal cancer, or colorectal cancer. We described the studies individually and performed a meta-analysis whenever it was considered appropriate. RESULTS: For colonic cancer, overall survival improved with increasing hospital caseload, odds ratio (OR) 1.22 [95% confidence interval (CI) 1.16-1.28], and surgeon's education. For rectal cancer, overall survival improved with increasing hospital caseload, OR 1.38 (95% CI 1.19-1.60), and, possibly by surgeon' education and experience. Cancer-free survival was strongly influenced by surgeon's education. The colostomy rate was less in high caseload hospitals, OR 0.76 (95% CI 0.68-0.85). For colorectal cancer, overall survival improved with surgeon's education. CONCLUSION: The data have provided evidence that long-term survival following colorectal cancer surgery in general improved significantly with increasing hospital caseload and surgeon's education.     

Enteric pathogens and their isolation at a cancer hospital in Pakistan

Diarrhoeal diseases remain a major cause of mortality and morbidity in developing countries. However, due to lack of funds, supply problems and some inexperience, some laboratories have difficulty identifying a causative agent in stool samples. In the year following the opening of the Shaukat Khanum Memorial Cancer Hospital and Research Centre in Lahore, Pakistan, the microbiology department had not isolated a single enteric pathogen. From January 1996, new culture techniques were introduced, with a resulting increase (10%) in identification of these pathogens. In addition, the introduction of formol-ether concentration made a significant contribution to the number of intestinal parasites seen. This report demonstrates how simple microbiology methods made a difference to the running of the department and, ultimately, to the patients.     

Identification of a type 1 diabetes-associated CD4 promoter haplotype with high constitutive activity

CD4 is a candidate gene in autoimmune diseases, including Type 1 diabetes mellitus (T1DM), because the CD4 receptor is crucial for appropriate antigen responses of CD4(+) T cells. We previously found linkage between a CD4-1188(TTTTC)(5-14) promoter polymorphism and T1DM. In the present study, we screened the human CD4 promoter for mutations and identified three frequent single nucleotide polymorphisms (SNPs): CD4-181C/G, CD4-521C/G and CD4-1050T/C. The SNPs are in strong linkage disequilibrium (LD) and association with the CD4-1188(TTTTC)(5-14) alleles, and we observed nine CD4 promoter haplotypes, of which four are frequent. We genotyped the SNPs in 253 Danish T1DM families (1129 individuals) and found evidence for linkage and association of a CD4 (A4(-1188)T(-1050)G(-521)C(-181)) haplotype to T1DM. In reporter studies, we show that (1) the T1DM-associated CD4 haplotype encodes high constitutive promoter activity and (2) the CD4-181G variant encodes higher stimulated promoter activity than the CD4-181C variant. This difference is in part neutralized in the frequently occurring CD4 promoter haplotypes by the more upstream genetic variants. Thus, we report functional impact of a novel CD4-181C/G SNP on stimulated CD4 promoter activity and the identification of a novel CD4 haplotype with high constitutive promoter activity that is linked and associated with T1DM.     

Lack of association between single polymorphic variants of the mitochondrial nicotinamide adenine dinucleotide dehydrogenase 3, and 4L (MT-ND3 and MT-ND4L) and male infertility

Male infertility is a multifactorial condition associated with different genetic abnormalities in at least 15%–30% of cases. The purpose of this study was to identify suspected correlations between infertility and polymorphisms in mitochondrial NADH dehydrogenase subunits 3 and 4L (MT-ND3 and MT-ND4L) in subfertile male spermatozoa. Sanger sequencing of the mitochondrial DNA target genes was performed on 68 subfertile and 44 fertile males. Eight single nucleotide polymorphisms (SNPs) in MT-ND3 (rs2853826, rs28435660, rs193302927, rs28358278, rs41467651, rs3899188, rs28358277 and rs28673954) and seven SNPs in MT-ND4L (rs28358280, rs28358281, rs28358279, rs2853487, rs2853488, rs193302933 and rs28532881) were detected and genotyped. The genotypes and allele frequencies of the study population have shown a lack of statistically significant association between MT-ND3 and MT-ND4L SNPs and male infertility. However, no statistically significant association was found between the asthenozoospermia, oligozoospermia, teratozoospermia, asthenoteratozoospermia, oligoasthenoteratozoospermia and oligoteratozoospermia subgroups of subfertile males. However, rs28358278 genotype of the MT-ND3 gene was reported in the subfertile group but not in the fertile group, which implies a possible role of this SNP in male infertility. In conclusion, the investigated polymorphic variants in the MT-ND3 and MT-ND4L genes did not show any significant association with the occurrence of male infertility. Further studies are required to evaluate these findings. Moreover, the subfertile individuals who exhibit a polymorphism at rs28358278 require further monitoring and evaluation.     

Reconstruction of distal fibula with osteoarticular allograft after tumor resection

BackgroundInvolvement of distal fibula by benign aggressive and malignant tumors usually necessitates resection of the involved segment of fibula. Numerous techniques have been proposed to reconstruct the ankle joint after this procedure, which can result in complications. We introduce reconstruction of ankle joint by fibular osteoarticular allograft.MethodsReconstruction of the distal fibula after wide resection of tumor was carried out in four patients. There were two cases of Ewing sarcoma, one case of osteosarcoma and one giant cell tumor. After wide resection of tumor, we reconstructed the lateral side of the ankle joint by osteoarticular fibular allograft, which was applied and internally fixed with semitubular plate and screws. In the follow up period, we did assessment of complications, pain and ankle joint instability.ResultsThe mean age of our patients was 24.2 years (12–31). The mean follow-up was 3.2 years (1.5–6.7). In follow up visits there were no signs of infection or wound healing problems. Union was achieved in all patients.ConclusionIn cases of benign aggressive and malignant tumors involving the distal fibula, we can recommend resection of the distal fibula and reconstruction of the ankle with osteoarticular allograft of the distal fibula.Level of evidenceCase series level IV.