Effects of an allicin-based product on cryptosporidiosis in neonatal calves

OBJECTIVE: To evaluate effectiveness of an allicin-based product in neonatal calves inoculated with Cryptosporidium parvum. DESIGN: Randomized controlled study. ANIMALS: 43 neonatal calves. PROCEDURE: Calves were inoculated with 1.5 x 10(8) or 7.5 x 10(5) C parvum oocysts within 2 days after birth. Calves were given an allicin-based product once after inoculation or daily for 7 days after inoculation or were not treated. Calves that developed diarrhea were treated by administration of the product. Fecal consistency scores and weight gains were statistically evaluated. RESULTS: Mean daily weight gain and severity of diarrhea in calves 4 to 21 days old were unaffected by prophylactic use of the product. However, intensive prophylactic administration may have delayed onset of C parvum-induced diarrhea in calves inoculated with the lower dose of oocysts. CLINICAL IMPLICATIONS: Administration of an allicin-based product did not alter duration of C parvum-induced diarrhea or enhance weight gain in neonatal calves. However, intensive prophylactic administration of an allicin-based product may delay onset of diarrhea in calves exposed to C parvum oocysts.     

Stimulus specific adaptation in inferior temporal and medial temporal cortex of the monkey

We studied the early immunity induced by a live glycoprotein E (gE) negative bovine herpesvirus 1 (BHV1) marker vaccine. Three groups of specific-pathogen-free calves were either not vaccinated, or vaccinated two days or two hours before the introduction of a calf that was intranasally infected with wild-type BHV1 the day before. We quantified the shedding of gE-negative vaccine virus and of wild-type virus, using a double-staining immunoassay. In calves vaccinated two hours before the introduction of the infected calf, the shedding of wild-type virus was reduced, compared with that of the unvaccinated control calves. The shedding of wild-type virus was most significantly reduced in the calves that were vaccinated two days before: only very small amounts of wild-type virus were isolated. Wild-type virus was not detected at all in the samples from one of the five calves of that group. Furthermore, this calf was the only one in which we did not detect antibodies against gE. Hence, intranasal vaccination with a live gE-negative vaccine induced early immunity against a BHV1 contact infection. This suggests that this vaccine can be used efficaciously in the early stages of a BHV1 outbreak.     

Development of a highly infective Babesia bigemina vaccine of reduced virulence

The virulence of a strain of Babesia bigemina was reduced by syringe passaging at 3 to 16-week intervals in a series of 7 calves. The calves were splenectomised 1 to 14 weeks after inoculation to induce the relapse parasitaemias used for passaging. Parasites taken at relapse from the last 3 calves in the series were inoculated into splenectomised calves from which highly parasitised blood for vaccine was obtained. The vaccine produced mild infections in 32 recipient cattle. When challenged either 5 weeks or 7 months after vaccination, the cattle had substantial immunity to a heterologous strain of B. bigemina.     

Babesial antibody dynamics after cattle immunisation with live vaccines, measured with an indirect immunofluorescence test

The efficacy of vaccination of Argentinean cattle against babesiosis and anaplasmosis using live immunogens was tested to detect specific antibodies in samples obtained about 60 days after vaccination. Under these conditions a higher than expected proportion of cattle failed to show antibodies against Babesia bigemina. Therefore, a study was designed to evaluate if this failure was due to insensitivity of the routine test to detect antibodies to B. bigemina or to lack of infectivity of the live vaccine. Four groups (G) of cattle were each inoculated subcutaneously with 10 million Babesia bovis (vaccinal strain R1A), 10 million B. bigemina (vaccinal strain S1A) and 10 million Anaplasma centrale (strain M1). G1 and G2 consisted of ten Angus bulls 20-24 months old and ten Angus bulls 15-18 months old, respectively; G3 and G4 consisted of ten and 16 Holstein 1-month-old male calves, respectively. Blood samples were obtained on days 0, 10, 20, 30, 40, 50 and 60 after vaccination and the sera were analysed with an indirect immunofluorescent (IFA) test to detect antibodies to B. bovis (baseline dilution for a positive result 1:60) and B. bigemina (baseline dilution 1:120). Positive IFA titres were considered as evidence of the infectivity of the Babesia vaccinal strains contained in the vaccine. All Angus bulls were found positive to antibodies against both Babesia species, by day 20 (B. bovis) and day 30 (B. bigemina), whereas 10-25% of Holstein calves were negative throughout. The partial lack of vaccine infectivity in the calves was considered to be a consequence of innate resistance of young calves to Babesia. Antibody titres to B. bovis and B. bigemina declined by day 60 after vaccination. However, all cattle that were positive to B. bovis antibodies on day 50 were still positive to the IFA test 10 days later while 10%, 30% and 12% of cattle of G1, G2 and G3 that were positive to B. bigemina antibodies on day 50 after vaccination were found negative to the IFA test on day 60. In future, samples taken on days 40-50 will be used for detection of B. bigemina antibodies in vaccinated cattle, on day 60 for A. centrale and on either occasion for B. bovis. The reaction to the inoculation of B. bigemina S1A strain appears to lag behind the reaction to B. bovis R1A strain. It is not certain if this is a normal reaction to this B. bigemina strain or the result of interaction with the B. bovis strain.     

Attitudes of oncologists, family doctors, medical students and lawyers to euthanasia

OBJECTIVE: To evaluate clearance of the vaccine strain, immunologic responses, and potential shedding of Brucella abortus strain RB51 organisms after vaccination of bison calves. ANIMALS: Fourteen 7-month-old female bison calves. PROCEDURE: 10 bison calves were vaccinated SC with 1.22 x 10(10) colony-forming units of B abortus strain RB51. Four bison calves were vaccinated SC with 0.15M NaCl solution. Rectal, vaginal, nasal, and ocular swab specimens were obtained to evaluate potential shedding by vaccinated bison. The superficial cervical lymph node was biopsied to evaluate clearance of the vaccine strain. Lymphocyte proliferative responses to strain RB51 bacteria were evaluated in lymph node cells obtained from biopsy specimens and also in peripheral blood mononuclear cells. RESULTS: Strain RB51 was recovered from superficial cervical lymph nodes of vaccinates examined 6, 12, and 18 weeks after vaccination (4/4, 3/4, and 1/4, respectively) but not in vaccinates examined at 24 weeks (0/3) after vaccination or nonvaccinates examined at all sample collection times (n = 1 bison/sample period). Serologic, immunologic, and bacterial culture techniques failed to reveal shedding of strain RB51 by vaccinates or infection of nonvaccinated bison. Lymphocyte proliferative responses were evident in lymph node cells and blood mononuclear cells from strain RB51-vaccinated bison beginning 12 weeks after vaccination. CONCLUSION: Strain RB51 was cleared from bison by 18 to 24 weeks after vaccination. Bison vaccinated with strain RB51 did not shed the vaccine strain to nonvaccinated bison housed in close proximity. Strain RB51 did not induce antibody responses in bison that would interfere with brucellosis surveillance tests, but did stimulate cell-mediated immunity.     

Fecal recovery following oral administration of Lactobacillus strain GG (ATCC 53103) in gelatine capsules to healthy volunteers

Recovery of the suggested probiotic strain Lactobacillus GG in feces was studied after oral administration. Lactobacillus GG was given to 20 healthy human volunteers for 7 days in gelatine capsules with daily doses of 1.6 x 10(8) cfu and 1.2 x 10(10) cfu. All the volunteers in the higher dose group had detectable numbers of Lactobacillus GG in their feces during the test period. The strain was detected in feces of all the volunteers after 3 days of administration. No effect was observed on the total number of fecal lactobacilli. Fecal detection of the strain may facilitate dose-response studies and provide a useful tool in dietary studies utilizing the strain in foods or food-type products.     

Clinical and immunologic responses of vaccinated and unvaccinated calves to infection with a virulent type-II isolate of bovine viral diarrhea virus

OBJECTIVE: To determine efficacy of a modified-live type-I isolate of bovine viral diarrhea virus (BVDV) vaccine in protecting calves from infection with a virulent type-II isolate, and to determine which type of immune response (i.e., humoral or cellular) correlates with protection. DESIGN: Prospective study. ANIMALS: 28 neonatal Holstein and Holstein-cross calves. PROCEDURE: Within 18 hours of birth, calves received maternal colostrum or were fed pooled colostrum. On days 7 to 10 after birth, calves were determined to be seropositive (n = 16) or seronegative (12) for antibodies to BVDV on the basis of ELISA and virus neutralization test results. Seropositive and seronegative 10- to 14-day-old calves were then given a combined vaccine that contained a modified-live type-I isolate of BVDV or a similar vaccine that lacked protection against bovine viral diarrhea. All calves were inoculated intranasally approximately 21 days after vaccination with a virulent type-II isolate of BVDV. Clinical and immunologic variables, including clinical scores, rectal temperatures, results of CBC with lymphocyte subset analysis, antibody responses, and cell-mediated immune responses, were monitored for 14 days after inoculation. RESULTS: Seronegative-unvaccinated calves developed severe disease and required euthanasia. Vaccination of seronegative calves with a modified-live type-I isolate had a disease-sparing effect as did passive transfer of colostral antibodies to BVDV. Clinical scores were not significantly different between seropositive-vaccinated and seropositive-unvaccinated calves after viral inoculation. CLINICAL IMPLICATIONS: A single dose of a modified-live type-I isolate of BVDV vaccine protects young calves from clinical signs of disease associated with type-II isolates.     

Bone mineral assessments in the calcaneus after anterior cruciate ligament injury. An investigation of 92 male patients before and two years after reconstruction or revision surgery

Dairy calves under 14 days of age with naturally occurring, uncomplicated diarrhea were treated for 3 days with a hypertonic oral electrolyte solution with (n = 15) or without (n = 12) psyllium. Clinical response and clinical pathology data were compared between the 2 groups. Glucose absorption was evaluated on days 1 and 3 by measurement of plasma glucose and lactate and serum insulin concentrations for 4 hours after formula administration. On day 1, glucose, lactate, and insulin concentrations were lower in psyllium-fed calves than in control calves, with significant differences noted in glucose and lactate concentrations at several time points (P < 0.05). Plasma lactate concentrations were higher at several times in both treatment groups on day 3 than on day 1 (P < 0.05). Fecal consistency was markedly different in psyllium-fed calves as compared with control calves within 24 hours of psyllium supplementation. Fecal percent dry matter content was lower in psyllium-fed calves than in control calves at least once a day during supplementation and on day 3 compared with day 0 in the psyllium-fed calves (P < 0.05). There were no significant differences in clinical performance scores, hydration status, arterial blood gas, serum anion gap, electrolyte, or total CO2 concentrations. Addition of psyllium to an oral electrolyte solution resulted in immediate alterations in glucose absorption without impairing rehydration in diarrheic calves, but differences were transient and did not affect clinical outcome.     

Protective immunity induced by oral immunization with a rotavirus DNA vaccine encapsulated in microparticles

DNA vaccines are usually given by intramuscular injection or by gene gun delivery of DNA-coated particles into the epidermis. Induction of mucosal immunity by targeting DNA vaccines to mucosal surfaces may offer advantages, and an oral vaccine could be effective for controlling infections of the gut mucosa. In a murine model, we obtained protective immune responses after oral immunization with a rotavirus VP6 DNA vaccine encapsulated in poly(lactide-coglycolide) (PLG) microparticles. One dose of vaccine given to BALB/c mice elicited both rotavirus-specific serum antibodies and intestinal immunoglobulin A (IgA). After challenge at 12 weeks postimmunization with homologous rotavirus, fecal rotavirus antigen was significantly reduced compared with controls. Earlier and higher fecal rotavirus-specific IgA responses were noted during the peak period of viral shedding, suggesting that protection was due to specific mucosal immune responses. The results that we obtained with PLG-encapsulated rotavirus VP6 DNA are the first to demonstrate protection against an infectious agent elicited after oral administration of a DNA vaccine.     

Treatment of multiple myeloma with high-dose chemotherapy and transplantation of autologous hematopoietic stem cells and subsequent maintenance therapy with interferon alfa-2b or interferon alfa 2b and dexamethasone. Report of the ongoing study of the "4W" Czech Myeloma Group

We report our results with high-dose chemotherapy in previously untreated multiple myeloma patients (4 courses of VAD chemotherapy, collection of PBSC after priming with cyclophosphamide, 5 g/m2, high-dose chemotherapy with melphalan, 200 mg/m2). Second transplantation was indicated only for patients who did not achieve remission after the first high-dose therapy (paraprotein lower than 25% of the pretreatment value). For the second transplantation melphalan (200 mg/m2) with methylprednisolone (1.5 g for 5 days) were used as conditioning regimen. After high-dose therapy all patients were randomized into two arms of maintenance therapy: interferon alpha-2b or sequential maintenance therapy (interferon alpha-2b for 3 months followed after 4 week pause by 40 mg of dexamethasone days 1-4, 10-13 and 20-23. The administration of interferon alpha was resumed four weeks after the last dexamethasone for next three months. The maintenance therapy continued for 48 months or until the progression. Fifty-five patients were enrolled in the study from January 1996 to August 1997. Thirty-five patients have undergone the first transplantation and 57% of them reached complete remission. There were 10% of non-responders after the first high-dose regimen. The mean time to reach white blood cell count above 1 x 10(9)/L after the application of high dose melphalan and platelets more than 50 x 10(9)/L were 12.2 (range 6-16 days) and 12.4 (range 0-25 days), respectively. Grade 4 mucositis according to SWOG classification requiring total parenteral nutrition was presented in 40% of the patients. The mean number of 1 unit of platelets and 2 units of packed red blood cells transfusions were given within the posttransplant period. Early transplant related mortality was 3%. This paper describes the response and tolerance of each particular step of therapy. The follow-up has been too short to evaluate event-free and overall survivals.     

Efficacy of a temperature-sensitive modified-live bovine herpesvirus type-1 vaccine against abortion and stillbirth in pregnant heifers

OBJECTIVE: To evaluate the efficacy of a commercially available temperature-sensitive modified-live bovine herpesvirus type-1 (BHV-1) vaccine against BHV-1 challenge-induced abortion and stillbirth. DESIGN: Prospective randomized control trial. ANIMALS: 20 cycling, nonpregnant, BHV-1 seronegative heifers of various breeds and weights, 12 to 15 months old. PROCEDURE: Heifers were randomly assigned to a vaccinate (n = 10) or nonvaccinate control (n = 10) group. Seventeen to 26 days after members of the vaccinate group received a second dose of vaccine, all heifers were artificially inseminated. Heifers were challenged intravenously with Cooper strain BHV-1 between days 177 and 187 of gestation. Aborted fetuses and stillborn calves were necropsied, and tissues collected for histologic examination and virus isolation. Heifers, calves, and fetuses were tested for BHV-1 antibody throughout the study. RESULTS: The difference in number of abortions or stillbirths between vaccinated heifers (1/10) and control heifers (10/10) was significant (P < 0.003). Seven of 10 control heifers had a virus neutralization antibody titer to BHV-1 at abortion or stillbirth that declined or remained unchanged from their titer at a previous serologic evaluation (7 to 66 days earlier). CLINICAL IMPLICATIONS: Prebreeding vaccination of replacement heifers with modified-live BHV-1 vaccine provides fetal protection at 6 months of gestation (7 months after vaccination) and appears to be a reasonable precaution to control economic losses associated with BHV-1 infection. Abortions induced by BHV-1 are not necessarily associated with rising or markedly high virus neutralization antibody titers. These titers should be used cautiously when assessing the role of BHV-1 in bovine abortion and stillbirth.     

Peripheral blood antibody-secreting cells in the evaluation of the immune response to an oral vaccine

Specific antibody-secreting cells (ASC) appear in the blood as a response to oral vaccination in humans. Based on information from animal experiments, these cells are believed to be migrating to the mucosa. This review summarizes a series of studies aimed at a detailed characterization of the ASC response to a prototype oral vaccine Salmonella typhi Ty21a, with respect to its kinetics, Ig-class distribution, antigen specificity, influence of the administration route and nature of the antigen, and the corresponding antibody responses in serum. Different vaccine formulations as well as dosage schedules are compared, and the response to booster immunization is described. The response manifested by ASC in blood is shown to be independent from serum antibody responses. Moreover, it is shown to parallel with the results obtained for protection in field trials. Finally, some data on the homing receptor expression of these cells are presented, giving further evidence for the mucosal homing of these cells. The ASC assay offers a practical means for assessing immune response to oral vaccines in humans. It can be used as a laboratory parameter correlated with protection conferred by an oral typhoid vaccine. It can even be applied to measure active mucosal immunity, i.e., protective immunity by showing the relative reduction of the ASC response to an oral dose of live vaccine.     

Prevention of Eimeria alabamensis coccidiosis by a long-acting baquiloprim/sulphadimidine bolus

Twelve calves aged 6-10 months, and 12 calves aged 10-16 months were turned out onto a permanent pasture known to have been contaminated with oocysts of Eimeria alabamensis during the previous year. Two days after turnout, six of the older calves and six of the younger were each treated with one bolus per 200 kg bodyweight containing 1.6 g baquiloprim and 14.4 g sulphadimidine. The other 12 calves were left untreated. The excretion of Eimeria oocysts, the faecal dry matter and the weight gain of treated and untreated calves within each age group were compared during the first 3 weeks on pasture to assess the efficacy of the bolus in preventing E. alabamensis coccidiosis. All the older of the untreated calves and four of the younger developed gruel-like to watery diarrhoea 4-7 days after turnout. The faecal consistency of the treated calves remained firm and they lost significantly less weight than the control calves during the first 13 days on pasture. The treated calves also excreted significantly fewer oocysts during the first 20 days of grazing; their oocyst excretion remained low during days 8-10 when all but one of the diarrhoeic control calves excreted more than 850,000 oocysts per gram faeces (OPG). Starting on days 12 to 14 the oocyst excretion of 8 of the treated calves increased to 20,000-65,000 OPG and of 2 calves to 210,000-240,000 OPG. There was no difference in oocyst output between treated and untreated calves from the fourth week of grazing and no difference in weight gain among the younger calves. In the older calves there was a tendency for the untreated calves to gain more weight than treated calves.     

Artificial rearing of double purpose calves of the beef-dairy type. 1. Effects of the length of the milk-rearing period and of the amount of milk substitutes needed for the rearing of the calf

Reducing the period of Milk rearing of calves from 90 days (time of weaning) as practised today to 50 days or 70 days (and thus reducing the amount of regenerated milk which is needed to rear the calf from 400 litres to 200 litres or 300 litres) would limit the rate of weight gains of the calves in the first 3 months of age. This delay is, within certain limits, compensated for by the calf in the growth period up to 6 months of age. Therefore, the authors believe that with cattle of the Hungarian breed "Ungarische Fleckviehrasse" weaning after 50 days and rearing the calves with 200 litres of milk seems to be possible. The method of early weaning and then feeding stock mixtures of concentrates seems to be also applicable provided that the conditions of veterinary hygiene would allow this. This, in turn, would require supplementation of the food with minerals and vitamins. Due to the results obtained supplementation of concentrate mixtures with urea for calf rearing is also possible, even under practical conditions. Aromatization of the concentrate mixtures, as practised in the present series of trials, did not substantiate the favourable results obtained by the authors in previous trials with respect to the effect of aromatics on food consumption and the development of weight gains.     

Podiatric casts used for surgery and trauma. Part II: Boot cast

Between April 18 and May 20, 1975, 16 cases of measles occurred in pupils in an elementary school in Baltimore County, Md., and 1 case occurred in a sibling at a junior high school. Measles was serologically confirmed in 16 of these pupils. Attack rates were determined by grade and by vaccine status. The measles attack rate was 2.1 percent for the 377 children who had been given measles vaccine at 1 year of age or later. The rates were 27.8 percent (13 times higher) for those vaccinated at less than 10 months of age and 20.0 percent (10 times higher) for those with no definite history of vaccine. The higher attack rates for children who were vaccinated only before 10 months of age supports the 1972 recommendation of the Public Health Service Advisory Committee on Immunization Practices that children vaccinated before this age need to be revaccinated with live measles virus vaccine to assure full protection. The finding that 2 of 10 children with a history of measles became ill during the outbreak suggests that such histories are not a totally reliable indicator of immunity. Containment of the outbreak was attributed to the high level of immunity in the community and prompt initiation of control measures.     

Long-term efficacy and immune responses following immunization with the RTS,S malaria vaccine

The malaria sporozoite vaccine candidate RTS,S, formulated with an oil-in-water emulsion plus the immunostimulants monophosphoryl lipid A and the saponin derivative QS21 (vaccine 3), recently showed superior efficacy over two other experimental formulations. Immunized volunteers were followed to determine the duration of protective immune responses. Antibody levels decreased to between one-third and one-half of peak values 6 months after the last dose of vaccine. T cell proliferation and interferon-gamma production in vitro were observed in response to RTS,S or hepatitis B surface antigen. Seven previously protected volunteers received sporozoite challenge, and 2 remained protected (1/1 for vaccine 1, 0/1 for vaccine 2, and 1/5 for vaccine 3). The prepatent period was 10.8 days for the control group and 13.2 days for the vaccinees (P < .01). Immune responses did not correlate with protection. Further optimization in vaccine composition and/or immunization schedule will be required to induce longer-lasting protective immunity.     

Efficacy of a subcutaneously administered, ultraviolet light-killed Pasteurella multocida A:3-containing bacterin against transthoracic challenge exposure in goats

OBJECTIVE: To determine the effectiveness of Pasteurella multocida biovar A, serovar 3 (Pm A:3) killed by exposure to UV light and incorporated with a polyacrylate bead carrier as a vaccine. ANIMALS: 18 weanling male Spanish goats. PROCEDURE: Prospective, randomized controlled study with 3 treatment groups: positive-control (PC), negative-control (NC), and principal Pm A:3 bacterin (PA) groups. Six PC goats each received live Pm A:3 and polyacrylate beads twice, 22 days apart, by transthoracic injection into the left lung. Six NC goats each received only PA beads twice, 22 days apart, by transthoracic injection. Six principal goats each received Pm A:3 vaccine SC twice, 22 days apart. Fourteen days after the second vaccination, all goats were challenge exposed with live Pm A:3 by transthoracic injection into the right lung, and 4 days later they were euthanatized and necropsied. RESULTS: Mean volume of consolidated lung tissue at the challenge site was 1.75 cm3 for the PC group, 15.18 cm3 for the NC group, and 3.9 cm3 for the PA vaccine group. The NC group had a significantly (P < or = 0.002) larger mean volume of consolidated lung tissue than did the PC and PA groups after challenge exposure. CONCLUSIONS: The PA bacterin and the PC groups developed protective immunity against live Pm A:3 challenge exposure. An SC administered, UV light-killed, Pm A:3 bacterin induced protective immunity similar to that induced by virulent live Pm A:3 injected into the target organ, the lung.     

Vaccine genotype and route of administration affect pseudorabies field virus latency load after challenge

The influence of vaccine genotype and route of administration on the efficacy of pseudorabies virus (PRV) vaccines against virulent PRV challenge was evaluated in a controlled experiment using five genotypically distinct modified live vaccines (MLVs) for PRV. Several of these MLVs share deletions in specific genes, however, each has its deletion in a different locus within that gene. Pigs were vaccinated with each vaccine, either via the intramuscular or intranasal route, and subsequently challenged with a highly virulent PRV field strain. During a 2-week period following challenge with virulent PRV, each of the vaccine strains used in this study was evaluated for its effectiveness in the reduction of clinical signs, prevention of growth retardation and virulent virus shedding. One month after challenge, tissues were collected and analyzed for virulent PRV latency load by a recently developed method for the electrochemiluminescent quantitation of latent herpesvirus DNA in animal tissues after PCR amplification. It was determined that all vaccination protocols provided protection against clinical signs resulting from field virus challenge and reduced both field virus shedding and latency load after field virus challenge. Our results indicated that vaccine efficacy was significantly influenced by the modified live vaccine strain and route of administration. Compared to unvaccinated pigs, vaccination reduced field virus latency load in trigeminal ganglia, but significant differences were found between vaccines and routes of administration. We conclude that vaccine genotype plays a role in the effectiveness of PRV MLVs.     

Treatment of advanced gastric cancer with oral etoposide, leucovorin and tegafur: experience with an oral modification of the etoposide, leucovorin and 5-fluorouracil (ELF) regimen

Recent data have suggested enhanced therapeutic activity with prolonged administration of both etoposide as well as fluoropyrimidines in the treatment of gastrointestinal malignancies. Based on this rationale, we investigated the clinical effectiveness and tolerance of an oral modification of the widely applied etoposide, leucovorin and 5-fluorouracil (ELF) regimen in patients with advanced gastric cancer. 32 patients with advanced gastric cancer were treated with oral etoposide (100 mg), leucovorin (3 x 100 mg), and tegafur (3 x 200 mg) over 14-21 days for a maximum of six cycles. Objective response was seen in only 5 patients (16%), stable disease was documented in 7 (22%), while the remaining patients progressed during therapy. The median time to progression was 2.8 months (range 0.7-12 months) and median overall survival was 6 months (range 1-18+ months). Due to grade 3 nausea/emesis, 8 patients discontinued treatment prematurely, while 12 patients experienced anorexia and progressive weight loss. Haematological toxicity was modest, with 4 patients developing asymptomatic grade 3-4 granulocytopenia. We conclude that this oral combination regimen cannot be recommended for the treatment of advanced gastric cancer.     

Safety and immunogenicity of a recombinant hepatitis B vaccine administered to infants at 2, 4 and 6 months of age. The Kaiser-UCLA Vaccine Study Group

A recombinant hepatitis B vaccine was administered to over 5000 infants in a prospective, randomized and blinded study. Infants were given either recombinant hepatitis B vaccine (Engerix-B, SmithKline Beecham Pharmaceuticals, 10 micrograms dose-1) or a Haemophilus influenzae type b (Hib) conjugate vaccine at 2, 4 and 6 months of age simultaneously with diphtheria-tetanus-pertussis and oral polio vaccines. Adverse reactions were ascertained by parental reports and interviews, and review of medical records. Blood specimens collected from 269 infants given hepatitis B vaccine were assayed for antibody to hepatitis B surface antigen (anti-HBs) by enzyme immunoassay. Infants given hepatitis B vaccine experienced low rates of adverse reactions that were similar or lower than the rates in infants given Hib conjugate vaccine. The geometric mean anti-HBs concentrations were 9.6 mIU ml-1 after one dose, 333 mIU ml-1 after two doses and 1812 mIU ml-1 after three doses (99% had levels > or = 10 mIU ml-1). Antibody responses to diphtheria and tetanus toxoids were unaffected by simultaneous administration of hepatitis B or Hib conjugate vaccine. Engerix-B vaccine was safe and immunogenic when given with other routine childhood immunizations at 2, 4 and 6 months of age, and should provide long-term protection against hepatitis B virus infection.