Maintaining measles elimination in Canada: Moving forward.

Due to the success of immunization and timely surveillance, Canada has not reported any cases of endemic measles since 1998. However, recent large outbreaks of imported-related measles have highlighted the risks of reintroduction of disease through travel and immunization coverage gaps in sub-populations. Building on its 2011 Elimination Report and in collaboration with provincial and territorial partners, the Public Health Agency of Canada has been promoting immunization, expanding the information gathered in immunization coverage surveys, piloting enhanced surveillance with real-time notifications of suspected and confirmed cases to enable early detection of outbreaks and strengthening its laboratory capacity. As these efforts are consolidated, this approach may become a model for other countries around the world as they seek to achieve measles elimination goals.

Collaboration on a public health-driven vaccine initiative.

Disease surveillance can be used as an opportunity to determine priorities for research and the development of new therapeutics. This is evident in the work underway to develop a new vaccine to combat a serious invasive childhood disease: Haemophilus influenzae serotype a (Hia). Following the introduction of Hib vaccine into the routine childhood immunization schedule in Canada in the early 1990's, the Public Health Agency of Canada (PHAC) began to document the dropping rates of H influenzae serotype b (Hib) infection. However, invasive H. influenzae diseases due to non-Hib strains began to increase and in 2007, surveillance for invasive H. influenzae disease due to all serotypes as well as non-typeable strains was initiated. Current data suggests Hia is a cause of serious invasive disease, particularly in Aboriginal populations. Similar to Hib, Hia causes severe illnesses such as meningitis, sepsis and bacteremic pneumonia in young children under the age of five. Given the emerging threat due to Hia in Aboriginal populations in Canada, PHAC formed a partnership with the National Research Council of Canada (NRC) to investigate the potential of creating a capsular polysaccharide vaccine against Hia. At the present time, candidate vaccine seed strains have been identified and PHAC and the NRC are working with the Northern Ontario School of Medicine, the US Centers for Disease Control and Prevention and others. The goal of this research is to identify and prepare a candidate vaccine against Hia while increasing the understanding of how such a vaccine would improve the health of a vulnerable population.

The temporal unraveling of autobiographical memory narratives in patients with temporal lobe epilepsy or excisions.

Medial temporal lobe epilepsy (TLE), a condition known to affect the integrity and function of medial temporal lobe structures such as the hippocampus, has been shown to disrupt memory for real-life episodes. Here, patients with unilateral TLE, patients who received a unilateral temporal lobe resection to cure TLE, and healthy controls produced free narratives of autobiographical memories (AMs). To assess temporal resolution, narratives were segmented into bits of information, or details, which were classified according to how precisely they could be located within the time course of the AM. Categories included details corresponding to the entire AM, to parts or subevents within the AM, and to actions taking place within seconds to minutes. The number of details per category was tallied and compared between patients and controls. Temporal order was assessed by determining the correct (internally consistent) chronological order of the sequence of events within the narrative. Results indicate that while patients' memory for the parts or subevents of personal episodes was intact, as was their temporal order, their memory for the minute-by-minute unraveling of the episode was impaired. We believe this loss of temporally specific details may contribute to the reduced vividness of AM recollection in TLE patients. Our findings provide further evidence that patients with hippocampal damage retrieve skeletal AMs for which the gist of the memory is maintained, but the specific details are lost.

Reduction of the spin-orbit splittings at the n = 28 shell closure.

The N = 28 shell closure has been investigated via the 46Ar(d,p)47Ar transfer reaction in inverse kinematics. Energies and spectroscopic factors of the neutron p(3/2), p(1/2), and f(5/2) states in 47Ar were determined and compared to those of the 49Ca isotone. We deduced a reduction of the N = 28 gap by 330(90) keV and spin-orbit weakenings of approximately 10(2) and 45(10)% for the f and p states, respectively. Such large variations for the f and p spin-orbit splittings could be accounted for by the proton-neutron tensor force and by the density dependence of the spin-orbit interaction, respectively. This contrasts with the picture of the spin-orbit interaction as a surface term only.

Gallbladder carcinoma producing alpha-fetoprotein.

Alpha-feto protein (AFP) is a clinically useful marker for hepatocellular carcinoma, hepatoblastoma, and nonseminomatous testicular tumors. Elevated serum AFP can also occur with tumors of the gastrointestinal tract, pancreas, lung, kidney, and urachus. Serum AFP can also be minimally elevated in nonmalignant conditions including acute and chronic hepatitis, cirrhosis, and pregnancy. Reports of gallbladder carcinoma that elaborate AFP are extremely rare, and almost all represent papillary carcinomas. Until now, there have been only two reports in the world literature that describe undifferentiated gallbladder carcinoma with elevated serum AFP. The authors present one case of undifferentiated gallbladder carcinoma and another case of poorly differentiated gallbladder carcinoma with increased serum AFP. In both cases, serum AFP was particularly useful in documenting metastatic recurrence of gallbladder carcinoma.

A new salvage procedure for peritoneal dialysis catheters with exit site infections.

The management of catheter-related infections has become a major challenge in continuous ambulatory peritoneal dialysis treatment. We identified five patients on continuous ambulatory peritoneal dialysis who failed conservative medical management for exit site infections. Each patient underwent incision and debridement along the subcutaneous course of the catheter, exteriorization of the superficial cuff, and establishment of a new exit site at the medial aspect of the wound. This novel technique of incision and debridement along the subcutaneous tunnel and relocation of the exit site has not been described in the literature. In four of five patients, this technique controlled the exit site infection and arrested the progression of the infection to peritonitis, preventing the need for catheter removal.

Endoscopic biliary stent migration with small bowel perforation in a liver transplant recipient.

Intestinal perforation from a migrated biliary stent is a rare complication after endoscopic stent placement for benign biliary stricture. We provide the first description of stent migration and distal small-bowel perforation after stent placement for biliary anastomotic stricture in a liver transplant recipient. We review the current literature on the diagnosis and management of stent migration and intestinal perforation after endoscopic or percutaneous stent placement for benign and malignant biliary strictures. Early diagnosis and treatment of biliary stent migration and subsequent intestinal perforation are essential in transplant patients, in whom immunosuppression sometimes blunts signs and symptoms of intestinal perforation.

[Sensitivity and specificity of thyreostimuline (TSH) determination on filter paper for the diagnosis of hypothyroidism in the elderly]. / Sensibilité et spécificité du dosage de la thyréostimuline (TSH) sur papier filtre pour le diagnostic d'hypothyroïdie chez la personne âgée.

The aim of this study was to measure the prevalence of hypothyroidism in 239 elderly patients and to determine the validity of TSH assay on blood dried on filter paper (spot-test) for the diagnosis of hypothyroidism. The sensitivity and specificity of the spot-test were evaluated in a subgroup of 177 subjects. The prevalence of hypothyroidism was 14.2% (34/239). The spot-test did not give satisfactory results for the diagnosis of hypothyroidism in elderly subjects. Due to the lack of specificity, most of the positive results were false positives and the clinician had to rely on laboratory determination of plasma TSH level to confirm hypothyroidism in half of the patients. We do not recommend the spot-test for the diagnosis of hypothyroidism in the elderly. Laboratory assay of plasma TSH is required for confirming hypothyroidism in the elderly.

The Drug Utilization Review Network of Quebec.

Drug utilization review programs have been recognized as an effective way to control health care spending while maintaining quality services. This article describes the structure, mandate and activities of Quebec's Drug Utilization Review Network. This 112-member network, which represents 45% of health care facilities in the province, was established to promote the optimal utilization of drugs through the provision of support to pharmacology committees, therapeutic committees and pharmacy departments. The network's main role is to coordinate multi-centre drug utilization studies. Future challenges include maintaining member interest and evaluating the clinical and economic impact of the network's efforts.

Anti-DNA.RNA antibodies: an efficient tool for non-isotopic detection of Listeria species through a liquid-phase hybridization assay.

This study was undertaken to evaluate the potential of a new approach using anti-DNA.RNA monoclonal antibodies to detect Listeria in both pure culture and inoculated meat and meat products. A sensitive liquid-phase assay was first developed, based on the formation in solution of a hybrid between a 784-bp DNA probe, specific for the genus Listeria, and target rRNA. Monoclonal antibody and antisera raised against hybrid nucleic acids were then used in various immunoenzymatic assays to detect specific hybrids formed in solution. System 2, using a double sandwich enzyme-linked immunosorbent assay, and system 1, using a biotinylated probe, proved to be very effective. The method using biotin-streptavidin complex, however, resulted in a higher background signal. System 2 described here, using unlabeled probe, was more effective. This strategy allowed the detection of as little as 2.5 pg target RNA from pure culture and 500 cells from inoculated meat homogenate, even in the presence of other contaminating bacteria. The assay was more sensitive and could be completed within 3 h, as opposed to several days when conventional culture methods were used.

Production and characterization of anti-DNA-RNA monoclonal antibodies and their application in Listeria detection.

Murine monoclonal antibodies (MAbs) specific for DNA-RNA hybrids were successfully produced with two different heteropolymers as antigens, cDNA-mRNA and phi X174 DNA-RNA heteroduplexes. The former was simpler to prepare. Both had shown similar immunogenicities. Two different immunoglobulin M MAbs were isolated. The 20D3 MAb, generated with the phi X174 DNA-RNA hybrid, showed association constants of 1.05 x 10(12), 2.12 x 10(10), and 1.68 x 10(7) for the antigens phi X174 DNA-RNA, cDNA-mRNA, and poly(rA)-poly(dT), respectively. The 6B5 MAb, obtained with the cDNA-mRNA hybrid, showed association constants of 1.59 x 10(5), 5 x 10(12), and 7.1 x 10(8) for the above-described antigens, respectively. With the 20D3 MAb, an immunoassay was developed for the detection of Listeria DNA-RNA hybrids. In brief, a biotinylated rRNA gene probe specific for the genus Listeria was hybridized with rRNA in the solution phase. The hybrids thus formed were then captured in microtiter plate wells precoated with the purified 20D3 MAb, and the probe-target hybrids were detected with a streptavidin-alkaline phosphatase conjugate. This assay was shown to be specific for the genus Listeria and highly sensitive, allowing the detection of as little as 2.5 pg of target rRNA.

Radical pancreatic resection for benign and malignant disease.

From 1972 to 1990 a total of 44 patients (24 men and 20 women) underwent pancreatic resections at our institution. We undertook a retrospective review to discover what prognostic indicators would predict long-term survival for patients with malignancy. Prognostic indicators included primary tumor location and size, tumor differentiation and grade, tumor invasion, number of positive lymph nodes, and postoperative radiation and chemotherapy. Overall, three patients died within the 30-day postoperative period (7%). One- and five-year survival rates following resection for malignancy were 67.5 and 31 per cent, respectively. Multivariate analysis identified primary tumor origin, nuclear grade, and preoperative bilirubin level greater than 2 mg/dl as the only statistically significant factors in determining survival. One- and five-year survival for tumor location and tumor grade were as follows: [table: see text] Our experience indicates that pancreatic resections are potentially curative in a significant percentage of patients with nonpancreatic primaries and, to a lesser extent, in those individuals with pancreatic adenocarcinoma. Other prognostic indicators examined in our series, however, did not affect long-term survival.

Pharmacokinetics and pharmacodynamics of ranitidine and famotidine in healthy elderly subjects: a double-blind, placebo-controlled comparison.

The pharmacokinetics and pharmacodynamics of ranitidine and famotidine were studied in 13 healthy elderly volunteers. On 3 mornings separated by a 1-week wash-out period, each subject received a single oral dose of ranitidine 300 mg, famotidine 40 mg, and placebo in a crossover, randomized fashion with double-dummy administration. Plasma and urine concentrations of ranitidine and famotidine were determined by high-performance liquid chromatography. Intragastric pH was measured for 24-hours with an antimony probe. Famotidine's plasma half-life (4.42 hrs) was significantly longer than ranitidine's (3.14 hrs, p < 0.05, paired t test). The 24-hour, area under the curve of pH profiles of the two drugs were significantly different from placebo (p < 0.05, analysis of variance and Fisher PLSD test) but not from each other. The duration of effect (defined as median pH > 4) was similar for ranitidine and famotidine, 10.3 and 9.9 hours, respectively (p = 0.713, paired Student's t test). Thus both agents exhibited a similar duration of 24-hour antisecretory response under these study conditions.

Functional cooperation among human IgG-specific murine monoclonal antibodies for the detection of weak blood group antibodies in routine agglutination tests.

Seven monoclonal antibodies (MAbs) selected from a large panel of human IgG-specific murine MAbs were characterized serologically and studied for their ability to cooperate in routine antihuman globulin agglutination tests. In binding inhibition experiments, three of these MAbs were shown to bind simultaneously to immobilized human IgG molecules. Cooperation among these MAbs increased significantly the capacity of the individual MAbs to agglutinate red cells sensitized with weak blood group antibodies. These results demonstrate the usefulness of selected MAb blending for the preparation of potent antihuman IgG reagents from murine monoclonal antibodies.

Increased avidity of mutant IgM antibodies caused by the absence of COOH-terminal glycosylation of the mu H chain.

We have previously described the isolation of two hybridoma variants secreting higher avidity IgM (D5 and 7F5), starting from the E11 hybridoma cell line, which produces an antibody specific for the A Ag of the ABO blood group system. In order to explain at the molecular level this increased reactivity, cDNA encoding the H and L chains of the E11, D5, and 7F5 mAb were cloned and sequenced. Comparison of the nucleotide sequences showed a single point mutation in each of the two mAb produced by the hybridoma variants. The mutations were both located in the H chain C region and caused a Ser to Phe substitution at position 565 in the D5 mAb and a Asn to Tyr substitution at position 563 in the 7F5 mAb. Both substitutions modified the consensus glycosylation sequence (Asn-X-Ser/Thr) located in the tail piece of the secretory mu-chain. The absence of glycosylation at this site was confirmed by CNBr cleavage of the [14C]mannose-labeled mAb. The two single point mutations were solely responsible for the increased avidity of the antibodies, as confirmed by site-directed mutagenesis of the E11 mu-chain and serologic analysis of the mutated E11 antibodies. We conclude that the absence of glycosylation at Asn 563 is responsible for the increased avidity of the mutant, possibly by altering the quaternary structure of the IgM polymer. To our knowledge, this is the first report that point mutations in the H chain C region can influence the reactivity of IgM mAb.

Influence of lomefloxacin on the pharmacokinetics of theophylline.

The effect of multiple doses of lomefloxacin (400 mg twice a day) on the clearance of theophylline and the urinary excretion of its metabolites was investigated in 15 healthy male subjects. Concentrations of theophylline in plasma were measured by TDx (Abbott Diagnostics, Mississauga, Ontario, Canada). Urinary excretion of theophylline and its three major metabolites and lomefloxacin in plasma were assayed by high-performance liquid chromatography. Total theophylline clearance remained unchanged before lomefloxacin treatment and after lomefloxacin single- and multiple-dose treatments (58.02, 56.57, 54.07 ml/min, respectively). The urinary recovery of unchanged theophylline and its major metabolites stayed stable during the study. We conclude that lomefloxacin can be added to the list of fluoroquinolones that can be administered safely with theophylline.

Safety of fleroxacin coadministered with theophylline to young and elderly volunteers.

The influence of multiple doses of fleroxacin on the plasma clearance and the urinary excretion of theophylline was studied in 19 young and 18 elderly male volunteers. A theophylline dosage individualized to obtain a mean theophylline concentration in plasma of 10 +/- 3 micrograms/ml was administered for 1 week to each subject. At week 2, oral fleroxacin (400 mg once daily) was added. Theophylline concentrations in plasma were measured with TDx (Abbott Diagnostics, Mississauga, Ontario, Canada), and urinary excretion of theophylline and its three major metabolites was measured by high-performance liquid chromatography. Total theophylline clearance remained essentially unchanged throughout the study period (3.5 and 2.9 liters/h in the young and the elderly, respectively) both after a single fleroxacin dose and after multiple doses. Although significant changes occurred in the urinary excretion of unchanged theophylline and its metabolites after a single fleroxacin dose, no changes were observed after multiple doses. Side effects consisted mainly of gastrointestinal and sleep disturbances, more related to theophylline; photosensitivity was observed in six subjects and was attributed to fleroxacin. We conclude that fleroxacin may be administered concomitantly with theophylline in either young or elderly patients. Close monitoring of theophylline concentrations in serum should be performed, particularly in patients with chronic obstructive pulmonary disease, for whom data are currently lacking.

Normal pressure hydrocephalus in geriatric medicine: a challenge.

Normal pressure hydrocephalus (NPH) in elderly patients is reviewed. Since the clinical signs that characterize NPH--incontinence, difficulty walking, and dementia--occur frequently in the elderly in association with a wide variety of disorders, attention is paid to the differential diagnosis of NPH on the basis of both clinical findings and laboratory tests. Success rates for treatment of NPH using surgical shunting are discussed, as are mortality rates and complication rates for this type of surgery in the elderly. Factors that may be of value in predicting which NPH patients are most likely to benefit from surgical intervention are reviewed, and the need for the development of pharmacological alternatives to surgery for elderly NPH patients is emphasized. As one of the most treatable causes of dementia in the elderly, NPH should be considered in the diagnosis of demented elderly patients with continence and gait disturbances, and it merits further research.