Assessing the impact of mailing self-sampling kits for human papillomavirus testing to unscreened non-responder women in Manitoba.

Background: CervixCheck, Manitoba's cervical cancer screening program, conducted a pilot study to assess whether screening participation could be improved in unscreened women by offering a mailed self-sampling kit for human papillomavirus (hpv) testing instead of a Pap test. Methods: In a prospective cohort study design, a sample of unscreened women (n = 1052) who had been sent an invitation letter from CervixCheck in the past but who did not respond were randomized to either an intervention group or a control group. The intervention group received a mailed hpv self-sampling kit; the control group received no additional communication. Returned hpv self-sampling swabs were analyzed by a provincial laboratory. After 6 months, screening participation in the two study groups was compared using a logistic regression model adjusted for age and area of residence (urban or rural). Secondary outcomes included hpv positivity, specimen inadequacy, compliance with follow-up, and time to colposcopy. Results: Screening participation was significantly higher in the intervention group than in the control group (n = 51, 9.6%, vs. n = 13, 2.5%; odds ratio: 4.7; 95% confidence interval: 2.56 to 8.77). Geographic area of residence (urban or rural) and age were not statistically significant. Conclusions: The study demonstrated that hpv self-sampling kits can enhance screening participation in unscreened non-responder women in the setting of an organized screening program. Next steps should include additional research to determine the best implementation strategy for hpv self-sampling in Manitoba.

Glatiramer acetate-reactive T lymphocytes regulate oligodendrocyte progenitor cell number in vitro: role of IGF-2.

Glatiramer acetate (GA) is an immunomodulator approved for therapy of relapsing-remitting multiple sclerosis (RRMS), but recent findings indicate that it may also have additional, neurotrophic effects. Here, we found that supernatants from human GA-reactive T lymphocytes potentiated oligodendrocyte numbers in rodent and human oligodendrocyte progenitor (OPC) cultures. Effects of Th2-polarized lines were stronger than Th1-polarized cells. Microarray and ELISA analyses revealed that neurotrophic factors induced in Th2- and Th1-polarized GA-reactive lines included IGF-2 and BMP-7 respectively, and functional studies confirmed IGF-2 as trophic for OPCs. Our results support the concept that GA therapy may result in supportive effects on oligodendrocytes in RRMS patients.

Serial combination therapy: is immune modulation in multiple sclerosis enhanced by initial immune suppression?

BACKGROUND: Although the concept that an initial course of immune-suppression facilitates subsequent immune-modulation (such as Th1 to Th2 deviation) is attractive for several autoimmune diseases, such a mechanism for serial-combination therapy has never been formally demonstrated. Recently, brief mitoxantrone induction-chemotherapy followed by immune-modulation with glatiramer acetate (GA) was significantly more effective at reducing multiple sclerosis disease activity than with GA alone. OBJECTIVE: To examine whether the benefit of initial immune suppression with mitoxantrone before GA treatment is associated with more efficient immune modulation. METHODS: IgG1/IgG4 GA-reactive antibody profiles, previously established as markers of GA-induced Th2 immune-deviation, were prospectively measured in vivo in patients treated with GA alone or with mitoxantrone induction therapy followed by GA. RESULTS: Significant and sustained increase in IgG4 antibodies (and the anticipated reversal of the IgG1/IgG4 ratio) was seen in patients treated with GA alone. Combination therapy resulted in lesser IgG4 induction (and no reversal of IgG1/IgG4 ratio). Thus, the enhanced efficacy of mitoxantrone-GA combination regimen was associated with decreased, rather than increased, efficiency of shifting the GA-reactive IgG1/IgG4 antibody profile. CONCLUSION: These results provide important insights into mechanisms of combination therapy and therapeutic strategies for autoimmune diseases.

Diet texture modifies outcome of a primary infection with Heligmosomoides polygyrus (nematoda) in mice.

To determine if dietary texture altered the establishment, survival and reproduction of Heligmosomoides polygyrus during a primary infection, commercial mouse chow (Purina Chow) was fed in either pelleted or powdered form to 2 groups of infected BALB/c mice, and a semipurified, biotin-fortified, egg-white-based diet was provided in powdered form to a third group of mice. Diet texture (powdered vs. pelleted) modified parasite establishment, as evidenced by higher worm recovery 6 days postinfection (PI) in both groups of mice fed powdered diets compared with the group fed the pelleted diet, but diet texture had no detectable effect on net or per capita egg production or on day 30 worm survival. However, almost twice as many worms were recovered from mice fed the semipurified, powdered diet than those fed either textural formulation of the commercial mouse chow on day 30 PI, indicating that a dietary component in the semipurified diet, such as the single fiber source cellulose, facilitated parasite survival, or that other ingredients in the commercial mouse chow, perhaps the more complex fiber components, reduced worm survival, or both. We conclude that dietary texture influences parasite establishment and that specific fibers that change texture can individually and independently modify H. polygyrus survival.

The efficacy of ivermectin against laboratory strains of Heligmosomoides polygyrus (Nematoda).

A susceptible strain of Heligmosomoides polygyrus was selected for 15 generations with increasing doses of ivermectin (0-6 mg/kg). A passage strain was developed, parallel with the ivermectin-selected strain, to control for changes due to rapid passage from mouse to mouse. The LD50s of the 8th and 15th generations of the ivermectin-selected strain were 1.5 times that of the susceptible strain. The LD50 of the passage strain at generations 8 and 15 remained similar to that of the susceptible strain. Ivermectin efficacy was lower against the LA stage than against the adult stage in the susceptible strain, the Ivermectin-selected strain and the passage strain at generation 8.

Medium-chain triglycerides and total parenteral nutrition in the management of infants with congenital chylothorax.

Enriched MCT (medium-chain triglycerides) formula has been used in the management of infants with congenital chylothorax (CC). Administration of total parenteral nutrition (TPN) has also been suggested. I evaluated the effect of these two regimens on the course of infants with CC described in the literature, in addition to two new cases reported herein. There were 29 infants who received non-MCT formulas. Twelve infants were given MCT formulas and/or parenteral nutrition. The total volume and duration of pleural effusion were decreased with these regimens, and there were no associated deaths. Data suggest that infants with CC must initially be given an enriched MCT formula. If pleural effusion persists, then total parenteral nutrition should be considered.

Free fatty acids in the development of breast milk jaundice.

The incubation of milk, at 4 degrees C, from mothers of infants with breast milk jaundice (BMJ) is reported to result in significantly higher levels of free fatty acids (FFA) compared with milk from controls. Single milk samples collected under standard conditions were obtained from four mothers of infants with BMJ and 14 control donors matched for stage of lactation. Milk samples were analyzed for the concentrations of FFA, using thin-layer gas chromatographic techniques. In addition, serum total fatty acids were measured in mothers and infants. The concentrations of FFA increased after storage of the milk from both the jaundiced and control groups. No differences were observed in the composition of milk FFA before or after incubation, when respective values were compared between these two groups. Similarly, no differences were detected in serum total fatty acids in either infants or mothers. The observation that increased levels of FFA in milk are associated with BMJ was not confirmed.

Malnutrition in infants with acute diarrheal syndrome.

The data from the charts of 109 infants who were younger than 9 months of age and who had been hospitalized with acute diarrheal syndrome in 1978 were compared with data from the charts of 108 healthy infants of the same age range with the same sex and ethnic distributions who were attending well-child clinics serving the same geographic area during the same year. In a comparison of weight percentiles, 45.3% of the acute diarrheal syndrome patients and 11.3% of the well children were below the 10th percentile. When height percentiles were compared, 41.8% of the acute diarrheal syndrome patients and 15.3% of the well children were below the 10th percentile. The data indicate that malnutrition was a characteristic of infants with acute diarrheal syndrome who required hospitalization.

Comparison of acquired monosaccharide intolerance and acute diarrheal syndrome.

In a retrospective study, 9% of the admissions to Ben Taub General Hospital for diarrhea were found to have acquired monosaccharide intolerance (AMI). The course of AMI was compared with that of acute diarrheal syndrome (ADS). The patients with AMI were younger at the time of admission, and, although the mean birthweight and percent of prematurity were approximately the same in the two groups, the AMI patients were found to be malnourished (p less than 0.02). Data suggest that the nutritional insult had occurred between birth and admission, and that malnutrition was a contributing factor in the development of AMI.