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Biomedical subjects

J Lang

Publications and source records attributed to J Lang.

At least 127 records · Page 7Linked to original sources
PubMed1999

[Recurrent epithelial ovarian cancer].

OBJECTIVE: To evaluate the factors of influence on recurrent epithelial ovarian cancer and to make strategy of treatment. METHODS: Retrospective study of 189 cases of ovarian cancer admitted in our hospital from Jan, 1987 to Dec, 1997. All of these cases had postoperative pathological diagnosis. RESULTS: Of 31 recurrent cases, 19 cases had first cytoreductive surgery in our hospital, while other 12 cases were done in other hospitals. According to FIGO criteria, stage I, II 4 cases (12.9%), III, IV 27 cases (87.1%). The mean recurrent time of no-residual disease was 17.2 months, while that of residual disease < or = 2 cm was 10.1 months (P < 0.01). The mean recurrent time of those having chemotherapy > or = 6 cycles was 13.1 months, while that of those having chemotherapy < 6 cycles was 10.1 months (P > 0.05). The five-year survival rate of 18 cases having secondary cytoreductive surgery was 27.3%, while that of 4 cases having chemotherapy only was 7.1% (P < 0.01). The five-year survival rate of 7 cases abandoning any therapy was 4.8% (P < 0.01). 2 cases had only irradiation therapy. CONCLUSIONS: Histology, stage, degree of tumor differentiation, chemotherapy and the residual disease of cytoreductive surgery all influence recurrence of epithelial ovarian cancer. Secondary cytoreductive surgery along with chemotherapy can raise recurrent epithelial ovarian cancer's five-year survival rate.

Antineoplastic Agents↗
PubMed1999

[Diagnosis and treatment of endodermal sinus tumor of the vagina].

OBJECTIVES: To describe the clinical characteristics and the role of chemotherapy in endodermal sinus tumor of the vagina. METHOD: Two patients with endodermal sinus tumor of the vagina were presented focusing on the clinical manifestations and outcome of the chemotherapy. RESULTS: Patient's age was quite young, 2 and 3 years old respectively. Vaginal bleeding and a polypoid and fragile tumor of the vagina were main clinical features. Elevated serum alpha-FP was found before chemotherapy and dropped dramatically to normal if the tumor was sensitive to chemotherapy. Diagnosis was made by pathology and alpha-FP immunohistochemical staining. Both two patient was well responded to cisplatin vincristine bleomycin (PVB) and cisplatin etoposide bleomycin (PEB) chemotherapy. Clinical and pathological complete remission was obtained after 2-3 courses of chemotherapy without radical surgery and radiotherapy. CONCLUSIONS: Endodermal sinus tumor of vagina in infant was very sensitive to the chemotherapy. Serum alpha-FP was very useful in diagnosis and monitoring of the disease.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1999

[Vaginal hysterectomy for large uterus].

OBJECTIVE: The technique and experience of vaginal hysterectomy for large uterus of 25 cases was reported. METHODS: Vaginal hysterectomy for 25 cases of uterine fibroids and adenomyosis were performed. The uterine sizes enlarged as large as 6-16 weeks of pregnancy, mobile, no adhesion by estimation. The technique used for reducing the uterine bulk included bisection, myomectomy, morcellation and coring. The most common way to reducing the uterine bulk was bisection combined with myomectomy and morcellation. RESULTS: Twenty four cases of vaginal hysterectomy were performed successfully. The average weight of uterus for the 25 cases was 360 g(range from 155 g to 755 g), the mean time for the operation was 95 minutes(range from 60 to 150 minutes), the average quantity of blood loss was 150 ml (range from 50 to 400 ml), the average admission duration of postoperation was 5.3 days(range from 3 to 8 days). CONCLUSION: Vaginal hysterectomy is a safe and effective option for removing enlarged uterus. The successful operation was related to the uterine sizes, mobile, operator' skill and experiences.

Adult↗
PubMed1999

[Diagnosis, treatment and prevention of postoperative deep venous thrombosis in gynecologic onocology].

OBJECTIVE: To describe the clinical profile of deep venous thrombosis (DVT) after operation on pelvic tumours and to study how to choose the methods of diagnosis, treatment and prevention of DVT. METHODS: The clinical characteristics, the methods of diagnosis, treatment and prevention of 11 cases with DVT and 18 cases with the tendency to DVT were analyzed retrospectively. RESULTS: Old age, fatness and oringinal pelvic malignant tumours were the high risk factors for postoperative DVT. Especially the patients with endometrial carcinoma were with the high incidence of DVT. Colour-code Doppler ultrasonography was the best choice to diagnose DVT. Heparin or low molecule weight heparin (LMWH) anticoagulation was effective treatment in postoperative DVT. CONCLUSIONS: Old age, fatness and gynecologic malignant tumours should be considered as highrisk factors for postoperative DVT. Preoperative or postoperative prophylatic treatment of DVT should be considered in high risk population. Anticoagulation was effective in postoperative DVT.

Adult↗
PubMed1998

Cysteine-string proteins regulate exocytosis of insulin independent from transmembrane ion fluxes.

Cysteine-string proteins (Csps) are vesicle proteins involved in exocytosis of synaptic vesicles in Drosophila and modulation of presynaptic calcium influx. As both the contribution of calcium channel regulation to the role of Csp in exocytosis and a function of Csp outside the nervous system are unknown, we studied its function in endocrine exocytosis from large dense core vesicles (LDCVs) using insulin-secreting pancreatic beta-cells. Csps were expressed in primary and derived beta-cell lines on insulin-containing LDCVs. Suppression of Csp expression reduced not only depolarisation induced insulin release but also exocytosis in permeabilised cells directly stimulated by Ca2+. Thus, Csp is a secretory granule protein and is required for endocrine exocytosis independent of the modulation of transmembrane calcium fluxes.

Animals↗
PubMed1998

Optimization of temperature distributions for regional hyperthermia based on a nonlinear heat transfer model.

We describe an optimization process specially designed for regional hyperthermia of deep seated tumors in order to achieve desired steady-state temperature distributions. A nonlinear three-dimensional heat-transfer model based on temperature-dependent blood perfusion is applied to predict the temperature. Optimal heating is obtained by minimizing an integral object function which measures the distance between desired and model predicted temperatures. Sequential minima are calculated from successively improved constant-rate perfusion models employing a damped Newton method in an inner iteration. Numerical results for a Sigma 60 applicator are presented.

Humans↗
PubMed1998

Evaluation of the safety, immunogenicity, and pharmacokinetic profile of a new, highly purified, heat-treated equine rabies immunoglobulin, administered either alone or in association with a purified, Vero-cell rabies vaccine.

A clinical evaluation of a new, purified, heat-treated equine rabies immunoglobulin (PHT-Erig), F(ab')2 preparation, was carried out in Thailand and in the Philippines-two countries where rabies is endemic. An initial prospective, randomised, controlled trial (Study 1), compared the safety and pharmacokinetics (serum concentrations of rabies antibodies) after administration either of PHT-Erig or of a commercially-available, equine rabies immune globulin (Erig PMC). A second trial (Study 2) simulated post-exposure rabies prophylaxis by using a reference cell culture vaccine, the purified Vero-cell rabies vaccine (PVRV), administered in association with either Erig PMC or PHT-Erig. In Study 1, 27 healthy, Thai adults received a 40 IU kg(-1) dose of either Erig PMC (n = 12) or PHT-Erig (n = 15) via the intramuscular (i.m.) route; half of the dose was injected into the deltoid area and the other half into the buttocks. Serum for rabies antibody determination and F(ab')2 concentration was collected at hours (H) 0, 6 and 12, and on day (D) 2, 3, 4, 6, 8, 10, 12 and 15. Both products were safe, with no serious adverse events, and in particular, no anaphylactic reactions or serum sickness was reported. A statistical comparison of the pharmacokinetic parameters did not demonstrate bioequivalence of the two products. Nonetheless, the relative bioavailability of 93% and the similar absorption rates suggest the pharmacokinetic profiles of Erig and PHT-Erig are similar. The antibody level in either group were low throughout the 15-day study period. The geometric mean titer (GMT) values ranged from group 0.027-0.117 IU ml(-1) in the Erig group and from 0.029 to 0.072 IU ml(-1) in the PHT-Erig. There was no significant difference between the evolution of GMT values for the two groups. In Study 2, 71 healthy volunteers received 40 IU kg(-1) via the intramuscular route of either Erig PMC (n = 36) or PHT-Erig (n = 35) on D0, in association with five doses of PVRV on D0, D3, D7, D14 and D28. The safety evaluation was performed during the 28-day follow-up and serum samples for anti-rabies antibody titration were collected on D0 (before injection) D3, D7, D14 and D28. No serious reactions were reported in either group. In particular, no immediate (anaphylactic type) or delayed (serum sickness) allergic reactions were observed. Over the 28-day follow-up period, GMT profiles of the two groups were statistically equivalent. On D14, 100% of the subjects had protective antibody titers (anti-rabies antibodies > or = 0.5 IU ml(-1), which is the WHO-recommended level of seroconversion), and Erig PMC and PHT-Erig were indistinguishable according to the clinical definition chosen. On D28, the GMT values were 33.2 IU ml(-1) (95% CI, 23.8-46.1 IU ml(-1)) in the Erig PMC/PVRV group and 31.4 IU ml(-1) (95% confidence interval, CI, 23.4-42.2 IU ml(-1)) in the PHT-Erig/PVRV group, showing evidence of adequate vaccine-induced antibody responses in both groups. The increased purity, the heat-treatment step introduced in the manufacturing process of PHT-Erig, and the good clinical results substantiate the use of this new generation, purified equine F(ab')2 preparation in the post-exposure prophylaxis of rabies.

Adolescent↗
PubMed1998

The BirthPlace collaborative practice model: results from the San Diego Birth Center Study.

Objective: The search for quality, cost-effective health care programs in the United States is now a major focus in the era of health care reform. New programs need to be evaluated as alternatives are developed in the health care system. The BirthPlace program provides comprehensive perinatal services with certified nurse-midwives and obstetricians working together in an integrated collaborative practice serving a primarily low-income population. Low-risk women are delivered by nurse-midwives in a freestanding birth center (The BirthPlace), which is one component of a larger integrated health network. All others are delivered by team obstetricians at the affiliated tertiary hospital. Wellness, preventive measures, early intervention, and family involvement are emphasized. The San Diego Birth Center Study is a 4-year research project funded by the U.S. Federal Agency for Health Care Policy and Research (#R01-HS07161) to evaluate this program. The National Birth Center Study (NEJM, 1989; 321(26): 1801-11) described the advantages and safety of freestanding birth centers. However, a prospective cohort study with a concurrent comparison group of comparable risk had not been conducted on a collaborative practice-freestanding birth center model to address questions of safety, cost, and patient satisfaction.Methods: The specific aims of this study are to compare this collaborative practice model to the traditional model of perinatal health care (physician providers and hospital delivery). A prospective cohort study comparing these two health care models was conducted with a final expected sample size of approximately 2,000 birth center and 1,350 traditional care subjects. Women were recruited from both the birth center and traditional care programs (private physicians offices and hospital based clinics) at the beginning of prenatal care and followed through the end of the perinatal period. Prenatal, intrapartum, postpartum and infant morbidity and mortality are being compared along with cost-effectiveness and acceptance of the model by patients. Data collection occurred primarily through medical record abstraction with the addition of two patient questionnaires. Comparability of the cohorts was established by using a validated methodology to determine medical/perinatal risk and birth center eligibility, which included assessment by two CNMs and an independent blind review by a perinatologist. The cost analysis uses a resource-utilization approach and new methodologies such as activity-based-costing to compare costs from both the perspective of the payor and the health care provider. Patient satisfaction was measured using a self-administered patient questionnaire.Results: Current preliminary results from approximately 38% of the final expected study sample are available. Crude and adjusted analysis have been conducted. Overall, the preliminary results suggest similar morbidity and mortality in the two groups. Fetal deaths are 0.75% in the index and 0.64% in the comparison group, with early neonatal deaths at 0.26% and 0.23%, respectively. The traditional care group showed adjusted rate differences of 5.83% more major maternal intrapartum complications and 9% more NICU admissions. While the birth center group showed adjusted rate differences of 5.5% more low birth weight and 0.95% more preterm birth. For other outcomes, the birth center group showed an adjusted rate difference of 22.34% more exclusive breastfeeding at discharge. Also, there was less utilization of cesarean section and assisted delivery in the birth center group as compared to the traditional care group. The adjusted rate difference for normal spontaneous vaginal deliveries in nulliparas was 10.23% more in the birth center group, with similar results in multiparas with and without history of cesarean (28.88% and 7.84%, respectively). Preliminary results also show that the average total cost for pregnancy-related services paid by California Medicaid was $4,550 for the birth center and $5,535 for the traditional care group. Final results based on the full study sample (full data available February 1998) details of payor costs such as provider, facility, NICU, and ancillary along with costs from the health care system perspective and patient satisfaction results will be presented.Conclusion: Current results suggest similar morbidity and mortality between the birth center program and traditional care groups, with less resource utilization translating to lower costs in the collaborative practice model. Results suggest that collaborative practice using a freestanding birth center as an adjunct to an integrated perinatal health care system may provide a quality, lower-cost alternative for the provision of perinatal services.

Journal Article↗
PubMed1998

G-protein betagamma-binding domains regulate insulin exocytosis in clonal pancreatic beta-cells.

We have tested the putative role of G-protein beta-subunits in insulin exocytosis by transient expression of betagamma-binding proteins targeted to the plasma membrane. The PH domain of the G-protein-linked receptor kinase 2 fused to the transmembrane domain of a cell surface receptor and the alpha-subunit of the retinal G-protein transducin inhibited stimulated insulin release from intact and permeabilised HIT-T15 cells. This effect cannot be imputed to an increase in free Galpha, as the RGS protein RGS3 did not reverse this effect. Among the isoforms of Gbeta examined, Gbeta2 was detected on the plasma membrane by confocal immunomicroscopy. These observations suggest a role for G-protein betagamma-subunits in insulin exocytosis.

Animals↗
PubMed1998

Ca2+-independent insulin exocytosis induced by alpha-latrotoxin requires latrophilin, a G protein-coupled receptor.

alpha-Latrotoxin (alpha-LTX) induces exocytosis of small synaptic vesicles (SSVs) in neuronal cells both by a calcium-independent mechanism and by opening cation-permeable pores. Since the basic molecular events regulating exocytosis in neurons and endocrine cells may be similar, we have used the exocytosis of insulin-containing large dense core vesicles (LDCVs) as a model system. In primary pancreatic beta-cells and in the derived cell lines INS-1 and MIN6, alpha-LTX increased insulin release in the absence of extracellular calcium, but the insulin-secreting cell lines HIT-T15 and RINm5F were unresponsive. alpha-LTX did not alter membrane potential or cytosolic calcium, and its stimulatory effect on exocytosis was still observed in pre-permeabilized INS-1 cells kept at 0.1 microM Ca2+. Consequently, pore formation or ion fluxes induced by alpha-LTX could be excluded. The Ca2+-independent alpha-LTX-binding protein, latrophilin, is a novel member of the secretin family of G protein-coupled receptors (GPCR). Sensitivity to alpha-LTX correlated with expression of latrophilin, but not with synaptotagmin I or neurexin Ialpha expression. Moreover, transient expression of latrophilin in HIT-T15 cells conferred alpha-LTX-induced exocytosis. Our results indicate that direct stimulation of exocytosis by a GPCR mediates the Ca2+-independent effects of alpha-LTX in the absence of altered ion fluxes. Therefore, direct regulation by receptor-activated heterotrimeric G proteins constitutes an important feature of the endocrine exocytosis of insulin-containing LDCVs and may also apply to SSV exocytosis in neurons.

Animals↗
PubMed1998

Encapsulation of Inorganic Particles by Dispersion Polymerization in Polar Media

Polymer encapsulation of small silica particles, using dispersion polymerization of styrene in aqueous ethanol medium with poly(N-vinyl pyrrolidone) (PVP) as stabilizer, is described. Silica particles, directly synthesized by the Stober process in an aqueous ethanol medium, are either unreacted (hydrophilic character) or coated with 3-(trimethoxysilyl)propyl methacrylate (MPS) (hydrophobic character), which is grafted at the silica particle surface. When the bare silica particles are used as the seed, there is a strong tendency of the silica beads to cover the surface of the polystyrene particles and obviously encapsulation does not occur. On the contrary, when the silica surface is made hydrophobic by coating, the inorganic particles are entirely contained in the polystyrene particles as evidenced by microscopy techniques (TEM, SEM, AFM). It is shown that some polystyrene chains are then chemically bonded to the silica particles, through the coupling agent MPS, and that only a small amount of bonded polystyrene, compared to the total polystyrene synthesized, is sufficient to obtain encapsulation of the silica particles with the entire amount of polystyrene synthesized during the polymerization. Under our experimental conditions, each polystyrene latex particle contains, on average, 4 to 23 silica beads depending, in particular, on the size of the silica. We believe that it is possible to control the composite particle size and morphology by a convenient choice of the composition of the system. Moreover, this new polymer-encapsulation process could be used to synthesize other organic-inorganic composite particles, using, for example, other monomers or minerals. Copyright 1998 Academic Press. Copyright 1998Academic Press

Journal Article↗
PubMed1998

Evaluation of the safety and immunogenicity of a new, heat-treated human rabies immune globulin using a sham, post-exposure prophylaxis of rabies.

A double-blind, controlled, randomized trial was conducted to evaluate the safety and immunogenicity of a new human rabies immune globulin (HTRIG). This product, manufactured by Pasteur Merieux Connaught, PMC, has undergone a heat-treatment step (10 h at 60 degrees C) and removal of mercurothiolate. The corresponding unheated product available from the same manufacturer (human rabies immune globulin, HRIG, IMOGAM RABIES[spr2]) was used for comparison. These two rabies immune globulins (RIGs) were administered either alone or in association with the human diploid cell rabies vaccine (HDCV, IMOVAX[spr2] RABIES, PMC) according to a standard, post-exposure rabies prophylaxis schedule. Sixty-four healthy adults were randomly assigned to four groups of 16 to receive either HRIG/placebo, HTRIG/placebo, HRIG/HDCV or HTRIG/HDCV. RIG was administered at the recommended dose of 20 IU/kg by three intramuscular (i.m.) injections in the gluteus. HDCV or placebo was given on day (D) 0, D3, D7, D14, and D28 into the deltoid by the intramuscular (i.m.) route. Any local reaction from D0 to D3 at the immune globulin injection site, and any systemic reaction from D0 to D42, were monitored by subject diaries. Rabies-neutralizing serum antibody levels were assessed by the rapid fluorescent focus inhibition test (RFFIT) before treatment and on D3, D7, D14, D28, D35, and D42. No serious adverse reactions and, in particular, no allergic-type reactions were reported. The safety profiles of HTRIG and HRIG were similar, except that complaints of pain, or tenderness at the injection site were half as common in the HTRIG group. Most of the local reactions were mild or moderate. After the administration of HTRIG/placebo or HRIG/placebo, 60% of subjects had detectable rabies antibodies levels, but by D42 all titres were below the seroprotective level (i.e. below 0.5 IU/ml). In the groups HTRIG/HDCV and HRIG/HDCV, the antibody titres rose markedly from D7, and reached a maximum value of 19 IU/ml (95% CI, 11 to 38 IU/ml) and 31 IU/ml (95% CI, 20 to 48 IU/ml), respectively, on day 14. All subjects who received RIG and vaccine maintained a protective antibody level from D14 to D42. No significant difference in immunogenicity results between these two groups (HTRIG/HDCV and HRIG/HDCV) was observed, and no interference of immune globulin with vaccine was reported. The safety and immunogenicity profiles of PMC HTRIG appear comparable with the current reference product. The heat-treatment step will enhance the safety by further reducing the probability of virus transmission through immune globulin treatment. The low levels of rabies antibodies obtained by intramuscular administration of either PMC HTRIG or of PMC HRIG support the recommendations that call for local infiltration of wounds with RIG.

Adolescent↗
PubMed1998

Immunogenicity and safety in adults of a new chromatographically purified Vero-cell rabies vaccine (CPRV): a randomized, double-blind trial with purified Vero-cell rabies vaccine (PVRV).

Recent improvements in chromatographic purification procedures have made it possible to develop a new chromatographically purified rabies vaccine (CPRV) by further purifying the current rabies vaccine prepared from Vero-cell culture (Verorab; Pasteur Mérieux Connaught). The immunogenicity and safety of primary immunization, followed by a booster at one year, with CPRV was compared to that of the purified Vero cell vaccine (PVRV) in a randomized, double-blind study carried out at four veterinary schools in France. A total of 330 healthy, male and female, first-year veterinary students, aged at least 18 years and who required pre-exposure rabies prophylaxis, were enrolled in this study. Included subjects were randomly assigned either CPRV (n = 163) or PVRV (n = 167) to be given as a primary immunization series of three intramuscular injections (D0, D7, D28), followed by a booster after 1 year (D365). Blood samples for serological analysis were taken at D0 (before first injection), D28, D42, D180, D365 (before booster) and D379. All subjects developed a strong immune response to the primary series, and at D42, all subjects had seroconverted for rabies neutralizing antibody (serum titre > or = 0.5 IU/ml). The rabies virus-neutralizing antibody GMT value at D42 in the CPRV group (23.0 IU/ml) was non-inferior to that in the PVRV group (29.6 IU/ml), according to a one-sided non-inferiority test. While antibody titres tended to decrease over the period of follow-up, at D365 (before booster), 97.5% subjects in the CPRV group and 98.8% of subjects in the PVRV group remained seroconverted. After booster, although the rabies antibody GMT value in the CPRV group was lower than that in the PVRV group, all subjects in both groups were seroconverted, and the difference is probably not clinically important. The incidence of local and systemic reactions tended to decrease with each dose during the primary immunization series, followed by a slight increase after booster (significant time-effect in an exploratory logistic regression analysis). Although mild or moderate local reactions tended to be more frequent after injection with CPRV compared to PVRV, systemic reactions were reported less often (significant group-effects in exploratory logistic regression analyses). One serious adverse event possibly related to vaccine occurred during this study (severe asthenia after the third dose of PVRV). This comparative study in healthy young adults demonstrates that the new chromatographically purified rabies vaccine is as immunogenic as PVRV, and seems to be associated with fewer systemic reactions.

Adolescent↗
PubMed1998

Safety and efficacy of purified Vero cell rabies vaccine given intramuscularly and intradermally. (Results of a prospective randomized trial).

OBJECTIVES: To determine adverse reactions as a result of pre- and post-exposure rabies vaccination, using the conventional intramuscular, and reduced dose intradermal regimens and purified Vero cell rabies vaccine. DESIGN: A prospective and randomized study of patients exposed to rabies and of subjects in need of pre-exposure rabies vaccination. SETTING: A metropolitan rabies control center in a canine rabies endemic country. PATIENTS: 1198 subjects were recruited between May, 1994 and March, 1996. They were divided into four groups. Patients with suspected or proven rabies exposures were given the vaccine intramuscularly using the conventional regimen, or intradermally using the World Health Organization approved Thai Red Cross schedule. Human or equine rabies immune globulin was administered where indicated. Pre-exposure and post-exposure vaccine recipients were divided randomly into two groups each and given the vaccine either by the intramuscular or intradermal schedules. MEASUREMENTS: All local and systemic adverse reactions were recorded and statistically analyzed. RESULTS: Pruritus at injection sites was the only significant local reaction. It was more common in the intradermal groups. Low-grade fever, the only significant adverse systemic event, was more common in the intramuscular groups and was noted in 8% of all subjects. Eighty-four patients bitten by proven rabid animals were found to be alive and well 3 years later. Forty-four of these had received the intramuscular and 40 the intradermal postexposure regimens with human or equine immune globulin injected into wounds on the first day of treatment. CONCLUSIONS: Purified Vero cell rabies vaccine is safe, carries a very low adverse reaction rate and is effective in preventing rabies in severely exposed subjects when used with human or equine rabies immune globulin.

Adult↗
PubMed1998

[Snake bite by European vipers. A multicenter study of tolerance to Viperfav, a new intravenous antivenom].

OBJECTIVES: To evaluate the tolerance and the effectiveness of i.v. Viperfav, a new antivenom containing F(ab')2 fragments of equine antibodies, for the treatment of European viper envenomed patients. STUDY DESIGN: Open, multicentre field trial, associated with a cohort study. PATIENTS: The study included 46 patients of either gender, nine aged less then 10 years, eight between 10 and 15 years, and 28 adults, who sustained a moderate or severe viper envenomation (Grade 2 or 3). METHOD: At the inclusion, a single infusion of Viperfav was given. Depending on the clinical course, up to four additional infusions were to have been administered at 4-hour intervals. To evaluate tolerance, all symptoms were recorded. There were three effectiveness evaluation criterion (duration of hospitalisation, course of the severity grade, recovery (sequelae)) and one subjective criteria (value of the antivenom as ascertained by investigators). RESULTS: In the 46 included patients, 79 infusions were administrated. Concerning tolerance, six mild symptoms were associated to the antivenom infusions. No severe reaction occurred. The mean duration of hospitalisation was 4 days 19 hours +/- 13 hours. A severity grade decrease by at least one point was observed in 35 patients, and all were discharged without sequelae. For the investigators the antivenom was inefficient in only two patients (grade 3 with tissue lesions). CONCLUSIONS: In comparison with literature data (5 to 10% of severe reactions attributable to the antivenom), the tolerance of Viperfav can be considered as satisfactory. As all criteria were in favour of a positive benefit to risk ratio, the authors recommend the use of Viperfav i.v. for the grade 2 and 3 envenomations instead of the current less purified antivenom, which can only be administered by the intramuscular route.

Adolescent↗
PubMed1998

Preclinical assessment of immunoreactivity of a new purified equine F(ab')2 against European viper venom.

The immunological and pharmacokinetic properties of a new, further purified, pasteurized preparation of equine F(ab')2 (VIPERFAV) against Vipera aspis, Vipera berus, and Vipera ammodytes venom were compared with the current equine F(ab')2 preparation (IPSER Europe). Affinity constants of the V. aspis-specific F(ab')2 were determined using biosensor technology and found to be in the range of 10(8) M-1 for the four antigenic fractions of V. aspis toxins and for both F(ab')2 preparations. The improvement of 51% in the specific activity (LD50 mg-1) of the new F(ab')2 was in close agreement with the 1.8-fold increase in the immunoreactive fraction of the new preparation. In vivo investigations of venom immunocomplexation by F(ab')2 in rabbits confirmed the ability of F(ab')2 to neutralize and redistribute toxin venom. Infusion of a stoichiometric molar ratio (i.e., 1 mg kg-1) of the new antivenom induced a 2.3-fold elevation of the plasma venom concentration with a Tmax observed 8 h after F(ab')2 administration and a decline in the terminal half-life from 31.92 +/- 4.49 h to 16.73 +/- 4.34 h, in contrast, for the venom alone. The area under the curve was 1.4-fold greater in the VIPERFAV group than in the IPSER Europe group during the post-F(ab')2 infusion period. Increasing the F(ab')2 dose to 3 mg kg-1 increased by 27% the percent of venom bound to F(ab')2. Finally, the greater the venom distribution, the smaller and less pronounced the plasma redistribution. These results demonstrate that the purification and pasteurization steps involved in the preparation of the new F(ab')2 have no deleterious influence on F(ab')2 affinity but, on the contrary, improve the protective efficacy. Alteration of viper venom kinetics by specific F(ab')2 antivenom was also shown to be dependent on the interval between of F(ab')2 administration and venom bite and on the specific F(ab')2 dose administered.

Animals↗