Neurologic crises in hereditary tyrosinemia

Hereditary tyrosinemia results from an inborn error in the final step of tyrosine metabolism. The disease is known to cause acute and chronic liver failure, renal Fanconi's syndrome, and hepatocellular carcinoma. Neurologic manifestations have been reported but not emphasized as a common problem. In this paper, we describe neurologic crises that occurred among children identified as having tyrosinemia on neonatal screening since 1970. Of the 48 children with tyrosinemia, 20 (42 percent) had neurologic crises that began at a mean age of one year and led to 104 hospital admissions. These abrupt episodes of peripheral neuropathy were characterized by severe pain with extensor hypertonia (in 75 percent), vomiting or paralytic ileus (69 percent), muscle weakness (29 percent), and self-mutilation (8 percent). Eight children required mechanical ventilation because of paralysis, and 14 of the 20 children have died. Between crises, most survivors regained normal function. We found no reliable biochemical marker for the crises (those we evaluated included blood levels of tyrosine, succinylacetone, and hepatic aminotransferases). Urinary excretion of delta-aminolevulinic acid, a neurotoxic intermediate of porphyrin biosynthesis, was elevated during crises but also during the asymptomatic periods. Electrophysiologic studies in seven patients and neuromuscular biopsies in three patients showed axonal degeneration and secondary demyelination. We conclude that episodes of acute, severe peripheral neuropathy are common in hereditary tyrosinemia and resemble the crises of the neuropathic porphyrias.     

Trypanosoma brucei brucei: a model for cerebral trypanosomiasis in mice--an immunological, histological and electronmicroscopic study.

The successful induction of cerebral trypanosomiasis in ordinary laboratory mice using Trypanosoma brucei brucei is reported. Sequential studies demonstrated the presence of trypanosomes in the interstitium of the choroid plexus at the fourth week after infection which correlated with the appearance of anti-trypanosomal antibodies, a rise of IgM and IgG serum levels and a rise of Clq binding activity as well as a decrease of C3 levels. Electronmicroscopic studies showed that the parasites were flagellated and localized extracellularly mainly in the interstitium of the choroid plexus. Granular immunofluorescent deposits of Ig and C3 were most marked in the choroid plexus. Electron-dense deposits suggestive of immune complexes were seen in subendothelial, interstitial and subependymal areas of the choroid plexus. Since autoantibodies to the brain were found in the serum of some mice, the possible involvement of autoimmune manifestations in the pathogenesis of cerebral lesions has to be considered. The pattern of inflammatory foci at the eighth week after infection was very similar to that observed in cerebral African trypanosomiasis in man. After treatment with ethidium bromide, trypanosomes persisted in the tissues when circulating parasites could no longer be detected. These observations suggest a sequential involvement of brain structures during African trypanosomiasis. Trypanosomes may first migrate from the vascular compartment into the interstitium of the choroid plexus, possible favoured by increased vascular permeability. Circulating immune complexes and complement activation may be involved at this state. Trypanosomes localized in the choroid plexus may then trigger a local immunologically mediated inflammatory reaction favouring the migration of trypanosomes into the CSF and further invasion of other cerebral structures.     

Selective media in the isolation of tubercle bacilli from tissues

Direct culture on Lowenstein-Jensen slopes and on three media made selective for tubercle bacilli by the addition of four antibacterial agents was compared with guinea-pig inoculation on 490 tissue specimens. Tubercle bacilli were obtained from 15 specimens by culture and 14 by guinea-pig inoculation; only one specimen was positive by guinea-pig and not by culture. The most efficient culture medium was a selective 7H11 slope. Routine guinea-pig inoculation has been replaced by a wider range of culture procedures.     

Purification of soluble immune complexes from serum using polymethylmetacrylate beads coated with conglutinin or C1q. Application to the analysis of the components of in vitro formed immune complexes and of immune complexes occurring in vivo during leishmaniasis.

A procedure for the isolation of immune complexes from human sera has been developed. Two steps are involved: (1) lipid-free serum is precipitated by polyethylene glycol; (2) the solubilized precipitate is absorbed on a column of polymethylmethacrylate beads coated with conglutinin (K) or C1q; the column is washed, the complexes are then eluted, using 0.02 M EDTA (for K column) or 0.5 M NaCl (for C1q column). This procedure permitted the purification and the characterization of soluble 125I-BSA-anti-BSA, 125 I-tetanus toxoid-anti-tetanus toxoid, and 125-I-HBsAg-anti-HBsAg complexes made in vitro in the presence of fresh human serum. The isolated complexes were shown to contain antigen, antibody, C1q, C1r, C1s and C3. When normal human serum was submitted to such a procedure, no detectable amount of protein was present in the final eluted fraction. Immune complexes formed in vivo were also purified by conglutinin column from the serum of a patient with disseminated leishmaniasis. The isolated material was found to contain IgM, IgG, C1q, C1r, C1s, C3c and C3d. The purified complexes dissociated at acid pH were found to contain anti-IgG and anti-leishmania antibodies.     

Effect of target size on anomalous sensory responses in the Bagolini striated lens test

Different results obtained by different methods of retinal correspondence testing are generally accepted to be a sign of the depth of the anomalous sensory adaptation. The Bagolini striated lens test is considered a standard "natural" test to which others are compared. In this study, the Bagolini striated lens test was performed on 25 strabismic subjects using three target sizes in order to determine if target size might be a factor in response variability. Kappa Measure of Agreement, used to analyze the results statistically, showed a moderately high to high level of agreement among the three targets. This indicates that practitioners can feel confident of consistent test results on the striated lens test using any of the three readily available target sizes selected. A brief literature review has been provided as a guide to the theories of strabismus and correspondence and to emphasize the purpose of this research.     

Evaluating Short-Term Outcomes Post–Intra-Articular Calcaneal Fracture Fixation via a Sinus Tarsi Approach in a Non-Exclusively Selected Cohort

Management of intra-articular calcaneal fractures remains a debated topic in orthopedics, with operative fixation often held in reserve due to concerns regarding perioperative morbidity and potential complications. The purpose of this study was to identify the characteristics of patients who developed surgical complications to inform the future stratification of patients best suited to operative treatment for intra-articular calcaneal fractures. All patients who underwent open reduction and internal fixation of calcaneal fractures utilizing the Sinus Tarsi approach between March 2014 and July 2018 were identified using theatre records. Patient imaging was used to assess pre- and postoperative fracture geometry with computed tomography used for preoperative planning. Each patient's clinical presentation was established through retrospective analysis of medical records. Patients provided verbal consent to participation and patient reported outcome measures were recorded using the Maryland Foot Score. Fifty-eight intra-articular calcaneal fractures (53 patients; 5 bilateral, mean age = 46.91 years) with a mean follow-up of 35.4 months (6-57) were included. Five patients (9.4%) had wound complications; 2 superficial (3.7%), 3 deep (5.6%); 4 of whom were smokers. Smokers were statistically more likely to have wound infections than nonsmokers (p = .04). Intra-articular fractures of the calcaneus should be considered for surgical intervention in order to improve long-term functional outcomes. The Sinus Tarsi approach provides the potential to decrease the operative complication rate whilst maintaining adequate fixation, however, the decision to surgically manage these fractures should be carefully balanced against the risk of postoperative complications. This increased risk of complication associated with smoking may tip the balance against benefit from surgical management.     

The anatomy of the anterior inferior tibiofibular ligament and its relationship with the Wagstaffe fracture

BackgroundOur aim in this study was to identify the fibular footprint of the Anterior Inferior Tibiofibular Ligament (AITFL) and its relation to Wagstaffe fracture fragment size.MethodsWe examined 25 cadaveric lower limbs which were carefully dissected to identify the lateral ankle ligaments. The AITFL anatomy was compared to 40 Wagstaffe fractures identified from our ankle fracture database.ResultsThe AITFL origin was from the anterior fibular tubercle with an average length of 21.61 mm (95% CI 20.22, 22.99). The average distance of the distal aspect of the AITFL footprint to the distal fibula margin was 11.60 mm (95% CI 10.49, 12.71). In the ankle fractures analyzed, the average length of the Wagstaffe fragment was 17.88 mm (95% CI 16.21, 19.54). The average distance from the distal tip of the fibula to the Wagstaffe fracture fragment was 21.40 mm (95% CI 19.78, 23.01).In total there were 22 syndesmosis injuries. There was no statistical difference in Wagstaffe fragment size between stable and unstable groups.ConclusionThe AITFL fibular origin was both larger and more distal than the Wagstaffe fracture fragments seen in our institution. Therefore, this suggests that a ligamentous failure will also have to occur to result in syndesmotic instability. The size of fracture fragment also did not confer to syndesmotic instability on testing.Level of Evidence - 3     

Prevalence of HIV and sexually transmitted and blood-borne infections,and related preventive and risk behaviours,among gay,bisexual and other men who have sex with men in Montreal,Toronto and Vancouver: results from the Engage Study

ObjectivesThe last Canadian biobehavioural surveillance study of HIV and other sexually transmitted and blood-borne infections (STBBI) among gay, bisexual and other men who have sex with men (GBM) was conducted in 2010. We designed a study to measure STBBI prevalence among GBM in metropolitan Montreal, Toronto and Vancouver and to document related preventive and risk behaviours.MethodsThe Engage Cohort Study used respondent-driven sampling (RDS) to recruit GBM who reported sex with another man in the past 6 months. At baseline, we examined recruitment characteristics of the samples, and the RDS-II-adjusted distributions of socio-demographics, laboratory-confirmed HIV and other STBBI prevalence, and related behaviours, with a focus on univariate differences among cities.ResultsA total of 2449 GBM were recruited from February 2017 to August 2019. HIV prevalence was lower in Montreal (14.2%) than in Toronto (22.2%) or Vancouver (20.4%). History of syphilis infection was similar across cities (14–16%). Vancouver had more HIV-negative/unknown participants who reported never being HIV tested (18.6%) than Toronto (12.9%) or Montreal (11.5%). Both Montreal (74.9%) and Vancouver (78.8%) had higher proportions of men who tested for another STBBI in the past 6 months than Toronto (67.4%). Vancouver had a higher proportion of men who used pre-exposure prophylaxis (PrEP) in the past 6 months (18.9%) than Toronto (11.1%) or Montreal (9.6%).ConclusionThe three largest cities of Canada differed in HIV prevalence, STBBI testing and PrEP use among GBM. Our findings also suggest the need for scale-up of both PrEP and STI testing among GBM in Canada.