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PubMed2001

SB-277011 GlaxoSmithKline.

It is presumed that GlaxoSmithKline has taken over from SmithKline Beecham in investigating the highly selective dopamine D3 antagonist SB-277011 and its analogs for the potential treatment of schizophrenia [284490] following the merger of Glaxo Wellcome and SmithKline Beecham in December 2000 [394715]. In June 2000, it was reported that novel 2,3,4,5-tetrahydro-1H-benzazepines and 2,3-dihydro-1H-isoindoles, including SB-277011, had shown high affinity and selectivity for the dopamine D3 receptor. All compounds were suggested to have further potential roles in the treatment of drug abuse and psychosis [372205]. In November 2000, data presented at the 30th Neuroscience meeting in New Orleans, LA, demonstrated that D3 receptor blockade with SB-277011 specifically altered neurochemical effects in the nucleus accumbens without the non-selective effects, such as catalepsy, seen with some other antagonists [390460].

Animals↗
PubMed2001

Rotavirus vaccine AVANT/GlaxoSmithKline.

AVANT Immunotherapeutics (formerly Virus Research Institute) and GlaxoSmithKline are developing a live oral rotavirus vaccine with potential to elicit a broadly-protective immune response against the most prevalent strains of rotavirus. Following successful completion of a phase II clinical efficacy trial in June 1999, SmithKline Beecham (now GlaxoSmithKline) assumed responsibility for all subsequent clinical and other development activities [328635], [333677]. Following a licensing agreement, the vaccine was refined and renamed RIX-4414 [371713]. In May 2000, AVANT reported the results of a second-year surveillance extension of the phase II study. The results suggested that AVANT's two-dose oral rotavirus vaccine should be helpful in preventing rotavirus gastroenteritis (RGE) disease in young children for at least two years following administration [365202]. In March 2000, SmithKline Beecham reported that it had initiated phase I/II bridging studies in Europe and the company planned to start phase III safety and efficacy studies in 2001 after review with the health authorities [358963]. In October 2000, Dain Rauscher Wessels stated that an estimated market penetration of 30 to 40% suggested potential sales in excess of US $500 million pa. As a result, the analysts also estimated that incremental revenues to AVANT could be over US $50 million pa [411122].

Administration, Oral↗
PubMed2001

Repifermin. Human Genome Sciences/GlaxoSmithKline.

Human Genome Sciences (HGS) and GlaxoSmithKline (formerly SmithKline Beecham) are developing topical and injectable formulations of repifermin, keratinocyte growth factor-2 (KGF-2), also known as fibroblast growth factor-10 (FGF-10) for the potential treatment of wound care, oral and intestinal mucositis, and inflammatory bowel diseases [385959,396786]. A phase IIb trial of the topical formulation in chronic venous ulcers is ongoing, as well as phase II trials for the systemic, injectable formulation in ulcerative colitis and in the prevention of mucositis after chemotherapy with bone marrow transplantation [352908,368013, 385959,404294]. In May 2001, UBS Warburg predicted that HGS would receive approval of repifermin for the treatment of venous ulcers by yearend 2004, mucositis in 2005, and ulcerative colitis in the second half of 2004 [412015]. In October 2000, SmithKline Beecham exercised an option to codevelop repifermin for phase III trials and beyond [385959,399183]. In May 2001, UBS Warburg valued repifermin's worldwide market at 2 billion dollars for treating venous ulcers and predicted sales of 33 million dollars in 2004 and 118 million dollars in 2005 for this indication. In addition, the analysts regarded repifermin as having potential in the treatment of diabetic foot ulcers and pressure ulcers (a market valued at over 1.8 billion dollars) and estimated that the drug might earn another 103.5 million dollars for these indications in 2005. Furthermore, the analysts predicted sales of 6.8 million dollars for repifermin's mucositis indication and, for ulcerative colitis, sales of 27.3 million dollars in 2004 and 54.8 million dollars in 2005. Overall, the analysts estimated that repifermin represented a 3.5 billion dollars market opportunity for HGS/ GlaxoSmthKline and that commercialization of the drug might earn more than 61 million dollars by 2004 [412015].

Journal Article↗
PubMed2001

Technology evaluation: C242-DM1, ImmunoGen Inc.

C242-DM1 is a tumor-activated immunotoxin under development by GlaxoSmithKline plc (formerly SmithKline Beecham plc), under licence from ImmunoGen Inc, as a potential treatment for colon tumor. It consists of a colon cancer-specific humanized antibody, C242, conjugated to the maytansine derivative DM1. In preclinical studies, C242-DM1 caused complete tumor regression in animal models of both human pancreatic and non-small cell lung cancer (NSCLC) at non-toxic doses. C242-DM1 has also been evaluated in an immunoconjugate combination with J-591 (Cornell University). The J591-DM1 immunoconjugate demonstrated effective, antigen-specific delivery of a highly cytotoxic drug to PSMA-positive Pca cells in vitro and in vivo with low systemic toxicity. Results from studies in monkeys showed that C242-DM1 had no significant toxicity or side effects, when administered at doses higher than those that were previously shown to completely eradicate human colon tumors in mice [271420]. ImmunoGen acquired the right to evaluate, and an option to license, technology related to maytansines from Takeda. In February 1999, ImmunoGen and SmithKline Beecham signed a US $45 million development and commercialization agreement for C242-DM1 [313493]. In August 1997, Immunogen received an SBIR grant to advance development of huC242-DM1 [258356]. EP-00425235, held by ImmunoGen, covers conjugated forms of ansamitocin (maytansine) derivatives. Takeda holds several patents for the production of ansamitocin and its analogs, the first one being JP-53124692.

Animals↗
PubMed1996

Clinical experience of a tricomponent acellular pertussis vaccine combined with diphtheria and tetanus toxoids for primary vaccination in 22,505 infants.

OBJECTIVES: To assess the safety and tolerability of 12 lots of SmithKline Beecham Biologicals' diphtheria-tetanus-tricomponent acellular pertussis vaccine (DTaP) in a large cohort of 22,000 vaccinees, with detailed analyses of reactivity, immunogenicity, and immune response to pertussis toxin in subsets. METHODS: In a prospective, double-blind, multicenter trial in Germany, 22,505 healthy infants received three vaccinations of DTaP at age 3, 4, and 5 months. Serious adverse events were followed for 1 month after each vaccination, and neurologic events for 1 year or longer. Serum IgG antibodies were assayed before vaccination and 1 month after vaccination. RESULTS: After 67,000 doses, 153 serious adverse events (0.23%) were reported, 8 considered possibly related, and 5 related to vaccination, including 1 hypotonic-hyporesponsive episode. Incidence rates of sudden infant death syndrome (7; 0.01%) or acute neurologic events (20; 0.030%) were no higher than expected and not considered to be related to vaccination. Redness and swelling of 20 mm or greater occurred after 44 (0.6%) and 40 (0.6%) of the 7270 doses, respectively, and high fever (> 39.5 degrees C) in 6 (0.08%) subjects within 48 hours of vaccination. In the immunogenicity analysis of 580 infants, 98% responded to pertussis toxin, 96% to filamentous hemagglutinin, and 98% to pertactin. In an additional 5712 infants, the response rate to pertussis toxin was 99%. CONCLUSIONS: In a large cohort of 22,505 infants vaccinated, SmithKline Beecham Biologicals' tricomponent DTaP vaccine was shown to be safe, well-tolerated, and immunogenic for all component antigens.

Diphtheria-Tetanus-Pertussis Vaccine↗
PubMed2000

Ropinirole versus bromocriptine for levodopa-induced complications in Parkinson's disease.

BACKGROUND: Long-term levodopa therapy for Parkinson's disease is complicated by the development of motor fluctuations and abnormal involuntary movements. One approach is to add a dopamine agonist at this stage of the disease to reduce the time the patient spends immobile or off and to reduce the dose of levodopa in the hope of reducing such problems in the future. OBJECTIVES: To compare the efficacy and safety of adjuvant ropinirole therapy with bromocriptine in patients with Parkinson's disease already established on levodopa therapy and suffering from motor complications. SEARCH STRATEGY: Electronic searches of MEDLINE, EMBASE and the Cochrane Controlled Trials Register. Handsearching of the neurology literature as part of the Cochrane Movement Disorders Group's strategy. Examination of the reference lists of identified studies and other reviews. Contact with SmithKline Beecham. SELECTION CRITERIA: Randomised controlled trials of ropinirole versus bromocriptine in patients with a clinical diagnosis of idiopathic Parkinson's disease and long-term complications of levodopa therapy. DATA COLLECTION AND ANALYSIS: Data was abstracted independently by the authors and differences settled by discussion. The outcome measures used included Parkinson's disease rating scales, levodopa dosage, 'off' time measurements and the frequency of withdrawals and adverse events. MAIN RESULTS: No significant differences between ropinirole and bromocriptine were found in off time reduction, dyskinesia as an adverse event, motor impairment and disability, or levodopa dose reduction. Withdrawal rates and adverse event frequency were similar with the two agents apart from significantly less nausea with ropinirole (odds ratio 0.50; 0.29, 0. 84 95% CI; p =0.01). REVIEWER'S CONCLUSIONS: Ropinirole is at least as good as bromocriptine in patients with Parkinson's disease with motor complications in terms of improving off time and reducing levodopa dose, without increasing adverse events including dyskinesia. However, these comparitor studies may have been underpowered to detect clinically meaningful differences between the agonists. Further, much larger, phase IV studies are required to examine the efficacy, effectiveness, and safety of all of the dopamine agonists as adjuvant therapy in Parkinson's disease.

Antiparkinson Agents↗
PubMed2000

Ropinirole for levodopa-induced complications in Parkinson's disease.

BACKGROUND: Long-term levodopa therapy for Parkinson's disease is complicated by the development of motor fluctuations and abnormal involuntary movements. One approach is to add a dopamine agonist at this stage of the disease to reduce the time the patient spends immobile or off and to reduce the dose of levodopa in the hope of reducing such problems in the future. OBJECTIVES: To compare the efficacy and safety of adjuvant ropinirole therapy versus placebo in patients with Parkinson's disease already established on levodopa therapy and suffering from motor complications. SEARCH STRATEGY: Electronic searches of MEDLINE, EMBASE and the Cochrane Controlled Trials Register. Handsearching of the neurology literature as part of the Cochrane Movement Disorders Group's strategy. Examination of the reference lists of identified studies and other reviews. Contact with SmithKline Beecham. SELECTION CRITERIA: Randomised controlled trials of ropinirole versus placebo in patients with a clinical diagnosis of idiopathic Parkinson's disease and long-term complications of levodopa therapy. DATA COLLECTION AND ANALYSIS: Data was abstracted independently by the authors and differences settled by discussion. The outcome measures used included Parkinson's disease rating scales, levodopa dosage, 'off' time measurements and the frequency of withdrawals and adverse events. MAIN RESULTS: Three double-blind, parallel group, randomised, controlled trials have been conducted on 263 patients. The two phase II studies were relatively small, were conducted over the short term (12 weeks), and used relatively low doses of ropinirole. The other phase III study was medium term (26 weeks) and used ropinirole doses in line with the current UK licensed maximum. Additional data from the manufacturer showed that the difference in the reduction in off time was non-significantly greater with ropinirole than placebo (weighted mean difference [WMD] 0.19 hours; -0.63, 1.00 95% CI). As an adverse event, dyskinesia was significantly increased in those who received ropinirole (odds ratio [OR] 2.59; 1.35, 4.96 95% CI; p < 0.004). Measurements of motor impairments and disability were poor in these studies with incomplete information available. Levodopa dose could be reduced in two studies with a significantly larger reduction on ropinirole than on placebo (WMD 136.5mg/d; 74.5, 198.6 95% CI; p =0.00002). No significant differences in the frequency of adverse event reports were noted between ropinirole and placebo apart from the increase in dyskinesia with ropinirole. There was a trend towards fewer withdrawals from ropinirole but this did not reach statistical significance. REVIEWER'S CONCLUSIONS: Ropinirole therapy can reduce levodopa dose but at the expense of increased dyskinetic adverse events. No significant effect on off time reduction was found but this may have been due to under-powered trials and the low doses of ropinirole used in the phase II studies. Inadequate data on motor impairments and disability was collected to assess these outcomes. These conclusions apply to short and medium term treatment, up to 26 weeks. Further longer term trials are required, with measurements of effectiveness, and also studies to compare the newer with the older dopamine agonists.

Antiparkinson Agents↗
PubMed1996

A controlled trial of two acellular vaccines and one whole-cell vaccine against pertussis. Progetto Pertosse Working Group.

BACKGROUND: Concern about both safety and efficacy has made the use of whole-cell pertussis vaccines controversial. In some European countries, including Italy, the rate of vaccination against pertussis is low. METHODS: We conducted a double-blind trial in Italy in which infants were randomly assigned to vaccination at two, four, and six months of age with an acellular pertussis vaccine together with diphtheria and tetanus toxoids (DTP); a DTP vaccine containing whole-cell pertussis (manufactured by Connaught Laboratories); or diphtheria and tetanus toxoids without pertussis (DT). The acellular DTP vaccine was either one containing filamentous hemagglutinin, pertactin, and pertussis toxin inactivated with formalin and glutaraldehyde (SmithKline Beecham) or one with filamentous hemagglutinin, pertactin, and genetically detoxified pertussis toxin (Chiron Biocine). Pertussis was defined as 21 days or more of paroxysmal cough, with infection confirmed by culture or serologic testing. RESULTS: The efficacy of each vaccine, given in three doses, against pertussis was determined for 14,751 children over an average of 17 months, with cases included in the analysis if cough began 30 days or more after the completion of immunization. For both of the acellular DTP vaccines, the efficacy was 84 percent (95 percent confidence intervals, 76 to 89 percent for Biocine DTP and 76 to 90 percent for SmithKline DTP), whereas the efficacy of the whole-cell DTP vaccine was only 36 percent (95 percent confidence interval, 14 to 52 percent). The antibody responses were greater to the acellular vaccines than to the whole-cell vaccine. Local and systemic adverse events were significantly more frequent after the administration of the whole-cell vaccine. For the acellular vaccines, the frequency of adverse events was similar to that in the control (DT) group. CONCLUSIONS: The two acellular DTP vaccines we studied were safe, immunogenic, and efficacious against pertussis, whereas the efficacy of the whole-cell DTP vaccine was unexpectedly low.

Antibodies, Bacterial↗
PubMed1998

Allergic reactions after systemic administration of glucocorticosteroid therapy.

OBJECTIVE: To describe patients who developed allergic reactions (ie, erythema on their face and body, itching, flushing, drop in blood pressure, respiratory distress, and cold sweats) immediately after intravenous injection of prednisolone hemisuccinate (SoluDecortin H, E Merck, Darmstadt, Germany). SETTING: Academic medical center. RESULTS: Three of 4 patients had a positive reaction to an intracutaneous test with prednisolone hemisuccinate (SoluDecortin H) but no reaction to the additive sodium succinate. The results of the prick test were negative for all patients. Although no specific IgE antibodies were detected in the serum of these patients, allergic reaction was noted in 3 cases, since standardized techniques to detect antibodies in the serum for hydrocortisone acetate (ie, prednisolone) are lacking. One female patient had a cross-reaction to prednisolone and dexamethasone (Fortecortin, E Merck, Darmstadt, Germany). A renewed application of prednisolone hemisuccinate was well tolerated by all patients when histamine1 and histamine2 receptors were blocked with the use of cimetidine hydrochloride, 200 mg twice per day (1-0-1 ampules, Tagamet, SmithKline Beecham Pharmaceuticals, Philadelphia, Pa) and dimethindene maleate, 4 mg twice per day (1-0-1 ampules, Fenistil, Novartis, Munich, Germany); calcium was given for membrane stabilization. CONCLUSIONS: Allergic reactions to glucocorticoid therapy are only occasionally mentioned in the literature. These reactions appear more often when glucocorticoids are applied topically and may lead to dangerous complications in patients if administered systemically. Therefore, when allergic reactions result from glucocorticoid therapy, (immediate-type reactions should be suspect), consider corticosteroid allergy as a differential diagnosis.

Adult↗
PubMed1997

Cell-mediated and antibody responses to Bordetella pertussis antigens in children vaccinated with acellular or whole-cell pertussis vaccines. The Progetto Pertosse-CMI Working Group.

OBJECTIVE: To examine induction and persistence of cell-mediated immunity (CMI) and antibody responses to Bordetella pertussis antigens in infants receiving antipertussis vaccines. DESIGN AND SETTING: A randomized, blinded study of 142 children receiving acellular pertussis vaccines combined with diphtheria-tetanus toxoids (DTaP) (DTaP manufactured by SmithKline Beecham [DTaP-SB], Rixensart, Belgium, and DTaP manufactured by Chiron Biocin [DTaP-CB], Siena, Italy), or a whole-cell pertussis vaccine (DTwP) (Connaught Laboratories Inc, Swiftwater, Pa), or a diphtheria-tetanus (DT) (Chiron Biocine) only vaccine. Three doses of each vaccine were given at 2, 4, and 6 months of age, and CMI and antibody responses were evaluated before and at 1 and 14 months after vaccination. METHODS AND MAIN OUTCOME MEASURES: Cell-mediated immunity was assessed by proliferation of peripheral blood mononuclear cells stimulated in vitro by B pertussis antigens (pertussis toxin, filamentous hemagglutinin, and pertactin). Antibody titers against pertussis toxin, filamentous hemagglutinin, and pertactin were determined by a standardized enzyme-linked immunosorbent assay. RESULTS: A CMI-positive response to at least 1 B pertussis antigen at 1 or both postvaccination assays was detected in 46%, 55%, and 83% of DTwP, DTaP-SB, and DTaP-CB vaccine recipients, respectively. Frequency of CMI response to individual antigens ranged from less than 4.9% against pertussis toxin in DTwP recipients to 52% against pertactin in DTaP-CB recipients. The postvaccination responses measured at 14 months equalled, or had increased frequency or intensity, that of the 1-month postvaccination responses. Elevated antibody titers against the 3 antigens were present in all DTaP recipients 1 month after vaccination and were higher in CMI-positive children than in CMI-negative children. They fell, however, to low, if not negligible, levels 14 months after vaccination. CONCLUSIONS: Acellular pertussis vaccines were better inducers of CMI response than the whole-cell vaccine, particularly against pertussis toxin. Once acquired, CMI persisted, in contrast with the rapid antibody decline. Thus, CMI responses could be a useful adjunct to serology in the evaluation of pertussis vaccine immunogenicity and a better correlate of long-term immunity to B pertussis than antibody titers.

Bordetella pertussis↗
PubMed2005

Comparing effects of methylphenidate, sertraline and placebo on neuropsychiatric sequelae in patients with traumatic brain injury.

BACKGROUND: This study aimed to investigate the effects of methylphenidate and sertraline compared with placebo on various neuropsychiatric sequelae associated with traumatic brain injury (TBI). METHODS: This was a 4 week, double-blind, parallel-group trial. Thirty patients with mild to moderate degrees of TBI were randomly allocated to one of three treatment groups (n = 10 in each group) with matching age, gender and education, i.e. methylphenidate (starting at 5 mg/day and increasing to 20 mg/day in a week), sertraline (starting at 25 mg/day and increasing to 100 mg/day in a week) or placebo. At the baseline and at the 4 week endpoint, the following assessments were administered: subjective (Beck Depression Inventory) and objective (Hamilton Depression Rating Scale) measures of depression; Rivermead Postconcussion Symptoms Questionnaire for postconcussional symptoms; SmithKline Beecham Quality of Life Scale for quality of life; seven performance tests (Critical Flicker Fusion, Choice Reaction Time, Continuous Tracking, Mental Arithmetic, Short-Term memory, Digit Symbol Substitution and Mini-Mental State Examination); subjective measures of sleep (Leeds Sleep Evaluation Questionnaire) and daytime sleepiness (Epworth Sleepiness Scale). All adverse events during the study period were recorded and their relationships to the drugs were assessed. RESULTS: Neuropsychiatric sequelae seemed to take a natural recovery course in patients with traumatic brain injury. Methylphenidate had significant effects on depressive symptoms compared with the placebo, without hindering the natural recovery process of cognitive function. Although sertraline also had significant effects on depressive symptoms compared with the placebo, it did not improve many tests on cognitive performances. Daytime sleepiness was reduced by methylphenidate, while it was not by sertraline. CONCLUSIONS: Methylphenidate and sertraline had similar effects on depressive symptoms. However, methylphenidate seemed to be more beneficial in improving cognitive function and maintaining daytime alertness. Methylphenidate also offered a better tolerability than sertraline.

Adult↗
PubMed1998

Urine drug screening results from volunteers in phase I clinical pharmacology studies: are we being misled?

The general intent of phase I clinical pharmacology studies is to demonstrate the safety and tolerability of investigational new drugs in healthy human volunteers. There is emerging evidence that people who volunteer for these studies are not always truthful with investigators during the screening process. All healthy volunteers who participate in studies at the SmithKline Beecham Clinical Pharmacology Unit in Philadelphia, Pennsylvania, are required to submit to urine drug testing. During 11 months of 1996, a total of 1,469 urine samples were collected and tested for eight different drugs or classes of drugs of abuse. The urine samples collected during the first five months of 1996 were all analyzed using EMIT (Syva Corporation) and interpreted according to the guidelines established by the National Institutes of Drug Abuse (NIDA). Of 534 samples, 12 (2.2%) were reported as positive. During the last 6 months of 1996, a new methodology using a fluorescence polarization immunoassay (FPIA) was used. This assay had lower limits of quantification than EMIT, and more stringent interpretation guidelines than those of the NIDA were used. Of 935 samples analyzed by FPIA, 89 (9.5%) were positive. Of the 89 positive test results, 59 were below the cut-offs specified by the NIDA guidelines and would have been reported as negative. Interpretation of urine drug screen results according to the NIDA guidelines is not acceptable for clinical pharmacology investigations.

Clinical Trials, Phase I as Topic↗
PubMed1994

Inactivated hepatitis A vaccine: reactogenicity, immunogenicity, and long-term antibody persistence.

This trial evaluated the reactogenicity, kinetics of antibody induction, and long-term immunogenicity of a 720 enzyme-linked immunosorbent assay units (EL.U.) antigen dose of an inactivated hepatitis A vaccine (Havrix, SmithKline Beecham Biologicals, Rixensart, Belgium). One hundred six healthy adult volunteers were enrolled to receive vaccine intramuscularly according to a 0, 1, and 6-month schedule. The vaccine was well tolerated. The most frequently reported local symptom was soreness, observed following 37.1% of all doses. Headache was the most frequently reported general symptom observed following 12.9% of documented vaccine doses. The administration of one vaccine dose induced seropositivity (anti-hepatitis A virus [HAV] > or = 20 mIU/ml) in 91% of all vaccinees 1 month later. The second vaccine dose resulted in seropositivity of the remaining vaccinees at month 2. All subjects remained seropositive for HAV antibodies at month 6, at which time the booster vaccine dose was given. At month 7, all vaccinees had anti-HAV titres > 200 mIU/ml. Serological results obtained at months 12, 18, 24, and 36 showed that antibodies against HAV induced by the vaccine booster dose persist for at least 30 months following its administration. All 49 subjects followed up until month 36 had antibody titres > or = 20 mIU/ml. The geometric mean titre (GMT) decreased by 60% from month 7 to month 12; between month 12 and 36, the GMT decreased by approximately 14% per period of 12 months. According to the vaccine-induced antibody kinetics and the magnitude of antibody level decrease over time, the predicted duration of antibody persistence is estimated to be at least 20 years.

Adolescent↗
PubMed1996

Analysis of the antibody response in humans with a new inactivated hepatitis A vaccine.

Sera from subjects vaccinated with the Pasteur Merieux (PM) inactivated hepatitis A vaccine (AVAXIM) have been analysed in order: (1) to assess comparability of the results provided by a modified radio-immunoassay (mRIA) in the different laboratories involved in testings of sera during clinical trials and by enzyme-linked immunoabsorbent assay (ELISA) used during development of other inactivated hepatitis A vaccines; (2) to describe the IgM responses elicited by this vaccine compared with one control vaccine [HAVRIX, 720 ELISA antigens units; Smithkline Beecham (SB), Rixensart, Belgium]; (3) to provide comparative data between the PM vaccine and the SB vaccine on neutralizing activities of vaccine-induced antibodies. Vaccine-induced antibody titres evaluated by a mRIA in different laboratories correlated well and validated the comparability of the results obtained in various vaccine trials conducted by PM. Geometric mean titres (GMTs) expressed as milli-international units (mlU/ml) were higher with ELISA especially after the first dose, but seroconversion rates were similar and a good correlation was found between the two assays. IgM vaccine-induced antibodies were detectable in nearly all vaccinated subjects from week 2 after vaccination, with a peak titre between weeks 2 and 4 after the first dose. Comparison of GMTs by the Student Fisher t-test was statistically significant (P < 0.05) only at week 2 with higher titres in PM vaccinees. Neutralizing antibodies were detected after vaccination with the PM inactivated hepatitis A vaccine. The titres gradually increased between the second week after the first dose and the booster dose (week 24). A strong booster effect of the second dose on neutralizing titres was observed. Seroneutralizing titres induced at week 2 in subjects vaccinated with the PM inactivated hepatitis A vaccine were statistically significantly higher (P < 0.05) from those induced by the SB vaccine.

Adolescent↗
PubMed1996

Immunogenicity and reactogenicity of a combined DTPw-hepatitis B vaccine in Lithuanian infants.

UNLABELLED: A total of 120 healthy Lithuanian infants were enrolled in a double-blind, randomized trial to receive one of two lots of SmithKline Beecham Biologicals' combined diphtheria, tetanus, whole cell Bordatella pertussis hepatitis B (DTPw-HB) candidate vaccine administered according to a 0, 1.5, 3-month, primary immunization schedule (beginning at approximately 3-4 months of age). The immunogenicity (based on the antibody responses elicited by each of the four vaccine components) and the reactogenicity (based on documented solicited and unsolicited symptoms) of this candidate vaccine were evaluated. Of the 120 subjects enrolled, 100 were included in the analysis of immunogenicity. One month after the third vaccine dose, all infants had protective levels of antibodies against HBsAg and tetanus toxoid and all, except one infant, had protective levels of antibodies against the diphtheria toxoid (98.9%). At this time all subjects had responded to the B. pertussis component with antibody titres greater than or equal to the assay cut-off. Data collected for all enrolled infants were included in the analysis of reactogenicity. Most local symptoms were mild and occurred within the first 48 h following vaccination. Redness was the most frequently reported local symptom and irritability was the most frequently reported general symptom. One vaccine-related serious adverse event was reported (fever, diarrhea, vomiting and irritability). This event resolved within 20 h without any complications. CONCLUSION: The combined DTPw-HB vaccine was safe, well-tolerated and immunogenic for all four antigens when administered to a population of healthy infants beginning at 3-4 months of age.

Antibody Formation↗
PubMed1992

Effects of an anthelmintic treatment programme on sheep productivity in the Middle Atlas, Morocco.

This study evaluated the production advantages of the strategic anthelmintic treatment of both lambs and ewes in an area endemic for gastro-intestinal nematodes, lungworms and liver flukes. The liver fluke infections were generally chronic. The lambs were treated with albendazole (SmithKline Beecham), fenbendazole (Hoechst Roussel) or a vitamin supplement and their weight gains were followed over the next 7 months. The control group, which received a vitamin supplement only, gained 6.67 kg from July to January. The group that received fenbendazole, an anthelmintic with no activity against liver flukes, gained 10.42 kg over the study period. The third group which received albendazole, an anthelmintic with efficacy against liver flukes, gained 13.07 kg over the same period. Lamb deaths apparently due to liver flukes were 12, 4, and zero for the control, fenbendazole and albendazole groups, respectively. Similar advantages were observed in the ewes. Deaths were 16, 8, and zero in the control, fenbendazole and albendazole groups, respectively. The lambing rate in the control group was significantly lower than that in either of the 2 treated groups. The number of services per conception was significantly lower in the albendazole treated group than that in either of the other groups. These studies demonstrated the advantages of anthelmintic treatment in sheep in a helminth endemic area. While removing gastro-intestinal nematodes and lungworms improved production, the additional removal of liver flukes enhanced production gains as well as reducing deaths.

Albendazole↗
PubMedDate not supplied

Comparative study of reactogenicity and immunogenicity of new and established measles, mumps and rubella vaccines in healthy children.

Concerns about the association of aseptic meningitis with measles-mumps-rubella (MMR) vaccines containing the Urabe Am 9 strain and the increasing worldwide demand for MMR vaccines, prompted the development of a new mumps vaccine strain (RIT 4385) by SmithKline Beecham Biologicals (SB) as part of a trivalent live attenuated MMR vaccine. The present study assessed the immunogenicity and reactogenicity of two lots of 'Priorix' with a widely used and established vaccine M-M-R II (Merck & Co. Inc.) as comparator vaccine. 255 healthy children, 12 to 24 months of age, were enrolled in a single-blind study and randomly allocated to receive a single dose of one of two lots of "Priorix" or M-M-R II vaccine. Vaccinees were followed up for six weeks post-vaccination for solicited and unsolicited symptoms. Immunogenicity was determined in pre- and 60 days post-vaccination sera using commercial immunoassays for measles, mumps and rubella antibodies. There were no significant differences in immune responses between groups for any of the three vaccine components. In initially seronegative subjects, the respective post-vaccination seroconversion rates for 'Priorix' lots 1 and 2, and M-M-R II were 100, 100 and 97.6% for measles antibodies, 91.7, 95.1 and 94% for mumps antibodies and 100, 100 and 100% for rubella antibodies, respectively. GMTs for the three groups were 3,076, 3,641 and 3,173 mIU/ml for measles antibodies, 934, 900 and 1,043 U/ml for mumps antibodies, and 86.4, 87.5 and 97.1 IU/ml for rubella antibodies, respectively. The incidence of local symptoms was significantly lower for both 'Priorix' lots (17.6 and 15.3% for lots 1 and 2, respectively) than for M-M-R II (37.6%). Fever > or = 38.1 degrees C during the six-week observation period occurred in approximately 25% of all subjects in all groups with no differences between the groups. No parotid/salivary gland swelling or signs of suspected meningism were reported, and there were no serious adverse events related to vaccination. The new MMR vaccine 'Priorix' containing the new RIT 4385 mumps strain was safe and had a significantly improved local tolerability profile over the comparator vaccine, M-M-R II, while eliciting an at least equivalent immune response.

Antibodies, Viral↗
PubMed1995

Plasma concentrations after high-dose (45 mg.kg-1) rectal acetaminophen in children.

Although the recommended dose of rectal acetaminophen (25-30 mg.kg-1) is twice that for oral administration (10-15 mg.kg-1), the literature justifies the use of a higher dose when acetaminophen is administered via the rectal route. We measured venous plasma acetaminophen concentrations resulting from 45 mg.kg-1 of rectal acetaminophen in ten ASA 1, 15 kg paediatric patients undergoing minor surgery with a standardized anaesthetic. After induction of anaesthesia, a single 650 mg suppository (Abenol, SmithKline Beecham Pharma Inc.) was administered rectally. Plasma was sampled at t = 0, 15, 30, 45, 60, 90, 120, 180, 240 min in the first five patients and at t = 0, 30, 60, 90, 120, 180, 240, 300, 420 min in the subsequent five. Acetaminophen plasma concentrations were determined using a TDxFLx fluorescence polarization immunoassay (Abbott Laboratories, Toronto, Ontario). The maximum plasma concentration was 88 +/- 39 mumol.L-1 (13 +/- 6 micrograms.ml-1) and the time of peak plasma concentration was 198 +/- 70 min (mean +/- SD). At 420 min, the mean plasma concentration was 46 +/- 18 mumol.L-1 (7.0 +/- 0.9 micrograms.ml-1). No plasma concentrations associated with toxicity (> 800 mumol.L-1) were identified. A 45 mg.kg-1 rectal dose of acetaminophen resulted in peak plasma concentrations comparable with those resulting from 10-15 mg.kg-1 of oral acetaminophen at three hours after suppository insertion. It is concluded that the delayed and erratic absorption of acetaminophen after rectal administration leads to unpredictable plasma concentrations. Rectal acetaminophen will not be consistently effective for providing rapid onset of analgesia in children.

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