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Biomedical subjects

R Clemens

Publications and source records attributed to R Clemens.

At least 55 records · Page 3Linked to original sources
PubMed1995

Clinical experience with an inactivated hepatitis A vaccine.

Clinical trials of an inactivated hepatitis A vaccine have encompassed 104 studies completed by December 1993 in 27 countries. Studies involved 50,677 subjects and administration of > 120,000 vaccine doses. Results show that the vaccine is safe, clinically well-tolerated, and highly immunogenic in all age groups. A seroconversion rate of 100% is achieved 1 month after primary vaccination. Vaccine-induced antibody titers persist after a primary vaccination course for > or = 1 year with a single dose of 1440 ELISA units (EL.U.) in adults and after two doses of 360 EL.U. in children. A booster dose 6-12 months after the first vaccine dose induces very high antibody titers, which according to a mathematical model, are expected to protect against hepatitis A for > 20 years. The vaccine is equally immunogenic when administered simultaneously with other traveler vaccines, therefore enabling flexible and convenient vaccination against hepatitis A.

Adult↗
PubMed1995

Effects of antithrombin III and antivenom on procoagulant activity of Russell's viper venom in a whole blood model.

The procoagulant activities of Russell's viper venom were assessed in an in vitro whole blood model. Sequential samplings showed that the generation of fibrinopeptide A (FPA), a marker of thrombin activity, and platelet factor 4 (PF4), a marker of platelet activity, exhibited bi-phasic kinetics with an initial slow phase followed by a rapid phase of secretion. In the presence of Russell's viper venom, the generation of both FPA and PF4 was accelerated with the bi-phasic kinetics of PF4 being maintained while that of FPA completely disappeared. Administration of either antivenom (1,600 ng) or 10 IU antithrombin III (AT-III) had no antagonistic effect against the venom but combination of both resulted in a significant prolongation of both FPA and PF4 release (p < 0.05). High dose AT-III (20 IU) resulted in normalization of both FPA and PF4 kinetics and serial levels of both parameters were lower than those treated with the combined regimen, although these were not statistically significant. Unlike the untreated venom activated whole blood, there was no clot formation following treatment with either the combined regimen or high dose AT-III. The results of this study suggested that the effect of Russell's viper venom on the clotting cascade is more potent and direct than that on platelet activity. There were complementary effects between antivenom and AT-III is controlling of both FPA and PF4 release induced by the venom. Furthermore, in this in vitro experiment, AT-III alone when administered in a sufficient dose, abolished the procoagulant effects of Russell's viper venom.

Animals↗
PubMed1994

Antithrombin III and antivenom reversal of coagulopathy in rats envenomated with Malayan pit viper venom.

The therapeutic effects of antithrombin III (AT-III) and unrefined equine antivenom in the treatment of coagulopathy induced by Malayan pit viper (Calloselasma rhodostoma) venom were assessed in 42 adult Wistar rats. Following intramuscular venom injection (2 micrograms/g body weight), serial blood samples were taken from the femoral vein for measurement of whole blood clotting time and AT-III activity. There was progressive depletion of AT-III and blood ceased to clot a mean (S.E.) of 164 (8.3) min after venom injection. Coagulopathy was reversed by a high dose antivenom (10 micrograms/g) or a lower dose of antivenom (5 micrograms/g) in combination with AT-III (> or = 0.1 U/g; P < 0.01) but not 5 micrograms/g antivenom or AT-III alone. Following successful treatment, the mean plasma AT-III activity remained above 90%. In this animal model, systemic envenomation by the Malayan pit viper causes uncoagulable blood associated with AT-III consumption. The dose of antivenom required to reverse this coagulopathy can be reduced by half by the addition of AT-III sufficient to maintain blood concentrations within the normal range.

Animals↗
PubMed1994

Blood stage antimalarial efficacy of primaquine in Plasmodium vivax malaria.

The blood stage antimalarial efficacy of primaquine (0.25 mg of base/kg of body weight/day over 14 days) and chloroquine (25 mg of base/kg over 3 days) were compared in 85 adult Thai men with acute Plasmodium vivax malaria. Most (75%) had at least one malaria episode previously. Parasite clearance times after primaquine alone (n = 30) were slower than after chloroquine (n = 30) or combined chloroquine-primaquine (n = 25), but all patients had a satisfactory initial therapeutic response. P. vivax malaria recurred in 10 (17%) of 60 patients followed for > or = 2 months and Plasmodium falciparum malaria developed in another 5 (8%) without reexposure to infection. Recurrences occurred < or = 5 weeks after primaquine treatment (n = 4), suggesting recrudescence, whereas recurrences after chloroquine treatment (n = 6) occurred > or = 5 weeks later, suggesting relapse. Vivax malaria responds well initially to either primaquine or chloroquine. The blood stage antimalarial activity of primaquine may mask chloroquine resistance in combined regimens.

Adolescent↗
PubMed1994

Activation of the coagulation cascade in severe falciparum malaria through the intrinsic pathway.

The mechanisms involved in the activation of the coagulation cascade in severe falciparum malaria were studied in 22 adult patients (19 male, three female) aged 18-45 (mean +/- SD 31 +/- 11) years. Of these, nine had multiple vital organ dysfunction, and bleeding occurred in four patients, two of whom died. During acute illness the reduction in plasma antithrombin III (AT III) concentrations and elevation in thrombin-AT III complexes were associated with significant reductions in factor XII and prekallikrein activities, and an increase in the C1 inhibitor antigen/activity ratio. Serial plasminogen activity remained within the normal range in all patients while protein C activity was significantly reduced. All patients had markedly elevated plasma polymorphonuclear leucocyte elastase (PMN-elastase) levels with mild depletion of alpha-2 macroglobulin but normal concentrations of alpha-1 antitrypsin. There was no correlation between PMN-elastase concentrations and any of the coagulation parameters or concentrations of proteinase inhibitors. These results suggest that the intrinsic pathway of the clotting cascade is activated in severe malaria. This may cause activation of the complement system and release of bradykinin and PMN-elastase and could contribute to the pathogenesis of severe malaria.

Adolescent↗
PubMed1993

[Active immunization against hepatitis A. Comparison of various immunization schedules].

Three different immunization schedules were compared in 144 young, healthy adults (81 men, 63 women; mean age 28.5 years). They were randomly assigned to one of three groups: group 1, immunization shots on day 0 and day 14 (n = 47), group 2, on day 0 and day 28 (n = 50), and group 3, on day 0, 14 and 28 (n = 47). All participants had a booster shot after one year. The seroconversion rate was 40-46% after first shot, 95-100% after the second one; all were anti-HAV positive after the booster injection. All subjects had specific antibodies in a mean concentration of > 400 IU/l two weeks after the second shot. In almost all subjects antibodies were demonstrable up to the 12th month after the first immunization (> 20 IU/l). Mean antibody concentration during the interval between the second and third immunization after basal immunization on day 0 and 14 or 0 and 28, respectively, was comparable. Three initial immunizations 14 days apart did not achieve much higher anti-HAV levels. The vaccine was equally well tolerated in all three groups. Thus basal immunization shortened to two injections two weeks apart presents a good alternative to the standard scheme of two injections four weeks apart. Three injections two weeks apart bring no demonstrable advantage.

Adult↗
PubMed1993

[Halofantrine in the treatment of imported malaria in nonimmune travelers].

The efficacy (criteria: cure rate, time to resolution of fever or absence of parasites) and safety (criteria: clinical side effects, altered laboratory parameters) of halofantrin were investigated in a multi-centre study of 96 non-immune patients (71 men, 25 women, mean age 34.3 [21-62] years) with malaria imported from regions of high resistance into Germany or Switzerland. The initial 63 patients received one-day treatment (three doses of 500 mg halofantrin), while the last 33 patients received an additional course of treatment one week later. Treatment was curative in all patients in the second group, but relapses occurred in five of the 41 patients (12.2%) with falciparum malaria who received one-day therapy. Fever resolved after a mean of 45 hours and parasites were absent after a mean of 66 hours. There were small increases in transaminase values (most probably because of the infection) in five patients, but all became normal again within a few days. Halofantrin is a safe drug and is suitable for both therapy and stand-by therapy of resistant Plasmodium infections. Treatment should be repeated after 7 days.

Adolescent↗
PubMed1993

Hemodynamic profile of intravenous fenoldopam in patients with hypertensive crisis.

Fenoldopam, a newly developed intravenous dopaminergic DA1 receptor agonist, was used in an open, prospective study for blood pressure control in 12 patients presenting with hypertensive crisis. At a dose of 0.2-0.5 microgram kg-1 min-1 fenoldopam decreased systolic blood pressure from 209 +/- 13 to 151 +/- 17 mmHg and diastolic blood pressure from 114 +/- 10 to 78 +/- 10 mmHg. Blood pressure was controlled in all 12 patients within 5-50 min. In none of the patients did rebound hypertension occur upon termination of the study medication, nor was any adverse event reported. Major hemodynamic changes induced by fenoldopam were a decrease in total peripheral resistance from 1853 +/- 611 to 1193 +/- 368 and in pulmonary vascular resistance from 252 +/- 170 to 180 +/- 74 dyne s-1 cm-5. In patients with high left ventricular filling pressure at study pulmonary capillary wedge pressure decreased while the stroke volume index and mixed venous oxygen saturation increased under fenoldopam. Thus, fenoldopam appears to be a rapid-acting, well-tolerated, and highly effective intravenous substance for the treatment of severe hypertension.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1992

Influence of vaccination schedules and host factors on antibody response following hepatitis B vaccination.

In a prospective multicentre trial, the influence of schedule, compliance, age, sex and weight on the antibody response to hepatitis B vaccination was investigated. Comparison of the vaccination schedules 0, 1, 6 months (group 1; n = 143) and 0, 1, 2, 12 months (group 2; n = 141) was performed in months 3, 7 and 12. In addition, the antibody response was compared one month after the third and one and six months after the last vaccination. Seroprotection rates (anti-HBs greater than 10 IU/l) and antibody titres, given as geometric means (GMTs), were higher in group 1 at month 12 as well as one month after completion of three immunizations. More vaccinees of group 2, however, showed seroprotection at month 3 with higher GMTs. In addition, GMTs in group 2 were higher both one month and six months after the last vaccine dose. Determination of parallel corrected correlation factors demonstrated that age was the most important single factor, followed by body weight and sex. However, no more than 3% of the variation in the GMT can be explained by the influence of age. Due to decreased compliance with the four-dose schedule with a drop-out rate of approximately 10% of the vaccinees, the total percentage of initial vaccinees who in the end developed protective antibody levels was higher in the 0, 1, 6 months schedule. Thus, it can be concluded that subjects likely to comply will benefit from the 0, 1, 2, 12 months schedule as more rapid protection is obtained and the higher antibody levels after the booster vaccination at month 12 provide longer protection. However, vaccinees whose compliance might be questionable over a period of 12 months, should be selected for the vaccination 0, 1, 6 months schedule as compliance is at a higher level over this period and advantage can be taken of the booster effect of the third dose given in month 6.

Adolescent↗
PubMed1992

Immunogenicity, reactogenicity and consistency of a new, inactivated hepatitis A vaccine--a randomized multicentre study with three consecutive vaccine lots.

We investigated immunogenicity, reactogenicity and consistency of three consecutive lots of an inactivated hepatitis A vaccine in 204 seronegative volunteers. Each volunteer received a total of three doses of vaccine (720 EIU) according to a 0, 1 month primary vaccination schedule with a booster dose given at month 6. Mild, moderate and mostly local side effects were reported in 49.7% after the first and in less than 30% after the third injection. Seroconversion rate after one vaccine dose was as high as 91%. All subjects but one had already seroconverted by 1 month after the second injection, corresponding to a seroconversion rate of 99%. The geometric mean titres (GMT) increased with each dose of vaccine administered. Our results show that this inactivated hepatitis A vaccine is highly immunogenic, safe and well tolerated. Furthermore, there were no significant differences between the three vaccine lots in respect to seroconversion rate, size of antibody titre or reactogenicity.

Antibodies, Viral↗
PubMed1992

Vaccination against hepatitis A: comparison of different short-term immunization schedules.

A total of 114 healthy young adults were immunized with hepatitis A vaccine using different vaccination schedules. Individuals received either a single dose (group 1), two doses given simultaneously (group 2), two doses at days 0 and 14 (group 3) or at days 0 and 28 (group 4), or three doses at days 0, 7 and 21 (group 5). Two weeks after a single dose, seroconversion rates between 77 and 85% were achieved (groups 1, 3, 4). All individuals immunized with two doses within two weeks (groups 2, 3, 5) had antibodies to hepatitis A vaccine (anti-HAV positive) by week 3; these participants also showed clearly higher mean anti-HAV values (geometric mean titres, GMTs) at this time than those individuals vaccinated only once. GMTs at week 8 were 560 IU/l in group 5, 236, 339 and 428 IU/l in groups 2-4 and 102 IU/l in group 1. Of participants with anti-HAV at week 8, 82 were again tested 4 months later; all were still seropositive. Ten individuals were tested during the first three weeks at 3-4 day intervals for anti-HAV immunoglobulin M (IgM); specific IgM responses were not detectable before day 10 but were present in eight of 10 vaccinees by day 14.

Adult↗
PubMed1992

Russell's viper venom: effects on coagulating whole blood in vitro.

Russell's viper venom (RVV) leads to a strong activation of the coagulation system with consumptive coagulopathy and thrombopenia. For better comprehension of the pathophysiologic process, the effect of RVV was examined in an in vitro model of hemostasis. The stimulation of the coagulation system and of platelet activity can be discriminated by sequential measuring of fibrinopeptide A (FPA) generation and platelet factor 4 (PF 4) release, respectively. In coagulating whole blood both parameters show a parallel response curve in the control series (n = 6) with an initial slow phase followed by a rapid phase after 4.7 +/- 0.8 min (FPA) and 6.0 +/- 0.9 min (PF 4) of the incubation period. Varying concentrations of RVV (15, 50, 100 and 1,000 ng/ml; n = 6 each) cause a dose-dependent stimulation of FPA generation as well as of PF 4 secretion. Clot formation time shows a decrease from 9 min (controls) to 6.3 +/- 2.0 min (100 ng/ml RVV) and 2.7 +/- 0.5 min (1,000 ng/ml), respectively. The concomitant addition of antithrombin III (AT III, 20 U/ml) and RVV (100 ng/ml) leads to a nearly complete normalization of hemostasis in vitro. The beginning of the rapid activation phase is comparable to that of the control group, clot formation does not occur during the 10-min incubation period. Heparin (1 IU/ml) acts as an antagonist not only of the venom-induced FPA generation, but also of the PF 4 release. Prostaglandin E1 (PGE1) (150 ng/ml) does not inhibit the RVV-stimulated FPA generation, but causes a moderate inhibition of PF 4 secretion, especially during the rapid phase.(ABSTRACT TRUNCATED AT 250 WORDS)

Dose-Response Relationship, Drug↗
PubMed1992

The efficacy of halofantrine in the treatment of acute malaria in nonimmune travelers.

A multicenter prospective trial was performed to investigate the efficacy and the tolerability of halofantrine in nonimmune patients with malaria imported from areas with drug-resistant falciparum parasites (mainly Africa). Forty-five of the 74 subjects were treated with a one-day regimen (3 x 500 mg) of halofantrine, and the other 29 received the same regimen with an additional treatment on day 7. In the second group, a 100% efficacy rate was demonstrated, but in the group receiving the one-day regimen, four recrudescences were observed in patients with falciparum malaria. Only five mild adverse reactions were seen, which disappeared spontaneously after the end of the treatment. We conclude that halofantrine is highly effective in curing malaria in nonimmune subjects. The treatment scheme for such persons should include an additional treatment on day 7 for nonimmune individuals. This drug was well tolerated in our patients, indicating that halofantrine will be useful in the treatment of multidrug-resistant malaria in nonimmune persons.

Acute Disease↗
PubMed1991

Coagulation disorders in experimentally induced acute mouse malaria.

The development of coagulation disorders was studied in murine malaria. Plasmodium vinckei was chosen following an initial experiment because onset and duration of parasitemia were more suitable for hemostasiological studies than in the short-lasting infection, caused by P. berghei. Evaluation of the time courses of hematocrit, platelets, antithrombin (AT) III activity, Factor V activity and parasitemia showed a significant decrease in platelets, hematocrit, Factor V and AT III activity during the course of infection. The obtained data strongly suggest the development of a disseminated intravascular coagulation in mice during the terminal phase of murine malaria.

Animals↗
PubMed1989

Active immunization of homosexual men using a recombinant hepatitis B vaccine.

Twenty homosexual men [13 anti-human immunodeficiency virus (HIV)-positive, seven anti-HIV negative] without HBsAg, anti-HBs, and anti-HBc were vaccinated with three 20 micrograms doses of a recombinant hepatitis B vaccine. All anti-HIV-positive homosexuals were nonresponders independent of the initial number of CD4-positive cells. Among seven anti-HIV-negative individuals, five responded. After three doses of the vaccine, CD4-positive cells fell in anti-HIV positive individuals by 22.4%. A similar fall in CD4-positive cells of an average 24.9% was noted in 17 matching, but nonvaccinated, anti-HIV-positive homosexuals. The study indicates that the efficacy of vaccination in anti-HIV-positive individuals is questionable. There is, however, no evidence that vaccination against hepatitis B might be harmful to anti-HIV-positive subjects.

Adolescent↗