Frontoethmoidal meningoencephaloceles: a review of 14 consecutive patients

Over a period of 4.5 years, 14 patients with frontoethmoidal meningoencephaloceles were treated. Most patients came from Northern Namibia. Precise delineation of all cranial abnormalities was obtained by modern imaging techniques, and specific patterns of cerebral abnormality were found. The malformation was corrected in a single stage, and significant modifications have been developed to render the procedure simpler and safer. Information from our series favors delayed neural tube closure as the primary pathogenesis of the defect and suggests a common teratogen as the most probable etiological agent. Our experience leads us to advocate early correction of even small defects.     

The additivity of substrate fragments in enzyme-ligand binding

BACKGROUND: Enzymes have evolved to recognise their target substrates with exquisite selectivity and specificity. Whether fragments of the substrate--perhaps never available to the evolving enzyme--are bound in the same manner as the parent substrate addresses the fundamental basis of specificity. An understanding of the relative contributions of individual portions of ligand molecules to the enzyme-binding interaction may offer considerable insight into the principles of substrate recognition. RESULTS: We report 12 crystal structures of Escherichia coli thymidylate synthase in complexes with available fragments of the substrate (dUMP), both with and without the presence of a cofactor analogue. The structures display considerable fidelity of binding mode and interactions. These complexes reveal several interesting features: the cofactor analogue enhances the localisation of substrate and substrate fragments near the reactive thiol; the ribose moiety reduces local disorder through additional specific enzyme-ligand interactions; the pyrimidine has multiple roles, ranging from stereospecificity to mechanistic competence; and the glycosidic linkage has an important role in the formation of a covalent attachment between substrate and enzyme. CONCLUSIONS: The requirements of ligand-protein binding can be understood in terms of the binding of separate fragments of the ligand. Fragments which are subsystems of the natural substrate for the enzyme confer specific contributions to the binding affinity, orientation or electrostatics of the enzymatic mechanism. This ligand-binding analysis provides a complementary method to the more prevalent approaches utilising site-directed mutagenesis. In addition, these observations suggest a modular approach for rational drug design utilising chemical fragments.     

Guidelines for surgical procedures after liver transplantation

The ability to acquire a motor and cognitive skill was investigated in 26 patients with schizophrenia and 26 normal participants using repeated testing on the Tower of Toronto puzzle. Seven patients with defective performance were retested using additional trials and immediate feedback designed to facilitate problem solving. A component analysis of performance was used based on J. R. Anderson's (1987) model of cognitive skill learning. Patients exhibited a performance deficit on both motor and cognitive skills. However, their acquisition rate was similar to that of normal participants on most parameters, indicating that skill learning suffered little or no impairment. Performance deficit was accounted for by poor problem-solving ability, explicit memory, and general intellectual capacities. It was remediable in some, but not all, patients. Remediation failure was also related to severe defects of cognitive functions.     

Questionnaire for the identification of back pain for epidemiological purposes

OBJECTIVES: To design a questionnaire for the identification and assessment of severity of back pain for epidemiological purposes, and gain preliminary experience of its use. METHODS: A group of specialists, experienced in the epidemiology and clinical assessment of back pain, designed the questionnaire, and tested it individually. It was also given cross sectionally by interview to a population of male coal mine workers. RESULTS: The questionnaire comprised a maximum of 12 questions on the presence, radiation, frequency, and severity of back pain with reference to difficulty with specific activities, interference with normal work, and absence from work. 471 coal miners answered the questionnaire (66% of those invited). 56% (265 men) of the responders reported pain or ache in the back during the previous 12 months, and the incidence of first ever attacks during the same period was reported to be 34%. 69% reported having had back pain at some time. The responses to the questionnaire were partially validated by comparison with certified sickness absence for two days or more attributed to back pain. In men who were symptomatic in the previous 12 months, for the question relating to absence from work because of back pain, the sensitivity was 82% and specificity was 84%. CONCLUSION: The questionnaire is easy to administer and generates clear cut data that could be useful for epidemiological or screening purposes. Preliminary, limited, studies of its validity are reasonably encouraging, although further validation is required. It is hoped that researchers will find the questionnaire useful, will extend its validation, and continue to develop it.     

A common genetic variation in the 3'-untranslated region of the prothrombin gene is associated with elevated plasma prothrombin levels and an increase in venous thrombosis

We have examined the prothrombin gene as a candidate gene for venous thrombosis in selected patients with a documented familial history of venous thrombophilia. All the exons and the 5'- and 3'-UT region of the prothrombin gene were analyzed by polymerase chain reaction and direct sequencing in 28 probands. Except for known polymorphic sites, no deviations were found in the coding regions and the 5'-UT region. Only one nucleotide change (a G to A transition) at position 20210 was identified in the sequence of the 3'-UT region. Eighteen percent of the patients had the 20210 AG genotype, as compared with 1% of a group of healthy controls (100 subjects). In a population-based case-control study, the 20210 A allele was identified as a common allele (allele frequency, 1.2%; 95% confidence interval, 0.5% to 1.8%), which increased the risk of venous thrombosis almost threefold {odds ratio, 2.8; 95% confidence interval, 1.4 to 5.6}. The risk of thrombosis increased for all ages and both sexes. An association was found between the presence of the 20210 A allele and elevated prothrombin levels. Most individuals (87%) with the 20210 A allele are in the highest quartile of plasma prothrombin levels (> 1.15 U/mL). Elevated prothrombin itself also was found to be a risk factor for venous thrombosis.     

Oxidant damage to erythrocyte membrane in glucose-6-phosphate dehydrogenase deficiency: correlation with in vivo reduced glutathione concentration and membrane protein oxidation

Chronic nonspherocytic hemolytic anemia has been observed in a recently described glucose-6-phosphate dehydrogenase (G6PD) variant, G6PDWayne. The mechanical properties of these erythrocytes and other G6PD variants were examined. The deformability of G6PD-deficient erythrocytes was normal, as determined by osmotic scan ektacytometry, and was not significantly affected by hemolytic crisis. In the common varieties of G6PD deficiency, the mechanical stability of the red blood cell (RBC) membrane was greater than normal, but G6PDWayne membranes were abnormally susceptible to shear-induced fragmentation. There was no evidence for a concurrent genetic defect in spectrin, because self-association constants and tryptic digests were normal. The fragility of G6PDWayne membranes appeared to be a consequence of oxidative damage to membrane thiol groups associated with a low glutathione (GSH) level in these RBCs. Associations among GSH level, thiol oxidation, and membrane instability were also found when a larger group of G6PD-deficient RBCs were examined. In normal erythrocytes, 1-chloro-2,4-dinitrobenzene was used to reduce GSH levels by 50%. Membrane thiol oxidation and membrane fragility both increased when these cells were kept at 4 degrees C for 3 to 5 days. Our findings suggest that chronic depletion of GSH leads to the destabilization of membrane skeleton through oxidation of membrane protein thiols.     

Risk factors for osteoporosis in men

Three months after the launch of the MMR programme in the United Kingdom and the Republic of Ireland, a postal questionnaire was sent to all GP scheme trainees in both Northern Ireland and the Republic of Ireland. The response rate was 81%. All trainees were enthusiastic about promoting MMR immunisation; with 27% favouring compulsory immunisation. 9% had never seen a patient with measles. This did not alter their attitude towards the beneficial effects of MMR immunisation. Of pre-practice year trainees 26% felt their level of knowledge of immunisation was inadequate, 59% claimed to have received no education on immunisation during their vocational training to date. This may reflects deficiencies in their medical curriculum to-date. 95% of third-year trainees indicated that their practice experience had been the source of at least some of their education on immunisation. Only 46% of trainees in the Republic of Ireland were aware of their Department of Health's aims in launching the MMR immunisation campaign.     

In vivo surface analysis of titanium and stainless steel miniplates and screws

OBJECTIVE: To determine the results peranal excision for rectal carcinoma. DESIGN: Retrospective case series. SETTING: A university-affiliated hospital. PATIENTS: Of 178 patients who presented for curative resection of rectal carcinoma between 1975 and 1993, 19 (10.7%) were deemed suitable for local excision. There were 10 men and 9 women with a mean age of 71.2 years. The follow-up ranged from 13 to 184 months. INTERVENTION: Peranal excision. MAIN OUTCOME MEASURES: Histologic differentiation, gross morphology, depth of invasion and size of the carcinoma, adequacy of margins of excision, complications of operation, rates of recurrence, results of salvage therapy and 5-year survival. RESULTS: There were no intraoperative complications. Postoperative complications included urinary retention (one patient) and bleeding (one patient). There were five local recurrences (26%). Salvage operations were performed in three (60%) patients and were successful in two of them. The 5-year cancer-specific survival rate was 82%. The recurrence rate was higher in patients with inadequate margins of excision and ulcerative lesions. Neither size nor grade of the carcinoma correlated with recurrence. CONCLUSIONS: Local excision of rectal carcinoma can be performed successfully in selected patients. Diligent follow-up is required, because up to 60% of local recurrences can be treated successfully.