Advance care planning: identifying system-specific barriers and facilitators.

BACKGROUND: Advance care planning (acp) is an important process in health care today. How to prospectively identify potential local barriers and facilitators to uptake of acp across a complex, multi-sector, publicly funded health care system and how to develop specific mitigating strategies have not been well characterized. METHODS: We surveyed a convenience sample of clinical and administrative health care opinion leaders across the province of Alberta to characterize system-specific barriers and facilitators to uptake of acp. The survey was based on published literature about the barriers to and facilitators of acp and on the Michie Theoretical Domains Framework. RESULTS: Of 88 surveys, 51 (58%) were returned. The survey identified system-specific barriers that could challenge uptake of acp. The factors were categorized into four main domains. Three examples of individual system-specific barriers were "insufficient public engagement and misunderstanding," "conflict among different provincial health service initiatives," and "lack of infrastructure." Local system-specific barriers and facilitators were subsequently explored through a semi-structured informal discussion group involving key informants. The group identified approaches to mitigate specific barriers. CONCLUSIONS: Uptake of acp is a priority for many health care systems, but bringing about change in multi-sector health care systems is complex. Identifying system-specific barriers and facilitators to the uptake of innovation are important elements of successful knowledge translation. We developed and successfully used a simple and inexpensive process to identify local system-specific barriers and enablers to uptake of acp, and to identify specific mitigating strategies.

Assessment of the effects of a stannous fluoride dentifrice on gingivitis in a two-month positive-controlled clinical study.

OBJECTIVE: The purpose of this study was to evaluate the anti-gingivitis effectiveness of a 0.454% stannous fluoride test dentifrice relative to a marketed positive-control triclosan-containing dentifrice in adults with gingivitis. METHODS: This was a two-month, randomized and controlled, double-blind, parallel group, single-center investigation involving 150 adults with existing mild to moderate gingivitis. Pre-treatment gingivitis levels were assessed at baseline using the Lobene Modified Gingival Index (MGI) and the Gingival Bleeding Index (GBI). Qualified subjects were randomly assigned to either a 0.454% stannous fluoride test dentifrice or a marketed, positive-control 0.30% triclosan/copolymer dentifrice. Subjects then brushed for two months unsupervised in the home setting with their assigned dentifrice per manufacturer's instructions. At Month 2, subjects were re-evaluated for gingivitis via MGI and GBI examinations. RESULTS: All 150 enrolled subjects completed the trial and were evaluable. Both the stannous fluoride test and triclosan/copolymer control dentifrices provided statistically significant reductions in average MGI, GBI, and number of bleeding sites relative to pre-treatment (p < 0.0001) at Month 2. The adjusted mean improvement from baseline at Month 2 for the stannous fluoride test dentifrice group was 65% greater for number of bleeding sites, 62% greater for GBI, and 45% greater for MGI compared to the triclosan/copolymer positive-control group, with groups differing significantly (p < 0.0001) via each of the three gingivitis measures. Both dentifrices were well-tolerated. CONCLUSION: An advanced stannous fluoride test dentifrice provided superior reductions in gingival inflammation and gingival bleeding compared to a commercially available triclosan/copolymer positive-control dentifrice after two months of tooth brushing.

The plaque removal efficacy of a novel power brush head.

OBJECTIVE: To assess the plaque removal efficacy of an oscillating/rotating power toothbrush with novel brush head (Oral-B Precision Clean) in comparison to an American Dental Association (ADA) reference manual toothbrush. METHODS: This was a replicate-use, single-brushing, two-treatment, examiner-blind, randomized, four-period (visit) study with a crossover design. At each visit, subjects disclosed their plaque with disclosing solution for one minute, and an examiner performed a baseline (pre-brushing) plaque examination (Rustogi, et al. Modification of the Navy Plaque Index). Subjects were then instructed to brush for two minutes (according to manufacturer's instructions) with their assigned power toothbrush or as they normally do with the ADA manual brush under supervision, after which they again disclosed their plaque and were given a post-brushing plaque examination. RESULTS: Both the power brush and manual brush showed statistically significant plaque reductions from baseline for the whole mouth, along the gingival margin, and on approximal surfaces. The power brush showed statistically significant advantages (p < 0.001) over the manual brush in plaque reduction for whole mouth (28.8%), gingival margin (44.3%), and approximal surfaces (20.7%). CONCLUSION: The oscillating/rotating power toothbrush with a novel brush head showed statistically significantly superior plaque reduction (whole mouth, gingival margin, and approximal surfaces) compared to a manual toothbrush.

A clinical evaluation of the plaque removal efficacy of five manual toothbrushes.

OBJECTIVE: To assess and compare the plaque removal efficacy of five different Oral-B manual toothbrushes: CrossAction Pro-Health (CAPH), CrossAction (CA), Exceed (EX), Advantage 123 (ADV 123), and Indicator (IND). METHODS: This was a single-use, five-treatment, examiner-blind, randomized, five-period (visit) crossover study, with 10 different treatment sequences (groups) that determined the order in which the five toothbrushes were assigned at study visits. Three toothbrushes had an advanced CrissCross bristle design (CAPH, CA, EX), while two had more standard designs with straight bristles (ADV 123 and IND). At the first visit, subjects disclosed their plaque with disclosing solution, and an examiner performed a baseline plaque examination using the Rustogi, et al. Modification of the Navy Plaque Index (RMNPI). Subjects brushed for one minute with their assigned toothbrush under supervision, after which they again disclosed their plaque and were given a second plaque examination. The same procedure was followed for each of the visits in turn. RESULTS: All five manual toothbrushes showed a statistically significant (p < 0.0001) reduction in plaque from baseline for the whole mouth (84% to 93%), gingival margin (74% to 88%), and approximal surfaces (95% to 99%). For pair-wise treatment comparisons for all three plaque measures, CAPH, CA, and EX demonstrated statistically significantly better plaque removal than ADV 123 and IND (all p < 0.018). No other treatment comparisons were statistically significant. CONCLUSION: All five manual toothbrushes showed highly effective plaque reduction for whole mouth, gingival margin, and approximal surfaces. Comparisons between brushes showed consistent advantages for CAPH, CA, and EX compared to ADV 123 and IND for all three plaque measures, indicating that advances in toothbrush design can further enhance plaque removal.

Evaluation of spinopelvic parameters in lumbar prolapsed intervertebral disc.

BACKGROUND: Sacro-pelvic morphology and orientation are usually described in terms of pelvic incidence (PI), pelvic tilt (PT), and sacral slope (SS). Orientation and morphology of pelvis can affect degenerative changes in the lumbar spine. Thus, here we investigated the relationships between various sagittal spinopelvic parameters and the degree of disc degeneration in young adults. MATERIAL AND METHODS: A hospital-based cross-sectional study with a total of 60 cases was done. Patients presenting with back or leg pain having prolapsed disc on magnetic resonance imaging (MRI) were included in the study. A standing X-ray of LS spine from dorso-lumbar junction to mid-thigh was taken. Various spinopelvic parameters were assessed from the scannogram using the software. RESULTS: The mean age was 39.27 years. L5S1 was the most common level. Mean SS, PT, PI, and LL were 37.78°, 13.52°, 51.33°, and 41.01°. Disc pathologies at L1L2, L2L3, and L4L5 level showed a positive correlation with PT, PI, and LL. Disc pathology at the L5S1 level shows a positive correlation with PT and LL. A statistically significant correlation between SS and degenerative spondylolisthesis at L4L5 was found from data with P = 0.023. DISCUSSION: An increase in SS statistically significantly increases the chance of development of degenerative spondylolisthesis at L4L5. An increase in PT, PI, and LL will cause an increase in disc pathology at L1L2. An increase in SS, PT, PI, and LL will cause an increase in disc pathology at L2L3. An increase in SS, PT, PI, and LL will cause an increase in disc pathology at L4L5. An increase in PT and LL will cause an increase in disc pathology at L5S1. CONCLUSION: Standing lateral view radiograph from dorso-lumbar junction to the mid-thigh is as good as standing whole spine radiograph for measurement of spinopelvic parameters. Degenerative spondylolisthesis at L4L5 has a statistically significant correlation with an increase in SS.

Changing profile of Vibrio cholerae O1, O139 in Delhi & its periphery (2003-2005).

BACKGROUND & OBJECTIVE: Cholera caused by either Vibrio cholerae O1 or O139 is endemic in Delhi and its peripheral areas. The present study was carried out to understand the changing epidemiology of V. cholerae in terms of prevalence of serotypes, antibiogram pattern and phage types. METHODS: A total of 9858 stool samples from the admitted diarrhoea patients were used for the isolation of V. cholerae O1 and O139. Subsets of isolates were tested against thirteen antimicrobials and phage typed. RESULTS: Among 4251 (43.1%) confirmed cases, 41.6 per cent were V. cholerae O1 and rest (1.5 %) V. cholerae O139. Detection of V. cholerae O1 serotype Inaba was 87.7 per cent during 2005 and rest were serotype Ogawa. Majority of cases (93.1%) were from Delhi. Male:Female ratio remained 1.5:1.0. Children below 5 yr age group constituted 32.7 per cent cases. Shift in the age groups and seasonal incidence were recorded. All 226 strains of V. cholerae O1 and O139 were resistant to nalidixic acid; 96 per cent V. cholerae O1 isolates were multidrug resistant (FX NA SXT). Phage type 27 (98.7%) was the most prevalent and the new phage types were 4, 16 and 25 in this area. INTERPRETATION & CONCLUSION: Enhanced surveillance helped in bringing down cases from 47.7 per cent in 2003 to 36.8 per cent in 2005. Additionally, the changing epidemiology of V. cholerae O1 and O139 infections and drug resistance need regular monitoring.

Bacteriological & epidemiological characteristics of diphtheria cases in & around Delhi -a retrospective study.

BACKGROUND & OBJECTIVE: Diphtheria infections caused by the different toxigenic biotypes of Corynebacterium diphtheriae are endemic in Delhi. Information on biochemical identification, toxigenicity and antimicrobial susceptibility to this bacterium is scanty. This retrospective study was carried out to identify isolated Corynebacteria biochemically, determine their toxigenicity, drug sensitivity and some epidemiological characteristics of diphtheria cases from Delhi and adjoining States for the period 1998-2004. METHODS: A total of 1118 throat and 585 nasal swabs were used to detect human pathogenic corynebacteria. WHO recommended methods were used for the detection, screening, toxigenicity and antibiogram pattern of the isolates. RESULTS: Among 493 (44.1%) cases detected positive for corynebacteria 71.8 per cent were pharyngeal, 20.9 per cent nasopharyngeal and rest 7.3 per cent nasal diphtheria cases. Biochemical identification revealed two species i.e., C. diphtheriae and C. pseudodiphtheriticum. In C. diphtheriae three biotypes were detected viz., intermedius (95.5%), gravis (3.4%) and mitis (1.1%). Toxin was expressed by 96 per cent isolates of C. diphtheriae. Cases were recorded from Delhi and four adjoining States. Sex ratio among male to female was 1.6:1. Prime victims were less than 9 yr old children (93.3%). Unvaccinated children (70.2%) were the main sufferers. Fatality rate was highest in Delhi cases (16.8%) followed by UP (14.6%) and Haryana (5.9%). INTERPRETATION & CONCLUSION: Standard methods revealed the replacement of C. diphtheriae var mitis with var intermedius and occurrence of diphtheria infections due to other human pathogenic corynebacteria. It is imperative to have good bacteriological facilities to have better surveillance with regular monitoring in the endemic areas to keep the disease under control.

Zinc oxide nanoparticles (ZnONPs) alleviate heavy metal-induced toxicity in Leucaena leucocephala seedlings: A physiochemical analysis.

The present study describes the role of zinc oxide nanoparticles (ZnONPs) in reversing oxidative stress symptoms induced by heavy metal (Cd and Pb) exposure in Leucaena leucocephala (Lam.) de Wit. Seedling growth was significantly enhanced with the augmentation of ZnONPs following Cd and Pb exposure. Heavy metal accumulations were recorded as 1253.1 mg Cd per kg DW and 1026.8 mg Pb per kg DW for the respective treatments. Results demonstrated that ZnONPs augmentation caused an increase in photosynthetic pigment and total soluble protein contents while a significant decrease in malondialdehyde (MDA-lipid peroxidation) content in leaves. Antioxidative enzymes such as superoxide dismutase (SOD), catalase (CAT) and peroxidase (POX) were, in turn, elevated in heavy metal-exposed leaves amended with ZnONPs. The ameliorating effect of ZnO nanoparticles on oxidative stress induced toxicity was also confirmed by the reduced MDA content and the elevated level of antioxidative enzyme activities in leaf tissues of L. leucocephala seedlings. Further, addition of ZnONPs in combination with Cd and Pb metals induced distinct genomic alterations such as presence of new DNA bands and/or absence of normal bands in the RAPD pattern of the exposed plants. This study uniquely suggests a potential role of zinc oxide nanoparticles in the remediation of heavy metal contaminated media.

Characterization of Vibrio cholerae O1 strains that trace the origin of Haitian-like genetic traits.

Vibrio cholerae O1 is the etiological agent of the severe diarrheal disease cholera. The bacterium has recently been causing outbreaks in Haiti with catastrophic effects. Numerous mutations have been reported in V. cholerae O1 strains associated with the Haitian outbreak. These mutations encompass among other the genes encoding virulence factors such as the pilin subunit of the toxin-co-regulated pilus (tcpA), cholera toxin B subunit (ctxB), repeat in toxins (rtxA), and other genes such as the quinolone resistance-determining region (QRDR) of gyrase A (gyrA), rstB of RS element along with the alteration in the number of repeat sequences at the promoter region of ctxAB. Given the numerous genetic changes in those Haitian isolates, we decided to investigate the possible origins of those variations in the Indian subcontinent. Thus, we determined the genetic traits among V. cholerae O1 strains in Delhi, India. A total of 175 strains isolated from cholera patients during 2004 to 2012 were analysed in the present study. Our results showed that all the tested strains carried Haitian type tcpA (tcpACIRS) and variant gyrA indicating their first appearance before 2004 in Delhi. The Haitian variant rtxA and ctxB7 were first detected in Delhi during 2004 and 2006, respectively. Interestingly, not a single strain with the combination of El Tor rtxA and ctxB7 was detected in this study. The Delhi strains carried four heptad repeats (TTTTGAT) in the CT promoter region whereas Haitian strains carried 5 such repeats. Delhi strains did not have any deletion mutations in the rstB like Haitian strains. Overall, our study demonstrates the sequential accumulation of Haitian-like genetic traits among V. cholerae O1 strains in Delhi at different time points prior to the Haitian cholera outbreak.

Single-use plaque removal efficacy of three power toothbrushes.

OBJECTIVES: To compare the safety and plaque removal efficacy of two oscillating/rotating/pulsating toothbrushes (Oral-B ProfessionalCare 7000 [PC 7000] and Oral-B 3D Excel [3DE]) and a high-frequency toothbrush (Sonicare Advance, Philips Oral Healthcare; SA) in a single-use, examiner-blind, three period crossover study. METHODS: After refraining from all oral hygiene procedures for 23-25 hours, subjects received an oral tissue examination and those with pre-brushing whole mouth mean plaque scores > or = 0.6 based on the Rustogi et al. Modified Navy Plaque Index were randomly assigned to treatment sequence. After brushing with the assigned toothbrush and a commercially available dentifrice for 2 minutes, oral tissues were then re-examined and post-brushing plaque scores recorded. Following a brief washout period between two additional visits, the above procedures were repeated with the two alternate toothbrushes. One examiner, blinded to the treatment sequence, performed all clinical measurements. RESULTS: A total of 79 subjects (28 males and 51 females) were enrolled and completed the study. Each toothbrush was found to be safe and significantly reduced plaque levels after a single brushing. The PC 7000 and 3DE were equally more effective in plaque removal than the SA, at all tooth areas, reducing plaque by 59.0%, 59.7% and 51.8%, respectively on whole mouth surfaces, and by 67.5%, 67.8% and 59.4%, respectively on approximal surfaces. CONCLUSIONS: The action of the oscillating/rotating/pulsating toothbrushes (Oral-B ProfessionalCare 7000 and Oral-B 3D Excel) was more effective in plaque removal than the high-frequency toothbrush (Sonicare Advance).

Plaque removal efficacy of two electric toothbrushes with different brush head designs.

OBJECTIVES: To compare the safety and plaque removal efficacy of two electric toothbrushes, one a rechargeable oscillating/pulsating toothbrush with a small round brush head (Oral-B ProfessionalCare 7000; PC 7000), the other a battery-operated toothbrush with a dual moving brush head (Crest SpinBrush Pro; SBP). METHODS: The study had a randomised, examiner-blind, two-arm crossover design. All subjects received an oral prophylaxis and used both toothbrushes on alternating days for a two-week practice period. After abstaining from all oral hygiene procedures for 23-25 hours, subjects received an oral tissue examination and those with pre-brushing whole mouth mean plaque scores > or = 0.60 measured by the Rustogi et al. Modified Navy Plaque Index were randomly assigned to treatment sequence. Subjects brushed with their assigned toothbrush for 2 minutes using a commercially available dentifrice. Oral tissues were then re-examined and post-brushing plaque scores recorded. After a brief washout period, the above procedures were repeated with the alternate toothbrush. One examiner, blinded to the treatment sequence, performed all clinical measurements. RESULTS: A total of 70 subjects (24 males and 46 females) were enrolled and completed the study. Each toothbrush was found to be safe and significantly reduced plaque levels after a single brushing. The PC 7000 was significantly more effective in plaque removal than the SBP at all tooth areas, reducing whole mouth plaque by 61% versus 58% and plaque from approximal surfaces by 69% versus 65%, respectively. CONCLUSIONS: The action of the oscillating/pulsating toothbrush with a small round brush head, Oral-B ProfessionalCare 7000, is more effective in plaque removal than the battery-operated Crest SpinBrush Pro toothbrush with a larger dual moving brush head.

Efficacy of a novel brush head in the comparison of two power toothbrushes on removal of plaque and naturally occurring extrinsic stain.

OBJECTIVES: To compare the safety and efficacy of an oscillating/pulsating power toothbrush (Oral-B ProfessionalCareTM 7000; PC 7000) fitted with either the standard FlexiSoft (PC 7000/EB17) brush head or the novel Pro Polisher (PC 7000/ EB-Prophy) and a high-frequency toothbrush (Philips Sonicare Elite; SE), in their relative ability to remove plaque and naturally occurring extrinsic dental stain over a six-week period. METHODS: This randomised, examiner-blind, parallel group study involved 90 healthy subjects from a general population. All subjects received a baseline plaque (Turesky et al. modified Quigley-Hein Plaque Index), stain (Lobene Stain Index) and tooth shade (VITAPAN Shade Guide) [Vita] assessment and an oral tissue examination. After training in the use of their randomly assigned device, subjects were instructed to brush twice daily for 2 min and returned after 3, 4 and 6 weeks of product use for a repeat of each clinical assessment. RESULTS: Reductions from baseline in mean plaque and extrinsic dental stain scores were significant at Weeks 3, 4 and 6 in all three treatment groups. By Week 6, mean reductions from baseline in whole mouth plaque scores were 32%, 27% and 14% in the PC 7000/EB-Prophy, PC 7000/EB17 and SE groups, respectivety. For the body of the tooth, mean reductions from baseline at Week 6 in total stain were 89%, 89% and 80%, respectively. Between treatment group comparisons consistently revealed that the PC 7000 toothbrush plus the EB-Prophy or EB17 brush head removed significantly more plaque and extrinsic stain (total stain, stain area and stain intensity) than the SE toothbrush at 3, 4 and 6 weeks. The EB-Prophy group had a greater proportion of subjects showing a 2-3+ change in Vita shade scores at each time point compared to the other two brushes; at Week 6 the proportions were 67% in the PC 7000/EB-Prophy group, 30% in the PC 7000/EB17 group, and 7% in the SE group. The PC 7000/EB17, PC 7000/EB-Prophy and the SE were found to be safe as used in the study. CONCLUSIONS: The oscillating/rotating/pulsating PC 7000 (fitted with either the standard EB17 or novel EB-Prophy brush head) is more effective at removal of plaque and naturally occurring extrinsic tooth stain, and the PC 7000 plus EB-Prophy in the improvement of tooth shade, than the high-frequency SE toothbrush.

A comparison of the plaque removal efficacy of two power toothbrushes: Oral-b Professional Care Series versus Sonicare Elite.

AIM: To compare the safety and plaque removal efficacy of an oscillating/ pulsating toothbrush (Professional Care Series, Oral-B Laboratories; PCS) and a high frequency toothbrush (Sonicare Elite, Philips Oral Healthcare; SE). METHODS: The study had a randomised, examiner-blind, crossover design. Sixty-one subjects aged 19-64 years were enrolled. After 23-25 hours of no oral hygiene, subjects received an oral tissue examination and those with pre-brushing whole mouth mean plaque scores > or = 0.60 measured by the Rustogi modified Navy Plaque Index were randomly assigned to treatment sequence. Subjects brushed with their assigned toothbrush for 2 minutes using a commercially available dentifrice. Oral tissues were then re-examined and post-brushing plaque scores recorded. After a brief washout period, the above procedures were repeated with the alternate toothbrush. One examiner blinded to the treatment sequence performed all clinical measurements. RESULTS: All 61 subjects completed the study. Both toothbrushes significantly reduced plaque levels after a single brushing (t-test, p < 0.0001). However, the PCS was significantly more effective than the SE in whole mouth plaque removal and in reducing plaque from marginal, buccal, lingual and approximal surfaces (ANOVA, p < 0.0001). Whole mouth plaque was reduced by 88% versus 61% and approximal plaque by 97% versus 73% for the PCS and SE toothbrushes, respectively. There was no evidence of hard or soft tissue trauma after a single-use of either toothbrush. CONCLUSION: Based on the findings of this single-use clinical evaluation, the action of the oscillating/ pulsating power toothbrush is more effective at plaque removal than a high frequency power toothbrush.

Antibody response and characteristics of antibodies in women immunized with three contraceptive vaccines inducing antibodies against human chorionic gonadotropin.

Data are presented on antibody titers generated in 88 women immunized with three formulations of antihuman chorionic gonadotropin (hCG) vaccine, namely, beta-hCG (formulation B); beta-hCG associated with alpha-subunit of ovine luteinizing hormone (LH) (formulation A) and beta-hCG + beta-ovine LH (formulation M), each linked to tetanus toxoid and cholera toxin chain B as carriers. Each formulation was tested at two dose levels (100 and 500 micrograms). All women without exception developed anti-hCG antibodies having hCG-binding capacity above 20 ng mL-1 (0.5 nM), a level considered to be the threshold for prevention of pregnancy. Formulations A and B gave relatively better immunogenic response in human subjects than M. In each case, the antibody response was reversible. The mean duration of response above 20 ng was 35 to 37 weeks for formulation A, 34 weeks for B, and 17 to 20 weeks for M. Antibodies induced by three formulations of the vaccine had high-affinity (Ka 10(9)-10(10)M-1) for binding with hCG. They were devoid of cross-reaction with human follicle-stimulating hormone and thyroid-stimulating hormone but, as expected, cross-reacted with human LH. Antibodies were competent to block the hCG induced ovarian hyperemia.

Enhancement of antigonadotropin response to the beta-subunit of ovine luteinizing hormone by carrier conjugation and combination with the beta-subunit of human chorionic gonadotropin.

Previous studies have demonstrated the control of fertility in monkeys on immunization with the beta subunit of ovine luteinizing hormone (beta-oLH) along with Freund's complete adjuvant (CFA). An eventual birth control vaccine would demand immunization without CFA. Beta-oLH linked to tetanus toxoid (TT) adsorbed on alum-induced antibody response in bonnet monkeys with detoxified sodium phthalyl derivative of Salmonella enteritidis lipopolysaccharide added only in the first injection. The antibodies reacted with both LH and human chorionic gonadotropin (hCG). A higher immune response was obtained with the use of a conjugate of beta-oLH and beta-hCG linked to a common carrier (TT) or with a mixture of beta-hCG/TT and beta-oLH/TT. In both cases, the antibodies were of high affinity with Ka ranging from 5 X 10(9) to 6 X 10(10) M-1. The antibodies were devoid of reactivity with human thyroid-stimulating hormone and human follicle-stimulating hormone. Monkeys with titers above 120 ng/ml hCG binding capacity (greater than 60 ng/ml in most cases) were protected from becoming pregnant during repeated mating with males of proven fertility in ovulatory cycles.

PIP: The potential for immunizing against gonadotropins without using Freund's complete adjuvant was explored in bonnet monkeys by using tetanus toxoid (TT) as carrier and Salmonella lipopolysaccharide (LPS) as adjuvant. Pure hCG beta subunit and or sheep LH beta subunit was coupled with TT by employing N-succinimidyl-pyridyl-dithio-propionate reagent. Fertile female bonnet monkeys were injected with 50 mcg gonadotropin equivalent monthly. 1 mg sodium phthalyl derivative of LPS was added to the 1st injection. Animals with low titers were also given a booster on Day 145 with Leiras adjuvant. 3 of 5 monkeys immunized with ovine beta-LH subunit bonded to TT had strong responses, and 2 produced high antibody titers after a booster with Leiras adjuvant. A 2nd group of 3 monkeys treated with both ovine beta LH and beta hCG conjugated to a common carrier, TT, showed high titers, between 750 and 1300 ng/ml, which were sustained for nearly a year. Scathard analysis indicated that the combined antigens raised antibodies of high affinity, with Ka values ranging from 5 x 109 to 6 x 1010 per M. There were no cross reactions with either human FSH or TSH. 2 of the monkeys immunized against the combined antigens remained infertile for 6 and 3 cycles respectively, or until their antibody titers fell to 35 and 5 Monkeys in the 1st group also were infertile for several cycles before their antibody levels fell below 120 ng/ml against hCG.

Survival of animals injected with Pr-beta-HCG-TT.

PIP: 115 male Swiss strain mice were injected with Pr-B-HCG-TT vaccine and observed for 1 month. In another group of mice, a 2nd injection was given after 1 month and observation continued 8 weeks. Each injection was equivalent to 32 human doses. 6 of the 84 given 1 injection died; 1 of 31 given 2 injections died. A 10% mortality had been observed in the colony of untreated mice for this length of time. Autopsies showed no g ross or microscopic abnormalities. Anti-HCG antibodies were demonstrated in the animals' sera. 6 rabbits were each given 1-3 doses of the vaccine equivalent to 6-10 human doses. No deaths occurred up to 20 months of observation. 19 monkeys were each given 1-4 injections, each equivalent to 1 human dose, together with Freund's complete adjuvant or alum plus SO. At 2-16 months postinjections, survival was 100%. All animals tolerated the vaccine satisfactorily. Results show lack of toxicity of the vaccine.^ieng

Metabolic, endocrine and organ functions in monkeys immunized with Pr-beta-HCG-TT vaccine.

PIP: The vaccine Pr-beta-HCG-TT was injected into 12 rhesus monkeys; 10 monkeys were used as controls. At 3-13 months after immunization, blood and urine samples were examined. Hemoglobulin and packed call volumes were unaltered. Total leukocyte counts were similar but the percentage of neutrophils was reduced in immunized animals. Serum bilirubin, alkaline phosphastase, glutamic oxaloacetic, and glutamic pyruvic transaminases, true and pseudocholinesterases, lactic acid dehydrogenase and its isozymes, blood glucose, cholesterol, free fatty acids, serum proteins, plasma cortisol, serum creatinine, and blood urea were also measured. Physical, chemical, and microscopic examinations of the urine were done. Except for insignificant variation in serum transaminases all tests were comparable in control and vaccinated animals. Findings demonstrate that antibodies generated by the vaccine do not interfere with normal body functions.^ieng

Processing of the preparations of beta-subunit of human chorionic gonadotropin for minimization of cross-reactivity with human luteinizing hormone.

PIP: The immunological reactivity of various components of beta-human cho rionic gonadotropin (beta-HCG) preparations with antisera developed against HCG and human luteinizing hormone (HLH) was assessed. Anti-beta-HCG reactivity was primarily located in 2 or 3 adjacent fractions. Anti-HLH reactivity was partly found in a fraction co-migrating with 1 of the anti-beta-HCG fractions, and also in a fraction migrating more slowly than the anti-beta-HCG fractions. Preparations with no, or minimal, cross-reactivity with anti-HLH were obtained upon absorption of beta-HCG with anti-ovine LH.^ieng

Clinical profile and toxicology studies on four women immunized with Pr-beta-HCG-TT.

PIP: Clinical profile and toxicology studies on 4 women immunized with processed beta human chorionic gonadotropin conjugated to tetanus toxoid (Pr-beta-HCG-TT) are presented. The women responded to active isoimmunization by production of anti-hcg and anti-TT antibodies. The women were followed for 1 year with monthly clinical examinations including laboratory hepatic function tests, renal function tests, metabolic studies, endocrinal studies, and hematological studies. No abnormality was seen, indicating that active isoimmunization with Pr-beta-HCG-TT has no adverse or undesirable side effects in women of childbearing age.^ieng

Phase I clinical trials with three formulations of anti-human chorionic gonadotropin vaccine.

Comparative phase I clinical trials were carried out in 5 centres with three formulations of beta-hCG-based vaccines inducing antibodies against human chorionic gonadotropin. The objectives of these trials were to determine their relative immunogenicity, duration, reversibility and safety. A total of 116 tubal ligated women volunteers were enrolled in the study and 101 subjects were followed-up for one year or more until the antibody titres declined to near zero levels. Every woman receiving the vaccine produced anti-hCG and anti-tetanus antibodies. Clinical examination carried out at intervals of 4-6 weeks revealed no abnormality. No serious side effects or adverse reactions were reported with any of the formulations during primary immunization with three monthly injections of the vaccine. Eleven women, however, demonstrated hypersensitivity to test dose at the time of the booster injection. The reaction was to tetanus toxoid; gonadotropin subunits conjugated to another carrier did not evoke any such reaction. Progesterone in bleeds taken at midluteal phase, as well as complete progesterone and estradiol done in two immunized women, indicated normal ovulatory cycles. Immunization with these formulations had no significant effect on haematological, clinical chemistry and other metabolic parameters. In summary, the results indicate that none of the three beta-hCG-based contraceptive vaccines had any adverse effects clinically, on endocrine status and metabolic parameters. Formulations A and B induced comparatively higher anti-hCG titres than M. Thus, further work can be undertaken to study the efficacy of these vaccines in humans for preventing pregnancy.