Disseminated cutaneous infection due to Mycobacterium tuberculosis in a person with AIDS.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to A McLeod.
Explore the source record for details and available documents.
Conformationally constrained environment-dependent amino acid residue substitution tables have been constructed from a database comprising 33 homologous families of protein sequences aligned on the basis of their three-dimensional structures. Residues are allotted to one of 216 (or 54) classes of combinations of structural features. These include nine main-chain conformation classes, three classes of side-chain accessibility and eight (or two) classes of side-chain involvement in three types of hydrogen bond. Seven different main-chain conformational classes outside of regions of regular structure were identified in an analysis of the distributions of phi-psi torsion angles in 84 high-resolution crystallographic structures. Residue substitutions at equivalent positions in the structural alignments are included where the main-chain conformational class is conserved. Frequency data in the form of 216 (or 54) environment specific (20 x 20 residue type) matrices are then converted to probabilities. Two smoothing regimes incorporating entropy-driven weights were applied to the set of 54 tables. Predicted residue substitutions have been generated for individual residue positions in beta-hairpins and the hypervariable regions of the immunoglobulins. These have been compared with the observed sequence variation at the same positions using rank correlation methods. Measurements of chi 2 distances demonstrate the considerable improvement in predictive power at key residue positions identified from interactive graphics studies when compared to the Dayhoff MDM250 mutation matrix. An illustrative example is given of an application of the method in the ranking of loop fragments in model building studies of structurally variable regions in two subtilisins. A combined template scoring procedure is found to be 26-fold more discriminatory than the Dayhoff matrix. The success rate is approximately 85%.
Routinely collected peripheral neuropathy data entered on a diabetic clinical information system since 1979 have been audited for completeness, consistency, accuracy (inter-observer variation), validity by comparison with biothesiometry, and relevance by life table analysis for foot ulceration. Peripheral neuropathy was defined by a neuropathy disability score > or = 4. The data were 98% complete. Forty-nine of 3405 (1.4%) had inconsistent records. Agreement between observers for clinical examination was significant (p < 0.05) for aggregate neuropathy score and its individual components except the knee jerk: Kappa score for observer variation for neuropathy score 0.56 (95% confidence interval 0.36-0.76). There was good agreement between neuropathy defined as aggregate score > or = 4, and as combined vibration perception thresholds for both feet > 60 V: Kappa statistic 0.62 (95% confidence interval 0.44-0.80). The chance of developing a foot problem in 3 years increased from 3% for patients with a score of zero to 45% for people with a score of between 9 and 12. We conclude that the calculation of a clinical neuropathy score is a simple, valid and relevant method for diabetes care both in hospital and the community. When combined with palpation of peripheral pulses most patients at risk of foot ulceration can be identified allowing targeting of preventive chiropody and orthotic resources.
Explore the source record for details and available documents.
The relative anti-inflammatory effect of dexamethasone and a prodrug, dexamethasone-beta-D-glucoside, has been assessed in guinea-pigs with experimentally-induced inflammatory bowel disease (IBD). The glucoside prodrug is designed to reach the large intestine following oral administration. The active agent is liberated when the prodrug is hydrolysed by glycosidases of colonic bacteria. Guinea-pigs were administered degraded carrageenan in their drinking water to produce experimental IBD. Starting on day 15, dexamethasone (1.3 mumol kg-1) or dexamethasone-beta-D-glucoside (1.3 or 0.65 mumol kg-1) was administered by gastric intubation once daily for 5 days. Relative to control animals, the drug and prodrug treatments significantly (P less than 0.05) reduced the total number of caecal ulcers. While there was no difference statistically between the drug and prodrug treatments, the data suggest that a lower dose of dexamethasone, administered as its glucoside prodrug, could reduce side-effects without reduced efficacy. These results support the hypothesis that localized delivery of dexamethasone to the large bowel can improve pharmacotherapy of IBD by reducing the side-effects associated with corticosteroids.
The stages in the design, procurement and implementation of a micro-computer-based animal health information system are described. The scenario presented is that of a national Director of Veterinary Services taking his first steps in the computerisation of an epidemiology unit, but sub-national and international issues are also discussed. The administrative and management aspects are considered and the need to incorporate computers into a carefully designed and appropriate information system is emphasised. The principles of the specification of initial systems and their subsequent development are described; suggestions are made for the procurement and continuing support of both hardware and software.
Explore the source record for details and available documents.
The insulin molecule was derivatised by reaction with trinitrobenzenesulphonic acid (TNBS), which is known to react predominantly with free primary amino groups. The products of the reaction were analysed by reversed-phase chromatography and by further derivatisation with dansyl chloride. Under the conditions of these experiments, TNBS was found to react preferentially with glycine at position A1. This finding is discussed in terms of the tertiary structure and immunogenicity of this derivative.
The pharmacokinetics of the quinolone pefloxacin were determined following a 400 mg oral dose given to each of six male volunteers. Concentrations were determined in serum and urine by high-performance liquid chromatography, and in cantharidin-induced inflammatory fluid by a microbiological assay. The mean peak serum level of 6.6 micrograms/ml was attained rapidly 0.8 h after administration. The mean serum elimination half-life was 11.6 h. Inflammatory fluid was penetrated quickly with a mean peak level of 3.9 micrograms/ml occurring at 2.4 h. Pefloxacin was excreted in the urine as the parent compound and its two metabolites, norfloxacin and pefloxacin N-oxide (24 h urinary recovery being 8.0%, 12.0% and 13.1% respectively of the dose). This study suggests that a twice or possibly once daily dosage may be sufficient to treat systemic infections caused by susceptible pathogens. Once daily dosing should be sufficient for urinary tract infections.
The long-term effects of HIV infection were evaluated by comparing data from two visits a mean of 18 months apart in groups of 148 persistently seropositive and 287 persistently seronegative homosexual men. At each visit, the seropositive men exhibited lower CD4 counts, CD4/CD8 ratios, hemoglobin concentrations and lymphocyte counts, and higher C1q binding, IgG and IgA levels. More important, the decline of the CD4/CD8 ratio and the rise of the C1q binding, IgG and IgA, progressed significantly in the seropositive group between visits. Seropositive men were at elevated risk of developing constitutional symptoms and generalized lymphadenopathy. An association was present between development of symptoms and inversion of the CD4/CD8 ratio. The 11 seropositive men who have progressed to AIDS had lower CD4 counts and CD4/CD8 ratios, and higher C1q binding, IgG and IgA, than 134 seropositive AIDS-free men a mean of 21.4 months prior to diagnosis. The AIDS group demonstrated greater decline between visits in the CD4 count, hemoglobin and white blood count (WBC) than the seropositive AIDS-free group. The present data document the long-term effects of HIV infection in a seropositive cohort and suggest the possibility of a subgroup particularly susceptible to the progressive effects of HIV that precede the development of the acquired immunodeficiency syndrome (AIDS).
In an ongoing prospective study of homosexual men conducted since November 1982 in Vancouver, we identified 345 men who did not have antibody to human immunodeficiency virus (HIV) at the time of enrolment and for whom results of follow-up serologic testing were available. A total of 66 cases of seroconversion were documented among the 345 men between November 1982 and October 1985. Methods of survival data analysis that take into account the varying durations of follow-up were used to study the epidemiologic features of seroconversion in this group. The probability of seroconversion during the entire observation period was 23.1%. The seroconversion rates remained stable, at 10.5% and 10.0% during the last 2 years of the observation period. Cox regression analysis revealed the following variables to be independently associated with risk of seroconversion: frequent receptive anal intercourse, elevated number of male sexual partners in the year before enrolment, use of illicit drugs, a history of gonorrhea and age less than 30 years in November 1982. Multivariate analysis failed to reveal any role of oral sexual activity in the transmission of HIV. Oral ingestion of semen was not associated with seroconversion in either univariate or multivariate analysis. The observation that younger men were more likely to seroconvert suggests that young homosexual men were less likely than older men to modify their sexual behaviour.
In a group of homosexual men in Vancouver studied prospectively since November 1982, 26 cases of acquired immune deficiency syndrome (AIDS) have arisen. To identify behavioural, clinical and laboratory findings that might predict the development of AIDS in people with antibody to human immunodeficiency virus (HIV), we compared data for 25 patients with AIDS with corresponding data for 80 controls serologically positive for HIV selected from the cohort. The clinical and laboratory data for the patients with AIDS preceded the diagnosis of the syndrome by a mean of 17.5 months. The controls had been both seropositive and AIDS-free for a mean of 16.7 months after acquisition of their data. We detected significant differences between the patients with AIDS and the controls in IgG and IgA levels, absolute number of helper T cells and ratio of helper to suppressor T cells but not in lifetime number of male sexual partners, frequency of receptive anal intercourse or receptive fisting, illicit drug use or history of infectious disease. We also detected an increased risk of AIDS among those who had an elevated number of sexual contacts in AIDS-endemic areas in the 5 years before enrollment. A history of increased early sexual contact in AIDS-endemic areas is likely to be associated with early infection and with an increased risk of AIDS among men with HIV infection of unknown duration. Thus, although our analysis had limited statistical power, we conclude that most lifestyle variables appear to act as exposure factors in HIV infection but not as cofactors in the development of AIDS.
Explore the source record for details and available documents.
Enlarged fetal kidneys are characteristic of more than one possible diagnosis. Though infantile polycystic kidney disease is probably the most well known entity and is associated with oligohydramnios, Beckwith-Wiedemann syndrome should be considered in the differential diagnosis especially if a normal or increased amount of amniotic fluid is present. The presence of an omphalocele with a normal karyotype should also arouse suspicion. This constellation of findings carries potential morbidity including macrosomia, fetal hypoglycemia, mental retardation, microcephaly, increased risk of subsequent neoplasia, and even neonatal death. Beckwith-Wiedemann syndrome may not be obvious in the newborn period.
The demand for the reversal of vasectomy in the treatment of sterility has been increasing over the past decade. Microsurgery is acknowledged to be the best non-traumatic procedure for this reconstruction. This article reviews 115 patients treated by microvasovasostomy over a period of six years. Evaluation of the results shows 76% of patients with a positive seminal analysis, and 52% informed the authors that their partners were pregnant. In addition to the technical aspects (i.e. the non-traumatic manipulation of tissues using microsurgical procedures) the titer of antisperm bodies in the patient's serum and seminal plasma seems to play some part in the recovery of fertility.
The elution behaviour of a selection of sequence variant and modified insulins has been compared on a C18 reversed-phase column. Observed elution times were compared with those expected from the nature of the differences from bovine insulin. In some cases prediction rules established for peptides are adequate to explain the observed elution and in others detailed knowledge of the structure of the protein is of considerable importance in understanding elution behaviour.
A rapid, selective and reproducible high-performance liquid chromatographic method has been developed for the measurement of the beta-adrenoceptor blocking drug atenolol in small (400 microliters) volumes of plasma. Following solid phase sample preparation using Bond-ElutTM mini-columns the compound is separated by high-performance column liquid chromatography on a microparticulate (6 microns) cyano column using acetonitrile--ammonium dihydrogen phosphate (4:96) containing triethylamine (0.25%, v/v) as the mobile phase, and the absorption of the column effluent is monitored at 224 nm. The practical limit of quantitation, based upon an assay volume of 400 microliters, is 25 ng/ml for atenolol. The average coefficient of variation is 3.1%.
Changes in pulmonary function and the development of atelectasis in the postoperative period have been well documented in the adult population. The use of incentive spirometry has been shown to be effective in the prevention of these postoperative complications. At the Hospital of Sick Children, we studied 17 children (8 control and 9 study) to determine if the same trends occurred. Baseline and follow-up roentgenograms and pulmonary function tests (PFTs) were documented for both groups. In addition, the study group followed the protocol for incentive spirometry. There was significantly less atelectasis in the study group (33%) than in the control group (88%). There was a significant loss of pulmonary function postoperatively in both groups. However, there were no statistically significant differences between the groups either in the degree of pulmonary function loss postoperatively or in the recovery baseline pulmonary function to discharge. We conclude that incentive spirometry is as effective in reducing the incidence of atelectasis in children undergoing cardiac surgery as in adults.