Mutation screening of manganese superoxide dismutase in amyotrophic lateral sclerosis

Seventy-seven cases of ALS were screened for mutations in the manganese superoxide dismutase gene (SOD2). DNA was extracted from CNS tissue and screened using single stranded conformation polymorphism and heteroduplex analysis. No mutations were identified in the entire coding region of the SOD2 gene. The known polymorphism in the mitochondrial targeting sequence was identified. No association was found between this polymorphism and ALS. A further polymorphism was detected in the intronic sequence upstream of exon 4, though no association with ALS was demonstrated. We therefore conclude that mutations in SOD2 do not appear to cause ALS.     

A study of cytokine gene polymorphisms and protein secretion in renal transplantation

Although there is evidence that cytokine gene polymorphisms are associated with varying quantities of cytokine protein production, the exact role of these polymorphisms in allograft rejection remains unclear. In a previous study, we demonstrated a significant association between high IL-10 secretion in mixed lymphocyte culture (MLC), together with HLA mismatching for at least 4-6 antigens, with the occurrence of acute rejection following renal transplantation. We, therefore, wished to ascertain whether cytokine gene polymorphisms are associated with varying levels of protein secretion and/or allograft rejection in the same group of patients. Cytokine protein secretion in MLC for IL-4, IL-6, IL-10 and IFN-gamma was measured by ELISA in 49 patient-donor pairs. Protein secretion for the above cytokines was also measured in phytohaemagglutinin (PHA) stimulated cultures in 30 normal controls. In both patient and control groups, single nucleotide polymorphism analysis for IL-4 G(-590)T, IL-6 G(-174)C, IL-10 G(-1082)A, IL-10 C(-819)T, IL-10 C(-592)A, TNF-alpha G(-308)A and microsatellite analysis for IFNG (CA repeat) was performed. No correlation was found between cytokine gene polymorphisms and cytokine protein secretion in either mitogen stimulated cultures (control group) or MLC (patient group). In addition, no correlation was demonstrated between cytokine gene polymorphisms and renal allograft rejection.     

Peri-operative risk factors for acute lung injury after elective oesophagectomy

Acute lung injury after oesophagectomy is well recognized butthe risk factors associated with its development are poorlydefined. We analysed retrospectively the effect of a numberof pre-, peri- and post-operative risk factors on the developmentof lung injury in 168 patients after elective oesophagectomyperformed at a single centre. The acute respiratory distresssyndrome (ARDS) developed in 14.5% of patients and acute lunginjury in 23.8%. Mortality in patients developing ARDS was 50%compared with 3.5% in the remainder. Features associated withthe development of ARDS included a low pre-operative body massindex, a history of cigarette smoking, the experience of thesurgeon, the duration of both the operation and of one-lungventilation, and the occurrence of a post-operative anastomoticleak. Peri-operative cardiorespiratory instability (measuredby peri-operative hypoxaemia, hypotension, fluid and blood requirementsand the need for inotropic support) was also associated withARDS. Acute lung injury after elective oesophagectomy is associatedwith intraoperative cardiorespiratory instability. Br J Anaesth 2001; 86: 633–8     

The delivery of surgical cleft care in the United Kingdom

BACKGROUND AND PURPOSE: A national survey of cleft teams was undertaken as part of the Clinical Standards Advisory Group investigation of the current status of cleft care in the United Kingdom (UK). METHODS: Fifty-seven cleft teams were identified, of which 90% responded to the survey. MAIN FINDINGS: Nine cleft teams had been established since 1992. Only one region, Northern Ireland, had a centralised cleft service and, despite 82% of teams having databases, only four were able to produce corroborated evidence of receiving at least 30 annual new referrals during 1995. There was a wide variation in the facilities provided by individual cleft teams--only six teams were able to provide all of the key facilities recommended by the Royal College of Surgeons Steering Group on cleft lip and palate. Facilities such as antenatal and neonatal counselling, protocols for record keeping and long-term treatment were similar for high and low volume teams. High volume teams were more likely to have established links with a full range of specialities including psychology, clinical genetics and paediatrics than low volume teams. CONCLUSION: A national survey of cleft services has demonstrated a need for reorganisation. This is now in process and once established will require continual monitoring and assessment.     

Aquaporins and the surgeon: cautionary tales

Nephrogenic diabetes insipidus (NDI) presents an uncommon but formidable clinical challenge in the surgical patient. Two recent cases of NDI with differing aetiology are presented. These cases and a review of the literature illustrate well the diagnosis, fluid and electrolyte imbalances seen and the strategy of treatment required in the post-operative setting. The central role of the recently discovered aquaporin channels in this condition is briefly outlined. Nephrogenic diabetes insipidus has a diverse aetiology and many of the hazards of the condition are peculiar to the surgical setting. The importance of management in a high dependency environment is highlighted.     

Genetic epidemiology of visceral leishmaniasis in northeastern Brazil

Familial clustering of disease, racial differences in asymptomatic:disease ratios, and studies of mice all point to a genetic component for disease susceptibility in visceral leishmaniasis. Analysis of 87 multi-case pedigrees (824 individuals; 138 nuclear families) from a region of northeastern Brazil endemic for Leishmania chagasi demonstrates a high relative risk ratio (lambda(2S) = 34) to further siblings of affected sibling pairs. Complex segregation analysis using POINTER and COMDS show that all single locus models, as well as polygenic and multifactorial models, provide a significantly (P < 0.001) better fit to the data than a sporadic model. Of the genetic models, the general single locus model was not significantly different from additive or dominant single locus models, all of which gave a gene frequency for the putative disease susceptibility allele of approximately 0.002. The general single locus model was strongly favored (P < 0.001) over a recessive single gene model. Using POINTER, polygenic and multifactorial models were clearly rejected (P < 0.001 in all cases) in favor of the general single locus model. Using COMDS, the analysis was extended to consider two locus models. Results under a general two-locus model did not differ significantly from the dominant, additive, or general single locus models. Under this model, one locus was estimated at a gene frequency of 0.0017, i.e., in the same range as the disease susceptibility locus for the most favored single gene models, with the second locus at a much lower frequency of 0.0002. Hence, the data support the hypothesis that a single major gene may be important in determining disease susceptibility in this population. To identify the gene(s) involved, a genome scan with replication using two subsets of these larger pedigrees with power to detect linkage is in progress.     

TP53 deletions but not trisomy 12 are adverse in B-cell lymphoproliferative disorders

Abnormalities of the TP53 tumor suppressor gene at 17p13.1 are prognostically adverse in a variety of hematolymphoid malignancies. The present study utilized interphase fluorescence in situ hybridization (I-FISH) to detect TP53 deletions and trisomy 12 in 101 clinical specimens from 98 patients with B-cell lymphoproliferative disorders (B-LPDs). Twelve patients had TP53 deletions (group A), 23 had trisomy 12 (group B), and 63 had neither (group C). The groups did not significantly differ in age, duration of disease, absolute lymphocyte count, or percentage with an immunophenotype or cytology atypical for chronic lymphocytic leukemia (CLL). The clinical stage of disease and lactate dehydrogenase (LDH) level were higher in group A, with less response to therapy. After a median follow-up of 19 months, seven of the patients in group A had died of disease (another patient subsequently has had large cell transformation) compared with none in group B and nine in group C. Multivariate analysis found the stage of disease and TP53 deletions as the only parameters independently associated with shortened survival (P < 0.001). Thirty-nine patients had conventional cytogenetic analysis (CCA) which was complexly abnormal in 11 patients; 6 of whom died of disease. There was a trend for complex cytogenetics to be seen more frequently in group A, often with 17p involvement. For most laboratories, CCA may be the preferable initial study to identify prognostically different subgroups of B-LPDs. However, as more probes and clinical outcome data become available, I-FISH will likely play an increasingly important ancillary role.     

Comprehensive gynecologic endoscopic hospital privileging program. Implementation and assessment

OBJECTIVE: To describe a comprehensive gynecologic endoscopic privileging program at an urban teaching hospital and evaluate its effect on complication rates. STUDY DESIGN: In 1996, a gynecologic endoscopy privileging program was instituted. Initially, experienced surgeons were invited to apply for advanced privileges based on submission of a case list. Afterwards, new applications were approved by proctorship. Since 1995, charts have been reviewed using the following indicators; operating time, estimated blood loss, length of stay, readmission, diagnosis of cancer, reexploration and admission for hysteroscopic fluid overload. Cases were also independently identified when a major vascular or visceral injury occurred. RESULTS: Among the 3,880 gynecologic endoscopic procedures performed during the review period, 2,702 medical records were randomly screened. Following institution of the program, there was no change noted in rates of hysteroscopic fluid overload, readmission, reexploration or unrecognized diagnosis of cancer. However, a decrease was noted in excess blood loss (odds ratio [OR] 0.6, 90% confidence interval [CI] 0.4, 0.9) and operating time greater than four hours (OR 0.6, CI 0.4, 0.9). Length of hospital stay was also reduced in the year following implementation of the privileging process (OR 0.2, CI 0.1, 0.3). Fifty-four cases of visceral or major vascular injury occurred during the three-year period. The risk of visceral injury revealed a trend from 1.9% to 1.0% after institution of the privileging process (OR 0.5, CI 0.3, 1.0). CONCLUSION: Establishment of a comprehensive gynecologic endoscopic hospital privileging program was associated with a reduction in rates of excess blood loss and operating times and a decreasing trend in visceral injuries.