Simultaneous Correction of Multivalvular Cardiac Lesions

Cardiac surgery, once confined to pure and isolated mitral stenosis, can now be carried out on all valvular lesions irrespective of their number or complexity. At the Montreal Heart Institute, simultaneous surgical correction of multivalvular lesions was carried out in 16 instances and 13 patients survived. All of the survivors have remained almost asymptomatic. However, if significant associated valvular lesions were not corrected at the same operation, the survival rate dropped to 28%. Moreover, such survivors have required constant medical therapy.

This experience emphasizes the necessity of correcting completely and simultaneously all significant valvular malfunctions. Extrapleural median sternotomy appears to be the best single approach for all cases of valve replacement.

     

Limbic dementia

This is the second reported case, known to the authors, of complete, but selective, limbic lobe destruction in previously normally functioning central nervous systems. Both cases had an amnestic syndrome, whose characteristics were essentially similar to amnestic syndromes previously documented with less complete limbic destruction, with one difference—confabulation remained a prominent feature in the chronic stages of the memory disorder. Our patient exhibited a behavioural syndrome similar to that reported by Klüver and Bucy in monkeys with bilateral anterior temporal lobectomies. Klüver-Bucy like syndromes in man have usually been reported with surgical lesions, usually in patients with pre-existent brain disorder. Our case illustrates that the syndrome can be produced by necrotizing encephalitic lesions. We suggest that the combination of the above two syndromes is essentially a `limbic dementia'.     

Acquired perinatal leukoencephalopathy

Between 36 and 44 weeks after conception, telencephalic white matter in the newborn appears to be particularly vulnerable to insults that result in morphological disturbances. Available evidence indicates that this disorder (or group of disorders), named acquired perinatal leukoencephalopathy, reflects a decrease in blood flow through the distal vessels supplying paraventricular white matter and/or a metabolic disturbance produced by, or in response to, an infectious agent. Major advances in our understanding of the causes, mechanisms, and sequelae of acquired perinatal leukoencephalopathy may be made in the next decade because of improvement in brain imaging techniques, improved survival of high-risk babies, and relatively routine follow-up of these high-risk babies.     

Acyclovir-Glycoprotein conjugates are potent inhibitors of hepatitis B virus replication

Receptor-mediated targeting to the liver using galactose-terminated ligands is a promising strategy for site-specific delivery of antiviral drugs for treatment of hepatitis B virus infection. Optimization of drug conjugates for receptor-mediated delivery depends, in part, on judicious selection of coupling chemistry between drug and receptor-specific ligand. We synthesized three chemically distinct conjugates: acyclovir linked through a γ-aminobutyryl ester to asialoorosomucoid; acyclovir linked through a succinyl ester to polylysine-asialoorosomucoid; and acyclovir linked to polylysine-asialoorosomucoid through a monophosphoryl linkage (ACV-MP-PL-ASOR). All conjugates were rapidly cleared by the liver when tail-vein injected in mice. The conjugates inhibited replication of hepatitis B virus (HBV) DNA in cultured cells at concentrations that were dependent on the structure of the cross-linker and the extent of modification that the protein endured during coupling with drug. ACV-MP-PL-ASOR displayed more than 80 times the potency of unconjugated acyclovir.     

An approach for evaluating and increasing the informational content of mutagenicity and clastogenicity data bases

A method is described for using the fragments identified bythe CASE structure-activity relational expert system to identifythe type of chemicals that require further testing in mutagenicityand clastogenicity assays. Inclusion of such chemicals willincrease the informational content of databases with respectto structural features that are under-represented in currentlyavailable data bases. The method is applied to existing databases(mutagenicity in Salmonella, chromosomal aberrations in Chinesehamster ovary cells, unscheduled DNA synthesis hi rat hepatocytes,in vivo induction of micronuclei, somatic mutations in Drosophilamelanogaster) to identify structural determinants that are absent.     

22q11.2 duplication syndrome: two new familial cases with some overlapping features with DiGeorge/velocardiofacial syndromes

Twenty-one patients, including our two cases, with variable clinical phenotype, ranging from mild learning disability to severe congenital malformations or overlapping features with DiGeorge/velocardiofacial syndromes (DG/VCFS), have been shown to have a chromosome duplication 22q11 of the region that is deleted in patients with DG/VCFS. The reported cases have been identified primarily by interphase FISH and could have escaped identification and been missed by routine cytogenetic analysis. Here we report on two inherited cases, referred to us, to rule out 22q11 microdeletion diagnosis of VCFS. The first patient was a 2-month-old girl, who presented with cleft palate, minor dysmorphic features including short palpebral fissures, widely spaced eyes, long fingers, and hearing loss. Her affected mother had mild mental retardation and learning disabilities. The second patient was a 7(1/2)-year-old boy with velopharyngeal insufficiency and mild developmental delay. He had a left preauricular tag, bifida uvula, bilateral fifth finger clinodactyly, and bilateral cryptorchidism. His facial features appeared mildly dysmorphic with hypertelorism, large nose, and micro/retrognathia. The affected father had mild mental retardation and had similar facial features. FISH analysis of interphase cells showed three TUPLE1-probe signals with two chromosome-specific identification probes in each cell. FISH analysis did not show the duplication on the initial testing of metaphase chromosomes. On review, band q11.2 was brighter on one chromosome 22 in some metaphase spreads. The paucity of reported cases of 22q11.2 microduplication likely reflects a combination of phenotypic diversity and the difficulty of diagnosis by FISH analysis on metaphase spreads. These findings illustrate the importance of scanning interphase nuclei when performing FISH analysis for any of the genomic disorders.     

Virological and pharmacological factors associated with virological response to salvage therapy after an 8-week of treatment interruption in a context of very advanced HIV disease (GigHAART ANRS 097)

Both highly potent antiretroviral drug rescue multi therapy and treatment interruption (TI) have been suggested to be effective in HIV-1 infected-patients with multiple treatment failure. GigHAART-ANRS 097 was the only randomized trial during which an 8-week TI was beneficial in heavily pre-treated patients with multi-drug resistant virus on resuming a multiple-drug salvage regimen. The aim of this study was to analyze virological and pharmacological factors associated with a virological response. Clonal resistance analysis showed that although the viral population was highly mutated and nearly monoclonal at baseline, the 8-week interruption therapy allowed the re-emergence of more susceptible quasispecies to the subsequent salvage therapy, which were not detected by classical genotypic resistance testing. The fact that not every viral clone harbored all resistance viral mutations could explain a part of the virological response to a six to eight drug regimen for patients enrolled in the TI group. This phenomenon was associated with a transient virological response after the use of a GigHAART therapy, but was followed by the re-emergence of baseline resistance pattern and acquisition of additional mutations in patients failing this strategy. A combined factor of protease inhibitor (PI) concentration and genotypic score, expressed as a genotypic inhibitory quotient (GIQ), was used to assess the importance of genotypic resistance and plasma drug levels in the rate of response to multiple PI combination. The GIQ of each PI used in the regimen was not associated with virological success. However, the sum of PI GIQs was predictive of a virological response. These results suggest that pharmacological enhancement might overcome viral resistance and that there is some benefit in adding the activity of several boosted-PIs to improve the response to a salvage regimen.     

Therapeutic hypothermia for coma after cardiorespiratory arrest caused by hanging

We report a case in which mild therapeutic hypothermia was used successfully in a patient with coma after cardiorespiratory arrest induced by hanging.