Effect of different levels of oral pyridoxine supplementation on plasma pyridoxal-5'-phosphate and pyridoxal levels and urinary vitamin B-6 excretion

Plasma pyridoxal-5'-phosphate and pyridoxal levels increased significantly (p less than 0.05) when single, oral bolus doses of pyridoxine were increased from 10 to 25 and from 25 to 50 mg in nine female volunteers. However, when the dose was increased to 100 mg, plasma pyridoxal-5'-phosphate levels did not differ significantly from those recorded after the 50 mg dose. Within 3 h plasma pyridoxal levels rose with a factor of 3.85 compared with the 50 mg dose but high pyridoxal levels were eliminated from the circulation. Renal clearance of pyridoxal remained a constant, low percentage (less than 2.0%) of each pyridoxine supplement in spite of the observed very high circulating pyridoxal levels. Pyridoxine supplementation is discussed in relation to circulating pyridoxal-5'-phosphate and pyridoxal availability for cellular metabolism.     

Management of older patients presenting after a fall--an accident and emergency department audit.

BACKGROUND: It is common for older patients to present to accident and emergency (AE) departments after a fall. Management should include assessment and treatment of the injuries and assessment and correction of underlying risk factors in order to prevent recurrent falls. OBJECTIVES: To determine management of older patients presenting after a fall to the AE department of Groote Schuur Hospital in Cape Town, South Africa. METHOD: Hospital records were reviewed for a random sample of 100 patients aged 65 years and older presenting to the AE department after a fall, between December 2001 and May 2002. RESULTS: The mean age of the sample was 78.6 years (range 65-98 years); 72% of subjects were female. History of a previous fall, and history of drug or alcohol intake, were recorded in less than 20% of cases. Blood pressure and pulse rate were recorded in approximately 90% of cases, and pulse rhythm and postural blood pressure in 2%. Examination of the musculoskeletal system was done in 86% of cases and that of other systems in less than 50%; cognitive assessment was conducted in less than 30%. Radiological investigations were performed in 89% of cases, glucose and haemoglobin in 32%, renal profile and electrocardiogram in 5%, and urinalysis in 4%. Three-quarters of the patients were referred for further management: 52% to orthopaedic surgery, 12% to other surgical subspecialties, 6% to the general medical department, and 6% to other hospitals and clinics. No referrals were made to geriatric medicine, physiotherapy or occupational therapy. CONCLUSIONS: In managing elderly patients after a fall, the AE department focused on injuries sustained. Little effort was made to establish and manage risk factors, hence to prevent recurrent falls. Guidelines are needed for the management of such patients in AE departments.     

Gadolinium ring enhancement and mass effect in acute disseminated encephalomyelitis

A 9-year-old boy presented with a subacute history of optic neuritis followed by brainstem involvement, with fever and a lymphocytic pleocytosis in the cerebrospinal fluid. Gadolinium-enhancing ring lesions were demonstrate in the white matter of the cerebrum, brainstem and cerebellum on day 17 of the illness, all appearing simultaneously as part of a monophasic illness. A parietal lesion exerted mass effect. Needling and biopsy yielded no evidence of a pyogenic lesion, tumour or tuberculosis and showed vasculitis. There was insufficient material for myelin staining. Dexamethasone therapy lead to rapid improvement of the radiological lesions: MRI and CT on day 34 of the illness showed complete clearing of the lesions except for residual abnormality at the biopsy site.     

Trauma systems and emergency medicine

The impact of trauma is a major public health challenge which is likely to escalate in the early 21st century. A systematic approach to this problem is required. This review explains the conceptual framework that defines a trauma system, gives a brief historical perspective and describes some of the essential elements of the system which should make a difference to patient outcome. Emergency physicians are well placed to play a leading role in the development and implementation of trauma systems.     

Stab wounds to the temporal fossa

Stab wounds to the temporal fossa appear as a characteristic clinical entity. Patients admitted with stab wounds to the head during the period 1970 to 1986 were reviewed retrospectively. Of these, 10 met the criteria of having suffered a stab wound that penetrated the skull and dura mater of the temporal fossa. Injury to the internal carotid artery-cavernous sinus complex (3 patients) or to the basilar artery-pons region (5 patients) was frequent. Two other patients experienced injury to the trigeminal nerve and the petrous ridge. The mechanical, neurological, radiological, and prognostic features of knife wounds to this region are discussed.     

Postpartum sterilisation and demographic progress at Paarl Hospital

The success of the postpartum sterilisation campaign at Paarl Hospital, CP, irrefutably supports the claim that a quality family planning programme can in itself reduce fertility. In 1971 only 10% of women undergoing sterilisation had 4 or fewer children--this incidence increased to 71% in 1986. Women with more than 10 children are now very rarely found--in 1970 they still accounted for 20% of all patients sterilised. Parity at time of sterilisation has levelled to about 4 in contrast with 7.52 in 1971. It is probable that as many as 15,000 unwanted and unplanned pregnancies have been prevented in Paarl as a result of this sustained effort. The ideal of the 2-child family is increasingly possible.     

Light-emitting diodes and half-cell electrodes in experimental recording of electroretinogram c-wave

A method of electroretinogram c-wave recording in the rat was developed that uses a contact lens electrode connected through a saline bridge with a silver-silver chloride half-cell. A cluster of light-emitting diodes, regulated by an electronic light-emitting diode stimulator, was used as a light source. The method enables recordings of c-waves of 0.4–1.6 mV amplitude as well as other electroretinogram components in narrow limits of variation. The two main sources of response variability are voltage shunting and eyeball protrusion.     

Anti-tumor immunotherapy via antigen delivery from a live attenuated genetically engineered Pseudomonas aeruginosa type III secretion system-based vector.

Immunotherapy requiring an efficient T lymphocyte response is initiated by antigen delivery to antigen-presenting cells. Several studies have assessed the efficiency of various antigen loading procedures, including microbial vectors. Here a live strain of Pseudomonas aeruginosa was engineered to translocate a recombinant antigenic protein into mammalian cells via the type III secretion system, a bacterial device translocating effector proteins into host cells. Optimization of the vector included virulence attenuation and determination of the N-terminal sequence allowing translocation of fused antigens into cells. In vitro delivery of an ovalbumin fragment by the bacterial vector into dendritic cells induced the activation of ovalbumin-specific CD8(+) T lymphocytes. Mice injected with the ovalbumin-delivering vector developed ovalbumin-specific CD8(+) T lymphocytes and were resistant to a subsequent challenge with an ovalbumin-expressing melanoma. Moreover, in a curative assay, injection of the vaccine vector 5 and 12 days after tumor implantation led to a complete cure in five of six animals. These results highlight the utility of type III secretion system-based vectors for anti-tumor immunotherapy.     

Predominance of a 6 bp deletion in exon 2 of the LDL receptor gene in Africans with familial hypercholesterolaemia

In South Africa, the high prevalence of familial hypercholesterolaemia (FH) among Afrikaners, Jews, and Indians as a result of founder genes is in striking contrast to its reported virtual absence in the black population in general. In this study, the molecular basis of primary hypercholesterolaemia was studied in 16 Africans diagnosed with FH. DNA analysis using three screening methods resulted in the identification of seven different mutations in the coding region of the low density lipoprotein (LDLR) gene in 10 of the patients analysed. These included a 6 bp deletion (GCGATG) accounting for 28% of defective alleles, and six point mutations (D151H, R232W, R385Q, E387K, P678L, and R793Q) detected in single families. The Sotho patient with missense mutation R232W was also heterozygous for a de novo splicing defect 313+1G→A. Several silent mutations/polymorphisms were detected in the LDLR and apolipoprotein B genes, including a base change (g→t) at nucleotide position −175 in the FP2 LDLR regulatory element. This promoter variant was detected at a significantly higher (p<0.05) frequency in FH patients compared to controls and occurred in cis with mutation E387K in one family. Analysis of four intragenic LDLR gene polymorphisms showed that the same chromosomal background was identified at this locus in the four FH patients with the 6 bp deletion. Detection of the 6 bp deletion in Xhosa, Pedi, and Tswana FH patients suggests that it is an ancient mutation predating tribal separation approximately 3000 years ago.


Keywords: apolipoprotein B; hypercholesterolaemia; low density lipoprotein receptor; mutation     

OH treatment of tetanus toxin reduces its susceptibility to limited proteolysis with more efficient presentation to specific T cells

At inflammatory sites, before their processing, antigens are exposed to oxygen free radicals released by activated cells. The effect of hydroxyl radicals (OH·) on the structure of a protein antigen, tetanus toxin (TT) was investigated, as well as the consequences on processing and presentation. A chemical system composed of Fe-EDTA, ascorbate and H₂O₂ was used to produce physiological amounts of OH^• radicals. TT exposed to OH· radicals presented a marked decrease of its intrinsic fluorescence with a concomitant increase of the content of bityrosine, but no fragmentation of the protein was detected by SDS-PAGE. Processing of the modified TT was analysed, by incubating TT at acidic pH with fractions enriched in plasma membranes and lysosomes obtained from a lymphoblastoid cell line (LCL). Proteolysis of OH·-treated TT was less important than proteolysis of native TT, especially upon prolonged incubations. Oxidized TT presented by LCL cells induced a greater proliferation of three different TT specific T cell clones, compared to native TT. When proteolytic digests of TT were presented by fixed LCL cells to a homologous T cell line, the proliferative response obtained in the presence of digests of OH·-treated TT was sustained, even in the case of prolonged proteolysis, whereas the response to digests of native TT fell rapidly. The relative resistance of OH·-treated TT to proteolysis appears thus responsible for its greater presentation to specific T cells, probably by protecting epitopes.